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  • 1.
    Abdelaal, Abdelrahman
    et al.
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    Abusabeib, Abdelrahman
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Farghaly, Hanan
    Department of Lab Medicine & Pathology, Hamad General Hospital, Doha, Qatar.
    Tabeb, Abdelhakem A. M.
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Simultaneous occurrence of follicular and papillary thyroid carcinomas in same thyroid lobe: A case series of six patients from Qatar2020Ingår i: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 73, s. 65-70Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the first and second most common thyroid cancers comprising about 85% and 10% of all thyroid cancers. Simultaneous occurrence of medullary and papillary thyroid cancer has been reported with various presentations, but simultaneous occurrence of FTC in addition to PTC as differentiated cancers, is an unusual event that is rarely reported. Presentation of cases: We report our experience of six rare cases of synchronous coexistence of FTC and PTC with unique features. Case 1 is 31 old Egyptian female. Case 2 is a 61 year old Sudanese male. Case 3 is a 59 year old Sudanese male. Case 4 is a 56 years old Indian female. Case 5 is a 35 years old Filipina female. Case 6 is a 52 years old Qatari female. The six cases are special in their co-occurrence of two thyroid carcinoma, consisting of histologic features of follicular thyroid carcinomas, and classical papillary thyroid carcinoma, possibly the first case series of simultaneous occurrence of these two types of thyroid cancer in the Middle East and North Africa Region. Conclusions: We present rare cases of concurrent FTC and PTC. These six cases add more data highlighting the coincidental simultaneous coexistence of FTC and PTC. Endocrinologists and pathologists should be aware of and vigilant to this variety. © 2020 The Author(s)

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  • 2.
    Abusabeib, Abdelrahman
    et al.
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar ; College of Medicine, Qatar University, Doha, Qatar.
    Al Hassan, Mohamed S.
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Petkar, Mahir
    Department of Laboratory Medicine & Pathology, Hamad Medical Corporation, Doha, Qatar.
    Mohamed, Sugad
    Department of Laboratory Medicine & Pathology, Hamad Medical Corporation, Doha, Qatar.
    First case of huge classic papillary thyroid cancer rupturing spontaneously leading to ischemic necrosis, perforation and inflammation of overlying skin: Case report and review of the literature2021Ingår i: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 85, artikel-id 106136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Papillary thyroid cancer (PTC) is the commonest form of well-differentiated endocrine carcinoma. It is categorized into indolent and aggressive, where the indolent subtypes (classic, follicular) rarely demonstrate aggressive behavior. We present a classic PTC presenting with a rapidly growing huge anterior neck mass that subsequently spontaneously ruptured subcutaneously resulting in ischemia, necrosis, and perforation of overlying skin leading to inflammation. Presentation of case: A 37-year-old female with no comorbidities presented to our emergency department with a neck swelling of 2 years duration that rapidly enlarged one week prior to presentation. Though the mass initially appeared of inflammatory nature, the tumor was a PTC, and she underwent total thyroidectomy with selective right side neck dissection and debridement of necrotic skin. The gross specimen revealed a fragmented non-intact right thyroid lobe mass causing pressure ischemia, necrosis and perforation of the skin. Histopathology showed a 9 × 9 × 5 cm classic PTC staged as pT3b N1b. Postoperative course was uneventful, she was discharged by the eighth postoperative day, and then she received a high dose of radioactive iodine ablation (RAI). Discussion: Classic PTC is usually of a smaller size and a relatively benign course compared to other PTC subtypes and thyroid cancers. It is indolent with favorable prognosis. Although it is associated with increased risk of lymph node metastases at the time of diagnosis, it is slow growing with high survival rates approaching 95%. Conclusion: Despite that classic PTC progresses slowly, it should still be suspected in neck swellings presenting with rapid and aggressive behavior. Prompt and systematic assessment is required with surgical intervention and radioactive iodine ablation therapy. 

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  • 3.
    Al Hassan, Mohamed S.
    et al.
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad General Hospital, Doha, Qatar ; College of Medicine, Qatar University, Doha, Qatar ; Weill Cornell Medicine – Qatar, Doha, Qatar.
    Alater, Ahmad
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    Darweesh, Adham
    Department of Clinical Imaging, Hamad General Hospital, Doha, Qatar.
    Abdelaal, Abdelrahman
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    Choroidal metastasis as initial presentation of aggressive medullary thyroid carcinoma with widespread mediastinal, brain, pituitary, bone, lung, and liver metastasis: Case report and literature review2021Ingår i: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 87, nr October 2021, artikel-id 106419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that originates from the parafollicular C cells of the thyroid gland. MTC can be due to sporadic or hereditary causes due to gain of function germ line mutations in the RET proto-oncogene. MTC presenting as ocular symptoms due to choroidal mass is rare with bad prognosis. Presentation of case: A 38-year-old Sudanese male presented to Hamad General Hospital, complaining of sudden painless decrease of vision of the right eye of 3 weeks duration. After investigations using imaging methods, the patient was discovered to have metastatic MTC that presented as choroidal mass and metastasized to his lung, bone, brain, pituitary, liver and mediastinum. Discussion: In terms of investigations, serum levels of calcitonin have superior diagnostic accuracy. Our patient undertook diagnostic imaging including ultrasonography, fine needle aspiration and computerized tomography (CT) scan and/or MRI imaging. He undertook total thyroidectomy and left neck dissection followed by stereotactic radiosurgery for the right orbit and pituitary. He then received systemic anti-RET therapy (Selpercatinib). At 5 months follow up there was dramatic drop in CEA from 888 μg/L to 164 μg/L, and calcitonin from >585.2 pmol/L to 354 pmol/L. Conclusion: Choroidal metastasis as initial presentation of MTC is extremely rare and challenging to diagnose. Surgeons need a high index of suspicion when ocular symptoms accompany a neck mass or thyroid-related symptoms. MTC has a progressive course with involvement of blood vessels and neck lymph nodes. Choroidal metastasis of MTC is challenging to manage.

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  • 4.
    Al Hassan, Mohamed S.
    et al.
    Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar ; College of Medicine, Qatar University, Doha, Qatar ; Weill Cornell Medicine – Qatar, Doha, Qatar.
    El Baba, Hamzah
    Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Petkar, Mahir
    Department of Laboratory Medicine and Pathology, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Abdelaal, Abdelrahman
    Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    What you see might not be what you get: Analysis of 15 prospective cases of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)2022Ingår i: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 91, artikel-id 106751Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Noninvasive follicular thyroid neoplasm with papillary-like nuclear (NIFTP) is a new entity. No previous study reported prospective cases, outlining using many quantitative and qualitative variables. Methods: Retrospective analysis of all (15) prospective NIFTP cases diagnosed between 2017 and 2021 at our institution. Statistical quantitative analysis outlined demographic, history, ultrasound, histopathology and treatment characteristics. Qualitative analysis examined the cases, with details provided on three cases to highlight the different possible presentations and configurations. Results: Mean age was 41.5 ± 9.91 years, 73.3% were females, and mean BMI was 29.49 ± 5.74 kg/m2. About 87% patients were symptomatic; 86.6% had neck swelling. Ultrasound (US) showed multiple nodules in 71.4% of cases. Fine-needle aspiration cytology (FNAC) showed that follicular lesion of undetermined significance (42.8%) was most common, followed by benign nodule (21.3%). Using the Bethesda System for Reporting Thyroid Cytopathology, 7 cases were category III, 3 category IV, 3 category II, and 1 category I. 60% of patients underwent total thyroidectomy. All cases were diagnosed postoperatively, 2 patients had additional papillary microcarcinoma. In 3 cases, the NIFTP site in the histopathology of resected specimen was different than the US-recommended site of the FNAC. Conclusion: We found discrepancies in the site and diagnosis of the preoperative US recommendation for the FNAC vs the postoperative histopathology of the specimen. These suggest that NIFTP might be incidentally and postoperatively diagnosed, irrespective of US or FNAC findings, hence its ‘true’ incidence might remain underestimated. As NIFTP cases higher BMI, Future research could predict preoperative diagnosis of NIFTP and explore associations with BMI. 

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  • 5.
    Al Hassan, Mohamed S.
    et al.
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad General Hospital, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    Elshafeey, Abdallah
    Weill Cornell Medicine – Qatar, Doha, Qatar.
    Petkar, Mahir
    Department of Laboratory Medicine & Pathology, Hamad General Hospital, Doha, Qatar.
    Abdelaal, Abdelrahman
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    First bilateral non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) co-occurring with bilateral papillary thyroid microcarcinoma: Case report and literature review2021Ingår i: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 78, s. 411-416Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Non-invasive follicular thyroid neoplasm with papillary-like features (NIFTP) is a recently characterized lesion with very low malignant potential. This has allowed for less aggressive management of this tumor subtype. Papillary thyroid carcinoma (PTC) has malignant potential and requires different considerations in management. Presentation of case: A 33-year-old woman presented to our Thyroid Surgery Clinic with a left neck swelling slowly enlarging over 4 years, and recent right-sided neck pain. Neck ultrasound and fine needle aspiration for cytology found bilateral thyroid nodules, labelled as ‘follicular lesion of undetermined significance’ (FLUS). Final pathology report after total thyroidectomy identified four distinct tumors: bilateral NIFTP lesions and bilateral papillary microcarcinomas. Discussion: Management of NIFTP comprises partial or total thyroidectomy without further intervention. Management of PTC is the same but with the possible addition of radioactive ablation due to the increased malignant potential. This is the first report of bilateral NIFTP lesions and bilateral papillary microcarcinomas co-occurring together in the same patient, so management was challenging. The decision was made to give the patient low dose radioactive iodine ablation and continue monitoring. Ultrasound of the neck follow up 6 months later showed no residual thyroid tissue or local recurrence. Conclusion: Although rare, NIFTP can co-occur with PTC. Bilateral NIFTP with bilateral PTC is extremely rare. Surgeons and pathologists need to be aware of this rare entity that can co-occur in both thyroid lobes. Total thyroidectomy is the definitive treatment. Post-surgery surveillance is important and follow up needs to be watchful for any recurrence or metastasis. © 2020 The Author(s)

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  • 6.
    Aleter, Ammar
    et al.
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad General Hospital, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    Incidental appendiceal mucinous neoplasm mimicking a left adnexal mass: A case report2020Ingår i: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 74, s. 132-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Appendiceal mucinous neoplasm is a rare type of appendiceal tumors which can present in a variety of symptoms and is difficult to diagnose. Preoperative diagnosis depends mainly on diagnostic imaging such as ultrasonography and computerized tomography (CT) scan. This uncommon case report discusses an appendiceal mucinous neoplasm mimicking a left adnexal mass on presentation, physical examination and diagnostic imaging findings. Presentation of case: This is a 61-year-old female found to have a large left adnexal mass during follow up ultrasonography. The patient refused further imaging, and during laparotomy, she was found to have an appendicular mucocele with normal left and right ovaries. Discussion: Appendectomy was done and the final pathology came as appendiceal mucinous neoplasm. Her post-operative course and 3 years follow up were uneventful. Conclusions: The equivocal signs and symptoms along with the anatomical position of appendiceal mucocele makes it difficult to diagnose and can mimic other types of tumors. Therefore, it should be considered in the deferential diagnosis of lower abdominal and pelvic masses. 

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  • 7.
    Aleter, Ammar
    et al.
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar ; College of Medicine, Qatar University, Doha, Qatar.
    Toffaha, Ali
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Ammar, Adham
    Department of Laboratory Medicine and Pathology, Hamad General Hospital, Doha, Qatar.
    Shahid, Fakhar
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Abdelaal, Abdelrahman
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Epidemiology, histopathology, clinical outcomes and survival of 50 cases of appendiceal mucinous neoplasms: Retrospective cross-sectional single academic tertiary care hospital experience2021Ingår i: Annals of Medicine and Surgery, E-ISSN 2049-0801, Vol. 64, artikel-id 102199Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Appendicular neoplasms are rare, most commonly as carcinoids followed by appendicular mucinous neoplasms (AMN). To date, there remains controversy regarding the best treatment of AMN and factors affecting its prognosis. Method: Retrospective chart review of patients operated for appendicular pathology (January 2011–December 2018, follow up to December 2020) at our institution. For all AMN patients, data included pre-operative clinical presentation, and operative/post-operative findings. Results: 12454 patients underwent appendectomy, of whom 50 (0.4%) had AMN histopathologically (mean age = 47.2). Most patients had laparoscopic appendectomy as primary surgery. Low grade AMN was the most common subtype (n = 41, 82%), and pseudomyxoma peritonei (PMP) was found in 8 (16%) patients. Based on histopathology and margin involvement, the 50 patients were categorized into 3 prognostic categories of recurrence risk (no risk, 24 patients; low risk, 8; high recurrence risk, 18 patients). Disease-free survival (DFS) was lowest for high recurrence risk group (P < 0.001). Eleven (22%) patients had AMN involving resection margin, of whom 3 had no completion surgery and had no recurrence. Higher tumor markers were associated with lower DFS, however it was not statistically significant. Conclusion: AMNs are rare but serious due to the risk of PMP. Laparoscopic approach for AMN may be feasible. Prognostic categories were significantly inversely correlated with recurrence risk; hence useful in predicting prognosis. Contrary to previous proposals, AMNs with acellular mucin at margin or local acellular mucin spillage may not require secondary surgery, especially if the patient is in low recurrence risk group. Tumor markers may predict risk of recurrence. 

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  • 8.
    Al-Yahri, Omer
    et al.
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    Abdelaal, Abdelrahman
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad General Hospital, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    Farghaly, Hanan
    Department of Lab Medicine & Pathology, Hamad General Hospital, Doha, Qatar.
    Murshed, Khaled
    Department of Lab Medicine & Pathology, Hamad General Hospital, Doha, Qatar.
    Zirie, Mahmoud A.
    Department of Endocrinology, Hamad General Hospital, Doha, Qatar.
    Al Hassan, Mohamed S.
    Department of General Surgery, Hamad General Hospital, Doha, Qatar.
    First ever case report of co-occurrence of hobnail variant of papillary thyroid carcinoma and intrathyroid parathyroid adenoma in the same thyroid lobe2020Ingår i: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 70, s. 40-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The hobnail variant of papillary thyroid cancer (PTC) is rare. Intrathyroid parathyroid adenoma (ITPA) is also rare. Co-ocurrence of PTC and ITPA in the same thyroid lobe is extremely rare. Likewise, primary hyperparathyroidism with such non-medullary thyroid carcinoma is rare. The specific molecular profile of hobnail PTC (HPTC) is different from the classic, poorly differentiated and anaplastic variants and may contribute to its aggressive behavior. HPTC's genetic profile remains unclear. Presentation of case: A 61-year-old woman presented to our endocrine clinic with generalized aches, bone pain, polyuria, and right neck swelling of a few months’ duration. Laboratory findings revealed hypercalcemia and hyperparathyroidism. Ultrasound of the neck showed 4.6 cm complex nodule within the right thyroid lobe. Sestamibi scan suggested parathyroid adenoma in the right thyroid lobe. Fine-needle aspiration (FNA) revealed atypical follicular lesion of undetermined significance. She underwent right lobectomy, which normalized the intraoperative intact parathyroid hormone levels. Final pathology with immunohistochemical stains demonstrated HPTC and IPTA (2 cm each). Next-generation sequencing investigated the mutation spectrum of HPTC and detected BRAFV600E mutation. Conclusions: A parathyroid adenoma should not exclude the diagnosis of thyroid carcinoma. Thyroid evaluation is needed for patients with primary hyperparathyroidism to prevent missing concurrent thyroid cancers. Cytomorphologic features to distinguish thyroid from parathyroid cells on FNA cytology must be considered. Immunohistochemical stains are important. BRAFV600E is the most common mutation in HPTC. This is possibly the first reported case of HPTC and ITPA co-occurring within the same thyroid lobe. Studies that define other molecular abnormalities may be useful as therapeutic targets. © 2020 The Author(s)

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  • 9.
    Andersson, John
    et al.
    Scandinavian Surgical Outcomes Research Group, Department of Surgery, Sahlgrenska University Hospital/Östra, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden ; Department of Surgery, Alingsås Hospital, Alingsås, Sweden.
    Abis, G
    Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands.
    Gellerstedt, Martin
    Scandinavian Surgical Outcomes Research Group, Department of Surgery, Sahlgrenska University Hospital/Östra, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Angenete, Eva
    Scandinavian Surgical Outcomes Research Group, Department of Surgery, Sahlgrenska University Hospital/Östra, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Angerås, Ulf
    Scandinavian Surgical Outcomes Research Group, Department of Surgery, Sahlgrenska University Hospital/Östra, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Cuesta, M. A.
    Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands.
    Jess, P
    Roskilde Hospital, Roskilde, Denmark.
    Rosenberg, Jakob
    Herlev Hospital, Copenhagen University, Copenhagen, Denmark.
    Bonjer, H. J.
    Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands.
    Haglind, Eva
    Scandinavian Surgical Outcomes Research Group, Department of Surgery, Sahlgrenska University Hospital/Östra, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Patient-reported genitourinary dysfunction after laparoscopic and open rectal cancer surgery in a randomized trial (COLOR II)2014Ingår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 101, nr 10, s. 1272-1279Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: This article reports on patient-reported sexual dysfunction and micturition symptoms following a randomized trial of laparoscopic and open surgery for rectal cancer.

    METHODS: Patients in the COLOR II randomized trial, comparing laparoscopic and open surgery for rectal cancer, completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR38 questionnaire before surgery, and after 4 weeks, 6, 12 and 24 months. Adjusted mean differences on a 100-point scale were calculated using changes from baseline value at the various time points in the domains of sexual functioning, sexual enjoyment, male and female sexual problems, and micturition symptoms.

    RESULTS: Of 617 randomized patients, 385 completed this phase of the trial. Their mean age was 67·1 years. Surgery caused an anticipated reduction in genitourinary function after 4 weeks, with no significant differences between laparoscopic and open approaches. An improvement in sexual dysfunction was seen in the first year, but some male sexual problems persisted. Before operation 64·5 per cent of men in the laparoscopic group and 55·6 per cent in the open group reported some degree of erectile dysfunction. This increased to 81·1 and 80·5 per cent respectively 4 weeks after surgery, and 76·3 versus 75·5 per cent at 12 months, with no significant differences between groups. Micturition symptoms were less affected than sexual function and gradually improved to preoperative levels by 6 months. Adjusting for confounders, including radiotherapy, did not change these results.

    CONCLUSION: Sexual dysfunction is common in patients with rectal cancer, and treatment (including surgery) increases the proportion of patients affected. A laparoscopic approach does not change this.

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  • 10.
    Andersson, John
    et al.
    Department of General and Orthopaedic Surgery, Alingsås Hospital, Sweden ; Department of Surgery, SSORG - Scandinavian Surgical Outcomes Research Group, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Angenete, Eva
    Department of Surgery, SSORG - Scandinavian Surgical Outcomes Research Group, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden ; Department of Surgery, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden.
    Gellerstedt, Martin
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Haglind, Eva
    Department of Surgery, SSORG - Scandinavian Surgical Outcomes Research Group, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden ; Department of Surgery, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden.
    Developing a multivariable prediction model of global health-related quality of life in patients treated for rectal cancer: a prospective study in five countries2024Ingår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 39, artikel-id 35Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Rectal cancer and its treatment have a negative impact on health-related quality of life (HRQoL). If risk factors for sustained low HRQoL could be identified early, ideally before the start of treatment, individualised interventions could be identified and implemented to maintain or improve HRQoL. The study aimed to develop a multivariable prediction model for global HRQoL 12 months after rectal cancer treatment.

    Methods Within COLOR II, a randomised, multicentre, international trial of laparoscopic and open surgery for rectal cancer, a sub-study on HRQoL included 385 patients in 12 hospitals and five countries. The HRQoL study was optional for hospitals in the COLOR II trial. EORTC QLQ-C30 and EORTC QLQ-CR38 were analysed preoperatively and at 1 and 12 months postoperatively. In exploratory analyses, correlations between age, sex, fatigue, pain, ASA classification, complications, and symptoms after surgery to HRQoL were studied. Bivariate initial analyses were followed by multivariate regression models.

    Results Patient characteristics and clinical factors explained 4–10% of the variation in global HRQoL. The patient-reported outcomes from EORTC QLQ-C30 explained 55–65% of the variation in global HRQoL. The predominant predictors were fatigue and pain, which significantly impacted global HRQoL at all time points measured.

    Conclusion We found that fatigue and pain were two significant factors associated with posttreatment global HRQoL in patients treated for rectal cancer T1-T3 Nx. Interventions to reduce fatigue and pain could enhance global HRQoL after rectal cancer treatment.

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  • 11.
    Awe, Julius Adebayo
    et al.
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi. University of Manitoba, CancerCare Manitoba, Canada ; Sahlgrenska Academy, University of Gothenburg, Sweden.
    Xu, Mark Chu
    University of Manitoba, CancerCare Manitoba, Canada.
    Wechsler, Janine
    ScreenCell, Paris, France ; Hôpital Henri Mondor, Créteil, France.
    Benali-Furet, Naoual
    ScreenCell, Paris, France.
    Cayre, Yvon E
    ScreenCell, Paris, France ; Hôpital Robert Debré and Pierre, Marie Curie University, Paris, France.
    Saranchuk, Jeff
    University of Manitoba, Canada.
    Drachenberg, Darrel
    University of Manitoba, Canada.
    Mai, Sabine
    University of Manitoba, CancerCare Manitoba, Canada.
    Three-Dimensional Telomeric Analysis of Isolated Circulating Tumor Cells (CTCs) Defines CTC Subpopulations2013Ingår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 6, nr 1, s. 51-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Circulating tumor cells (CTCs) have been identified with the potential to serve as suitable biomarkers for tumor stage and progression, but the availability of effective isolation technique(s) coupled with detailed molecular characterization have been the challenges encountered in making CTCs clinically relevant. For the first time, we combined isolation of CTCs using the ScreenCell filtration technique with quantitative analysis of CTC telomeres by TeloView. This resulted in the identification and molecular characterization of different subpopulations of CTCs in the same patient. Three-dimensional (3D) telomeric analysis was carried out on isolated CTCs of 19 patients that consisted of four different tumor types, namely, prostate, colon, breast, melanoma, and one lung cancer cell line. With telomeric analysis of the filter-isolated CTCs, the level of chromosomal instability (CIN) of the CTCs can be determined. Our study shows that subpopulations of CTCs can be identified on the basis of their 3D telomeric properties.

  • 12.
    Behboudi, Afrouz
    Department of Cell and Molecular Biology - Genetics, Lundberg Laboratory, Göteborg University, Gothenburg, Sweden.
    Cytogenetic and Molecular Changes Involving Rat Chromosome 10 in Experimental Endometrial Adenocarcinoma2002Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • 13.
    Behboudi, Afrouz
    et al.
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Enlund, Fredrik
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Winnes, Marta
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Andrén, Ywonne
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Nordkvist, Anders
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Leivo, Ilmo
    Departmentof Pathology, Haartman Institute and Helsinki University Central Hospital, Universityof Helsinki, Finland.
    Flaberg, Emilie
    Microbiologyand Tumor Biology Center (MTC), Stockholm, Sweden.
    Szekely, Laszlo
    Microbiologyand Tumor Biology Center (MTC), Stockholm, Sweden.
    Mäkitie, Antti
    Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.
    Grenman, Reidar
    Department of Otorhinolaryngology — Head and Neck Surgery and Medical Biochemistry, University of Turku, Finland.
    Mark, Joachim
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Stenman, Göran
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Molecular classification of mucoepidermoid carcinomas—prognostic significance of the MECT1–MAML2 fusion oncogene2006Ingår i: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 45, nr 5, s. 470-481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mucoepidermoid carcinomas (MECs) of the salivary and bronchial glands are characterized by a recurrent t(11;19)(q21;p13) translocation resulting in a MECT1–MAML2 fusion in which the CREB-binding domain of the CREB coactivator MECT1 (also known as CRTC1, TORC1 or WAMTP1) is fused to the transactivation domain of the Notch coactivator MAML2. To gain further insights into the molecular pathogenesis of MECs, we cytogenetically and molecularly characterized a series of 29 MECs. A t(11;19) and/or an MECT1–MAML2 fusion was detected in more than 55% of the tumors. Several cases with cryptic rearrangements that resulted in gene fusions were detected. In fusion-negative MECs, the most common aberration was a single or multiple trisomies. Western blot and immunohistochemical studies demonstrated that the MECT1–MAML2 fusion protein was expressed in all MEC-specific cell types. In addition, cotransfection experiments showed that the fusion protein colocalized with CREB in homogeneously distributed nuclear granules. Analyses of potential downstream targets of the fusion revealed differential expression of the cAMP/CREB (FLT1 and NR4A2) and Notch (HES1 and HES5) target genes in fusion-positive and fusion-negative MECs. Moreover, clinical follow-up studies revealed that fusion-positive patients had a significantly lower risk of local recurrence, metastases, or tumor-related death compared to fusion-negative patients (P = 0.0012). When considering tumor-related deaths only, the estimated median survival for fusion-positive patients was greater than 10 years compared to 1.6 years for fusion-negative patients. These findings suggest that molecularly classifying MECs on the basis of an MECT1–MAML2 fusion is histopathologically and clinically relevant and that the fusion is a useful marker in predicting the biological behavior of MECs. © 2006 Wiley-Liss, Inc.

  • 14.
    Behboudi, Afrouz
    et al.
    Göteborg University Inst. of Biomedicine, Clinical Genetics, Gothenburg, Sweden.
    Nordlander, Carola
    Göteborg University Inst. of Cell and Molecular Biology, Genetics, Gothenburg, Sweden.
    Klinga-Levan, Karin
    Högskolan i Skövde, Institutionen för vård och natur.
    Karlsson, Sandra
    Högskolan i Skövde, Institutionen för vård och natur.
    Evidence for a tumor suppressor locus distal to Tp53 – a study in experimental endometrial adenocarcinoma2007Ingår i: European Journal of Cancer Supplements, ISSN 1359-6349, E-ISSN 1878-1217, Vol. 5, nr 4, s. 62-62Artikel i tidskrift (Övrigt vetenskapligt)
  • 15.
    Behboudi, Afrouz
    et al.
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Roshani, Leyla
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Kost-Alimova, Marija
    Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
    Sjöstrand, Eleonor
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Montelius-Alatalo, Kerstin
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Röhme, Dan
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Klinga-Levan, Karin
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Ståhl, Fredrik
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human2002Ingår i: Mammalian Genome, ISSN 0938-8990, E-ISSN 1432-1777, Vol. 13, nr 6, s. 302-309Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes. Deletions in the proximal part of RNO10 were repeatedly found in a rat model for endometrial cancer. To identify functional and positional candidate genes in the affected region, we used radiation hybrid (RH) mapping and single- and dual-color fluorescence in situ hybridization (FISH) techniques to construct a detailed chromosomal map of the proximal part of RNO10. The regional localization of 14 genes, most of them cancer-related (Grin2a, Gspt1, Crebbp, Gfer, Tsc2, Tpsb1, Il9r, Il4, Irf1, Csf2, Sparc, Tp53, Thra1, Gh1), and of five microsatellite markers ( D10Mit10, D10Rat42, D10Rat50, D10Rat72, and D10Rat165) was determined on RNO10. For a fifteenth gene, Ppm1b, which had previously been assigned to RNO10, the map position was corrected to RNO6q12-q13.

  • 16.
    Behboudi, Afrouz
    et al.
    Department of Clinical Genetics, Institute of Biomedicine, Göteborg University, Sweden.
    Stenman, Göran
    Department of Clinical Genetics, Institute of Biomedicine, Göteborg University, Sweden.
    CRTC1 (CREB regulated transcription coactivator 1)2006Ingår i: Atlas of Genetics and Cytogenetics in Oncology and Haematology, E-ISSN 1768-3262, nr 2006-05-01Artikel, forskningsöversikt (Refereegranskat)
  • 17.
    Behboudi, Afrouz
    et al.
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göeborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Winnes, Marta
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göeborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Gorunova, Ludmila
    Department of Clinical Genetics, Lund University Hospital, Sweden.
    van den Oord, Joost J.
    Department of Pathology, Laboratory of Morphology and Molecular Pathology, University Hospital Leuven, Katholieke Universiteit Leuven, Belgium.
    Mertens, Fredrik
    Department of Clinical Genetics, Lund University Hospital, Sweden.
    Enlund, Fredrik
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göeborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Stenman, Göran
    Lundberg Laboratory for Cancer Research, Department of Pathology, Göeborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Clear cell hidradenoma of the skin—a third tumor type with at (11; 19)‐associated TORC1–MAML2 gene fusion2005Ingår i: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 43, nr 2, s. 202-205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent studies have shown that the t(11;19)(q21;p13) translocation in mucoepidermoid carcinomas and benign Warthin's tumors results in a fusion of the N-terminal CREB-binding domain of the cAMP coactivator TORC1 (a.k.a. MECT1 and WAMTP1) to the Notch coactivator MAML2. Here we show that a third tumor type, clear cell hidradenoma of the skin, also expresses this gene fusion. RT-PCR analysis of a clear cell hidradenoma with a t(11;19)(q21;p13) translocation revealed expression of a TORC1–MAML2 fusion transcript consisting of exon 1 of TORC1 fused to exons 2–5 of MAML2. Because the fusion was only detected in a single case, the frequency of this aberration in clear cell hidradenomas remains unknown. These results demonstrate that the t(11;19) in mucoepidermoid carcinoma, Warthin's tumor, and clear cell hidradenoma targets the same genes and results in identical gene fusions, indicating that at least subgroups of these glandular tumors evolve through activation of the same molecular pathways. © 2005 Wiley-Liss, Inc.

  • 18.
    Bergman, Annika
    et al.
    Department of Medical and Clinical genetics, Sahlgrenska Academy, Gothenburg, Sweden.
    Abel, Frida
    Department of Medical and Clinical genetics, Sahlgrenska Academy, Gothenburg, Sweden.
    Behboudi, Afrouz
    Department of Medical and Clinical genetics, Sahlgrenska Academy, Gothenburg, Sweden.
    Yhr, Maria
    Department of Medical and Clinical genetics, Sahlgrenska Academy, Gothenburg, Sweden.
    Mattsson, Jan
    Department of Surgery, Sahlgrenska University hospital, Gothenburg, Sweden.
    Svensson, Jan H.
    Department of Surgery, Skaraborg hospital, Skövde, Sweden.
    Karlsson, Per
    Department of Oncology, Sahlgrenska University hospital, Gothenburg, Sweden.
    Nordling, Margareta
    Department of Medical and Clinical genetics, Sahlgrenska Academy, Gothenburg, Sweden.
    No germline mutations in supposed tumour suppressor genes SAFB1 and SAFB2 in familial breast cancer with linkage to 19p2008Ingår i: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 9, nr 1, artikel-id 108Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The scaffold attachment factor B1 and B2 genes, SAFB1/SAFB2 (both located on chromosome 19p13.3) have recently been suggested as tumour suppressor genes involved in breast cancer development. The assumption was based on functional properties of the two genes and loss of heterozygosity of intragenic markers in breast tumours further strengthened the postulated hypothesis. In addition, linkage studies in Swedish breast cancer families also indicate the presence of a susceptibility gene for breast cancer at the 19p locus. Somatic mutations in SAFB1/SAFB2 have been detected in breast tumours, but to our knowledge no studies on germline mutations have been reported. In this study we investigated the possible involvement of SAFB1/SAFB2 on familiar breast cancer by inherited mutations in either of the two genes.

    Results

    Mutation analysis in families showing linkage to the SAFB1/2 locus was performed by DNA sequencing. The complete coding sequence of the two genes SAFB1 and SAFB2 was analyzed in germline DNA from 31 affected women. No missense or frameshift mutations were detected. One polymorphism was found in SAFB1 and eight polymorphisms were detected in SAFB2. MLPA-anlysis showed that both alleles of the two genes were preserved which excludes gene inactivation by large deletions.

    Conclusion

    SAFB1 and SAFB2 are not likely to be causative of the hereditary breast cancer syndrome in west Swedish breast cancer families.

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  • 19.
    Bharadwaj, Mausumi
    et al.
    Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), NOIDA, India.
    Hussain, Showket
    Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), NOIDA, India.
    Tripathi, Richa
    Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), NOIDA, India.
    Singh, Neha
    Department of Biotechnology, Panjab University, Chandigarh, India.
    Mehrotra, Ravi
    Division of Cytopathology, Institute of Cytology & Preventive Oncology (ICMR), NOIDA, India.
    Human Papillomavirus (HPV): Diagnosis and Treatment2014Ingår i: Animal Biotechnology: Models in Discovery and Translation / [ed] Ashish Verma & Anchal Singh, Elsevier, 2014, s. 95-120Kapitel i bok, del av antologi (Refereegranskat)
  • 20.
    Björk, Maria
    et al.
    Högskolan i Skövde, Institutionen för vård och natur.
    Johansson Sundler, Annelie
    Högskolan i Skövde, Institutionen för vård och natur.
    Hammarlund, Kina
    Högskolan i Skövde, Institutionen för vård och natur.
    Hallström, Inger
    Lund University, Department of Health Sciences, Lund, Sweden.
    Living an everyday life shaded with traces from the cancer trajectory – families' lived experiences in a six year follow up2012Ingår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 59, nr 6, s. 1130-1130Artikel i tidskrift (Refereegranskat)
  • 21.
    Borgmästars, Emmy
    et al.
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.
    Jacobson, Sara
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.
    Simm, Maja
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden ; Department of Clinical Sciences/Obstetrics and Gynecology, Umeå University, Sweden.
    Johansson, Mattias
    Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
    Billing, Ola
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.
    Lundin, Christina
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.
    Nyström, Hanna
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden ; Wallenberg Centre for Molecular Medicine, Umeå University, Sweden.
    Öhlund, Daniel
    Wallenberg Centre for Molecular Medicine, Umeå University, Sweden ; Department of Radiation Sciences/Oncology, Umeå University, Sweden.
    Lubovac-Pilav, Zelmina
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Jonsson, Pär
    Department of Chemistry, Umeå University, Sweden.
    Franklin, Oskar
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden ; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA.
    Sund, Malin
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden ; Department of Surgery, University of Helsinki and Helsinki University Hospital, Finland.
    Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank2024Ingår i: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 15, nr 2, s. 755-767Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.

    Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.

    Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].

    Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.

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  • 22.
    Borgmästars, Emmy
    et al.
    Department of Diagnostics and Intervention/Surgery, Umeå University, Sweden.
    Ulfenborg, Benjamin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Johansson, Mattias
    Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
    Jonsson, Pär
    Department of Chemistry, Umeå University, Sweden.
    Billing, Ola
    Department of Diagnostics and Intervention/Surgery, Umeå University, Sweden.
    Franklin, Oskar
    Department of Diagnostics and Intervention/Surgery, Umeå University, Sweden ; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA.
    Lundin, Christina
    Department of Diagnostics and Intervention/Surgery, Umeå University, Sweden.
    Jacobson, Sara
    Department of Diagnostics and Intervention/Surgery, Umeå University, Sweden.
    Simm, Maja
    Department of Diagnostics and Intervention/Surgery, Umeå University, Sweden ; Department of Clinical Sciences/Obstetrics and Gynecology, Umeå University, Sweden.
    Lubovac-Pilav, Zelmina
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Sund, Malin
    Department of Diagnostics and Intervention/Surgery, Umeå University, Sweden ; Department of Surgery, University of Helsinki and Helsinki University Hospital, Finland.
    Multi-omics profiling to identify early plasma biomarkers in pre-diagnostic pancreatic ductal adenocarcinoma: a nested case-control study2024Ingår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 48, artikel-id 102059Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.

    A nested case-control study within the Northern Sweden Health and Disease Study was designed. Pre-diagnostic plasma samples from 37 future PDAC patients collected within 2.3 years before diagnosis and 37 matched healthy controls were included. We analyzed metabolites using liquid chromatography mass spectrometry and gas chromatography mass spectrometry, microRNAs by HTG edgeseq, proteins by multiplex proximity extension assays, as well as three clinical biomarkers using milliplex technology. Supervised and unsupervised multi-omics integration were performed as well as univariate analyses for the different omics types and clinical biomarkers. Multiple hypothesis testing was corrected using Benjamini-Hochberg's method and a false discovery rate (FDR) below 0.1 was considered statistically significant.

    Carbohydrate antigen (CA) 19-9 was associated with PDAC risk (OR [95 % CI] = 3.09 [1.31–7.29], FDR = 0.03) and increased closer to PDAC diagnosis. Supervised multi-omics models resulted in poor discrimination between future PDAC cases and healthy controls with obtained accuracies between 0.429–0.500. No single metabolite, microRNA, or protein was differentially altered (FDR < 0.1) between future PDAC cases and healthy controls.

    CA 19-9 levels increase up to two years prior to PDAC diagnosis but extensive multi-omics analysis including metabolomics, microRNAomics and proteomics in this cohort did not identify novel early biomarkers for PDAC.

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  • 23.
    Browall, Maria
    et al.
    Högskolan i Skövde, Institutionen för vård och natur. Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Nursing, Stockholm, Sweden.
    Östlund, Ulrika
    Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Nursing, Stockholm, Sweden / Umeå University, Department of Nursing, Umeå, Sweden.
    Henoch, Ingela
    The Sahlgrenska Academy, University of Gothenburg, Institute of Health and Care Sciences, Gothenburg, Sweden.
    Wengström, Yvonne
    Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Nursing, Stockholm, Sweden.
    The course of health related quality of life in postmenopausal women with breast cancer from breast surgery and up to five years post-treatment2013Ingår i: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 22, nr 5, s. 952-957Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Previous studies include too few patients over 70 years to be able to assess treatment effects on Health Related Quality Of Life (HRQOL) in the older age group. We aimed to follow HRQOL in postmenopausal women (55-80 years) with breast cancer receiving adjuvant treatment, until five years post-treatment, and compare with a general population. Patients and methods: The patient sample included 150 women (adjuvant CT n=75 and RT n=75) and two reference samples from the Swedish SF-36 norm database. Results: Data from baseline showed significantly higher levels of physical functioning and general health among the patients compared to the reference sample, and significantly lower levels of bodily pain, emotional role functioning and mental health. Longitudinal analyses showed significant changes in all scales, and three different patterns (a decrease-stable, a decrease-increase, and a stable- increase pattern) were identified. Conclusion: Postmenopausal women seem to successfully manage the effects of adjuvant treatment on HRQOL.

  • 24.
    Carlsson, Jessica
    et al.
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Davidsson, Sabina
    Orebro Univ Hosp, Dept Urol, Orebro, Sweden / Univ Orebro, Sch Hlth & Med Sci, Orebro, Sweden.
    Helenius, Gisela
    Orebro Univ Hosp, Dept Lab Med, Orebro, Sweden.
    Karlsson, Mats
    Orebro Univ Hosp, Dept Lab Med, Orebro, Sweden.
    Lubovac, Zelmina
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Andren, Ove
    Orebro Univ Hosp, Dept Urol, Orebro, Sweden .
    Olsson, Björn
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Klinga-Levan, Karin
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    A miRNA expression signature that separates between normal and malignant prostate tissues2011Ingår i: Cancer Cell International, E-ISSN 1475-2867, Vol. 11, s. 14-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that post-transcriptionally regulate genes involved in several key biological processes and thus are involved in various diseases, including cancer. In this study we aimed to identify a miRNA expression signature that could be used to separate between normal and malignant prostate tissues. Results: Nine miRNAs were found to be differentially expressed (p < 0.00001). With the exception of two samples, this expression signature could be used to separate between the normal and malignant tissues. A cross-validation procedure confirmed the generality of this expression signature. We also identified 16 miRNAs that possibly could be used as a complement to current methods for grading of prostate tumor tissues. Conclusions: We found an expression signature based on nine differentially expressed miRNAs that with high accuracy (85%) could classify the normal and malignant prostate tissues in patients from the Swedish Watchful Waiting cohort. The results show that there are significant differences in miRNA expression between normal and malignant prostate tissue, indicating that these small RNA molecules might be important in the biogenesis of prostate cancer and potentially useful for clinical diagnosis of the disease.

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    Carlsson_et_al_2011
  • 25.
    Carlsson, Jessica
    et al.
    Department of Urology, Örebro University Hospital, Sweden ; School of Health and Medical Sciences, Örebro University, Sweden ; Transdisciplinary Prostate Cancer Partnership (ToPCaP), Örebro University hospital, Clinical research centre (KFC), Örebro, Sweden.
    Helenius, Gisela
    Department of Laboratory Medicine, Örebro University Hospital, Sweden ; School of Health and Medical Sciences, Örebro University, Sweden.
    Karlsson, Mats G.
    Department of Laboratory Medicine, Örebro University Hospital, Sweden ; School of Health and Medical Sciences, Örebro University, Sweden.
    Andrén, Ove
    Department of Urology, Örebro University Hospital, Sweden ; School of Health and Medical Sciences, Örebro University, Sweden ; Transdisciplinary Prostate Cancer Partnership (ToPCaP), Örebro University hospital, Clinical research centre (KFC), Örebro, Sweden.
    Klinga-Levan, Karin
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Olsson, Björn
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate2013Ingår i: BMC Cancer, E-ISSN 1471-2407, Vol. 13, artikel-id 362Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate. Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers. Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified. Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.

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  • 26.
    Chaudhari, Aditi
    et al.
    University of Gothenburg.
    Ejeskär, Katarina
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande.
    Wettergren, Yvonne
    University of Gothenburg, Sahlgrenska University Hospital/Östra.
    Kahn, Ronald
    Joslin Diabetes Center and Harvard Medical School, United States.
    Rotter Sopasakis, Victoria
    University of Gothenburg / Joslin Diabetes Center and Harvard Medical School, United states.
    Hepatic deletion of p110α and p85α results in insulin resistance despite sustained IRS1-associated phosphatidylinositol kinase activity2017Ingår i: F1000 Research, E-ISSN 2046-1402, Vol. 6, artikel-id 1600Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Class IA phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is an integral mediator of insulin signaling. The p110 catalytic and p85 regulatory subunits of PI3K are the products of separate genes, and while they come together to make the active heterodimer, they have opposing roles in insulin signaling and action. Deletion of hepatic p110α results in an impaired insulin signal and severe insulin resistance, whereas deletion of hepatic p85α results in improved insulin sensitivity due to sustained levels of phosphatidylinositol (3,4,5)-trisphosphate. Here, we created mice with combined hepatic deletion of p110α and p85α (L-DKO) to study the impact on insulin signaling and whole body glucose homeostasis.Methods: Six-week old male flox control and L-DKO mice were studied over a period of 18 weeks, during which weight and glucose levels were monitored, and glucose tolerance tests, insulin tolerance test and pyruvate tolerance test were performed. Fasting insulin, insulin signaling mediators, PI3K activity and insulin receptor substrate (IRS)1-associated phosphatidylinositol kinase activity were examined at 10 weeks. Liver, muscle and white adipose tissue weight was recorded at 10 weeks and 25 weeks.Results: The L-DKO mice showed a blunted insulin signal downstream of PI3K, developed markedly impaired glucose tolerance, hyperinsulinemia and had decreased liver and adipose tissue weights. Surprisingly, however, these mice displayed normal hepatic glucose production, normal insulin tolerance, and intact IRS1-associated phosphatidylinositol kinase activity without compensatory upregulated signaling of other classes of PI3K.Conclusions: The data demonstrate an unexpectedly overall mild metabolic phenotype of the L-DKO mice, suggesting that lipid kinases other than PI3Ks might partially compensate for the loss of p110α/p85α by signaling through other nodes than Akt/Protein Kinase B.

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  • 27.
    Chen, Lei
    et al.
    Högskolan i Skövde, Institutionen för kommunikation och information.
    Nordlander, Carola
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Behboudi, Afrouz
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Olsson, Björn
    Högskolan i Skövde, Institutionen för kommunikation och information.
    Klinga Levan, Karin
    Högskolan i Skövde, Institutionen för vård och natur.
    Deriving evolutionary tree models of the oncogenesis of endometrial adenocarcinoma2007Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 120, nr 2, s. 292-296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the fourth leading cause of cancer death in women worldwide, but not much is known about the underlying genetic factors involved in the development of this complex disease. In the present work, we used 3 different algorithms to derive tree models of EAC oncogenesis from data on the frequencies of genomic alterations in rat chromosome 10 (RNO10). The tumor material was derived from progenies of crosses between the EAC susceptible BDII inbred rat strain and two non susceptible inbred rat strains. Data from allelic imbalance scans of RNO10 with microsatellite markers on solid tumor material and corresponding tissue cultures were used. For the analysis, RNO10 was divided into 24 segments containing a total of 59 informative microsatellite markers. The derived tree models show that genomic alterations have occurred in 11 of the 24 segments. In addition, the models provide information about the likely order of the alterations as well as their relationship with each other. Interestingly, there was a high degree of consistency among the different tree models and with the results of previous-studies, which supports the reliability of the tree models. Our results may be extended into a general approach for tree modeling of whole genome alterations during oncogenesis. (c) 2006 Wiley-Liss, Inc.

  • 28.
    Cheng, Xiaoxiao
    et al.
    Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
    Veverka, Vaclav
    Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom, the Institute of Organic Chemistry and Biochemistry, Flemingovo Namesti 2, 166 10 Prague 6, Czech Republic.
    Radhakrishnan, Anand
    Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
    Waters, Lorna C.
    Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom.
    Muskett, Frederick W.
    Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom.
    Morgan, Sara H.
    Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
    Huo, Jiandong
    Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
    Yu, Chao
    Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
    Evans, Edward J.
    Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
    Leslie, Alasdair J.
    Radcliffe Department of Medicine [Oxford].
    Griffiths, Meryn
    UCB Pharma, Slough SL1 4EN, United Kingdom.
    Stubberfield, Colin
    UCB Pharma, Slough SL1 4EN, United Kingdom.
    Griffin, Robert
    UCB Pharma, Slough SL1 4EN, United Kingdom.
    Henry, Alistair J.
    UCB Pharma, Slough SL1 4EN, United Kingdom.
    Jansson, Andreas
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Ladbury, John E.
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Ikemizu, Shinji
    Division of Structural Biology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862 0973, Japan.
    Carr, Mark D.
    Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom.
    Davis, Simon J.
    Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
    Structure and Interactions of the Human Programmed Cell Death 1 Receptor2013Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, nr 17, s. 11771-11785Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PD-1, a receptor expressed by T cells, B cells, and monocytes, is a potent regulator of immune responses and a promising therapeutic target. The structure and interactions of human PD-1 are, however, incompletely characterized. We present the solution nuclear magnetic resonance (NMR)-based structure of the human PD-1 extracellular region and detailed analyses of its interactions with its ligands, PD-L1 and PD-L2. PD-1 has typical immunoglobulin superfamily topology but differs at the edge of the GFCC' sheet, which is flexible and completely lacks a C '' strand. Changes in PD-1 backbone NMR signals induced by ligand binding suggest that, whereas binding is centered on the GFCC' sheet, PD-1 is engaged by its two ligands differently and in ways incompletely explained by crystal structures of mouse PD-1.ligand complexes. The affinities of these interactions and that of PD-L1 with the costimulatory protein B7-1, measured using surface plasmon resonance, are significantly weaker than expected. The 3-4-fold greater affinity of PD-L2 versus PD-L1 for human PD-1 is principally due to the 3-fold smaller dissociation rate for PD-L2 binding. Isothermal titration calorimetry revealed that the PD-1/PD-L1 interaction is entropically driven, whereas PD-1/PD-L2 binding has a large enthalpic component. Mathematical simulations based on the biophysical data and quantitative expression data suggest an unexpectedly limited contribution of PD-L2 to PD-1 ligation during interactions of activated T cells with antigen-presenting cells. These findings provide a rigorous structural and biophysical framework for interpreting the important functions of PD-1 and reveal that potent inhibitory signaling can be initiated by weakly interacting receptors.

  • 29.
    Deland, Lily
    et al.
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Keane, Simon
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Bontell, Thomas O.
    Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden ; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Fagman, Henrik
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden ; Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sjögren, Helene
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lind, Anders E.
    Clinical Genomics Gothenburg, SciLife Labs, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Carén, Helena
    Sahlgrenska Center for Cancer Research, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Tisell, Magnus
    Department of Clinical Neuroscience and Rehabilitation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nilsson, Jonas A.
    Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Ejeskär, Katarina
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Sabel, Magnus
    Childhood Cancer Centre, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden ; Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Abel, Frida
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Novel TPR::ROS1 Fusion Gene Activates MAPK, PI3K and JAK/STAT Signaling in an Infant-type Pediatric Glioma2022Ingår i: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 19, nr 6, s. 711-726Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/AIM: Although fusion genes involving the proto-oncogene receptor tyrosine kinase ROS1 are rare in pediatric glioma, targeted therapies with small inhibitors are increasingly being approved for histology-agnostic fusion-positive solid tumors. PATIENT AND METHODS: Here, we present a 16-month-old boy, with a brain tumor in the third ventricle. The patient underwent complete resection but relapsed two years after diagnosis and underwent a second operation. The tumor was initially classified as a low-grade glioma (WHO grade 2); however, methylation profiling suggested the newly WHO-recognized type: infant-type hemispheric glioma. To further refine the molecular background, and search for druggable targets, whole genome (WGS) and whole transcriptome (RNA-Seq) sequencing was performed. RESULTS: Concomitant WGS and RNA-Seq analysis revealed several segmental gains and losses resulting in complex structural rearrangements and fusion genes. Among the top-candidates was a novel TPR::ROS1 fusion, for which only the 3' end of ROS1 was expressed in tumor tissue, indicating that wild type ROS1 is not normally expressed in the tissue of origin. Functional analysis by Western blot on protein lysates from transiently transfected HEK293 cells showed the TPR::ROS1 fusion gene to activate the MAPK-, PI3K- and JAK/STAT- pathways through increased phosphorylation of ERK, AKT, STAT and S6. The downstream pathway activation was also confirmed by immunohistochemistry on tumor tissue slides from the patient. CONCLUSION: We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse. 

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  • 30.
    Deland, Lily
    et al.
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Keane, Simon
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Olsson Bontell, Thomas
    Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Sjögren, Helene
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Fagman, Henrik
    Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Øra, Ingrid
    Department of Clinical Sciences, Lund University Hospital, Sweden ; HOPE/ITCC Phase I/II Trial Unit, Pediatric Oncology, Karolinska Hospital, Stockholm, Sweden.
    De La Cuesta, Esther
    Pharmaceuticals, Global Medical Affairs–Oncology, Bayer U.S, Whippany, United States.
    Tisell, Magnus
    Department of Clinical Neuroscience and Rehabilitation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nilsson, Jonas A.
    Sahlgrenska Cancer Center, Department of Laboratory Medicine Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Ejeskär, Katarina
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Sabel, Magnus
    Childhood Cancer Centre, Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Abel, Frida
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Discovery of a rare GKAP1-NTRK2 fusion in a pediatric low-grade glioma, leading to targeted treatment with TRK-inhibitor larotrectinib2021Ingår i: Cancer Biology & Therapy, ISSN 1538-4047, E-ISSN 1555-8576, Vol. 22, nr 3, s. 184-195Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here we report a case of an 11-year-old girl with an inoperable tumor in the optic chiasm/hypothalamus, who experienced several tumor progressions despite three lines of chemotherapy treatment. Routine clinical examination classified the tumor as a BRAF-negative pilocytic astrocytoma. Copy-number variation profiling of fresh frozen tumor material identified two duplications in 9q21.32–33 leading to breakpoints within the GKAP1 and NTRK2 genes. RT-PCR Sanger sequencing revealed a GKAP1-NTRK2 exon 10–16 in-frame fusion, generating a putative fusion protein of 658 amino acids with a retained tyrosine kinase (TK) domain. Functional analysis by transient transfection of HEK293 cells showed the GKAP1-NTRK2 fusion protein to be activated through phosphorylation of the TK domain (Tyr705). Subsequently, downstream mediators of the MAPK- and PI3K-signaling pathways were upregulated in GKAP1-NTRK2 cells compared to NTRK2 wild-type; phosphorylated (p)ERK (3.6-fold), pAKT (1.8- fold), and pS6 ribosomal protein (1.4-fold). Following these findings, the patient was enrolled in a clinical trial and treated with the specific TRK-inhibitor larotrectinib, resulting in the arrest of tumor growth. The patient’s condition is currently stable and the quality of life has improved significantly. Our findings highlight the value of comprehensive clinical molecular screening of BRAF-negative pediatric low-grade gliomas, to reveal rare fusions serving as targets for precision therapy. 

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  • 31.
    Diaz Cruz, Maria Araceli
    et al.
    Research School of Health and Welfare, School of Health and Welfare, University of Jönköping, Sweden.
    Karlsson, Sandra
    Department of Natural Science and Biomedicine, School of Health and Welfare, University of Jönköping, Sweden.
    Szekeres, Ferenc
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Faresjö, Maria
    Department of Natural Science and Biomedicine, School of Health and Welfare, University of Jönköping, Sweden.
    Lund, Dan
    Department of Natural Science and Biomedicine, School of Health and Welfare, University of Jönköping, Sweden.
    Larsson, Dennis
    Sahlgrenska University Hospital, Gothia Forum - for Clinical Research, Gothenburg, Sweden.
    Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer2021Ingår i: Molecular Biology Reports, ISSN 0301-4851, E-ISSN 1573-4978, Vol. 48, nr 3, s. 2429-2436Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)2D3. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression. 

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  • 32.
    Elaiwy, Orwa
    et al.
    Department of laboratory medicine and pathology, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Surgery, Hamad Medical Corporation, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    AlKhalil, Moustafa
    Department of Oral and Cranio-Maxillo-Facial Surgery, Hamad Medical Corporation, Doha, Qatar / Weill Cornell Medicine in Qatar, Doha, Qatar.
    Ammar, Adham
    Department of laboratory medicine and pathology, Hamad Medical Corporation, Doha, Qatar.
    Epidemiology and pathology of oral squamous cell carcinoma in a multi-ethnic population: Retrospective study of 154 cases over 7 years in Qatar2020Ingår i: Annals of Medicine and Surgery, E-ISSN 2049-0801, Vol. 60, s. 195-200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Oral cancer (OC) is a neoplastic process of the oral cavity that has high mortality and significant effects on patients’ aesthetics. The majority of OC is oral squamous cell carcinoma (OSCC) and resection remains the most frequent treatment. Recurrence is the main cause of tumor-related mortality. Material and methods: A retrospective review of patients’ charts at Hamad Medical Corporation examined 154 adults who were diagnosed as OSCC and referred to the national head and neck cancer multi-disciplinary team meetings between 2012 and 2018. The data extracted was demographic, pathologic and clinical. All patients with oral cavity tumors other than squamous cell carcinoma were excluded. Results: Males comprised the majority of the sample, mean age was 46.93 years. Tongue was the most common location. The majority of the patients were diagnosed at early stages, and a small subset of patients had histologically-proven local recurrence. Conclusion: The young male predominance of OSCC patients in Qatar is unprecedented worldwide. Most patients were non-Qataris, mainly from South Asia. Loss of follow-up was a challenge in assessing the long-term outcomes of OSCC. Our findings suggest the need for a more vigilant surveillance approach to oral lesions particularly in male South-Asian patients, as well as improving the follow-up strategies. 

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  • 33.
    Enlund, Fredrik
    et al.
    Department of Pathology, Lundberg Laboratory for Cancer Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Behboudi, Afrouz
    Department of Pathology, Lundberg Laboratory for Cancer Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Andrén, Ywonne
    Department of Pathology, Lundberg Laboratory for Cancer Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Öberg, Camilla
    Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
    Lendahl, Urban
    Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
    Mark, Joachim
    Department of Pathology, Lundberg Laboratory for Cancer Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Stenman, Göran
    Department of Pathology, Lundberg Laboratory for Cancer Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors2004Ingår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 292, nr 1, s. 21-28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chromosome translocations in neoplasia commonly result in fusion genes that may encode either novel fusion proteins or normal, but ectopically expressed proteins. Here we report the cloning of a novel fusion gene in a common type of salivary and bronchial gland tumor, mucoepidermoid carcinomas (MEC), as well as in benign Warthin's tumors (WATs). The fusion, which results from a t(11;19)(q21–22;p13) translocation, creates a chimeric gene in which exon 1 of a novel gene of unknown function, designated WAMTP1, is linked to exons 2–5 of the recently identified Mastermind-like Notch coactivator MAML2. In the fusion protein, the N-terminal basic domain of MAML2, which is required for binding to intracellular Notch (Notch ICD), is replaced by an unrelated N-terminal sequence from WAMTP1. Mutation analysis of the N-terminus of WAMTP1-MAML2 identified two regions of importance for nuclear localization (amino acids 11–20) and for colocalization with MAML2 and Notch1 ICD in nuclear granules (amino acids 21–42). Analyses of the Notch target genes HES5 and MASH1 in MEC tumors with and without the WAMTP1-MAML2 fusion revealed upregulation of HES5 and downregulation of MASH1 in fusion positive MECs compared to normal salivary gland tissue and MECs lacking the fusion. These findings suggest that altered Notch signaling plays an important role in the genesis of benign and malignant neoplasms of salivary and bronchial gland origin.

  • 34.
    Falck, Eva
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Genomic Alterations in Experimental Endometrial Adenocarcinoma2012Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
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  • 35.
    Falck, Eva
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Genomic and genetic alterations in endometrial adenocarcinoma2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The most frequently diagnosed cancer of the female genital tract is cancer of the endometrium (endometrial cancer), ranking fourth among the invasive tumors that affect women in Europe and North America. As most other cancer types, endometrial cancer is a complex genetic disease influenced by both genetic and environmental factors.

    The human population is genetically heterogeneous and studies of complex diseases in human are proven to be difficult. By using a model system such as the BDII rat, some of the obstacles related to the study of complex diseases can be avoided. The BDII rat strain is prone to spontaneously develop endometrial adenocarcinoma (EAC) and more than 90% of the virgin females develop EAC during their lifetime. Development of EAC tumors in BDII rats is comparable in pathogenesis and histopathological properties to that of human.

    The aims of this thesis were i/ to characterize EAC in the BDII rat experimental model system by analyzing structural and numerical chromosome aberrations, ii/ to evaluate the importance of the genetic set-up in EAC development, and iii/ to determine the impact of genomic and genetic alterations on the functionality of candidate genes in rat EAC and in human endometrial tumors of different FIGO grades.

    Non-random numerical and structural aberrations that could contribute to tumor formation were identified, and evidence that the genetic background had a significant influence on the genome make-up of tumor cells was provided. Certain genes (Gpx3/GPX3, Met/MET, Phf5a/PHF5A, and Gja1/GJA1) were selected for further analysis and aberrant expression of some of them were found in both rat and human EACs. By separating EAC cell lines according to the genetic cross background, for two of the genes (Phf5 and Met), we showed that the expression pattern differed significantly between different cross backgrounds, which clearly pinpoint the importance of using animal models as a complement to clinical studies in identification of cancer-related genes.

  • 36.
    Falck, Eva
    et al.
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi. Schoolof Health and Medical Sciences, Örebro University, Sweden.
    Behboudi, Afrouz
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Medical and Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Sweden.
    Klinga-Levan, Karin
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    The impact of the genetic background on the genome make-up of tumor cells2012Ingår i: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 51, nr 5, s. 438-446Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the most common form of malignancy in the female genital tract, ranking as the fourth leading form of invasive tumors that affect women. The BDII inbred rat strain has been used as a powerful tumor model in studies of the genetic background of EAC. Females from the BDII strain are prone to develop tumors with an incidence of more than 90%. Development of EAC in BDII female rats has similarities in pathogenesis, histopathological, and molecular properties to that of human, and thus represents a unique model for analysis of EAC tumorigenesis and for comparative studies in human EACs. In a previous study, a set of rat EAC cell lines derived from tumors developed in female crossprogenies between BDII and nonsusceptible rat strains were analyzed by spectral karyotyping (SKY). Here we present an analysis with specific focus on the impact of different genetic backgrounds on the rate and occurrence of genetic aberrations in experimental tumors using data presented in the previous report. We could reveal that the ploidy state, and the abundance and type of structural as well as numerical change differed between the two genetic setups. We have also identified chromosomes harboring aberrations independent of genetic input from the nonsusceptible strains, which provide valuable information for the identification of the genes involved in the development of EAC in the BDII model as well as in human endometrial tumors.

  • 37.
    Falck, Eva
    et al.
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för vård och natur.
    Karlsson, Sandra
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Carlsson, Jessica
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi. Tumor biology.
    Helenius, Gisela
    Department of Pathology, Örebro University Hospital, Sweden.
    Karlsson, Mats
    Department of Pathology, Örebro University Hospital, Sweden.
    Klinga-Levan, Karin
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Loss of Glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma2010Ingår i: Cancer Cell International, E-ISSN 1475-2867, Vol. 10, artikel-id 46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment. Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions.

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  • 38.
    Falck, Eva
    et al.
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Klinga-Levan, Karin
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Expression patterns of PHF5A/Phf5a and GJa1/Gja1 in rat and human endometrial cancer2013Ingår i: Cancer Cell International, E-ISSN 1475-2867, Vol. 13, nr 1, artikel-id 43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endometrial adenocarcinoma is the most frequently diagnosed cancer of the female genital tract in the western world. Studies of complex diseases can be difficult to perform on human tumor samples due to the high genetic heterogeneity in human. The use of rat models is preferable since rat has similarities in pathogenesis and histopathological properties to that of human.

    A genomic region including the highly conserved Phf5a gene associated to development of EAC has previously been identified in an association study. PHF5A has been suggested to acts as a transcription factor or cofactor in the up regulation of expression of Gja1 gene in the presence of estrogen. It has earlier been shown that the Phf5a gene is down regulated in rat EAC derived cell lines by means of expression microarrays.

    We analyzed the expression of Phf5a and Gja1 by qPCR, and potential relations between the two genes in EAC tumors and non-malignant cell lines derived from the BDII rat model. In addition, the expression pattern of these genes was compared in rat and human EAC tumor samples.

    Changes in expression for Phf5a/PHF5A were found in tumors from both rat and human even though the observed pattern was not completely consistent between the two species. By separating rat EAC cell lines according to the genetic background, a significant lower expression of Phf5a in one of the two cross backgrounds was revealed, but not for the other. In contrast to other studies, Phf5a/PHF5A regulation of Gja1/GJA1 was not revealed in this study.

  • 39.
    Fransson, S.
    et al.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden.
    Uv, A.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden.
    Eriksson, H.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden.
    Andersson, M. K.
    Department of Pathology, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
    Wettergren, Y.
    Department of General Surgery, University of Gothenburg SE-40530 Gothenburg, Sweden.
    Bergo, M.
    Department of Medicine, Sahlgrenska Cancer Center, University of Gothenburg, SE-40530 Gothenburg, Sweden.
    Ejeskär, Katarina
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    p37δ is a new isoform of PI3K p110δ that increases cell proliferation and is overexpressed in tumors2012Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 31, nr 27, s. 3277-3286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The phosphatidylinositol 3-kinases (PI3Ks) regulate cell growth, proliferation and survival, and are frequently affected in human cancer. PI3K is composed of a catalytic subunit, p110, and a regulatory subunit, p85. The PI3K catalytic subunit p110δ is encoded by PIK3CD and contains p85- and RAS-binding domains, and a kinase domain. Here we present an alternatively spliced PIK3CD transcript encoding a previously unknown protein, p37δ, and demonstrate that this protein is expressed in human ovarian and colorectal tumors. p37δ retains the p85-binding domain and a fraction of the RAS-binding domain, lacks the catalytic domain, and has a unique carboxyl-terminal region. In contrast to p110δ, which stabilizes p85, p37δ promoted p85 sequestering. Despite the truncated RAS-binding domain, p37δ bound to RAS and we found a strong positive correlation between the protein levels of p37δ and RAS. Overexpressing p37δ, but not p110δ, increased the proliferation and invasive properties of HEK-293 cells and mouse embryonic fibroblasts. Cells overexpressing p37δ showed a quicker phosphorylation response of AKT and ERK1/2 following serum stimulation. Ubiquitous expression of human p37δ in the fruit fly increased body size, DNA content and phosphorylated ERK1/2 levels. Thus, p37δ appears to be a new tumor-specific isoform of p110δ with growth-promoting properties.

  • 40.
    Fransson, Susanne
    et al.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Gothenburg University, Gothenburg, Sweden.
    Abel, Frida
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Gothenburg University, Gothenburg, Sweden.
    Kogner, Per
    Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
    Martinsson, Tommy
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Gothenburg University, Gothenburg, Sweden.
    Ejeskär, Katarina
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Stage-dependent expression of PI3K/Akt‑pathway genes in neuroblastoma2013Ingår i: International Journal of Oncology, ISSN 1019-6439, E-ISSN 1791-2423, Vol. 42, nr 2, s. 609-616Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The phosphoinositide-3 kinase (PI3K) pathway plays a critical role in cancer cell growth and survival and has also been implicated in the development of the childhood cancer neuroblastoma. In neuroblastoma high mRNA expression of the PI3K catalytic isoform PIK3CD is associated to favorable disease. Yet, activation of Akt is associated with poor prognosis. Since the contribution of the numerous members of this pathway to neuroblastoma pathogenesis is mainly unknown, genes of the PI3K/Akt pathway were analyzed at the mRNA level through microarrays and quantitative real-time RT-PCR (TaqMan) and at the protein level using western blot analysis. Five genes showed lower mRNA expression in aggressive compared to more favorable neuroblastomas (PRKCZ, PRKCB1, EIF4EBP1, PIK3RI and PIK3CD) while the opposite was seen for PDGFRA. Clustering analysis shows that the expression levels of these six genes can predict aggressive disease. At the protein level, p110δ (encoded by PIK3CD) and p85α isomers (encoded by PIK3R1) were more highly expressed in favorable compared to aggressive neuroblastoma. Evaluation of the expression of these PI3K genes can predict aggressive disease, and indicates stage-dependent involvement of PI3K-pathway members in neuroblastoma.

  • 41.
    Fransson, Susanne
    et al.
    Sahlgrenska Cancer Center, University of Gothenburg, Sweden.
    Ejeskär, Katarina
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi. Sahlgrenska Cancer Center, University of Gothenburg, Sweden.
    High level of p37δ-mRNA relative to p110δ-mRNA in neuroblastoma tumors correlates with poor patient survival2013Ingår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 30, nr 4, artikel-id 724Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alterations in the PI3K/Akt pathway, a pathway that promotes proliferation and oncogenic transformation, are common in various cancers. In neuroblastoma, activation of Akt is correlated with aggressive disease although mutations in genes of this pathway are rare. Previous findings include a few mutations in PIK3CD, the gene encoding PI3K catalytic subunit delta, p110delta. We recently reported that an alternatively spliced form of p110delta, called p37delta, had cell proliferative properties and was over-expressed in ovarian and colorectal tumors. Here, we investigated p37delta in neuroblastoma primary tumors of different stages using qPCR (TaqMan) for gene expression analysis (46 samples) and Western blot for protein analysis (22 samples). Elevated levels of both p37delta-mRNA and p110delta-mRNA were detected in metastasizing neuroblastoma tumors compared to normal adrenal gland (P<0.05), and higher expression of p37delta-mRNA relative to p110delta-mRNA in neuroblastoma non-survivor patients compared to survivors (P<0.01). p37delta-Protein levels but not p110delta levels correlated with increased pAKT(T308) and pERK levels. The p37delta-mRNA levels did not correlate with the protein levels, indicating major regulation at the translational/protein level. Deregulation of signaling pathways is a hallmark of cancer development. Here, we show that p37delta, a kinase-dead isoform of the PI3K catalytic subunit p110delta, is over-expressed in neuroblastoma tumors, and that it correlates with the activation of both PI3K/Akt- and RAS-signaling pathways.

  • 42.
    Fransson, Susanne
    et al.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Medical and Clinical Genetics, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Kogner, Per
    Department of Women’s and Children’s Health, Childhood Cancer Research Unit, Karolinska Institutet, Stockholm, Sweden.
    Martinsson, Tommy
    Department of Medical and Clinical Genetics, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ejeskär, Katarina
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Aggressive neuroblastomas have high p110alpha but low p110delta and p55alpha/p50alpha protein levels compared to low stage neuroblastomas2013Ingår i: Journal of Molecular Signaling, E-ISSN 1750-2187, Vol. 8, nr 1, artikel-id 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The phosphoinositide 3-kinase (PI3K)/Akt pathway is involved in neuroblastoma development where Akt/PKB activation is associated with poor prognosis. PI3K activity subsequently activates Akt/PKB, and as mutations of PI3K are rare in neuroblastoma and high levels of PI3K subunit p110delta is associated with favorable disease with low p-Akt/PKB, the levels of other PI3K subunits could be important for Akt activation.Methods: Protein levels of Type IA PI3K catalytic and regulatory subunits were investigated together with levels of phosphorylated Akt/PKB and the PI3K negative regulator PTEN in primary neuroblastoma tumors. Relation between clinical markers and protein levels were evaluated through t-tests. Results: We found high levels of p-Akt/PKB correlating to aggressive disease and p-Akt/PKB (T308) showed inverse correlation to PTEN levels. The regulatory isomers p55alpha/p50alpha showed higher levels in favorable neuroblastoma as compared with aggressive neuroblastoma. The PI3K-subunit p110alpha was found mainly in advanced tumors while p110delta showed higher levels in favorable neuroblastoma.Conclusions: Activation of the PI3K/Akt pathway is seen in neuroblastoma tumors, however the contribution of the different PI3K isoforms is unknown. Here we show that p110alpha is preferentially expressed in aggressive neuroblastomas, with high p-Akt/PKB and p110delta is mainly detected in favorable neuroblastomas, with low p-Akt/PKB. This is an important finding as PI3K-specific inhibitors are suggested for enrollment in treatment of neuroblastoma patients.

  • 43.
    Gaston-Johansson, Fannie
    et al.
    Johns Hopkins University, Department of Acute and Chronic Care, School of Nursing, Baltimore, MD, USA.
    Fall-Dickson, Jane M.
    National Institute of Health, Symptom Management Branch, National Institute of Nursing, Research, Bethesda, MD, USA.
    Nanda, Joy P.
    Johns Hopkins Medical Institutions, Baltimore, MD, USA.
    Kenne Sarenmalm, Elisabeth
    Skaraborg Hospital, Department of Research and Development Centre, Skövde, Sweden.
    Browall, Maria
    Högskolan i Skövde, Institutionen för vård och natur.
    Goldstein, Nancy
    Johns Hopkins University, Department of Acute and Chronic Care, School of Nursing, Baltimore, MD, USA.
    Long-term effect of the self-management comprehensive coping strategy program on quality of life in patients with breast cancer treated with high-dose chemotherapy2012Ingår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 22, nr 3, s. 530-539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: This study aims to examine the effectiveness of a self-management multimodal comprehensive coping strategy program (CCSP) on quality of life (QOL) among breast cancer patients 1 year after treatment.

    METHODS: Patients (n = 110) with stage II, III, or IV breast cancer scheduled to receive high dose chemotherapy and autologous hematopoietic stem cell transplantation were randomized to either CCSP treatment or control group. The CCSP intervention was taught 2 week before hospital admission with reinforcement at specified times during treatment and 3 months after discharge. The CCSP components included educational information, cognitive restructuring, coping skills enhancement, and relaxation with guided imagery. Instruments administered at baseline included the following: Quality of Life Index-Cancer Version (QOLI-CV), State-Trait Anxiety Inventory, Beck Depression Inventory, and Coping Strategies Questionnaire. At 1-year follow-up, patients (n = 73) completed and returned the follow-up QOLI-CV.

    RESULTS: Patients were mainly ≥40 years of age, married, Caucasian, and diagnosed with advanced breast cancer. A model measuring effectiveness of CCSP on QOL (total and subscale) at 1-year follow-up showed that the CCSP group (n = 38) had significant improvement in overall QOL (p < 0.01), health and functioning (p < 0.05), and socioeconomic (p < 0.05) and psychological/spiritual well-being (p < 0.01) compared with the control group (n = 35). The CCSP patients frequently used the CCSP to manage psychological (51%) and sleep problems (60%).

    CONCLUSIONS: The CCSP improved QOL for patients at 1-year follow-up. Patients overwhelmingly reported that CCSP was beneficial. The CCSP as an effective coping intervention has potential as a self-management program for breast cancer survivors.

  • 44.
    Gnosa, Sebastian
    et al.
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
    Shen, Yang-Mei
    Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
    Wang, Chao-Jie
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
    Zhang, Hong
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för vård och natur.
    Stratmann, Johannes
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
    Arbman, Gunnar
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sun, Xiao-Feng
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden / Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Country Council of Östergötland, University of Linköping, Linköping, Sweden.
    Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines2012Ingår i: Journal of Translational Medicine, E-ISSN 1479-5876, Vol. 10, artikel-id 109Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been shown to be overexpressed in several types of cancers. In colorectal cancer (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to normal mucosa, showing prognostic significance. Since little is known about the transcriptional level of AEG-1 expression and its biological pathway in CRC the aim of the present study was to examine the relationship of AEG-1 mRNA expression, the protein level and clinicopathological variables as well as its biology pathway in CRC. Material and methods: The mRNA expression of AEG-1 was analysed by qPCR in fresh frozen patient samples including 156 primary tumours, along with the corresponding normal mucosa, and in five colon cancer cell lines, SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was investigated by immunohistochemistry in paraffin-embedded materials from 74 distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein expression was elucidated in the cell lines by Western blot. Results: The lymph node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 +/- 0.02) expression compared to the primary tumour cell line SW480 (0.17 +/- 0.04, p = 0.026). AEG-1 expression at the mRNA level and/or the protein level was significantly up-regulated gradually from normal mucosa to primary CRC, and then to lymph node metastasis and finally to liver metastasis (p < 0.05). There were significant associations of AEG-1 mRNA expression with tumour location (p = 0.047), as well as mRNA and protein expression with the tumour stage (p < 0.03). Furthermore AEG-1 protein expression was positively related to biological variables including NF-kappa B, p73, Rad50 and apoptosis (p < 0.05). Conclusion: AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development and aggressiveness, and is related to tumour location and stage. It may play its role in CRC through the NF-kappa B signaling pathway.

  • 45.
    Hagberg, Malin
    et al.
    Högskolan i Skövde, Institutionen för vård och natur.
    Holmén, Jonathan
    Högskolan i Skövde, Institutionen för vård och natur.
    Olausson, Josefin
    Högskolan i Skövde, Institutionen för vård och natur.
    Karlsson, Sandra
    Högskolan i Skövde, Institutionen för vård och natur.
    Johansson, Viktoria
    Högskolan i Skövde, Institutionen för vård och natur.
    Larsson, Dennis
    Högskolan i Skövde, Institutionen för vård och natur.
    Rapid activation of JNK/SAPK in LNCaP prostate cancer cells by 1α,25-dihydroxyvitamin D3 is independent of PDIA3 (1,25-MARRS)2008Ingår i: Current Topics in Steroid Research, ISSN 0972-4788, Vol. 5, s. 17-24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    1α,25-dihydroxyvitamin D3 (1,25D3 ) is a highly potential anti-cancerous agent for prevention and treatment of prostate cancer, the most commonly diagnosed cancer type of males in western countries. A recent study by our laboratory, demonstrates that LNCaP cancer cells treated with 1,25D3, evoked dose-dependent activation of the JNK/SAPK MAPK signaling pathway within 10 minutes after hormone treatment, indicative of membrane-initiated steroid signaling (MISS) by 1,25D3. This confirms previous reports on intestinal-, chondrocyte- and osteoblast cells, where 1,25D3 operates through pharmacologically distinct nuclear-initiated mechanisms (NISS) and plasma membrane-initiated mechanisms. NISS is mediated via the vitamin D receptor (nVDR) and MISS is mediated through 1,25D3-MARRS (PDIA3, 1,25D3-membraneassociated rapid response steroid binding protein) or nVDR. The aims of the present study were to investigate the mechanisms of MISS evoked effects on alkaline phosphatase (ALP) and activation of the JNK/SAPK by 1,25D3, and the involvement of PDIA3 in 1,25D3 initiated activation of the JNK/SAPK signaling pathway. Furthermore, 1,25D3-treated LNCaP cells were transfected with siRNA against PDIA3 and phosphorylated JNK/SAPK was estimated by western analysis. Western analysis and ALP-assays demonstrated rapid activation of both JNK/SAPK as well as ALP. Silencing of PDIA3 did not affect 1,25D3 mediated activation of JNK/SAPK, suggesting that PDIA3 is not involved in the 1,25D3-initiated activation of the JNK/SAPK signaling pathway.

  • 46.
    Horning, Aaron M.
    et al.
    University of Texas Health Science Center, San Antonio, USA.
    Awe, Julius Adebayo
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada / Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wang, Chiou-Miin
    University of Texas Health Science Center, San Antonio, USA.
    Liu, Joseph
    University of Texas Health Science Center, San Antonio, USA.
    Lai, Zhao
    University of Texas Health Science Center, San Antonio, USA.
    Wang, Vickie Yao
    University of Texas Health Science Center, San Antonio, USA.
    Jadhav, Rohit R.
    University of Texas Health Science Center, San Antonio, USA.
    Louie, Anna D.
    University of Texas Health Science Center, San Antonio, USA.
    Lin, Chun-Lin
    University of Texas Health Science Center, San Antonio, USA.
    Kroczak, Tad
    University of Manitoba, Winnipeg, Manitoba, Canada.
    Chen, Yidong
    University of Texas Health Science Center, San Antonio, USA.
    Jin, Victor X.
    University of Texas Health Science Center, San Antonio, USA.
    Abboud-Werner, Sherry L.
    University of Texas Health Science Center, San Antonio, USA.
    Leach, Robin J.
    University of Texas Health Science Center, San Antonio, USA.
    Hernandez, Javior
    University of Texas Health Science Center, San Antonio, USA.
    Thompson, Ian M.
    University of Texas Health Science Center, San Antonio, USA.
    Saranchuk, Jeff
    University of Manitoba, Winnipeg, Canada.
    Drachenberg, Darrel
    University of Manitoba, Winnipeg, Canada.
    Chen, Chun-Liang
    University of Texas Health Science Center, San Antonio, USA.
    Mai, Sabine
    University of Manitoba, Winnipeg, Canada.
    Huang, Tim Hui-Ming
    University of Texas Health Science Center, San Antonio, USA.
    DNA Methylation Screening of Primary Prostate Tumors Identifies SRD5A2 and CYP11A1 as Candidate Markers for Assessing Risk of Biochemical Recurrence2015Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 75, nr 15, s. 1790-1801Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND. Altered DNA methylation in CpG islands of gene promoters has been implicated in prostate cancer (PCa) progression and can be used to predict disease outcome. In this study, we determine whether methylation changes of androgen biosynthesis pathway (ABP)-related genes in patients' plasma cell-free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR). METHODS. Methyl-binding domain capture sequencing (MBDCap-seq) was used to identify differentially methylated regions (DMRs) in primary tumors of patients who subsequently developed BCR or not, respectively. Methylation pyrosequencing of candidate loci was validated in cfDNA samples of 86 PCa patients taken at and/or post-radical prostatectomy (RP) using univariate and multivariate prediction analyses. RESULTS. Putative DMRs in 13 of 30 ABP-related genes were found between tumors of BCR (n = 12) versus no evidence of disease (NED) (n = 15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci-SRD5A2 and CYP11A1, which also correlated with their decreased expression, in tumors with subsequent BCR development. Their aberrant cfDNA methylation was also associated with detectable levels of PSA taken after patients' post-RP. Multivariate analysis of the change in cfDNA methylation at all of CpG sites measured along with patient's treatment history predicted if a patient will develop BCR with 77.5% overall accuracy. CONCLUSIONS. Overall, increased DNA methylation of SRD5A2 and CYP11A1 related to androgen biosynthesis functions may play a role in BCR after patients' RP. The correlation between aberrant cfDNA methylation and detectable PSA in post-RP further suggests their utility as predictive markers for PCa recurrence. (C) 2015 Wiley Periodicals, Inc.

  • 47.
    Hu, Chun
    et al.
    Xiamen Univ, Coll Med, Canc Res Ctr, Xiamen 361005, Peoples R China .
    Song, Gang
    Xiamen Univ, Coll Med, Canc Res Ctr, Xiamen 361005, Peoples R China .
    Zhang, Bing
    Xiamen Univ, Coll Med, Dept Basic Med, Xiamen 361005, Peoples R China.
    Liu, Zhongchen
    Xiamen Univ, Coll Med, Zhongshan Affiliated Hosp, Xiamen 361005, Peoples R China .
    Chen, Rong
    Wuhan Inst Technol, Minist Educ, Key Lab Green Chem Proc, Wuhan, Peoples R China and Wuhan Inst Technol, Minist Educ, Sch Chem Engn & Pharm, Wuhan, Peoples R China .
    Zhang, Hong
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Hu, Tianhui
    Xiamen Univ, Coll Med, Canc Res Ctr, Xiamen 361005, Peoples R China .
    Intestinal metabolite compound K of panaxoside inhibits the growth of gastric carcinoma by augmenting apoptosis via Bid-mediated mitochondrial pathway2012Ingår i: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 16, nr 1, s. 96-106Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of panaxoside, has been shown to inhibit tumour growth in a variety of tumours. However, the mechanisms involved are largely unknown. We use human gastric carcinoma cell lines BGC823, SGC7901 and human gastric carcinoma xenograft in nude mice as models to study the mechanisms of CK in gastric cancers. We found that CK significantly inhibits the viabilities of BGC823 and SGC7901 cells in dose- and time-dependent manners. CK-induced BGC823 and SGC7901 cells apoptosis and cell cycle arrest in G2 phase by up-regulation of p21 and down-regulation of cdc2 and cyclin B1. Further studies show that CK induces apoptosis in BGC823 and SGC7901 cells mainly through mitochondria-mediated internal pathway, and that CK induces the translocation of nuclear Bid to mitochondria. Finally, we found that CK effectively inhibited the tumour formation of SGC7901 cells in nude mice. Our studies show that CK can inhibit the viabilities and induce apoptosis of human gastric carcinoma cells via Bid-mediated mitochondrial pathway.

  • 48.
    Hussain, Showket
    et al.
    Institute of Cytology & Preventive Oncology (ICMR), Noida, Uttar Pradesh, India.
    M., Yuvaraj
    Institute of Cytology & Preventive Oncology (ICMR), Noida, Uttar Pradesh, India.
    Thakur, Nisha
    Institute of Cytology & Preventive Oncology (ICMR), Noida, Uttar Pradesh, India.
    Salam, Irfana
    Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
    Singh, Neha
    Panjab University, Chandigarh, India.
    Mir, Mohammad Muzaffar
    Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
    Bhat, Mohammad Akbar
    Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
    Siddiqi, Mushtaq A.
    Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
    Das, Bhudev C.
    Dr. B.R. Ambedkar Research Centre for Biomedical Research (ACBR), University of Delhi, India.
    Bharadwaj, Mausumi
    Institute of Cytology & Preventive Oncology (ICMR), Noida, Uttar Pradesh, India.
    Association of cyclin D1 gene polymorphisms with risk of esophageal squamous cell carcinoma in Kashmir Valley: a high risk area2011Ingår i: Molecular Carcinogenesis, ISSN 0899-1987, E-ISSN 1098-2744, Vol. 50, nr 7, s. 487-98Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Investigation of potential association of SNPs (G870A, rs9344; G1722C, rs678653) of cyclin D1 gene (CCND1) with susceptibility to esophageal squamous cell carcinoma (ESCC) in Kashmir valley (India). The study included 302 subjects comprising 151 ESCC cases and 151 controls. PCR-RFLP and direct sequencing were employed for genotyping. The G870A polymorphism, the individuals carrying GA + AA genotype was having 2.80-fold increased risk for development of ESCC (OR 2.8, 95% CI = 1.77-4.4; P = 0.0001) compared to GG genotype. Further a significantly higher risk was observed in individuals who consume >3 cups per day of salted tea (OR = 5.1; 95% CI = 1.6-16.7; P = 0.0016) and had smoking habits (OR = 6.3; 95% CI = 2.9-13.9; P = 0.0005). We also demonstrate for the first time in CCND1 1722 locus, the CC genotype was strongly associated with increased risk of developing ESCC (OR = 2.58; 95% CI = 1.61-4.15; P = 0.0001). In addition, the frequency of polymorphic C allele was also found to be higher in cases (OR = 1.92; 95% CI = 1.37-2.69; P = 0.0002). There appears to be an influence of CCND1 G870A/G1772C genotypes on genetic susceptibility to ESCC.

  • 49.
    Hussain, Showket
    et al.
    Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
    Singh, Neha
    Department of Biotechnology, Panjab University, Chandigarh, India.
    Salam, Irfana
    Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
    Bandil, Kapil
    Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
    Yuvaraj, M
    Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
    Akbar Bhat, Mohammad
    Department of Cardiovascular Thoracic Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
    Muzaffar Mir, Mohammad
    Department of Biotechnology, Panjab University, Chandigarh, India.
    Siddiqi, Mushtaq A.
    Department of Cardiovascular Thoracic Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
    Sobti, Ranbir C.
    Department of Biotechnology, Panjab University, Chandigarh, India.
    Bharadwaj, Mausumi
    Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
    Das, Bhudev C.
    Dr. B.R. Ambedkar Centre for Biomedical Research (ACBR) University of Delhi (North Campus), Delhi, India.
    Methylation-mediated gene silencing of suppressor of cytokine signaling-1 (SOCS-1) gene in esophageal squamous cell carcinoma patients of Kashmir valley2011Ingår i: Journal of Receptor and Signal Transduction Research, ISSN 1079-9893, E-ISSN 1532-4281, Vol. 31, nr 2, s. 147-56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir. The negative regulation of tumor suppressor gene leading to change in signaling pathway is one of the major mechanisms responsible for tumorigenic transformation.

    OBJECTIVE: In the present study, the role of silencing of suppressor of cytokine signaling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway, was analyzed in ESCC.

    METHODS: The expression pattern of SOCS-1 gene was analyzed in esophageal tumor biopsies although normal adjacent tissues that served as controls. Reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, methylation-specific PCR (MSP), and human papillomavirus (HPV) detection were performed to assess the expression pattern and promoter methylation of SOCS-1 gene including HPV status in a total of 75 surgically resected tissue specimens.

    RESULTS: Compared with the level of SOCS-1 expression in normal tissues, 53% (40/75) of the tumor tissues expressed either undetectable or reduced SOCS-1 expression (>50% loss of expression), which was significantly associated with advanced clinical stage or severe histopathological grade of the disease (P < 0.01). Aberrant promoter methylation of the SOCS-1 gene was found in 45% (34/75) of the esophageal tumor tissues, which was also found to be significantly associated with advanced stage of esophageal carcinoma (P < 0.01). The prevalence of HPV infection was found in 19% of tumor cases, whereas no HPV could be detected in any of the normal adjacent tissues.

    CONCLUSION: Transcriptional inactivation of SOCS-1 gene, primarily due to its promoter hypermethylation although HPV infection, may play an important role in esophageal carcinogenesis in Kashmir.

  • 50.
    Hussain, Showket
    et al.
    ICPO (ICMR), NOIDA, India.
    Singh, Neha
    Department of Biotechnology, Panjab University, Chandigarh, India.
    Salam, Irfana
    Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Kashmir, India.
    Bhat, Mohammad A.
    Department of Cardiovascular Thoracic Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India.
    Kakkar, Nandita
    Department of Histopathology, PGIMER, Chandigarh, India.
    Mir, Mohammad M.
    Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India.
    Siddiqi, Mushtaq A.
    Department of Immunology and Molecular Medicine Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India.
    Basir, Seemi F.
    Department of Biosciences Jamia Millia Islamia, Delhi, India.
    Bharti, Alok C.
    ICPO (ICMR), NOIDA, India.
    Bharadwaj, Mausumi
    ICPO (ICMR), NOIDA, India.
    Das, Bhudev C.
    Dr. B.R. Ambedkar Research Centre for Biomedical Research (ACBR), University of Delhi (North Campus), Delhi, India.
    Abstract 2722: Transcription factor NF-kB in esophageal squamous cell carcinoma: Alterations in activity and expression during Human Papillomavirus infection2011Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 71, nr 8 Suppl, artikel-id Abstract 2722Artikel i tidskrift (Refereegranskat)
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