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1.
TRIM28 variants and Wilms' tumour predisposition.
Hol, JA, Diets, IJ, de Krijger, RR, van den Heuvel-Eibrink, MM, Jongmans, MC, Kuiper, RP
The Journal of pathology. 2021;(4):494-504
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Abstract
TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of familial WT cases. TRIM28 variants are associated with epithelial WT, but the presence of other tumour components or anaplasia does not exclude the presence of a germline or somatic TRIM28 variant. In children with WT, TRIM28 acts as a classical tumour suppressor gene, with both alleles generally disrupted in the tumour. Therefore, loss of TRIM28 (KAP1/TIF1beta) protein expression in tumour tissue by immunohistochemistry is an effective strategy to identify patients carrying pathogenic TRIM28 variants. TRIM28 is a ubiquitously expressed corepressor that binds transcription factors in a context-, species-, and cell-type-specific manner to control the expression of genes and transposable elements during embryogenesis and cellular differentiation. In this review, we describe the inheritance patterns, histopathological and clinical features of TRIM28-associated WT, as well as potential underlying mechanisms of tumourigenesis during embryonic kidney development. Recognizing germline TRIM28 variants in patients with WT can enable counselling, genetic testing, and potential early detection of WT in other children in the family. A further exploration of TRIM28-associated WT will help to unravel the diverse and complex mechanisms underlying WT development. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: Case report and review.
Zeng, MF, Chen, LL, Ye, HY, Gong, W, Zhou, LN, Li, YM, Zhao, XL
Medicine. 2017;(44):e8426
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RATIONALE Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system. PATIENT CONCERNS A 54-year-old male with renal clear cell carcinoma was treated with nivolumab intravenously. Routine monitoring showed elevated thyroid-stimulating hormone and low free thyroxine after the 6th administration of nivolumab. After the 12th administration, he developed general fatigue, recurrent hypoglycemia, and relative hypotension. Laboratory tests showed low sodium, low morning cortisol without correspondence increase of corticotrophin (ACTH). Other pituitary hormones were normal. MRI showed no space-occupying lesions, but heterogeneous enhancement of the pituitary gland. DIAGNOSES Primary hypothyroidism and isolated ACTH deficiency. The etiologies were assumed to be nivolumab induced autoimmune lymphocytic thyroiditis and hypophysitis, respectively. INTERVENTIONS Hormone replacements with levothyroxine and acetate cortisone were given orally. Nivolumab was adjusted to lower dose and longer interval. OUTCOMES The patient felt good after adequate replacement. Nivolumab was returned to routine dose and interval six months later. And the metastasis was not obviously progressed during this time. LESSONS The present report provides the first detailed presentation of combined hypothyroidism and isolated ACTH deficiency induced by nivolumab. Adrenal deficiency often develops insidiously. We suggest routine monitoring of fasting blood-glucose, blood pressure and serum sodium as well as thyroid function during nivolumab and other cancer immunotherapies. When unexpected fatigue, hypoglycemia, hypotension or hyponatremia appeared, adrenal deficiency should be taken into consideration.
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Upper tract urothelial carcinoma topical issue 2016: treatment of metastatic cancer.
Pham, MN, Apolo, AB, De Santis, M, Galsky, MD, Leibovich, BC, Pisters, LL, Siefker-Radtke, AO, Sonpavde, G, Steinberg, GD, Sternberg, CN, et al
World journal of urology. 2017;(3):367-378
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Abstract
PURPOSE To review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, co-sponsored by the Société Internationale d'Urologie and International Consultation on Urological Diseases. METHODS A PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion. RESULTS The management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients. CONCLUSIONS The management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.
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4.
Englerins: A Comprehensive Review.
Wu, Z, Zhao, S, Fash, DM, Li, Z, Chain, WJ, Beutler, JA
Journal of natural products. 2017;(3):771-781
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In the decade since the discovery of englerin A (1) and its potent activity in cancer models, this natural product and its analogues have been the subject of numerous chemical, biological, and preclinical studies by many research groups. This review summarizes published findings and proposes further research directions required for entry of an englerin analogue into clinical trials for kidney cancer and other conditions.
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The Therapeutic Aspects of the Endocannabinoid System (ECS) for Cancer and their Development: From Nature to Laboratory.
Khan, MI, Sobocińska, AA, Czarnecka, AM, Król, M, Botta, B, Szczylik, C
Current pharmaceutical design. 2016;(12):1756-66
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Abstract
The endocannabinoid system (ECS) is a group of neuromodulatory lipids and their receptors, which are widely distributed in mammalian tissues. ECS regulates various cardiovascular, nervous, and immune system functions inside cells. In recent years, there has been a growing body of evidence for the use of synthetic and natural cannabinoids as potential anticancer agents. For instance, the CB1 and CB2 receptors are assumed to play an important role inside the endocannabinoid system. These receptors are abundantly expressed in the brain and fatty tissue of the human body. Despite recent developments in molecular biology, there is still a lack of knowledge about the distribution of CB1 and CB2 receptors in the human kidney and their role in kidney cancer. To address this gap, we explore and demonstrate the role of the endocannabinoid system in renal cell carcinoma (RCC). In this brief overview, we elucidate the therapeutic aspects of the endocannabinoid system for various cancers and explain how this system can be used for treating kidney cancer. Overall, this review provides new insights into cannabinoids' mechanisms of action in both in vivo and in vitro models, and focuses on recent discoveries in the field.
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Comparing comparators: a look at control arms in kidney cancer studies over the years.
Bracarda, S, Porta, C, Sisani, M, Marrocolo, F, Paglino, C, Hamzaj, A, D Buono, S, Sternberg, CN
British journal of cancer. 2015;(1):14-9
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In the past decade, an increasing number of frequently positive randomised clinical trials have been completed, allowing new consideration of the present therapeutic armamentarium for advanced renal cell carcinoma. These studies were predominantly designed to compare the experimental drugs with 1 of 2 active control arms: interferon alpha-2a or sorafenib. Different from expectations, the final results of some of these studies were not in line with the predictions, and the reasons have not been fully investigated. Consequently, there is a great need for careful analysis of the studies carried out so far, chiefly the role and validity of the control arms. In this regard, the examination of patient baseline characteristics and other factors of potential interest seems fundamental for a correct analysis of the results of these trials and consequent optimal use of the available targeted agents.
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Clinicopathologic features of renal epithelioid angiomyolipoma: report of one case and review of literatures.
Tan, G, Liu, L, Qiu, M, Chen, L, Cao, J, Liu, J
International journal of clinical and experimental pathology. 2015;(1):1077-80
Abstract
Epithelioid angiomyolipoma (EAML) is a rare renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis complex (TSC). As metastasis of the tumor cells occur early, EAML is considered a potentially malignant tumor type and intrigues further research on it. Under the microscope, we could find the tumor was composed of atypical polygonal cells sheet mixed with classic angiomyolipoma (AML) components such as blood vessels with notable thick vascular walls, smooth muscle-like cells and adipocytes. Immunohistochemical studies showed that epithelioid cells were focally positive for vimentin, melanocytic markers (HMB-45), myoid markers (α-smooth muscle actin), CD34 and CD68; negative for cytokeratin, epithelial membrane antigen, CD10, and S-100. And the Ki67 index showed approximately 3%. Here, we report the morphological and immunohistochemical features of clinically or histologically malignant renal EAML and discuss its diagnosis, differential diagnosis and the prognosis.
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Renal angiomyolipoma with epithelial cysts: a rare entity and review of literature.
Wei, J, Li, Y, Wen, Y, Li, L, Zhang, R
International journal of clinical and experimental pathology. 2015;(9):11760-5
Abstract
Renal angiomyolipoma (AML) with epithelial cysts (AMLEC) is a comparatively rare benign renal tumor that is recently recognized as a distinct entity and there are relatively few reported cases in the English-language literature. To date 19 cases of AMLEC have been reported in 2 case series and a few case reports. AMLEC has been described as a cystic variant of AML. Herein we reported an AMLEC in a 25-year-old female patient, and to the best of our knowledge this is the first case report of AMLEC in Chinese. She was incidentally found to have a kidney-occupying lesion during a routine medical examination for 1 month. CT examination demonstrated a multilocular cystic lesions arising from right-kidney lower pole. The patient underwent the partial nephrectomy. Histological examination of the tumor was composed of epithelial cysts, compact subepithelial mullerian-like stroma and muscle-predominant AML. Immunohistochemically, epithelial cysts were positive for CK but negative for ER, PR, CD10 and HMB-45; the subepithelial stroma and muscle-predominant AML were positive for ER, PR and HMB-45; the subepithelial stroma was negative for SMA, but muscle-predominant AML was positive for SMA. The final histopathological diagnosis was AMLEC.
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Vitamin D receptor gene polymorphisms in breast and renal cancer: current state and future approaches (review).
Khan, MI, Bielecka, ZF, Najm, MZ, Bartnik, E, Czarnecki, JS, Czarnecka, AM, Szczylik, C
International journal of oncology. 2014;(2):349-63
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Cancer is a major health problem and cause of death worldwide that accounted for 7.6 million deaths in 2008, which is projected to continue rising with an estimated 13.1 million deaths in 2030 according to WHO. Breast cancer is the leading cause of cancer-based death among women around the world and its incidence is increasing annually with a similar tendency. In contrast, renal cell carcinoma accounts for only 3% of total human malignancies but it is still the most common type of urological cancer with a high prevalence in elderly men (>60 years of age). There are several factors linked with the development of renal cell cancer only, while others are connected only with breast cancer. Genetic risk factors and smoking are the factors which contribute to carcinogenesis in general. Some evidence exists indicating that vitamin D receptor (VDR) gene polymorphisms are associated with both breast and renal cancer; therefore, we put forward the hypothesis that polymorphisms in the VDR gene may influence both the occurrence risks of these cancers and their prognosis. However, the relationship between VDR polymorphisms and these two specific cancers remains a controversial hypothesis, and consequently needs further confirmation via clinical research together with genetic investigations. Here, we aimed to assess the correlation between the different alleles of VDR gene polymorphisms and renal cell cancer and breast cancer risks separately through a systematic review of the present literature. In contrast, this analysis has revealed that some VDR gene polymorphisms, such as: Bsm1, poly(A), Taq1, Apa1, are to some extent associated with breast cancer risk. Other polymorphisms were found to be significantly associated with renal cell cancer. Namely, they were Fok1, Bsm1, Taq1 and Apa1, which encode proteins participating mainly in proliferation, apoptosis and cell cycle regulation. However, data concerning renal cancer are not sufficient to firmly establish the VDR gene polymorphism association.
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10.
A rare complication of transitional cell carcinoma of the renal pelvis: parathyroid hormone-related peptide-induced hypercalcaemia.
O Sullivan, E, Plant, W
BMJ case reports. 2014
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We describe a rare occurrence of parathyroid hormone-related peptide (PTHrp) associated hypercalcaemia with a recurrence of transitional cell carcinoma of the renal pelvis. Our patient presented with serum calcium of 3.9 mmol/L, PTH of 5 ng/L and a PTHrp of 9.8 pmol/L (<2 pmol/L). He had no evidence of metastatic disease. His hypercalcaemia responded to bisphosphonate therapy. He chose to be treated conservatively and died 5 weeks after presentation. This is the seventh such case described in the literature. PTHrp-induced hypercalcaemia is associated with a grave prognosis, with a mean survival of 65 days from presentation.