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1.
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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Abstract
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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2.
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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3.
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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Abstract
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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Outcome and Safety of Sorafenib in Metastatic Renal Cell Carcinoma Dialysis Patients: A Systematic Review.
Leonetti, A, Bersanelli, M, Castagneto, B, Masini, C, Di Meglio, G, Pellegrino, B, Buti, S
Clinical genitourinary cancer. 2016;(4):277-83
Abstract
Few data are available about sorafenib use in patients with metastatic renal cell carcinoma (mRCC) undergoing hemodialysis. No systematic review has been previously performed about this issue. The objective of the present review is to investigate pharmacokinetics and clinical outcomes of sorafenib in mRCC patients undergoing hemodialysis. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, all the literature about mRCC dialysis patients receiving sorafenib, published from January 1946 to August 2015, was evaluated. Applying inclusion/exclusion criteria, 11 articles were selected for the analysis; 1 patient from our department was also included. The investigated outcomes were pharmacokinetics, toxicity, response rate, progression-free survival, and overall survival where available. A total of 36 patients were included. Median treatment duration was 6.0 months on overall population; median progression-free survival was 6.3 months (calculated on 19 patients); response rate was 22% (on 29 patients); median overall survival was 14.9 months (on 28 patients). Of note, 24 patients started sorafenib at reduced dose; 6 of 36 patients (17%) required dose reduction due to adverse events (AEs). Sorafenib treatment was discontinued in 7 patients (19%) because of AEs. Most of AEs were Grade 1-2; severe toxicities (Grade 4-5) included G4 anemia (1 case), G4 hypertension (1 case), G4 cerebellar hemorrhage (1 patient), and a case of G5 subarachnoid hemorrhage. This review confirmed the efficacy of sorafenib treatment in mRCC patients receiving hemodialysis. Nevertheless, drug toxicity seems to be increased in these patients, despite the initiation of therapy at reduced doses; therefore, sorafenib should be used with caution in dialysis patients.
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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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Imaging the renal lesion with dual-energy multidetector CT and multi-energy applications in clinical practice: what can it truly do for you?
Mileto, A, Sofue, K, Marin, D
European radiology. 2016;(10):3677-90
Abstract
OBJECTIVE Many fortuitously detected renal lesions are incompletely characterised at traditional MDCT imaging, thus posing daily challenges to radiologists and referring physicians. There is burgeoning evidence that dual-energy MDCT and multi-energy applications provide an added value over traditional MDCT imaging in renal lesion characterisation and throughput. This special report gives a vendor-neutral outlook on technical essentials, recommended protocols, high-yield clinical opportunities and reviews radiation dose aspects of dual-energy MDCT imaging and multi-energy applications in renal lesions. In addition to a guide on interpretative traps and emerging problems, we provide an update on new, potential imaging horizons. CONCLUSION Dual-energy MDCT and multi-energy applications can facilitate the imaging interpretation and throughput of renal lesions. Conjointly with capitalisation on the benefits, familiarity with dual- and multi-energy data sets as well as continuous scrutiny of interpretative traps can be the keys to the successful implementation and enhanced clinical acceptance of this powerful technique in the imaging community. Continuous advances in hardware and computer interfaces are expected to pave the way for the further expansion of the application spectrum. KEY POINTS • Optimal protocols must be adopted for leveraging dual-energy benefits in renal imaging. • Virtual monochromatic imaging can overcome renal cyst pseudoenhancement. • Iodine maps help to interpret renal lesions incompletely characterised at traditional MDCT. • Interpretative traps need to be weighed-up in dual-energy renal lesions imaging. • Technical advances are expanding the dual-energy applications spectrum for renal lesions imaging.
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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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Abstract
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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8.
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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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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Kidney cancer: Temsirolimus fails to expand its role in patients with mRCC.
Payton, S
Nature reviews. Urology. 2014;(1):2