Urogenital Tumors Research Articles

Primum non Nocere: How to ensure continuity of care and prevent cancer patients from being overlooked during the COVID- 19 pandemic.

BackgroundCoronavirus disease 2019 (COVID‐19) has spread to all countries since December 2019, triggering a pandemic within weeks of the initial outbreak. Doctors were presented with the challenge of having to reimagine the traditional hospital organisation in order to effectively manage patients.Patients and MethodsDuring the months of the COVID‐19 pandemic our Institution was assisted by a call‐center (CC) that triaged cancer patients planned for follow‐up in our outpatient clinics: C1 (for female cancers), C2 (for gastrointestinal, urogenital, and thoracic tumours), and D1 (for melanoma and for patients with tumours in over 5 years follow up). Data refers to the period between 15 April and 3 July 2020.ResultsA total of 1054 patients have been included in our study and 1005 (95%) of the contacts were successful. The analysis showed a majority of female patients (74%) and patients affected by breast cancer (56%). Among the options provided 646 patients (92.4%) opted for online consultancy.ConclusionThis study has shown that cancer patients valued technology‐mediated follow‐up visits mainly during the beginning of the pandemic because patients themselves were afraid to come to the hospital. Although telemedicine has intrinsic limitations, it is important for providing assistance and preventing cancer patients from feeling isolated during an emergency.

Human papillomavirus vaccination - limatations and opportunities in countries with low vaccine coverage.

Persistent infection with oncogenic Human papillomavirus (HPV) types can lead to neoplasms involving urogenital and laryngeal tumors, which account for approximately 5% of all cancers worldwidely. Effective measures to reduce the morbidity and mortality associated with HPV cancers are regular examinations including the Papanicolaou test and preventive vaccination. However, despite the registration of the first HPV vaccine already in 2006, there is still huge disparity in the vaccination coverage between countries. In Poland, vaccination coverage is still very low in comparison to other European Union countries (only a few percent). Constraints exist on the part of the state and health system organizations, as well as in the attitudes of health professionals and parents. One of the primary factors influencing the decision to vaccinate against HPV is the presence of the vaccine in The National Immunization Program, while often with financial support. Formalization of vaccination also forces physicians to be more attentive to informing and recommending immunization, increasing their level of education. The role of medical workers is crucial from a social point of view. For parents, an adequate discussion with the physician is a vital factor influencing HPV vaccination decisions. At the same time, health care workers express the need to change their work organization due to insufficient time for health promotion and prophylaxis during visits. A thorough understanding of the barriers can allow for the development of effective strategies to increase vaccination coverage.

\u2018I thought I had fibroids, and now I don\u2019t\u2019: a mixed method study on health-related quality of life in uterine sarcoma patients

BackgroundUterine sarcomas are rare subtypes of primary urogenital tumours and need tailored treatment. This study aimed to examine the impact of diagnosis and treatment on health-related quality of life (HRQoL) in patients with uterine sarcoma and measures available to assess HRQoL in this group.MethodsThirteen patients with uterine sarcoma and 23 health care professionals were purposively sampled from sarcoma reference centers and participated in a semi-structured interview exploring HRQoL. Patients were also asked to review the EORTC QLQ-C30 and EORTC QLQ-EN24 for relevance. Data were analysed using thematic analysis and descriptive statistics.ResultsThe most commonly reported physical health issues were related to sexual dysfunction and urological symptoms. Hormone-related issues and gastrointestinal symptoms were also identified. Cancer-generic issues such as functional problems, fatigue, pain, and treatment-related adverse effects were also reported. Regarding mental health, fears (about having sex, of recurrence, or of death), altered body-image, and dealing with lacking knowledge regarding sarcoma had an impact on HRQoL. Social health issues were related to the impact on relationships with others, limitations in undertaking activities, loss of independence, changes in work or study capacity, and financial difficulties. Most of the items of the EORTC QLQ-C30 and EORTC QLQ-EN24 questionnaires were rated as relevant. Questions about lack of knowledge about sarcoma, shock of diagnosis, and menopausal symptoms were lacking from existing measures.ConclusionsUterine sarcoma patients experience a variety of concerns covering the physical, mental, and social domains of HRQoL that are in the main EORTC instruments, but not all of them. Combining cancer-generic, location- and sarcoma-specific items is recommended to assess HRQoL in this patient group.Trial registration NCT04071704.

Circ-AFAP1 promote clear cell renal cell carcinoma growth and angiogenesis by the Circ-AFAP1/miR-374b-3p/VEGFA signaling axis

Clear cell renal cell carcinoma (ccRCC) is one of the most common urogenital tumors with high mortality. Circular RNA (circRNA), as an emerging endogenous RNA, has been proved to play a crucial role in the clear cell renal cell carcinoma (ccRCC) progression. In this study, we obtained circAFAP1 upregulated in ccRCC by high-sequencing and verified by qRT-PCR in several renal cancer cell lines. In situ hybridization (ISH) assays and Kaplan–Meier plot showed a higher level of circAFAP1 was linked to shorter overall survival. Moreover, CCK8, colony formation, and EdU experiments showed circAFAP1 promoted ccRCC growth while tube formation displayed circAFAP1 contributed to ccRCC angiogenesis. We predicted the downstream miR-374b-3p and VEGFA by bioinformatic analysis and validated further by qRT-PCR, RNA pull-down, RIP, and dual-luciferase. Downregulation miR-374b-3p or overexpression VEGFA could restore proliferation, vascular formation after circAFAP1 silencing. Consistently with the results in vitro, silencing circAFAP1 suppressed ccRCC growth in vivo. In conclusion, the circAFAP1/miR-374b-3p/VEGFA axis played a critical role in the progression and development of ccRCC which might be novel biological marks and therapeutical targets.

Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes

IntroductionMetastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs.The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors. MethodsThis study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed. Results22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n=9), bladder tumor (n=7), testis tumors (n=4), and prostate cancer (n=2). There was no intraoperative complication. Postoperative complications were seen in 2 patients. ConclusionsAlthough pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches.

Central vascular access in pediatric patients

Local treatment plays a key role for patients’ outcome in tumors of the urogenital tract in children. Despite a great variety of different etiologies, the specific localization of pediatric urogenital tumors renders several characteristic demands to the treating personnel. Surgery and radiotherapy are the main elements of local treatment in this group of neoplasms. Numerous new guidelines and innovative technical developments of surgery and radiotherapy have recently been integrated into treatment concepts for pediatric urogenital tumors. Due to the broadness of the field it is not possible to give a full overview over all aspects. Therefore, this article highlights the most important innovations and new guidelines of surgery and radiotherapy of pediatric urogenital tumors.

Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.

An important approach in tumor therapy is combining substances with different action mechanisms aiming to enhance the antineoplastic effect, decrease the therapeutic dosage, and avoid resistance mechanisms. Moreover, evaluating compounds already approved for the treatment of non-neoplastic diseases is promising for new antineoplastic therapies. Sodium dichloroacetate (DCA) reactivates oxidative phosphorylation in the cancer cell mitochondria, reducing apoptosis resistance in cancer cells. Furthermore, metformin inhibits the proliferation of tumor cells and CD133+ cancer -stem-like cells. In the present study, we evaluated the independent and synergistic effect of metformin and DCA on the metabolic activity, cell proliferation, and apoptosis of a canine prostate adenocarcinoma (Adcarc1258) and a transitional cell carcinoma cell line (TCC1506) in comparison to a primary canine fibroblast culture. Determining metformin uptake in tumor cells was performed by quantitative HPLC. Depending on the dosage, metformin as a single agent inhibited the metabolic activity and cell proliferation of the tumor cells, showing only minor effects on the fibroblasts. Furthermore, 1 mM metformin increased apoptosis over 96 h in the tumor cell lines but not in fibroblasts. Additionally, metformin uptake into the tumor cells in vitro was measurable by quantitative HPLC. Synergistic effects for the combination therapy were observed in both neoplastic cell lines as well as in the fibroblasts. Based on these results, metformin might be a promising therapeutic agent for canine urogenital tumors. Further studies on kinetics, toxicology, bioavailability, and application of metformin in dogs are necessary.

New aspects and innovations in the local treatment of renal and urogenital pediatric tumors

Local treatment plays a key role for patients’ outcome in tumors of the urogenital tract in children. Despite a great variety of different etiologies, the specific localization of pediatric urogenital tumors renders several characteristic demands to the treating personnel. Surgery and radiotherapy are the main elements of local treatment in this group of neoplasms. Numerous new guidelines and innovative technical developments of surgery and radiotherapy have recently been integrated into treatment concepts for pediatric urogenital tumors. Due to the broadness of the field it is not possible to give a full overview over all aspects. Therefore, this article highlights the most important innovations and new guidelines of surgery and radiotherapy of pediatric urogenital tumors.

Molecular pathology of urogenital tumors : Recommendations from the 2019 International Society of Urological Pathology (ISUP) Consensus Conference

Das zunehmende Verständnis molekularer Grundlagen von Tumoren sowie der Fortschritt in der Diversifizierung der onkologischen Therapien versprechen individualisierte Therapieoptionen, welche bislang jedoch nur ansatzweise in die Therapieplanung von urologischen Tumoren eingegangen sind. Daher hat die Internationale Gesellschaft für Urologische Pathologie (ISUP) im März 2019 eine Konsenskonferenz zur Erarbeitung evidenzbasierter Handlungsempfehlungen zur molekularpathologischen Diagnostik beim Urothelkarzinom, Nierenzellkarzinom, Prostatakarzinom, Peniskarzinom und testikulären Keimzelltumoren durchgeführt. Die auf dieser Konsenskonferenz erarbeiteten Empfehlungen sind kürzlich in 5 separaten Manuskripten veröffentlich worden und werden in der vorliegenden Arbeit zusammengefasst.Im Rahmen der Konferenzvorbereitung wurde eine umfassende Umfrage zur derzeitigen Praxis molekularer Testungen bei urogenitalen Tumoren unter den Mitgliedern der ISUP durchgeführt. Auf der Konferenz wurden die Ergebnisse und die entsprechenden Hintergrundinformationen durch 5 Arbeitsgruppen präsentiert und Handlungsempfehlungen für die Diagnostik erarbeitet. Eine Übereinstimmung von 66 % der Konferenzteilnehmer wurde als Konsens definiert.

Pulchinenoside B4 exerts the protective effects against cisplatin-induced nephrotoxicity through NF-κB and MAPK mediated apoptosis signaling pathways in mice

Cisplatin (cis-Dichlorodiammine platinum, CP), as the first-line chemotherapy drug of choice for many cancers such as urogenital system tumors and digestive tract tumors, also causes toxicity and side effects to the kidney. Previous studies have shown that Pulsatilla chinensis has significant anti-inflammatory and antioxidant activities, but the mechanism of cisplatin induced acute kidney injury (AKI) in vivo has not been thoroughly studied. The purpose of this study is to investigate the protective effect of pulchinenoside B4 (PB4), a representative and major component with a content of up to 10% in root of P. chinensis, on AKI induced by CP in mice. Our results indicated the significant protective effect of PB4 by evaluating renal function indicators, inflammatory factor levels and renal histopathological changes. In addition, PB4 may mainly act on NF-κB signaling pathway to reduce the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in the kidney after CP exposure, thus exerting anti-inflammatory activity. Furthermore, PB4 regulated MAPK signaling pathway and its downstream apoptotic factors to inhibit the occurrence of apoptosis, such as Bax, Bcl-2, caspase 3 and caspase 9. Notably, the activations of caspase 3 induced by cisplatin were strikingly reduced in PB4-treated mice. Therefore, the above evidence suggested that PB4 is a potential renal protectant with significant anti-inflammatory and anti-apoptotic effects.

Abstract PO-039: Technology-mediated communication with patients is a challenge for oncologists in the digital and pandemic era… and the winner is WhatsApp!

Abstract Introduction: Since December 2019, coronavirus disease 2019 (COVID-19) has spread to every country, taking on pandemic proportions in few months. Physicians were asked to redefine ordinary hospital organization, reprogramming clinically differentiable activities. Materials and Methods: During the COVID pandemic our Institution was supported by a call center (CC, named TOPS s.r.l.) to make a triage for cancer patients (pts) scheduled for follow-up in our outpatient clinics: C1 (dedicated to female tumors), C2 (for gastrointestinal, urogenital,and thoracic tumors) and D1 (for tumors in over 5 years’ follow-up). We report preliminary data referred to the period 7th April-24th May, 2020. The activity was divided into two phases (F): April (F1) and May (F2). In F2 pts were interviewed about their preferred visit modality. Physical examination was not postponed in case of clinical needs and first visits. Moreover, CC asked about programmed radiologic examinations and collected patients’ feedback about the service. Results: A total of 587 pts have been contacted: 341 during F1 and 246 in F2. 317/341 (93%) of the contacts in F1 were successful. A gender-stratified analysis showed a majority of patients were female (72.4%). The CC was able to get in touch with 42.8% C1 pts, 34.6% C2 pts, and 22.6% D1 pts. During F2 246 pts (96.5%) of 255 planned were efficiently contacted; female maintained the predominance (74.5%). 170 pts (69.1%) were scheduled in C1, 53 pts (21.5%) in C2, and 23 pts (9.4%) in D1. During F2, among the options provided 97 pts (39.4%) selected the phone call, 142 pts (57.7%) decided for video chat (whatsapp), and 2 (0.8%) for video conference with a dedicated platform (google.meet). Only 5 pts (2.1%) expressed their intention to come to the hospital for examination. In 69.1% of cases (170 pts) the programmed radiologic examinations were confirmed during the pandemic. According to some favorable reports, the service was helpful in preserving continuum of care and preventing cancer pts from being left aside in the emergency. Conclusions: This study show that cancer patients do appreciate technology-mediated follow-up visits, mainly including video chat (whatsapp), and therefore we should take this into consideration. Furthermore, a dedicated CC may be helpful to organize follow-up activities during COVID-19 and to strengthen the doctor-patient relationship in such a critical moment. Citation Format: Mariangela Torniai, Giulia Marcantognini, Ilaria Fiordoliva, Giulia Mentrasti, Veronica Agostinelli, Alessandra Pagliacci, Rossana Berardi, Michele Caporossi. Technology-mediated communication with patients is a challenge for oncologists in the digital and pandemic era… and the winner is WhatsApp! [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-039.

Osteítis por radiación y fracturas por insuficiencia pélvica en paciente con adenocarcinoma de próstata tratado con radioterapia. Aspectos clínicos y radiográficos de la enfermedad.

Radiation osteitis is an anatomopathological term first coined by Ewing in 1926, refers to a radiation-induced inflammatory response in blood vessels, nerve tissue, and bone cells that can lead to fractures of the trabecular and cortical bone. Pelvic insufficiency fracture is a stress fracture over a weakened bone, seen in patients who have certain risk factors such as osteoporosis, connective tissue disease, use of corticosteroids, and especially in patients who have been treated with pelvic radiation therapy for rectal, anal, urogenital, and prostate tumors. We present the case of a 73-year-old patient with fractures due to pelvic failure treated four years before prostate adenocarcinoma with radiotherapy and hormone therapy. Clinical and radiographic diagnostic aspects are discussed.

Expression of VEGF, CD73 and their relationship with clinical pathology, microvessel density, and prognosis in renal cell carcinoma.

BackgroundRenal cell carcinoma (RCC), a tumor originating from renal tubular epithelial cells, has the second highest incidence of all adult urogenital tumors. However, in most cases, patients show no obvious symptoms in the early or even the late stages of RCC, which seriously impacts the prognosis. This study aimed to analyze the expression of vascular endothelial growth factor (VEGF) and ecto-5'-nucleotidase (CD73) and their relationship with clinical pathology, microvessel density (MVD), and prognosis in RCC.MethodsThe clinical data of 76 patients with RCC who underwent radical nephrectomy in our hospital between October, 2011 and October, 2013 were retrospectively analyzed. The postoperative paraffin specimens were collected; the expression levels of VEGF and CD73 in the tumor tissues were detected, and the MVD was measured. T the expression of VEGF and CD73 and their relationship with clinical pathology, MVD, and prognosis in RCC.ResultsThe positive expression rates of VEGF and CD73 in RCC patients with grades G3–G4 were higher than those in patients with grades G1–G2 (P<0.05). The rates in RCC patients with stages III~IV were higher than those in patients with stages I–II (P<0.05). The rates in RCC patients with lymph node metastasis were higher than those in patients without lymph node metastasis (P<0.05). The MVD count of patients with positive expressions of VEGF and CD73 was higher than that of patients with negative expressions (P<0.05). The expressions of VEGF and CD73 in RCC tissues were significantly positively correlated with MVD count (P<0.05). The five-year mortality rate of patients with positive expressions of VEGF and CD73 was higher than that of patients with negative expressions (P<0.05).ConclusionsThe expressions of VEGF and CD73 in RCC tissues can reflect the degree of tumor malignancy, invasion, and metastasis, and are closely related to the formation of microvessels in tumor tissues and the poor prognosis of patients.

The Role of Pathology in Predicting Immunotherapy Response in Urogenital Tumors

The Role of Pathology in Predicting Immunotherapy Response in Urogenital Tumors

Efficacy of Mesenchymal Stem Cell Therapy for Steroid-Refractory Acute Graft-versus-Host Disease: A Systematic Review and Meta-Analysis

Background: Mesenchymal stem cells (MSCs) shows great potential in the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD). However, the outcomes of clinical trials evaluating the efficiency of MSCs treatment remain controversial, and the long-term benefits remain unclear. Methods: In this systematic review and meta-analysis, we assessed the survival and response after MSCs treatment in SR-aGVHD patients. We searched PubMed, Embase, Cochrane Central, Chinese National Knowledge Infrastructure, Wanfang, the National Diet Library of Japan and J-STAGE for published studies. Both prospective and retrospective studies were included. Response and survival data were extracted independently by three investigators. Pooled outcomes were estimated using a random effects model. Study quality was evaluated using the ROBINS-I tool. Findings: 34 studies comprising 768 patients were included. Pooled overall survival (OS) at the last follow-up was 52% (95% CI 43-61; I²=73%). Pooled survival at 6 months, 1 year and 2 years were 64% (95% CI 57-70; I²=11%), 43% (95% CI 34-53; I²=55%) and 29% (95% CI 19-40; I²=52%), respectively. Overall response rate (ORR) and complete response rate (CRR) were 71% (95% CI 65-76; I²=52%) and 41% (95% CI 33-51; I²=75%), respectively. OS differed significantly with respect to patient age (p=0.008) and MSCs source (p=0.016). Interpretation: Available evidence suggests that MSCs could be an acceptable second-line therapy for SR-aGVHD treatment. Large-scale randomized clinical trials are needed to validate our findings. Funding Statement: This work was supported by Sanming Project of Medicine in Shenzhen (SZSM201412020), Special Funds for the Construction of High Level Hospitals in Guangdong Province (2019), Fund for High Level Medical Discipline Construction of Shenzhen (2016031638), Guangdong Key Laboratory funds of Systems Biology and Synthetic Biology for Urogenital Tumors (2017B030301015). Declaration of Interests: The authors stated: None. Ethics Approval Statement: This systematic review and meta-analysis were prepared according to a prespecified protocol registered with PROSPERO ( number CRD42019139360) for the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement.

Preclinical rationale and clinical efficacy of antiangiogenic therapy and immune checkpoint blockade combination therapy in urogenital tumors.

In recent years, immune checkpoint blockade (ICB) therapies have shown good clinical responses in various solid cancers. However, a major challenge in the process of ICB treatment is when tumors do not have enough infiltrating T cells. Antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) and its receptors have been approved for the treatment of various malignant solid tumors alone or in combination with other therapies. Our review mainly discusses the preclinical rationale and clinical efficacy of antiangiogenic and ICB combination therapy in urogenital tumors. We reviewed relevant literature on preclinical research and clinical trial results regarding antiangiogenic and ICB combination therapy in urogenital tumors from PubMed. In addition, we searched ongoing clinical trials on ClinicalTrials.gov to collect information related to this specific topic. Antiangiogenesis therapy could enhance T cell recruitment and increase T cell infiltration into the tumor microenvironment by blocking VEGF-VEGF receptor 2 binding and downstream signaling pathways to normalize tumor blood vessels. The combination of ICB and antiangiogenesis therapy could improve antitumor activity according to subsequent preclinical experiments and several phase I/II/III clinical trials on urogenital tumors. Combined therapy has shown some antitumor efficacy in several urogenital tumors, such as metastatic renal cell carcinoma, metastatic urothelial and genitourinary tumors, endometrial carcinoma, ovarian cancer, and fallopian tube cancer. Combination therapy is a promising strategy that can be used to improve the therapeutic efficacy, and the identification of precise biomarkers of this combined therapy is the direction of future studies.

Extracellular vesicles in urologic malignancies-Implementations for future cancer care.

Extracellular vesicles (EVs), a heterogeneous group of vesicles differing in size and shape, cargo content and function, are membrane‐bound and nano‐sized vesicles that could be released by nearly all variations of cells. EVs have gained considerable attention in the past decades for their functions in modulating intercellular signalling and roles as potential pools for the novel diagnostic and prognostic biomarkers, as well as therapeutic targets in several cancers including urological neoplasms. In general, human and animal cells both can release distinct types of EVs, including exosomes, microvesicles, oncosomes and large oncosomes, and apoptotic bodies, while the content of EVs can be divided into proteins, lipids and nucleic acids. However, the lack of standard methods for isolation and detection platforms rein the widespread usage in clinical applications warranted furthermore investigations in the development of reliable, specific and sensitive isolation techniques. Whether and how the EVs work has become pertinent issues. With the aid of high‐throughput proteomics or genomics methods, a fully understanding of contents contained in EVs from urogenital tumours, beyond all doubt, will improve our ability to identify the complex genomic alterations in the process of cancer and, in turn, contribute to detect potential therapeutic target and then provide personalization strategy for patient.

Can intravesical application of paracetamol benefit the chemotherapy treatment of bladder cancer?

Bladder cancer is one of the most common urogenital tumors. Its prevalence is increasing worldwide, especially men. The cyclooxygenase-2 (COX-2) enzyme has been shown to increase in bladder cancer and has a direct relationship with tumor progression. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the growth of the tumor by inhibiting the COX-2 enzyme. NSAIDs have other effects unrelated to COX that provide anticancer properties. Also, similar to NSAIDs, anticancer effects of paracetamol have been shown in many studies. Therefore we hypothesize intravesical paracetamol application will have beneficial effects in the treatment of non-muscle invasive bladder cancer (NMBIC).

Long non-coding RNA GHET1 contributes to chemotherapeutic resistance to Gemcitabine in bladder cancer.

Bladder cancer (BC) ranks first in the incidence of urogenital tumors in China and second only to prostate cancer in the West. This study will clarify the roles and mechanism of lncRNA GHET1 in chemotherapeutic resistance of BC to Gemcitabine. The expression of GHET1 was examined using real-time quantitative PCR. Cell Counting Kit-8 assay was applied to analyze cell proliferation and Gemcitabine sensitivity. Cell apoptosis was detected using Annexin V-FITC/PI double-stained flow cytometry. The expression of ABCC1 protein was examined using Western blotting. Firstly, the expression of GHET1 was up-regulated in BC, its high expression was relevant to high grade and muscle invasion of BC patients. Secondly, high expression of GHET1 was related to low Gemcitabine sensitivity of BC patients, and GHET1 was highly expressed in Gemcitabine-resistant BC cell lines. Thirdly, knockdown of GHET1 decreased the IC50 of Gemcitabine in Gemcitabine-resistant BC cell lines and advanced the Gemcitabine-induced cytotoxicity; GHET1 promoted Gemcitabine resistance in BC. Finally, knockdown of GHET1 also inhibited the expression of ABCC1 protein in Gemcitabine-resistant BC cells. High expression of GHET1 was related with the low sensitivity to Gemcitabine of BC; GHET1 contributed to chemotherapeutic resistance to Gemcitabine in BC through up-regulating ABCC1 expression. Our findings are helpful to expound the molecular mechanism of chemotherapeutic resistance in BC.

Spectrum of urogenital tumors in males in Sub-Himalayan region: An institutional experience.

The clinical presentation and frequency of urogenital tumors varies in different regions of the world. This study was undertaken to analyze the frequency, clinical presentation, and the histopathological spectrum of the various male urogenital tumors diagnosed over a period of 3 years in a tertiary care institute. Three-year data were collected from the histopathology laboratory, which included all the cases of male urogenital tumors which were diagnosed histopathologically between November 2012 and October 2015. A total of 10,297 surgical specimens of male patients were received in 3 years, of which 1749 were tumors of various organs in males. Of 1749 surgical specimens, 455 were genitourinary tumors. Frequency of urogenital tumors in males was 13.05%. Malignant tumors comprised the majority (99.53%). The age of the patients ranged from 19 to 98 years. The maximum number of patients was in the 5th-7th decade and the mean age of presentation was 64 years. Urinary bladder was the most common site for urogenital tumors (61.09%), with urothelial carcinoma being the most common histological type. Prostatic adenocarcinoma, renal cell carcinoma, and penile squamous cell carcinoma accounted for a significant number of cases. Testicular tumors were the least common and included predominantly mixed germ cell tumors. This study can be taken as a small step toward making the registry of patients with urogenital tumors providing valuable information regarding the frequency, clinical presentation, and histological spectrum. Large population-based studies for a longer duration of time across both males and females are needed in the ever-changing trends of urogenital tumors.