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Prostate-specific membrane antigen (PSMA), whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma, is also highly expressed in the neovessels of various solid tumors, including clear cell renal cell carcinoma (ccRCC). In the VISION phase III clinical trial, PSMA-targeted radioligand therapy (PRLT) with lutetium 177 demonstrated a 4-month overall survival OS benefit compared to the best standard of care in heavily pretreated metastatic prostate cancer. Despite the improvement in the management of metastatic clear cell renal cell carcinoma (mccRCC) with antiangiogenic tyrosine kinase inhibitor (TKI) and immunotherapy, there is still a need for new treatments for patients who progress despite these drugs. In this study, we discuss the rationale of PRLT applied to the treavtment of mccRCC. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA–targeted chimeric antigen receptor T-cells, PSMA–targeted antibody drug conjugates, and PSMA–targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Background: High‐dose chemotherapy (HDCT) with TI‐CE regimen is a valid option for the treatment of relapsed advanced germ cell tumors (GCT). We report a phase II trial with therapeutic drug monitoring of carboplatin for optimizing area under the curve (AUC) of this drug. Methods: Patients with unfavorable relapsed GCT were treated according to TI‐CE regimen: two cycles combining paclitaxel and ifosfamide followed by three cycles of HD carboplatin plus etoposide administered on 3 days. Carboplatin dose was adapted on day 3 based on carboplatin clearance (CL) at day 1 in order to reach a target AUC of 24 mg.min/mL per cycle. The primary endpoint was the complete response (CR) rate. Results: Eighty‐nine patients who received HDCT were included in the modified intent‐to‐treat (mITT) analysis. Measured mean AUC was 24.4 mg.min/mL per cycle (22.4 and 26.8 mg.min/mL for 10th and 90th percentiles). Thirty‐five (44.3%) patients achieved a CR with or without surgery of residual masses and 20 patients achieved a partial response with negative tumor markers. With a median follow‐up of 44 months (m), median PFS was 12.3 m (95% CI: 7.5–25.9) and OS was 46.3 m (95% CI: 18.6–not reached). For high‐ and very high‐risk patients, according to the International Prognostic Score at first relapse or treated after at least one salvage treatment (n = 51), 2‐year PFS rate was 41.1%. Conclusion: The rates of complete and favorable responses were clinically relevant in this very poor risk population. Individual monitoring of carboplatin plasma concentration permitted to control more accurately the target AUC and avoided both underexposure and overexposure to the drug. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA–targeted chimeric antigen receptor T-cells, PSMA–targeted antibody drug conjugates, and PSMA–targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The incidence of testicular germ cell tumors (TGCT), the most common cancer in men aged 15 to 45 years, has doubled over the last 30 years in developed countries. Reasons remain unclear but a role of environmental factors, especially during critical periods of development, is strongly suspected. Reliable data on environmental exposure during this critical time period are sparse. Little is known on whether it could be a combined effect of early and later-life exposures. Methods/Design: Our research aims to study the association between TGCT risk and pesticide exposures (domestic, occupational and environmental) during critical time periods of development and combined early and later-life exposures. The study design, developed during a 2-year pilot study, is a multicenter case-control study of 500 cases (ascertained through histology) and 1000 fertile/fecund controls recruited through 21 French 'Centres d'Etude et de Conservation des OEufs et de Sperme humain' (CECOS). Trained professional interviewers interview the subjects and their mothers by phone. Using a geographic information system developed and tested for application in this study design, environmental pesticides exposure assessment is based on life-time residential history. Occupational pesticides exposures are assessed by an industrial hygienist based on parents' occupations and tasks. Exposures during the prenatal period, early childhood and puberty are focused. A blood sample is collected from each participant to assess genetic polymorphisms known to be associated with TGCT risk, as well as to explore gene-environment interactions. Discussion: The results of our study will contribute to better understanding the causes of TGCT and the rapid increase of its incidence. We explore the effect of combined early and later-life pesticides exposure from multiple sources, as well as potential gene-environment interactions that have until now been rarely studied for TGCT. Our design allows future pooled studies and the bio-bank allows additional genetic or toxicological analyses. [ABSTRACT FROM AUTHOR]

Background: Small cell bladder carcinoma is an uncommon tumor. In this retrospective study we report our experience dealing with this disease at the Leon-Berard Cancer Centre. Materials and Methods: We retrospectively analyzed various characteristics of small cell bladder carcinoma: patient demographics, histological diagnosis, disease stage, treatment effects and outcome, in 14 non-metastatic small cell bladder carcinoma patients treated at our institution between 1995 and 2006. Results: The mean age at diagnosis was 60 years (range, 45-77). All patients were male. Seventy-five per cent were smokers. All had locally advanced disease. Ten patients (71.4%) were treated by cystoprostatectomy and bilateral pelvic lymph node resection, one by cystoprostatectomy alone. Two patients received neoadjuvant chemotherapy and four received adjuvant chemotherapy. One patient was treated by radiotherapy with concomitant cisplatin after transurethral resection of bladder tumor (TURBT). One patient refused surgery and was treated by chemotherapy alone. One patient was lost to follow-up after TURBT. After 49- month median follow-up, 12 patients had relapsed. Disease-free survival was 5.7 months. The most frequent sites of relapse were the retroperitoneal lymph node (seven patients) and the liver (three patients). Nine patients died of metastasis. Median overall survival was 29.5 months. Survival probability at two years was 58%. Median overall survival was 34 months in the mixed small carcinoma group, as compared with 9.5 months in the pure small cell carcinoma group ( P=0.01). Mean overall survival was 27.2 months for all patients and 38.6 months for patients treated with cystectomy and adjuvant chemotherapy. Conclusion: To date, the optimal treatment for locally advanced small cell bladder carcinoma is not clear. Cystectomy with neoadjuvant or adjuvant chemotherapy appears as a viable option. [ABSTRACT FROM AUTHOR]

Bladder cancer is the fifth most common cancer in adult patients. Two-thirds of patients have superficial tumors and their treatment is conservative. Nevertheless, 30% of superficial tumors become infiltrative and represent a third of tumors at initial diagnosis. Overall mortality from bladder cancer is 30%. Important molecular events may explain the carcinogenesis and evolution of these tumors. Infiltrating bladder cancers are currently treated by radical cystectomy. Neoadjuvant chemotherapy has demonstrated a positive impact on patients' outcomes before cystectomy. Adjuvant chemotherapy after cystectomy is currently being studied in an international randomized trial. Patients with advanced disease are treated by chemotherapy with palliative intentions. Two regimens are standard: the combination of methotrexate, vinblastine, adriamycin and cisplatin, and the combination of gemcitabine and cisplatin. The addition of paclitaxel to the latter regimen is the subject of ongoing study. Only a few patients have long-term nonevolutive disease. Research must be focused on the combination of chemotherapy and targeted drugs directed through gene methylation, cytokine-receptor activation and signaling pathways. [ABSTRACT FROM AUTHOR]

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Adhesion to the digestive mucosa has often been considered as necessary for persistence of lactobacili in the gut and associated benefits. The behaviour of Lactobacillus fermentum strains isolated from pigs was investigated in the digestive contents and gastric epithelium of monoassociated and gnotobiotic mice. LEMPL9, a colonising strain, was adherent in both conditions. LEM1.16A, a non-colonising strain, and LEM1.16ANTG, a colonising mutant of LEM1.16A, were both non-adherent in monoassociation conditions, indicating that adhesion to the gastric mucosa is not essential for durable establishment in the gastrointestinal tract. The presence of a microflora was shown to have a positive impact on the Lactobacillus adhesion ability. [ABSTRACT FROM AUTHOR]

The expression of cytokeratin- and vimentin-type intermediate filaments was studied by means of immunohistochemistry in Sertoli cells cultured on two types of reconstituted basement membrane in two-compartment culture chambers. In situ, the Sertoli cells of 17-day-old rats contained only vimentin intermediate filaments. During culture, a gradual reorganization of intermediate filaments accompanied by an increased cytokeratin immunoreactivity was observed. After 6 days, Sertoli cells contained both cytokeratin and vimentin, and the same cytokeratin type as in fetal and newborn testis was revealed by electrophoresis and immunoblotting. The present study shows that the isolation and culture of Sertoli cells causes, even in an improved culture system qualitative changes in the expression of intermediate filament proteins. [ABSTRACT FROM AUTHOR]

We have developed a culture system for early bovine embryos in serum-free media conditioned by oviduct cell monolayers. A gentle mechanical procedure for oviduct cell isolation has been applied for this purpose avoiding the use of proteolytic enzymes. The aim of the present study was to identify the cell types present in the monolayers and to examine their fate in primary culture in serum-free or in serum-containing media by means of electronmicroscopical, immunocytochemical, and biochemical analyses. The cell dissociation procedure yielded two cell populations: ciliary cells and secretory cells that gradually dedifferentiate during culture. These cells formed a confluent monolayer after 6 d of culture in Tissue Culture Medium 199 medium supplemented with 10% fetal calf serum. Confluent cells displayed a typical epithelial cell morphology as assessed by phase contrast and electron microscopy and all the cells contained cytokeratin filaments as determined by immunocytochemistry. The overall histoarchitecture of the monolayer was preserved after washing and further culture for 7 d in serum-free medium. However, some degenerative signs indicate that the serum-free culture should not be extended for more than 7 d. Confluent oviduct cells also maintained their metabolic and protein secretory activity when deprived of serum. Total protein content in the culture supernatant linearly increased as a function of time and numerous peaks were detected after separation of proteins by high performance ion exchange chromatography. Protein elution patterns were reproducible and most of the proteins present in the culture medium were neosynthesized as determined by the incorporation of radiolabeled amino acids into nondialyzable proteins. [ABSTRACT FROM AUTHOR]

Background: Micropapillary bladder cancer is a rare and aggressive variant of urothelial carcinoma. A retrospective review of our experience in management of patients with muscle-invasive or metastatic micropapillary bladder cancer was performed to better define the behavior of this disease.Methods: We reviewed the records of the 11 patients with micropapillary bladder cancer who were evaluated and treated at Léon Bérard Cancer Center between 1994 and 2007, accounting for 1,2% of all urothelial tumors treated in this institution.Results: Mean patients age was 60 years. The majority of patients (72%) were diagnosed after 2004. After a median follow-up of 31.7 months, median overall survival was 19 months. Two patients presented with stage II, one with stage III and eight with stage IV disease All 5 patients who had node positive metastases and treated with radical surgery and adjuvant chemotherapy relapsed and had a disease free survival of 9.6 months.Conclusion: Micropapillary bladder cancer is probably an underreported variant of urothelial carcinoma associated with poor prognosis. Adjuvant chemotherapy might have a questionable efficacy and the optimal treatment strategy is yet to be defined. [ABSTRACT FROM AUTHOR]

Background: The incidence of testicular germ cell tumors (TGCT), the most common cancer in men aged 15 to 45 years, has doubled over the last 30 years in developed countries. Reasons remain unclear but a role of environmental factors, especially during critical periods of development, is strongly suspected. Reliable data on environmental exposure during this critical time period are sparse. Little is known on whether it could be a combined effect of early and later-life exposures.Methods/design: Our research aims to study the association between TGCT risk and pesticide exposures (domestic, occupational and environmental) during critical time periods of development and combined early and later-life exposures. The study design, developed during a 2-year pilot study, is a multicenter case-control study of 500 cases (ascertained through histology) and 1000 fertile/fecund controls recruited through 21 French 'Centres d'Etude et de Conservation des Œufs et de Sperme humain' (CECOS). Trained professional interviewers interview the subjects and their mothers by phone. Using a geographic information system developed and tested for application in this study design, environmental pesticides exposure assessment is based on life-time residential history. Occupational pesticides exposures are assessed by an industrial hygienist based on parents' occupations and tasks. Exposures during the prenatal period, early childhood and puberty are focused. A blood sample is collected from each participant to assess genetic polymorphisms known to be associated with TGCT risk, as well as to explore gene-environment interactions.Discussion: The results of our study will contribute to better understanding the causes of TGCT and the rapid increase of its incidence. We explore the effect of combined early and later-life pesticides exposure from multiple sources, as well as potential gene-environment interactions that have until now been rarely studied for TGCT. Our design allows future pooled studies and the bio-bank allows additional genetic or toxicological analyses. [ABSTRACT FROM AUTHOR]