Dynamics of Cancer-Related Proteins in Patients with Bladder Cancer

Bladder cancer (BC) is the second most common malignancy in the urologic field. Preoperative predictive biomarkers of cancer progression and prognosis are imperative for optimizing appropriate treatment for patients with BC. The prediction of patient outcomes before initial treatment would enable physicians to choose better modalities and avoid unnecessary aggressive treatments. In addition, preoperative molecular markers are expected to be a minimally invasive tool for predicting precise prognosis and progression in patients with BC. The proteins secreted from the tumor cells reflect various states of tumors in real time and at given conditions, and those expression patterns are different from normal cell components. Approximately 20–25% of cellular proteins are in extracellular spaces, and these proteins have important roles in invasion, angiogenesis, regulation of cell-to-cell interactions, and metastasis. It has been suggested that tumor-secreting proteins are a promising source for tumor diagnostic biomarkers. Proteomic analysis was utilized to identify the secreted proteins in sera from patients with BC. Several biomarkers associated with BC are reviewed here

Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk + ganciclovir gene therapy for prostate cancer

ObjectiveCytopathic effects and local immune response were analyzed histologically in prostatic carcinoma (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). MethodsFour high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, n = 3) or without neoadjuvant therapy (NT, n = 4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values. ResultsssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of ssDNA LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ = 0.656, p < 0.0001) as well as CD4+ T cells and CD20+ B cells (ρ = 0.644, p < 0.0001) in PCa with GT. ConclusionsEnhanced cytopathic effect and local immune response were might be indicated in PCa patients with HSV-tk/GCV gene therapy.Cytopathic effects and local immune response were analyzed histologically in prostatic carcinoma (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT..

Racial differences in the outcome of patients with urothelial carcinoma of the upper urinary tract: an international study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86897/1/j.1464-410X.2011.10188.x.pd

Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial

BackgroundTo investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test.MethodsCORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020–October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200  μg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models.ResultsOverall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years [ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval [CI] 0.70–1.32; p = 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0 (13.0–16.0) and 14.0 (12.0–16.0) days for ivermectin and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, respectively.ConclusionIn patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test.Clinical Trial RegistrationClinicalTrials.gov, NCT04703205

特発性血小板減少性紫斑病に対する経尿道的尿管砕石術および体外衝撃波砕石術

特発性血小板減少性紫斑病(ITP)は, 抗血小板抗体により血小板減少を来たす自己免疫性疾患である。血小板減少による出血性素因は, 各種治療を困難にする。今回われわれは, 本疾患2症例に対し, ガンマグロブリン大量療法を行った後, 経尿道的尿管砕石術(TUL)および体外衝撃波砕石術(ESWL)が施行可能であったので報告する。症例1は52歳, 女性, 症例2は65歳, 女性, 静脈性腎盂造影にて左尿管結石症および両側尿管結石症と診断された。ガンマグロブリン大量療法と血小板輸血により血小板数は増加し, TULおよびESWLを合併症なく施行可能であった。ITPに対するガンマグロブリン大量療法後のESWL施行例は, 本報告が初めてである。ガンマグロブリン大量療法は, ITP症例において外科的治療を施行するにあたり, 十分な血小板数を得られる有効な方法であると考えられた。(著者抄録)Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease defined by a low platelet count secondary to accelerated platelet destruction by anti-platelet antibodies. The resulting bleeding diathesis can present a therapeutic dilemma. We have treated two cases of ITP in which ureteral stones were successfully extracted by transurethral ureterolithotripsy (TUL) and extracorporeal shock wave lithotripsy (ESWL) after high-dose gamma-globulin therapy. The first case was in a 52-year-old woman and the second case was in a 65-year-old woman. Intravenous pyelography revealed a left ureteral stone in the first case and bilateral ureteral stones in the second case. High-dose gamma-globulin therapy and platelet transfusion elevated their platelet counts to safe levels; TUL and ESWL were then performed successfully with no bleeding complications. This is the first case report of ITP being treated by ESWL after high-dose gamma-globulin therapy. High-dose gamma-globulin therapy effectively provides adequate platelet counts for surgical treatment in patients with ITP

A Fatal Case of Life-Threatening Interstitial Pneumonitis Induced by Everolimus for Metastatic Renal Cell Carcinoma: A Comment about the Increased Risk of Interstitial Lung Disease in Japanese

We describe an 81-year-old woman with metastatic renal cell carcinoma who did not recover from life-threatening interstitial pneumonitis induced by everolimus therapy. She received everolimus due to disease progression after sunitinib, but 2 months after starting everolimus treatment, she visited the emergency department after developing a sudden fever and dyspnea. Chest CT revealed diffuse ground-glass opacities, thickening of the interlobular septa, and consolidation throughout both lung fields. The diagnosis was surmised to be everolimus-induced interstitial pneumonitis. Everolimus administration was stopped and 3 courses of steroid pulse therapy were administered, along with intensive care, but the patient died due to rapid respiratory failure

Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen

Objectives. To discover whether the proteolytic activity of prostate- specific antigen (PSA) affects the structure and function of parathyroid hormone-related protein (PTHrP), as both are abundant components of human seminal plasma. Methods. The ability of PTHrP to act as a substrate was studied by incubating a synthetic polypeptide, consisting of 34 amino acid residues of the amino-terminal domain of PTHrP, with purified PSA. The incubate was then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, high-pressure liquid chromatography separation, amino- terminal peptide sequencing, and mass spectrometry. The physiologic effect of the proteolytic activity of PSA on PTHrP was studied by measuring any alteration in PTHrP (1-34)-induced elevation of cyclic adenosine monophosphate (cAMP) production by UMR-106 rat osteosarcoma cells in culture. All cell culture experiments were performed with PSA and PTHrP (1-34) at physiologic concentrations. Results. Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments. Both cleavages occur carboxy terminally of a phenylalanine residue. The cAMP production in rat osteosarcoma cells, induced by the amino- terminal portion of PTHrP (1-34), as a result of its structural similarity with parathyroid hormone (PTH), was abated by PSA in a dose- and time- dependent fashion. In contrast, heat-inactivated PSA had no effect on cAMP production. Conclusions. Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. The proteolytic processing of PTHrP by PSA may play an important role in the post-translational/post-secretional regulation of prostatic PTHrP activities, which are believed to include regulation of prostate growth and differentiation