Cell Carcinoma Of Bladder Research Articles

P291 Treatment outcomes of non-metastatic small cell carcinoma of the urinary bladder treated with multimodal treatments treated with multimodal treatments

P291 Treatment outcomes of non-metastatic small cell carcinoma of the urinary bladder treated with multimodal treatments treated with multimodal treatments

Copper Nanoparticles Green-Formulated byCurcuma longa Extract Induce Apoptosis via P53 and STAT3 Signaling Pathways in Bladder Carcinoma Cell.

The study outlines the production of new copper nanoparticles infused with Curcuma longa extract to trigger apoptosis through P53 and signal transducer and activator of transcription 3 (STAT3) signaling pathways in bladder carcinoma cells. The structural characteristics of the nanoparticles that were synthesized were analyzed through various sophisticated methods such as transmission electron microscopy (TEM), field emission-scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy (FT-IR). During the antioxidant evaluation, the IC50 values for copper nanoparticles and butylated hydroxytoluene (BHT) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals were found to be 116µg/mL and 31µg/mL, respectively. The cells treated with copper nanoparticles underwent evaluation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for 48h to determine their anticancer properties on TCCSUP bladder carcinoma cell. The TCCSUP cell line exhibited an IC50 of 290µg/mL when exposed to copper nanoparticles. The viability of malignant cells decreased upon treatment with copper nanoparticles. Furthermore, the copper nanoparticles presence led to a 65-75% increase in cell apoptosis, along with an increase in Bax and cleaved caspase-8 and a decrease in the Bcl-2. Furthermore, the copper nanoparticles presence resulted in the suppression of colony formation. Notably, the molecular pathway analysis in cells treated with copper NPs demonstrated an increase in p53 expression, along with a decrease in the expression of both total and phosphorylated STAT3. This offers that p53 and STAT3 play a crucial role in the biological efficacies induced by the nanoparticles in human carcinoma cells. The data of our research suggest that copper NPs could have significant potential as an anticancer treatment for human bladder carcinoma cells.

Concurrent Urothelial Carcinoma of the Bladder and Renal Cell Carcinoma of the Kidney: A Diagnostic and Therapeutic Challenge

Concurrent Urothelial Carcinoma of the Bladder and Renal Cell Carcinoma of the Kidney: A Diagnostic and Therapeutic Challenge

SURVIVAL IN PATIENTS WITH HISTOLOGIC VARIANTS OF UROTHELIAL TYPE BLADDER CANCER

Objective: This study aims to determine the life expectancy of patients with histologic variants in urothelial type bladder cancer and the highest or lowest mortality rate in Hasan Sadikin Academic Medical Centre. Material & Methods: A cross-sectional study with total sampling. The samples in this study were patients with histologic variants of urothelial cell carcinoma bladder who received treatment at Hasan Sadikin Academic Medical Centre during the period of 2011 to 2022. Results: A total of 470 patients with a diagnosis of urothelial bladder cancer, 62 patients (13.19%) with histologic variants of urothelial bladder cancer treated with radical cystectomy or TURBT + intravesical chemotherapy at Hasan Sadikin Academic Medical Centre. The highest survival rate was in patients diagnosed with giant cell (66.7%) followed by small cell (50%) and glandular differentiation (40.0%). The 5-yearr survival rate of patients treated with radical cystectomy alone had a higher survival rate of 75.3% followed by radical cystectomy and adjuvant therapy, which was 75.2%. Conclusion: Histologic variants of bladder carcinoma that have the highest mortality rate are tropoblastic differentiation, nested type, micropappilary, and sarcomatoid with the lowest survival rate of 0%. Also, histologic variant of bladder carcinoma that has the lowest mortality rate is giant cell with a survival rate of 66.7%. Keywords: Bladder carcinoma, chemotherapy, trophoblastic differentiation.

Quality by design approach of apocynin loaded clove oil based nanostructured lipid carrier as a prophylactic regimen in hemorrhagic cystitis in vitro and in vivo comprehensive study

Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (23 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases.

Giant cell carcinoma of the urinary bladder

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60–90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50–90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

A New Strategy to Authenticate Prognosis and Tumor Immunity Model Based on Cancer-Associated Fibroblasts lncRNA in Bladder Cancer

There is growing evidence indicating that long noncoding RNAs (lncRNAs) play a pivotal role in regulating both cancer immunity and the cancer microenvironment. Specifically, cancer-associated fibroblasts (CAFs) have been found to have a significant impact on a variety of tumor types. However, the specific lncRNAs associated with CAFs have not yet been thoroughly studied in the context of bladder cancer. This study examined specific lncRNAs derived from TCGA data for the bladder tumor immune microenvironment (TME). Through our analysis, we identified 67 fibroblast-specific lncRNAs (referred to as FIBLnc), and further identified ten gene signatures that include RGS5, EPB41L4A-AS1, SNHG5, MAGI2-AS3, PVT1, EMX2OS, NEAT1, DLEU1, TMEM99, and A1BG-AS1. To establish the robustness of our findings, we also analyzed the gene expression profiles in the GSE13507, GSE19915, GSE31684, GSE48276, and GSE48277A datasets. The results from these datasets, along with the TCGA dataset, were highly accurate in detecting differences in overall survival using the FIBLnc signatures. In functional analysis, FIBLnc revealed its association with immune checkpoints and tumor progression. Furthermore, patients who were treated with anti-PD-1 or anti-CTLA4 could benefit from the FIBLnc score to predict their immunotherapy response. We further investigated the expression and prognostic power of lncRNAs EPB41L4A-AS1, TMEM99, and A1BG-AS1 in TCGA, bladder cell lines, and 24 paired tissues. Our results showed lower expression of EPB41L4A-AS1 and higher expression of TMEM99 and A1BG-AS1 in bladder malignancy, which correlated with a worse prognosis. Furthermore, we found that lncRNAEPB41L4A-AS1 could inhibit bladder cell carcinoma invasion in vitro. Overall, our study highlights the value of FIBLnc in assessing the immune environment status of individuals with bladder cancer and predicting their immunotherapy response. This investigation sheds light on the intricate processes involved in bladder cancer and underscores the importance of considering the FIBLnc score in the prognosis and management of this malignant tumor.

Halogenated Boroxine K2[B3O3F4OH] Modulates Metabolic Phenotype and Autophagy in Human Bladder Carcinoma 5637 Cell Line.

Halogenated boroxine K2[B3O3F4OH] (HB), an inorganic derivative of cyclic anhydride of boronic acid, is patented as a boron-containing compound with potential for the treatment of both benign and malignant skin changes. HB has effectively inhibited the growth of several carcinoma cell lines. Because of the growing interest in autophagy induction as a therapeutic approach in bladder carcinoma (BC), we aimed to assess the effects of HB on metabolic phenotype and autophagy levels in 5637 human bladder carcinoma cells (BC). Cytotoxicity was evaluated using the alamar blue assay, and the degree of autophagy was determined microscopically. Mitochondrial respiration and glycolysis were measured simultaneously. The relative expression of autophagy-related genes BECN1, P62, BCL-2, and DRAM1 was determined by real-time PCR. HB affected cell growth, while starvation significantly increased the level of autophagy in the positive control compared to the basal level of autophagy in the untreated negative control. In HB-treated cultures, the degree of autophagy was higher compared to the basal level, and metabolic phenotypes were altered; both glycolysis and oxidative phosphorylation (OXPHOS) were decreased by HB at 0.2 and 0.4 mg/mL. Gene expression was deregulated towards autophagy induction and expansion. In conclusion, HB disrupted the bioenergetic metabolism and reduced the intracellular survival potential of BC cells. Further molecular studies are needed to confirm these findings and investigate their applicative potential.

An Erratic Path Toward Discovery

Through a series of accidents of history, my career began just when the revolution in molecular biology was taking place. The allure of molecular biology attracted me to exploiting tumor viruses as experimental models of the nucleic acid metabolism of cells. The fact that these viruses cause cancer was incidental but eventually led to an interest in cancer pathogenesis, exploiting them to understand the mechanisms of cell transformation. This made it possible to test the speculation that cell transformation derived from the mutation of cellular genes and that cancer cell behavior is driven by the actions of resulting mutant alleles of these genes. In 1979, we showed that cells that had been transformed by 3-methylcholanthrene carried a mutant oncogenic allele. This work progressed so that by 1982 my research group and others demonstrated that human bladder carcinoma cells carried a point-mutated RAS oncogene, providing a direct proof of the mutational theory of cancer pathogenesis.

Clinical Presentation, Tumor Characteristics, and Management of Intradiverticular Transitional Cell Carcinoma of the Urinary Bladder: A Systematic Review.

Intradiverticular transitional cell carcinoma (TCC) of the bladder poses unique challenges due to its presentation within the bladder diverticula. This review synthesizes current knowledge on the diagnosis and management of this condition, emphasizing the need for early detection to optimize patient outcomes. The literature underscores the importance of tailored treatment strategies, ranging from radical surgeries to adjuvant chemotherapy, to combat the aggressive nature of intradiverticular TCC. Additionally, stringent post-treatment surveillance protocols are vital in addressing high recurrence rates. Future research directions include biomarker identification, comparative efficacy studies of treatment modalities, and the exploration of innovative therapeutic approaches such as immunotherapy. Longitudinal studies analyzing patient outcomes will provide valuable insights into survival rates and quality of life post-treatment, informing future clinical guidelines. This comprehensive review aims to enhance understanding and management strategies for intradiverticular TCC, paving the way for improved patient care and outcomes in this challenging form of bladder cancer.

A phase I/II, first-in-human study of VLS-1488, an oral KIF18A inhibitor, in patients with advanced cancer.

TPS3181 Background: Chromosomal instability (CIN) is a hallmark of cancer characterized by high rates of chromosomal segregation errors during mitosis. This creates structural and numerical changes to chromosomes, driving genetic heterogeneity and cancer evolution. KIF18A is a mitotic kinesin protein shown to be important for successful division of cancer cells with CIN but not required for mitosis in normal diploid cells. Pre-clinical studies demonstrated that treatment of chromosomally unstable cancer cells in vitro and in xenograft models (HCC15 and OVCAR-3) with a KIF18A inhibitor resulted in failure of chromosomal congression, mitotic arrest, cell death and dose-dependent inhibition of tumor growth. VLS-1488 is an oral small molecule inhibitor of KIF18A that is being examined in an open-label, phase I/II, first-in-human study evaluating the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity in advanced solid tumors with high prevalence of CIN. Methods: Key eligibility criteria include specific histologically confirmed metastatic or advanced tumor types with at least one site of measurable disease per RECIST 1.1, adequate organ function, and mismatch repair proficient/microsatellite stable.Eligible tumor types include high grade serous ovarian/fallopian tube/primary peritoneal cancer, squamous non-small cell lung cancer, triple negative breast cancer, gastric adenocarcinoma, gastroesophageal cancer, esophageal cancer, colorectal adenocarcinoma, transitional cell carcinoma of bladder, head and neck squamous cell carcinoma, ovarian or uterine carcinosarcoma, and uterine serous carcinoma. Subjects will receive VLS-1488 monotherapy continuously for 28-day cycles once daily. The study consists of two parts, Dose Escalation and Dose Expansion. Utilizing a Bayesian Optimal Interval (BOIN) design, Dose Escalation will examine the safety and tolerability of VLS-1488 at various dose levels (DLs) to identify the Maximum Tolerated Dose (MTD) and to select DLs for Dose Expansion. Dose Expansion may commence after the MTD or DLs of interest are identified. Dose Expansion will examine the safety, tolerability, preliminary efficacy and preliminary drug-drug interaction (DDI) and food effect risk of VLS-1488 in selected tumor types. Subjects enrolled to specific tumor type cohorts may be randomized to DLs of interest. Enrollment to Dose Escalation began in September 2023 and is ongoing. Clinical trial information: NCT05902988 .

EGFR/TKIs induce excessive apoptosis of bladder carcinoma cells by arresting cell cycle and promoting mitochondrial peroxidation damage.

In recent years, bladder carcinoma (BC) has shown an increasing incidence, with poor patient outcomes. In clinical practice, BC is still mainly treated by surgery combined with chemoradiotherapy. However, as chemotherapy resistance of tumor cells becomes more and more obvious, it is urgent to find more effective BC treatment regimes. With the increasing application and growing attention paid to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in various neoplastic diseases, EGFR-TKIs have been considered as a new treatment direction in the future. In this study, the research team used AG1478, an EGFR-TKI, to intervene with the BC cell line T24. It was found that the cell activity was statistically decreased, the apoptosis was enhanced, and the cells were dominantly arrested in the G0/G1 phase, confirming the future therapeutic potential of EGFR-TKIs in BC. Besides, the research team further observed that AG1478 also promoted pyroptosis in T24 cells, and its mechanism is related to the induction of mitochondrial oxidative stress damage. The findings lay a more reliable foundation for the future application of EGFR-TKIs in BC.

Discovery of new 13(17)-epoxymyrsinane diterpenes from aerial flowering parts of euphorbia spinidens Bornm. ex Prokh. with proapoptotic activities against human bladder cancer EJ138 cells

Phytochemical analysis of aerial flowering parts of Euphorbia spinidens Bornm. ex Prokh. from Euphorbiaceae family (local name: Farfion-e-dandaneh-khari) led to the isolation of five diterpenes based on myrsinane backbone. Using HRESI-MS, 1D, and 2D NMR, they were identified as two previously unreported: 33,7,14,15(β)-tetraacetyl-5(α)-butanoyl-13α(17)epoxy-8,10(18)-myrsinadiene (1), 7,14,15(β)-triacetyl-3(β),5(α)-dibutanoyl-13α(17)epoxy-8,10(18)-myrsinadiene (2), and three known diterpenes: 3,7,14,15(β)-tetraacetyl-5(α)-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (3), and 3,7,10,14,15(β)-Pentaacetyl-5(α)-butanoyl-13,17-epoxy-8-myrsinene (4), 3,7,10,14,15(β)-pentaacetyl-5(α)-propanoyl-13,17-epoxy-8-myrsinene (5). Compound 5 was previously reported in the roots of the same plant but without NMR data. Therefore, its mass pattern,1H-, and 13C-NMR data are reported. The cytotoxicity and proapoptotic properties of 1-3 were evaluated against EJ-138 bladder carcinoma cells through standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for cytotoxicity screening and annexin V-FITC/PI apoptosis detection kit. In the cytotoxicity assay, the IC50 values found against EJ-138 were: (1) 41.6 ± 3.54 μM; (2) 38.4 ± 2.54 μM; (3) 57.3 ± 5.4 μM, whilst the IC50 value of doxorubicin was 1.7 ± 0.3 μM, respectively. In apoptosis assay, total apoptosis of compounds 1-3 at higher concentrations (100 μM) were 57.6 ± 3.54, 46.3 ± 2.82, and 57.2 ± 4.35%, respectively.

Long term outcomes and impact on renal function following radical cystectomy.

To assess clinical, oncological outcomes and impact on renal function in patients who underwent the radical cystectomy with pelvic lymphadenectomy for muscle invasive and high risk non-muscle invasive transitional cell carcinoma of urinary bladder without evidence of non-regional lymph nodes and distant metastasis. With curative intent total 156 patients underwent radical cystectomy with pelvic lymphadenectomy from January 2015 to December 2022. Total 132/156 patients had primary transitional cell carcinoma of bladder. Thirty patients, presented with obstructive nephropathy, operated after stabilization of renal function. Pre-operatively and post-operatively eGFR calculated using modified diet in renal disease formula. In present study 114 (86.36%) patients had high grade TCC, 70 (53.02%) patients had organ confined disease. Nodal extension seen in 74 (56.06%) patients. Perioperative mortality noted in 36 (27.2%) patients. The overall survival and recurrence free survival (RFS) over 5 years was 66.67 and 45.45%. RFS was significantly related to pathological stage, nodal status, histological-grade, positivity of surgical margin and time of surgery from diagnosis. Total 92/132 (69.7%) patients had recurrence. Pelvic recurrence in 10/92 (10.87%) whereas 82/92 (89.13%) patients had distant recurrence. Pre-operatively mean creatinine was 2.6 mg/dl and mean eGFR was 38.9 ml/h in patients who presented with obstructive nephropathy after stabilization of renal function. Post-operatively in 46/132 (34.8%) patients had improvement in eGFR while 86/132 (65.2%) patients had deterioration of eGFR over 62 months of median follow up. Radical cystectomy provides good overall survival outcomes. Pre-operative eGFR has significant impact on post-operative renal function in long term.

An Expedition on Synthetic Methodology of FDA-approved Anticancer Drugs (2018-2021).

New drugs being established in the market every year produce specified structures for selective biological targeting. With medicinal insights into molecular recognition, these begot molecules open new rooms for designing potential new drug molecules. In this review, we report the compilation and analysis of a total of 56 drugs including 33 organic small molecules (Mobocertinib, Infigratinib, Sotorasib, Trilaciclib, Umbralisib, Tepotinib, Relugolix, Pralsetinib, Decitabine, Ripretinib, Selpercatinib, Capmatinib, Pemigatinib, Tucatinib, Selumetinib, Tazemetostat, Avapritinib, Zanubrutinib, Entrectinib, Pexidartinib, Darolutamide, Selinexor, Alpelisib, Erdafitinib, Gilteritinib, Larotrectinib, Glasdegib, Lorlatinib, Talazoparib, Dacomitinib, Duvelisib, Ivosidenib, Apalutamide), 6 metal complexes (Edotreotide Gallium Ga-68, fluoroestradiol F-18, Cu 64 dotatate, Gallium 68 PSMA-11, Piflufolastat F-18, 177Lu (lutetium)), 16 macromolecules as monoclonal antibody conjugates (Brentuximabvedotin, Amivantamab-vmjw, Loncastuximabtesirine, Dostarlimab, Margetuximab, Naxitamab, Belantamabmafodotin, Tafasitamab, Inebilizumab, SacituzumabGovitecan, Isatuximab, Trastuzumab, Enfortumabvedotin, Polatuzumab, Cemiplimab, Mogamulizumab) and 1 peptide enzyme (Erwiniachrysanthemi-derived asparaginase) approved by the U.S. FDA between 2018 to 2021. These drugs act as anticancer agents against various cancer types, especially non-small cell lung, lymphoma, breast, prostate, multiple myeloma, neuroendocrine tumor, cervical, bladder, cholangiocarcinoma, myeloid leukemia, gastrointestinal, neuroblastoma, thyroid, epithelioid and cutaneous squamous cell carcinoma. The review comprises the key structural features, approval times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches of these approved drugs. These crucial details will benefit the scientific community for futuristic new developments in this arena.

Exposure of Bladder Cancer Cells to Blue Light (λ = 453 nm) in the Presence of Riboflavin Synergistically Enhances the Cytotoxic Efficiency of Gemcitabine.

Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success.

Advancing Evidence Generation for Circulating Tumor DNA: Lessons Learned from A Multi-Assay Study of Baseline Circulating Tumor DNA Levels across Cancer Types and Stages.

Circulating tumor DNA (ctDNA) holds promise as a biomarker for predicting clinical responses to therapy in solid tumors, and multiple ctDNA assays are in development. However, the heterogeneity in ctDNA levels prior to treatment (baseline) across different cancer types and stages and across ctDNA assays has not been widely studied. Friends of Cancer Research formed a collaboration across multiple commercial ctDNA assay developers to assess baseline ctDNA levels across five cancer types in early- and late-stage disease. This retrospective study included eight commercial ctDNA assay developers providing summary-level de-identified data for patients with non-small cell lung cancer (NSCLC), bladder, breast, prostate, and head and neck squamous cell carcinoma following a common analysis protocol. Baseline ctDNA levels across late-stage cancer types were similarly detected, highlighting the potential use of ctDNA as a biomarker in these cancer types. Variability was observed in ctDNA levels across assays in early-stage NSCLC, indicative of the contribution of assay analytical performance and methodology on variability. We identified key data elements, including assay characteristics and clinicopathological metadata, that need to be standardized for future meta-analyses across multiple assays. This work facilitates evidence generation opportunities to support the use of ctDNA as a biomarker for clinical response.

Taurine Rescues Cancer-induced Atrophy in Human Skeletal Muscle Cells via Ameliorating the Inflammatory Tumor Microenvironment.

Cancer cachexia is a wasting syndrome that has a devastating impact on the prognosis of patients with cancer. It is well-documented that pro-inflammatory cytokines are involved in the progression of this disorder. Therefore, this study was conducted to investigate the protective effect of taurine, an essential nonprotein amino acid with great anti-inflammatory properties, in attenuating muscle atrophy induced by cancer. Conditioned media (CM) derived from T24 human bladder carcinoma cells with or without 5 mM taurine were incubated with human skeletal muscle cells (HSkMCs) and their differentiation was examined. The intracellular reactive oxygen species (ROS), morphology, and the catabolic pathway were monitored. T24-derived CM with high levels of TNF-α and IL-6 caused aberrant ROS accumulation and formation of atrophic myotubes by HSkMCs. In T24 cancer cells, taurine significantly inhibited the production of TNF-α and IL-6. In HSkMCs, taurine increased ROS clearance during differentiation and preserved the myotube differentiation ability impaired by the inflammatory tumor microenvironment. In addition, taurine ameliorated myotube atrophy by regulating the Akt/FoxO1/MuRF1 and MAFbx signaling pathways. Taurine rescues cancer-induced atrophy in human skeletal muscle cells by ameliorating the inflammatory tumor microenvironment. Taurine supplementation may be a promising approach for intervening with the progression of cancer cachexia.

Radiation toxicity grading after chemoradiotherapy of canine urinary tract carcinomas: Comparing VRTOG to VRTOG_v2.0.

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive-intent chemoradiotherapy (12 × 3.8 Gy, various first-line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme "VRTOG" as well as the updated version, "VRTOG_v2.0". Fourteen dogs with transitional cell carcinoma of bladder ± urethra (n = 8), +prostate (n = 3) or solely urethra (n = 3), were included. Median follow-up was 298 days (range 185-1798 days), median overall survival 305 days (95%CI = 209;402) and 28.6% deaths were tumour-progression-related. Acute radiation toxicity was mild and self-limiting with both classification systems: In VRTOG, 5 dogs showed grade 1, and 1 dog grade 2 toxicity. In VRTOG_v2.0, 2 dogs showed grade 1, 3 dogs grade 2, and 3 dogs grade 3 toxicity. Late toxicity was noted in 14.2% of dogs (2/14) with the VRTOG, both with grade 3 toxicity. With VRTOG_v2.0, a larger proportion of 42.9% of dogs (6/14) showed late toxicities: Four dogs grade 3 (persistent incontinence), 2 dogs grade 5 (urethral obstructions without PD resulting in euthanasia). At time of death, 5 dogs underwent further workup and only 3 were confirmed to have PD. With the updated VRTOG_v2.0 classification system, more dogs with probable late toxicity are registered, but it is ultimately difficult to distinguish these from disease progression as restaging remains to be the most robust determinant.

Anti-Proliferative Effects of Lidocaine as an Autophagy Inducer in Bladder Cancer via Intravesical Instillation: In Vitro and Xenograft Mouse Model Experiments.

Lidocaine exerts potential anti-tumor effects on various cancer cell lines, and its intravesical instillation is considered safer than intravenous administration for bladder cancer. However, the mechanisms underlying its anti-tumor effects have not been fully elucidated. Here, we aimed to elucidate the anti-tumor molecular mechanisms of lidocaine in bladder cancer cells and a xenograft model to substantiate the efficacy of its intravesical administration. We investigated the anti-proliferative and autophagyinducing activities of lidocaine in Nara Bladder Tumor No. 2 (NBT-II) rat bladder carcinoma cells using cell viability, flow cytometry, a wound healing assay, and western blotting. We also established a xenograft mouse model of bladder cancer, and cancer growth was examined using in vivo bioluminescence imaging. Lidocaine decreased cell viability, induced G0/G1 phase cell cycle arrest, and inhibited cell migration partially via glycogen synthase kinase (GSK) 3β phosphorylation. Moreover, a combination of lidocaine and SB216763 (a GSK3β inhibitor) suppressed autophagy-related protein expression. Bafilomycin-A1 with lidocaine significantly enhanced microtubule-associated protein 1A/1B-light chain (LC3B) expression; however, it decreased LC3B expression in combination with 3-methyladenine compared to lidocaine alone. In the xenograft mouse model, the bladder cancer volume was reduced by lidocaine. Overall, lidocaine exerts anti-proliferative effects on bladder cancer via an autophagy-inducing mechanism.