Cell Carcinoma Of Bladder Research Articles

A mutational signature and significantly mutated driver genes associated with immune checkpoint inhibitor response across multiple cancers

Immune checkpoint inhibitor (ICI) treatments dramatically prolong the survival outcomes of several advanced cancers. However, as multiple studies reported, only a subset of patients could benefit from the ICI treatment. In this study, we aim to uncover novel molecular biomarkers predictive of immunotherapy efficacy across multiple cancers. Pre-treatment somatic mutational profiles and immunotherapy clinical information were obtained from 1097 samples of multiple cancers, including melanoma, non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC), bladder carcinoma (BLCA), and head and neck squamous cell carcinoma (HNSCC). Mutational signatures, molecular subtypes, and significantly mutated genes (SMGs) were determined, and their connections with ICI response and outcome were also evaluated. We extracted a total of six mutational signatures across all samples. Among, a mutational signature featured by T > C substitutions was identified to associate with an ICI resistance. A molecular subtype determined based on mutational activities was connected with a significantly improved ICI response rate and outcome. Totaling 50 SMGs were identified, and we observed that patients with COL11A1 or COL4A6 mutations exhibited a superior ICI treatment efficacy than those without such mutations. In this study, we uncovered several novel molecular determinants of cancer immunotherapy response under a multiple-cancer setting, which provides clues for enrolling patients to receive immunotherapy and customizing personalized treatment strategies.

Mechanism of cis-Nerolidol-Induced Bladder Carcinoma Cell Death.

Nerolidol is a naturally occurring sesquiterpene alcohol with multiple properties, including antioxidant, antibacterial, and antiparasitic activities. A few studies investigating the antitumor properties of nerolidol have shown positive results in both cell culture and mouse models. In this study, we investigated the antitumor mechanism of cis-nerolidol in bladder carcinoma cell lines. The results of our experiments on two bladder carcinoma cell lines revealed that nerolidol inhibited cell proliferation and induced two distinct cell death pathways. We confirmed that cis-nerolidol induces DNA damage and ER stress. A mechanistic study identified a common cAMP, Ca2+, and MAPK axis involved in signal propagation and amplification, leading to ER stress. Inhibition of any part of this signaling cascade prevented both cell death pathways. The two cell death mechanisms can be distinguished by the involvement of caspases. The early occurring cell death pathway is characterized by membrane blebbing and cell swelling followed by membrane rupture, which can be prevented by the inhibition of caspase activation. In the late cell death pathway, which was found to be caspase-independent, cytoplasmic vacuolization and changes in cell shape were observed. cis-Nerolidol shows promising antitumor activity through an unorthodox mechanism of action that could help target resistant forms of malignancies, such as bladder cancer.

Comparison of fdg pet-ct with conventional imaging in the staging of high-risk renal cancers and transitional cell carcinoma of bladder (COPPER-T): A prospective randomized controlled trial – trial protocol and initial short-term analysis of results

Comparison of fdg pet-ct with conventional imaging in the staging of high-risk renal cancers and transitional cell carcinoma of bladder (COPPER-T): A prospective randomized controlled trial – trial protocol and initial short-term analysis of results

Rare histological types of bladder carcinoma from a tertiary care hospital: Case reports

Bladder carcinoma is one of the most common urological malignancies with many rare histological variants associated with various prognosis. The recognition of these rare histological variants of bladder carcinoma may be helpful in selecting appropriate therapeutic approach and to predict the prognosis of the patients. We present three such rare entities of urothelial carcinoma with squamous differentiation, squamous cell carcinoma of bladder and metastatic bladder carcinoma which are associated with bad prognosis.

KLHL21/CYLD signaling confers aggressiveness in bladder cancer through inactivating NF-κB signaling

Bladder carcinoma (BC) is one of the most commonly diagnosed malignant cancers worldwide. Kelch-like protein 21 (KLHL21) has been shown to be involved in a number of human tumors. The study aimed to investigate the effects and mechanism of KLHL21 on BC progression. We found that KLHL21 expression was significantly decreased in human BC tissues and cell lines compared with the paired normal samples, and patients with lower KLHL21 expression exhibited poorer overall survival. In vitro studies then showed that KLHL21 over-expression significantly reduced the proliferation, migration and invasion in BC cells, while KLHL21 knockdown markedly accelerated the proliferative, migratory and invasive properties of BC cells. Animal studies confirmed that KLHL21 exhibited anti-tumor function in the xenograft mouse models, as indicated by the reduced tumor growth rates, and mice with KLHL21 knockdown showed the opposite tumor growth profile. Additionally, we found that KLHL21 negatively mediated the nuclear factor-κB (NF-κB) signaling activation, as well as its down-streaming molecules involved in the biological regulation of cell survival, death and migratory processes. Mechanistically, cylindromatosis (CYLD) expression levels were significantly up-regulated in BC cells over-expressing KLHL21, but were down-regulated upon KLHL21 knockdown. We further uncovered that KLHL21 directly interacted with CYLD in BC cells. Of note, we found that KLHL21 mainly in cytoplasm could restrain CYLD degradation by prohibiting its ubiquitination in BC cells. More importantly, our in vitro experiments displayed that KLHL21-inhibited progression and NF-κB/p65 activation in BC cells were completely abolished by CYLD deletion, revealing that CYLD expression was required for KLHL21 to perform its anti-tumor function in BC. Collectively, all these findings uncovered that KLHL21/CYLD axis may be a promising therapeutic target for BC treatment.

TBX3 stimulates proliferation and stem cell self-renewal in bladder carcinoma.

With the change of people's lifestyle in recent years, bladder carcinoma has been the second leading cause of death for men. Nevertheless, surgical results of bladder carcinoma are unsatisfying with recurrence and distant metastasis. Therefore, it is urgent to find a new target for bladder carcinoma treatment. The protein and mRNA expression levels of TBX3 in bladder carcinoma tissue samples and cells were tested using western blot and qRT-PCR assays, respectively. Cancer stem cells (CSCs) were separated with immunomagnetic beads. Expression levels of cell stemness-associated proteins CD44, CD24 and ESA in T24 CSCs and T24 cells were detected by western blot assay. Cell self-renewal ability was detected by stem cell sphere formation assay. CCK-8 and colony formation assays examined cell viability and proliferation. Cell apoptotic level was examined by flow cytometry. Elevated TBX3 expression in bladder carcinoma stimulated cell proliferation and inhibited cell apoptosis. Stemness-related proteins and TBX3 were highly expressed in T24 CSCs relative to those in normal bladder carcinoma cells. In addition, TBX3 promoted stem cell self-renewal and inhibited cell apoptosis. Finally, qRT-PCR, western blot and cell sphere formation assays revealed that the potential role of TGF-β1 in the regulation of TBX3. TBX3, mediated by TGF-β1, can promote bladder carcinoma cell proliferation, inhibit apoptosis, and enhance cell stemness. Hence, TBX3 is a potential target to stem cells of bladder carcinoma.

Urinary Bladder Primary Squamous Cell Carcinoma: A Rare Case Description and Literature Review

Cancer of the urinary bladder is a commonly encountered malignancy of the urinary tract. The most common histologic type is Transitional cell carcinoma (TCC). It accounts for 90-95% of all bladder cancers. It is usually seen in the sixth and seventh decades of life. Men are affected three to four times more than women. The remaining 5-10% of the bladder tumors are other types of epithelial and mesenchymal tumors. Squamous cell carcinoma (SCC) of the urinary bladder is a very uncommon malignancy.

Metastatic non-muscle invasive transitional cell carcinoma of urinary bladder: a case report

BackgroundAxillary lymphadenopathy is a common clinical presentation of variety of benign and malignant diseases. However, majority of patients with unilateral axillary lymph node enlargement have an underlying malignancy in which association with breast carcinoma being the commonest one. In most of these patients there will be a discernible primary tumor, either clinically or radiologically. However, in axillary lymphadenopathy with negative mammogram is not very common, and in this case other malignant causes should also be considered in addition to occult breast cancer and these can be metastases from other primary tumors for, e.g., lung, genitourinary tract, gastrointestinal, ovarian, thyroid carcinomas and malignant melanoma.Axillary node is an uncommon site of metastases from Transitional cell carcinoma (TCC) of urinary bladder even from its muscle invasive form, and distant metastasis from low grade superficial tumors without muscle invasion or regional metastasis is a very rare occurrence. Here we present a case of axillary nodal metastases from non-muscle invasive (superficial) bladder cancer without history of local recurrence and regional metastases.Case presentationWe present a case of female patient who complaint of hard swelling in right axilla and right breast enlargement. Patient had past history of non-muscle invasive transitional cell carcinoma of urinary bladder (pTa, grade II A) which had been treated accordingly. No recurrence of bladder growth had been observed on serial check cystoscopies. On clinical examination of breast and axilla, right breast appears enlarged and there were palpable hard fixed axillary lymph nodes. Ultrasound showed enlarged malignant looking lymph nodes. Occult breast carcinoma with metastatic axillary lymph nodes was our initial impression; however, subsequent biopsy of axillary lymph nodes showed Transitional cell carcinoma.ConclusionsThis patient’s case emphasizes the importance of having sound knowledge of natural behavior of primary tumor and common and uncommon sites of distant metastases. The causes of unilateral axillary lymphadenopathy include both benign and malignant disease.

Development of a 7-miRNA prognostic signature for patients with bladder cancer

Bladder carcinoma (BC) represents one of the most prevalent malignant cancers, while predicting its clinical outcomes using traditional indicators is difficult. This study aimed to develop a miRNA signature for the prognostic prediction of patients with BC. MiRNAs that expressed differentially were identified between 413 BC and 19 non-tumor patients, whose prognostic values were evaluated using univariate and multivariate Cox regression analyses. The independent prognostic factors were screened out and were used to establish a signature. The risk score of the signature was calculated. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used to verify the predictive performance of the miRNA signature and the risk score. A nomogram was constructed which integrated with the miRNA signature and clinical parameters. Experiments were performed. 7 prognosis related miRNAs were selected as independent risk factors, and a 7-miRNA signature was constructed, with an area under ROC (AUC) of 0.721. The 7-miRNA-signature based risk score acts as an independent prognostic factor, with satisfactory predictive performance (AUC = 0.744). Increased miR-337-3p expressions were detected in tumor samples and BC cell lines than in non-tumorigenic tissues and cell lines. Experiments suggested that miR-337-3p induces the proliferation, migration, and invasion of BC cells. The constructed 7-miRNA signature is a promising biomarker for predicting the prognosis of patients with BC, and miR-337-3p may act as a candidate therapeutic target in BC treatments.

Squamous Cell Carcinoma of Bladder

Squamous Cell Carcinoma of Bladder

Clear evidence of the carcinogenic potential of anthracene: A 2-year feeding study in rats and mice.

Anthracene is an environmental pollutant and its adverse effects on human health have long been a concern due to its persistence and bioaccumulation properties. However, there is insufficient evidence for its chronic toxicity, especially carcinogenicity, in either humans or experimental animals. In this study, its carcinogenicity and chronic toxicity were investigated in compliance with the OECD test guideline 451 (OECD TG 451) and Good Laboratory Practice Standards. Fifty male and 50 female F344 rats and 50 female BDF1 mice were administrated 0, 8000, 20000, or 50000 ppm anthracene in the diet for 104 weeks, and 50 male BDF1 mice were fed diets containing anthracene at 0, 3200, 8000, or 20000 ppm. Anthracene treatment had no adverse effect on either the survival rate or general condition of the rats or mice during the study period. Body weights were lower or tended to be lower in the anthracene-treated groups than in the control groups. Increased incidence of hepatocellular carcinoma and hepatocellular adenoma was observed in male rats and female mice. Renal cell carcinoma and renal cell adenoma, fibroadenoma in the mammary gland, and uterine endometrial stromal sarcoma were increased in female rats. Transitional cell carcinoma and transitional cell papilloma in the urinary bladder were also increased in male and female rats. In addition, several different pre-neoplastic lesions were increased in the anthracene-treated male and female rats and female mice. These results provide clear evidence that oral administration of anthracene for 104 weeks has a carcinogenic effect in male and female rats and female mice.

PXDNL activates the motility of urothelial bladder carcinoma cells through the Wnt/β-catenin pathway and has a prognostic value

AimsAlthough aberrant expression of peroxidasin-like (PXDNL) has been associated with carcinogenesis, its potential role in the Urothelial Carcinoma of the Bladder (UCB) remains unknown. The present study aimed to explore the role of PXDNL in UCB carcinogenesis and its potential clinical value. Main methodsBased on The Cancer Genome Atlas (TCGA) data, bioinformatics was used to explore the potential clinical value of PXDNL. Wound healing and Transwell invasion assays were employed for the purpose of assessing the cell motility, while the Western Blotting experiments were utilized for investigating the protein expression pattern of PXDNL in UCB and investigating the Epithelial-to-Mesenchymal Transition (EMT) and Wnt/β-catenin pathways for understanding the probable mechanisms involved. Key findsPXDNL mRNA was overexpressed in UCB tissues and indicated a poor prognosis. High PXDNL mRNA levels were also associated with advanced clinicopathological features and were regarded as independent prognostic factors for UCB. However, PXDNL showed a weak correlation with immune cell infiltration in UCB. In addition, the findings of the study verified that the existing form of the PXDNL protein was 57-kDa and it was upregulated in the UCB cell lines and tissue samples. Furthermore, silencing PXDNL inhibited, while overexpressing PXDNL promoted EMT and motility of UCB cells in vitro. Mechanistic studies showed that PXDNL activated UCB cell motility via the Wnt/β-catenin pathway. SignificanceThe results reveal a novel molecular target that could be further explored for developing preventive, predictive, and individualized treatment strategies for UCB.

Histopathological Study on Patients with Transitional Cell Carcinoma of Urinary Bladder in Al-Diwaniyah City/ Iraq

This study conducted on inpatients admitted to Al-Diwaniyah teaching hospital at period from January to June 2010 to recognize the histopathological changes of tumor cells of urinary bladder in comparison with normal cells. The histopathological examination of urinary tract infections (UTIs) showed normal thickness of urothelium, in addition, the submucosa and the muscular tissue were congested and oedematous. The present study showed that the transitional cell carcinoma of the bladder divided into three major grades: Grade І , Grade ІІ, Grade ІІІ. In this study, the immunehistochemical expression of cytokeratin 7 used to confirm the diagnosis of urinary bladder cancer. The results revealed a positive and negative reaction between tumor cells and cytokeratin7 antibody.

Enhancement of human bladder carcinoma cell chemosensitivity to Mitomycin C through quasi-monochromatic blue light (λ=453±10nm).

Human urothelial bladder carcinoma (uBC) is the second most tumor entity of the urogenital tract. As far as possible, therapy for non-muscle invasive uBC takes place as resection of the tumor tissue, followed by intravesical chemotherapy or immunotherapy. Because of the high recurrence rate of uBC, there is a need for improved efficiency in the treatment. In the present in vitro study we have evaluated a new approach to enhance the cytotoxic efficiency of Mitomycin C (MMC), which is commonly used for intravesical treatment of uBC on the relevant urothelial cancer cell line RT112. For that we used quasi-monochromatic blue light (453±10nm) at its non-toxic dose of 110J/cm2 as an additive stimulus to enhance the therapeutic efficiency of MMC (10μg/ml). We found, that blue light exposure of RT112 cells led to a very strong increase in intracellular production of reactive oxygen species (ROS) and to a significant reduction (p<0.05) of all function parameters of mitochondrial respiration, including basal activity and ATP production. Although not being toxic when used as a single impact, together with MMC blue light strongly enhanced the therapeutic efficiency of MMC in the form of significantly enhanced cytotoxicity via apoptosis and secondary necrosis. Our results clearly show that blue light, most likely due to its ability to increase intracellular ROS production and reduce mitochondrial respiration, increased the cytotoxic efficiency of MMC and therefore might represent an effective, low-side-effect, and success-enhancing therapy option in the local treatment of bladder cancer.

Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report

BackgroundThe use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers.Case presentationA 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient’s inadequate compliance, and within 2 years, the patient’s cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient’s basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection.ConclusionsOur patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.

EMERGING ROLE OF URINARY BIOMARKERS IN DETECTION OF UROTHELIAL BLADDER CARCINOMA IN SOUTH INDIAN POPULATION

Urine cytology is used for screening of exfoliated bladder cells from voided urine but lacks sensitivity. This study aims to check the efficacy of 5-aminolevulinic acid (5- ALA) fluorescence cytology and establish a high sensitivity approach in detecting flat, in-situ and/or small lesions that are hardly visible under conventional cystoscopy. Intracellular PPIX allows red fluorescence detection. In this study, 5-ALA fluorescent cytology using urine was compared with conventional cytology in the diagnosis of bladder tumors. In this prospective study, we compared the sensitivity and specificity between conventional cytology, 5-ALA fluorescent cytology and FDA approved commercially available kits (NMP-22 and BTA). The percentage of Protoporphyrin IX facilitated by 5-ALA was amplified in cancer urothelial cells compared to normal urothelial cells. The sensitivity of conventional cytology and 5-ALA fluorescent cytology was 64% and 96% respectively, whereas the specificity was 92% and 98.67% respectively. In conclusion, 5-ALA induced fluorescent urine cytology demonstrated promising outcomes in the detection of bladder carcinoma cells. Furthermore, low grade and low stage tumor cells as well as flat lesions were also positively and accurately interpreted using 5-ALA fluorescent cytology.

Synthesis, Anticancer Evaluation and Pharmacokinetic Studies of Quinoline‐Triazole Hybrid Derivatives

AbstractSynthesis of effective and target‐selective biologically active molecules through conjugation of diversely substituted triazoles and 5‐aminoquinoline was achieved successfully with 1,4‐disubstituted regioisomer products in the 3+2 cycloaddition reaction, as expected. Seven quinoline‐1,2,3‐triazole hybrid compounds which bear different substituent groups were subjected to FTIR, 1HNMR, 13CNMR and MALDI‐MS spectroscopic characterization methods. All quinoline‐1,2,3‐triazole hybrid derivatives (8 a–g) were explored for their anti‐cancer activity towards Human urinary bladder carcinoma (T24) cells through cell viability, fluorescent imaging and colony formation analyses. Some chemical reactivity potentials and the pharmacokinetic properties of the quinoline‐1,2,3‐triazole hybrid compounds were analyzed. The frontier molecular orbital energies gap and chemical behaviour indices based on HOMO and LUMO energy values were analyzed via in‐silico methods. All in vitro and in silico results are in agreement that quinoline‐triazole derivative 8 f has potent anticancer activity and could serve for further investigation to enhance its potential biological activities.

Effect of Surgery Combined with Gemcitabine and Oxaliplatin Chemotherapy on Primary Signet Ring Cell Carcinoma of Bladder: A Case Report

Background: Primary signet ring cell carcinoma of the bladder is an extremely rare and highly invasive variant of primary bladder cancer. When tumors are found, they usually show high level and high-stage lesions and diffuse invasion of the bladder wall, and most tumors do not grow in the cavity. Most patients have no specific symptoms at the beginning, which leads to delayed diagnosis and treatment and poor prognosis.

Discriminating bladder cancer cells through rheological mechanomarkers at cell and spheroid levels

The stiffening or softening of cancers observed in nanoindentation experiments has been recognized as a marker of cancer-related changes. In bladder cancers, continuous stretching/destretching is observed due to its functionality, indicating that shear forces dominate the mechanical response of these cells. Thus, nanoindentation and microrheological measurements conducted in parallel allow for a fully reliable mechanomarker of cancer progression. Here, bladder cancer cell lines, i.e., non-malignant cell cancer of the ureter (HCV29), bladder carcinoma (HT1376), and transitional cell carcinoma (T24), were studied. Nanoindentation and microrheological experiments were conducted on individual cells, cell monolayers, and spheroids that were formed using non-adherent surface plates. The results show that nanoindentation experiments can only differentiate between non-malignant HCV29 (stiffer) and cancerous HT1376 and T24 (softer) cells. Applying microrheology recognizes the type of grade 3 bladder cancers (carcinoma HT1376 or transitional cell carcinoma T24 cells). We showed that actin filaments are a vital element defining the rheological properties of spheroids. Differences in mechanical properties of cell monolayers could be associated with thick actin bundles and intercellular connections, with some extracellular matrix (ECM) contributing to the stiffening of such monolayers. Our findings demonstrate that a complete image of how cancer cells respond to mechanical stress (compressive and shear forces) can only be obtained after microrheological measurements using the transition frequency separating elastic and viscous regimes as a non-labeled biomarker of bladder cancer progression.

Surgical resection of mediastinal metastasis from small cell carcinoma of bladder: case report

BackgroundIsolated mediastinal metastasis from a malignant tumor and small cell carcinoma of the bladder are both very rare.Case presentationA 76-year-old woman who had undergone surgery for bladder cancer twice was referred to our hospital for a right paracardiac mass noted in chest computed tomography findings, and resection of the tumor was performed. Histological analysis of the mediastinal tumor revealed it to be a metastatic small cell carcinoma of the bladder. At 4 months after surgery, multiple metastatic lesions were found in the chest and liver, and chemotherapy for small cell carcinoma was started.ConclusionsWe present this case of mediastinal metastasis of small cell carcinoma of the bladder, which is very rare, to show the importance of surgical resection of an isolated mediastinal tumor. Such a procedure should be considered, as histological diagnosis of the tumor could be useful for determining therapeutic options.