Structures already discussed alongside bladder transitional cell carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
Surgery remains the mainstay of managing bladder transitional cell carcinoma, with cystoscopy and transurethral resection required for diagnosis and staging. A 2006 retrospective cohort of 198 Chinese patients with primary superficial (Ta or T1) disease treated between 1980 and 2000 reported recurrence rates of 28.32% at three years, 35.31% at five years, and 42.48% at ten years. Progression rates were 8.89%, 15.16%, and 23.88% at the same intervals. Cancer-related survival was 95.02% at three years, 90.70% at five years, and 77.14% at ten years. Bladder-preservation rates were 94.68%, 93.87%, and 91.51% respectively. Metastasis rates rose from 8.25% at three years to 28.94% at ten years.
The same 2006 study identified different risk factors for each outcome. Histological grade, blood transfusion during surgery, and duration of symptoms were main risk factors for recurrence. Progression was affected by blood transfusion, histological grade, number of re-examinations, and length of recurrence-free period. Metastasis was associated with tumor multifocality, hydronephrosis, microscopic growth pattern, and recurrence-free period. Cancer-related survival was influenced by microscopic growth pattern and recurrence-free period. Bladder preservation involved only the recurrence-free period. Canonical correlation analysis showed the dominant prognostic outcomes were cancer-related survival, metastasis, and progression, while the dominant risk factors were histological grade, tumor multifocality, and blood transfusion.
A 2002 review noted that despite advances in medical oncology, radiation therapy, and molecular biology, surgery continues to be critical. A 2013 review stated that management of transitional cell carcinoma of the bladder remains challenging due to diversity of patient factors, stage at presentation, and propensity for recurrence and progression. It selected only advances already in clinical use. A 1997 overview described promising new treatment approaches under evaluation but provided no trial data or outcomes for any specific therapy.
No drug therapy is evaluated in any of these abstracts. The evidence consists entirely of surgical outcomes and prognostic factor analyses from a single retrospective Chinese cohort, now nearly two decades old. What is missing are prospective trials testing repurposed drugs in stratified patient populations, funding for such trials, and any modern biomarker-driven or molecularly targeted approach that might improve upon the recurrence, progression, and metastasis rates reported here.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer Control · 2002 · 35 citations · open access
Surgical Management of Bladder Carcinoma
AbstractBACKGROUND: Despite advances in medical oncology, radiation therapy, and molecular and cell biology, the mainstay in the management of bladder cancer continues to be surgery. METHODS: The authors reviewed the literature regarding the endoscopic diagnosis and management of bladder cancer as well the role of partial and radical cystectomy. RESULTS: Cystoscopy and transurethral resection are required to diagnose and stage bladder cancer. The indications for random bladder biopsies, prostatic urethral biopsy, and re-resection of the tumor bed are examined. The results and complications of endoscopic resection in the management of Ta, T1, and T2 or greater bladder cancer are reported. The roles of partial cystectomy, radical cystectomy, extent of lymphadenectomy, and indications for urethrectomy are also examined. The results and complications of radical cystectomy for the management of T2, T3, T4, and N+ bladder cancer are reported. CONCLUSIONS: Surgery remains a critical element in the management of bladder cancer. Improvements in surgical technique, urinary reconstruction, and multimodal therapy continue to improve the prognosis and quality of life of patients with transitional cell cancer of the bladder.
https://doi.org/10.1177/107327480200900403BioMed Research International · 2013 · 21 citations · open access
Synergistic Effect between Cisplatin and Sunitinib Malate on Human Urinary Bladder-Cancer Cell Lines
AbstractThe aim of this paper is to analyse sunitinib malate in vitro ability to enhance cisplatin cytotoxicity in T24, 5637, and HT1376 human urinary bladder-cancer cell lines. Cells were treated with cisplatin (3, 6, 13, and 18 μM) and sunitinib malate (1, 2, 4, 6, and 20 μM), either in isolation or combined, over the course of 72 hours. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, acridine orange, and monodansylcadaverine staining and flow cytometry were performed. The combination index (CI) was calculated based on the Chou and Talalay method. In isolation, cisplatin and sunitinib malate statistically (P < 0.05) decrease cell viability in all cell lines in a dose-dependent manner, with the presence of autophagic vacuoles. A cell cycle arrest in early S-phase and in G0/G1-phase was also found after exposure to cisplatin and sunitinib malate, in isolation, respectively. Treatment of urinary bladder-cancer cells with a combination of cisplatin and sunitinib malate showed a synergistic effect (CI < 1). Autophagy and apoptosis studies showed a greater incidence when the combined treatment was put into use. This hints at the possibility of a new combined therapeutic approach. If confirmed in vivo, this conjugation may provide a means of new perspectives in muscle-invasive urinary bladder cancer treatment.
https://doi.org/10.1155/2013/791406International Journal of Surgery · 2013 · 16 citations
Recent advances in diagnosis and treatment of transitional cell carcinoma of the bladder
AbstractThe management of transitional cell carcinoma of the bladder (TCCB) presents a challenge to urological surgeons due to the diversity of patient factors, stage at presentation and propensity for disease recurrence and progression. Advances in the last decade have seen an evolution in techniques for diagnosis, treatment and ongoing surveillance. A good understanding of our patients, the disease and the available diagnostic and therapeutic options is essential for the management of this condition. We review the current literature focusing on the merits of recent advances in this field. Given the breadth of the subject, we have deliberately selected only the most relevant and recent advances already in clinical use.
https://doi.org/10.1016/j.ijsu.2013.08.018Chinese Medical Journal · 2006 · 7 citations · open access
Prognostic factors for primary superficial transitional cell carcinoma of the bladder: a retrospective cohort study
AbstractBACKGROUND: Previous studies showed that the prognostic factors for superficial transitional cell carcinoma of the bladder varied with the findings of different cohorts. Few multivariate analyses of prognostic factors for superficial bladder tumors have been reported in China and bladder preservation as a prognostic index of superficial bladder tumors is limited and scarce in Chinese patients. This study was conducted to analyze a group of risk factors for prognostic outcomes for patients with primary superficial transitional cell carcinoma of the bladder. METHODS: Between January 1980 to December 2000, 198 patients [172 men and 26 women; mean age (52.98 +/- 11.28) years] with primary superficial transitional cell carcinoma who were pathologically classified as Ta or T1 in Hunan Provincial Tumor Hospital (Changsha, China) were enrolled in this study. Surgical methods included local resection and electric coagulation of bladder tumors, transurethral resection of bladder tumors and partial cystectomy. After initial surgical treatment, patients were followed through a cystoscopy every three months during the first two years and every six months thereafter in the design of retrospective cohort. Survival analysis was performed to analyze risk factors of the prognostic outcomes for transitional cell carcinoma of the bladder. Canonical correlation analysis was conducted to present and interpret synthetically the multi-correlation between all kinds of prognostic outcomes and risk factor in multiply dimensions. RESULTS: The average follow-up period was (6.65 +/- 4.74) years. Assessments at three, five, and 10 years showed recurrence rates, respectively, of (28.32 +/- 3.45)%, (35.31 +/- 3.83)%, and (42.48 +/- 4.40)%; progression rates of (8.89 +/- 2.14)%, (15.16 +/- 2.94)%, and (23.88 +/- 4.19)%; bladder-preservation rates of (94.68 +/- 1.74)%, (93.87 +/- 1.91)%, and (91.51 +/- 2.49)%; metastasis rates of (8.25 +/- 2.05)%, (11.24 +/- 2.47)%, and (28.94 +/- 4.93)%; and cancer-related survival rates of (95.02 +/- 1.62)%, (90.70 +/- 2.45)%, and (77.14 +/- 4.88)%. The main risk factors for recurrence were histological grade, blood transfusion during surgery and the duration of symptoms. Progression was affected by blood transfusion during surgery, histological grade, the number of re-examinations, and the length of the recurrence-free period. Metastasis was associated with tumor multifocality, hydronephrosis, microscopic growth pattern, and the recurrence-free period. Cancer-related survival was influenced by microscopic growth pattern and the recurrence-free period. Bladder preservation involved only the recurrence-free period. The comprehensive results from canonical correlation analysis showed that the main prognostic outcomes were cancer-related survival, metastasis and progression respectively, while the dominate risk factors were histological grade, tumor multifocality and blood transfusion. CONCLUSIONS: The risk factors were different for each prognostic outcome of transitional cell carcinoma of the bladder. This is helpful for predicting the prognosis of transitional cell carcinoma of the bladder and designing therapeutic and follow-up strategies for this cancer.
https://doi.org/10.1097/00029330-200611010-00010BMC Research Notes · 2016 · 7 citations · open access
Dasatinib enhances tumor growth in gemcitabine-resistant orthotopic bladder cancer xenografts
AbstractSystemic chemotherapy with gemcitabine and cisplatin is standard of care for patients with metastatic urothelial bladder cancer. However, resistance formation is common after initial response. The protein Src is known as a proto-oncogene, which is overexpressed in various human cancers. Since there are controversial reports about the role of Src in bladder cancer, we evaluated the efficacy of the Src kinase inhibitor dasatinib in the urothelial bladder cancer cell line RT112 and its gemcitabine-resistant sub-line RT112 r GEMCI 20 in vitro and in vivo. RT112 urothelial cancer cells were adapted to growth in the presence of 20 ng/ml gemcitabine (RT112 r GEMCI 20 ) by continuous cultivation at increasing drug concentrations. Cell viability was determined by MTT assay, cell growth kinetics were determined by cell count, protein levels were measured by western blot, and cell migration was evaluated by scratch assays. In vivo tumor growth was tested in a murine orthotopic xenograft model using bioluminescent imaging. Dasatinib exerted similar effects on Src signaling in RT112 and RT112 r GEMCI 20 cells but RT112 r GEMCI 20 cells were less sensitive to dasatinib-induced anti-cancer effects (half maximal inhibitory concentration (IC 50 ) of dasatinib in RT112 cells: 349.2 ± 67.2 nM; IC 50 of dasatinib in RT112 r GEMCI 20 cells: 1081.1 ± 239.2 nM). Dasatinib inhibited migration of chemo-naive and gemcitabine-resistant cells. Most strikingly, dasatinib treatment reduced RT112 tumor growth and muscle invasion in orthotopic xenografts, while it was associated with increased size and muscle-invasive growth in RT112 r GEMCI 20 tumors. Dasatinib should be considered with care for the treatment of urothelial cancer, in particular for therapy-refractory cases.
https://doi.org/10.1186/s13104-016-2256-3Cancer Cell International · 2015 · 6 citations · open access
Human urothelial carcinoma cell response to Sunitinib malate therapy in vitro
AbstractOBJECTIVES: Bladder transitional cell carcinoma (TCC) is one of the most common solid malignancies in China. This study examined the antitumor effect and underlying mechanism of action of sunitinib malate in human bladder TCC in vitro. METHODS: Bladder TCC cell lines 5637 and BIU87 were maintained in 1640 medium and T24 cell lines in DMEM/F12 medium. All 3 cell lines were then exposed to graded concentrations (0.625-20 μmol/L) of sunitinib malate, sorafenib and cisplatin for 24-96 hours to determine the sensitivities to each drug. Cell viability was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] assay, and apoptosis was analyzed by flow cytometry. Cell apoptotic morphology was observed by a fluorescence microscope after DAPI (4',6-diamidino-2-phenylindole) staining. Protein concentrations were measured by western blot. RESULTS: Sunitinib malate showed a concentration-dependent inhibitory effect on the 5637, T24 and BIU87 cell lines with IC50's of 1.74 μmol/L, 4.22 μmol/L, and 3.65 μmol/L, respectively. Cisplatin also exhibited good antitumor activity, but whereas sorafenib suppressed proliferation of the cells at concentrations of 10 μmol/L or higher, there was practically no response at lower concentrations. Sunitinib malate treatment resulted in an accumulation of cells in the sub-G1 phase, especially with the T24 and BIU87 cell lines, which induced apoptosis of the cells. CONCLUSIONS: Sunitinib malate exerted marked inhibitory activity against bladder cancer cells. The cell growth inhibitory effect of the drug was related to induction of apoptosis. These results suggest that clinical application of sunitinib-based therapy for advanced bladder cancer is possible.
https://doi.org/10.1186/s12935-015-0179-zSeminars in Surgical Oncology · 1997 · 2 citations
Future therapies for the treatment of bladder neoplasms
AbstractThe last several decades have witnessed an exponential growth in the understanding of the biology of human neoplasms. As a consequence, a number of new strategies for the treatment of urologic cancers are currently under evaluation. We provide an overview of promising new treatment approaches as they apply to the management of transitional cell carcinoma of the urinary bladder.
https://doi.org/10.1002/(sici)1098-2388(199709/10)13:5<376::aid-ssu12>3.0.co;2-lOncology Times · 2015 · 0 citations · open access
Adding Sunitinib to BCG Found Promising in High-Risk Nonmuscle-Invasive Bladder Cancer
AbstractFigureThe addition of the tyrosine kinase inhibitor sunitinib to standard intravesical Bacillus Calmette-Guerin (BCG) instillation appears to allow a high percentage of patients with bladder cancer that has not invaded muscle to achieve biopsy-proven complete responses at three months, researchers reported at the Genitourinary Cancers Symposium. In the Phase II trial, which was supported by Pfizer, 26 of 36 patients (72%) were able to achieve a complete response, reported Alexander Helfand, a fourth-year medical student at Sackler School of Medicine at Tel Aviv University and an oncology clinical research fellow at the University of Michigan. “It is possible to give sunitinib in this setting with mostly minor toxicity but with frequent delays in treatment,” Helfand said. “Combination treatment of nonmuscle-invasive bladder cancer can have good short-term outcomes.” Speaking in a telephone interview after the meeting, he said that one third of the patients had previously been treated for bladder cancer, and one quarter had previously undergone therapy with intravesical BCG, although it had been at least 12 months since that treatment.Figure‘Excellent Results but Numbers Very Small’ Asked for his opinion, Manish Vira, MD, Director of the Fellowship Program in Urologic Oncology at North Shore-LIJ's Arthur Smith Institute for Urology in Lake Success, New York, said: “These are excellent results in a small, prospective study, but the numbers of patients are really too small to say that this is ready for prime time. I think this study is a good start that would warrant further study, but it is not enough at this time to change practice. “Ultimately we will need a bigger study to see how well patients tolerate this combination. Whenever we have tried to combine two modes of therapy—whether it be in bladder cancer or kidney cancer or any other cancer—the big problem is toxicity.” Helfand, who presented the research as both a poster and an oral report, noted that of the approximately 50,000 new cases of nonmuscle-invasive bladder cancer diagnosed annually, 18,000 (about 35%) will be high-risk cases—i.e., those diagnosed with high-risk Ta, T1, and Tis cancers. “For those patients Bacillus Calmette-Guerin induction and maintenance therapy is the mainstay of treatment,” he said. “We believed there was significant room for improvement in clinical outcomes for these high-risk patients. We know that sunitinib blocks the vascular endothelial growth factor receptors on vascular endothelium and may work synergistically with BCG to inhibit angiogenesis.” Study Details In an attempt to prove the theory, he and his colleagues recruited patients who were adults and had been diagnosed with the nonmuscle-invasive high-risk cancer in the bladder or in the prostatic urethra within six weeks of enrollment in the prospective trial. Patients had to have an ECOG performance status of less than 2, and, in fact, 92 percent of the patients had a performance status of 0 and the remaining patients had a status of 1, Helfand reported. Any T2 tumor presentation made the patients ineligible for the study. Patients were not permitted in the trial if they had prior radiation for bladder cancer, or if they had received sunitinib or active treatment for other cancer diagnoses in the previous year. After pathologic assessment to determine tumor stage, patients were treated with six weeks of BCG therapy followed by a two-week hiatus and then 28 days of oral sunitinib. If there was an incomplete response or a recurrence in three months, a second cycle was given. When complete response was achieved, patients then went on a BCG maintenance protocol, which could include up to 15 instillations of BCG. If recurrence or progression occurred following a complete response, patients were treated at the discretion of their physician. The median age of the patients in the study was 66; 83 percent were men; about 53 percent of the patients were diagnosed with T1 disease; 25 percent were found to have high-grade Ta disease; and 22 percent had Tis cancer. Grade 3 adverse events included rashes on the hands and feet, hand and foot syndrome, thrombocytopenia, febrile diarrhea, sores on the hands and feet, and zoster reactivation. About 4.5 percent of the patients experienced these adverse events. There were no Grade 4 or 5 adverse events in the study. Of the 127 minor adverse events, systemic and gastrointestinal events were observed most frequently. Fourteen patients required delays in sunitinib therapy and 11 were unable to complete the 28-day course of sunitinib therapy. The major reason for delays was the elevation of liver enzymes in 28 percent of patients and thrombocytopenia in 19 percent. The researchers sought to improve outcomes beyond the historical comparator of a 55 percent complete response rate at three months based on the 2000 SWOG study by Donald L. Lamm, MD (Eur Urol 2000;37 suppl 1:9-15). Helfand noted that data from various studies have found complete response rates with BCG therapy of 28 to 85 percent. Originally the research team enrolled 43 patients for the study, but seven withdrew before receiving the combination therapy. “There is certainly a role for complementary therapies alongside BCG in order to improve complete response, which has been shown to predict future recurrence and progression of disease,” Helfand said. ‘Real Issue is Durability of Response’ “There has been a lot of study in this area of high-risk bladder cancer because we really don't have a clear winner in terms of treatment,” Vira said. “Should we be using BCG again in cases of patients who have undergone one course of treatment with BCG? Should we be using some other agent, such as a biologic, or should we be using another chemotherapy? Or should we use some kind of immune system modifier such as interferon or newer agents? “The results we see here are good for the first endpoint, but the real issue is the durability of the treatment response,” he continued. “We need to see what the results are at 12 months. Are there patients who go on to develop muscle-invasive bladder cancer? That will make or break whether this treatment will change the standard of care. If adding sunitinib does improve the 12-month progression-free survival or recurrence-free survival, then that would be a significant step forward.” He pointed out, though, that the landscape is littered with trials that looked good at three months and then failed: “In previous studies with drugs such as gemcitabine inside the bladder, the immediate response has been good but then the long-term benefit is not there. This is a different approach, using an immune modulator with a biologic therapy, and perhaps we will see a better response.” Vira noted that sunitinib has been used in the metastatic setting but the response rate has been modest at best: “I have not used sunitinib in this type of patient with bladder cancer. Sunitinib is not a benign drug. A lot of patients can't tolerate it for a variety of reasons; there were a lot of delays in treatment in this study, and a lot of dose reductions. Until you can really show a durable response at 12 months or 24 months or a real significant change in the progression of the disease, this treatment should not be used outside of a clinical trial.”
https://doi.org/10.1097/01.cot.0000464343.47775.1eDisease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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