Early bladder cancer: concept, diagnosis, and management

Kitamura, Hiroshi; Tsukamoto, Taiji

doi:10.1007/s10147-006-0552-y

Cited by 35 publications

(30 citation statements)

References 85 publications

(101 reference statements)

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“…It is largely known that recurrence rate of these tumors after primary treatment is 55-75%, with progression to muscle invasion observed in about 25% of cases. 39 This leads to the use of intravesical administrated agents which-although better tolerated than systemic regimens-are not exempt from side effects. The validation of this assay may solve this problem, providing a higher treatment success rate while sparing patients unnecessary toxicity from drugs that are not suited for their tumors.…”

Section: Cancer Therapymentioning

confidence: 99%

Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors

Gazzaniga

Naso

Gradilone

et al. 2010

Intl Journal of Cancer

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The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch TM technology raise additional issues regarding the biological value of this information. We postulated that a drugresistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.In 2007, cancer killed 7.6 million people (about 20,000 cancer deaths a day), despite the extended use of chemotherapy. 1Excluding skin malignancies, $85% of solid tumors are of epithelial origin. The main cause of death of our cancer patients is undoubtedly the appearance of metastasis, a subset of cancer cells that, detaching from the primary mass, survive in blood and bone marrow eluding immune surveillance and apoptosis. 2 This is the demonstration that systemic chemotherapy is often ineffective, particularly in controlling the metastatic process, and that in $50% of patients with solid tumors, the treatment will be palliative, associated with modest benefit and extremely toxic.3 Therefore, it is important to develop novel models that would allow the proper selection of systemic treatment and predict the outcome in the individual patient. This could lead to achieving the goal of truly personalized therapy.Prospective studies have demonstrated that the number of these circulating tumor cells (CTCs) is predictive of progression-free survival and overall survival [4][5][6] ; this led to the Food and Drug Administration (FDA) approval of the CellSearch TM as the 1st platform used as a counter of CTCs in the peripheral blood of patients with advanced epithelial cancers, which provides prognostic information and is useful to monitor treatment efficacy. [7][8][9] The prognostic value of CTCs in different epithelial malignancies suggests a common biological backgrou...

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Section: Cancer Therapymentioning

confidence: 99%

Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors

Gazzaniga

Naso

Gradilone

et al. 2010

Intl Journal of Cancer

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“…BCG therapy remains the most effective treatment for eradication and prophylaxis of recurrence of superficial bladder cancer, including carcinoma in situ and residual papillary tumors, after transurethral resection of bladder tumors (2,3). However, 30% to 50% of cancers either fail to respond to or relapse from the therapy within the first 5 years of treatment.…”

Section: Intravesical Instillation Of Bacillus Calmette-guerin (Bcg) Ismentioning

confidence: 99%

“…The modified gene expression of these professional cells stimulates the secretion of particular cytokines and presentation of BCG antigens via human leukocyte antigen (HLA) class I and II to CD8 + and CD4 + T cells, respectively. Then, up-regulation of the Th2 response may occur and adversely affect the functioning of the Th1 response, introducing recruitment and maturation of cytotoxic effector cells (2). Thus, various immune systems play important roles in the efficacy of intravesical BCG therapy.…”

Section: Intravesical Instillation Of Bacillus Calmette-guerin (Bcg) Ismentioning

confidence: 99%

Effect of Human Leukocyte Antigen Class I Expression of Tumor Cells on Outcome of Intravesical Instillation of Bacillus Calmette-Guerin Immunotherapy for Bladder Cancer

Kitamura

Torigoe

Honma

et al. 2006

Clinical Cancer Research

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Purpose: Various immune systems play important roles in the clinical efficacy of intravesical Bacillus Calmette-Guerin (BCG) instillation for bladder cancer. However, human leukocyte antigen (HLA) class I molecules on tumor cells and various immune system cells infiltrating to/around the tumor have not been evaluated, although many prognostic factors, including clinical, pathologic, and molecular ones, have been investigated. The aim of this study was to determine immunologic prognostic factors of BCG immunotherapy for bladder cancer. Experimental Design: Immunohistochemical staining for HLA class I, CD4, CD8, CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients who underwent BCG immunotherapy from whom both pretreatment and posttreatment specimens were obtained.We did univariate and multivariate analyses of factors affecting recurrence-free survival. The positive, weakly positive, and negative groups of cells that infiltrated to/around the tumor were compared with recurrence-free survival using the Kaplan-Meier method and log-rank test. Results: HLA class I was a significant prognostic factor both in univariate and multivariate analyses. The 5-year recurrence-free survivals of the patients with HLA class I^positive tumors and those with HLA class I^negative tumors were 55.7% and 19.1%, respectively (P = 0.019). There was a significant association between infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and therapeutic effects. Conclusions: Our data show that expression of HLA class I molecules on tumor cells contributes significantly to the therapeutic effect of BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of main effectors in this therapy.

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“…Not only this technique is invasive, but also 10% to 40% of malignancies may be undetected by this procedure (3). Alternatively, urine cytology is known for its good specificity but poor sensitivity for early stages and low grades.…”

Section: Introductionmentioning

confidence: 99%

Aberrant Methylation ofRARβ2andAPCGenes in Voided Urine as Molecular Markers for Early Detection of Bilharzial and Nonbilharzial Bladder Cancer

Eissa

Swellam²,

El-Khouly³

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Bladder cancer cells illustrate major disruptions in their DNA methylation patterns as compared with normal ones. Authors aimed to identify epigenetic molecular markers in urine for early detection of bladder cancer.Materials and Methods: We retrospectively analyzed the methylation status of RARb 2 and APC genes in urine samples from 210 bladder cancer patients, 61 patients with benign urological diseases, and 49 healthy volunteers by using methylation-specific PCR.Results: Methylated RARb 2 and APC were significantly higher in bladder cancer patients (62.8%, 59.5%) than benign (16.4%, 5%) but not detected in healthy volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant difference among clinicopathologic factors; however, they were detected in all grades and stages. Among the 128 patients with bilharzial bladder cancer, 94 (73.4%) showed methylated RARb 2 and 86 (67.2%) showed methylated APC. Homoplasmic methylation pattern of both genes were only detected in bilharzial bladder cancer cases. Both sensitivities and specificities of the methylated genes for bladder cancer detection were superior to urine cytology and when altogether combined, the sensitivities improved to (91.8%), (93.5%), (91.9%), and (80.9%) in detection of: bladder cancer, non-muscle invasive bladder cancer, low-grade tumors, and bilharzial associated bladder cancer, respectively.Conclusion: Thus, methylated RARb 2 and APC genes might be valuable urinary molecular markers for early detection of bilharzial and nonbilharzial bladder cancer. Cancer Epidemiol Biomarkers Prev; 20(8); 1657-64. Ó2011 AACR.

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Early bladder cancer: concept, diagnosis, and management

Cited by 35 publications

References 85 publications

Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors

Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors

Effect of Human Leukocyte Antigen Class I Expression of Tumor Cells on Outcome of Intravesical Instillation of Bacillus Calmette-Guerin Immunotherapy for Bladder Cancer

Aberrant Methylation ofRARβ2andAPCGenes in Voided Urine as Molecular Markers for Early Detection of Bilharzial and Nonbilharzial Bladder Cancer

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