Biomedical subjects

Kent G Krejci

Publications and source records attributed to Kent G Krejci.

4 recordsLinked to original sources

PubMed2004

Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.

Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.

Antigens, CD↗

PubMed2004

Immunotherapy for urological malignancies.

PURPOSE: For decades urologists have successfully used immunotherapy in the battle against cancer. Interleukin-2 in renal cell carcinoma and bacillus Calmette-Guerin in bladder cancer are standard primary and/or adjunctive therapies for these diseases. Recent advances in our understanding of mechanisms governing immune system activation have fostered a myriad of novel immunotherapeutic approaches that show great promise in vivo but have had limited success in human trials to date. This review highlights current immunotherapy strategies that may prove to be successful treatments for urological cancers. MATERIALS AND METHODS: We performed a MEDLINE literature search for articles relating to immunotherapy in bladder, prostate and renal cell carcinoma in animals and humans. We included the most promising developments in this review. RESULTS: In addition to combining existing therapies to improve their efficacy, novel approaches that attempt to exploit the immune system ability to identify, target and eradicate malignancies are now being developed. These therapies include the use of antitumoral monoclonal and bi-specific antibodies, manipulation of T-lymphocyte costimulatory molecules and the administration of newly discovered cytokines as well as the development of antitumor vaccines. CONCLUSIONS: To date the full potential of immunotherapy for the treatment of urological malignancies has not been recognized. As our knowledge of the immune system expands, so too may our ability to manipulate it to affect tumor regression. This review describes the most recent and most promising developments in immunotherapy for urological malignancies.

Animals↗

PubMed2003

Should there be a size limit for elective nephron-sparing surgery?

Nephron-sparing surgery (NSS) is a mandatory procedure for patients with solid renal masses who also have coexisting urologic or medical conditions that pose a threat to overall renal function. The excellent results observed with this procedure have led patients with normal contralateral kidneys to choose elective NSS as a treatment modality. However, the optimal selection criteria for NSS have not yet been defined. We review the developments in and recent results of NSS and discuss features critical in selecting patients for this procedure on an elective basis. Current data clearly support the use of elective NSS for localized solid renal masses under 4 cm in size.

Carcinoma, Renal Cell↗

PubMed2003

Nephron-sparing surgery for renal cell carcinoma: clinicopathologic features predictive of patient outcome.

OBJECTIVES: To determine the clinicopathologic features associated with outcome in patients with sporadic renal cell carcinoma (RCC) treated with nephron-sparing surgery. METHODS: We studied 344 patients treated with nephron-sparing surgery between 1970 and 2000. The pathologic features of the tumors were reviewed by two urologic pathologists who recorded the histologic subtype, 2003 TNM stage, tumor size, and grade. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method, and log-rank tests were used to compare the outcome by histologic subtype. Univariate Cox proportional hazards models were fit to assess the associations between the clinicopathologic features and death from RCC, distant metastases, and local recurrence. RESULTS: The CSS rate at 5 and 10 years for patients with clear cell RCC was 94.4% and 91.5%, respectively. In contrast, the CSS rate at 5 and 10 years for patients with papillary or chromophobe RCC was 99.0%, because only 1 patient died of papillary RCC and no patient died of chromophobe RCC (P = 0.029). Among the patients with localized clear cell RCC, tumor stage and grade were significantly associated with death from RCC and metastases. Grade was significantly associated with local recurrence for clear cell RCC, but not for papillary RCC. CONCLUSIONS: In our series of patients with RCC treated with nephron-sparing surgery, patients with clear cell RCC had a significantly worse CSS than did patients with papillary and chromophobe RCC. Tumor stage and grade were associated with outcome among patients with localized clear cell RCC. These findings are similar to the results for patients with localized clear cell RCC treated with radical nephrectomy.

Adult↗