Purpose: Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy.

We attempted to describe, in a series of clear cell renal cell carcinoma (RCC), the relationship between CAIX expression, VHL gene mutations, tumor characteristics and outcome. Radical nephrectomy was performed in 100 patients. Genomic DNA was extracted from frozen tumor samples. Four amplimers covering the whole coding sequence of the VHL gene were synthesized by PCR and sequenced. The monoclonal antibody M75 was used to evaluate CAIX protein expression immunohistochemically. VHL mutations were identified in 58 patients (58%) and high CAIX expression (>85%) was observed in 78 (78%). Tumors with VHL mutation showed higher CAIX expression than those without (p = 0.02). Low CAIX expression and absence of VHL mutation were associated with a more advanced tumors e.g., higher T stages and presence of metastases. VHL mutation and high CAIX expression predicted longer progression‐free survival (p = 0.037) and disease‐specific survival (p = 0.001), respectively. In combination, they defined three prognostic groups (p = 0.002): (i) good prognosis, defined as VHL mutation and high CAIX (2‐year survival: 86%), (ii) intermediate prognosis with either VHL mutation or high CAIX (69%), and (iii) poor prognosis with no VHL mutation and low CAIX (45%, median survival 18 months). CAIX expression, but not VHL mutational status, was an independent prognostic factor in multivariate analysis. Taken together, CAIX expression and VHL mutational status are able to stratify patients with clear cell RCC into distinct groups with regards to clinicopathological variables and prognosis, with low CAIX expression and absence of VHL mutation being associated with a poor clinicopathological phenotype and diminished survival.

BACKGROUND.: Patients with renal cell carcinoma brain metastases (RCCBM) are frequently excluded from trials and to the authors' knowledge no guidelines currently exist regarding central nervous system (CNS) surveillance or treatment. The objective of the current study was to assist in the creation of treatment guidelines.METHODS.: Patients undergoing evaluation for RCCBM from 1989 to 2006 were identified. Their characteristics, symptoms, pathologic variables, number and size of RCCBM, CNS treatment, CNS recurrence, overall survival, and use of systemic therapy were reviewed.RESULTS.: A total of 138 patients were identified with RCCBM, of whom 92% had clear cell RCC and 95% had synchronous extracranial metastases. CNS symptoms were noted in 67% of patients. Symptomatic CNS tumors were larger (2.1 cm vs 1.3 cm; P < .001) and more frequently required a craniotomy (P < .001). The median overall survival after a diagnosis of RCCBM was 10.7 months; the 1‐year, 2‐year, and 5‐year survival rates were 48%, 30%, and 12%, respectively. Median CNS recurrence was 9 months after RCCBM treatment. The initial number of tumors (>1 tumor) was found to be an independent predictor of CNS recurrence (hazards ratio of 3.72; P < .001). Those patients with 1 and >1 lesion had a median CNS recurrence‐free survival of 13 months and 4 months, respectively (P < .001). Patients receiving interleukin‐2 after CNS treatment had a response rate of 17%.CONCLUSIONS.: Patients with metastatic RCC should undergo CNS screening to allow the identification of smaller lesions that are more amenable to treatment. Those patients with solitary RCCBM are less likely to develop CNS recurrence after local therapy. Selected patients with good performance status may exhibit prolonged survival and should be offered aggressive therapy. Cancer 2008. © 2008 American Cancer Society.

Combination chemotherapy is a cornerstone of cancer treatment. Optimizing its effectiveness requires dose‐ and time‐dependent regulation of drug synergy. In this report, CURATE.AI, an artificial intelligence platform, is used to prospectively guide the dosing of a bromodomain inhibitor (ZEN‐3694) and enzalutamide administered in combination to a patient with metastatic castration‐resistant prostate cancer to reduce serum prostate‐specific antigen (PSA) levels. CURATE.AI successfully identifies substantial ZEN‐3694 and enzalutamide dose adjustments, increasing both treatment efficacy and tolerance. CURATE.AI analysis also confirms that the patient's durable response is mediated by ZEN‐3694 inclusion in the regimen. Due to CURATE.AI‐enhanced efficacy and safety, the patient was able to continue with the combination regimen, resulting in a durable response and no disease progression based on CURATE.AI‐sustained control over PSA levels and reduced lesion size.

BACKGROUND: The objective of this study was to evaluate the role of carbonic anhydrase IX (CAIX) in urothelial carcinoma of the bladder.METHODS: A tissue microarray was constructed that contained 724 tissue samples from 340 patients. Immunohistochemical staining was performed using the antibody MN‐75, the percentage of positive cells was evaluated, and their association with tumor (T) classification, grade, and survival was assessed.RESULTS: All normal urothelial tissue samples were negative for CAIX expression, whereas 71% of bladder cancers expressed CAIX. CAIX expression was higher in noninvasive (Ta) versus invasive (T1‐T4) tumors (P < .001), in low‐grade versus high‐grade bladder cancer (P < .001), and in metastases versus the corresponding primary tumor (P = .032). For patients with nonmuscle invasive carcinoma who underwent transurethral resection (TUR), higher CAIX expression was associated with poorer recurrence‐free survival (P = .001). In addition, for patients with T1 tumors who underwent TUR, higher CAIX expression conveyed a 6.5‐fold higher risk of progression into muscle‐invasive disease (P = .006). In patients who underwent cystectomy, higher CAIX expression was associated with worse overall survival (P = .003). Multivariate Cox models revealed that CAIX expression was the strongest, independent prognostic factor of recurrence‐free survival (hazard ratio, 2.29; P = .001) and overall survival (hazard ratio, 1.9; P < .001).CONCLUSIONS: CAIX was expressed differentially in noninvasive versus invasive tumors, in low‐grade versus high‐grade bladder cancer, and in primary tumors versus metastases. The current results indicated that CAIX is a strong predictor of recurrence, progression, and overall survival of patients with bladder cancer; and the integration of CAIX expression into conventional prognostic models significantly improved their predictive accuracy. The data suggest a tripartite role of CAIX as a diagnostic, prognostic, and therapeutic molecular marker in bladder cancer. Cancer 2009. © 2009 American Cancer Society.