A long-term tissue culture cell line has been derived from a human prostate adenocarcinoma metastatic to the brain. The cell line, DU 145, has been passaged 90 times in vitro over a period of 2 years. The cells are epithelial, grow in isolated islands on plastic Petri dishes, and form colonies in soft agar suspension culture. Karyotypic analysis demonstrates an aneuploid human karyotype with a modal chromosome number of 64. Distinctive marker chromosomes (a translocation Y chromosome, metacentric minute chromosomes and three large acrocentic chromosomes) have been identified. Electron microscopy of the original tumor tissue and of the tissue culture cell line show a remarkable similarity in cell organelle structure.

These findings support a protective role for the GSTM1 gene in bladder cancer. From these findings, it is estimated that 25% of all bladder cancer may be attributable to the at-risk GSTM1 0/0 genotype.

A total of 44 patients with renal cell carcinoma and vena caval tumor thrombus underwent surgical resection. Of these patients 27 had primary tumor confined within Gerota's fascia, negative lymph nodes and no distant metastases (stage T3cN0M0). Patients who underwent extraction of a mobile tumor thrombus from the vena cava had a 69% 5-year survival rate (median 9.9 years) but patients with tumor thrombus directly invading the vena cava had a 26% 5-year survival rate (median 1.2 years), which improved to 57% (median 5.3 years) if the involved vena caval side wall was resected successfully. Of these patients 17 had renal cell carcinoma with vena caval thrombus as well as extrafascial extension, regional lymphadenopathy or distant metastases, and the 5-year survival rate was less than 18% in all groups (median survival less than 0.9 years). Prognosis was determined by the pathological stage of the renal cell carcinoma and by the presence or absence of vena caval side wall invasion but not by the level of tumor thrombus extension. Patients with incomplete resection of localized renal cell carcinoma with tumor thrombus do not survive any longer than those with extensive cancer, positive lymph nodes or distant metastases. However, when partial venacavectomy establishes negative surgical margins then survival markedly improves.

Platinum-based drugs that induce DNA damage are commonly used first-line chemotherapy agents for testicular, bladder, head and neck, lung, esophageal, stomach, and ovarian cancers. The inherent resistance of tumors to DNA damage often limits the therapeutic efficacy of these agents, such as cisplatin. An enhanced DNA repair and telomere maintenance response by the Mre11/Rad50/Nbs1 (MRN) complex is critical in driving this chemoresistance. We hypothesized therefore that the targeted impairment of native cellular MRN function could sensitize tumor cells to cisplatin. To test this, we designed what we believe to be a novel dominantnegative adenoviral vector containing a mutant RAD50 gene that significantly downregulated MRN expression and markedly disrupted MRN function in human squamous cell carcinoma cells. A combination of cisplatin and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage and telomere shortening. In cisplatin-resistant human squamous cell cancer xenografts in nude mice, this combination therapy caused dramatic tumor regression with increased apoptosis. Our findings suggest the use of targeted RAD50 disruption as what we believe to be a novel chemosensitizing approach for cancer therapy in the context of chemoresistance. This strategy is potentially applicable to several types of malignant tumors that demonstrate chemoresistance and may positively impact the treatment of these patients.

Setting: A tertiary care academic medical center. Patients: The study included 90 patients who underwent a hemithyroidectomy from 1999 to 2004. Main Outcome Measures: Hypothyroidism was defined as a serum thyrotropin level greater than 6.0 mIU/L at least 8 weeks after hemithyroidectomy. All patients were analyzed for age, sex, surgical indications, preoperative and postoperative thyrotropin levels, weight of resected specimen, final pathologic analysis, and length of followup. Multivariate analysis was performed to identify multiple risk factors for the development of hypothyroidism. Results: The final pathologic analysis demonstrated 49 follicular adenomas, 17 cases of Hashimoto thyroiditis, 10 multinodular goiters, and 14 other abnormalities. The overall incidence of the development of hypothyroid

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Cancer of the prostate is the leading cancer among American men, yet few risk factors have been established. Hair growth and development are influenced by androgens, and it has long been suspected that prostate cancer also is responsive to these hormones. A blinded, case‐control study was undertaken to determine if hair patterning is associated with risk of prostate cancer, as well as specific hormonal profiles. The study accrued 315 male subjects who were stratified with regard to age, race, and case‐control status (159 prostate cancer cases/156 controls). Hair‐patterning classification and serum levels of total and free testosterone (T), sex hormone binding globulin, and dihydrotestosterone (DHT) were performed. Data indicate that hair patterning did not differ between prostate cancer cases and controls; however, significant hormonal differences were detected between the two groups. Free T was greater among cases than in controls (16.4 ± 6.1 vs. 14.9 ± 4.8 pg/ml, P = 0.02). Conversely, DHT‐related ratios were greater among controls (P = 0.03 for DHT/T and P = 0.01 for DHT/free T). Several strong associations also were found between hormone levels and hair patterning. Men with vertex and frontal baldness had higher levels of free T (16.5 ± 5.5 and 16.2 ± 8.0 pg/ml, respectively) when compared to men with either little or no hair loss (14.8 ± 4.7 pg/ml) (P = 0.01). Data suggest that increased levels of free T may be a risk factor for prostatic carcinoma. In addition, although no differences in hair patterning were detected between cases and controls within this older population, further research (i.e., prospective trials or case‐control studies among younger men) may be necessary to determine if hair patterning serves as a viable biomarker for this disease, especially given the strong association between free T levels and baldness.