This paper reviews the history of xenografts, the endpoints commonly used to evaluate response and chemotherapeutic results obtained with serially maintained human tumor xenografts from different laboratories, and discusses the potential clinical relevance of the heterotransplant model for cancer chemotherapy. Specifically, an attempt is made to correlate the published xenograft data with the clinical data. Drug testing with different types of xenotransplanted tumors has shown that the response of xenografts obtained in immune-deficient animals is comparable to that in clinical practice. In addition, xenografts of a particular tumor type are able to identify agents of known clinical activity against that disease.

Purpose: To examine the incidence, prognosis, clinical and histological characteristics, treatment, and outcome of patients with bilateral testicular cancer in the referral center in Hungary, to determine which parameters might predict a second testicular tumor. Methods: Clinical parameters-such as time of original surgery, histology of primary tumor, extent of the disease, serum marker concentrations, history of testicular abnormalities, treatment, response to treatment, followup period, data on second carcinoma-of bilateral testicular tumors among the 2,386 patients with testicular cancer treated between November 1988 and November 1998 were analyzed. Results: The incidence of patients with synchronous testicular tumor was 0.8% (19 of 2,386 patients). The clinical stages were 8 I/A, 5 I/B, 1 II/A, 2 II/ B, 1 III/A, and 2 III/B. Median follow-up time was 93 months and the 5-year overall survival was 84%. The incidence of patients with metachronous testicular cancer (median age 28 years and 35 years at first and second tumor diagnosis) was 2.2% (53 of 2,386 patients) and the median time to second tumor was 76 months (range 18-203 months). The clinical stages at the first and second tumor diagnosis were: 14 I/A, 21 I/B, 15 II/A, 2 II/B, and 1 III/B, and 26 I/A, 16 I/B, 3 II/A, 1 II/B, 7 III/B, respectively. The median follow-up time was 42 months and the 5-year overall survival was 93%. In thirteen patients with metachronous cancers, two family histories of testicular cancer, five cases of undescended testicles, seven cases of testicular atrophy, and one case of azoospermia were detected. There was a non-significant trend to a longer cancer interval after chemotherapy and radiotherapy and a tendency to a greater incidence of asynchronous seminoma after chemotherapy. Clinical stage I tumors were more frequent in the surveyed group than among patients not followed up according to the institutional protocol (P = 0.01), but the survival rate was good in both groups. Seminoma as a second tumor was diagnosed in an older age group (median 38 years, range 25-49 years) than nonseminoma (median 32 years, range 21-51 years, P < 0.045).The interval till the appearance of a metachronous testicular cancer depended on tumor histology: in seminoma cases it was longer than in nonseminoma cases (median time: 121 months versus 50 months, P = 0.002). Conclusions: The overall incidence of bilateral testicular cancer in the referral center in Hungary was 3%. We could not identify clinical factors which predicted a higher risk for metachronous testicular cancer. With regular follow-up the early diagnosis of second testicular tumors is probable; therefore education, self-examination of the remaining testicle, and long-term follow-up are important in early detection.

Abstract. Retinoids as important growth and differentiation regulating agents have a potential role in the chemoprevention of head and neck squamous cell carcinoma (HNSCC). Despite the promising preclinical and early clinical findings, limitations of application are raised by intrinsic resistance acquired during carcinogenesis. Retinoic acid receptor ß2 (RARß2) is one of the proximate mediators of retinoid signalling and its expression is often diminished in early stages of head and neck carcinogenesis. One form of retinoid resistance has been associated with the methylation-induced silencing of the RARß gene. We studied primary HNSCC samples of different anatomical sites in respect of methylation, expression and allelic loss of RARß gene. A strong correlation (p<0.01) was found between hypermethylation and reduced expression of RARß2, however the allelic loss at 3p24, the locus of RARß, did not considerably influence its mRNA level. Hypopharynx tumors showed significantly lower hypermethylation (p<0.05) and higher mRNA expression levels of RARß2 compared to the tumors located at other sites of the head and neck. We could also provide evidence that poorly differentiated grade 3 tumors had significantly higher RARß2 expression and lower methylation levels (p<0.05) than better differentiated grade 1 and grade 2 tumors. In addition, we found a good correlation between the methylation degree of the RARß2 promoter and the ages of patients. Collectively, our results suggest that evaluation of several factors such as tumor location, age, histology and methylation state of the RARß gene might contribute to the selection of patients for retinoid-based chemoprevention.

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