Regulatory role of CCAAT/enhancer binding protein-beta in the production of plasma proteins in yolk sac tumor.

Yolk sac tumor (endodermal sinus tumor) is a malignant germ cell tumor characterized by AFP production, in which histologic foci similar to hepatocellular carcinoma occasionally coexist. We assumed a possible contribution of CCAAT/enhancer binding protein (C/EBP)-beta, a transcription factor implicated in the regulation of plasma proteins in the liver, to the regulation of AFP production and to the expression of other plasma proteins in yolk sac tumor cells because our immunohistochemical analysis revealed nuclear expression of C/EBP-beta in human yolk sac tumors. Overexpression of C/EBP-beta in a rat yolk sac tumor cell line, AT-2-TC, increased production of AFP and other plasma proteins, including albumin, alpha-1-antitrypsin, hepatoglobin, and transferrin. Liver-enriched transcription factors, including hepatocyte nuclear factors (HNF)-1alpha, -1 beta, and -4, were also induced. The induction of this protein expression was only evident in xenografts, where C/EBP-beta was phosphorylated and the activating isoform of C/EBP-beta was relatively predominant. These results indicate that C/EBP-beta plays a role in the production of plasma proteins of yolk sac tumors.

[Neurotoxicity of weekly TP (weekly paclitaxel + consecutive low-dose CDDP) therapy].

OBJECTIVES: To evaluate drug-induced neurotoxicity with combination consecutive low-dose CDDP (CLD-CDDP) and weekly paclitaxel in comparison with TJ therapy. Neurotoxicity was judged according to accumulative scores on questionnaires. SUBJECTS AND METHODS: Weekly TP therapy (CDDP: 10 mg/m2, days 1-7, paclitaxel: 60-80 mg/m2, days 1, 8, 15) and TJ therapy (paclitaxel: 170-180 mg/m2, 3 hours, carboplatin AUC 4-5) were given to 24 subjects in 57 courses and 19 subjects in 30 courses as previously reported, respectively. RESULTS: 1. Significant differences were found in numbness accumulative scores (p = 0.011) between weekly TP and TJ therapy, but not in pain accumulative scores (p = 0.926) between weekly TP and TJ therapy. 2. Peak pain at days 3-4 of paclitaxel that appeared during TJ therapy disappeared during weekly TP therapy, while numbness persisted to a lesser extent with weekly TP therapy than with TJ therapy. 3. Numbness was observed to accumulate in some subjects but not in others during weekly TP therapy. CONCLUSION: The patients' subjective symptoms were able to be objectively evaluated with the questionnaires. Weekly paclitaxel was observed to reduce neurotoxicity, which might be reinforced in combination with CDDP.

Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia: a cohort study in Japan.

One hundred and eighty-five Japanese women with cervical intraepithelial neoplasia (CIN) were enrolled in this follow-up study. On the basis of the prevalence of human papillomavirus (HPV) DNA in Japanese cervical cancer patients, HPV types were categorized into three groups as follows: (1) high risk (types 16, 18, 33, 52, and 58), (2) intermediate risk (types 31, 35, 39, 51, 56, 59, 68, and 70), (3) low risk (type 6, 30, 42, 53, 54, 55, 66 and unclassified types). High-risk HPV infection was a risk factor for progression of the disease. The regression rate in the HPV negative group was higher (83.3%) than those in the HPV positive groups, but the differences in regression were no longer significant after adjustment for age and CIN grade. It is also noted that a lower cytomegalovirus IgG level and a smaller number of past pregnancies might be associated with the regression of CIN lesions.