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The clinical evaluation of human granulocyte colony-stimulating factor (G-CSF) in 38 patients treated with chemotherapy for ovarian cancer stage III was investigated among 3 groups. G-CSF was not given in group A (19 courses), was administered from day 5 of chemotherapy in group B (53 courses), and was given when the WBC count decreased to below 2,000/mm3 in group C (29 courses). The time to nadir was significantly shorter in group B compared with groups A and C and revealed 10 days for the WBC count and 11 days for the neutrophil count (p

Human papillomavirus (HPV) type 16 and 18 DNAs are reported to be associated with uterine cervical cancer. In order to investigate the relationship between the presence of HPV DNA and cervical intraepithelial neoplasia (CIN), we attempted the cytological detection of HPV DNAs in uterine cervical smear samples. The samples included those of severe dysplasia and carcinoma in situ (CIS). They were analysed by DNA-DNA in situ hybridization using biotinylated HPV DNA probes. The results of in situ hybridization analysis revealed that HPV sequences were present in the nuclei of cells with koilocytotic atypia. When probed for HPV type 6, 11, 16 and 18, the nuclei of dysplastic cells and cancer cells were positive for HPV type 16 and 18 DNA. Out of 26 CIN cases, 17 contained HPV type 16 DNA and 5 contained HPV type 18 DNA. We suggest that cytological analysis for HPV sequences by the in situ hybridization technique might provide a molecular diagnosis for assessment in uterine cervical intraepithelial neoplasia., This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan (No.01579833, No.04671004).

The nonreceptor protein tyrosine kinase c-Abl regulates cell proliferation and survival. Recent studies provide evidence that implicate c-Abl as a mediator for fibrotic responses induced by transforming growth factor-beta (TGF-beta), but the precise mechanisms underlying this novel oncogene function are unknown. Here, we report that when expressed in normal fibroblasts, a constitutively active mutant of Abl that causes chronic myelogenous leukemia (CML) stimulated the expression and transcriptional activity of the early growth response factor 1 (Egr-1). Mouse embryonic fibroblasts (MEFs), lacking c-Abl, were resistant to TGF-beta stimulation. Responsiveness of these MEFs to TGF-beta could be rescued by wild-type c-Abl, but not by a kinase-deficient mutant form of c-Abl. Furthermore, Abl kinase activity was necessary for the induction of Egr-1 by TGF-beta in normal fibroblasts, and Egr-1 was required for stimulation of collagen by Bcr-Abl. Lesional skin fibroblasts in mice with bleomycin-induced fibrosis of skin displayed evidence of c-Abl activation in situ, and elevated phospho-c-Abl correlated with increased local expression of Egr-1. Collectively, these results position Egr-1 downstream of c-Abl in the fibrotic response, delineate a novel Egr-1-dependent intracellular signaling mechanism that underlies the involvement of c-Abl in certain TGF-beta responses, and identify Egr-1 as a target of inhibition by imatinib. Furthermore, the findings show in situ activation of c-Abl paralleling the upregulated tissue expression of Egr-1 that accompanies fibrosis. Pharmacological targeting of c-Abl and its downstream effector pathways may, therefore, represent a novel therapeutic approach to blocking TGF-beta-dependent fibrotic processes.