Takuma Fujii

Current approaches to the treatment of cancer (radiation and chemotherapy) are limited by the toxicity to normal tissues and the sensitivity of tumor cells to these treatments. The use of gene delivery vector systems for the introduction of genetic elements into normal and neoplastic tissues which code for proteins that protect the normal chemotherapy-sensitive tissues and sensitize the tumor cells to radiation and chemotherapy, may contribute to an overall improvement in the outcome of cancer treatment programs. This chapter will review the clinical trials either completed or about to be initiated which are designed to accomplish these goals.

OBJECTIVE: Our purpose was to investigate the metabolic background of the expression of sulfoglycolipids in human endometrium during the luteal phase. STUDY DESIGN: We investigated the expression of sulfoglycolipids by thin-layer chromatography immunostaining and the activities of galactosylceramide sulfotransferase and arylsulfatase A, which regulate the synthesis and degradation of sulfoglycolipid. In addition, arylsulfatase A messenger ribonucleic acid was studied by reverse transcriptase polymerase chain reaction. RESULTS: Sulfoglycolipid expression showed a marked increase in the luteal phase but not in the follicular phase, whereas sialoglycolipids remained relatively constant. The increase of sulfoglycolipids was found to be due to 4.5-fold increased activation of sulfotransferase and a concurrent reduction of arylsulfatase A activity in the luteal phase. Arylsulfatase A messenger ribonucleic acid was detected in both phases and showed no significant changes. CONCLUSIONS: These findings suggest that increased sulfoglycolipid expression in the luteal phase is due to the simultaneous regulation of sulfotransferase and arylsulfatase A, probably by sex steroid hormones.

A case of undifferentiated carcinoma of the broad ligament is reported. The patient was a 28-year-old Japanese woman who underwent laparotomy for a cystic and solid tumor of the left broad ligament. The tumor measured 9 cm in diameter and was unattached to the uterus, ipsilateral ovary, or salpinx. Histological examination revealed tumor tissue consisting of solid nests of irregular configuration and rather small to medium-sized undifferentiated epithelial cells. The tumor cells were positive for cytokeratin, but negative for CA125, epithelial membrane antigen, S-100 protein, amylase, carcinoembryonic antigen, chromogranin A, synaptophysin, HHF35, desmin, and vimentin. Electron-microscopic examination revealed gap junctions and primitive cellular junctions, but no intracytoplasmic mucous granules or microvilli on the surface of the tumor cells. This is the first report of undifferentiated carcinoma of the broad ligament as far as we have been able to determine from a search of the literature.

HPV-16 is implicated in the development of progressive cervical neoplasia, and E6 and E7 proteins of this virus play important roles in its oncogenic activity. Reverse transcriptase-nested-polymerase chain reaction (RT-nested PCR) method was applied to detect the major transcript (E6*I/E7) from E6/E7 ORFs of HPV-16 in the exfoliated cervical and vaginal cells from cervical neoplasia patients. The incidence of the E6*I/E7 transcript was proportional to the class of cytologic diagnosis. Further analysis revealed that the incidence of the E6*I/E7 transcript in Pap smears of class I or II was 5/28 (18%) patients who had previously been diagnosed as having cervical neoplasia but was 1/37 (3%) patients who had never been diagnosed (P < 0.05). These findings suggest that some patients followed up for cervical neoplasia were infected with transcriptionally active HPVs even when their Pap smears were negative. In addition, the E6*I/E7 transcript could not be detected after surgical treatment in any of the cases that were able to be followed up. The E6*I/E7 transcript in the exfoliated cells may prove valuable for epidemiological studies of the pathogenesis of HPV infection. © 1995 Academic Press. All rights reserved.

Sera were examined for the presence of antibody against E7 protein of human papillomavirus type 16 (HPV‐16) by Western blot analysis using the bacterially derived unfused protein. The occurrence rates of anti‐E7 antibody against HPV‐16 were 14.1% (10/71) in cervical cancer patients, 0% (0/48) in cervical intraepithelial neoplasia patients, and 0% (0/41) in female non‐malignant patients. Three patients (one with endometrial cancer, one with breast cancer, and one male patient with colon polyp) out of 115 patients with tumors in organs other than the cervix, had antibody against E7 protein of HPV‐16. The serum antibody, once positive, could be detected for a long time after surgical removal of the cancers in all cases that could be followed up. HPV‐16 DNA could be detected in 50% (13/26) of cervical cancer patients. Sixty‐nine percent (9/13) of patients with HPV‐16 DNA in cancers had the antibody and all the patients with stages II, III, and IV cervical cancer (8/8) harboring HPV‐16 DNA showed the presence of the antibody against E7 protein of HPV‐16. In contrast, only 20% (1/5) of cervical cancer patients with stage Ia or Ib harboring HPV‐16 DNA showed positive for the anti‐E7 antibody in sera. These findings suggest that the presence of anti‐E7 antibody in serum depends on the staging of cervical cancer and extent of HPV infection. Copyright © 1995, Wiley Blackwell. All rights reserved

With the use of reverse transcriptase-polymerase chain reaction techniques focused on a unique kinase insert sequence, the complementary DNA for a mouse tyrosine kinase receptor gene, designated sam3> was isolated from a mouse brain complementary DNA library as a member of the heparin-binding growth factor receptor family or fibroblast growth factor receptor family. The kinase insert region was selected as the probe synthesized by polymerase chain reaction techniques because it composes a unique structure in this receptor family. The sam3 protein, 800 amino acids long, has high homology to mouse K-sam/bek (67%) and N-sam/flg (63%), which we also cloned as the mouse counterparts of human K-sam/ bek and N-sam/flg genes, other members of this family. The sam3 protein also has high homology to human FGFR3 (92%) and chicken cek2 (80%) proteins. The sam3 protein is most likely to be a mouse counterpart of human FGFR3 and chicken cek2 proteins. mRNAs of K-samlbek, N-sam/ flg, and sam3/FGFR3 genes were detected in mouse embryo through some adult tissues. The relative amounts of these mRNAs were different depending on the organs examined. Thus, these gene products may have different biological functions in organ development including the central nervous system. © 1993, American Association for Cancer Research. All rights reserved.