ABSTRACT
We have previously identified a novel gene WAPL that is inducible by human papillomavirus (HPV) E6 and E7 oncoproteins, and is associated with uterine cervical carcinogenesis. A WAPL splice variant named Friend of EBNA2 (FOE) has also been characterized as a binding partner of the Epstein-Barr virus transformation-related protein EBNA2. On the other hand, recent studies have revealed that WAPL is a cohesin-binding protein and promotes sister-chromatid resolution in mitotic prophase. These data demonstrate that WAPL plays an important role in tumorigenesis and cell cycle progression. In this study, we have isolated a large number of additional alternatively spliced WAPL variants from various cervical epithelia. Each variant consists of a variable 5'-terminal region and the conserved remainder. In addition, we have confirmed the genomic organization of the 5'-region of the WAPL gene, and have investigated the characteristic features of the WAPL variants and their products. Furthermore, we have determined the HPV types of the expressed E6/E7 transcripts in the cervical epithelia with a novel PCR protocol. These results should shed light on a novel aspect of WAPL function.
Subject(s)
Carrier Proteins/genetics , Cervix Uteri/metabolism , Nuclear Proteins/genetics , Proto-Oncogene Proteins/genetics , Alternative Splicing , Amino Acid Sequence , Base Sequence , Cell Line , Cervix Uteri/virology , DNA, Complementary/genetics , Epithelium/metabolism , Epithelium/virology , Female , Gene Expression , Humans , Molecular Sequence Data , Papillomaviridae/genetics , Papillomaviridae/pathogenicity , RNA, Messenger/genetics , RNA, Viral/genetics , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Uterine Cervical Neoplasms/etiology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/virologyABSTRACT
Advanced cervical cancer has been predominantly treated with a combination of external beam and brachytherapy in Japan. Recent studies suggest concurrent use of cisplatin and radiation treatment has superior disease control to radiation only treatment. We have conducted a phase I pilot study of concurrent use of weekly nedaplatin (30 mg/m2) and sequential external beam and brachytherapy in advanced stage or recurrent uterine cervical cancer patients (n = 6). All patients completed the treatment without serious complications. Five patients had complete responses and one a partial response. The average AUC of nedaplatin after one administration was 5.0 micrograms/ml.hr. The therapeutic index was 2. We concluded that concurrent use of weekly nedaplatin and radiation is well tolerated by Japanese women, and may well be an excellent therapeutic modality for selected cases of advanced or recurrent cervical cancer.
Subject(s)
Antineoplastic Agents/administration & dosage , Brachytherapy , Organoplatinum Compounds/administration & dosage , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Aged , Combined Modality Therapy , Drug Administration Schedule , Female , Humans , Middle Aged , Pilot Projects , Radiotherapy DosageABSTRACT
Carcinosarcoma of the ovary is a very rare and highly malignant neoplasm that accounts for less than 1% of ovarian neoplasms. Survival of patients with advanced stage cancer is poor and the best treatment is not clear. We report the case of a 60-year-old woman who had Stage IV advanced heterogeneous ovarian carcinosarcoma with lung and liver metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy of combination CPT-11 (60 mg/m2, day 1, 15) and CDDP (60 mg/m2, day 1). Tumor markers of CA125 and LDH decreased remarkably to the normal level after 3 and 4 courses of chemotherapy, respectively. After 7 courses of chemotherapy, the ovarian tumor was obviously reduced, and the lung and liver metastases had disappeared. The patient was then able to undergo surgery. The current case suggests that combination CPT-11 and CDDP is effective against advanced ovarian carcinosarcoma.
