Conservative treatment followed by chemotherapy with doxorubicin and ifosfamide for cervical sarcoma botryoides in young females.
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Sarcoma botryoides of the cervix is an extremely rare tumour and seems to be associated with a better prognosis than its vaginal counterpart. Recent studies have suggested that it is possible to limit surgery to local excision in stage I cases. We report three cases of young subjects treated successfully with polypectomy or diathermy loop excision followed by adjuvant chemotherapy. One patient had a local recurrence which was treated with further local excision. All subjects remain alive without evidence of recurrence and with normal menstrual function 36, 38 and 38 months following initial diagnosis. A conservative surgical approach to early cervical sarcoma botryoides is possible. The efficacy of adjuvant chemotherapy and the regimen of choice still need to be investigated. (+info)
Alteration of p16 and p15 genes in human uterine tumours.
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The roles of the p16 and p15 inhibitor of cyclin-dependent kinase tumour suppressor genes were examined in human uterine cervical and endometrial cancers. p16 mRNA, examined by reverse transcription polymerase chain reaction (RT-PCR), was significantly reduced in five of 19 (26%) cervical and four of 25 (16%) endometrial tumours. Reduced expression of p16 protein, detected by immunohistochemistry, occurred even more frequently, in nine of 33 (27%) cervical and seven of 37 (19%) endometrial tumours. Hypermethylation of a site within the 5'-CpG island of the p16 gene was detected in only one of 32 (3%) cervical tumours and none of 26 endometrial tumours. Homozygous p16 gene deletion, evaluated by differential PCR analysis, was found in four of 40 (10%) cervical tumours and one of 38 (3%) endometrial tumours. Homozygous deletion of p15 was found in three of 40 (8%) cervical tumours and one of 38 (3%) endometrial tumours. PCR-SSCP (single-strand conformation polymorphism) analysis detected point mutations in the p16 gene in six (8%) of 78 uterine tumours (four of 40 (10%) cervical tumours and two of 38 (5%) endometrial tumours). Three were mis-sense mutations, one in codon 74 (CTG-->ATG) and one in codon 129 (ACC-->ATC), both in cervical carcinomas, and the other was in codon 127 (GGG-->GAG) in an endometrial carcinoma. There was one non-sense mutation, in codon 50 (CGA-->TGA), in an endometrial carcinoma. The remaining two were silent somatic cell mutations, both in cervical carcinomas, resulting in no amino acid change. These observations suggest that inactivation of the p16 gene, either by homologous deletion, mutation or loss of expression, occurs in a subset of uterine tumours. (+info)
Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan.
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Various risk factors were investigated in 167 cervical intra-epithelial neoplasia (CIN) case and control pairs in Japan. CIN cases showed evidence of nine known risk factors including smoking and sexual behaviour. However, after adjustment for papillomavirus infection, the highest determinant, the only remaining risk factors were: being married, early age at first pregnancy and multiparity. (+info)
Correlation between EGFR and c-erbB-2 oncoprotein status and response to neoadjuvant chemotherapy in cervical carcinoma.
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Neoadjuvant chemotherapy prior to definitive radical surgery or radiotherapy may be effective in reducing tumor volume or clinical stage and may even enhance pelvic control and survival. However, there are significant limitations to the use of neoadjuvant therapy in the non-responder group. They include delayed total treatment course, the presence of drug resistant clones which result in accelerated tumor growth, and limited bone marrow reserve for subsequent definitive therapy. Thus, there is a need to identify parameters providing a more precise indication of the response to neoadjuvant chemotherapy in patients with invasive cervical cancer. From Jan. 1995 to Jan. 1996, neoadjuvant chemotherapy with 3 courses of cisplatin and vincristine was used in 32 patients with invasive cervical cancer (FIGO stage Ib to IIIb; tumor size greater than 2 cm). Prior to chemotherapy, quantitative tissue levels of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene protein were measured by using an enzyme-linked immunosorbent assay (ELISA). Tumor size was estimated before and after chemotherapy. Relations between oncoproteins and reductions of tumor size were evaluated. Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c-erbB-2 oncoprotein. As well, the tumor reduction index did not manifest any correlation with EGFR, it did had an inverse linear correlation with the c-erbB-2 oncoprotein levels (Rs = -0.71, P < 0.05). The results of this study suggest that c-erbB-2 oncoprotein is associated with a reduced response to neoadjuvant chemotherapy in primary treatment of invasive cervical cancer and may be useful in directing therapeutic approaches. (+info)
T2-weighted fast spin-echo MR findings of adenocarcinoma of the uterine cervix: comparison with squamous cell carcinoma.
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The purpose of this study was to investigate the differences in MR findings of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix and to compare MR findings with pathologic findings. MR images of 17 patients with pathologically proven AC, using a fast spin-echo (FSE) T2-weighted image (T2WI) with pelvic phased-array coil on a 1.5-T unit, were retrospectively evaluated. After measurement of the signal intensity (SI) ratios of the region of interest between tumors and gluteus maximus muscle, we compared the ratios of AC with those of 16 patients with SCC. AC showed relatively high SI on FSE T2WI with multiseptated lesions in four cases and hydrometrocolpos in three cases. The mean SI ratio was 3.82 +/- 1.68 in AC and 2.35 +/- 0.42 in SCC (p < 0.0001, t-test). Multiple tumorous glands with cytoplasmic and intraglandular mucin or serous fluid were pathologically found in AC, but SCC revealed the compact cellularity of stratified squamous tumor cells. The cervical AC showed higher SI than SCC on FSE T2WI with occasional multiseptated lesions and hydrometrocolpos. If the SI ratio of the tumor was more than 3.0, AC could be diagnosed with a sensitivity of 68.8% and a specificity of 100%. (+info)
Potential drugs against cervical cancer: zinc-ejecting inhibitors of the human papillomavirus type 16 E6 oncoprotein.
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BACKGROUND: The principal agent in the etiology of cervical cancer, i.e., human papillomavirus (HPV) type 16, encodes three oncoproteins, E5, E6, and E7. Structural and mutational studies have identified two potential zinc-finger domains as critical for E6 protein function. We investigated several assays to identify and characterize compounds that interfere with the binding of zinc to E6. METHODS: Thirty-six compounds were selected on the basis of their structure, which would facilitate their participation in sulfhydryl residue-specific redox reactions, and were tested for their ability to release zinc from E6 protein. The zinc-ejecting compounds were then tested for their ability to inhibit E6 binding to E6-associated protein (E6AP) and E6-binding protein (E6BP), two coactivators of E6-mediated cellular transformation. The binding of E6 to E6BP and E6AP was measured by use of surface plasmon resonance (a technique that monitors molecular interactions by measuring changes in refractive index) and by use of in vitro translation assays. The compounds were also tested for their effects on the viability of HPV-containing cell lines. RESULTS: Nine of the 36 tested compounds ejected zinc from E6. Two of the nine compounds inhibited the interaction of E6 with E6AP and E6BP, and one of these two, 4, 4'-dithiodimorpholine, selectively inhibited cell viability and induced higher levels of p53 protein (associated with the induction of apoptosis [programmed cell death]) in tumorigenic HPV-containing cells. CONCLUSION: We have described assay systems to identify compounds, such as 4,4'-dithiodimorpholine, that can potentially interfere with the biology and pathology of HPV. These assay systems may be useful in the development of drugs against cervical cancer, genital warts, and asymptomatic infections by genital HPVs. (+info)
Prognostic value of genomic alterations in invasive cervical squamous cell carcinoma of clinical stage IB detected by comparative genomic hybridization.
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The clinical behavior of invasive cervical carcinoma of clinical stage IB varies considerably in tumors presenting without regional lymph node metastases. The early identification of patients at higher risk for poor outcome may prove useful because these patients would benefit from aggressive adjuvant treatments. In this study, comparative genomic hybridization was applied to evaluate whether genomic aberrations have prognostic significance in cervical carcinoma. Genomic alterations were evaluated in 62 cervical carcinomas of clinical stage IB. DNA sequence losses were most prevalent at chromosomes 4q (53%), 3p (52%), 13q (45%), 4p (44%), Xq (44%), 5q (40%), 18q (37%), and 6q (35%). Several genomic alterations were associated with poor clinical outcome or metastasis. The total number of DNA aberrations/tumor (P < 0.02) and the number of DNA sequence losses/tumor (P < 0.04) were associated with disease-specific survival. 9p deletions were significantly more frequent in carcinomas with lymph node metastasis than in node-negative tumors (P < 0.03). Losses of chromosome 11p (P < 0.0001) and 18q (P < 0.01) were associated with poor prognosis in cervical carcinomas without lymph node metastasis. These data suggest that inactivation of tumor suppressor genes on chromosomes 9p, 11p, and 18q may play a role in the progression of cervical carcinoma. (+info)
A dose-finding study of nedaplatin and cyclophosphamide for patients with gynecological malignancies.
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BACKGROUND: Nedaplatin is a new analogue of cisplatin with similar efficacy but less renal toxicity. We investigated the appropriate dose of nedaplatin in combination with cyclophosphamide for patients with gynecological malignancies. METHODS: Nine patients (five with ovarian cancer and four with uterine cervical cancer) were studied. Three patients received 60 mg/m2 of nedaplatin combined with 500 mg/m2 of cyclophosphamide every 4 weeks. Another three patients were each administered 80 or 100 mg/m2 of nedaplatin with the same dose of cyclophosphamide. A total of 27 courses was given. RESULTS: No patient needed dose reduction due to myelosuppression and no severe adverse events were observed. CONCLUSIONS: Treatment with 100 mg/m2 of nedaplatin and 500 mg/m2 of cyclophosphamide is feasible for patients with gynecological malignancies. However, phase II studies are needed to clarify the efficacy of this combination chemotherapy. (+info)