Biomedical subjects

S K Chambers

Publications and source records attributed to S K Chambers.

61 records · Page 4Linked to original sources

PubMed1987

Circulating tumor markers in the monitoring of gynecologic malignancies.

Plasma from 262 patients with gynecologic malignancies was assayed for levels of circulating tumor markers (CA 125, LSA [lipid associated sialic acid in plasma, LASA-P (Dianon Systems, Inc., Stratford, CT )], Ca 19-9, and carcinoembryonic antigen [CEA]) and correlated with the patients' clinical status. In the patients with ovarian cancer the sensitivities of LSA and CA 125 for patients with clinical evidence of disease were 71% and 76% respectively; the specificities for patients with no clinical evidence of disease were 90% and 86% respectively. Using both tumor markers, a sensitivity of 84% and specificity of 85% was obtained. Additionally, CA 125 was elevated in 59% of patients with clinically advanced or recurrent endometrial cancer, and LSA was elevated in 63% of patients with clinical evidence of cervical cancer. Neither CEA nor CA 19-9 levels correlated with clinical status in patients with ovarian or cervical cancer. The values of Ca 125 and LSA were examined in relation to the findings at second-look surgery in patients with ovarian cancer. Absence of elevated tumor markers does not obviate the need for second-look surgery; the false negative rate for CA 125 was 40% (6/15). However, the finding of two elevated plasma markers 1 month or more apart, in ovarian cancer patients who were clinically free of disease, was strongly suggestive of recurrent cancer; 13 of 14 such patients showed this association. This latter finding may help to identify a group of patients in whom early surgical intervention is indicated.

Antibodies, Monoclonal↗

PubMed1987

Prognostic factors and sites of failure in FIGO Stage I, Grade 3 endometrial carcinoma.

The results of therapy and patterns of failure were analyzed for 60 patients with Stage I, Grade 3 endometrial cancer seen at Yale-New Haven Hospital between 1960 and 1980. Fifty-eight patients were treated with a combination of surgery and radiation; one was treated with surgery only; and one received radiation only. The overall absolute 5-year survival rate was 72.9% with poorer prognosis noted for patients greater than 65 years of age, older at time of their menopause, and with Stage IA disease. Of the 14 patients who recurred, distant sites were involved in 93% (13/14), with the lung the most common site of distant failure (5/14), followed by the upper abdomen (4/14). Pelvic sites were involved in 43% (6/14) of the treatment failures. The use of pelvic external beam radiation resulted in a reduction in pelvic recurrences, but did not improve overall survival. The predominance of distant failures despite pelvic radiation suggests the possibility of early vascular and transcoelomic spread in Stage I, Grade 3 endometrial adenocarcinomas. Thorough exploration of the upper abdomen, paraaortic nodes, and the obtaining of pelvic washings for cytology at the time of initial surgery, are recommended in addition to chest CT scans to help identify those patients with occult metastases. Prospective randomized trials in Stage I, Grade 3 patients employing adjuvant cytotoxic chemotherapy, hormonal therapy, and/or whole abdominal-pelvic radiation, should be considered in an attempt to improve survival in high-risk patients.

Carcinoma↗

PubMed1987

Etoposide (VP-16-213) plus cis-diamminedichloroplatinum as salvage therapy in advanced epithelial ovarian cancer.

Twenty-two patients with advanced epithelial ovarian cancer were treated with etoposide and cis-platinum. Each had failed one to three regimens of combination chemotherapy including cis-platinum-based combinations. Prior total cis-platinum doses ranged from 50 to 1600 mg/m2 with a median of 440 mg/m2. One of 18 evaluable patients had a complete response lasting 8 months, 1 had a partial response lasting 3 months, 8 had stable disease for a mean of 5.6 months, and 8 had progressive disease. The 4 unevaluable patients had undetectable clinical disease for a mean of 6.7 months. Bone marrow suppression was seen in 4 of 22 patients; two of whom had serious sequelae. The poor objective response rate (9.1%) seen with this combination in patients heavily pretreated with cis-platinum is similar to that seen for single agent etoposide in patients pretreated with alkylating agents. The difficulty of obtaining a good objective response in the face of prior cis-platinum-based combination chemotherapy failure is again verified.

Adult↗

PubMed1986

Neutropenia and fever in patients undergoing combination chemotherapy for malignant germ cell tumors of the ovary.

Fifteen neutropenic febrile episodes occurred in 29 patients undergoing chemotherapy for malignant germ cell tumors of the ovary. Vincristine, actinomycin-D, and cyclophosphamide were used in 24 patients; cis-diamminedichloroplatinum, vinblastine, and bleomycin in three; and both regimens in two. All 15 patients were treated with antibiotic combinations (gentamicin and clindamycin in 12 cases), usually until neutropenia resolved. The mean nadir total granulocyte count was 123/mm3. There was no septicemia or drug-related deaths. With reduction in chemotherapy dosage, 87% of patients tolerated subsequent courses. The survival rates in this disease are excellent, although toxicity is substantial from both regimens. These neutropenic febrile episodes can be managed successfully without interrupting chemotherapy.

Adolescent↗

PubMedDate not supplied

A pilot study of topotecan in the treatment of serous carcinoma of the uterus.

A pilot study investigated topotecan (Hycamtin, GlaxoSmithKline, Philadelphia, PA), a topoisomerase I inhibitor, in treating uterine serous carcinoma, a typically unresponsive aggressive tumor. Fifteen patients were surgically staged, then treated with topotecan (1.5 mg/m2, Days 1-5 every 21 days) as first-line therapy (n = 12) or secondary to platinum failure (n = 3). Patients received topotecan through six courses, disease progression, or unacceptable toxicity. Grade 3/4 hematologic toxicity prompted dose adjustments. Thirteen patients exhibited no gross evidence of residual disease postoperatively. At topotecan initiation, one patient had 5-cm and one had < 1-cm residual disease. Seventy-eight courses (median, six) were administered; 12 (80%) patients completed the specified protocol. Common serious toxicities included grade 3 neutropenia (33%), anemia (13%), and thrombocytopenia (13%). Eight patients received erythropoietin and/or granulocyte colony-stimulating factor. Median follow-up for 14 evaluable patients was 26 months (range, 13-40). Of 11 evaluable first-line topotecan patients, nine were alive at follow-up; five were disease-free. Of three second-line topotecan patients, two died and one was alive with disease 31 months post-treatment. One patient with measurable disease achieved a complete and one a partial response as assessed by computed tomography scan. Median progression-free survival was 25 months; median survival has not been reached at 26 months. Although topotecan's antitumor activity cannot yet be quantified, disease-free interval and survival outcomes compare favorably with other therapies in uterine serous carcinoma. Further evaluation of topotecan in this population is warranted.

Aged↗

PubMedDate not supplied

Messenger RNA decay of macrophage colony-stimulating factor in human ovarian carcinomas in vitro.

OBJECTIVE: Recently, the importance of the macrophage colony-stimulating factor (CSF-1) and its receptor (encoded by the c-fms proto-oncogene) in patients with epithelial ovarian cancer has been recognized. Overexpression of CSF-1 denotes poor prognosis. Macrophage colony-stimulating factor may be one of a group of inflammatory cytokines, whose 3' untranslated region (UTR) contains AU-rich stretches and whose expression may be largely dependent on mRNA decay. The purposes of this study were to investigate the effect of protein synthesis inhibition on CSF-1 transcript expression, to help determine whether there is a role for labile intermediary proteins in the regulation of CSF-1 expression, and to explore the transcriptional or post-transcriptional mechanisms that could underlie such overexpression of CSF-1 transcripts by protein synthesis inhibitors. Although regulation of CSF-1 gene expression has been investigated in hematopoietic cells, such studies have not been carried out in any epithelial cancer. METHODS: Northern blot analyses for CSF-1 expression were performed on total cellular RNA extracted from primary and established ovarian cancer cell lines in the absence or presence of proteins synthesis inhibitors with different modes of action. The probe for the AU-rich exon 10 of CSF-1 was prepared by amplification of the terminal 143 bp of the 3' UTR of human CSF-1 by polymerase chain reaction. Transcription rates were assessed in the presence or absence of cycloheximide (CH) in nuclei of ovarian cancer cells by run-off analyses. The effect of CH on CSF-1 mRNA half-life was measured by actinomycin D chase experiments in SKOV3 cells. RESULTS: We demonstrate that CSF-1 mRNA was expressed by all of a panel of primary and established ovarian cancer cell lines. There are at least three CSF-1 transcripts expressed by ovarian cancer cells; we demonstrate that the 4.2-kb CSF-1 transcript contains exon-6 sequences, which are spliced from the 3.4- and 1.9-kb transcripts, whereas both the 4.2- and 3.4-kb CSF-1 transcripts contain the 3' AU-rich exon 10. Treatment with several different protein synthesis inhibitors resulted in marked overexpression of CSF-1 transcript levels, suggesting a potential role for labile proteins in the regulation of CSF-1 expression. The predominant effect of CH is on the two CSF-1 transcripts that contain exon 10. Although CH does not change the rate of CSF-1 gene transcription, measurement of CSF-1 mRNA stability reveals a prolongation of CSF-1 transcript half-life by CH from 4.5 hours to significantly greater than 6 hours in ovarian cancer cells. CONCLUSIONS: Augmented CSF-1 transcript stability underlies the marked overexpression of CSF-1 seen with protein synthesis inhibitors. Our results suggest the involvement of a labile regulatory protein that contributes to CSF-1 mRNA decay in ovarian cancer cells. Our data suggest further that exon 10 (not the spliced exon-6 sequences) of the CSF-1 transcript may contain an instability determinant.

Cycloheximide↗

PubMedDate not supplied

Oncogene expression in vivo by ovarian adenocarcinomas and mixed-mullerian tumors.

Six-micron paraffin sections of paraformaldehyde-fixed specimens of 24 ovarian benign and neoplastic specimens were assayed for tumor cell-specific oncogene expression by a sensitive, quantitative in situ hybridization technique with probes for 17 oncogenes, beta-actin, and E. coli beta-lactamase. In the benign, borderline, and invasive adenocarcinomas, multiple oncogenes, including neu, fes, fms, Ha-ras, trk, c-myc, fos, and PDGF-A chains, were expressed at significant levels relative to a housekeeping gene (beta-actin). In the mixed-Mullerian tumors, a rather different pattern of oncogene expression was observed, characterized primarily by expression of sis (PDGF-B chain). For the adenocarcinomas, statistical analysis demonstrated that expression of several genes (fms, neu, PDGF-A) was closely linked to others (c-fos, c-myc) known to have important roles in the control of cell proliferation, but only one gene, fms, correlated very strongly with clinicopathologic features (high FIGO histologic grade and high FIGO clinical stage) predictive of aggressive clinical behavior and poor outcome. The authors discuss the role that tumor epithelial cell expression of the fms gene product might play in the auto- and paracrine control of growth and dissemination of ovarian adenocarcinomas.

Adenocarcinoma↗