Biomedical subjects

S K Chambers

Publications and source records attributed to S K Chambers.

At least 55 records · Page 3Linked to original sources

PubMed1991

Sequelae of lateral ovarian transposition in irradiated cervical cancer patients.

Lateral ovarian transposition (LOT) is a useful technique for preserving ovarian function in "high-risk" premenopausal Stage I cervix cancer patients who undergo hysterectomy and subsequent postoperative whole pelvic radiation therapy. From 1978 to 1988, 38 FIGO Stage I cervical cancer patients underwent LOT as part of their initial operative procedure and 14 of these patients (37%) subsequently received pelvic radiation therapy (LOT + RT) because of pathological findings such as metastatic pelvic lymph node involvement or positive surgical margins (13 patients) or recurrent disease (1 patient). Ten (71%) of the 14 (LOT + RT) patients have maintained ovarian function with a median follow-up of 35 months. Preservation of ovarian function was directly related to the estimated scatter dose to the ovaries. For patients whose estimated ovarian dose was 300 cGy or less, only 1 of 9 patients (11%) underwent menopause, whereas 3 of 5 patients (60%) became menopausal if the ovarian dose was more than 300 cGy. The placement of the ovaries was also crucial for preservation of ovarian function, with 100% of the patients developing menopause if the ovaries were placed below the iliac crest. A major side effect of LOT was the development of symptomatic ovarian cysts in 7 (18%) of the 38 Stage I patients who underwent LOT. In the 24 patients who underwent LOT alone without RT, the incidence of symptomatic ovarian cysts was 25% compared to only 7% of the patients who underwent LOT + RT, although this difference was not statistically significant (p = .18).

Combined Modality Therapy↗

PubMed1991

Molecular biology of ovarian cancer.

This minireview, which due to the limitations of space cannot claim to be exhaustive, summarizes major advances in molecular biologic research on ovarian surface epithelial (adeno)carcinomas communicated approximately between the beginning of April 1990 through the end of March 1991. We focus primarily on studies of oncogenes, peptide hormone growth factors and their receptors, steroid hormone receptors, cytogenetics and flow cytometry, and resistance to therapy with cytotoxic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1991

FMS (CSF-1 receptor) and CSF-1 transcripts and protein are expressed by human breast carcinomas in vivo and in vitro.

The expression in vivo of FMS transcripts and antigen by neoplastic epithelial cells was demonstrated immunohistochemically or by in situ hybridization in sixteen of seventeen human breast carcinoma specimens and one case of sclerosing adenosis. Expression of CSF-1 receptor (FMS) transcripts and protein was also observed in vitro in two or three breast carcinoma-derived cell lines and was dramatically increased by dexamethasone, a potent glucocorticoid and inducer of mammary epithelial cell differentiation. Immunohistochemical staining with an anti-CSF-1 antibody identified neoplastic epithelial cell co-expression of fms and CSF-1 antigens in more than one-third of the fms-positive invasive carcinoma specimens. These results suggest that autocrine and paracrine interactions of the lymphohematopoietic cytokine CSF-1 and its receptor may participate in the biology of human mammary neoplasms.

Blotting, Northern↗

PubMed1990

Correlation between measured creatinine clearance and calculated creatinine clearance in ovarian cancer patients.

In 84 patients with advanced ovarian cancer, the measured 24-hr urinary creatinine clearance and a calculated creatinine clearance were compared prior to cis-platinum-based chemotherapy. The overall correlation between the two methods was excellent, using Pearson's coefficient of correlation test, r = 0.508 and P less than 0.000001. In a subset of 59 patients with adequate 24-hr urine collections, analysis showed a correlation of r = 0.526 and P = 0.000018. Furthermore, in this group of patients using a creatinine clearance of 45 ml/min as a threshold for dose adjustment, there was only a 3.3% error in accepting the calculated creatinine clearance for the measured creatinine clearance. In summary, in patients with advanced ovarian cancer, even in the postoperative state, an evaluation of renal function with a calculated creatinine clearance prior to chemotherapy is sufficient.

Adult↗

PubMed1990

Neoadjuvant chemotherapy in stage X ovarian carcinoma.

Seventeen patients with presumed advanced ovarian cancer were treated initially with platinum-based chemotherapy. All patients had either cytologic or histologic findings consistent with an ovarian adenocarcinoma. Eight patients subsequently had surgery: one patient had a complete pathological response and one patient had microscopic disease; both are alive without evidence of disease. Five patients were surgically debulked to less than 1 cm, and one patient had large residual disease after surgery. Four of these patients are alive with disease and one died of disease. Nine patients did not have surgery; two patients had no response to chemotherapy and four patients had stabilization of disease. These six patients have died. Two patients had initial partial responses and are alive with disease. One patient with a complete clinical response at autopsy was without evidence of disease. The follow-up ranged from 7 to 109 months; the median survival was 15 months. Comparison of these 17 patients with 21 patients with stage IV disease and 38 suboptimally debulked patients with stage III disease treated during the same period with aggressive surgery followed by chemotherapy revealed no statistical difference in overall survival between these 17 patients and the two groups of patients. The postoperative hospital stay and complication rate were significantly lower for the 9 patients who had surgery than for the 21 patients with stage IV disease. This report suggests that in patients with presumed ovarian cancer and significant medical problems or with a priori nondebulkable tumor, initial chemotherapy and then surgery should be considered.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Sequelae of lateral ovarian transposition in unirradiated cervical cancer patients.

The sequelae of lateral ovarian transposition (LOT) in cervical cancer patients has been examined only in the light of the effect of pelvic radiation therapy on ovarian preservation. Preservation of ovarian function has not been examined in the absence of radiation therapy, and symptomatic ovarian cyst formation in transposed ovaries with the need for subsequent surgery has not been addressed in either radiated or unirradiated cervical cancer patients. We studied 84 premenopausal FIGO stage IA or IB cervical cancer patients treated by primary radical hysterectomy between the years 1978 and 1988. None of these patients received adjuvant radiation therapy. Fifty-nine of eight-four patients had radical hysterectomy (RH) without LOT. These patients were compared to 25 of 84 patients who had LOT in addition to RH. The incidence of symptomatic ovarian cysts, the majority requiring operative intervention, was 24% in the ovarian transposition patients as compared to 7.4% in those who had RH alone. This threefold increase in symptomatic benign ovarian cyst formation in the translocated ovary was significant (P = .048). On the other hand, LOT in these RH patients does not appear to increase the incidence of early menopause (P greater than 0.05). On follow-up of those patients who did not incur additional surgery or radiation, 4.3% became menopausal, as compared to 4.1% of those patients undergoing RH alone, with the mean ages of the two groups being comparable.

Adult↗

PubMed1990

The cytokine CSF-1 (M-CSF) expressed by endometrial carcinomas in vivo and in vitro, may also be a circulating tumor marker of neoplastic disease activity in endometrial carcinoma patients.

Endometrial epithelial cell expression of CSF-1 and FMS antigens was studied in vivo and in vitro in 24 human endometrial carcinoma and 11 benign endometrial biopsy specimens. Twenty-one of 24 adenocarcinomas and 4 of 11 benign lesions stained positively (by IHC) with rabbit anti-human CSF-1 antibodies, while all 24 carcinomas and 3 out of 11 benign lesions (all secretory endometrial specimens) showed significant IHC staining (1+ or greater) of epithelial elements and tissue macrophages with a mouse anti-FMS (CSF-1 receptor) monoclonal antibody. CSF-1 levels in plasma from endometrial carcinoma patients (85 samples, 24 patients) were also found to be markedly elevated (some greater than 100 ng/ml) in patients with active or recurrent disease. In vitro, several endometrial carcinoma cell lines were shown to express FMS complementary transcripts and FMS antigen which were very similar if not identical to those expressed in choriocarcinoma cell line positive controls. Autocrine and paracrine effects mediated by tumor or stromally produced CSF-1 and a tumor epithelial cell CSF-1 receptor may therefore contribute to the biological behavior of endometrial neoplasms in vivo and in vitro.

Adenocarcinoma↗

PubMed1990

Ovarian adenocarcinomas express fms-complementary transcripts and fms antigen, often with coexpression of CSF-1.

In earlier studies of oncogene expression in ovarian and endometrial neoplasms, the authors reported that high tumor levels of fms-complementary transcripts correlate with high histologic grade and advanced clinical stage presentations. In this communication, they pursue these initial clinicopathologic investigations to demonstrate by in situ hybridization and immunohistochemistry that malignant epithelial cells of 14 of 14 invasive adenocarcinomas of the ovary express fms-complementary transcripts. By Northern blotting and by reverse transcription, followed by polymerase chain reaction amplification, the authors also were able to demonstrate fms transcript expression in several ovarian and endometrial carcinoma-derived cell lines. Because about half (6/14) of the invasive adenocarcinoma specimens were shown to coexpress fms and colony-stimulating factor 1, the authors propose that the expression of this lymphohematopoietic cytokine and its receptor by ovarian adenocarcinomas could contribute to their proliferative and invasive characteristics in vivo.

Adenocarcinoma↗

PubMed1989

Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer.

Alkylating agents have been the major group of chemotherapeutic agents associated with an increased incidence of secondary leukemias. In ovarian cancer alkylating agents have resulted in a lesser, although still increased, risk of secondary malignancies. This paper reports two cases of ovarian cancer treated with cisplatin and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and the subsequent development of an acute nonlymphocytic leukemia and a preleukemia syndrome. This regimen does not contain alkylating agents, and has not been associated with leukemia in patients with ovarian cancer. In these two cases, abnormalities of chromosomes 5, 7, 11, and 17 are reported which have been shown to occur in therapy-related leukemia.

Adenocarcinoma↗

PubMed1989

Enhancement of anthracycline growth inhibition in parent and multidrug-resistant Chinese hamster ovary cells by cyclosporin A and its analogues.

Cyclosporins have been shown to sensitize multidrug-resistant cells to chemotherapeutic agents but, generally, have minimal effect on sensitive lines. We studied the effect of cyclosporin A (CsA) and two nonimmunosuppressive analogues, 11-methyl-leucine- (11-Me-Leu-CsA) and 6-methyl-alanine-cyclosporin A (6-Me-Ala-CsA), on the action of doxorubicin (DOX) and 4'-epidoxorubicin against parent (AuXB1) and multidrug-resistant (CHRC5) Chinese hamster ovary cells. CsA and its two analogues reduced the IC50 values for DOX in sensitive AuXB1 cells from 0.1 to 0.01-0.02 microM. Cyclosporins reduced the IC50 of DOX in resistant CHRC5 cells from 9 to 0.1 (CsA), 0.7 (6-Me-Ala-CsA), and 1.2 microM (11-Me-Leu-CsA). Similar results were seen when cyclosporins were combined with 4'-epidoxorubicin. The cyclosporins alone had no effect at these concentrations (1-2.0 micrograms/ml). Dose-response curves suggested that CsA was a more potent modifying agent than 11-Me-Leu-CsA towards resistant CHRC5 cells. The ability of the cyclosporins to enhance anthracycline growth inhibition in parent AuXB1 cells may be related to an increase in drug uptake and an increase in anthracycline-induced DNA damage. CsA increased DOX accumulation as well as DOX-associated DNA single-strand breaks in AuXB1 cells over those seen in cells exposed to DOX alone. The degree of increase in DNA breaks paralleled the degree of growth inhibition seen in cells exposed to the same concentrations of drugs. In contrast, CsA had no effect on DOX accumulation or DNA single-strand breaks in CHRC5 cells. These findings imply that, in the resistant cell line, the enhanced anthracycline growth inhibition in the presence of CsA is independent of DOX accumulation and single-strand DNA breaks. These studies demonstrate that CsA and two nonimmunosuppressive analogues can sensitize both sensitive and resistant Chinese hamster ovary cells to anthracyclines. Furthermore, the mechanisms underlying this effect may differ between sensitive and multidrug-resistant cells.

Animals↗

PubMed1989

Tamoxifen in combination with cytotoxic chemotherapy in advanced epithelial ovarian cancer. A prospective randomized trial.

One hundred patients with Stage III and IV epithelial ovarian cancer participated in a prospective randomized study to determine whether the addition of tamoxifen, an estrogen agonist-antagonist, to standard cytotoxic chemotherapy (doxorubicin, cis-diamminedichloroplatinum) would significantly improve survival. Fifty-one patients received the standard cytotoxic chemotherapy and 49 received tamoxifen as well. No significant difference in overall or progression-free survival between these two patient groups was observed. Cytosol steroid receptor determinations were performed on tumor samples from 72 patients. No correlation was evident between therapy and cytosol estrogen and progestin receptor content of the tumors. This study suggests that the strategy of combining an antiproliferative, hormonally active agent with cytotoxic chemotherapy for management of advanced ovarian cancer may be inappropriate.

Adult↗

PubMed1989

Bleomycin, vincristine, mitomycin C, and cis-platinum in gynecologic squamous cell carcinomas: a high incidence of pulmonary toxicity.

Twenty-three patients with gynecologic squamous cell carcinomas (20 cervical, 2 vulvar, 1 ovarian) were treated with bleomycin, vincristine, mitomycin-C, and cis-platinum. Twenty-one patients had prior radiation therapy. Of the 21 evaluable patients, the response rate was 48% with a median duration of 4 months. Toxicity in the 23 patients was high, with the most significant being that of pulmonary toxicity. Eight patients had pulmonary toxicity with 5 of 8 dying a respiratory death while free of disease. Bleomycin is excreted primarily by the kidneys, and its half-life is known to increase in patients with renal insufficiency. Patients with advanced, recurrent cervical cancer who have failed radiation therapy often have underlying renal compromise. Extreme caution should be exercised when administering bleomycin with nephrotoxic chemotherapeutic agents in this setting.

Adult↗

PubMed1989

Radiation treatment of FIGO stage IVA carcinoma of the cervix.

Forty-eight patients with FIGO stage IVA cervix cancer were treated with radiation therapy at the Hunter Radiation Therapy Center, Yale--New Haven Hospital from 1966 to 1985. Nine of the 48 patients are alive without recurrence (NED) and the 5-year actuarial survival rate is 18% (+/- 6%, standard error). There was a substantial difference in outcome based on treatment technique. Thirty-five patients were treated with external beam (EB) plus intracavitary (IC) and 8 of these patients (23%) are NED. None of the 12 patients treated with EB alone are alive. One patient treated with preoperative EB plus exenteration is NED. The severe complication rate was 22% and most complications were vesicovaginal fistulas due to successful treatment for bladder involvement. There was a significant difference in survival for patients with minimal parametrial disease (stage IVA1) versus patients with significant parametrial disease (stage IVA2) which was defined as fixation to one or both pelvic sidewalls or hydronephrosis on IVP. The 5-year survival for stage IVA1 disease was 46% (+/- 14%) versus only 5% (+/- 4%) for stage IVA2 disease. Our results indicate that superior survival for stage IVA cervix cancer patients is associated with two factors: minimal parametrial disease and radiation treatment which combines EB plus IC.

Adenocarcinoma↗

PubMed1989

Circulating levels of CSF-1 (M-CSF) a lymphohematopoietic cytokine may be a useful marker of disease status in patients with malignant ovarian neoplasms.

We have previously reported our observations of epithelial tumor cell expression of transcripts and protein antigens of CSF-1 and transcripts of a protein closely related--if not identical--to the CSF-1 receptor in ovarian and endometrial neoplasms in vivo and in vitro. In the present communication, we extend these investigations to analyze the clinical utility of determinations of plasma CSF-1 concentrations in 125 samples from 33 patients with ovarian neoplasms and one patient with benign endometriosis. We observed that plasma CSF-1 levels in patients with active and recurrent neoplastic disease were markedly elevated and follow changes in disease status in individual patients. These and other results presented in this communication suggest that not only could CSF-1 be a useful circulating tumor marker in ovarian carcinoma patients, but also that in combination with measurements of other markers--such as CA-125--determinations of plasma CSF-1 levels might actually improve the accuracy of "tumor marker"-based assessments of disease status in patients with malignant ovarian neoplasms.

Adenocarcinoma↗

PubMed1989

Surgical transposition of the ovaries: imaging findings in 14 patients.

Pelvic radiation therapy for cervical or vaginal cancer often leads to ovarian failure. To remove the ovaries from the radiation portal and preserve their function, they can be transposed to the lateral abdomen. Serial imaging studies in 14 patients who had undergone ovarian transposition (five bilateral, nine unilateral) were reviewed. Images obtained included 32 CT scans, 20 sonograms, and one MR image. Most transposed ovaries were located along the paracolic gutters near the iliac crests, creating an extrinsic mass effect on adjacent bowel. Detection of surgical clips on the ovary on CT scans allowed confident recognition of all 19 transposed ovaries. Cysts in the transposed ovaries, noted on most imaging studies, did not correlate with complications of pain or hormonal dysfunction. In one case, a large physiologic cyst in a transposed ovary distorted the cecum and was mistaken for a mucocele of the appendix. In another case, a large ovarian cyst was thought to be tumor recurrence or a lymphocele. These findings indicate that although the transposed ovaries can be recognized on CT scans by the surgical clips attached to the ovaries, the appearance of the ovary does not predict reliably the development of complications.

Adult↗

PubMed1989

CA 125 in peritoneal washings and fluid: correlation with plasma CA 125 and peritoneal cytology.

Sixty-four women with ovarian cancer and 46 controls with benign gynecologic conditions underwent cytologic and CA 125 evaluations of peritoneal fluid or peritoneal washings at laparotomy. These parameters were correlated with preoperative disease status, intraoperative findings, and preoperative plasma CA 125 levels to determine their value in assessing occult disease. No false-positive cytology reports were observed. Cytology specimens were positive in 20 of 23 patients (87%) with clinical evidence of disease who had peritoneal fluid present, but in only 18 of 29 (62%) of similar patients with no peritoneal fluid present (P less than .05). CA 125 values were elevated in 16 of 23 (69.5%) and 15 of 29 (52%) of these samples, respectively (P greater than .05). Levels of CA 125 in peritoneal fluid washings correlated poorly with the presence of obvious intraperitoneal cancer and had questionable reliability when used to evaluate patients clinically free of disease. Positive peritoneal cytology reflected the presence of ovarian cancer, but its absence did not mean that an objective response to chemotherapy treatment had occurred. Disease status correlated best with physical examination and circulating levels of CA 125.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1988

Urinary human chorionic gonadotropin free beta-subunit and beta-core fragment: a new marker of gynecological cancers.

Many investigators have shown that a small proportion (13-36%) of subjects with nontrophoblastic gynecological cancers have elevated serum levels of human chorionic gonadotropin (hCG). The low proportion with detectable levels and the accompanying low titers have limited the use of hCG as a tumor marker. hCG is a glycoprotein composed of two noncovalently linked subunits (alpha and beta), which are the products of separate genes. With the intent of expanding the use of hCG as a tumor marker we investigated levels of hCG free beta-subunit and asialo free beta-subunit and its core glycopeptide (composed of beta-subunit residues 6-40 disulfide-linked to 55-92), collectively called urinary gonadotropin fragments (UGF), in healthy and cancer patients. An immunoradiometric assay was developed, using the core glycopeptide-directed antibody B204, that similarly measures the hCG free beta-subunit and the asialo free beta-subunit and its core glycopeptide. Parallel urine and serum samples were collected from 87 women with active gynecological cancer and hCG and UGF were measured. Just 18% of the women tested had detectable serum levels of hCG (greater than 0.2 ng/ml); none had elevated serum levels in the UGF assay (greater than 0.2 ng/ml). Of the same group, 32% had detectable urine hCG levels (mean titer, 0.50 ng/ml) and 74% exhibited elevated urinary levels in the UGF assay (mean titer, 2.0 ng/ml). In a control group (urines from 50 nonpregnant healthy women), 47 negative and three borderline positive results (0.30, 0.35, and 0.48 ng/ml) were observed in the UGF assay. These results suggested a sensitivity of 74% and specificity of 92% for the UGF test for gynecological cancers. By disease, 70% of those with cervical, 73% of those with ovarian, and 77% of those with endometrial cancers had detectable UGF levels (greater than 0.2 ng/ml). By stage, 50, 62, 75, 86, and 100% of those with stage 1, 2, 3, 4, or recurrent disease, respectively, had positive results. UGF is a promising new marker of gynecological malignancies.

Adult↗

PubMed1988

Evaluation of the role of second-look surgery in ovarian cancer.

The role of second-look surgery in the management of patients with ovarian cancer has come under question. One hundred one patients have undergone the operation at Yale University over the last decade. Of 67 who had epithelial ovarian cancer, 43% had positive and 57% had negative second-look surgery. Multivariate analysis revealed that stage was a significant prognostic factor with regard to second-look surgery findings, as well as absolute and disease-free survival. We found initial tumor size and results of cytology at second-look surgery to be prognostic factors with regard to survival after a positive second-look surgery. Survival after negative second-look surgery was significantly greater than that after a positive operation. However, no improvement in survival accrued to the group of advanced-stage, platinum-treated patients who underwent second-look surgery, compared with a similar group of patients who were eligible but did not undergo the procedure. We conclude that second-look surgery in epithelial ovarian cancer patients should be limited to experimental protocol situations in which precise measurement of tumor size may be important. In ovarian germ cell malignancies, second-look surgery, in the absence of tumor markers, can be justified.

Adolescent↗