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Biomedical subjects

M S Piver

Publications and source records attributed to M S Piver.

At least 109 records · Page 6Linked to original sources
PubMed1993

Galaptin and galaptin-binding glycoconjugates in serum and effusions of carcinoma patients.

The objectives of this study were (1) to quantify galaptin, an endogenous lectin, and galaptin-binding glycoconjugates present in normal serum, (2) to determine if these components were altered in the serum and effusions of carcinoma patients with advanced disease, and (3) to determine if ovarian carcinoma cells synthesize and release soluble galaptin inhibitors. Serum from healthy females (n = 10) had a mean galaptin content of 96 +/- 40 ng/ml. Galaptin levels in carcinoma patient serum (n = 29) were depressed (mean 21 +/- 23 ng/ml; p < 0.0001). Galaptin was not detected in 6 of 8 ovarian carcinoma patient sera. Effusions (n = 17) had a mean galaptin content of 358 +/- 326 ng/ml. Assays involving inhibition of binding of galaptin-peroxidase conjugates to asialofetuin were carried out to evaluate the levels of galaptin-binding glycoconjugates in serum and effusions. The mean inhibition titer of normal serum (n = 12) was 75 +/- 38. Patient serum (n = 28) had an elevated inhibitor content (mean titer = 304 +/- 155; p < 0.0001). Effusions (n = 17) also had a higher inhibitor content relative to normal serum (mean titer = 247 +/- 202; p = 0.0037). Ovarian carcinoma cells isolated from effusions and cultured in vitro were shown to synthesize and release into the medium galaptin-binding glycoconjugates of molecular mass 100-200 kD. An ovarian carcinoma cell line, A121, released galaptin-binding glycoconjugates of molecular mass > or = 200 kD into the medium. The data presented show that the levels of soluble galaptin and galaptin-binding glycoconjugates in the serum of advanced cancer patients are perturbed relative to normal female serum.

Breast Neoplasms↗
PubMed1993

Response to Taxol chemotherapy in resistant ovarian carcinoma.

Taxol was administered to 25 patients with progressive ovarian cancer who had failed three or more lines of chemotherapy. A response rate of 27% was noted in 22 evaluable patients (5 partial responders; 1 complete responder). Median duration of response was only eight weeks. The impact of Taxol's use in this disease awaits the result of trials in which it is administered as first line therapy.

Adult↗
PubMed1993

The addition of etoposide and ifosfamide to cisplatin as second line therapy in ovarian carcinoma.

Forty-five patients with progressive or recurrent ovarian carcinoma received cisplatin, etoposide, and ifosfamide as salvage chemotherapy. The primary purpose of this trial was to evaluate if etoposide and ifosfamide added to cisplatin was effective second line therapy in the 20 patients with progressive or recurrent ovarian cancer after first line cisplatin-based chemotherapy. The overall response in the 20 patients was 20%, all of which were complete responses. However, responses were seen only in patients who had previously responded to first line cisplatin-based chemotherapy and then developed recurrent cancer, whereas none of the patients whose cancer progressed during first line cisplatin-based chemotherapy responded. The addition of etoposide and ifosfamide to cisplatin as second line therapy does not potentiate cisplatin in patients demonstrating first line cisplatin resistance and most likely does not contribute to the second line responses in those patients who demonstrated first line cisplatin sensitivity. This combination is also ineffective as third, forth, fifth or sixth line salvage chemotherapy with a response rate of only 8%.

Adult↗
PubMed1992

A prospective trial of progesterone therapy for malignant peritoneal cytology in patients with endometrial carcinoma.

From February 1982 to February 1991, 45 patients with endometrial carcinoma confined to the uterus except for malignant peritoneal cytology were treated with 1 year of progesterone therapy. Thirty-six patients have undergone planned second-look laparoscopy with repeat peritoneal washings and the remaining 9 patients either refused second-look laparoscopy or the procedure was medically contraindicated. Of the 36 who underwent second-look laparoscopy, 34 (94.5%) were NED (no evidence of disease) and had negative repeat peritoneal cytology and 2 (5.5%) had persistent malignant cytology. The latter two patients, after an additional year of progesterone therapy, were found to be NED and had negative peritoneal cytology at third-look laparoscopy. Of the 45 women enrolled in this protocol, no patient has developed recurrent endometrial cancer, and the expected 5-year disease-free survival was 88.6%.

Adenocarcinoma↗
PubMed1992

Conservative surgery plus adjuvant therapy for vulvovaginal rhabdomyosarcoma, diethylstilbestrol clear cell adenocarcinoma of the vagina, and unilateral germ cell tumors of the ovary.

Significant progress has been made in the 1980s in early-stage vulvovaginal rhabdomyosarcoma, diethylstilbestrol (DES) clear cell adenocarcinoma of the vagina, and unilateral germ cell tumors of the ovary. In an early state of vulvovaginal rhabdomyosarcoma, systemic vincristine, dactinomycin, and cyclophosphamide (VAC) chemotherapy followed by local excision or local radiation results in a high cure rate with retention of future fertility. Similarly, early-stage DES-related adenocarcinoma of the vagina treated by wide local excision and localized vaginal radiation also results in retention of fertility and a high cure rate. Finally, significant progress has been made in unilateral germ cell tumors of the ovary in which surgical treatment by unilateral salpingo-oophorectomy followed by cisplatin, etoposide, and bleomycin results in not only high cure rates and retention of fertility but will probably be standard therapy for all germ cell tumors of the ovary, including dysgerminoma, a disease most frequently treated in the past by radiation therapy with loss of subsequent fertility.

Adenocarcinoma↗
PubMed1992

Leukemia following cisplatin-based chemotherapy for ovarian carcinoma at Roswell Park.

Three cases of leukemia following cisplatin-based chemotherapy are reported. All three patients received cyclophosphamide, a known leukemogen. In two cases, the leukemia was diagnosed after second line chemotherapy with intraperitoneal cisplatin and cytarabine, one of which is the first report of a chronic granulocytic leukemia as a result of cytotoxic chemotherapy.

Adult↗
PubMed1991

Cervical implantation metastasis by endometrial adenocarcinoma.

A distinct type of cervical involvement by endometrial cancer is reported and termed cervical implantation metastasis. It is believed to result from implantation of endometrial cancer on the denuded endocervix after fractional dilatation and curettage (D & C). The histologic criteria for diagnosis are: (1) the cervical implantation metastasis must be imbedded in the endocervical epithelium or superficial stroma surrounded by an implantation site of inflammatory cells and granulation tissue (free-floating cancer cells above the cervical mucosa are not acceptable as implantation tissue), (2) the histologic findings of the cervical implantation metastasis must be similar to those of the endometrial adenocarcinoma in the uterine corpus, (3) the cervical implantation metastasis must be separate from the primary tumor with no evidence of direct extension, and (4) the cervical implantation metastasis should be surrounded by nonneoplastic endocervical glands with no transition between the two. Of the 176 patients who underwent fractional D & C before hysterectomy, nine (5%) were found to have cervical implantation metastasis. No patients had cervical implantation metastasis who did not undergo fractional D & C before hysterectomy. When stratified according to stage, grade, and myometrial invasion, there was no statistically significant difference in the recurrence rate between patients with or without cervical implantation metastasis. It appears that cervical implantation metastasis does not alter prognosis or require specific treatment.

Adenocarcinoma↗
PubMed1991

The interferon system in carcinoma of the cervix. Effect of radiation and chemotherapy.

Thirteen patients with advanced carcinoma of the cervix were studied for parameters of the interferon system compared with 40 age-matched and sex-matched controls. All patients had measurable serum interferon levels; controls did not. All patients had non-antibody-type interferon-inhibitory activity, and controls had none. Interferon-synthesizing potential was higher in controls than in patients. After successful radiation and chemotherapy, these parameters normalized in the patients. No change was seen in one patient who did not respond to therapy.

Adenocarcinoma↗
PubMed1991

Prognostic significance of the extent of cervical involvement by endometrial cancer.

The prognostic significance of the extent of cervical involvement by endometrial cancer is impossible to determine from the literature because previous reports have included fractional dilatation and curettage for staging, preoperative radiotherapy, and surgical stage III and IV disease. Therefore, we reviewed and restaged according to the new FIGO system all patients with endometrial cancer from January 1981 to December 1989. Of 180 patients undergoing hysterectomy for endometrial cancer, 20 had surgical stage II disease. No patient received preoperative radiotherapy. None of 12 patients (0%) with stage IIA disease developed recurrence, while 5 of 8 (63%) with stage IIB disease recurred (P less than 0.01). All 5 recurrences were in extrapelvic sites. Endocervical stroma invasion appears to import a statistically significant worse prognosis than endometrial glandular involvement.

Adenocarcinoma↗
PubMed1991

Phase II trial of cisplatin, adriamycin, and etoposide for metastatic endometrial adenocarcinoma.

Twenty patients with metastatic or recurrent endometrial adenocarcinoma not amenable to surgery or radiation were treated with monthly cisplatin (20 mg/m2 x 3), etoposide (75 mg/m2 x 3), Adriamycin (40 mg/m2) (PAV) and Megace. Patient characteristics were as follows: grade 3 differentiation, 55%; papillary subtype, 15%; prior radiotherapy, 70%; prior chemotherapy, 10%; and prior hormonal therapy, 20%. Hematologic toxicity was significant but acceptable: WBC nadirs, 50%; platelet nadirs, 40%. There was no hematologic mortality. There was a 75% objective response rate and a 55% complete response rate with PAV. The median survival was 15+ months, the 2-year survival was 42%, and the 2-year progression-free survival was 20%. PAV appears to be an active combination with acceptable toxicity in the treatment of metastatic or recurrent endometrial cancer, and we believe that phase III evaluation is indicated.

Adenocarcinoma↗
PubMed1991

Prospective trial of cisplatin, adriamycin, and dacarbazine in metastatic mixed mesodermal sarcomas of the uterus and ovary.

Twenty-four patients with advanced or recurrent uterine (13) and ovarian (11) mixed mesodermal sarcomas received a combination of cisplatin. Adriamycin and dacarbazine (PAD) as initial therapy after surgical debulking. Of the 13 patients with metastatic uterine sarcoma, six (46.1%) remained without evidence of disease (NED) from 8 to 36 months from the start of PAD. The estimated 1-, 2-, and 3-year survivals for these patients were 68%, 68%, and 51%, respectively. Of the 11 ovarian sarcoma patients, five (45.4%) were NED at 5, 7, 32, 56, and 59 months from the start of PAD. The estimated 1-, 2-, and 3-year survivals for these patients were 70%, 35%, and 35%, respectively. The PAD regimen is an active regimen in patients with metastatic uterine and ovarian mixed mesodermal sarcomas and progression-free survival may be improved by maximum debulking surgery prior to the initiation of PAD chemotherapy.

Aged↗
PubMed1991

Serial CA 125 levels during chemotherapy for metastatic or recurrent endometrial cancer.

The purpose of this study was to evaluate the role of serial CA 125 in monitoring disease status during chemotherapy in women with metastatic or recurrent endometrial cancer. CA 125 was measured in 21 women receiving cisplatin, etoposide, and Adriamycin for a total of 275 courses of chemotherapy (median eight). Eight of ten patients had elevated pre-therapy CA 125 levels (median 233 U/mL). CA 125 became and/or remained negative in all 20 women with responding or stable disease and was elevated in all nine patients who relapsed. The median level at the time of relapse was 56 U/mL. Levels were elevated before clinical relapse in five of nine patients (56%). Serial CA 125 may aid in the management of women receiving chemotherapy for advanced or recurrent endometrial cancer.

Aged↗
PubMed1991

Antigenic studies on an enzymatically sialylated carbohydrate: NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc.

Sialic acid residues are often the end moiety of the carbohydrate chain of biologically important glycoconjugates. It is difficult to study sialylated glycoconjugates because the purification of these compounds is often laborious yielding only very small amounts of oligosaccharides for study. Chemical synthesis of sialylated compounds is complicated by the labile nature of the sialic acid bond. In both of these cases the sialylated compounds would need to be conjugated to a polypeptide to be an effective immunogen, and again, such conjugation is fraught with problems due to the instability of the sialic acid linkage. We have developed a combined enzymatic and synthetic route for obtaining quantities of sialylated carbohydrates conjugated to a protein carrier in amounts sufficient for antigenic studies. The notable novelty of this protocol is the addition of sialic acid after the carbohydrate-protein conjugation step. Antiserum to the compounds was developed and after absorption, antibodies that demonstrate a requirement for sialic acid for their binding were produced and studied. CA 125 has been shown to be a prognostically significant marker for ovarian adenocarcinoma. The nature of the epitope involved has been analyzed with conflicting results. To attempt to resolve this conflict, we initiated studies on sialylated antigens with NeuAc alpha 2-3Gal beta 1-3GalNAc. This trisaccharide occupies the terminal region in a series of complex carbohydrates which have been suggested to be involved as the epitope. Hanisch et al. reported that the neuraminic acid was important for the reaction.

Animals↗
PubMed1991

Antigenic studies on an enzymatically sialylated carbohydrate: NeuAc(alpha 2-3)Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc.

The CA 125 antigenic determinant has been shown to be elevated in the serum of ovarian cancer patients and is a useful prognostic marker. The chemical epitope which characterizes the CA 125 antigen is found on a high molecular weight glycoprotein and has been suggested to be carbohydrate in nature. This study was undertaken to establish the relationship of a carbohydrate to the epitope recognized by the monoclonal antibody, OC 125. Along this line a carbohydrate structure conjugated to bovine serum albumin (BSA), was enzymatically sialylated using a purified sialyltransferase to yield NeuAcGal[GlcNAc]GalNAc-OC6H4N = N-BSA. This sialylated product was used to immunize a goat and two rabbits for the development of polyclonal antisera. The resultant antisera were tested against related carbohydrates in EIA biased competitive inhibition assays. It was determined that the GlcNAc(beta 1-6)GalNAc residue was immunologically dominant for all antisera tested. As the immune response matured (greater than 40 days), there was an increase in the proportion of the antibodies that were directed to the NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc residue compared to the nonsialylated form. Known CA 125 molecules did not inhibit the binding of raised antisera to the sialylated product, nor did the sialylated product react with OC 125 monoclonal antibodies. It was therefore concluded that the carbohydrate structure in question is not the epitope, or is not a large enough part of the epitope to be recognized in these assays by the OC 125 monoclonal antibodies.

Animals↗
PubMed1991

Synthesis and release of cell surface-derived and sulfated lactosaminoglycans by human ovarian carcinoma cells.

Ovarian carcinoma cell clusters were isolated from patient effusions. Cell-surface glycoconjugates were radiolabelled by a galactose oxidase-borotritide method. The surface-labelled glycoconjugates and metabolically labelled glycoconjugates released to culture medium were characterized. The surface-derived glycoconjugates were highly heterodisperse and had the same molecular weight distribution as the metabolically labelled components. Lectin precipitation assays showed that both classes of glycoconjugates contained N-linked oligosaccharides bearing N-acetyllactosamine moieties. A121 ovarian carcinoma cells also synthesized and released a heterodisperse array of glycoconjugates to culture medium. Ricinus communis agglutinin I (RCAI) precipitated glycoconjugates of MW greater than 100 kDa for both A121 cells and cells from effusions. Cells of different ovarian carcinoma histology yielded similar results. Metabolic labelling experiments with 35SO4 showed that the RACI-bound glycoconjugates released by A121 cells were sulfated. The RCAI-bound sulfated lactosaminoglycans may be associated with malignant transformation and/or metastasis since similar components were not produced by mesothelial cells isolated from effusions [Allen, H.J., M. Gamarra M.S. Piver and E.A.Z. Johnson (1989). Cancer Biochem. Biophys. 10, 219-226].

Amino Sugars↗
PubMed1991

Characterization of glycoconjugates released in vitro by human ovarian carcinoma cells isolated from effusions.

Ovarian carcinoma cell clusters were isolated from patient effusions. The glycoconjugates released to culture medium in vitro were characterized by electrophoretic, immunoassay and gel filtration procedures. Metabolically radiolabelled glycoconjugates were heterodisperse with respect to molecular weight and this heterodispersity was independent of incubation time in vitro. This heterodispersity was also characteristic of mixed Mullerian tumor cells of endometrial origin whereas mesothelial cells released a discrete glycoconjugate of MW 65-70 kDa. Multiple Coomassie blue-stained polypeptides were released by the carcinoma cells. These polypeptides were not adsorbed serum components as assessed by immunodiffusion analyses. Periodic acid-Schiff-reactive macromolecules appeared only at the top of electrophoresis gels. The high molecular weight glycoconjugates synthesized by ovarian carcinoma cells precipitated with an effusion globulin fraction at low ionic strength, but the low molecular weight components (40-70 kDa) were soluble. Immunoprecipitation with anti-Ig failed to precipitate carcinoma glycoconjugates. Antisera raised against the released carcinoma macromolecules precipitated carcinoma glycoconjugates and normal ovarian polypeptides. Antisera raised against normal ovarian macromolecules precipitated ovarian polypeptides but reacted only slightly with carcinoma glycoconjugates. Immunodiffusion analyses showed the presence of alpha 1-acid glycoprotein and carcinoembryonic antigen (CEA)-like components in the carcinoma glycoconjugates. The presence of CEA-like glycoconjugates was confirmed by immunoprecipitation. The antigens and antisera for different histologic types of ovarian carcinoma were cross-reactive. The presence of beta 2-microglobulin suggested that some of the glycoconjugates were shed from the cell surface.

Ascitic Fluid↗