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M Bhattacharya

Publications and source records attributed to M Bhattacharya.

14 recordsLinked to original sources

Treatment and immunodiagnosis of advanced ovarian adenocarcinoma: a preliminary report.

High-dose methotrexate with leucovorin rescue plus cyclophosphamide resulted in a 66.6% objective response rate with a 50% complete response rate. These preliminary results are higher than our previous results with melphalan alone or actinomycin D, 5-fluorouracil, and cyclophosphamide in women with advanced ovarian adenocarcinoma. Circulating ovarian cystadenocarcinoma-associated antigen serum levels were positive in 69.8% of patients and correlated with response to chemotherapy in 70% of patients. To date, all of the patients with advanced ovarian adenocarcinoma were found to have elevated galactosyltransferase levels. Galactosyltransferase levels correlated with response to therapy in the first five patients followed serially.

Adenocarcinoma

Glycosyltransferase and glycosidase activities in ovarian cancer patients.

In order to elucidate the mechanism of appearance of abnormal glycoproteins in cancer, activities of glycoprotein glycosyltransferases and glycosidases were determined in the homogenates prepared from normal ovaries and ovarian epithelial adenocarcinoma. Significantly high activities (more than normal mean + 2 S.D.) of these enzymes were found as follows: galactosyltransferase and sialytransferase in 100%; fucosyltransferase 1 (exogenous acceptor, fetuin minus sialic acid and galactose) in 86%; fucosyltransferase 2 (fetuin minus sialic acid, acceptor) in 45%; N-acetylglucosaminyltransferase 1 (ovalbumin acceptor) in 53%; N-acetylglucosaminyltransferase 2 (ribonuclease A as acceptor) in 10% of the samples analyzed. Among the glycosidases, substantially elevated activities above normal controls were found as follows: N-acetyl-beta-D-glucosaminidase in 85%; N-acetyl-beta-D-galactosaminidase in 63%; N-acetyl-beta-D-galactosidase in 50%, and those of alpha-L-fucosidase in 35% of the tumors. In serum of these cancer patients, only levels of galactosyltransferase were consistently elevated compared to controls. Increases in serum levels for other transferases were as follows: fucosyl-1, 10%; fucosyl-2, 60%; sialyl-, 20%; N-acetylglucosaminyl-1, 90%; N-acetylglycosaminyl-2, in 80% of the serum samples from ovarian carcinoma patients. Galactosyltransferase thus appears to be an excellent marker for ovarian carcinoma.

Adenocarcinoma

Tumor markers for ovarian cancer.

The literature on tumor distinctive markers in ovarian cancer has been reviewed. Various immunological and biochemical approaches have been attempted for the diagnosis and management of patients with ovarian cancer. The complex spectrum of antigens that can be detected in human ovarian cancer consists of several tumor-associated antigens, fetal or carcinoembryonic antigens, carcinoplacental markers, and normal tissue antigens. We have described and partially characterized two ovarian tumor-associated antigens designated as OCAA and OCAA-1, which seem to have potential for the immunodiagnosis of ovarian cancer. Several other investigators have carried out similar studies, but in general their serological characterization of these antigens has been limited. The well-defined embryonic proteins that have been examined in the ovarian cancer include carcinoembryonic antigen (CEA), alpha-fetoprotein (alpha-fp), beta-oncofetal antigen (BOFA), Regan and Nagao isoenzymes and human chorionic gonadotropin (HCG). The presence of pregnancy-zone protein (PZP) has also been reported in ovarian cancer. In addition, several normal tissue components include fibrin-fibrinogen degradation products (FDP), alpha 1-globulin, and urokinase have been found associated with ovarian cancer. Both humoral antibodies and cell-mediated immune responses against tumor-associated antigens can be measured in ovarian cancer patients. In addition, serum factors, which block cellular immune reactions, have been identified. However, progress in this area has been hampered by the complexity of the antigens associated with ovarian tumors and the lack of standardized, well-characterized sources of antigens or target cells. Enzymes, especially those involved in glycoprotein biosynthesis, (eg, glycoprotein:glycosyltransferases and glycosidase) have been explored as possible early biochemical indicators of ovarian neoplasia. A serum specific deficiency of alpha-L-fucosidase has been found in patients with ovarian cancers. Of all the glycoprotein:glycosyltransferases studied, galactosyltransferase has been found to be the best enzyme marker for ovarian adenocarcinoma. The determination of serum levels of this enzyme reflected the clinical status of the patient with respect of tumor progression as well as tumor burden. Recently, assay of a phosphodiesterase, which specifically hydrolyzes cytidine 5'-monophospho-N-acetylneuraminic acid, has been found promising in the detection and management of patients with ovarian cancer.

Antigens, Neoplasm

Ovarian tumor antigens.

Evidence has been reported for at least two common tumor-associated antigens, or antigenic determinants, in human cystadenocarcinomas of the ovary that are apparently absent in tissues of normal reproductive organs. These antigenic determinants are immunologically distinct from carcinoembryonic antigen, alpha-fetoprotein, ferritins and histocompatibility antigens. One of these two ovarian cystadenocarcinoma-associated antigens (OCAA) is not detectable in any ovarian carcinomas except serous or mucinous types, other gynecologic or nongynecologic malignancies thus far tested, while the second antigen is present in about 90% of all gynecologic tumors and occasionally in breast and colon tumors. OCAA has been purified and partially characterized. It is a high molecular weight glycoprotein which carries the unique ovarian tumor-specific antigenic determinant along with some normal cross-reacting determinants. High levels of this glycoprotein antigen have been detected in the sera of ovarian cancer patients with advanced disease by the radioimmunoassay inhibition technique. The serial determination of circulating OCAA appeared to correlate with tumor volume as well as the clinical status of the patients.

Antigens, Neoplasm

Correlation of UDP-galactose glycoprotein:galactosyltransferase levels in the sera with the clinical status of ovarian cancer patients.

Uridine diphosphate-galactose : glycoprotein galactosyltransferase (EC 2.4.1.22) was measured serially prior to and after surgery in 4 patients with ovarian epithelial cancer. The levels of this enzyme in the sera correlated well with the clinical status of the patients. In 2 other patients, the follow-up was designed to detect recurrence, and the enzyme assay was started when the patients were clinically disease free. Elevation of galactosyltransferase preceded the clinical appearance of disease by 3-7 months. Serial determination of glycoprotein galactosyltransferase in serum may be useful for evaluating the effectiveness of therapeutic programs.

Adenocarcinoma

Uridine 5'-diphosphate-galactose:glycoprotein galactosyltransferase activity in the ovarian cancer patient.

Uridine 5'-diphosphate-galactose:glycoprotein galactosyltransferase activity was demonstrated in homogenates of normal ovary and ovarian epithelial adenocarcinomas. The specific activity of the enzyme in ovarian tumors was 3 to 5 times higher than in normal ovaries when the enzyme was assayed under identical conditions. The glycoprotein fetuin, from which terminal sialic acid and penultimate galactose were removed (fetuin minus N-acetylneuraminis acid and galactose), acted as an excellent exogenous acceptor. Galactosyltransferase from normal ovary and ovarian tumor cells had similar properties. Both required Mn2+ and Triton X-100 and had broad pH optima between 5.5 and 7. Galactosyltransferase activity was also measured in serum samples from ovarian cancer patients and normal healthy individuals in the presence of fetuin minus N-acetylneuraminic acid and galactose as exogenous acceptor. The enzyme levels were significantly elevated in the sera of ovarian cancer patients as compared to normal controls. The differences in the levels of this enzyme in the tissues and sera of normal individuals and ovarian cancer patients were not due to differential levels of the degrading enzymes such as uridine 5'-diphosphate-galactose pyrophosphatase or beta-D-galactosidase. Serial determinations were carried out on the sera of 5 ovarian cancer patients over a long period of time. The serum level of galactosyltransferase activity appeared to correlate with tumor volume as well as with the clinical status of the patient, which suggests possible leakage of the tumor enzyme into the host sera. Serial determination of this enzyme level in ovarian cancer patients seems promising in measuring tumor progression or success of therapeutic approaches.

Adenocarcinoma

Tumor-associated antigen for cystadenocarcinomas of the ovary.

An ovarian cystadenocarcinoma-associated antigen (OCAA) was found to be common to all serous and mucinous cystadenocarcinomas of the ovary. It was apparently absent in tissues of normal reproductive organs. Furthermore, OCAA was not detected in benign ovarian serous and mucinous cyst-adenomas or in any other gynecologic or nongynecologic cancers thus far tested. The antigenic determinant of OCAA was immunologically unrelated to the carcinoembryonic antigen, other known tumor antigens, or the histocompatibility antigens. We purified and partially characterized OCAA. The antigen was a high-molecular-weight glycoprotein soluble in 0.6 M perchloric acid. It consisted of about 50-60% protein (based on dry wt). Amino acid composition in OCAA was characterized by a high percentage of threonine, serine, proline, and valine. Galactose and N-acetylglucosamine were the principal carbohydrate constituents. The antigenic activity was resistant to treatment with trypsin and protease and also to treatment with DNase, RNase, and N-acetylneuraminidase. The antigenicity was considerably reduced by mild periodate oxidation.

Amino Acids