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Biomedical subjects

J J Barlow

Publications and source records attributed to J J Barlow.

At least 19 recordsLinked to original sources

Postirradiation squamous cell carcinoma in situ of the vagina: treatment by topical 20 percent 5-fluorouracil cream.

Eight patients with squamous cell carcinoma in situ of the vagina were treated with monthly 5 day courses of 20% 5-fluorouracil cream applied to the vagina. Seven (87.5%) of the women had an initial complete response; however, three subsequently developed recurrence after the treatment was stopped. They were retreated, and two of these three patients achieved a subsequent complete response. The overall response to therapy was 75% (6/8) with six women off therapy from 1.1 to 6.9 years. Total follow-up of all patients was 3.1 to 6.9 years with no patients having developed invasive carcinoma. Because of the high success rate with no associated serous sequelae, this is believed to be a satisfactory method of therapy for women with squamous cell carcinoma in situ of the vagina occurring after pelvic irradiation.

Administration, Topical

Adriamycin in localized and metastatic uterine sarcomas.

Seventeen women with metastatic uterine sarcomas were treated with Adriamycin chemotherapy. Only one (6%) had an objective response. In addition, 12 patients with early uterine sarcomas were randomized to Adriamycin versus no adjuvant chemotherapy in order to evaluate the effect of Adriamycin in reducing the incidence of subsequent distant recurrences. Of those women receiving Adriamycin, two developed distant metastasis and two developed life-threatening congestive heart failure. Also, two of the six women who did not receive Adriamycin developed distant metastasis. Therefore, continuation of the randomized trial was considered unjustified.

Clinical Trials as Topic

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

Melphalan chemotherapy in advanced ovarian carcinoma.

One hundred and eleven consecutive women with FIGO Stages III and IV ovarian adenocarcinoma were treated with melphalan as their initial chemotherapy. The response rate was 19.8% with 10.8% having a complete response. There was a statistically significant improvement in response in those women with no prior radiation therapy. Moreover, there was a statistically significant improvement in median survival in those patients achieving a complete response to melphalan as compared to those with a partial response, with no change or progression of their malignancy. A review of the results of maximal surgery and combination chemotherapy is presented as a plan of therapy to improve upon the results of melphalan chemotherapy in women with advanced ovarian carcinoma.

Antineoplastic Agents

Leo 1031 (NSC-134087) in gynecologic malignancies.

Thirty-nine patients with gynecological malignancies who had failed on conventional chemotherapeutic agents were treated with Leo 1031 to study the effective dosage and toxicity of the compound in gynecological malignancies. Six patients with ovarian adenocarcinoma were also treated subsequently by using this compound as primary therapy. Comparable results (33% response rate) were obtained with excellent subjective response rate) were obtained with excellent subjective response and minimal hematologic toxicity. Leo 1031 given 30 mg per day was well tolerated by most of the patients but increasing the dose to 40 mg per day led to development of severe hematologic toxicity with no change in response rate. No patients developed clinical evidence of steroid toxicity.

Chlorambucil