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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 235 records · Page 13Linked to original sources
PubMed1980

Survival and response to chemotherapy for advanced colorectal adenocarcinoma: an Eastern Cooperative Oncology Group report.

A series of 1,314 cases of advanced measurable colon or rectal cancer were evaluated for objective tumor response and survival. All patients received chemotherapy according to protocols conducted by the Eastern Cooperative Oncology Group during the period between 1974 and 1977. For those patients who had not received chemotherapy prior to study entry, no therapy program under evaluations was significantly more active than the oral or intravenous 5-fluorouracil treatment programs with respect to survival or objective tumor response. The survival and response rates therapy programs under study, including methyl-CCNU, appeared to be comparable. Initial performance status (P < 0.01), weight loss in the six months prior to study entry (P < 0.001), and prior chemotherapy status were shown to be most prognostic for survival, and thus merit inclusion as stratification factors in any comparative trial involving this population. These factors were shown to have a cumulatively greater influence upon survival than the treatment program. Treatment differences were most accentuated within the favorable subgroups of the leading prognostic factors. The location of the primary tumor had a significant effect upon the eventual sites of metastatic disease involvement at the time of study entry (P < 0.001). The consequences of this analysis suggest that investigators need to address characteristics of the population under study. It is also noted that patients with chemotherapy prior to study entry are best suited for survival studies, while patients with no chemotherapy prior to study entry are well suited for both objective tumor response and survival studies.

Antineoplastic Agents↗
PubMed1980

Chemotherapy of advanced, hormonally resistant prostatic carcinoma.

9 advanced prostate cancer patients were given a dose of 1-(2-chlorethyl-3[4-methyl cyclohexyl]-1-nitrosourea) (MeCCNU) 175 mg/m2 orally every 6 weeks. All of them had previously failed on hormonal therapy. 8 patients have progressed during the chemotherapy and only 1 was considered to be stable during a period of 18 weeks. Hematologic toxicity was seen in 3 patients. 21 patients with advanced prostatic carcinoma who failed hormonal therapy were treated with a combination of estracyt (600 mg/m2/day) plus MeCCNU (175 mg/m2/6 weeks) in oral doses. 1 patient had stable disease for about 30 weeks and another one had a subjective response for 12 weeks. 11 patients had hematologic toxicity and 5 of them required dose modification. 10 patients with stage D carcinoma of the prostate were given oral estracyt at a dose of 600 mg/m2/day plus cis-diamminedichloroplatinum (DDP) at an intravenous dose of 60 mg/m2 twice a week repeated every 3 weeks plus methotrexate (MTX) at an i.v. dose of 100 mg/m2 twice a week, repeated every 3 weeks. All of the patients had failed on prior therapy. 9 patients are evaluable, 4 patients had an objective response and 2 others had a subjective response. 2 patients had hematologic toxicity (life threatening) and 2 others had a decrease in creatinine clearance to 60 mg/min and required dose modification. The combination of estracyt + DDP + MTX or a modification seems to be promising.

Antineoplastic Agents↗
PubMed1980

Effects of testosterone on estracyt localization in rat prostate.

Testosterone administration to castrated rats leads to increased concentrations of radioactivity associated with estracyt (a conjugate of carbamate with E2) in the prostate gland, particularly the ventral prostate. This contracts with the decreased concentrations of labeled E2. The findings appear to shed further light on the possible mechanism of action of estracyt in cancer of the prostate.

Adipose Tissue↗
PubMed1980

Hypothalamo-pituitary-adrenal axis in patients with prostatic carcinoma.

Insulin-induced pituitary growth hormone (GH), adrenocorticotrophic hormone (ACTH) and adrenal cortical response were studied in 12 patients with prostatic carcinoma. 3 patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. 5 patients showed lack of ACTH-cortisol response to insulin-induced hypoglycemia. Those patients subsequently presented clinically with rapidly progressing disease.

Adenocarcinoma↗
PubMed1980

Plasminogen activator content of human colon tumors and normal mucosae: separation of enzymes and partial purification.

Plasminogen activator content was determined quantitatively in extracts of 23 pairs of surgically removed colon tumors and adjacent normal mucosa specimens. The activator content averaged 4.4 times higher in the tumor samples than in the corresponding normal tissue. Polyps removed with the adenocarcinomas gave values intermediate between those for tumors and those for the normal mucosae. The enzyme content of the group of tumors that showed invasive propagation or metastatic spread was significantly higher (P < 0.05) than was the enzyme content of the group not manifesting these conditions. Activator activity of the tumor extracts was completely inhibited by rabbit antibody formed against human urokinse. The activity of the normal mucosae was variably inhibited, suggesting the presence of several kinds of activator in normal tissues. The activator from the normal tissues could be separated into a completely refractory fraction and a completely inhibitable fraction by means of an affinity column made of Sepharose-linked, rabbit antiurokinase antibody. The activator, eluted from this column with 1 M acetic acid in 0.5 M NaCl (pH 2.2), was highly purified and had an isoelectric point of 8.6, as does authentic urokinase. The details of the isoelectric profile of the two, however, differed. The data are discussed in relation to earlier studies on the fibrinolytic system in colon cancer.

Adenocarcinoma↗
PubMed1980

The chemotherapy of prostatic carcinoma.

Results of the first randomized trial of the National Prostatic Cancer Project (NPCP) revealed an advantage for cytoxan and 5-FU over standard therapy in hormonally resistant stage D prostate carcinoma. A subsequent trial for patients previously irradiated, receiving the less myelosuppressive agents estracyt or streptozotocin also revealed an advantage over standard therapy. Other completed randomized trials have revealed activity for prednimustine and DTIC. Trials underway for newly diagnosed stage D disease or for stage D disease clinically stable to diethylstilbestrol (DES) show promising activity for cytoxan and DES combined. Current randomized trials in advanced disease are comparing methyl CCNU and hydroxyurea wih cytoxan, and estracyt or vincristine alone or in combination. Chemotherapy in earlier staged patients as adjuvants to definitive surgery or irradiation is underway in two trials, comparing the effects of cytoxan or estracyt as long-term therapies with no additional treatment.

Antineoplastic Agents↗
PubMed1980

Modern concepts of acid and alkaline phosphatase measurement.

Three new assay methods for prostatic acid phosphatase are described relative to results of biochemical methods. Methods for total and isozymes of alkaline phosphatase are also described. Results of a field trial for acid phosphatase tests among multiple institutions in the United States revealed a marked increase in sensitivity for one assay (CIEP) over biochemical methods. which was positive with increasing frequency as the clinical and surgical stage advanced beyond B. Only for stage D did the biochemical method approach the sensitivity of the CIEP assay. The CIEP assay has potential value as a screen for prostate cancer. Another acid phosphatase assay (RIA) proved difficult to perform for many institutions in the field trial. A new solid phase immunofluorescent assay recently introduced may on further testing be more sensitive than the CIEP assay. Total alkaline phosphatase levels studied in patients with advanced disease were markedly elevated in over one-third of the cases. Higher levels were associated with poor survival or response to chemotherapy. Alkaline phosphatase isozyme levels were of added value in locating the site of the increased alkaline phosphatase activity in soft tissue, bone, or liver. Occasionally in the face of a normal total value, increased isozyme activity in one of the aforementioned compartments preceded clinical ability to detect the metastatic foci.

Acid Phosphatase↗
PubMed1980

Analytical survey of N-nitroso contaminants in pesticide products.

1. Levels of N-nitroso dialkylamines in dinitroaniline derivatives were high (up to 153 mg/kg) in the past, but have been decreased considerably in current production, due to process changes. 2. Butralin and pendimethalin contain significant amounts of N-nitroso parent compounds. 3. Most dimethylamine salts of phenoxyalkanoic acids presently contain low or non-detectable levels of NDMA. 4. Quaternary ammonium compounds contain NDMA levels up to 16.8 mg/kg. 5. Two morpholine derivatives appear to contain N-nitrosomorpholine. 6. The triethanolamine salt of dinoseb contains over 200 mg/kg N-nitrosodiethanolamine. 7. A large number of amides, carbamates, organophosphates, triazines, urea derivatives and miscellaneous nitrogen-containing pesticides do not contain N-nitrosamines above 1 mg/kg. 8. Most N-nitroso contaminants in pesticides can be avoided by simple process changes and the elimination of nitrite salts in the formulation.

Chromatography, Gas↗
PubMed1979

Prospective comparison of intralesional and multipuncture BCG in recurrent intradermal melanoma.

Fifty-nine patients with metastatic melanoma predominantly localized in the skin were randomly assigned to treatment with BCG given either intralesionally (IL-BCG) or by multiple puncture vaccination at a nontumor bearing site in the skin (MPV-BCG). Half the patients with IL-BCG experienced moderate fever, chills and malaise, suggesting systemic exposure to this live organism. However, only three of these patients required systemic antituberculous chemotherapy and all responded to it. MPV-BCG treated patients experienced significantly less systemic toxicity. Among fully evaluable patients 45% objective response rate was seen in the IL-BCG group and a 9% response rate in the MPV-BCG group, a significant difference. The only complete responses were seen in the IL-BCG group. Among fully evaluable patients, median survival was 21.1 months in the IL-BCG group and 13.3 months in the MPV-BCG groups (NSD). No patients with pretreatment anergy to all skin tests utilized, experienced objective response to BCG.

Adult↗
PubMed1979

Metabolic fate of N6-benzyladenosine and N6-benzyladenosine-5'-phosphate in rats.

The radiolabeled antitumor nucleoside (14C-8)-N6-benzyladenosine and its (14C-8)-5'-phosphate were administered to rats intravenously, and their metabolic fate was studied. Twenty-nine percent of the radioactivity was recovered in the 48-hr urine collection after (14C-8)-N6-benzyladenosine administration. The following metabolites were isolated: unchanged N6-benzyladenosine (20%), adenine (12%), uric acid (5%), and N6-benzyladenine (0.3%). In the case of (14C-8)-N6-benzyladenosine-5'-phosphate, a total of 28% of the radioactivity was recovered in the 48-hr urine collection and the following metabolites were isolated: N6-benzyladenosine (40%), uric acid (12%), adenine (trace), and unidentified urea derivatives (30%). Metabolism of N6-benzyladenosine appears to involve N-debenzylation to some extent, followed by conversion to adenine and uric acid. N6-Benzyladenosine and its 5'-phosphate differ from other adenosine analogs in being retained in significant amounts by the animals.

Adenosine↗
PubMed1979

Insulin-induced growth hormone responses in patients with prostatic carcinoma.

Insulin-induced pituitary growth hormone (GH) response was studied in 12 patients with prostatic carcinoma. Three patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. The patients subsequently presented clinically with rapidly progressing disease. Such observations are compatible with the viewpoint that abnormally high or low GH levels systemically present, may be associated with a particularly bad clinical prognosis. Further studies will clarify this relationship.

Adenocarcinoma↗
PubMed1979

Relationship of prior hormonal therapy to subsequent estramustine phosphate treatment in advanced prostatic cancer.

The relationship of prior hormonal therapy to subsequent response on estramustine phosphate (Estracyt) was examined in 107 patients with advanced prostatic cancer treated in two different Phase II chemotherapy trials. In both trials patients with the longest prior hormonal treatment were the least likely to respond to estramustine phosphate. Patients in the series from the National Prostatic Cancer Project with a response classification to prior hormonal therapy had only a 26 per cent response to subsequent estramustine phosphate therapy, whereas 40 per cent of those with no prior response to hormonal therapy responded to estramustine phosphate. This latter group had the shortest average disease duration from diagnosis. The sample of prostate cancers studied appeared to include groups that were sensitive to both hormones and cytotoxic activity as well as to either of these two alone. These data support the contention that estramustine phosphate may act both as an estrogenic and a cytotoxic agent.

Aged↗
PubMed1979

Phase II evaluation of diglycoaldehyde, VP-16-213, and the combination of methyl-CCNU and beta-2'-deoxythioguanosine in previously treated patients with colorectal cancer: an Eastern Cooperative Oncology Group study (EST-1275).

The Eastern Cooperative Oncology Group assessed the activity of diglycoaldehyde (DGA), VP-16-213, and the combination of methyl-CCNU and beta-2'-deoxythioguanosine in previously treated patients with advanced colorectal cancer. Objective responses were seen in two of 40 evaluable patients receiving methyl-CCNU and beta-2'-deoxythioguanosine and in one of 35 patients receiving DGA. None of 33 patients responded to VP-16-213, but one death related to sepsis and bone marrow failure occurred. Survival of patients whose previous chemotherapy included a nitrosourea was markedly shortened compared to those who had not been exposed to nitrosoureas. With the possible exception of DGA, further treatment of patients with colorectal cancer with these therapies is not warranted.

Aldehydes↗
PubMed1978

Pre- and postoperative uses of CEA.

CEA plasma levels obtained prior to definitive surgery in patients with colorectal cancer in our hands have predictive ability. An elevated CEA greater than 2.5 ng/ml recorded by our laboratory means an increased risk of subsequent local recurrence or of later metastatic disease. The question as to whether or not this is additive as a prognostic variable when tested against careful histopathological staging remains. As a monitor, CEA will detect recurrence. Again, the problem as to how accurate this is remains. If we use two consecutive elevations of plasma CEA greater than 2.5 ng/ml as a criteria, we encounter about 15% false positives which must be weighed against finding disease significantly earlier in about one-third of the patients followed. Our data for second-look procedures indicate clearly that when used in patients with an elevated CEA laparotomy may be useful and further studies showed the presence of disease in 11 of 14 patients with an elevation following surgery for two consecutive tests were greater than 2.5 ng/ml. Two were operable. The significance of these findings is described.

Carcinoembryonic Antigen↗