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Biomedical subjects

M Rotman

Publications and source records attributed to M Rotman.

At least 37 records · Page 2Linked to original sources
PubMed1990

Diminished survival of young blacks with adenocarcinoma of the prostate.

The survival rates of 117 black and white patients treated by primary radiation for carcinoma of the prostate at the State University of New York Health Science Center at Brooklyn and Kings County Hospital Center were analyzed according to age and race. In addition, stage, grade, and delay time in seeking medical attention were analyzed. Survival was similar in both young (less than 60 years) and old (greater than or equal to 60 years) patients, with 45% and 41% 5-year-survival rates, respectively. Survival was better in white patients, 48% 5-year survival, than in blacks, 35% 5-year survival. Black patients presented with higher stage disease than whites (p less than 0.01). This trend was even greater in young black males, who had higher grade (64% versus 11%; p less than 0.04) and higher stage tumors (p less than 0.05). In addition, young blacks delayed seeking medical attention greater than 3 months 72% of the time, as compared to 0% in white young males (p less than 0.005). A survival difference was also seen in young blacks as compared with young whites: 3.9-year median survival versus 6.0-year median survival, respectively.

Black or African American↗
PubMed1990

Solitary brain metastasis: results of an RTOG/SWOG protocol evaluation surgery + RT versus RT alone.

From 1983 through 1986, the Southwest Oncology Group and Radiation Therapy Oncology Group conducted an intergroup study designed to evaluate the effectiveness of surgical resection in those patients with solitary central nervous system (CNS) metastases. The study was initially designed as a prospective randomized trial. Because of difficulty accruing patients, the registration format was altered and the patients were placed on study according to physician preference. Ninety-seven patients were registered on study and 80 patients were eventually analyzed. Fifty-five patients underwent radiation therapy alone and 25 patients received surgery and radiation. Fifty-nine percent of those patients undergoing radiation therapy alone improved or stabilized while 79% of those patients undergoing surgery and radiation therapy improved or stabilized. Eventually, 22% of the surgically treated patients failed in the brain while 45% of the patients undergoing radiation therapy exhibited a CNS relapse. Survival was improved when corrected for other prognostic factors in those patients undergoing surgical resection. Although not a prospective randomized trial, this study does suggest an improvement in the survival of a select group of patients able to tolerate neurosurgical resection.

Brain Neoplasms↗
PubMed1989

Dictyostelium erasure mutant HI4 abnormally retains development-specific mRNAs during dedifferentiation.

The Dictyostelium mutant HI4 progresses through morphogenesis normally, but is defective in the reverse program of dedifferentiation. In contrast to dedifferentiating wild-type cells, HI4 cells retain the capacity to rapidly reaggregate well after the "erasure event" employing a nonchemotactic aggregation mechanism involving random collisions and cohesion. They also do not lose contact sites A (gp80) at the prescribed time in the dedifferentiation program. HI4 cells accumulate transcripts of the cysteine protease gene CP2 (formerly referred to as 16G1) and the cohesion glycoprotein gene gp80 at the correct times in the morphogenetic program, but abnormally retain these transcripts at high levels well after the prescribed times at which they are lost in wild-type cells during the reverse program of dedifferentiation. The retention of these mRNAs in HI4 cells after the erasure event is not due to abnormal maintenance of a high level of intracellular cAMP during dedifferentiation. The rapid reduction in the level of gp80 transcript which can be effected by the addition of cAMP prior to the erasure event in wild-type cells is also retained by HI4 cells well after the erasure event. The results suggest that cells possess at least two mechanisms for the reduction of gp80 transcript. One involves the immediate response to cAMP and may function during the forward program of development. The second functions specifically during the reverse program of dedifferentiation. It is this latter, erasure-specific mechanism which is selectively defective in the HI4 variant.

Blotting, Northern↗
PubMed1988

Characterization of Na+-linked and Na+-independent Cl-/HCO3- exchange systems in Chinese hamster lung fibroblasts.

The PS120 variant of Chinese hamster lung fibroblasts which lacks Na+/H+ exchange activity was used to investigate bicarbonate transport systems and their role in intracellular pH (pHi) regulation. When pHi was decreased by acid load, bicarbonate caused pHi increase and stimulated 36Cl- efflux from the cells, both in a Na+-dependent manner. These results together with previous findings that bicarbonate stimulates 22Na+ uptake in PS120 cells (L'Allemain, G., Paris, S., and Pouyssegur, J. (1985) J. Biol. Chem. 260, 4877-4883) demonstrate the presence of a Na+-linked Cl-/HCO3- exchange system. In cells with normal initial pHi, bicarbonate caused Na+-independent pHi increase in Cl(-)-free solutions and stimulated Na+-independent 36Cl- efflux, indicating that a Na+-independent Cl-/HCO3- exchanger is also present in the cell. Na+-linked and Na+-independent Cl-/HCO3- exchange is apparently mediated by two distinct systems, since a [(tetrahydrofluorene-7-yl)oxy]acetic acid derivative selectively inhibits the Na+-independent exchanger. An additional distinctive feature is a 10-fold lower affinity for chloride of the Na+-linked exchanger. The Na+-linked and Na+-independent Cl-/HCO3- exchange systems are likely to protect the cell from acid and alkaline load, respectively.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Preparation of 6-125I-labeled amiloride derivatives.

Amiloride and certain of its derivatives are effective inhibitors of Na/H antiporters and of epithelial Na channels. We describe a simple method for the preparation of a variety of pharmacologically active 6-iodoamiloride derivatives that are labeled with 125I at high specific radioactivity. 6-Dechloroamiloride derivatives (bearing a hydrogen atom instead of the chlorine at the 6 position of the amiloride molecule) are reacted with 125ICl, prepared by the oxidation of the iodide in Na125I preparations. The 125I-labeled derivatives are separated from free 125I by anion exchange chromatography, or purified by thin layer chromatography. Both 6-dechloroamiloride and 5-(N-alkyl)-6-dechloroamiloride derivatives can be labeled by this method, with yields varying between 10 and 70%, depending on the ICl concentration and the structure of the 5-N-alkyl group. Efficient radiolabeling at high specific radioactivity also depends on the use of freshly prepared batches of 125I. Using carrier-free 125I, [125I]6-iodoamiloride and [125I]6-iodo-5-(N-tert-butyl)amiloride were prepared with yields of 27 and 22%, respectively. Potential applications of the 125I-labeled amiloride derivatives include ligand binding and affinity labeling experiments.

Amiloride↗
PubMed1988

Radiation-treated carcinoma of prostate. Comparison of survival of black and white patients by Gleason's grading system.

The survival of 117 black and white patients treated by radiation for carcinoma of the prostate at SUNY Health Science Center at Brooklyn (SUNY/HSCB) and Kings County Hospital Center (KCHC) was analyzed according to Gleason's grading system. The effect of total pattern score and its relationship to stage and survival and to race were intercompared. In both black and white racial groups, there was strong correlation between high pattern score and high stage p = less than 001. The percentage of black patients presenting with high pattern score (7-10) was significantly greater, 43 versus 27%; this adversely affected stage and survival. The median survival for white and black patients was 4.8 and 3.2 years, respectively; p = 0.007. Stage for stage and grade for grade, survival was similar in both racial groups.

Adenocarcinoma↗
PubMed1988

Peritoneal carcinomatosis: imaging with intraperitoneal injection of I-131-labeled B72.3 monoclonal antibody.

Monoclonal antibody (MoAb) B72.3 is reactive with a variety of carcinomas such as colorectal and ovarian carcinoma and not reactive with a range of normal tissues in adults. Twelve patients, ranging in age from 16 to 63 years, with metastatic colorectal or appendiceal carcinoma were studied by means of radioimmunoscintigraphy after injection of 5-10 mCi (185-370 MBq) of iodine-131-labeled B72.3 immunoglobulin G (IgG). Eight of the 12 patients had positive scans. In three of these patients the MoAb scan depicted tumors that were not found by other means. Positive scans had excellent correlation with surgical findings in seven patients and caused underestimation of the extent of disease in one patient. In one patient the scan was technically inadequate and could not be evaluated. In three patients the scan was negative. No adverse reactions were associated with the infusions.

Adenocarcinoma↗
PubMed1988

Choroidal melanoma: I-125 plaque therapy.

An iodine-125 eye plaque was used to treat 58 patients with choroidal melanoma. Patients were followed up for a mean of 48.7 months. Fifty patients had medium-sized lesions (height between 3.1 and 8.0 mm and base diameter less than 16.0 mm), and six patients had large lesions. There were 24 lesions less than 3.0 mm from the optic nerve. The average radiation dose to the apex of the tumor was 8,468 cGy (dose rate, 71 cGy per hour). Initial local disease control was achieved in 50 patients (86.2%). One patient with local treatment failure received another plaque treatment, which controlled disease, so the total disease control rate was 87.9%. Only eight patients died of their disease. Complications were similar to those with other treatment methods, but none of the patients in this study developed optic nerve atrophy.

Brachytherapy↗
PubMed1988

Pilot study of interaction of radiation therapy with doxorubicin by continuous infusion.

Doxorubicin was initially administered alone by continuous infusion for 5 days every 3 weeks in escalating doses to 13 patients with advanced metastatic and/or recurrent malignancies. The maximum tolerable dosage was 13 mg/m2 per day for 5 days. Kinetic data showed a steady level of 60 ng/ml for 4 days and a biphasic disappearance curve. Radiation therapy (150-200 cGy per session) was then administered in 5-day cycles, every 3 weeks, concomitantly with continuous infusion of doxorubicin (12 mg/m2 per day) to 21 patients with various advanced unresectable recurrent or metastatic malignancies. Four of 9 patients with soft tissue sarcomas achieved complete response after a radiation dose of 2,206 +/- 590 (SD) cGy and 3 had partial response; the median durations of the response were 142 +/- 65 (SD) weeks for complete response and 28 +/- 10 weeks for partial response. Of 4 patients with primary hepatoma, 2 achieved partial response after 1,290 +/- 210 cGy. No response was seen in any of the 7 patients with adenocarcinoma of the gastrointestinal tract or breast. Complications of this regimen included moderate leukopenia and thrombocytopenia, mucositis, skin erythema, and decrease of the ventricular ejection fraction at a cumulative doxorubicin dose of 840 mg/m2. We conclude that doxorubicin given by protracted infusion can be safely administered with concomitant radiation and appears to enhance the effects of radiation on most soft tissue sarcomas and on some hepatocellular carcinomas.

Adolescent↗
PubMed1987

Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group.

This report details the patterns of tumor recurrence in two prospective randomized studies involving 551 patients with histologically proven unresectable or medically inoperable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Patients were treated according to two protocols, depending on the stage of the tumor: (1) Patients with T1, 2, 3-NO, 1, 2 tumors were randomized to four different regimens: 4000 cGy split course (2000 cGy in five fractions, per 1 week, 2 weeks rest and additional 2000 cGy in five fractions, per 1 week) or 4000, 5000, or 6000 cGy continuous courses, five fractions per week. (2) Patients with T4, any N or N3, any T stage tumors were randomized to be treated with 3000 cGy tumor dose (TD), ten fractions in 2 weeks, 4000 cGy split course (described above), or 4000 cGy continuous course. In the patients with less advanced tumors (Study 1) the intrathoracic failure rate within the irradiated volume was 48% with 4000 cGy continuous, 38% with 4000 cGy split course or 5000 cGy continuous, and 27% for patients receiving 6000 cGy continuous course. The failure rate in the nonirradiated lung ranged from 25% to 30% in the various groups. Patients with adenocarcinoma or large cell undifferentiated carcinoma had better intrathoracic tumor control (35%) than those with squamous cell carcinoma (20%). The incidence of distant metastases was 75% to 80% in all histologic groups. Distant metastases appeared sooner after therapy in the patients with adenocarcinoma or large cell undifferentiated carcinoma. The initial failure rate in the brain was 7% in patients with squamous cell carcinoma, 19% with adenocarcinoma, and 13% in patients with large cell carcinoma. The ultimate incidence of brain metastases was 16% in squamous cell carcinoma, and 30% for adenocarcinoma or large cell undifferentiated carcinoma. Higher doses of irradiation will be necessary in order to improve the intrathoracic tumor control. Clinical trials by the Radiation Therapy Oncology Group, some of them involving multiple daily fractionation, are in progress. Furthermore, because of the high incidence of distant metastases, effective systemic cytotoxic agents are critically needed to improve survival of lung cancer patients. The high frequency of brain metastases suggests that, as in small cell carcinoma of the lung, elective irradiation of the brain may be necessary, if not to improve survival to enhance the quality of life of patients with adenocarcinoma and large cell carcinoma.

Adenocarcinoma↗
PubMed1987

A dextran-bound amiloride derivative is a selective inhibitor of Na+/H+ antiport. Application for studying the role of the antiporter in cellular proliferation in human fibroblasts.

Inhibitors of Na+/H+ exchange from the amiloride series are known to accumulate within the cell and cause an inhibition of a variety of cellular functions. In order to render the amiloride molecule impermeable to cells, we have synthesized a potent amiloride analog, 5-N-(3-aminophenyl)amiloride (compound A35, Ki = 60 nM). The isothiocyanate derivative of A35 (A35-NCS) was coupled to soluble dextrans of 15-20 kDa that have been derivatized with diaminoalkane spacer groups. Dextran-bound amiloride derivatives showed good inhibition of Na+/H+ exchange in human foreskin fibroblasts and A431 cells. Among several spacer groups tested, dextran derivatized with ethylenediamine showed the highest inhibitory activity. The intrinsic inhibitory potency of this polymer increased with increasing degree of substitution with A35, approaching that of free A35 with substitution of approximately 3 mol of A35 per mole of dextran. Coupling to dextran largely diminished side effects of the amiloride derivative on cells such as the inhibition of protein synthesis. A35-dextran was an effective inhibitor of serum-induced reinitiation of DNA synthesis in human foreskin fibroblasts in a bicarbonate-free medium, pH 7.1, but had little effect when either the pH of the medium was more alkaline or when the medium contained a bicarbonate buffer. These findings suggest that the selective inhibition of Na+/H+ antiport by A35-dextran prevents the reinitiation of DNA synthesis when the external conditions are such that the antiporter activity is required for the establishment of a permissive intracellular pH. Polymer-bound amiloride analogs should be useful as selective inhibitors in studies of the physiological role of the Na+/H+ antiporter, as well as for affinity purification of the antiporter.

Amiloride↗
PubMed1987

Treatment of advanced bladder carcinoma with irradiation and concomitant 5-fluorouracil infusion.

Nineteen patients with locally advanced bladder cancer were treated with irradiation and concomitant 5-fluorouracil intravenous infusion with or without bolus mitomycin. Eighteen of the 19 patients were evaluated for local response. Eleven of the 18 patients (61%) obtained a complete local response within 3 to 6 months. An additional five patients (28%) showed tumor regression to a superficial state controlled by local transurethral resection and intravesical chemotherapy making the overall local clearance rate 16/18 (89%). The remaining two patients (11%) required salvage cystectomy for persistent disease and presently show no evidence of disease. Nine patients have died. Two patients died of intercurrent disease, six patients died of metastatic disease, and one patient who died from regional disease showed no evidence of local bladder tumor at the time of death. Berkson-Gage life-table analysis yields an adjusted survival of 62.5% at 5 years. Late complications included five patients with hemorrhagic cystitis, two patients with a contracted bladder, and one patient with a hemorrhagic radiation proctitis.

Aged↗