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Biomedical subjects

M Rotman

Publications and source records attributed to M Rotman.

At least 19 recordsLinked to original sources
PubMed1992

Does extent of surgery influence outcome for astrocytoma with atypical or anaplastic foci (AAF)? A report from three Radiation Therapy Oncology Group (RTOG) trials.

103 patients with the diagnosis of AAF were identified from the RT/BCNU arms of 3 RTOG malignant glioma trials. Pre-treatment tumor size was less than 5 cm for 48% and greater than or equal to 5 cm for 52%, and tumor sites were frontal lobe in 55%, temporal in 25%, and parietal in 16%. Surgery consisted of biopsy for 30%, partial resection for 56%, and total resection for 14%. Extent of surgery correlated with age, with 81% of patients less than 40 undergoing partial/total resection vs. 60% of those over 40 (P = 0.019). The median survival time (MST) of patients undergoing partial/total resection was 49 mo., vs. 18 mo. for those biopsied only (P = 0.002). Patients with frontal location had longer MST than those with non-frontal lesions (MST: 49 vs. 25 mo., P = 0.047), while no survival difference was apparent by univariate analysis of tumor size. Multivariate analysis demonstrated that only younger age, frontal location, and smaller tumor size correlated significantly with extended survival. Extent of surgery was not predictive. The close correlation between young age and extensive surgery obscures the survival advantage for greater surgery seen with univariate analysis. Smaller tumor size and frontal location favorably influence outcome even when adjusted by age.

Adult↗
PubMed1992

A report of RTOG 8206: a phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases.

Hemibody irradiation (HBI) in a single exposure is an effective and safe technique for palliation of symptoms due to widespread bony metastases (RTOG 78-10). The present study (82-06) sought to explore the possibility that HBI added to local-field irradiation might delay the onset of metastases in the hemibody effected, as assessed by bone scans and X rays, and decrease the frequency of further treatment. The results of this clinical trial establish that 800 cGy of HBI is indeed causes micro-metastases to regress, perhaps completely. A total of 499 patients were randomized to receive either HBI or no further treatment following completion of standard palliative local field irradiation (300 cGy x 10) to the symptomatic site. Improvement was seen in time-to-disease progression at one year, 35% for local + HBI versus 46% on the local-only control arm. Time-to-new disease in the targeted hemibody was also improved. At one year, 50% of patients on the local + HBI arm showed new disease compared to 68% on the local-only arm. Furthermore, the median time-to-new disease within the targeted HBI area was 12.6 months for the local + HBI arm versus 6.3 months for patients in the local-only arm. Time-to-new treatment within the hemibody segment was also delayed. At one year, 76% of the local only group had been retreated versus 60% in the local + HBI arm. There were no fatalities and no radiation pneumonitis was seen in the local + HBI arm. Overall, the incidence of toxicities was low (5-15%). The occurrence of severe hematopoetic toxicities were significantly different in the local + HBI arm, but they were transitory. One life-threatening thrombocytopenia occurred, for a limited time, indicating excellent tolerance to HBI. This clinical trial demonstrates that HBI has the potential to be used to treat systemic and occult metastases, particularly if both halves of the body can be treated.

Aged↗
PubMed1992

The prognostic significance of race and survival from prostate cancer based on patients irradiated on Radiation Therapy Oncology Group protocols (1976-1985).

A number of studies have identified race as a prognostic factor for survival from prostate cancer. To evaluate the prognostic significance of race in a controlled setting, we evaluated 1294 patients treated on three prospective randomized trials conducted by the Radiation Therapy Oncology Group between 1976 to 1985. One-hundred and twenty (9%) of the patients were coded as black, while 1077 (83%) of the patients were coded as white. Protocol 7506 included 607 patients with clinical Stage T3-T4Nx or T1b-T2N1-2. Protocol 7706 included 484 patients with clinical Stage T1b or T2 who were node negative. Protocol 8307 included 203 Stage T2b-T4 patients with no lymph node involvement beyond the pelvis. Univariate and multivariate analyses were used to assess the possible independent significance of race and other prognostic factors, including Gleason score, serum acid phosphatase, nodal status, and hormonal status. Protocols 7706 and 8307 revealed that race was not of prognostic significance for disease-free or overall survival by either univariate or multivariate analysis. Univariate analysis of Protocol 7506 revealed that the median survival for blacks was somewhat shorter (5.4 years vs. 7.1 years, p = 0.02). This difference persisted after a multivariate analysis. A higher percentage of blacks treated on 7506 had an abnormally elevated serum acid phosphatase compared to whites (p = 0.006), and the time to distant failure tended to be shorter (p = 0.07). These findings suggest that blacks treated on 7506 may have had more extensive disease at presentation. Based on these prospective randomized trials, it is most likely that the lower survival noted for black Americans with prostate cancer reflects the tendency for blacks to present with more advanced disease. Differences in access to care, the quality of care received, and the impact of co-morbid conditions may explain the lower survival reported for black Americans elsewhere in the literature.

Black or African American↗
PubMed1992

High grade adenocarcinoma of prostate in smokers of ethnic minority groups and Caribbean Island immigrants.

The degree of differentiation of 670 blacks and white patients treated from 1980-1990 for curative and palliative external beam radiation therapy and surgery at State University of New York Health Science Center at Brooklyn and Kings County Hospital were analyzed retrospectively, stratified according to race, age, smoking, and grade. In addition stage, birth place and median survival were also analyzed. Overall mean age was 69 years (Std. Dev. 8.97). 69% were blacks and 27.8% were whites. 65.4% were smokers and 34.6% were non-smokers. Smokers had high incidence of more invasive and high grade adenocarcinoma of prostate (p < or = 0.00005) compared to control group (non-smokers with prostate carcinoma). Statistically significant difference was found in the degree of differentiation of carcinoma of prostate in smokers compared to non-smokers. Smokers had 15.04% well, 27.07% moderate, and 57.89% poorly differentiated adenocarcinoma compared to non-smokers in which 37.1% were well, 45.16% moderate, and 17.74% poorly differentiated cancer of prostate (p < or = 0.00005). Sixty-three percent blacks and 40.16% whites had Stage D cancer (p < or = 0.00005). 68.3% smokers and 53.3% non-smokers had Stage D cancer (p = 0.01). Overall median survival for blacks was 74.04 months compared to whites of 115.73 months (p < or = 0.00005).

Adenocarcinoma↗
PubMed1992

Potentiation of radiation lethality in mouse melanoma cells by mild hyperthermia and chloroquine.

To test the hypothesis that radiosensitization by combined mild hyperthermia and chloroquine may be increased by the presence of melanin in treated cells, Cloudman melanotic mouse melanoma S91/6 cells, and the amelanotic S91/amel cells were incubated during a 3 h post-irradiation period with 0.03 mM chloroquine at 41 degrees C. A considerable increase in radiation lethality was observed (radiation potentiation factor > 1.6) in both cases. Addition of 0.1 mM isobutyl-methyl xanthine (IBMX), a promoter of melanin synthesis, to the growth medium of S91/6 cells 10 days before irradiation, did not further increase the lethality of radiation followed by combined heat and chloroquine treatment. Under these conditions, toxicity to unirradiated cells was slight. On the other hand, 10 microM chloroquine showed similar toxicity to unirradiated B-16 mouse melanoma cells, but did not increase radiation lethality. Factors other than melanin content therefore play a role in the potentiation of radiation lethality by mild hyperthermia and chloroquine.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Potentiation of radiation lethality in HeLa cells by combined mild hyperthermia and chloroquine.

Evidence is presented for the interaction of X irradiation, slightly toxic levels of chloroquine, and mild hyperthermia in the inactivation of colony-forming ability in asynchronous HeLa cells. A three-way interaction was observed which resulted in the potentiation of radiation-induced lethality. There was little evidence of toxicity in unirradiated cells incubated for 3 h with 0.1 mM chloroquine at either 37 or 41 degrees C. The radiopotentiation factor, which is similar to the dose modification factor, was determined from dose-response curves by relating the reciprocal of the slope (D0) of the reference survival curve to that of the survival curve of cells receiving the combined postirradiation treatment with chloroquine and mild hyperthermia. Radiopotentiation factors larger than 1.7 were obtained irrespective of whether the reference D0's were obtained from survival curves for cells irradiated at 37 degrees C without drug or from cells receiving postirradiation treatment with heat or drug only.

Cell Survival↗
PubMed1991

Locally advanced paranasal sinus and nasopharynx tumors treated with hyperfractionated radiation and concomitant infusion cisplatin.

Fourteen patients with paranasal sinus complex and nasopharynx tumors were treated at State University of New York Health Science Center at Brooklyn (Brooklyn, NY) with a regimen of split-course hyperfractionated radiation (120 cGy/fraction) and concomitant cisplatin infusion (5 to 7 mg/m2/24 hours). All of the patients had T4 tumors or massively recurrent disease with base of skull or facial bone involvement. Twelve patients were treated with curative intent receiving total doses of 6000 to 6960 cGy (modal 6750 cGy), whereas two patients were treated with less than 5000 cGy as palliation. Eleven of the 12 patients (92%) achieved a complete response, and 7 of 12 (58%) are alive at 35 to 72 months (mean, 47 months). Five patients are alive with no evidence of disease, and two with a local recurrence. Three patients died of distant disease, and two died from a local recurrence. When the response to treatment was analyzed based on tumor volume and radiation dose, only two of nine lesions measuring between 4 to 10 cm failed locally. The two palliative patients had almost complete local clearance of the disease but died at 2 and 8 months, respectively. In nine patients, the eye or optic nerve was included in the treatment field and received between 2000 to 6960 cGy. Only one of these nine patients had ophthalmic complication and this was confined to the cornea.

Carcinoma, Adenoid Cystic↗
PubMed1991

Leishmania donovani: characterization of a 38-kDa membrane protein that cross-reacts with the mammalian G-protein transducin.

We investigated the presence in Leishmania donovani promastigotes of proteins with homology to the G-proteins known to mediate signal transduction in other organisms. [alpha 32P]GTP binding experiments revealed the presence in the promastigote membrane of GTP-binding sites with high affinity and specificity. Experiments with antisera directed against mammalian G-proteins showed that the promastigotes possess a 38-kDa protein (p38) which strongly reacts with an antiserum directed against a decapeptide containing the C-terminal sequence of transducin, the G-protein that mediates visual signal transduction. The interaction of p38 with the antiserum is specifically blocked by the decapeptide antigen. p38 is enriched in plasma membranes and is absent in cytosol and in a mitochondria-enriched fraction. p38 was also detected in two other Leishmania species, L. mexicana and L. major. The migration of p38 upon sucrose gradient centrifugation of detergent extract of L. donovani membranes corresponded to Mr of approximately 70,000, indicating that p38 is part of an oligomeric structure. The findings suggest that p38 may be a component of a transmembrane signal transduction system in Leishmania.

Amino Acid Sequence↗
PubMed1991

Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses.

Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens.

Absorption↗
PubMed1990

Concomitant continuous infusion chemotherapy and radiation.

Attempts to duplicate the cytotoxic effect of oxygen on radioresistant tissues spurred a search by radiation oncologists for other radiosensitizing techniques. This led to large-scale investigations using neutrons and other heavy particle radiations, hyperthermia, altered fractionation schedules, and the systemic use of the halogenated pyrimidines and the electron-affinic compounds. Unfortunately, the promise that the nitroimidazole compounds would selectively sensitize the radioresistant tumor cells and prove to be an effective systemic agent has not been borne out in clinical trials thus far. Existing pharmokinetic and cytokinetic studies have suggested that continuous infusion chemotherapy given concomitantly (CCIC) with irradiation (RT) acts synergistically, resulting in a significant increase in tumor cell killing. These observations have been supported by clinical research studies treating certain epithelial cancers that have resulted in considerably higher locoregional control rates and improved survival. Although initially used in treatment of only advanced or inoperable epithelial carcinomas, CCIC and RT are now being employed in the treatment of lower staged cancers as an organ-sparing procedure. Carcinoma of the anus treated by anteroposterior (AP) resection alone have reported 5-year survival rates of 30% to 60%. CCIC and RT using 5-fluorouracil (5-FU) and mitomycin C have achieved a local control rate of 90% to 100% and a 5-year survival rate of 80% to 86% with sphincter preservation in 90% of these cases. The 5-year survival rate in advanced urinary bladder carcinoma is 25% to 30% for either radiation or surgery and 42% when combined in a preoperative radiation schedule. Using 5-FU CCIC and RT, the local control rate of transitional cell carcinoma of the bladder has been 71% to 86% with a 5-year survival of 62%. 5-FU CCIC and cisplatin and RT used in the treatment of Stages III and IV carcinoma of the cervix yields a locoregional control of 74% compared with the radiation alone local control of 63% for Stage III and 30% for Stage IV disease. Advanced head and neck and paranasal sinus carcinomas treated by cisplatin CCIC and RT show improved tumor clearance even in the presence of bone destruction. A complete response rate of 87% has been reported with the use of cisplatin CCIC and hyperfractionated radiation. Hyperfractionated radiation also appears to improve the local control of advanced head and neck cancers over patients treated with single fractions of radiation with 66% surviving at 22 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Developmental mechanisms regulating the rapid decrease in a cohesion glycoprotein mRNA in Dictyostelium function primarily at the level of mRNA degradation.

During the morphogenetic program in Dictyostelium discoideum, the transcript of the gene encoding the cohesion glycoprotein gp80 accumulates to a maximum level between 4 and 6 hr, (just prior to the onset of aggregation), remains high between 6 and 10 hr (the ripple to loose aggregate stages), and then decreases to less than 10% of the maximum level between 10 and 12 hr (the tight aggregate stage). The level of gp80 transcript also decreases precipitously at the time of the erasure event in the program of dedifferentiation, or when cAMP is added to a dedifferentiating cell population prior to the erasure event. In the dedifferentiation-defective mutant HI4, the cAMP-stimulated system for rapidly reducing the level of gp80 transcript is intact, but the mechanism functioning at the time of the erasure event is defective, demonstrating that the two reduction mechanisms are dissociable. By comparing the levels of gp80 transcript with the levels of in vitro transcription of the gene in isolated nuclei, it is demonstrated that the rapid reduction of gp80 transcript immediately after aggregation and immediately after addition of 10(-4) M cAMP are the result of increased transcript degradation. The rapid reduction of gp80 transcript at the erasure event may also be due to increased transcript degradation, but transcriptional regulation cannot be completely ruled out in this case.

Cell Adhesion Molecules↗
PubMed1990

Adjunctive radiation after radical hysterectomy in stage IB squamous cell carcinoma of the cervix.

The clinical-pathologic records of 178 women with stage IB squamous cell carcinoma treated by radical hysterectomy and pelvic node dissection were reviewed to assess prognostic factors and outcome in relation to adjunctive pelvic radiation. Among 32 women with pelvic nodes metastases, 19 treated with adjunctive radiation had longer recurrence-free intervals and more extrapelvic metastases than 13 nonirradiated women. However, among irradiated women recurrences were more rapidly fatal, so that the survival of the two groups was similar. Among 54 women with deeply invading (10 mm or more) carcinomas confined to the uterus, 17 with adjunctive radiation had recurrence-free intervals and survivals similar to 37 women without radiation, despite more high-risk factors in the irradiated group. The findings suggest that adjunctive pelvic radiation may control pelvic recurrence but not extend survival.

Carcinoma, Squamous Cell↗
PubMed1990

Preliminary results of concurrent radiotherapy and chemotherapy in advanced cervical carcinoma: a phase I-II prospective intergroup NCOG-RTOG Study.

Thirty-eight patients with advanced carcinoma of the cervix were prospectively treated with a concurrent combination of radiotherapy (RT) and chemotherapy (CT) using the drugs 5-fluorouracil (5FU), mitomycin C and cis-platinum as part of a Northern California Oncology Group (NCOG) and Radiation Therapy Oncology Group (RTOG) intergroup study. RT consisted of 36.00 Gy to the pelvis in 4 weeks followed by a 9.00-Gy parametrial boost. This was followed by two intracavitary applications for a total of 4000 mg hr of radium equivalent when possible. 5FU (1000 mg/m2/24 hr for 96 hr by iv infusion) and mitomycin C (10 mg/m2/iv bolus) were given during the second week of external RT. 5FU (dose as above) and cis-platinum (75 mg/m2/iv over 6 hr) were given during the first intracavitary application. Of 36 patients evaluable for toxicity, 11% had grade 3 nonhematological toxicity and 11% had reversible grade 4 hematological toxicity. There were no toxic deaths. A complete response rate of 62.5% was obtained overall (median survival not reached). This study suggests that this particular combination of RT and CT in advanced cervical carcinoma is effective and well tolerated.

Adult↗
PubMed1990

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

Twenty patients with advanced transitional cell carcinoma of the bladder were treated with radiation and concomitant continuous infusion of 5-fluorouracil with or without Mitomycin. Nineteen of 20 patients were assessed for response. Fourteen of 19 patients (74%) obtained a complete response within 3 to 6 months. An additional three patients (15%) acquired and maintained a complete response after local transurethral resection of the tumor and intravesical chemotherapy, raising the overall complete response (CR) rate to 17/19 (89%). Of the two patients with persistent disease, one is alive and well after salvage cystectomy. Eighteen of 20 patients were evaluated for survival with a median follow-up of 38 months. Seven patients remain alive and well 51 to 78 months, whereas three patients died from intercurrent disease. Eight patients died of either distant metastatic disease (7 patients) or regional disease (1 patient). An adjusted survival calculated by the Life Table Method was 53.6% at 5 years, whereas the overall survival was 39%. The combined modality therapy was well tolerated with no need for treatment interruption or reduction in dose. Late bladder complications include one patient with hemorrhagic cystitis, two patients with dysuria, and two with symptoms of irritable bladder. One patient required a colostomy for a chronic hemorrhagic proctitis. Bladder preservation was achieved in 19/20 patients.

Aged↗
PubMed1990

Prophylactic irradiation of the para-aortic lymph node chain in stage IIB and bulky stage IB carcinoma of the cervix, initial treatment results of RTOG 7920.

From November 1979 to October 1986, 367 patients were entered onto RTOG 7920 and randomized to receive either pelvic irradiation alone or pelvic plus para-aortic radiation. Patients with Stage IIB cervical carcinoma who had not undergone curative surgery and patients with Stages IB and IIA cervical carcinoma who were determined by digital exam to have primary tumors measuring 4 cm or greater in lateral dimension were eligible for this study. Clinically apparent or surgically involved para-aortic nodes were reason for exclusion from the study. Pelvic irradiation consisted of 1.6-1.8 Gy per day for 5 days per week to a total of 40-50 Gy. Para-aortic irradiation delivered 44 to 45 Gy in 1.6-1.8 Gy per day, 5 days per week. Pelvic irradiation was to be completed in 4 1/2 to 6 1/2 weeks and para-aortic irradiation in 4 1/2 to 5 1/2 weeks. Intracavitary brachytherapy delivered a total of 4000-5000 mg hr of radium-equivalents or 30-40 Gy to point A. Patients were stratified prior to random treatment assignment by histology, para-aortic nodal status (negative vs. unevaluated), and FIGO stage. As of June 1, 1989, 30 cases were excluded, including five patients who were inevaluable. Two patients who refused the assigned treatment were also excluded. Therefore, a total of 330 cases were analyzable. At 5 years the estimates of survival, the primary endpoint, for the pelvic only and pelvic plus para-aortic irradiation arms are 55% and 65%, respectively (p = 0.043). Several secondary endpoints were also analyzed. Estimates for loco-regional control at 5 years are, for pelvic irradiation only, 66%, and for pelvic plus para-aortic irradiation, 75% (p = 0.21). Distant metastases are estimated in 32% of pelvic irradiation only patients and 25% of pelvic plus para-aortic irradiation patients at 5 years (p = 0.17). When the first disease failure patterns are examined, more patients fail distally when treated only with pelvic radiation than when using pelvic plus para-aortic fields (p = .04). In analysis of patients with grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal complications), 8% of the patients in both groups had grade 3 severe complications. In the pelvic plus para-aortic group, 11 patients had grade 4 and 2 had grade 5 complications, whereas 6 had grade 4 and none had grade 5 in the pelvic only treatment group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗