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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↗
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

Radiotherapy with or without misonidazole for patients with stage IIIB or stage IVA squamous cell carcinoma of the uterine cervix: preliminary report of a Radiation Therapy Oncology Group randomized trial.

Between August 1980 and November 1984, 119 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (4600 cGy pelvis plus 1000 cGy parametrial boost) followed by intracavitary or external boost to the primary with or without misonidazole (MISO) (400 mg/m2 daily 2 to 4 hours prior to radiation therapy). Patients in the two treatment groups were evenly distributed with respect to stratification variables including stage, Karnofsky Performance score, and positivity of para-aortic nodes. Eighty-nine percent of patients had Stage IIIB disease and 88% had a Karnofsky score of 80 or better. Seventy-five percent of patients treated with radiation therapy alone and 79% of patients treated with radiation therapy plus MISO received a boost via intracavitary application. Life threatening (Grade 4) complications occurred in 5 patients receiving radiation therapy alone and one patient receiving radiation therapy plus MISO. MISO toxicity (Grade 3) was limited to severe nausea and vomiting in two patients. With 119 evaluable patients and a median follow-up of 33 months, 64% of patients receiving radiation therapy alone are alive at 18 months compared with 54% for patients assigned to radiation therapy plus MISO. The median survival for patients treated with radiation therapy alone and radiation therapy plus MISO was 1.9 years and 1.6 respectively. At this point in the study the difference in survival is inconsistent with the hypothesis of an improvement associated with MISO. There have been 23 deaths among the 49 patients treated with radiation therapy plus MISO who have been followed for at least 18 months compared with 17 deaths in 48 patients treated with radiation therapy alone. The chance of observing this number of deaths with radiation therapy plus MISO if the addition of MISO improves survival by 10 to 20% is 0.003 and less than 0.001, respectively. The addition of MISO to radiation failed to improve survival for these patients. The results cannot be explained by an uncharacteristically high survival on the radiation therapy alone arm or by an imbalance in the distribution of prognostic factors. Local-regional control remains a problem in the management of patients with advanced cervical carcinoma. More effective and less toxic radiosensitizing agents are needed.

Adolescent↗
PubMed1986

Depletion of cellular ATP inhibits Na+/H+ antiport in cultured human cells. Modulation of the regulatory effect of intracellular protons on the antiporter activity.

The metabolic energy dependency of Na+/H+ exchange activity was investigated in cultured human A431 carcinoma cells and foreskin fibroblasts. Following the activation of Na+/H+ exchange which results from loading cells with Na+ or Li+, depletion of cellular ATP by incubation with metabolic inhibitors causes an inhibition of Na+/H+ exchange activity. This inhibition is reversible and correlates with the extent of the reduction in the ATP pool. On the other hand, reduction of the intracellular pH (pHi) to approximately 6.0-6.2 results in a similar effective activation of Na+/H+ exchange in both control and ATP-depleted cells. Na+/H+ exchange activity in ATP-depleted cells that either have or have not been loaded with Na+ shows a steep dependency on pHi, being essentially abolished above pHi of 6.4-6.5, whereas control cells show a considerable activity also at more alkaline pHi values. Thus, Na+/H+ exchange activity in ATP-depleted cells shows an increased dependency on intracellular protons. These findings suggest that although metabolic energy is not required as a driving force for Na+/H+ antiport, depletion of metabolic energy substrates inhibits the antiporter activity due to a modulation of an intracellular proton-dependent regulatory mechanism.

Adenosine Triphosphate↗
PubMed1986

Comparison of 32P therapy and sequential hemibody irradiation (HBI) for bony metastases as methods of whole body irradiation.

We report a retrospective study of 15 patients with prostate carcinoma and diffuse bone metastases treated with sodium 32P for palliation of pain at Downstate Medical Center and Kings County Hospital from 1973 to 1978. The response rates, duration of response, and toxicities are compared with those of other series of patients treated with 32P and with sequential hemibody irradiation. The response rates and duration of response are similar with both modalities ranging from 58 to 95% with a duration of 3.3 to 6 months with 32P and from 75 to 86% with a median duration of 5.5 months with hemibody irradiation. There are significant differences in the patterns of response and in the toxicities of the two treatment methods. Both methods cause significant bone marrow depression. Acute radiation syndrome, radiation pneumonitis, and alopecia are seen with sequential hemibody irradiation and not with 32P, but their incidence can be reduced by careful treatment planning. Hemibody irradiation can provide pain relief within 24 to 48 h, while 32P may produce an initial exacerbation of pain. Lower hemibody irradiation alone is less toxic than either upper hemibody irradiation or 32P treatment.

Bone Neoplasms↗
PubMed1985

Complications of combined surgery and radiation therapy for carcinoma of the endometrium.

Long-term gastrointestinal (GI) and urinary tract (UT) complications were evaluated in 133 women with carcinoma of the endometrium who were treated by both radiotherapy and hysterectomy. Major complications developed in 8% of patients who received external pelvic radiation but in none with intracavitary radiation. GI complications were more frequent and more severe in patients receiving external pelvic radiation than in those who received only intracavitary radiotherapy, irrespective of the sequence of treatment. UT complications were more frequent with prehysterectomy external radiotherapy (N = 39) than with posthysterectomy external radiotherapy (N = 21).

Brachytherapy↗
PubMed1977

Supportive therapy in radiation oncology.

Measures for supportive care of the radiation therapy patient are presented. These include emotional support prior to and during the course of therapy facilitated by a written interview that allows the radiation oncologist to be a supportive communicator of realistic information. A discussion is made of the support of body tissues affected by combination radiation and chemotherapy. These tissues usually include skin, oral, esophageal and intestinal mucosa, and teeth. Means of maintaining nutritional support following weight loss of patients during therapy are described.

Adult↗
PubMed1977

Radiation therapy of choroidal melanoma.

During the past 8 years, 32 patients with melanoma of the choroid have been treated with cobalt-60 ophthalmic applicators. Excluding three patients lost to follow-up, 24 patients who have now been observed for at least 3 years after treatment form the subject of this study. Each application but two delivered 8,500 to 10,000 rads to the tumour apex. A second application was performed in large tumours showing a poor response to the initial plaque treatment. The factors affecting results include age of the patient, tumour size, total dose delivered, and dose rate. Three out of seventeen patients with tumour diameters greater than 12 mm died of their disease with pulmonary and/or liver metastasis. Three eyes required enucleation and no residual tumour was found in two specimens. Three patients, average age 76 years, died from causes other than melanoma. An 83 per cent relative survival, excluding the three patients lost to follow-up, compares favourably with enucleation. The low incidence of metastasis after radiotherapy suggests augmentation and/or continuation of the host's immune response. Low energy radiation using Iodine-125, with its unusual protective characteristics is ideal for treatment of choroidal melanoma.

Aged↗