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J Rotmensch

Publications and source records attributed to J Rotmensch.

71 records · Page 4Linked to original sources

Cytogenetic observations of a human ovarian carcinoma clinically resistant to therapy.

Resistance of a cancer cell to therapy represents an important problem in tumor biology. Hypotheses concerning the mechanism of resistance have included genetic instability, gene amplification, aneuploidy, and altered cell growth kinetics. Cytogenetic assays allow for the analysis of each of these parameters and provide important information concerning tumor heterogeneity. In using cytogenetic analysis, we have analyzed a human ovarian carcinoma clinically resistant to therapy. The ovarian carcinoma had a complex but stable karyotype with a mean chromosome number of 61.7 chromosomes/cell. Approximately 50% of the metaphase preparations examined had double-minute chromosomes, which have sometimes been associated with gene amplification. The frequency of double minutes varied from one pair to hundreds of pairs per cell. Cell cycle kinetic analysis revealed an average generation time of 38 hours. The cells were relatively resistant to doxorubicin in vitro, and the baseline sister chromatid exchange frequency, a measure of genetic instability, was elevated. These results suggest that cytogenetic assays have potential as predictive assays of tumor chemoresistance and may provide information regarding the biologic aggressiveness encountered clinically.

Cell Cycle↗

Evaluation of bolus cis-platinum and continuous 5-fluorouracil infusion for metastatic and recurrent squamous cell carcinoma of the cervix.

The combination of cis-platinum and 5-fluorouracil has been reported to act synergistically with improved response rates in squamous cell carcinomas of the head and neck. The activity of bolus cis-platinum and continuous infusion of 5-fluorouracil in 24 patients with recurrent and metastatic squamous cell carcinoma of the cervix was evaluated. Twelve patients were stage I, 3 were stage II, 5 were stage III, and 4 were stage IV cervical carcinomas. Among the 24 patients, there were 4 complete and 8 partial responses (50%). The overall median response was 24 weeks. The overall cumulative survival was 55% at 40 weeks and 40% at 1 year after beginning this regimen. Complications included 4 patients who developed leukopenia, 3 thrombocytopenia, 11 stomatitis, 14 nephrotoxicity, 4 peripheral neuropathy, and 6 ototoxicity. The combination of cis-platinum and continuous infusion of 5-fluorouracil appears to have useful activity in patients with recurrent or metastatic squamous cell carcinoma of the cervix.

Adult↗

Comparison of human chorionic gonadotropin regression in molar pregnancies and post-molar nonmetastatic gestational trophoblastic neoplasia.

The rate of regression of the beta subunit of human chorionic gonadotropin in patients successfully treated by single-agent chemotherapy with methotrexate (MTX) for postmolar nonmetastatic gestational trophoblastic neoplasia (NMGTN) has not previously been described. In 21 patients with NMGTN treated with MTX, the rate of regression was determined. Nineteen patients had a log-exponential disappearance of serum beta-hCG titers within 100 days. There was a 50% probability of a negative titer at 50 days. Two patients had plateauing titers within 63 days after therapy. There was no difference in beta-hCG disappearance whether MTX with citrovorum factor or MTX alone was administered. Also, the regression rate of beta-hCG titer in the treated patients was compared to 63 patients with spontaneous decline of titers postevacuation of trophoblastic disease. In the postevacuation group there was a 50% probability at 49 days of negative serum titers. All 63 patients had negative titers within 105 days after evacuation.

Chorionic Gonadotropin↗

Faster repair of DNA double-strand breaks in radioresistant human tumor cells.

To investigate the molecular basis of radiation resistance in human tumor cells, the induction and repair of radiation-induced DNA single- and double-strand breaks was determined by DNA elution analysis in two normal human cell lines and 12 early-passage human tumor cell lines of varying radiosensitivities. The radiosensitivities (D0) of the cell lines ranged from 1 to 2.9 Gy. Inherent cellular radiosensitivity was found to directly correlate with the rate at which the DNA double-strand breaks were repaired. Radioresistant cell lines repaired approximately 90% of their radiation-induced DNA double-strand breaks within 1 hr of irradiation while more radiosensitive cell lines required 2-4 hr to repair the same fraction of damage. Radioresistant cell lines also had lower initial DNA double-strand break frequencies. DNA single-strand break induction and repair was not found to be an important factor in the radiation response of human tumor and normal cell lines. Therefore, the rate at which DNA double strand breaks are repaired is a critical factor underlying radioresistance in human tumor cell lines.

Cell Line↗

Sequential methotrexate and 5-fluorouracil in advanced ovarian carcinoma.

Experimental studies have demonstrated that the combined effects of methotrexate and 5-FU may be optimized in schedules of administration where the antifolate is administered prior to the fluoropyrimidine. Seventeen patients with ovarian carcinoma refractory to standard chemotherapy were treated with a sequence of moderate dose MTX (200 mg/m2) and 5-FU. No responses were seen, although the hematologic and gastrointestinal toxicity which was observed was very mild. Because of prior nephrotoxic chemotherapy and the frequent presence of large amounts of "third space" fluid in the form of malignant ascites, patients with ovarian cancer are at high risk for MTX toxicity. In this study, eight patients with significant ascites had higher plasma MTX concentrations measured at 48 and 72 hr following drug administration than nine similar patients without ascites. This suggested delayed excretion of MTX in patients with ascites although this difference was not statistically significant. MTX concentrations in ascites exceeded those in plasma between 6 and 12 hr and remained near 1 microM for 24 hr. Although the lack of response is disappointing, the modest toxicity encountered with the careful drug level monitoring and the favorable pharmacologic findings suggest that this combination of drugs each with established activity in untreated ovarian cancer deserves further study in primary treatment.

Adult↗

Uterine hemangiopericytoma.

In a clinicopathologic analysis of previously unreported uterine hemangiopericytomas, malignant behavior was observed in four of 21 followed patients. Recurrent disease occurred in the pelvis, abdomen, and lungs. The role of chemotherapy in the treatment of recurrences was not substantiated. No specific histologic features could be identified that correlated with malignant potential.

Adult↗

Plasma methotrexate levels in patients with gestational trophoblastic neoplasia treated by two methotrexate regimens.

Plasma methotrexate levels were measured in six patients with nonmetastatic and three patients with "low-risk" metastatic gestational trophoblastic neoplasia who were treated by two different methotrexate regimens. Five patients were treated with 16 cycles consisting of methotrexate, 1 mg/kg (days 1, 3, 5, and 7) followed in 24 hours by citrovorum factor, 0.1 mg/kg (days 2, 4, 6, and 8). Cycles alternated between intravenous and intramuscular administration. Statistical differences in plasma levels were found at 1 and 48 hours between the two routes of administration but probably were not of clinical importance. The plasma levels at the time of citrovorum factor administration were below that necessitating citrovorum factor rescue. Four patients were treated with alternating cycles of intravenous or intramuscular methotrexate, 0.5 mg/kg for 5 consecutive days without citrovorum factor. A total of 15 cycles demonstrated no difference in plasma levels at 1, 12, and 24 hours between intravenous and intramuscular administration. Statistical differences in plasma methotrexate levels were noted between the two methotrexate regimens only with intramuscular administration but were not of clinical importance. The reduced toxicity of the methotrexate-citrovorum factor may be due to the scheduling of the methotrexate and not to the citrovorum factor.

Antineoplastic Combined Chemotherapy Protocols↗

Cervical sarcoma: a review.

Ninety-six cases of cervical sarcomas have been reviewed. No standard criteria has been used in the diagnosis of these tumors. A variety of therapies has been employed in their management with an overall prognosis which is poor. Thus, this rather complex group of tumors needs better definition with the establishment of rigid criteria for diagnosis in order to evaluate various therapies.

Adolescent↗

Carcinoma arising in the neovagina: case report and review of the literature.

Carcinoma arising in the neovagina is unusual. A case of squamous cell cancer arising in a neovagina constructed by split-thickness dermal graft is reported. This is the fifth reported case of primary cancer of the neovagina; 2 adenocarcinomas and 2 squamous cell carcinomas were reported previously. Primary carcinoma of the neovagina is a distinct clinical entity because of the younger age of occurrence and the histopathologic type.

Adult↗

Comparison of urinary estrogens, contraction stress tests and nonstress tests in the management of postterm pregnancy.

In a retrospective review of 697 postterm pregnancies we attempted to validate three tests used to identify the fetus at increased risk: the 24-hour urinary estrogen per gram creatinine (E/Cr), the nonstress test (NST) and the contraction stress test (CST). Using the corrected perinatal mortality rate (PMR) among term pregnancies (0.23%) as a standard for comparison, we found the PMRs among postterm patients with negative screening tests to be as follows: 0.23% with normal E/Crs, 0.65% with negative CSTs (not significantly different) and 2.4% with reactive NSTs (p less than 0.005). When we used intrapartum fetal distress as a standard for comparison, the E/Cr exhibited the highest sensitivity (88%) whereas those of the CST and NST were much lower (7-10%). The specificities were 63%, 98% and 92%, respectively. From this retrospective study the E/Cr appears to be of most assistance in identifying fetuses at increased risk, the CST is of intermediate assistance, and the NST is of least assistance.

Estrogens↗

Urinary estrogens in postterm pregnancy.

A 40-month retrospective review of 677 postterm pregnancies was undertaken to determine the usefulness of 24-hour urinary estrogen per gram of creatinine (E/Cr) in monitoring such pregnancies. The cutoff value between normal and low E/Cr values was chosen at the tenth percentile (18 mg/gm). The corrected perinatal mortality rate (PMR) in post-term pregnancies with normal E/Cr was 0.23% (1/426) and was not different from that at term (0.23%; 4/1,775). However, in post-term pregnancies with low E/Cr, the corrected PMR was 9.2% (4/43), representing a 40-fold increase (P less than 0.001). The incidence of fetal distress was also significantly higher in patients with low E/Cr (57%) than in those with normal E/Cr (5.5%; P less than 0.001). It was worrisome to note that three of four stillborn infants had antepartum fetal heart testing within 4 days, which indicated fetal well-being. The E/Cr appears to be a reliable test for identifying those postterm pregnancies at risk that might benefit from obstetric intervention.

Adolescent↗

Significance of the sinusoidal fetal heart rate pattern.

The sinusoidal fetal heart rate pattern has been reported to be an indication of fetal compromise. In this review of 31 cases, drawn from a total of 559 monitored cases of normal and at-risk women, only one resulted in poor outcome, and this was attributable to a difficult breech delivery. An association with administration of analgesics is confirmed. The sinusoidal fetal heart rate pattern does not appear to be uniformly associated with fetal distress. Its presence should be an indication for meticulous assessment of other electrocardiographic, biochemical, or clinical evidence of fetal status.

Analgesics↗

Primary, papillary peritoneal neoplasia.

Subsequent to the recognition of the intraperitoneal tumors of low malignant potential, clinicians have repeatedly faced the ambiguities inherent in a disease that seems aggressive on the basis of its wide distribution in the peritoneal cavity but benign on the basis of its histopathology and clinical course. Whereas the occasional case has been associated with extensive local reaction and ascites, except for a rare exception these tumors result in prolonged survival and in an absence of extraabdominal extension. The current review of 154 cases followed from 2 to 40 years, performed in an attempt to understand this perplexing disease, leads to the following conclusions: 1) Whereas frequently beginning on the ovary and showing a predilection for the pelvis, there are examples of widely disseminated peritoneal disease with minimal, if any, ovarian involvement; 2) the outcome without adjunctive therapy is excellent and thus such therapy is contraindicated in view of the death of only 2 of the 154 patients with disease, 1 of whom had had adjunctive intraperitoneal isotope therapy; and 3) this disease is best understood as a diffuse primary peritoneal tumor probably developing on the basis of irritating agents' reaching the abdominal cavity from the lower genital canal, a process similar to that proposed for the genesis of endometriosis. Such a low-grade primary in situ tumor that may involve the entire peritoneal cavity is compatible with prolonged survival.

Adolescent↗