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M J Straus

Publications and source records attributed to M J Straus.

At least 19 recordsLinked to original sources
PubMed1984

Correlation of cell-cycle kinetics, hormone receptors, histopathology, and nodal status in human breast cancer.

DNA ploidy and percent of (%S-phase) S-phase cells were determined from the DNA content distribution of 21 benign and 76 malignant (69 primary, 7 metastatic) breast tumors using flow cytometry. All of the benign tumors were diploid, whereas 89% of the malignant tumors had measurable aneuploidy. Multiple stem-lines were observed in approximately 10% of the malignant tumors. The ploidy distribution of the malignant tumors was bimodal with an increased frequency of tumors with a near diploid DNA index (DI), and a second group with DI ranging from triploid to tetraploid. The percentage of cells in S-phase ranged from less than 1% to 37.4%. DI and %S were significantly higher in poorly differentiated duct carcinomas, medullary carcinomas, and recurrent tumor metastases. DI and %S were also significantly higher in estrogen-receptor-negative tumors. There was no correlation between DI or %S and the extent of axillary nodal metastases. However, within the groups of node-negative and node-positive patients, DI and %S were not randomly distributed but were significantly correlated with degree of nuclear differentiation. Both parameters were higher in poorly differentiated tumors compared with well-differentiated tumors, indicating significant intrastage heterogeneity in tumor ploidy and proliferation characteristics. Determination of the prognostic significance of DI and %S will require a longer follow-up time.

Breast Neoplasms↗
PubMed1983

Multimodality treatment of adenocarcinoma of the vagina Stage IV: potential for cure.

A 26-year-old nulligravida presented with a Stage IV adenocarcinoma of the vagina with a frozen pelvis and positive lymph nodes in the right external iliac and inguinal regions. Following transposition of the ovaries laterally, a successful treatment program of cyclic radiotherapy and 5-fluorouracil was undertaken. Patient is now alive 3 years posttherapy with a functional vagina, return of menses, and without evidence of tumor. She experienced a small-bowel stricture 5 months posttherapy which required small-bowel resection. This case suggests that an integrated multimodality program is feasible and that 5-fluorouracil may be synergistic with radiation.

Adenocarcinoma, Mucinous↗
PubMed1983

Labeling indices of human lung cancer. Correlation with histologic type and survival.

The labeling index (LI) of tumor specimens from 28 patients (9 primary, 21 metastases) with lung cancer was analyzed after in vivo 3H-thymidine labeling. The mean LI was 11.1 (range, 1.4 to 37.6), and the median was 10.6. The average LI for adenocarcinoma (1.8) was significantly lower than those of small-cell, large-cell and poorly differentiated epidermoid carcinoma (12.8, 11.5 and 13.6, respectively). The variation in LI from site to site was less than 50% in 72% of lesions. Among the nonadenocarcinomas, no significant differences in average LI were observed between primary and metastatic tumors. For 17 previously untreated patients, mean survival times for patients with tumors whose LIs were below and above the mean were 63 and 30 weeks, respectively (0.10 greater than P greater than 0.05).

Adenocarcinoma↗
PubMed1982

Estrogen receptor heterogeneity and the relationship between estrogen receptor and the tritiated thymidine labeling index in human breast cancer.

Tissue from 54 patients with breast cancer was analyzed for estrogen receptor (ER). From 38 patients, tissue from multiple tumor sites was analyzed to determine ER heterogeneity. In 13 patients (34%) both positive and negative ER values were obtained. ER negative (ER-) results were observed more frequently in metastatic lesions. In 28 patients both the ER and [3H]-thymidine labeling index (LI) were measured in the metastatic lesion. [3H]-Thymidine was administered in vivo. There was a positive correlation between ER positivity and low LI. The mean LI of 8 ER positive (ER+) tumors was 3.4 in contrast to a mean LI of 10.0 for 14 ER- tumors (p less than 0.01). LI of 6 mixed ER tumors (ER+/-) was intermediate (mean 5.7). High LI (greater than or equal to 8) was associated with decreased survival regardless of the stage of disease at the time of study. ER with LI may provide an improved basis for treatment selection.

Breast Neoplasms↗
PubMed1982

Chemotherapy and cyclic radiation therapy in locally advanced non-small cell lung carcinoma.

Nine patients with non-small cell lung carcinoma (4 squamous, 4 adenocarcinoma, 1 large cell) were treated with a combination of radiation therapy and cyclic chemotherapy with 5-fluorouracil, methotrexate and platinum. Four previously untreated patients had stage III, 2 having distant metastases, 5 previously treated patients were restaged as stage III with distant metastasis in one. Moderate hematologic toxicity was noted. Objective responses occurred in 67 per cent, regardless of previous treatment or performance status. Responders survived for a median of 11 months with one complete response patients surviving at 14 months while 5 partial response patients survived for a median of 10 months. This regimen is feasible and its utility as the initial treatment of locally advanced disease should be further investigated.

Adenocarcinoma↗
PubMed1982

Treatment of advanced prostate cancer with cyclophosphamide, doxorubicin, and methotrexate.

Twenty-three patients with advanced prostate cancer who had failed previous hormone therapy were treated with cyclophosphamide, doxorubicin, and methotrexate on a 3-week course. Of the 22 evaluable patients, over one-half had poor performance status, increased acid and alkaline phosphatase levels, and pain. Parameters which improved in greater than 50% of cases included acid and alkaline phosphatase levels, pain, performance status, and measurable lesions (lung and soft tissue). Initial parameters associated with a significantly decreased survival were age greater than 66 years, increased pain, poor performance status, and increasing alkaline phosphatase. Prior radiation therapy was associated with increased drug toxicity, lower doses of chemotherapy, and decreased survival (not significant). There was a significant relationship between the degree of improvement of acid phosphatase, alkaline phosphatase, pain, and performance status to increased survival. Three categories of response were defined based on these parameters. The mean survival of seven patients with partial response (106 weeks) is significantly longer than that of seven with measurable response (57 weeks) and eight with no response (26 weeks). Four patients had severe leukopenia and one died of sepsis. These results compare favorably with previous reports of chemotherapy treatment of advanced prostate cancer.

Acid Phosphatase↗
PubMed1981

Effects of pulse and continuous intravenous infusion of cis-diamminedichloroplatinum on L1210 leukemia in vivo.

The in vivo effects of cis-diamminedichloroplatinum on L1210 leukemia were determined using DNA content distribution analysis by flow microfluorometry and pulse [3H]thymidine labeling indices. Pulse and continuous infusion schedules were investigated. Pulse cis-diamminedichloroplatinum (2 and 6 mg/kg) resulted in progression delay of cells in S and G2 phases and at higher doses (greater than or equal to 12 mg/kg) in G1 as well. Equivalent total doses administered by continuous infusion over 24 to 72 hr delayed cells in G2 with little apparent affect on G1 or S progression. A maximum survival of 70% increased life span over controls was achieved with a 12-mg/kg pulse. Infusion doses at least 2-fold higher were required to achieve similar increases in survival. Cell cycle changes did not predict for therapeutic benefit, suggesting that, at suboptimal doses, cells were capable of repair. The therapeutic index for both modes of administration was narrow.

Animals↗
PubMed1980

The cell cycle kinetics of human breast cancer.

Cell kinetic parameters were determined in 32 patients with breast cancer following intravenous [3H]thymidine injection. The mean labelling index (LI) was 8.6, range 1.2 to 24.1. The LI increased significantly with increased stage of disease. The highest values were noted in patients with chest wall metastases with a mean LI of 15.9. In one patient with multiple discrete tumor foci, the larger foci had significantly decreased LI consistent with classic cytokinetic theory. The intralesional variation in LI was measured in 31 lesions. The average variation of LI/lesion was 1.2. Therefore, three samples should provide a representative LI. The interlesional LI was compared by taking multiple samples of two or three lesions per patient in seven patients. For each patient, there was little variation in mean LI from lesion to lesion. The data suggest that higher LI are associated with a poorer prognosis. Among patients with advanced T4 or metastatic disease, the median survivals for patients with LI less than 8 and greater than or equal to 8 were 79 weeks and 21 weeks, respectively. For patients with metastatic disease, the survivals were 56 and 9 weeks, respectively. The tumor growth fraction analyzed in one patient was 40%. In summary, the growth rate of this cancer in an individual patient is relatively homogeneous and LI may provide important prognostic information. Further studies are required to establish the value of LI in the staging and treatment of breast cancer.

Age Factors↗
PubMed1980

Synchronization of L1210 leukemia with hydroxyurea infusion and the effect of subsequent pulse dose chemotherapy.

Studies were performed to synchronize L1210 tumor cells in S phase in an effort to maximize the effect of subsequent pulse dose chemotherapy. Hydroxyurea (HU) was administered by continuous iv infusion 5 days after tumor implantation. Perturbation effects on the S-phase cells were measured by serial tritiated thymidine labeling indices. Effects on cell-cycle progression were measured by DNA content distribution analysis using flow cytometry. Synchronization of tumor cells was achieved with HU infusion (48 mg/kg/hour x 24 hours), resulting in 90% of the cells in S phase. Following infusion, synchronous progression of S-phase cells into G2/M and then G1 was apparent from +0 to +10 hours later. The susceptibility of HU-synchronized cells to subsequent chemotherapy was determined by treating mice with cytosine arabinoside (Ara-C), methotrexate (MTX), or Adriamycin (ADR) pulse doses at various intervals following infusion. Synergy, measured by prolongation of survival times, resulted when Ara-C was administered immediately after the end of the infusion. Survival times then decreased as the fraction of cells in S phase decreased. In contrast, the survival times of mice treated with MTX or ADR pulse doses after HU infusion were additive at best and did not correlate with fluctuations in the S phase compartment. Therefore, prior synchronization of tumor cells in S phase was therapeutically advantageous when coupled with appropriately timed Ara-C pulse doses. There was little advantage in combining HU infusion with subsequent MTX or ADR therapy.

Animals↗
PubMed1980

A method for establishing prolonged intravenous infusions in mice.

A simple and rapid method for establishing prolonged intravenous infusions in mice was developed. The major advantages of this system were ease of establishing infusions, ability to infuse large numbers of mice simultaneously, low incidence or perivenous infiltration, and little apparent stress to the mouse.

Animals↗
PubMed1979

Cytokinetic chemotherapy design for the treatment of advanced lung cancer.

Sixty patients with lung cancer, 48 with extensive disease and 12 with regional disease, were treated with cyclophosphamide and methotrexate on a schedule based on cellular kinetics concepts. Initial therapy was with cyclophosphamide (1.1 g/m2 iv) followed by methotrexate (20 mg/m2 orally twice weekly) beginning 9 days later when the tumor was considered to be most susceptible to an S-phase-specific drug. The overall objective response rate was 62% (25% complete responses and 37% partial responses) with an estimated median survival time (MST) of 46 weeks. Seventeen of 19 patients with small cell carcinoma (89%) responded (ten complete responses and seven partial responses). The MST was 62 weeks. The last nine patients entered in the study with small cell carcinoma had an MST of 71 weeks, reflecting additional responses to subsequent treatment. The objective response rate of large cell carcinoma (nine of 16 patients) and adenocarcinoma (ten of 18 patients) was 56%. The MST of patients with the former cell type was longer (57 weeks) than that of patients with the latter cell type (34 weeks). One of seven patients with epidermoid carcinoma responded. The MSTs of patients with a complete response and those with regional disease were 70 and 63 weeks respectively. Patients with a performance status of 0 or 1 survived longer (MST, 56 weeks) than those with a performance status of 2 or 3 (MST, 29 weeks). The mean dose of cyclophosphamide per course was 1.275 g/m2 and the mean nadir leukocyte count per patient was 2890/mm3. The incidence per course of leukocytes less than 1000/mm3 or platelets less than 50,000/mm was less than 3%. Mucositis was common. This schedule provides excellent maintenance therapy without undue toxicity. These survival time distributions compare favorably with those of previous reports, particularly for patients with small cell or large cell carcinoma, regional disease, or complete responses.

Cyclophosphamide↗
PubMed1978

Dose-dependent cytokinetic changes following 1-beta-D-arabinofuranosylcytosine and hydroxyurea in L1210 and S-180 in vivo.

DNA synthesis inhibition and recovery in L1210 and S-180 ascites tumors following 1-beta-D-arabinofuranosylcytosine (Ara-C) and hydroxyurea (HU) were measured autoradiographically as a basis for optimizing drug schedules. Tumor bearing mice, 10(6) cells day 0, were treated on day 4 with 20, 200 or 2000 mg/kg Ara-C or 50, 300 or 1800 mg/kg HU. At various intervals following drug, [3H]thymidine was administered i.p. and mice were killed 1 hr later. Tumor cells were analyzed for labeling index (LI) and grain count (GC) to determine the percentage of cells in S phase and the distribution of DNA synthesis rates among the labeled cells, respectively. Following each dose of HU, DNA synthesis was inhibited completely. Recovery of LI was rapid and approached control values by 6 hr. Following each dose of Ara-C, DNA synthesis was inhibited completely for at least 6 hr. Recovery of LI was first noted 6 hr following 20 mg/kg Ara-C and 9 hr following 200 mg/kg. Following both doses the LI reached 100% of the control value by 26 hr. GC analysis indicated that following Ara-C treatment, DNA synthesis was reinitiated first with cells with low GC from 6 to 12 hr followed by cells with increasing GC from 12 to 20 hr. The labeling intensity reached control values by 20 hr and an 'overshoot' occurred by 26 hr. These data suggest that the recovery of DNA synthesis rate is a gradual process. Survival data for mice receiving two doses of Ara-C indicated that the optimal interval for retreatment following the lower dose of Ara-C occurred by 6 hr as compared to 12--16 hr for the higher dose. These times coincided in both instances with recovery of LI to 33--50% of control values. Early recovery of LI may be the best method currently available for estimating the optimal time for retreatment with an S phase specific drug.

Animals↗
PubMed1977

The uptake, excretion, and radiation hazards of tritiated thymidine in humans.

Nine patients with malignant disease were given i.v. injections of tritiated thymidine, 0.2 mCi/kg, for tumor cell kinetics studies. Serial plasma, urine, saliva, and air vapor samples were collected variously for up to 79 days, and tritium activity was measured. The initial half-life of plasma activity was rapid. After 1 day, the activity decayed with a half-life of 10.8 days, indicating equilibration of activity with the total body water. Urine activity was over 100 times the plasma activity within 1 hr, with equilibration approaching the plasma activity after 2 days, and then decayed at a similar rate. Saliva and air vapor activity increased to plasma levels and then decayed at the same rate as did plasma activity. In the first 24 hr, approximately one-third of the total injected activity was excreted in the urine. During the first 12 days there were 54.2% urinary and 10.6% insensible losses. Maximum losses determined by extrapolation of observed data were 68% urinary and 19.5% insensible losses, or a total of 87.5%. Approximately 7% of the injected activity may represent material initially incorporated into DNA but later metabolized and excreted. The radiation dose from total body water is estimated at 0.69 rad. The estimated dose absorbed by cell nuclei from incorporated material is a maximum of 20.5 rads. These radiation doses would not seem to contraindicate injection of 0.2 mCi tritiated thymidine per kg to patients in this clinical and experimental setting. Measurements of activity in personnel and room air indicate that the use of such doses is not hazardous if appropriate precautions are followed.

Adult↗
PubMed1976

Combination chemotherapy in advanced lung cancer with increased survival.

Twenty-eight patients with lung cancer, 26 with extensive disease, were treated with the drugs Cytoxan (Cyt) and methotrexate (MTX). The schedule was based on cellular kinetics concepts. Initial therapy was with Cyt 1.1 g/m2 (intravenously) followed by MTX 20 mg/m2 orally, twice weekly, started 9 days later, when the tumor was considered to be most susceptible to an S-phase-specific drug. The course was repeated at three-week intervals. Based on dose response curves, Cyt and MTX dose modifications were individually adjusted to the whit blood cell counts and platelet counts over a 3-week period. Twenty of 28 patients (five of seven large cell, five of eight adenocarcinoma, 10 or 11 small cell, none of two epidermoid) responded with greater than or equal 50% tumor reduction. Ten patients had complete responses, seven of whom had small cell carcinoma. Two of the nonresponders were nonevaluable. Five patients were alive and the extimated median survival time of the patients is almost 1 year, which compares quite favorably to previous reports. On this schedule of therapy, very high doses of Cyt and MTX were maintained with less than 3% incidence per course of a WBC less than 1,500/mm3 or a platelet count less than 50,000/mm3.

Adenocarcinoma↗