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Biomedical subjects

R S Gelman

Publications and source records attributed to R S Gelman.

43 records · Page 3Linked to original sources
PubMed1984

Dietary seaweed (Laminaria) and mammary carcinogenesis in rats.

To test the potential in vivo antitumor effect of dietary seaweed, we induced mammary tumors in female Sprague-Dawley rats with the carcinogen 7,12-dimethylbenz(a)anthracene. Twenty-one-day-old rats (n = 108) were divided into two groups. Controls were fed a standard semipurified diet, and experimental rats received the control diet with 5% Laminaria, a brown seaweed, replacing 5% alphacel . At 55 days of age, each rat received 5 mg 7,12-dimethylbenz(a)anthracene intragastrically. Rats were palpated for mammary tumors and weighed weekly for 26 weeks. Complete autopsies were then done on all rats. The seaweed diet did not alter weight gain or weights of body organs at autopsy. Experimental rats had a significant delay in the time to tumor (p = 0.007); median time until tumor was 19 weeks in experimental rats and 11 weeks in control animals. Among mammary adenocarcinoma tumor-bearing animals, experimental rats had fewer adenocarcinomas/individual (p less than 0.05). There was also an overall 13% reduction in the number of experimental rats with histologically confirmed adenocarcinomas (76% among the control rats compared to 63% among the experimental rats). Components of Laminaria which might account for the observed difference in mammary tumor growth are varied and include the sulfated polysaccharide fucoidan . Rats in the top row of cages had a significant (p = 0.01) delay in time to tumor compared to rats in the lower four rows. In each row, the seaweed-fed rats had a longer time to tumor than did the control rats.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Increased risk of malignancy and uterine disease following perimenarchal hospitalization: an estrogen window effect.

The estrogen window hypothesis postulates that tumor induction by environmental carcinogens is facilitated by the endocrine effects of incomplete ovarian maturation at menarche. To determine if illness and operation at or near menarche might modify ovarian maturation and thus increase cancer risk, we studied the subsequent reproductive, surgical, and malignancy history of 125 women who were aged 10 to 15 years when admitted for possible appendicitis during 1945 to 1951. Total operative experience and cholecystectomy rates were within expectation, but excess rates for dilatation and curettage (98 versus 57 expected, P less than 0.001) and hysterectomy (41 versus 23 expected, P less than 0.0006) suggest disturbed endocrine maturation. In addition, one patient developed Cushing's syndrome and five patients developed rheumatoid arthritis. Eight malignancies were observed (twice the expected rate of 3.4, P = 0.047); six occurred before age 40 years (versus 1.54 expected, P = 0.001). Tumors and age at diagnosis were: lymphoma (20), ovarian (28), breast (32), thyroid (34), lung (36), cervix (39), endometrium (48), and colon (50). Compared with standard rates, the peak incidence in those who were menarchal at hospitalization was 20 times the expected incidence; in those who were premenarchal the rate was five times the expected incidence, and in those who were postmenarchal the rate was as expected. The results of this study support the validity of the estrogen window hypothesis and indicate the serious consequences of perimenarchal illness. Enteric disease requiring hospitalization at or near menarche appears to define a group of women at risk for gynecologic disease and malignancy; further study is needed to determine if there is an appropriate prophylactic therapy to reduce that risk.

Adolescent↗
PubMed1983

The effect of thyroid hormone administration upon survival in patients with differentiated thyroid carcinoma.

Seven hundred sixty-one patients with operable differentiated thyroid carcinoma were treated between 1931 and 1970. Median follow-up time was 18 years and ranged from 5 to 40 years. Sixty-three percent of the patients were followed more than 15 years, and 46% were followed more than 20 years. Because resections usually spared sufficient thyroid tissue for homeostasis, thyroid hormone was not routinely prescribed after operations performed before 1960. Altogether 244 patients with papillary carcinoma and 76 patients with follicular carcinoma received thyroid hormone, while 296 patients with papillary carcinoma and 45 patients with follicular carcinoma did not receive thyroid hormone after operation. With papillary carcinoma, 14% of men greater than 40 and women greater than 50 years of age (high risk) but only 2% of men less than or equal to 40 years of age and women less than or equal to 50 years of age (low risk) died of disease (P 0.0001). Twenty-six percent of high-risk but only 4% of patients with low-risk follicular cancer died (P 0.0001). However, there was no statistically significant improvement in survival times with use of thyroid hormone when patients were categorized by risk group and pathology. These data support the importance of age and sex in previously described risk groups; these factors supersede the effects of adjuvant treatment. This absence of effect on survival times calls into question current recommendations for routine use of thyroid hormone after surgical therapy. Conceptually, such absence of adjunctive hormone effect on survival time after operation is similar to hormonal effects in other endocrine cancers, which may nevertheless provide good palliation in some cases.

Adenocarcinoma↗
PubMed1982

Tamoxifen and aminoglutethimide in advanced breast cancer.

Tamoxifen (TAM), a standard endocrine treatment for advanced breast cancer, probably acts by competing for the estrogen receptor protein in the breast tumor cells. If so, resistance to TAM may be a function of the level of the available endogenous estrogen. Inhibition of estrogen synthesis by aminoglutethimide may therefore facilitate the action of the antiestrogen. To test this hypothesis, the two agents were given concurrently (a) to patients who had become resistant to TAM and (b) to patients who had never received TAM in a randomized cross-over study against TAM alone. Patients with estrogen receptor protein-negative disease were excluded. Estrogen and aminoglutethimide levels were measured serially. In the first study, four of 26 patients experienced partial responses, and four of 26, stabilization of their disease. In the randomized study, four of 11 patients on the combination and three of nine on TAM alone had responses. Two patients on the combination and three on TAM alone had stabilization of disease. In the first group, the low rate of response may be attributed to extensive prior treatment. In the randomized study, there is presently no clear advantage for one treatment, and overall, there was no statistically significant correlation between degree of estrogen suppression, aminoglutethimide level, and response. The findings do not exclude the possibility that these agents may act in breast cancer by mechanisms other than inhibition of estrogen receptor.

Adult↗
PubMed1981

Relationship between time to treatment failure and survival and between time to response and response duration in metastatic breast cancer. Implications for treatment.

The hypothesis that longer times to response (TTR) and times to treatment failure (TTF) are associated with a more chronic disease resulting in progressively longer response durations (TRTF) and times from treatment failure to death (TFTD) was evaluated in metastatic breast carcinoma. Data from 553 patients across two similar Eastern Cooperative Group combination chemotherapy trials was utilized to evaluate the relationship between TTR and TRTF, and TTF and TFTD. The TTR did not appear to predict for TRTF, which was approximately 7.6 months irrespective of TTR durations from 1 to 6+ months. The TFTD increased to approximately 8 months as the TTF increased to 6 months; thereafter, the TFTD remained stable up to at least 17 months of TTF. The discordance in the results of the two analyses suggests that the operational hypothesis is not necessarily true. However, these data, along with the subset analyses and previous animal and human studies, were taken as evidence that ultimate survival is selected by the response to the first regimen employed, that the primary therapeutic impact of a regimen is in the first 3-6 months, and that the regimen should maximize therapy early to achieve rapid complete remissions.

Adult↗
PubMedDate not supplied

Mitomycin and tamoxifen versus mitolactol, doxorubicin, and tamoxifen in patients with previously treated breast cancer.

One hundred thirty patients with previously treated advanced breast cancer were treated in a cooperative trial to investigate the effect of mitomycin plus tamoxifen (MT) and to compare its relative value to combination therapy with mitolactol, doxorubicin (ADM), and tamoxifen. An additional 76 patients who had had prior exposure to ADM were randomized to receive MT or MT plus fluoxymesterone. MT versus mitolactol, ADM, and tamoxifen was not significantly different in efficacy; however, there were significant differences in toxicity. This study showed that MT is an effective and acceptable second-line treatment for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗