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M A Tanner

Publications and source records attributed to M A Tanner.

71 records · Page 4Linked to original sources

Anti-carcinogenic activity of d-limonene during the initiation and promotion/progression stages of DMBA-induced rat mammary carcinogenesis.

d-Limonene was found to be effective in reducing the average number of rat mammary carcinomas that developed in 7,12-dimethylbenz[a]anthracene-treated rats when the terpene was fed during the initiation or during the promotion/progression stage of carcinogenesis. The time to the appearance of the first tumor was extended only when d-limonene was fed during the initiation stage. These effects could not be attributed to changes in mammary-relevant endocrine functions.

9,10-Dimethyl-1,2-benzanthracene↗

Inhibition of carcinoma formation and of vascular invasion in grafts of radiation-initiated thyroid clonogens by unirradiated thyroid cells.

Quantitative transplantation techniques have been employed to study radiogenic cancer initiation frequency and cell interactions during promotion/progression in grafted clonogenic rat thyroid epithelial cells. The graft recipients were surgically thyroidectomized and maintained on a diet containing less than 50 ng iodine per g. The results confirm that radiogenic initiation is a common cellular event; one of approximately 32 surviving 5-Gy-irradiated thyroid clonogens gave rise to cancer in grafts initially containing approximately 11 clonogens per transplantation site. The data demonstrate that the efficiency of promotion/progression is inversely related to grafted irradiated cell number. As the number of transplanted surviving irradiated clonogens was increased progressively from approximately 11 to approximately 720 clonogens per graft site, the carcinoma frequency per grafted clonogen progressively decreased to one per approximately 920. Addition of unirradiated thyroid cells to the transplant inocula further suppressed promotion/progression of radiation-initiated thyroid clonogens. Furthermore, the probability of vascular invasion, a reflection of metastatic potential in carcinomas which arose from irradiated grafted thyroid clonogens, was reduced by addition of unirradiated thyroid cells to the transplant inocula. Assays of thyroid stimulating hormone (TSH) titers in the sera of thyroidectomized rats 44 weeks after transplantation of clonogenic thyroid cells indicate that the suppression of neoplastic promotion/progression observed with increased numbers of cells per graft site is due at least in part to feed-back inhibition of TSH production by thyroid hormone of graft origin. Whether local cellular interactions are also involved in this inhibitory process is currently under investigation.

Animals↗

Diagnostic schemes for fine needle aspirates of breast masses.

A comparison was made of four statistically based schemes for classifying epithelial cells from 243 fine needle aspirates of breast masses as benign or malignant. Two schemes were computer-generated decision trees and two were user generated. Eleven cytologic characteristics described in the literature as being useful in distinguishing benign from malignant breast aspirates were assessed on a scale of 1 to 10, with 1 being closest to that described as benign and 10 to that described as malignant. The original computer-generated dichotomous decision tree gave 6 false negatives and 12 false positives on the data set; another tree generated from the current data improved performance slightly, with 5 false negatives and 10 false positives. Maximum diagnostic overlap occurred at the cut-point of the original dichotomous tree. The insertion of a third node evaluating additional parameters resulted in one false negative and seven false positives. This performance was matched by summing the scores of the eight characteristics that individually were most effective in separating benign from malignant. We conclude that, while statistically designed, computer-generated dichotomous decision trees identify a starting sequence for applying cytologic characteristics to distinguish between benign and malignant breast aspirates, modifications based on human expert knowledge may result in schemes that improve diagnostic performance.

Biopsy, Needle↗

Enhancement of misonidazole chemopotentiation by mild hyperthermia (41 degrees C) in vitro and selective enhancement in vivo.

Experiments were designed to test the hypothesis that mild heat treatment would selectively increase misonidazole (MISO) chemopotentiation of CCNU toxicity in hypoxic versus aerobic cells in vitro and in tumours in vivo via an augmentation of nitroreduction. EMT-6 cells were exposed to CCNU +/- 1.0 mM MISO under aerobic or hypoxic conditions for 4 h either at a constant 37 degrees C or at 41 degrees C for the first hour followed by 37 degrees C for the remaining 3 h. Chemopotentiation was not observed under aerobic conditions and heat treatment did not modify CCNU toxicity. Co-incubation with MISO and CCNU under hypoxic conditions resulted in enhanced toxicity (i.e. chemopotentiation) with either incubation protocol; however, the magnitude of the enhancement was significantly larger (P less than 0.025) when 41 degrees C incubation was included. Systemic heat treatment produced a similar enhancement of chemopotentiation in KHT tumours in C3H/HeN mice treated with MISO (0.5 mg g-1) and whole body hyperthermia (41 degrees C, 1 h) prior to administration of CCNU (15 mg kg-1). Heating had no effect on CCNU response but doubled the median growth delay produced by the CCNU-MISO combination. Heat treatment did not enhance myelosuppression of the combination. Both the in vitro and in vivo data indicate that mild hyperthermia can selectively enhance the magnitude of MISO chemopotentiation.

Aerobiosis↗

Factors influencing options in primary breast cancer treatment.

Primary breast cancer treatment is determined by tumor factors and by patient preference. Breast cancer treatments that preserve the cosmetic appearance of the breast are appealing and effective for appropriately selected patients; long-term survival following tumor excision and breast irradiation appears to be comparable to that for mastectomy. Since April 1981, when a protocol was developed and treatment options were offered, factors influencing treatment selection have been analyzed in 206 consecutive primary breast cancer patients. Mastectomy was dictated by tumor-related factors in 96 patients (47%); 110 patients (53%) had the option of mastectomy or conservation--tumor excision plus radiotherapy to the breast. Among these 110 eligible patients, 54 chose conservation (49%) and 56 chose mastectomy (51%). Intraoperative findings for ten patients electing conservation necessitated mastectomy, so conservation was accomplished for 44 (21%) of those treated for breast cancer. Beginning in July 1982, breast cancer patients took a battery of psychosexual assessments before any operation (Profile of Mood States [POMS], Health Locus of Control Scale [HLCS] Locke-Wallace Marital Adjustment Test [MAT], Psychosocial Adjustment to Illness Scale [PAIS], Derogatis Sexual Function Inventory [DSFI], Millon Clinical Multiaxial Inventory [MCMI], and a Breast Cancer Information Test [BCIT]). Comparisons of psychologic and demographic variables were made between patients who chose mastectomy and those who chose conservation. No demographic variable was statistically significantly related to choice, although older women tended to select mastectomy more than younger women. Compared with those who elected conservation, women who elected mastectomy were more tense and anxious (P less than .01), more introverted (P less than .01), felt more depressed and dejected (P less than .05), and reported more sexual problems (P less than .05). Those who elected conservation valued their physical appearance more highly (P less than .01) and were generally more self-interested (P less than .05). Mastectomy was dictated by medical considerations for approximately half of patients with breast cancer. Among candidates for breast conservation, the importance of retaining the breast appeared to be determined to a significant degree by measurable psychological factors.

Body Image↗

Radiation survival of human mammary carcinoma cells: criteria for an agar-based clonogenic assay.

A human in vivo-in vitro model for breast cancer has been developed based on culture methods that were systematically optimized for solid breast carcinomas. A V-79 cell clonal agar-based model was used to define the analysis problem encountered with agar based clonogenic survival assays. Based on this, we established methods for the generation and analysis of the survival of primary and recurrent breast carcinomas following irradiation. Four out of five primary breast carcinomas studied had similar radiation-cell survival curves. The fifth tumor was more radioresistant. Interestingly, a recurrent breast carcinoma arising in a heavily irradiated chest wall was no more radioresistant than our series of unirradiated primary carcinomas. These methods may be useful both for the study of the radiobiology of human neoplasms and for customizing the treatments and prognosis of individual patients.

Breast Neoplasms↗

Mouse skin tumor promoting activity of orange peel oil and d-limonene: a re-evaluation.

Orange peel oil has previously been shown to be a promoter of mouse skin tumors. It has been assumed that this activity is due to its major (95%) constituent, d-limonene. We have tested both orange peel oil and purified d-limonene as skin tumor promoters in a two-stage skin carcinogenesis model in which tumors were initiated with 7,12-dimethylbenz[a]-anthracene. We confirmed that topically applied orange peel oil is a very weak promoter of both skin papillomas and carcinomas. However, this promotional activity could not be accounted for by topically applied d-limonene. We thus feel that one or more minor components of orange peel oil has promotional activity. Neither orange peel oil nor d-limonene had promotional activity when given via the diet.

9,10-Dimethyl-1,2-benzanthracene↗

Systematic optimization of the clonal growth of human primary breast carcinoma cells.

Human breast carcinomas have been one of the most difficult tumor types to culture in agar-based clonogenic assays. This fact has limited their clinical applicability. We have used statistically motivated experimental designs to systematically improve the clonal culture of enzymatically monodispersed primary human carcinoma cells in an anchorage-independent agar system. Based upon an initial comparison of two basal media, we selected one which gave the best colony growth and then sought to optimize the individual additives in the medium. Hydrocortisone, fetal bovine serum, and red blood cells all improved both plating efficiency and median size of colonies derived from breast carcinoma cells. Next, the concentrations of these three components were simultaneously idealized using response surface methodology. By these methods, it was found that the optimal concentration of hydrocortisone was 0.35 microgram/ml, fetal bovine serum was 6.5%, and red blood cells was 2.1 X 10(7) cells/ml. Using these culture conditions, we have achieved plating efficiencies of 0.39% and 0.19% for colonies with diameters greater than 50 (50 cells) or 70 (130 cells) micron, respectively.

Animals↗

Regression of rat primary mammary tumors following dietary d-limonene.

The effects of d-limonene on rat mammary tumors were investigated. Following the appearance of mammary tumors induced by 7,12-dimethylbenz[a]anthracene in female (W/Fu X F344)F2 rats, animals were assigned to pairs in which 1 rat was fed a diet containing 10% d-limonene and the other was pair fed an isocaloric diet containing 10% cellulose. There was a highly significant increase in the regression of the first tumors in the rats fed d-limonene. In addition, d-limonene given at this time inhibited the formation of subsequent multiple tumors in these rats.

9,10-Dimethyl-1,2-benzanthracene↗

Assessment of radiogenic cancer initiation frequency per clonogenic rat mammary cell in vivo.

Radiogenic initiation of mammary cancer is here shown to be a common cellular event. With the aid of a rat mammary clonogen transplant system designed to maximize progression of initiated cells to overt neoplasia, the estimated absolute cancer risk per surviving 7 Gy-irradiated mammary clonogen was [4.1 +/- 1.2 (SE)] X 10(-3), that is (5.8 +/- 1.7) X 10(-4) initiated cells per clonogen-Gy. To maximize neoplastic progression, all clonogen graft recipient rats were glucocorticoid deficient (adrenalectomized with minimal mineralocorticoid replacement) and hyperprolactinemic (implanted intrasplenically with pituitary tissue and an estrone capsule). Each rat was grafted with 4 X 10(6) "morphologically intact" monodispersed mammary cells in the interscapular white fat pad. Group A received cells which had been irradiated 1 day earlier with 7 Gy 137Cs gamma-rays. Groups B and C received unirradiated mammary cells. On day 35 after transplantation, the graft sites of group B were locally exposed to 7 Gy 140 kVp X-rays. Kaplan-Meier estimates (11) of the survivor functions were used to calculate the final tumor incidences corrected for intercurrent animal loss. Estimated mammary carcinoma frequencies so calculated were 65 tumors/131 graft sites in group A, 93/119 in group B, and 13/129 in group C. The relative cancer risks per rat due to the radiation exposure of the grafted cells were 5.0 for group A and 7.8 for group B. These data on neoplasia incidence in grafted mammary clonogens and data on autologous neoplasia in the host rat mammary glands were subjected to statistical analysis. The results indicate that both neoplasm frequency and latency are in large part dependent on initiation target cell number. The high frequency of radiogenic initiation per mammary clonogen observed in this study is in accord with findings with a similar thyroid clonogen transplant system.

Adrenalectomy↗

Dietary aflatoxins, intelligence and school performance in southern Georgia.

In a region of southern Georgia known for poor school performance, the mothers of the mentally retarded children had diets that differed from the average in terms of foods, but did not differ in terms of critical nutrients. The consumption of large amounts of corn, rice, peanuts and milk (foods potentially high in aflatoxins) was significantly related to mental retardation of children in one county having high levels of aflatoxins in the food supply. However, no such relationship was found in a county having trivial levels of aflatoxins in the diet.

Aflatoxins↗

Irradiation and prolactin effects on rat mammary carcinogenesis: intrasplenic pituitary and estrone capsule implants.

The implantation of silicone capsules that contained estrone and that were adjacent to grafts of anterior pituitary tissue in the spleens of adrenalectomized glucocorticoid-deficient inbred F344 rats resulted in high circulating prolactin (Prl) levels without the untoward effects of chronic hyperestrogenism or of grafts of Prl-secreting pituitary tumors. All peripheral serum estrone titers were below the titers in sera of proestrous untreated intact rats. Peripheral serum estrone and Prl levels were, however, a function of capsule surface area over the capsule sizes tested (12-74 mm2); the elevated Prl levels persisted for as long as 700 days. In adrenalectomized glucocorticoid-deficient female rats, both 5 Gy gamma-irradiation alone and intrasplenic pituitary-estrone implants alone induced mammary carcinomas; the combination of these treatments induced a greater incidence of first carcinomas and reduced first carcinoma latency. There were, however, no marked differences in tumor incidence or latency due to differences in estrone capsule size. Finally, ovariectomy reduced first carcinoma risk in irradiated, pituitary-estrone-implanted rats but did not change the time of maximum risk. Ovarian secretory activity thus persisted in such rats and ovarian hormones synergized with Prl in mammary carcinoma induction.

Adenofibroma↗

Inhibition of DMBA-induced mammary cancer by the monoterpene d-limonene.

We investigated whether the addition of d-limonene to the diets of rats would modify the process of mammary tumor induction by 7,12-dimethylbenz[a]anthracene (DMBA). When diets containing 1000 or 10 000 p.p.m. d-limonene were fed to rats from one week before DMBA administration to the end of the experiment (27 weeks post DMBA treatment), a significant reduction in mammary carcinogenesis was observed at each level. The inhibition of carcinogenesis was mainly due to an increase in latency; however, major differences in incidence could be seen during the follow-up period. For example, rats fed 10 000 p.p.m. of d-limonene had a 72% reduction in mammary tumors when compared to controls at 18 weeks post DMBA treatment. In addition to inhibiting the appearance of mammary tumors, d-limonene was also found to cause the regression of frank mammary tumors. No toxicity was evident in these rats even at the highest d-limonene dose. Control and all treated rats gained weight at the same rate throughout the experiment. In addition, no differences were found in their peripheral blood counts (Hct, total white cell and differential count).

9,10-Dimethyl-1,2-benzanthracene↗

Maternal diet and mental retardation in southern Georgia, USA.

The diet of each of 250 mothers was correlated with the I.Q. (intelligence quotient) of her child. When the I.Q. was above 90, no systematic relationship was observed. Below an I.Q. of 70, all mothers consumed a similar diet--one with a smaller amount and variety of fruits and vegetables, but larger amounts of yams, greens, corn, rice and dry legumes. This diet was uniquely deficient in none of the common nutrients. It seems more possible, therefore, that the correlation with diet could be due to the presence of a toxicant, such as aflatoxin.

Aflatoxins↗

Operational definitions of schizophrenia: what do they identify?

Several studies have shown that different systems for diagnosing schizophrenia produce diagnoses with relatively low agreement. This, however, does not necessarily imply that the different systems are identifying conceptually different diagnostic groups. They may, in fact, identify a single entity, but with different degrees of accuracy. One-hundred ninety-six inpatients were diagnosed by multiple diagnostic systems. The pattern of relationship among the diagnoses was studied with latent class analysis, a statistical methodology which has not previously been applied to this type of data. Results indicated that the diagnoses of the Research Diagnostic Criteria, Flexible 6, Schneider, and 1978 Taylor and Abrams diagnostic systems all estimated a single underlying diagnosis. The Taylor and Abrams system identified this core diagnosis with high accuracy. The results also suggest that blunted affect and the absence of an affective syndrome are related to latent class schizophrenia, while the presence of only nonspecific delusions and/or hallucinations is not related. The appropriateness of the latent class definition of schizophrenia for selecting patients for research is discussed.

Affect↗

Statistical approach to fine needle aspiration diagnosis of breast masses.

A statistical algorithm was used for recursively partitioning a consecutive series of 37 benign and 69 malignant fine needle aspirates to produce a decision tree for diagnosing breast masses. Optimal separation between benign and malignant cytology was accomplished by evaluating clump characteristics when clumps were present and evaluating cell integrity when clumps were absent. The 1.5% false-negative and 9.7% false-positive rates obtained through this scheme are better than those reported for most series.

Algorithms↗