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D A Berry

Publications and source records attributed to D A Berry.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741.

PURPOSE: To investigate whether dose escalation of megestrol acetate (MA) improves response rate and survival in comparison with standard doses of MA. PATIENTS AND METHODS: Three hundred sixty-eight patients with metastatic breast cancer, positive and/or unknown estrogen and progesterone receptors, zero or one prior trial of hormonal therapy, and no prior chemotherapy for metastatic disease were prospectively randomized into three groups. The groups of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day). RESULTS: Patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were included in the analyses. The response rates were 23%, 27%, and 27% for the 160-mg, 800-mg, and 1,600-mg arms, respectively. Response duration correlated inversely with dose. Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively. No significant differences in the treatment arms were noted for time to disease progression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The most frequent and troublesome toxicity, weight gain, was dose-related, with approximately 20% of patients on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm. CONCLUSION: With a median follow-up of 8 years, these results demonstrate no advantage for dose escalation of MA in the treatment of metastatic breast cancer.

Adult↗
PubMed1999

Attitudes, knowledge, and risk perceptions of women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2.

PURPOSE: This study examined baseline knowledge, beliefs, and risk perceptions among a group of 200 women with breast and/or ovarian cancer who participated in a trial designed to improve decision making about genetic testing for BRCA1 and BRCA2. PATIENTS AND METHODS: Women were identified by self-referral, physician referral, and tumor registry extraction and invited to participate in a randomized trial in which testing for BRCA1 and BRCA2 was offered free of charge. Subjects completed baseline questionnaires and interviews that assessed knowledge, attitudes, and perceptions of risk of having an alteration in BRCA1 or BRCA2. RESULTS: Sixty percent of women overestimated their chances of having a BRCA1 or BRCA2 mutation compared with estimates from a BRCA1/BRCA2 risk model. Women who have at least three relatives with breast or ovarian cancer were one third (95% confidence interval, 0.2 to 0.6) as likely to overestimate their risk of having a BRCA1 or BRCA2 mutation compared with women who have two or fewer affected relatives. Knowledge was limited about BRCA1 and BRCA2 mutations and cancer risk associated with gene mutations. Eighty-four percent of the women indicated a probable or definite interest in testing. CONCLUSION: A high proportion of the high-risk women in this study had knowledge deficits about BRCA1 and BRCA2 and overestimated their risk of having a mutation. Although some degree of caution should be used in generalizing the results of this study to practice settings, the data provide insight into the challenges clinicians will face in communicating with patients about cancer genetics.

Adult↗
PubMed1999

Safety and efficacy of using a single agent or a phase II agent before instituting standard combination chemotherapy in previously untreated metastatic breast cancer patients: report of a randomized study--Cancer and Leukemia Group B 8642.

PURPOSE: We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF. RESULTS: The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm. CONCLUSION: The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.

Adenine↗
PubMed1999

Is axillary lymph node dissection indicated for early-stage breast cancer? A decision analysis.

PURPOSE: Axillary lymph node dissection (ALND) has been a standard procedure in the management of breast cancer. In a patient with a clinically negative axilla, ALND is performed primarily for staging purposes, to guide adjuvant treatment. Recently, the routine use of ALND has been questioned because the results of the procedure may not change the choice of adjuvant systemic therapy and/or the survival benefit of a change in adjuvant therapy would be small. We constructed a decision model to quantify the benefits of ALND for patients eligible for breast-conserving therapy. METHODS: Patients were grouped by age, tumor size, and estrogen receptor (ER) status. The model uses the Oxford overviews and three combined Cancer and Leukemia Group B studies. We assumed that patients who did not undergo ALND received axillary radiation therapy and that the two procedures are equally effective. All chemotherapy combinations were assumed to be equally efficacious. RESULTS: The largest benefits from ALND are seen in ER-positive women with small primary tumors who might not be candidates for adjuvant chemotherapy if their lymph nodes test negative. Virtually no benefit results in ER-negative women, almost all of whom would receive adjuvant chemotherapy. When adjusted for quality of life (QOL), ALND may have an overall negative impact. In general, the benefits of ALND increase with the expected severity of adjuvant therapy on QOL CONCLUSION: Our model quantifies the benefits of ALND and assists decision making by patients and physicians. The results suggest that the routine use of ALND in breast cancer patients should be reassessed and may not be necessary in many patients.

Adult↗
PubMed1999

A finite element model of the soft palate.

OBJECTIVE: As a step toward better understanding of normal and abnormal velar control, a finite element model of the soft palate was developed. DESIGN: A static two-dimensional midsagittal model of the velum was given physical dimensions to match that of a 10-year-old boy. Biomechanical properties of the tissues were inferred based on previous histologic studies. Velar movements were induced by the influence of three extrinisic velar muscles: the levator veli palatini, the palatoglossus, and the palatopharyngeus, which were simulated as external forces acting on the velar model. RESULTS AND CONCLUSIONS: Velopharyngeal opened and closed positions were simulated as well as a variety of intermediate steps between the two configurations. Velopharyngeal closure was also simulated in a manner appropriate for both high and low vowels. Future extensions of the model will incorporate the muscles as an intrinsic component of the model and will include a full time-dependent implementation, including inertial effects. Future studies will compare model predictions with experimental data from the laboratory, including both kinematic data and velopharyngeal closure forces.

Algorithms↗
PubMed1998

erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer.

BACKGROUND: We have previously reported that high expression of the erbB-2 gene (also known as HER-2/neu and ERBB2) in breast cancer is associated with patient response to dose-intensive treatment with cyclophosphamide, doxorubicin (Adriamycin), and 5-flurouracil (CAF) on the basis of short-term follow-up of 397 patients (set A) with axillary lymph node-positive tumors who were enrolled in Cancer and Leukemia Group B (CALGB) protocol 8541. METHODS: To validate those findings, we conducted immunohistochemical analyses of erbB-2 and p53 protein expression in an additional cohort of 595 patients (set B) from CALGB 8541, as well as a molecular analysis of erbB-2 gene amplification in tumors from all patients (sets A and B). Marker data were compared with clinical, histologic, treatment, and outcome data. RESULTS: Updated analyses of data from set A (median follow-up, 10.4 years) showed an even stronger interaction between erbB-2 expression and CAF dose, by use of either immunohistochemical or molecular data. A similar interaction between erbB-2 expression and CAF dose was observed in all 992 patients, analyzed as a single group. However, for set B alone (median follow-up, 8.2 years), results varied with the method of statistical analysis. By use of a proportional hazards model, the erbB-2 expression-CAF dose interaction was not significant for all patients. However, in the subgroups of patients randomly assigned to the high- or the moderate-dose arms, significance was achieved. When patient data were adjusted for differences by use of a prognostic index (to balance an apparent failure of randomization in the low-dose arm), the erbB-2 expression-CAF dose interaction was significant in all patients from the validation set B as well. An interaction was also observed between p53 immunopositivity and CAF dose. CONCLUSIONS: The hypothesis that patients whose breast tumors exhibit high erbB-2 expression benefit from dose-intensive CAF should be further validated before clinical implementation. Interactions between erbB-2 expression, p53 expression, and CAF dose underscore the complexities of predictive markers where multiple interactions may confound the outcome.

Adult↗
PubMed1998

Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B.

BACKGROUND: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. METHODS: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. RESULTS: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. CONCLUSION: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Reduced mortality following bone marrow transplantation for breast cancer with the addition of peripheral blood progenitor cells is due to a marked reduction in veno-occlusive disease of the liver.

Clinical trials involving breast cancer in the Duke University Bone Marrow Transplant Program were evaluated to assess the association between type of hematopoietic support and treatment-related morbidity/mortality. Case histories of patients treated with high-dose chemotherapy and hematopoietic rescue on three separate protocols between 1986 and 1994 were reviewed. This included 307 patients with stage IV disease and 85 patients with high-risk (10 or more positive axillary lymph nodes) stage II or III disease. One hundred and twenty-eight of these patients were rescued with autologous bone marrow (BM) alone and 264 additionally received autologous peripheral blood progenitor cells (PBPC). The 100 day transplant-related mortality rate in those patients who received BM alone was 20.3%, with an overall mortality rate due to the high-dose chemotherapy procedure of 24.2%. The PBPC-treated group experienced a 100 day transplant-related mortality of only 6.1% and an overall trans-plant- related mortality of 10.2%. Sixteen of 31 deaths were attributed to veno-occlusive disease (VOD) in the group that received BM alone compared to only one VOD-related death in the PBPC group. These data demonstrate a marked improvement in transplant-related mortality which is related to the use of PBPC. This effect has been almost entirely due to a reduction in mortality from hepatic veno-occlusive disease.

Adult↗
PubMed1998

Assessing the benefits of testing for breast cancer susceptibility genes: a decision analysis.

Tests for the presence of mutations of genes BRCA1 and BRCA2 are increasingly available. Genetic testing creates dilemmas for women and men who regard themselves to be at high risk for breast cancer. Who will benefit from genetic testing? What is the benefit? Does testing improve quality of life? An important consideration in addressing these questions is the woman's chance of carrying a mutation at BRCA1 or BRCA2. Also important are the effectiveness and cost of the testing procedure, the availability of prophylactic interventions, the effectiveness and negative aspects of interventions, the impact of testing on other family members, and the impact of testing on the woman's ability to obtain insurance coverage. In this article we review the development of a statistical model for predicting whether a woman is a carrier of a BRCA1 or a BRCA2 mutation. We also show how this calculation can be used to assess the benefit of testing, and we quantify the size of the benefit in terms of its improvement on quality-adjusted life years (QALYs).

Journal Article↗
PubMed1998

Screening mammography for women in their forties.

Nonrandomized screening studies and some analyses of randomized data are subject to enormous biases. Many such analyses have the goal of showing that screening mammography is beneficial. They masquerade as science but are extreme examples of lying with statistics. Randomized trials have provided mixed results concerning whether screening reduces breast cancer mortality. Estimates from these trials are subject to a great deal more variability than traditional meta-analyses belie. A blanket recommendation for the screening of women in their forties is inappropriate, and it is a disservice to these women. Regular screening mammography of women in this age group is not an imperative health measure. If it is beneficial, its benefits are limited: taking the results of the randomized trials at face value, regular screening adds about five days in life expectancy per woman. In addition, screening has many significant risks. Those who are most concerned about their health will probably discount the risks and choose regular screening, and reasonably so. Others will eschew screening, also reasonably so.

Journal Article↗
PubMed1997

Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history.

BACKGROUND: Heritable mutations of the breast cancer gene BRCA1 are rare, occurring in fewer than 1% of women in the general population, and therefore account for a small proportion of cases of breast and ovarian cancers. Nevertheless, the presence of such mutations is highly predictive of the development of these cancers. PURPOSE: We developed and applied a mathematic model for calculating the probability that a woman with a family history of breast and/or ovarian cancer carries a mutation of BRCA1. METHODS AND RESULTS: As a basis for the model, we use Mendelian genetics and apply Bayes' theorem to information on the family history of these diseases. Of importance are the exact relationships of all family members, including both affected and unaffected members, and ages at diagnosis of the affected members and current ages of the unaffected members. We used available estimates of BRCA1 mutation frequencies in the general population and age-specific incidence rates of breast and ovarian cancers in carriers and noncarriers of mutations to estimate the probability that a particular member of the family carries a mutation. This probability is based on cancer statuses of all first- and second-degree relatives. We first describe the model by considering single individuals: a woman diagnosed with breast and/or ovarian cancer and also a woman free of cancer. We next considered two artificial and two actual family histories and addressed the sensitivity of our calculations to various assumptions. Particular relationships of family members with and without cancer can have a substantial impact on the probability of carrying a susceptibility gene. Ages at diagnosis of affected family members and their types of cancer are also important. A woman with two primary cancers can have a probability of carrying a mutation in excess of 80%, even with no other information about family history. The number and relationships of unaffected members, along with their current ages or ages at death, are critical determinants of one's carrier probability. An affected woman with several cancers in her family can have a probability of carrying a mutation that ranges from close to 100% to less than 5%. CONCLUSION: Our model gives informative and specific probabilities that a particular woman carries a mutation. IMPLICATIONS: This model focuses on mutations in BRCA1 and assumes that all other breast cancer is sporadic. With the cloning of BRCA2, we now know that this assumption is incorrect. We have adjusted the model to include BRCA2, but the use of this version must await publication of penetrance data for BRCA2, including those for male breast cancer that are apparently associated with BRCA2 but not with BRCA1. The current model is, nevertheless, appropriate and useful. Of principal importance is its potential and that of improved versions for aiding women and their health care providers in assessing the need for genetic testing.

Adult↗
PubMed1997

The domestic pig as a model for evaluating olestra's nutritional effects.

Experimental conditions for measuring the effect of the noncaloric fat substitute olestra on the availability of dietary nutrients were established in the weanling domestic pig. To evaluate the tolerance of the pig for dietary fat levels similar to those in the human diet, groups were fed a standard corn-soy-based swine feed with and without 14% (30% of energy) added fat for 4 wk. To evaluate the adequacy of a purified diet to produce good growth, groups of pigs were fed purified diets providing 30% of energy from fat and micronutrients at 1, 1.3 or 1.6 times the NRC's requirements for 5- to 10-kg swine. Cumulative body weight gain, digestible feed efficiency and a lack of adverse effects showed that the pig can tolerate diets providing 30% of energy from fat and that a purified diet providing the NRC's requirements for micronutrients produces growth comparable to a nutritionally complete swine feed. To determine whether tissue concentrations of vitamins A, D, E and K in the pig respond to olestra and dietary concentrations of the vitamins, two groups were fed purified diet providing 1 or 1.6 times the NRC's requirements for micronutrients and 4.8% olestra. Significant increases occurred in the serum concentration of 25-hydroxyergocalciferol and liver concentrations of retinol and alpha-tocopherol with increasing dietary concentrations of the vitamins. Olestra reduced the tissue concentrations of vitamins A, D and E. Prothrombin time was not affected by dietary concentration of either phylloquinone or olestra. To determine the amount of UV light exposure required to produce 50-80% of vitamin D status from vitamin D3, a range typical of humans, two groups of pigs were fed the NRC requirement for vitamin D and exposed to 15 or 45 min/d of UV light. Serum concentration of 25-hydroxycholecalciferol increased with increased exposure time. UV exposure of 1-2 min/d was calculated to be sufficient to produce 50-80% of total vitamin D status from vitamin D3. No antemortem observations indicated an adverse olestra effect.

25-Hydroxyvitamin D 2↗
PubMed1997

Olestra dose response on fat-soluble and water-soluble nutrients in the pig.

Groups of weanling pigs were fed a purified diet containing graded concentrations of olestra ranging from 1.1 to 7.7% (wt/wt) and the NRC's requirements for micronutrients for 12 wk. Each group consisted of 12 pigs, with the exception of the control group, which had 20, with equal numbers of females and castrated males. The purpose of the study was to determine the dose-response effects of olestra on fat-soluble vitamins and selected water-soluble micronutrients. At wk 0, 4, 8 and 12, hematology, clinical chemistry and blood concentrations of vitamins A, E, K and B12, and 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, folate, calcium, iron, zinc and adipose concentration of vitamin E were measured. Cumulative weight gain and feed efficiency were determined weekly. Prothrombin time was measured weekly for the control group and the groups fed 5.5 or 7.7% olestra, and monthly for other groups. Liver concentrations of vitamins A, E, and B12 and iron and bone concentrations of calcium, phosphorus, zinc and ash were measured for 12 pigs killed at wk 0 and for all animals at wk 12. By wk 12, the pigs were eating from 20 to 155 g/d of olestra. Olestra did not affect the pigs' growth or feed efficiency, indicating that the digestion and absorption of macronutrients were unaffected. Olestra reduced tissue concentrations of vitamin A, vitamin E and 25-hydroxyergocalciferol in a dose-responsive manner but did not affect prothrombin time. Olestra had no effect on the status of folate, vitamin B12, zinc or iron. Statistically reduced liver concentrations of vitamin B12 and iron in groups fed 5.5 or 7.7% olestra and a significant trend in bone ash content with olestra intake were possibly due to the poor vitamin A and/or vitamin E status of the pigs.

25-Hydroxyvitamin D 2↗
PubMed1997

Olestra's effect on the status of vitamins A, D and E in the pig can be offset by increasing dietary levels of these vitamins.

Groups of weanling pigs (5 castrated males, 5 females per group) were fed purified diets containing the NRC's requirements for nutrients and 0, 1.1, 4.4 or 7.7% olestra for 12 wk. Graded concentrations of vitamins A, D2 and E were added at each olestra concentration. The primary purpose of the study was to establish relationships between dietary concentration of olestra and the amounts of vitamins A, D2 and E needed to restore tissue concentrations of these vitamins to control concentrations. A secondary purpose was to confirm that olestra does not affect the status of vitamin K or water-soluble nutrients. Liver concentrations of vitamins A, E and B12, iron and zinc and bone concentrations of ash, zinc, calcium and phosphorus, were measured in a group of pigs killed at the start of the study and in all pigs killed at wk 12. Growth, feed efficiency, hematology, clinical chemistry, blood concentrations of retinol, alpha-tocopherol, 25-hydroxyergocalciferol, 25-hydroxycholecalciferol, 1,25-dihydroxyvitamin D, folate, iron, total iron-binding capacity, zinc and calcium and adipose concentration of vitamin E were measured at 4-wk intervals. Prothrombin time was measured weekly for the control and 7.7% olestra groups, monthly for others. Relationships derived from measured tissue concentrations of vitamins A and E showed that constant amounts of the vitamins were required per unit mass of olestra in the diet to restore tissue concentrations to control values. Such a relationship could not be determined for vitamin D because exposure of the pigs to UV light resulted in an apparent interaction between vitamin D2 and vitamin D3. Olestra did not affect growth, digestible feed efficiency, vitamin K status or the status of the water-soluble micronutrients, in agreement with other studies in the pig.

Animals↗
PubMed1997

Nutritional status of pigs fed olestra with and without increased dietary levels of vitamins A and E in long-term studies.

In a 26-wk study, five groups (n = 10) of domestic pigs were fed 0.25, 0.5, 1.1, 3.3 or 5.5% olestra; three groups were fed 0.25% with graded levels of vitamins A and E; and one group was fed 5.5% with added vitamins A and E and exposed to UV light. In a 39-wk study, two groups (n = 10) were fed 0.25% olestra with or without added vitamins A and E. In each study, a control group was fed basal diet with no olestra, and a group was killed at d 0 for base-line nutrient measurements. The diets provided the NRC's requirements of micronutrients for 5- to 10-kg pigs, with the following two exceptions: vitamin D was provided at twice the requirement in the 26-wk study and vitamin K was provided at 20% of the requirement in the 39-wk study. One purpose of the studies was to determine the amounts of vitamins A and E required to restore tissue concentrations of those vitamins to control concentrations. A second purpose was to determine the effects of olestra on the status of vitamins A, D, E, K and B12, and folate, iron, calcium and zinc when pigs eat olestra at intakes similar to estimated human intake for a period covering major growth and developmental phases, including sexual maturation. Olestra reduced tissue concentrations of vitamins A, D and E but did not affect prothrombin time or the status of the water-soluble nutrients. The amount of vitamin A required to restore liver concentration to control concentration was 93 microg retinyl palmitate/g olestra. Restoration levels for serum and liver concentrations of vitamin E were 2.2 and 2.1 mg d-alpha-tocopheryl acetate/g olestra. Olestra did not affect growth or digestible feed efficiency in either study, indicating that the absorption and utilization of macronutrients were unaffected. There were no antemortem observations or changes in clinical chemistry or hematology that would indicate an adverse effect of olestra.

25-Hydroxyvitamin D 2↗
PubMed1997

Olestra affects serum concentrations of alpha-tocopherol and carotenoids but not vitamin D or vitamin K status in free-living subjects.

Normal, healthy, free-living adults ingested either 18 g/d olestra, with or without 1.1 mg tocopheryl acetate/g olestra, or 18 g/d triglyceride placebo, for 16 wk in a double-blind, placebo-controlled study. Serum concentrations of alpha-tocopherol, alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, retinol and cholesterol were measured biweekly. Serum 25-hydroxyvitamin D concentration, prothrombin time, partial thromboplastin time and plasma concentration of functional prothrombin (Simplastin-Ecarin assay) were measured at wk 0, 8 and 16. Relative to the placebo group, serum alpha-tocopherol concentration was reduced 6% for the group given 18 g/d olestra. Addition of tocopheryl acetate to olestra partially offset the effect of olestra. For the group given 18 g/d olestra plus 1.1 mg tocopheryl acetate/g olestra, serum alpha-tocopherol concentration was 4% less than the placebo value. Olestra reduced serum concentration of beta-carotene by 27%; the other carotenoids were similarly affected. Serum cholesterol concentration was reduced approximately 4.5% in the olestra groups, relative to placebo, but the differences were not significant. Serum triglycerides, serum 25-hydroxyvitamin D, prothrombin time, partial thromboplastin time or the plasma concentration of under-gamma-carboxylated prothrombin were unaffected by olestra. Clinical observations and laboratory measures indicated no health-related effects of olestra; mild-to-moderate transient gastrointestinal symptoms such as bloating, cramping, loose stools and diarrhea were reported by all groups.

Adult↗
PubMed1997

Relation of glutathione S-transferase alpha and mu isoforms to response to therapy in human breast cancer.

Glutathione S-transferase (GST) represents a multifunctional enzyme family consisting of four known cytosolic isoforms (alpha, mu, pi, and Phi) that detoxify a variety of xenobiotic chemicals and may confer resistance to both chemotherapeutic drugs and carcinogens in various experimental models. GST-pi has already been extensively studied in clinical specimens, including breast cancer. We studied the immuno-histochemical distribution and relative immunopositivity of GST-alpha and GST-mu, based on a grading system for immunointensity, in samples of 51 neoplastic and 46 normal breast samples and 12 lymph node metastases from patients treated with intensive chemotherapy and bone marrow transplant. In normal breast tissue, GST-alpha localized predominantly to the cytoplasm of scattered cells lining the luminal aspects of the ducts. Occasional cells showed both cytoplasmic and nuclear GST-alpha immunoreactivity. GST-mu was stained in myoepithelial cells preferentially as well as in occasional ductal cells (including apocrine epithelium), vascular smooth muscle, and plasma cells. GST-alpha and GST-mu were detected in 22 of 51 (43%) and 24 of 48 (50%) invasive cancers, respectively. In paired samples of normal and malignant tissue from the same patient, GST-alpha immunostaining in cancers was significantly less intense compared to that of normal breast tissue in 13 of 41 (32%) cases. No such trend was found for GST-mu in paired samples. Neither GST-alpha nor GST-mu immunopositivity in tumor or nonneoplastic breast was found to correlate with relapse-free or overall survival in this clinical context; however, the apparent decreased expression of GST-alpha in malignant versus normal breast epithelial cells could have important implications in breast carcinogenesis.

Adult↗