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R S Mehta

Publications and source records attributed to R S Mehta.

At least 19 recordsLinked to original sources
PubMed2001

Breast cancer survival and in vitro tumor response in the extreme drug resistance assay.

PURPOSE: To determine whether in vitro extreme drug resistance (EDR) assay results for patients with breast carcinoma were associated with clinical outcome after chemotherapy. PATIENTS AND METHODS: EDR assays were performed on tumor tissue obtained from 103 newly diagnosed breast cancer cases. EDR scores of 2 for low, 1 for intermediate, or 0 for extreme drug resistance were determined for each agent tested. In vitro EDR scores for 4-hydroxycyclophosphamide (4HC) and doxorubicin were summed for patients treated with AC, or for 4HC and 5-FU for patients treated with CMF. Treatment selection was blinded to assay results. RESULTS: Median time to progression was significantly shorter for patients with extreme or intermediate in vitro resistance (n = 55, 48 months), compared to patients with low in vitro resistance, (n = 41, 100 months, p = 0.022). Patients demonstrating extreme to intermediate drug resistance also showed poorer survival than the low resistance group (49.5 months vs. not reached, median follow-up 48 months, p =0.011). Summed EDR scores, stage, and number of lymph nodes were significantly associated with survival in univariate and multivariate analysis. Compared to EDR scores of 4, summed EDR scores of 0-1 and summed EDR scores of 2-3 were associated with a relative risk of death of 3.09 (95%, CI 1.05-9.06, Cox proportional hazards model, p = 0.040) and 2.35 (95%, CI 1.07-5.15, Cox proportional hazards model, p = 0.033), respectively. CONCLUSION: Extreme drug resistance testing identified patients with individual patterns of drug resistance prior to therapy. In this cohort of breast cancer patients treated with chemotherapy, summed EDR scores were significantly associated with time to tumor progression and overall survival. EDR results may offer a method for optimizing treatment selection.

Adult↗
PubMed2000

Biomarker conservation in primary and metastatic epithelial ovarian cancer.

PURPOSE: The aim of this study was to compare the overexpression of specific biomarkers in primary advanced and recurrent epithelial ovarian cancers. METHODS: Biomarker expression by epithelial ovarian cancer specimens from primary and metastatic sites was examined by immunohistochemistry and flow cytometry. Biomarker expression by subpopulations of tissues consisting of matched pairs of synchronous and metachronous lesions was also studied. RESULTS: A total of 3173 epithelial ovarian cancer specimens were retrieved from women with FIGO Stage III/IV disease. These included lesions from 1036 primary and 2137 metastatic sites. The percentages of biomarker expression for primary and metastatic lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%; EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately 73% of both primary and metastatic specimens were aneuploid, and approximately 57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were found to be significantly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid primary lesions were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between primary and metastatic sites. Pairings of metachronous cases (n = 66) revealed that nearly 80% of primary aneuploid tumors (n = 39) retained their aneuploid status at the time of relapse. Furthermore, there were no significant changes in MDR1, p53, or HER2 expression at relapse. CONCLUSIONS: With the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer. These particular genes likely undergo alterations early in the tumorigenesis process before metastases have become established.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Failure of high fat diets to promote mammary cancers in spontaneously hypertensive rats.

Rat strains differ in their susceptibilities to chemically-induced mammary carcinogenesis. The present study tested the hypothesis that the spontaneously hypertensive rat (SHR) strain is resistant to mammary carcinogenesis. Resistance would imply the presence of the mammary carcinoma suppressor (MCS) gene. Therefore, we also wanted to test the ability of this gene to inhibit mammary tumor promotion in the presence of high fat diets. Female SHRs were treated with DMBA (5 mg/rat) at 50 days of age and transferred to either a 20% corn oil or 19% menhaden oil + 1% corn oil diet one week later. At 17 weeks post-DMBA none of the rats in either group developed mammary carcinomas. Multiple palpable nodules formed in the mammary gland indicating that initiation had occurred. We conclude that the SHR strain is genetically resistant to DMBA-induced mammary carcinogenesis by mechanisms involving a blockade of promotion.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Effects of total fasting or chronic food restriction on plasma endothelin levels in rats.

We tested the effects of 24- and 48-h fasting and 40% calorie restriction stresses on plasma endothelin (ET)-1,2 levels in male Sprague-Dawley rats. Plasma ET-1,2 levels in pg/ml were lower in 24-h fasted rats (15.48 +/- 3.49), 48-h fasted rats (5.28 +/- 4.32), and in chronically food-deprived rats (R) (10.49 +/- 6.28) compared to ad lib-fed (AL) rats (21.23 +/- 9.38). The R rats were pair-fed 40% fewer calories than AL rats. We conclude that calorie restriction or total food deprivation stress decreases plasma ET-1,2 levels, unlike many other forms of physiological stress that have been shown to increase plasma ET-1,2 levels.

Animals↗
PubMed1994

High fish oil diet increases oxidative stress potential in mammary gland of spontaneously hypertensive rats.

1. The purpose of this study was to determine whether high omega-3 (19% menhaden oil, 1% corn oil) or high omega-6 (20% corn oil) fatty acid diets would decrease expression of hypertension in the female spontaneously hypertensive rat (SHR), promote tumourigenesis in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model of mammary cancer or increase the susceptibility of the mammary gland to lipid peroxidation. A group of rats on a 5% corn oil diet served as the low fat control group. 2. We found that the high omega-3 and high omega-6 fatty acid diets did not significantly decrease mean arterial pressure. Marked differences occurred between the effects of omega-3 and omega-6 high fatty acid diets on baseline oxidation, auto-oxidation and iron-ascorbate catalyzed oxidation. The omega-3 diet showed 675% increase in basal oxidation, a 2624% increase in auto-oxidation and a 4244% increase in iron-ascorbate catalyzed oxidation compared to the omega-6 diet in mammary tissue homogenates. Although all rats were given 5 mg DMBA (i.g.), no mammary tumours were observed in any of the dietary groups. 3. We conclude that: (i) high polyunsaturated fatty acid diets do not decrease blood pressure in the female SHR; (ii) high fish oil diet markedly increases oxidative potential in the mammary gland; and (iii) the female SHR is resistant to DMBA-induced tumourigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats.

Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period. After 10 weeks, tumor incidences were: AL, 63%; CR, 27%; CC, 57% (AL versus CR, P < 0.05; CC versus CR, P < 0.05; AL versus CC, NSD). ET levels (pg/ml plasma) were: AL, 16.0 +/- 6.54; CR, 32.31 +/- 0.34; CC, 23.44 +/- 5.04 (AL versus CR, P < 0.01; CC versus CR, P < 0.01; AL versus CC, P < 0.05). Plasma ET levels were independent of tumor incidence and tumor burden, but plasma ET levels were significantly increased in rats with a prior history of calorie restriction. As expected, maintained caloric restriction reduced mammary tumor incidence but intermittent caloric restriction (caloric cycling or yo-yo dieting) was without similar benefit.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

The pathogenesis of retinopathy of prematurity as it relates to surgical treatment.

Our current surgical treatment for threshold retinopathy of prematurity (ROP) is based upon three concepts which emerged from morphologic and biochemical study of 250 pairs of whole eye donations obtained over a ten year period. 1) Spindle cells normally migrate and canalize to form inner retinal vessels, but when stressed, spindle cells secrete angiogenic factors. The clinical implication is that transretinal cryotherapy to the avascular retina is efficacious because it obliterates spindle cells. The number and timing of cryosessions are determined by the migration and kinetics of spindle cells. 2) Myofibroblasts originate from the shunt, are the major cellular component of extraretinal fibrovascular proliferation (EFP), and contract to produce retinal distortion and detachment. The clinical implication is that a second transretinal cryotherapy session should obliterate the shunt and the EFP, and should eliminate the source of retinal traction. 3) Anterior ocular growth occurs exponentially during the period when ROP develops and is treated. The clinical implication is that a prophylactic scleral buckle supports the fixed surface area of the developing retina while the choroid and sclera enlarge anteriorly. Retinal distortion produces misaligned photoreceptors, and retinal detachment results in rapid retinal death.

Animals↗
PubMed1989

Morphologic changes of K-Sol preserved human corneas.

Supplementation of tissue culture medium with chondroitin sulfate has been shown to enhance donor corneal preservation. We assessed the efficacy of one of these chondroitin-supplemented media (K-Sol) in comparison with McCarey-Kaufman (MK) medium in maintaining corneal cellular morphology. Thirty-six human corneas, obtained within 8.6 h after death, were placed into K-Sol medium for up to 20 days preservation, and five paired control corneas were placed into MK medium for up to 6 days preservation. Specular photomicrographs were obtained every second to third day for a predetermined storage interval, then studied morphologically in a masked protocol by light microscopy, transmission electron microscopy, and scanning electron microscopy. Endothelial cell loss by specular microscopy averaged 5.8% after 1 week (6 to 8 days) and 7.4% after 13 days in K-Sol medium. Epithelial changes were erratic throughout the 20 day K-Sol preservation period. However, substantial keratocyte changes occurred after 10 days, and endothelial morphology uniformly deteriorated after 17 days. The morphologic data suggest that human corneas may be able to be preserved in K-Sol medium at 4 degrees C for up to 10 days but should be cautiously used thereafter.

Adult↗
PubMed1986

Abnormal sperm and photoreceptor axonemes in Usher's syndrome.

Axonemes are organelles that are composed of microtubule doublets and singlets with a complex assembly of associated proteins. This study was designed to investigate the possibility that an abnormal axoneme is involved in the pathogenesis of Usher's syndrome. A masked structural and functional analysis of sperm was performed on samples from ten patients with Usher's syndrome and 33 controls, including duplicate samples from six patients and three controls. In the functional analyses, there was a significant decrease in patient sperm motility and velocity. Structurally, there was a significant increase in tail abnormalities at both the light and electron microscopic levels. Ejaculate volume and sperm concentration were normal in the patient population. The presence of abnormal axonemes was also confirmed in remnant photoreceptors of a whole eye donation from a patient with Usher's syndrome. The data suggest that defective connecting cilia axonemes may be involved in the irreversible, progressive loss of photoreceptors in Usher's syndrome.

Adult↗
PubMed1983

Bilateral retinal ischemia in Kawasaki disease. Postmortem findings and electron microscopic observations.

A 4-month-old infant died of cardiovascular complications of Kawasaki disease (KD). At autopsy, aneurysmal dilatation with recent thromboses were found in coronary arteries, abdominal aorta, brachial and left common carotid arteries. A vasculitis with thrombosis of a branch of the ophthalmic artery was demonstrated in the right orbital apex. Light microscopy disclosed that the ocular abnormalities were confined to the retinas of both eyes that exhibited inner retinal ischemia. By electron microscopy, the inner retina showed clumping of nuclear chromatin, mitochondrial swelling, rupture of plasma membranes, and increased number of lipid figures. Müller cell processes were intact. Stereologic analysis of the mitochondria in the retinal pigment epithelium, photoreceptor inner segment, and ganglion cells in the KD infant demonstrated that identical mitochondrial changes occurred in the retina from an adult woman who had a recent central retinal artery occlusion.

Adult↗
PubMed1982

Variable expressivity of autosomal dominant anterior segment mesenchymal dysgenesis in six generations.

Of 58 members in a six-generation family with anterior segment mesenchymal dysgenesis with variable expressivity, 21 of 35 members (60%) at risk were affected. Of the 15 living affected family members, nine (60%) had visual acuities of 6/12 (20/40) or better in at least one eye, five (33%) had visual acuities between 6/15 and 6/60 (20/50 and 20/200) in at least one eye, and one (7%) had a visual acuity of less than counting fingers at one foot in both eyes. All nine affected patients who underwent slit-lamp examinations had corneal abnormalities with and without synechiae. All 15 affected patients also had cataracts, and three of the 15 (20%) had optic nerve abnormalities. In a corneal button from the severely affected proband, Descemet's layer and endothelial cells were absent even in the periphery. Other corneal and lenticular changes were secondary to the primary endothelial defect. Anterior segment mesenchymal dysgenesis in this family appeared to be caused by an aberration of the first wave of mesenchyme from the rim of the optic cup.

Adolescent↗