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1.
J Cancer Res Clin Oncol ; 150(2): 63, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38300343

ABSTRACT

PURPOSE: Skeletal metastases are increasingly reported in metastatic triple-negative breast cancer (BC) patients. We previously reported that TGF-ß1 sustains activating transcription factor 3(ATF3) expression and is required for cell proliferation, invasion, and bone metastasis genes. Increasing studies suggest the critical regulatory function of microRNAs (miRNAs) in governing BC pathogenesis. TGF-ß1 downregulated the expression of miR-4638-3p, which targets ATF3 in human BC cells (MDA-MB-231). In the present study, we aimed to identify the functional role of miR-4638-3p in BC bone metastasis by the caudal artery injection of the MDA-MB-231 cells overexpressing mir-4638 in the mice. METHODS: MDA-MB-231 cells overexpressing miR-4638 were prepared by stable transfections. Reverse transcriptase quantitative PCR was carried out to determine the expression of endogenous miR-4638-3p and bone resorption marker genes. X-ray, micro-CT, and Hematoxylin & Eosin studies were used to determine osteolytic lesions, trabecular structure, bone mineral density, and micrometastasis of cells. RESULTS: The mice injected with MDA-MB-231 cells overexpressing miR-4638-3p decreased the expression of bone resorption marker genes, compared to MDA-MB-231 cells injection. Reduced osteolytic lesions and restored bone density by MDA-MB-231 cells overexpressing miR-4638-3p were observed. Similarly, the mice injected with MDA-MB-231 cells overexpressing miR-4638-3p showed a better microarchitecture of the trabecular network. A few abnormal cells seen in the femur of MDA-MB-231 cells-injected mice were not found in MDA-MB-231 cells overexpressing miR-4638. CONCLUSION: The identified functional role of ATF3 targeting miR-4638-3p in BC bone metastasis in vivo suggests its candidature as BC therapeutics in the future.


Subject(s)
Bone Neoplasms , MicroRNAs , Triple Negative Breast Neoplasms , Animals , Humans , Mice , Bone Neoplasms/secondary , Bone Resorption , MicroRNAs/metabolism , Neoplasm Micrometastasis , Transforming Growth Factor beta1 , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology
2.
Front Plant Sci ; 12: 719381, 2021.
Article in English | MEDLINE | ID: mdl-34659290

ABSTRACT

Urdbean (Vigna mungo L. Hepper) is one of the important pulse crops. Its cultivation is not so popular during summer seasons because this crop is unable to withstand excessive heat stress beside lack of humidity in the atmosphere. Therefore, a panel of 97 urdbean diverse genotypes was assessed for yield under stress and non-stress conditions with an aim to identify heat tolerant genotypes. This study identified 8 highly heat tolerant and 35 highly heat sensitive genotypes based on heat susceptibility index. Further, physiological and biochemical traits-based characterization of a group of six highly heat sensitive and seven highly heat tolerant urdbean genotypes showed genotypic variability for leaf nitrogen balance index (NBI), chlorophyll (SPAD), epidermal flavnols, and anthocyanin contents under 42/25°C max/min temperature. Our results showed higher membrane stability index among heat tolerant genotypes compared to sensitive genotypes. Significant differences among genotypes for ETR at different levels of PAR irradiances and PAR × genotypes interactions indicated high photosynthetic ability of a few genotypes under heat stress. Further, the most highly sensitive genotype PKGU-1 showed a decrease in different fluorescence parameters indicating distortion of PS II. Consequently, reduction in the quantum yield of PS II was observed in a sensitive one as compared to a tolerant genotype. Fluorescence kinetics showed the delayed and fast quenching of Fm in highly heat sensitive (PKGU 1) and tolerant (UPU 85-86) genotypes, respectively. Moreover, tolerant genotype (UPU 85-86) had high antioxidant activities explaining their role for scavenging superoxide radicals (ROS) protecting delicate membranes from oxidative damage. Molecular characterization further pinpointed genetic differences between heat tolerant (UPU 85-86) and heat sensitive genotypes (PKGU 1). These findings will contribute to the breeding toward the development of heat tolerant cultivars in urdbean.

3.
Mol Biol Rep ; 48(3): 2209-2221, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33675464

ABSTRACT

Rice varietal identification is a crucial aspect in breeding, seed production and trade in order to protect the interests of the farmers and consumers. As the number of varieties released is rising every year, the need to identify them unambiguously also increases. Here, we developed a novel barcode system to identify 62 rice genotypes using agro-morphological descriptors and molecular markers. In all, 62 rice genotypes, for 22 agro-morphological traits were recorded. In addition, 19 molecular markers were used for developing genotype-specific DNA fingerprints. The descriptor notes of 10 essential agro-morphological traits and allele codes of the polymorphic markers were used to generate two-dimensional (2-D) barcodes for the rice genotypes. Using agro-morphological traits, 31 rice genotypes were unambiguously distinguished while, with the polymorphic markers we were able to distinguish all rice genotypes except BPT2295 and Jaya. However, using both agro-morphological descriptors and molecular markers in combination, it was possible to distinguish all the rice genotypes used in the present study. These agro-morphological notes and allele codes from the molecular marker data together were used to develop QR (Quick Response) codes for rapid identification of rice genotypes as they facilitate storage of more data. In the present investigation, we have demonstrated the potentiality of agro-morphological traits and molecular markers in distinguishing rice genotypes. The novel QR code system proposed in the present study can also be extended to other crops not only for varietal identification but also for germplasm management and trade.


Subject(s)
Agriculture , DNA Barcoding, Taxonomic , Oryza/anatomy & histology , Oryza/genetics , DNA Fingerprinting , Genetic Markers , Genotype , Plant Breeding
4.
J Health Econ ; 76: 102396, 2021 03.
Article in English | MEDLINE | ID: mdl-33412455

ABSTRACT

We examine responses to the ACA subsidy for Marketplace health insurance in the first year of subsidy availability. Drawing on federal tax data and focusing on a notch in the schedule where eligibility is lost, we document that taxpayers lowered their income to remain eligible for the subsidy. The observed bunching is modest relative to the size of the notch, which, consistent with larger responses we detect in additional analyses among certain subgroups, is likely explained by significant optimization frictions. Finally, we find suggestive evidence that increased deductions drive some of the response, while reduced labor supply also plays a role.


Subject(s)
Insurance Coverage , Patient Protection and Affordable Care Act , Eligibility Determination , Humans , Income , Insurance, Health , United States
5.
Mol Biol Rep ; 47(3): 1935-1948, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32067160

ABSTRACT

Rice production in recent years is highly affected by rapidly increasing temperatures in the tropical and sub-tropical countries, which threatens the sustainable production in near future. Hence, understanding the heat tolerance mechanism and evolving tolerant varieties is an immense need in the staple crop rice. An experiment has been conducted to identify differentially expressed genes in rice under heat stress conditions by employing a diverse set of 32 rice genotypes that includes reported heat tolerant genotypes Nagina 22 (N22) and Dular. Screening of the genotypes at field conditions during Summer-2018 for reproductive stage heat tolerance (wherein the mean minimum (29.8 °C) and maximum (38.4 °C) temperatures surpassed optimum temperatures (25 °C night/30 °C day) required for rice flowering and grain filling stages) and lab conditions employing thermal induction response (TIR) technique to know the genotype's acquired thermal tolerance revealed that the genotype FR13A (indica landrace) showed highest overall performance for multitude of traits viz., 95.29% of spikelet fertility (SF-%) at field level and 100% seedling survival percentage (SSP) at sub-lethal temperatures under laboratory conditions. The relative performance (under TIR) across all the three traits viz., relative shoot length (RSL) (4.91), relative root length (RRL) (equal to the control) and relative seedling dry weight (RSDW) (6.94) over control is high when compared to the other genotypes under study. However, the highly susceptible genotype PUSA1121 performed with 43.59 of SF%, 73.33% SSP, - 43.59 of RSL, - 36.02 of RRL over control. Hence, these contrasting genotypes were used for molecular analysis for identification of differentially expressed genes by employing 29 heat related gene specific primers. Five genes viz., OsGSK1, TT1, HSP70-OsEnS-45, OsHSP74.8 and OsHSP70 have shown differential expression between the two genotypes. Hence, the genotype FR13A, an 'indica' genotype, can be utilized in heat tolerance breeding programmes as donor parent in addition to the reported 'aus' genotypes, N22 and Dular. To our knowledge this is the first indica genotype identified for heat tolerance. The HSP70s, TT1 and OsGSK1 that proved with differential expression might be used for identification of gene specific InDels and thereby to develop functional markers that help in the marker assisted introgression breeding to develop heat tolerant varieties that can sustain production under dramatically changing climatic conditions.


Subject(s)
Gene Expression Profiling/methods , Oryza/growth & development , Quantitative Trait Loci , Gene Expression Regulation, Plant , Genotype , Heat-Shock Response , Oryza/genetics , Plant Breeding , Plant Proteins/genetics
6.
J Nanosci Nanotechnol ; 18(10): 7064-7071, 2018 10 01.
Article in English | MEDLINE | ID: mdl-29954534

ABSTRACT

In the co-precipitation method, the morphology of nano Hydroxyapatite (HAp) is usually being controlled by parameters like pH, temperature, concentration, and the ratio of the mixed surfactants. In the present work, effective tailoring of morphology has been done by exploiting the electrostatic interaction between surfactants by grouping them as catanionic (Cetrimide and SDS) and bicationic (Cetrimide and CTAB), with weight ratio of 1:1 and total concentration of 0.28 g/100 ml. The prepared samples were subjected to various characterizations like FTIR, XRD, FESEM, HRTEM, TGA/DTA, and BET analysis. The results show that the samples are in HAp phase, nano size and mesoporous in nature. The FESEM images reveal the fact that the catanionic surfactant enhances the growth of particle from sphere to hexagonal rod whereas bicationic mixture suppresses the growth and results in a disk-like HAp. The samples were subjected to AAS test for finding the Ca2+ ion release rate in SBF and were compared with a commercial nanocrystalline HAp sample. The Ca2+ ion release test of the samples shows signs of better bioactivity of disk-like HAp than that of commercial one.

7.
Oncotarget ; 8(43): 74244-74262, 2017 Sep 26.
Article in English | MEDLINE | ID: mdl-29088782

ABSTRACT

Among different types of EGFR dimers, EGFR-HER2 and HER2-HER3 are well known in different types of cancers. Targeting dimerization of EGFR will have a significant impact on cancer therapies. A symmetric peptidomimetic was designed to inhibit the protein-protein interaction of EGFR. The peptidomimetic (Cyclo(1,10)PpR (R) Anapa-FDDF-(R)-Anapa)R, compound 18) was shown to exhibit antiproliferative activity with an IC50 of 194 nM in HER2-expressing breast cancer cell lines and 18 nM in lung cancer cell lines. The peptidomimetic has a Pro-Pro sequence in the structure to stabilize the ß-turn and a ß-amino acid, amino napthyl propionic acid. To investigate the effect of the chirality of ß-amino acid on the structure of the peptide and its antiproliferative activity, diastereoisomers of compound 18 were designed and synthesized. Structure-activity relationships of these compounds indicated that there is a chiral switch at ß-amino acid in the designed compound. The peptidomimetic with R configuration at ß-amino acid and with a L-Pro-D-Pro sequence was the most active compound (18). Using enzyme complement fragmentation assay and proximity ligation assay, we show that compound 18 inhibits HER2:HER3 and EGFR:HER2 dimerization. Surface plasmon resonance studies suggested that compound 18 binds to the HER2 extracellular domain and in particular to domain IV. The anticancer activity of compound 18 was evaluated using a xenograft model of breast cancer in mice; compound 18 suppressed the tumor growth in mice compared to control. Compound 18 was also shown to have a synergistic effect with erlotinib on EGFR mutated lung cancer cell lines.

8.
Technol Health Care ; 24(5): 639-46, 2016 Sep 14.
Article in English | MEDLINE | ID: mdl-27080214

ABSTRACT

The incidence of Acute Leukemia (AL) subtypes varies according to geographical distribution and more predominant in developing countries. The aim here was to evaluate the usefulness of cost effective diagnostic tools in characterization of Acute Lymphoblastic Leukemia (ALL) in resource poor population. One hundred and two AL cases were diagnosed. For diagnosis, cytochemical analysis and immunohistochemistry were performed. Among the children < 12 years, ALL was 64.3% while AML accounted for 30%. In patients > 12 years, ALL was 59.4% and AML was 31.3%. The B-ALL occurred most frequently than T-ALL in both the age groups while based on immunophenotyping in AML, CD13 was the most commonly expressed antigen. Hence, cost effective diagnostic tools namely the immunophenotyping and cytochemistry are useful and improve accuracy and rapidly risk-stratify patients that were diagnosed with acute leukemia.


Subject(s)
Cytological Techniques/economics , Cytological Techniques/methods , Leukemia, Myeloid, Acute/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Adolescent , Child , Child, Preschool , Developing Countries , Female , Histocytochemistry , Humans , Immunophenotyping , India , Leukemia, Myeloid, Acute/pathology , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Receptors, Immunologic/immunology
9.
J Health Polit Policy Law ; 40(5): 1061-85, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26195603

ABSTRACT

This article examines the impact of the Affordable Care Act on premiums by studying a segment of the nongroup market, the self-employed. Because self-employed health insurance premiums are deductible, tax data contain comprehensive individual-level information on the premiums paid by this group prior to the establishment of health insurance exchanges. We compare these prior premiums to reference silver premiums available on the exchanges and find that exchange premiums are 4.2 percent higher on average among the entire sample but 42.3 percent lower on average after taxes and subsidies. We also examine which type of exchange coverage would cost less than the individual's prior health insurance premiums and find that almost 60 percent of families could purchase bronze plans for less than their prior premiums, though only about a quarter could purchase platinum plans. After taxes and subsidies, the fractions increase to over 85 percent for bronze plans and over half for platinum plans.


Subject(s)
Health Insurance Exchanges/economics , Insurance Coverage/economics , Insurance, Health/economics , Patient Protection and Affordable Care Act/economics , Humans , Income Tax , Models, Econometric , United States
10.
Indian J Hematol Blood Transfus ; 28(1): 37-41, 2012 Mar.
Article in English | MEDLINE | ID: mdl-23449388

ABSTRACT

Cytogenetics and polymerase chain reaction (PCR) based assays provide important information regarding biologically defined and prognostically relevant subgroups in acute leukemias. We utilized karyotyping and molecular analysis by reverse transcriptase PCR for the BCR-ABL translocation, in addition to morphological study, cytochemistry and immunophenotyping, to study 24 cases of pediatric acute lymphoblastic leukemia (ALL). Our objective was to determine the frequency of the BCRABL translocation in childhood ALL from southern India. Karyotyping showed one case of hyperdiploidy, one case of t (12; 21) translocation and one case of 46, XY-21+mar. The BCR-ABL translocation was found in 8.3% of these cases. One of these was a cryptic translocation, the karyotype being normal. BCR-ABL positivity in ALL is associated with aggressive disease and has been shown to be a poor prognostic factor, especially in children.

11.
Surg Oncol ; 20(4): 223-30, 2011 Dec.
Article in English | MEDLINE | ID: mdl-20149639

ABSTRACT

In the last 250 years, the treatment of rectal cancer has changed dramatically. Once considered an incurable disease, combined modality therapy has improved mortality from 100% to less than 4% for locally advanced rectal cancer. This dramatic reduction paralleled surgical techniques based on a growing understanding of anatomy and disease pathology. In order to understand modern treatment, it is necessary to recognize the achievements of preceding surgeons.


Subject(s)
Rectal Neoplasms/surgery , Humans , Prognosis , Time Factors
12.
Asian Pac J Cancer Prev ; 11(4): 1091-8, 2010.
Article in English | MEDLINE | ID: mdl-21133630

ABSTRACT

OBJECTIVE: To conduct a retrospective analysis of disease free survival (DFS) of locally advanced cervical cancer (LACC) in relation to evolution of treatment and related factors. METHODS: A total of 3,892 cases of LACC treated at the Cancer Institute (WIA), Chennai, India, during 1990-1999 were analyzed. Management of LACC including concurrent chemo-radiation (CCRT) has evolved through trials conducted at the institute. DFS and risk of second cancer were elicited using actuarial and Kaplan-Meier methods, respectively. RESULTS: A majority belonged to stage III (54%) and complete follow-up at 5-years was 90%. DFS at 5, 10 and 15-years were 58%, 49% and 42% for stage IIB and 43%, 35% and 31% for stage III, respectively. External beam radiotherapy (EBRT) alone as treatment modality reported the poorest 5-year DFS (37%). Addition of chemotherapy to EBRT resulted in marginal increase in survival (41%) but inclusion of brachytherapy to EBRT enhanced survival (58%) significantly (p<0.001). CCRT with brachytherapy as a planned component resulted in the best DFS (69%), irrespective of disease stage. In a carefully selected group of patients who were suitable for salvage surgery, the long-term DFS was 71%, 63% and 63% at 5, 10 and 15 years, respectively, for stages IIB and III together. Complete response was achieved in 67% and 15% of them recurred. Remote metastasis occurred in 13%. The cumulative risk of developing any second cancer was 0.5% at 5 years, 1.9% at 10 years and 2.8% at 15 years of follow up. CONCLUSION: Our data indicates satisfactory treatment outcome even in advanced disease and with the present state of knowledge, the recommended standard treatment for LACC is careful pre-treatment evaluation followed by CCRT which includes brachytherapy.


Subject(s)
Adenocarcinoma/therapy , Carcinoma, Adenosquamous/therapy , Carcinoma, Squamous Cell/therapy , Neoplasm Recurrence, Local , Uterine Cervical Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Brachytherapy , Carcinoma, Adenosquamous/mortality , Carcinoma, Adenosquamous/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Hysterectomy , India , Kaplan-Meier Estimate , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Pelvic Exenteration , Retrospective Studies , Salvage Therapy , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology , X-Ray Therapy
13.
J Colloid Interface Sci ; 350(1): 39-43, 2010 Oct 01.
Article in English | MEDLINE | ID: mdl-20599205

ABSTRACT

Macromolecules of various surfactants and polymers are being used to prepare nano hydroxyapatites (HAp) of varied morphology. Here we report the successful preparation of shell-like nano HAp spheres with fine morphology, uniform size around 200 nm, and stoichiometry ratio 1.7 with 56% nano- (<5 nm) and 44% mesoporosity using the surfactant tetradecyltrimethylammonium bromide (Cetrimide), which was not reported earlier. The critical micelle concentration (CMC) of Cetrimide was calculated as 3.88 mM at room temperature, and based on that, the other parameters of the experiment were determined. The experiment was conducted at ambient temperature and normal pressure without any temperature control, which was considered a crucial parameter in the earlier works. Thus, this method is suitable to bulk production of HAp. All the inspections confirm the successful preparation of shell-like nano HAp spheres that are suitable for biomedical applications.

14.
Inflammopharmacology ; 16(1): 21-35, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18256802

ABSTRACT

The present study was performed in order to establish the efficacy of Kalpaamruthaa (KA), a modified indigenous Siddha preparation in adjuvant induced arthritic rat (AIA) model with reference to mediators of inflammation (lysosomal enzymes) and its effect on proteoglycans. Albino rats of Wistar strain were divided into seven Groups of six animals each. Arthritis was induced to rats by subcutaneous injection of 0.1 ml of Complete Freund's Adjuvant into the plantar surface of the left hind paw. Group I served as normal control rats receiving 0.5 ml of olive oil as vehicle, Group II arthritic rats served as induced-untreated and Group III (50 mg/kg), Group IV (100 mg/kg), Group V (150 mg/kg), Group VI (200 mg/kg) and Group VII (250 mg/kg) were KA treated rats at different dose levels orally in 0.5 ml of olive oil from 14(th) day of adjuvant injection and was terminated on day 28. Animals were then sacrificed on the day 29, blood was collected, liver and kidney were dissected out, washed and 10% homogenates were prepared. The activities of lysosomal enzymes (beta-glucuronidase, beta-galactosidase, acid phosphatase, beta-N-acetyl glucosaminidase and cathepsin-D), aminotransferases (alkaline phosphatase, aspartate and aminotransferases) and levels of plasma protein bound carbohydrate components of glycoproteins were determined and were found to be elevated in arthritic rats when compared to control animals. After administration of KA, the activities of lysosomal enzymes, aminotransferases and protein-bound carbohydrate component levels were significantly normalized. The data obtained evidently indicate that Kalpaamruthaa is effective at the dose of 150 mg/kg b.wt. in AIA and plays an important role in lysosomal membrane stabilization. This was further confirmed by radiological, histological and electron microscopic studies.


Subject(s)
Arthritis, Experimental/drug therapy , Plant Extracts/therapeutic use , Plant Preparations/therapeutic use , Acetylglucosaminidase/metabolism , Animals , Ankle Joint/diagnostic imaging , Ankle Joint/drug effects , Ankle Joint/ultrastructure , Arthritis, Experimental/blood , Connective Tissue/drug effects , Connective Tissue/metabolism , Connective Tissue/pathology , Dose-Response Relationship, Drug , Edema/chemically induced , Edema/metabolism , Edema/prevention & control , Enzyme Activation/drug effects , Glucuronidase/metabolism , Glycoproteins/blood , Hindlimb/drug effects , Hindlimb/pathology , Hindlimb/ultrastructure , Lysosomes/drug effects , Lysosomes/enzymology , Male , Microscopy, Electron , Osteitis/metabolism , Osteitis/prevention & control , Plant Extracts/pharmacology , Plant Preparations/pharmacology , Proteoglycans/metabolism , Radiography , Rats , Rats, Wistar , Transaminases/metabolism , Treatment Outcome
15.
Vascul Pharmacol ; 46(6): 419-26, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17337360

ABSTRACT

The early stages of invasion are characterized by the extracellular proteolysis and the accumulation of specialized extracellular matrix (ECM) scaffold, that are responsible for the development of vascular bed, endothelial cell proliferation and invasion of tumour cells. The ground substance of provisional matrix consists of collagen, elastin, glycoaminoglycans and proteoglycans that facilitate the interaction of tumour cells with the host environment. In the present work, we have studied the influence of Semecarpus anacardium nut milk extract on localized differentials of ECM component and proteases involved in matrix metabolism of tumour tissue. Mammary carcinoma was induced in Sprague Dawley rats with 7,12, dimethyl benz(a)anthracene and treated with S. anacardium nut milk extract administered orally for 14 days. The altered amount of ECM components in tumour tissues was almost reverted back to normal level in the drug treated animals. The activities of reported proteases and glycohydrolases were also decreased on treatment with S. anacardium nut milk extract indicating decreased turnover of the matrix. Also, the factors associated with the matrix turnover and expression of MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-2 were restored back to near normal values. The stabilization of the ECM with the decreased activity of proteases might inhibit the epithelial-endothelial interaction and tumour cell migration thus, preventing the adjacent invasion and tumour growth and might be regarded as antineoplastic agent which demands further studies.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Extracellular Matrix/drug effects , Mammary Neoplasms, Experimental/drug therapy , Peptide Hydrolases/metabolism , Semecarpus , 9,10-Dimethyl-1,2-benzanthracene , Administration, Oral , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Extracellular Matrix/metabolism , Female , Glycoside Hydrolases/metabolism , Mammary Neoplasms, Experimental/chemically induced , Mammary Neoplasms, Experimental/metabolism , Mammary Neoplasms, Experimental/pathology , Matrix Metalloproteinases, Secreted/metabolism , Neoplasm Invasiveness , Nuts , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Tissue Inhibitor of Metalloproteinases/metabolism
16.
Environ Toxicol Pharmacol ; 23(3): 328-34, 2007 May.
Article in English | MEDLINE | ID: mdl-21783776

ABSTRACT

Breast cancer is the major cause of cancer death in women worldwide. Environmental risk factors particularly genotoxic chemicals such as polycyclic aromatic hydrocarbons (PAH) are likely to account for a much higher mortality. Xenobiotic metabolising enzymes in breast tissue are potentially important determinants in both the susceptibility to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. The well known carcinogen 7,12-dimethylbenz(a)anthrazene of PAH family was given (25mg/ml) orally by gastric intubation to induce mammary carcinoma in Sprague-Dawley rats. Increased level of cytochromes (P(450), B(5)), EROD, PROD activities, Phase I biotransformation enzymes (NADPH-cytochrome (P(450)) reductase, NADPH-cytochrome (b(5)) reductase, epoxide hydrolase) and expression of CYP1A1, CYP1A2 and CYP1B1 in liver and breast tissue microsome were documented in DMBA treated group. Phase II enzyme activities (glutathione-S-transferase, gluthatione peroxidase, gluatathione reductase, UDP-glucuronyl transferease) were decreased markedly in cancerous rats. The nut extract of Semecarpus anacardium was administered orally (200mg/kg body wt/day) to the mammary carcinoma rats for 14 days. Drug treatment restored back the altered Phase I and II biotransformation enzymes thus achieving complete detoxification of the carcinogen. These findings suggest that S. anacardium can effectively modulate the catabolism of xenobiotics in rats.

17.
Indian J Hematol Blood Transfus ; 23(3-4): 73-8, 2007 Dec.
Article in English | MEDLINE | ID: mdl-23100919

ABSTRACT

The multidrug resistance 1 (MDR1) gene product, P-glycoprotein (Pgp/p170) is a membrane protein, which acts as an ATP dependant efflux pump that expels a wide variety of organic compounds including chemotherapeutic agents from the cell. Pgp over expression has been demonstrated to be linked with poor treatment outcome and poor prognosis in a number of malignant tumors. AgNORs is a simple, reliable and inexpensive method of evaluating the proliferative activity of a tumor. We have studied MDR1 expression and AgNORS in 41 cases of acute leukemia in children. In this study, AgNOR counts in patients with acute lymphoblastic leukemia (ALL) L2 subtype (FAB classification) were significantly higher as compared to the ALL L1 subtype. Similarly, mean AgNOR count in the acute myeloid Leukemia (AML) M2 subtype was significantly higher as compared to the ALL L1 subtype. However, there was no correlation between AgNOR and treatment outcome or between AgNOR counts and MDR1 expression in any of the subtypes of acute leukemia included in this series. In AML, MDR1 gene expression was found to be related to reduced remission induction rates and hence poorer prognosis. In ALL, our study has shown no difference in remission induction between MDR1 positive and MDR1 negative cases. This would suggest that factors other than MDR1 may be of relevance in Pediatric ALL.

18.
Exp Oncol ; 28(2): 141-5, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16837906

ABSTRACT

AIM: To study the effect of gallium nitrate in the treatment of flare hypercalcemia in rats, bearing mammary tumor with bone metastasis. MATERIALS AND METHODS: Female Sprague-Dawley albino rats were used in the study. Animals were divided into 5 groups: normal control; hypercalcemic rats bearing DMBA-induced mammary tumors; flare hypercalcemic animals bearing DMBA-induced mammary tumors (hypercalcemic rats, treated with tamoxifen at the dose of 10 mg/kg); flare hypercalcemic rat bearing DMBA-induced mammary tumors, treated with gallium nitrate at the dose of 2.5 mg/kg; control rats, treated with gallium nitrate at the dose of 2.5 mg/kg. Eligibility criteria - serum calcium levels were 11.0 mg% or above. Biochemical parameters were measured, using standard methods. Urinary excretion of calcium, creatinine ratio, urinary bone marker were also evaluated by using standard method. RESULTS: All flare hypercalcemic rats were treated with gallium nitrate and developed normocalcemia. Biochemical parameters were measured in hypercalcemic and flare hypercalcemic animals. Calcium level in blood serum, alkaline phosphatase were significantly higher in flare hypercalcemia than in hypercalcemic rats. Urinary pyridinoline, deoxypyridinoline and hydroxyproline were also elevated in flare hypercalcemic rats. In contrast, intact parathyroid hormone and albumin levels were lowered in flare as well as hypercalcemic groups when compared with normal control groups. After gallium nitrate treatment all the above parameters returned to normal level. CONCLUSIONS: Administration of gallium nitrate in vivo is highly effective in treatment of flare hypercalcemia.


Subject(s)
Antineoplastic Agents, Hormonal/toxicity , Antineoplastic Agents/therapeutic use , Gallium/therapeutic use , Hypercalcemia/drug therapy , Mammary Neoplasms, Animal/complications , Tamoxifen/toxicity , Animals , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Calcium/blood , Calcium/urine , Female , Hypercalcemia/chemically induced , Mammary Neoplasms, Animal/drug therapy , Mammary Neoplasms, Animal/pathology , Rats , Rats, Sprague-Dawley
19.
J Med Food ; 9(2): 265-9, 2006.
Article in English | MEDLINE | ID: mdl-16822214

ABSTRACT

Reduced glutathione (GSH) is a ubiquitous thiol-containing tripeptide that plays a key role in the etiology of many diseases and, in particular, cancer. GSH, the foremost internal protective system, participates directly in the destruction of free radical compounds and detoxification of carcinogens. The effect of Semecarpus anacardium nut milk extract was studied for gaining insight into the disease relationship to GSH and its metabolizing enzymes. Mammary carcinoma was induced by giving 7,12-dimethylbenz[a]anthracene (DMBA) (25 mg/mL of olive oil) perorally by gastric intubation, and nut milk extract of S. anacardium was administered orally (200 mg/kg of body weight/day) for 14 days to mammary carcinoma-bearing rats. The levels of GSH and its metabolizing enzyme activities were determined in liver and kidney homogenates. Significant decreases in GSH, glutathione peroxidase, glutathione S-transferase, glutathione reductase, and gamma-glutamylcysteine synthetase and a concomitant increase in oxidized glutathione, gamma-glutamyl transpeptidase, and glucose 6-phosphate dehydrogenase were observed in DMBA-induced mammary carcinoma in rats, while drug treatment reversed the conditions to near normal levels. There was a marked increase in GSH level and gamma-glutamylcysteine synthetase activity in drug control rats. These findings suggest that S. anacardium can exert its protective effect in maintaining the glutathione redox status by restoring the associated enzymes against oxidative stress in experimental mammary carcinoma.


Subject(s)
Glutathione/analysis , Mammary Neoplasms, Experimental/chemistry , Plant Extracts/pharmacology , Seeds/chemistry , Semecarpus/chemistry , 9,10-Dimethyl-1,2-benzanthracene , Animals , Carcinogens , Female , Glucosephosphate Dehydrogenase/analysis , Glutamate-Cysteine Ligase/analysis , Glutathione Peroxidase/analysis , Glutathione Reductase/analysis , Glutathione Transferase/analysis , Kidney/chemistry , Kidney/enzymology , Liver/chemistry , Liver/enzymology , Mammary Neoplasms, Experimental/chemically induced , Mammary Neoplasms, Experimental/enzymology , Oxidation-Reduction , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , gamma-Glutamyltransferase/analysis
20.
Cell Biochem Funct ; 24(4): 333-40, 2006.
Article in English | MEDLINE | ID: mdl-15912568

ABSTRACT

Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA) and various inflammatory conditions, by accumulation and liberation of active proteolytic enzymes. The effect of milk extract of Semecarpus anacardium Linn. nuts (SA) at a dosage of 150 mg kg(-1) body weight day(-1) for 14 days on adjuvant arthritis was studied to gain some insight into this intriguing disease in relation to neutrophil functions. The decreased phagocytic function of neutrophils (phagocytic index and avidity index) found in adjuvant arthritis was significantly increased by the administration of the drug SA. Increased levels of reactive oxygen species (superoxide radical, hydroxyl radical, H2O2 and myeloperoxidase), lysosomal enzymes (acid phosphatase and cathepsin D) and increased accumulation of neutrophils in the joints observed in adjuvant arthritic animals were reverted back to near normal levels by treatment with SA. The results of this study indicate that SA can be considered to be a good therapeutic agent for inflammation and arthritis.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Neutrophils/drug effects , Phytotherapy , Semecarpus , Animals , Antioxidants/pharmacology , Antirheumatic Agents/pharmacology , Arthritis, Experimental/immunology , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/metabolism , Free Radicals , Lipid Peroxidation/drug effects , Lipid Peroxidation/physiology , Male , Neutrophils/immunology , Nuts , Phagocytosis/drug effects , Plant Extracts/pharmacology , Rats , Rats, Wistar , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism
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