ABSTRACT
PURPOSE: Cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer and the chemotherapeutic drugs available have high toxicity and have reported side effects hence, there is a need for the synthesis of novel drugs in the treatment of cancer. METHODS: The current research work dealt with the synthesis of a series of 3-(3-acetyl-2-oxoquinolin-1-(2H)-yl-2-(substitutedphenyl)thiazolidin-4-one (Va-j) derivatives and evaluation of their in-vitro anticancer activity. All the synthesized compounds were satisfactorily characterized by IR and NMR data. Compounds were further evaluated for their in-vitro anticancer activity against A-549 (lung cancer) cell lines. The in-vitro anticancer activity was based upon the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay method. RESULTS: The synthesized compounds exhibited satisfactory anticancer properties against the A-549 cell line. The compound (VH): showed the highest potency amongst the tested derivatives against the A-549 cell line with IC50 values of 100 µg/ml respectively and was also found to be more potent than Imatinib (150 µg/ml) which was used as a standard drug. Molecular docking studies of the titled compounds (Va-j) were carried out using AutoDock Vina/PyRx software. The synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of the EGFRK tyrosine kinase domain (PDB 1m17). CONCLUSION: Among all the synthesized analogues, the binding affinity of the compound (Vh) was found to be higher than other synthesized derivatives and a molecular dynamics simulation study explored the stability of the docked complex system.
Subject(s)
Antineoplastic Agents , ErbB Receptors , Lung Neoplasms , Molecular Docking Simulation , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Structure-Activity Relationship , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Cell Line, Tumor , A549 Cells , Thiazolidines/pharmacology , Thiazolidines/chemistry , Thiazolidines/chemical synthesis , Drug Screening Assays, Antitumor , Cell Proliferation/drug effectsABSTRACT
BACKGROUND: Current markers (carcinoembryonic antigen [CEA] and carbohydrate antigen 15-3 [CA15-3]) lack sensitivity in diagnosis of breast cancer. The aberrantly expressed circulating miRNAs were shown as diagnostic markers in breast cancer. However, there are very few studies from the Indian population. We studied the diagnostic utility of miRNA-21, miRNA-155 and miRNA-205 compared to CEA and CA15-3 in stage I and II breast cancer patients. MATERIALS AND METHODS: Sixty newly diagnosed women with stage I/II breast cancer and 20 healthy controls were recruited. Expression of circulating miRNAs was studied using reverse transcription-polymerase chain reaction, whereas CEA and CA 15-3 were analyzed by enzyme-linked immunosorbent assay. RESULTS: miRNA-21 and miRNA-155 were upregulated, miRNA-205 down-regulated (P < 0.05) and serum CEA and CA15-3 levels increased in breast cancer patients (P < 0.001). Receiver operating characteristic curve analysis showed significant area under curve (AUC) for all markers (0.656 to 0.993; P = 0.015 to <0.001) validating their diagnostic potential. Unlike CEA and CA15-3, miRNAs retained their sensitivity even at higher cut-offs (95% CI of mean). Logistic regression analysis showed significant association between disease and marker positivity for miRNA-21 and miRNA-205 but not for miRNA-155. Combining CA15-3 with miRNAs did not improve their diagnostic performance. However, combining CEA with either miRNA-21 (AUC = 0.742; P < 0.001 versus AUC = 0.656; P = 0.018) or miRNA-205 (AUC = 0.733; P < 0.001 versus AUC = 0.700; P < 0.001) increased its diagnostic performance. CONCLUSION: Our study shows miRNA-21 and miRNA-205, are useful as diagnostic markers for breast cancer in the Indian population and combination of these miRNAs with CEA but not with CA 15-3 improved their diagnostic performance.
ABSTRACT
Phyllodes tumors are rare biphasic fibroepithelial lesions of the breast and account for 0.3%-0.5% of primary breast tumors. Malignant phyllodes tumor has a 10%-26% risk of distant metastasis. The most common site of metastasis is lungs followed by bone and soft tissue. This is a rare case of a 42-year-old female with a previous history of malignant phyllodes tumor breast. She presented after 10 years with metastases to multiple sites including lung, abdominal wall, retroperitoneum, bone, and brain. These tumors have a poor overall survival. Accurate diagnosis and aggressive management of malignant phyllodes tumors can help in effective treatment at diagnosis and for close follow-up of the patients.
Subject(s)
Breast Neoplasms , Lung Neoplasms , Phyllodes Tumor , Female , Humans , Adult , Phyllodes Tumor/diagnosis , Phyllodes Tumor/surgery , Phyllodes Tumor/pathology , Breast/pathology , Treatment Outcome , Lung Neoplasms/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Breast Neoplasms/pathologyABSTRACT
Homologous recombination (HR) is one of the important mechanisms in repairing double-strand breaks to maintain genomic integrity and DNA stability from the cytotoxic effects and mutations. Various studies have reported that single nucleotide polymorphisms (SNPs) in the HR-associated genes may have a significant association with ovarian cancer (OCa) risk but the results were inconclusive. In the present study, five polymorphisms of HR-associated genes (RAD51, XRCC2 and XRCC3) were genotyped by allelic discrimination assay in 200 OCa cases and 200 healthy individuals. The association with OCa risk was evaluated by unconditional logistic regression analyses. The results revealed that the mutant allele in both rs1801320 (CC) and rs1801321 (TT) of RAD51 gene was associated with increased risk of OCa (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.21-11.78, p = 0.014 and OR 1.61, 95% CI 1.06-2.45, p = 0.025, respectively). Moreover, a significant association of TT allele (OR 4.68, 95% CI 1.27-17.15, p = 0.011) of rs3218536 of XRCC2 gene with OCa was observed. Stratified analysis results showed that patients with early menarche and stages 3 and 4 were found to be associated with rs1801321 of RAD51 gene and rs1799794 of XRCC3 gene. In silico analysis predicted that the two missense SNPs (rs3218536 and rs1799794) were found to have an impact on the protein structure, stability and function. The present study suggested that RAD51 and XRCC2 gene polymorphisms might have an impact on the OCa risk in the South Indian population. However, studies with a larger sample and on different populations are needed to support the conclusions.
Subject(s)
DNA-Binding Proteins/genetics , Ovarian Neoplasms/genetics , Polymorphism, Single Nucleotide , Rad51 Recombinase/genetics , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Computer Simulation , DNA Repair/genetics , DNA-Binding Proteins/metabolism , Female , Genetic Predisposition to Disease/genetics , Homologous Recombination , Humans , India/epidemiology , Middle Aged , Ovarian Neoplasms/blood , Ovarian Neoplasms/epidemiology , Protein Interaction Maps/genetics , Rad51 Recombinase/metabolism , Risk Factors , Young AdultABSTRACT
BACKGROUND: Herbal supplements (HS) are one of the most commonly used complementary and alternative medicines in cancer. Reduced therapeutic efficacy of prescription anticancer agents through unwarranted herb-drug interactions is a major efficacy/safety concern. In view of the rising cancer prevalence in India along with a high degree of reliance and cultural acceptability in favor of traditional medicine drugs, prevalence data exclusively of HS usage during cancer treatment are of considerable epidemiological significance. METHODOLOGY: This questionnaire-based prospective observational study aimed at estimating the prevalence of HS among cancer patients during treatment at our tertiary care medical center. Taken on a population of 220 patients within a period of 9 months, data were generated by a customized validated questionnaire and the same processed by IBM SPSS Statistics for Windows, version XXIV, Armonk, NY: IBM Corp. Differences between HS use and nonuse with respect to demographic, disease, and treatment characteristics were assessed by Chi-square test. For examining the latter variables as possible predictors of HS usage, they were entered into bivariate logistic regression with odds ratio and confidence intervals calculated for each. RESULTS: Out of 220 patients, 57 (26%) were HS users and 163 (74%) were nonusers. Majority of the users (42.1%) were on self-prepared folklore herbal medicine postdiagnosis of cancer (57.9%), the most common reason cited being symptom palliation (35.1%) on the advice of friends and family (64.9%). Fear of disapproval was the most common reason cited (68.4%) for not disclosing HS usage to the physician. CONCLUSION: Chemotherapy and unemployment are predictors of HS usage, and there is a significant association between occupation status and HS usage. This first study on HS prevalence among South Indian population proposes the need for a more robust evidence base for understanding all aspects of HS use in cancer.
Subject(s)
Dietary Supplements/statistics & numerical data , Employment/statistics & numerical data , Health Knowledge, Attitudes, Practice , Neoplasms/drug therapy , Phytotherapy/methods , Surveys and Questionnaires/statistics & numerical data , Adult , Female , Humans , India , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
Plant carotenoid cleavage oxygenase (CCO) is an enzyme which catalyzes carotenoids to apocarotenoid products that are involved in several vital physiological functions. The CCO exists in two forms, namely, CCD (Carotenoid Cleavage Dioxygenase) and NCED (Nine-Cis Epoxycarotenoid Dioxygenase). This paper relates to a comparative study on CCD and NCED genes through phylogeny and codon usage analysis. The result of the phylogenetic analysis indicates a closer relationship between CCD and NCED subclass genes, while the RSCU values indicate a high preference for CUC codon in both CCD and NCED gene families. The mean ENc value of NCED genes was found to be 48.76, suggesting a higher codon bias compared to CCD genes. However, the ENc-GC3S plot suggests that both the gene families are under mutational pressure with variations according to their species-specific role. Similarly, the multivariate analysis also suggests that nucleotide mutation bias influences codon usage. Correlation analysis of Axis I and codon adaptation index values indicate a significant correlation between critical indices. Even though the prominence of the variations in codon usage between the two gene families, they are exerted towards the time-specific functional requirement for that plant species. This is evident from the cleaving roles of these enzymes against various carotenoids at different growth stages. The result of this investigation indicates that CCD and NCED genes are under mutational pressure. This codon bias study paves the way for increasing the production of apocarotenoids, which have a great significance in the industry.
Subject(s)
Codon/genetics , Genes, Plant/genetics , Oxygenases/genetics , Arabidopsis Proteins/genetics , Mutation/genetics , Oxygenases/classification , Phylogeny , Plants/classification , Plants/geneticsABSTRACT
Single nucleotide polymorphisms (SNPs) in adiponectin gene [rs1501299 (+276G/T) and rs266729 (-11377C/G)] and one SNP of leptin gene [rs7799039 (-2548G/A)] are known to influence plasma levels of adiponectin and leptin respectively. Literature is scarce on the association of adiponectin gene polymorphism rs266729 with breast cancer. The present study was taken up to study these polymorphisms and their association with breast cancer. Ninety-three patients diagnosed with malignant breast cancer were included as cases along with 186 age matched healthy controls. Adiponectin +276G/T, -11377C/G and leptin -2548G/A polymorphism were studied using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Adipokine levels in blood were measured using enzyme linked immunosorbent assay. Adiponectin +276G/T and leptin -2548G/A showed a significant increased risk for breast cancer even after adjusting for confounding variables like present age, age at menarche, age at first child birth and age at menopause. In the subset analysis, based on menopausal state, stronger association was observed between SNP in adiponectin gene +276G/T with the breast cancer in post-menopausal women after adjusting for all other variables. No association was found with adiponectin -11377C/G. No association of the gene polymorphisms with adipokine levels was observed. Also, no significant association was seen for the effect of gene-environment interaction i.e. presence of polymorphism with obesity and menopausal state for any of the SNPs studied. Adiponectin +276G/T is strongly associated with breast cancer in postmenopausal women while leptin -2548G/A polymorphisms is significantly associated with breast cancer irrespective of the menopausal state in south Indian subjects.
Subject(s)
Adiponectin/genetics , Breast Neoplasms/genetics , Genetic Predisposition to Disease , Leptin/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Alleles , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Case-Control Studies , Female , Gene Frequency , Gene-Environment Interaction , Genetic Association Studies , Genotype , Humans , Mammography , Middle Aged , Neoplasm Staging , Risk FactorsABSTRACT
AIMS AND OBJECTIVES: This retrospective study aims at correlating the pre- and post-therapy maximal standardized uptake values (SUVmax) of the whole-body 18-flourodeoxy glucose positron emission tomography (FDG-PET) scan with tumor response in patients with head and neck squamous cell cancer undergoing chemoradiotherapy. MATERIALS AND METHODS: Data for this retrospective study were taken from the clinical records of 20 evaluable head and neck cancer patients who had availed treatment and evaluation at our institute during the previous year (March 2017-April 2018). All these above-mentioned patients had undergone chemoradiation at our center for locally advanced squamous cell carcinoma of the head and neck and had undergone pre- and post-therapy whole-body FDG PET scan. The posttherapy PET-computed tomography (CT) was advised after 8 weeks' postcompletion of therapy. During the PET CT scan, images were acquired 1 h after injection of FDG. Pre- and post-therapy SUVmax were recorded and correlated with immediate treatment response. RESULTS: The mean pretherapy SUVMax of the primary tumor was 10.27 ranging from 4.5 to 26.17. The mean pretherapy SUVMax of the node was 5.34 ranging from 0 to 17.9. The mean time of recording the posttherapy SUVMax was 3 months (range 2-5 months). The mean posttherapy SUVMax of the primary tumor was 1.05 ranging from complete metabolic response to 6.4. The mean posttherapy SUVMax of the node was 0.7 ranging from complete metabolic response to 5.43. The statistical analysis based on Wilcoxon-Signed Rank test revealed a statistically significant difference in the pre- and post-therapy SUVmax values for both primary tumor (P < 0.001) and regional node (P = 0.001). Majority of patients (n = 15) showed clinical remission; however, five patients had progressive disease at the time of evaluation. CONCLUSION: Although the retrospective study revealed that complete responders had a statistically significant reduction in the posttherapy SUVmax in comparison to the pretherapy SUVmax it failed to identify a cutoff value for pretherapy SUVmax which could predict the probable outcome of therapy. In view of the same further prospective studies need to be conducted with larger patient numbers including various other tumor metabolic markers for greater clarity.
ABSTRACT
A generation of nanoparticles research has discussed recently. It is mandatory to elaborate the applications of biogenic nanoparticles in general and anticancereous property in particular. The present study was aimed to investigate the in vitro cytotoxicity effect of biogenic silver nanoparticles (AgNPs) against human breast cancer (MCF-7) cells towards the development of anticancer agent. Biogenic AgNPs were achieved by employing Sesbania grandiflora leaf extract as a novel reducing agent. It was well characterized by FESEM, EDAX and spectral studies showed spherical shaped nanoparticles in the size of 22 nm in slightly agglomerated form. It was surprising that biogenic AgNPs showed cytotoxic effect against MCF-7 cell lines were confirmed by MTT, AO-EB, Hochest and COMET assays. There was an immediate induction of cellular damage in terms of loss of cell membrane integrity, oxidative stress and apoptosis were found in the cell which treated with AgNPs. This may be a first report on anti-MCF-7 property of biogenic AgNPs in the fourth generation of nanoparticles research. It is necessary to study the formulation and clinical trials to establish the nano drug to treat cancer cells.
Subject(s)
Breast Neoplasms/pathology , Metal Nanoparticles , Silver/chemistry , Apoptosis , Breast Neoplasms/therapy , Cell Line, Tumor , Comet Assay , Female , Humans , Microscopy, Electron, Scanning , Plant Extracts/pharmacology , Sesbania/chemistry , Spectrophotometry, UltravioletABSTRACT
Direct regeneration from explants without an intervening callus phase has several advantages, including production of true type progenies. Axillary bud explants from 6-month-old sugarcane cultivars Co92061 and Co671 were co-cultivated with Agrobacterium strains LBA4404 and EHA105 that harboured a binary vector pGA492 carrying neomycin phosphotransferase II, phosphinothricin acetyltransferase (bar) and an intron containing beta-glucuronidase (gus-intron) genes in the T-DNA region. A comparison of kanamycin, geneticin and phosphinothricin (PPT) selection showed that PPT (5.0 mg l(-1)) was the most effective selection agent for axillary bud transformation. Repeated proliferation of shoots in the selection medium eliminated chimeric transformants. Transgenic plants were generated in three different steps: (1) production of putative primary transgenic shoots in Murashige-Skoog (MS) liquid medium with 3.0 mg l(-1) 6-benzyladenine (BA) and 5.0 mg l(-1) PPT, (2) production of secondary transgenic shoots from the primary transgenic shoots by growing them in MS liquid medium with 2.0 mg l(-1) BA, 1.0 mg l(-1) kinetin (Kin), 0.5 mg l(-1) alpha-napthaleneacetic acid (NAA) and 5.0 mg l(-1) PPT for 3 weeks, followed by five more cycles of shoot proliferation and selection under same conditions, and (3) rooting of transgenic shoots on half-strength MS liquid medium with 0.5 mg l(-1) NAA and 5.0 mg l(-1) PPT. About 90% of the regenerated shoots rooted and 80% of them survived during acclimatisation in greenhouse. Transformation was confirmed by a histochemical beta-glucuronidase (GUS) assay and PCR amplification of the bar gene. Southern blot analysis indicated integration of the bar gene in two genomic locations in the majority of transformants. Transformation efficiency was influenced by the co-cultivation period, addition of the phenolic compound acetosyringone and the Agrobacterium strain. A 3-day co-cultivation with 50 micro M acetosyringone considerably increased the transformation efficiency. Agrobacterium strain EHA105 was more effective, producing twice the number of transgenic shoots than strain LBA4404 in both Co92061 and Co671 cultivars. Depending on the variety, 50-60% of the transgenic plants sprayed with BASTA (60 g l(-1) glufosinate) grew without any herbicide damage under greenhouse conditions. These results show that, with this protocol, generation and multiplication of transgenic shoots can be achieved in about 5 months with transformation efficiencies as high as 50%.