The genetic identity of the Vedda: A language isolate of South Asia.

Linguistic data from South Asia identified several language isolates in the subcontinent. The Vedda, an indigenous population of Sri Lanka, are the least studied amongst them. Therefore, to understand the initial peopling of Sri Lanka and the genetic affinity of the Vedda with other populations in Eurasia, we extensively studied the high-resolution autosomal and mitogenomes from the Vedda population of Sri Lanka. Our autosomal analyses suggest a close genetic link of Vedda with the tribal populations of India despite no evidence of close linguistic affinity, thus suggesting a deep genetic link of the Vedda with these populations. The mitogenomic analysis supports this association by pointing to an ancient link with Indian populations. We suggest that the Vedda population is a genetically drifted group with limited gene flow from neighbouring Sinhalese and Sri Lankan Tamil populations. Interestingly, the genetic ancestry sharing of Vedda neglects the isolation-by-distance model. Collectively, the demography of Sri Lanka is unique, where Sinhalese and Sri Lankan Tamil populations excessively admixed, whilst Vedda largely preserved their isolation and deep genetic association with India.

In silico identification and in vitro validation of alpha-hederin as a potent inhibitor of Wnt/ß-catenin signaling pathway in breast cancer stem cells.

Cancer stem cells (CSCs) play a vital role in metastasis, recurrence and chemoresistance in breast cancer. ß-catenin, which is a frequently over activated protein in CSCs, binds to T-cell factor/lymphoid enhancer factor (Tcf/Lef) family transcription factors leading to ectopic expression of Wnt pathway responsive genes necessary for the maintenance and action of CSCs. With the aim of identifying a small molecules that can effectively eliminate CSCs, molecular docking studies were performed against the Tcf/Lef binding hotspot on ß-catenin using a library of 100 natural or synthetic small molecules. Small molecule ligands giving docking energy better than - 7 kcal/mol were further investigated by binding interactions analysis and molecular dynamics (MD) simulations. These compounds were then investigated in vitro, for cytotoxicity against CSCs isolated from MDA-MB-231 triple negative breast cancer cells. Alpha-hederin (AH) was identified as the only compound in the selected library that has cytotoxicity against breast CSCs. AH was further investigated for it's ability to regulate Wnt pathway target genes (Cyclin D1 and CD44)and the tumor suppressor p53by real-time quantitative PCR. Absorption, distribution, metabolism, excretion and toxicity properties of the AH was predicted in silico. AH significantly down regulated the transcription of Cyclin D1 and CD44 while up-regulating the transcription of p53. AH was predicted to have acceptable drug likeness. Although AH is currently known to inhibit the growth of various cancer cells in vitro, present study demonstrated for the first time that it is a potent inhibitor of Wnt/ß-catenin signaling pathway and induce apoptosis in breast CSCs.

Factors affecting iron absorption and the role of fortification in enhancing iron levels.

Iron is an important micronutrient required for a number of biological processes including oxygen transport, cellular respiration, the synthesis of nucleic acids and the activity of key enzymes. The World Health Organization has recognised iron deficiency as the most common nutritional deficiency globally and as a major determinant of anaemia. Iron deficiency anaemia affects 40% of all children between the ages of 6 and 59 months, 37% of mothers who are pregnant and 30% of women between the ages of 15 and 49 years worldwide. Dietary iron exists in two main forms known as haem iron and non-haem iron. Haem iron is obtained from animal sources such as meat and shows higher bioavailability than non-haem iron, which can be obtained from both plant and animal sources. Different components in food can enhance or inhibit iron absorption from the diet. Components such as meat proteins and organic acids increase iron absorption, while phytate, calcium and polyphenols reduce iron absorption. Iron levels in the body are tightly regulated since both iron overload and iron deficiency can exert harmful effects on human health. Iron is stored mainly as haemoglobin and as iron bound to proteins such as ferritin and hemosiderin. Iron deficiency affects individuals at increased risk due to factors such as age, pregnancy, menstruation and various diseases. Different solutions for iron deficiency are applied at individual and community levels. Iron supplements and intravenous iron can be used to treat individuals with iron deficiency, while various types of iron-fortified foods and biofortified crops can be employed for larger communities. Foods such as rice, flour and biscuits have been used to prepare fortified iron products. However, it is important to ensure the fortification process does not exert significant negative effects on organoleptic properties and the shelf life of the food product.

Reconstructing the population history of the Sinhalese, the major ethnic group in Sri Lanka.

The Sinhalese are the major ethnic group in Sri Lanka, inhabiting nearly the whole length and breadth of the island. They speak an Indo-European language of the Indo-Iranian branch, which is held to originate in northwestern India, going back to at least the fifth century BC. Previous genetic studies on low-resolution markers failed to infer the genomic history of the Sinhalese population. Therefore, we have performed a high-resolution fine-grained genetic study of the Sinhalese population and, in the broader context, we attempted to reconstruct the genetic history of Sri Lanka. Our allele-frequency-based analysis showed a tight cluster of Sinhalese and Tamil populations, suggesting strong gene flow beyond the boundary of ethnicity and language. Interestingly, the haplotype-based analysis preserved a trace of the North Indian affiliation to the Sinhalese population. Overall, in the South Asian context, Sri Lankan ethnic groups are genetically more homogeneous than others.

Mitochondrial genome in sporadic breast cancer: A case control study and a proteomic analysis in a Sinhalese cohort from Sri Lanka.

Breast cancer is the commonest malignancy in women and the majority occurs sporadically with no hereditary predisposition. However, sporadic breast cancer has been studied less intensively than the hereditary form and to date hardly any predictive biomarkers exist for the former. Furthermore, although mitochondrial DNA variants have been reported to be associated with breast cancer, findings have been inconsistent across populations. Thus we carried out a case control study on sporadic breast cancer patients and healthy controls of Sinhalese ethnicity (N = 60 matched pairs) in order to characterize coding region variants associated with the disease and to identify any potential biomarkers. Mitochondrial genome was fully sequenced in 30 pairs and selected regions were sequenced in the remaining 30 pairs. Several in-silico tools were used to assess functional significance of the variants observed. A number of variants were identified among the patients and the controls. Missense variants identified were either polymorphisms or rare variants. Their prevalence did not significantly differ between patients and the healthy controls (matched for age, body mass index and menopausal status). MT-CYB, MT-ATP6 and MT-ND2 genes showed a higher mutation rate. A higher proportion of pre-menopausal patients carried missense and pathogenic variants. Unique combinations of missense variants were seen within genes and these occurred mostly in MT-ATP6 and MT-CYB genes. Such unique combinations that occurred exclusively among the patients were common in obese patients. Mitochondrial DNA variants may have a role in breast carcinogenesis in obesity and pre-menopause. Molecular dynamic simulations suggested the mutants, G78S in MT-CO3 gene and T146A in MT-ATP6 gene are likely to be more stable than their wild type counterparts.

Cytotoxicity against Human Hepatocellular Carcinoma (HepG2) Cells and Anti-Oxidant Activity of Selected Endemic or Medicinal Plants in Sri Lanka.

Hepatocellular carcinoma (HCC) is the most fatal cancer globally with limited treatment options. Plants and herbs have been used to treat cancer and other diseases for a long time by traditional practitioners in Sri Lanka. In the present study, leaf and bark extracts of selected plants were investigated for cytotoxic properties on HepG2 cells. Anti-oxidant activity and total phenolic and flavonoid contents were also determined. Plant extracts that exerted cytotoxic effects on the HepG2 cell line with IC50 <100 µg/mL were tested on normal liver epithelial cells (THLE-3). Out of the 56 extracts, 21 exhibited potent cytotoxic effects (IC50 < 100 µg/mL) on HepG2 cells after 48 h exposure, and 12 were less toxic (IC50 > 100 µg/mL) to THLE-3 normal liver cells. Six extracts exhibited potent radical scavenging activity with EC50 < 100 µg/mL against 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, while 17 extracts showed potent anti-oxidant activity (Trolox equivalents > 100 mg/g) against ferric reducing anti-oxidant power (FRAP) assay. Out of the 56 extracts, 15 had total phenolic content above 100 mg/g of gallic acid equivalents, and 4 had flavonoid content above 100 mg/g of quercetin equivalents. Among the extracts screened, hexane, dichloromethane, ethyl acetate, and methanol extracts of Allophylus cobbe leaves (IC50 - 9.388, 6.8, 19.95, and 11.3 µg/mL, respectively), Madhuca longiflora bark (IC50 - 14.42 µg/mL), methanol extract of Munronia pinnata bark (IC50 - 52.06 µg/mL), and hexane, dichloromethane, ethyl acetate, and methanol extracts of Adenanthera bicolor (IC50 - 45.86, 27.35, 24.56, and 61.83 µg/mL, respectively) exerted potent cytotoxicity against HepG2 with less toxicity (IC50 > 100 µg/mL) to THLE-3 cells after 48 h of incubation. These findings provide a direction to isolate possible anti-cancer compounds for hepatocellular carcinoma.

Mitochondrial DNA (CA)n dinucleotide repeat variations in Sinhalese and Vedda populations in Sri Lanka.

Sinhalese and Vedda people are respectively the major ethnic group and the descendants of the probably earliest inhabitants of Sri Lanka, both believed to have a long history of settlement on the island. However, very little information is available on the origin and possible migration patterns of the two populations. Some studies have focused on (CA) dinucleotide repeat variations located in the mitochondrial hypervariable region 3 (HVS3) (base pairs 514-524) as a useful biomarker to understand migration patterns of different populations. Hence, here we analyze these repeat variations in these two ethnic groups to understand their historical roots and possible patterns of gene flow. Blood samples were collected from healthy, maternally unrelated individuals (N = 109) and mitochondrial D-loop was amplified and sequenced. The (CA)4 dinucleotide repeat in hypervariable region 3 was detected in the majority of Vedda samples while the remaining samples were defined by a (CA)5 cluster. In contrast, the (CA)5 repeat was the most frequent among Sinhalese followed by (CA)4 and (CA)7 repeats. Haplogroup diversity of (CA)4 variation indicated that the majority of Sinhalese individuals grouped into the M30 haplogroup while Vedda clustered into the R5a2b and U7a2 haplogroups. No significant differences in diversity measures were observed among the two populations. However, Multidimensional Scaling indicated a separate clustering for aboriginal Vedda and contemporary Sinhalese populations. Results from this study can be used together with mitochondrial DNA information from hypervariable regions 1 and 2 to perform anthropological and forensic investigations in the two populations studied.

A new liposomal nanocarrier for co-delivery of gedunin and p-glycoprotein siRNA to target breast cancer stem cells.

Gedunin is a secondary metabolite found in neem tree. Since the first discovery of this compound, its bio-active properties have been continuously evaluated. However, the low hydrophobicity of gedunin decreases its bioavailability and pharmacokinetic profile. In the present investigation, a new liposomal nanocarrier for co-delivery of gedunin and P-glycoprotein (P-gp) siRNA [siRNA coated liposomal gedunin (Lipo-Ged-siRNA)] was developed to improve the anti-proliferative activity of gedunin. Characteristics of prepared Lipo-Ged-siRNA demonstrated promising effects. Lipo-Ged-siRNA showed greater anti-proliferative effects (IC50-8.5 µg/mL) followed by pure gedunin (IC50- 40.2 µg/mL) in breast cancer stem cells (bCSCs). Immunofluorescence analysis demonstrated reduced expression of P-gp following exposure to Lipo-Ged-siRNA. Furthermore, Lipo-Ged-siRNA affected the expression of ABCB1, Cyclin D1, Bax, p53, and surviving genes in bCSCs.

Novel gross deletion at the LHX4 gene locus in a child with growth hormone deficiency.

OBJECTIVE: To identify and characterize a novel deletion at the LHX4 gene locus in a proband with growth hormone deficiency (GHD). METHODS: Long range polymerase chain reaction (PCR) amplification was used to confirm the suspected deletion and to identify the rough locations of the end points. Sanger sequencing was carried out to identify the exact end points of the deletion. RESULTS: Suspected deletion was confirmed via long range PCR amplification. Sanger sequencing identified the end points of the deletion within three nucleotide repeat sequences ("CTT"). The total length of the deleted segment was 12 127 base pairs and it includes complete exon 5 and exon 6 of the LHX4 gene. Therefore the homeodomain motif coded by exons 4 and 5, might be affected. CONCLUSION: We have identified a novel deletion that spans exon 5 and exon 6 of the LHX4 gene that could have occurred via microhomology mediated non-recurrent rearrangement. The deletion characterized does not appear to have been reported before. To our knowledge this novel deletion is the first identified LHX4 variant from Sri Lanka and it explains the phenotype of the proband characterized by growth hormone deficiency, hypoplastic anterior pituitary and subsequent deficiency of thyroid stimulating hormone and adrenocorticotropic hormone (ACTH).

Identification of 3-O-α-l-arabinosyl oleanolic acid, a triterpenoid saponin, as a new breast cancer stem cell growth inhibitor.

This study was conducted to determine the anti-cancer activity of 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO), a triterpenoid saponin, isolated from the leaves of Schumacheria castaneifolia Vahl in breast cancer stem cells (bCSCs) grown in hypoxia. Anti-proliferative effects of 3-O-L-AO in bCSCs were determined using WST-1 assay. Real-time PCR was employed to evaluate the effects of 3-O-L-AO on apoptosis. Compound 3-O-L-AO exerted greater anti-proliferative effect in bCSCs grown under hypoxic conditions. Treatment of bCSCs with 3-O-L-AO resulted in a significant up-regulation of Bax and p53 and a significant down-regulation of survivin, HIF-1α and HIF-2α. Activation of caspase 3/7 activity and apoptosis-related morphological changes in bCSCs exposed to 3-O-L-AO further confirmed that 3-O-L-AO can induce apoptosis. Collectively, the results obtained indicated that 3-O-L-AO can be considered as a new anti-cancer agent to target chemo- and radio-therapy-resistant bCSCs.

Interaction of Gut Microbiome and Host microRNAs with the Occurrence of Colorectal and Breast Cancer and Their Impact on Patient Immunity.

Breast and colorectal cancers are two primary malignancies on which most of the research done worldwide investigates the potential genetic and environmental risk factors and thereby tries to develop therapeutic methods to improve prognosis. Breast cancer is the most diagnosed cancer type in women, while colorectal cancer is diagnosed in males as the third most and females as the second most cancer type. Though these two cancer types are predominantly seen in adult patients worldwide, in the current context, these malignancies are diagnosed at a younger age with a significant rate of incidents than previous. Such early-onset cancers are generally present at an advanced stage of the most aggressive type with a poor prognosis. In the past, the focus of the research was mainly on studying possible candidate genes to understand the onset. However, it is now recognized that genetics, epigenetics, and other environmental factors play a pivotal role in cancer susceptibility. Thus, most studies were diversified to study the behavior of host microRNAs, and the involvement of gut microbiota and good communication between them surfaced in the occurrence and state of the disease. It is understood that the impact of these factors affects the outcome of the disease. Out of the adverse outcomes identified relating to the disease, immunosuppression is one of the most concerning outcomes in the current world, where such individuals remain vulnerable to infections. Recent studies revealed that microbiome and microRNA could create a considerable impact on immunosuppression. This review focused on the behavior of host microRNAs and gut microbiome for the onset of the disease and progression, thereby influencing an individual's immunosuppression. Understanding the interactions among microRNA, microbiome, presentation of the disease, and impact on the immune system will be immensely useful for developing future therapeutic strategies based on targeting host microRNA and the patient's gut microbiome. Therapies such as inhibitory-miRNA therapies, miRNA mimic-based therapeutics, immune checkpoint blockade therapies, and bacteria-assisted tumor-targeted therapies help modulate cancer. At the same time, it paid equal attention to potential noninvasive biomarkers in diagnosis, prognosis, and therapeutics in both cancers.

Hexane Extract of Garcinia quaesita Fruits Induces Apoptosis in Breast Cancer Stem Cells Isolated from Triple Negative Breast Cancer Cell Line MDA-MB-231.

Development of therapy resistance is a major clinical issue in breast cancer treatments. Breast cancer stem cells (bCSCs) have a clearly defined role in the development of breast cancer therapy resistance and tumor recurrence. Therefore, discovery of new treatment strategies to circumvent cancer therapy resistance and tumor recurrence by targeting bCSCs is desperately needed. Fruits of many Garcinia species are edible and, possess a range of health benefits. Garcinia quaesita, a species in the genus Garcinia, is endemic to Sri Lanka. Dried fruits of G. quaesita are commonly used to flavor dishes in Sri Lanka. The present study assessed the potential anticancer and apoptotic properties of G. quaesita fruit extracts in bCSCs using WST-1 cell proliferation assay, sphere formation assay, caspase 3/7 assay, real-time PCR and fluorescent and phase-contrast microscopy. DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (Ferric Reducing Anti-oxidant Power) assays were used as anti-oxidant assays. The hexane extract of G. quaesita fruits was found to mediate cytotoxicity in bCSCs through induction of apoptosis. Furthermore, the hexane extract showed free radical scavenging ability. This pilot investigation provides a rationale to consume G. quaesita fruits as an anticancer dietary supplement for breast cancer patients.

Evaluation of non-coding region sequence variants and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in individuals of Sri Lankan Sinhalese ethnicity.

Mitochondrial DNA (mtDNA) mutations have been reported to be associated with various diseases, including cancer. The present study investigated the mtDNA non-coding region mutations and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in Sri Lankan Sinhalese women. Mitochondrial macro-haplogroups were determined using PCR-restriction fragment length polymorphism, whereas non-coding region sequences were determined using Sanger sequencing. The sequence of the non-coding region was also used to confirm haplogroup status. Neither the mutations in the non-coding region nor the mitochondrial haplogroups that were reported as risk factors in other populations, were determined to be potential risk factors for sporadic breast cancer in the present study. Furthermore, several novel mutations were identified in the present matched pairs case-controlled study. The M65a haplogroup with an additional mutation at position 16311 (P=0.0771) and mutations at the ori-b site (P=0.05) were considered a weak risk factor and protective factor, respectively, for sporadic breast cancer in Sinhalese women. Previous studies have indicated the use of mtDNA mutations as a biomarker; however, the present study showed that such biomarkers need to be validated for individual ethnic groups before they can be recommended for use in the prediction of disease.

Evaluation of anticancer effects of a pharmaceutically viable extract of a traditional polyherbal mixture against non-small-cell lung cancer cells.

OBJECTIVE: The present work tested organic solvents to prepare an extract with anticancer properties from a polyherbal mixture containing Nigella sativa (seeds), Hemidesmus indicus (roots) and Smilax glabra (rhizomes). We evaluate anticancer effects in non-small-cell lung cancer cells (NCI-H292), and discuss optimization for pharmaceutical use in the context of efficacy, yield and toxicity. METHODS: Using different organic solvents, six extracts were prepared from the polyherbal mixture. Based on the cytotoxic effects of these extracts on NCI-H292 cells and normal lung cells (MRC-5), as evaluated by the sulphorhodamine B assay, the total ethyl acetate (T-EA) extract was selected for further analysis. The possible anticancer mechanisms were assessed by evaluating the extract's effects on apoptosis (through fluorescent microscopic analysis, DNA fragmentation analysis, caspase 3/7 assay and analysis of expression levels of apoptosis-related genes p53, Bax, survivin, Hsp70 and Hsp90), colony formation and antioxidant activity. RESULTS: The extract had cytotoxic effects against NCI-H292 cells in a time- and dose-dependent manner. Significant antioxidant activity and inhibition of colony formation were also observed. The expression level of caspase 3/7 significantly (P < 0.001) increased in NCI-H292 cells treated with 50 µg/mL of the extract. The same dosage led to a significant increase in expression levels of Bax and p53 (P < 0.05 and P < 0.01 respectively), accompanied by a significant decrease (P < 0.0001) in survivin, Hsp70 and Hsp90. CONCLUSION: T-EA extract of the above polyherbal mixture has cytotoxicity against NCI-H292 cells via induction of apoptosis, antioxidant effects and inhibition of colony formation.

Pattern of nucleotide variants of TP53 and their correlation with the expression of p53 and its downstream proteins in a Sri Lankan cohort of breast and colorectal cancer patients.

BACKGROUND: Breast cancer (BC) is known to be the most common malignancy in females whereas colorectal cancer (CRC) incidence also higher in both genders in Sri Lanka. TP53 is an important tumour suppressor gene and its somatic mutations are reported in approximately 27% of BC and 43% of CRC cases. Analysis of TP53 gene variants not only provides clues for the aetiology of the tumour formation, but also has an impact on treatment efficacy. The current study was conducted to investigate the pattern of TP53 variants in patients with BC and CRC from Sri Lanka. METHODS: 30 patients with BC, 21 patients with CRC and an equal number of healthy controls were screened for mutational status of TP53 by polymerase chain reaction (PCR) followed by direct sequencing. In addition, a subset of these samples were analysed for the protein expression of p53 and comparison made with the mutational status of TP53. We also analysed the protein expression of p21 and MDM2 as potential indicators of p53 functional status and compared it with the protein expression of p53. Additionally, hotspot codons of the KRAS, BRAF and PIK3CA genes were also analysed in a subset of CRC patients. RESULTS: Twenty seven sequence variants, including several novel variants in the TP53 gene were found. Nine BC and seven CRC tumour samples carried pathogenic TP53 variants. Pathogenic point missense variants were associated with strong and diffuse positive staining for p53 by immunohistochemistry (IHC), whereas, wild type TP53 showed complete absence of positive IHC staining or rare positive cells, regardless of the type of cancer. There was no direct correlation between p21 or MDM2 expression and p53 expression in either BCs or CRCs. Four of the CRC patients had pathogenic hotspot variants in KRAS; three of them were on codon 12 and one was on codon 61. CONCLUSION: The prevalence of pathogenic somatic TP53 variants was 31 and 33.33% in the studied BC and CRC cohorts respectively. All of them were located in exons 5-8 and the pathogenic missense variants were associated with strong immuno-positive staining for p53.

The Genome of Setaria digitata: A Cattle Nematode Closely Related to Human Filarial Parasites.

Here we present the draft genome sequence of Setaria digitata, a parasitic nematode affecting cattle. Due to its similarity to Wuchereria bancrofti, the parasitic nematode that causes lymphatic filariasis in humans, S. digitata has been used as a model organism at the genomic level to find drug targets which can be used for the development of novel drugs and/or vaccines for human filariasis. Setaria digitata causes cerebrospinal nematodiasis in goats, sheep, and horses posing a serious threat to livestock in developing countries. The genome sequence of S. digitata will assist in finding candidate genes to use as drug targets in both S. digitata and W. bancrofti. The assembled draft genome is ∼90 Mb long and contains 8,974 genomic scaffolds with a G+C content of 31.73%.

Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance.

Ovarian cancer (OC) is a lethal gynecological cancer. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the regulation of cell survival, growth, and proliferation. Irregularities in the major components of the PI3K/AKT/mTOR signaling pathway are common in human cancers. Despite the availability of strong pre-clinical and clinical data of PI3K/AKT/mTOR pathway inhibitors in OC, there is no FDA approved inhibitor available for the treatment of OC. Here, we outline the importance of PI3K/AKT/mTOR signaling pathway in OC tumorigenesis, proliferation and progression, and pre-clinical and clinical experience with several PI3K/AKT/mTOR pathway inhibitors in OC.

Nucleotide variants and protein expression of TP53 in a Sri Lankan cohort of patients with head and neck cancer.

Head and neck cancer (HNC) is the leading cancer in Sri Lankan males and second most common cancer among Sri Lankan females. This is the first study, to the best of our knowledge, that has focused on investigating the association between TP53 somatic DNA variants, with p53 protein expression and risk factors in a cohort of Sri Lankan patients with HNC. A total of 44 patients with cancer and 20 healthy controls were studied. In total, 36 genomic DNA sequence variants were found, including several novel variants (two deletions in exons 4 and 6, two in the 3' untranslated region and several intronic variants). A total of 14 tumour samples carried pathogenic TP53 mutations. A random selection of 24 samples was analysed immunohistochemically for p53 protein expression. All the samples with point missense variants were strongly immuno­positive, whereas, samples with nonsense and frameshift TP53 variants were immuno­negative for p53 immunohistochemical staining. Although, the human papilloma virus is a known risk factor for HNC, results from the present study identified an absence or lower level of infection in the Sri Lankan cohort.

Overview of the genetic basis toward early detection of breast cancer.

Cancer is a socioeconomical burden in any nation. Out of that, breast cancer is identified as the most common malignancy worldwide among women irrespective of age. As women are an important segment in a community, the weakening of their strength toward the development of a nation is a critical problem in each nation. In this review, it was aimed to discuss the characteristics of cancer genome, cancer genetics, and cancer epigenetics in general and then focus on discussing both genetic and nongenetic factors responsible for the predisposition of breast cancer in humans. More emphasis was placed on genes responsible for the early onset of the disease and which can be used as genetic tools in the identification of the disease at an early stage. Then the context of genetic involvement toward the breast cancer occurrence before age of 40 years was highlighted accordingly. In addition to genetic testing, the review paid adequate attention to mention novel liquid biopsy techniques and other clinical, laboratory, and radiologic assessments. These techniques can be used in early detection and recurrence as well as the surveillance of the patients after primary therapies.

Emerging role of histone deacetylase inhibitors as anti-breast-cancer agents.

Breast cancer (BC) remains the most frequently diagnosed cancer in women. A balance in the opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs) is necessary for epigenetic regulation of gene expression. Impairment in the balance between the actions of HATs and HDACs has been reported in the development of BC. By targeting histone and several non-histone proteins, histone deacetylase inhibitors (HDACi) can maintain the cellular acetylation profile and reverse the function of several proteins responsible for BC development. Preclinical and clinical data show that HDACi can evoke different anticancer mechanisms in distinct BC types.