• Title/Summary/Keyword: Human genetics

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Association of Immunohistochemically Defined Molecular Subtypes with Clinical Response to Presurgical Chemotherapy in Patients with Advanced Breast Cancer

  • Khokher, Samina;Qureshi, Muhammad Usman;Mahmood, Saqib;Nagi, Abdul Hannan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3223-3228
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    • 2013
  • Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with different clinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive and not available in the developing countries where the majority of patients present at advanced stage. The St Gallen Consensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR, HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like and HER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively. Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer (TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed by HER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity was observed within each subgroup, being most marked in the TNBC although the most responding tumors, 8% developing clinical-progressive-disease. The study supports association of molecular subtypes with response to chemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.

A Novel Mutation in the DNA Binding Domain of NFKB is Associated with Speckled Leukoplakia

  • Govindarajan, Giri Valanthan Veda;Bhanumurthy, Lokesh;Balasubramanian, Anandh;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3627-3629
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    • 2016
  • Background: Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation. Materials and Methods: Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample. Conclusions: The identification of a substitution mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB mutation may be relatively an early event during transformation. To the best of our knowledge, this study is the first to have identified a missense mutation in NFKB in OL.

In Vitro Studies on Phytochemical Content, Antioxidant, Anticancer, Immunomodulatory, and Antigenotoxic Activities of Lemon, Grapefruit, and Mandarin Citrus Peels

  • Diab, Kawthar AE
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3559-3567
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    • 2016
  • Background: In recent years, there has been considerable research on recycling of agro-industrial waste for production of bioactive compounds. The food processing industry produces large amounts of citrus peels that may be an inexpensive source of useful agents. Objective: The present work aimed to explore the phytochemical content, antioxidant, anticancer, antiproliferation, and antigenotxic activities of lemon, grapefruit, and mandarin peels. Materials and Methods: Peels were extracted using 98% ethanol and the three crude extracts were assessed for their total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant activity using DPPH (1, 1-diphenyl-2-picrylhydrazyl). Their cytotoxic and mitogenic proliferation activities were also studied in human leukemia HL-60 cells and mouse splenocytes by CCK-8 assay. In addition, genotoxic/antigenotoxic activity was explored in mouse splenocytes using chromosomal aberrations (CAs) assay. Results: Lemon peels had the highest of TPC followed by grapefruit and mandarin. In contrast, mandarin peels contained the highest of TFC followed by lemon and grapefruit peels. Among the extracts, lemon peel possessed the strongest antioxidant activity as indicated by the highest DPPH radical scavenging, the lowest effective concentration 50% ($EC_{50}=42.97{\mu}g\;extract/mL$), and the highest Trolox equivalent antioxidant capacity (TEAC=0.157). Mandarin peel exhibited moderate cytotoxic activity ($IC_{50}=77.8{\mu}g/mL$) against HL-60 cells, whereas grapefruit and lemon peels were ineffective anti-leukemia. Further, citrus peels possessed immunostimulation activity via augmentation of proliferation of mouse splenocytes (T-lymphocytes). Citrus extracts exerted non-cytotoxic, and antigenotoxic activities through remarkable reduction of CAs induced by cisplatin in mouse splenocytes for 24 h. Conclusions: The phytochemical constituents of the citrus peels may exert biological activities including anticancer, immunostimulation and antigenotoxic potential.

Increasing the Pig Market Weight: World Trends, Expected Consequences and Practical Considerations

  • Kim, Y.S.;Kim, S.W.;Weaver, M.A.;Lee, C.Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.4
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    • pp.590-600
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    • 2005
  • The present report has been aimed at reviewing important factors which need to be closely analyzed or considered when increasing the market weight of finishing pigs. The pig market weight has increased worldwide during the past few decades, which is attributable primarily to an increased lean gain potential of finishing pigs. To increase the market weight, however, the acceptability of larger pigs by the packer as well as pork consumers should be met first. By increasing the market weight, total number of breeding stock, as well as the facility for them, necessary for producing a given weight of pork can be reduced, whereas more building space for finishing pigs and an additional nutrition program for the later finishing period are needed. Additionally, a more thorough disease prevention program especially against ileitis and mycoplasma pneumonia may also be needed, because outbreaks of these are known to increase with increasing body weight over 110 kg. Some larger finishing pigs may deposit excessive fat that may be reduced or prevented by using hormonal and/or nutritional agents. Backfat thickness increases linearly with increasing body weight between 110 and 130 kg, whereas intramuscular fat content does not change significantly. With increasing live weight within this range, the ratios of belly and loin to carcass weight also are known to increase. Some physicochemical characteristics related to fresh and cooked meat quality including color, firmness, juiciness, etc. are known to be unaffected or slightly changed following an increase of slaughter weight. In conclusion, ratios of primal cuts and pork quality characteristics are not significantly affected by increasing the market weight. Moreover, increasing the market weight of lean-type pigs approximately up to 130 kg is normally profitable to producers, as long as packers and consumers accept larger pigs.

Interferon Stimulated Gene - ISG15 is a Potential Diagnostic Biomarker in Oral Squamous Cell Carcinomas

  • Laljee, Rupesh Puthenparambil;Muddaiah, Sunil;Salagundi, Basavaraj;Cariappa, Ponappa Muckatira;Indra, Adarsh Surendran;Sanjay, Venkataram;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.1147-1150
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    • 2013
  • Background: Cancer diagnostic biomarkers have a wide range of applications that include early detection of oral precancerous lesions and oral squamous cell carcinomas, and assessing the metastatic status of lesions. The interferon stimulated ISG15 gene encodes an ubiquitin-like protein, which conjugates to stabilize activation status of associated proteins. Hence a deregulated expression of ISG15 may promote carcinogenesis. Indeed overexpression of ISG15 has been observed in several cancers and hence it has been proposed as a strong candidate cancer diagnostic biomarker. Given the emerging relationship between malignant transformation and ISG15, we sought to examine the expression pattern of this gene in tumor biopsies of oral squamous cell carcinoma (OSCC) tissues collected from Indian patients. Materials and Methods: Total RNA isolated from thirty oral squamous cell carcinoma tissue biopsy samples were subjected to semi-quantitative RT-PCR with ISG15 specific primers to elucidate the expression level. Results: Of the thirty oral squamous cell carcinomas that were analyzed, ISG15 expression was found in twenty four samples (80%). Twelve samples expressed low level of ISG15, six of them expressed moderately, while the rest of them expressed very high level of ISG15. Conclusions: To the best of our knowledge, the results show for the first time an overexpression of ISG15 in up to 80% of oral squamous cell carcinoma tissues collected from Indian patients. Hence ISG15 may be explored for the possibility of use as a high confidence diagnostic biomarker in oral cancers.

Lack of RING Finger Domain (RFD) Mutations of the c-Cbl Gene in Oral Squamous Cell Carcinomas in Chennai, India

  • Rajendran, Senthilnathan;Muthupalani, Rajendran Shanmugam;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.1073-1075
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    • 2013
  • Background: In normal cells, activated epidermal growth factor receptor (EGFR) molecules are subjected to ubiquitination-mediated proteasome degradation pathway by c-Cbl, an ubiquitin ligase that checks uncontrolled proliferation. Hence expression of wild type c-Cbl molecule is essential to keep this degradation machinery in a functional state. Loss of expression or function of c-Cbl may consequently lead to sustained activation of EGFR and promote carcinogenesis, loss of function mutations in the c-Cbl gene already being reported in lung and hematopoietic cancers. However, the genetic status of c-Cbl in oral squamous cell carcinoma (OSCC) is not known. Hence in the present study we investigated the genomic DNA isolated from OSCC tissue biopsy samples for mutations in the RING finger domain coding region of c-Cbl gene, which has also been reported to be most frequently mutated in other cancers. Materials and Methods: Total genomic DNA isolated from thirty two post surgical OSCC tissue samples were amplified using primers flanking the exon 8 of c-Cbl gene that codes for the RING finger domain. The PCR amplicons were then resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: The sequencing data of the thirty two OSCC samples did not identify mutations in the RING finger domain coding region of c-Cbl gene. Conclusions: To the best of our knowledge, this is the first time that the genetic status of c-Cbl gene in OSCC samples has been investigated. The present data indicates that genetic alteration of RING finger domain coding region of c-Cbl gene is relatively infrequent in OSCC samples.

Detection of Ocular Toxoplasma gondii Infection in Chronic Irregular Recurrent Uveitis by PCR

  • Lee, Sang-Eun;Hong, Sung-Hee;Lee, Seong-Ho;Jeong, Young-Il;Lim, Su-Jin;Kwon, Oh-Woong;Kim, Sun-Hyun;You, Young-Sung;Cho, Shin-Hyeong;Lee, Won-Ja
    • Parasites, Hosts and Diseases
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    • v.50 no.3
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    • pp.229-231
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    • 2012
  • Toxoplasma gondii is a zoonotic parasite resulting in human infections and one of the infectious pathogens leading to uveitis and retinochoroiditis. The present study was performed to assess T. gondii infection in 20 ocular patients with chronic irregular recurrent uveitis (20 aqueous humor and 20 peripheral blood samples) using PCR. All samples were analyzed by nested PCR targeting a specific B1 gene of T. gondii. The PCR-positive rate was 25% (5/20), including 5% (1) in blood samples, 25% (5) in aqueous humor samples, and 5% (1) in both sample types. A molecular screening test for T. gondii infection in ocular patients with common clinical findings of an unclear retinal margin and an inflammatory membrane over the retina, as seen by fundus examination, may be helpful for early diagnosis and treatment.

HyperConv: spatio-spectral classication of hyperspectral images with deep convolutional neural networks (심층 컨볼루션 신경망을 사용한 초분광 영상의 공간 분광학적 분류 기법)

  • Ko, Seyoon;Jun, Goo;Won, Joong-Ho
    • The Korean Journal of Applied Statistics
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    • v.29 no.5
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    • pp.859-872
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    • 2016
  • Land cover classification is an important tool for preventing natural disasters, collecting environmental information, and monitoring natural resources. Hyperspectral imaging is widely used for this task thanks to sufficient spectral information. However, the curse of dimensionality, spatiotemporal variability, and lack of labeled data make it difficult to classify the land cover correctly. We propose a novel classification framework for land cover classification of hyperspectral data based on convolutional neural networks. The proposed framework naturally incorporates full spectral features with the information from neighboring pixels and has advantages over existing methods that require additional feature extraction or pre-processing steps. Empirical evaluation results show that the proposed framework provides good generalization power with classification accuracies better than (or comparable to) the most advanced existing classifiers.

Intrauterine diabetic milieu instigates dysregulated adipocytokines production in F1 offspring

  • Tawfik, Shady H.;Haiba, Maha M.;Saad, Mohamed I.;Abdelkhalek, Taha M.;Hanafi, Mervat Y.;Kamel, Maher A.
    • Journal of Animal Science and Technology
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    • v.59 no.1
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    • pp.1.1-1.11
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    • 2017
  • Background: Intrauterine environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome. Diabetes is associated with low-grade inflammatory state and dysregulated adipokines production. The aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-${\alpha}$) production in F1 offspring in rats. Methods: The offspring groups were as follows: F1 offspring of control mothers under control diet (CD) (CF1-CD), F1 offspring of control mothers under high caloric diet (HCD) (CF1-HCD), F1 offspring of diabetic mothers under CD (DF1-CD), and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks post-natal, 10 pups of each subgroup were culled to obtain blood samples for biochemical analysis. Results: The results indicate that DF1-CD and DF1-HCD groups exhibited hyperinsulinemia, dyslipidemia, insulin resistance and impaired glucose homeostasis compared to CF1-CD (p > 0.05). DF1-CD and DF1-HCD groups had high hepatic and muscular depositions of TGs. The significant elevated NEFA level only appeared in offspring of diabetic mothers that was fed HCD. DF1-CD and DF1-HCD groups demonstrated low serum levels of adiponectin, high levels of leptin, and elevated levels of TNF-${\alpha}$ compared to CF1-CD (p > 0.05). These results reveal the disturbed metabolic lipid profile of offspring of diabetic mothers and could guide further characterization of the mechanisms involved. Conclusion: Dysregulated adipocytokines production could be a possible mechanism for the transgenerational transmittance of diabetes, especially following a postnatal diabetogenic environment. Moreover, the exacerbating effects of postnatal HCD on NEFA in rats might be prone to adipcytokine dysregulation. Furthermore, dysregulation of serum adipokines is a prevalent consequence of maternal diabetes and could guide further investigations to predict the development of metabolic disturbances.

Heritability Estimated Using 50K SNPs Indicates Missing Heritability Problem in Holstein Breeding

  • Shin, Donghyun;Park, Kyoung-Do;Ka, Sojoeng;Kim, Heebal;Cho, Kwang-hyeon
    • Genomics & Informatics
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    • v.13 no.4
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    • pp.146-151
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    • 2015
  • Previous studies in Holstein have shown 35% to 51.8% heritability in milk production traits, such as milk yield, fat, and protein, using pedigree data. Other studies in complex human traits could be captured by common single-nucleotide polymorphisms (SNPs), and their genetic variations, attributed to chromosomes, are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analyzed three quantitative Holstein traits relevant to milk production in Korean Holstein data harvested from 462 individuals genotyped for 54,609 SNPs. For all three traits (milk yield, fat, and protein), we estimated a nominally significant (p = 0.1) proportion of variance explained by all SNPs on the Illumina BovineSNP50 Beadchip ($h^2_G$). These common SNPs explained approximately most of the narrow-sense heritability. Longer genomic regions tended to provide more phenotypic variation information, with a correlation of 0.46~0.53 between the estimate of variance explained by individual chromosomes and their physical length. These results suggested that polygenicity was ubiquitous for Holstein milk production traits. These results will expand our knowledge on recent animal breeding, such as genomic selection in Holstein.