Tissue Expression Of LPHN3 in Breast Cancer: An Immunohistochemistry Method.

OBJECTIVE: Breast cancer is one of the most important public health problems among women worldwide. It is a major cause of morbidity especially among women in developing countries including Thailand. The purpose of this study was to study the expression of LPHN3 protein in normal breast tissue compared to breast cancer tissue. METHODS: We had studied the expression of LPHN3 in 65 breast tissues using an immunohistochemistry method. The association between LPHN3 expression and breast cancer metastasis to nearby axillary lymph nodes was also examined. RESULTS: Among the 65 breast cancer and normal breast tissues examined, LPHN3 expression with an immunohistochemistry index (IHC index) greater than 4 was more frequently found in breast cancer tissues than in normal breast tissues (P-value = 0.001, OR (95% CI) = 7.04 (2.16-23)). Moreover, a high expression of LPHN3 (IHC index > 4) was more frequently found in breast cancer tissues with negative axillary lymph nodes than in those with positive ones (P-value = 0.038, OR (95% CI) = 0.25 (0.07-0.96)). LPHN3 protein might be a new metastasis suppressor gene in breast cancer and a marker for breast cancer metastasis prevention. CONCLUSIONS: The present study indicated that a decrease of LPHN3 protein expression in breast cancer tissue might be a marker indicating the aggressiveness of breast cancer. These results also suggested that a decrease of LPHN3 expression could be functionally involved in breast cancer progression and metastasis.

Mutation Screening and Association Study of the Folylpolyglutamate Synthetase (FPGS) Gene with Susceptibility to Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: Folylpolyglutamate synthetase (FPGS), an important enzyme in the folate metabolic pathway, plays a central role in intracellular accumulation of folate and antifolate in several mammalian cell types. Loss of FPGS activity results in decreased cellular levels of antifolates and consequently to polyglutamatable antifolates in acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: During May 1997 and December 2003, 134 children diagnosed with ALL were recruited from one hospital in Thailand. We performed a mutation analysis in the coding regions of the FPGS gene and the association between single nucleotide polymorphisms (SNPs) within FPGS in a case-control sample of childhood ALL patients. Mutation screening was conducted by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently with direct sequencing (n=72). Association analysis between common FPGS variants and ALL risk was done in 98 childhood ALL cases and 95 healthy volunteers recruited as controls. RESULTS: Seven SNPs in the FPGS coding region were identified by mutation analysis, 3 of which (IVS13+55C>T, g.1297T>G, and g.1508C>T) were recognized as novel SNPs. Association analysis revealed 3 of 6 SNPs to confer significant increase in ALL risk these being rs7039798 (p= 0.014, OR=2.14), rs1544105 (p=0.010, OR= 2.24), and rs10106 (p=0.026, OR= 1.99). CONCLUSIONS: These findings suggested that common genetic polymorphisms in the FPGS coding region including rs7039789, rs1544105, and rs10106 are significantly associated with increased ALL risk in Thai children.

Effects of malaria parasite density on blood cell parameters.

Changes in blood cell parameters are already a well-known feature of malarial infections. To add to this information, the objective of this study was to investigate the varying effects that different levels of parasite density have on blood cell parameters. Patients diagnosed with malaria at Phobphra Hospital, Tak Province, Thailand between January 1st 2009 and January 1st 2012 were recruited as subjects for data collection. Blood cell parameters of 2,024 malaria-infected patients were evaluated and statistically analyzed. Neutrophil and platelet counts were significantly higher, however, RBC count was significantly lower in patients with P. falciparum infection compared to those with P. vivax infection (p<0.0001). Leukocyte counts were also significantly higher in patients with high parasitemia compared to those with low and moderate parasitemia. In terms of differential leukocyte count, neutrophil count was significantly higher in patients with high parasitemia compared to those with low and moderate parasitemia (p<0.0001). On the other hand, both lymphocyte and monocyte counts were significantly lower in patients with high parasitemia (p<0.0001). RBC count and Hb concentration, as well as platelet count were also significantly reduced (p<0.05) and (p<0.0001), respectively. To summarize, patients infected with different malaria parasites exhibited important distinctive hematological parameters, with neutrophil and eosinophil counts being the two hematological parameters most affected. In addition, patients infected with different malarial densities also exhibited important changes in leukocyte count, platelet count and hemoglobin concentration during the infection. These findings offer the opportunity to recognize and diagnose malaria related anemia, help support the treatment thereof, as well as relieve symptoms of severe malaria in endemic regions.

Knowledge, attitudes and practice of breast cancer screening among female personnel of Walailak University.

BACKGROUND: Breast cancer is the most common cancer among women worldwide. METHODS: This study aimed to assess the knowledge, awareness and practice of breast cancer screening for early detection of breast cancer among female personnel at a university. A cross-sectional descriptive study was administered to female personnel of Walailak University in Nakhon Si Thammarat, Thailand. Data were analysed by SPSS version 16. RESULTS: Among total of 217 female personnel, the lecturers and laboratory scientists and general officers had a significantly higher mean knowledge score about the practice of breast cancer screening than temporary employees (P < 0.0001). The level of education and income of respondents may be involved with this difference in knowledge (P < 0.05). CONCLUSION: This study concludes that knowledge about the practice of breast cancer screening could be attributed to different career groups, level of education and income of respondents. There is a very urgent need for regular learning courses for personnel concerning knowledge about the practice of breast cancer screening especially for those personnel with less formal education and low income.

Histopathology analysis of benign colorectal diseases and colorectal cancer in Hatyai Hospital, Songkhla, Thailand.

BACKGROUND: Colorectal cancer (CRC) is a major cause of morbidity and mortality in the western world and also ranks as the fifth-leading malignancy and death in Thailand. This study aimed to provide a present outlook of colorectal diseases among Thai patients with special emphasis on CRC in Hatyai, Songkhla, southern Thailand. MATERIALS AND METHODS: This retrospective study covered ten year data of CRC, benign colorectal tumors and non-colorectal tumors from the Department of Pathology in Hatyai Hospital, Songkhla, Thailand, between years 2003-2012. Incidence rates based on age, gender, ten year incidence trends, and distribution of histopathological characteristics of patients were calculated and demonstrated. RESULTS: Out of 730 biopsies, 100 cases were benign colorectal tumors, 336 were CRC and 294 were non-colorectal tumors. Colorectal tumors (both benign and CRC) (60.1%) were more common than non-colorectal tumors (39.9%). CRC (77.1%) were more common than benign colorectal tumors (32.9%). Colorectal tumors were mainly found in patients aged over sixty whereas non-colorectal and benign colorectal tumors were found in those under sixty (P=0.01). sAmong CRC, adenocarcinoma contributed about 97.3% of all cases with well differentiated tumors being the most frequent (56.9%). Both benign colorectal tumors and CRC were more commonly found in males (63%) than females (37%). The incidence trend of CRC demonstrated increase from 2003-2012. CONCLUSIONS: The incidence of CRC increased in Hatyai from 2003-2012. CRC tends to be more common in people older than sixty, thus, screening programs, cost-effective analysis of treatment modalities, and treatment protocols for the elderly should be examined. Proper implementation of preventive measures such as changing lifestyle factors might enhance control of colorectal disease.

Candidate gene association analysis of acute lymphoblastic leukemia identifies new susceptibility locus at 11p15 (LMO1).

To determine the contribution of susceptibility loci in explaining the genetic basis of acute lymphoblastic leukemia (ALL), we genotyped 29 high-potential candidate genes with 672 tagged single-nucleotide polymorphisms (SNPs) in a sample (163 cases and 251 healthy controls) of Caucasian children. Fifty SNPs in 15 genes were significantly associated with ALL risk at the P < 0.05 level. After correction for multiple testing, rs442264 within the LIM domain only 1 (LMO1) gene at 11p15 remained significant [odds ratio (OR) = 1.90, P = 3 × 10(-5)]. In addition, a major haplotype within LMO1 comprising 14 SNPs with individual risk associations was found to significantly increase ALL risk (OR = 1.79, P = 0.0006). A stratified analysis on subtype indicated that risk associations of LMO1 variants are significant in children with precursor B-cell leukemia. These data show that genetic variants within LMO1 are associated with ALL and identify this gene as a strong candidate for precursor B-cell leukemogenesis.

Multilocus association of genetic variants in MLL, CREBBP, EP300, and TOP2A with childhood acute lymphoblastic leukemia in Hispanics from Texas.

BACKGROUND: Hispanic children have both a higher incidence and a poorer outcome in acute lymphoblastic leukemia (ALL). Moreover, a higher incidence for therapy-related acute myeloid leukemia with 11q23 translocations after treatment with topoisomerase II (topo II) inhibitors has been observed in Hispanic children with ALL. We sought to determine the potential role of genetic variants within the topoisomerase IIα gene (TOP2A), within the mixed lineage leukemia gene (MLL) and two of its translocation partners, cyclin AMP response element-binding protein gene (CREBBP) and E1A binding protein gene (EP300) in the increased sensitivity of Hispanic children with ALL to topo II inhibitors. METHODS: Fifty-two tagged single nucleotide polymorphisms (SNP) covering the four genes were genotyped in 241 samples (66 children with ALL and 175 age matched controls) of self-identified Hispanic origin. RESULTS: Two SNPs within MLL (rs525549 and rs6589664) and three SNPs within EP300 (rs5758222, rs7286979, and rs20551) were significantly associated with ALL (P = 0.001-0.04). A significant gene-dosage effect for increasing numbers of potential high-risk genotypes (OR = 16.66; P = 2 × 10(-5)) and a major haplotype significantly associated with ALL (OR = 5.68; P = 2 × 10(-6)) were found. Replication in a sample of 137 affected White children and 239 controls showed that only rs6589664 (MLL) was significantly associated in this ethnic group. CONCLUSIONS: Our findings indicate that the association between ALL and common genetic variants within MLL and EP300 is population specific. IMPACT: Replication of our findings in independent Hispanic populations is warranted to elucidate the role of these variants in ALL susceptibility and define their importance in the ethnic specific differences in ALL risk.