ABSTRACT
Papillary thyroid carcinoma (PTC) is the most common thyroid carcinoma and is derived from thyroid follicular cells. In contrast, medullary thyroid carcinoma (MTC) is rare and originates from the parafollicular C-cells. Synchronous occurrence of these two carcinomas is uncommon and occurs as either discrete lesions or as a mixed lesion. The current case report describes a 50-year-old woman with synchronous multiple discrete MTC and PTC with lymph nodes metastasis. Pathologists and treating physicians should be aware of the synchronous coexistence of these entities to avoid possible misdiagnosis.
Subject(s)
Carcinoma, Neuroendocrine/pathology , Carcinoma, Papillary/pathology , Neoplasms, Multiple Primary/pathology , Thyroid Neoplasms/pathology , Female , Humans , Lymphatic Metastasis/pathology , Middle Aged , Thyroid Cancer, PapillaryABSTRACT
A number of studies have pointed to the association of BDNF (brain-derived neurotrophic factor) and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) with schizophrenia. The purpose of this study was to determine whether these two genes are involved in the pathogenesis of schizophrenia in the Malay population. Two single nucleotide polymorphisms Val66Met of BDNF, -2036C>G and g.1238delG of DARPP-32 were genotyped in the Malay population in 200 patients with schizophrenia and 256 healthy controls. Analysis of allele and genotype frequencies in these two groups revealed no significant association of BDNF or DARPP-32 polymorphisms with schizophrenia in Malays. This is the first such association study in the Malay population.
Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Dopamine and cAMP-Regulated Phosphoprotein 32/genetics , Schizophrenia/genetics , Adult , Alleles , Asian People/genetics , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Malaysia , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
Hypoxia, frequently found in the center of solid tumors, may lead to enhance the production of key factor in cell survival, invasion, angiogenesis and loss of apoptosis. The low oxygen tension in hypoxic tumors is also known to interfere with the efficacy of chemotherapy, but the underlying mechanisms are not very clear. Paclitaxel (PTX) is an active agent used in breast cancer chemotherapy, which disturbs microtubule dynamics and impairs the transition of cells from metaphase to anaphase in mitosis, leading to cell death by apoptosis. In the present study, we try to determine whether hypoxia can decrease the chemosensitivity of human breast carcinoma cells to PTX and elucidate the underlying mechanism. We found that hypoxia could decrease PTX-induced cell death and G(2)/M arrest. Furthermore, our results showed that hypoxia inhibit PTX-induced soluble tubulin polymerized. In addition, we also found hypoxia could suppress PTX-induced cell cycle protein-cyclin B1 expression in MCF-7 cells. To further investigate whether the inhibitory effect of hypoxia on PTX-induced cell death is mediated by decreasing levels of cyclin B1, cyclin B1-transfected MCF-7 cells were used under hypoxic condition. The data showed that the hypoxia-based decreasing chemosensitivity of breast cancer cells to PTX was reversed by cyclin B1. We also found that overexpression of cyclin B1 could significantly increase the sensitivity of MCF-7 cells to PTX by stimulating soluble polymerized tubulin. Overall, hypoxia decreases cyclin B1, which could in turn reverse hypoxia-induced decreasing chemosensitivity to PTX in breast cancer cell line MCF-7.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/drug therapy , Cyclin B1/metabolism , Paclitaxel/pharmacology , Apoptosis/drug effects , Breast Neoplasms/pathology , Cell Hypoxia , Cell Line, Tumor , Drug Resistance, Neoplasm , Female , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , M Phase Cell Cycle Checkpoints/drug effects , Tubulin/metabolism , Tubulin Modulators/pharmacologyABSTRACT
Molecular components of the dopamine D3 receptor (DRD3) may play an important role in the pathophysiology of schizophrenia. Previous studies have demonstrated an association between DRD3 Ser9Gly and cathechol-o-methyltransferase (COMT, SNP = rs165656) polymorphisms and schizophrenia but the results were inconclusive. We investigated this apparent association between Ser9Gly (A/G) polymorphism and an intronic SNP (dbSNP or rs165656) in 261 Malay patients diagnosed with schizophrenia and 216 controls, using PCR-RFLP. The genotype distribution of the polymorphism DRD3 Ser9Gly was in Hardy-Weinberg equilibrium (HWE) for patients (P = 0.1251) and out of HWE for controls (P = 0.0137). However, both healthy controls and schizophrenia patients were out of HWE for the polymorphism COMT rs165656. Based on allele and genotype frequencies in both groups, we found no significant association of DRD3 Ser9Gly polymorphisms and COMT (rs165656) with schizophrenia in Malays. Further studies should examine the association between other dopamine-related genes and the behavioral phenotypes of schizophrenia.
Subject(s)
Catechol O-Methyltransferase/genetics , Receptors, Dopamine D3/genetics , Schizophrenia/genetics , Adult , Aged , Female , Genetic Variation , Genotype , Humans , Malaysia , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Schizophrenia/ethnologyABSTRACT
The serotoninergic system has been implicated in the etiology of schizophrenia and other behavioral disorders. Association studies have focused on the tryptophan hydroxylase 2 gene (TPH2) and the 5-hydroxytryptamine receptor 2A gene (5-HTR2A). We genotyped two single-nucleotide polymorphisms, A1438G of 5-HTR2A and intronic rs1386494 of TPH2 in the Malay population, using a sample size of 289 schizophrenic patients and 130 healthy controls. We found a significant association of A1438G of 5-HTR2A with schizophrenia in Malays. On the other hand, TPH2 polymorphism was not associated with schizophrenia. This is the first genetic association study concerning schizophrenia in the Malay population.