ABSTRACT
Patients with biliary tract cancer (BTC) were associated with poor prognosis and limited therapeutic options after first-line therapy currently. In this study, we sought to evaluate the feasibility and tolerability of sintilimab plus anlotinib as the second-line treatment for patients with advanced BTC. Eligible patients had histologically confirmed locally advanced unresectable or metastatic BTC and failed after the first-line treatment were recruited. The primary endpoint was overall survival (OS). Simultaneously, association between clinical outcomes and genomic profiling and gut microbiome were explored to identify the potential biomarkers for this regimen. Twenty patients were consecutively enrolled and received study therapy. The trail met its primary endpoint with a median OS of 12.3 months (95% CI: 10.1-14.5). Only four (20%) patients were observed of the grade 3 treatment-related adverse events (TRAEs) and no grade 4 or 5 TRAEs were detected. Mutation of AGO2 was correlated with a significantly longer OS. Abundance of Proteobacteria was associated with inferior clinical response. Therefore, sintilimab plus anlotinib demonstrated encouraging anti-tumor activity with a tolerable safety profile and deserved to be investigated in larger randomized trials for patients with advanced BTC subsequently.
Subject(s)
Bile Duct Neoplasms , Biliary Tract Neoplasms , Humans , Feasibility Studies , Bile Duct Neoplasms/drug therapy , Biliary Tract Neoplasms/genetics , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
BACKGROUND: Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. METHODS: The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. RESULTS: We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. CONCLUSIONS: We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Methylation , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/genetics , Protein Processing, Post-Translational , Biomarkers , Homeodomain Proteins/geneticsABSTRACT
[This corrects the article DOI: 10.3389/fonc.2020.00311.].
ABSTRACT
BACKGROUND AND OBJECTIVES: A standardized data set for esophageal carcinoma pathology reporting was developed based on the approach of the International Collaboration on Cancer Reporting (ICCR) for the purpose of improving cancer patient outcomes and international benchmarking in cancer management. MATERIALS AND METHODS: The ICCR convened a multidisciplinary international expert panel to identify the best evidence-based clinical and pathological parameters for inclusion in the data set for esophageal carcinoma. The data set incorporated the current edition of the World Health Organization Classification of Tumours of the Digestive System, and Tumour-Node-Metastasis staging systems. RESULTS: The scope of the data set encompassed resection specimens of the esophagus and esophagogastric junction with tumor epicenter ≤20 mm into the proximal stomach. Core reporting elements included information on neoadjuvant therapy, operative procedure used, tumor focality, tumor site, tumor dimensions, distance of tumor to resection margins, histological tumor type, presence and type of dysplasia, tumor grade, extent of invasion in the esophagus, lymphovascular invasion, response to neoadjuvant therapy, status of resection margin, ancillary studies, lymph node status, distant metastases, and pathological staging. Additional non-core elements considered useful to report included clinical information, specimen dimensions, macroscopic appearance of tumor, and coexistent pathology. CONCLUSIONS: This is the first international peer-reviewed structured reporting data set for surgically resected specimens of the esophagus. The ICCR carcinoma of the esophagus data set is recommended for routine use globally and is a valuable tool to support standardized reporting, to benefit patient care by providing diagnostic and prognostic best-practice parameters.
Subject(s)
Carcinoma/surgery , Datasets as Topic/standards , Esophageal Neoplasms/surgery , Esophagectomy , Esophagogastric Junction/surgery , Research Design/standards , Stomach Neoplasms/surgery , Benchmarking/standards , Carcinoma/secondary , Chemoradiotherapy, Adjuvant , Cooperative Behavior , Data Accuracy , Esophageal Neoplasms/pathology , Esophagogastric Junction/pathology , Evidence-Based Medicine/standards , Humans , International Cooperation , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging , Stomach Neoplasms/pathology , Treatment OutcomeABSTRACT
Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide. Recent studies have shown that cancer stem cells (CSCs) are present in ESCC, are thought to lead to aggressive tumor behavior and the prognosis. The CXC chemokine receptor 4 (CXCR4), is regarded as a putative CSCs marker in various malignancies. Here, we demonstrate that CXCR4 played a key role in ESCC progression and CXCR4 positive ESCC cells possessed stem-like properties. Furthermore, the anti-malarial agent chloroquine (CQ) targeted CXCR4-positive ESCC cells via STAT3 pathway. Therefore, CQ with anti-CSCs effects may be an effective adjunct to current ESCC chemotherapy regimens.
ABSTRACT
INTRODUCTION: Clear cell adenocarcinoma of the cervix (CCAC), a rare and more severe type of gynecological cancer, is especially rare in pediatric patients. Traditionally, surgery following chemotherapy (CT) and radiation therapy is the preferred treatment for CCAC; however, patients have poor 5-year survival rates than other types of cervical cancers. PATIENT CONCERNS: A 6-year-old girl with a history of vaginal discharge for 18 months was diagnosed with CCAC by histological examination. Her parents refused the traditional treatment of radical hysterectomy and lymph node dissection because of her young age. DIAGNOSIS: The patient's tests revealed negative human papilloma virus and negative methylated paired box 1 gene results. The tumor mass histopathology revealed stage IIA1 CCAC that originated from the cervix. INTERVENTIONS: Tumor mass excision with preservation of the cervix by electrosurgical biopsy under hysteroscopy was performed. Four cycles of docetaxel and oxaliplatin CT were administered every 3 weeks. OUTCOMES: No signs of recurrence were observed in the 28 months after final treatment and diagnosis on magnetic resonance imaging, color ultrasonic imaging, and gynecological examination. Serologic tumor biomarkers were also within normal ranges. CONCLUSIONS: This is the first reported CCAC case in which the primary treatment included electrosurgical biopsy of the polypoid mass under hysteroscopy, followed by CT without traditional treatment: radical surgery with pelvic and/or lymphadenectomy for fertility preservation. This is a new treatment approach for young CCAC patients without the use of surgery.
Subject(s)
Adenocarcinoma/surgery , Hysteroscopy , Organ Sparing Treatments , Uterine Cervical Neoplasms/surgery , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antineoplastic Agents/therapeutic use , Cervix Uteri/pathology , Child , Docetaxel/therapeutic use , Female , Humans , Oxaliplatin/therapeutic use , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathologyABSTRACT
BACKGROUND: This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia induced-chemoresistance in T-cell non-Hodgkin's lymphoma (T-NHL), as well as the underlying molecular mechanisms. METHODS: Expression of AEG-1, LC3-II, and Beclin-1 were initially examined in human T-NHL tissues (n = 30) and normal lymph node tissues (n = 16) using western blot, real-time PCR and immunohistochemistry. Western blot was also performed to analyze the expression of AEG-1, LC3-II, and Beclin-1 in T-NHL cells (Hut-78 and Jurkat cells) under normoxia and hypoxia. Additionally, the proliferation and apoptosis of Hut-78 cells exposed to different concentration of Adriamycin (ADM) in normoxia and hypoxia were evaluated by MTT and Annexin-V FITC/PI staining assay. Finally, the effects of AEG-1 on Hut-78 cells exposed to ADM in hypoxia were assessed by MTT and Annexin-V FITC/PI staining assay, and 3-MA (autophagy inhibitor) was further used to determine the underlying mechanism. RESULTS: AEG-1, LC3-II and Beclin-1 expression were significantly increased in T-NHL tissues compared with normal tissues. Incubation of Hut-78 and Jurkat cells in hypoxia obviously increased AEG-1, LC3-II and Beclin-1 expression. Hypoxia induced proliferation and reduced apoptosis of Hut-78 cells exposed to ADM. AEG-1 overexpression further increased proliferation and decreased apoptosis of Hut-78 cells exposed to ADM in hypoxia. Moreover, overexpression of AEG-1 significantly inversed 3-MA induced-changes in cell proliferation and apoptosis of Hut-78 cells exposed to ADM in hypoxia. CONCLUSIONS: This study suggested that AEG-1 is associated with hypoxia-induced T-NHL chemoresistance via regulating autophagy, uncovering a novel target against hypoxia-induced T-NHL chemoresistance.
Subject(s)
Beclin-1/metabolism , Cell Adhesion Molecules/metabolism , Drug Resistance, Neoplasm , Hypoxia/metabolism , Lymphoma, T-Cell/metabolism , Microtubule-Associated Proteins/metabolism , Antibiotics, Antineoplastic/pharmacology , Autophagy , Beclin-1/genetics , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Doxorubicin/pharmacology , Humans , Hypoxia/genetics , Lymph Nodes/metabolism , Lymphoma, T-Cell/genetics , Membrane Proteins , Microtubule-Associated Proteins/genetics , RNA-Binding ProteinsABSTRACT
The aim of this study was to assess the functional role of SPARC in T-cell non-Hodgkin's lymphoma (T-NHL), as well as the underlying molecular mechanisms. Here, we first identified SPARC expression in T-NHL tissues and cell lines through western blot and real-time PCR (RT-PCR). Overall survival of T-NHL patients with different levels of SPARC was assessed by Kaplan-Meier survival curves. Then cell proliferation, apoptosis, migration and invasion of T-NHL cells with either knockdown or overexpression of SPARC were determined by MTT, flow cytometry, transwell migration and invasion assay, respectively. Finally, the molecular mechanism by which SPARC modulated T-NHL cell progression was assessed. We confirmed that SPARC was significantly down-regulated in T-NHL tissues and cell lines. T-NHL patients with high levels of SPARC demonstrated a favorable clinical outcome. SPARC significantly suppressed cell proliferation, migration and invasion, and EMT process, but facilitated cell apoptosis in T-NHL cells. Further, we found that loss of SPARC expression in T-NHL tissues and cell lines, both in mRNA and protein levels, was associated with the aberrant DNA methylation in SPRAC gene, and the disrupted SPARC expression could be rescued after treatment with the demethylating agent 5-Aza-2'-deoxycitydine (5-Aza-Cdr). Additionally, 5-Aza-Cdr reversed SPARC hypermethylation to restore its biological role as a tumor suppressor in T-NHL cells, including inhibiting cell proliferation, invasion and migration, while promoting cell apoptosis. Our data provided evidence that DNA methylation in SPARC gene may play a role in the progression of T-NHL.
Subject(s)
DNA Methylation , Down-Regulation , Lymphoma, T-Cell/metabolism , Osteonectin/metabolism , Cell Line , Cell Survival , DNA Methylation/genetics , Decitabine/pharmacology , Down-Regulation/genetics , Humans , Lymphoma, T-Cell/diagnosis , Osteonectin/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
The associations between occupational noise exposure and hypertension remain controversial because of the differences in study designs, exposure assessments, and confounding controls. This prospective study investigated the relationship between noise exposure and the 10-year risk of hypertension. A cohort of 578 male workers in Taiwan was followed from 1998 to 2008. All subjects were divided into high-, intermediate-, and low-exposure groups on the basis of noise exposure assessment. Cox regression models were used to estimate the relative risks of hypertension after adjustment for potential confounders. During the 7,805 person-years of follow-up, 141 hypertension cases were identified. Significant increases of 3.2 (95% confidence interval (CI): 0.2, 6.2) mm Hg in systolic blood pressure and 2.5 (95% CI: 0.1, 4.8) mm Hg in diastolic blood pressure between the baseline and follow-up measurements were observed in the high-exposure group. Participants exposed to ≥85 A-weighted decibels (dBA) had a 1.93-fold (95% CI: 1.15, 3.22) risk of hypertension compared with those exposed to <80 dBA. There was a significant exposure-response pattern (P = 0.016) between the risk of hypertension and the stratum of noise exposure. Prolonged exposure to noise levels ≥85 dBA may increase males' systolic and diastolic blood pressure levels. This association may translate into a higher incidence of hypertension.
Subject(s)
Blood Pressure , Hypertension/epidemiology , Hypertension/etiology , Noise, Occupational/adverse effects , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Adult , Aircraft , Alcohol Drinking/adverse effects , Cohort Studies , Confidence Intervals , Follow-Up Studies , Humans , Hypertension/physiopathology , Incidence , Industry , Male , Occupational Diseases/physiopathology , Proportional Hazards Models , Prospective Studies , Risk Assessment , Risk Factors , Smoking/adverse effects , Surveys and Questionnaires , Taiwan/epidemiologyABSTRACT
Our aim in this study was to assess the status of TOP2A gene aberrations (no change/amplification or deletion) and its correlations with topoisomerase IIα (Topo IIα) protein and TOP2A mRNA expression, respectively. TOP2A amplification, Topo IIα protein expression and TOP2A mRNA expression were assessed using samples of 86 cases of breast cancer by fluorescence in fluorescence in situ hybridization, quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Twenty two (22.57%) had amplification/deletion of TOP2A gene. Twenty eight (32.56%) tumor samples were 17q polysomy or monosomy. Topo IIα protein was expressed in 57 cases (66.27%, 57/86): 22 cases (38.62%, 22/57) and 35 cases (61.40%, 35/57) had amplification/deletion and no change of TOP2A gene, respectively. These three groups showed significant differences by one-way analysis of variance (P < 0.001). The average Ct values of TOP2A mRNA expression in the tumors with deletion, amplification and no change of TOP2A gene were 27.00, 27.33 and 31.66, respectively. We demonstrated that the TOP2A gene was amplified or deleted in breast cancer, with a significant correlation with high expressions of Topo IIα protein and TOP2A mRNA expression. Ki-67 expression index (mean = 14.9) decreased significantly in cases wherein TOP2A gene had no change and Her2/neu protein expression was weakly positive (0-1+, P < 0.001).
Subject(s)
Antigens, Neoplasm/genetics , Breast Neoplasms/genetics , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Lobular/genetics , DNA Topoisomerases, Type II/genetics , DNA-Binding Proteins/genetics , Gene Amplification , Gene Deletion , Antigens, Neoplasm/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Intraductal, Noninfiltrating/mortality , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/mortality , Carcinoma, Lobular/pathology , China/epidemiology , DNA Topoisomerases, Type II/metabolism , DNA-Binding Proteins/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence/methods , Middle Aged , Poly-ADP-Ribose Binding Proteins , RNA, Messenger/metabolism , Retrospective Studies , Survival RateABSTRACT
AIM: To investigate the relationship between c.343A>G and c.2216A>C polymorphism sites in the CDH17 gene and colorectal carcinoma. METHODS: Ninety-three non-consanguineous colorectal carcinoma patients admitted to the Department of Oncology at the First Affiliated Hospital of Zhengzhou University were included in this study. Ninety-three peripheral venous blood samples, of approximately one milliliter from each patient, were collected between December 2009 and August 2010. The genomic DNA of these peripheral venous blood samples were extracted and purified using a Fermentas Genomic DNA Purification Kit (Fermentas, CA) according to the manufacturer's protocol. The single nucleotide polymorphisms (SNPs) of the liver-intestine cadherin (CDH17) gene c.343A>G and c.2216A>C were determined by the polymerase chain reaction-single strand conformation polymorphism method (PCR-SSCP) in 93 peripheral venous blood samples from patients suffering with colorectal carcinoma. Typical samples that showed different migration bands in SSCP were confirmed by sequencing. Directed DNA sequencing was used to check the correctness of the genotype results from the PCR-SSCP method. RESULTS: There was a significant association between the c.2216 A>C SNPs of the CDH17 gene and the tumor-node-metastasis (TNM) grade, as well as with lymph node status, in 93 peripheral venous blood samples from colorectal carcinoma patients. The genotype frequencies of A/C, A/A, and C/C were 12.90%, 33.33% and 53.76%, respectively. There was a significant correlation between lymph node metastasis, TNM grade, and the genotype distribution (P < 0.05). The C/C genotype raised the risk of lymph node metastasis and the TNM grade. There was a significant difference in the TNM grade and lymph node metastasis between the A/A and C/C genotypes (P = 0.003 and P = 0.013, respectively). Patients with colorectal carcinoma carrying the C allele tended to have a higher risk of lymph node metastasis and have a higher TNM grade. The difference between the TNM grades, as well as the lymph node metastasis of the two alleles, was statistically significant (P < 0.01). CONCLUSION: The SNPs of the CDH17 gene c.2216 A>C might be clinically important in the prognosis of colorectal carcinoma.
Subject(s)
Cadherins/genetics , Carcinoma/genetics , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Polymorphism, Single Nucleotide , Adult , Aged , Alleles , Base Sequence , Carcinoma/blood , Colorectal Neoplasms/blood , Female , Genotype , Humans , Lymphatic Metastasis , Male , Middle Aged , Molecular Sequence Data , Mutation , Neoplasm Metastasis , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , PrognosisABSTRACT
BACKGROUND: The potential application of retinoic acid receptor activators, such as all trans-retinoic acid (ATRA), for treating various cancers have been studied both pre-clinically and clinically. Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown. We have explored the anticancer effect of ATRA in ESCC, and in this study, the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line, EC9706, in nude mice. METHODS: The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues. RESULTS: Compared to the control group, the tumor inhibition rates in the low dose ATRA, high dose ATRA, and 5-FU groups were 83.21%, 88.32%, 91.02%, respectively. The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P < 0.05). The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31, CD34, and CD105 (component of the TGF-ß receptor) in ESCC xenograft tissues (P < 0.05). CONCLUSIONS: ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.
Subject(s)
Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , Tretinoin/therapeutic use , Animals , Blotting, Western , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Esophageal Neoplasms/metabolism , Humans , Immunohistochemistry , Mice , Mice, Nude , Neovascularization, Pathologic/metabolism , Real-Time Polymerase Chain Reaction , Vascular Endothelial Growth Factor A/metabolism , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: The association between occupational noise exposure and hypertension is inconsistent because of an exposure bias caused by outer-ear measurements of noise levels among workers. This study used hearing loss values (HLVs) measured at 4 kHz and 6 kHz in both ears as a biomarker to investigate the chronic effects of noise exposure on hypertension in 790 aircraft-manufacturing workers. METHODS: Participants were divided into a high hearing loss (HL) group (n = 214; average HLVs ≥ 30 decibel [dB] at 4 kHz or 6 kHz bilaterally; 83.1 ± 4.9 A-weighted decibel [dBA]), a median HL group (n = 302; 15 ≤ average HLVs < 30 dB at 4 kHz or 6 kHz bilaterally; 83.1 ± 4.4 dBA) and a low HL group (n = 274; average HLVs < 15 dB at 4 kHz or 6 kHz bilaterally; 82.2 ± 5.1 dBA) based on the results of pure tone audiometry. Multivariate logistic regressions were used to estimate the risk of hypertension between groups. RESULTS: The prevalence rates of hypertension were significantly higher in the high HL (43.5%; p = 0.021) and median HL (42.1%; p = 0.029) groups than in the low HL group (33.2%). The high HL and median HL workers had 1.48-fold (95% confidence interval [95%CI] = 1.02-2.15; p = 0.040) and 1.46-fold (95%CI = 1.03-2.05; p = 0.031) higher risks of hypertension relative to the low HL workers. Employment duration was significantly and positively correlated with the risk of hypertension among workers with average HLVs ≥ 15 dB at 4 kHz (p < 0.001) and 6 kHz (p < 0.001) bilaterally. CONCLUSIONS: Our findings suggest that high-frequency hearing loss is a good biomarker of occupational noise exposure and that noise-induced hearing loss may be associated with the risk of hypertension.
Subject(s)
Hearing Loss, High-Frequency/epidemiology , Hypertension/etiology , Noise, Occupational/adverse effects , Occupational Diseases/epidemiology , Aircraft , Biomarkers , Cross-Sectional Studies , Hearing Loss, High-Frequency/etiology , Hearing Loss, Noise-Induced/epidemiology , Hearing Loss, Noise-Induced/etiology , Humans , Hypertension/epidemiology , Logistic Models , Male , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Prevalence , Risk Factors , TaiwanABSTRACT
Molecular heterogeneity of neuropeptide Y (NPY) and its three receptors (1, 2 and 5) has recently been discovered. NPY2R polymorphisms have been shown to be related to cocaine and alcohol dependence in European Americans. To test our hypothesis that these polymorphisms influence the smoking behavior of Japanese population, we investigated the prevalence of the rs4425326 and rs6857715 polymorphisms, which have been suggested to be related to alcohol dependence in European Americans, in 2517 Japanese elderly subjects for whom information on smoking behaviors was available. The prevalence of current smokers was greater among Japanese men having the rs4425326 C allele than ex-smokers. Among the ever-smokers, the Fagerström Test for Nicotine Dependence scores were higher in men having the rs4425326 homozygous T allelotype, and the numbers of cigarettes smoked per day were also significantly higher in the male smokers having the TT genotype. No correlations between the Tobacco Dependence Screener scores and any genotypes were detected. These results suggest that rs4425326 polymorphism may be related to smoking behavior in the Japanese elderly population. This study for the first time suggests NPY2R genotype as a possible genetic factor in nicotine dependence.
Subject(s)
Asian People/genetics , Polymorphism, Genetic , Receptors, Neuropeptide Y/genetics , Smoking/epidemiology , Tobacco Use Disorder/epidemiology , Tobacco Use Disorder/genetics , Aged , Aged, 80 and over , Female , Genotype , Humans , Japan/epidemiology , Male , Middle Aged , Smoking/geneticsSubject(s)
Asian People/genetics , Cell Adhesion Molecules, Neuronal/genetics , Genetic Predisposition to Disease , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide/genetics , Smoking/genetics , Aged , Aged, 80 and over , Calcium-Binding Proteins , Female , Humans , Japan , Male , Middle Aged , Neural Cell Adhesion MoleculesABSTRACT
OBJECTIVE: To explore novel cancer gene therapy by retrovirus-mediated RNAi technique to suppress the endogenous EphA2 oncogene expression in colon adenocarcinoma HCT-8 cells. METHODS: Sequence information of EphA2 mRNA was selected and two complementary oligonucleotides with hairpin loop were designed. Retrovirus-mediated RNAi expression vector (pSIREN-EphA2) was then constructed and transfected into the HCT-8 cells. Inhibition of EphA2 protein expression was quantitatively determined by Western blot and immunohistochemistry assay (SP method). RESULTS: The construction of pSIREN-EphA2 vector was successful and confirmed by restriction enzyme analysis and DNA sequencing. The post-transfection level of EphA2 protein expressions was greatly reduced in HCT-8 cells transfected with pSIREN-EphA2, as compared with those of untransfected cells and the vector control (P < 0.001). CONCLUSIONS: EphA2 protein expression in HCT-8 cell line can be suppressed using recombinant retrovirus-mediated RNAi technique. This approach may provide a novel gene therapy against colonic adenocarcinoma.