Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

Pericardiectomy for Constrictive Pericarditis with or without Cardiopulmonary Bypass.

Aim: We aim to access the effect of pericardiectomy for constrictive pericarditis with or without cardiopulmonary bypass. Methods: This was a review of pericardiectomy for constrictive pericarditis. Results: Cardiopulmonary bypass is actually an important maneuver to attain complete relief of the constriction. The short additional time of cardiopulmonary bypass during the procedure has very little effect on the risk of morbidity of the main operation. Conclusion: Incomplete pericardiectomy perhaps was the cause of postoperative remnant constriction and high diastolic filling pressure leading to multiorgan failure. Complete pericardiectomy (removal of phrenic-to-phrenic and the postero-lateral and inferior wall pericardial thickening) using cardiopulmonary bypass should be the routine for total relief of the constriction of the heart.

Preoperative albumin-alkaline phosphatase ratio affects the prognosis of patients undergoing hepatocellular carcinoma surgery.

BACKGROUND: The correlation between the preoperative albuminalkaline phosphatase ratio (AAPR) and the prognosis of hepatocellular carcinoma (HCC) patients after radical resection is still not comprehensive. OBJECTIVE: This study aims to observe the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. METHODS: We constructed a retrospective cohort study and included 656 HCC patients who underwent radical resection. The patients were grouped after determining an optimum AAPR cut-off value. We used the Cox proportional regression model to assess the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. RESULTS: The optimal cut-off value of AAPR for assessing the prognosis of HCC patients after radical resection was 0.52 which was acquired by using X-tile software. Kaplan-Meier analysis curves showed that a low AAPR (⩽ 0.52) had a significantly lower rate of overall survival (OS) and recurrence-free survival (RFS) (P< 0.05). Multiple Cox proportional regression showed that an AAPR > 0.52 was a protective factor for OS (HR = 0.66, 95%CI 0.45-0.97, p= 0.036) and RFS (HR = 0.70, 95% CI 0.53-0.92, p= 0.011). CONCLUSIONS: The preoperative AAPR level was related to the prognosis of HCC patients after radical resection and can be used as a routine preoperative test, which is important for early detection of high-risk patients and taking personalized adjuvant treatment.

Sex Differences in the Impact of Metabolic Dysfunction-associated Fatty Liver Disease on the of Patients with Hepatocellular Carcinoma After Radical Resection.

Background: International experts have put forward a new definition for metabolic dysfunction-associated fatty liver disease (MAFLD). Nonetheless, sex differences in MAFLD function in hepatocellular carcinoma (HCC) survival is still unknown. Therefore, the current work focused on exploring the gender-specific association of MAFLD effect on prognosis after radical resection of liver cancer. Methods: The long-term prognostic outcomes of 642 HCC patients undergoing hepatectomy were analyzed retrospectively. To calculate overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier (KM) curve was plotted. Further, using Cox proportional model to explore the prognostic factors. Sensitivity analysis was performed using propensity score matching (PSM) to balance the confounding bias. Results: For MAFLD patients, median OS and RFS times were 6.8 years and 6.1 years, respectively, compared to 8.5 years and 2.9 years in non-MAFLD patients. KM curve shown that compare with non-MAFLD patients, MAFLD patients had a higher survival rate in men, but had a lower survival rate in women (P<0.05). Multivariate analysis showed that MAFLD was significantly risk factor with mortality in the female (HR = 5.177, 95%CI: 1.475-18.193). However, MAFLD was not related to RFS This correlation was consistent after PSM analysis. Conclusions: MAFLD can improve the mortality of women undergoing radical resection for liver cancer, which independently estimate disease prognosis but is not related to recurrence-free survival.

Correlation of Q223R and K109R polymorphisms in leptin receptor gene with susceptibility of breast cancer: A systematic review and meta-analysis.

BACKGROUND: Increasing evidence has suggested a strong association of Q223R (rs1137101) and K109R (rs1137100) polymorphisms in leptin receptor (LEPR) gene with susceptibility of breast cancer (BC), but inconsistent results were obtained. To provide a quantitative assessment of this association, a systematic review and meta-analysis was performed. METHODS: A literature search of PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure was collected. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 20 case-control studies for Q223R polymorphism and 8 case-control studies for K109R polymorphism were included. Significant association between Q223R polymorphism and BC risk was not found in total, Asian or Caucasian population, but in African population: allelic model, OR = 0.72, 95% CI = 0.60-0.86, p < 0.001; recessive model, OR = 0.67, 95%CI = 0.52-0.87, P = 0.003; dominant model, OR = 1.58, 95% CI = 1.15-2.17, p = 0.004; homozygous model, OR = 0.51, 95% CI = 0.36-0.78, p < 0.001. Significant association between K109R polymorphism and BC risk was not found in total or Caucasian population, but in Asian population: dominant model, OR = 0.24, 95% CI = 0.07-0.84, p = 0.03; heterozygous model, OR = 1.87, 95% CI = 1.07-3.26, p = 0.03. CONCLUSION: The available evidence suggests that Q223R polymorphism may be significantly associated with BC risk in African population. K109R polymorphism may be significantly associated with BC risk in Asian population.

Correlation of DEPDC5 rs1012068 and rs5998152 Polymorphisms with Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Emerging evidence has shown that two common genetic polymorphisms within the pleckstrin domain-containing protein 5 (DEPDC5), rs1012068 and rs5998152, may be associated with the risk of hepatocellular carcinoma (HCC), especially in those individuals chronically infected with the hepatitis C virus (HCV) or the hepatitis B virus (HBV). However, these findings have not been consistently replicated in the literature due to limited sample sizes or different etiologies of HCC. Thus, the present systematic review and meta-analysis were performed to resolve this inconsistency. Methods: The databases PubMed, Embase, Web of Science, the China National Knowledge Infrastructure, and Scopus were searched up to December 12, 2022. Data from relevant studies were pooled, and odds ratios and 95% confidence intervals were calculated. Results: A total of 11 case-control studies encompassing 2,609 cases and 8,171 controls on rs1012068 and three encompassing 411 cases and 1,448 controls on rs5998152 were included. Results indicated that the DEPDC5 rs1012068 polymorphism did not significantly increase HCC risk in the total population (allelic model (OR = 1.32, 95% CI = 1.04-1.67, P = 0.02); the recessive model (OR = 1.42, 95% CI = 0.96-2.10, P = 0.08); the dominant model (OR = 1.43, 95% CI = 1.09-1.87, P = 0.01); the homozygous model (OR = 1.61, 95% CI = 1.01-2.57, P = 0.05); the heterozygous model (OR = 1.39, 95% CI = 1.09-1.79, P = 0.009)). Subgroup analyses based on ethnicity and etiology revealed that the rs1012068 polymorphism, under all five genetic models, was associated with increased HCC risk in Asians or in individuals with chronic HBV infection but not in individuals with chronic HCV infection. A significant association was also observed between rs5998152 and HCV-related HCC risk in Asians chronically infected with HCV under allelic, dominant, and heterozygous models. Conclusion: Our study suggests that the DEPDC5 rs1012068 polymorphism increases HCC risk, especially in Asians with chronic HBV infection, while the rs5998152 polymorphism increases HCC risk in Asians with chronic HCV infection.

Comprehensive pan-cancer analysis identifies cellular senescence as a new therapeutic target for cancer: multi-omics analysis and single-cell sequencing validation.

Although cellular senescence has long been recognized as an anti-tumor mechanism, mounting evidence suggests that in some circumstances, senescent cells promote tumor growth and malignancy spread. Therefore, research into the exact relationship between cellular senescence and tumor immunity is ongoing. We analyzed changes in the expression, copy number variation, single-nucleotide variation, methylation, and drug sensitivity of cellular senescence-related genes in 33 tumor types. The cellular senescence score was calculated using the single-sample gene-set enrichment analysis. The correlations between cellular senescence score and prognosis, tumor immune microenvironment (TIME), and expression of tumor immune-related genes were comprehensively analyzed. Single-cell transcriptome sequencing data were used to assess the activation state of cellular senescence in the tumor microenvironment (TME). The expression of cellular senescence-associated hub genes varied significantly across cancer types. In these genes, missense mutation was the major type of single nucleotide polymorphism, and heterozygous deletion and heterozygous amplification were the major types of copy number variation. Moreover, the cellular senescence pathway in tumors was sensitive to drugs such as XMD13-2, TPCA-1, methotrexate, and KIN001-102. Furthermore, the cellular senescence score was significantly higher in most cancer types, related to poor prognosis. The expression of immune checkpoint molecules such as NRP1, CD276, and CD44 was significantly correlated with the cellular senescence score. Monocyte cellular senescence was significantly higher in the TME of kidney renal clear cell carcinoma cells than in normal tissues. The findings of this study provide insights into the important role of cellular senescence in the TIME of human cancers and the effect of immunotherapy.

MicroRNA-7-5p Inhibits Migration, Invasion and Metastasis of Intrahepatic Cholangiocarcinoma by Inhibiting MyD88.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor derived from intrahepatic bile duct epithelial cells. Accumulating studies report that microRNAs are widely involved in tumor migration and metastasis by regulation of target genes. miR-7-5p has been confirmed to inhibit tumor metastasis and to be related to prognosis for several malignant tumors. Our study investigated the underlying functions of miR-7-5p in ICC. METHODS: The expression of miR-7-5p in ICC tissues but also in ICC cell lines was analyzed by real-time PCR. By analyzing the relationship between the clinicopathological parameters of 60 ICC patients and the expression level of miR-7-5p, the effect of miR-7-5p on the prognosis was clarified. After transfected with miR-7-5p mimics or miR-7-5p inhibitor, cell counting kit-8 assay was applied to evaluate the cells proliferation, flow cytometry was applied to analyze the cells apoptosis, wound healing assay and transwell chamber assay were applied to analyze the cell invasion and migration. A luciferase reporter assay was identified the relationship of miR-7-5p and myeloid differentiation factor 88 (MyD88). Western blotting was used to analyze the proteins expression. And immunochemistry was performed to determine the expression of MYD88 in ICC tissues. RESULTS: Our data showed the expression of miR-7-5p was down-regulated not only in ICC tissues but also in ICC cell lines compared with normal controls. Low expression of miR-7-5p was notably associated with poor prognosis in ICC patients. miR-7-5p negatively regulated cell proliferation, migration, invasion and apoptosis in ICC cells. We further verified that MyD88 was a novel target of miR-7-5p and was significantly overexpressed in ICC tissues. Overexpression of MyD88 counteracted the effects of miR-7-5p in ICC cells. CONCLUSIONS: The present findings suggest that miR-7-5p plays a pivotal role in ICC invasion by regulating MyD88. Ampliative insight into the key factors of ICC invasion may result in the development of new treatment options for ICC.

Clinical stages of recurrent hepatocellular carcinoma: A retrospective cohort study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and has relatively high recurrence rates. Few studies have been published on the clinical stages of recurrent HCC. AIM: To assess the applicability of the Barcelona Clinic Liver Cancer (BCLC) staging for recurrent HCC and the need to establish clinical stage criteria for recurrent HCC. METHODS: The clinicopathological data of 81 patients with recurrent HCC who were admitted to the Hospital of Guangxi Zhuang Autonomous Region from January 2013 to December 2017 were collected. The patients were divided into three groups according to the BCLC staging system as follows: (1) Group A with BCLC stage A, 51 patients; (2) Group B with BCLC stage B, 14 patients; and (3) Group C with BCLC stage C, 16 patients. The median time to tumor recurrence and the median overall survival were compared. RESULTS: The median time to tumor recurrence in groups A, B, and C was 16 ± 1.5 mo, 10 ± 2.8 mo, and 6 ± 0.5 mo, respectively, with a statistically significant difference among them (χ 2 = 70.144, P < 0.05); no statistically significant difference was noted between group A and group B (χ 2 = 2.659, P > 0.05), although there were statistically significant differences between group A and group C and between group B and group C (χ 2 = 62.110, and 19.972, P < 0.05). The median overall survival in groups A, B, and C were 42 ± 5.1 mo, 22 ± 3.1 mo, and 13 ± 1.8 mo, respectively, with a statistically significant difference among them (χ 2 = 38.949, P < 0.05); there were statistically significant differences between group A and group B, group A and group C, and group B and group C (χ 2 = 9.577, 37.172, and 7.183, respectively; P < 0.05). CONCLUSION: There are different prognoses in recurrent HCC patients according to the BCLC staging. Therefore, BCLC staging is applicable to recurrent HCC and it is essential to formulate clinical stage criteria for recurrent HCC.

Clinical Study on the Efficacy of Laparoscopic Hepatectomy and Its Influence on the Expression of Serum VEGF, FGF, and Immune Function.

Liver cancer is one of the most common malignant tumors. Partial hepatectomy is the most basic and effective treatment for hepatocellular carcinoma because of its high operative effect and perioperative safety. Open surgery is the most traditional hepatectomy. Although it can completely remove tumor lesions and prolong patient survival, it has disadvantages such as large trauma and long postoperative recovery time. Meanwhile, long-term bed rest can increase the risk of complications such as venous thrombosis and infection. The advantages of laparoscopic partial hepatectomy, such as clear operative field, simple operation, little trauma, light surgical stress, quick postoperative recovery, and low complications, can avoid damage to vital organs, blood vessels, and nerves, which has been widely accepted and recognized in clinical practice.

Targeting of the COX-2/PGE2 axis enhances the antitumor activity of T7 peptide in vitro and in vivo.

T7 peptide is considered as an antiangiogenic polypeptide. The presents study aimed to further detect the antiangiogenic mechanisms of T7 peptide and determine whether combining T7 peptide and meloxicam (COX-2/PGE2 specific inhibitor) could offer a better therapy to combat hepatocellular carcinoma (HCC). T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3ß1 and αvß3 pathways. Cell proliferation, migration, apoptosis, or tube formation ability were detected, and the expression of integrin-associated regulatory proteins was detected. The anti-tumor activity of T7 peptide, meloxicam, and their combination were evaluated in HCC tumor models established in mice. T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3ß1 and αvß3 pathways. Meloxicam enhanced the activity of T7 peptide under hypoxic condition. T7 peptide partly inhibited COX-2 expression via integrin α3ß1 not αvß3-dependent pathways under hypoxic condition. T7 peptide regulated apoptosis associated protein through MAPK-dependent and -independent pathways under hypoxic condition. The MAPK pathway was activated by the COX-2/PGE2 axis under hypoxic condition. The combination of T7 and meloxicam showed a stronger anti-tumor effect against HCC tumors in mice. The data highlight that meloxicam enhanced the antiangiogenic activity of T7 peptide in vitro and in vivo.

MiR-19b-3p facilitates the proliferation and epithelial-mesenchymal transition, and inhibits the apoptosis of intrahepatic cholangiocarcinoma by suppressing coiled-coil domain containing 6.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatocellular carcinoma, and microRNAs (miRNAs) play a vital role in its development. This study aimed to explore the molecular mechanism and clinical value of miR-19b-3p in ICC. METHODS: From March 2014 to October 2016, 94 pairs of specimens of ICC tissues and adjacent tissues were collected. Moreover, 5 ml of peripheral blood of 342 ICC patients who underwent ICC resection were collected before and one week after surgery. Luciferase activity assay was performed to confirm the regulation of miR-19b-3p on coiled-coil domain containing 6 (CCDC6). BALB/c nude mice were injected with CCLP-1 cells which were transfected with NC, miR-19b-3p mimic, miR-19b-3p inhibitor, pcDNA-CCDC6, si-CCDC6 or miR-19b-3p mimic + pcDNA-CCDC6. RESULTS: Results showed that miR-19b-3p levels were significantly higher in ICC tissues compared with adjacent tissues. Moreover, serum miR-19b-3p levels of ICC patients tended to decline after surgery, and were correlated with lymph node metastasis and histological grading of ICC. CCDC6, a new target gene of miR-19b-3p, was identified by four prediction databases. We confirmed that miR-19b-3p promoted cell proliferation and epithelial-mesenchymal transition (EMT), and inhibited apoptosis in ICC, while knockdown of CCDC6 reversed these effects. We also observed that miR-19b-3p/CCDC6 axis regulated the nuclear translocation of ß-catenin. Furthermore, in vivo study also demonstrated that the miR-19b-3p/CCDC6 axis regulated EMT to promote ICC progression. CONCLUSION: These results indicate that serum miR-19b-3p level is a crucial biomarker for ICC diagnosis and targeting miR-19b-3p-CCDC6 axis might be a promising strategy in ICC therapy.

Limonin provokes hepatocellular carcinoma cells with stemness entry into cycle via activating PI3K/Akt signaling.

The inhibitory roles of limonin have been revealed in various tumors. However, the roles and related mechanism of limonin in hepatocellular carcinoma (HCC) progression are still confused. Here, we collected non-adherent spheroids formed by HCC cells and found that the proportion of spheroids in G0 phase was remarkably higher than that in HCC cells. Additionally, limonin increased EdU incorporation without affecting apoptosis in spheroids. Notably, upon limonin treatment, the proportion of spheroids in G0 was decreased and S/G2/M increased. Furthermore, we found that limonin attenuated the stemness of HCC cells, characterized as the decreased ALDH1 activity, stemness marker expression and spheroid formation ability. Moreover, an integrated transcriptional analysis based on RNA-sequencing data was employed to gain mechanistic insight into limonin functioning, and we found that the most significant pathways identified centered on PI3K/Akt signaling. qRT-PCR and western blot obtained the consistent results. Overall, these data suggest that limonin attenuates the stemness of HCC cells by reducing cellular quiescence through activating PI3K/Akt signaling.

CDK2 positively regulates aerobic glycolysis by suppressing SIRT5 in gastric cancer.

Although significant progress has been made in the diagnosis and treatment of gastric cancer, the overall survival rate of the disease remains unchanged at approximately 20%-25%. Thus, there is an urgent need for a better understanding of the molecular biology aspects of the disease in the hope of discovering novel diagnosis and treatment strategies. Recent years have witnessed decisive roles of aberrant cancer cell metabolism in the maintenance of malignant hallmarks of cancers, and cancer cell metabolism has been regarded as a novel target for the treatment of cancer. CDK2, a cell cycle-dependent kinase that usually regulates cell cycle progression and the DNA damage response, is reported to be upregulated in many cancers. However, little is known about its role in cancer cell metabolism. In the present study, we showed that silencing CDK2 inhibited the aerobic glycolytic capacity of gastric cancer cell lines. Mechanism explorations showed that silencing CDK2 increased expression of the SIRT5 tumor suppressor. In addition, the physiological roles of SIRT5 in the regulation of proliferation and glycolysis were studied in gastric cancer cells. Taken together, the present study uncovered novel roles of the CDK2/SIRT5 axis in gastric cancer and suggests future studies concerning gastric cancer cell metabolism.

[Application of Ligasure vessel sealing instrument in laparoscopic hepatectomy for liver cancer].

OBJECTIVE: To investigate the indication and effect of the application of Ligasure vessel sealing instrument in laparoscopic hepatectomy for liver cancer. METHODS: Eleven patients with liver cancer undergoing laparoscopic hepatectomy were analyzed for the tumor size and location, operation time, volume of intraoperative bleeding, postoperative hospital stay and short-term clinical outcomes. RESULTS: All the operations were performed successfully in the 11 cases. All the tumors were less than 7 cm in diameter, locating at the segments II, III, V, VI and VII. The mean operation time was 91 min (80-126 min), and the intraoperative blood loss averaged 82 ml (20-200 ml). The average postoperative hospital stay of the patients was 8 days (7-9 days). No complications were observed in these cases. CONCLUSION: Ligasure vessel sealing instrument in laparoscopic hepatectomy is applicable in cases of perimeter liver cancer. This instrument can decrease the operation time, reduce the intraoperative blood loss and postoperative hospital stay with good safety and minimal invasiveness.

Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China.

BACKGROUND: Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China. METHODS: A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques. RESULTS: Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22-6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05). CONCLUSION: Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China.

[Expression of human novel gene CT120 in lung cancer and its effects on cell growth].

BACKGROUND & OBJECTIVE: A novel membrane-associated gene CT120 was isolated from chromosome 17p13.3 locus in our laboratory. Its mRNA was not expressed in human normal lung tissues, but was abundant in human lung cancer cell line SPC-A-1. This study was designed to investigate the differential expression patterns of CT120 in different lung cancer and noncancerous tissues using immunohistochemistry and to explore the effects of ectopic expression and overexpression of CT120 on cell growth in vitro and in vivo. METHODS: A polypeptide at the C-terminus of CT120 was selected by bioinformatics, then was synthesized and conjugated to KLH (a high molecular carrier). The chicken anti-CT120 antibody IgY was prepared with the synthesized antigen and was used to determine the different expression patterns of CT120 in various tumor cell lines and in lung cancer and noncancerous tissues. The effects of ectopic expression of CT120 on NIH/3T3 cell growth were investigated through colony formation analysis. The effect of overexpression of CT120 on the cell growth of A549 was analyzed using growth curve assay and tumor formation assay of transfected cells in nude mice. RESULTS: The novel gene CT120 expressed in various tumor cell lines and expressed remarkably higher in lung cancers than in noncancerous tissues as well as normal lung tissues. Also, it promoted the proliferation of NIH/3T3 and A549 cells in vitro and in vivo. CONCLUSION: CT120 gene may be a novel candidate gene closely related to lung carcinogenesis.

Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism.

Within the minimum LOH region on chromosome 17p13.3 deleted in hepatocellular carcinoma, a novel human plasma membrane-associated gene, named CT120, was isolated from a human kidney cDNA library using electronical cloning and RACE. The novel gene CT120 consists of 2145bp and encodes a protein with 257 amino acids. Database search revealed that homologs of CT120 exist in different organisms from plant to animal kingdoms, which suggests that CT120 is a highly conserved gene during biological evolution. Different expression patterns of CT120 were observed in many different human normal tissues and in various human tumor cell lines. Transcript of CT120 was not detectable in normal lung tissue, but was abundant in SPC-A-1 (human epithelial-like lung adenocarcinoma) cell line, suggesting that CT120 may be involved in lung cancer development. Subcellular localization analysis showed that CT120 is a novel membrane-associated protein. CT120 can interact with SLC3A2 (member 2 of solute carrier family 3) and GGTL3B (isoform of gamma-glutamyltranspeptidase-like 3) in eukaryotic cells by yeast two-hybrid screen and co-immunoprecipitation assay, which suggested that CT120 may assume very essential physiological functions involved in amino acid transport and glutathione metabolism.