AIM:To compare intensity-modulated radiotherapy (IMRT) with conformal radiotherapy (CRT) by investigating the dose profiles of primary tumors,electively treated regions,and the doses to organs at risk. METHODS:CRT and...AIM:To compare intensity-modulated radiotherapy (IMRT) with conformal radiotherapy (CRT) by investigating the dose profiles of primary tumors,electively treated regions,and the doses to organs at risk. METHODS:CRT and IMRT plans were designed for five patients with upper esophageal carcinoma.For each patient, target volumes for primary lesions (67.2 Gy) and electively treated regions (50.4 Gy) were predefined.An experienced planner manually designed one CRT plan.Four IMRT plans were generated with the same dose-volume constraints,but with different beam arrangements.Indices including dose distributions,dose volume histograms (DVHs) and conformity index were compared. RESULTS:The plans with three intensity-modulated beams were discarded because the doses to spinal cord were lager than the tolerable dose 45Gy,and the dose on areas near the skin was up to 50Gy.When the number of intensity beams increased to five,IMRT plans were better than CRT plans in terms of the dose conformity and homogeneity of targets and the dose to OARs.The dose distributions changed little when the beam number increased from five to seven and nine. CONCLUSION:IMRT is superior to CRT for the treatment of upper esophageal carcinoma with simultaneous integrated boost (SIB).Five equispaced coplanar intensity-modulated beams can produce desirable dose distributions.The primary tumor can get higher equivalent dose by SIB technique. The SIB-IMRT technique shortens the total treatment time, and is an easier,more efficient,and perhaps a less error- prone way in delivering IMRT.展开更多
Gastric cardia adenocarcinoma (GCA) is an under-studied subject. The pathogenesis, molecular changes in the early stage of carcinogenesis and related risk factors have not been well characterized. There is evidence, h...Gastric cardia adenocarcinoma (GCA) is an under-studied subject. The pathogenesis, molecular changes in the early stage of carcinogenesis and related risk factors have not been well characterized. There is evidence, however, that GCA differs from cancer of the rest of the stomach in terms of natural history and histopathogenesis. Adenocarcinomas of the lower esophagus, esophagogastric junction (EGJ)and gastric cardia have been given much attention because of their increasing incidences in the past decades, which is in striking contrast with the steady decrease in distal stomach adenocarcinoma. In China, epidemiologically, GCA shares very similar geographic distribution with esophageal squamous cell carcinoma (SCC), especially in Linzhou (formerly Linxian County), Henan Province, North China,the highest incidence area of esophageal SCC in the world.Historically, both GCA and SCC in these areas were referred to as esophageal cancer (EC) by the public because of the common syndrome of dysphagia. In Western countries,Barrett's esophagus is very common and has been considered as an important precancerous lesion of adenocarcinoma at EGJ. Because of the low incidence of Barrett's esophagus in China, it is unlikely to be an important factor in early stage of EGJ adenocarcinoma development.However, Z line up-growth into lower esophagus may be one of the characteristic changes in these areas in early stage of GCA development. Whether intestinal metaplasia (IM) is a premalignant lesion for GCA is still not clear. Higher frequency of IM observed at adjacent GCA tissues in Henan suggests the possibility of IM as a precancerous lesion for GCA in these areas. Molecular information on GCA,especially in early stage, is very limited. The accumulated data about the changes of tumor suppressor gene, such as p53 mutation, and ontogeny, such as C-erbB2, especially the similar alterations in GCA and SCC in the same patient,indicated that there might be some similar risk factors,such as nitrosamine, involved in both GCA and SCC in Henan population. The present observations also suggest that GCA should be considered as a distinct entity.展开更多
AIM: To investigate the signal pathway of honokiol-induced apoptosis on human colorectal carcinoma RKO cells and to evaluate whether p53 and p53-related genes were involved in honokiol-treated RKO cells.METHODS: Cell ...AIM: To investigate the signal pathway of honokiol-induced apoptosis on human colorectal carcinoma RKO cells and to evaluate whether p53 and p53-related genes were involved in honokiol-treated RKO cells.METHODS: Cell cycle distribution and subdiploid peak were analyzed with a flow cytometer and DNA fragment with electrophoresis on agarose gels. Transcriptional level of Bax, Bcl-2, Bid and Bcl-xl was accessed by RT-PCR.Western blotting was used to measure p53 protein expression and other factors related to apoptosis.Proliferation inhibition of two cell lines (RKO, SW480) with high expression of p53 and one cell line with p53 negative expression (LS180) was monitored by MTr assay.RESULTS: Honokiol induced RKO cell apoptosis in a dosedependent manner. The mRNA expression level and proteinlevel of Bid were up-regulated while that of Bcl-xl wasdown-regulated, but no changes in Bax and Bcl-2 were observed. Western blotting showed p53 expression had no remarkable changes in honokiol-induced RKO cell apoptosis. LS180 cells treated with honokiol exhibited apparent growth inhibition like RKO ceils and Sw480 ceils.CONCLUSION: Honokiol can induce RKO cells apoptosis through activating caspase cascade by p53-indepenent pathway.展开更多
AIM:To elucidate the distinctive pathobiological behavior between signet ring cell carcinoma (SRC) and mucinous adenocarcinoma of the stomach.METHODS: Based on the histological growth patterns and cell-functional diff...AIM:To elucidate the distinctive pathobiological behavior between signet ring cell carcinoma (SRC) and mucinous adenocarcinoma of the stomach.METHODS: Based on the histological growth patterns and cell-functional differentiation classifications of stomach carcinoma, we conducted a series of comparative studies.All paraffin-embedded and frozen blocks were collected from the files of Cancer Institute of China Medical University. On the basis of histopathological observation, we applied enzymatic and mucous histochemistry, immunohistochemistry,flow cytometry (FCM) and molecular biology to compare these two categories of gastric cancers in terms of the DNA ploidy, proliferative kinetics, the expression of gastric carcinoma associated gene product and instabilities of mitochondrial DNA (mtDNA).RESULTS:Gastric SRC was commonly seen in females below 45 years, mostly presenting diffuse growth and ovary or uterine cervix metastasis. The majority of SRC were absorptive and mucus-producing functional differentiation type (AMPFDT), which growth relied on estrogen. Meanwhile,stomach mucinous adenocarcinomas were mostly observed in males over 50 years, prone to massive growth or nest growth and extensive peritoneal infiltration, showing two categories of cell-functional differentiation types: AMPFDT and mucus-secreting functional differentiation type (MSFDT).Expressions of ER, enzyme c-PDE and 67kDaLN-R in SRC were evidently higher than that in mucinous adenocarcinoma,while expressions of LN, CN-Ⅳ, CD44v6, and PTEN protein were obviously lower in SRC than that in mucinous adenocarcinoma (P<0.05).There was no statistic significance in VEGF, ECD and instabilities of mtDNA (P>0.05) between the above two gastric carcinomas.CONCLUSION: Though SRC and mucinous adenocarcinoma were both characterized by abundant mucus-secretion, they were quite different in morphology, ultrastructure, cell-functional differentiation and protein expression, indicating different mechanisms of carcinogenesis. We concluded that combining histological growth patterns, cell-functional differentiation type with tumor related markers might be significant in early diagnosis and prognosis assessment for SRC and mucinous adenocarcinoma of the stomach.展开更多
AIM: To characterize cytochrome P4501A1 (CYPIA1), glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEH) polymorphisms in Chinese esophageal cancer patients. METHODS: Multiplex polymerase chain react...AIM: To characterize cytochrome P4501A1 (CYPIA1), glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEH) polymorphisms in Chinese esophageal cancer patients. METHODS: Multiplex polymerase chain reaction (PCR) and PCR based restriction fragment length polymorphisms (PCRRFLP) were used to detect polymorphism changes of CYP,GSTs and mEH on esophageal cancerous and precancerous lesions as well as in case control group. All the examination samples were obtained from Linzhou (formerly Linxian), Henan Province, the highest incidence area for esophageal. RESULTS: The frequency of CYP1A1 3'' polymorphism in case control group (26/38, 68 %) was significantly higher than in esophageal squamous cell carcinoma^roup (ESCC) (29/62, 47 %) (P<0.05). A significant difference in the incidence of mEH slow allele variant was observed between case control group (15/38, 39 %) and esophageal dysplasiagroup (22/32, 69 %) or ESCC group (39/62, 63 %) (P<0.05). However, no significant difference was observed among different groups in the polymorphisms of CYPIA1 exon 7, GSTM1, GSTT1, GSTP1 and mEH fast allele. CONCLUSION: The present results suggest that CYPIA1 3'' polymorphism may be one of the promising protectivef actors and its wild gene type may be an indicator for higher susceptibility to esophageal cancer, mEH slow allele variant,associated with the progression of esophageal precancerous lesions, may conthbute to the high susceptibility to esophageal carcinoma.展开更多
AIM: To investigate the anticancer activity of Honokiol on RKO,a human colorectal carcinoma cell line in vitro and in vivo,and to evaluate its possible use in clinic.METHODS: In vitro anticancer activity of honokiol w...AIM: To investigate the anticancer activity of Honokiol on RKO,a human colorectal carcinoma cell line in vitro and in vivo,and to evaluate its possible use in clinic.METHODS: In vitro anticancer activity of honokiol was demonstrated by its induction of apoptosis in tumor cells.We analyzed cell proliferation with MTT assay, cell cycle with flow cytosmeter, DNA fragment with electrophoresis on agarose gels. To test the mechanism of honokiol-induced apoptosis, Westem blotting was used to investigate the factors involved in this process. The pharmacokinetics study of honokiol was tested by high phase liquid chromatography.In in vivo study, Balb/c nude mice were incubated with RKO cells. Honokiol was injected intraperitoneally every other day into tumor bearing Balb/c nude mice.RESULTS: Our results showed that honokiol induced apoptosis of RKO cells in a time- and dose-dependent manner. At 5-10 ug/mL for 48 h, honokiol induced apoptosis through activating Caspase cascades. Pharmacokinetics study demonstrated that, honokiol could be absorbed quickly by intraperitoneal injection, and maintained in plasma for more than 10 h. In nude mice bearing RKO-incubated tumor, honokiol displayed anticancer activity by inhibiting tumor growth and prolonging the lifespan of tumor bearing mice.CONCLUSION: With its few toxicity to normal cells and potent anticancer activity in vitroand in vivo, honokiol might be a potential chemotherapy candidate in treating human colorectal carcinoma.展开更多
AIM: To observe the expression of cyclooxygenase-2 (COX-2) and to investigate the association between COX-2expression and infection with cytotoxic-associated gene A( cagA) positive strair Helicobacter pylori ( Hp) in ...AIM: To observe the expression of cyclooxygenase-2 (COX-2) and to investigate the association between COX-2expression and infection with cytotoxic-associated gene A( cagA) positive strair Helicobacter pylori ( Hp) in humangastric cancer, and subsequently to provide fresh ideas forthe early prevention of gastric cancer.METHODS: 32 Specimens of gastric cancer andcorresponding adjacent normal gastric mucosa were obtainedfrom patients who had undergone surgical operations ofgastric cancer. All the samples including 1 case of stomachmalignant lymphoma and 31 cases of gastric adenocarcinomawere confirmed by pathology diagnosis. The expression ofCOX-2 in 32 specimens of gastric cancer and correspondingadjacent normal gastric mucosa was quantitativelydetermined and analyzed with Flow Cytometry, and the levelsof COX-2 protein were compared between specimens withcagA+ Hp infection and those without cagA+ Hp infection.The cagA gene in 32 specimens of gastric cancer wasdetected bypolymerase chain reaction (PCR) method.RESULTS: Twenty-seven of 32 (84 %) specimens of gastriccancer showed over-expression of COX-2, compared withthe adjacent normal gastric mucosa. cagA+ gene weredetected from 19 specimens of gastric cancer, but not fromthe other 13 specimens. The levels of COX-2 protein in 19specimens of gastric cancer with cagA+ Hp infection (thenumber of positive cells was 73.82±18.2) were significantlyhigher than those in the 13 specimens without cagA+ Hpinfection (the number of positive cells was 35.92±22.1).CONCLUSION: COX-2 is overexpressed in gastric cancerand cagA+Hp infection could up-regulate the expression ofCOX-2 in gastric cancer in human. There may also existanother way or channel to regulate the expression of COX-2 in gastric cancer in addition to cagA+Hp infection.Therefore, applying COX-2 selective inhibitors could be aneffective and promising way to prevent gastric cancer.展开更多
AIM: To find new potential biomarkers and to establish patterns for early detection of colorectal cancer.METHODS: One hundred and eighty-two serum samples including 55 from colorectal cancer (CRC) patients, 35 from co...AIM: To find new potential biomarkers and to establish patterns for early detection of colorectal cancer.METHODS: One hundred and eighty-two serum samples including 55 from colorectal cancer (CRC) patients, 35 from colorectal adenoma (CRA) patients and 92 from healthy persons (HP) were detected by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The data of spectra were analyzed by bioinformatics tools like artificial neural network (ANN) and support vector machine (SVM).RESULTS: The diagnostic pattern combined with 7 potential biomarkers could differentiate CRC palJents from CRA patients with a specificity of 83%, sensitivity of 89% and positive predictive value of 89%. The diagnostic pattern combined with 4 potential biomarkers could differentiate CRC patients from HP with a specificity of 92%, sensitivity of 89% and positive predictive value of 86%.CONCLUSION: The combination of SELDI with bioinformatics tools could help find new biomarkers and establish patterns with high sensitivity and specificity for the detection of CRC.展开更多
To investigate the roles of maspin and kai1 expression in tumorigenesis and progression of gastric cancer. Methods Maspin and kai1 expressions were detected in normal gastric mucosa (n = 182), gastric dysplasia (n = 6...To investigate the roles of maspin and kai1 expression in tumorigenesis and progression of gastric cancer. Methods Maspin and kai1 expressions were detected in normal gastric mucosa (n = 182), gastric dysplasia (n = 69), and gastric cancer (n = 113) by immunohisto-chemistry. Their expressions were compared with clinicopathological parameters of tumors. Relationship between maspin and kai1 expression was also concerned in gastric cancer. Results The positive rates of maspin expression were 79.8% (145/182), 75.4% (52/69), and 50.4% (57/113) in normal gastric mucosa, gastric dysplasia, and gastric cancer, while those of kai1 expression were 81.9% (149/182), 65.2% (49/69), and 58.4% (66/113) in corresponding tissues respectively. Gastric cancer less frequently expressed maspin than the normal gastric mucosa and gastric dysplasia (P < 0.05), while dysplasia and cancer showed less frequent expression of kai1 than normal mucosa (P < 0.05). Maspin expression showed negative association with invasive depth, metastasis, Lauren’s and histological classifications (P < 0.05), but not with tumor size, Borrmann’s classification, growth pattern or TNM staging (P > 0.05). Kai1 expression was negatively correlated with invasive depth, metastasis, growth pattern, Lauren’s and histo-logical classifications (P < 0.05), but not with tumor size, Borrmann’s classification or TNM staging (P > 0.05). Maspin and kai1 were collaboratively expressed in gastric cancer (P < 0.05). Conclusions Down-regulated expressions of maspin and kai1 play an important role in gastric carcinogenesis. Abnormal expression of maspin and kai1 might have inhibitory effects on invasion and metastasis of gastric cancer and act as an effe-ctive and objective marker to indicate the pathobiological behaviors of gastric cancer.展开更多
AIM: To study the mechanisms responsible for inactivation of a novel esophageal cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC).METHODS: A pair of primers was designed to amplify a 220 bp fr...AIM: To study the mechanisms responsible for inactivation of a novel esophageal cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC).METHODS: A pair of primers was designed to amplify a 220 bp fragment, which contains 16 CpG sites in the core promoter region of the ECRG 4 gene. PCR products of bisulfite-modified CpG islands were analyzed by denaturing high-performance liquid chromatography (DHPLC), which were confirmed by DNA sequencing. The methylation status of ECRG 4 promoter in 20 cases of esophageal cancer and the adjacent normal tissues, 5 human tumor cell lines (esophageal cancer cell line-NEC, EC109, EC9706; gastric cancer cell line- GLC; human embryo kidney cell line-Hek293)and 2 normal esophagus tissues were detected. The expression level of the ECRG 4 gene in these samples was examined by RT-PCR.RESULTS: The expression level of ECRG 4 gene was varied.Of 20 esophageal cancer tissues, nine were unexpressed,six were lowly expressed and five were highly expressed compared with the adjacent tissues and the 2 normal esophageal epithelia. In addition, 4 out of the 5 human cell lines were also unexpressed. A high frequency of methylation was revealed in 12 (8 unexpressed and 4 lowly expressed)of the 15 (80%) downregulated cancer tissues and 3 of the 4 unexpressed cell lines. No methylation peak was observed in the two highly expressed normal esophageal epithelia and the methylation frequency was low (3/20) among the 20 cases in the highly expressed adjacent tissues. The methylation status of the samples was consistent with the result of DNA sequencing.CONCLUSION: These results indicate that the inactivation of ECRG 4gene by hypermethylation is a frequent molecular event in ESCC and may be involved in the carcinogenesis of this cancer.展开更多
大肠癌是我国常见肿瘤，其发病率已位居恶性肿瘤谱的第3—5位，且呈继续上升趋势。我国20多年大肠癌的流行病学研究明确了中国人大肠癌的危险因素为肠息肉史、慢性腹泻、慢性便秘、粘液血便、精神刺激史、饮不洁水史、阑尾手术史和家族...大肠癌是我国常见肿瘤，其发病率已位居恶性肿瘤谱的第3—5位，且呈继续上升趋势。我国20多年大肠癌的流行病学研究明确了中国人大肠癌的危险因素为肠息肉史、慢性腹泻、慢性便秘、粘液血便、精神刺激史、饮不洁水史、阑尾手术史和家族肿瘤史等，并在此基础上建立了数量化的评价模式AD值，结合RPHA-FOB为初筛，肠镜为精筛，建立并优化了大肠癌的序贯筛检方案，在人群中应用取得了较好的结果，适合全国推广。同时，以人群为基础，以队列研究和整群随机对照试验的方法，对两个大肠癌现场进行群体防治，从普通人群中检出大肠癌高危人群或癌前病变，对癌前病变腺瘤和息肉进行摘除(即对高危人群进行干预)，有效预防了大肠癌的发生并大幅度降低全人群大肠癌死亡率与发病率。 Summary Colorectal cancer(CRC) is one of the most common causes of death from cancer in China. During the past twenty years, several case-control studies revealed the high risk factors of CRC in China, which were personal history of intestinal polyp,chronic diarrhea, feces with mucin and blood, psychic attack, drinking of unclear water, operation on appendix, history of chronic constipation and family history of cancer. From these factors, a risk-asessment mode (AD value) was constructed, combined with RPHA-FOB, a mass screening mode was established and applied into common people, awarded with a good result. The populationbased CRC prevention including randomized trial has been conducted in two fields( Haining city and Jiashan city in Zhejiang province), which demonstrated that removal of CRC pre-cancer lesions such as adenomas and polyps could reduce CRC incidence and mortalitv remarkablv.展开更多
AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa a...AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113cases of gastric cancers were studied for the expression of PTEN and Caspase-3 andmicrovessel density (MVD)by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.RESULTS: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9％ vs89.4％; P=0.000, χ2=33.474). PTEN expression was significantly associated with invasive depth (P=0.003,rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren′s classification (P=0.000,rs=0.345), and histological classification (P=0.005, rs=0.262)of tumors, but not with tumor size (P=0.639, rs=0.045),Borrmann′s classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020,F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 ％ vs 50.4 ％; P=0.007,χ2=7.286).Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, χ2=15.266).CONCLUSION: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth,differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.展开更多
AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gast...AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.展开更多
AIM: To evaluate the preliminary effects of comprehensive prevention of gastric cancer in Zhuanghe County epidemiologically.METHODS: Stratified sampling and cluster sampling were applied to define the intervention gro...AIM: To evaluate the preliminary effects of comprehensive prevention of gastric cancer in Zhuanghe County epidemiologically.METHODS: Stratified sampling and cluster sampling were applied to define the intervention group and the control group. The prospective cohort study was used for evaluating the effect of preventing gastric cancer. The relative risk (RR)and attributable risk percent (AR %) of intervention on gastric cancer death were calculated. Potential years of life lost (PLYY) of the disease was analyzed, and the RR and AR %of PYLL were calculated. Survival analysis was applied among the screened patients.RESULTS: In the first 4 years after intervening, the relative risk (RR) of intervention on death was 0.5059 (95 % CI:0.3462～0.7392,P＜0.05) with significance statistically. AR %of the intervention on death was 49.41%. The RR of intervention on cumulative PYLL was 0.6778 (95 % CI:0.5604～0.8198,P＜0.05) with statistic significance. AR %of the intervention on cumulative PYLL was 30.32 %. The four-year survival rate of the screened patients was 0.6751(95 % CI: 0.5298～0.9047).CONCLUSION: The initiative intervention results showed that the intervention approach used in the trial was effective, it reduced mortality and increased survival rate, and alleviated the adverse effect of gastric cancer on the health and life of screened population.展开更多
Migration inhibitory factor-related protein 14 (MRP 14) is one of calcium-binding proteins,referred as S 100A9. The heterodimeric molecule formed by MRP 14 with its partner MRP8 (S 100A8) is the major fatty acid carri...Migration inhibitory factor-related protein 14 (MRP 14) is one of calcium-binding proteins,referred as S 100A9. The heterodimeric molecule formed by MRP 14 with its partner MRP8 (S 100A8) is the major fatty acid carrier in neutrophils.The MRP8/14 complex has been also implicated in the intracellular transport of arachidonic acid and its precursors in keratinocytes. We show here the involvement of MRP14 in human esophageal cancer. In an initial study,mRNA differential display - reverse transcription polymerase chain reaction (DD-PCR) was performed with two esophageal carcinomas,one esophageal adenocarcinoma and matched normal adjacent mucosa. DD-PCR with the arbitrary primer OPA3 showed that one cDNA band was highly expressed in normal tissues,but disappeared or substantially decreased in tumor counterparts. It was later identified to be the 3'-end of migration inhibitory factor-related protein 14 (MRP14).Northern blotting,RT-PCR and Western blotting corroborated the down-regulation of MRP14 in 58/64 squamous cell carcinomas and 2/2 adenocarcinomas as compared with adjacent normal epithelia of the esophagus. MRP14 was undetectable in 3/3 esophageal-carcinoma cell lines. Immunochemistry demonstrated that expression of MRP14 was restricted to normal esophageal epithelia. No mutation was found in the genomic DNA of the MRP14 gene by PCR and directed DNA sequencing. Our finding suggested that the reduction of MRP14 expression is a frequent event in Chinese human esophageal cancer.展开更多
Objective To investigate the association of microcystin (MC) in drinking water with the incidence of colorectal cancer. Methods The study was designed as a retrospective cohort. Eight townships or towns were random...Objective To investigate the association of microcystin (MC) in drinking water with the incidence of colorectal cancer. Methods The study was designed as a retrospective cohort. Eight townships or towns were randomly selected as the study sites in Haining City of Zhejiang Province, China. 408 cases of colon and rectum carcinomas diagnosed from 1977 to 1996 in the study sites were included, and a survey on types of drinking water of these patients was conducted. Samples of different water sources (well, tap, river and pond) were collected separately and microcystin concentrations were determined by indirect competitive ELISA method. Results The incidence rate of colorectal cancer was significantly higher in population who drank river and pond water than those who drank well and tap water. Compared to well water, the relative risk (RR) for colorectal cancer was 1.88 (tap), 7.94 (river) and 7.70 (pond) respectively. The positive rate (>50 pg/mL) of microcystin in samples of well, tap, river and pond water was 0, 0, 36.23% and 17.14% respectively. The concentration of microcystin in river and pond water was significantly higher than that in well and tap water (P<0.01). Spearman rank correlation analysis showed that in the study sites, the microcystin concentration of river and pond water was positively associated with the incidence of colorectal cancer (rs= 0.881, P<0.01). Conclusions The types of drinking water are positively associated with the incidence of colorectal cancer in the study sites, and this may be related to microcystin contamination of drinking water. Further biological study is needed to support the possible causative role of mycrocystin in carcinogenesis of colon and rectum.展开更多
AIM:To study the expression of myeloid-related proteins (MRP)8 and myeloid-related proteins(MRP)14 in human esophageal squamous cell carcinoma and to investigate if there was any correlation between MRP8 and MRP14 exp...AIM:To study the expression of myeloid-related proteins (MRP)8 and myeloid-related proteins(MRP)14 in human esophageal squamous cell carcinoma and to investigate if there was any correlation between MRP8 and MRP14 expression level and histopathological grade in these tumors. METHODS:In this study,65 cases of advanced esophageal squamous cell carcinoma were assessed for MRP8 and MRP14 expression using immunohistochemistry.Statistical analysis was performed for the comparison of MRP8 and MRP14 expression in normal and tumor tissues,and their relationship with clinicopathological features. RESULTS:Reduced or absent expression of MRP8 and MRP14 was observed in esophageal squamous cell carcinoma,with a significant difference between tumor tissues and normal tissues (P<0.01 and P<0.01 for MRP8 and MRP14,respectively). Poorly differentiated tumors presented a greater decrease than well and moderately differentiated tumors,with a correlation between their protein level and histopathological grading (P<0.001 and P<0.001,respectively).However,no significant association was found between MRP8 and MRP14 expression and age or gender (P>0.05). CONCLUSION:These findings suggest that the decreased expression of MRP8 and MRP14 might play an important role in the pathogenesis of human esophageal squamous cell carcinoma,being particularly associated with poor differentiation of tumor cells.展开更多
AIM: To examine the aberrant expression of fragile histidine triad (FHIT) gene and protein in gastric cancer, and to evaluate the role of FHIT gene and the relationship between FHIT gene and EBV infection in gastric c...AIM: To examine the aberrant expression of fragile histidine triad (FHIT) gene and protein in gastric cancer, and to evaluate the role of FHIT gene and the relationship between FHIT gene and EBV infection in gastric carcinogenesis. METHODS: FHIT transcripts were detected by nested RT-PCR in 30 cases of gastric cancer and their products were sequenced.FHIT protein was detected by Western blot. EBV infection was detected by PCR method in 50 cases of gastric cancer. RESULTS: The wild type transcripts were detected in all 30 matched normal tissues of gastric cancer.Aberrant transcripts were found in 11/30 (36.7%) gastric cancerous tissues. Sequencing analysis of the aberrant fragments found an RT-PCR product missing exons 5-7 in one case of gastric cancer, and another product missing exons 4-7. Four of ten (40.0%) cases of primary gastric cancer showed absent or decreased expression of FHIT protein as compared with their matched normal tissues.EBV was detected in 5/50 (10%) gastric cancers,among which 4/5 (80%) had aberrant transcripts of FHIT gene. CONCLUSION: Loss of FHIT gene or FHIT protein plays an important role in carcinogenesis,development and progression of gastric cancer.EBV infection might influence carcinogenesis of gastric cancer by inducing the abnormality of FHIT gene.展开更多
In this study, we examined the expression of inducible nitric oxide s ynthase (iNOS) and vascular endothelial growth factor (VEGF) by immunohistoc hemi cal staining in 76 tissue sections collected from hepatocellula...In this study, we examined the expression of inducible nitric oxide s ynthase (iNOS) and vascular endothelial growth factor (VEGF) by immunohistoc hemi cal staining in 76 tissue sections collected from hepatocellular carcinoma (HCC) patients undergoing hepatectomy. Microvascular density (MVD) was determined by counting endothelial cells immunostained using anti-CD34 antibody. We performe d DNA-flow cytometric analyses to elucidate the impact of iNOS and VEGF expressi o n on the cell cycle of HCC. Most of the HCC cells that invaded stroma were mark edly immunostained by iNOS antibody. The iNOS stain intensity of the liver tissu e close to the tumor edge was stronger than that of HCC tissue, and the stronges t was the hepatocytes closer to the tumor tissue. However, iNOS expression in 10 normal hepatic samples was undetectable. VEGF positive expression ratio was 84. 8% in iNOS positive expression cases, and the ratio was 35.3% in negative cases. There was significant correlation (P=0.000) between iNOS and VEGF expressi on. Moreover, iNOS expression was significantly associated with bcl-2 and MVD, but w ithout p53 expression. DNA-flow cytometric analyses showed that combined expres s ion of iNOS and VEGF had significant impact on the cell cycle in HCC. PI (Proli ferating Index) and SPF (S-phase fraction) in the combined positive expression o f iNOS and VEGF group was significantly higher than that in the combined negativ e group. The present findings suggested that iNOS expression was significantly a ssociated with angiogenesis, bcl-2 and cell proliferation of HCC.展开更多
AIM:To study the role of hypermethylation in the loss of retinoic acid receptor β2(RARβ2) in esophageal squamous cell carcinoma (ESCC).METHODS:The role of hypermethylation in RARβ2 gene silencing in 6 ESCC cell lin...AIM:To study the role of hypermethylation in the loss of retinoic acid receptor β2(RARβ2) in esophageal squamous cell carcinoma (ESCC).METHODS:The role of hypermethylation in RARβ2 gene silencing in 6 ESCC cell lines was determined by methylation-specific PCR (MSP),and its methylation status was compared with RARβ2 mRNA expression by RT-PCR.The MSP results were confirmed by bisulfite sequencing of RARβ2promoter regions.RESULTS:Methylation was detected in 4 of the 6 cell lines,and the expression of RARβ2 was markedly downregulated in 3 of the 4 methylated cell lines. The expression of RARβ2 was restored in one RARβ2-downregulated cell line with the partial demethylation of promoter region of RARβ2 after 5-aza-2′-deoxycytidine (5-aza-dc) treatment.CONCLUSION:The methylation of the 5′ region may play an important role in the downregulation of RARβ2 in some ESCC cell lines, suggesting that multiple mechanisms contribute to the loss of RARβ2expression in ESCC cell lines.This study may have clinical applications for treatment and prevention of ESCC.展开更多
文摘AIM:To compare intensity-modulated radiotherapy (IMRT) with conformal radiotherapy (CRT) by investigating the dose profiles of primary tumors,electively treated regions,and the doses to organs at risk. METHODS:CRT and IMRT plans were designed for five patients with upper esophageal carcinoma.For each patient, target volumes for primary lesions (67.2 Gy) and electively treated regions (50.4 Gy) were predefined.An experienced planner manually designed one CRT plan.Four IMRT plans were generated with the same dose-volume constraints,but with different beam arrangements.Indices including dose distributions,dose volume histograms (DVHs) and conformity index were compared. RESULTS:The plans with three intensity-modulated beams were discarded because the doses to spinal cord were lager than the tolerable dose 45Gy,and the dose on areas near the skin was up to 50Gy.When the number of intensity beams increased to five,IMRT plans were better than CRT plans in terms of the dose conformity and homogeneity of targets and the dose to OARs.The dose distributions changed little when the beam number increased from five to seven and nine. CONCLUSION:IMRT is superior to CRT for the treatment of upper esophageal carcinoma with simultaneous integrated boost (SIB).Five equispaced coplanar intensity-modulated beams can produce desirable dose distributions.The primary tumor can get higher equivalent dose by SIB technique. The SIB-IMRT technique shortens the total treatment time, and is an easier,more efficient,and perhaps a less error- prone way in delivering IMRT.
基金National Distinguished Young Scientist Foundation of China,No.30025016Foundation of Henan Education Committee.No.1999125
文摘Gastric cardia adenocarcinoma (GCA) is an under-studied subject. The pathogenesis, molecular changes in the early stage of carcinogenesis and related risk factors have not been well characterized. There is evidence, however, that GCA differs from cancer of the rest of the stomach in terms of natural history and histopathogenesis. Adenocarcinomas of the lower esophagus, esophagogastric junction (EGJ)and gastric cardia have been given much attention because of their increasing incidences in the past decades, which is in striking contrast with the steady decrease in distal stomach adenocarcinoma. In China, epidemiologically, GCA shares very similar geographic distribution with esophageal squamous cell carcinoma (SCC), especially in Linzhou (formerly Linxian County), Henan Province, North China,the highest incidence area of esophageal SCC in the world.Historically, both GCA and SCC in these areas were referred to as esophageal cancer (EC) by the public because of the common syndrome of dysphagia. In Western countries,Barrett's esophagus is very common and has been considered as an important precancerous lesion of adenocarcinoma at EGJ. Because of the low incidence of Barrett's esophagus in China, it is unlikely to be an important factor in early stage of EGJ adenocarcinoma development.However, Z line up-growth into lower esophagus may be one of the characteristic changes in these areas in early stage of GCA development. Whether intestinal metaplasia (IM) is a premalignant lesion for GCA is still not clear. Higher frequency of IM observed at adjacent GCA tissues in Henan suggests the possibility of IM as a precancerous lesion for GCA in these areas. Molecular information on GCA,especially in early stage, is very limited. The accumulated data about the changes of tumor suppressor gene, such as p53 mutation, and ontogeny, such as C-erbB2, especially the similar alterations in GCA and SCC in the same patient,indicated that there might be some similar risk factors,such as nitrosamine, involved in both GCA and SCC in Henan population. The present observations also suggest that GCA should be considered as a distinct entity.
基金Supported by the Cheung Kong Scholars Program,National Ministry of Education of China,and Li Ka Shing Foundation,Hong Kong
文摘AIM: To investigate the signal pathway of honokiol-induced apoptosis on human colorectal carcinoma RKO cells and to evaluate whether p53 and p53-related genes were involved in honokiol-treated RKO cells.METHODS: Cell cycle distribution and subdiploid peak were analyzed with a flow cytometer and DNA fragment with electrophoresis on agarose gels. Transcriptional level of Bax, Bcl-2, Bid and Bcl-xl was accessed by RT-PCR.Western blotting was used to measure p53 protein expression and other factors related to apoptosis.Proliferation inhibition of two cell lines (RKO, SW480) with high expression of p53 and one cell line with p53 negative expression (LS180) was monitored by MTr assay.RESULTS: Honokiol induced RKO cell apoptosis in a dosedependent manner. The mRNA expression level and proteinlevel of Bid were up-regulated while that of Bcl-xl wasdown-regulated, but no changes in Bax and Bcl-2 were observed. Western blotting showed p53 expression had no remarkable changes in honokiol-induced RKO cell apoptosis. LS180 cells treated with honokiol exhibited apparent growth inhibition like RKO ceils and Sw480 ceils.CONCLUSION: Honokiol can induce RKO cells apoptosis through activating caspase cascade by p53-indepenent pathway.
基金Supported by the National Natural Science Foundation of China,No.30070845 and No.30371607
文摘AIM:To elucidate the distinctive pathobiological behavior between signet ring cell carcinoma (SRC) and mucinous adenocarcinoma of the stomach.METHODS: Based on the histological growth patterns and cell-functional differentiation classifications of stomach carcinoma, we conducted a series of comparative studies.All paraffin-embedded and frozen blocks were collected from the files of Cancer Institute of China Medical University. On the basis of histopathological observation, we applied enzymatic and mucous histochemistry, immunohistochemistry,flow cytometry (FCM) and molecular biology to compare these two categories of gastric cancers in terms of the DNA ploidy, proliferative kinetics, the expression of gastric carcinoma associated gene product and instabilities of mitochondrial DNA (mtDNA).RESULTS:Gastric SRC was commonly seen in females below 45 years, mostly presenting diffuse growth and ovary or uterine cervix metastasis. The majority of SRC were absorptive and mucus-producing functional differentiation type (AMPFDT), which growth relied on estrogen. Meanwhile,stomach mucinous adenocarcinomas were mostly observed in males over 50 years, prone to massive growth or nest growth and extensive peritoneal infiltration, showing two categories of cell-functional differentiation types: AMPFDT and mucus-secreting functional differentiation type (MSFDT).Expressions of ER, enzyme c-PDE and 67kDaLN-R in SRC were evidently higher than that in mucinous adenocarcinoma,while expressions of LN, CN-Ⅳ, CD44v6, and PTEN protein were obviously lower in SRC than that in mucinous adenocarcinoma (P<0.05).There was no statistic significance in VEGF, ECD and instabilities of mtDNA (P>0.05) between the above two gastric carcinomas.CONCLUSION: Though SRC and mucinous adenocarcinoma were both characterized by abundant mucus-secretion, they were quite different in morphology, ultrastructure, cell-functional differentiation and protein expression, indicating different mechanisms of carcinogenesis. We concluded that combining histological growth patterns, cell-functional differentiation type with tumor related markers might be significant in early diagnosis and prognosis assessment for SRC and mucinous adenocarcinoma of the stomach.
基金National Outstanding Young Scientist Award of China 30025016(China)State Key Project for Basic Research G 1998051206(China)+1 种基金Foundation of Henan Education Committee 1999125the U.S.NIH Grant CA65871
文摘AIM: To characterize cytochrome P4501A1 (CYPIA1), glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEH) polymorphisms in Chinese esophageal cancer patients. METHODS: Multiplex polymerase chain reaction (PCR) and PCR based restriction fragment length polymorphisms (PCRRFLP) were used to detect polymorphism changes of CYP,GSTs and mEH on esophageal cancerous and precancerous lesions as well as in case control group. All the examination samples were obtained from Linzhou (formerly Linxian), Henan Province, the highest incidence area for esophageal. RESULTS: The frequency of CYP1A1 3'' polymorphism in case control group (26/38, 68 %) was significantly higher than in esophageal squamous cell carcinoma^roup (ESCC) (29/62, 47 %) (P<0.05). A significant difference in the incidence of mEH slow allele variant was observed between case control group (15/38, 39 %) and esophageal dysplasiagroup (22/32, 69 %) or ESCC group (39/62, 63 %) (P<0.05). However, no significant difference was observed among different groups in the polymorphisms of CYPIA1 exon 7, GSTM1, GSTT1, GSTP1 and mEH fast allele. CONCLUSION: The present results suggest that CYPIA1 3'' polymorphism may be one of the promising protectivef actors and its wild gene type may be an indicator for higher susceptibility to esophageal cancer, mEH slow allele variant,associated with the progression of esophageal precancerous lesions, may conthbute to the high susceptibility to esophageal carcinoma.
基金Supported by Cheung Kong Scholars Programme of National Ministry of Education,China,and Li Ka Shing Foundation,Hong Kong Co-first-authors: Fei Chen and Tao Wang
文摘AIM: To investigate the anticancer activity of Honokiol on RKO,a human colorectal carcinoma cell line in vitro and in vivo,and to evaluate its possible use in clinic.METHODS: In vitro anticancer activity of honokiol was demonstrated by its induction of apoptosis in tumor cells.We analyzed cell proliferation with MTT assay, cell cycle with flow cytosmeter, DNA fragment with electrophoresis on agarose gels. To test the mechanism of honokiol-induced apoptosis, Westem blotting was used to investigate the factors involved in this process. The pharmacokinetics study of honokiol was tested by high phase liquid chromatography.In in vivo study, Balb/c nude mice were incubated with RKO cells. Honokiol was injected intraperitoneally every other day into tumor bearing Balb/c nude mice.RESULTS: Our results showed that honokiol induced apoptosis of RKO cells in a time- and dose-dependent manner. At 5-10 ug/mL for 48 h, honokiol induced apoptosis through activating Caspase cascades. Pharmacokinetics study demonstrated that, honokiol could be absorbed quickly by intraperitoneal injection, and maintained in plasma for more than 10 h. In nude mice bearing RKO-incubated tumor, honokiol displayed anticancer activity by inhibiting tumor growth and prolonging the lifespan of tumor bearing mice.CONCLUSION: With its few toxicity to normal cells and potent anticancer activity in vitroand in vivo, honokiol might be a potential chemotherapy candidate in treating human colorectal carcinoma.
基金The National Basic Research Program(973)of China, No.G1998051203
文摘AIM: To observe the expression of cyclooxygenase-2 (COX-2) and to investigate the association between COX-2expression and infection with cytotoxic-associated gene A( cagA) positive strair Helicobacter pylori ( Hp) in humangastric cancer, and subsequently to provide fresh ideas forthe early prevention of gastric cancer.METHODS: 32 Specimens of gastric cancer andcorresponding adjacent normal gastric mucosa were obtainedfrom patients who had undergone surgical operations ofgastric cancer. All the samples including 1 case of stomachmalignant lymphoma and 31 cases of gastric adenocarcinomawere confirmed by pathology diagnosis. The expression ofCOX-2 in 32 specimens of gastric cancer and correspondingadjacent normal gastric mucosa was quantitativelydetermined and analyzed with Flow Cytometry, and the levelsof COX-2 protein were compared between specimens withcagA+ Hp infection and those without cagA+ Hp infection.The cagA gene in 32 specimens of gastric cancer wasdetected bypolymerase chain reaction (PCR) method.RESULTS: Twenty-seven of 32 (84 %) specimens of gastriccancer showed over-expression of COX-2, compared withthe adjacent normal gastric mucosa. cagA+ gene weredetected from 19 specimens of gastric cancer, but not fromthe other 13 specimens. The levels of COX-2 protein in 19specimens of gastric cancer with cagA+ Hp infection (thenumber of positive cells was 73.82±18.2) were significantlyhigher than those in the 13 specimens without cagA+ Hpinfection (the number of positive cells was 35.92±22.1).CONCLUSION: COX-2 is overexpressed in gastric cancerand cagA+Hp infection could up-regulate the expression ofCOX-2 in gastric cancer in human. There may also existanother way or channel to regulate the expression of COX-2 in gastric cancer in addition to cagA+Hp infection.Therefore, applying COX-2 selective inhibitors could be aneffective and promising way to prevent gastric cancer.
基金Supported by the Major State Basic Research Development Program of China 973 program,No.G1998051200
文摘AIM: To find new potential biomarkers and to establish patterns for early detection of colorectal cancer.METHODS: One hundred and eighty-two serum samples including 55 from colorectal cancer (CRC) patients, 35 from colorectal adenoma (CRA) patients and 92 from healthy persons (HP) were detected by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The data of spectra were analyzed by bioinformatics tools like artificial neural network (ANN) and support vector machine (SVM).RESULTS: The diagnostic pattern combined with 7 potential biomarkers could differentiate CRC palJents from CRA patients with a specificity of 83%, sensitivity of 89% and positive predictive value of 89%. The diagnostic pattern combined with 4 potential biomarkers could differentiate CRC patients from HP with a specificity of 92%, sensitivity of 89% and positive predictive value of 86%.CONCLUSION: The combination of SELDI with bioinformatics tools could help find new biomarkers and establish patterns with high sensitivity and specificity for the detection of CRC.
文摘To investigate the roles of maspin and kai1 expression in tumorigenesis and progression of gastric cancer. Methods Maspin and kai1 expressions were detected in normal gastric mucosa (n = 182), gastric dysplasia (n = 69), and gastric cancer (n = 113) by immunohisto-chemistry. Their expressions were compared with clinicopathological parameters of tumors. Relationship between maspin and kai1 expression was also concerned in gastric cancer. Results The positive rates of maspin expression were 79.8% (145/182), 75.4% (52/69), and 50.4% (57/113) in normal gastric mucosa, gastric dysplasia, and gastric cancer, while those of kai1 expression were 81.9% (149/182), 65.2% (49/69), and 58.4% (66/113) in corresponding tissues respectively. Gastric cancer less frequently expressed maspin than the normal gastric mucosa and gastric dysplasia (P < 0.05), while dysplasia and cancer showed less frequent expression of kai1 than normal mucosa (P < 0.05). Maspin expression showed negative association with invasive depth, metastasis, Lauren’s and histological classifications (P < 0.05), but not with tumor size, Borrmann’s classification, growth pattern or TNM staging (P > 0.05). Kai1 expression was negatively correlated with invasive depth, metastasis, growth pattern, Lauren’s and histo-logical classifications (P < 0.05), but not with tumor size, Borrmann’s classification or TNM staging (P > 0.05). Maspin and kai1 were collaboratively expressed in gastric cancer (P < 0.05). Conclusions Down-regulated expressions of maspin and kai1 play an important role in gastric carcinogenesis. Abnormal expression of maspin and kai1 might have inhibitory effects on invasion and metastasis of gastric cancer and act as an effe-ctive and objective marker to indicate the pathobiological behaviors of gastric cancer.
基金grant from State Key Basic Program(G1998051204)the Ministry of Education,China
文摘AIM: To study the mechanisms responsible for inactivation of a novel esophageal cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC).METHODS: A pair of primers was designed to amplify a 220 bp fragment, which contains 16 CpG sites in the core promoter region of the ECRG 4 gene. PCR products of bisulfite-modified CpG islands were analyzed by denaturing high-performance liquid chromatography (DHPLC), which were confirmed by DNA sequencing. The methylation status of ECRG 4 promoter in 20 cases of esophageal cancer and the adjacent normal tissues, 5 human tumor cell lines (esophageal cancer cell line-NEC, EC109, EC9706; gastric cancer cell line- GLC; human embryo kidney cell line-Hek293)and 2 normal esophagus tissues were detected. The expression level of the ECRG 4 gene in these samples was examined by RT-PCR.RESULTS: The expression level of ECRG 4 gene was varied.Of 20 esophageal cancer tissues, nine were unexpressed,six were lowly expressed and five were highly expressed compared with the adjacent tissues and the 2 normal esophageal epithelia. In addition, 4 out of the 5 human cell lines were also unexpressed. A high frequency of methylation was revealed in 12 (8 unexpressed and 4 lowly expressed)of the 15 (80%) downregulated cancer tissues and 3 of the 4 unexpressed cell lines. No methylation peak was observed in the two highly expressed normal esophageal epithelia and the methylation frequency was low (3/20) among the 20 cases in the highly expressed adjacent tissues. The methylation status of the samples was consistent with the result of DNA sequencing.CONCLUSION: These results indicate that the inactivation of ECRG 4gene by hypermethylation is a frequent molecular event in ESCC and may be involved in the carcinogenesis of this cancer.
文摘大肠癌是我国常见肿瘤，其发病率已位居恶性肿瘤谱的第3—5位，且呈继续上升趋势。我国20多年大肠癌的流行病学研究明确了中国人大肠癌的危险因素为肠息肉史、慢性腹泻、慢性便秘、粘液血便、精神刺激史、饮不洁水史、阑尾手术史和家族肿瘤史等，并在此基础上建立了数量化的评价模式AD值，结合RPHA-FOB为初筛，肠镜为精筛，建立并优化了大肠癌的序贯筛检方案，在人群中应用取得了较好的结果，适合全国推广。同时，以人群为基础，以队列研究和整群随机对照试验的方法，对两个大肠癌现场进行群体防治，从普通人群中检出大肠癌高危人群或癌前病变，对癌前病变腺瘤和息肉进行摘除(即对高危人群进行干预)，有效预防了大肠癌的发生并大幅度降低全人群大肠癌死亡率与发病率。 Summary Colorectal cancer(CRC) is one of the most common causes of death from cancer in China. During the past twenty years, several case-control studies revealed the high risk factors of CRC in China, which were personal history of intestinal polyp,chronic diarrhea, feces with mucin and blood, psychic attack, drinking of unclear water, operation on appendix, history of chronic constipation and family history of cancer. From these factors, a risk-asessment mode (AD value) was constructed, combined with RPHA-FOB, a mass screening mode was established and applied into common people, awarded with a good result. The populationbased CRC prevention including randomized trial has been conducted in two fields( Haining city and Jiashan city in Zhejiang province), which demonstrated that removal of CRC pre-cancer lesions such as adenomas and polyps could reduce CRC incidence and mortalitv remarkablv.
文摘AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113cases of gastric cancers were studied for the expression of PTEN and Caspase-3 andmicrovessel density (MVD)by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.RESULTS: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9％ vs89.4％; P=0.000, χ2=33.474). PTEN expression was significantly associated with invasive depth (P=0.003,rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren′s classification (P=0.000,rs=0.345), and histological classification (P=0.005, rs=0.262)of tumors, but not with tumor size (P=0.639, rs=0.045),Borrmann′s classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020,F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 ％ vs 50.4 ％; P=0.007,χ2=7.286).Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, χ2=15.266).CONCLUSION: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth,differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.
基金Supported by the National Natural Science Foundation of China,No. 30070845
文摘AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.
基金National Ninth Five-year Study Program for Taking Key Scientific Problems,No.96-906-01-04National Tenth Fiveyear Study Program for Taking Key Scientific Problems,No.2001BA703B06(B)
文摘AIM: To evaluate the preliminary effects of comprehensive prevention of gastric cancer in Zhuanghe County epidemiologically.METHODS: Stratified sampling and cluster sampling were applied to define the intervention group and the control group. The prospective cohort study was used for evaluating the effect of preventing gastric cancer. The relative risk (RR)and attributable risk percent (AR %) of intervention on gastric cancer death were calculated. Potential years of life lost (PLYY) of the disease was analyzed, and the RR and AR %of PYLL were calculated. Survival analysis was applied among the screened patients.RESULTS: In the first 4 years after intervening, the relative risk (RR) of intervention on death was 0.5059 (95 % CI:0.3462～0.7392,P＜0.05) with significance statistically. AR %of the intervention on death was 49.41%. The RR of intervention on cumulative PYLL was 0.6778 (95 % CI:0.5604～0.8198,P＜0.05) with statistic significance. AR %of the intervention on cumulative PYLL was 30.32 %. The four-year survival rate of the screened patients was 0.6751(95 % CI: 0.5298～0.9047).CONCLUSION: The initiative intervention results showed that the intervention approach used in the trial was effective, it reduced mortality and increased survival rate, and alleviated the adverse effect of gastric cancer on the health and life of screened population.
基金supported by State Key Basic Research programme of China(G1998051205)National Key Technologies R&D Programme of China(2002BA711A06)+2 种基金The National High Technology Research and Development Program of China(2001AA221151)National Natural Science Foundation of China(30125026)Doctoral Program Fund of China(20010023016).
文摘Migration inhibitory factor-related protein 14 (MRP 14) is one of calcium-binding proteins,referred as S 100A9. The heterodimeric molecule formed by MRP 14 with its partner MRP8 (S 100A8) is the major fatty acid carrier in neutrophils.The MRP8/14 complex has been also implicated in the intracellular transport of arachidonic acid and its precursors in keratinocytes. We show here the involvement of MRP14 in human esophageal cancer. In an initial study,mRNA differential display - reverse transcription polymerase chain reaction (DD-PCR) was performed with two esophageal carcinomas,one esophageal adenocarcinoma and matched normal adjacent mucosa. DD-PCR with the arbitrary primer OPA3 showed that one cDNA band was highly expressed in normal tissues,but disappeared or substantially decreased in tumor counterparts. It was later identified to be the 3'-end of migration inhibitory factor-related protein 14 (MRP14).Northern blotting,RT-PCR and Western blotting corroborated the down-regulation of MRP14 in 58/64 squamous cell carcinomas and 2/2 adenocarcinomas as compared with adjacent normal epithelia of the esophagus. MRP14 was undetectable in 3/3 esophageal-carcinoma cell lines. Immunochemistry demonstrated that expression of MRP14 was restricted to normal esophageal epithelia. No mutation was found in the genomic DNA of the MRP14 gene by PCR and directed DNA sequencing. Our finding suggested that the reduction of MRP14 expression is a frequent event in Chinese human esophageal cancer.
基金This project was supported by the Scientific Foundation of Ministry of Health China (No. 96-1-350)
文摘Objective To investigate the association of microcystin (MC) in drinking water with the incidence of colorectal cancer. Methods The study was designed as a retrospective cohort. Eight townships or towns were randomly selected as the study sites in Haining City of Zhejiang Province, China. 408 cases of colon and rectum carcinomas diagnosed from 1977 to 1996 in the study sites were included, and a survey on types of drinking water of these patients was conducted. Samples of different water sources (well, tap, river and pond) were collected separately and microcystin concentrations were determined by indirect competitive ELISA method. Results The incidence rate of colorectal cancer was significantly higher in population who drank river and pond water than those who drank well and tap water. Compared to well water, the relative risk (RR) for colorectal cancer was 1.88 (tap), 7.94 (river) and 7.70 (pond) respectively. The positive rate (>50 pg/mL) of microcystin in samples of well, tap, river and pond water was 0, 0, 36.23% and 17.14% respectively. The concentration of microcystin in river and pond water was significantly higher than that in well and tap water (P<0.01). Spearman rank correlation analysis showed that in the study sites, the microcystin concentration of river and pond water was positively associated with the incidence of colorectal cancer (rs= 0.881, P<0.01). Conclusions The types of drinking water are positively associated with the incidence of colorectal cancer in the study sites, and this may be related to microcystin contamination of drinking water. Further biological study is needed to support the possible causative role of mycrocystin in carcinogenesis of colon and rectum.
基金Supported by China Key Program on Basic Research,No.G1998051021the Chinese Hi-tech R&D Program, No. 2001AA231041National Science Foundation of China,No.30170519
文摘AIM:To study the expression of myeloid-related proteins (MRP)8 and myeloid-related proteins(MRP)14 in human esophageal squamous cell carcinoma and to investigate if there was any correlation between MRP8 and MRP14 expression level and histopathological grade in these tumors. METHODS:In this study,65 cases of advanced esophageal squamous cell carcinoma were assessed for MRP8 and MRP14 expression using immunohistochemistry.Statistical analysis was performed for the comparison of MRP8 and MRP14 expression in normal and tumor tissues,and their relationship with clinicopathological features. RESULTS:Reduced or absent expression of MRP8 and MRP14 was observed in esophageal squamous cell carcinoma,with a significant difference between tumor tissues and normal tissues (P<0.01 and P<0.01 for MRP8 and MRP14,respectively). Poorly differentiated tumors presented a greater decrease than well and moderately differentiated tumors,with a correlation between their protein level and histopathological grading (P<0.001 and P<0.001,respectively).However,no significant association was found between MRP8 and MRP14 expression and age or gender (P>0.05). CONCLUSION:These findings suggest that the decreased expression of MRP8 and MRP14 might play an important role in the pathogenesis of human esophageal squamous cell carcinoma,being particularly associated with poor differentiation of tumor cells.
基金Supported by the National Natural Science Foundation of China,No. 30371607
文摘AIM: To examine the aberrant expression of fragile histidine triad (FHIT) gene and protein in gastric cancer, and to evaluate the role of FHIT gene and the relationship between FHIT gene and EBV infection in gastric carcinogenesis. METHODS: FHIT transcripts were detected by nested RT-PCR in 30 cases of gastric cancer and their products were sequenced.FHIT protein was detected by Western blot. EBV infection was detected by PCR method in 50 cases of gastric cancer. RESULTS: The wild type transcripts were detected in all 30 matched normal tissues of gastric cancer.Aberrant transcripts were found in 11/30 (36.7%) gastric cancerous tissues. Sequencing analysis of the aberrant fragments found an RT-PCR product missing exons 5-7 in one case of gastric cancer, and another product missing exons 4-7. Four of ten (40.0%) cases of primary gastric cancer showed absent or decreased expression of FHIT protein as compared with their matched normal tissues.EBV was detected in 5/50 (10%) gastric cancers,among which 4/5 (80%) had aberrant transcripts of FHIT gene. CONCLUSION: Loss of FHIT gene or FHIT protein plays an important role in carcinogenesis,development and progression of gastric cancer.EBV infection might influence carcinogenesis of gastric cancer by inducing the abnormality of FHIT gene.
文摘In this study, we examined the expression of inducible nitric oxide s ynthase (iNOS) and vascular endothelial growth factor (VEGF) by immunohistoc hemi cal staining in 76 tissue sections collected from hepatocellular carcinoma (HCC) patients undergoing hepatectomy. Microvascular density (MVD) was determined by counting endothelial cells immunostained using anti-CD34 antibody. We performe d DNA-flow cytometric analyses to elucidate the impact of iNOS and VEGF expressi o n on the cell cycle of HCC. Most of the HCC cells that invaded stroma were mark edly immunostained by iNOS antibody. The iNOS stain intensity of the liver tissu e close to the tumor edge was stronger than that of HCC tissue, and the stronges t was the hepatocytes closer to the tumor tissue. However, iNOS expression in 10 normal hepatic samples was undetectable. VEGF positive expression ratio was 84. 8% in iNOS positive expression cases, and the ratio was 35.3% in negative cases. There was significant correlation (P=0.000) between iNOS and VEGF expressi on. Moreover, iNOS expression was significantly associated with bcl-2 and MVD, but w ithout p53 expression. DNA-flow cytometric analyses showed that combined expres s ion of iNOS and VEGF had significant impact on the cell cycle in HCC. PI (Proli ferating Index) and SPF (S-phase fraction) in the combined positive expression o f iNOS and VEGF group was significantly higher than that in the combined negativ e group. The present findings suggested that iNOS expression was significantly a ssociated with angiogenesis, bcl-2 and cell proliferation of HCC.
基金Supported by China Key Program on Basic Research,G1998051021the Chinese Hi-tech R&D program,2001AA231041National Science Foundation of China,30170519
文摘AIM:To study the role of hypermethylation in the loss of retinoic acid receptor β2(RARβ2) in esophageal squamous cell carcinoma (ESCC).METHODS:The role of hypermethylation in RARβ2 gene silencing in 6 ESCC cell lines was determined by methylation-specific PCR (MSP),and its methylation status was compared with RARβ2 mRNA expression by RT-PCR.The MSP results were confirmed by bisulfite sequencing of RARβ2promoter regions.RESULTS:Methylation was detected in 4 of the 6 cell lines,and the expression of RARβ2 was markedly downregulated in 3 of the 4 methylated cell lines. The expression of RARβ2 was restored in one RARβ2-downregulated cell line with the partial demethylation of promoter region of RARβ2 after 5-aza-2′-deoxycytidine (5-aza-dc) treatment.CONCLUSION:The methylation of the 5′ region may play an important role in the downregulation of RARβ2 in some ESCC cell lines, suggesting that multiple mechanisms contribute to the loss of RARβ2expression in ESCC cell lines.This study may have clinical applications for treatment and prevention of ESCC.
