OBJECTIVETo evaluate the expression and activity of TNF-related apoptosis-inducing ligand (TRAIL) gene expressed from the hTERT promoter on colon cancer cell line HT-29.

METHODSGFP/TRAIL gene expressed from the hTERT promoter was transfected into HT-29 with adenoviral vectors system, expression and apoptosis inducing ability of GFP/TRAIL protein were determined with fluorescence-activated cell sorting (FACS) method.

RESULTSThe expression of GFP gene was 31.4 % and 67.0 % with either hTERT promoter or CMV promoter in DLD1 cells; GFP/TRAIL gene was able to inhibit cell growth (74.2%) and induce apoptosis (25.8%) of HT-29 cells. There was significant difference between Ad/hTERT-gTRAIL and the other two control groups (PBS and Ad/CMV-GFP, P<0.05).

CONCLUSIONThe GFP/TRAIL gene with hTERT promoter transfected by adenoviral vector was successfully expressed in HT-29 cell, which can both inhibit cell growth and induce apoptosis of colon cancer cell line HT-29.

Adenoviridae ; genetics ; Apoptosis ; physiology ; Colonic Neoplasms ; enzymology ; pathology ; Genetic Vectors ; Green Fluorescent Proteins ; biosynthesis ; genetics ; HT29 Cells ; Humans ; Promoter Regions, Genetic ; genetics ; TNF-Related Apoptosis-Inducing Ligand ; biosynthesis ; genetics ; Telomerase ; genetics ; Tumor Cells, Cultured

OBJECTIVEThis study aimed to review the available literature on fertility-preserving treatment and pregnancy outcomes in patients with early-stage endometrial carcinoma who desired to preserve their fertility.

DATA SOURCESThe PubMed database (1992-2012) was searched for the words "conservative "OR" fertility sparing "OR" fertility preserving" AND "endometrial neoplasms" (MeSH). All relevant articles in English and the relevant references were collected.

STUDY SELECTIONData from published articles about fertility-preserving treatment of endometrial cancer, including the response and recurrence rate of conservative treatment, strategies of infertility treatment, pregnancy, and obstetric outcomes, were selected. Data were mainly extracted from 41 studies, which are listed in the reference section of this review.

RESULTSHormone therapy was the most common method used for early-stage endometrial carcinoma in patients who wished to preserve fertility. Sixty percent of the patients became pregnant after remission of the carcinoma. The percentage of patients who conceived in the assisted reproductive technology group was higher than that of the natural pregnancy group (80.0% vs. 43.2%, P < 0.01). A higher rate of preterm labor and multiple pregnancies was observed in the assisted reproductive technology group than that in the natural pregnancy group. The majority of pregnancies (71.4%) in the assisted reproductive technology group were achieved by in vitro fertilization-embryo transfer. The clinical pregnancy rate of transfer cycles in patients with endometrial carcinoma was 34.1%.

CONCLUSIONSAssisted reproductive technology is a good option in well-selected patients with early-stage endometrial carcinoma who have completed conservative treatment. In vitro fertilization-embryo transfer offers an opportunity to achieve an immediate pregnancy.

Endometrial Neoplasms ; therapy ; Female ; Fertility Preservation ; methods ; Humans ; Neoplasm Staging ; Pregnancy ; Pregnancy Complications, Neoplastic ; Pregnancy Outcome ; Reproductive Techniques, Assisted

OBJECTIVETo investigate the role of B7-H1 expression in IL-10 production, the B7-H1 and IL-10 expression levels in pancreatic carcinoma tissues and to analyze the correlation between B7-H1 expression and IL-10 level.

METHODSThe mRNA and protein levels expressions of B7-H1 and IL-10 in 35 cases of pancreatic cancer and corresponding paracarcinoma tissues and 5 cases of normal pancreas tissues were detected by RT-PCR, Western blot and immunohistochemistry respectively.

RESULTSThe findings for the first time provided the evidences that there was a clear trend for B7-H1 and IL-10 expressions to be most highly expressed in carcinoma tissue, intermediately expressed in paracarcinoma tissue, and expressed at the lowest level in normal pancreatic tissue at mRNA and protein levels. Moreover, there were statistically significant differences in B7-H1 and IL-10 expression between pancreatic carcinoma tissues, corresponding paracarcinoma tissues and normal pancreatic tissues at mRNA and protein levels (P < 0.05). Furthermore, the immunohistochemistry indicated that there were high expression levels of B7-H1 (60.5% +/- 12.7%) and IL-10 (65.3% +/- 16.2%) in pancreatic carcinoma tissues while there were no significant expressions in normal pancreatic tissues. Meanwhile, correlation analysis revealed that B7-H1 expression was significant associated with IL-10 level in tumor tissues at mRNA (P = 0.008, r = 0.841) and protein levels (P = 0.007, r = 0.838).

CONCLUSIONSOver-expression of B7-H1 may be responsible for the increasing IL-10 production in pancreatic cancer, which caused reduced immune response to tumor cells and contributed to pancreatic carcinoma escape from immune attack.

Antigens, CD ; immunology ; B7-H1 Antigen ; Humans ; Immune Evasion ; Interleukin-10 ; immunology ; Pancreatic Neoplasms ; immunology

OBJECTIVETo investigate the effect of small interfering RNA on cell proliferation and apoptosis in gastric cancer cell lines with high expression of RegIα.

METHODSTotal RNA was isolated from six gastric cancer cell lines,and the expression of RegI α mRNA was detected by RT-PCR. RegI α RNAi expression vector was constructed and stably transfected into MKN45 and AGS cells with high RegI α expression, empty-vector was used as control. RegI α mRNA and protein expression was measured by RT-PCR and Western blot respectively in stable transfected cell lines. Cell proliferation and apoptosis were detected with MTT assay and flow cytometry.

RESULTRT-PCR results indicated that RegI α mRNA expression was significantly inhibited by RNAi in both cell lines compared with empty-vector. Western blot results showed that RegIα protein was down-regulated to (44 ± 4)% and (25 ± 4)% respectively in MKN45 and AGS cells compared to empty-vector. MTT results showed that cell growth was significantly inhibited in MKN45 and AGS cells. The apoptosis rate in MKN45 and AGS cells was remarkable increased compared to that of empty-vector (12.96 ± 0.50)% compared with (3.99 ± 0.30)% and (11.59 ± 1.10)% compared with (4.22 ± 0.40)% (P < 0.05).

CONCLUSIONSmall interfering RNA of RegI α gene can efficiently down-regulate RegI α expression in MKN45 and AGS cell lines, and further inhibit cell growth and induce cell apoptosis.

Animals ; Apoptosis ; genetics ; Cell Cycle ; genetics ; Cell Line, Tumor ; Cell Proliferation ; Genetic Vectors ; Lithostathine ; genetics ; metabolism ; Mice ; Plasmids ; genetics ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Transfection

OBJECTIVETo construct RegIα over-expression vector and to evaluate the effect of RegIα on the proliferation and apoptosis of gastric cancer MKN28 cells in vitro.

METHODSFull sequence of RegIα cDNA was amplified from normal gastric tissue samples by RT-PCR and cloned into pIRES2-EGFP vector. RT-PCR and Western blot were performed to detect expression levels of RegIα in MKN28 cells. The effects of over-expression RegIα on cell proliferation was measured by MTT assay and apoptosis was detected by flow cytometry.

RESULTRegIα cDNA over-expression vector of pIRES2-RegIα-EGFP was successfully constructed. The expressions of RegIα in MKN28 cells, including mRNA and protein levels, were significantly increased after stable transfection, which resulted in cell proliferation and anti-apoptotic effect induced by H(2)O(2).

CONCLUSIONThe over-expression of RegIα can promote cell proliferation and reduce cell apoptosis when induced by H(2)O(2) in gastric cancer cells.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Genetic Vectors ; Humans ; Plasmids ; genetics ; Stomach Neoplasms ; metabolism ; pathology ; Transfection

OBJECTIVE5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system.

DATA SOURCESAll articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed. The search terms were "autophagy" and "5-FU" and ("colorectal cancer" or "hepatocellular carcinoma" or "pancreatic adenocarcinoma" or "esophageal cancer" or "gallbladder carcinoma" or "gastric cancer").

STUDY SELECTIONCritical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency of autophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized. The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy; (2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers; and (3) immunogenic cell death for anticancer chemotherapy.

RESULTSMost cell and animal experiments showed inhibition of autophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death. Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce. The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials.

CONCLUSIONAutophagy might be a therapeutic target that sensitizes the 5-FU treatment in gastrointestinal cancer.

Antimetabolites, Antineoplastic ; therapeutic use ; Autophagy ; physiology ; Drug Resistance, Neoplasm ; Fluorouracil ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; pathology ; Humans

BACKGROUNDA new procedure of colonic anastomosis with a degradable stent has already been proven to be simple, feasible, and safe in our porcine model. In this study, we evaluated its impact on the colonic physiologic functions.

METHODSA total of 20 pigs were assigned randomly to either a stent anastomosis group (SA, n = 10) or a conventional anastomosis group (CA, n = 10). Colonic anastomosis with a degradable stent was performed in the SA group, and conventional hand-sewn anastomosis was performed in the CA group. Body weight, fecal weight, total colonic transit time, immunohistochemistry staining of interstitial cells of Cajal (ICC), plasma diamine oxidases (DAO) levels, and Western blotting analysis of occludin were evaluated before and after anastomosis.

RESULTSNo obvious diarrhea or constipation was observed in all pigs. No significant difference in body weight between the groups was detected at any time. Yet, the fecal weight was less in the CA group compared with the SA group on postoperative day (POD) 7. No observable colonic paralysis or retention occurred. For total colonic transit time, there was no significant difference between the two groups at any time or among different time points in the same group. The integrated optical density of ICC showed no significant difference on either POD 14 or 30. The plasma DAO levels were remarkably elevated after surgery, and began to decrease since POD 3. However, there was no significant difference between both two groups in plasma DAO levels at any time either. For both groups, the expression of occludin was not significantly different from their pre-surgery level on either POD 14 or 30.

CONCLUSIONSAccording to these results, this procedure with a degradable stent was supposed to be the same as the conventional hand-sewn procedure in their impact on the colonic physiologic functions.

Anastomosis, Surgical ; methods ; Animals ; Colon ; surgery ; Stents ; Swine

Female ; Gastric Mucosa ; Humans ; Middle Aged ; Stomach ; abnormalities

Angioplasty, Balloon, Coronary ; adverse effects ; Aspirin ; pharmacology ; therapeutic use ; Coronary Angiography ; Drug-Eluting Stents ; adverse effects ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; therapeutic use ; Sirolimus ; pharmacology ; therapeutic use ; Ticlopidine ; analogs & derivatives ; pharmacology ; therapeutic use ; Treatment Outcome ; Tyrosine ; analogs & derivatives ; pharmacology ; therapeutic use

OBJECTIVETo study the effects of decreased leptin expression on liver fibrosis.

METHODSThe small interfering RNA, targeting leptin gene, was designed according to the secondary structure of leptin gene. The recombinant plasmids were encapsulated with lipofectamine and then injected into carbon tetrachloride (CCl4) induced rat liver fibrosis models. Leptin and I, III collage were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).

RESULTSThe mRNA and protein levels of leptin in the fibrotic liver transfected with leptin shRNA were significantly decreased compared with those in controls (P less than 0.01). The depositions of type I and type III collagens were also decreased (P less than 0.01).

CONCLUSIONDecreased leptin expression prevents liver fibrosis.

Animals ; Leptin ; genetics ; Liver Cirrhosis, Experimental ; therapy ; Male ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley