Combined use of chemotherapeutics and oncolytic adenovirus in treatment of AFP-expressing hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) which is always refractory to most chemotherapeutic agents may result in poor survival of patients with advanced HCC. Oncolytic adenovirus is a new form for cancer gene therapy via its ability to replicate and kill tumor cells in a tumor-specific manner. In order to eradicate tumors effectively, the combination of chemotherapeutic agents and oncolytic adenovirus has been considered. This study aimed to systematically analyze the possibility of synergistic cytotoxicity of oncolytic adenoviruses in combination with chemotherapeutic agents. METHODS: Several types of human HCC cell lines were used to determine the specificity and cytotoxicity of oncolytic adenovirus Ad5-HC and Ad5-AFP (IRES) by measuring cell viability in vitro and antitumor efficiency in vivo. The cytotoxicity of Ad5-HC and Ad5-AFP (IRES) combined with chemotherapeutic agents were also assessed by the methyl thiazolyl tetrazolium assay. RESULTS: Both Ad5-HC and Ad5-AFP (IRES) were significantly cytotoxic to HCC cells with great specificity in vitro and in vivo. The combination of oncolytic adenovirus with 5-FU, doxorubicin, and paclitaxel was synergistically effective for the killing of HCC cells. CONCLUSIONS: These data suggest that oncolytic adenovirus sensitize tumors to chemotherapy and the combination therapy of chemotherapeutic agents and oncolytic adenovirus has an enhanced antitumor effect on HCC cells. (Hepatobiliary Pancreat Dis Int 2009; 8: 282-287)

Role of RECK methylation in gastric cancer and its clinical significance

AIM:To investigate the relation between RECK methylation and clinicopathological characteristics of gastric cancer patients and evaluate the role of RECK methylation in peritoneal metastasis of gastric cancer.METHODS:Methylation of RECK gene in 40 paired samples of gastric cancer and its corresponding adjacent normal mucosa,lymph nodes and peritoneal irrigation fluid was detected by methylation-specific polymerase chain reaction.RESULTS:Aberrant methylation of RECK gene was detected in 27.5%(11/40)of the adjacent normal mucosa samples,in 47.5%(19/40)of gastric cancer samples,in 57.1%(12/21)of the lymph node samples,and in 35%(14/40)of peritoneal irrigation fluid samples,respectively,with a significant difference between the adjacent normal mucosa and lymph node samples(P=0.023).Presence of RECK methylation in the primary tumor samples was significantly correlated with tumor invasion(P=0.023).The accuracy of RECK methylation in peritoneal lavage fluid samples for the diagnosis of peritoneal metastasis of gastric cancer was 72.5%(26/40),with a sensitivity of 66.7%(6/9) and a specificity of 74.2%(23/31).CONCLUSION:Aberrant methylation of RECK gene may provide useful information for the early diagnosis and treatment of peritoneal metastasis of gastric cancer.

Role of BMP3 in progression of gastric carcinoma in Chinese people

AIM:To investigate the relation between gastric cancer and microsatellite instability(MSI),loss of heterozygosity(LOH)and promoter region methylation.METHODS:Fifty primary gastric carcinoma specimens were collected from patients with no family history of cancer.In addition,normal tissues were also collected from patients as controls.DNA was extracted by polymerase chain reaction for single-strand conformation polymorphism,bisulfite DNA sequencing,and methylation-specific band analysis.RESULTS:The positive rate for MSI and LOH in gastric carcinoma was 16%and 20%,respectively.According to the tumor,node and metastasis staging system,the LOH frequency was higher in gastric carcinoma at stages Ⅲ and Ⅳ than in gastric carcinoma at stagesⅠ and Ⅱ(P=0.01),which was also significantly correlated with lymph node metastasis and clinicopathological characteristics of gastric carcinoma.Methylation of bone morphogenetic protein 3(BMP3)gene promoter was detected in 64.44% of gastric carcinoma tissue samples.However,no statistical significance was observed between promoter region methylation and carcinoma differentiation.Interestingly,the BMP3 gene methylation rate was 71.05% and 28.58%,respectively,in MSI positive and negative cases(P=0.031),suggesting that BMP3 genetic instability and promoter methylation are initiated during gastric carcinogenesis.LOH was detected mostly in the late stages of gastric carcinoma,indicating that gastric carcinoma at late stages has a higher infiltration and a poorer prognosis.CONCLUSION:Promotor region methylation of the BMP3 gene may cause gastric carcinoma in Chinese people.

Abdominal separation in an adult male patient with acute abdominal pain

We report a male patient with prolonged post-prandial abdominal distension and a sudden onset of epigastric pain initially diagnosed as acute abdomen. The patient had no history of surgery. Physical examination revealed peritonitis and abdominal computed tomography scan showed upper abdominal mesentery intorsion. The patient then underwent surgical intervention. It was found that the descending mesocolon dorsal root was connected to the ascending colon and formed a membrane encapsulating the small intestine. The membrane also formed an orifice in the ileal pars caeca, from which a 30 cm herniated ileum formed a "C"-shaped loop which was strangulated by the orifice. An abdominal separation was diagnosed after surgery. We liberated the membranous peritoneum which incarcerated the intestinal canal from the root ofileocecal junction to Treitz ligament, and reduced the small intestinal malrotation. The patient had an uneventful recovery after opera-tion with his abdominal distention disappeared during the follow-up. Abdominal separation is a rare situation, which may be related with embryo development. Surgery is a choice of treatment for it.

Thyroid and parathyroid gland

Objective To investigate tures and treatment of thyroid Methods From January 1997 patients who underwent surgery the clinicopathologic feamicrocarcinoma （TMC）. to December 2006, 311 and defined as TMC（tumot size≤1 cm） were enrolled. Results TMC was identified incidentally by frozen pathologic examination on thyroidectomy specimens in tentative benign goiters in 181 patients; another 130 patients with clinically detectable primary tumors or suspected nodal metastases were grouped to as clinically overt TMC. The clinically overt TMC had a higher incidence of bilateral multifocal tumors （18.5 % vs 9.4 %, P = 0.03）, and cervical lymph node metastases（27.7% vs 10.5%, P = 0. 000） than that in clinically occult TMC group.

Impact of multidisciplinary team working on the management of colorectal cancer

Background The continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline.Colorectal cancer multidisciplinary team （MDT） working model is recommended by UK and other countries,but there is little information on the impact of MDT working on management of colorectal cancer in China.The aim of this study was to assess the effect on management of colorectal cancer after the inception of an MDT.Methods A total of 595 consecutive colorectal cancer patients were referred to the Department of Gastroenterological Surgery,the pre-MDT cohort include 297 patients,recruited from January 1999 to November 2002,and the MDT cohort had 298 patients enrolled from December 2002 to September 2006.Information recorded included：TNM stage from histological reports,degree of differentiation,the number of examined lymph nodes and CT TNM staging performed or not,and its accuracy,including local and distant recurrence.Results The number of examined lymph nodes and the accuracy of TNM staging by CT in the MDT group were significantly more than those in pre-MDT group.CT TNM staging was more accurate in the MDT group compared to the pre-MDT group （P=-0.044）.The rate of tumor recurrence in the MDT group was lower than pre-MDT group （log-rank test,P 〈0.001）.Multivariate analysis revealed that age （P=0.001）,management after inception of the MDT （P=0.002）,degree of differentiation （P=0.003）,number of examined lymph nodes （P=0.002）,and TNM stage （P=0.000） were important factors that independently influence overall survival.Conclusions The inception of MDT working improved the diagnostic accuracy and overall survival of colorectal cancer patients.MDT working promoted communication and cooperation between disciplines and ensured high-quality diagnosis,evidence-based decision making,and optimal treatment planning.

Integrase interactor 1 regulates proliferation, apoptosis and invasion in gastric cancer cells

Background Integrase interactor 1 （INI1）,which encodes a component of the ATP-dependent chromatin remodeling hSWI-SNF complex,has been identified as a tumor suppressor in many tumors.Nonetheless,the role of INI1 in gastric tumor progression is not known exactly.The aim of this research was to investigate the effect of INI1 in the carcinogenesis and progression of gastric cancer.Methods Gastric tumor tissues with different differentiation levels from clinical gastric carcinoma samples and adjacent control normal tissues were taken. Expression levels of INI1 were detected by quantitative reverse transcriptation-polymerase chain reaction （RT-PCR） and Western blotting.Gastric cancer cell line SGC7901 was transfected with INI1 eukaryotic expressing vector INI1-GFP.Cell proliferation activities were assessed by MTT; cell count and cell cycle were detected by flow cytometry （FCM）; cell apoptosis were measured by TUNEL and FCM; cell migration and invasiveness were evaluated by wound healing and transwell assays.Expression levels of INI1 and proliferation-related genes including p16,p21,cyclin D1 and cyclin A,apoptosis genes p53,B-cell non-Hodgkin lymphoma-2 （Bc/-2）,Bcl-2-associated x protein （Bax） and caspase-3,and invasion-related genes including intercellular adhesion molecule 1 （ICAM1）,matrix metalloproteinase 2 （MMP2）,MMP9 and tissue inhibitor of matrix metalloproteinase 1 （T/MP1）,were detected by quantitative RT-PCR and Western blotting.Results INI1 expression levels were lower in gastric carcinoma compared with adjacent control normal tissues.Overexpression of INI1 in SGC7901 cells inhibited its proliferation and invasiveness,but increased anoikis and Go/G1 cell number.INI1-GFP transfection upregulated expression of INI1 and proliferation related genes p16 and p21,apoptosis genes p53 and Bax,and invasion-related genes TIMP1; cyclin D1,cyclin A,Bcl2,ICAM1,MMP2 and MMP9 were downregulated,and there was no significant change in caspase 3 levels.Conclusion INI1 plays a key role in gastric carcinogenesis by affecting proliferation,apoptosis and invasion.

Nature：研究鉴定出侵袭性胰腺癌细胞及其弱点

在一项新的研究中，来自美国德州大学MD安德森癌症中心的研究人员利用患者源性肿瘤异种移植（patient—derived tumorxenograft,PDx）和模式小鼠开展一系列临床前实验，鉴定出一种门卫蛋白（gatekee Perprotein）阻止胰腺癌细胞转化为一种极具侵袭性的细胞类型，并且也发现剔除这种门卫蛋白的疗法能够阻止这些癌细胞。这些发现有助为携带这种进展迅速的治疗抵抗性的胰腺癌细胞亚群的患者开发出潜在的疗法。