Purpose: The proinflammatory cytokine interleukin-32 (IL-32) is a novel tumor marker highly expressed in various human carcinomas, including gastric cancer. However, its effects on prognosis of patients with gastric cancer and cancer metastasis are virtually unknown at present. The main aim of this study was to explore the clinical significance of IL-32 in gastric cancer and further elucidate the molecular mechanisms underlying IL-32-mediated migration and invasion.Experimental Design: Gastric cancer cells with ectopic expression or silencing of IL-32 were examined to identify downstream molecules and establish their effects on cell motility, invasion, and lung metastasis in vivo.Results: IL-32 was significantly upregulated in gastric cancer and positively correlated with aggressiveness of cancer and poor prognosis. Ectopic expression of IL-32 induced elongated morphology and increased cell migration and invasion via induction of IL-8, VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 expression via phosphor-AKT/phospho-glycogen synthase kinase 3b/active b-catenin as well as hypoxiainducible factor 1a (HIF-1a) signaling pathways. Conversely, depletion of IL-32 in gastric cancer cells reversed these effects and decreased lung colonization in vivo. Examination of gene expression datasets in oncomine and staining of gastric cancer specimens demonstrated the clinical significance of IL-32 and its downstream molecules by providing information on their coexpression patterns.Conclusions: IL-32 contributes to gastric cancer progression by increasing the metastatic potential resulting from AKT, b-catenin, and HIF-1a activation. Our results clearly suggest that IL-32 is an important mediator for gastric cancer metastasis and independent prognostic predictor of gastric cancer. Clin Cancer Res; 20(9); 2276-88. Ó2014 AACR.

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Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

AIM:To analyze the risk factors for central port failure in cancer patients administered chemotherapy, using univariate and multivariate analyses. 1.079-2.083, P = 0.016) when correlated with variables of age, sex and catheter type. Close-ended (Groshong) catheters had a lower thrombosis rate than open-ended catheters (2.5% vs 5%, P = 0.015). METHODS:Hematogenous malignancy had higher infection rates than solid malignancy (10.5% vs 2.5%, P < 0.001). CONCLUSION:Increasing age, male gender, openended catheters and hematogenous malignancy were risk factors for TIVAD failure. Close-ended catheters had lower thrombosis rates and hematogenous malignancy had higher infection rates.

Human papilloma virus infection is critical but not sufficient to cause cervical cancer. Molecular markers of cervical carcinogenesis are essential. The aim of this study was to identify aberrantly expressed proteins in cervical cancer and determine their clinical significance. A two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomic strategy was used for screening candidate proteins. Immunoblotting and immunohistochemical (IHC) analyses were performed to confirm the results of 2-DE, and the clinical significance was estimated. Glucose-regulated protein 58 (Grp58) was overexpressed in 73% of cancers. The IHC staining showed that the Grp58 histoscore was significantly higher in patients with adenocarcinoma (AD) compared with squamous cell carcinoma (P < 0.05). Grp58 staining was intense in AD with a penetration depth greater than half of the cervical stroma (P = 0.033). High Grp58 expression was associated with low overall survival and recurrence-free survival (RFS) rates (P = 0.007 and P = 0.013, respectively). In multivariate analysis, high Grp58 expression (P = 0.042) and lymph node metastasis (P = 0.026) were determined as independent prognostic factors for RFS. Patients exhibiting both high Grp58 expression and lymph node metastasis displayed poorer outcomes than the other patient groups. In functional studies, knockdown of Grp58 in HeLa cells led to decreased cell invasiveness and inhibition of lung metastasis in a xenograft mouse model. In conclusion, Grp58 serves as a potent prognostic factor of cervical AD. Estimation of the Grp58 index in conjunction with the lymph node metastasis status might aid in predicting the prognosis of cervical AD. (Cancer Sci 2011; 102: 2255-2263 C ervical cancer is one of the most common cancers among women worldwide. Approximately 500 000 diagnoses of cervical cancer are made each year, leading to 274 000 deaths, although the incidence and death rate have declined markedly in the past three decades because of effective screening.(1) Human papillomaviruses (HPV) are the causative agents of over 99% of cervical cancers containing viral sequences. Infection by highrisk HPV types is necessary but not sufficient for progression to cancer. Most HPV infections are transient without clinical manifestation and are cleared naturally; <1% of women become HPV carriers and remain at high risk of developing cervical cancer.(2)The mechanisms underlying the progression and regression of lesions caused by HPV infection are unknown, and further investigation of the molecular alterations in cervical cancer is needed.Glucose-regulated protein 58 (Grp58) is a glycoprotein-specific thiol-oxidoreductase belonging to the disulfide isomerase family of proteins. Grp58 is a multifunctional protein.(3) Recent studies suggest that Grp58 plays a role in cancer, although related information is limited. Hirano et al.(4) demonstrated that enhanced expression of Grp58 was associated with oncogenic transformation in normal rat kidney cells. Grp58 overexpression modulates STAT3 signaling in cancer...

The postoperative intrahepatic remnant rate is very high; 80% by 5 years after resection. The preoperative serum alpha-fetoprotein level and adequacy of the cut margin significantly influenced the recurrence rate.

We report our experience of the surgical treatment of intrahepatic cholangiocarcinoma (ICC) in Taiwanese patients. A total of 162 patients with histologically proven ICC were treated of whom 106 (65. 4%) had associated hepatolithiasis. Patients with hepatolithiasis were in earlier stages than those without hepatolithiasis. Two-thirds of the patients with hepatolithiasis presented with acute cholangitis, and two-thirds of those without hepatolithiasis presented with hepatomegaly. The rate of hepatic resection was 29.6% (48 of 162), and these rates were 31.1% and 26.8% for the patients with and without hepatolithiasis, respectively. Ninety-three percent of the patients with hepatolithiasis underwent common bile duct exploration, compared with 18% of those without hepatolithiasis. The surgical mortality rates were 3.7% (6/162), for all patients, and 3. 8% and 3.6% for patients with and without hepatolithiasis, respectively. The morbidity rate was much higher in the patients with hepatolithiasis (37.7% vs 16.1%). The 1-, 3-, and 5-year survival rates were 35.5%, 20.5%, and 16.5% in the patients with hepatolithiasis and 27.2%, 8.8%, and 7.8% in those without hepatolithiasis. Concomitant hepatolithiasis prevented precise diagnosis preoperatively and precipitated biliary sepsis, which affected resectability and increased postoperative morbidity. Hepatolithiasis per se did not influence long-term survival.

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