Background:
We previously demonstrated that the reduced expression in immortalized
cells (REIC)/dikkopf-3 (Dkk-3) gene was downregulated in various malignant tumors, and that an adenovirus
vector carrying the REIC/Dkk-3 gene, termed Ad-REIC induced cancer-selective apoptosis
in pancreatic cancer and hepatocellular carcinoma.
Objective:
In this study, we examined the therapeutic effects of Ad-REIC in biliary cancer using a second-
generation Ad-REIC (Ad-SGE-REIC).
Methods:
Human biliary cancer cell lines (G-415, TFK-1) were used in this study. The cell viability
and apoptotic effect of Ad-SGE-REIC were assessed in vitro using an MTT assay and Hoechst staining.
The anti-tumor effect in vivo was assessed in a mouse xenograft model. We also assessed the
therapeutic effects of Ad-SGE-REIC therapy with cisplatin. Cell signaling was assessed by Western
blotting.
Results:
Ad-SGE-REIC reduced cell viability, and induced apoptosis in biliary cancer cell lines via
the activation of the c-Jun N-terminal kinase pathway. Ad-SGE-REIC also inhibited tumor growth in a
mouse xenograft model. This effect was further enhanced in combination with cisplatin.
Conclusions:
Ad-SGE-REIC induced apoptosis and inhibited tumor growth in biliary cancer cells.
REIC/Dkk-3 gene therapy using Ad-SGE-REIC is an attractive therapeutic tool for biliary cancer.
The γ-secretase inhibitor blocks Notch activity by preventing its cleavage at the cell surface. In the present study, the effect of the γ-secretase inhibitor on the viability of gastric cancer cells when administered in combination with cisplatin was investigated, with particular focus on CD44Lgr-5 cancer cells. The four gastric cancer cell lines, MKN45, MKN74, SC-6-JCK and SH-10-TC, were used for the experiments. In the MTT assay, treatment with 25 µM dipeptide γ-secretase inhibitor (DAPT) alone did not affect cell proliferation in any of the four cell lines. Gastric cancer cells subjected to combination treatment with DAPT and cisplatin exhibited decreased viability when compared with those treated with cisplatin alone. Flow cytometry was performed to evaluate the expression of cluster of differentiation (CD)-44 and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr-5), two cancer stem cell markers in gastric cancers. Treatment with cisplatin alone significantly increased the proportion of CD44Lgr-5 cells. However, the addition of DAPT to cisplatin reduced the CD44Lgr-5 fraction, suggesting that DAPT reduced the number of gastric cancer cells. In conclusion, the present study demonstrated the synergistic effects of DAPT in combination with cisplatin by decreasing the survival of gastric cancer cells. In addition, combination treatment with DAPT reduced the number of CD44Lgr-5 cells, which are thought to exhibit cancer stem cell properties. These results highlight the therapeutic potential of DAPT in gastric cancer treatment.
An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.
An 80-year-old man underwent follow-up examinations after endoscopic submucosal dissection (ESD) for esophageal cancer. Computed tomography (CT) showed enlarged lymph nodes of the right recurrent nerve. The patient had esophageal stenosis due to repeated ESD for multiple esophageal tumors. The stenosis made the passage of an endoscopic ultrasound (EUS) scope through the esophagus difficult. Thus, an endobronchial ultrasound bronchoscope, which had a thinner diameter than that of the EUS scope, was used for transesophageal endoscopic ultrasound with bronchoscope-guided fine-needle aspiration. This technique led to the diagnosis of mediastinal lymph node metastasis of esophageal cancer.
A 58-year-old woman had disseminated intravascular coagulation (DIC) and septic shock caused by Japanese spotted fever (JSF). Following treatment with minocycline, her general condition gradually improved; however, her disorientation persisted. Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) type II was diagnosed based on brain magnetic resonance imaging (MRI) showing a hyperintense area in the splenium of the corpus callosum and bilateral cerebral white matter on diffusion-weighted imaging. Thereafter, her consciousness gradually improved, but she continued to experience difficulty concentrating and attention deficits. MERS type II may take longer to improve than type I, and long-term follow-up is required.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.