Gene expression profile of terminal end buds in rat mammary glands exposed to diethylstilbestrol in neonatal period

Diethlstilbestrol (DES) is a synthetic estrogen prescribed to several millions of pregnant women worldwide. The risk for breast cancer after age 40 in women prenatally exposed to DES has been reported; however, the precise mechanism of susceptibility to breast cancer remains to be resolved. We investigated the global gene expression profile of terminal end buds (TEBs), the target of carcinogen, in rat mammary glands neonatally exposed to a low- or high-dose DES at postnatal days (PND) 35 and 45, equivalent to the peripubertal stage in humans. In all groups, the number of TEBs gradually increased, peaked at PND35 and decreased at PND49. At PND35 and 49, the low-dose DES-treated group (low-DES group) showed the highest number of TEBs. In the low-DES group at PND35, β-casein, γ-casein and whey acidic protein (WAP) mRNA expression increased 8.2-fold, 26.1-fold and 13.3-fold, respectively, whereas γ-casein and WAP mRNA decreased 17.6-fold and 27.7-fold, respectively, at PND49. The most significant network revealed by Ingenuity Pathway Analysis (IPA) software showed the relevance of NF-κB in low-DES group. The present findings suggest that the deregulation of mammary gland differentiation and development-related genes could be induced and cause the increased number of terminal duct lobular units (TDLUs) in human mammary glands of DES daughters in a critical period of mammary gland development.     

Resistance of colon cancer to 5-fluorouracil may be overcome by combination with chloroquine, an in vivo study

Autophagy is a complex of adaptive cellular response that enhances cancer cell survival in the face of cellular stresses such as chemotherapy. Recently, chloroquine diphosphate (CQ), a widely used antimalarial drug, has been studied as a potential inhibitor of autophagy. Here, we aimed to investigate the role of CQ in potentiating the effect of 5-fluorouracil (5-FU), the chemotherapeutic agent of first choice for the treatment of colorectal cancer, in an animal model of colon cancer. The mouse colon cancer cell line colon26 was used. For the in-vivo study, colon26 cells were injected subcutaneously into BALB/c mice, which were treated with saline as a control, CQ (50 mg/kg/day), 5-FU (30 mg/kg/day), or the combination therapy (CQ plus 5-FU). The tumor volume ratio and body weight were monitored. After the sacrifice, tumor tissue protein extracts and tumor sections were prepared and subjected to immunoblotting for the analysis of autophagy-related and apoptosis-related proteins, and the terminal transferase uridyl end labeling assay. The combination of CQ resulted in the inhibition of 5-FU-induced autophagy and a significant enhancement in the 5-FU-induced inhibition of tumor growth. Furthermore, the combination treatment of CQ and 5-FU resulted in a significant increase in the ratio of apoptotic cells compared with other treatments. The expression levels of the proapoptotic proteins, namely Bad and Bax, were increased by the CQ treatment in the protein extracts from tumors. Our findings suggest that the combination therapy of CQ and 5-FU should be considered as an effective strategy for the treatment of colorectal cancer.     

Successful utilization of coronary covered stents to treat a common hepatic artery pseudoaneurysm secondary to pancreatic fistula after Whipple’s procedure: Report of a case

A 73-year-old man underwent a pylorus-preserving Whipple’s procedure for distal cholangiocarcinoma. His postoperative course was complicated by the formation of a pancreatic fistula, which was initially managed conservatively. On postoperative day (POD) 86, he lost 100 ml of blood from the site of the pancreatic fistula. Contrast-enhanced computed tomography (CT) showed a pseudoaneurysm, 12 mm in diameter, in the common hepatic artery. The diameter of the pseudoaneurysm increased to 15 mm on POD 89, so we implanted coronary covered stents to prevent massive bleeding from rupture and to retain hepatic arterial flow. Six days after implantation, computed tomography findings confirmed a thrombosed pseudoaneurysm as well as patent hepatic arterial flow. Follow-up CT 18 months after surgery showed patent hepatic arterial flow. There have been no signs of rebleeding or abnormal liver function.     

Gastric cancer surgery for patients with liver cirrhosis

AIM: To elucidate the influence of liver cirrhosis (LC) on the prognosis of patients with gastric cancer (GC).METHODS: Of the 1347 GC patients who underwent curative gastrectomy for GC between January 1984 and June 2007, 25 patients (21 men and 4 women with a median age of 67 years; range 54-77 years) with LC were enrolled in this study. Using the Child-Pugh classification, 15 patients were evaluated as grade A and 10 patients as grade B. No grade C patient underwent gastrectomy in this series. Clinical outcomes, including postoperative morbidity and survival, were retrospectively analyzed based on medical records and surgical files.RESULTS: There was no significant difference in operative blood loss and perioperative blood transfusion between the two groups. The most common postoperative complication was intractable ascites, which was the single postoperative morbidity noted more frequently in grade B patients (40.0%) than in grade A patients (6.7%) with statistical significance (P = 0.041). Operative mortality due to hepatic failure was seen in one grade A patient. Three patients had hepatocellular carcinoma (HCC) at presentation and two patients developed HCC after surgery. Overall 5-year survival rate was 58.9% in patients with early GC and 33.3% in patients with advanced GC (P = 0.230). GC-specific 5-year survival rate of early GC patients was 90.0% while that of advanced GC patients was 58.3% (P = 0.010). Four patients with early GC died of uncontrolled HCC, of which two were synchronous and two metachronous.CONCLUSION: The risk of postoperative intractable ascites is high, particularly in grade B patients. Early detection and complete control of HCC is vital to improve a patient’s prognosis.     

Delivery of sodium borocaptate to glioma cells using immunoliposome conjugated with anti-EGFR antibodies by ZZ-His

Nanoparticles are effective of delivering cargo into cells. Here, sodium borocaptate (BSH) was encapsulated in liposomes composed of nickel lipid, and anti-epidermal growth factor receptor (EGFR) antibodies were conjugated to the liposomes using the antibody affinity motif of protein A (ZZ) as an adaptor (immunoliposomes). The immunoliposomes were used to deliver BSH into EGFR-overexpressing glioma cells. Immunohistochemical analysis using an anti-BSH monoclonal antibody revealed that BSH was delivered effectively into the cells but not into EGFR-deficient glioma or primary astrocytes. In an animal model of brain tumors, both the liposomes and the BSH were only observed in the tumor. Moreover, the efficiency of ¹⁰B's delivery into glioma cells was confirmed by inductively coupled plasma-atomic emission spectrometry (ICP-AES) both in vitro and in vivo. The results suggest that this system utilizing immunoliposomes provides an effective means of delivering ¹⁰B into glioma cells in boron neutron capture therapy (BNCT).     

Usage of granulocyte colony-stimulating factor every 2 days is clinically useful and cost-effective for febrile neutropenia during early courses of chemotherapy

Background  

In order to analyze the clinical activity and cost-effectiveness of granulocyte colony-stimulating factors (G-CSF), the prophylactic usage of G-CSF in patients treated with a single chemotherapy regimen during early courses was prospectively evaluated.     

Incidental inverted papilloma during the clinical follow-up of superficial transitional cell carcinoma in the urinary bladder

A 76-year-old woman presented with gross hematuria. She had received transurethral resections (TURBT) twice for superficial bladder tumors near the right orifice. All pathologic findings demonstrated low grade superficial transitional cell carcinoma (TCC). Cystoscopy showed the tumor lesions during the follow-up. Bladder tumors were completely harvested and pathologic examination revealed inverted papilloma. However, recurrent tumors were detected at the same location after 4 months' follow up. Although she came to our hospital for the purpose of TURBT, she complained of severe neck pain and was suddenly dead. Autopsy findings showed that dissecting aortic aneurism was the cause of death and the bladder tumor was low grade superficial TCC. The case reported here had a very rare pathologic finding with a history of superficial tumors located in the same areas in the urinary bladder.