Tissue methylated DNA markers for sporadic pancreatic cancer are strongly associated with familial and genetically predisposed pancreatic cancer

High-risk individuals (HRIs) with familial and genetic predisposition to pancreatic ductal adenocarcinoma (PDAC) are eligible for screening. There is no accurate biomarker for detecting early-stage PDAC. We previously demonstrated that a panel of methylated DNA markers (MDMs) accurately detect sporadic PDAC. In this study we compared the distribution of MDMs in DNA extracted from tissue of PDAC cases who carry germline mutations and non-carriers with family history, with control tissue and demonstrate high discrimination like that seen in sporadic PDAC. These results provide scientific rationale for examining plasma MDMs in HRIs with the goal of developing a minimally-invasive early detection test.     

热化疗对人直肠癌细胞遗传物质的损伤

将体外培养的人直肠癌细胞进行反复热化疗处理,观察处理前后癌细胞染色体和AgNOR的变化。结果显示热化疗后癌细胞染色体有明显畸变,培养后期染色体断片明显增加,且AgNOR颗粒显著减少。提示染色体是人直肠癌细胞热化疗死亡的重要靶部位之一。     

Adenylate cyclase activity in human pancreatic adenocarcinoma cell lines

Summary Conclusion BxPC-3, Hs 766T, Capan-2, Panc-1, and Capan-1 cells possess receptors for VIP and β-adrenergic agonists that are functionally coupled to adenylate cyclase. In this respect, they resemble pancreatic duct cells. However, we speculate that the process of neoplastic transformation has either downregulated the expression of secretin receptors or led to a defect in the receptor itself, placing a question mark over the usefulness of these adenocarcinoma cell lines as models of the pancreatic ductal epithelium. Background Because of the importance of ducts in pancreatic disease, we wished to establish which duct cells receptors are functional on adenocarcinoma cell lines. Methods We investigated the expression of agonist-stimulated adenylate cyclase activity in six human pancreatic adenocarcinoma cell lines. Known stimulants of pancreatic ductal secretion, VIP, PHI, secretin, β-adrenergic, and dopamine, were tested. Results For responsive cell lines, VIP was the most effective stimulant followed by adrenaline, isoprenaline, PHI, and secretin. Dopamine was without effect. Since high concentrations of PHI and secretin were required to stimulate cyclase activity, their effect is probably mediated by VIP receptors. Based on the degree of stimulation observed with the individual agonists, Hs 766T and BxPC-3 were the most responsive cell lines, followed by Capan-2 and Capan-1, and finally Panc-1. MIAPaCa-2 cells did not respond to any of the agonists tested.     

Survival After Curative Resection for Mucinous Adenocarcinoma of the Colorectum

PURPOSE: Previous reports have suggested that mucinous colorectal adenocarcinomas are more advanced at diagnosis and have a poorer prognosis than nonmucinous colorectal adenocarcinomas. The purpose of this study was to clarify whether the mucin-producing histologic type of carcinoma is associated with a worse prognosis than nonmucinous, differentiated colorectal adenocarcinoma for patients who undergo curative surgery. METHODS: Using a database of 2,678 surgical patients with colorectal cancers operated on at Aichi Cancer Center between 1965 and 1994, we investigated 97 cases of mucinous adenocarcinoma and 2,197 cases of nonmucinous adenocarcinoma. We also evaluated the outcomes of patients who underwent surgery with curative intent. To determine whether the mucinous adenocarcinoma itself was an independent prognostic factor in the curative resected patients, a multivariate analysis was performed. RESULTS: The mucinous adenocarcinoma patients were found to be younger (P = 0.0003), have more lymph node involvement (48.5 vs. 40.3 percent; P = 0.0564), more peritoneal dissemination (19.6 vs. 5.6 percent; P < 0.0001), greater frequency of advanced stage disease (P = 0.0006), a lower rate of curative resection (76.3 vs. 84.4 percent; P = 0.0450), and lower overall 5-year survival rates (41 vs. 62.4 percent; P = 0.0002) than nonmucinous adenocarcinoma patients. In the subjects who underwent curative resection, the 5-year survival rate for those with mucinous adenocarcinoma was significantly worse than for those with nonmucinous adenocarcinoma (54 vs. 73.3 percent; P = 0.0020). Multivariate analysis using the Cox proportional hazards model showed that the clinically significant predictive factors were stage at diagnosis, mucinous histology, tumor location, gender and age. The mucinous histologic type itself was an independent factor for poor prognosis for patients who underwent curative surgery. CONCLUSIONS: In patients with colorectal carcinomas who underwent surgery with curative intent and who had colorectal carcinomas of the mucinous histologic type, there was significant correlation with prognosis as measured by overall survival rate after adjustment had been made for major confounders.     

Mixed (composite) glandular-endocrine cell carcinoma of the gallbladder

Background

A mixed pattern of glandular and neuroendocrine elements is rare in tumours at any site within the gastrointestinal tract but particularly so in the gallbladder.

Case outline

A 72-year-old woman presented with abdominal pain and jaundice and was found to have a large mass in the fundus of the gallbladder.The mass was radically excised to include a wedge of liver and the hepatoduodenal lymph nodes. Histopathological examination of the resected gallbladder showed an invasive tumour composed of both adenocarcinoma and endocrine cell carcinoma, with apparent transitions between them. The patient received no further treatment and died two months later.

Discussion

There are 14 previous case reports of mixed adeno/endocrine carcinoma of the gallbladder. Histochemical similarities between the two neoplastic components of the present tumour would support their origin from a common precursor cell, but the alternative hypothesis of coincidental neoplastic change in two different cell types cannot be excluded.     

Interleukin 12B rs3212227 T > G polymorphism was associated with an increased risk of gastric cardiac adenocarcinoma in a Chinese population

Gastric cardiac adenocarcinoma (GCA) is one of common malignant tumors in the world. Multiple genes that play critical roles in inflammatory pathways probably are associated with GCA risk. We conducted a hospital‐based case–control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): interleukin 9 (IL9) rs31563 C > T, IL9 rs31564 G > T, IL10 rs1800872 T > G, IL12A rs2243115 T > G, IL12B rs3212227 T > G, and IL13 rs1800925 C > T on the development of GCA. Two hundred and forty‐three GCA cases and 476 controls were recruited. Their genotypes were determined using a custom‐by‐design 48‐Plex SNPscan kit. IL12B rs3212227 T > G polymorphism was associated with the increased risk of GCA. However, there was no significant association between the other five SNPs and GCA risk. Stratified analyses indicated that the risk of GCA associated with the IL12B rs3212227 T > G polymorphism was evident among female patients and patients who never smoked or consumed alcoholic drinks. These findings indicated that functional polymorphism IL12B rs3212227 T > G might correlate with GCA risk. However, our results were obtained with a limited sample size; the power of our analysis was low. Larger studies are required to confirm the current findings.     

A cross sectional study of p504s,CD133, and Twist expression in the esophageal metaplasia dysplasia adenocarcinoma sequence

The incidence of esophageal adenocarcinoma has increased dramatically over recent years and Barrett's esophagus is considered the most established risk factor for its development. Endoscopic surveillance of Barrett's esophagus is therefore recommended but hinges on histological interpretation of randomly taken biopsies which is poorly reproducible. The use of biomarkers presents an opportunity to improve our ability to risk‐stratify these patients.We examined three biomarkers namely p504s, CD133, and Twist in the setting of Barrett's esophagus, low‐grade dysplasia, and esophageal adenocarcinoma to evaluate differential expression between benign, dysplastic, and malignant Barrett's tissue in an exploratory cross‐sectional study. Twenty‐five cases each of Barrett's esophagus, low‐grade dysplasia, and esophageal adenocarcinoma were included along‐with 25 cases of esophagectomy resections for Barrett's adenocarcinoma. The biomarkers were immunostained on automated Ventana^® immunostainer. The biopsies were assessed for biomarker expression by two independent observers. Granular cytoplasmic staining of p504s was observed in dysplastic Barrett's biopsies and esophageal adenocarcinoma but not in Barrett's esophagus. Apical and membranous CD133 expression was also observed in dysplastic Barrett's and esophageal adenocarcinoma. Nuclear Twist expression was seen predominantly in stromal cells. There was increased p504s expression in dysplastic Barrett's esophagus and esophageal adenocarcinoma compared with controls. CD133 expression was detected for the first time in esophageal adenocarcinoma and dysplastic Barrett's esophagus. Twist expression was not convincing enough to be labeled as Barrett's biomarker. p504s and CD133 have the potential to differentiate benign from malignant Barrett's tissue in this exploratory study. Their validity should be established in prospective longitudinal studies.