The effect of adenovirus expressing wild-type p53 on 5-fluorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.

Pain sensation in pancreatic diseases is not uniform: The different facets of pancreatic pain

AIM: To systematically characterize specific pain patterns in the most frequent pancreatic diseases.

Complex pattern of colon cancer recurrence including a kidney metastasis: A case report

We report a case of a 77-year-old female with a local recurrence of cancer after right hemicolectomy which infiltrated the pancreatic head affording pancreatoduodenectomy, who developed 3 years later recurrent tumor masses localized in the mesentery of the jejunum and in the lower pole of the left kidney. Partial nephrectomy and a segment resection of the small bowel were performed. Histological examination of both specimens revealed a necrotic metastasis of the primary carcinoma of the colon. Although intraluminal implantation of colon cancer cells in the renal pelvic mucosa from ureteric metastasis has been described, metastasis of a colorectal cancer in the kidney parenchyma is extremely rare and can be treated in an organ preserving manner. A complex pattern of colon cancer recurrence with unusual and rare sites of metastasis is reported.

Quantitative analysis of RNA levels from single hepatocytes in vivo: combined use of real-time RT-PCR and laser microdissection

AIM: The manner in which a cell responds to and influences its environment is ultimately determined by the genes that are expressed. To better understand cellular functions, the isolation of single cells and subsequent quantification of the expressed genes is essential. METHODS: Normal liver tissue was obtained from operation, snap-frozen in liquid nitrogen and sectioned in crystat. Individual hepatocytes were microdissected. RNA was extracted, then reverse transcribed and amplified using real-time quantitative polymerase chain reaction (PCR). RESULTS: Single hepatocytes were dissected by laser beam and catapulted to the microcentrifuge cap which was put above the slide. In this way, cells were collected, RNA was extracted, reverse transcribed to cDNA and used for analysis of RNA expression by real-time quantitative PCR. The amplification results showed that quantitation of the RNA inside the cell was compatible with the number of cells. CONCLUSION: The expression of RNA in single cells can be quantitated successfully by using laser microdissection and real-time PCR. These techniques provide an opportunity to monitor in vivo gene expression levels in single hepatocytes.

Pancreatic cancer–Surgery for recurrent disease

Recurrence of pancreatic ductal adenocarcinoma （PDAC） after a resection with curative intent is inevitable in the majority of cases. Approximately three-quarters of patients ultimately die from metastatic, local, or combined tumor recurrence . This may be due to the insufficient control over the disease after resecting the tumor and/or the existence of micrometastases at the time of the initial diagnosis. Even multimodality approaches including surgery, neoadjuvant radio-chemotherapy, adjuvant therapy, and novel targeted therapies offer only limited benefit and are not able to prevent recurrence in most of the patients.

Noninvasive indocyanine green plasma disappearance rate predicts early complications,graft failure or death after liver transplantation

BACKGROUND:Early detection of graft malfunction or postoperative complications is essential to save patients and organs after orthotopic liver transplantation (OLT).Predictive tests for graft dysfunction are needed to enable earlier implementation of organ-saving interventions following transplantation.This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications,graft dysfunction and patient survival following OLT.METHODS:Eighty-six patients undergoing OLT were included in this single-centre trial.ICG-PDR was assessed daily for the first 7 days following OLT.Endpoints were graft loss or death within 30 days and postoperative complications,graft loss,or death within 30 days.RESULTS:Postoperative complications of 31 patients included deaths (12 patients) or graft losses.ICG-PDR was significantly different in patients whose endpoints were graft loss or death beginning from day 3 and in those whose endpoints were graft loss,death,or postoperative complications beginning from day 4 after OLT.For day 7 measurements,receiver operating characteristic curve analysis revealed an ICG-PDR cut-off for predicting death or graft loss of 9.6% per min (a sensitivity of 75.0%,a specificity of 72.6%,positive predictive value 0.35 negative predictive value 0.94).For prediction of graft loss,death or postoperative complications,the ICG-PDR cut-off was 12.3%per min (a sensitivity of 68.9%,a specificity of 66.7%,positive predictive value 0.57,negative predictive value 0.77).CONCLUSIONS:ICG-PDR measurements on postoperative day 7 are predictive of early patient outcomes following OLT.The added value over that of routinely determined laboratory parameters is low.

Pancreatic cancer–Curative resection

Resecting pancreatic cancer is the only chance for cure for this devastating disease . It increases survival significantly and may also contribute to a better quality of life . While median survival for patients with unresectable pancreatic cancer is only about 4-8 months, resective surgery improves prognosis to a median survival of 14-20 months and 5-year survival rates of up to 25% . A few studies compared curative resection versus incomplete （R1 and R2） resections whereas only one randomized trial was conducted comparing surgery versus chemoradiation . All these studies confirmed the survival benefit seen in the retrospective data analyses：

Pancreatic cancer: Clinical and basic research

With its incidence (10–11 per 100, 000 people) almost equaling its prevalence, pancreatic cancer is one of the most aggressive human tumors. Understanding the exceptionally aggressive behavior has been the objective of clinical and basic research elucidating in detail the molecular changes that lead to the development and the progression of this disease. The molecular alterations

胰腺癌细胞起源和演进的新实验证据

目的大量研究证实导管样复合体就是胰腺癌的前体病变,因此,本研究旨在探索植入致癌剂后胰腺癌前体病变的产生和发展。方法采用手术方法将致癌剂DMBA植入SD大鼠胰腺,从第1天开始,在不同的时间点获取胰腺进行组织学研究,同时,分别以糜蛋白酶和细胞角蛋白作为胰腺腺泡细胞和导管细胞的标记物,通过免疫组化方法进行定位。结果在包埋致癌剂第2天就可以观察到正常胰腺小叶向导管复合体移型的现象,第4天出现典型的导管复合体,同时,胰岛也参与了这一过程。小叶中的非导管细胞迅速转分化为导管细胞的特征。在1个月时观察到导管腺癌的形成。与对照组相比,腺泡-导管转分化过程在DMBA包埋组持续存在。结论胰腺癌前体病变(导管复合体)除了由已经存在于小叶内的导管细胞组成外,主要通过腺泡细胞转分化形成,同时,胰岛细胞在某种程度上也参与了导管复合体的形成。因此,胰腺腺泡细胞、胰岛细胞和导管细胞共同参与了胰腺导管腺癌前体细胞的起源,转分化可以不需要细胞分裂迅速发生,而恶性转化需要较长的时间。

软骨寡聚基质蛋白在慢性胰腺炎损伤中退变腺泡细胞内的表达

目的 研究正常胰腺、慢性胰腺炎与胰腺癌组织中软骨寡聚基质蛋白 (cartilageoligomericmatrixprotein ,COMP)mRNA和蛋白表达水平的差异 ,揭示COMP在慢性胰腺炎样损伤中的意义。 方法 采用Northern印迹法、Western印迹法、原位杂交法与免疫组化方法对 14例慢性胰腺炎、14例胰腺癌及 15例正常胰腺组织进行分析。 结果 在慢性胰腺炎组织中和胰腺癌组织中类似慢性胰腺炎损伤的退变腺泡细胞胞浆内 ,存在高水平的COMPmRNA信号与免疫反应 ;而在胰腺癌细胞、正常胰腺组织的导管细胞与胰岛细胞的胞浆内 ,COMPmRNA信号与免疫反应微弱或缺如。结论 COMP在慢性胰腺炎及胰腺癌中类似慢性胰腺炎损伤的退变腺泡细胞内高表达 ,可能与慢性胰腺炎中腺泡细胞功能异常有关。