摘要:

IntroductionIndocyanine green (ICG) is a clinically-approved, water-soluble dye that generates reactive singlet oxygen when activated by infrared light. Infrared light offers the advantage of deeper tissue penetration making ICG photodynamic therapy (PDT) ideal for treatment of intra-abdominal cancers such as pancreatic adenocarcinoma.AimsTo determine the cytotoxicity of ICG PDT in human pancreatic cancer.MethodologyMIA PaCa-2, PANC-1, and BxPC-3 pancreatic cancer cells were incubated for 1 hour with 0 to 50 &mgr;g/mL ICG, serially washed to remove unbound dye, and then briefly exposed to infrared light from a diode laser at 0.45 W. MTT cell viability assays were performed at 72 hours post-treatment.ResultsToxicity to ICG or infrared laser alone was not observed in any of the cell lines. Cell viability assays showed an ICG dose-dependent ablation when combined with laser exposure (+L). In all 3 cancer cell lines, significant growth inhibition was seen at 10 &mgr;g/mL ICG + L with nearly total ablation at 20 &mgr;g/mL ICG + L (P< 0.01).ConclusionICG PDT induces consistent and dramatic pancreatic cancer cell death. Since neither ICG nor laser alone caused toxicity, combination therapy may offer effective control of tumor growth with minimal side effects in patients with unresectable primary or metastatic pancreatic cancer.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionSevere acute pancreatitis (SAP) remains a serious disease state difficult to manage. Laparoscopic surgery represents a relatively new solution to this problem. This study was aimed to investigate the feasibility of laparoscopic treatment of SAP and the selection of laparoscopic procedures in various stages of SAP according to different pathologic alterations.MethodsThirteen patients, 9 men and 4 women with an average age of 46 years old, were diagnosed with SAP. Laparoscopic necrosectomy followed by external drainage were performed on 7 patients with massive fluid collections and/or infected necrosis in acute reaction phase of SAP. For 2 cases in subacute phase characterized by fresh-formed adhesions and encapsulation, laparoscopic intracavitary debridement experienced difficulty. For the other 4 patients in late phase with well-defined pancreatic or peripancreatic pseudocyst/abscess, ultrasound-guided, directly visualized laparoscopic intracavitary debridement, and external drainage were carried out with ease and efficiency.ResultsLaparoscopic procedures were accomplished successfully on 12 patients (92.3%), except for 1 conversion (7.7%) to open laparotomy owing to poor exposure and hard maneuvers in subacute phase. There was no mortality in this group. Patients were witnessed to have accelerated recovery following laparoscopic surgery.ConclusionLaparoscopic technique offers new hope for the treatment of SAP. It is recommended as a feasible, effective, and less traumatic therapeutic means on condition that the strategy of individualization is followed.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesProspective organ donors are exposed to various stress types. The effect of endotoxin pretreatment (ETX) on pancreatic ischemia/reperfusion injury (IRI) is unclear. We investigated, using a rat model of pancreatic IRI of an in situ isolated pancreatic tail segment, the effect of ETX on postischemic microcirculation and organ damage.MethodsTwenty-four hours before pancreatic dissection, either intraperitoneal application of ETX (1 mg/kg in 0.9% NaCl) or saline only (control) was performed. Two-hour normothermic ischemia of the pancreatic tail was induced by clamping the splenic vessels and was followed by a reperfusion period of 2 hours. Microcirculatory parameters were measured by intravital epifluorescence microscopy [functional capillary density (FCD), adherent leukocytes (ALs), and histology]. The presented data represent the mean ± SEM/SD as appropriate.ResultsETX pretreatment caused a significantly greater decrease in FCD (497 ± 6 cm/cm2baseline versus 326 ± 15 cm/cm22 hours of reperfusion) compared with controls (498 ± 8 versus 258 ± 15 cm/cm2) 2 hours after reperfusion (P< 0.01). Two hours after reperfusion, ALs were significantly decreased in ETX animals compared with controls (ETX: 141 ± 37 versus 273 ± 36 cells/mm2,P< 0.05). Histologic damage was less in ETX (6.4 score points ± 0.32 versus 8.8 ± 0.33 control,P< 0.05).ConclusionETX preconditioning decreases microcirculatory deterioration caused by IRI by means of less loss of nutritive tissue perfusion, decrease in ALs, and less histologic damage. This indicates a protective effect of ETX preconditioning in pancreatic IRI.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionK-rasmutations are present in most ductal adenocarcinomas (DACs) of the pancreas and may also be found in ductal precursor lesions and even in normal ductal epithelium. The question is addressed whether mutated K-rasinterferes with the regulation of apoptosis or proliferation.MethodologyIn 50 Whipple resection specimens, tissue adjacent to DACs was histologically screened for ductal lesions that were classified as pancreatic intraepithelial neoplasia (PanIN) according to WHO criteria. PanIN lesions were microdissected and analyzed for K-rasmutations by means of a nested PCR. Apoptosis was identified by the TUNEL method. Proliferation and the expression of p53 and Bcl-2 were immunohistochemically determined.ResultsOn average, 30% of PanIN-1A and B lesions showed mutated K-ras.In PanIN-2 and PanIN-3 lesions, the rate of mutated K-rasincreased to 45% and 56%, respectively. Apoptosis was present only in 2 of 26 PanIN-3 lesions. There was a gradual increase in proliferative activity from PanIN-1 to PanIN-3. p53 expression was found in 11% of PanIN-2 and 44% of PanIN-3 lesions. Bcl-2 expression was lacking in PanIN lesions of all grades. In invasive DACs, the apoptotic rate correlated with the degree of tumor differentiation and proliferation, with grade 3 carcinomas showing the highest apoptotic rate.ConclusionIn view of the discrepancy between the considerable rate of K-rasmutations in PanIN-1 and PanIN-2 lesions and the lack of apoptosis and Bcl-2 expression, coupled with very low p53 immunoreactivity, it is unlikely that mutated K-rasaffects the apoptotic activity in low grade PanINs. Instead, K-rasmutations may have an effect on proliferation in PanIN-1 and PanIN-2.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The 3rd Annual Rachmiel Levine Symposium entitled “Advances in Islet Cell Biology—From Stem Cell Differentiation to Clinical Transplantation” was organized by the Department of Diabetes, Endocrinology and Metabolism at the City of Hope National Medical Center, with the support of the Southern California Islet Cell Resources Center, American Diabetes Association–David Shapiro Research Fund, Ross Foundation, the National Center for Research Resources (NCRR), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health. The symposium was held at the Hilton Anaheim Hotel in Anaheim, CA, in October 2002, and was attended by nearly 400 participants from 23 countries and 30 U.S. states. The symposium consisted of 11 sessions focusing on 3 areas: (1) pancreas and islet cell differentiation and islet generation, (2) &bgr; cell biology and insulin synthesis and/or secretion, and (3) pancreatic islet transplantation in patients with type I diabetes. Thirty-nine world experts lectured on the most current information in each field. Fifty-three abstracts were selected for presentation and discussed at the poster session. The first author of each of the top 10 posters received a Young Investigator Travel Award provided by the National Center for Research Resources and the Southern California Islet Cell Resources Center. The symposium also offered special Meet the Professor sessions, which gave the attendees an opportunity to closely interact with the participating speakers of the day.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionNitric oxide (NO) synthases (NOSs) are expressed in insulin secreting &bgr;-cells. However, physiologic role of NO in insulin release is still controversial. We previously reported that argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL), together with NOS, constitute the citrulline-argininosuccinate-arginine (Cit-AS-Arg) cycle in &bgr;-cells and that this cycle metabolizes citrulline to produce NO and increase cytosolic Ca2+concentration ([Ca2+]i) in islet &bgr;-cells.AimsThis study examined whether this cycle could be linked to insulin release.MethodologyIslets of Langerhans were isolated from Wistar rats by collagenase digestion and further dispersed into single &bgr;-cells. [Ca2+]iin &bgr;-cells was measured by dual-wavelength fura-2 microfluorometry combined with digital imaging. NO production was assayed by DAF-2 microfluorometry. Insulin release was determined by ELISA.ResultsCitrulline at a physiologic concentration (0.1 mM) increased insulin release from rat islets and increased [Ca2+]iin rat &bgr;-cells in the presence of 8.3 mmol/l glucose, and they were inhibited by a NOS inhibitor, NG-monomethyl-L-arginine (NMMA). Citrulline induced NO production in rat &bgr;-cells. A NO-donor increased insulin release and [Ca2+]iin rat islet &bgr;-cells.ConclusionThe metabolism of physiologic concentrations of citrulline by the Cit-AS-Arg cycle leads to NO production and resultant potentiation of glucose-induced insulin release, in which a Ca2+-mediated pathway could be involved.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

PurposeWe conducted a phase 1 trial to determine the maximum tolerated dose (MTD) of weekly docetaxel delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreas.Patients and MethodsThirteen patients with histologically proven locally non-resectable advanced adenocarcinoma of the pancreas were enrolled in this study. Patients received 4 weekly doses of docetaxel by 1-hour intravenous (IV) infusion with 40 Gy of external beam radiation therapy during 4 weeks. Patients who were stabilized or in response, received 2 additional cycles of docetaxel with a 10 Gy boost of radiotherapy. Doses were escalated at 10 mg/m2increments in successive cohorts of 3 new patients until MTD was observed.ResultsFour patients received docetaxel at 20 mg/m2/week, 3 at 25 mg/m2/week, 3 at 30 mg/m2/week, and 3 at 35 mg/m2/week. All patients, except 2, were given the treatment in its integrity. The most common toxicities were nausea, vomiting, asthenia, and abdominal pains. Except for 1 patient, all toxicity was reversible and did not exceed grade 3. Hematologic toxicity was mild and has not required treatment interruption. 28% of the patients had to be rehospitalized. A total of 73 cycles was administered with a mean of 4 cycles per patient (2–6).ConclusionEven the MTD was not reached, dose escalation was stopped at 35 mg/m2/week. This dose is comparable to the ones previously published using docetaxel in combination with radiotherapy in other tumors. Three patients achieved stable disease and 1 patient an objective response. This combination of weekly docetaxel and radiotherapy shows a feasible and well-tolerated regimen, with, nonetheless, a significant rate of rehospitalization, for patients with locally advanced pancreatic cancer.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

To date, no therapy has been found to which pancreatic cancer responds with the exception of surgical resection in early stages. Recently, gemcitabine has become the standard of care for chemotherapy in those patients with advanced disease. Most pancreatic tumors however, develop resistance to gemcitabine. The aim of this study is to clarify the mechanism of resistance to gemcitabine in human pancreatic cells. Using a cell selection method, a human pancreatic cancer cell line resistant to gemcitabine was established. Cellular proliferation and viability were determined by MTT assay. The cell line with acquired resistance was also found to have cross resistance to fluorouracil. Brefeldin-A (BFA) has been used as a tool for studies of intracellular protein traffic, rather than as an anticancer drug. BFA displays the same effects on wild type cells and those with acquired resistance. Gemcitabine combined with BFA in low doses is significantly more effective than gemcitabine alone against MIA PaCa-2 cell line. Our data suggest that the gemcitabine-resistant and 5-FU-resistant pathways may partially overlap each other. In short, BFA may be used as a modulator of gemcitabine.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionPancreatic cancer invasion via neural routes (perineural invasion) has been studied extensively, but detailed research on the morphology of innervation of the pancreas related to perineural invasion is scarce.AimsTo clarify the morphology of neural distribution in the human pancreas.MethodologyThe pancreas and surrounding structures were dissected in 9 cadavers, the specimens were immersed in a 0.001% solution of alizarin red S in ethanol to stain the peripheral nerves, and the detailed distribution was studied to confirm the extrapancreatic and intrapancreatic plexus using a binocular microscope.ResultsThe innervation of the uncinate process of the pancreas originated from the superior mesenteric plexus (SMPlx) along the inferior pancreaticoduodenal artery (IPDA), but did not form a wide offshoot of nerve bundles as reported. Concerning the innervation of the body and tail, it was found that the nerve fibers entered the pancreas immediately after leaving the celiac plexus, and were distributed around the pancreatic duct in a twig-like manner.ConclusionIt was emphasized that the nerve originating from SMPlx to the uncinate process chiefly ran along the IPDA and it was necessary to focus one's attention not only on the extrapancreatic perineural invasion but also on the intrapancreatic perineural invasion in carcinoma of the body and tail of the pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID