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Hiroyuki Kobayashi,
Ryuichiro Doi,
Ryo Hosotani,
Yoshiharu Miyamoto,
Takatomo Koshiba,
Koji Fujimoto,
Jun Ida,
Shoichiro Tsuji,
Sanae Nakajima,
Michiya Kawaguchi,
Kohei Shiota,
Masayuki Imamura
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ABSTRACT: Background. The growth of both cancer cells and fetal tissue is rapid; however, cancer cells de-differentiate and proliferate in a disorderly
manner, whereas fetal tissues differentiate and proliferate in an orderly manner. Thus, there may be both common and different
factors that are involved in the process of the uncontrolled cell growth of pancreatic cancers and the development of the
fetal pancreas. The common part of the mechanisms should be in the regulation of the cell cycle, resulting in rapid proliferation
via such mechanisms as growth stimulation and avoidance of apoptosis. Therefore, in the current study we investigated the
expression of apoptosis-related proteins in fetal pancreatic tissues.
Methods. Sixteen human embryonic and fetal pancreatic tissues obtained between 6 and 32 wk of gestation were used. We immunohistochemically
examined the protein expression of Bcl-2, Bcl-XL, Mcl-1, and Bax. Further, the expression of insulin, glucagon, and proliferting
cell nuclear antigen (PCNA), and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining were examined.
Results. In embryonic and fetal pancreatic tissues, Bcl-2 was not detected in any type of pancreatic cell (acinar, ductal, or islet).
Bcl-XL was expressed in all types of pancreatic cells throughout the gestation. Mcl-1 was expressed in all types of pancreatic
components, and strongly expressed in the margin of the islets. Bax, a pro-apoptotic protein, was expressed in all components.
PCNA was strongly expressed in the embryonic and fetal pancreas, especially in early stages of gestation; however, TUNEL staining
was negative in all samples. At least one antiapoptotic protein was expressed in all types of pancreatic cells.
Conclusion. The results of the current study indicate that active proliferation and avoidance of apoptosis take place in embryonic
and fetal pancreatic tissues, which may be controlled by particular combinations of apoptosis-related proteins. Among these
proteins, Bcl-XL and Mcl-1 may play an important role in the proliferation and differentiation of the embryonic and fetal
pancreas.
International Journal of Gastrointestinal Cancer 04/2012; 27(2):113-122.
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ABSTRACT: Local recurrence is one of the most frequent forms of pancreatic cancer recurrence, although local recurrence is rare for other periampullary cancers. Because the type of recurrence and outcome differ depending on the type of cancer, these factors should be considered when the type of reconstruction is chosen. Fifty-four pancreatoduodenectomies were performed in patients with ductal adenocarcinoma of the pancreas from 1994 to 2001. Billroth I reconstruction was performed in 27 consecutive patients before 1999, and thereafter Billroth II reconstruction was performed in another consecutive 27 patients. Postoperative nasogastric intubation and the duration before oral ingestion were longer for Billroth I patients than Billroth II patients. Seven complications occurred in Billroth I patients, whereas there were two complications in Billroth II patients. Disease-free survival and overall survival were not different between the two groups; however, bypass operations were required in nine patients of the Billroth I group and in one patient of the Billroth II group. Percutaneous transhepatic cholangio-drainage (PTCD) procedures were required in six patients of the Billroth I goup and in two patients of the Billroth II group. The Billroth II reconstruction may have some advantages over the Billroth I reconstruction in terms of postoperative oral ingestion and avoiding bypass surgery and PTCD at the time of recurrence.
World Journal of Surgery 05/2005; 29(4):500-4. · 2.36 Impact Factor
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ABSTRACT: Pancreas-preserving total duodenectomy (PPTD) was first described by Chung et al. in 1994. Since then, several surgeons have used PPTD to treat diseases that involve the duodenum diffusely but not the head of the pancreas, mostly familial adenomatous polyposis (FAP). The PPTD method has been changed in each report and seems to have improved over time. We performed PPTD on three patients with different diseases--one with intestinal hemorrhage due to small intestinal amyloidosis; another with numerous duodenal gastrinomas in a patient with multiple endocrine neoplasia type 1 (MEN-1) and Zollinger-Ellison syndrome (ZES); and the third with numerous duodenal polyposis and FAP--using a new method that is simpler and safer than those previously reported. When resecting the whole duodenum, we performed mucosectomy of the major papillar portion and saved the structure of the major papilla. After an approximately 8 mm long sphincteropapillotomy, the opened major papilla was anastomosed to an incisional opening of the small intestine. The orifice of the main pancreatic duct (MPD) was stented by a catheter, and the MPD was kept intact under direct vision during the operative procedures. The head of the pancreas was fixed with the small intestine by interrupted 4-0 silk sutures. Reconstruction of the alimentary tract was performed after either the Billroth I or the Billroth II method. This is the first report of PPTD in which the entire MPD was preserved to simplify the biliopancreatic-ductal reconstruction.
World Journal of Surgery 03/2005; 29(2):203-7. · 2.36 Impact Factor
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Shoichiro Tsuji,
Ryo Hosotani,
Shin Yonehara,
Toshihiko Masui,
Sidhartha S Tulachan,
Sanae Nakajima, Hiroyuki Kobayashi,
Masayuki Koizumi,
Eiji Toyoda,
Daisuke Ito,
Kazuhiro Kami,
Tomohiko Mori,
Koji Fujimoto,
Ryuichiro Doi,
Masayuki Imamura
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ABSTRACT: Many cancers are resistant to Fas-mediated apoptosis despite the expression of Fas. To investigate the mechanisms by which Fas signals are attenuated, we focused on decoy receptor 3 (DcR3). DcR3 is a soluble receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily and overexpresses in some forms of cancers. Exogenous DcR3 inhibits Fas-mediated apoptosis in Fas-sensitive Jurkat cells. In our study, we examined the expression and function of DcR3 in pancreatic cancers. TaqMan RT-PCR showed that DcR3 mRNA was highly expressed in pancreatic cancer cell lines (71%) and tissues (67%). Its expression significantly correlated with cancer invasion to veins. Western blotting showed that the DcR3 protein was produced and secreted in 4 of 6 cell lines. The protein expressions were compatible with the mRNA expression. Five of 7 pancreatic cancer cell lines became sensitive to agonistic anti-Fas antibody (CH-11) to various extents, without Fas upregulation, when exposed to CH-11 for 48 hr after pretreatment with IFNgamma. Four of 7 pancreatic cancer cell lines were inhibited from growing, compared to control cells, when cocultured with membrane-bounded Fas ligand (mFasL) transfected lymphomas for 48 hr after pretreatment with IFNgamma. DcR3 reduced this growth inhibition when added exogenously. Regression analysis showed that the DcR3 expression significantly correlated with the sensitivity to mFasL, and not to CH-11. These results suggest that DcR3 is highly expressed in many pancreatic cancers and endogenous DcR3 blocks the growth inhibition signals mediated by mFasL. DcR3 can be a candidate target molecule for the therapeutic intervention.
International Journal of Cancer 09/2003; 106(1):17-25. · 5.44 Impact Factor
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The European journal of surgery. Supplement.: = Acta chirurgica. Supplement 08/2003;
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Toshihiko Masui,
Ryo Hosotani,
Ryuichiro Doi,
Yoshiharu Miyamoto,
Shoichiro Tsuji,
Sanae Nakajima, Hiroyuki Kobayashi,
Masayuki Koizumi,
Eiji Toyoda,
Sidhartha Sin Tulachan,
Masayuki Imamura
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ABSTRACT: Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic growth factors and its expression is correlated with MVD (microvascular density) in malignant tumors, including pancreatic adenocarcinoma. On the other hand, serum interleukin-6 (IL-6) is elevated in many patients with pancreatic cancer in accordance with their disease progression. In this study, we examined whether IL-6 and its receptors have any involvement in the induction of VEGF in pancreatic cancer.
Two human pancreatic cancer cell lines were examined for the induction of VEGF after treatment with IL-6. Thirty-two pancreatic cancer surgical specimens were stained immunohistochemically with VEGF, IL-6 and IL-6 receptor antibodies.
CFPAC-1 cells expressed IL-6 receptor whereas AsPC-1 cells rarely expressed it. IL-6 treatment induced VEGF expression significantly and dose-dependently in CFPAC-1 cells, while it did not change in AsPC-1 cells. The intensity of VEGF expression in CFPAC-1 also increased time-dependently with IL-6 treatment. In 32 surgical pancreatic cancer tissues, 19 (59%) stained positive for VEGF and 26 (87%) positive for IL-6 receptor beta subunit. The correlation between IL-6 receptors and VEGF was significant (p = 0.0002 and p = 0.0019) while less correlation was seen between IL-6 and VEGF (p = 0.1937).
Our results suggest that IL-6 is likely to take part in VEGF expression in both paracrine and autocrine fashion in pancreatic cancer. Induction of VEGF seems to be regulated by the extent of the IL-6 receptor expression on cancer cells.
Anticancer research 22(6C):4093-100. · 1.73 Impact Factor
