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Masaki Kitajima

Publications and source records attributed to Masaki Kitajima.

At least 55 records · Page 3Linked to original sources
PubMed2006

Diagnostic validity of radio-guided sentinel node mapping for gastric cancer: a review of current status and future direction.

Diagnostic validity of sentinel node (SN) mapping has been recently introduced into the field of various solid tumors, including gastrointestinal (GI) cancer. In gastric cancer, acceptable detection rates of SNs, as well as sensitivity in detecting micrometastasis based on SN status, was reported using the dye-guided method, as well as the radio-guided method. Gastric cancer is currently one of the suitable targets of SN navigation surgery among visceral tumors. Despite the multi-directional and complicated lymphatic flow from gastric mucosa, the anatomical situation of the stomach is relatively suitable for SN mapping in comparison with organs embedded in closed spaces, such as the esophagus and rectum. In particular, clinically T1N0 gastric cancer seems to be a good entity for which to try to modify the therapeutic approach. From the data reported in the literature, micro-metastases tend to be limited within the sentinel basins in cT1N0 gastric cancer. Sentinel basins are, therefore, good targets of selective lymphadenectomy for cT1N0 gastric cancer with the potential risk of micrometastasis. Furthermore, laparoscopic local resection is theoretically feasible for curative treatment of SN negative early gastric cancer. For laparoscopic application of SN mapping of gastric cancer, a radio-guided method is essential. Although recent single institutional studies support the validity of the SN concept, a multi-centric prospective validation study based on a standardized protocol is essential for further clinical application. Currently, two major well-designed clinical trials of SN mapping for gastric cancer open surgery have been initiated in Japan. Radio-guided SN mapping for gastric cancer has a great potential to provide a new paradigm shift for surgical management of an early gastric cancer.

Forecasting↗
PubMed2005

A genetic variant in the gene encoding the stress70 protein chaperone family member STCH is associated with gastric cancer in the Japanese population.

Association analysis, based on linkage disequilibrium between specific alleles in the candidate loci and nearby genetic markers, has been proposed to identify genes conferring susceptibility to multifactorial diseases. Using the affected sib-pair method, we previously mapped four candidate chromosomal regions, 1p32, 2q33-q35, 11p13-p14, and 21q21, for gastric cancer by linkage analysis. To identify genes involved in the disease, we performed a gene-based association analysis of 66 genes, located on 21p11-21q22, using 126 single nucleotide polymorphisms (SNPs) as genetic markers in 373 patients with 250 controls. We found a significant association of five SNPs in the stress70 protein chaperon family member STCH gene with gastric cancer, especially with the non-cardia localization subgroup (P=0.0005-0.02, odds ratio=1.44-1.72). Comparisons of haplotype frequency showed significant association between TTGGC haplotype and gastric cancer (P=0.0001, odds ratio=1.59). These results suggest that, in the Japanese population, STCH might be a new candidate for conferring susceptibility to this disease.

Alleles↗
PubMed2005

Soft x-ray spectroscopy of Ba24Ge100: electronic phase transition and Ba-atom rattling.

The electronic states of Ba24Ge100 are studied by soft x-ray photoelectron spectroscopy (XPS) at a high-energy photon factory. A large reduction in the density of states (DOS) at the Fermi level is clearly shown before and after the electronic phase transition at 200 K. The changes in the spectrum widths and the fine structures of the core-level Ba 4d spectra give a very reasonable indication of the Ba-atom rattlings in the clathrate polyhedra. On-resonance experiments using the excitation from Ba 3d to 4f levels display that the wave functions of Ba 5d and 6s orbitals give only a small contribution to make a Fermi surface through the hybridization with the Ge20 cluster orbitals. Importantly, reliable values of the DOS at the Fermi level NEF are successfully deduced, using two data sets of DOS obtained from high-resolution XPS and the total magnetic susceptibilities by a superconducting quantum interference device, to be 0.149 and 0.0427 states eV(-1) (Ge atom)(-1) for a high-temperature and for a low-temperature phase.

Journal Article↗
PubMed2005

Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis.

AIM: To examine the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) expression on canals of Hering (CoH) and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis (PBC). METHODS: Ten wedged liver biopsies of PBC (five cases each of stages 2 and 3) were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse mAbs. In situ hybridization was done to examine the messenger RNA expression of ICAM-1 in formalin-fixed, paraffin-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification (CSA) technique. Immunogold-silver staining for electron microscopy was performed using anti-ICAM and anti-LFA-1 mouse mAbs. The immunogold particles on epithelial cells of bile ductules and cholangiocytes of CoH cells were counted and analyzed semi-quantitatively. Western blotting was performed to confirm ICAM-1 protein expression. RESULTS: In liver tissues of PBC patients, immunohistochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules, and also on mature cholangiocytes but not on hepatocytes in CoH. LFA-1-positive lymphocytes were closely associated with epithelial cells in bile ductules. ICAM-1 expression at protein level was confirmed by Western blot. In situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the bile ductules. By immunoelectron microscopy, ICAM-1 was demonstrated on the basal surface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged CoH. Cells with intermediate morphology resembling progenitor cells in CoH were not labeled with ICAM-1 and LFA-1. CONCLUSION: De novo expression of ICAM-1 both on mature cholangiocytes in CoH and epithelial cells in bile ductules in PBC implies that lymphocyte-induced destruction through adhesion by ICAM-1 and binding of LFA-1-expressing activated lymphocytes takes place not only in bile ductules but also in the CoH.

Aged↗
PubMed2005

High expressions of caveolins on the proliferating bile ductules in primary biliary cirrhosis.

AIM: An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes including cholesterol transport. This study aims to examine the role of caveolin in PBC. METHODS: Immunohistochemical and Western blotting studies were performed on human liver specimens obtained from patients with PBC and normal liver samples. The expression of caveolin (CAV)-1 and -2 was determined using specific antibodies. RESULTS: In normal liver, scanty immunostaining for CAV-1 and -2 was observed in bile ductules. In PBC liver samples, the expression levels of CAV-1 and -2 were increased on proliferating bile ductules especially in stage 3 cases, but was sparse on interlobular bile duct in stage 1 specimens. Especially, the regenerating bile ductules at the interface of portal tracts and necrotic areas were immunostained intensely for CAV-1 and -2. These phenomena were confirmed by Western blot. CONCLUSION: The present results demonstrate increased expression of caveolins in proliferating bile ductules in PBC, which may be related to the homeostasis of cholesterol transport in regenerating bile ductules in PBC liver.

Adult↗
PubMed2005

Anti-angiogenic effect of an insertional fusion protein of human basic fibroblast growth factor and ribonuclease-1.

Human pancreatic ribonuclease-1 (RNase1) does not exhibit its cytotoxicity unless it is artificially internalized into the cytosol. Furthermore, once it encounters the cytosolic RNase inhibitor (RI), the activity of RNase1 is seriously reduced. To achieve the cellular targeting of RNase1 and the blocking of RI binding simultaneously, the basic fibroblast growth factor (bFGF) sequence was inserted into RNase1 at the RI binding site using a gene fusion technique. The effect of this fusion protein, CL-RFN89, on the angiogenesis, which was accelerated by FGF-FGF receptor interaction, was investigated. It was shown by using fluorescein-labeled CL-RFN89, that the binding to human umbilical vein endothelial cells (HUVECs) was dependent on the existence of the FGF receptors. In addition, CL-RFN89 inhibited the cellular growth of HUVECs in vitro and also inhibited the tube formation, using a three-dimensional tube formation assay. Furthermore, this fusion protein was shown to prevent in vivo tumor cell-induced angiogenesis, using the mouse dorsal air sac assay. These results demonstrated that CL-RFN89 inhibits angiogenesis in vitro and in vivo and that it can be expected to be a potent antiangiogenic agent.

Angiogenesis Inhibitors↗
PubMed2005

Recent advances in sentinel node navigation for gastric cancer: a paradigm shift of surgical management.

The sentinel node (SN) is defined as the first draining node from the primary lesion and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. In the past 5 years, the validity of SN concept for gastric cancer has been demonstrated by a number of single institutional studies. Using a dual tracer method as the optimal procedure, the radio-guided method allows us to confirm the complete harvest of SNs by gamma probing, while the dye procedure enables us to perform real time observation of the lymphatic vessels. From previous reports, clinically staged T1N0 gastric cancer seems to be a good entity on which to try to change the therapeutic approach based on SN biopsy. At present, two large scale prospective multicenter trials are on-going in Japan. To overcome some remaining issues, such as limited sensitivity of intra-operative diagnosis of metastasis, and technical difficulty in laparoscopic SN detection, further technical and instrumental developments will be required. During this transitional phase, focused lymph node dissection targeted to sentinel lymphatic basins and modified resection of the stomach is an acceptable approach. Although there are several remaining issues, SN navigation should provide a paradigm shift for the surgical management of early gastric cancer in near future.

Clinical Trials as Topic↗
PubMed2005

Effects of immunosuppressants on induction of regulatory cells after intratracheal delivery of alloantigen.

BACKGROUND: We previously reported that intratracheal delivery (ITD) of alloantigen generated regulatory cells in mice. Here, we examined the effect of various doses of conventional immunosuppressants (FK506, cyclosporine A, azathioprine, mycophenolate mofetil, and rapamycin) on inducing regulatory cells in our model. METHODS: CBA mice (primary recipients) were given C57BL/6 splenocytes by ITD and either no additional treatment or various doses of an immunosuppressant. Seven days later, splenocytes from these mice were adoptively transferred into naive secondary CBA recipients that underwent C57BL/6 cardiac grafting the same day. RESULTS: Adoptive transfer from primary recipients given ITD of splenocytes alone induced prolonged allograft survival in secondary recipients (median survival time [MST], 50 days), suggesting that regulatory cells were generated. When ITD of alloantigen was combined with daily administration of 0.1 mg/kg FK506 or 0.2 mg/kg rapamycin, graft survival was similarly prolonged (MST 55 and 50 days, respectively). When combined with 20 or 40 mg/kg MMF or 0.4 mg/kg rapamycin, the majority of recipients demonstrated indefinite survival (MST, >100 days in all groups). When ITD of alloantigen was combined with 0.3, 0.5, or 1.0 mg/kg FK506; 5, 10, or 25 mg/kg cyclosporine A; or 1.0 or 2.0 mg/kg azathioprine, allografts were rejected acutely (MST 7-13 days). CONCLUSION: Generation of regulatory cells by ITD of alloantigen was facilitated by mycophenolate mofetil and high doses of rapamycin but abrogated by cyclosporine A, azathioprine, and high doses of FK506. Low doses of rapamycin and of FK506 did not interfere with generation of regulatory cells.

Adoptive Transfer↗
PubMed2005

Prognostic significance of tissue factor in pancreatic ductal adenocarcinoma.

Tissue factor (TF) is a transmembrane glycoprotein that plays roles in the blood coagulation and intracellular signaling pathways, and has also been suggested to modulate the biological behavior of cancer cells. In order to examine the clinicopathologic significance of TF expression in pancreatic ductal adenocarcinoma, TF expression was determined by immunohistochemistry using a newly raised anti-TF monoclonal antibody in 113 patients who had undergone surgical resection of pancreatic ductal adenocarcinoma. According to the incidence of tumor cell immunopositivity, patients were divided into "negative TF" (0%), "weak TF" (<25%), or "high TF" (25% or more) groups, which accounted for 11.6% (n = 13), 44.2% (n = 50), and 44.2% (n = 50) of the total, respectively. Increased TF expression was correlated with the extent of the primary tumor (P = 0.0043), lymph node metastasis (P = 0.0043), lymphatic distant metastasis (P = 0.0039), advanced tumor-node-metastasis stage (P = 0.0002), and high tumor grade (P = 0.0164). Multivariate analysis using the Cox proportional hazards model showed that high TF expression was an independent negative predictor for survival (hazard ratio, 2.014; P = 0.0076). Moreover, patients with TF-negative tumors had a significantly better prognosis even if lymph node metastasis was present (P < 0.0001). We also showed that TF knockdown by RNA interference suppressed the invasiveness of a pancreatic adenocarcinoma cell line in vitro. These results indicate that TF expression may contribute to the aggressiveness of pancreatic ductal adenocarcinoma by stimulating tumor invasiveness, and that evaluation of the primary tumor for TF expression may identify patients with a poor prognosis.

Aged↗
PubMed2005

Enhanced ghrelin secretion in rats with cysteamine-induced duodenal ulcers.

Ghrelin, produced and secreted by the A-like cells of the stomach, stimulates growth hormone secretion, gastric motility, and food intake. Cysteamine inhibits the release of somatostatin and induces the formation of duodenal ulcers in rats. The present study was conducted to investigate the dynamics of ghrelin secretion in rats treated with cysteamine. Male Wistar rats (7 wk old) were administered three doses of cysteamine (400 mg/kg) orally; at 50 h after the first dose, duodenal ulcers were induced, and the plasma level of somatostatin and gastric density of somatostatin-immunoreactive cells were significantly reduced. The plasma total and active ghrelin levels were significantly higher in the cysteamine-treated rats than in the control rats, whereas the gastric ghrelin levels, number of gastric ghrelin-immunoreactive cells, and preproghrelin mRNA expression levels were significantly lower. Even at the time points of 2 and 10 h after the first dose of cysteamine, at which time no significant ulcer formation or antral neutrophil accumulation was yet noted, a significant increase in the plasma ghrelin level and decrease in the gastric ghrelin level were observed. Furthermore, although lansoprazole treatment attenuated the duodenal ulceration induced by cysteamine, the increase in the plasma level of ghrelin could still be demonstrated. Because an inverse correlation was found between the plasma ghrelin and somatostatin levels, the inhibition of somatostatin secretion may be associated with the increased ghrelin secretion. In conclusion, an increase in the plasma ghrelin level precedes the formation of duodenal ulcers in rats treated with cysteamine.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Interleukin-10 but not transforming growth factor-beta is essential for generation and suppressor function of regulatory cells induced by intratracheal delivery of alloantigen.

BACKGROUND: We previously reported that intratracheal delivery of alloantigen-induced regulatory cells in mouse heart-transplantation model. Here, we investigated roles of interleukin (IL)-10 and transforming growth factor (TGF)-beta in induction and effector phases of the regulatory cells. METHODS: CBA mice were pretreated with intratracheal delivery of C57BL/10 splenocytes and administration of neutralizing anti-IL-10 or anti-TGF-beta monoclonal antibody (mAb). Seven days after the pretreatment, naive CBA mice (secondary recipients) were given adoptive transfer of splenocytes from the pretreated mice and underwent heart grafting from C57BL/10 mice. To determine roles of these cytokines in the effector phase of the regulatory cells, anti-IL-10 or anti-TGF-beta mAb was administered weekly into the secondary recipients after the adoptive transfer. RESULTS: Adoptive transfer of splenocytes from CBA mice that had been pretreated with intratracheal delivery of C57BL/10 splenocytes significantly prolonged the survival of C57BL/10 allograft (median survival time [MST] 68 days) as compared with adoptive transfer from untreated CBA mice (MST 12 days). In the induction phase, anti-IL-10 mAb abrogated development of the regulatory cells that afforded prolonged allograft survival in the secondary recipients (MST 20 days), whereas anti-TGF-beta mAb did not abrogate it (MST 88 days). In the effector phase, anti-IL-10 mAb abrogated prolonged allograft survival afforded by adoptive transfer of the regulatory cells in the secondary recipients (MST 27 days), whereas anti-TGF-beta mAb did not abrogate suppressor function of the regulatory cells (MST 53 days). CONCLUSION: IL-10 but not TGF-beta was required for generation and suppressor function of the regulatory cells induced by intratracheal delivery of alloantigen.

Animals↗
PubMed2005

Imatinib blocks spontaneous mechanical activities in the adult mouse small intestine: possible inhibition of c-Kit signaling.

Interstitial cells of Cajal (ICCs) are postulated to serve as pacemakers that physiologically generate electrical slow waves in the gastrointestinal tract. Imatinib is a novel and potent inhibitor of c-Kit tyrosine kinase and a new therapeutic agent for gastrointestinal stromal tumors (GIST) which presumably arise from ICCs. The effects of imatinib on the basal rhythmic mechanical activities of small intestinal circular muscles were investigated in ring preparations of the gut. The small intestinal rings of BALB/c mice exhibited spontaneous contractile activity at a rate of 40.8 +/- 4.9 contractions/min. Imatinib (1- 81 micromol/l) dose-dependently abolished spontaneous contractile activity in the 9- to 27-micromol/l concentration range. Contraction was restored by washing imatinib out with a fresh buffer. High K(+)-induced contraction was not affected by imatinib, suggesting that the drug does not have nonspecific inhibitory actions on the smooth muscles. The small intestinal rings of adult W/W(v)mice, which lack a functional c-Kit activity,exhibited only small and irregular spontaneous contractions. These results demonstrate that imatinib affects bowel contractions, and suggest that the c-Kit signaling of ICCs plays an essential role in the spontaneous movements in circular muscles of the mouse small intestine.

Animals↗
PubMed2005

Credentialing of nuclear medicine physicians, surgeons, and pathologists as a multidisciplinary team for selective sentinel lymphadenectomy.

There are several possible applications of the sentinel lymph node (SLN) concept with different technological aspects such as individualized surgical management of solid tumors, multidisciplinary treatments, and novel therapeutic approaches. To achieve these clinical applications, multidisciplinary teamwork with surgeons, nuclear medicine physicians, and pathologists would be critically required. Interdisciplinary issues should be resolved in order to develop optimal standard procedures of SLN dissection for various solid tumors.

Credentialing↗
PubMed2005

Sentinel lymph node mapping in esophageal and gastric cancer.

In recent years, the sentinel lymph node (SLN) concept has been widely investigated in a variety of solid tumors including gastrointestinal (GI) cancer. This chapter reviews the rationale and refined technical aspects for SLN mapping in upper GI cancer for the intraoperative accurate diagnosis of nodal status to perform individualized minimally invasive surgical approaches. We have described the technical details of the procedure as we have performed it in over 350 consecutive patients with esophageal and gastric cancer and introduced pitfalls and issues remaining. The technical details and clinical applications of SLN mapping differfor patients with esophageal cancer and gastric cancer. Radio-guided method with lymphoscintigraphy using radioisotope-labeled colloid (RI) is essential for SLN mapping for esophageal cancer. Selective lymphadenectomy and SLN-targeted chemoradiotherapy would be feasible and beneficial for the patients with esophageal cancer. For gastric cancer, combined method with dye and RI is recommended for stable and accurate sampling of SLN in the laparoscopic setting. Laparoscopic local resection for superficial gastric cancer with negative SN status would be a reasonable and less-invasive novel procedure based on the SLN concept. We can utilize this procedure not only for an accurate staging but also as a great tool to change the patient care of upper GI cancer by individualized minimally invasive treatments.

Esophageal Neoplasms↗
PubMed2005

Oblique view of preoperative lymphoscintigraphy improves detection of sentinel lymph nodes in esophageal cancer.

Because sentinel lymph nodes (SLNs) of esophageal cancer can be widely located between the neck and the upper abdomen, lymphoscintigraphy plays an important role in their detection, but some modifications are required to clearly visualize their locations. Recently, we applied the stereoscopic imaging method by adding the 10-degree oblique view to the conventional lymphoscintigraphy for SLNs, so that we could better determine SLN locations on the basis of depth information. In this report, we describe a case in which the oblique view of the lymphoscintigram contributed to improving the visualization of a mediastinal SLN of esophageal cancer. Evaluation of the patient's chest CT image validated the notion that gamma rays from SLN are less absorbed by the surrounding soft tissues and the sternum in acquisition from the oblique view than from the true anterior view. The additional oblique view of the lymphoscintigram is useful for evaluation of the SLNs of esophageal cancer.

Aged↗