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Biomedical subjects

Yuji Nimura

Publications and source records attributed to Yuji Nimura.

At least 19 recordsLinked to original sources
PubMed2005

TNM classification for perihilar cholangiocarcinoma: comparison between 5th and 6th editions of the AJCC/UICC staging system.

BACKGROUND: A few investigators have evaluated the TNM classification for perihilar cholangiocarcinoma. The new sixth edition of the American Joint Committee on Cancer (AJCC)/Internal Union Against Cancer (UICC) staging system focuses on vascular invasion and regional lymph node metastasis. METHODS: For 166 patients with perihilar cholangiocarcinoma undergoing R0 resection, survival curves stratified according to TNM classifications were compared between fifth and sixth editions. RESULTS: The previous T3 now is divided into T3 and T4. Most new pT4 patients had invasion of the portal bifurcation; their survival was poorer than that for new pT3 patients. The 5-, 10-, and 15-year survival rates were worse in the previous stage III than in the previous stage IVA, although the difference fell short of significance. The previous stage IVA (T3 Any NM0) is divided into new stages: IIA (T3N0M0), IIB (T1-3N1M0), and III (T4 Any NM0). All patients in stage III had invasion of the portal bifurcation. Survival was similar between stages IA, IB, and IIA, while patients with T4N0M0 tumors survived longer than those with T4N1M0 tumors and similarly to those with stage IIB tumors. CONCLUSIONS: The sixth edition provided improved prediction of survival in patients with perihilar cholangiocarcinoma; for still better prediction, cancer invasion of the portal bifurcation and regional lymph node metastasis should be weighted equally.

Adult↗
PubMed2005

Impaired expression of hepatic multidrug resistance protein 2 is associated with posthepatectomy hyperbilirubinemia in patients with biliary cancer.

BACKGROUND AND AIMS: Hyperbilirubinemia is a critical complication following hepatectomy for biliary cancer. Hepatic multidrug resistance protein 2 (MRP2), a bilirubin transporter, is shown to be down-regulated by acute biliary obstruction in rats. However, little is known about the effect of chronic obstruction by malignancy on the MRP2 expression in patients or the association of MRP2 expression with posthepatectomy hyperbilirubinemia. MATERIALS AND METHODS: The MRP2 expression before hepatectomy was determined by immunostaining and Western blotting in patients with biliary cancer. To directly determine the effect of chronic bile duct obstruction on the MRP2 expression, the expression levels were compared between the cholestatic and noncholestatic lobes in each of seven patients. In another 39 patients, the correlation of the MRP2 expression of the anticipated remnant liver with the posthepatectomy severe hyperbilirubinemia, defined as a serum total bilirubin concentration>or=200 micromol/l, was evaluated. RESULTS: The MRP2 staining in the cholestatic lobes was weak and not restricted to the canalicular membrane, unlike the noncholestatic lobes. The expression levels in the cholestatic lobes were 45% of those in the noncholestatic lobes. Postoperative maximum bilirubin levels were significantly correlated with MRP2 expression of the anticipated remnant liver. The MRP2 expression had been already impaired before hepatectomy in all patients who eventually developed severe hyperbilirubinemia. CONCLUSIONS: Decreased MRP2 expression, caused by biliary obstruction due to cancer, is a possible risk factor for posthepatectomy severe hyperbilirubinemia.

Adult↗
PubMed2005

Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2.

We studied the effect of TNF-alpha stimulation on a cholangiocarcinoma cell line, CCKS1. CCKS1 expressed only one type TNF receptor, TNFR2. Treatment of CCKS1 with TNF-alpha substantially activated NFkappaB, MAPK and Akt signalings which in turn activated matrix metalloproteinase-9 (MMP-9) secretion and in vitro invasiveness of CCKS1. Pretreatment of cells with anti-TNFR2 neutralizing antibody inhibited the TNF-alpha-dependent signaling and MMP-9 secretion and subsequently blocked invasion in vitro. Moreover, an inhibitor for matrix metalloproteinase, Galardin, suppressed the invasion in a dose-dependent manner. Similarly, pharmacological inhibition of signaling clearly suppressed the TNF-alpha dependent MMP-9 secretion. These results strongly suggest that TNF-alpha-TNFR2 signaling plays an important role to convert the cholangiocarcinoma cells to be more aggressive one.

Cholangiocarcinoma↗
PubMed2005

Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy.

BACKGROUND AND AIMS: The clinical value of synbiotics in surgical patients remains unclear. The aim of this study was to investigate the effect of synbiotics on intestinal integrity and microflora, as well as on surgical outcome, in patients undergoing high-risk hepatectomy. METHODS: Fifty-four patients with biliary cancer were randomly allocated to two groups before hepatectomy. One group received postoperative enteral feeding that included synbiotics; the other received enteral feeding only. Lactulose/mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, and fecal microflora and organic acid concentrations were determined. Postoperative infectious complications were recorded. RESULTS: Of the 54 patients, 44 completed the trial (21 receiving synbiotics and 23 others as controls). Postoperative changes in L/M ratios and serum DAO activities were identical between the two groups. Numbers of beneficial bacteria increased in the synbiotics group after surgery but decreased in controls. Numbers of harmful microorganisms decreased in the synbiotics group but increased in controls. Total organic acid concentrations increased in the synbiotics group but decreased in controls. Incidence of infectious complications was 19% (4/21) in the synbiotics group and 52% (12/23) in controls (P<0.05). All study patients tolerated surgery (mortality 0%). CONCLUSIONS: Synbiotics, combined with early enteral nutrition, can reduce postoperative infections. This beneficial effect presumably involves correction of an intestinal microbial imbalance induced by surgical stress.

Aged↗
PubMed2005

Dutch surgery in Japan.

An isolation policy was adopted in feudal Japan from 1639 to 1853 owing to the fear of foreign influence. During those 200 years of isolation, all foreigners were withheld from the country with the exception of the Dutch, who were permitted to establish a trading post on a small island in the Bay of Nagasaki, called Decima. Western culture and science reached the Japanese exclusively through the Dutch on Decima. Health care on Decima was provided by Dutch barber-surgeons, who introduced Western surgical practice in Japan. Official interpreters were the only Japanese allowed on Decima. It was from among these interpreters that the first Japanese surgeons arose who, having mastered the Dutch language, translated several Dutch anatomic and surgical texts. Genpaku Sugita translated a Dutch anatomy textbook into Japanese, which was completed in 1774. This book, entitled Kaitai Shinsho [New Book on Anatomy], was the first Western scientific monograph to be translated entirely into Japanese. Several Dutch surgical schools were founded through which Dutch surgery, known in Japan as "surgery of the red-haired" was propagated. According to the custom of the surgical guilds in Holland, certificates were granted to Japanese apprentices who had completed their training in Dutch surgery. About 60 Dutch surgeons had served on Decima up to 1850, providing the basis for surgery to develop in Japan. Among them, Philipp Franz von Siebold was an exceptional scholar who also had a great impact in making Japanese culture known to the Western world.

Anatomy↗
PubMed2005

Current understanding of gender dimorphism in hepatic pathophysiology.

Studies have shown gender dimorphic response of the liver for various hepatic stresses including ischemia/reperfusion, hemorrhagic shock-resuscitation, hepatectomy, liver cirrhosis, endotoxemia, and chronic alcoholic consumption. The mechanisms responsible for the gender dimorphic response include differences in pro-inflammatory cytokine release, production of reactive oxygen species, and alteration in hepatic vasoregulatory action. These effects were shown to be modulated by circulating sex steroid levels. In this regard, modulation of sex steroid levels by agents/drugs has been proposed as a therapeutic option for preventing hepatic damage in various hepatic stress models. Further elucidation of precise mechanisms responsible for the gender-related differences in the hepatic pathophysiology is essential for the potential clinical application of sex hormone modulation therapy. In this article, current progress in our understanding the gender difference in the hepatic pathophysiology under the condition of hepatic stress is reviewed and discussed.

Estrogens↗
PubMed2005

Surgical treatment for colorectal liver metastases involving the paracaval portion of the caudate lobe.

BACKGROUND: Hepatic neoplasms in the paracaval portion of the caudate lobe (S1r) are usually difficult to treat surgically because such neoplasms often invade the hepatic veins and/or inferior vena cava (IVC). We reevaluated resected cases of colorectal liver metastases involving S1r to confirm the significance of aggressive surgical treatments. METHODS: Between July 1977 and December 2002, 95 consecutive patients with colorectal liver metastases underwent hepatic resection. Seven patients with liver metastases involving the S1r underwent resection. RESULTS: The surgical procedures for liver metastases comprised 3 isolated caudate lobectomies, 2 right hepatectomies, and 2 right hepatic trisectionectomies with caudate lobectomy. Combined resections included partial resection of the hepatic vein in 2 patients, wedge resection of the IVC in 3, and segmental resection of the IVC in 1. Six of the 7 patients with S1r metastasis had recurrent disease in liver and/or lung. A second hepatectomy was carried out in 4 patients and a partial lung resection in 2 patients. Four of the 7 patients survived more than 5 years, but 2 of them died of recurrent disease at 61 and 95 months after initial hepatectomy. The remaining 2 patients are alive 72 and 118 months without any sign of recurrence. The median survival time of the 7 patients was 60 months. CONCLUSION: Liver metastases involving the S1r could be resected radically with en bloc resection of the major hepatic veins and/or the inferior vena cava. An aggressive surgical approach with combined resection of the adjacent major vessels may offer a better chance of long-term survival in selected patients with caudate lobe metastasis from colorectal cancer.

Aged↗
PubMed2005

One hundred consecutive hepatobiliary resections for biliary hilar malignancy: preoperative blood donation, blood loss, transfusion, and outcome.

BACKGROUND: Many reports on blood loss and transfusion requirements during hepatectomy for metastatic liver cancer or hepatocellular carcinoma have been published; however, there are no reports on these issues in hepatectomy for biliary hilar malignancy. The aim of this study was to review our experience with blood loss and perioperative blood requirements in 100 consecutive hepatectomies for biliary hilar malignancy. METHODS: One hundred consecutive hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for hilar malignancies were performed, including 81 perihilar cholangiocarcinomas and 19 advanced gallbladder carcinomas involving the hepatic hilus. Fifty-eight hilar resections were combined with other organ and/or vascular resection. Data on preoperative blood donation, intraoperative blood loss, and perioperative transfusion were collected and analyzed. RESULTS: Preoperative autologous blood donation was possible in 73 patients (3.4 +/- 1.2 U). Intraoperative blood loss was 1850 +/- 1000 mL (range, 677-5900 mL), and it was < 2000 mL in 62 patients. Intraoperatively, only 7 of the 73 patients (10%) who donated blood received transfusion of unheated, homologous blood products (packed red blood cells or fresh frozen plasma), whereas 18 the 23 patients (67%) without donation received homologous transfusions. Only 16 patients received transfusion postoperatively, and overall, 35 patients received unheated homologous blood products. Total serum bilirubin concentrations after hepatectomy in patients receiving autologous blood transfusion only was similar to those in patients who did not receive transfusion. The incidence of postoperative complications was higher in the 35 patients who received perioperative homologous transfusion than in 65 patients who did not (94% vs 52%; P <.0001). The mortality rate (including all deaths) was 3% (myocardial infarction, intra-abdominal bleeding, and liver failure, 1 patient each). CONCLUSIONS: Despite the technical difficulties arising from hepatectomy for biliary hilar malignancy, approximately two thirds of hepatectomies can be performed in an experienced center without perioperative homologous blood transfusion using preoperative blood donation.

Adult↗
PubMed2005

Intrahepatic cholangiocarcinoma escapes from growth inhibitory effect of transforming growth factor-beta1 by overexpression of cyclin D1.

Transforming growth factor-beta1 (TGF-beta1) is involved in tumor progression by promoting angiogenesis or suppressing the immune system; yet TGF-beta1 also has a growth-inhibitory effect on epithelial cells including carcinoma cells. Several mechanisms of impaired TGF-beta1 responsiveness of carcinoma cells have been reported. In this study, we examined how TGF-beta1 participates in the development and progression of intrahepatic cholangiocarcinoma (ICC) associated with hepatolithiasis, and how ICC cells escape from growth inhibitory effect of TGF-beta1. A total of 40 cases of hepatolithiasis were studied, including 16 cases of ICC, and in vitro studies were conducted with cultured murine non-neoplastic biliary epithelial cells (MBEC) and three ICC cell lines. Immunohistochemically, TGF-beta1 was expressed in mononuclear cells and mesenchymal cells around the stone-containing bile ducts and invasive ICC, and also in biliary epithelial cells (hyperplastic and precursor lesions, and ICC). TGF-beta type II receptor (TbetaR-II) was constantly expressed on biliary epithelial cells irrespective of biliary lesions. In cell culture studies, TGF-beta1 significantly inhibited proliferation of MBEC via downregulation of cyclin D1, cdk4, and cdk6, while TGF-beta1 did not influence the proliferation of ICC cells. After suppression of cyclin D1 expression in one ICC cell line using cyclin D1 small interfering RNA, TGF-beta1 significantly inhibited the proliferation of ICC cells. In conclusion, high levels of TGF-beta1 around ICC or its precursors may be involved in development and progression of ICC in hepatolithiasis. ICC cells could escape the growth inhibitory effect of TGF-beta1 by overexpression of cyclin D1.

Cell Division↗
PubMed2005

Proposal of histological criteria for intraepithelial atypical/proliferative biliary epithelial lesions of the bile duct in hepatolithiasis with respect to cholangiocarcinoma: preliminary report based on interobserver agreement.

Biliary lining epithelia of the bile ducts in biliary diseases are known to have intraepithelial atypical/proliferative lesions related to the development of cholangiocarcinoma. The purpose of the present study was to determine the histological criteria for these lesions based on interobserver agreement. Digital images of 30 intraepithelial atypical/proliferative lesions in the stone-containing intrahepatic bile ducts of hepatolithiasis (30 cases) were sent to 10 pathologists. At first, 10 pathologists made a diagnosis (either of reactive/regenerative change, low-grade or high-grade biliary intraepithelial neoplasia (BilIN-1 and BilIN-2), or in situ carcinoma (BilIN-3)) based on their own criteria. The histological criteria for these four lesions were then determined, and the digital images of the same lesions with proposed criteria were re-distributed. Interobserver agreement on these four lesions was slightly improved (kappa = 0.44, first diagnosis; 0.49, second diagnosis) and intraobserver agreement was 'almost perfect' (kappa = 0.82 at both first and second diagnosis). Interobserver agreement between BilIN-1 and BilIN-2 and that between BilIN-2 and BilIN-3 were 'moderate', although the agreement between regenerative/reactive change and BilIN-1 was 'fair'. In this report, we propose histological criteria for reactive/regenerative change, BilIN-1, BilIN-2 and BilIN-3. Improvement of interobserver agreement suggests their applicability in diagnostic and research fields.

Bile Duct Neoplasms↗
PubMed2005

Aberrant expression of pyloric gland-type mucin in mucin-producing bile duct carcinomas: a clear difference between the core peptide and the carbohydrate moiety.

The authors have recently defined the clinopathological entity of a mucin-producing bile duct tumor (MPBT), and divided MPBT into two distinct subtypes: 'columnar-type' and 'cuboidal-type' MPBT. Mucin core protein 6 (MUC6), which is present in normal pyloric glands, had higher expression levels in cuboidal-type tumors than in columnar-type tumors. In the pyloric glands, a carbohydrate antigen detected by monoclonal antibody HIK1083 (CA/HIK1083) is also expressed. In order to evaluate the coexpression pattern of MUC6 and CA/HIK1083 in MPBT, expression profiles were evaluated in 38 surgically excised mucin-producing bile duct carcinomas (MPBC; cuboidal-type, n = 15; columnar-type, n = 23), using immunohistochemistry. The staining rate was graded as follows: -, <5% of neoplastic cells stained; +, 5% to <20%; + +, 20% to <50%; + + +, > or =50%. In cuboidal-type MPBC, MUC6 was positive in all cases (+ + +, 13/15; + +, 1/15; +, 1/15), whereas CA/HIK1083 was negative in all cases (-, 15/15; P < 0.0001). In columnar-type MPBC, MUC6 was positive in 65% of cases (+ + +, 6/23; + +, 8/23; +, 1/23; -, 8/23), and CA/HIK1083 was positive in 52% (+ +, 3/23; +, 9/23; -, 11/23; not significant). Our results clearly demonstrate that cuboidal-type MPBC have an aberrant pyloric glandular phenotype, that is, MUC6+/CA/HIK1083-. This unique profile may be related to different outcomes of patients with MPBC.

Adenocarcinoma, Mucinous↗
PubMed2005

Acid and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction.

OBJECTIVE: Patients who undergo esophagectomy with gastric tube reconstruction incur increased risk for acid reflux and duodenogastroesophageal reflux. Few postesophagectomy studies of gastroesophageal reflux disease have included simultaneous 24-h pH and bilirubin monitoring. The aim of this study is to evaluate acid reflux and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction. METHODS: Reflux symptom evaluation, endoscopy, and simultaneous 24-h pH and bilirubin monitoring in the cervical esophagus were performed in 25 patients who underwent Ivor Lewis esophagectomy, intrathoracic esophagogastrostomy, and digital dilation of the pyloric ring as treatment for esophageal cancer. RESULTS: Reflux symptoms were severe, mild, and absent in 2, 7, and 16 patients, respectively. Reflux esophagitis and Barrett's esophagus was observed in 11 and 1 patients, respectively. Elevated acid reflux occurred in 7 patients (28%). Elevated duodenogastroesophageal reflux was recorded in 11 patients (44%). Reflux profile analysis identified three patterns: 4 subjects (16%) with both elevated acid reflux and duodenogastroesophageal reflux; 3 (12%) with only elevated acid reflux; and 7 (28%) with only elevated duodenogastroesophageal reflux. Of 7 patients with only elevated duodenogastroesophageal reflux, 4 developed reflux esophagitis. Although reflux symptoms did not correlate with endoscopic esophagitis, a significant correlation was observed between endoscopic esophagitis and acid reflux and/or duodenogastroesophageal reflux. CONCLUSIONS: Reflux symptoms represented a poor indication of esophagitis in patients with esophagectomy and gastric tube reconstruction. Simultaneous 24-h pH and bilirubin monitoring can help in identifying patients at high risk for reflux esophagitis, as well as indicating the cause of esophagitis.

Aged↗
PubMed2004

Mechanotransduction by integrin is essential for IL-6 secretion from endothelial cells in response to uniaxial continuous stretch.

We previously reported that uniaxial continuous stretch in human umbilical vein endothelial cells (HUVECs) induced interleukin-6 (IL-6) secretion via IkappaB kinase (IKK)/nuclear factor-kappaB (NF-kappaB) activation. The aim of the present study was to clarify the upstream signaling mechanism responsible for this phenomenon. Stretch-induced IKK activation and IL-6 secretion were inhibited by application of alpha(5)beta(1) integrin-inhibitory peptide (GRGDNP), phosphatidylinositol 3-kinase inhibitor (LY-294002), phospholipase C-gamma inhibitor (U-73122), or protein kinase C inhibitor (H7). Although depletion of intra- or extracellular Ca(2+) pool using thapsigargin (TG) or EGTA, respectively, showed little effect, a TG-EGTA mixture significantly inhibited stretch-induced IKK activation and IL-6 secretion. An increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) upon continuous stretch was observed even in the presence of TG, EGTA, or GRGDNP, but not in a solution containing the TG-EGTA mixture, indicating that both integrin activation and [Ca(2+)](i) rise are crucial factors for stretch-induced IKK activation and after IL-6 secretion in HUVECs. Furthermore, while PKC activity was inhibited by the TG-EGTA mixture, GRGDNP, LY-294002, or U-73122, PLC-gamma activity was retarded by GRGDNP or LY-294002. These results indicate that continuous stretch-induced IL-6 secretion in HUVECs depends on outside-in signaling via integrins followed by a PI3-K-PLC-gamma-PKC-IKK-NF-kappaB signaling cascade. Another crucial factor, [Ca(2+)](i) increase, may at least be required to activate PKC needed for NF-kappaB activation.

Calcium↗
PubMed2004

Changes in splenic volume during liver regeneration.

Little is known about the relation between liver regeneration and splenic size. We monitored serial changes in liver and spleen volumes using computed tomography in 24 patients with biliary cancer who underwent right hepatectomy or more extensive liver resection following portal vein embolization (PVE). Nonembolized hepatic segments increased in volume from 316 +/- 97 cm3 (34% +/- 8% of total liver volume) before PVE to 410 +/- 115 cm3 (44% +/- 8%) after PVE. The volume of nonembolized hepatic segments (i.e., remnant liver) increased to 617 +/- 111 cm3 (59% +/- 10% of total liver volume before PVE) 14 days after hepatectomy and then increased slowly to reach 795 +/- 231 cm3 (76% +/- 16%) 1 year after hepatectomy. Splenic volume increased from 87 +/- 29 cm3 before PVE to 104 +/- 38 cm3 (119% +/- 17% of original volume) after PVE. Splenic volume increased to 137 +/- 65 cm3 (155% +/- 40%) by 14 days after hepatectomy and to 155 +/- 67 cm3 (179% +/- 41%) by 28 days after hepatectomy, with no further change at 1 year after hepatectomy (153 +/- 92 cm3; 174% +/- 79%). The rate of increase in splenic volume within the first 14 days after hepatectomy was 2.7 +/- 3.6 cm3/day, correlating well with increases in remnant liver volume ( r = 0.64, p = 0.0006). These data indicate that the spleen is enlarged during liver regeneration, suggesting that the liver and spleen share certain common growth regulatory mechanisms.

Aged↗
PubMed2004

Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival.

In this study, we report for the first time reduced expression of the let-7 microRNA in human lung cancers. Interestingly, 143 lung cancer cases that had undergone potentially curative resection could be classified into two major groups according to let-7 expression in unsupervised hierarchical analysis, showing significantly shorter survival after potentially curative resection in cases with reduced let-7 expression (P = 0.0003). Multivariate COX regression analysis showed this prognostic impact to be independent of disease stage (hazard ratio = 2.17; P = 0.009). In addition, overexpression of let-7 in A549 lung adenocarcinoma cell line inhibited lung cancer cell growth in vitro. This study represents the first report of reduced expression of let-7 and the potential clinical and biological effects of such a microRNA alteration.

Adult↗
PubMed2004

Survival after surgical treatment of early gastric cancer, surgical techniques, and long-term survival.

Early gastric cancer (EGC) is well accepted as having a favorable prognosis after surgical treatment. Difference in treatment strategies for EGC between Japan and western countries indicates a need for current information to be evaluated with regard to long-term survival rates of EGC patients throughout the world. To analyze survival rates and recurrence after resection of EGC, we investigated 51 reports in English that each included more than 50 cases of EGC treated by gastrectomy and had been published during the past 12 years (1992-2003). Prevalence of EGC among all gastric cancers was 45%-51% in Japan, but only 7%-28% in western countries. Mean age at diagnosis was less than 60 years in Japan and Korea, but was more than 60 in most of the Western countries. Actuarial and disease-specific 5-year survival rates for EGC were 72%-95.8% and 88%-98.3%, respectively. Those for EGC that were invading the submucosal layer were 71.6%-94.1% and 82%-96.6%, respectively. Those for EGC with lymph node metastasis were 57%-89.1% and 72%-93.5%, respectively. Prevalence of recurrence ranged from 1.0% to 13.8%. Larger clinical series with more EGC cases showed a lower prevalence of recurrence (P=0.531, P=0.0026). Liver and blood-borne distant metastasis represented the predominant pattern of relapse, accounting for over half (54%). Local recurrence and peritoneal dissemination represented 20% and 18% of all recurrences, respectively. Clinicopathological studies have shown lymph node metastasis to be closely related to depth of invasion, size of lesion, histological type, presence of ulcer or ulcer scar, and vessel involvement. Information on these factors is the key to successful treatment of EGC. When sufficient information has been assessed preoperatively, surgeons can select patients for whom less-invasive surgery should not increase the risk of recurrence.

Aged↗
PubMed2004

Expression of CD109 in human cancer.

It was recently reported that the human CD109 gene encodes a glycosyl-phosphatidylinositol-anchored glycoprotein that is a member of the alpha(2)-macroglobulin/C3, C4, C5 family of thioester-containing proteins. In this study, we found that the expression of mouse CD109 gene was upregulated in NIH3T3 cells expressing RET tyrosine kinase with a multiple endocrine neoplasia 2B mutation. Northern blot analysis showed a high level of expression of the CD109 gene only in the testis in normal human and mouse tissues. In addition, its expression was high in some human tumor cell lines, which included squamous cell carcinoma and glioblastoma cell lines, whereas it was undetectable in neuroblastoma and small-cell lung carcinoma cell lines. When CD109 expression was examined in 33 cases of human lung cell carcinomas by quantitative RT-PCR, a significant high expression of CD109 was detected in about half of squamous cell carcinomas examined, but not in adenocarcinoma, large-cell carcinoma and small-cell carcinoma. Similarly, upregulation of CD109 was observed in nine out of 17 esophageal squamous cell carcinomas. Thus, these results suggested that CD109 might be a useful molecular target for the development of new therapeutics for malignant tumors, such as squamous cell carcinoma.

Amino Acid Sequence↗