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Masato Sakon

Publications and source records attributed to Masato Sakon.

At least 19 recordsLinked to original sources

Combination of IFN-alpha and 5-fluorouracil induces apoptosis through IFN-alpha/beta receptor in human hepatocellular carcinoma cells.

PURPOSE: Several studies showed the effectiveness of combination therapy with IFN-alpha and 5-fluorouracil (5-FU) for advanced hepatocellular carcinoma. However, only little is known about the underlying mechanism of combination therapy. In the present study, we examined whether apoptosis through IFN-alpha/beta receptor (IFN-alpha/betaR) was associated with the effects of combination therapy. EXPERIMENTAL DESIGN: HuH7, PLC/PRF/5, HLE, and HLF were treated with IFN- (500 units/mL), 5-FU (0.5 microg/mL), or their combination for 10 days. In addition, IFN-alpha/betaR gene transfer with combination therapy was done. RESULTS: Ten-day treatment by combination therapy resulted in >80% cell growth inhibition. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis showed synergistic effects for combination therapy on PLC/PRF/5, HLE, and HLF. Concordant results were obtained with DNA fragmentation. Moreover, there was an evidence showing that changes in the expression of Bcl-2 family lead to apoptosis. On the other hand, the expression of IFN-alpha/betaR and up-regulation of alpha-phospho-signal transducer and activator of transcription 1, IFN regulatory factor-1 by combination therapy were observed in all cell lines. Furthermore, IFN-alpha/type 2 IFN receptor long form-transfected HuH7 cells treated with combination therapy showed strong DNA fragmentation compared with nontransfected or transfected with IFN-alpha- and 5-FU-treated HuH7. CONCLUSIONS: Our results showed that combination of IFN-alpha plus 5-FU strongly induced cell growth inhibition of human hepatocellular carcinoma cells and indicated that one of the direct mechanisms of combination therapy may in part be attributable to alterations in induction of apoptosis through IFN-alpha/betaR.

Apoptosis↗

Portal venous reconstruction in a living liver donor with an anomalous hepatic arterial and portal venous anatomy.

Hepatic arterial and portal venous anomalies in living liver donors are not uncommon. Modified surgical techniques may be required in such circumstances, although the safety of the living donor must always be given top priority. We describe here a successful portal venous reconstruction in a living donor with an anomalous hepatic arterial and portal venous anatomy in which the right anterior and posterior hepatic arteries encircled the main portal vein. Although such an anomaly of hepatic vessels was not frequently encountered, we should be able to alter the surgical strategy to deal with it. This case illustrates the importance of preoperative hepatic artery and portal venous evaluation in all living donors to identify the feasibility of modifying vessel anastomoses in living donors, as well as recipients, before living donor liver transplantation.

Adult↗

Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation.

Several studies reported that Id (Inhibitor of DNA binding or Differentiation) proteins, helix-loop-helix transcription factors, have important roles in differentiation, cell cycle and angiogenesis in various cells. However, the role of Id proteins in hepatocellular carcinoma (HCC) remains unclear. We examined the immunohistochemical expression of Id1, Id2 and Id3 proteins in 54 surgically resected HCCs with surrounding HCV or HBV-related chronic hepatitis (n=30) and liver cirrhosis (n=24). All non-cancerous livers exhibited immunoreactivity for Id proteins and the expression increased from chronic hepatitis to cirrhosis. In HCCs (n=45), well-differentiated tumors mostly exhibited strong or moderate immunostaining for all Id proteins, while proportion of the samples with weak or no expression increased with tumor dedifferentiation and frequently observed in poorly (66.7, 93.3 and 93.3% respectively for Id1, 2, 3) or undifferentiated (100% for all Ids) HCCs. Clinicopathological survey demonstrated a significant correlation between Id1, 2 and 3 expression and differentiation of carcinoma (p=0.0044, 0.0014 and 0.0014, respectively) although univariate analysis indicated that high expression of Id1 was significant predictive factor for longer disease-free survival of the patients (p=0.047). A similar tendency was also observed with Id2 and Id3. The present study demonstrate high expression of Id1, 2 and 3 in well-differentiated HCC and low expression in advanced dedifferentiated HCC, in contrast to its continuous expression during breast, prostate and colon carcinogenesis. These findings suggested that Id1, 2 and 3 might play a role in the early stages of hepatocarcinogenesis, but not in the development of advanced carcinoma, and might consequently be related to HCC dedifferentiation.

Blotting, Western↗

[Postoperative pulmonary thromboembolism and its prevention from the perspective of the establishment of Japanese guidelines].

The incidence of venous thromboembolism (VTE) is rapidly increasing in Japan. Ideally, the guidelines for its prevention should be based on solid evidence, but there are few clinical data on the prevalence and prophylaxis of VTE in Japan. Comprehensive, standard guidelines for the prevention of VTE were recently established by applying the risk-prophylaxis relationship of the sixth American College of Chest Physicians (ACCP) consensus recommendations. Since patients undergoing cancer surgery make up a relatively homogenous, "highest-risk" group, we could precisely evaluate the difference in VTE risk between Japan and the West. The risk of clinical PE in Japanese cancer surgery was found to be one or two risk levels lower than that in the West. Therefore the Japanese risk stratification was set to be one level lower than that in the sixth ACCP guidelines. For prophylaxis, the recommendations of the Japanese guidelines are basically identical to those of the sixth ACCP guidelines. Since the present guidelines are not sufficiently based on Japanese evidence, they should be reviewed in a prospective, nationwide epidemiologic study. In this review article, the theoretical background of and future perspectives on the Japanese guidelines are discussed.

Humans↗

Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferon-alpha/5-fluorouracil against Hepatocellular Carcinoma.

PURPOSE: Our purpose was to explore the contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of IFNalpha and 5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Susceptibility of HCC cell lines to TRAIL and/or 5-FU was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of 5-FU, IFNalpha, or both on the expression of TRAIL receptors (R1, R2, R3, and R4) on HCC cells or TRAIL in peripheral blood mononuclear cells (PBMC) were examined by flow cytometry. IFNalpha-induced cytotoxic effects of PBMC on HCC cell lines were examined by (51)Cr release assay. TRAIL expression in peripheral blood mononuclear cells and liver tissue from patients was examined by real-time reverse transcription-PCR or immunohistochemistry. RESULTS: HLE and HepG2 were sensitive to TRAIL, but HuH7, PLC/PRF/5, and HLF were resistant. 5-FU had synergistic effect on TRAIL in HLF and additive effect in four other HCC cell lines. TRAIL receptors on HCC cells were up-regulated by 5-FU, and IFNalpha induced TRAIL on CD4(+) T cells, CD14(+) monocytes, and CD56(+) NK cells. Treatment of effector cells by IFNalpha and target HCC cells by 5-FU enhanced the cytotoxicity of CD14(+) monocytes and CD56(+) NK cells against HCC cells via a TRAIL-mediated pathway. TRAIL mRNA overexpression was noted in PBMC of HCC patients who clinically responded to IFNalpha/5-FU combination therapy, and TRAIL(+) mononuclear cells were found in cancer tissue of a responder. CONCLUSION: Our results suggest that modulation of TRAIL/TRAIL receptor-mediated cytotoxic pathway might partially contribute to the anti-HCC effect of IFNalpha and 5-FU combination therapy.

Adult↗

Molecular prediction of response to 5-fluorouracil and interferon-alpha combination chemotherapy in advanced hepatocellular carcinoma.

PURPOSE: The prognosis of hepatocellular carcinoma (HCC) is very poor, particularly in patients with tumors that have invaded the major branches of the portal vein. Combination chemotherapy with intra-arterial 5-fluorouracil and subcutaneous interferon-alpha has shown promising results for such advanced HCC, but it is important to develop the ability to accurately predict chemotherapeutic responses. EXPERIMENTAL DESIGN: We analyzed the expression of 3,080 genes using a polymerase chain reaction-based array in 20 HCC patients who were treated with combination chemotherapy after reduction surgery. After unsupervised analyses, a supervised classification method for predicting chemotherapeutic responses was constructed. To minimize the number of predictive genes, we used a random permutation test to select only significant (P < 0.01) genes. A leave-one-out cross-validation confirmed the gene selection. We also prepared an additional 11 cases for validation of predictive performance. RESULTS: Hierarchical clustering analysis and principal component analysis with all 3,080 genes revealed distinct gene expression patterns in responders (those with complete response or partial response) and nonresponders (those with stable disease or progressive disease) to the combination chemotherapy. Using a weighted-voting classification method with either all genes or only significant genes as assessed by permutation testing, the objective responses to treatment were correctly predicted in 17 of 20 cases (accuracy, 85%; positive predictive value, 100%; negative predictive value, 80%). Moreover, patients in the validation dataset could be classified into two distinct prognostic groups using 63 predictive genes. CONCLUSIONS: Molecular analysis of 63 genes can predict the response of patients with advanced HCC and major portal vein tumor thrombi to combination chemotherapy with 5-fluorouracil and interferon-alpha.

Adult↗

Expression level of valosin-containing protein (p97) is associated with prognosis of esophageal carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) frequently shows a poor prognosis because of the occurrence of systemic metastasis, mainly via lymphatic vessels. Valosin-containing protein (VCP) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, we examined the association of VCP with the recurrence and prognosis of ESCC. EXPERIMENTAL DESIGN: VCP expression in 156 ESCC patients [139 males and 17 females; age range, 38-82 (median, 60) years] was analyzed by immunohistochemistry. Staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 12 patients. RESULTS: Fifty-seven (37.3%) cases showed level 1 and 96 (62.7%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCP mRNA expression in level 2 (n = 6) than level 1 cases (n = 6; P < 0.05). ESCC with level 2 expression showed higher rates of lymph node metastasis (P < 0.01) and deep tumor invasion (P < 0.01), and poorer disease-free and overall survival rates (P < 0.001 for both analyses) than ESCC with level 1 expression. Multivariate analysis revealed that VCP expression level is an independent prognosticator for disease-free and overall survival. Furthermore, VCP level was an indicator for disease-free survival in the early (pT1) and the advanced (pT2-pT4) stage groups. CONCLUSION: This study demonstrated the prognostic significance of VCP expression in ESCC.

Adenosine Triphosphatases↗

Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma.

PURPOSE: Akt is a serine/threonine kinase that plays a central role in tumorigenesis. Among the members of Akt family, Akt2 is associated with the development of human cancers. The present study was designed to clarify the prognostic significance of Akt2 and activated Akt expression in pancreatic ductal adenocarcinoma (PDAC). In addition, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and the proliferation activity of tumor cells detected by Ki-67 immunohistochemistry were examined. EXPERIMENTAL DESIGN: Immunohistochemical analysis was performed on paraffin-embedded specimens from 65 patients with PDAC; 36 males and 29 females with ages ranging from 48 to 79 years (median, 66 years) of age. Expression levels of Akt2, phosphorylated Akt (p-Akt), and phosphorylated ERK 1/2 (p-ERK 1/2) were categorized as either weaker (low intensity) or equal to stronger (high intensity) compared with those in the endothelial cells of the same specimens. For Ki-67 immunohistochemistry, cases were divided into two groups: level 1, Ki-67 labeling index (LI), <20%; level 2, Ki-67 LI, > or = 20%. RESULTS: Twenty-six (42.6%), 28 (45.9%), 39 (63.9%), and 46 (75.4%) of the tumors showed high intensity of Akt2, p-Akt, and p-ERK 1/2 expression, and Ki-67 LI level 2, respectively. A significant positive correlation was observed between Akt2 and p-Akt expression (P < 0.01). Multivariate analysis revealed that p-Akt expression, Ki-67 LI, and histological differentiation are independent prognosticators for PDAC. CONCLUSIONS: p-Akt expression is a significant prognostic indicator for PDAC. Inhibition of Akt is a possible molecular approach for treatment of PDAC.

Adenocarcinoma↗

Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis.

PURPOSE: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma. EXPERIMENTAL DESIGN: We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35-84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci. RESULTS: Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T(1-2) versus T(3-4), P < 0.05), presence or absence of venous invasion (P < 0.05), and tumor stage (I and II versus III and IV; P < 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P < 0.001) and poorer disease-free and overall survival (P < 0.01 and P < 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P < 0.05 and <0.01, respectively). CONCLUSIONS: A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.

Adenoma↗

Hepatic expression of ANG2 RNA in metastatic colorectal cancer.

We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci. Metastatic CRC exhibited notable blood flow and tumor vessel formation at tumor frontiers. Reverse-transcription polymerase chain reaction assays indicated that the ANG2 RNA content was greater in metastatic CRC than in primary CRC. Investigation of metastatic foci using laser capture microdissection revealed that the RNA content of ANG2, but not ANG1, increased from the bordering liver region to the periphery of the metastatic disease, and also from the periphery to the intermediate portion of the metastatic lesion; immunohistochemical analysis confirmed that there was a corresponding gradual increase in Ang-2 protein expression. Tie-2, a receptor for angiopoietins, was preferentially expressed in the bordering liver region rather than in metastatic CRC. Vascular endothelial growth factor (VEGF) also exhibited an expression pattern similar to that of Ang-2, and there was a significant correlation between the RNA content of ANG2 and that of VEGF in dissected samples (P =.002). Western blot analysis suggested that expression of Ang-1, Ang-2, Tie-2, and VEGF may be regulated at a transcriptional level. The increase in ANG2 RNA content from the peripheral portion of the tumor to the intermediate portion, coinciding with the decrease in recruitment of periendothelial supporting cells around the vascular endothelial cells, suggests that Ang-2 may play a role in the immaturity of tumor vessels. In conclusion, the current study suggests that Ang-2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver.

Angiopoietin-1↗

Interstitial pneumonia induced by combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma.

Previously we reported combined chemo-immunotherapy, using interferon (IFN)-alpha and 5-fluorouracil (5-FU) for patients with advanced hepatocellular carcinoma (HCC), and this regimen improved the prognosis. Recently, we experienced an HCC patient who died of severe interstitial pneumonia during the combined IFN-alpha and 5-FU therapy. This is the first report of the occurrence of interstitial pneumonia during combined IFN-alpha and 5-FU treatment. A 60-year-old-man was admitted to Osaka University Hospital to receive systemic chemo-immunotherapy for recurrent HCC. In the second week of the chemo-immunotherapy, he showed a decreased level of consciousness, and respiratory insufficiency. Emergency roentgenogram revealed diffuse infiltration in both lungs. Respiratory dysfunction due to interstitial pneumonia was suspected, and steroid pulse therapy was started. However, the patient showed respiratory failure, and he died 32 days after the start of the therapy. Autopsy findings showed atelectasis in the bilateral lungs, which showed elastic hard solidity and a dark red color; esophageal varices were also shown, and there was cirrhosis with a large tumor in the liver. Microscopically, the alveolar wall showed marked fibrous thickness and moderate inflammatory change, which is consistent with acute interstitial pneumonia, and the acute pulmonary change was suspected to have been the cause of death. The association of IFN with the development of interstitial pneumonia has been reported. However, the prognosis of IFN-induced interstitial pneumonia has mostly been favorable when the medication was discontinued. It has been postulated that interstitial pneumonia induced by the combination of IFN and 5-FU may be therapy-resistant. The combination of IFN-alpha and 5-FU is a useful therapy for patients with advanced HCC, such as that with portal vein invasion or multiple metastatic foci. Thus, interstitial pneumonia in these patients should be carefully managed.

Antineoplastic Combined Chemotherapy Protocols↗

Current status of pulmonary embolism in general surgery in Japan.

The true incidence of pulmonary embolism (PE) after general surgery in Japan is unknown. We searched the PubMed and Japana Centra Revuo Medicina 1985-2002 databases, entering "surgery" and "pulmonary embolism" or "thromboembolism", and reviewed the reported incidence of clinical PE associated with general surgery in Japan. The overall incidence of PE after general surgery was 0.33%. Fatal PE was reported in 0.08% of the surgical population and the mortality rate of patients with PE was 31%. The incidence of PE after cancer surgery ranged from 0.57% after colon malignancy to 3.85% after pancreatic cancer surgery, and was significantly higher than that after surgery for noncancerous conditions (0.20%). The incidence of PE after various cancer operations corresponded to a moderate or high risk, as defined by the 6th American College of Chest Physicians consensus recommendations. There was no significant difference in the incidence of PE after laparoscopic and open abdominal surgery. The incidence of PE was four to six times lower in patients who had received mechanical prophylaxis, although the difference was not significant. In conclusion, the incidence of PE in Japanese surgical patients is not as low as previously thought. Perioperative prophylaxis against venous thromboembolism is important, but its benefits need to be confirmed by prospective clinical studies.

Humans↗

In vivo real-time microangiography of the liver in mice using synchrotron radiation.

BACKGROUND/AIMS: The aim of this study was to visualize hepatic microvessels (less than 100 microm in diameter) in vivo, which could not be visualized by conventional X-ray angiography, by using synchrotron radiation (ultra-bright and monochromatic X-ray). METHODS: Five female Balb/c nu/nu mice were used. To investigate the hepatic microvessels under nearly physiologic conditions, we performed in vivo aortography under anesthesia with 370 mgI/ml nonionic iodine contrast medium using monochromatic 17-keV X-rays generated by a synchrotron. Images were captured with a pixel matrix size of 1024 x 1024 at a rate of 30 pictures/s. The field of view was 7 mm x 7 mm and thus the pixel size was approximately 7 microm. Captured images were evaluated both qualitatively and quantitatively. RESULTS: Small hepatic arterial and portal venous branches of the liver were visualized separately during one sequential aortogram. The minimum diameter of the vessels observed was approximately 20 microm, and the vessels which ran parallel to the hepatic artery were observed and it seemed to be intrahepatic peribiliary arterial plexus. CONCLUSIONS: Our new experimental model would be useful for visualization of changes in the hepatic microcirculation under nearly physiologic conditions.

Angiography↗

Molecular-based prediction of early recurrence in hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has a very poor prognosis, due to the high incidence of tumor recurrence. As the current morphological indicators are often insufficient for therapeutic decisions, we sought to identify additional biologic indicators for early recurrence. METHODS: We analyzed gene expression using a PCR-based array of 3,072 genes in 100 HCC patients. Informative genes predicting early intrahepatic recurrence were selected by random permutation testing, and a weighted voting prediction method was constructed. Following estimation of prediction accuracy, a multivariate Cox analysis was performed. RESULTS: By permutation testing, we selected 92 genes demonstrated distinct expression patterns differing significantly between recurrence cases and recurrence-free cases. Our prediction method, using the 20 top-ranked genes, correctly predicted the early intrahepatic recurrence for 29 of 40 cases within the validation group, and the odds ratio was 6.8 (95%CI 1.7-27.5, P = 0.010). The 2-year recurrence rates in the patients with the good signature and those with the poor signature were 29.4 and 73.9%, respectively. Multivariate Cox analysis revealed that molecular-signature was an independent indicator for recurrence (hazard ratio 3.82, 95%CI 1.44-10.10, P = 0.007). CONCLUSIONS: Our molecular-based prediction method using 20 genes is clinically useful to predict early recurrence of HCC.

Aged↗

Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model.

BACKGROUND: The role of portal hemodynamics on liver regeneration after partial hepatectomy is not fully understood. The aim of our study was to characterize the effects of portal hemodynamics using a novel rat model. METHODS: We established a rat model of a portohepatic shunt with a 70% hepatectomy (PHS model), in which the portal pressure remained stable during and after the 70% hepatectomy. To assess the effect of portal hemodynamics on liver injury and regeneration in the first 24 hours, we compared PHS rats with those with a simple 70% hepatectomy. RESULTS: Biochemical and histopathologic changes were similar between the 2 groups. Liver weight increased in the control, whereas it did not in the PHS group (P = .0021). Hepatocytes were enlarged in the control but not in the PHS group, although DNA synthesis was similar in both groups. Apoptotic hepatocytes increased markedly in PHS at 24 hours, whereas minimal apoptosis was noted throughout the course of the study in the control group. Hepatocyte growth factor increased similarly, except that it was not activated in PHS. CONCLUSIONS: Our results suggested that a portal hyperdynamic state early after a 70% hepatectomy was necessary for liver regeneration through activation of hepatocyte growth factor, promoting hepatocyte hypertrophy and avoiding apoptosis, while DNA synthesis in hepatocytes was independent of portal hemodynamics.

Animals↗

Xenon-inhalation computed tomography for noninvasive quantitative measurement of tissue blood flow in hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to separately measure the arterial and portal venous tissue blood flow (TBF) of hepatocellular carcinoma (HCC) with a noninvasive method using xenon inhalation CT (xenon-CT) and to differentiate between well-differentiated HCCs and moderately and poorly differentiated HCCs. MATERIALS AND METHODS: Total, arterial and portal venous TBFs of 38 surgically proven HCC nodules from 38 patients were measured by means of xenon-CT. Serial abdominal CT scans were obtained before and after inhalation of nonradioactive xenon gas. TBF was computed using the Fick principle, after which the correlation between TBF and pathologic features of the tumors was determined. RESULTS: Total, arterial, and portal venous TBFs of HCC were 125.7 +/- 59.9 mL/min/100g, 102.5 +/- 37.3, and 22.2 +/- 11.4, respectively, and the corresponding findings for hepatic parenchyma were 67.3 +/- 13.1, 25.2 +/-9.6, and 42.4 +/- 11.0. Total and arterial TBFs of HCC were significantly higher than those of the hepatic parenchyma (P < 0.01), whereas portal venous TBF of HCC was significantly lower than that of hepatic parenchyma (P < 0.01). Arterial TBF of moderately or poorly differentiated HCC (120.4 +/- 38.2) was significantly higher than that of well-differentiated HCC (60.4 +/- 43.5) (P < 0.01). CONCLUSIONS: Arterial and portal venous TBFs of HCC could be measured separately, noninvasively, and safely with xenon-CT. Correlation between TBF and pathologic features of tumors indicate that xenon-CT can be used to differentiate between well-differentiated HCCs and moderately and poorly differentiated HCCs.

Adult↗

Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinoma.

The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry in 40 cases of pancreatic ductal adenocarcinoma. WT1 protein was expressed in 30 (75%) of the 40 pancreatic ductal adenocarcinomas, but not in the remaining 10 (25%). In normal pancreatic ductal cells, WT1 protein was undetectable. No correlations between WT1 expression and clinicopathological parameters such as age, sex, T or N stage, tumor location, and tumor differentiation were observed. Treatment with WT1 antisense oligomers significantly inhibited the growth of five human pancreatic cancer cell lines, PSN1, MiaPaCa2, ASPC1, BxPC3, and PCI6, expressing the WT1 gene. These results indicate an important role of the WT1 gene in the tumorigenesis of pancreatic ductal adenocarcinoma expressing WT1 and provide a rationale for new treatment strategies to treat pancreatic ductal adenocarcinoma by targeting the WT1 gene and its product.

Adenocarcinoma↗