Biomedical subjects

Morito Monden

Publications and source records attributed to Morito Monden.

At least 109 records · Page 6Linked to original sources

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

Aggressive multimodal treatment for peritoneal dissemination and needle tract implantation of hepatocellular carcinoma: a case report.

We encountered a patient with hepatocellular carcinoma (HCC) with peritoneal dissemination and needle tract implantation, both of which were strongly suspected to have been caused by percutaneous needle biopsy. The patient was a 65-year-old man. Partial hepatectomy of subsegment VI had been performed following the diagnosis of HCC by percutaneous needle biopsy in February 1997. After this first surgery, the patient additionally underwent five further surgeries for the treatment of intrahepatic recurrences, peritoneal recurrences and needle tract implantation caused by the percutaneous needle biopsy. The intrahepatic and peritoneal recurrences were surgically controlled for 3 years after the fifth operation. The needle tract implantation was first resected in February 2001. Since then, treatment by surgery and radiotherapy has been administered twice for local recurrences forming tumor thrombosis of the abdominal wall. Now, 7 years after the first surgery, the patient remains alive without any evidence of recurrence. This case report serves to emphasize that needle tract implantation and peritoneal seeding caused by percutaneous needle biopsy are rare but possible complications. When such iatrogenic spreading of malignant cells occurs, aggressive multimodal treatment is well worth considering. Wide resection of the tumor including the adjacent soft tissues should be performed in these cases, considering that the tumor spreads along the subcutaneous veins in needle tract implantation of HCC and repeated aggressive surgeries could provide good local control.

Aged↗

PubMed2004

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↗

PubMed2004

mRNA expression level of estrogen-inducible gene, alpha 1-antichymotrypsin, is a predictor of early tumor recurrence in patients with invasive breast cancers.

We previously identified 18 genes that correlated with ER positivity by adapter-tagged competitive-PCR analysis of 2412 genes in human breast cancer tissues. The aim of the present study was to determine the prognostic significance of these genes. mRNA expression levels of 12 of the above 18 genes were quantified in breast cancer tissues by real-time PCR assay, and their association with patients' prognosis (n = 110) was studied according to hormone receptor (HR) status. In addition, the genes found to influence prognosis were further investigated to examine whether their mRNA expression could be induced by estrogen in MCF-7 cells in vitro. Of the 12 genes, mRNA expression levels of two [alpha 1-antichymotrypsin (ACT) and stanniocalcin 2 (STC2)] were significantly (P = 0.002 and P = 0.007, respectively) associated with good prognosis in HR-positive (ER and/or PR positive) breast cancer patients treated with adjuvant hormone therapy. Multivariate analysis showed that ACT mRNA level, but not STC2 mRNA level, in HR-positive patients, was a significant prognostic factor (P = 0.042), which was independent of tumor size and lymph node metastases. On the other hand, mRNA expressions of ACT and STC2 were not significantly associated with prognosis in HR-negative patients. Estradiol treatment resulted in a significant increase in the mRNA levels of both ACT and STC2 in MCF-7 cells. The mRNA level of ACT, which is an estrogen-inducible gene, is a significant predictor of good prognosis in HR-positive, but not HR-negative, patients with breast cancers. Since HR-positive patients were treated with adjuvant hormone therapy, we suggest that ACT mRNA level could potentially be used as a predictor of response to hormone therapy, rather than a prognostic factor (predictor of metastatic potential).

Breast Neoplasms↗

PubMed2004

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↗

PubMed2004

Adenovirus-mediated p53AIP1 gene transfer as a new strategy for treatment of p53-resistant tumors.

The p53AIP1 gene, which we recently identified as a novel p53-target, mediates p53-dependent apoptosis. We evaluated the effects of adenovirus-mediated introduction of p53AIP1 (Ad-p53AIP1) on 30 human cancer-cell lines in vitro, and two cell lines in vivo, in comparison with the effects of p53 (Ad-p53). In 20 of the 30 cell lines, p53AIP1-induced apoptosis was observed, and in 12 of these p53AIP1-sensitive cancer cell lines, the apoptotic effects of p53AIP1 were greater than those of p53 itself. Cancers with wild-type p53, which were thought to be p53-resistant, were likely to be sensitive to p53AIP1-induced apoptosis. p53-resistant cancers such as LS174T (p53 +/+) and A549 (p53 +/+), in which no increase of p53AIP1 mRNA expression was observed when Ad-p53 was introduced, were killed effectively by Ad-p53AIP1. Furthermore, co-introduction of p53 and p53AIP1 had a synergistic effect on the induction of apoptosis, regardless of p53 status. Finally, adenovirus-mediated introduction of p53AIP1 suppressed tumor growth in vivo. These results suggested that p53AIP1 gene transfer might become a new strategy for the treatment of p53-resistant cancers.

Adenoviridae↗

PubMed2004

Expression of uridine diphosphate N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase 3 in adenocarcinoma of the pancreas.

Uridine diphosphate (UDP) N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), one of the enzymes that catalyze the initial glycosylation of mucin type O-linked proteins, was shown to associate with the differentiation of cancer cell lines and the prognosis of some kinds of cancers. In the present study, the association of GalNAc-T3 expression with clinicopathologic features of pancreatic adenocarcinoma and patients' survival was examined. The level of expression of GalNAc-T3 was analyzed immunohistochemically in paraffin-embedded tumor samples from surgically resected specimens of 59 patients with pancreatic ductal adenocarcinoma. The correlations of GalNAc-T3 expression with clinicopathologic features and prognosis were studied. Thirty-five tumors showed high- intensity GalNAc-T3 staining, whereas 24 showed low-intensity staining. A close association was observed between GalNAc-T3 staining intensity and histologic differentiation and the stage of the tumors. The low-intensity group showed a high rate of the poorly differentiated subtype (p < 0.001) and T4 of the pTNM staging system (p < 0.05). These findings indicate that the expression of GalNAc-T3 is associated with the differentiation and aggressiveness of ductal adenocarcinoma of the pancreas.

Aged↗

PubMed2004

Association between expression levels of CA 19-9 and N-acetylglucosamine-beta;1,3-galactosyltransferase 5 gene in human pancreatic cancer tissue.

OBJECTIVE: CA 19-9, equivalent to Sialyl Lewis antigen, is a well-known tumor marker in pancreatic cancer. At the initial step of the biosynthesis of CA 19-9, N-acetylglucosamine-beta1,3-galactosyltransferase (beta3Gal-T) transfers galactose to N-acetylglucosamine (GlcNAc). Recently, beta3Gal-T5 has been presumed to be related to the formation of the type 1 chain in an in vitro experiment in terms of kinetic enzyme characterization. The purpose of this study was to investigate which beta3Gal-T is related to the synthesis of CA 19-9 in human pancreatic cancer tissues. METHODS: We examined beta;3Gal-T1, T2, T3, T4, and beta;3Gal-T5 mRNA expressions in 13 noncancerous and cancerous tissues of the human pancreas using real-time polymerase chain reaction, and compared those gene expression levels with the immunoreactivity of CA 19-9 and its precursor DUPAN-2 in cancerous tissues. RESULTS: Beta;3Gal-T5 gene expression significantly augmented in cancerous tissues, when compared with the adjacent noncancerous tissues. Additionally, there was a good correlation between BETA;3GAL-T5 gene transcription levels and immunohistochemical grades of CA 19-9 or its precursor DUPAN-2 in cancerous tissues. However, no correlation was observed between beta;3Gal-T1, T2, T3, and beta;3Gal-T4 gene expression levels and CA 19-9 or DUPAN-2 immunoreactive grades in cancerous tissue. CONCLUSION: beta3Gal-T5 is presumed to be responsible for the synthesis of CA 19-9 in pancreatic cancer tissue.

Aged↗

PubMed2004

Valosin-containing protein (p97) and Ki-67 expression is a useful marker in detecting malignant behavior of pancreatic endocrine neoplasms.

OBJECTIVE: To determine the prognostic value of valosin-containing protein (VCP) expression and the Ki-67 labeling index (LI) in pancreatic endocrine neoplasms (PENs), the present analysis was employed. METHODS: The Ki-67 LI and VCP expression at the mRNA and protein level were evaluated in 32 patients (12 male and 20 female) with PENs aged from 22 to 73 years (median 49 years). VCP staining intensity in tumor cells was categorized as weaker (level 1) or equal to stronger (level 2) compared to nontumorous islet cells. Ki-67 LI was divided into two categories: level 1, Ki-67 LI < 5%, and level 2, > or = 5%. RESULTS: Five cases (15.6%) showed level 1 and 25 (84.4%) level 2 VCP expression by immunohistochemistry. A significant association was observed between VCP expression and the malignant behavior of PENs (p < 0.01). All level 1 VCP tumors were benign PENs. Quantitative reverse transcription polymerase chain reaction analysis showed higher VCP mRNA expression in malignant PENs (n = 5) than benign cases (n = 5) (p < 0.05). For Ki-67 LI, 28 cases (87.5%) showed level 1 and 4 (12.5%) level 2 expression. All patients with level 2 Ki-67 LI had metastasis. CONCLUSION: VCP expression analysis and Ki-67 LI are useful prognosticators for PENs.

Adenosine Triphosphatases↗

PubMed2004

Increased expression of valosin-containing protein (p97) is associated with lymph node metastasis and prognosis of pancreatic ductal adenocarcinoma.

BACKGROUND: Valosin-containing protein (VCP, also known as p97) exhibits antiapoptotic function and metastasis by activation of nuclear factor kappa-B signaling pathway. Our previous study showed that VCP expression level correlated with prognosis of hepatocellular and gastric carcinoma. In the present study, association of VCP expression with lymph node metastasis and prognosis of pancreatic ductal adenocarcinoma (PDAC) was examined. METHODS: VCP expression in 83 patients (46 males and 37 females) of ages ranging from 43 to 80 (median, 66) years who had undergone curative surgery for primary PDAC was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker or equal to (low expression) or stronger (high expression) than that in noncancerous ductal tissue. RESULTS: Thirty-two tumors (38.6%) and 51 tumors (61.4%) were classified as low-VCP-expressing and high-VCP-expressing tumors, respectively. VCP expression correlated significantly with lymph node metastasis (P <.01) but not with various clinicopathologic factors, including age, gender, and histologic differentiation. Multivariate analysis revealed VCP expression as an independent prognosticator for both disease-free and overall survival, along with histologic differentiation, T stage of pathologic tumor-node-metastasis (pTNM) classification, and lymph node metastasis. Furthermore, VCP expression was a prognosticator for disease-free and overall survival in each relatively early stage (I or II) and advanced stage (III) group of pTNM classification. CONCLUSIONS: Our results indicate the potential usefulness of VCP expression as a marker of metastasis and overall prognosis of PDAC.

Adenosine Triphosphatases↗

PubMed2004

Expression level of valosin-containing protein (p97) is correlated with progression and prognosis of non-small-cell lung carcinoma.

BACKGROUND: Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptosis and metastasis via activation of a nuclear factor-kappaB signaling pathway. Our previous study showed that the VCP expression level correlated with the disease recurrence rate and prognosis of patients with hepatocellular carcinoma and gastric carcinoma. This study was designed to evaluate the prognostic significance of VCP expression in non-small-cell lung carcinoma (NSCLC). METHODS: VCP expression in 207 patients with NSCLC (133 men and 74 women) aged 35 to 78 years (median, 62 years) was examined by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker than (level 1) or equal to or stronger than (level 2) that in endothelial cells. RESULTS: Sixty-nine (33.8%) cases showed level 1 and 135 (66.2%) showed level 2 VCP expression. The frequency of the following was higher in patients with level 2 expression than in those with level 1 expression: male sex (P <.01), histological subtype of squamous cell carcinoma (P <.05), and smoking (P <.05). Patients with level 2 expression had poorer disease-free and overall survival rates (P <.05 and P <.01, respectively) than those with level 1 expression. Multivariate analysis revealed VCP expression and pathologic T (pT) and pN classifications to be independent prognostic factors for both disease-free and overall survival and showed vascular invasion to be an independent prognostic factor for overall survival. VCP level was a prognosticator for overall survival in both the early (pT1) and advanced (pT2-3) group of the pT classification (P <.05 for both). CONCLUSIONS: The prognostic significance of VCP expression in NSCLC was demonstrated.

Adenosine Triphosphatases↗

PubMed2004

Rapid genetic diagnosis with the transcription-reverse transcription concerted reaction system for cancer micrometastasis.

BACKGROUND: Detection of cancer micrometastases is required for improvement of cancer therapy. The aim of this study was to establish a rapid and practical genetic assay to detect micrometastasis in gastric cancer and to assess its clinical significance with respect to prognosis. METHODS: A novel RNA amplification system with transcription-reverse transcription concerted reaction (TRC) was introduced for quantitative detection of cancer-specific carcinoembryonic antigen messenger RNA. The sensitivity and quantitative aspects of the assay were assessed with the full-length carcinoembryonic antigen messenger RNA, a gastric cancer cell line (MKN-45), and metastatic lymph nodes obtained from patients with gastric cancer. Peritoneal lavage fluid specimens that were collected from gastric cancer surgery were subjected to the assay, and the clinical significance of the results was examined for prediction of recurrence and survival. RESULTS: The quantification, sensitivity, and reproducibility of the assay with the TRC reaction were equal to those of quantitative reverse transcriptase-polymerase chain reaction with LightCycler. The most important advantages of the assay were its simplicity and rapidity. Molecular diagnosis of peritoneal lavage fluid by the TRC reaction significantly correlated with depth of invasion, peritoneal metastasis, clinical stage, overall survival, and peritoneal recurrence-free survival. CONCLUSIONS: Molecular diagnosis of peritoneal lavage fluid with the TRC reaction could be a useful prognostic indicator for peritoneal recurrence and survival. Because the TRC reaction is more rapid and simpler than reverse transcriptase-polymerase chain reaction as a format for detecting RNA sequences, it may enhance the genetic diagnosis of cancer micrometastasis and may improve cancer therapy.

Biomarkers, Tumor↗

PubMed2004

Akt2 expression correlates with prognosis of human hepatocellular carcinoma.

Akt, a down-stream target of phosphatidylinositol-3 kinase, plays multiple roles in carcinogenesis. To elucidate its role in hepatocarcinogenesis, we immunohistochemically investigated the expression of Akt protein (Akt1 and Akt2) in tumor and non-tumor tissues from 56 patients with hepatocellular carcinoma (HCC). High expression of Akt2 in HCC tissues was detected in 21 cases (38%) while Akt1 expression was moderate or less in all cases. Low expression of Akt2 was associated with histopathological differentiation, portal invasion and number of tumor nodules (p=0.026, 0.023, and 0.001, respectively). Univariate analysis showed that Akt2, histopathological differentiation, and portal vein invasion were significant prognostic factors (p=0.001, 0.028, and 0.006, respectively). Multivariate analysis revealed that in addition to histopathological differentiation, Akt2 was an independent prognostic marker (risk ratio for cancer relapse, 6.35, p=0.012). In contrast, Akt1 expression did not correlate with any clinicopathological features. Our findings suggest that Akt2, but not Akt1, is a novel independent predictor for the development and progression of HCC.

Adult↗

PubMed2004

Antitumor effects of peroxisome proliferator activate receptor gamma ligands on anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma is an aggressive neoplasm and resistant to all sorts of treatment due to its rapid growth and invasive potential. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor modulating variety of biological properties, such as regulating of adipogenesis, inhibition of cancer cell proliferation or differentiation of tumor cells. The purpose of this study was to evaluate the possibility for the therapeutic effect of PPARgamma ligands against anaplastic thyroid tumor in vitro. Expressions of the PPARc gene and protein were examined in 5 human anaplastic carcinoma cell lines (MSA, IAA, ROA, K119 and KOA-2). We next evaluated the effects of PPARgamma ligands (Thiazolidinedione, Prostaglandin J2 and RS1303) on proliferation, differentiation, apoptosis and invasion. Five cell lines showed higher level of the PPARc gene and protein expression than papillary thyroid carcinoma. PPARgamma ligands inhibited cell proliferation by inducing apoptosis instead of differentiation in dose-dependent manner. PPARgamma ligands also down regulated the invasive potential of 5 cell lines. The inhibitory effect of proliferation or invasion was prominent in 3 cell lines, which exhibited higher expression level of the PPARc gene or protein. Our results indicated that PPARgamma ligands modify malignant potential of anaplastic carcinoma cell lines altering growth or invasive properties, suggesting that PPARgamma could be potentially the novel molecular target for human thyroid anaplastic carcinoma.

Antineoplastic Agents↗

PubMed2004

Clinical value of alterations in p73 gene, related to p53 at 1p36, in human hepatocellular carcinoma.

A novel gene, p73, encoding a protein with significant homology to p53 and showing functional similarities to p53, was identified at chromosome 1p36, at which tumor suppressor gene of hepatocellular carcinoma (HCC) is supposed to be. Involvement of p73 in hepatocarcinogenesis is controversial and clinical value of p73 alterations remains obscure. We investigated allelic status of p73 in 63 patients with HCC. Loss of heterozygosity (LOH) in p73 was analyzed by PCR-RFLP analysis. The results were compared with LOH on chromosome 1p surrounding p73 locus, mutations of p53 and p73, and clinicopathologic characteristics. LOH on p73 was observed in 33% of informative tumors. LOH in p73 was not always observed between the regions with LOH on chromosome 1p examined despite the significant association of LOH in p73 with LOH on chromosome 1p. No mutations were detected in p73. Tumors with LOH in p73 were more frequently detected in liver without cirrhosis than that with cirrhosis. There was no significant statistic association between the presence of LOH in p73 and six different clinicopathologic characteristics such as age, sex, histological type, T stage, tumor diameter, and virus status. Disease-free survival rates of the patients with LOH in p73 were significantly poorer than those without LOH in p73. Multivariate analysis indicated that presence of LOH in p73 was independent prognostic factor in patients with HCC. These findings suggested that p73 might play some role in tumor progression of HCC even though p73 should not be considered a candidate gene on chromosome 1p of HCC and does not function as a tumor suppressor gene like p53. Identifying the patients with LOH of p73 in tumors could be useful to predict early recurrence and to stratify the patients who need adjuvant therapy after operation.

Adult↗