Determination of the best surgical strategy for thoracic esophageal resection concurrent with double aortic arch using a three-dimensional model: a case report.

Background: A double aortic arch (DAA) is a relatively rare vascular malformation, which rarely causes problems once the patients reach adulthood. However, a DAA makes an esophageal cancer surgery difficult to perform, especially during upper mediastinal dissection. Herein, we report a strategy for surgery in esophageal cancer patients concurrent with DAA. Case Description: A 73-year-old man was diagnosed with middle thoracic esophageal cancer of cT3N4M0 stage III (UICC-TNM 7th) concurrent with DAA. After two courses of neoadjuvant chemotherapy, surgical intervention was planned. To develop a surgical strategy for an esophagectomy with this complicated malformation, we created a three-dimensional printer model for this case. According to this simulation, the bilateral thoracoscopic approach with prone position seemed to be an ideal method for upper mediastinal dissection. As we expected, the dissection of upper mediastinum was difficult only with the right-side approach; especially, the oral side of esophagus posterior to the right aortic arch (RAA) was impossible to dissect from the right side. By switching the approach from left side, oral esophagus was easily dissected by retracting the oral esophagus from the cranial side of the left aortic arch (LAA). Surgery was successfully performed, and the patient was discharged 26 days after surgery without major complications. Conclusions: To the best of our knowledge, this is the first surgical report using a three-dimensional printer for esophageal cancer. The bilateral approach is appropriate for esophageal cancer surgery concurrent with a DAA. A three-dimensional printer is useful for simulating esophageal surgery with major vascular malformations.

Risk for cardiovascular disease in Japanese patients with rheumatoid arthritis: a large-scale epidemiological study using a healthcare database.

OBJECTIVES: To study risk for cardiovascular disease (CVD) in Japanese patients with rheumatoid arthritis (RA). METHODS: We used a Medical Data Vision database mainly composed of health insurance claim data and diagnosis-procedure combination data from Japan. Patients with RA diagnosed from April 2011 to March 2014 at 71 hospitals were identified with the International Classification of Diseases 10th revision (ICD-10) and history of anti-RA drug prescription. Hospitalizations for CVD including ischemic heart disease, heart failure, and stroke were identified by a combination of diagnosis (ICD-10) and diagnostic procedures. CVD incidence rate ratio (IRR) for RA versus osteoarthritis was calculated. Risk factors were analyzed using univariate and multivariate Cox proportional hazard models with baseline C-reactive protein (CRP) and traditional risk factors as covariates. RESULTS: We identified 8658 patients with RA. The age-sex adjusted IRR for RA versus osteoarthritis was high for total CVD [2.12; 95 % confidence interval (CI) 1.93-2.32], ischemic heart disease (2.16; 95 % CI 1.86-2.50), heart failure (2.34; 95 % CI 2.07-2.65), and stroke (1.68; 95 % CI 1.41-2.00). Risk factor analysis showed a tendency for cardiovascular risk to increase with higher baseline CRP, although the difference was not statistically significant (hazard ratio 1.43; 95 % CI 0.99-2.07). CONCLUSION: Our study indicates an increased risk for CVD and an association between systemic inflammation and CVD in Japanese RA patients.

[A case report of undifferentiated carcinoma of the sigmoid colon with rhabdoid features].

A 45-year-old woman with persistent abdominal pain was admitted to our hospital. Detailed examination revealed a type 4 lesion with circumferential narrowing, which was diagnosed as a poorly differentiated carcinoma following forceps biopsy and ascitic fluid cytology. Although the lesion was surgically resected, the ascites increased rapidly, and her general condition deteriorated in the postoperative period. She died 6 weeks after the appearance of her symptoms. Autopsy and histological examination confirmed a very rare undifferentiated colon carcinoma with rhabdoid features, which is a high-grade malignant lesion associated with a poor prognosis.

Downregulation of uPARAP mediates cytoskeletal rearrangements and decreases invasion and migration properties in glioma cells.

To identify molecular therapeutic targets for glioma, we performed gene expression profiling by using a complementary DNA (cDNA) microarray method and identified the urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180) as a gene expressed highly in glioma tissue compared with the normal brain tissue. The uPARAP is an endocytic receptor for collagen. In certain cell types, uPARAP occurs in a complex with the urokinase plasminogen activator receptor (uPAR) where it fulfills other functions in addition to collagenolysis. Quantitative PCR analysis using a cDNA panel revealed higher expression levels of uPARAP in glioma tissue compared with normal brain tissue. Western blot analysis revealed that the uPARAP protein was expressed in glioma samples and two glioma cell lines, KNS42 and KNS81, but not expressed in control tissue from the normal brain. Introduction of small interfering RNA-targeted uPARAP into the two different glioma cell lines, KNS42 and KNS81, resulted in downregulation of uPARAP expression, and it significantly suppressed glioma cell migration and invasion in vitro. Control glioma cells showed small cell bodies, whereas uPARAP siRNA-treated glioma cells exhibited large and flat morphology. Most of the polymeric actin in the control glioma cells was concentrated in the lamellipodia that are observed in mobile cells. In contrast, in the uPARAP siRNA-treated glioma cells, polymeric actin became organized in stress fibers and the lamellipodia disappeared, characteristic of immobile cells. Our present study suggests that uPARAP may be involved in glioma cell invasiveness through actin cytoskeletal rearrangement. downregulation of uPARAP may be a novel anti-invasion therapeutic strategy for malignant gliomas.

Induction chemoradiotherapy followed by surgery for locally advanced non-small cell lung cancer.

We examined the efficacy and toxicity of a divided schedule of cisplatin and vinorelbine with concurrent radiotherapy followed by surgery in patients with locally advanced non-small cell lung cancer (NSCLC). Patients with clinical stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Patients were treated with cisplatin (40 mg/m2) and vinorelbine (20 mg/m2) on days 1 and 8 every 3 weeks. Thoracic radiotherapy (2 Gy per fraction; total dose, 40 Gy) was given concurrently. Surgical resection was performed after induction therapy had been completed. If disease was considered clinically inoperable after induction therapy, patients received 2 additional cycles of the chemotherapy and 20 Gy of additional radiotherapy. Twenty-three patients (20 men and 3 women; median age, 63 years; age range, 45-72 years) were enrolled. The overall response rate was 78.3%. Although grade 3-4 toxicities included neutropenia in 95.7% of patients and anemia in 39.1%, no grade 3-4 radiation pneumonitis or esophagitis occurred. Thirteen patients (56.5%) underwent thoracotomy and complete resection. There were no treatment-related deaths. The median survival time was 36 months (range, 4-78 months), the 2-year survival rate was 74%, and the median time to disease progression was 15 months (range, 2-59 months). This trimodality therapy is effective and well tolerated and is an acceptable therapeutic option for patients with locally advanced NSCLC.

A case of intimal sarcoma of the pulmonary artery treated with chemoradiotherapy.

We report on a 45-year-old woman with intimal sarcoma of the pulmonary artery. She presented with a chief complaint of shortness of breath. Computed tomography (CT) of the chest showed an intraluminal hypoattenuated area extending from the main pulmonary artery into the right main pulmonary artery and bilateral lobar pulmonary arteries. She underwent resection of the lobulated mass from the pulmonary artery. The tumor was diagnosed as an intimal sarcoma. Although she received chemotherapy with amrubicin and carboplatin when the tumor recurred, the tumor enlarged. After radiotherapy was performed, CT of the chest showed shrinkage of the tumor and the regression of consolidation and ground-glass opacity. Radiotherapy and chemotherapy are treatment option for patients with pulmonary artery sarcoma.

[Improvement of body diffusion image using addition technique].

It is difficult to obtain body diffusion weighted images (BDWI) using MRI that does not support parallel imaging and multi-NEX in clinical usage. Therefore, we evaluated whether a multiple image additions technique on the workstation could improve BDWI image quality and be good for clinical use by considering SNR and image distortion. We added 2 to 5 images on the same slice location with changing FOV, slice thickness, or reconstruction matrix in the phantom studies, and confirmed SNR improvement under all conditions. We also confirmed that this addition technique did not affect image distortion. We found that in 16 of the 18 clinical cases, BDWI with 5 images addition match pathology and T2 weighted images. We believe that this addition technique in available in the clinical practice.

Liver metastasis models of colon cancer for evaluation of drug efficacy using NOD/Shi-scid IL2Rgammanull (NOG) mice.

To examine the drug efficacy of a novel farnesyltransferase inhibitor (FTI), CH4512600, in vivo, we developed a reliable liver metastasis model of human colon cancer using NOD/Shi-scid IL2Rgamma(null) (NOG) mice. Eleven human colon cancer cell lines were examined for their ability to form diverse metastatic foci in the livers of NOG mice. When inoculated with 10(4) COLO320DM, HCT 116, HT-29, WiDr, LoVo and LS174T cells, liver metastasis was evident in 100% (6/6), 100% (6/6), 88.9% (8/9), 87.5% (7/8), 83.3% (5/6) and 50.0% (3/6) of the NOG mice, respectively. CaCo2, COLO201, LS123, SW48 and SW1417 showed no metastasis when seeded at 10(4) cells even in NOG mice. The mRNA expression levels and genetic mutations of N, H and K-RAS genes, which directly affect the levels of cellular RAS protein that would be molecular target for FTI, were also examined in these six metastatic human colon cancer cell lines for molecular biological and genotypic characteristics. Only three cell lines had a point mutation in the RAS oncogene. LS174T cell line had a point mutation of the K-RAS gene at codon 12 (gly12 --> asp; G12D), and HCT 116 and LoVo cell lines had a point mutation of the K-RAS gene at codon 13 (gly13 --> asp; G13D). Relative gene expression levels of N, H and K-RAS genes in the HCT 116 cell line were 2.6-5.0-fold lower than that of LS174T and LoVo cell lines. We selected HCT 116 cell line from our liver metastasis model for evaluation of FTI CH4512600 efficacy in vivo. Using the NOG mouse liver metastasis model, we demonstrated the effectiveness of FTI CH4512600 to suppress tumor growth in vivo and to prolong mouse survival significantly from 36.9+/-2.9 to 50.3+/-9.4 days.

Identification of a neuron-specific human gene, KIAA1110, that is a guanine nucleotide exchange factor for ARF1.

To identify neuron-specific genes, we performed gene expression profiling, cDNA microarray and in silico ESTs (expressed sequence tags) analyses. We identified a human neuron-specific gene, KIAA1110 (homologue of rat synArfGEF (Po)), that is a member of the guanine nucleotide exchange factor (GEF) for the ADP-ribosylation factor (ARF). RT-PCR analysis showed that the KIAA1110 gene was expressed specifically in the brain among adult human tissues, whereas no apparent expression was observed in immature neural tissues/cells, such as fetal brain, glioma tissues/cells, and neural stem/precursor cells (NSPCs). The KIAA1110 protein was shown to be expressed in mature neurons but not in undifferentiated NSPCs. Immunohistochemical analysis also showed that KIAA1110 was expressed in neurons of the human adult cerebral cortex. Furthermore, the pull-down assay revealed that KIAA1110 has a GEF activity toward ARF1 that regulates transport along the secretion pathway. These results suggest that KIAA1110 is expressed specifically in mature neurons and may play an important role in the secretion pathway as a GEF for ARF1.

Growth regulation via insulin-like growth factor binding protein-4 and -2 in association with mutant K-ras in lung epithelia.

Gain-of-function point mutations in K-ras affect early events in pulmonary bronchioloalveolar carcinoma. We investigated altered mRNA expression on K-Ras activation in human peripheral lung epithelial cells (HPL1A) using oligonucleotide microarrays. Mutated K-Ras stably expressed in HPL1A accelerated cell growth and induced the expression of insulin-like growth factor (IGF)-binding protein (IGFBP)-4 and IGFBP-2, which modulate cell growth via IGF. Other lung epithelial cell lines (NHBE and HPL1D) revealed the same phenomena as HPL1A by mutated K-ras transgene. Lung cancer cell growth was also accelerated by mutated K-ras gene transduction, whereas IGFBP-4/2 induction was weaker compared with mutated K-Ras-expressing lung epithelial cells. To understand the differences in IGFBP-4/2 inducibility via K-Ras-activated signaling between nonneoplastic lung epithelia and lung carcinoma, we addressed the mechanisms of IGFBP-4/2 transcriptional activation. Our results revealed that Egr-1, which is induced on activation of Ras-mitogen-activated protein kinase signaling, is crucial for transactivation of IGFBP-4/2. Furthermore, IGFBP-4 and IGFBP-2 promoters were often hypermethylated in lung carcinoma, yielding low basal expression/weak induction of IGFBP-4/2. These findings suggest that continuous K-Ras activation accelerates cell growth and evokes a feedback system through IGFBP-4/2 to prevent excessive growth. Moreover, this growth regulation is disrupted in lung cancers because of promoter hypermethylation of IGFBP-4/2 genes.

Esophageal squamous cell carcinomas with distinct invasive depth show different gene expression profiles associated with lymph node metastasis.

We examined the gene expression profiles of esophageal squamous cell carcinomas (ESCCs) with respect to degree of invasive depth and lymph node (LN) involvement in a large cohort. We used high-density oligonucleotide microarrays to examine the expression of 22,115 genes in 54 ESCCs and 11 non-cancerous esophageal tissues. We found that 4,155 genes were biologically significant in both ESCC and non-cancerous esophageal tissue by analysis of Present Call (hybridization quality by Affymetrix) throughout all samples. From these genes, we used a supervised learning method to select genes responsible for the development of ESCC. We found that 999 genes were expressed differentially in pT1/pN0 tumors vs. non-cancerous esophageal tissue. In the same manner, 48, 66 and 30 genes were expressed differentially in pT1/pN0 tumors vs. pT1/pN1 tumors, pT1/pN0 tumors vs. pT2-4/pN0 tumors and pT2-4/pN0 tumors vs. pT2-4/pN1 tumors, respectively. Intriguingly, there were no overlaps between the 48 LN metastasis-related genes of pT1 tumors and the 30 LN metastasis-related genes of pT2-4 tumors, suggesting that ESCCs with distinct invasive depths express different genes linked to LN metastasis. Our present results suggest that the degree of invasive depth must be considered when predicting LN metastasis of ESCC from gene expression profiles.

Patterns of expression of cytochrome P450 genes in progression of hepatitis C virus-associated hepatocellular carcinoma.

Cytochrome P450 (CYP) genes are involved in the pathogenesis of hepatocellular carcinoma (HCC). To examine changes in expression of CYPs in HCC arising from hepatitis C virus (HCV)-infected liver, we used oligonucleotide array data of 27 CYPs from samples of 50 HCV-associated HCCs, five HCV-infected non-tumorous livers, and six HCV-negative normal livers. Progression of primary HCC can be characterized by decrease in the grade of tumor differentiation, increased frequency of venous invasion and increased tumor size. On the basis of tumor differentiation, the self-organizing map (SOM) classified the 27 CYPs into four groups. The first group contained 11 CYPs, including the CYP2C and CYP4F families, that showed decreased expression in parallel with progression of HCV-infected liver to HCC with less differentiation. The second group contained CYP-IID, CYP3A7 and CYP27A1, genes that showed high levels of expression specific to well differentiated HCC. The third group contained 5 sterol-metabolizing CYPs with levels lower in HCV-infected livers than in HCV-uninfected livers. The last group included the CYP2E1 and CYP3A families. Among the 27 CYPs, levels of 7 (CYP2B6, CYP-IIC, CYP2C9, CYP2C19, CYP3A5, CYP4F3 and CYP27A1) were significantly lower and levels of 2 (CYP2E1 and CYP4F2) were slightly lower in HCC with venous invasion than in HCC without venous invasion. Levels of CYP-IIC and CYP2C9 were inversely associated with tumor size. In contrast, levels of CYP51A1 were positively associated with tumor size. Our present study revealed that expression of specific CYPs was altered in conjunction with progression of HCV-associated HCC. These CYPs may serve as markers of progression and molecular targets for treatment of HCV-associated HCC.

Self-organizing-map-based molecular signature representing the development of hepatocellular carcinoma.

Using high-density oligonucleotide array, we comprehensively analyzed expression levels of 12600 genes in 50 hepatocellular carcinoma (HCC) samples with positive hepatitis C virus (HCV) serology (well (G1), moderately (G2), and poorly (G3) differentiated tumors) and 11 non-tumorous livers (L1 and L0) with and without HCV infection. We searched for discriminatory genes of transition (L0 vs. L1, L1 vs. G1, G1 vs. G2, G2 vs. G3) with a supervised learning method, and then arranged the samples by self-organizing map (SOM) with the discriminatory gene sets. The SOM arranged the five clusters on a unique sigmoidal curve in the order L0, L1, G1, G2, and G3. The sample arrangement reproduced development-related features of HCC such as p53 abnormality. Strikingly, G2 tumors without venous invasion were located closer to the G1 cluster, and most G2 tumors with venous invasion were located closer to the G3 cluster (P=0.001 by Fisher's exact test). Our present profiling data will serve as a framework to understand the relation between the development and dedifferentiation of HCC.

Gene expression analysis of renal carcinoma: adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma.

The gene expression profiles of 33 renal cell carcinomas (RCCs) and nine normal kidney samples were examined using high-density oligonucleotide microarrays in an attempt to identify biomolecular markers for the diagnosis of tumour subtypes and also for prediction of prognosis. Hierarchical clustering demonstrated that clear-cell RCC, chromophobe RCC, and normal kidney tissue showed distinctive gene expression profiles. The mean expression levels of 149 of 12 500 genes were more than three times higher in clear-cell RCC than in chromophobe RCC and normal kidney tissue. Among the genes whose expression was upregulated in clear-cell RCC, adipose differentiation-related protein (ADFP) and nicotinamide N-methyltransferase (NNMT) were selected for further analysis. Consistent with the results of the microarray, increased levels of ADFP and NNMT mRNA were found more frequently in clear-cell RCCs than in other non-clear-cell tumour subtypes using real-time quantitative PCR. Immunohistochemistry for ADFP showed strong and unique tumour cell staining patterns in the majority of clear-cell RCCs. More importantly, patients bearing tumours with higher AFDP mRNA levels showed significantly better survival in both univariate and multivariate analyses. ADFP is a lipid storage droplet-associated protein and its transcription is considered to be regulated by the von Hippel-Lindau/hypoxia-inducible factor pathway. It is known that clear-cell RCC contains abundant lipids and cholesterols. Thus it is likely that sustained upregulation of ADFP following VHL inactivation is involved in the morphological appearance of clear-cell RCC. Moreover ADFP expression status may provide useful prognostic information as a biomolecular marker in patients with clear-cell RCC.

Sex-based molecular profiling of hepatitis C virus-related hepatocellular carcinoma.

It has been suggested that sex affects not only the incidence of hepatocellular carcinoma (HCC) but also the outcome after treatment. However, no sex-specific therapeutic targets for HCC have been identified. Identification of sex-specific genes will allow for the development of more personalized therapies. To this end, we investigated the expression of approximately 6000 genes in 50 samples of hepatitis C virus (HCV)-related HCC by oligonucleotide microarray. Our supervised learning method and subsequent random permutation test identified 27 genes that were differentially expressed in samples from male (n=34) and female (n=16) patients. Our gene selection was validated by a false discovery rate of only 0.5%. For the 27 genes, expression levels of 12 were higher and expression levels of 15 were lower in HCC samples from men than in HCC samples from women. For the cell proliferation-related genes identified, expression levels of PRDX1 were relatively high in HCC samples from men, and expression levels of PRDX3 were relatively high in HCC samples from women. The DNA microarray data for PRDX1 and PRDX3 were reproduced by reverse transcription-PCR analysis. Our results suggest that these 27 genes may serve as molecular targets or markers for sex-specific treatment of HCV-related HCC. Further studies are needed to elucidate their possible roles in male and female patients with HCV-related HCC.

Neuroserpin (PI-12) is upregulated in high-grade prostate cancer and is associated with survival.

We carried out Genechip analysis using prostate cancer and non-malignant tissue to identify specific genes related to prostate cancer. We focused on neuroserpin (PI-12), which has been identified as one of the genes with high expression in prostate cancer. We analyzed the relationship between its expression pattern and clinical characteristics. Prostate cancer and normal prostate tissue were analyzed by Affymetrix GeneChip technology. We carried out real-time quantitative PCR on a total of 102 specimens: 45 of normal prostate, 45 of previously untreated prostate cancer (constituting 45 pairs of samples obtained at radical prostatectomy, with each pair dissected from the same prostate specimen) and 12 of recurrent hormone refractory prostate cancer (HRPC). Results showed that the neuroserpin gene was more highly expressed in prostate cancer than in normal prostate tissue. Neuroserpin expression in untreated prostate cancer was significantly higher than that in normal prostate. In HRPC it was significantly higher than that in untreated prostate cancer and normal prostate. In untreated prostate cancer, neuroserpin expression was significantly higher in high grade tumors such as poorly differentiated adenocarcinoma than in lower grade tumors such as well or moderately differentiated adenocarcinoma. Higher neuroserpin expression was associated with shorter recurrence-free survival after radical prostatectomy, shorter recurrence-free survival in HRPC patients and shorter overall survival in HRPC patients. The neuroserpin gene may be associated with the development, progression and aggressiveness of prostate cancer. Our present data suggests that higher neuroserpin expression may predict an unfavorable outcome after radical prostatectomy or hormone therapy.

Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia.

Adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type 1 (HTLV-1) infection, occurs in 2% to 4% of the HTLV-1 carriers with a long latent period, suggesting that additional alterations participate in the development of ATL. To characterize and identify novel markers of ATL, we examined the expression profiles of more than 12 000 genes in 8 cases of acute-type ATL using microarray. One hundred ninety-two genes containing interleukin 2 (IL-2) receptor alpha were up-regulated more than 2-fold compared with CD4(+) and CD4(+)CD45RO(+) T cells, and tumor suppressor in lung cancer 1 (TSLC1), caveolin 1, and prostaglandin D2 synthase showed increased expression of more than 30-fold. TSLC1 is a cell adhesion molecule originally identified as a tumor suppressor in the lung but lacks its expression in normal or activated T cells. We confirmed ectopic expression of the TSLC1 in all acute-type ATL cells and in 7 of 10 ATL- or HTLV-1-infected T-cell lines. Introduction of TSLC1 into a human ATL cell line ED enhanced both self-aggregation and adhesion ability to vascular endothelial cells. These results suggested that the ectopic expression of TSLC1 could provide a novel marker for acute-type ATL and may participate in tissue invasion, a characteristic feature of the malignant ATL cells.

Molecular signature in three types of hepatocellular carcinoma with different viral origin by oligonucleotide microarray.

Chronic infection with hepatitis B or C virus (HBV or HCV) is the most clearly established risk factor for hepato-cellular carcinoma (HCC). One type of HCC (non-B, non-C HCC) also appears to develop in patients negative for both HBV and HCV. Using a supervised learning method, we investigated gene expression in 11 non-B, non-C HCCs with high-density oligonucleotide microarrays, and compared the patterns of gene expression with those of HBV-infected HCCs (B-type HCCs) and HCV-infected HCCs (C-type HCCs) in the previous dataset. Our gene selection identified 112 and 64 genes that were differentially expressed in non-B, non-C HCC in comparison with B- and C-type HCCs, respectively. In both gene selections, we found that the false discovery rate, the percentage of genes identified by chance, was less than 5%. Additionally, in combination with the previous data, our present data revealed a set of genes specific to each type of B- and C-type HCCs and non-B, non-C HCC. Among these, an interferon-induced gene, IFI27, was differentially expressed among all three types of HCCs, and this result was confirmed by RT-PCR. Thus, our present study provides a framework to characterize the molecular features in the three subtypes of HCC with different viral origin.

Altered Levels of Cytochrome P450 Genes in Hepatitis B or C Virus-infected Liver Identified by Oligonucleotide Microarray.

BACKGROUND: Molecular pathogenesis of hepatocellular carcinoma (HCC) remains to be clarified. Many studies with DNA chip technology have revealed altered levels of several cytochrome P450 (CYP) family genes in human HCC. However, little is known about their alterations in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected livers. MATERIALS AND METHODS: We here used high-density oligonucleotide arrays to evaluate alterations of CYP genes in five of each HBV- or HCV-infected livers in comparison with six normal livers. We extracted the data of 32 CYP genes from those of 12600 genes. RESULTS: Among these 32 CYPs, expression levels of four genes were insignificant. The expressions of CYP1B1 and CYP3A7 were up-regulated, whereas the expressions of 12 other CYPs, including CYP2A6, CYP2A7 and CYP2C19, were down-regulated in HBV- and/or HCV-infected livers compared with normal livers. CONCLUSION: These data will allow us to better understand the roles of CYPs in the pathogenesis of HBV- and HCV-related HCCs.

Increased Expression of the Genes for Mitotic Spindle Assembly and Chromosome Segregation in Both Lung and Pancreatic Carcinomas.

Genes whose expression was modulated in two different tumor types, lung or pancreatic carcinoma, were identified by DNA microarray and subsequent expression correlation analyses. For more accurate comparison of the gene expression between tumor and normal cells, tumor cells and normal epithelium cells were isolated by laser-captured microdissection. Genes whose expression was significantly altered in lung carcinomas or pancreatic carcinomas as compared to their normal counterparts were ranked by the T-values calculated from the Fisher's ratios and their corresponding background Fisher's ratios, followed by statistical confirmation using the Welch's t-test. Among the genes that were ranked in the top 150, either in lung carcinomas or pancreatic carcinomas, expressions of MAD2, BUB1, BUB1B, HEC, CENPE, ZWINT, KNSL1, SMC4, CCNB, TK and PMS2L6 were found to be significantly up-regulated in both tumor types. Interestingly, 8 of the above 11 genes code for the proteins involved in the mitotic spindle assembly and chromosome segregation. Furthermore, the search for genes whose expression correlated with one of the above 5 genes yielded additional genes that are also considered to be involved in mitotic spindle assembly and chromosome segregation. Thus, increased expression of the genes for mitotic spindle assembly and chromosome segregation are a common feature of at least lung carcinomas and pancreatic carcinomas and, therefore, such genes may be potential targets for widely effective anticancer agents.