Microarray reveals differences in both tumors and vascular specific gene expression in de novo CD5+ and CD5- diffuse large B-cell lymphomas

Malignant lymphoma is a heterogeneous disease with different clinical features. Among diffuse large B-cell lymphomas (DLBCLs), a unique subtype has been identified recently based on cell surface marker CD5 and clinicopathological features. These de novo CD5(+) DLBCLs account for approximately 10% of all of the DLBCLs and have poorer prognosis. To additionally understand this subtype of DLBCLs at the molecular level and to find genes that are differentially expressed in de novo CD5(+) DLBCLs, CD5(-) DLBCLs, and mantle cell lymphomas, which also have poor prognosis, we performed gene expression profiling using cDNA microarray technology. Data from a total of 9 samples of CD5(-) DLBCLs, 11 samples of de novo CD5(+) DLBCLs, and 10 samples of mantle cell lymphomas were acquired. A series of genes were identified that distinguish these three types of lymphomas. Among DLBCL cases, integrin beta1 and/or CD36 adhesion molecules were overexpressed in most cases of CD5(+) DLBCL. An immunohistochemical confirmation study revealed that integrin beta1 was expressed on lymphoma cells, which may account for the high extranodal involvement and poor prognosis of CD5(+) DLBCLs. In contrast, CD36 was overexpressed on vascular endothelia in CD5(+) DLBCLs, although there was no difference in vascularity detected by von Wilbrand factor antibody between CD5(+) and CD5(-) DLBCLs. Those results suggest that CD5(+) and CD5(-) DLBCLs have different gene expression signatures in both tumor cells and their vascular systems.     

Reduced expression of GNA11 and silencing of MCT1 in human breast cancers

Alteration in the methylation status of a gene is often associated with its altered expression. Based on a genome scanning technique for differences in CpG methylations, methylation-sensitive representational difference analysis, DNA fragments hypermethylated in a human breast cancer were isolated. A DNA fragment was isolated from intron 1 of guanine-nucleotide-binding protein alpha-11 (GNA11). mRNA expression of GNA11 was shown to be decreased in 10 of 16 breast cancers by RT-PCR analysis, and the immunoreactivity of the GNA11 product, Galpha11 subunit of heterotrimeric G-protein, was observed to be reduced in 14 of the 16 cancers by immunohistochemistry. Methylation of a CpG island (CGI) in the 5' region of GNA11 or that of intron 1 did not show a clear correlation with its decreased expression. Another DNA fragment was isolated from a CGI in the 5' upstream region of monocarboxylate transporter 1 (MCT1), and was methylated in 4 of 20 breast cancers. The CGI was also methylated in a human breast cancer cell line, MDA-MB-231, and quantitative RT-PCR showed that its expression was almost lost in the cell line. By treatment of the cells with a demethylating agent, 5-aza-2'-deoxycytidine, the methylation was removed and the expression was restored. GNA11 is involved in signalling of gonadotropin-releasing hormone receptor, which negatively regulates cell growth. MCT1 is involved in cellular transportation of butyrate, which induces cellular differentiation. Downregulation of these two genes was suggested to be involved in human breast cancers.     

Past medical history and risk of death due to hepatocellular carcinoma, univariate analysis of JACC study data

The relationship between the past history of selected diseases and the risk of dying from hepatocellular carcinoma (HCC) was analyzed using 110,792 cohort members (46,465 males and 64,327 females) recruited between 1988 and 1990 by the JACC Study (the Japan Collaborative Cohort Study for Evaluation of Cancer Risk). Significantly elevated hazard ratios (HRs) were observed in both genders for the past history of kidney diseases, liver diseases, gallstones or cholecystitis, diabetes mellitus, and blood transfusion. Further, when analyzed by age group (those 40-59 years of age were "younger" and those 60-79 years of age were "older"), although the significant associations were generally maintained, the magnitude of the HRs for liver diseases and diabetes mellitus seemed to be considerably different between the younger and older age groups for male cohort members. When the analyses were limited to cohort members without the past history of liver diseases, the past histories which had significantly elevated HRs were hypertension (HR = 3.14, 95% confidence interval (CI): 1.25-7.89), diabetes mellitus (HR = 4.17, 95% CI: 1.22-14.25), and blood transfusion (HR = 7.69, 95% CI: 3.09-19.15) in the younger male age group and gallstone or cholecystitis (HR = 2.58, 95% CI: 1.11-5.98) in the older male age group. On the other hand, for females, the significantly elevated HRs were gastric or duodenal ulcer (HR = 4.33, 95% CI: 1.09-17.25) in the younger age group and diabetes mellitus (HR = 6.16, 95%CI: 2.25-16.90) and blood transfusion (HR = 3.86, 95%CI: 1.58-9.41) in the older age group. However, since the evidence from our univariate analyses might not be decisive, multivariate Cox proportional hazards models controlling for potential confounders and effect modifiers will be required to obtain more valid or unbiased hazard ratios.     

Histological and Genetic Diagnosis of Gliomatosis Cerebri: Case Report

Gliomatosis cerebri is considered grade III astrocytoma because of the short survival period of patients with this tumor, while the tumor histologically consists of widespread low grade astrocytoma cells. The authors tried to clarify this discrepancy by applying genetic analysis of the tumor. A 29-year-old man originally presented with mild headache and showed diffuse high intensity areas in both hemispheres and in the cerebellum by T2-weighted magnetic resonance imaging (MRI) without gadolinium-dimeglumine (Gd)-enhancement in T1-weighted imaging. Histological diagnosis was gliomatosis cerebri with diffuse grade II astrocytoma. Seven months after temporary improvement following irradiation and chemotherapy, he developed progressive mental deterioration, and died in one year after the surgery. At this time T1-weighted imaging showed Gd-enhanced lesions with enlargement only of the cerebellar tumor. Genetic analysis demonstrated positive FGFR 1 and less FGFR 2 mRNA in the tumor tissue, and FGFR 1 mRNA was type dominant. These results indicated that the genetic features of this tumor are similar to those of glioblastoma multiforme concerning FGFR expression. The authors conclude that genetic investigation of the tumor tissue is required to predict the prognosis of gliomatosis cerebri patients, in addition to imaging and histological examinations.     

Molecular analysis of G3 rotavirus among infants and children in Dhaka City, Bangladesh after 1993

Between 2004 and 2005, 917 fecal specimens were collected from children below age 5 who presented to Child Health Institute for treatment of diarrhoea in Dhaka City, Bangladesh. The specimens were screened by RT-PCR for the presence of group A rotavirus and positive stools genotyped. Group A rotavirus was detected in 307 stools and serotype G3P[8] strains were detected in nine specimens. Sequence analysis clustered the G3 strains into one distinct lineage (lineage I) with other Asian G3 strains. In addition, one amino acid change at position 96 in antigenic region A, similar to lineage II G3 Chinese strains, was noted. To our knowledge this is the first report of serotype G3 strains in Bangladesh since 1993 and the first report of the molecular characterization of these strains.     

A Receptor-Independent Effect of Estrone Sulfate on the hERG Channel

We recently reported that physiological concentrations of 17β-estradiol partially down-regulate cardiac rapidly-activating delayed rectifier K⁺ currents (hERG currents) independently of estrogen-receptor signaling. To determine if other estrogens have the same effect as that of 17β-estradiol, we investigated receptor-independent effects of estrone, estrone 3-sulfate, and estriol on hERG currents in patch-clamped estrogen-negative HEK293 cells. Only estrone 3-sulfate partially suppressed hERG currents in a receptor-independent manner by modifying the gating. The concentration-dependence of estrone 3-sulfate revealed that physiological levels of circulating estrone 3-sulfate can modulate hERG currents to the maximal extent in both women and men at any age.     

A case of endocrine carcinoma of the sigmoid colon]

We report a case of endocrine carcinoma of the sigmoid colon. A 71-year-old man was admitted to our hospital because of constipation and bloody stool. Colonoscopy showed a mass lesion with irregular ulceration in the sigmoid colon. He was given a diagnosis of the poorly differentiated adenocarcinoma of the colon, and underwent sigmoidectomy with dissection of the lymph nodes. Histological and immunohistochemical examinations of the resected specimen revealed endocrine carcinoma. Endocrine carcinoma of the colon is rare, and the prognosis is very poor. We discuss this case with references.