Agricultural Pesticide Use and Risk of t(14;18)-Defined Subtypes of Non-Hodgkin Lymphoma

Pesticides have been specifically associated with the t(14;18)(q32;q21) chromosomal translocation. To investigate whether the association between pesticides and risk of non-Hodgkin lymphoma (NHL) differs for molecular subtypes of NHL defined by t(14; 18) status, we obtained 175 tumor blocks from case subjects in a population-based case-control study conducted in Nebraska between 1983 and 1986. The t(14;18) was determined by interphase fluorescence in situ hybridization in 172 of 175 tumor blocks. We compared exposures to insecticides, herbicides, fungicides, and fumigants in 65 t(14;18)-positive and 107 t(14;18)-negative case subjects with those among 1432 control subjects. Multivariate polytomous logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Compared with farmers who never used pesticides, the risk of t(14;18)-positive NHL was significantly elevated among farmers who used animal insecticides (OR = 2.6; 95%CI, 1.0-6.9), crop insecticides (OR = 3.0; 95% CI, 1.1-8.2), herbicides (OR = 2.9; 95% CI, 1.1-7.9), and fumigants (OR = 5.0; 95% CI, 1.7-14.5). None of these pesticides were associated with t(14;18)-negative NHL. The risk of t(14;18)-positive NHL associated with insecticides and herbicides increased with longer duration of use. We conclude that insecticides, herbicides, and fumigants were associated with risk of t(14;18)-positive NHL but not t(14;18)-negative NHL. These results suggest that defining subsets of NHL according to t(14;18) status is a useful approach for etiologic research. (Blood. 2006; 108:1363-1369

ADA3 regulates normal and tumor mammary epithelial cell proliferation through c-MYC

Background: We have established the critical role of ADA3 as a coactivator of estrogen receptor (ER), as well as its role in cell cycle progression. Furthermore, we showed that ADA3 is predominantly nuclear in mammary epithelium, and in ER+, but is cytoplasmic in ER- breast cancers, the latter correlating with poor survival. However, the role of nuclear ADA3 in human mammary epithelial cells (hMECs), and in ER+ breast cancer cells, as well as the importance of ADA3 expression in relation to patient prognosis and survival in ER+ breast cancer have remained uncharacterized.Methods: We overexpressed ADA3 in hMECs or in ER+ breast cancer cells and assessed the effect on cell proliferation. The expression of ADA3 was analyzed then correlated with the expression of various prognostic markers, as well as survival of breast cancer patients.Results: Overexpression of ADA3 in ER- hMECs as well as in ER+ breast cancer cell lines enhanced cell proliferation. These cells showed increased cyclin B and c-MYC, decreased p27 and increased SKP2 levels. This was accompanied by increased mRNA levels of early response genes c-FOS, EGR1, and c-MYC. Analysis of breast cancer tissue specimens showed a significant correlation of ADA3 nuclear expression with c-MYC expression. Furthermore, nuclear ADA3 andc-MYC expression together showed significant correlation with tumor grade, mitosis, pleomorphism, NPI, ER/PR status, Ki67 and p27 expression. Importantly, within ER+ cases, expression of nuclear ADA3 and c-MYC also significantly correlated with Ki67 and p27 expression. Univariate Kaplan Meier analysis of four groups in the whole, as well as the ER+ patients showed that c-MYC and ADA3 combinatorial phenotypes showed significantly different breast cancer specific survival with c-MYC-high and ADA3-Low subgroup had the worst outcome. Using multivariate analyses within the whole cohort and the ER+ subgroups, the significant association of ADA3 and c-MYC expression with patients’ outcome was independent of tumor grade, stage and size, and ER status.Conclusion: ADA3 overexpression enhances cell proliferation that is associated with increased expression of c-MYC. Expression patterns with respect to ADA3/c-MYC can divide patients into four significantly different subgroups, with c-MYC High and ADA3 Low status independently predicting poor survival in patients

Molecular diagnosis of Burkitt\u27s lymphoma.

BACKGROUND: The distinction between Burkitt\u27s lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt\u27s lymphoma from diffuse large-B-cell lymphoma. METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation. RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt\u27s lymphoma. Burkitt\u27s lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-kappaB target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt\u27s lymphoma, suggesting they represent cases of Burkitt\u27s lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt\u27s lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens. CONCLUSIONS: Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt\u27s lymphoma from diffuse large-B-cell lymphoma

Primary retroperitoneal hydatid cyst: A case report

Retroperitoneal echinococcal cyst is a rare manifestation of hydatid disease. Hydatid disease is an endemic parasitic disease of the Mediterranean countries [1]. Although the liver and lungs are the most commonly involved organs, the disease may be found in any part of the body. We present here an experience of treating a patient with retroperitoneal hydatid presenting as al tumor. Keywords: echinococcosis, retroperitoneal hydatid cyst, India.Nigerian Journal of Parasitology Vol. 29 (1) 2008 pp. 29-3

Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma

Pesticides have been specifically associated with the t(14;18)(q32;q21) chromosomal translocation. To investigate whether the association between pesticides and risk of non-Hodgkin lymphoma (NHL) differs for molecular subtypes of NHL defined by t(14; 18) status, we obtained 175 tumor blocks from case subjects in a population-based case-control study conducted in Nebraska between 1983 and 1986. The t(14;18) was determined by interphase fluorescence in situ hybridization in 172 of 175 tumor blocks. We compared exposures to insecticides, herbicides, fungicides, and fumigants in 65 t(14;18)-positive and 107 t(14;18)-negative case subjects with those among 1432 control subjects. Multivariate polytomous logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Compared with farmers who never used pesticides, the risk of t(14;18)-positive NHL was significantly elevated among farmers who used animal insecticides (OR = 2.6; 95% CI, 1.0-6.9), crop insecticides (OR = 3.0; 95% CI, 1.1-8.2), herbicides (OR = 2.9; 95% CI, 1.1-7.9), and fumigants (OR = 5.0; 95% CI, 1.7-14.5). None of these pesticides were associated with t(14;18)-negative NHL. The risk of t(14;18)-positive NHL associated with insecticides and herbicides increased with longer duration of use. We conclude that insecticides, herbicides, and fumigants were associated with risk of t(14;18)-positive NHL but not t(14;18)-negative NHL. These results suggest that defining subsets of NHL according to t(14;18) status is a useful approach for etiologic research

HACE1 Is a Tumor Suppressor Gene Candidate in Natural Killer Cell Neoplasms

HACE1 is an E3 ubiquitin ligase located in 6q21, the genomic region frequently deleted in natural killer (NK) cell malignancies. Here, we report HACE1 as a candidate tumor suppressor gene silenced through a combination of deletion and cytosine phosphate guanine island hypermethylation. We detected deletion of HACE1 in malignant NK cell lines (6 of 9, 67%) and primary biopsies (5 of 15, 33%) by quantitative PCR, with most of the specimen showing cytosine phosphate guanine island hypermethylation in the remaining allele, Leading to Low mRNA transcription. The ectopic expression of HACE1 in an HACE1-null NK cell Line led to apoptosis and G(2)/M cell cycle arrest. Moreover, HACE1 expression was up-regulated in IL-2-activated normal NK cells and NK cells cocultured with an engineered NK cell target, K562 Clone 9.mbIL21, suggesting its rote in the regulation of NK cell homeostasis. In conclusion, HACE1 is another potent tumor suppressor gene located within the 6q21 region, and loss of function of multiple tumor suppressor genes within 6q21 may be a critical determinant of NK cell Lymphomagenesis. (Am J Pathol 2013, 182: 49-55; http://dx.doi.org/10.1016/j.ajpath.2012.09.012)PathologySCI(E)9ARTICLE149-5518

Biotinylation of Histones Represses Transposable Elements in Human and Mouse Cells and Cell Lines and in \u3ci\u3eDrosophila melanogaster\u3c/i\u3e

Transposable elements such as long terminal repeats (LTR) constitute ;45% of the human genome; transposition events impair genome stability. Fifty-four promoter-active retrotransposons have been identified in humans. Epigenetic mechanisms are important for transcriptional repression of retrotransposons, preventing transposition events, and abnormal regulation of genes. Here, we demonstrate that the covalent binding of the vitamin biotin to lysine-12 in histone H4 (H4K12bio) and lysine-9 in histone H2A (H2AK9bio), mediated by holocarboxylase synthetase (HCS), is an epigenetic mechanism to repress retrotransposon transcription in human and mouse cell lines and in primary cells from a human supplementation study. Abundance of H4K12bio and H2AK9bio at intact retrotransposons and a solitary LTR depended on biotin supply and HCS activity and was inversely linked with the abundance of LTR transcripts. Knockdown of HCS in Drosophila melanogaster enhances retrotransposition in the germline. Importantly, we demonstrated that depletion of H4K12bio and H2AK9bio in biotin-deficient cells correlates with increased production of viral particles and transposition events and ultimately decreases chromosomal stability. Collectively, this study reveals a novel diet-dependent epigenetic mechanism that could affect cancer risk

Biotinylation of Histones Represses Transposable Elements in Human and Mouse Cells and Cell Lines and in \u3ci\u3eDrosophila melanogaster\u3c/i\u3e

Transposable elements such as long terminal repeats (LTR) constitute ;45% of the human genome; transposition events impair genome stability. Fifty-four promoter-active retrotransposons have been identified in humans. Epigenetic mechanisms are important for transcriptional repression of retrotransposons, preventing transposition events, and abnormal regulation of genes. Here, we demonstrate that the covalent binding of the vitamin biotin to lysine-12 in histone H4 (H4K12bio) and lysine-9 in histone H2A (H2AK9bio), mediated by holocarboxylase synthetase (HCS), is an epigenetic mechanism to repress retrotransposon transcription in human and mouse cell lines and in primary cells from a human supplementation study. Abundance of H4K12bio and H2AK9bio at intact retrotransposons and a solitary LTR depended on biotin supply and HCS activity and was inversely linked with the abundance of LTR transcripts. Knockdown of HCS in Drosophila melanogaster enhances retrotransposition in the germline. Importantly, we demonstrated that depletion of H4K12bio and H2AK9bio in biotin-deficient cells correlates with increased production of viral particles and transposition events and ultimately decreases chromosomal stability. Collectively, this study reveals a novel diet-dependent epigenetic mechanism that could affect cancer risk