Association of body mass index and height with risk of prostate cancer among middle-aged Japanese men

In a population-based prospective study of 49 850 Japanese men, body mass index and height were not significantly associated with risk of prostate cancer (311 cases), although small positive effects could not be ruled out in advanced cases (91 cases)

Imaginal Discs – A New Source of Chromosomes for Genome Mapping of the Yellow Fever Mosquito Aedes aegypti

Dengue fever is an emerging health threat to as much as half of the human population around the world. No vaccines or drug treatments are currently available. Thus, disease prevention is largely based on efforts to control its major mosquito vector Ae. aegypti. Novel vector control strategies, such as population replacement with pathogen-incompetent transgenic mosquitoes, rely on detailed knowledge of the genome organization for the mosquito. However, the current genome assembly of Ae. aegypti is highly fragmented and requires additional physical mapping onto chromosomes. The absence of readable polytene chromosomes makes genome mapping for this mosquito extremely challenging. In this study, we discovered and investigated a new source of chromosomes useful for the cytogenetic analysis in Ae. aegypti – mitotic chromosomes from imaginal discs of 4th instar larvae. Using natural banding patterns of these chromosomes, we developed a new band-based approach for physical mapping of DNA probes to the precise chromosomal positions. Further application of this approach for genome mapping will greatly enhance the utility of the existing draft genome sequence assembly for Ae. aegypti and thereby facilitate application of advanced genome technologies for investigating and developing novel genetic control strategies for dengue transmission

Abrogation of Junctional Adhesion Molecule-A Expression Induces Cell Apoptosis and Reduces Breast Cancer Progression

Intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A) is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A−/− tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target

Allergic conditions and risk of hematological malignancies in adults: a cohort study

BACKGROUND: Two contradictory hypotheses have been proposed to explain the relationship between allergic conditions and malignancies, the immune surveillance hypothesis and the antigenic stimulation hypothesis. The former advocates that allergic conditions may be protective against development of cancer, whereas the latter proposes an increased risk. This relationship has been studied in several case-control studies, but only in a few cohort studies. METHODS: The association between allergic conditions and risk of developing leukemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma was investigated in a cohort of 16,539 Swedish twins born 1886–1925. Prospectively collected, self-reported information about allergic conditions such as asthma, hay fever or eczema was obtained through questionnaires administered in 1967. The cohort was followed 1969–99 and cancer incidence was ascertained from the Swedish Cancer Registry. RESULTS: Hives and asthma tended to increase the risk of leukemia (relative risk [RR] = 2.1, 95% Confidence Interval [CI] 1.0–4.5 and RR = 1.6, 95% CI 0.8–3.5, respectively). There was also an indication of an increased risk of non-Hodgkin's lymphoma associated with eczema during childhood (RR = 2.3, 95% CI 1.0–5.3). CONCLUSION: In contrast to most previous studies, our results do not indicate a protective effect of allergic conditions on the risk of developing hematological malignancies. Rather, they suggest that allergic conditions might increase the risk of some hematological malignancies

Antibiotic use and risk of non-Hodgkin's lymphoma: a population-based case–control study

Antibiotic use in 759 non-Hodgkin's lymphoma (NHL) patients and 589 controls was compared. Neither total antibiotic use (odds ratio=0.7, 95% confidence interval=0.5–1.2), nor antibiotic use by site, was associated with total NHL, or NHL subtypes. There were no trends with frequency or age at first use (P trend=0.23 and 0.26, respectively)

Seasonal variations in the diagnosis of childhood cancer in the United States

Seasonal trends in month of diagnosis have been reported for childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). This seasonal variation has been suggested to represent an underlying viral aetiology for these malignancies. Some studies have shown the highest frequency of diagnoses in the summer months, although this has been inconsistent. Data from the Children's Cancer Group and the Pediatric Oncology Group were analysed for seasonal incidence patterns. A total of 20 949 incident cancer cases diagnosed in the USA from 1 January 1989 through 31 December 1991 were available for analyses. Diagnosis-specific malignancies available for evaluation included ALL, acute myeloid leukaemia (AML), Hodgkin's disease, NHL, rhabdomyosarcoma, neuroblastoma, retinoblastoma, osteosarcoma, Wilms' tumour, retinoblastoma, Ewings' sarcoma, central nervous system (CNS) tumours and hepatoblastoma. Overall, there was no statistically significant seasonal variation in the month of diagnosis for all childhood cancers combined. For diagnosis-specific malignancies, there was a statistically significant seasonal variation for ALL (P = 0.01; peak in summer), rhabdomyosarcoma (P = 0.03; spring/summer) and hepatoblastoma (P = 0.01; summer); there was no seasonal variation in the diagnosis of NHL. When cases were restricted to latitudes greater than 40° (‘north’), seasonal patterns were apparent only for ALL and hepatoblastoma. Notably, 33% of hepatoblastoma cases were diagnosed in the summer months. In contrast, for latitudes less than 40° (‘south’), only CNS tumours demonstrated a seasonal pattern (P = 0.002; winter). Although these data provide modest support for a summer peak in the diagnosis of childhood ALL, any underlying biological mechanisms that account for these seasonal patterns are likely complex and in need of more definitive studies. © 1999 Cancer Research Campaig

Comprehensive Assessment of Immune Phenotype and Its Effects on Survival Outcomes in HER2-Low versus HER2-Zero Breast Cancer

Heidi Chwan Ko,1,* RJ Seager,2,* Sarabjot Pabla,2 Maria-Fernanda Senosain,2 Erik Van Roey,2 Shuang Gao,2 Kyle C Strickland,1,3 Rebecca Ann Previs,1,4 Michelle F Green,1 Maureen Cooper,1 Mary K Nesline,1 Stephanie B Hastings,1 Kobina Agyaful Amoah,1 Shengle Zhang,2 Jeffrey M Conroy,2 Taylor J Jensen,1 Marcia Eisenberg,5 Brian Caveney,5 Eric A Severson,1 Shakti Ramkissoon,1,6 Shipra Gandhi7 1Labcorp Oncology, Durham, NC, USA; 2Labcorp Oncology, Buffalo, NY, USA; 3Department of Pathology, Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA; 4Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA; 5Labcorp, Burlington, NC, USA; 6Department of Pathology, Wake Forest Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA; 7Department of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA*These authors contributed equally to this workCorrespondence: Heidi Chwan Ko, Email [email protected]: The understanding of molecular characteristics of HER2-low breast cancer is evolving since the establishment of trastuzumab deruxtecan. Here, we explore the differences in expression patterns of immune-related genes in the tumor immune microenvironment (TME) and survival between HER2-low and HER2-zero breast cancers.Methods: Comprehensive genomic and immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on FFPE samples from 129 patients with advanced HER2-negative (immunohistochemistry (IHC) 0, 1+ or 2+ with negative ERBB2 amplification by in-situ hybridization) breast cancer. Both estrogen receptor (ER) and HER2 statuses were obtained from available pathology reports. mRNA expressions of immune biomarkers, except for PD-L1 IHC and TMB, were derived from RNA-seq. Statistical comparisons were performed using the Kruskal–Wallis or Wilcoxon Rank-Sum test or the two-sample test for equality of proportions with continuity correction (p≤ 0.05 for significance). Survival differences were calculated using Kaplan-Meier analysis (p≤ 0.05 for significance).Results: There were no significant differences in mRNA expressions of immune-related genes between HER2-low and HER2-zero breast cancers. However, HER2-low breast cancers were associated with a higher proportion of ER-positivity. When ER was analyzed along with HER2, we observed a significantly higher tumor immunogenic signature (TIGS) expression in HER2-zero/ER-negative tumors than in HER2-low/ER-positive tumors (p=0.0088). Similarly, lower expression of PD-L1 and T cell immunoglobulin and ITIM domain (TIGIT) mRNA was observed in HER2-low/ER-positive tumors when compared to HER2-zero/ER-negative tumors (p=0.014 and 0.012, respectively). Patients with HER2-low tumors had a longer median OS than those with HER2-zero tumors (94 months vs 42 months, p=0.0044).Conclusion: Patients with HER2-low breast cancer have longer survivals yet display no differences in immune-related gene expression when compared to those with HER2-zero cancers. The differences in survival can be attributed to the higher rate of ER-positivity seen in HER2-low breast cancers, compared to HER2-zero tumors.Keywords: HER2-low breast cancer, estrogen receptor, tumor immune microenvironment, immune checkpoint biomarkers, gene expression profiling, immune profilin

The Aurora Kinase in Trypanosoma brucei Plays Distinctive Roles in Metaphase-Anaphase Transition and Cytokinetic Initiation

Aurora B kinase is an essential regulator of chromosome segregation with the action well characterized in eukaryotes. It is also implicated in cytokinesis, but the detailed mechanism remains less clear, partly due to the difficulty in separating the latter from the former function in a growing cell. A chemical genetic approach with an inhibitor of the enzyme added to a synchronized cell population at different stages of the cell cycle would probably solve this problem. In the deeply branched parasitic protozoan Trypanosoma brucei, an Aurora B homolog, TbAUK1, was found to control both chromosome segregation and cytokinetic initiation by evidence from RNAi and dominant negative mutation. To clearly separate these two functions, VX-680, an inhibitor of TbAUK1, was added to a synchronized T. brucei procyclic cell population at different cell cycle stages. The unique trans-localization pattern of the chromosomal passenger complex (CPC), consisting of TbAUK1 and two novel proteins TbCPC1 and TbCPC2, was monitored during mitosis and cytokinesis by following the migration of the proteins tagged with enhanced yellow fluorescence protein in live cells with time-lapse video microscopy. Inhibition of TbAUK1 function in S-phase, prophase or metaphase invariably arrests the cells in the metaphase, suggesting an action of TbAUK1 in promoting metaphase-anaphase transition. TbAUK1 inhibition in anaphase does not affect mitotic exit, but prevents trans-localization of the CPC from the spindle midzone to the anterior tip of the new flagellum attachment zone for cytokinetic initiation. The CPC in the midzone is dispersed back to the two segregated nuclei, while cytokinesis is inhibited. In and beyond telophase, TbAUK1 inhibition has no effect on the progression of cytokinesis or the subsequent G1, S and G2 phases until a new metaphase is attained. There are thus two clearly distinct points of TbAUK1 action in T. brucei: the metaphase-anaphase transition and cytokinetic initiation. This is the first time to our knowledge that the dual functions of an Aurora B homolog is dissected and separated into two clearly distinct time frames in a cell cycle

A review and meta-analysis of prospective studies of red and processed meat intake and prostate cancer

Over the past decade, several large epidemiologic investigations of meat intake and prostate cancer have been published. Therefore, a meta-analysis of prospective studies was conducted to estimate potential associations between red or processed meat intake and prostate cancer. Fifteen studies of red meat and 11 studies of processed meat were included in the analyses. High vs. low intake and dose-response analyses were conducted using random effects models to generate summary relative risk estimates (SRRE). No association between high vs. low red meat consumption (SRRE = 1.00, 95% CI: 0.96-1.05) or each 100 g increment of red meat (SRRE = 1.00, 95% CI: 0.95-1.05) and total prostate cancer was observed. Similarly, no association with red meat was observed for advanced prostate cancer (SRRE = 1.01, 95% CI: 0.94-1.09). A weakly elevated summary association between processed meat and total prostate cancer was found (SRRE = 1.05, 95% CI: 0.99-1.12), although heterogeneity was present, the association was attenuated in a sub-group analysis of studies that adjusted for multiple potential confounding factors, and publication bias likely affected the summary effect. In conclusion, the results of this meta-analysis are not supportive of an independent positive association between red or processed meat intake and prostate cancer