International journal of cancer. Journal international du cancer
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Multicenter Study Comparative Study
Prognostic role of adjuvant radiotherapy in triple-negative breast cancer: A historical cohort study.
The value of adjuvant radiotherapy in triple-negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N = 1,138) were included. ⋯ Following multivariable adjustment, BCT and mastectomy with radiotherapy remained significantly associated with lower mortality risk compared to mastectomy only. Overall, adjuvant radiotherapy was associated with higher survival in women aged <40 years, but not in older women. Adjuvant radiotherapy appears to be independently associated with a survival gain in locally advanced as well as in very young TNBC.
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Pediatric high-grade gliomas (HGGs) are highly malignant tumors that remain incurable and relatively understudied. The crucial role of noncoding RNAs (ncRNAs) has been reported in various cancers. However, the study on miRNAs in pediatric HGGs is scant and there is no report till date on the status of other small ncRNAs. ⋯ Remarkably, a significant downregulation of HBII-52 snoRNA cluster was found in pediatric HGGs, and was specific to H3F3A nonmutants. This is the first genome-wide profiling study on miRNAs and snoRNAs in pediatric HGGs with respect to H3F3A and TP53 mutations. The comparison of miRNA profiles of pediatric HGGs and adult GBM reiterates the overlaps and differences as also seen with their gene expression and methylation signatures.
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Cancer Incidence in Five Continents (CI5), a longstanding collaboration between the International Agency for Research on Cancer and the International Association of Cancer Registries, serves as a unique source of cancer incidence data from high-quality population-based cancer registries around the world. The recent publication of Volume X comprises cancer incidence data from 290 registries covering 424 populations in 68 countries for the registration period 2003-2007. In this article, we assess the status of population-based cancer registries worldwide, describe the techniques used in CI5 to evaluate their quality and highlight the notable variation in the incidence rates of selected cancers contained within Volume X of CI5. We also discuss the Global Initiative for Cancer Registry Development as an international partnership that aims to reduce the disparities in availability of cancer incidence data for cancer control action, particularly in economically transitioning countries, already experiencing a rapid rise in the number of cancer patients annually.
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Pharmacological inhibition of phosphatiylinositide-3-kinase (PI3K)-mediated signaling holds great promise for treating chronic lymphocytic leukemia (CLL). Therefore we assessed three structurally related PI3K inhibitors targeting the PI3K-δ isoform for their ability to inhibit the survival of freshly isolated CLL cells. The purely PI3K-δ-selective inhibitor idelalisib was compared to copanlisib (BAY 80-6946) and duvelisib (IPI-145), with isoform target profiles that additionally include PI3K-α or PI3K-γ, respectively. ⋯ Similarly copanlisib and duvelisib reduced the survival of CLL cells in co-cultures with the bone marrow stroma cell line HS-5 more strongly than idelalisib. Survival inhibition by copanlisib and idelalisib was enhanced by the monoclonal CD20 antibodies rituximab and obinutuzumab (GA101), while antibody-dependent cellular cytotoxicity mediated by alemtuzumab and peripheral blood mononuclear cells was not substantially impaired by both PI3K inhibitors for the CLL-derived JVM-3 cell line as target cells. Taken together, targeting the α- and δ- p110 isoforms with copanlisib may be a useful strategy for the treatment of CLL and warrants further clinical investigation.
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Leukemic stem cells (LSC) might be the source for leukemic disease self-renewal and account for disease relapse after treatment, which makes them a critical target for further therapeutic options. We investigated the role of cytotoxic T-lymphocytes (CTL) counteracting and recognizing LSC. Leukemia-associated antigens (LAA) represent immunogenic structures to target LSC. ⋯ In a proof of principle xenotransplant mouse model, PRAME-stimulated CTL targeted AML stem cells, reflected by a delayed engraftment of leukemia (p = 0.0159). Taken together, we demonstrated the expression of several LAA in LSC. LAA-specific T cells are able to hamper LSC in immunoassays and in a mouse model, which suggests that immunotherapeutic approaches have the potential to target malignant stem cells.