Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma, nasal type: a triple-center study

The prognostic significance of ABO blood type for lymphoma is largely unknown. We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL).

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Synthetic lethal short hairpin RNA screening reveals that ring finger protein 183 confers resistance to trametinib in colorectal cancer cells

The mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer (CRC) is limited. Synthe...

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Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)

Abstract

Background

Chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK) are rare oncogenic events found in 3–5% of non-small-cell lung cancers (NSCLC). Limited data have been published on the management of these patients outside clinical trials.

Objective

To investigate the clinical characteristics and management of patients with NSCLC harboring ALK translocations (ALK+) in a real-life setting in France.

Methods

This multicenter, observational, retrospective study included all NSCLC patients harboring ALK translocations diagnosed in participating centers between January 2012 and December 2014. Patient data include clinical characteristics, disease management, and outcomes [progression-free survival (PFS) and overall survival (OS)].

Results

The 31 participating centers reported data on 132 patients, of whom 51% (n = 67) were male. The median age was 60.1 ± 14.5 (standard deviation) years; 89% (n = 106/119) had performance status 0/1 at diagnosis; 79% (n = 103/130) were non- or former smokers; 93% (n = 120/129) had adenocarcinomas and 74%(n = 97)/19%(n = 25)/7%(n = 10) had disease stages IV/III/I-II at diagnosis, respectively; co-mutations included EGFR (n = 2), BRAF (n  = 2), KRAS (n = 1), and HER2 (n = 1). Of the patients with stage IV NSCLC (n = 97), 96% received first-line treatment [75% chemotherapy-based, 21% ALK tyrosine kinase inhibitor (TKI)], with an associated response rate (RR), disease-control rate (DCR), and PFS of 42%, 64%, and 7.5 [95% confidence interval (CI) 5.9–9.5] months, respectively; 62% received second-line treatment (28% chemotherapy, 72% ALK TKI) with an associated RR, DCR, and PFS of 43.4%, 70%, and 4.7 (95% CI 4.0–8.1) months, respectively. The 2-year OS was 56.7% (95% CI 45.5–70.4%); median OS was not reached.

Conclusion

The results of this real-life analysis suggest that the prognosis of NSCLC patients with theALK translocation may be better than that of the overall NSCLC population, but the outcomes were poorer than those of ALK+ NSCLC patients included in clinical studies.

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Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention

Abstract

After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.

http://ift.tt/2tW19AE

Nutritional Risk Factors in the Pathogenesis of Parenteral Nutrition-Associated Liver Disease

Abstract

Purpose of Review

Parenteral nutrition has been a lifesaving therapy for individuals who cannot sustain adequate oral or enteral nutrient intake to maintain fluid, electrolyte, and nutrient balance. Nonetheless, parenteral nutrition can lead to an increased risk of complications, such as parenteral nutrition-associated liver disease (PNALD). The pathogenesis of PNALD has been associated with multiple risk factors, such as longer duration, reduced small bowel length, decreased enteral intake, and bacterial infections. Nutritional risk factors also play an important role in the development of PNALD. This review presents several nutrient deficiencies and excesses that have been associated with PNALD.

Recent Findings

Deficiencies in certain nutrients (amino acids, essential fatty acids, enteral intake), excesses of certain nutrients (calories, carbohydrates, lipids), types of lipid emulsions, and mineral toxicities (aluminum, copper, manganese) have been associated with PNALD. Strategies to address PNALD require correction of these risk factors. The use of newer mixed lipid emulsions (including soybean, medium-chain triglycerides, olive oil, and fish oil) may also have less hepatotoxicity than traditional soybean oil-based lipid emulsions.

Summary

Knowledge of nutritional risk factors for PNALD will help the clinician in the systematic evaluation and treatment of these specific risk factors. Moreover, an understanding of their effects guides the balance between addressing the patient's nutritional needs and reducing the risk of PNALD.

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Targeted next-generation sequencing identifies clinically relevant mutations in patients with chronic neutrophilic leukemia at diagnosis and blast crisis

Abstract

Purpose

Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification.

Materials and methods

A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients.

Results

Next-generation sequencing confirmed the CSF3R T618I in all patients with identification of concurrent SRSF2, SETBP1, NRAS and CBL mutations at diagnosis. At blast crisis, clonal evolution was evidenced by an increased CSF3R T618I allele frequency and by loss or acquisition of CBL and NRAS mutations.

Conclusion

The diagnostic utility of a targeted next-generation sequencing approach was clearly demonstrated with the identification of additional mutations providing the potential for therapeutic stratification of chronic neutrophilic leukemia patients.

http://ift.tt/2vkTcFt

Considerations in T Cell Therapy Product Development for B Cell Leukemia and Lymphoma Immunotherapy

Abstract

Based on laboratory and clinical research findings and investments in immunotherapy by many institutions in academia, government-funded laboratories, and industry, there is tremendous and deserved excitement in the field of cell and gene therapy. In particular, understanding of immune-mediated control of cancer has created opportunities to develop new forms of therapies based on engineered T cells. Unlike conventional drugs or biologics, the source material for these new therapies is collected from the patient or donor. The next step is commonly either enrichment to deplete unwanted cells, or methods to positively select T cells prior to polyclonal expansion or antigen-specific expansion. As the first generation of engineered T cell therapies have demonstrated proof of concept, the next stages of development will require the integration of automated technologies to enable more consistent manufacturing and the ability to produce therapies for more patients.

http://ift.tt/2eZEBZa