Self-tanning cells, the new SPF.

A skin-penetrant small molecule activates melanin production to protect cells from cancer-inducing ultraviolet damage.

A GEMA of a personalized medicine strategy.

A screening method can identify tumors susceptible to synthetic lethality via PARP inhibition.

Coronary artery disease is associated with an increased mortality rate following video-assisted thoracoscopic lobectomy.

Objective: To compare the incidence of major adverse cardiac events (MACE) and mortality following video-assisted thoracoscopic surgery (VATS) lobectomy in patients with and without coronary artery disease (CAD).

Methods: Multicentre retrospective analysis of 1699 patients undergoing VATS lobectomy (January 2012-March 2015). CAD definition: previous acute myocardial infarct (AMI), angina, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).

Vitamin C puts the pedal to the metal.

Increased iron in cancer cells drives selective sensitization of tumors to ascorbate treatment to prolong survival.

Astrocytes light up glial heterogeneity.

Functionally diverse subpopulations of astrocytes have correlates in the neoplastic adult brain.

Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer.

Detection of methylated free-circulating DNA (mfcDNA) for hyperplastic polyposis 1 (HPP1) in blood is correlated with a poor prognosis for patients with metastatic colorectal cancers (mCRC). Here, we analyzed the plasma levels of HPP1 mfcDNA in mCRC patients treated with a combination therapy containing a fluoropyrimidine, oxaliplatin and bevacizumab to test whether HPP1 mfcDNA is a suitable prognostic and response biomarker. From 467 patients of the prospective clinical study AIO-KRK-0207, mfcDNA was isolated from plasma samples at different time points and bisulfite-treated mfcDNA was quantified using methylation specific PCR.

Poly(glycoamidoamine) brush nanomaterials for systemic siRNA delivery in vivo.

Delivery is the key challenge for siRNA based therapeutics. Here, we report the development of new poly(glycoamidoamine) brush nanomaterials for efficient siRNA delivery. GluN4C10 polymer brush nanoparticles, a lead material, demonstrated significantly improved delivery efficiency for siRNA against factor VII (FVII) in mice compared to poly(glycoamidoamine) brush nanomaterials reported previously.

Prevalence and correlates of vaginal estrogenization in postmenopausal women in the United States.

Objective: This work aims to establish current population-based vaginal estrogenization norms for postmenopausal US women.

Methods: Using a US national probability sample of 868 postmenopausal women ages 57 to 85 years (mean age 67.6 ± 0.

Atypical Apocrine Adenosis: Diagnostic Challenges and Pitfalls.

Apocrine change in the breast is an extremely common finding. In most cases, the benign or malignant nature of the lesion is easily recognized. Apocrine adenosis is used to describe sclerosing adenosis with apocrine change.

Morphologic, Molecular, and Taxonomic Evolution of Renal Cell Carcinoma: A Conceptual Perspective With Emphasis on Updates to the 2016 World Health Organization Classification.

Molecular and morphologic interrogation has driven a much-needed reexamination of renal cell carcinoma (RCC). Indeed, the recently released 2016 World Health Organization classification now recognizes 12 distinct RCC subtypes, as well as several other emerging/provisional RCC entities. From a clinical perspective, accurate RCC classification may have important implications for patients and their families, including prognostic risk stratification, targeted therapeutics selection, and identification for genetic testing.

Maintenance therapy with decitabine in younger adults with acute myeloid leukemia in first remission: a phase 2 Cancer and Leukemia Group B Study (CALGB 10503).

In this prospective phase 2 clinical trial conducted by Cancer and Leukemia Group B (CALGB, now the Alliance), we studied decitabine as maintenance therapy for younger adults with acute myeloid leukemia (AML) who remained in first complete remission (CR1) following intensive induction and consolidation. Given that decitabine is clinically active in AML and with hypomethylating activity distinct from cytotoxic chemotherapy, we hypothesized that 1 year of maintenance therapy would improve disease-free survival (DFS) for AML patients <60 years, who did not receive allogeneic stem cell transplantation in CR1. After blood count recovery from final consolidation, patients received decitabine at 20 mg/m intravenously daily for 4-5 days, every 6 weeks for eight cycles.

Effects of Cold Ischemia on Gene Expression: A Review and Commentary.

Frequently investigators request that tissues be collected and processed in less than one hour following removal from a patient. Some biorepositories expend significant personnel time and other resources in trying to meet such goals; however, it is unclear whether the perceived benefits of relatively short cold ischemia times warrant these added costs. The literature of human surgical tissues prospectively exposed to cold ischemia at several time points was reviewed to compare the changes in transcripts/genes and microRNA with time of cold ischemia.

Adult BMI and Access to Built Environment Resources in a High-Poverty, Urban Geography.

Introduction: The purpose of this study is to examine the relationship between BMI and access to built environment resources in a high-poverty, urban geography.

Methods: Participants (aged ≥35 years) were surveyed between November 2012 and July 2013 to examine access to common health-enabling resources (grocers, outpatient providers, pharmacies, places of worship, and physical activity resources). Survey data were linked to a contemporaneous census of built resources.

Patterns of major wound complications following multidisciplinary therapy for lower extremity soft tissue sarcoma.

Background And Objectives: The purpose of this study was to determine the pattern and timing of major wound complications (MWCs) in patients at our institution who received multimodality treatment for lower extremity soft tissue sarcoma (LE-STS) and to evaluate the impact of MWCs on tumor control and patient outcomes.

Methods: The medical records of 102 LE-STS patients treated with limb-sparing surgery and radiation therapy were reviewed. MWCs were defined as secondary operations with anesthesia, seroma/hematoma aspiration, admission for IV antibiotics, or persistent deep packing.

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer.

Breast cancer is the second leading cause of cancer deaths among women. Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabinoid system. Although CNR2 is highly expressed in the breast cancer tissues as well as breast cancer cell lines, its functional role in breast tumorigenesis is not well understood.

Coming of age: ten years of next-generation sequencing technologies.

Since the completion of the human genome project in 2003, extraordinary progress has been made in genome sequencing technologies, which has led to a decreased cost per megabase and an increase in the number and diversity of sequenced genomes. An astonishing complexity of genome architecture has been revealed, bringing these sequencing technologies to even greater advancements. Some approaches maximize the number of bases sequenced in the least amount of time, generating a wealth of data that can be used to understand increasingly complex phenotypes.

Malignancies after mitoxantrone for multiple sclerosis: A retrospective cohort study.

Objective: To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis.

Methods: This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010.

Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma.

Malignant mesothelioma (MM), is an intractable disease with limited therapeutic options and grim survival rates. Altered metabolic and mitochondrial functions are hallmarks of MM and most other cancers. Mitochondria exist as a dynamic network, playing a central role in cellular metabolism.

DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia.

Unlabelled: Cytogenetically normal acute myeloid leukemia (CN-AML) represents nearly 50% of human AML. Co-occurring mutations in the de novo DNA methyltransferase DNMT3A and the FMS related tyrosine kinase 3 (FLT3) are common in CN-AML and confer a poorer prognosis. We demonstrate that mice with Flt3-internal tandem duplication (Flt3(ITD)) and inducible deletion of Dnmt3a spontaneously develop a rapidly lethal, completely penetrant, and transplantable AML of normal karyotype.

Effects of Chemically Modified Messenger RNA on Protein Expression.

Chemically modified nucleotides play significant roles in the effectiveness of mRNA translation. Here, we describe the synthesis of two sets of chemically modified mRNAs [encoding firefly Luciferase (FLuc) and enhanced green fluorescent protein (eGFP), respectively], evaluation of protein expression, and correlation analysis of expression level under various conditions. The results indicate that chemical modifications of mRNAs are able to significantly improve protein expression, which is dependent on cell types and coding sequences.

Midostaurin, bortezomib and MEC in relapsed/refractory acute myeloid leukemia.

Targeting aberrant tyrosine kinase activity may impact clinical outcome in acute myeloid leukemia (AML). We conducted a phase I study of the tyrosine kinase inhibitor midostaurin with bortezomib alone and in combination with chemotherapy in patients with AML. Patients on dose levels 1 and 2 (DL1 & 2) received midostaurin 50 mg bid and escalating doses of bortezomib (1 to 1.

MiT Family Translocation-Associated Renal Cell Carcinoma: A Contemporary Update With Emphasis on Morphologic, Immunophenotypic, and Molecular Mimics.

Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulates differentiation in melanocytes and osteoclasts, and MiT family gene fusions activate unique molecular programs that can be detected immunohistochemically. Although the overall clinical behavior of t-RCC is variable, emerging molecular data suggest the possibility of targeted approaches to advanced disease.

Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC).

Despite the promise of targeted therapies, there remains an urgent need for effective treatment for esophageal cancer (EC) and triple-negative breast cancer (TNBC). Current FDA-approved drugs have significant problems of toxicity, safety, selectivity, efficacy and development of resistance. In this manuscript, we demonstrate that rationally designed peptide vaccines/mimics are a viable therapeutic strategy for blocking aberrant molecular signaling pathways with high affinity, specificity, potency and safety.

Prion Protein Protects against Renal Ischemia/Reperfusion Injury.

The cellular prion protein (PrPC), a protein most noted for its link to prion diseases, has been found to play a protective role in ischemic brain injury. To investigate the role of PrPC in the kidney, an organ highly prone to ischemia/reperfusion (IR) injury, we examined wild-type (WT) and PrPC knockout (KO) mice that were subjected to 30-min of renal ischemia followed by 1, 2, or 3 days of reperfusion. Renal dysfunction and structural damage was more severe in KO than in WT mice.

Predicting Response to Histone Deacetylase Inhibitors Using High-Throughput Genomics.

Background: Many disparate biomarkers have been proposed as predictors of response to histone deacetylase inhibitors (HDI); however, all have failed when applied clinically. Rather than this being entirely an issue of reproducibility, response to the HDI vorinostat may be determined by the additive effect of multiple molecular factors, many of which have previously been demonstrated.

Methods: We conducted a large-scale gene expression analysis using the Cancer Genome Project for discovery and generated another large independent cancer cell line dataset across different cancers for validation.