Different clinical effects upon separate inhibition of coexisting EGFR and PI3KCA mutations in a lung adenocarcinoma patient.

We present a very interesting case of lung adenocarcinoma carrying an uncommon EGFR exon 19 insertion with concomitant PIK3CA mutation showing dramatic and persisting improvement upon erlotinib therapy, after progression during PI3K inhibitor.

Acute stress affects the global DNA methylation profile in rat brain: modulation by physical exercise.

The vulnerability of epigenetic marks of brain cells to environmental stimuli and its implication for health have been recently debated. Thus, we used the rat model of acute restraint stress (ARS) to evaluate the impact of stress on the global DNA methylation and on the expression of the Dnmt1 and Bdnf genes of hippocampus, cortex, hypothalamus and periaqueductal gray (PAG). Furthermore, we verified the potential of physical exercise to modulate epigenetic responses evoked by ARS.

Myocardial interleukin-6 in the setting of left ventricular mechanical assistance: relation with outcome and C-reactive protein.

Background: In left ventricular assist device (LVAD) recipients, plasma levels of interleukin (IL)-6 are associated with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles, reflecting post-operative risk. However, it is not clear how the cardiac level of IL-6, detectable on the tissue samples at the time of implantation, can contribute to predict the post-operative outcome.

Methods: In 40 LVAD recipients, blood and myocardial samples from LV-apex were collected at the time of implantation to assess plasma and cardiac IL-6 levels.

Available evidence and new biological perspectives on medical treatment of advanced thymic epithelial tumors.

Thymic epithelial tumors (TETs) are rare primary mediastinal tumors arising from thymic epithelium. Their rarity and complexity hinder investigations of their causes and therapy development. Here, we summarize the existing knowledge regarding medical treatment of these tumors, and thoroughly review the known genetic aberrations associated with TETs and the present status of potential biological treatments.

Therapeutic biomarkers in lung neuroendocrine neoplasia.

The well-known classification of neuroendocrine neoplasms of the lung into four major subtypes (including typical and atypical carcinoids and small- and large-cell neuroendocrine carcinomas) has a proven prognostic validity but only partially helps to predict the response to specific therapies. Therapeutic biomarkers are incompletely known and include morphological, immunophenotypic, and molecular markers. Morphology alone has no specific predictive role, nor has any immunophenotypic marker been proven to bear predictive implications.

Inference on germline BAP1 mutations and asbestos exposure from the analysis of familial and sporadic mesothelioma in a high-risk area.

Inherited loss-of-function mutations in the BAP1 oncosuppressor gene are responsible for an inherited syndrome with predisposition to malignant mesothelioma (MM), uveal and keratinocytic melanoma, and other malignancies. Germline mutations that were inherited in an autosomal dominant fashion were identified in nine families with multiplex MM cases and 25 families with multiple melanoma, renal cell carcinoma, and other tumors. Germline mutations were also identified in sporadic MM cases, suggesting that germline mutations in BAP1 occur frequently.

Germline polymorphisms and survival of lung adenocarcinoma patients: a genome-wide study in two European patient series.

In lung cancer, the survival of patients with the same clinical stage varies widely for unknown reasons. In this two-phase study, we examined the hypothesis that germline variations influence the survival of patients with lung adenocarcinoma. First, we analyzed existing genotype and clinical data from 289 UK-resident patients with lung adenocarcinoma, identifying 86 single nucleotide polymorphisms (SNPs) that associated with survival (p < 0.

Gingival metastasis as first sign of multiorgan dissemination of epithelioid malignant mesothelioma.

Introduction: Metastatic malignant mesothelioma to the oral cavity is extremely rare. They are more common in the jaw bones than the soft tissue. Occurrence of the malignant disease typically carries an average survival rate of 9-12 months

Methods: : Thirteen patients underwent neoadjuvant chemotherapy and radical pleurectomy decortication, followed by radiotherapy from August 2012 to September 2013.

Reproducibility of histopathological diagnosis in poorly differentiated NSCLC: an international multiobserver study.

Introduction: The 2004 World Health Organization classification of lung cancer contained three major forms of non-small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non-small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis.

Methods: Resection specimens (n = 37) with SqCC, large cell carcinoma, basaloid carcinoma, sarcomatoid carcinoma, lymphoepithelial-like carcinoma, and solid AdC, were contributed by the participating pathologists.

A new entry to asymmetric platinum(IV) complexes via oxidative chlorination.

Pt(IV) complexes are usually prepared by oxidation of the corresponding Pt(II) counterparts, typically using hydrogen peroxide or chlorine. A different way to synthesize asymmetrical Pt(IV) compounds is the oxidative chlorination of Pt(II) counterparts with N-chlorosuccinimide. The reaction between cisplatin cis-[PtCl2(NH3)2], carboplatin, cis-[PtCl2(dach)] and cis-[Pt(cbdc)(dach)] (cbdc = cyclobutane-1,1'-dicarboxylato; dach = cyclohexane-1R,2R-diamine) with N-chlorosuccinimide in ethane-1,2-diol was optimized to produce the asymmetric Pt(IV) octahedral complexes [PtA2Cl(glyc)X2] (A2 = 2 NH3 or dach; glyc = 2-hydroxyethanolato; X2 = 2 Cl or cbdc) in high yield and purity.

Cinnamaldehyde and cuminaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes: a study to understand their biological activity.

This paper reports the synthesis and characterization of trans-cinnamaldehyde thiosemicarbazone (Htcin), cuminaldehyde thiosemicarbazone (Htcum) and their copper and nickel complexes. All the compounds, which on healthy cells (human fibroblasts) show a neglectable cytotoxicity, were screened in vitro in cell line U937 for their antileukemic activity. These compounds, in spite of their molecular similarity, present variegated behaviors.

Thulium laser versus staplers for anatomic pulmonary resections with incomplete fissures: negative results of a randomized trial.

Aims: This randomized trial evaluated the feasibility and safety of thulium 2010-nm laser to perform anatomic lung resections in patients with incomplete fissures, as compared to mechanical staplers with or without sealants.

Study Design: Seventy-two patients scheduled for segmentectomy or lobectomy were enrolled. After intraoperative confirmation of the extent of resection and incomplete fissures (Craig type 2, 3 or 4), they were randomized and allocated to one of the following arms: laser resection by thulium (group A) or standard resection with mechanical staplers with or without sealants (group B).

Exploring the vinylogous reactivity of cyclohexenylidene malononitriles: switchable regioselectivity in the organocatalytic asymmetric addition to enals giving highly enantioenriched carbabicyclic structures.

Modulation of the complex reactivity of cyclohexenylidene malononitriles using diverse β-aryl-substituted enals and proper organocatalytic modalities resulted in divergent asymmetric reaction patterns to furnish angularly fused or bridged carbabicyclic frameworks. In particular, use of remotely enolizable dicyanodienes 1, under one-pot sequential amine/NHC catalysis, led to [3 + 2] cycloaddition to afford ε,δ-bonded spiro[4.5]decanone structures 5.

FOLFOX-4 chemotherapy for patients with unresectable or relapsed peritoneal pseudomyxoma.

Purpose: The standard treatment of peritoneal pseudomyxoma is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma. The aim of our study was to assess the activity of chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX-4 regimen) in terms of response rate in this subset of patients.

Ewing sarcoma of the small bowel: a study of seven cases, including one with the uncommonly reported EWSR1-FEV translocation.

Aims: Primary Ewing sarcoma of the ileum has rarely been documented. Little is known about its pathogenesis and clinical implications, and it would be helpful to identify novel molecular markers. EWSR1-FEV translocation is exceedingly rare in Ewing sarcoma, as FEV expression is restricted to prostate, brain and serotonin neuroendocrine cells (NE) and related tumours.

Novel epigenetic target therapy for prostate cancer: a preclinical study.

Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine), hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects.

Inflammation blood and tissue factors of plaque growth in an experimental model evidenced by a systems approach.

Purpose: The multifactorial pathogenesis of coronary atherosclerotic lesion formation has been investigated in a swine model of high cholesterol diet induced atherogenesis and data processed by a systems approach.

Methods: Farm pigs were fed on standard or high cholesterol diet of 8 and 16 weeks duration. Plasma assessment of total cholesterol, HDL, LDL, and ELISA of some cytokines and ICAM-1 were performed on baseline and end-diet samples.

Unraveling tumor grading and genomic landscape in lung neuroendocrine tumors.

Currently, grading in lung neuroendocrine tumors (NETs) is inherently defined by the histological classification based on cell features, mitosis count, and necrosis, for which typical carcinoids (TC) are low-grade malignant tumors with long life expectation, atypical carcinoids (AC) intermediate-grade malignant tumors with more aggressive clinical behavior, and large cell NE carcinomas (LCNEC) and small cell lung carcinomas (SCLC) high-grade malignant tumors with dismal prognosis. While Ki-67 antigen labeling index, highlighting the proportion of proliferating tumor cells, has largely been used in digestive NETs for assessing prognosis and assisting therapy decisions, the same marker does not play an established role in the diagnosis, grading, and prognosis of lung NETs. Next generation sequencing techniques (NGS), thanks to their astonishing ability to process in a shorter timeframe up to billions of DNA strands, are radically revolutionizing our approach to diagnosis and therapy of tumors, including lung cancer.

trans,cis,cis-bis(benzoato)dichlorido(cyclohexane-1R,2R-diamine)platinum(IV): a prodrug candidate for the treatment of oxaliplatin-refractory colorectal cancer.

The gold standard for the treatment of metastatic colorectal cancer consists of combination chemotherapy. Over time, however, the development of chemoresistant tumor clones leads to relapse. It may be possible to overcome oxaliplatin chemoresistance in colorectal cancer cells by exploiting a complex obtained from the insertion of the cyclohexane-1R,2R-diamine carrier ligand (the same diamine present in oxaliplatin) into an octahedral Pt(IV) scaffold with high lipophilicity conferred by two benzoate axial ligands.

Up-regulation of heme oxygenase-1 after infarct initiation reduces mortality, infarct size and left ventricular remodeling: experimental evidence and proof of concept.

Background: Up-regulation of HO-1 by genetic manipulation or pharmacological pre-treatment has been reported to provide benefits in several animal models of myocardial infarction (MI). However, its efficacy following MI initiation (as in clinical reality) remains to be tested. Therefore, this study investigated whether HO-1 over-expression, by cobalt protoporphyrin (CoPP) administered after LAD ligation, is still able to improve functional and structural changes in left ventricle (LV) in a rat model of 4-week MI.

Gain of ALK gene copy number may predict lack of benefit from anti-EGFR treatment in patients with advanced colorectal cancer and RAS-RAF-PI3KCA wild-type status.

Introduction: Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations.

Patients And Methods: We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number--defined as mean of 3 to 5 fusion signals in ≥ 10% of cells).

Apo-neocarzinostatin: a protein carrier for Cu(II) glycocomplexes and Cu(II) into U937 and HT29 cell lines.

In the field of pharmaceuticals there is an increasing need for new delivery systems to overcome the issues of solubility, penetration, toxicity and drug resistance. One of the possible strategies is to use biocarriers such as proteins to encourage the cell-penetration of drugs. In this paper, the use of the apo-protein neocarzinostatin (apo-NCS) as a carrier-protein for two Cu(II) glycocomplexes, previously characterized, and Cu(II) ions was investigated.

Napsin-A, TTF-1, EGFR, and ALK Status Determination in Lung Primary and Metastatic Mucin-Producing Adenocarcinomas.

Pulmonary mucin-producing adenocarcinomas may be indistinguishable on conventional histology from a metastasis, as thyroid transcription factor-1 (TTF-1) expression often is lacking and KRAS mutations are widely present even in extrapulmonary sites. Few data have been reported on the diagnostic role of napsin-A and epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations in this challenging differential diagnosis. Seventy-seven surgically resected cases, including 53 primary and 24 metastatic tumors from different sites, were evaluated for napsin-A, TTF-1, and ALK by immunohistochemistry and for EGFR mutations by direct sequencing.