MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin.

Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases.

Autoimmune lymphoproliferative syndrome in pregnancy: a case of favorable mother-fetal outcome in a well-controlled disease.

The autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by the dysregulation of the Fas apoptotic pathway. The Fas gene is expressed at the maternal-fetal interface and is involved in the regulation of immune response and implantation. Altered Fas expression may result in altered apoptosis and, ultimately, affect both the immune response and implantation; it is in fact associated with recurrent pregnancy loss, preterm premature rupture of membranes and pre-eclampsia.

Complete pathological response after FOLFIRINOX for locally advanced pancreatic cancer. The beginning of a new era? Case report and review of the literature.

Neoadjuvant treatments (chemo or chemoradiation therapy) are used for patients with locally advanced Pancreatic Ductal Adeno-Carcinoma (PDAC). FOLFIRINOX is now considered an effective treatment modality for patients with metastatic pancreatic cancer and a promising option for patients with locally advanced PDAC. Complete pathologic response after neoadjuvant therapies is anecdotic and its prognostic impact is completely unclear.

HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment.

Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay.

Can platelet-rich plasma enhance anterior cruciate ligament and meniscal repair?

The use of platelet-rich plasma (PRP) to improve clinical outcome following a soft tissue injury, regeneration, and repair has been the subject of intense investigation and discussion. This article endeavors to relate clinical and basic science strategies focused on biological augmentation of the healing response in anterior cruciate ligament (ACL) and meniscus repair and replacement using PRP. Therein, a translational feedback loop is created in the literature and targeted towards the entire multidisciplinary team.

Biodiversity of Aspergillus section Flavi in Europe in relation to the management of aflatoxin risk.

Aflatoxins and the producing fungi Aspergillus section Flavi are widely known as the most serious and dangerous mycotoxin issue in agricultural products. In Europe, before the outbreak of aflatoxins on maize (2003-2004) due to new climatic conditions, their contamination was confined to imported foods. Little information is available on molecular biodiversity and population structure of Aspergillus section Flavi in Europe.

Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients.

Background: MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types.

Methods: We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n = 150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.

The polyene antifungals, amphotericin B and nystatin, cause cell death in Saccharomyces cerevisiae by a distinct mechanism to amphibian-derived antimicrobial peptides.

Background: There is a pressing need to identify novel antifungal drug targets to aid in the therapy of life-threatening mycoses and overcome increasing drug resistance. Identifying specific mechanisms of action of membrane-interacting antimicrobial drugs on the model fungus Saccharomyces cerevisiae is one avenue towards addressing this issue. The S.

Effect of almond processing on levels and distribution of aflatoxins in finished products and byproducts.

The fate of aflatoxins during processing of contaminated almonds into nougat, pastries, and almond syrup was evaluated by testing the effect of each processing step (blanching, peeling, roasting, caramelization, cooking, and water infusion) on the distribution and levels of aflatoxins. Blanching and peeling did not reduce total aflatoxins that were distributed between peeled almonds (90-93%) and skins (7-10%). Roasting of peeled almonds reduced up to 50% of aflatoxins.

Genome-wide analysis of Saccharomyces cerevisiae identifies cellular processes affecting intracellular aggregation of Alzheimer's amyloid-β42: importance of lipid homeostasis.

Amyloid-β (Aβ)-containing plaques are a major neuropathological feature of Alzheimer's disease (AD). The two major isoforms of Aβ peptide associated with AD are Aβ40 and Aβ42, of which the latter is highly prone to aggregation. Increased presence and aggregation of intracellular Aβ42 peptides is an early event in AD progression.

Population structure and aflatoxin production by Aspergillus Sect. Flavi from maize in Nigeria and Ghana.

Aflatoxins are highly toxic carcinogens that contaminate crops worldwide. Previous studies conducted in Nigeria and Ghana found high concentrations of aflatoxins in pre- and post-harvest maize. However, little information is available on the population structure of Aspergillus Sect.

Hypoxia inducible factor-1 alpha as a therapeutic target in multiple myeloma.

The increasing importance of hypoxia-inducible factor-1α (HIF-1α) in tumorigenesis raises the possibility that agents which specifically inhibit this transcription factor, would provide significant therapeutic benefit. The constitutive expression of HIF-1α in about 35% of Multiple Myeloma (MM) patients suggests HIF-1α suppression might be part of a therapeutic strategy. Accordingly, we explored the effect of EZN-2968, a small 3rd generation antisense oligonucleotide against HIF-1α, in a panel of MM cell lines and primary patients samples.

Autoimmune diseases during treatment with immunomodulatory drugs in multiple myeloma: selective occurrence after lenalidomide.

Immunomodulatory drugs (IMiDs) may favor autoimmune disease (AD) occurrence. We conducted a retrospective study to evaluate AD occurrence among IMiD-treated patients with myeloma. Patients were grouped into three classes depending on the type of IMiD engaged.

Proteomic analysis of A2780/S ovarian cancer cell response to the cytotoxic organogold(III) compound Aubipy(c).

Unlabelled: Aubipyc is an organogold(III) compound endowed with encouraging anti-proliferative properties in vitro that is being evaluated pre-clinically as a prospective anticancer agent. A classical proteomic approach is exploited here to elucidate the mechanisms of its biological actions in A2780 human ovarian cancer cells. Based on 2-D gel electrophoresis separation and subsequent mass spectrometry identification, a considerable number of differentially expressed proteins were highlighted in A2780 cancer cells treated with Aubipyc.

Identification and characterization of the polyketide synthase involved in ochratoxin A biosynthesis in Aspergillus carbonarius.

Ochratoxin A (OTA) is a potent mycotoxin produced by Aspergillus and Penicillium species and is a common contaminant of a wide variety of food commodities, with Aspergillus carbonarius being the main producer of OTA contamination in grapes and wine. The molecular structure of OTA comprises a dihydroisocoumarin ring linked to phenylalanine and, as shown in different producing fungal species, a polyketide synthase (PKS) is a component of the OTA biosynthetic pathway. Similar to observations in other filamentous ascomycetes, the genome sequence of A.

Hepatic toll-like receptor 4 expression is associated with portal inflammation and fibrosis in patients with NAFLD.

Background & Aims: Notwithstanding evidences implicating the lipopolysaccharides (LPS)/toll-like receptor-4 (TLR4) axis in the pathogenesis of NAFLD, there are no studies aimed to characterize hepatic TLR4 expression in NAFLD patients. We aimed to analyse hepatic TLR4 expression and to verify its relationship with disease activity/evolution in NAFLD patients.

Methods: Liver tissue from 74 patients with NAFLD and 12 controls was analysed by immunohistochemistry (IHC) for TLR4, α-smooth muscle actin (α-SMA) and cytokeratin-7.

The use of silk-based devices for fracture fixation.

Metallic fixation systems are currently the gold standard for fracture fixation but have problems including stress shielding, palpability and temperature sensitivity. Recently, resorbable systems have gained interest because they avoid removal and may improve bone remodelling due to the lack of stress shielding. However, their use is limited to paediatric craniofacial procedures mainly due to the laborious implantation requirements.

Emergence of Prochloraz-Resistant Populations of Calonectria pauciramosa and Calonectria polizzii in Ornamental Nurseries of Southern Italy.

Management of Calonectria spp. infections in nurseries requires scheduled fungicide applications, particularly with methyl benzimidazole carbamates (MBCs) and sterol demethylation inhibitors (DMIs). Due to rising concerns about the occurrence of MBC resistance in different Calonectria populations and variability in prochloraz efficacy in controlling these pathogens, a detailed study on prochloraz sensitivity distributions of Calonectria isolates belonging to the Calonectria scoparia complex was carried out.

Chemistry and biology of two novel gold(I) carbene complexes as prospective anticancer agents.

Two novel gold carbene compounds, namely, chlorido (1-butyl-3-methyl-imidazole-2-ylidene) gold(I) (1) and bis(1-butyl-3-methyl-imidazole-2-ylidene) gold(I) (2), were prepared and characterized as prospective anticancer drug candidates. These compounds consist of a gold(I) center linearly coordinated either to one N-heterocyclic carbene (NHC) and one chloride ligand (1) or to two identical NHC ligands (2). Crystal structures were solved for both compounds, the resulting structural data being in good agreement with expectations.

Autologous stem cell transplantation for T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of T-cell malignancies characterized by a very poor outcome. The optimal treatment for PTCLs remains controversial. The role of stem cell transplantation in PTCLs has been investigated; however, no randomized control studies specifically dedicated to PTCLs are currently available.

Misfolding of apoprotein B-100, LDL aggregation and 17-β -estradiol in atherogenesis.

The long quest for a missing mechanistic rationale accounting for the correlation between plasma cholesterol levels and cardiovascular disease (CVD) has been focused on various possible modifications of low density lipoprotein (LDL), turning this physiological cholesterol carrier into a damaging agent able to trigger atherogenesis and later the onset of the disease. In addition to the debated oxidized LDL (oxLDL), a modified LDL with a misfolded apoprotein B-100, called electronegative LDL(-) for its negative charge due to an increased amount of free fatty acids, is commonly present in plasma. LDL(-) is generated by the action of secretory calcium dependent phospholipase A2.

Tumor associated macrophages polarization dictates the efficacy of BCG instillation in non-muscle invasive urothelial bladder cancer.

Background: To evaluate the prognostic role of TAMs in patients affected by non-muscle invasive bladder cancer (NMIBC), undergone Trans Urethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) therapy.

Methods: Data from 40 patients (36 men, 4 women), mean age 69 years (40-83 years), treated for NMIBC with TURB and BCG instillation were collected. Two different groups were considered: group with and group without bladder cancer recurrence.