Neoadjuvant treatment of HER2 and hormone-receptor positive breast cancer - moving beyond pathological complete response.

Pathologic complete response (pCR) was noted to be prognostic in all but hormone receptor-positive (HR) breast cancer cases even when HER2 is overexpressed. Evocative data suggest that HER2-positive breast cancer patients are a heterogeneous population and a subset of HER2-positive and HR-positive tumors biologically behave more like HER2-negative. Identification and targeted monitoring of these patients is crucial to consolidate data aiming to optimize combination treatment with new agents, thereby avoiding overtreatment with chemotherapy.

The conformation of enkephalin bound to its receptor: an "elusive goal" becoming reality.

The availability of solid state structures of opioid receptors has prompted us to reconsider a crucial question concerning bioactive peptides: can their conformation be studied without any knowledge of the structure of their receptors? The possibility of giving a meaningful answer to this query rests ultimately on the ease of dealing with the flexibility of bioactive peptides, and amongst them one of the most flexible bioactive peptides, enkephalin. All solution studies of enkephalin hint at an inextricable mixture of quasi isoenergetic conformers. In this study we refer to the only NMR work that yielded inter-residue NOEs, performed at very low temperature.

Helicobacter pylori HP(2-20) induces eosinophil activation and accumulation in superficial gastric mucosa and stimulates VEGF-alpha and TGF-beta release by interacting with formyl-peptide receptors.

Eosinophils participate in the immune response against Helicobacter pylori, but little is known about their role in the gastritis associated to the infection. We recently demonstrated that the Hp(2-20) peptide derived from H. pylori accelerates wound healing of gastric mucosa by interacting with N-formyl peptide receptors (FPRs) expressed on gastric epithelial cells.

Pure 16q21q22.1 deletion in a complex rearrangement possibly caused by a chromothripsis event.

Background: Partial monosomies of chromosome 16q are rare and overlapping effects from complex chromosomal rearrangements often hamper genotype-phenotype correlations for such imbalances. Here, we report the clinical features of an isolated partial monosomy 16q21q22.1 in a boy with a complex de novo rearrangement possibly resulting from a chromothripsis event.

A polymer model explains the complexity of large-scale chromatin folding.

The underlying global organization of chromatin within the cell nucleus has been the focus of intense recent research. Hi-C methods have allowed for the detection of genome-wide chromatin interactions, revealing a complex large-scale organization where chromosomes tend to partition into megabase-sized "topological domains" of local chromatin interactions and intra-chromosomal contacts extends over much longer scales, in a cell-type and chromosome specific manner. Until recently, the distinct chromatin folding properties observed experimentally have been difficult to explain in a single conceptual framework.

[Epidemiology and prognosis of chronic kidney disease in Italy].

Because chronic kidney disease (CKD) is a major public health issue, it is important to make the available epidemiological data widely known for a proper understanding of its social impact, and to identify risk factors that can influence the prognosis of the disease. The data from the CARHES study show in the general population of Italy a prevalence of CKD (stage 1-5) of 8%, less than in other countries, a higher prevalence of proteinuria at early stages (1-2), and a cardiovascular risk profile in CKD patients characterized by metabolic syndrome. The prognosis of CKD is an essential element in clinical practice as it allows to better define the severity of the disease and to determine the most appropriate therapeutic approach.

[Limitations of blood pressure target in non-dialysis chronic kidney disease: a question of method?].

International guidelines recommend to reduce blood pressure (BP) levels below 130/80 mmHg in non-dialysis chronic kidney disease (CKD) patients. However, this BP target has not been validated by randomized controlled trials and is mainly driven by data obtained in observational and post-hoc analyses suggesting that it improves the renal and, to some extent, cardiovascular prognosis. The inconclusive results on the prognostic role of the BP target in patients with CKD might also relate to the limited ability of office BP readings to adequately stratify the global risk of this population.

[Amino acid loss during dialysis treatment].

Protein-calorie malnutrition is a widespread complication in hemodialysis (HD) patients and is associated with increased mortality. The pathogenesis of malnutrition is multifactorial. Intradialytic amino acid (AA) loss is considered one of the cofactors in the complex mechanisms that lead to malnutrition in HD patients.

Analysis and modelling of motility of cell populations with MotoCell.

Background: Cell motility plays a central role in development, wound-healing and tumour invasion. Cultures of eukaryotic cells are a complex system where most cells move according to 'random' patterns, but may also be induced to a more coordinate migration by means of specific stimuli, such as the presence of chemical attractants or the introduction of a mechanical stimulus. Various tools have been developed that work by keeping track of the paths followed by specific objects and by performing statistical analysis on the recorded path data.

TAZ is a coactivator for Pax8 and TTF-1, two transcription factors involved in thyroid differentiation.

Pax8 and TTF-1 are transcription factors involved in the morphogenesis of the thyroid gland and in the transcriptional regulation of thyroid-specific genes. Both proteins are expressed in few tissues but their simultaneous presence occurs only in the thyroid where they interact physically and functionally allowing the regulation of genes that are markers of the thyroid differentiated phenotype. TAZ is a transcriptional coactivator that regulates the activity of several transcription factors therefore playing a central role in tissue-specific transcription.

Hydrogen sulphide is involved in testosterone vascular effect.

Background: Testosterone (T) induces a rapid relaxation in vascular tissues of different species due to a nongenomic effect of this steroid on vessels. Different mechanisms have been proposed to explain T-induced vasodilatation but the effective mechanism(s) and the mediators involved are still a matter of debate.

Objectives: We have evaluated if H(2)S pathway is involved in T vascular effects.

Acute appendicitis: diagnostic value of nonenhanced CT with selective use of contrast in routine clinical settings.

The purposes of this study were to determine the (1) frequency with which nonenhanced computed tomography (CT) (NECT) permits conclusive diagnosis of acute appendicitis, (2) accuracy of NECT when findings are conclusive, and (3) overall accuracy of a CT protocol consisting of NECT with selective use of contrast. Five hundred and thirty-six patients underwent a NECT protocol with selective use of contrast. Diagnostic accuracy was then determined separately for (1) patients with conclusive initial NECT, (2) patients with inconclusive initial NECT, and (3) all patients.

Natural and synthetic retinoids in prostate cancer.

Prostate cancer (PCa) is the most common cancer for men in Europe, North America, and some parts of Africa. Initially, growth of prostate cancer is usually androgen-dependent, but often it becomes androgen-independent after androgen-deprivation therapy. Managing hormone-refractory prostate carcinoma remains a difficult challenge for clinicians.

Chitosan-whey protein edible films produced in the absence or presence of transglutaminase: analysis of their mechanical and barrier properties.

Chitosan-whey protein edible films with different protein concentrations were prepared in the absence or presence of microbial transglutaminase as cross-linking agent. The films prepared in the presence of the enzyme showed low solubility at a wide range of pH, a lower degree of swelling, and good biodegradability following protease treatments. The presence of transglutaminase induced also an enhancement in film mechanical resistance and a reduction in their deformability.

Specific targeting highly conserved residues in the HIV-1 reverse transcriptase primer grip region. Design, synthesis, and biological evaluation of novel, potent, and broad spectrum NNRTIs with antiviral activity.

Pyrrolobenzoxazepinones (PBOs) represent a new class of human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) whose prototype is 5. Molecular modeling studies based on the X-ray structures of HIV-1 RT prompted the synthesis of novel analogues which were tested as anti-HIV agents. The PBO derivatives specifically designed to target the highly conserved amino acid residues within the beta12-beta13 hairpin, namely primer grip, proved to be very potent against the most common mutant enzymes, including the highly resistant K103N mutant strain.

Lactoferrin: an important host defence against microbial and viral attack.

The first function attributed to lactoferrin (Lf), an iron binding protein belonging to the non-immune natural defences, was antimicrobial activity that depended on its capacity to sequester iron. Iron-independent microbicidal activities, requiring direct interaction between this cationic protein and microbial surface components, were later demonstrated. Many other anti-microbial and anti-viral functions have since been ascribed to Lf.

Receptor tyrosine kinases as targets for anticancer therapeutics.

Oncogenic conversion of receptor protein tyrosine kinases (RTK) is a frequent feature of malignant cells. This knowledge has fostered efforts to develop target-specific low molecular weight therapeutics able to obstruct RTK signalling. The clinical efficacy of the ABL- and KIT-inhibitors are paradigmatic of the power of this approach.

Use of autologous platelet-rich plasma (PRP) in periodontal defect treatment after extraction of impacted mandibular third molars.

Purpose: The extraction of mesioangular impacted third molars may cause multiple periodontal defects at the distal root of the second molar. Platelet-rich plasma (PRP) is a material containing many autologous growth factors that may be used in repairing and preventing periodontal complications at the distal root of the second molar adjacent to the extracted third molar.

Patients And Methods: We analyzed the effects of autologous PRP on periodontal tissues after extraction of the third molar in 18 young patients (age, 21-26 years).

CT appearance of the normal appendix in adults.

The aims of this study were to identify (1) the normal range of the appendix on computed tomography (CT), (2) the correlation of patient age and sex with the visibility and appearance of the appendix on CT, and (3) the normal variations in wall thickness, intraluminal content, and location of the appendix. Three hundred seventy-two outpatients underwent abdominopelvic CT. The scans were reviewed on the picture archiving and communication system and appendiceal outer-to-outer wall diameter, wall thickness, location, content and its correlation with appendix diameter were analyzed.

Case report: laparoscopic cholecystectomy in situs viscerum inversus.

Situs viscerum inversus is a rare condition, in which the organs are transposed from their normal location in the opposite side of the body. The inversion of L-R asymmetry may be complete (SVI totalis) or partial (SVI partialis), whereby transposition is confined to either the abdominal or thoracic viscera. The authors report a case of videolaparocholecystectomy for cholelithiasis successfully performed on a 41-year-old Caucasian woman with situs viscerum inversus totalis.

Vitelline envelope gps 63 and 75 specifically bind sperm in "in vitro" assays in Discoglossus pictus.

In Xenopus, conflicting data related to sperm-vitelline envelope (VE) binding suggest that further experiments should be performed to study the role of VE glycoproteins in sperm binding. In this article, we studied the VE of Discoglossus pictus, where gp63, the product of the Dp ZP2 gene, has high molecular identity to Xenopus gp69/64 and to mouse ZP2 and only A23187-treated sperm bind to VE. Sperm bind to VE all over the egg, yet a sperm tuft was found only in the animal half of the egg, where the dimple, the site of fertilization, is located and an intense immunostain was detected in VE by an antiserum directed against gp69/64.

All-trans retinoic acid- and N-(4-hydroxyphenil)-retinamide-induced growth arrest and apoptosis in orbital fibroblasts in Graves' disease.

In this study, we evaluated by reverse transcription-polymerase chain reaction (RT-PCR) the expression pattern of retinoic acid receptors (RAR) alpha, beta, and gamma and cellular retinoic acid binding protein-I (CRBP-I) genes in 12 primary cultures of fibroblasts (F) from orbital tissue of Graves' ophthalmopathy (GO) patients. We also studied the in vitro effects of all-trans retinoic acid (RA) and N-(4-hydroxyphenil)-retinamide (4HPR), a less toxic and better tolerated synthetic derivative of RA, on cell morphology, growth, apoptosis, and cyclic adenosine monophosphate (cAMP) accumulation. All primary cultures expressed RAR alpha, beta, gamma, and CRBP-I.

WBP-2, a WW domain binding protein, interacts with the thyroid-specific transcription factor Pax8.

The Pax gene family encodes transcription factors that are essential in organogenesis and in the differentiation of various organs in higher eukaryotes. Pax proteins have a DNA binding domain at the N-terminus, and a transcriptional activation domain at the C-terminus. How these domains interact with the transcriptional machinery of the cell is still unclear.