Nutraceutical Compounds as Sensitizers for Cancer Treatment in Radiation Therapy.

The improvement of diagnostic techniques and the efficacy of new therapies in clinical practice have allowed cancer patients to reach a higher chance to be cured together with a better quality of life. However, tumors still represent the second leading cause of death worldwide. On the contrary, chemotherapy and radiotherapy (RT) still lack treatment plans which take into account the biological features of tumors and depend on this for their response to treatment.

Gene Expression Profiles Induced by High-dose Ionizing Radiation in MDA-MB-231 Triple-negative Breast Cancer Cell Line.

Background/aim: Radiation therapy (RT) represents a therapeutic option in breast cancer (BC). Even if a great number of BC patients receive RT, not all of them report benefits, due to radioresistance that gets activated through several factors, such as the hormone receptor status. Herein, we analyzed the gene expression profiles (GEP) induced by RT in triple-negative BC (TNBC) MDA-MB-231, to study signalling networks involved in radioresistance.

New Insights into the Occurrence of Matrix Metalloproteases -2 and -9 in a Cohort of Breast Cancer Patients and Proteomic Correlations.

Matrix metalloproteases (MMPs) are a family of well-known enzymes which operate prevalently in the extracellular domain, where they fulfil the function of remodeling the extracellular matrix (ECM). Within the 26 family members, encoded by 24 genes in humans, MMP-2 and MMP-9 have been regarded as primarily responsible for the basement membrane and peri-cellular ECM rearrangement. In cases of infiltrating carcinomas, which arise from the epithelial tissues of a gland or of an internal organ, a marked alteration of the expression and the activity levels of both MMPs is known to occur.

Retrospective Proteomic Screening of 100 Breast Cancer Tissues.

The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The specimens were selected from patients with invasive ductal carcinoma of the breast, the most frequent and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers potentially useful for clinical applications. The proteomic screening; by 2D-IPG and mass spectrometry; allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients; and proteins expressed sporadically among the same patients.

Donor age and long-term culture do not negatively influence the stem potential of limbal fibroblast-like stem cells.

Background: In regenerative medicine the maintenance of stem cell properties is of crucial importance. Ageing is considered a cause of reduced stemness capability. The limbus is a stem niche of easy access and harbors two stem cell populations: epithelial stem cells and fibroblast-like stem cells.

Hospital admissions for hypertensive crisis in the emergency departments: a large multicenter Italian study.

Epidemiological data on the impact of hypertensive crises (emergencies and urgencies) on referral to the Emergency Departments (EDs) are lacking, in spite of the evidence that they may be life-threatening conditions. We performed a multicenter study to identify all patients aged 18 years and over who were admitted to 10 Italian EDs during 2009 for hypertensive crises (systolic blood pressure ≥220 mmHg and/or diastolic blood pressure ≥120 mmHg). We classified patients as affected by either hypertensive emergencies or hypertensive urgencies depending on the presence or the absence of progressive target organ damage, respectively.

Proteomic profiling of Trastuzumab (Herceptin(R))-sensitive and -resistant SKBR-3 breast cancer cells.

Background: The Human Epidermal Growth Factor Receptor 2 (HER-2), overexpressed in 25-30% of breast carcinomas (BC), is the therapeutic target for trastuzumab, a recombinant humanized monoclonal antibody. The initial response to trastuzumab is often followed by drug-insensitivity within one year. Several hypotheses have been raised to explain this event, but the mechanisms behind the responses to trastuzumab are still unclear.

Differential proteomic and phenotypic behaviour of papillary and anaplastic thyroid cell lines.

Thyroid carcinomas account for a minority of all malignant tumours but, after those of the gonads, they represent the most common forms of endocrine cancers. They include several types, among which the papillary thyroid cancer (PTC) and the anaplastic thyroid cancer (ATC) are the best known. The two hystotypes display significant biological and clinical differences: PTC is a well differentiated form of tumour with a high incidence and a good prognosis, while the ATC is less frequent but represents one of the most aggressive endocrine tumours with morphological features of an undifferentiated type.

Differential occurrence of S100A7 in breast cancer tissues: a proteomic-based investigation.

Purpose: The present study reports for the first time a large-scale proteomic screening of the occurrence, subcellular localization and relative quantification of the S100A7 protein among a group of 100 patients, clinically grouped for the diagnosis of infiltrating ductal carcinoma (IDC).

Experimental Design: To this purpose, the methods of differential proteomics, Western blotting, and immunohistochemistry were used.

Results: The identity of two isoforms of the protein was assessed by mass spectrometry and immunologically confirmed.

A prospective registry of European haemophilia B patients receiving nonacog alfa, recombinant human factor IX, for usual use.

Nonacog alfa, a recombinant factor IX (FIX) used for the treatment of haemophilia B, was approved in Europe in 1998. In accordance with European Medicines Agency requirements, a registry study was conducted from 2002 to 2009. A reformulated iso-osmotic version was approved for European use in 2007.

Intracranial haemorrhage in the Italian population of haemophilia patients with and without inhibitors.

Intracranial haemorrhage (ICH) is the most serious bleeding symptom in haemophiliacs, resulting in high rates of mortality and disabling sequelae. The Association of Italian Haemophilia Centres carried out a retrospective survey (1987-2008) of ICH occurring in haemophiliacs with the goals to establish: (i) incidence, location of bleeding, death rate and disabling sequels; (ii) risk factors for ICH; and (iii) treatment used during the acute phase of ICH and for recurrence prevention. A total of 112 ICH episodes had occurred in 88 patients (78 haemophilia A, 10 haemophilia B), 24 of whom experienced recurrences.

A retrospective study to describe the incidence of moderate to severe allergic reactions to factor IX in subjects with haemophilia B.

Using a patient chart review process, we conducted a retrospective study to describe the frequency of allergic reactions in individuals with haemophilia B receiving factor IX (FIX) replacement therapy. The number of allergic reactions in individuals receiving a recombinant FIX (rFIX) product (BeneFix(®)) was then compared with the number of reactions in patients receiving plasma-derived FIX (pdFIX) products. Of the 180 subjects in the study, 163 received rFIX, 88 received pdFIX; 71 received both product types.

Large-scale proteomic identification of S100 proteins in breast cancer tissues.

Background: Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements.

Patient preference for needleless factor VIII reconstitution device: the Italian experience.

Background: Needlestick injuries, mostly due to unsafe needle devices, are a frequent adverse event among health care workers and patients on chronic treatment, such as hemophiliacs. To improve the safety of these procedures, a needleless reconstitution system, Bio-Set((R)) has been implemented for the sucrose-formulated recombinant factor VIII (rFVIII-FS) Kogenate((R)) Bayer (Bayer Healthcare, Berlin, Germany). The aim of this study was to collect patients' satisfaction and safety data regarding the administration of rFVIII-FS with this new device.

High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study.

Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients achieve remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard- versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP.

Postmarketing surveillance study of KOGENATE Bayer with Bio-Set in patients with haemophilia A: evaluation of patients' satisfaction after switch to the new reconstitution system.

KOGENATE Bayer (rFVIII-FS) with Bio-Set is designed to prevent patient contact with exposed needles during recombinant factor VIII reconstitution. This postmarketing surveillance study evaluated patient satisfaction before and after switching to the new Bio-Set reconstitution method. Male children and adults with haemophilia A were enrolled from nine European countries.

Efficacy and safety of highly purified, doubly virus-inactivated VWF/FVIII concentrates in inherited von Willebrand's disease: results of an Italian cohort study on 120 patients characterized by bleeding severity score.

The efficacy of highly purified VWF/FVIII concentrates with standardized ristocetin cofactor content (VWF:RCo) has been already proven in patients with von Willebrand's disease (VWD). Aim of this retrospective study is to confirm efficacy and safety of two highly purified, doubly virus-inactivated VWF/FVIII concentrates in a large cohort of patients with VWD who were characterized at enrolment by bleeding severity score. Study drugs Alphanate or Fanhdi were given to 120 cases (51 males, 69 females, median age 50 years, range 6-83 years).

Efficacy and safety of recombinant factor VIII products in patients with hemophilia A.

The introduction of recombinant factor VIII (rFVIII) clotting factor concentrates nearly 20 years ago represented a significant advance in the treatment of hemophilia A. The major advantage of rFVIII products compared with plasma-derived FVIII products is related to product safety, with rFVIII products virtually eliminating bloodborne pathogen transmission. The most challenging aspect of hemophilia A management today is the development of FVIII inhibitors; previously untreated patients are at the highest risk for inhibitor formation.

Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: experience in the standard clinical setting.

The safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1-19 exposure days (EDs). Patients accumulated a mean (+/- SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days.

Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response.

Immune tolerance induction (ITI) is effective in approximately 70% of haemophilia patients with inhibitors. Poor prognostic factors are age >6 years, ITI started >1 year from inhibitor development, inhibitor peaks >200 BU, inhibitor titre >10 BU when ITI is started and previously failed ITI. The objective of this study was to identify the effectiveness in ITI of a high purity von Willebrand factor/factor VIII (VWF/FVIII) complex concentrate in inhibitor patients at high risk of failure.

The role of leptin in the etiopathogenesis of anorexia nervosa and bulimia.

Leptin is an adipocyte-derived signal factor (167 amino acid protein) encoded by the ob gene in chromosome 7q31 that regulates eating behaviour via central neuroendocrine mechanisms. It has been shown that serum leptin levels correlate with weight and percentage body fat in normal and obese individuals, but the exact correlation between leptin and body weight in anorexic and bulimic patients has not yet been clarified. We investigated leptin levels in the serum of 58 female subjects aged 15-36 years: 10 with bulimia nervosa (BN); 12 with anorexia nervosa (AN); 12 overweight controls (not BN); 12 weight-reduced controls (not AN); and 12 normal weight controls.

MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness.

May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families.