XELIRI or FOLFIRI as salvage therapy in advanced pancreatic cancer.

Background: More than half of patients with pancreatic adenocarcinoma (PA) are candidates for further treatment when they experience upfront treatment failure.

Patients And Methods: Patients with gemcitabine-resistant PA, age <76 years and Karnofski performance status (KPS) >50 were treated with a XELIRI or FOLFIRI regimen until progressive disease or a maximum of six months. As this was an observational study, no statistical design was performed.

Cryo-EM structure and rRNA model of a translating eukaryotic 80S ribosome at 5.5-A resolution.

Protein biosynthesis, the translation of the genetic code into polypeptides, occurs on ribonucleoprotein particles called ribosomes. Although X-ray structures of bacterial ribosomes are available, high-resolution structures of eukaryotic 80S ribosomes are lacking. Using cryoelectron microscopy and single-particle reconstruction, we have determined the structure of a translating plant (Triticum aestivum) 80S ribosome at 5.

Localization of eukaryote-specific ribosomal proteins in a 5.5-Å cryo-EM map of the 80S eukaryotic ribosome.

Protein synthesis in all living organisms occurs on ribonucleoprotein particles, called ribosomes. Despite the universality of this process, eukaryotic ribosomes are significantly larger in size than their bacterial counterparts due in part to the presence of 80 r proteins rather than 54 in bacteria. Using cryoelectron microscopy reconstructions of a translating plant (Triticum aestivum) 80S ribosome at 5.

Emerging sublingual immunotherapy drugs.

Importance Of The Field: There is epidemiological evidence that respiratory allergy has reached epidemic proportions; owing to the related socio-economic impact, this topic deserves particular attention. An integrated approach involving pharmacotherapy and the immunomodulatory effect of immunotherapy is expected to optimize the management of respiratory allergy, reducing its clinical and economic burdens. Sublingual immunotherapy (SLIT) has gained increasing interest for its efficacy comparable to traditional subcutaneous immunotherapy and its good safety profile.

Applications of the molecular dynamics flexible fitting method.

In recent years, cryo-electron microscopy (cryo-EM) has established itself as a key method in structural biology, permitting the structural characterization of large biomolecular complexes in various functional states. The data obtained through single-particle cryo-EM has recently seen a leap in resolution thanks to landmark advances in experimental and computational techniques, resulting in sub-nanometer resolution structures being obtained routinely. The remaining gap between these data and revealing the mechanisms of molecular function can be closed through hybrid modeling tools that incorporate known atomic structures into the cryo-EM data.

Interleukin-1β, C-x-C motif ligand 10, and interferon-gamma serum levels in mixed cryoglobulinemia with or without autoimmune thyroiditis.

The aim of this study was to evaluate serum levels of interleukin-1β (IL-1β), chemokine (C-X-C motif) ligand 10 (CXCL10), and interferon-gamma (IFN-γ) in a series of patients with "mixed cryoglobulinemia and hepatitis C virus chronic infection" (MC + HCV) in the presence or absence of autoimmune thyroiditis (AT) and to relate them to the clinical phenotype of these patients. Serum IL-1β, IFN-γ, and CXCL10 were assayed in 30 patients with MC + HCV without AT, in 30 patients with MC + HCV and AT, and in 30 sex- and age-matched controls. Cryoglobulinemic patients showed significantly higher mean IL-1β and CXCL10 levels than controls (P < 0.

Integration of cryo-EM with atomic and protein-protein interaction data.

Cryoelectron microscopy (cryo-EM) is an increasingly popular method to elucidate the structures of macromolecular complexes. However, in many applications the resolution of cryo-EM densities is limited to the low or intermediate resolution regime, that is, (10Å)(-1) or worse. Therefore, unambiguous molecular interpretation of cryo-EM densities requires efficient use of additional information, such as atomic structures of related subunits and protein-protein interaction data.

Antiangiogenic strategies in breast cancer management.

Angiogenesis is considered one of the key mechanisms of tumour growth and survival. Therefore it represents an ideal pharmaceutical target. Many antiangiogenic agents have been developed so far in several solid tumours and also in breast cancer.

May we strengthen the human natural defenses with bacterial lysates?

During the last twenty years bacterial lysates have gained a new interest and their use has obtained a progressively larger consensus in the medical practice. They are commonly used as immunomodulators, in order to up-regulate immune responses against infectious damages. As a matter of fact, the role of these lysate seems relevant in upper and lower respiratory tract infections prevention, frequently observed both in paediatric and elder ages, and which represent a relevant problem also in terms of socio-economical implications.

Immunomodulatory Agents with Antivascular Activity in the Treatment of Non-Small Cell Lung Cancer: Focus on TLR9 Agonists, IMiDs and NGR-TNF.

Standard treatments for nonsmall cell lung cancer (NSCLC), such as surgery, chemotherapy, and radiotherapy, often lead to disappointing results. Unfortunately, also the various immunotherapeutic approaches so far tested have not produced satisfactory results to be widely applied in the clinical practice. However, the recent development of new immunomodulatory agents may open promising therapeutic options.

Consolidation radiotherapy in primary central nervous system lymphomas: impact on outcome of different fields and doses in patients in complete remission after upfront chemotherapy.

Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined.

Methods And Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT).

Circulating endothelial cells and endothelial progenitors as predictive markers of clinical response to bevacizumab-based first-line treatment in advanced colorectal cancer patients.

Background: Despite the consistent clinical results demonstrated by studies on anti-angiogenic drugs targeted against the vascular endothelial growth factor in metastatic colorectal cancer (mCRC) patients, no specific direct/indirect biomarker of their efficacy has been validated. In this field, circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs) have recently been proposed as noninvasive biomarkers.

Patients And Methods: The absolute numbers of CEPs, total CECs (tCECs) and their resting (rCECs) and activated subsets were evaluated by multiparameter flow cytometry in 40 mCRC patients at baseline and before the administration of the third and sixth course of a bevacizumab-based first-line treatment.

The link between allergic rhinitis and asthma: the united airways disease.

Rhinitis and asthma are often associated and the two disorders interact at various levels. Rhinitis typically precedes the development of asthma and can contribute to unsatisfactory asthma control. The presence and type of asthma is influenced by sensitization, and the duration and severity of allergic rhinitis.

Intraoral laser welding: ultrastructural and mechanical analysis to compare laboratory laser and dental laser.

The Nd:YAG laser has been used since 1970 in dental laboratories to weld metals on dental prostheses. Recently in several clinical cases, we have suggested that the Nd:YAG laser device commonly utilized in the dental office could be used to repair broken fixed, removable and orthodontic prostheses and to weld metals directly in the mouth. The aim of this work was to evaluate, using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and dynamic mechanical analysis (DMA), the quality of the weld and its mechanical strength, comparing a device normally used in dental laboratory and a device normally used in the dental office for oral surgery, the same as that described for intraoral welding.

Treatment approaches for primary CNS lymphomas.

Importance Of The Field: Primary central nervous system lymphomas (PCNSL) are rare but potentially curable tumours. The overall outcome for PCNSL patients is unsatisfactory and several therapeutic questions remain open. Modest progress in outcome reflects difficulties in conducting randomized trials and scarce molecular and biological knowledge.

No inflammation? No cancer! Clear HBV early and live happily.

Commentary On: Clearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma in a cohort Chronically Infected with Hepatitis B Virus. Simonetti J, Bulkow L, McMahon BJ, Homan C, Snowball M, Negus S, Williams J, Livingston SE. Hepatology.

Medium-term results of systematic off-pump coronary surgery performed by trainee surgeons.

Objective: Our unit has used off-pump coronary artery bypass (OPCAB) surgery since 1998, and has consequently developed teaching methods for surgical trainees. This study aimed to compare the medium-term results of OPCAB performed by experts or supervised trainees.

Methods: We retrospectively analysed the data relating to 1333 OPCAB operations performed between January 1998 and January 2006 (mean patient age: 65.

Oxygen-isotope exchange rates for three isostructural polyoxometalate ions.

We compare oxygen-isotope exchange rates for all structural oxygens in three polyoxoniobate ions that differ by systematic metal substitutions of Ti(IV) --> Nb(V). The [H(x)Nb(10)O(28)]((6-x)-), [H(x)TiNb(9)O(28)]((7-x)-), and [H(x)Ti(2)Nb(8)O(28)]((8-x)-) ions are all isostructural yet have different Brønsted properties. Rates for sites within a particular molecule in the series differ by at least approximately 10(4), but the relative reactivities of the oxygen sites rank in nearly the same relative order for all ions in the series.

The cisplatin, epirubicin, 5-fluorouracil, gemcitabine (PEFG) regimen in advanced biliary tract adenocarcinoma.

Background: Biliary tract adenocarcinoma (BTA) is an uncommon tumor with a poor prognosis and no standard, systemic chemotherapy. The combined cisplatin, epirubicin, 5-fluorouracil, and gemcitabine (PEFG) regimen is an effective, upfront treatment for advanced pancreatic cancer. In this study, the authors assessed the activity and safety of this combination regimen in patients with advanced BTA.

Structural model and excitonic properties of the dimeric RC-LH1-PufX complex from Rhodobacter sphaeroides.

The light-harvesting apparatus of the purple bacterial photosynthetic unit consists of a pool of peripheral light-harvesting complexes that transfer excitation energy to a reaction center (RC) via the surrounding pigment-protein complex LH1. Recent electron microscopy and atomic force microscopy studies have revealed that RC-LH1 units of Rhodobacter sphaeroides form membrane-bending dimeric complexes together with the polypeptide PufX. We present a structural model for these RC-LH1-PufX dimeric complexes constructed using the molecular dynamics flexible fitting method based on an EM density map.

Pretreatment with pegylated interferon prevents emergence of lamivudine mutants in lamivudine-naive patients: a pilot study.

Background: In patients with advanced fibrosis, primary end points of long-term or possibly indefinite antiviral therapy are sustained inhibition of viral replication and avoidance of emergence of resistance. In lamivudine-treated patients, the strongest predictor of emergence of YMDD mutations is baseline hepatitis B virus (HBV) DNA viral load. We aimed to verify whether abatement of viraemia by a short course of pegylated interferon (PEG-IFN-alpha2a) treatment before lamivudine treatment could prevent the emergence of lamivudine-associated mutations during long-term therapy.