Systemic inflammation, nutritional status and survival in patients with cancer

Systemic inflammation, nutritional status and survival in patients with cance

Lipopeptidomimetics derived from teixobactin have potent antibacterial activity against Staphylococcus aureus

A series of lipopeptidomimetics derived from teixobactin have been prepared that probe the role of residues (1–6) as a membrane anchor and the function of enduracididine. The most active compounds, with a farnesyl tail and End10 to Lys10 or Orn10 substitution have potent activity (MIC 8 μg mL−1) against S. aureus. These results pave the way for the synthesis of simple, cost-effective yet potent lipopeptidomimetic antimicrobials

IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic reaction driven by pancreatic stellate cells (PSCs) that contributes to tumor progression. Here we sought to characterize the interactions between pancreatic cancer cells (PCCs) and PSCs that affect the inflammatory and immune response in pancreatic tumors. Conditioned media from mono- and cocultures of PSCs and PCCs were assayed for expression of cytokines and growth factors. IP-10/CXCL10 was the most highly induced chemokine in coculture of PSCs and PCCs. Its expression was induced in the PSCs by PCCs. IP-10 was elevated in human PDAC specimens, and positively correlated with high stroma content. Furthermore, gene expression of IP-10 and its receptor CXCR3 were significantly associated with the intratumoral presence of regulatory T cells (Tregs). In an independent cohort of 48 patients with resectable pancreatic ductal adenocarcinoma, high IP-10 expression levels correlated with decreased median overall survival. Finally, IP-10 stimulated the ex vivo recruitment of CXCR3+ effector T cells as well as CXCR3+ Tregs derived from patients with PDAC. Our findings suggest that, in pancreatic cancer, CXCR3+ Tregs can be recruited by IP-10 expressed by PSCs in the tumor stroma, leading to immunosuppressive and tumor-promoting effects

L'art de la correspondance anglaise et francaise, perfectionné ou Recueil de lettres en anglais et en francais, sur toutes sortes de sujets familiers, précédé d'une introduction sur le style épistolaire

Contiene vol. 1,311 p.Sign.: [8], 1*-13*(4), 2-13(8)La sign. mantiene la secuencia : 1, 1*, 2, 2*... donde los cuadernos con numeración sola están en formato cuarto y los que llevan añadido el asterisco tienen formato octavo.Procedencia: Biblioteca del Real Colegio de Cirugía de la Armada de Cádiz, 1748-1833Portada paralela, texto bilingue francés e inglé

Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase

Background In accord with the cancer stem cell (CSC) theory, only a small subset of cancer cells are capable of forming tumors. We previously reported that CD44 isolates tumorigenic cells from head and neck squamous cell cancer (HNSCC). Recent studies indicate that aldehyde dehydrogenase (ALDH) activity may represent a more specific marker of CSCs. Methods Six primary HNSCCs were collected. Cells with high and low ALDH activity (ALDH high /ALDH low ) were isolated. ALDH high and ALDH low populations were implanted into NOD/SCID mice and monitored for tumor development. Results ALDH high cells represented a small percentage of the tumor cells (1% to 7.8%). ALDH high cells formed tumors from as few as 500 cells in 24/45 implantations, whereas only 3/37 implantations of ALDH low cells formed tumors. Conclusions ALDH high cells comprise a subpopulation cells in HNSCCs that are tumorigenic and capable of producing tumors at very low numbers. This finding indicates that ALDH activity on its own is a highly selective marker for CSCs in HNSCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77970/1/21315_ftp.pd

DNA cleavage and antitumour activity of platinum(II) and copper(II) compounds derived from 4-methyl-2-N-(2-pyridylmethyl)aminophenol: spectroscopic, electrochemical and biological investigation

The reaction of the redox-active ligand, Hpyramol (4-methyl-2-N-(2-pyridylmethyl)aminophenol) with K2PtCl4 yields monofunctional square-planar [Pt(pyrimol)Cl], PtL-Cl, which was structurally characterised by single-crystal X-ray diffraction and NMR spectroscopy. This compound unexpectedly cleaves supercoiled double-stranded DNA stoichiometrically and oxidatively, in a non-specific manner without any external reductant added, under physiological conditions. Spectro-electrochemical investigations of PtL-Cl were carried out in comparison with the analogue CuL-Cl as a reference compound. The results support a phenolate oxidation, generating a phenoxyl radical responsible for the ligand-based DNA cleavage property of the title compounds. Time-dependent in vitro cytotoxicity assays were performed with both PtL-Cl and CuL-Cl in various cancer cell lines. The compound CuL-Cl overcomes cisplatin-resistance in ovarian carcinoma and mouse leukaemia cell lines, with additional activity in some other cells. The platinum analogue, PtL-Cl also inhibits cell-proliferation selectively. Additionally, cellular-uptake studies performed for both compounds in ovarian carcinoma cell lines showed that significant amounts of Pt and Cu were accumulated in the A2780 and A2780R cancer cells. The conformational and structural changes induced by PtL-Cl and CuL-Cl on calf thymus DNA and phi X174 supercoiled phage DNA at ambient conditions were followed by electrophoretic mobility assay and circular dichroism spectroscopy. The compounds induce extensive DNA degradation and unwinding, along with formation of a monoadduct at the DNA minor groove. Thus, hybrid effects of metal-centre variation, multiple DNA-binding modes and ligand-based redox activity towards cancer cell-growth inhibition have been demonstrated. Finally, reactions of PtL-Cl with DNA model bases (9-Ethylguanine and 5'-GMP) followed by NMR and MS showed slow binding at Guanine-N7 and for the double stranded self complimentary oligonucleotide d(GTCGAC)(2) in the minor groove

Status of Pandemic Influenza Vaccination and Factors Affecting It in Pregnant Women in Kahramanmaras, an Eastern Mediterranean City of Turkey

BACKGROUND: Pregnant women are a target group for receipt of influenza vaccine because there appears to be an elevated mortality and morbidity rate associated with influenza virus infection in pregnant women. The goal of this study is to determine the factors affecting the decisions of pregnant women in Turkey to be vaccinated or not for 2009 H1N1 influenza. METHODOLOGY: We enrolled 314 of 522 (60.2%) pregnant women who attended to the antenatal clinics of the Medical Faculty of Kahramanmaras Sutcuimam University's Department of Gynecology and Obstetrics between December 23, 2009, and February 1, 2010. We developed a 48-question survey which was completed in a face-to-face interview at the clinic with each pregnant woman. PRINCIPAL FINDINGS: Of the 314 pregnant women, 27.4% were in the first trimester, 33.8% were in the second trimester, and 38.8% were in the third trimester. Twenty-eight pregnant women (8.9%) got vaccinated. Of all the women interviewed, 68.5% stated that they were comfortable with their decisions about the vaccine, 7.3% stated they were not comfortable, and 24.2% stated that they were hesitant about their decisions. The probability of receiving the 2009 H1N1 vaccine was 3.46 times higher among working women than housewives, 1.85 times higher among women who have a child than those who do not, and 1.29 times higher among women with a high-school education or higher than those with only a secondary-school education and below. Correct knowledge about the minimal risks associated with receipt of influenza vaccine were associated with a significant increase in the probability of receiving the 2009 H1N1 vaccine. CONCLUSIONS/SIGNIFICANCE: The number of pregnant women in the study group who received the 2009 H1N1 vaccine was very low (8.9%) and two-thirds of them stated that they were comfortable with their decisions concerning the vaccine. Our results may have implications for public health measures to increase the currently low vaccination rate among pregnant women. Further studies are required to confirm whether our findings generalize to other influenza seasons and other settings

Evaluation of alternative solvents in common amide coupling reactions : replacement of dichloromethane and N,N-dimethylformamide

A range of alternative solvents have been evaluated within amidation reactions employing common coupling reagents with a view to identifying suitable replacements for dichloromethane and N,N-dimethylformamid

Pandemic (H1N1) 2009, Abu Dhabi, United Arab Emirates, May 2009–March 2010

To ascertain characteristics of pandemic (H1N1) 2009 virus infection, we reviewed medical records for all suspected or confirmed cases reported in Abu Dhabi during May 2009–March 2010. Overall case-fatality rate was 1.4/100,000 population. Most patients who died had ≥1 risk factor, and female decedents were considerably younger than male decedents

The ansamycin antibiotic, rifamycin SV, inhibits BCL6 transcriptional repression and forms a complex with the BCL6-BTB/POZ domain

BCL6 is a transcriptional repressor that is over-expressed due to chromosomal translocations, or other abnormalities, in ~40% of diffuse large B-cell lymphoma. BCL6 interacts with co-repressor, SMRT, and this is essential for its role in lymphomas. Peptide or small molecule inhibitors, which prevent the association of SMRT with BCL6, inhibit transcriptional repression and cause apoptosis of lymphoma cells in vitro and in vivo. In order to discover compounds, which have the potential to be developed into BCL6 inhibitors, we screened a natural product library. The ansamycin antibiotic, rifamycin SV, inhibited BCL6 transcriptional repression and NMR spectroscopy confirmed a direct interaction between rifamycin SV and BCL6. To further determine the characteristics of compounds binding to BCL6-POZ we analyzed four other members of this family and showed that rifabutin, bound most strongly. An X-ray crystal structure of the rifabutin-BCL6 complex revealed that rifabutin occupies a partly non-polar pocket making interactions with tyrosine58, asparagine21 and arginine24 of the BCL6-POZ domain. Importantly these residues are also important for the interaction of BLC6 with SMRT. This work demonstrates a unique approach to developing a structure activity relationship for a compound that will form the basis of a therapeutically useful BCL6 inhibitor