lunes, 27 de diciembre de 2010

Cancer e Inmunidad

CTL induction of tumoricidal nitric oxide production by intratumoral macrophages is critical for tumor elimination.


Vicetti Miguel RD1, Cherpes TL, Watson LJ, McKenna KC.

1Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

 

Abstract

To characterize mechanisms of CTL inhibition within an ocular tumor microenvironment, tumor-specific CTLs were transferred into mice with tumors developing within the anterior chamber of the eye or skin. Ocular tumors were resistant to CTL transfer therapy whereas skin tumors were sensitive. CTLs infiltrated ocular tumors at higher CTL/tumor ratios than in skin tumors and demonstrated comparable ex vivo effector function to CTLs within skin tumors indicating that ocular tumor progression was not due to decreased CTL accumulation or inhibited CTL function within the eye. CD11b(+)Gr-1(+)F4/80(-) cells predominated within ocular tumors, whereas skin tumors were primarily infiltrated by CD11b(+)Gr-1(-)F4/80(+) macrophages (Ms), suggesting that myeloid derived suppressor cells may contribute to ocular tumor growth. However, CD11b(+) myeloid cells isolated from either tumor site suppressed CTL activity in vitro via NO production. Paradoxically, the regression of skin tumors by CTL transfer therapy required NO production by intratumoral Ms indicating that NO-producing intratumoral myeloid cells did not suppress the effector phase of CTL. Upon CTL transfer, tumoricidal concentrations of NO were only produced by skin tumor-associated Ms though ocular tumor-associated Ms demonstrated comparable expression of inducible NO synthase protein suggesting that NO synthase enzymatic activity was compromised within the eye. Correspondingly, in vitro-activated Ms limited tumor growth when co-injected with tumor cells in the skin but not in the eye. In conclusion, the decreased capacity of Ms to produce NO within the ocular microenvironment limits CTL tumoricidal activity allowing ocular tumors to progress.

J Immunol. 2010 Dec 1;185(11):6706-18. doi: 10.4049/jimmunol.0903411. Epub 2010 Nov 1.

 http://www.jimmunol.org/content/185/11/6706.long

Md. Rodolfo Vicetti. Ex-miembro del GII.



martes, 27 de julio de 2010

Dieta y Sindrome Premenstrual

Dietary vitamin D intake, 25-hydroxyvitamin D3 levels and premenstrual syndrome in a college-aged population.


Bertone-Johnson ER1, Chocano-Bedoya PO, Zagarins SE, Micka AE, Ronnenberg AG.

1Division of Biostatistics and Epidemiology, Department of Public Health, University of Massachusetts, Amherst, MA 01003-9304, USA. ebertone@schoolph.umass.edu

 

Abstract

High dietary intake of vitamin D may reduce the risk of premenstrual syndrome (PMS), perhaps by affecting calcium levels, cyclic sex steroid hormone fluctuations, and/or neurotransmitter function. Only a small number of previous studies have evaluated this relationship and none have focused on young women. We assessed this relationship in a cross-sectional analysis within the UMass Vitamin D Status Study. Between 2006 and 2008, 186 women aged 18-30 (mean age=21.6 years) completed a validated food frequency questionnaire, additional questionnaires to assess menstrual symptoms and other health and lifestyle factors, and provided a fasting blood sample collected during the late luteal phase of their menstrual cycle. Among all study participants, results suggested the possibility of an inverse association between intake of vitamin D from food sources and overall menstrual symptom severity, though were not statistically significant; mean intakes in women reporting menstrual symptom severity of none/minimal, mild, and moderate/severe were 253, 214, and 194 IU/day, respectively (P=0.18). From among all study participants, 44 women meeting standard criteria for PMS and 46 women meeting control criteria were included in additional case-control analyses. In these women, after adjustment for age, body mass index, smoking status and total calcium intake, higher intake of vitamin D from foods was associated with a significant lower prevalence of PMS. Women reporting vitamin D intake from food sources of >or=100 IU/day had a prevalence odds ratio of 0.31 compared to those reporting<100 IU/day (95% confidence interval=0.10-0.98). Late luteal phase 25-hydroxyvitamin D3 levels were not associated with prevalent PMS. Results from this pilot study suggest that a relationship between vitamin D and PMS is possible, though larger studies are needed to further evaluate this relationship and to investigate whether 25-hydroxyvitamin D3 levels in the follicular or early luteal phases of the menstrual cycle may be related to PMS risk.
Copyright (c) 2010 Elsevier Ltd. All rights reserved.

J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):434-7. doi: 10.1016/j.jsbmb.2010.03.076. Epub 2010 Apr 14.

http://www.sciencedirect.com/science/article/pii/S0960076010001755

Md. PhD. Patricia Chocano. Ex miembro del GII.   

sábado, 24 de julio de 2010

Cancer y Citocinas

Actin cytoskeleton participation in the onset of IL-1beta induction of an invasive mesenchymal-like phenotype in epithelial MCF-7 cells.

 

Franco-Barraza J1, Valdivia-Silva JE, Zamudio-Meza H, Castillo A, García-Zepeda EA, Benítez-Bribiesca L, Meza I.

1Departamento de Biomedicina Molecular, CINVESTAV-IPN, Apartado, México, D.F., México.

Abstract

BACKGROUND:

Interleukin 1 beta (IL-1beta) and other inflammatory cytokines are reported to induce phenotypic changes in epithelial breast cancer tumor cells related to increased invasiveness. Mechanisms involved in the process are not well understood.

METHODS:

The noninvasive breast cancer epithelial cell line MCF-7 was used to investigate the IL-1beta-induced phenotype. Live cells expressing EGFP-actin were monitored for cell morphology changes and actin cytoskeleton dynamics by time-lapse video microscopy in the presence of IL-1beta and specific inhibitors of actin signaling pathways. Chemotaxis, invasion of Matrigel, MMP activity and expression of S100A4 in cells treated with IL-1beta were assessed by migration assays, zymograms and immunoblots.

RESULTS:

Exposure to IL-1beta specifically induced a change in MCF-7 cells from a typical epithelial morphology into elongated cells, showing numerous dynamic actin-rich lamellae and peripheral ruffles characteristic of fibroblasts. These cells could scatter from compact cell colonies and respond to chemoattractants such as the homing-associated chemokine CXCL-12. Pharmacological blockage of actin signaling pathways and negative mutants of RhoGTPases revealed that actin reorganization and enhanced motility are regulated via PI3K/Rac 1 activation. IL-1beta-stimulated cells expressed the metastasis promoter S100A4, increased secretion of active MMP-9 and MMP-2 and invasion of extracellular matrix proteins.

CONCLUSIONS:

IL-1beta induces a PI3K/Rac 1-regulated reorganization of the actin cytoskeleton of MCF-7 cells that is required for cell scattering, elongation and migration. The enhanced motility is accompanied by expression of protein markers correlated with invasive behavior.
Copyright 2010 IMSS. Published by Elsevier Inc. All rights reserved.

Arch Med Res. 2010 Apr;41(3):170-81. doi: 10.1016/j.arcmed.2010.04.010.

http://www.sciencedirect.com/science/article/pii/S0188440910001013

Md PhD Julio Valdivia Silva. Fundador del GII

Influenza

Changes in the viral distribution pattern after the appearance of the novel influenza A H1N1 (pH1N1) virus in influenza-like illness patients in Peru.

 

Laguna-Torres VA1, Gómez J, Aguilar PV, Ampuero JS, Munayco C, Ocaña V, Pérez J, Gamero ME, Arrasco JC, Paz I, Chávez E, Cruz R, Chavez J, Mendocilla S, Gomez E, Antigoni J, Gonzalez S, Tejada C, Chowell G, Kochel TJ; Peru Influenza working group.

 1Virology Department, United States Naval Medical Research Center Detachment, Lima, Perú. alberto.laguna@med.navy.mil

 

Abstract

BACKGROUND:

We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009.

METHODS:

At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR).

RESULTS:

We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case.

CONCLUSIONS:

The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.

PLoS One. 2010 Jul 27;5(7):e11719. doi: 10.1371/journal.pone.0011719.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011719

Md. Irmia Paz. Tutora del GII

Ojé y Coagulación sanguínea

 Efecto in vitro del látex de Ficus insipida sobre la cascada de la coagulación sanguínea.

Fernando Concha-Benavente 1



1Médico Cirujano miembro del Grupo de Investigación en Inmunología y Academia Peruana de Medicina Molecular. Facultad de Medicina de la Universidad Nacional de San Agustín. Arequipa, Perú.


SUMMARY
We need to search for new natural drugs yielding pharmacological active principles to be used as an alternative to conventional therapies. For this reason, we proposed to study Ficus insipida, an amazonian plant that its latex has been used for years as an Antihelmintic agent but its anticoagulant effect has been only superficially studied. Objective: To corroborate the in vitro anticoagulant effect and to determine upon which of the coagulation pathways acts the latex of Ficus insipida. Material and methods: The latex of Ficus insipida was obtained and prepared at different concentrations. Then, samples of peripheral blood from 5 donors were taken using sodium citrate to avoid blood clotting; the samples were mixed with the latex dilutions and centrifuged, after that, the plasma was extracted to form a plasma pool from each latex concentration. Finally, the Prothrombin Time (PT) and the Partial Thromboplastin Time (PTT) were determined, respectively. Results: The results obtained demonstrated that the latex of Ficus insipida delays the PT at concentrations equal or higher than 0.03125% (V/V), and both the PT and PTT at concentrations equal or higher than 0.15% (V/V). Conclusions: This data allow us to affirm that the latex of Ficus insipida has a dose-dependent in vitro anticoagulant effect upon the extrinsic coagulation pathway at concentrations equal or higher than
0.03125% (V/V). Additionally, at concentrations equal or higher than 0.15% (V/V) it has a potent anticoagulant effect over both coagulation pathways.(Rev Med Hered 2010;21:146-152).
KEY WORDS: Blood coagulation factors, prothrombin time, partial thromboplastin time, ficus, anticoagulant agents.
 

Rev Med Hered v.21 n.3 Lima jul. 2010

http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S1018-130X2010000300006

Md.PhD. Fernando Concha-Benavente. Ex-miembro del GII


miércoles, 27 de enero de 2010

HSV-1 y Hormonas

17-beta estradiol promotion of herpes simplex virus type 1 reactivation is estrogen receptor dependent.


Vicetti Miguel RD1, Sheridan BS, Harvey SA, Schreiner RS, Hendricks RL, Cherpes TL.

1Graduate Program in Immunology, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. [corrected].

 

Abstract

Correlations between estrogen and herpes simplex virus (HSV) reactivation from latency have been suggested by numerous clinical reports, but causal associations are not well delineated. In a murine HSV-1 corneal infection model, we establish 17-beta estradiol (17-betaE) treatment of latently infected ovariectomized mice induces viral reactivation, as demonstrated by increased viral load and increased immediate-early viral gene expression in the latently infected trigeminal ganglia (TG). Interestingly, the increased HSV reactivation occurred in the absence of inhibition of viral specific CD8(+) T-cell effector function. 17-betaE administration increased HSV reactivation in CD45(+) cell-depleted TG explant cultures, providing further support that leukocyte-independent effects on latently infected neurons were responsible for the increased reactivation. The drug-induced increases in HSV copy number were not recapitulated upon in vivo treatment of latently infected estrogen receptor alpha-deficient mice, evidence that HSV reactivation promoted by 17-betaE was estrogen receptor dependent. These findings provide additional framework for the emerging conceptualization of HSV latency as a dynamic process maintained by complex interactions among multiple cooperative and competing host, viral, and environmental forces. Additional research is needed to confirm whether pregnancy or hormonal contraceptives containing 17-betaE also promote HSV reactivation from latency in an estrogen receptor-dependent manner.

J Virol. 2010 Jan;84(1):565-72. doi: 10.1128/JVI.01374-09.

http://jvi.asm.org/content/84/1/565.long

Md. Rodolfo Vicetti. Ex-miembro del GII.