EGFR y Cáncer

EGFR-mediated tumor immunoescape: The imbalance between phosphorylated STAT1 and phosphorylated STAT3.

Concha-Benavente F¹, Srivastava RM², Ferrone S³, Ferris RL⁴.

¹Department of Immunology; University of Pittsburgh; Pittsburgh, PA USA.
²Department of Otolaryngology; University of Pittsburgh; Pittsburgh, PA USA.
³Department of Surgery; Massachusetts General Hospital; Harvard Medical School; Boston, MA USA.
⁴Department of Immunology; University of Pittsburgh; Pittsburgh, PA USA ; Department of Otolaryngology; University of Pittsburgh; Pittsburgh, PA USA ; Cancer Immunology Program; University of Pittsburgh Cancer Institute; Pittsburgh, PA USA.

 

Abstract

The epidermal growth factor receptor (EGFR) supports the escape of malignant cells from immunosurveillance by inhibiting the activation of signal transducer and activator of transcription 1 (STAT1) while promoting that of STAT3. We have recently demonstrated that protein tyrosine phosphatase, non-receptor type 11 (PTNP11, best known as SHP2), a phosphatase that operates downstream of EGFR, is responsible for the dephosphorylation of active STAT1 and for the inhibition of the antigen-processing machinery (APM), hence favoring tumor immunoescape. Thus, EGFR signaling may skew the tumor microenvironment to suppress cellular immune responses.

KEYWORDS:

APM; EGFR; SHP2; immunoescape; immunotherapy; pSTAT1; pSTAT3

Oncoimmunology. 2013 Dec 1;2(12):e27215. Epub 2013 Dec 5.

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913673/

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

Dieta y Depresión

Prospective study on long-term dietary patterns and incident depression in middle-aged and older women.

Chocano-Bedoya PO¹, O'Reilly EJ, Lucas M, Mirzaei F, Okereke OI, Fung TT, Hu FB, Ascherio A.

¹Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. pchocano@hsph.harvard.edu

 

Abstract

BACKGROUND:

Although individual nutrients have been investigated in relation to depression risk, little is known about the overall role of diet in depression.

OBJECTIVE:

We examined whether long-term dietary patterns derived from a food-frequency questionnaire (FFQ) predict the development of depression in middle-aged and older women.

DESIGN:

We conducted a prospective study in 50,605 participants (age range: 50-77 y) without depression in the Nurses' Health Study at baseline (1996) who were followed until 2008. Long-term diet was assessed by using FFQs every 4 y since 1986. Prudent (high in vegetables) and Western (high in meats) patterns were identified by using a principal component analysis. We used 2 definitions for clinical depression as follows: a strict definition that required both a reported clinical diagnosis and use of antidepressants (3002 incident cases) and a broad definition that further included women who reported either a clinical diagnosis or antidepressant use (7413 incident cases).

RESULTS:

After adjustment for age, body mass index, and other potential confounders, no significant association was shown between the diet patterns and depression risk under the strict definition. Under the broad definition, women with the highest scores for the Western pattern had 15% higher risk of depression (95% CI: 1.04, 1.27; P-trend = 0.01) than did women with the lowest scores, but after additional adjustment for psychological scores at baseline, results were no longer significant (RR: 1.09; 95% CI: 0.99, 1.21; P-trend = 0.08).

CONCLUSION:

Overall, results of this large prospective study do not support a clear association between dietary patterns from factor analysis and depression risk.

Am J Clin Nutr. 2013 Sep;98(3):813-20. doi: 10.3945/ajcn.112.052761. Epub 2013 Jul 24.

http://ajcn.nutrition.org/content/98/3/813.long

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

E. Coli Meningitis

E. coli Meningitis Presenting in a Patient with Disseminated Strongyloides stercoralis.

Gomez JB¹, Maque Y, Moquillaza MA, Anicama WE.

¹Department of Internal Medicine, Guillermo Almenara Irigoyen National Hospital, Lima, Peru.

 

Abstract

Introduction. Spontaneous Escherichia coli meningitis is an infrequent condition in adults and is associated with some predisposing factors, including severe Strongyloides stercoralis (SS) infections. Case Presentation. A 43-year-old Hispanic man, with history of travelling to the jungle regions of Peru and Brazil two decades ago, and who received prednisone due to Bell's palsy for three weeks before admission, presented to the Emergency Department with diarrhea, fever, and hematochezia. A week after admission he developed drowsiness, meningeal signs, abdominal distension, and constipation. A cerebrospinal fluid culture showed extended spectrum β -lactamase producing E. coli. A colonoscopy was performed and showed pancolitis. Three days after the procedure the patient became unstable and developed peritoneal signs. He underwent a laparotomy, which ended up in a total colectomy and partial proctectomy due to toxic megacolon. Three days later the patient died in the intensive care unit due to septic shock. Autopsy was performed and microscopic examination revealed the presence of multiple Strongyloides larvae throughout the body. Conclusion. Strongyloides stercoralis infection should be excluded in adults with spontaneous E. coli meningitis, especially, if gastrointestinal symptoms and history of travelling to an endemic area are present. Even with a proper diagnosis and management, disseminated strongyloidiasis has a poor prognosis. 

Case Rep Infect Dis. 2013;2013:424362. doi: 10.1155/2013/424362. Epub 2013 Nov 13.

http://www.hindawi.com/journals/criid/2013/424362/

Md. MSc. Yvan Maque. Ex-miembro del GII.

Chlamydia trachomatis e Inmunidad

Human female genital tract infection by the obligate intracellular bacterium Chlamydia trachomatis elicits robust Type 2 immunity.

Vicetti Miguel RD¹, Harvey SA, LaFramboise WA, Reighard SD, Matthews DB, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

 

Abstract

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4(+) T cells. Also among women with genital tract Chlamydia infection, peripheral CD3(+) CD4(+) and CD3(+) CD4(-) cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures.

PLoS One. 2013;8(3):e58565. doi: 10.1371/journal.pone.0058565. Epub 2013 Mar 13.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058565

Md. Rodolfo Vicetti. Ex-miembro del GII.

Dermatología e Inmunología

Melanocitos en vitíligo y melanoma: una lección

entre autoinmunidad e inmunidad tumoral

  Julio E Valdivia-Silva1, Claudia Ramírez1

1Chemokines Biology Research Laboratory, Instituto de Investigaciones Biomédicas, UNAM, México D.F., México.

ABSTRACT 

Classically, vitiligo has been deined as a skin disease in which melanocytes (MC) are eradicated from lesional epidermis by MC-reactive T cells, as well as other non-immune and immune components, resulting in disiguring loss of pigment. Moreover, the absence or damage on MC has frequently been associated to a major risk to develop skin cancer including melanoma. However, patients with vitiligo have also shown 'non-pigmented' MC in epidermis similar to individuals with albinism, and these cells are apparently conferring resistance of developing melanoma. These seemingly contradictory facts are further complicated because, the MC antigens which are immunologically recognized are shared for both diseases producing fairly different results. An analysis of the similarities and differences between the autoimmunity observed in vitiligo and the tumour immunity observed in melanoma might lead to a better understanding of the MC' roles and the development of new therapies for both diseases. 

Dermatol PerU 2013; vol 23 (3)

http://sisbib.unmsm.edu.pe/bvrevistas/dermatologia/v23_n3/pdf/a03v23n3.pdf

Md PhD Julio Valdivia Silva. Fundador del GII

Inmunoterapia y Cáncer

Efficacy of DNA vaccines forming e7 recombinant retroviral virus-like particles for the treatment of human papillomavirus-induced cancers.

Lescaille G¹, Pitoiset F, Macedo R, Baillou C, Huret C, Klatzmann D, Tartour E, Lemoine FM, Bellier B.

¹Research Unit UMR CNRS 7211/INSERM 959, 75013 Paris, France.

 

Abstract

Human papillomavirus (HPV) is involved in the development of anogenital tumors and also in the development of oropharyngeal head and neck carcinomas, where HPV-16, expressing the E6 and E7 oncoproteins, is the most frequent serotype. Although vaccines encoding L1 and L2 capsid HPV proteins are efficient for the prevention of HPV infection, they are inadequate for treating established tumors. Hence, development of innovative vaccine therapies targeting E6/E7 is important for controlling HPV-induced cancers. We have engineered a nononcogenic mutated E7-specific plasmo-retroVLP vaccine (pVLP-E7), consisting of plasmid DNA, that is able to form recombinant retrovirus-based virus-like particles (VLPs) that display E7 antigen into murine leukemia virus Gag proteins pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G). pVLP-E7 vaccinations were studied for their ability to generate specific immune responses and for induction of protective immunity against tumor cell challenge in preventive and therapeutic models. The produced VLPs induce the maturation of human dendritic cells in vitro and mount specific E7 T cell responses. Intradermic vaccinations of mice with pVLP-E7 show their efficacy to generate antigen-specific T cell responses, to prevent and protect animals from early TC-1 tumor development compared with standard DNA or VLP immunizations. The vaccine efficacy was also evaluated for advanced tumors in mice vaccinated at various time after the injection of TC-1 cells. Data show that pVLP-E7 vaccination can cure mice with already established tumors only when combined with Toll-like receptor-7 (TLR7) and TLR9 agonists. Our findings provide evidence that pVLPs, combining the advantages of DNA and VLP vaccines, appear to be a promising strategy for the treatment of HPV-induced cancers.

Hum Gene Ther. 2013 May;24(5):533-44. doi: 10.1089/hum.2012.037. Epub 2013 May 6.

http://online.liebertpub.com/doi/abs/10.1089/hum.2012.037 

Md. PhD. Rodney Macedo. Past-president del GII.

Dieta y Sindrome Premenstrual

Intake of selected minerals and risk of premenstrual syndrome.

Chocano-Bedoya PO¹, Manson JE, Hankinson SE, Johnson SR, Chasan-Taber L, Ronnenberg AG, Bigelow C, Bertone-Johnson ER.

¹Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.

 

Abstract

Iron, potassium, zinc, and other minerals might impact the development of premenstrual syndrome (PMS) through multiple mechanisms, but few studies have evaluated these relations. We conducted a case-control study nested within the prospective Nurses' Health Study II (1991-2001). Participants were free from PMS at baseline. After 10 years, 1,057 women were confirmed as PMS cases and 1,968 as controls. Mineral intake was assessed using food frequency questionnaires completed in 1991, 1995, and 1999. After adjustment for calcium intake and other factors, women in the highest quintile of nonheme iron intake had a relative risk of PMS of 0.64 (95% confidence interval (CI): 0.44, 0.92; P for trend = 0.04) compared with women in the lowest quintile. Women in the highest quintile of potassium intake had a relative risk of 1.46 (95% CI: 0.99, 2.15; P for trend = 0.04) compared with women in the lowest quintile. High intake of zinc from supplements was marginally associated with PMS (for intake of ≥25 mg/day vs. none, relative risk = 0.69, 95% CI: 0.46, 1.02; P for trend = 0.05). Intakes of sodium, magnesium, and manganese were unrelated to PMS risk. These findings suggest that dietary minerals may be useful in preventing PMS. Additional studies are needed to confirm these relations.

KEYWORDS:

dietary iron; minerals; premenstrual syndrome

Am J Epidemiol. 2013 May 15;177(10):1118-27. doi: 10.1093/aje/kws363. Epub 2013 Feb 26.

http://aje.oxfordjournals.org/content/177/10/1118.long

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