Jose A. Rodriguez

Bio: Jose A. Rodriguez is an academic researcher from Universidad Autónoma del Estado de Hidalgo. The author has contributed to research in topics: Medicine & Solar furnace. The author has an hindex of 63, co-authored 597 publications receiving 17218 citations. Previous affiliations of Jose A. Rodriguez include Polytechnic University of Valencia & University of Valencia.

Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers.

Abstract: Purpose: CD4 + T cells play a central role in initiating and maintaining anticancer immune responses However, regulatory CD4 + CD25 + T cells which express Foxp3 have also been shown to inhibit antitumor effector T cells In view of these heterogeneous CD4 + T-cell populations, this study was designed to determine the prognostic value of various tumor-infiltrating CD4 + T-cell populations in head and neck squamous cell carcinoma Experimental Design: Eighty-four newly diagnosed untreated patients with histologically proven primary head and neck squamous cell carcinoma were included in this study Double or triple immunofluorescence staining was done to assess and quantify the activated CD4 + CD69 + T cells, regulatory CD4 + Foxp3 + T cells, and mixed CD4 + CD25 + T cells comprising both activated and regulatory T cells Results: On univariate analysis, high levels of tumor-infiltrating CD4 + CD69 + T cells were correlated with both better locoregional control ( P = 001) and longer survival ( P = 001) Infiltration by regulatory Foxp3 + CD4 + T cells was positively associated with a better locoregional control of the tumor Multivariate analysis showed that the only significant prognostic factors related to locoregional control were T stage ( P = 002) and CD4 + Foxp3 + T-cell infiltration of the tumor ( P = 002) In the Cox multivariate analysis, only two variables influenced overall survival probability: T stage ( P = 0036) and CD4 + CD69 + T-cell infiltration ( P = 0017) Conclusion: This study shows that tumor-infiltrating activated CD4 + CD69 + T cells are associated with a good prognosis in head and neck squamous cell carcinoma In addition, regulatory Foxp3 + CD4 + T cells are positively correlated with locoregional control may be through down-regulation of harmful inflammatory reaction, which could favor tumor progression

Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: Limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways

Abstract: The epidermal growth factor receptor (EGFR) is an important novel target for anticancer therapy. In this study, we examined the molecular mechanisms that underlie the antitumor effects of the anti-EGFR monoclonal antibody C225 (Cetuximab) and the selective EGFR tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca) in non-small cell lung cancer (NSCLC) cell lines. Cell growth, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, was inhibited at low concentrations of ZD1839 and C225 in control A431 cells, whereas the NSCLC cell lines were comparatively more resistant. In A431 cells, but not in the NSCLC cells, ZD1839 treatment resulted in a modest increase in DNA fragmentation, the externalization of phosphatidyl serine, and the activation of caspase-3, known markers of apoptotic cell death. However, poly(ADP-ribose) polymerase cleavage was not detected, and caspase inhibition by carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone partially reduced ZD1839-generated DNA fragmentation. Overexpression of the antiapoptotic protein Bcl-2 in A431 cells suppressed the cytotoxicity upon anti-EGFR treatment. These results thus demonstrate that the toxic effect of ZD1839 in A431 cells is caused by a form of cell death that involves a mitochondrial step and is, at least in part, dependent on caspase activation. EGFR expression levels showed no significant correlation with sensitivity to ZD1839 and C225. Evaluation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and phosphatidylinositol 3'-kinase/Akt pathways showed considerable inhibition of these pathways by ZD1839 and C225 in A431 cells, whereas one or both of these pathways remained active upon anti-EGFR treatment in NSCLC cells. In addition, treatment with specific inhibitors of mitogen-activated protein kinase kinase or phosphatidylinositol 3'-kinase resulted in a smaller effect on proliferation than simultaneous treatment with both inhibitors, whereas induction of apoptosis was observed only when both pathways were blocked. Together, these data suggest that persistent activity of either of these signaling pathways is involved in the lack of sensitivity of NSCLC cell lines to EGFR inhibitors.

Global Histone Modifications Predict Prognosis of Resected Non–Small-Cell Lung Cancer

Abstract: Purpose Epigenetic modifications may contribute to the development and progression of cancer. We investigated whether epigenetic changes involving multiple histones influence prognosis of non–small-cell lung cancer (NSCLC) patients. Patients and Methods We used immunohistochemistry to assess histone 3 lysine 4 dimethylation (H3K4diMe), and acetylation of histone 2A lysine 5 (H2AK5Ac), histone 2B lysine 12, histone 3 lysine 9 (H3K9Ac), and histone 4 lysine 8 in resected tumor samples of 138 NSCLC patients. Data were analyzed using a recursive partitioning analysis (RPA). Results The RPA classified the patients into seven distinct prognostic groups based on TNM stage (first node), histology, and histone modifications: H3K4diMe (< or ≥ 85% tumor cells), H3K9Ac (< or ≥ 68% tumor cells), and H2AK5Ac (< or ≥ 5% tumor cells). The seven groups were associated with significantly different disease-free (P < .0001) and overall survival (P < .0001). Interestingly, the four groups determined by stage I patients (below...

Highly accurate protein structure prediction with AlphaFold

Abstract: Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort1–4, the structures of around 100,000 unique proteins have been determined5, but this represents a small fraction of the billions of known protein sequences6,7. Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are needed to address this gap and to enable large-scale structural bioinformatics. Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence—the structure prediction component of the ‘protein folding problem’8—has been an important open research problem for more than 50 years9. Despite recent progress10–14, existing methods fall far short of atomic accuracy, especially when no homologous structure is available. Here we provide the first computational method that can regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known. We validated an entirely redesigned version of our neural network-based model, AlphaFold, in the challenging 14th Critical Assessment of protein Structure Prediction (CASP14)15, demonstrating accuracy competitive with experimental structures in a majority of cases and greatly outperforming other methods. Underpinning the latest version of AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm. AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

Mechanical Alloying And Milling

Abstract: Mechanical alloying (MA) is a solid-state powder processng technique involving repeated welding, fracturing, and rewelding of powder particles in a high-energy ball mill. Originally developed to produce oxide-dispersion strengthened (ODS) nickel- and iron-base superalloys for applications in the aerospace industry, MA has now been shown to be capable of synthesizing a variety of equilibrium and non-equilibrium alloy phases starting from blended elemental or prealloyed powders. The non-equilibrium phases synthesized include supersaturated solid solutions, metastable crystalline and quasicrystalline phases, nanostructures, and amorphous alloys. Recent advances in these areas and also on disordering of ordered intermetallics and mechanochemical synthesis of materials have been critically reviewed after discussing the process and process variables involved in MA. The often vexing problem of powder contamination has been analyzed and methods have been suggested to avoid/minimize it. The present understanding of the modeling of the MA process has also been discussed. The present and potential applications of MA are described. Wherever possible, comparisons have been made on the product phases obtained by MA with those of rapid solidification processing, another non-equilibrium processing technique.

The immune contexture in human tumours: impact on clinical outcome

Abstract: Tumours grow within an intricate network of epithelial cells, vascular and lymphatic vessels, cytokines and chemokines, and infiltrating immune cells. Different types of infiltrating immune cells have different effects on tumour progression, which can vary according to cancer type. In this Opinion article we discuss how the context-specific nature of infiltrating immune cells can affect the prognosis of patients.