It has been proposed that cell-free nucleic acids in the plasma participate in tumorigenesis and the development of metastases via transfection-like uptake of such nucleic acids by susceptible cells. This putative phenomenon is tentatively referred to as "genometastasis." In the present study, we examined the effects on cultured cells of plasma from healthy individuals and from patients with colon cancer. Cultures of NIH-3T3 cells and human adipose-derived stem cells (hASC) were supplemented with samples of plasma from patients with K-ras-mutated colorectal tumors or from healthy subjects using two different protocols: direct addition of plasma to cultures in standard plates and addition in the absence of contact between plasma and cells, which were separated by a membrane with 0.4-μm pores. In plasma-treated hASCs, no K-ras-mutated sequences were detected by real-time PCR. In contrast, in most cultures of plasma-treated NIH-3T3 cells (murine cells), the transfer of human DNA occurred, as verified by the detection of human K-ras sequences, p53 sequences, and β-globin-encoding sequences. Moreover, NIH-3T3 cells that had been cultured with plasma from patients with colon cancer were oncogenically transformed, as shown by the development of carcinomas in nonobese diabetic-severe combined immunodeficient mice after the injection of such cells. Microscopic analysis of membranes that had separated plasma from cultured cells confirmed the complete absence of cells in the plasma. We only observed noncell particles, having diameters of <0.4 μm. Our results indicate that plasma from cancer patients is able to transform cultured cells oncogenically, supporting the previously proposed hypothesis of genometastasis. Cancer Res; 70(2); 560-7. ©2010 AACR.

This article reports, for the first time, a detailed molecular profile of genomic alterations in patients with HER2-positive advanced gastric cancer (AGC). PI3K/Akt/mTOR signaling pathway activation seems to have a differentially negative effect on overall survival and progression-free survival in AGC treated with trastuzumab-based chemotherapy. Combining different targeted agents could be a successful therapeutic strategy to improve the prognosis of HER2-positive AGC.

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BackgroundTransthyretin-related hereditary amyloidosis (ATTR) is a systemic disease characterized by extracellular deposits of amyloid due to the autosomal dominant inheritance of a mutation in the TTR gene (18q12.1). Although described worldwide, it is a rare disease, limited to certain parts of the world.The aim of this manuscript is to describe the presence and characteristics of ATTR in Mexico.MethodsFrom 2010 through the database of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán we selected cases that had the diagnosis of “amyloidosis”, with any etiology, reviewed the files and selected those with suspected hereditary etiology.ResultsWe identified 111 subjects with 5 different pathological mutations, none of them with the classic Val30Met mutation. Mutations found were Ser50Arg in 83 (74%), Gly47Ala in 14 (13%), Ser52Pro in 12 (11%) and V122I /Y116H in 2 (2%). The majority of positive patients were from the States of Morelos and Guerrero. Twenty different families were included. The most common causes of death was urosepsis and cardiac failure.ConclusionsIn Mexico there are endemic foci of ATTR, mainly in the states of Morelos and Guerrero. The major mutations are different from the most common global mutation Met30Val.

Aims To study programmed death ligand 1 (PD‐L1) expression, tumour‐infiltrating T lymphocytes (TILs) and the molecular context in patients with early‐stage squamous cell lung carcinomas (SCCs). Methods and results The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early‐stage SCC. PD‐L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next‐generation sequencing (NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD‐L1 IHC expression in tumour cells (TCs). Furthermore, high SP142 PD‐L1 expression in immune cells (ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD‐L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD‐L1‐positive TCs with the three antibodies were found in samples with cyclin‐dependent kinase 6 (CDK6) amplification, with high amplification of proto‐oncogene C‐Myc (CMYC) or with cyclin D1–PI3 kinase subunit alpha (CCND1–PIK3CA) co‐amplification. High SP142 PD‐L1 IHC expression in ICs showed a non‐significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 (FGFR1) amplification were negative for all PD‐L1 clones. Conclusions Our preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD‐L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors.

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Abstract:In this article we use insights from institutional bricolage and actornetwork theory to make sense of an Andean water user association (WUA) and its bricoleurs in the Region of Ayacucho, Peru. Rather than being designed and clearly defined, we see natural resource institutions as continuously performed and patched together, through heterogeneous elements and practices, by those that live, experience and enact these institutions every day and by those who make sense of them. We present three cases, three supra-community efforts to secure water livelihoods, in which the Ayacucho water user association is enacted differently. Similar actors and practices like, water law, local customs, water bodies, and ecological services are performed in alternate ways for diverse purposes. It is this range of co-existing performances or enactments and the fluidity of actors and bricoleurs which enables an institution to adapt and adjust. We hold that an Andean WUA can be a bureaucratic imposition, but in many ways the WUA is something else too: a strategic ally; a prerequisite for subsidy consideration, a marketplace for exchanging goods and services and more. In the setting of the contemporary Peruvian Andes, the durability of natural resource institutions can be understood through the fluidity and multiplicity of performances and purposes. This has normative and political implications for researchers and policymakers as to what enactment they consider and target.Keywords: Andes, Ayacucho, institutional bricolage, performativity, Peru, water user association Andres Verzijl and Carolina DominguezAcknowledgments: This article was written within the Netherlands Organisation for Scientific Research, the WOTRO Integrated Program ''Struggling for water security: Social mobilization for the defence of water rights in Peru and Ecuador.'' The program also provided financial support for our co-researchers, for which we are grateful. We are also grateful to Frances Cleaver, Jessica de Koning, the International Journal of the Commons' editors and the 3 anonymous reviewers for their insightful suggestions and comments on earlier drafts. Finally we thank our Ayacucho research collaborators for their cooperation and contribution to our work.

Abstract:In this article we use insights from institutional bricolage and actornetwork theory to make sense of an Andean water user association (WUA) and its bricoleurs in the Region of Ayacucho, Peru. Rather than being designed and clearly defined, we see natural resource institutions as continuously performed and patched together, through heterogeneous elements and practices, by those that live, experience and enact these institutions every day and by those who make sense of them. We present three cases, three supra-community efforts to secure water livelihoods, in which the Ayacucho water user association is enacted differently. Similar actors and practices like, water law, local customs, water bodies, and ecological services are performed in alternate ways for diverse purposes. It is this range of co-existing performances or enactments and the fluidity of actors and bricoleurs which enables an institution to adapt and adjust. We hold that an Andean WUA can be a bureaucratic imposition, but in many ways the WUA is something else too: a strategic ally; a prerequisite for subsidy consideration, a marketplace for exchanging goods and services and more. In the setting of the contemporary Peruvian Andes, the durability of natural resource institutions can be understood through the fluidity and multiplicity of performances and purposes. This has normative and political implications for researchers and policymakers as to what enactment they consider and target.Keywords: Andes, Ayacucho, institutional bricolage, performativity, Peru, water user association Andres Verzijl and Carolina DominguezAcknowledgments: This article was written within the Netherlands Organisation for Scientific Research, the WOTRO Integrated Program ''Struggling for water security: Social mobilization for the defence of water rights in Peru and Ecuador.'' The program also provided financial support for our co-researchers, for which we are grateful. We are also grateful to Frances Cleaver, Jessica de Koning, the International Journal of the Commons' editors and the 3 anonymous reviewers for their insightful suggestions and comments on earlier drafts. Finally we thank our Ayacucho research collaborators for their cooperation and contribution to our work.