Análisis sobre la responsabilidad de los Estados ante el combate de la trata de mujeres y niñas con fines de explotación, a partir del protocolo para prevenir, reprimir y sancionar la trata de personas, especialmente mujeres y niños aplicados en la región centroamericana. Periodo 2012-2017.

Antecedentes históricos del conceptos de trata de personas con base en los instrumentos jurídicos previos al protocolo para prevenir, reprimir y sancionar la trata de personas especialmente mujeres y niños – Principales retos de los Estados pertenecientes a la región centroamericana para la defensa de los derechos humanos de las víctimas de trata de mujeres y niñas – Situación actual de la responsabilidad de los Estados ante la defensa de las mujeres y niñas víctimas de Trata en la región centroamericana

Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy

Cancer microenvironment; Chemotherapy; Predictive markersMicroambient del càncer; Quimioteràpia; Marcadors predictiusMicroambiente del cáncer; Quimioterapia; Marcadores predictivosA substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased. We determine that CT accumulation in CAFs intensifies TGF-beta activity, leading to the production of multiple factors enhancing cancer aggressiveness. We establish periostin as a stromal marker of chemotherapeutic activity intrinsically upregulated in consensus molecular subtype 4 (CMS4) tumors and highly expressed before and/or after treatment in patients unresponsive to therapy. Collectively, our study underscores the ability of CT-retaining CAFs to support cancer progression and resistance to treatment.This work has been supported by grants from Fundación científica AECC -Asociación Española contra el Cáncer- (GCAEC20030CERV) to A.Ce., from Instituto de Salud Carlos III (ISCIII) co-funded by the European Union (CP16/00151, PI17/00211, PI20/00011; Spanish Ministry of Economy and Competitiveness) to A.Ca. and PI20/00625 to P.N., from la Caixa Foundation (LCF/PR/HR19/52160018) and MICINN (PID2020-119917RB-I00) to E.B., from Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds (PID2019-104948RB-I00) to R.R.G. This work was supported by Grant PT20/00023, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, and the Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC). A.Ca. is the recipient of funding from the Instituto de Salud Carlos III co-funded by the European Union (MS16/00151; CPII21/00012). J.L. is the recipient of a Junior Clinician fellowship from Fundación científica AECC (CLJUN19004LINA)

A proposal of an English class model using all the components of a macro and micro lesson plans to enhance eighth grade students speaking and writing production of Complejo Educativo Colonia Rio Za

Learning a second language is so difficult for beginners because as in the mother tongue, students are required to develop the four macro-skills to interact among others. Therefore, it is necessary to create an appropriate classroom environment using the latest strategies, methodologies and techniques to help students boost their productiveness in the language, especially in writing and speaking production. Unfortunately, teachers do not leave their comfort zone; rather, they continue teaching in the traditional way, using the textbook, lecturing long hours of grammar with no interactive activities in the classroom. For that reason, the investigators carried out the thesis project “A Proposal of an English Class Model Using all the Components of a Macro and Micro Lesson Plans to Enhance Eighth Grade Students' Speaking and Writing Production of Complejo Educativo Colonia Río Zarco during the Year 2020"

Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy

A substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased. We determine that CT accumulation in CAFs intensifies TGF-beta activity, leading to the production of multiple factors enhancing cancer aggressiveness. We establish periostin as a stromal marker of chemotherapeutic activity intrinsically upregulated in consensus molecular subtype 4 (CMS4) tumors and highly expressed before and/or after treatment in patients unresponsive to therapy. Collectively, our study underscores the ability of CT-retaining CAFs to support cancer progression and resistance to treatment.This work has been supported by grants from Fundación científica AECC -Asociación Española contra el Cáncer- (GCAEC20030CERV) to A.Ce., from Instituto de Salud Carlos III (ISCIII) co-funded by the European Union (CP16/00151, PI17/00211, PI20/00011; Spanish Ministry of Economy and Competitiveness) to A.Ca. and PI20/00625 to P.N., from la Caixa Foundation (LCF/PR/HR19/52160018) and MICINN (PID2020- 119917RB-I00) to E.B., from Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds (PID2019-104948RB-I00) to R.R.G. This work was supported by Grant PT20/00023, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, and the Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC). A.Ca. is the recipient of funding from the Instituto de Salud Carlos III co-funded by the European Union (MS16/00151; CPII21/00012). J.L. is the recipient of a Junior Clinician fellowship from Fundación científica AECC (CLJUN19004LINA)

Minimal residual disease, metastasis and immunity

Progression from localized to metastatic disease requires cancer cells spreading to distant organs through the bloodstream. Only a small proportion of these circulating tumor cells (CTCs) survives dissemination due to anoikis, shear forces and elimination by the immune system. However, all metastases originate from CTCs capable of surviving and extravasating into distant tissue to re-initiate a tumor. Metastasis initiation is not always immediate as disseminated tumor cells (DTCs) may enter a non-dividing state of cell dormancy. Cancer dormancy is a reversible condition that can be maintained for many years without being clinically detectable. Subsequently, late disease relapses are thought to be due to cancer cells ultimately escaping from dormant state. Cancer dormancy is usually associated with minimal residual disease (MRD), where DTCs persist after intended curative therapy. Thus, MRD is commonly regarded as an indicator of poor prognosis in all cancers. In this review, we examine the current understanding of MRD and immunity during cancer progression to metastasis and discuss clinical perspectives for oncology

Determinants and functions of CAFs secretome during cancer progression and therapy

Multiple lines of evidence are indicating that cancer development and malignant progression are not exclusively epithelial cancer cell-autonomous processes but may also depend on crosstalk with the surrounding tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are abundantly represented in the TME and are continuously interacting with cancer cells. CAFs are regulating key mechanisms during progression to metastasis and response to treatment by enhancing cancer cells survival and aggressiveness. The latest advances in CAFs biology are pointing to CAFs-secreted factors as druggable targets and companion tools for cancer diagnosis and prognosis. Especially, extensive research conducted in the recent years has underscored the potential of several cytokines as actionable biomarkers that are currently evaluated in the clinical setting. In this review, we explore the current understanding of CAFs secretome determinants and functions to discuss their clinical implication in oncology

Challenges and Therapeutic Opportunities in the dMMR/MSI-H Colorectal Cancer Landscape

About 5 to 15% of all colorectal cancers harbor mismatch repair deficient/microsatellite instability–high status (dMMR/MSI-H) that associates with high tumor mutation burden and increased immunogenicity. As a result, and in contrast to other colorectal cancer phenotypes, a significant subset of dMMR/MSI-H cancer patients strongly benefit from immunotherapy. Yet, a large proportion of these tumors remain unresponsive to any immuno-modulating treatment. For this reason, current efforts are focused on the characterization of resistance mechanisms and the identification of predictive biomarkers to guide therapeutic decision-making. Here, we provide an overview on the new advances related to the diagnosis and definition of dMMR/MSI-H status and focus on the distinct clinical, functional, and molecular cues that associate with dMMR/MSI-H colorectal cancer. We review the development of novel predictive factors of response or resistance to immunotherapy and their potential application in the clinical setting. Finally, we discuss current and emerging strategies applied to the treatment of localized and metastatic dMMR/MSI-H colorectal tumors in the neoadjuvant and adjuvant setting

The prognostic potential of CDX2 in colorectal cancer: Harmonizing biology and clinical practice

Adjuvant chemotherapy following surgical intervention remains the primary treatment option for patients with localized colorectal cancer (CRC). However, a significant proportion of patients will have an unfavorable outcome after current forms of chemotherapy. While reflecting the increasing complexity of CRC, the clinical application of molecular biomarkers provides information that can be utilized to guide therapeutic strategies. Among these, caudal-related homeobox transcription factor 2 (CDX2) emerges as a biomarker of both prognosis and relapse after therapy. CDX2 is a key transcription factor that controls intestinal fate. Although rarely mutated in CRC, loss of CDX2 expression has been reported mostly in right-sided, microsatellite-unstable tumors and is associated with aggressive carcinomas. The pathological assessment of CDX2 by immunohistochemistry can thus identify patients with high-risk CRC, but the evaluation of CDX2 expression remains challenging in a substantial proportion of patients. In this review, we discuss the roles of CDX2 in homeostasis and CRC and the alterations that lead to protein expression loss. Furthermore, we review the clinical significance of CDX2 assessment, with a particular focus on its current use as a biomarker for pathological evaluation and clinical decision-making. Finally, we attempt to clarify the molecular implications of CDX2 deficiency, ultimately providing insights for a more precise evaluation of CDX2 protein expression