Mesenchymal Stem Cells and Their Derived Products in Ageing and Diseases.

Despite the enormous efforts of the pharmaceutical industry in the generation of new drugs (55 new ones last year) [...].

Synergistic effect of human uterine cervical mesenchymal stem cell secretome and paclitaxel on triple negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer and, despite its adverse effects, chemotherapy is the standard systemic treatment option for TNBC. Since, it is of utmost importance to consider the combination of different agents to achieve greater efficacy and curability potential, MSC secretome is a possible innovative alternative. METHODS: In the present study, we proposed to investigate the anti-tumor effect of the combination of a chemical agent (paclitaxel) with a complex biological product, secretome derived from human Uterine Cervical Stem cells (CM-hUCESC) in TNBC. RESULTS: The combination of paclitaxel and CM-hUCESC decreased cell proliferation and invasiveness of tumor cells and induced apoptosis in vitro (MDA-MB-231 and/or primary tumor cells). The anti-tumor effect was confirmed in a mouse tumor xenograft model showing that the combination of both products has a significant effect in reducing tumor growth. Also, pre-conditioning hUCESC with a sub-lethal dose of paclitaxel enhances the effect of its secretome and in combination with paclitaxel reduced significantly tumor growth and even allows to diminish the dose of paclitaxel in vivo. This effect is in part due to the action of extracellular vesicles (EVs) derived from CM-hUCESC and soluble factors, such as TIMP-1 and - 2. CONCLUSIONS: In conclusion, our data demonstrate the synergistic effect of the combination of CM-hUCESC with paclitaxel on TNBC and opens an opportunity to reduce the dose of the chemotherapeutic agents, which may decrease chemotherapy-related toxicity.

Importancia de la investigación sobre el estroma tumoral en el cáncer de mama / Importance of investigating tumour stroma in breast cancer

A pesar de los avances conseguidos en el tratamiento del cáncer de mama, todavía sigue siendo una causa importante de mortalidad en las mujeres. Por tanto, resulta necesario plantear nuevos enfoques de la fisiopatología de la enfermedad que contribuyan a realizar una mejor evaluación pronóstica, y a la mejora de las estrategias terapéuticas. Para ello, deberíamos considerar que el cáncer no es solo una transformación maligna de las células epiteliales y su progresión meramente autónoma; sino que, hoy en día, existen datos que apoyan el concepto del cáncer como un ecosistema basado en una sociología de diferentes tipos celulares, con sus interacciones complejas. Entre los diversos tipos de células que conforman el estroma tumoral, y que tienen un papel relevante en la progresión del cáncer de mama, se encuentran los fibroblastos asociados al cáncer, las células inflamatorias y las células endoteliales. Existen diferentes factores moleculares expresados por esas células que se asocian con el desarrollo de metástasis, tales como las metaloproteasas de matriz y sus inhibidores tisulares, citoquinas o receptores tipo toll. En base a la expresión de todos ellos, aquí proponemos 2 fenotipos de estroma del cáncer de mama con influencias marcadamente diferentes sobre el pronóstico de las pacientes. También analizamos los mecanismos involucrados en la interrelación tumor-estroma que pueden llevarnos a mejorar las estrategias terapéuticas en el cáncer de mama

Despite advances in the treatment of breast cancer, it remains an important cause of mortality in women. Therefore, it is necessary to propose new approaches to the pathophysiology of the disease that could help to improve prognostic evaluation and therapeutic strategies. To do this, we should consider that cancer is not only a malignant transformation of the epithelial cells or their purely autonomous growth; nowadays, there are data that support the concept of cancer as a system based on a sociology of different cell types, with complex interactions. Among the various types of cells that make up the tumour stroma and which play an important role in the progression of breast cancer are cancer-associated fibroblasts, inflammatory cells and endothelial cells. Several molecular factors expressed by these cells are associated with the development of metastases, such as matrix metalloproteases and their tissue inhibitors, cytokines or toll-like receptors. Based on the expression of all of these factors, here we propose two types of stroma from breast cancer that display markedly different influences on patient prognosis. We also analyse mechanisms involved in the tumour-stroma interrrelationship that could help to improve therapeutic strategies in breast cancer

Matrix metalloproteases expression in different histological types of colorectal polyps

Introduction: Colorectal carcinoma (CC) may begin as benign polyps, which may be classified in different histological types with a different risk to develop cancer. Matrix metalloproteases (MMPs) are able to degrade all components in the extracellular matrix and are important tissue-remodeling enzymes and key elements in tumor invasion and metastasis. The aim of this study was to investigate the expression and clinical relevance of MMPs in different histological types of colorectal polyps. Methods: The expression levels of MMP-1, 2, 7, 9, 11, 13 and 14 were analyzed by real-time PCR, Western-blot and immunohistochemistry in 50 patients with different histological types of colorectal polyps, 28 of which developed CC. Results: The results indicate that hyperplastic polyps had the lowest levels of MMP-1 and MMP-7, tubular polyps showed higher levels of both MMP-7 and MMP-14, and tubulovillous adenoma showed higher levels of MMP-1, MMP-7 and MMP-14. Conclusion: MMP expression was decreased in hyperplastic, tubular and tubulovillous adenoma polyps from patients who developed CC. Our findings suggest that MMP expression may be a pathological marker of colorectal polyps and for cancer susceptibility, which may improve strategies for CC prevention based on screening colonoscopy (AU)

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Análisis de factores celulares y moleculares de la frontera tumoral relacionados con la afectación de los ganglios centinela y no centinela en el cáncer de mama / Analysis of cellular and molecular factors at the tumoral margin related to sentinel and non-sentinel lymph node involvement in breast cancer

Objetivos. Investigar el valor de predicción de afectación tumoral del ganglio linfático centinela (GLC) de factores celulares y moleculares determinados en la frontera tumoral de los tumores primarios, así como el valor de esas expresiones en los GLC para predecir la afectación de los ganglios linfáticos no centinela (GLNC) en el cáncer de mama. Pacientes y métodos. Se analizaron muestras tisulares de 59 pacientes que se sometieron a la fase de validación de la técnica de la biopsia selectiva del GLC por cáncer de mama. Se seleccionaron aquellas muestras tisulares de la frontera tumoral de los tumores primarios y de los GLC, sobre los que se realizaron estudios inmunohistoquímicos utilizando mallas de tejido y anticuerpos específicos frente a D2-40, CD3, CD20, CD68, CD138, metaloproteasa (MMP)-1, MMP-7, MMP-13 y inhibidor de metaloproteasas de tejido-1 (TIMP-1). Resultados. La invasión linfática tumoral, el número de células mononucleares inflamatorias (CMI) CD68-positivas o CD138-positivas, se asociaron de forma positiva y significativa con la afectación tumoral de los GLC; mientras que la expresión de TIMP-1, tanto por las células tumorales como por los CMI o fibroblastos del estroma tumoral, se asoció significativamente de forma negativa. La expresión de MMP-1 por las CMI del GLC neoplásico se asoció significativamente con la afectación tumoral de los GLNC. Conclusiones. La determinación de factores celulares y moleculares en la frontera tumoral puede contribuir a conocer mejor las diferentes fases de la metastatización ganglionar linfática en el cáncer de mama (AU)

Objectives. To investigate the predictive value of tumour involvement of the sentinel lymph node (SLN) in terms of specific cellular and molecular factors at the tumoural margin of primary tumours, as well as the value of expression of these factors in the SLNs to predict the involvement of non-SLNs in breast cancer. Patients and methods. Tissue samples from 59 patients who underwent the validation phase of SLN biopsy of breast cancer were analyzed. Tissue samples from the tumoural margin of primary tumours and from SLNs were selected. Immunohistochemical studies were performed using the tissue array technique and antibodies against D2-40, CD3, CD20, CD68, CD138, metalloprotease (MMP)-1, MMP-7, MMP-13 and the tissue inhibitor of metalloproteases-1 (TIMP-1). Results. Tumoural invasion of the lymph nodes and the number of CD68- or CD138-positive mononuclear inflammatory cells (MICs) were positively and significantly associated with tumoural involvement of the SLNs. TIMP-1 expression, both by tumour cells and by MICs or fibroblasts from the tumor stroma, was negatively and significantly associated with tumoural involvement. MMP-1 expression by MICs from neoplastic SLNs was significantly associated with tumoural involvement of non-SLNs. Conclusions. Determination of both cellular and molecular factors at the tumoural margin may contribute to better assessment of the different phases of lymph node metastases in breast cancer (AU)