IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas.

Introduction: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model.

Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome.

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells.

Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes.

In this paper, we summarize published articles and experiences related to the attempt to improve radiotherapy outcomes and, thus, to personalize the radiation treatment according to the individual characteristics of each patient. The evolution of ideas and the study of successively published data have led us to envisage new biophysical models for the interpretation of tumor and healthy normal tissue response to radiation. In the development of the model, we have shown that when mesenchymal stem cells (MSCs) and radiotherapy are administered simultaneously in experimental radiotherapy on xenotumors implanted in a murine model, the results of the treatment show the existence of a synergic mechanism that is able to enhance the local and systemic actions of the radiation both on the treated tumor and on its possible metastasis.

Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci.

Background: We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT).

Methods: We have measured tumor growth and metastasis formation, of subcutaneous human melanoma A375 xenografts on NOD/SCID-gamma mice, and the response of tumors to treatment with radiotherapy (2 Gy), mesenchymal cells (MSC), mesenchymal cells plus radiotherapy, and without any treatment.

ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients.

Background: Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood.

Direct and bystander radiation effects: a biophysical model and clinical perspectives.

In planning treatment for each new patient, radiation oncologists pay attention to the aspects that they control. Thus their attention is usually focused on volume and dose. The dilemma for the physician is how to protract the treatment in a way that maximizes control of the tumor and minimizes normal tissue injury.

Growth and spontaneous differentiation of umbilical-cord stromal stem cells on activated carbon cloth.

We have investigated the capacity of activated carbon cloth to support the growth and differentiation of human mesenchymal umbilical-cord stromal stem cells. Our results demonstrate that this scaffold provides suitable conditions for the development of cell-derived matrix proteins and facilitates the growth of undifferentiated stem cells with the ability to induce osteogenic and chondrogenic differentiation. Immunoflourescence staining revealed extensive expression of collagen in all the samples, and collagen type II and osteopontin within the samples cultivated in specific differentiation-inducing media.

The importance of bystander effects in radiation therapy in melanoma skin-cancer cells and umbilical-cord stromal stem cells.

Purpose: To examine direct and bystander radiation-induced effects in normal umbilical-cord stromal stem cell (HCSSC) lines and in human cancer cells.

Materials And Methods: The UCSSC lines used in this study were obtained in our laboratory. Two cell lines (UCSSC 35 and UCSSC 37) and two human melanoma skin-cancer cells (A375 and G361) were exposed to ionizing radiation to measure acute radiation-dosage cell-survival curves and radiation-induced bystander cell-death response.

Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis.

Background: Numerous hypermethylated genes have been reported in breast cancer, and the silencing of these genes plays an important role in carcinogenesis, tumor progression and diagnosis. These hypermethylated promoters are very rarely found in normal breast. It has been suggested that aberrant hypermethylation may be useful as a biomarker, with implications for breast cancer etiology, diagnosis, and management.

Quantitative detection of methylated ESR1 and 14-3-3-sigma gene promoters in serum as candidate biomarkers for diagnosis of breast cancer and evaluation of treatment efficacy.

The aim of the present study was to investigate the association between gene hypermethylation and main clinicopathological features of breast cancer, including diagnosis and treatment response. A sensitive SYBR green methylation-specific PCR technique was used to analyze the utility of circulating DNA with CpG island hypermethylation of ESR1, APC, RARB, 14-3-3-sigma and E-cad gene promoter regions as breast cancer biomarkers. Analyses were conducted of preoperative sera from 106 women with breast cancer, 34 with benign breast disease and 74 with no evidence of breast disease and of post-treatment sera from 60 of the breast cancer patients.

Inhibition of poly(ADP-ribose) polymerase modulates tumor-related gene expression, including hypoxia-inducible factor-1 activation, during skin carcinogenesis.

Poly(ADP-ribose) polymerase (PARP)-1, an enzyme that catalyzes the attachment of ADP ribose to target proteins, acts as a component of enhancer/promoter regulatory complexes. In the present study, we show that pharmacologic inhibition of PARP-1 with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) results in a strong delay in tumor formation and in a dramatic reduction in tumor size and multiplicity during 7,12-dimethylbenz(a)anthracene plus 12-O-tetradecanoylphorbol-13-acetate-induced skin carcinogenesis. This observation was parallel with a reduction in the skin inflammatory infiltrate in DPQ-treated mice and tumor vasculogenesis.

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes.

Introduction: Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients.

Prediction of normal tissue response and individualization of doses in radiotherapy.

In this work we estimate the therapeutic gain that could be obtained using a radiotherapy programme in which doses were based on a radiosensitivity test that was able to predict the final response of normal tissues to radiation for each particular patient. To date, no good radiosensitivity assay has been demonstrated and by way of example we use an assay based on initial DNA damage. The individualized programme we propose is based on an increase in the dose delivered to patients showing a resistant behaviour to radiation and on the adoption of alternative programmes or a careful monitoring of those patients in whom an excessive reaction is expected.

Individualization of radiotherapy in breast cancer patients: possible usefulness of a DNA damage assay to measure normal cell radiosensitivity.

Purpose: The purpose of this study was to determine whether the distribution of sensitivities in breast cancer patients, measured using a DNA damage assay on lymphocytes, is likely to provide sufficient discrimination to enable the reliable identification of patients with abnormal sensitivities.

Material And Methods: Radiosensitivity (x) was assessed in 226 samples of lymphocytes from unselected women with breast cancer and was quantified as the initial number of DNA double-strand breaks (dsb) induced per Gy and per DNA unit (200 Mbp).

Results: The existence of an inter-individual variation in the parameter (x) is described through the range (0.

Breast cancer acute radiotherapy morbidity evaluated by different scoring systems.

Reporting of the outcome of radiotherapy is not satisfactory without a description of the treatment-related side effects. The purposes of this paper were: (1) to evaluate the frequency and the severity of collateral skin reactions in a group of breast cancer patients; (2) to report the acute reactions using some current scoring systems and to compare the application of them, and (3) to investigate the variation between intra- and interobservers using these different scales. We studied 108 breast cancer patients who, after surgical treatment, received adjuvant radiotherapy.