El potencial impacto de la dieta en el desarrollo del cáncer de estudio de una población argentina / The potential impact of diet on the development of breast cancer: study of an argentine population

Fundamentos: el cáncer de mama constituye un serio problema sanitario. La exposición a ciertas condiciones ambientales y un estilo de vida nocivo, en parte son responsables de ello. Así, se considera necesario determinar los factores de riesgo que operan particularmente en cada población. Dada la falta de estudios locales, el objetivo fue establecer elementos y conductas de riesgo relevantes para el desarrollo del cáncer de mama, en una población argentina. Métodos: se realizó un estudio descriptivo de orden transversal. A través de una encuesta semiestructurada se indagaron hábitos alimentarios, de vida y antecedentes de 110 pacientes con cáncer de mama de la ciudad de La Plata y zona de influencia. Además, se tuvieron en cuenta parámetros antropométricos. Resultados: se comprobó la asociación entre la obesidad y esta patología, posiblemente debido a la insuficiencia de actividad física y la mala alimentación. Se estableció el patrón alimentario prevalente, reflejando semejanza a la dieta occidental, con potencial carcinogénico. Así, se observó un consumo excesivo en carne roja y pollo, cereales refinados y azúcares y al mismo tiempo deficiente en pescado y fitonutrientes. Conclusiones: a partir de estos hallazgos, se podrían impulsar cambios adecuados mediante el desarrollo de políticas sanitarias basadas en evidencia. (AU)

Background: breast cancer is a serious health problem. Exposure to certain environmental conditions and a harmful lifestyle are partly responsible for it. Thus, it is considered necessary to determine the risk factors that operate particularly in each population. Given the lack of local studies, the objective was to establish relevant elements and risk behaviors for the development of breast cancer in an Argentine population. Methods: a descriptive cross-sectional study was carried out. Through a semi-structured survey, eating habits, life and background of 110 patients with breast cancer, from the city of La Plata and area of influence were investigated. In addition, anthropometric parameters were taken. Results: the association between obesity and this pathology was verified, possibly due to insufficient physical activity and poor diet. The prevailing eating pattern was established, reflecting similarity to the Western diet, with carcinogenic potential. Thus, an excessive consumption of red meat and chicken, refined grains and sugars was observed, and at the same time deficient in fish and phytonutrients. Conclusions: We understand that based on our findings, appropriate changes could be promoted through the development of evidence-based health policies. (AU)

Cellular bases of hypofractionated radiotherapy protocols for lung cancer.

The extreme demand on health systems due to the COVID-19 pandemic has led to reconsider hypofractionation. Although the best clinical efficacy of these schemes is being demonstrated, the biological bases have not been established. Thus, after validating basic clinical parameters, through complementary in vitro models, we characterized the cellular and molecular mechanisms of hypofractionation protocols. Cell cultures of human lung cancer cell line A549 were irradiated with 0, 2, 4, 8, 12, 16 and 20 Gy. The clastogenic, cytotoxic, proliferative and clonogenic capacities and bystander effect were evaluated. In addition, we assessed survival and toxicity in a retrospective study of 49 patients with lung cancer. Our findings showed that the greater efficacy of ablative regimens should not only be attributed to events of direct cell death induced by genotoxic damage, but also to a lower cell repopulation and the indirect action of clastogenic factors secreted. These treatments were optimal in terms of 1- and 2-year overall survival (74 and 65%, respectively), and progression-free survival at 1 and 2 years (71 and 61%, respectively). The greater efficacy of high doses per fraction could be attributed to a multifactorial mechanism that goes beyond the 4Rs of conventional radiotherapy.

Successful use of three-dimensional conformal radiotherapy as adjuvant treatment for alveolar soft part sarcoma. A case report / Uso exitoso de la radioterapia conformada tridimensional como tratamiento adyuvante del sarcoma alveolar de partes blandas. Reporte de un caso

Abstract Introduction: Alveolar soft part sarcoma is a very rare and aggressive type of sarcoma. Although its histology and genetic characteristics have been identified, the benefits of adjuvant radiotherapy for its treatment are still being studied. Case presentation: In November 2007, a 21-year-old woman presented with a primary tumor in the right thigh, with histological and immunohistochemical confirmation of an alveolar soft part sarcoma, which was totally resected in December 2007. Also, the large size of the mass suggested an unfavorable evolution. Two years after the first surgery, two metastatic tumors were detected in the right lung, which were completely resected separately. Two years later, the patient had two independent relapse events, five months apart: a mass in the right tight, and a metastatic tumor in the adrenal gland, together with a relapse in the tight. All tumors were successfully resected. In June 2014, after the last local relapse, adjuvant radiotherapy was started because of the risk of thigh amputation. At the end of treatment, the patient's general condition was good. Currently, at age 34, the patient is monitored through periodic evaluations, showing disease regression and stabilization. Conclusions: Currently, it is known that radiation not only produces cytotoxic effects on the target region but also induces an immune system-mediated systemic response with potential antimetastatic properties. Emerging radiobiological paradigms should be considered, particularly since they could explain some encouraging and unexpected results, such as those described in this case.

Resumen Introducción. El sarcoma alveolar de partes blandas es un raro y agresivo tipo de sarcoma. Aunque se han identificado sus características histológicas y genéticas, todavía se están estudiando los beneficios de la radioterapia adyuvante en su tratamiento. Presentación del caso. En noviembre de 2007, una mujer de 21 años se presentó con un tumor primario en el muslo derecho, con confirmación histológica e inmunohistoquímica de sarcoma alveolar de partes blandas y que fue completamente removido en diciembre de 2007. La masa mostró un gran tamaño, sugiriendo una evolución desfavorable. Dos años después de la primera cirugía, se detectaron dos tumores metastásicos en el pulmón derecho, que también fueron removidos, de forma separada. Dos años después, la paciente tuvo dos relapsos, separados por cinco meses: una masa en el muslo derecho, y un tumor metastásico en la glándula suprarrenal junto con una recaída en el muslo. Todos los tumores fueron extirpados con éxito. En junio de 2014, después de la última recaída local, el muslo estaba en riesgo de ser amputado, por lo que se decidió iniciar radioterapia adyuvante. Al final del tratamiento, la condición general de la paciente fue buena. Actualmente, ya con 34 años, es evaluada periódicamente, mostrando regresión y estabilización de la enfermedad. Conclusiones. Actualmente, se sabe que la radiación no solo produce efectos citotóxicos en la región objetivo, sino que también induce una respuesta sistémica mediada por el sistema inmune, con propiedades potencialmente antimetastásicas. En este sentido, se sugiere considerar los paradigmas radiobiológicos emergentes, ya que estos podrían explicar algunos resultados alentadores e inesperados como los descritos en este caso.

Radiosensitivity of radiotherapy patients: The effect of individual DNA repair capacity.

Individual radiosensitivity is a critical problem in radiotherapy because of the treatment restrictions it imposes. We have tested whether induction/repair of genomic lesions correlates with the acute cutaneous effects of radiotherapy. Peripheral blood samples of 56 healthy volunteers and 18 patients with breast cancer were studied. DNA damage and DNA repair capacity were assessed in vitro (alkaline comet assay). Patients without skin reaction did not show significant differences from healthy individuals, with respect to either initial or radiation-induced DNA damage. Similar DNA repair kinetics, fitting a decreasing exponential response, were observed in both groups, and there were no significant differences in residual genotoxic damage. In contrast, patients exhibiting acute side effects showed significantly lower DNA repair ability and significantly more residual damage, compared to patients without radiotoxicity. This approach may help to identify patients who are at greater risk of radiotherapy side effects. However, many other factors, such as dosimetry, irradiated volume, and lifestyle should also be considered in the evaluation of individual radiosensitivity.

Modulation of ionizing radiation-induced damage in human blood lymphocytes by in vivo treatment with resveratrol.

Purpose: Radiotherapy is an effective tool for cancer control, but side effects on normal tissue limit its therapeutic effectiveness. Thus, the search for agents that may allow the use of high doses of radiation but exerting a differential protection to healthy tissue is of current concern. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) (RSV) is a polyphenol with pleiotropic benefits for health due to its antioxidant and anti-inflammatory properties. Recent findings suggest that RSV could be promising in the fight against cancer since it inhibits the growth of tumor cells and optimizes radiotherapy. However, evidence in rodents and human beings is inconsistent. The aim of this study was to evaluate the radiomodulatory capacity of RSV on human lymphocytes. Materials and methods: To study these properties of RSV, human peripheral blood lymphocytes from 20 healthy women undergoing in vivo RSV treatment with 50 mg/day doses were irradiated. The genotoxic damage was assessed by the comet assay, also called single cell gel electrophoresis (it makes it possible to measure the extent of the DNA migration from individual cells, detecting the genomic damage present in each cell). Results: No differences were observed in basal clastogenic damage among samples without irradiation. There was only a slight radiation-induced clastogenic damage. The damage index (DI) value had a statistically significant increase in the exposed groups in comparison with the control groups (p < .0001), but a statistically significant decrease of the DI value was observed in samples irradiated after treatment with RSV compared to pretreatment samples (p < .0001). Conclusion: The RSV used as a dietary supplement had radioprotective properties, without exerting a cytotoxic effect. The potential utility of RSV to optimize the radiotherapeutic ratio in cancer treatments using radiotherapy should be considered.

Evaluation of resveratrol radiomodifying potential for radiotherapy treatment.

Radiotherapy is widely used for cancer treatment. However, its adverse effects that may develop during the course of treatment have forced to search agents to protect biological systems against the deleterious effects of radiation. Resveratrol (3,4,5-trihydroxy-trans-stilbene; RSV) is a natural polyphenol currently promoted for its beneficial pleiotropic effects on health, which has been shown to exhibit antioxidant properties while inhibiting the growth of tumor cells. In radioresistant tumors, RSV could contribute to reduce recurrence and treatment failure. We evaluated the radiomodulatory and genotoxic effects of RSV in CHO-k1 and A549 cell lines and in peripheral human blood lymphocytes through both conventional and hypofractionated protocols, due to the widespread use of hypofractionation in recent years. RSV genotoxic and cytotoxic action was assessed at 15 and 60 µM concentrations with the comet and the MTT assay and in cell proliferation experiments. Our results show that RSV administration to tumor cells at a dose of 60 µM exerted a genotoxic effect and that this concentration also had the capacity of modulating the cytomolecular damage induced by 4 and 16 Gy. These doses are delivered in conventional and hypofractionated radiotherapy, respectively. In both treatments, a radiosensitizing effect was evidenced by the decrease in cell viability that was exacerbated over time. These effects were not found in peripheral blood, suggesting that RSV had a dual response. Although the results obtained in CHO-k1 transformed cells corroborated the genotoxic effect of the 60 µM dose of RSV observed in the tumor system, they also showed a radio-protective effect at the lowest dose (15 µM). While more studies are necessary, our results together with the good systemic tolerance of RSV and the lack of toxicity position the compound as a potential candidate for the prevention and treatment of cancer as well as for the optimization of the radiotherapeutic ratio.

Identification and characterization of two RNA silencing suppressors encoded by ophioviruses.

Citrus psorosis virus and Mirafiori lettuce big-vein virus are two members of the genus Ophiovirus, family Ophioviridae. So far, how these viruses can interfere in the antiviral RNA silencing pathway is not known. In this study, using a local GFP silencing assay on Nicotiana benthamiana, the 24K-25K and the movement protein (MP) of both viruses were identified as RNA silencing suppressor proteins. Upon their co-expression with GFP in N. benthamiana 16c plants, the proteins also showed to suppress systemic RNA (GFP) silencing. The MPCPsV and 24KCPsV proteins bind long (114 nucleotides) but not short-interfering (21 nt) dsRNA, and upon transgenic expression, plants showed developmental abnormalities that coincided with an altered miRNA accumulation pattern. Furthermore, both proteins were able to suppress miRNA-induced silencing of a GFP-sensor construct and the co-expression of MPCPsV and 24KCPsV exhibited a stronger effect, suggesting they act at different stages of the RNAi pathway.

Citrus psorosis virus 24K protein interacts with citrus miRNA precursors, affects their processing and subsequent miRNA accumulation and target expression.

Sweet orange (Citrus sinensis), one of the most important fruit crops worldwide, may suffer from disease symptoms induced by virus infections, thus resulting in dramatic economic losses. Here, we show that the infection of sweet orange plants with two isolates of Citrus psorosis virus (CPsV) expressing different symptomatology alters the accumulation of a set of endogenous microRNAs (miRNAs). Within these miRNAs, miR156, miR167 and miR171 were the most down-regulated, with almost a three-fold reduction in infected samples. This down-regulation led to a concomitant up-regulation of some of their targets, such as Squamosa promoter-binding protein-like 9 and 13, as well as Scarecrow-like 6. The processing of miRNA precursors, pre-miR156 and pre-miR171, in sweet orange seems to be affected by the virus. For instance, virus infection increases the level of unprocessed precursors, which is accompanied by a concomitant decrease in mature species accumulation. miR156a primary transcript accumulation remained unaltered, thus strongly suggesting a processing deregulation for this transcript. The co-immunoprecipitation of viral 24K protein with pre-miR156a or pre-miR171a suggests that the alteration in the processing of these precursors might be caused by a direct or indirect interaction with this particular viral protein. This result is also consistent with the nuclear localization of both miRNA precursors and the CPsV 24K protein. This study contributes to the understanding of the manner in which a virus can alter host regulatory mechanisms, particularly miRNA biogenesis and target expression.