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.

Clinical factors affecting the determination of radiotherapy-induced skin toxicity in breast cancer.

PURPOSE: Radiotherapy is essential for the treatment of breast cancer (BC). However, adverse effects may occur in healthy tissue, during treatment and even after several months. Although it is known that this clinical radiosensitivity is multifactorial, the factors involved are unknown yet. In this study, we evaluated the effect of these factors on the development of radiodermatitis in patients undergoing radiotherapy. MATERIALS AND METHODS: Demographic and lifestyle data collected during face-to-face interviews of 122 BC patients and data from clinical records were investigated. Most patients underwent conventional three-dimensional radiotherapy treatment. A total dose of 50 Gy was administered (2 Gy/day), followed by a boost in a tumor bed with a total dose of 18 Gy (2 Gy/day). Radiotoxicity was evaluated weekly using the Radiation Therapy Oncology Group classification system (range, 0 to 4, according to the severity). RESULTS: In the present study, 75.4% of patients presented acute skin toxic effects with different degrees of severity. In 25% of cases, these effects manifested at the end of the fourth week at a cumulative dose of 40 Gy. The association of grade ≥2 acute skin reactions with body mass index (BMI) and breast size and between grade 3-4 and age was positive compared with controls. However, the role of the other factors could not be confirmed. CONCLUSION: Analysis of the factors related to individual radiosensitivity suggests that age, BMI and breast size play an important role in the development of acute skin toxicity during treatment. Particular attention to patients who present these characteristics would help to control treatment effectiveness and therefore optimize their quality of life.

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.

Single nucleotide polymorphisms in ATM, TNF-α and IL6 genes and risk of radiotoxicity in breast cancer patients.

Although oncological therapies have improved in the last decades, breast cancer (BC) remains a serious health problem worldwide. Radiotherapy (RT) is one of the most frequently used treatments for cancer aimed at eliminating tumor cells. However, it can also alter the surrounding normal tissue, especially the skin, and patient reactions may vary as a result of extrinsic and intrinsic factors. We evaluated the association of gene polymorphisms ATM Asp1853Asn, IL-6 G-174C and TNF-α G-308A involved in central phenotype pathways and development of individual radiosensitivity in BC patients with an exacerbated response to RT. Although univariate analysis results did not show a significant association with this trait, the interaction analysis between polymorphisms showed an increased risk of patients presenting wild-type TNF-α G-308A genotype and mutant IL-6 G-174C genotype, and heterozygous TNF-α G-308A genotype and heterozygous IL-6G-174C genotype. On the other hand, our results showed that breast size and patient age influenced the determination of RT-associated effects. Considering that the trait is multifactorial, other significant elements for the determination of individual radiosensitivity should be considered, together with the establishment of specific polymorphic variants.

Polymorphic Variants in Oxidative Stress Genes and Acute Toxicity in Breast Cancer Patients Receiving Radiotherapy.

PURPOSE: Reactive oxygen species (ROS) are generated as an indirect product of radiation therapy (RT). Genetic variation in genes related to ROS metabolism may influence the level of RT-induced adverse effects. We evaluated the potential association of single nucleotide polymorphism (SNP)-related response to radiotherapy injury in breast cancer patients undergoing RT. MATERIALS AND METHODS: Eighty patients receiving conventional RT were included. Acute effects were evaluated according to the Radiation Therapy Oncology Group (RTOG) scores. DNA was extracted from blood and buccal swab samples. SNPs were genotyped for GSTP1, GSTA1, SOD2, and NOS3 genes by polymerase chain reaction-based restriction fragment length polymorphism. Univariate analysis (odds ratios [ORs] and 95% confidence interval [CI]) and principal component analysis were used for correlation of SNPs and factors related to risk of developing ≥ grade 2 acute effects. RESULTS: Sixty-five patients (81.2%) showed side effects, 32 (40%) presented moderate to severe acute skin toxicity, and 33 (41.2%) manifested minimal acute skin reactions by the end of treatment. In both univariate and multivariate analyses, nominally significant associations were found among body mass index (OR, 3.14; 95% CI, 8.5338 to 1.1274; p=0.022), breast size (OR, 5.11; 95% CI, 17.04 to 1.54; p=0.004), and grade ≥ 2 acute radiation skin toxicity. A significant association was also observed between NOS3 G894T polymorphism (OR, 9.8; 95% CI, 211.6 to 0.45; p=0.041) and grade ≥ 2 acute radiation skin toxicity in patients with neo-adjuvant chemotherapy treatment. CONCLUSION: The analysis of the factors involved in individual radiosensitivity contributed to the understanding of the mechanisms underlying this trait.

Evaluación de los arándanos como radioprotectores potenciales / Evaluation of blueberries as potential radioprotectors

Antecedentes: numerosos estudios han analizado la capacidad antioxidante de los arándanos. Considerando la citotoxicidad de las radiaciones ionizantes, mediada por radicales libres, es imperativo el análisis de fitocompuestos con efecto mitigante potencial. Objetivo: evaluar las propiedades radio-protectoras de de los arándanos, en relación con el daño genético inducido por rayos X. Materiales y métodos: el diseño experimental tuvo dos etapas: primero se ejecutó ensayo in vitro con diez muestras de sangre periférica de mujeres jóvenes no fumadoras. Cada muestra fue analizada mediante Ensayo Cometa en el siguiente grupo de tratamientos: control negativo, tratamiento con arándanos (0,232 mG/mL), irradiación con 4 Gy y tratamiento simultáneo arándanos/irradiación. Se contabilizaron 800 células/individuo, 200 por tratamiento, considerando su repetición. Posteriormente, se realizó ensayo in vivo con sangre periférica de dos mujeres, de condiciones similares a las anteriores, sometidas al consumo de extracto seco de arándanos durante 15 días consecutivos. El muestreo se realizó antes y después del tratamiento y se implementó el Cometa analizando 800 células/individuo, correspondientes al control negativo e irradiación con 4 Gy. Resultados: en ambas etapas, el tratamiento con arándanos demostró una reducción significativa (p<0,01) del daño genómico referido a las muestras irradiadas. Conclusiones: la suplementación dietaria con arándanos podría disminuir los efectos secundarios de la radioterapia, optimizando la calidad de vida del paciente oncológico.

Introduction: Numerous studies have analyzed the antioxidant capacity of blueberries. Considering the ionizing radiation cytotoxicity mediated by free radicals is imperative phytocompounds analysis with potential mitigating effect. Objective: To evaluate radio-protective properties of this fruit in relation to genetic damage induced by x-rays. Materials and methods: Experimental design had two stages. First an in vitro assay using 10 samples of peripheral blood of young and nonsmokers female. Each sample was analyzed by comet assay in the next set of treatments: negative control, treatment with blueberries (0,232 mG / mL), irradiation 4Gy and simultaneous blueberry/ irradiation treatment. Were counted 800 cells/individual, 200 per treatment, considering its repetition. Subsequently, an in vivo assay with peripheral blood of two women, of similar conditions and subject to the consumption of dried extract of blueberries for 15 consecutive days was performed. Sampling was performed before and after treatment and Comet was implemented by analyzing 800 cells / individual, corresponding to the negative control and irradiation with 4 Gy. Results: In both stages, treatment with blueberries showed a significant reduction (p <0.01) of genomic damage relative to irradiated samples. Conclusions: Dietary supplementation with blueberries may decrease the side effects of radiation therapy, optimizing the quality of life of cancer patients.

Cytotoxic and genotoxic effects of defence secretion of Ulomoides dermestoides on A549 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulomoides dermestoides (Fairmaire, 1893) is a cosmopolitan tenebrionid beetle reared by Argentine people who consume them alive as an alternative medicine in the treatment of different illnesses such as asthma, Parkinson's, diabetes, arthritis, HIV and specially cancer. AIM OF THE STUDY: To evaluate the cytotoxicity and DNA damage of the major volatile components released by Ulomoides dermestoides on human lung carcinoma epithelial cell line A549. MATERIALS AND METHODS: The defence compounds of Ulomoides dermestoides were extracted with dichloromethane and analyzed and quantified by capillary gas chromatography. The toxicity effects of the beetle's extract against A549 cell line were evaluated. Cytotoxicity was evaluated by MTT test and Trypan blue assay and genotoxicity was evaluated by the comet assay. The synthetic compounds, individually or combined, were also tested in A549 cells and normal mononuclear human cells. RESULTS: The defence compounds of Ulomoides dermestoides extracted with dichloromethane (methyl-1,4-benzoquinones, ethyl-1,4-benzoquinones and 1-pentadecene as major components) showed cytotoxic activity on A549 cells demonstrated by MTT test and Trypan blue assay, with IC(50) values of 0.26equivalent/ml and 0.34equivalent/ml, respectively (1equivalent=amount of components extracted per beetle). The inhibition of A549 cell proliferation with the synthetic blend (1,4-benzoquinone and 1-pentadecene) or 1,4-benzoquinone alone was similar to that obtained with the insect extract. 1-Pentadecene showed no inhibitory effect. Low doses of insect extract or synthetic blend (0.15equivalent/ml) inhibited mononuclear cell proliferation by 72.2±2.7% and induced significant DNA damage both in tumor and mononuclear cells. CONCLUSION: Results of this study demonstrated that defence compounds of Ulomoides dermestoides reduced cell viability and induced DNA damage. We also concluded that the insect benzoquinones are primarily responsible for inducing cytotoxicity and genotoxicity in culture cells.

Evaluation of radioadaptive response induced in CHO-K1 cells in a non-traditional model.

PURPOSE: The present study was designed to evaluate the effects of sequential exposures to low doses of gamma-radiation that induce a radioadaptive response to a later high-dose of radiation in CHO-K1 cells. MATERIALS AND METHODS: Cells were cultured in four dilution cycles and grown to confluency. Radiation treatment was performed once per cycle with 0.1 Gy gamma-rays. After the last radiation period (chronic radiation) the culture was irradiated with a higher dose (1 Gy). Each cell culture was immediately divided into two fractions: one of them was used to carry out the comet assay and the other for the structural chromosome aberration test. In the first fraction, genotoxic damage was evaluated by degree of damage in 300 cells per experimental point. The second assay was performed with 400 cells per treatment. The statistical analysis was carried out using the chi(2)-test. RESULTS: Results from these assays demonstrated a genotoxic effect for both the adaptive and acute treatments (p < 0.001). The comet assay showed a significant increase in damage for the combined treatment when compared with 1 Gy treatment (p < 0.001). The frequency of chromosomal aberrations (CA) was lower for the combined treatment than for that using the highest radiation dose. CONCLUSIONS: These results suggest the possible induction of a radioadaptive response after the sequential exposure to very low doses of radiation. The finding of decreased cytogenetic damage after one cell cycle and not immediately after radiation could indicate the eventual potentiation of repair mechanisms.

Assessment of genotoxic damage in lymphocytes of hospital workers exposed to ionizing radiation in Argentina.

The authors aimed to assess genotoxic damage in the lymphocytes of workers chronically exposed to ionizing radiation. The studied population included 15 exposed donors of the radiology unit of a public hospital in La Plata, Argentina. The control group included 15 nonexposed employers from administrative areas that the authors matched by age, sex, and smoking habits. The mean frequency of cytogenetic damage was higher in the exposed group than in the unexposed group for aneuploidy and structural chromosome aberrations. They observed the highest difference when achromatic lesions (or gaps) were considered. The comet assay showed that the frequency of cells with low damage was higher in the exposed group than in the unexposed group. A mean length analysis showed significant differences between exposed and nonexposed people. The results can be considered to be consistent evidence of occupational radiation exposure, and the results indicate that the workers must be advised to avoid or minimize their exposure.

Activación de los protooncogenes K-ras y c-erbB-2 en adenocarcinomas colónicos humanos / Activation of K-ras and c-erbB-2 protooncogenes in human colonic adenocarcinomas

Aunque los datos de las alteraciones genéticas que conducen al desarrollo de cáncer colorectal son abundantes, las alteraciones genéticas específicas para cada clase de tumor no han sido demostradas. El fenotipo cáncer colorectal es originado por la acumulación de diferentes alteraciones genéticas. La naturaleza de esas alteraciones, su orden de aparición y sus asociaciones, varian ampliamente de un tumor a otro, sugiriendo que el concepto de un modelo único de carcinogénesis no es aplicable a estos tumores. El objetivo del presente trabajo fue estudiar la asociación entre las mutaciones en los protooncogenes K-ras y c-erbB-2 con diferentes variables clinicopatológicas en 54 muestras de adenocarcinomas de colon. La detección de la activación de K-ras en 16 casos fue hecha mediante PCR alelo específica. Para la detección de la amplificación genética en c-erbB-2 se empleó un método de coamplificación por PCR con gen de copia única como referencia. Fueron detectadas mutaciones en K-ras en 16 casos (29,63 por ciento) y amplificación en c-erbB-2 en una muestra (1,85 por ciento). El análisis estadístico mostró una asociación significativa entre frecuencia de mutaciones en el codón 12 de K-ras y el estadio B de Dukes (p<0.005). Por otra parte, no se encontró asociación alguna con los otros parámetros estudiados. Estos resultados indicarian que la activación del protooncogén K-ras podría ocurrir en estadíos tempranos de la enfermedad. (Au)

Activación de los protooncogenes K-ras y c-erbB-2 en adenocarcinomas colónicos humanos / Activation of K-ras and c-erbB-2 protooncogenes in human colonic adenocarcinomas

Aunque los datos de las alteraciones genéticas que conducen al desarrollo de cáncer colorectal son abundantes, las alteraciones genéticas específicas para cada clase de tumor no han sido demostradas. El fenotipo cáncer colorectal es originado por la acumulación de diferentes alteraciones genéticas. La naturaleza de esas alteraciones, su orden de aparición y sus asociaciones, varian ampliamente de un tumor a otro, sugiriendo que el concepto de un modelo único de carcinogénesis no es aplicable a estos tumores. El objetivo del presente trabajo fue estudiar la asociación entre las mutaciones en los protooncogenes K-ras y c-erbB-2 con diferentes variables clinicopatológicas en 54 muestras de adenocarcinomas de colon. La detección de la activación de K-ras en 16 casos fue hecha mediante PCR alelo específica. Para la detección de la amplificación genética en c-erbB-2 se empleó un método de coamplificación por PCR con gen de copia única como referencia. Fueron detectadas mutaciones en K-ras en 16 casos (29,63 por ciento) y amplificación en c-erbB-2 en una muestra (1,85 por ciento). El análisis estadístico mostró una asociación significativa entre frecuencia de mutaciones en el codón 12 de K-ras y el estadio B de Dukes (p<0.005). Por otra parte, no se encontró asociación alguna con los otros parámetros estudiados. Estos resultados indicarian que la activación del protooncogén K-ras podría ocurrir en estadíos tempranos de la enfermedad.

Amplificación del proto-oncogén HER-2/neu asociada a la infección por VPH de bajo riesgo en citología exfoliativa cervical / HER-2/neu prot-oncogen amplification related to low risk VPH infection in cervical exfoliative cytology

Se analizaron 69 muestras positivas para el virus papiloma humano (VPH) tipos -6, -16 y -18, y 24 muestras con citología cervical normal negativas para el VPH como grupo control. El análisis de la amplificación génica del proto-oncogén HER-2/neu se realizó utilizando la técnica de coamplificación con locus de referencia. Se encontró una asociación entre la amplificación del gen HER-2/neu y el grupo viral de "bajo riesgo" (VPH-6) (p < 0.005). Dentro de este grupo, se observó una asociación entre la amplificación del proto-oncogén y el status citopatológico CIN I (p < 0.01). Debido a que la mayoría de las muestras CIN I analizadas presentaron un patrón coilocítico, la amplificación de HER-2/neu parecería estar relacionada con este tipo de alteración celular. Por otra parte, sería importante estudiar la amplificación génica y la expresión de HER-2/neu en los diferentes estadios de las neoplasias intraepiteliales cervicales a fin de poder evaluar su papel en la progresión del cáncer cervical.