[Food consumption patterns and risk of gallstone disease (GD): Case and Control Study in Rosario Argentina.] / Patrones de consumo alimentario y riesgo de enfermedad colelitiásica (EC): Estudio de Casos y Controles en Rosario Argentina.

Introduction: Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD). Aim: The aim of this study was to determine food intakes patters and estimate risk of GD. Methods: A nested case-control study was carried out within the framework of a previous screening study conducted on a representative sample in Rosario, Argentina. Participants underwent a personal interview. Average amount of each food intake and quantity nutrients were estimated applying a food-frequency questionnaire. Food consumption patterns were identified by principal component analysis, and logistic regression analysis was used to estimate risks. Results: The sample was conformed by 51 cases and 69 controls. Two dietary patterns were identified. Cases were characterised by the unhealthy intake pattern (high intakes of animal fats, sugar, cereals, grains, cold cuts, processed meats, chicken with skin, fat beef and low intake of red vegetables and yellows, cabbages, fruits and fish). Conclusion: Controls were characterised by the healthy intake pattern (high intake of skinless chicken, nuts, lean beef, vitamin A and C rich fruits, and low consumption of chicken with skin, green leaves vegetables and sprouts). The unhealthy pattern showed an increased risk of developing GD while healthy patter behaved as a protective factor.

Introducción: La exposición nutricional se considera la principal exposición ambiental que contribuye a la formación de cálculos biliares. Objetivo: El objetivo de este trabajo fue determinar el patrón de consumo alimentario de casos y controles de EC y estimar el riesgo de desarrollar la enfermedad según los distintos patrones constituidos. Métodos: Se llevó a cabo un estudio analítico retrospectivo transversal de casos y controles, anidado a un estudio de prevalencia realizado en Rosario. Todos los participantes fueron entrevistados personalmente. El consumo de alimentos se consignó a través de un cuestionario semi-cuantitativo de frecuencia de consumo. Para determinar patrones de consumo alimentario se realizó un análisis de componentes principales, y análisis de regresión logística múltiple para evaluar riesgos. Resultados: La muestra quedó conformada por 51 casos y 69 controles. Se determinaron dos componentes que permitían diferenciar los casos de los controles, a través de las cuales se establecieron 2 patrones de consumo. Los casos se caracterizaron por un consumo determinado por el Patrón Poco saludable (altas ingestas de grasas animales, azúcar, cereales, granos, fiambres y embutidos) y los controles por el consumo del patrón Saludable (altas ingestas de pollo sin piel, frutas secas, carne vacuna magra, frutas, lácteos enteros). El patrón Poco saludable, aumentó el riesgo de desarrollar EC mientras que el patrón Saludable, se comportó como protector. Conclusión principal: Los patrones constituidos diferencian los casos de los controles, y la ingesta propia de los casos se correlaciona con un perfil de consumo que caracteriza a las culturas occidentales modernas y urbanas.

Achievements and challenges in the use of metronomics for the treatment of breast cancer.

Two interesting therapeutic proposals for cancer treatment emerged at the beginning of the 21st century. The first one was metronomic chemotherapy, which refers to the chronic administration of chemotherapeutic agents, in low doses, without extended drug-free periods. Then, the idea of drug repositioning in oncology, the use of well-known drugs that were created for other uses to be utilized in oncology, gained strength. Shortly after, the two strategies were merged in one, named metronomics. Both approaches share several features which make metronomics an appealing choice for cancer treatment: use of known and approved drugs, thus diminishing the time necessary to enter to the clinic, therapeutic effect, low toxicity, oral administration, better life quality, low costs because of the use of, generally, out of patent drugs, possibility of use, even in countries with very low economic resources. Many chemotherapy and repurposed drugs were tested with metronomics approaches for the treatment of mammary cancer, the most common malignancy in women worldwide, leading to high rates of mortality. The wide range of therapeutic models studied, paralleled the wide range of responses obtained, like tumor growth and metastasis inhibition, overall survival increase, lack of toxicity, better life quality, among others. The accomplishments reached, and the challenges faced by researchers, are discussed.

Putative Biomarkers of Response to Treatment in Breast Cancer Patients: A Pilot Assay.

Identifying tumor biomarkers associated with clinical behavior in breast cancer patients may allow higher accuracy in the selection of treatment. Different types of cells were determined in the primary tumors of stage I, II, and III of breast cancer patients, who were assigned to one of the two groups: (1) disease-free or (2) relapsed/progressed, at 5 years after primary treatment. We studied 32 tumor samples. CD4+ lymphocytes and CD44+CD24-/low cells (cancer stem cells) showed a significant association with clinical outcome at 5 years of primary treatment, while CD8+, Foxp3+, CD34+, and myeloid-derived suppressor cells did not show any association. Coincident with the results of individual analysis, we identified CD4+ cells and CD44+CD24-/low cells as good predictors of long-term clinical outcome in a logistic regression.

Quality of life in patients with metastatic breast cancer treated with metronomic chemotherapy.

AIM: The objective of the study was to detect changes in quality of life (QoL) in metastatic breast cancer patients treated with metronomic chemotherapy with daily low doses of cyclophosphamide and celecoxib. MATERIAL & METHODS: Patients included in a Phase II trial, treated with metronomic cyclophosphamide and celecoxib were included in the QoL study. Assessment of QoL was carried out every 2 months by the Functional Assessment of Cancer Therapy Breast (FACT-B) questionnaire, Brief Pain Inventory and Eastern Cooperative Oncologic Group scale. Data were analyzed at three time points: baseline (BL); middle of treatment (MT); and end of treatment (ET). RESULTS: A total of 20 patients were included. All patients were heavily pretreated. Treatment showed a good and safe therapeutic profile. With FACT-B questionnaire, no significant differences were observed during the response period (BL-MT). However, a significant increase was observed in the Emotional well-being and Additional concerns axes, when the last time point was included in the analysis (BL-MT-ET). A significant decrease in the proportion of patients with pain was found when comparing BL with ET (p = 0.046). The assessment with Eastern Cooperative Oncologic Group scale showed that 26.7% (4/15) of the patients improved their functional status and 40% (6/15) showed no changes, while 33.3% (5/10) worsened it. CONCLUSION: Patients treated metronomically for several months did not worsen their QoL. A high proportion of patients showed improvement or no changes and there were less patients with pain at the end of the treatment.

Safety and therapeutic effect of metronomic chemotherapy with cyclophosphamide and celecoxib in advanced breast cancer patients.

Metronomic chemotherapy (MCT), the chronic administration, at regular intervals, of low doses of chemotherapeutic drugs without extended rest periods, allows chronic treatment with therapeutic efficacy and low toxicity. Our preclinical results suggested that combined MCT with cyclophosphamide and celecoxib could inhibit breast cancer growth. The aim of this study was to determine the toxicity, safety and efficacy of oral MCT with cyclophosphamide 50 mg per orem daily and celecoxib 400 mg (200 mg per orem two-times a day) in advanced breast cancer patients. During the first stage of the study, the therapeutic response consisted of prolonged stable disease for ≥24 weeks in six out of 15 (40%) patients with a median duration of 37.5 weeks and a partial response in one out of 15 (response rate: 6.7%) patients lasting 6 weeks. The overall clinical benefit rate was 46.7%. The median time to progression was 14 weeks. Progression-free survival at 24 weeks was 40% and the 1-year overall survival rate was 46.7%. The adverse events were mild (gastric, grade 1; and hematologic, grade 1 or 2). No grade 3 or 4 toxicities were associated with the treatment. Evaluation of patients' quality of life showed no changes during the response period. MCT with cyclophosphamide plus celecoxib is safe and shows a therapeutic effect in advanced breast cancer patients.

Patrón de consumo alimentario en una muestra de adultos con Enfermedad Colelitiasica (EC)

En un estudio realizado en una muestra aleatoria de adultos de Rosario se encontró una tasa de prevalencia de Enfermedad Colelitiásica (EC) del 20,5%. Con el objetivo de determinar el patrón de consumo alimentario de estas personas y compararlo con las Raciones Dietéticas Recomendadas (RDA) se entrevistaron 44 de dichas personas con EC. Se les realizó una encuesta sobre hábitos alimentarios 5 años previos al diagnóstico, empleando un cuestionario semi-cuantitativo de frecuencia de consumo (FFQ) y un Atlas fotográfico de porciones estandarizadas. Se calcularon los promedios (± desvío estándar) de la edad, del Índice de Masa Corporal (IMC), del consumo de cada nutriente y de la energía total consumida (Kilocalorías). La significación estadística de las diferencias entre sexos se evaluó aplicando pruebas t de student. La edad de las personas estudiadas (18 varones y 26 mujeres) fue 63,8±13,8 años y el IMC fue 28,2±5,8. Consumos promedio diarios: Kcalorias 2941±791,1 ; Carbohidratos 295,3±96,9 g; Proteínas 131,6±36,8 g; Grasa 128,9± 43 g; Ácidos grasos saturados 41,9±18,6 g; Ácidos grasos poliinsaturados 13,8±8,7 g; Colesterol 455,4±186,8 mg; Sodio 2730±1552,1 mg; Potasio 2912,8±1001,4 mg; Calcio 719,3±403,3 mg; Hierro 16±4,6 mg; Fósforo 801,6±320,3 mg; Vitamina A 3121,7±1811,9 mcg; Vitamina B1 0,80±0,30 mg; Vitamina B2 1,9±0,8 mg; Vitamina C 157,6±114,1 mg; Niacina 6,9±2,7 mg; Fibra total 12± 5,3 g; Café 70,7±104,3 cc. Se concluye que el patrón alimentario de las personas con EC se caracterizó por un alto consumo de Grasas, Ácidos grasos saturados y Colesterol, no alcanzando las recomendaciones para Carbohidratos, Calcio, Niacina y Fibra.

Food intake pattern in a sample of adults with Gallbladder Disease (GD). In Rosario, Argentina, a 20,5% prevalence rate of Gallbladder Disease (GD) was found in a random sample of adults. The aim of this study was to determine the food consumption pattern of subjects with GD nested in that sample for further comparison with the Recommended Dietary Allowances (RDA). Forty-four subjects were interviewed about the food consumption during the five years before their diagnosis, by applying a semi-quantitative food frequency questionnaire (FFQ) and a photographic atlas of standardized portions. Age, body mass index (BMI), all consumed nutrients, and total energy intake (kilocalories) were reported as Mean ± standard deviation. Comparisons according to sex (18 males and 26 females) revealed no significant differences in the variables under analysis. Age and BMI in the overall sample were as follows 63.8±13.8 years and 28.2±5.8, respectively. Mean daily consumption of nutrients was as follows: Carbohydrates 295.3±96.9 g , Protein 131.6±36.8 g , Fat 128.9±43 g , Saturated fatty acids 41.9±18,6 g, Polyunsaturated fatty acids 13.8±8.7 g, Cholesterol 455.4±186.8 mg, Sodium 2730±1552.1 mg, Potassium 2912.8±1001.4 mg, Calcium 719.3±403.3 mg, Iron 16±4.6 mg, Phosphorus 801.6±320.3 mg, Vitamin A 3121.7±1811.9 mcg, Vitamin B1 0.80±0.30 mg, Vitamin B2 1.9±0.8 mg, Vitamin C 157.6±114.1 mg, Niacin 6.9±2.7 mg, Fiber 5.3±12 g, Coffee 70.7±104.3 cc (total energy intake 2941±791.1 Kcal). Subjects with GD have a history of higher intake of fat, saturated fatty acids and cholesterol with consumption of carbohydrates, calcium, niacin and fiber below the recommended quantities.

Inmunomodulación y antiangiogénesis en la terapéutica oncológica: De la investigación básica a la clínica / Immunomodulation and antiangiogenesis in cancer therapy: From basic to clinical research

La investigación básica y pre-clínica en oncología celular y molecular son pilares fundamentales en los que se apoyan la mayoría de los adelantos en la terapéutica del cáncer. Los hallazgos obtenidos y su aplicación en la práctica clínica constituyen la causa del avance sostenido en el tratamiento de la enfermedad neoplásica. El objetivo de este trabajo es resumir y discutir los resultados pre-clínicos en inmunomodulación y anti-angiogénesis para el tratamiento de diversos tipos de tumores, obtenidos en nuestro Instituto durante los últimos 15 años, y la posterior traslación y aplicación del conocimiento experimental en un Ensayo Clínico Fase I/II. Se describen los resultados que contribuyeron a descifrar los mecanismos de acción de la inmunomodulación antimetastásica con ciclofosfamida, la quimioterapia metronómica con diferentes drogas únicas o combinaciones, y finalmente el diseño y resultados preliminares de un ensayo clínico de quimioterapia metronómica para pacientes con cáncer de mama avanzado.

Basic and pre-clinic research in cellular and molecular oncology are the main supports accounting for the advancement in cancer therapeutics. The findings achieved, and their implementation in clinical practice are responsible for the permanent improvement in the treatment of the neoplastic disease. Our present objective is to summarize and discuss the pre-clinical findings in immunomodulation and anti-angiogenesis for the treatment of several types of tumors obtained in our Institute during the last 15 years, and the subsequent translation and application of the acquired experimental knowledge in a Phase I/II Clinical Trial. We present the results and mechanisms of action of antimetastatic immunomodulation with cyclophosphamide, the metronomic chemotherapy with different single drugs and their combinations, and finally the design and preliminary results of a clinical trial with metronomic chemotherapy for patients with advanced breast cancer.

[Food intake pattern in a sample of adults with gallbladder disease (GD)]. / Patrón de consumo alimentario en una muestra de adultos con Enfermedad Colelitiasica (EC).

In Rosario, Argentina, a 20,5% prevalence rate of Gallbladder Disease (GD) was found in a random sample of adults. The aim of this study was to determine the food consumption pattern of subjects with GD nested in that sample for further comparison with the Recommended Dietary Allowances (RDA). Forty-four subjects were interviewed about the food consumption during the five years before their diagnosis, by applying a semi-quantitative food frequency questionnaire (FFQ) and a photographic atlas of standardized portions. Age, body mass index (BMI), all consumed nutrients, and total energy intake (kilocalories) were reported as Mean +/- standard deviation. Comparisons according to sex (18 males and 26 females) revealed no significant differences in the variables under analysis. Age and BMI in the overall sample were as follows 63.8 +/- 13.8 years and 28.2 +/- 5.8, respectively. Mean daily consumption of nutrients was as follows: Carbohydrates 295.3 +/- 96.9 g, Protein 131.6 +/- 36.8 g, Fat 128.9 +/- 43 g, Saturated fatty acids 41.9 +/- 18,6 g, Polyunsaturated fatty acids 13.8 +/- 8.7 g, Cholesterol 455.4 +/- 186.8 mg, Sodium 2730 +/- 1552.1 mg, Potassium 2912.8 +/- 1001.4 mg, Calcium 719.3 +/- 403.3 mg, Iron 16 +/- 4.6 mg, Phosphorus 801.6 +/- 320.3 mg, Vitamin A 3121.7 +/- 1811.9 mcg, Vitamin B1 0.80 +/- 0.30 mg, Vitamin B2 1.9 +/- 0.8 mg, Vitamin C 157.6 +/- 114.1 mg, Niacin 6.9 +/- 2.7 mg, Fiber 5.3 +/- 12 g, Coffee 70.7 +/- 104.3 cc (total energy intake 2941 +/- 791.1 Kcal). Subjects with GD have a history of higher intake of fat, saturated fatty acids and cholesterol with consumption of carbohydrates, calcium, niacin and fiber below the recommended quantities.