Diego Carlos dos Reis

Combination therapy with carboplatin and thalidomide suppresses tumor growth and metastasis in 4T1 murine breast cancer model.

Carboplatin, efficient cytostatics for cancer therapy, could induce apoptosis and inhibit the growth of vascular endothelium in several tumor cell lines and xenograft models. It has been suggested that the antitumor effect of chemotherapy could be increased by combining it with an antiangiogenesis agent in anticancer strategy. The present study explored the potential to increase the antitumor effect of carboplatin by combining it with thalidomide in mouse 4T1 breast cancer models, and the underlining mechanism was investigated. The systemic administration of carboplatin and thalidomide significantly decreased tumor growth through increased tumor cell apoptosis compared with either control group. Collectively, these findings suggest that combined treatment has shown synergistic suppression in tumor progression according to the analysis. Furthermore, also was observed reduction in number of lung metastases as compared to isolated treatments and increased survival of the animals. The present study may be important in future exploration of the potential application of the combined approach in the treatment of breast cancer.

Evaluation of 99mTc-HYNIC-βAla-Bombesin(7-14) as an agent for pancreas tumor detection in mice

Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr), including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP) may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using 99mTc-HYNIC-βAla-Bombesin(7-14) as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control), and the tumor-to-muscle ratio indicated that 99mTc-HYNIC-βAla-Bombesin(7-14) uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that 99mTc-HYNIC-βAla-Bombesin(7-14) may be useful for the detection of pancreatic adenocarcinoma.

Thalidomide promotes leukocytosis in mice inoculated with 4T1 mammary carcinoma

The aim of this study was to evaluate the therapy effect of thalidomide in the 4T1 murine mammary carcinoma. 4T1 cell suspension was injected into the posterior left flank of all animals to obtain solid tumors. Five days after inoculation, the treatment group was orally administered 150 mg/kg of thalidomide for seven days. Tumors were measured every 48 hours until the end of treatment. Whole blood was collected for hematology analysis. Our results suggest that thalidomide therapy increase the number of circulating leukocytes in the 4T1 murine mammary carcinoma, and this response is accompanied by a decrease in tumor growth.

Intestinal toxicity evaluation of long-circulating and pH-sensitive liposomes loaded with cisplatin

Abstract Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significant intestinal epithelium alterations in an experimental model. Our research group has proposed that the incorporation of CDDP into long‐circulating and pH‐sensitive liposomes (SpHL‐CDDP) could help to overcome some side effects induced by this drug. Thus, we evaluated signs of intestinal toxicity 24 h and 72 h after the administration of a single i.p dose of free CDDP or SpHL‐CDDP to healthy Swiss mice. Twenty‐four hours after administration of free CDDP, the mice showed signs of intestinal toxicity, principally weight loss, increased intestinal permeability associated with a decrease in expression of tight junctions, and histological damage with the presence of inflammatory infiltrates and activation of ERK1/2 and NF‐&kgr;B. These changes persisted after 72 h. While signs of intestinal toxicity were also observed 24 h after administration of SpHL‐CDDP, after 72 h body weight and intestinal permeability of mice in this group were similar to those of mice in the control group. In comparison with the free CDDP treatment group, 72 h after treatment mice in the SpHL‐CDDP group showed better histological parameters, lower levels of inflammatory infiltrate with increased IL‐10 and IgA levels, and less activation of caspase‐3, ERK1/2 and NF‐&kgr;B. These differences could account for the recovery of the intestinal epithelium observed in mice treated with SpHL‐CDDP but not in mice treated with free CDDP. In conclusion, here we show that encapsulation of CDDP in SpHL lessens intestinal damage and that, as such, SpHL‐CDDP is a promising candidate for clinical use. Graphical abstract Figure. No Caption available.

Evaluation of the improvement of quality of life with Azithromycin in the treatment of eosinophilic nasal polyposis

INTRODUCTION The Sino-Nasal Outcome Test 22 (SNOT-22) is an important tool in assessing the quality of life (QoL) of patients with chronic rhinosinusitis with a validated version in Brazil. The eosinophilic nasal polyposis (ENP) represents most of the cases of nasal polyposis (85-90%) and belongs to the group of chronic rhinosinusitis. It is a chronic inflammatory disease that impacts the QoL of patients, not only causing localized symptoms, but also resulting in a general malaise. The standard treatments (corticosteroids and nasal endoscopic surgery) lead to partial control of symptoms, but relapses are frequent. Macrolide acting as an immunomodulator is a promising tool for more effective control of this disease. Studies are still lacking to assess the real impact on the QoL in patients treated with macrolides. OBJECTIVE To evaluate the improvement of QL, evaluated using SNOT-22, in patients with PNSE treated with immunomodulatory dose azithromycin. METHODS This is a paired experimental study in patients with ENP. Comparison of pre-treatment and post-treatment with azithromycin was performed. Patients completed the SNOT-22 questionnaire before the start of treatment and returned for evaluation after eight weeks of treatment. Azithromycin was prescribed at a dose of 500 mg, orally, three times a week, for 8 weeks. RESULTS SNOT-22 score decreased 20.3 points on average. There was a significant decrease in the SNOT-22 (difference greater than 14 points) in 19 patients (57.6%). There was no significant difference in improvement in SNOT in subgroups with or without asthma/aspirin intolerance. CONCLUSION Azithromycin resulted in significant improvement of QoL, assessed by SNOT-22, in the studied population.

Conjugated linoleic acid prevents damage caused by intestinal mucositis induced by 5-fluorouracil in an experimental model

BACKGROUND Studies have showed the protective effects of conjugated linoleic acid (CLA) on intestinal epithelium, modulating host immune and inflammatory responses on intestinal diseases. OBJECTIVE To evaluate the preventive effects of CLA on the intestinal mucositis induced by 5-FU in a murine model. METHODS Sixty-four BALB/c mice were randomly divided into four groups: Control (CTL), fed a standard chow diet; CLAs, fed a diet supplemented with CLA; Mucositis (5-FU), fed a standard chow diet and underwent mucositis induction and CLAs 5-FU, fed a diet supplemented with CLA and underwent mucositis induction. Mucositis was induced by intraperitoneal injection of 300 mg/kg 5-FU. After 72 h, the animals were euthanized and intestinal permeability, bacterial translocation, inflammatory mediators, and intestinal histology were evaluated. RESULTS Mice in the CLAs 5-FU group showed reduced weight loss compared to those in the 5-FU group (p < 0.005). Furthermore, the results also showed that the treatment with CLA reduced intestinal permeability, bacterial translocation, and biomarkers of inflammatory response besides minor damage to ZO-1 and occludin with maintenance of the integrity of the intestinal epithelium and a favorable balance between the inflammatory and regulatory cytokines. CONCLUSION This study suggests that CLA reduced the adverse effects from 5-FU administration on the intestinal mucosa.

Azithromycin for the treatment of eosinophilic nasal polyposis: Clinical and histologic analysis

Introduction Macrolides used as immunomodulators are a promising tool for chronic inflammatory airway diseases. Eosinophilic nasal polyposis (ENP) is still considered a disease that is difficult to control with the currently standardized treatments. Objectives To evaluate prolonged treatment with low-dose azithromycin for ENP based on clinical and histopathologic variables. Methods The present investigation was a self-paired case study of 33 patients with ENP. A comparison was performed between patients before and after treatment with azithromycin for 8 weeks. The patients were subjected to clinical examinations, staging (three-dimensional imaging by endoscopy), application of the questionnaire, and biopsy of nasal polyps at the beginning and at the end of the treatment. Results The treatment yielded a clinical improvement regarding the two variables studied: polyposis staging (69.7%) and questionnaire (57.6%). We did not find significant differences in the inflammatory pattern and in the percentage or absolute number of eosinophils per field between samples obtained before and after the treatment (p > 0.05). There was no difference between the answers obtained from groups with and without asthma and/or aspirin intolerance (p > 0.3). The patients with advanced initial staging exhibited lower subjective improvement index and staging reduction (p = 0.031 and p = 0.012, respectively). Conclusion Based on this study, azithromycin may be considered as another therapeutic option for ENP. However, further studies are necessary to define the real mechanism of action involved.

Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

O cetoprofeno e uma droga anti-inflamatoria nao esteroidal (NSAID), que exerce efeito anti-inflamatorio, antiproliferativo e antitumoral em condicoes neoplasicas e nao neoplasicas. Foram investigados os efeitos desse composto sobre o desenvolvimento tumoral de camundongos Swiss previamente inoculados com celulas do tumor de Ehrlich. Para realizacao deste estudo, o tumor solido foi obtido a partir de celulas do fluido ascitico do tumor de Ehrlich suspendido em solucao salina fisiologica para se obter 2,5x106 de celulas em 0,05mL. Apos a inoculacao do tumor, os animais foram separados em dois grupos (n = 10). Os animais do grupo tratado receberam cetoprofeno 0,1μg/100μL/animal por via intraperitoneal, em intervalos de 24 horas durante 10 dias consecutivos, e o controle 100µL de solucao salina. No final do experimento, os animais foram sacrificados, e o tumor removido. Foram analisados o crescimento do tumor e as caracteristicas histomorfologicas e imunoistoquimicas para CDC47 (marcador de proliferacao celular) e para CD31 (marcador de vasos sanguineos). Os animais tratados com o cetoprofeno 0,1μg/100μL/animal apresentaram menor crescimento do tumor. O tratamento nao influenciou significativamente o tamanho das areas de neoplasia, inflamacao, necrose e hemorragia. Em contraste, uma menor taxa de proliferacao das celulas neoplasicas foi observada nos animais tratados com cetoprofeno em comparacao com o grupo controle. A participacao do cetoprofeno em controlar a proliferacao de celulas neoplasicas abre perspectivas para sua utilizacao em terapia clinica antineoplasica.

Incapacitating pollakiuria affecting daily life. A case report of tuberculosis of the bladder. Tuberculosis remains on the list of the differential diagnoses for most diseases

Tuberculosis (TB) is among the most serious human health concerns and is associated with poverty, limited availability of health care services and bad management, all of which negatively affect the possibility of reducing socially-determined diseases, such as HIV/AIDS epidemics and multidrug resistant M. tuberculosis. Extrapulmonary involvement occurs in 15% of TB cases and can develop with the same overall symptomatology of exclusively pulmonary involvement, with smaller variations depending on location and severity. This report presents a patient with hematuria and pollakiuria with incapacitating effects on social life, initially thought of as a malignancy and later identified as genitourinary TB. Diagnosis was based on histopathology of clinical specimens from the bladder. Time elapsed between onset and diagnosis led to considerable sequelae. This report aims at raising awareness of TB as a permanent concern in Brazil and of the need to always considered it as a differential diagnosis of pulmonary or extrapulmonary disease.