The flow cytometric detection of minimal residual disease (MRD) in precursor-B-acute lymphoblastic leukemias (precursor-B-ALL) mainly relies on the identification of minor leukemic cell populations that can be discriminated from their normal counterparts on the basis of phenotypic aberrancies observed at diagnosis. This technique is not very complex, but discordancies are frequently observed between laboratories, due to the lack of standardized methodological procedures and technical conditions. To develop standardized flow cytometric techniques for MRD detection, a European BIOMED-1 Concerted Action was initiated with the participation of laboratories from six different countries. The goal of this concerted action was to define aberrant phenotypic profiles in a series of 264 consecutive de novo precursor-B-ALL cases, systematically studied with one to five triple-labelings (TdT/CD10/CD19, CD10/CD20/CD19, CD34/CD38/CD19, CD34/CD22/CD19 and CD19/CD34/CD45) using common flow cytometric protocols in all participating laboratories. The use of four or five triple-stainings allowed the identification of aberrant phenotypes in virtually all cases tested (127 out of 130, 98%). These phenotypic aberrancies could be identified in at least two and often three triple-labelings per case. When the analysis was based on two or three triple-stainings, lower incidences of aberrancies were identified (75% and 81% of cases, respectively) that could be detected in one and sometimes two triple-stainings per case. The most informative triple staining was the TdT/CD10/CD19 combination, which enabled the identification of aberrancies in 78% of cases. The frequencies of phenotypic aberrations detected with the other four triple-stainings were 64% for CD10/CD20/CD19, 56% for CD34/CD38/CD19, 46% for CD34/CD22/CD19, and 22% for CD19/CD34/CD45. In addition, cross-lineage antigen expression was detected in 45% of cases, mainly coexpression of the myeloid antigens CD13 and/or CD33 (40%). Parallel flow cytometric studies in different laboratories finally resulted in highly concordant results (Ͼ90%) for all five antibody combinations, indicating the high reproducibility of our approach. In conclusion, the technique presented here with triple-labelings forms an excellent basis for standardized flow cytometric MRD studies in multicenter international treatment protocols for precursor-B-ALL patients. Leukemia (2001Leukemia ( ) 15, 1185Leukemia ( -1192

Introduction: Immune complex (IC) deposition in renal tissue is considered as a possible tumor marker. This raised the hypothesis that some tumor markers might be related to the patient prognosis, with emphasis in the possibility to detect them in tissue sample, not only in blood. We report a patient with membranous glomerulonephritis (MGN) and tumoral IC deposition that were detected previous to the diagnosis of melanoma. Case report: A 55-year-old male was admitted to our department with symptoms of renal disease; a kidney biopsy was performed and the diagnosis was phase II MGN. A few months later he returned to the hospital with ascites, dyspnea, anorexia, and macular erythematous skin lesions in the body. A new urinalysis showed proteinuria, hematuria, and leukocyturia; the chest X-ray showed a lung nodule; and a brain CT scan revealed a frontal nodular lesion, suggesting metastasis. The brain biopsy suggested the diagnosis of metastatic melanoma and a posterior kidney immunohistochemistry study with S-100 and HMB-45 antibodies showed glomerular and tubular positivity for these markers. Conclusions: MGN and deposition of tumoral IC as a first manifestation of melanoma has not been previously reported. This case reinforces the importance of a clinical evolution focused on the diagnosis of a hidden cancer in patients with MGN. Oncologists should also be aware of the potential occurrence of glomerular lesion in their patients and that could be important during tumor therapy.

To explore the effectiveness and possible toxicity of the use of epidermal growth factor receptor inhibitor (EGFR Inhibitor), Celecoxib (COX2 inhibitor) and Sirolimus (m-TOR inhibitor) as single agents and drug combinations for the treatment of lung cancer in an experimental model. Lung cancer was induced in Balb-C mice by intraperitoneal injection urethane. Mice were treated with water (control) , Erlotinib (E) (50 mg/kg), Celecoxib (X) (50 mg/kg), Sirolimus (R) (2 mg/kg) given alone and in the following doublet and triplet combinations in the same dosages for 7 days. The number of pulmonary nodules in the combined treatment was significantly inhibited compared with control (p=0.010); E (p=0.028), EX (p=0.010), ERX (p=0.040) showed a smaller number of statistically significant nodules. Regarding coat changes we observe statistically significant differences among groups (p less than 0.001) where ERX and ER had a higher occurrence of this change. There was a higher incidence of skin rashes in groups: E (p less than 0.001), ER (p less than 0.0001), and ERX (p less than 0.001). Regarding weight we identify weight loss in the ERX (p=0.025). The combination of EGFR inhibitor, COX-2 inhibitor and m-TOR inhibitor had anti-tumor activity in experimental lung cancer. The combination of Celecoxib treatment with Erlotinib is a suggestion for decrease of dermatological events in patients. The combination of EGFR inhibitor and Sirolimus does not decrease the number of lung nodules and potentiates adverse events.

Este artigo está publicado em acesso aberto (Open Access) sob a licença Creative Commons, que permite uso, distribuição e reprodução em qualquer meio, sem restrições, desde que o trabalho seja corretamente citado. Ações de prevenção primária e secundária relacionadas aos fatores de risco para osteoporose Primary and secondary prevention actions related to risk factors for osteoporosis Acciones de prevención primaria y secundaria relacionadas con los factores de riesgo para osteoporosis

Background: Membranous glomerulonephritis (MGN) can be found in patients with cancer as a paraneoplastic syndrome or it could be manifested clinically before tumor detection. The aim of this study was to evaluate the frequency and type of renal histopathological alterations in patients with malignancy that died without cancer treatment and were submitted to necropsy. Methods: Patient's demographical and clinical data collection and laboratory tests (serum creatinine and urine sample) were evaluated. Results: Kidney fragments from 21 patients were obtained and studied by light microscopy after habitual staining. Immunohistochemistry studies were performed with monoclonal immunoglobulin and tumor markers. Patients' mean age was 71 years and 62% were male. The most frequent tumor was gastric cancer (five cases), followed by colon and oral cavity (three cases each). In 67% of the cases, malignancy was the main cause of death. Serum creatinine was increased in 10 cases, proteinuria in 15, and hematuria was present in 8 cases. The most usual glomerular lesion found was thickening of basement membrane (BM) of the capillary loops. There were two cases of IgA nephropathy, three cases of focal segmental glomerulosclerosis, and one case of MGN. Only in the patient with MGN and metastatic melanoma specific tumor markers were identified in the kidney. Conclusions: We observed a wide range of glomerular pathological changes and abnormal urinary sediments in almost all patients, but we found tumor marker deposits only in the patient with MGN.