Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data

Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.

Three cases of extrapulmonary small cell carcinoma occurring in the prostate, stomach, and pancreas.

Small cell carcinomas are fairly common neoplasms in the lung, but tumors featuring similar histological profiles may occur in extrapulmonary organs. Three cases of small cell carcinomas occurring in the prostate (case 1), stomach (case 2), and pancreas (case 3) are presented. Production of hormones was demonstrated immunohistochemically in all cases. In case 2 alpha-fetoprotein (AFP) was elevated in the serum and observed immunohistochemically in tumor cells. Production of AFP is a distinctive feature, which has not been reported in the pulmonary and extrapulmonary cases of small cell carcinoma. Amplification and/or expression of myc gene family have been suggested to be related to the prognosis of pulmonary small cell carcinoma. Amplification of myc genes was not detected in any of our cases, but c-myc protein was demonstrated immunohistochemically in tumor cells of case 1.

Serological studies on schistosomiasis mansoni in the northeast Brazil. I

Soros de pacientes com esquistosomiase mansonica do Hospital das Clinicas da Universidade Federal de Pernambuco (N = 10), de residentes da cidade do Cabo (PE) - 51 casos ovo-positivo e 452 casos ovo-negativo -, de pacientes do Hospital Instituto Materno Infantil de Pernambuco (IMIP) (N = 37), de imigrantes japoneses residentes na cidade de Petrolina (PE) (N = 127), assim como de japoneses supostamente saudaveis (N = 30) foram examinados sorologicamente atraves de testes como ELISA; os antigenos utilizados foram preparados a partir de ovos (ELISA-ovo) e de vermes adultos de Schistosoma mansoni (ELISA-adulto). Em 100 por cento dos soros de individuos nao infectados residentes em areas nao endemicas, tanto na ELISA-ovo como na ELISA-adulto os resultados foram negativos. No tocante a reacoes cruzadas, em 78 soros provenientes de individuos portadores de diferentes parasitas intestinais, apenas um apresentou reatividade frente aos antigenos de vermes adultos e ovos. O ELISA-ovo realizado com o soro de 51 individuos portadores de ovos de S. mansoni revelou uma alta sensibilidade (98 por cento de casos ovo-positivos); contudo grande numero de resultados falso-negativos foi observado em reacoes como ELISA-adulto, Ouchterlony usando antigeno de verme adulto, reacao periovular e intradermo-reacao. Em casos de jovens portadores

Health status of Indochinese refugees in Japan: statistical analyses on anemia, eosinophilia and serum alkaline phosphatase.

Detailed statistical analyses were attempted on anemia, eosinophilia and elevation in serum alkaline phosphatase in the Indochinese refugees in Japan. A high statistical correlation was found between hemoglobin concentration and hematocrit for most of the refugees except the Cambodian females. Refugees with parasitic infections, particularly hookworm infection had significantly lower values for hemoglobin concentration and hematocrit. Significant eosinophilia was observed in the refugees infected with hookworms, Strongyloides stercoralis, Rhabditis sp., Endolimax nana and/or Hymenolepis nana. However, these parasites were found in the same subpopulations more frequently than expected by chance. Elevation in serum alkaline phosphatase was observed in young Cambodian immigrants. Analyses showed that the variations of this enzyme could be well predictable by those of enzymes such as serum glutamic oxaloacetic transaminase, which are good markers for liver functions, in Cambodian immigrants, 13-24 of age, whereas no such correlation was observed in non-Cambodians of the same age group.