This review provides a basis for substantiating both kinetically and pathologically the differences between chrysotile and amphibole asbestos. Chrysotile, which is rapidly attacked by the acid environment of the macrophage, falls apart in the lung into short fibers and particles, while the amphibole asbestos persist creating a response to the fibrous structure of this mineral. Inhalation toxicity studies of chrysotile at non-lung overload conditions demonstrate that the long (>20 µm) fibers are rapidly cleared from the lung, are not translocated to the pleural cavity and do not initiate fibrogenic response. In contrast, long amphibole asbestos fibers persist, are quickly (within 7 d) translocated to the pleural cavity and result in interstitial fibrosis and pleural inflammation. Quantitative reviews of epidemiological studies of mineral fibers have determined the potency of chrysotile and amphibole asbestos for causing lung cancer and mesothelioma in relation to fiber type and have also differentiated between these two minerals. These studies have been reviewed in light of the frequent use of amphibole asbestos. As with other respirable particulates, there is evidence that heavy and prolonged exposure to chrysotile can produce lung cancer. The importance of the present and other similar reviews is that the studies they report show that low exposures to chrysotile do not present a detectable risk to health. Since total dose over time decides the likelihood of disease occurrence and progression, they also suggest that the risk of an adverse outcome may be low with even high exposures experienced over a short duration.

Tuberculosis is a disease caused by a bacteria named Mycobacterium tuberculosis (M. tb). It is estimated by World Health Organization (WHO) that nearly a quarter of the world's population is infected. Tuberculoma of the brain is one of the most severe extrapulmonary forms that affects patients younger than 40 years of age. Brain parenchymal tuberculoma develops in nearly one of 300 non-treated cases of pulmonary tuberculosis cases. In endemic regions, tuberculomas account for as many as 50% of all intracranial masses. Tuberculoma results in a hematogenous spread of M. tb from an extracranial source. Tuberculomas can mimic a variety of diseases and can present themselves in a subacute or chronic course, from asymptomatic to severe intracranial hypertension. Diagnosis is based on computed tomography (CT) scan and magnetic resonance imaging (MRI) studies with a similar ring-enhancing lesion. Treatment is primarily medical, and the duration for brain tuberculoma can vary from six to 36 months. In certain cases, surgery is recommended.

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BackgroundMost of the knowledge about the mechanisms of multidrug resistance in lung cancer has been achieved through the use of cell lines isolated from tumours cultivated either in suspensions of isolated cells or in monolayers and following exposition to different cytostatic agents. However, tumour cell lines growing as multicellular tumour spheroids (MTS) frequently develop multicellular resistance in a drug-independent form. The aim of this study was to characterize the phenotypic and functional differences between two human NSCLC cell lines (INER-37 and INER-51) grown as traditional monolayer cultures versus as MTS.MethodsAfter 72 hours treatment with anticancer drugs, chemosensitivity in monolayers and tumour spheroids cultures was assessed using MTT assay. Reverse transcription-polymerase chain reaction was employed to detect the mRNAs of multidrug resistance-related genes. The expression of P-gp was analyzed by immunohistochemical staining and cell cycle profiles were analyzed using FACS.ResultsThe results indicate that when grown as MTS each lung cancer cell line had different morphologies as well as and abrogation of cell proliferation with decrease of the G2/M phase. Also, MTS acquired multicellular resistance to several chemotherapeutic agents in only a few days of culture which were accomplished by significant changes in the expression of MDR-related genes.ConclusionOverall, the MTS culture changed the cellular response to drugs nevertheless each of the cell lines studied seems to implement different mechanisms to acquire multicellular resistance.

Worldwide, lung cancer remains the most common cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for 85% of all diagnosed lung cancer cases. Chemotherapy is considered the standard of care for patients with advanced NSCLC; however, the tumors can develop mechanisms that inactivate these drugs. Comparative genomic analyses have revealed that disruptions in the kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid-2-related factor-2 (Nrf2) pathway are frequent in NSCLC, although Nrf2 mutations occur less frequently than Keap1 mutations. As the Keap1-Nrf2 pathway appears to be a primary regulator of key cellular processes that aid to resist the action of chemotherapy drugs, the clinical implementation of Nrf2 inhibitors in patients with advanced NSCLC may be a useful therapeutic approach for patients harboring KEAP1-NRF2 mutations. The aim of the present review was to highlight findings of how constitutive Nrf2 activation may be a specific biomarker for predicting patients most likely to benefit from classical chemotherapy drugs, overall improving patient survival rate. Contents 1. Introduction 2. Keap1-Nrf2 pathway 3. Mechanisms of Keap1-Nrf2 pathway deregulation 4. Keap1-Nrf2 pathway disruption and prognosis 5. Co-occurring aberrations 6. Crosstalk between the Keap1-Nrf2 and EGFR pathways 7. Drug resistance and clinical implications 8. Future directions and conclusions