Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC

Moderate pathogenic effect of Ligophorus uruguayense (Monogenoidea, Ancyrocephalidae) in juvenile mullet Mugil liza (Actinopterygii, Mugilidae) from Brazil

ABSTRACT Monogenoidea pathogenic activity can elicit various histological responses in fish. Species of Ligophorus are specific parasites of mullets, and its relationship with host fish may result in a moderate pathogenic action. In order to ascertain this relationship, estuarine mullets (Mugil liza) were collected in an estuary, reared in laboratory, for three weeks, and forwarded for histological and parasitological analyses. Ligophorus uruguayense (Monogenoidea) infestation in the gills of the mullets was identified. The severe infestation by only one species of Monogenoidea may result from the specificity of these parasites to mullets. Mullets submitted to histological analysis exhibited respiratory epithelium detachment; mild, moderate and severe hyperplasia of the respiratory epithelium; atrophy; and telangiectasia of the gills. This is the first study reporting that mullets highly infested by Monogenoidea can show mild (100%) to severe (20%) gill changes with a distinct frequency of occurrence. Because of the high prevalence of mild alterations observed, it is possible to accept that L. uruguayense is moderately pathogenic to M. liza, even during high prevalence and intensity of infestation, as a result of its specificity

Human Occupancy as a Source of Indoor Airborne Bacteria

Exposure to specific airborne bacteria indoors is linked to infectious and noninfectious adverse health outcomes. However, the sources and origins of bacteria suspended in indoor air are not well understood. This study presents evidence for elevated concentrations of indoor airborne bacteria due to human occupancy, and investigates the sources of these bacteria. Samples were collected in a university classroom while occupied and when vacant. The total particle mass concentration, bacterial genome concentration, and bacterial phylogenetic populations were characterized in indoor, outdoor, and ventilation duct supply air, as well as in the dust of ventilation system filters and in floor dust. Occupancy increased the total aerosol mass and bacterial genome concentration in indoor air PM10 and PM2.5 size fractions, with an increase of nearly two orders of magnitude in airborne bacterial genome concentration in PM10. On a per mass basis, floor dust was enriched in bacterial genomes compared to airborne particles. Quantitative comparisons between bacterial populations in indoor air and potential sources suggest that resuspended floor dust is an important contributor to bacterial aerosol populations during occupancy. Experiments that controlled for resuspension from the floor implies that direct human shedding may also significantly impact the concentration of indoor airborne particles. The high content of bacteria specific to the skin, nostrils, and hair of humans found in indoor air and in floor dust indicates that floors are an important reservoir of human-associated bacteria, and that the direct particle shedding of desquamated skin cells and their subsequent resuspension strongly influenced the airborne bacteria population structure in this human-occupied environment. Inhalation exposure to microbes shed by other current or previous human occupants may occur in communal indoor environments

Trends in healthy life expectancy in Hong Kong SAR 1996–2008

Although Hong Kong has one of the best life expectancy (LE) records in the world, second only to Japan for women, we know very little about the changes in the health status of the older adult population. Our article aims to provide a better understanding of trends in both chronic morbidity and disability for older men and women. The authors compute chronic morbidity-free and disability-free life expectancy and the proportion of both in relation to total LE using the Sullivan method to examine whether Hong Kong older adults are experiencing a compression of morbidity and disability and whether there is any gender difference in relation to mortality and morbidity. The results of this study show that Hong Kong women tend to outlive Hong Kong men but are also more likely to suffer from a ‘double disadvantage’, namely more years of life with more chronic morbidity and disability. There has also been a significant expansion of chronic morbidity, as chronic morbidity-free life expectancy (CMFLE) decreased substantially for both genders from 1996 to 2008. Although disability-free life expectancy (DFLE) increased during this period, it increased at a slower pace compared to LE. The proportion of life without chronic morbidity also declined remarkably during these 12 years. Among the advanced ages, the proportion of remaining life in good health without disability has decreased since 1996, indicating a relative expansion of disability

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Demographic, clinical, and pathological features of early onset pancreatic cancer patients.

BACKGROUND: Early onset pancreatic cancer (EOPC), i.e. pancreatic ductal adenocarcinoma (PDAC) occurring in patients below 50 years of age, is rare and there is limited information regarding risk factors, molecular basis and outcome. This study aimed to determine the demographic and clinicopathological features and survival figures for EOPC. METHODS: A retrospective analysis of patients treated at the Royal London Hospital for PDAC between September 2004 and September 2015 was performed. Data on demographics, risk factors, presentation, pathological features, treatment and survival outcome were compared in EOPC and older PDAC patients. RESULTS: Of 369 PDAC cases identified, 35 (9.5%) were EOPC. Compared to older patients, EOPC patients were more frequently male (71% vs 54%, p = 0.043) and less commonly of British origin (37% vs 70%, p = 0.002). There was no significant difference regarding the prevalence of any of the risk factors known to be associated with older PDAC patients. Fewer EOPC patients presented with resectable disease (23% vs 44%, p = 0.015) and more received adjuvant chemo/radiotherapy (60% vs 46%, p = 0.008). The overall median survival and stage specific survival did not differ significantly between the two groups, although a longer survival for localized disease was seen in EOPC patients (25 months (12.9-37, 95%CI) vs 13 months (10.5-15.5 95%CI) for older PDAC patients). CONCLUSIONS: The EOPC patients had different demographics and were more likely than their older PDAC counterparts to be male. Typically they presented with more advanced disease, received more aggressive treatment, and had on overall similar survival outcome