The Effects of Copper Pollution on Fouling Assemblage Diversity: A Tropical-Temperate Comparison

BACKGROUND: The invasion of habitats by non-indigenous species (NIS) occurs at a global scale and can generate significant ecological, evolutionary, economic and social consequences. Estuarine and coastal ecosystems are particularly vulnerable to pollution from numerous sources due to years of human-induced degradation and shipping. Pollution is considered as a class of disturbance with anthropogenic roots and recent studies have concluded that high frequencies of disturbance may facilitate invasions by increasing the availability of resources. METHODOLOGY/PRINCIPAL FINDINGS: To examine the effects of heavy metal pollution as disturbance in shaping patterns of exotic versus native diversity in marine fouling communities we exposed fouling communities to different concentrations of copper in one temperate (Virginia) and one tropical (Panama) region. Diversity was categorized as total, native and non-indigenous and we also incorporated taxonomic and functional richness. Our findings indicate that total fouling diversity decreased with increasing copper pollution, whether taxonomic or functional diversity is considered. Both native and non-indigenous richness decreased with increasing copper concentrations at the tropical site whereas at the temperate site, non-indigenous richness was too low to detect any effect. CONCLUSIONS/SIGNIFICANCE: Non-indigenous richness decreased with increasing metal concentrations, contradicting previous investigations that evaluate the influence of heavy metal pollution on diversity and invasibility of fouling assemblages. These results provide first insights on how the invasive species pool in a certain region may play a key role in the disturbance vs. non-indigenous diversity relationship

ZNF93 Increases Resistance to ET-743 (Trabectedin; Yondelis®) and PM00104 (Zalypsis®) in Human Cancer Cell Lines

ET-743 (trabectedin, Yondelis) and PM00104 (Zalypsis) are marine derived compounds that have antitumor activity. ET-743 and PM00104 exposure over sustained periods of treatment will result in the development of drug resistance, but the mechanisms which lead to resistance are not yet understood.Human chondrosarcoma cell lines resistant to ET-743 (CS-1/ER) or PM00104 (CS-1/PR) were established in this study. The CS-1/ER and CS-1/PR exhibited cross resistance to cisplatin and methotrexate but not to doxorubicin. Human Affymetrix Gene Chip arrays were used to examine relative gene expression in these cell lines. We found that a large number of genes have altered expression levels in CS-1/ER and CS-1/PR when compared to the parental cell line. 595 CS-1/ER and 498 CS-1/PR genes were identified as overexpressing; 856 CS-1/ER and 874 CS-1/PR transcripts were identified as underexpressing. Three zinc finger protein (ZNF) genes were on the top 10 overexpressed genes list. These genes have not been previously associated with drug resistance in tumor cells. Differential expressions of ZNF93 and ZNF43 genes were confirmed in both CS-1/ER and CS-1/PR resistant cell lines by real-time RT-PCR. ZNF93 was overexpressed in two ET-743 resistant Ewing sarcoma cell lines as well as in a cisplatin resistant ovarian cancer cell line, but was not overexpressed in paclitaxel resistant cell lines. ZNF93 knockdown by siRNA in CS-1/ER and CS-1/PR caused increased sensitivity for ET-743, PM00104, and cisplatin. Furthermore, ZNF93 transfected CS-1 cells are relatively resistant to ET-743, PM00104 and cisplatin.This study suggests that zinc finger proteins, and ZNF93 in particular, are involved in resistance to ET-743 and PM00104

Current role of surgery in small cell lung carcinoma

Small cell lung carcinoma represents 15–20% of lung cancer. Is is characterized by rapid growth and early disseminated disease with poor outcome. For many years surgery was considered a contraindication in Small Cell Lung Cancer (SCLC) since radiotherapy and chemoradiotherapy were found to be more efficient in the management of these patients. Never the less some surgeons continue to be in favor of surgery as part of a combined modality treatment in patients with SCLC. The revaluation of the role of surgery in this group of patients is based on clinical data indicating a much better prognosis in selected patients with limited disease (T1-2, N0, M0), the high rate of local recurrence after chemoradiotherapy with surgery considered eventually more efficient in the local control of the disease and the fact that surgery is the most accurate tool to access the response to chemotherapy, identify carcinoids misdiagnosed as SCLC and treat the Non Small Cell Lung Cancer component of mixed tumors. Performing surgery for local disease SCLC requires a complete preoperative assessment to exclude the presence of nodal involvement. In stage I surgery must always be followed by adjuvant chemotherapy, while in stage II and III surgery must be planned only in the context of clinical trials and after a pathologic response to induction chemoradiotherapy has been confirmed. Prophylactic cranial irradiation should be used to reduce the incidence of brain metastasi

Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chondrosarcoma is well-known to be primarily resistant to conventional radiation and chemotherapy.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old Caucasian man with clear cell chondrosarcoma who presented with symptomatic recurrence in his pelvis and metastases to his skull and lungs. Our patient underwent systemic therapy with sunitinib and then consolidation with proton beam radiation to his symptomatic site. He achieved complete symptomatic relief with a significantly improved performance status and had an almost complete and durable metabolic response on fluorine-18-fluorodeoxyglucose positron emission tomography.</p> <p>Conclusions</p> <p>Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.</p

Expression-Based In Silico Screening of Candidate Therapeutic Compounds for Lung Adenocarcinoma

BACKGROUND:Lung adenocarcinom (AC) is the most common form of lung cancer. Currently, the number of medical options to deal with lung cancer is very limited. In this study, we aimed to investigate potential therapeutic compounds for lung adenocarcinoma based on integrative analysis. METHODOLOGY/PRINCIPAL FINDINGS:The candidate therapeutic compounds were identified in a two-step process. First, a meta-analysis of two published microarray data was conducted to obtain a list of 343 differentially expressed genes specific to lung AC. In the next step, expression profiles of these genes were used to query the Connectivity-Map (C-MAP) database to identify a list of compounds whose treatment reverse expression direction in various cancer cells. Several compounds in the categories of HSP90 inhibitor, HDAC inhibitor, PPAR agonist, PI3K inhibitor, passed our screening to be the leading candidates. On top of the list, three HSP90 inhibitors, i.e. 17-AAG (also known as tanespimycin), monorden, and alvespimycin, showed significant negative enrichment scores. Cytotoxicity as well as effects on cell cycle regulation and apoptosis were evaluated experimentally in lung adenocarcinoma cell line (A549 or GLC-82) with or without treatment with 17-AAG. In vitro study demonstrated that 17-AAG alone or in combination with cisplatin (DDP) can significantly inhibit lung adenocarcinoma cell growth by inducing cell cycle arrest and apoptosis. CONCLUSIONS/SIGNIFICANCE:We have used an in silico screening to identify compounds for treating lung cancer. One such compound 17-AAG demonstrated its anti-lung AC activity by inhibiting cell growth and promoting apoptosis and cell cycle arrest

An integrative approach to identifying cancer chemoresistance-associated pathways

<p>Abstract</p> <p>Background</p> <p>Resistance to chemotherapy severely limits the effectiveness of chemotherapy drugs in treating cancer. Still, the mechanisms and critical pathways that contribute to chemotherapy resistance are relatively unknown. This study elucidates the chemoresistance-associated pathways retrieved from the integrated biological interaction networks and identifies signature genes relevant for chemotherapy resistance.</p> <p>Methods</p> <p>An integrated network was constructed by collecting multiple metabolic interactions from public databases and the k-shortest path algorithm was implemented to identify chemoresistant related pathways. The identified pathways were then scored using differential expression values from microarray data in chemosensitive and chemoresistant ovarian and lung cancers. Finally, another pathway database, Reactome, was used to evaluate the significance of genes within each filtered pathway based on topological characteristics.</p> <p>Results</p> <p>By this method, we discovered pathways specific to chemoresistance. Many of these pathways were consistent with or supported by known involvement in chemotherapy. Experimental results also indicated that integration of pathway structure information with gene differential expression analysis can identify dissimilar modes of gene reactions between chemosensitivity and chemoresistance. Several identified pathways can increase the development of chemotherapeutic resistance and the predicted signature genes are involved in drug resistant during chemotherapy. In particular, we observed that some genes were key factors for joining two or more metabolic pathways and passing down signals, which may be potential key targets for treatment.</p> <p>Conclusions</p> <p>This study is expected to identify targets for chemoresistant issues and highlights the interconnectivity of chemoresistant mechanisms. The experimental results not only offer insights into the mode of biological action of drug resistance but also provide information on potential key targets (new biological hypothesis) for further drug-development efforts.</p

Health status of the advanced elderly in six european countries: results from a representative survey using EQ-5D and SF-12

<p>Abstract</p> <p>Background</p> <p>Due to demographic change, the advanced elderly represent the fastest growing population group in Europe. Health problems tend to be frequent and increasing with age within this cohort.</p> <p>Aims of the study</p> <p>To describe and compare health status of the elderly population in six European countries and to analyze the impact of socio-demographic variables on health.</p> <p>Methods</p> <p>In the European Study of the Epidemiology of Mental Disorders (ESEMeD), representative non-institutionalized population samples completed the EQ-5D and Short Form-12 (SF-12) questionnaires as part of personal computer-based home interviews in 2001-2003. This study is based on a subsample of 1659 respondents aged ≥ 75 years from Belgium (n = 194), France (n = 168), Germany (n = 244), Italy (n = 317), the Netherlands (n = 164) and Spain (n = 572). Descriptive statistics, bivariate- (chi-square tests) and multivariate methods (linear regressions) were used to examine differences in population health.</p> <p>Results</p> <p>68.8% of respondents reported problems in one or more EQ-5D dimensions, most frequently pain/discomfort (55.2%), followed by mobility (50.0%), usual activities (36.6%), self-care (18.1%) and anxiety/depression (11.6%). The proportion of respondents reporting any problems increased significantly with age in bivariate analyses (age 75-79: 65.4%; age 80-84: 69.2%; age ≥ 85: 81.1%) and differed between countries, ranging from 58.7% in the Netherlands to 72.3% in Italy. The mean EQ VAS score was 61.9, decreasing with age (age 75-79: 64.1; age 80-84: 59.8; age ≥ 85: 56.7) and ranging from 60.0 in Italy to 72.9 in the Netherlands. SF-12 derived Physical Component Summary (PCS) and Mental Component Summary (MCS) scores varied little by age and country. Age and low educational level were associated with lower EQ VAS and PCS scores. After controlling for socio-demographic variables and reported EQ-5D health states, mean EQ VAS scores were significantly higher in the Netherlands and Belgium, and lower in Germany than the grand mean.</p> <p>Conclusions</p> <p>More than two thirds of the advanced elderly report impairment of health status. Impairment increases rapidly with age but differs considerably between countries. In all countries, health status is significantly associated with socio-demographic variables.</p

A Gene Expression Signature of Acquired Chemoresistance to Cisplatin and Fluorouracil Combination Chemotherapy in Gastric Cancer Patients

We initiated a prospective trial to identify transcriptional alterations associated with acquired chemotherapy resistance from pre- and post-biopsy samples from the same patient and uncover potential molecular pathways involved in treatment failure to help guide therapeutic alternatives.A prospective, high-throughput transcriptional profiling study was performed using endoscopic biopsy samples from 123 metastatic gastric cancer patients prior to cisplatin and fluorouracil (CF) combination chemotherapy. 22 patients who initially responded to CF were re-biopsied after they developed resistance to CF. An acquired chemotherapy resistance signature was identified by analyzing the gene expression profiles from the matched pre- and post-CF treated samples. The acquired resistance signature was able to segregate a separate cohort of 101 newly-diagnosed gastric cancer patients according to the time to progression after CF. Hierarchical clustering using a 633-gene acquired resistance signature (feature selection at P<0.01) separated the 101 pretreatment patient samples into two groups with significantly different times to progression (2.5 vs. 4.7 months). This 633-gene signature included the upregulation of AKT1, EIF4B, and RPS6 (mTOR pathway), DNA repair and drug metabolism genes, and was enriched for genes overexpressed in embryonic stem cell signatures. A 72-gene acquired resistance signature (a subset of the 633 gene signature also identified in ES cell-related gene sets) was an independent predictor for time to progression (adjusted P = 0.011) and survival (adjusted P = 0.034) of these 101 patients.This signature may offer new insights into identifying new targets and therapies required to overcome the acquired resistance of gastric cancer to CF