Integration of Gene Dosage and Gene Expression in Non-Small Cell Lung Cancer, Identification of HSP90 as Potential Target

BACKGROUND: Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease. METHODOLOGY AND PRINCIPAL FINDINGS: In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. CONCLUSIONS: We suggest that targeting HSP90 will have clinical impact for NSCLC patients

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters

Microbial Biotechnolog

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Polycycloalkylidene-Polycycloalkanes, Epidioxy Derivatives Thereof and Method of Preparation

The invention relates to a process for preparing substituted polycyclo-alkylidene polycyclo-alkanes, such as substituted adamantylidene adamantanes, and the corresponding epidioxy compounds, in which polycycloalkylidene polycyclo-alkanes are halogenated with an N-halosuccinimide, tert.-butylhypohalite or sodium hypohalite/CH3COOH, the halogenation product is optionally subjected to a substitution reaction, and the substituted polycycloalkylidene polycyclo-alkanes are converted to the corresponding epidioxy compounds in a way known per se. Further, the invention relates to compounds of formula 44 in which A and B represent alkylene radicals, which alkylene radicals may be attached to each other via an alkylene radical C, and R1 represents a substituent, which, in case of 4-eq.-R1-2,2'-adamantylidene adamantane cannot be chloro, hydroxy, oxo, D or a group of formula 1 as well as to compounds of formula 45 in which A, B and C are as defined above, and R2 is a substituent which, in case of 4-eq.-R2-2,2'-epidioxy-2,2'-adamantyl adamantane cannot be chloro or hydroxy. Compounds of formula 45 are useful as thermochemiluminescent labels and probes in the study of biological processes and in immuno-assays

Polycycloalkylidene-Polycycloalkanes, Epidioxy Derivatives Thereof and Method of Preparation

The invention relates to a process for preparing substituted polycyclo-alkylidene polycyclo-alkanes, such as substituted adamantylidene adamantanes, and the corresponding epidioxy compounds, in which polycycloalkylidene polycyclo-alkanes are halogenated with an N-halosuccinimide, tert.-butylhypohalite or sodium hypohalite/CH3COOH, the halogenation product is optionally subjected to a substitution reaction, and the substituted polycycloalkylidene polycyclo-alkanes are converted to the corresponding epidioxy compounds in a way known per se. Further, the invention relates to compounds of formula 44 in which A and B represent alkylene radicals, which alkylene radicals may be attached to each other via an alkylene radical C, and R1 represents a substituent, which, in case of 4-eq.-R1-2,2'-adamantylidene adamantane cannot be chloro, hydroxy, oxo, D or a group of formula 1 as well as to compounds of formula 45 in which A, B and C are as defined above, and R2 is a substituent which, in case of 4-eq.-R2-2,2'-epidioxy-2,2'-adamantyl adamantane cannot be chloro or hydroxy. Compounds of formula 45 are useful as thermochemiluminescent labels and probes in the study of biological processes and in immuno-assays.