Unsupervised Feature Selection by a Genetic Algorithm for Mid-Infrared Spectral Data.

Dimensional reduction of highly multidimensional datasets such as those acquired by Fourier transform infrared spectroscopy (FTIR) is a critical step in the data analysis workflow. To achieve this goal, numerous feature selection methods have been developed and applied in a supervised context, i.e.

Colorectal Cancer: The Contribution of CXCL12 and Its Receptors CXCR4 and CXCR7.

Colorectal cancer is one of the most common cancers, and diagnosis at late metastatic stages is the main cause of death related to this cancer. This progression to metastasis is complex and involves different molecules such as the chemokine CXCL12 and its two receptors CXCR4 and CXCR7. The high expression of receptors in CRC is often associated with a poor prognosis and aggressiveness of the tumor.

Automatic Identification of Paraffin Pixels on FTIR Images Acquired on FFPE Human Samples.

The transfer of mid-infrared spectral histopathology to the clinic will be possible provided that its application in clinical practice is simple. Rapid analysis of formalin-fixed paraffin-embedded (FFPE) tissue section is thus a prerequisite. The chemical dewaxing of these samples before image acquisition used by the majority of studies is in contradiction with this principle.

Impact of pemetrexed chemotherapy on the gut microbiota and intestinal inflammation of patient-lung-derived tumor xenograft (PDX) mouse models.

Chemotherapy remains the gold standard for advanced cancer. Pemetrexed, a chemotherapeutic agent used in non-small cell lung cancer, can induce significant side effects in patients. Although microbiota's role in the efficacy and/or toxicity of chemotherapy agents has been demonstrated, the impacts of pemetrexed on the gut microbiota and on gastrointestinal inflammation remain unknown.

Hypoxic Environment and Paired Hierarchical 3D and 2D Models of Pediatric -Mutated Gliomas Recreate the Patient Tumor Complexity.

Background: Pediatric high-grade gliomas (pHGGs) are facing a very dismal prognosis and representative pre-clinical models are needed for new treatment strategies. Here, we examined the relevance of collecting functional, genomic, and metabolomics data to validate patient-derived models in a hypoxic microenvironment.

Methods: From our biobank of pediatric brain tumor-derived models, we selected 11 pHGGs driven by the histone mutation.

Synergistic Anti-Tumor Effect of mTOR Inhibitors with Irinotecan on Colon Cancer Cells.

Advanced colorectal cancer has a poor prognosis because of metastasis formation and resistance to combined therapies. Downstream of PI3K/Akt and Ras/MAPK pathways, the mTOR kinase plays a decisive role in treatment failure. We previously established that irinotecan has antiangiogenic properties and it is known that new mammalian target of rapamycin (mTOR) catalytic AZD inhibitors, unlike rapamycin, target both mTORC1 and mTORC2.

RNA Aptamers Targeting Integrin α5β1 as Probes for Cyto- and Histofluorescence in Glioblastoma.

Nucleic acid aptamers are often referred to as chemical antibodies. Because they possess several advantages, like their smaller size, temperature stability, ease of chemical modification, lack of immunogenicity and toxicity, and lower cost of production, aptamers are promising tools for clinical applications. Aptamers against cell surface protein biomarkers are of particular interest for cancer diagnosis and targeted therapy.

Fireproofing of domestic upholstered furniture: Migration of flame retardants and potential risks.

Flame retardants (FRs) are widely incorporated in polyurethane foams to decrease their fire reaction. Currently, the risks associated with the use of FRs in domestic upholstered furniture (UF) are evaluated according to FRs volatility and potency to be emitted into the atmosphere. However, exposure via contact and dermal penetration, mediated by sweat, has not been considered so far.

A redox ruthenium compound directly targets PHD2 and inhibits the HIF1 pathway to reduce tumor angiogenesis independently of p53.

Targeting specific tumor metabolic needs represents an actively investigated therapeutic strategy to bypass tumor resistance mechanisms. In this study, we describe an original approach to impact the cancer metabolism by exploiting the redox properties of a ruthenium organometallic compound. This organometallic complex induced p53-independent cytotoxicity and reduced size and vascularization of patients-derived tumor explants that are resistant to platinum drugs.

Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinoma.

Background Information: Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma.

Results: By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth.

SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients.

Lymph node metastasis is an important prognosis factor in non-small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c-MET, and CAIX), and transcription factors (EMT-TF: SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2).

Characterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1α axis inhibition.

Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment.

The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors.

Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore.

Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS).

Histone hypoacetylation contributes to CXCL12 downregulation in colon cancer: impact on tumor growth and cell migration.

CXCL12 has been shown to be involved in colon cancer metastasis, but its expression level and molecular mechanisms regulating its expression remain controversial. We thus evaluated CXCL12 expression in a large cohort of colon adenomas and carcinomas, investigated for an epigenetic mechanism controlling its expression and evaluated the impact of CXCL12 levels on cell migration and tumor growth. CXCL12 expression was measured in human colon adenomas and carcinomas with transcriptome array and RT-qPCR.

Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†.

Objectives: The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status.

Methods: We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known.

Development of a memetic clustering algorithm for optimal spectral histology: application to FTIR images of normal human colon.

The coupling between Fourier-transform infrared (FTIR) imaging and unsupervised classification is effective in revealing the different structures of human tissues based on their specific biomolecular IR signatures; thus the spectral histology of the studied samples is achieved. However, the most widely applied clustering methods in spectral histology are local search algorithms, which converge to a local optimum, depending on initialization. Multiple runs of the techniques estimate multiple different solutions.

Fully unsupervised inter-individual IR spectral histology of paraffinized tissue sections of normal colon.

In label-free Fourier-transform infrared histology, spectral images are individually recorded from tissue sections, pre-processed and clustered. Each single resulting color-coded image is annotated by a pathologist to obtain the best possible match with tissue structures revealed after Hematoxylin-Eosin staining. However, the main limitations of this approach are the empirical choice of the number of clusters in unsupervised classification, and the marked color heterogeneity between the clustered spectral images.

Impact of EGFR mutations and KRAS amino acid substitution on the response to radiotherapy for brain metastasis of non-small-cell lung cancer.

Background: Our study aimed to evaluate response rate (RR) to brain metastasis radiotherapy (RT), depending on the genomic status of non-small-cell lung cancer.

Material & Methods: We retrospectively reviewed 1971 non-small-cell lung cancer files of patients with EGFR and KRAS testing and focused on 157 patients who had undergone RT for brain metastasis.

Results: A total of 16 patients (10.

An Innovative Fluorescent Semi-quantitative Methylation-specific PCR Method for the Determination of MGMT Promoter Methylation is Reflecting Intra-tumor Heterogeneity.

High grade gliomas (HGG) are usually associated with a very dismal prognosis, which was moderately improving in the last decade with the introduction of the alkylating agent temozolomide in their treatment. The methylation status of MGMT (O6 methylguanine DNA-methyltransferase) promoter is one of the strongest predictive and prognostic factors for the patient chemoresponse. For instance, the molecular method of assessment for MGMT promoter status is not standardized.

Correlation between MET protein expression and MET gene copy number in a Caucasian cohort of non-small cell lung cancers according to the new IASLC/ATS/ERS classification.

MET pathway is a promising target in non-small cell lung cancers (NSCLC) requiring companion tests. The aim of this study was to compare MET expression/gene copy number in a Caucasian population of NSCLC patients.We analysed 201 NSCLC, with 141 adenocarcinomas classified according to 2011 IASLC recommendations, for MET expression by immunohistochemistry (IHC) and gene copy number (GCN) by silver in situ hybridisation (SISH) on tissue microarrays.

PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer.

PIK3CA, which encodes the p110α catalytic subunit of PI3Kα, is one of the most frequently altered oncogenes in colon cancer (CC), but its prognostic value is still a matter of debate. Few reports have addressed the association between PIK3CA mutations and survival and their results are controversial. In the present study, we aimed to clarify the prognostic impact of PIK3CA mutations in stage I-III CC according to mismatch repair status.

Development of a hierarchical double application of crisp cluster validity indices: a proof-of-concept study for automated FTIR spectral histology.

Fourier-transform infrared (FTIR) spectral imaging is currently used as a non-destructive and label-free method for analyzing biological specimens. However, to highlight the different tissue regions, unsupervised clustering methods are commonly used leading to a subjective choice of the number of clusters. Here, we develop a hierarchical double application of 9 selected crisp cluster validity indices (CCVIs) using K-Means clustering.

Spatial organization of the tenascin-C microenvironment in experimental and human cancer.

The extracellular matrix (ECM) molecule tenascin-C (TNC) promotes tumor progression. This has recently been demonstrated in the stochastic murine RIP1-Tag2 insulinoma model, engineered to either express TNC abundantly or to be devoid of TNC. However, our knowledge about organization of the TNC microenvironment is scant.