Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors.

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. In this study, we characterize the mechanisms by which naïve mesenchymal stromal cells (MSCs) can acquire a CA-MSCs phenotype. Ovarian tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells, resulting in the secretion of high levels of CXC chemokine receptors 1 and 2 (CXCR1/2) ligands such as chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and interleukin 8 (IL-8).

The GLP1R Agonist Liraglutide Reduces Hyperglucagonemia Induced by the SGLT2 Inhibitor Dapagliflozin via Somatostatin Release.

The newest classes of anti-diabetic agents include sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor (GLP1R) agonists. The SGLT2 inhibitor dapagliflozin reduces glucotoxicity by glycosuria but elevates glucagon secretion. The GLP1R agonist liraglutide inhibits glucagon; therefore, we hypothesize that the cotreatment of dapagliflozin with liraglutide could reduce hyperglucagonemia and hyperglycemia.

Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression.

T cells responding to persistent tumor or viral antigens progressively lose their functional properties, a feature known as exhaustion. This state is also characterized by cell-surface expression of multiple inhibitory immune checkpoint receptors (IRs). Cancer immunotherapy by immune checkpoint targeting has shown impressive clinical outcomes, but requires substantial improvement given the limited number of patients who benefit from the treatment.

Oncogenic KIT mutations induce STAT3-dependent autophagy to support cell proliferation in acute myeloid leukemia.

Autophagy is associated with both survival and cell death in myeloid malignancies. Therefore, deciphering its role in different genetically defined subtypes of acute myeloid leukemia (AML) is critical. Activating mutations of the KIT receptor tyrosine kinase are frequently detected in core-binding factor AML and are associated with a greater risk of relapse.

The cholesterol-derived metabolite dendrogenin A functionally reprograms breast adenocarcinoma and undifferentiated thyroid cancer cells.

Dendrogenin A (DDA) is a tumor suppressor mammalian cholesterol-derived metabolite and a new class of ligand of the Liver X receptor (LXR), which displays tumor cell differentiation. In human MCF7 breast adenocarcinoma cells, DDA-induced cell differentiation was associated with an increased accumulation of neutral lipids and proteins found in milk indicating that DDA re-activates some functions of lactating cells. Active iodide transport occurs in the normal lactating mammary cells through the sodium/iodide symporter (NIS) and iodide (I) is secreted into milk to be used by the nursing newborn for thyroid hormones biosynthesis.

NCOA4-RET and TRIM27-RET Are Characteristic Gene Fusions in Salivary Intraductal Carcinoma, Including Invasive and Metastatic Tumors: Is "Intraductal" Correct?

Intraductal carcinoma (IC) is the new WHO designation for tumors previously encompassed by "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma." The relationship of IC to salivary duct carcinoma (SDC) is controversial, even though they are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with histopathological features reminiscent of atypical ductal hyperplasia or ductal carcinoma in situ of the breast, showing diffuse S100 protein and mammaglobin positivity, while it is partially defined genetically.

Alpha6-Integrin Regulates FGFR1 Expression through the ZEB1/YAP1 Transcription Complex in Glioblastoma Stem Cells Resulting in Enhanced Proliferation and Stemness.

Glioblastoma (GBM) is the most lethal primary brain tumor in adults and is known to be particularly aggressive and resistant to anti-cancer therapies, mainly due to the presence of GBM stem cells (GBMSC). By in vitro approaches supported by analysis from patients' databases, we determined how α6-integrin and Fibroblast Growth Factor Receptor 1 (FGFR1) work in concert to regulate proliferation and stemness of GBMSC. We showed that α6-integrin regulates the expression of FGFR1 and its target gene Fokhead Box M1 (FOXM1) via the ZEB1/YAP1 transcription complex.

Natural and semisynthetic oxyprenylated aromatic compounds as stimulators or inhibitors of melanogenesis.

It has been very recently shown how naturally occurring oxyprenylated coumarins are effective modulators of melanogenesis. In this short communication we wish to generalize the potentialities as skin tanning or whitening agents of a wider panel of natural and semisynthetic aromatic compounds, including coumarins, cinnamic and benzoic acids, cinnamaldehydes, benzaldehyde, and anthraquinone derivatives. A total number of 43 compounds have been tested assaying their capacity to inhibit or stimulate melanin biosynthesis in cultured murine Melan A cells.

The Prognostic Impact of the Aryl Hydrocarbon Receptor (AhR) in Primary Breast Cancer Depends on the Lymph Node Status.

Increasing evidence implicates the aryl hydrocarbon receptor (AhR) as a possible regulator of mammary carcinogenesis. This study aims to clarify its prognostic impact in breast cancer (BC). Meta-analyses performed at the mRNA level demonstrated that the predictive value of AhR expression in BC depends on the lymph node (LN) status.

Factors Affecting Tamoxifen Metabolism in Patients With Breast Cancer: Preliminary Results of the French PHACS Study.

In addition to the effect of cytochrome P450 (CYP) 2D6 genetic polymorphisms, the metabolism of tamoxifen may be impacted by other factors with possible consequences on therapeutic outcome (efficacy and toxicity). This analysis focused on the pharmacokinetic (PK)-pharmacogenetic evaluation of tamoxifen in 730 patients with adjuvant breast cancer included in a prospective multicenter study. Plasma concentrations of tamoxifen and six major metabolites, the genotype for 63 single-nucleotide polymorphisms, and comedications were obtained 6 months after treatment initiation.

HPLC Analysis and Skin Whitening Effects of Umbelliprenin-containing Extracts of , , and .

Umbelliprenin has recently been shown to have great potential as a skin whitening agent. Wishing to investigate the same effect in plant species known to biosynthesize this coumarin, three plants belonging to the Apiaceae family, namely L. (dill), L.

RCBTB1 Deletion Is Associated with Metastatic Outcome and Contributes to Docetaxel Resistance in Nontranslocation-Related Pleomorphic Sarcomas.

Half of soft-tissue sarcomas are tumors with complex genomics, which display no specific genetic alterations and respond poorly to treatment. It is therefore necessary to find new therapeutic targets for these sarcomas. Despite genetic heterogeneity across samples, oncogenesis may be driven by common pathway alterations.

Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity.

Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6.

Wnt targets genes are not differentially expressed in desmoid tumors bearing different activating β-catenin mutations.

Introduction: Sporadic desmoid-type fibromatosis (DTF) is a rare soft tissue tumor of mesenchymal origin. It is characterized by local invasive growth and unpredictable growth behavior. Three distinct mutations involving the CTNNB1 (β-catenin) gene have been identified in the vast majority of DTF tumors, which cause activation of the Wnt signaling pathway and impact prognosis.

CINSARC signature as a prognostic marker for clinical outcome in sarcomas and beyond.

Prognostication is a key issue for sarcoma patients' care as it triggers the therapeutic approach including chemotherapy, which is still not standard for localized patients. Current prognostic evaluation, based on the FNCLCC grading system, has recently been improved by the CINSARC signature outperforming histology-based grading system by identifying high-risk patients in every grade, even in those considered as low. CINSARC is an expression-based signature related to mitosis and chromosome integrity with prognostic value in a wide range of cancers additional to sarcoma.

p27 regulates the microtubule bundling activity of PRC1.

Cytokinesis begins in anaphase with the formation of the central spindle. PRC1 is a microtubule associated protein that plays an essential role in central spindle formation by crosslinking antiparallel microtubules. We have identified PRC1 as a novel binding partner for p27 (p27).

Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma.

The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS).

PARP-1-dependent RND1 transcription induced by topoisomerase I cleavage complexes confers cellular resistance to camptothecin.

RHO GTPases regulate essential functions such as the organization of the actin cytoskeleton. The classic members cycle between an active GTP-bound and an inactive GDP-bound conformation whereas atypical members are predominantly GTP-bound. Besides their well-established role, the classic RHO GTPases RHOB and RAC1, are rapidly induced and/or activated by genotoxic stress and contribute to the DNA damage response.

Cytoplasmic p27 promotes tumorigenesis via suppression of RhoB activity.

The cell cycle inhibitor p27 is a tumor suppressor via the inhibition of CDK complexes in the nucleus. However, p27 also plays other functions in the cell and may acquire oncogenic roles when located in the cytoplasm. Activation of oncogenic pathways such as Ras or PI3K/AKT causes the relocalization of p27 in the cytoplasm, where it can promote tumorigenesis by unclear mechanisms.

FGFR1/FOXM1 pathway: a key regulator of glioblastoma stem cells radioresistance and a prognosis biomarker.

Glioblastoma are known to be aggressive and therapy-resistant tumors, due to the presence of glioblastoma stem cells inside this heterogeneous tumor. We investigate here the involvement of FGFR1 in glioblastoma stem-like cells (GSLC) radioresistance mechanisms. We first demonstrated that the survival after irradiation was significantly diminished in FGFR1-silenced (FGFR1-) GSLC compared to control GSLC.

Alpha-6 integrin promotes radioresistance of glioblastoma by modulating DNA damage response and the transcription factor Zeb1.

Radiotherapy is the cornerstone of glioblastoma (GBM) standard treatment. However, radioresistance of cancer cells leads to an inevitable recurrence. In the present study, we showed that blocking α6-integrin in cells derived from GBM biopsy specimens cultured as neurospheres, sensitized cells to radiation.

The Effects of Cholesterol-Derived Oncometabolites on Nuclear Receptor Function in Cancer.

Epidemiologic studies are controversial concerning the roles played by cholesterol in cancer risk and development, possibly as it is not cholesterol per se that is pathologic in cancers. Indeed, recent data reveal that the cholesterol metabolism in cancer cells can generate endogenous oncopromoter metabolites at higher levels compared with normal tissues and/or can be deregulated in the production of endogenous oncosuppressor metabolites in an opposite way. These metabolites are oxysterols, which are cholesterol oxygenation products generated by enzymatic and/or autoxidation processes.