Investigating the C2 Modulation of the Imidazo[1,2-a]pyrazine-Based Hit Compound CTN1122: Synthesis, in vitro Antileishmanial Activity, Cytotoxicity and Casein Kinase 1 Inhibition.

Our research group previously discovered CTN1122, an imidazo[1,2-a]pyrazine compound with promising antileishmanial activity against intramacrophage amastigotes of Leishmania major and L. donovani strains. CTN1122 effectively targets Leishmania casein kinase 1 (L-CK1.

AML alters bone marrow stromal cell osteogenic commitment via Notch signaling.

Introduction: Acute myeloid leukemia (AML) is a highly heterogeneous malignancy caused by various genetic alterations and characterized by the accumulation of immature myeloid blasts in the bone marrow (BM). This abnormal growth of AML cells disrupts normal hematopoiesis and alters the BM microenvironment components, establishing a niche supportive of leukemogenesis. Bone marrow stromal cells (BMSCs) play a pivotal role in giving rise to essential elements of the BM niche, including adipocytes and osteogenic cells.

A Question of Frame: The Role of the Bone Marrow Stromal Niche in Myeloid Malignancies.

Until a few years ago, the onset of acute myeloid leukemia (AML) was entirely ascribed to genetic lesions in hematopoietic stem cells. These mutations generate leukemic stem cells, which are known to be the main ones responsible for chemoresistance and relapse. However, in the last years, increasing evidence demonstrated that dynamic interplay between leukemic cells and bone marrow (BM) niche is of paramount relevance in the pathogenesis of myeloid malignancies, including AML.

Selective homing of CAR-CIK cells to the bone marrow niche enhances control of the acute myeloid leukemia burden.

Acute myeloid leukemia (AML) is a hematological malignancy derived from neoplastic myeloid progenitor cells characterized by abnormal clonal proliferation and differentiation. Although novel therapeutic strategies have recently been introduced, the prognosis of AML is still unsatisfactory. So far, the efficacy of chimeric antigen receptor (CAR)-T-cell therapy in AML has been hampered by several factors, including the poor accumulation of the blood-injected cells in the leukemia bone marrow (BM) niche in which chemotherapy-resistant leukemic stem cells reside.

Location First: Targeting Acute Myeloid Leukemia Within Its Niche.

Despite extensive research and development of new treatments, acute myeloid leukemia (AML)-backbone therapy has remained essentially unchanged over the last decades and is frequently associated with poor outcomes. Eradicating the leukemic stem cells (LSCs) is the ultimate challenge in the treatment of AML. Emerging evidence suggests that AML remodels the bone marrow (BM) niche into a leukemia-permissive microenvironment while suppressing normal hematopoiesis.

Acute myeloid leukaemia niche regulates response to L-asparaginase.

Eradicating the malignant stem cell is the ultimate challenge in the treatment of leukaemia. Leukaemic stem cells (LSC) hijack the normal haemopoietic niche, where they are mainly protected from cytotoxic drugs. The anti-leukaemic effect of L-asparaginase (ASNase) has been extensively investigated in acute lymphoblastic leukaemia, but only partially in acute myeloid leukaemia (AML).

Rapid Synthesis and Antiproliferative Properties of Polyazamacrocycle-Based Bi- and Tetra-Gold(I) Phosphine Dithiocarbamate Complexes.

A family of bi- and tetrametallic gold(I) phosphine dithiocarbamate complexes were synthesized, starting from cyclam and dimethylcyclam polyazamacrocycles, respectively, along with their monometallic gold(I) chloridophosphine precursors. Their antiproliferative properties were evaluated on two cancer cell lines (A549 and NSCLC-N6-L16). Most of the mono- and bimetallic complexes displayed strong activities and, in particular, one bimetallic derivative showed antiproliferative properties in the low micromolar range.

Expressive writing. A tool to help health workers of palliative care.

Background And Aims: From a previous study (1) was highlighted that Expressive writing is an important strategy for preventing and managing the effects of compassion fatigue (2). It helps educate caregivers in recognising these feelings and providing them with a "space" and a time for their reflection. This, in turn, results in significant positive repercussions on the quality of service, reducing burnout risk, implementing coping strategies, and increasing perceived work satisfaction.

Discovery of Novel (Imidazo[1,2-a]pyrazin-6-yl)ureas as Antiproliferative Agents Targeting P53 in Non-small Cell Lung Cancer Cell Lines.

A series of (imidazo[1,2-a]pyrazin-6-yl)ureas were synthesized through 6-aminoimidazo[1,2-a]pyrazine as a key intermediate. 1-(Imidazo[1,2-a]pyrazin-6-yl)-3-(4-methoxy - phenyl)urea displayed a cytostatic activity against a non-small cell lung cancer cell line and was chosen for further mechanistic studies. Growth kinetics highlighted a selective dose-dependent response of P53-mutant NSCLC-N6-L16 cell line and overexpression of TP53 gene induced by this compound.

Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1.

Activation of cell signaling by reactive chemicals and pollutants is an important issue for human health. It has been shown that lipophilic nitro-benzoxadiazole (NBD) compounds rapidly move across the plasma membrane and enhance Epidermal Growth Factor Receptor (EGFR) tyrosine phosphorylation in cancer cells. Unlike ligand-dependent activation, the mechanism of this induction relies on the generation of hydrogen peroxide, which is involved in the activation of the catalytic site of the receptor and the inactivation of protein tyrosine phosphatase PTP-1B.

TP53 transcription factor for the NEDD9/HEF1/Cas-L gene: potential targets in Non-Small Cell Lung Cancer treatment.

Lung cancer is a serious public health problem. Although there has been significant progress in chemotherapy, non-small cell lung cancer is still resistant to current treatments, primarily because of the slow rate of cell development. It is thus important to find new molecules directed against targets other than proliferation agents.

Cucurbitacin-D-induced CDK1 mRNA up-regulation causes proliferation arrest of a non-small cell lung carcinoma cell line (NSCLC-N6).

Despite progress in chemotherapeutic agents, non-small cell lung cancers (NSCLC) still have a poor survival rate. Thus, development of new therapeutic strategies, specifically against cancer cells is still required. For this purpose, we treated the non-small cell lung cancer cell line NSCLC-N6 with the natural product cucurbitacin D (CucD) - extracted from the plant Ecballium elaterium in order first to assess its in vitro cytotoxicity, but also to study the genetic changes that it could bring out.

Synthesis and antiproliferative activity of benzofuran-based analogs of cercosporamide against non-small cell lung cancer cell lines.

A novel series of 3-methyl-1-benzofuran derivatives were synthesized and screened in vitro for their antiproliferative activity against two human NSCLC cell lines (NSCLC-N6 mutant p53 and A549 wild type p53). Most promising compounds presented a structural analogy with the west part of cercosporamide, a natural product of biological interest. In particular, compounds 10, 12 and 31 showed cytotoxic activities at micromolar concentrations (IC₅₀ < 9.

miRNAs, a potential target in the treatment of Non-Small-Cell Lung Carcinomas.

Lung cancer is a serious public health problem and Non Small Cell Lung Carcinoma, NSCLC, is particularly resistant to current treatments. So it is important to find new strategies that are active against NSCLC. miRNA is implicated in cancer and may be implicated in NSCLC.

Study of antiproliferative effects of synthetic substances against lens epithelial cell line (SRA 01/04).

A cataract is a clouded area of the eye, which impairs vision. Cataracts can be caused by a natural hardening of the lens in the elderly, or may be the result of eye injury. However there is a treatment by extracapsular surgery, almost 50% of operations are followed by another posterior capsule opacification.

A novel large regulator RNA, B2, partially overlaps the HEF1/NEDD9/Cas-L gene.

The non-coding RNAs are new players in cellular and molecular biology. Indeed, quantitative and functional non-coding RNA has long been underestimated. There is a great diversity and it seems that much of the genome is transcribed into RNA, while only 1.

Original triazine inductor of new specific molecular targets, with antitumor activity against nonsmall cell lung cancer.

Despite our growing insight into carcinogenesis, treatment of tumors, especially nonsmall cell lung cancer (NSCLC), remains limited and it is urgent to develop strategies that target tumor cells and their genetic features. Drug discovery efforts have historically focused on the search for compounds that modulate the protein products of genes. Current drug therapy targets only a few hundred endogenous targets, mainly proteins, such as receptors and enzymes.

Cultivated microalgae and the carotenoid fucoxanthin from Odontella aurita as potent anti-proliferative agents in bronchopulmonary and epithelial cell lines.

The antiproliferative activities of several extracts from cultivated microalgae in France have been studied against bronchopulmonary and epithelial cell lines, respectively (A549, NSCLC-N6 and SRA 01/04). The algal extracts, of Diatomae (Odontella aurita, Chaetoseros sp.), as well as of Haptophyceae: Isochrisys aff.

Identification of a novel putative non-coding RNA involved in proliferation arrest of a non-small cell lung carcinoma cell line treated with an original chemical substance, methyl-4-methoxy-3-(3-methyl-2-butanoyl) benzoate.

Non-small cell lung cancers remain particularly refractory to current treatments. Thus, characterisation of new molecular targets whose expression during chemotherapy could stop tumour growth, is required. In order to identify these new targets, we applied RT-PCR differential display (RT-PCR-DD) to a non-small cell lung cancer line (NSCLC-N6) treated by an original chemical substance, VT1, capable of arresting the proliferation of NSCLC-N6 cells in G1 phase.

Proliferation arrest in G1 phase of a non-small cell lung cancer cell line (NSCLC-N6) treated by an original compound methyl-4-methoxy-3-(3-methyl-2-butanoyl) benzoate (VT1) independently of the p53/p21 cascade.

Non-small cell lung cancers remain difficult to treat and have a high death rate and poor 5-year survival. New therapeutic strategies are urgently needed, which should be more specific for the cancer cell and less toxic for normal cells. In this respect, induction of the terminal differentiation of tumor cells appears to be a particularly suitable approach, which can only be achieved after proliferation arrest in G1 phase.

Effect of four genes (ALDH1, NRF1, JAM and KBL) on proliferation arrest in a non-small cell bronchopulmonary cancer line.

Despite new protocols, non-small cell bronchopulmonary cancers are still difficult to treat by current chemotherapeutic procedures. Thus, it is essential to define new treatment strategies and detect new therapeutic targets. In order to define these new targets, this study applied the "differential display" (DD) technique to the NSCLC-N6 cell line treated with VT1 [methyl-4-methoxy-3-(3-methyl-2-butanoyl)benzoate].

Up-regulation of a novel mRNA (NY-CO-1) involved in the methyl 4-methoxy-3-(3-methyl-2-butenoyl) benzoate (VT1)-induced proliferation arrest of a non-small-cell lung carcinoma cell line (NSCLC-N6).

It is now well known that treatment of tumors, especially non-small-cell lung cancer (NSCLC), remains limited and it is urgent to develop strategies that target tumor cells and their genetic features. In this regard, our work is about genetic modifications arising in an in vitro NSCLC cell line after treatment with a chemical substance, methyl 4-methoxy-3-(3-methyl-2-butenoyl) benzoate (VT1). First, we showed that VT1 induces arrest of proliferation by blocking cells in the G1 phase of the cell cycle.

Antiproliferative effects of a product isolated from the gorgonian Rumphella aggregata.

A fraction isolated from the gorgonian Rumphella aggregata (Plexauridae) was studied vitro on asynchronous cells of a human non-small-cell-bronchopulmonary-carcinoma line (NSCLC-N6). Cell growth appeared to be inhibited in the Gl phase of the cell cycle, and kinetic studies in pretreated cells showed that this growth arrest was irreversible. These events seem to show a terminal maturation induced by this new product.

Correlation between multidrug resistance and the degree of differentiation of non-small-cell bronchopulmonary carcinoma (NSCLC) in vitro and in vivo.

The correlation between the degree of expression of the multidrug resistance-1 (MDR-1) gene and the process of differentiation into non-small-cell, bronchopulmonary carcinoma was studied in vitro and in vivo. For this purpose, a technique for the quantitative analysis of MDR-1 gene expression was developed by competitive reverse-transcriptase polymerase chain reaction. The study of 9 epidermoid carcinomas with various degrees of differentiation did not enable us to establish a correlation in vivo in the patient.