CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells.

Upon progesterone stimulation, Endometrial Stromal Cells (EnSCs) undergo a differentiation program into secretory cells (decidualization) to release in abundance factors crucial for embryo implantation. We previously demonstrated that decidualization requires massive reshaping of the secretory pathway and, in particular, of the Golgi complex. To decipher the underlying mechanisms, we performed a time-course transcriptomic analysis of decidualizing EnSC.

Profound architectural and functional readjustments of the secretory pathway in decidualization of endometrial stromal cells.

Certain cell types must expand their exocytic pathway to guarantee efficiency and fidelity of protein secretion. A spectacular case is offered by decidualizing human endometrial stromal cells (EnSCs). In the midluteal phase of the menstrual cycle, progesterone stimulation induces proliferating EnSCs to differentiate into professional secretors releasing proteins essential for efficient blastocyst implantation.

Progressive waves of IL-1β release by primary human monocytes via sequential activation of vesicular and gasdermin D-mediated secretory pathways.

IL-1β is an essential cytokine, but its release needs to be strictly controlled to avoid severe inflammatory manifestations. Lacking a signal sequence, IL-1β does not follow the endoplasmic reticulum-Golgi route. Several pathways have been proposed to mediate its release.

Restoring microenvironmental redox and pH homeostasis inhibits neoplastic cell growth and migration: therapeutic efficacy of esomeprazole plus sulfasalazine on 3-MCA-induced sarcoma.

Neoplastic cells live in a stressful context and survive thanks to their ability to overcome stress. Thus, tumor cell responses to stress are potential therapeutic targets. We selected two such responses in melanoma and sarcoma cells: the xc- antioxidant system, that opposes oxidative stress, and surface v-ATPases that counteract the low pHi by extruding protons, and targeted them with the xc- blocker sulfasalazine and the proton pump inhibitor esomeprazole.

Dysregulated IL-1β Secretion in Autoinflammatory Diseases: A Matter of Stress?

Infectious and sterile inflammation is induced by activation of innate immune cells. Triggering of toll-like receptors by pathogen-associated molecular pattern or damage-associated molecular pattern (PAMP or DAMP) molecules generates reactive oxygen species that in turn induce production and activation of pro-inflammatory cytokines such as IL-1β. Recent evidence indicates that cell stress due to common events, like starvation, enhanced metabolic demand, cold or heat, not only potentiates inflammation but may also directly trigger it in the absence of PAMPs or DAMPs.

The maturation potential of NK cell clones toward autologous dendritic cells correlates with HMGB1 secretion.

Interaction of NK cells with autologous immature dendritic cells (iDCs) results in reciprocal activation. We have previously reported that NK cells trigger iDC to polarize and secrete IL-18; in turn, DC-activated NK cells secrete the nuclear protein/proinflammatory cytokine high mobility group box protein 1 (HMGB1), which induces DC maturation and prevents DC from lysis. However, activated NK cells can also kill iDC.

Histone deacetylase inhibitors prevent exocytosis of interleukin-1beta-containing secretory lysosomes: role of microtubules.

A number of agents reducing interleukin-1beta (IL-1beta) activity are being developed as novel immunomodulatory and anti-inflammatory therapies. However, the elucidation of their molecular mechanism of action is required in the context of medical management of inflammatory diseases. Inhibitors of histone deacetylases (HDACs) are promising anticancer agents with pleiotropic activities.

Initial staging of lymphoma with octreotide and other receptor imaging agents.

Somatostatin receptor scintigraphy is useful in diagnosing tumors with increased expression of somatostatin receptors. The correct use of this technique reveals the localization of neuroendocrine primary tumors and unknown metastases in approximately 90% of patients. However, somatostatin receptor scintigraphy also can image many other human tumors expressing somatostatin receptors, including malignant lymphomas and thymomas.

Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation.

To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst(2) and D(2)R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst(2) and the long isoform of the D(2)R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst(5) and to a lesser extent sst(3) and D(4)R.

In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines.

CI-994 (N-acetyldinaline) is a novel oral compound with a wide spectrum of antitumor activity in preclinical models, in vitro and in vivo. The mechanism of action may involve inhibition of histone deacetylation and cell cycle arrest. We studied the action of CI-994 on two non-small cell lung cancer (NSCLC) cell lines: A-549 (adenocarcinoma) and LX-1 (squamous cell carcinoma).

NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1.

Interaction of natural killer (NK) cells with autologous immature dendritic cells (DCs) results in reciprocal activation; however, the underlying mechanisms are so far elusive. We show here that NK cells trigger immature DCs to polarize and secrete interleukin 18 (IL-18), a cytokine lacking a secretory leader sequence. This occurs through a Ca2+-dependent and tubulin-mediated recruitment of IL-18-containing secretory lysosomes toward the adhering NK cell.

In vitro study of farnesyltransferase inhibitor SCH 66336, in combination with chemotherapy and radiation, in non-small cell lung cancer cell lines.

K-ras alterations have been reported in 20-30% of non-small cell lung cancer (NSCLC) and represent a suitable target for the development of novel anticancer agents, such as Farnesyl transferase inhibitors (FTi), a new class of agents inhibiting the post-translational modification of the K-ras proteins. The effectiveness of FTi SCH66336 in inhibiting cell proliferation and deranging cell cycle of NSCLC cell lines as well as its interaction with chemotherapy or radiation have been evaluated. The activity of FTi SCH66336, alone or in combination with paclitaxel, gemcitabine, and radiotherapy, was examined in 3 cell lines, A-549, LX-1 and CaLu-6, by colorimetric MTT assay.

Enhanced effectiveness of last generation antiblastic compounds vs. cisplatin on malignant pleural mesothelioma cell lines.

The purpose of this study was to examine the antiproliferative potentialities of a pool of new generation compounds (Paclitaxel, Docetaxel, Gemcitabine, Topotecan, SN-38) together with fenretinide, a synthetic derivative of retinoic acid, in comparison with the current first choice treatment cisplatin molecule, on a pool of human malignant pleural mesothelioma cell lines derived from either bioptic and pleural effusions samples. To evaluate the chemosensitivity features of malignant mesothelioma cells in vitro, we resorted to a rapid and reproducible colorimetric assay, a useful widely recognized tool for preclinical drug screening. In addition, by DNA content analysis and cellular morphologic assessment, we focused on the apoptosis as a potential mechanism of drug activity.

Expansion of natural killer cells in patients with head and neck cancer: detection of "noninhibitory" (activating) killer Ig-like receptors on circulating natural killer cells.

Background: In a group of patients with head and neck cancers (H&NC), the expansion of the population of CD3-,CD16+ natural killer (NK) cells in the peripheral blood was studied.

Methods: Cytofluorimetric analysis of the expression of killer Ig-like receptors (KIR, namely p58.1, p58.

T lymphocytes express B7 family molecules following interaction with dendritic cells and acquire bystander costimulatory properties.

Dendritic cells (DC) play a pivotal role in the initiation, maintenance and regulation of the immune response. Here we obtained the first evidence that DC, in the absence of any foreign antigens, induce the expression of B7 family costimulatory molecules, such as CD80, CD86, B7-H1, PD-L2, B7-H3, and B7RP-1, on autologous T lymphocytes. Cell-to-cell contact between DC and T cells was needed in order to obtain this expression on T cells.