Extracellular matrix components affect cell migration and invasive potential of cultured human pancreatic ductal adenocarcinoma cells

The tumor microenvironment influences cancer cell behavior in relation to tumor progression, as well as cell proliferation and invasion. Pancreatic ductal adenocarcinoma (PDAC) is characterized by an intense desmoplastic reaction and extracellular matrix (ECM) components in the tumor microenvironment are involved in a cross-talk between tumor cells, stromal fibroblasts and ECM components, influencing tumor cell behavior. We aimed at analyzing in vitro the effect of the crosstalk between PDAC cells and the ECM of the microenvironment by culturing PDAC cells on different ECM proteins used as a substrate, in order to better understand the relationship between cancer cell phenotype and the proteins occurring in the desmoplastic tissue. For this purpose, we analyzed some epithelial-to-mesenchymal transition (EMT) markers and the migration and invasive potential in human HPAF-II, HPAC and PL45 PDAC cells cultured on collagen type I (COL), laminin (LAM) and fibronectin (FN). Interestingly, the expression of E-cadherin was not significantly affected, but some differences were revealed by the wound healing assay. In fact, migration of HPAF-II and PL45 cells was decreased on FN and LAM, and increased on COL, compared to control cells grown on plastic (NC). By contrast, HPAC was very rapid and unaffected by the substrate. SDS-zymography showed that COL induced a strong upregulation of MMP-2 activity in HPAF-II and HPAC cells, and of MMP-9 in HPAF-II and PL45 cells, compared to NC. These preliminary results suggest that ECM components could differently affect PDAC migration and invasion, possibly depending on the differentiation grade. The characterization of the mutual effects elicited by the tumor-stroma interplay on the cancer cell will contribute to better understand the influence of the stroma on PDAC cancer cell phenotype, in order to develop new therapeutic strategies

Applicazione Della Droplet Digital Pcr Per La Quantificazione Della Malattia Residua Minima Nella Leucemia Linfoblastica Acuta Pediatrica

La real-time PCR quantitativa (RQ-PCR) viene attualmente utilizzata per la quantificazione relativa della Malattia Residua Minima (MRM) nei la quantificazione relativa della Malattia Residua Minima (MRM) nei pazienti pediatrici affetti da LeucemiaLinfoblastica Acuta (LLA). Il recente sviluppo della Droplet Digital PCR (ddPCR) per la quantificazione assoluta potrebbe consentire di caratterizzare meglio i pazienti attualmentedefiniti positivi non quantificabili (NQ) in RQ-PCR

Isotretinoin Plus Clindamycin Seem Highly Effective Against Severe Erlotinib-Induced Skin Rash in Advanced Non-small Cell Lung Cancer

Introduction:Erlotinib is useful in advanced non-small cell lung cancer although compliance and efficacy are diminished by skin rash in a high proportion of patients, often necessitating dose reduction or drug withdrawal. No effective treatment for the rash is available.Methods:We carried out a preliminary investigation on isotretinoin and clindamycin. Among 56 advanced lung cancer patients treated with erlotinib, 31 (53%) developed rash. Seven (35%) of the 20 G2/G3 cases agreed to treatment with clindamycin (450 mg/d, days 1–10; 300 mg/d, days 11–20) plus isotretinoin (20 mg/d, days 11–20) after being informed of the experimental nature of the combination.Results:In 6 of 7 (86%) patients, the rash resolved (G1/G0) without dose reduction; in the other patient (G3), the erlotinib dose also had to be reduced. Median time to resolution was 14 days (range 7–20 days). No rash-treatment adverse events occurred during 20 days of administration.Conclusions:Isotretinoin plus clindamycin promises to be the first effective treatment for erlotinib rash and is being tested further