Enzo Bonmassar - Academia.edu (original) (raw)

Papers by Enzo Bonmassar

Journal of Translational Medicine, 2015

International Journal of Molecular Sciences

The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune ... more The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune system interact, is influenced by signals from tumor cells, immunocompetent cells, and bacterial components, including LPS. A large amount of LPS is available in the colon, and this could promote inflammation and metastasis by enhancing tumor cell adhesion to the endothelium. Polydatin (PD), the 3-β-D-glucoside of trans-resveratrol, is a polyphenol with anti-cancer, anti-inflammatory, and immunoregulatory effects. This study was designed to explore whether PD is able to produce antiproliferative effects on three colon cancer lines, to reduce the expression of adhesion molecules that are upregulated by LPS on endothelial cells, and to decrease the proinflammatory cytokines released in culture supernatants. Actually, we investigated the effects of PD on tumor growth in a coculture model with human mononuclear cells (MNCs) that mimics, at least in part, an in vitro tumor microenvironment. T...

American Journal of Rhinology, 2004

Background The objective of this study was to assess if nasal polyps express telomerase activity ... more Background The objective of this study was to assess if nasal polyps express telomerase activity and whether a difference could be found between the polyp and the surrounding mucosa of the middle meatus and between different portions of the polyp itself. Methods Nine patients affected by nasal polyposis were included in this study; four of these patients had recurring polyposis. Telomerase activity was measured by telomeric repeat amplification protocol assay. In six patients, the telomeric repeat amplification protocol assay was performed on the polyp and on the mucosa from the ipsilateral middle meatus. In a polyp, we were able to investigate telomerase activity of its different portions, corresponding to pedicle and fundus. Results Telomerase activity observed in nasal polyps was higher than that observed in samples from the ipsilateral middle meatus mucosa. High or intermediate telomerase activity was found to be related to predominant recurring polyposis. Conclusion Therefore, ...

Mediators of Inflammation, 2019

Objective. Obesity is considered a clinic condition characterized by a state of chronic low-grade... more Objective. Obesity is considered a clinic condition characterized by a state of chronic low-grade inflammation. The role of macrophages and adipocytokines in adipose tissue inflammation is in growing investigation. The physiopathological mechanisms involved in inflammatory state in obesity are not fully understood though the adipocytokines seem to characterize the biochemical link between obesity and inflammation. The aim of this work is to analyze the effect of theobromine, a methylxanthine present in the cocoa, on adipogenesis and on proinflammatory cytokines evaluated in a model of fat tissue inflammation in vitro. Methods. In order to mimic in vitro this inflammatory condition, we investigated the interactions between human-like macrophages U937 and human adipocyte cell lines SGBS. The effect of theobromine on in vitro cell growth, cell cycle, adipogenesis, and cytokines release in the supernatants has been evaluated. Results. Theobromine significantly inhibits the differentiati...

Journal of translational medicine, 2015

Cell death & disease, 2014

The Journal of pharmacology and experimental therapeutics, 1996

Previous studies showed that 5-fluorouracil (5-FU) is capable of enhancing the membrane reactivit... more Previous studies showed that 5-fluorouracil (5-FU) is capable of enhancing the membrane reactivity of the human colon carcinoma cell line HT-29 with a monoclonal antibody (COL-1) directed against carcinoembryonic antigen (CEA). In the present study, we show that short-term exposure (i.e., 1 hr) of cancer cells to 5-FU mediates a marked increase of CEA expression, that is concentration-dependent and lasts up to day 5 after treatment. This phenomenon is the result of the drug-mediated enhancement of the CEA expression, but not of the selection of the CEA-positive cells operated by the antimetabolite. This is supported by the finding that the increase of the CEA expression detected by cytofluorimetric analysis is observed not only in the parental HT-29 line, but also in its C22.20 subclone, endowed with a low basal level of CEA and with chemosensitivity to 5-FU lower than that of the parental cell line. Moreover, increase of CEA expression occurs not only in the plasma membrane, but al...

Cancer research, 1981

In vivo treatment of leukemic mice with the antitumor agent 5-(3,3'-dimethyl-1-triazeno)-imid... more In vivo treatment of leukemic mice with the antitumor agent 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) results in early increase of tumor-associated immunogenicity which is expected to evoke host-versus-graft responses. However, transplantation immunity is severely impaired in DTIC-treated mice due to the immunodepressant activity of the drug. It follows that the DTIC-mediated increase of tumor immunogenicity effect cannot be of therapeutic value in ordinary conditions. In the present report, we describe the results of studies aimed at restoring immunocompetence of DTIC-treated mice by means of adoptive transfer of syngeneic lymphoid cells. Infusion of spleen cells into DTIC-treated mice failed to restore graft responsiveness even in allogeneic tumor-host combinations. However, when DTIC treatment was followed by administration of cytotoxic alkylating agents such as cyclophosphamide (CY) or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), graft responsiveness was pa...

Cancer research, 1976

LSTRA and RBL-5 lymphomas induced by Moloney and Rauscher leukemia viruses, respectively, were us... more LSTRA and RBL-5 lymphomas induced by Moloney and Rauscher leukemia viruses, respectively, were used to determine whether antigenically altered tumors induced by 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide in vivo would retain their original antigenic properties and/or have new antigenic properties. The tumors became highly immunogenic in the syngeneic hosts after 4 to 8 transplant generations with drug treatment. Syngeneic mice could be protected against challenge with the parental tumor by presensitization with the drug-altered sublines while unrelated tumor lines were incapable of protecting them. The drug-altered subline of LSTRA was used for treatment of the LSTRA in conjunction with chemotherapy, and this immunochemotherapy produced significant increases in number of survivors and increases in median survival time compared to either treatment alone. Tolerance studies indicated that there are novel antigens and parental tumor antigens associated with the drug-treated sub...

Cancer research, 1977

Several murine tumors were used to determine whether the phenomenon of tumor inhibition in athymi... more Several murine tumors were used to determine whether the phenomenon of tumor inhibition in athymic "nude" mice reported previously could be extended to other tumor systems in nude as well as conventional mice. The results with the L5MF-22 tumor line were confirmed, and similar data were obtained with the K36 leukemia of AKR mice and the LAF-17 leukemia of B10.A origin. This phenomenon of tumor inhibition has been called, tentatively, radioresistant inhibition of tumor and may be explained by one of several possibilities. The immunological origin of such tumor inhibition is supported by various observations. The data on tumor cell proliferation in spleens and liver of lethally irradiated mice were similar to previous findings on hemopoietic histocompatibility-incompatible lymphomas. Additionally, the nude mice were stronger responders against lymphoma cells than were conventional hosts. Another explanation is that the tumor inhibition is due to natural cytotoxicity.

International Journal of Oncology, 2006

A number of previous studies investigated the in vitro effects of resveratrol on malignant human ... more A number of previous studies investigated the in vitro effects of resveratrol on malignant human breast epithelial cell replication. The aim of the present study was to evaluate the activity of resveratrol on human metastatic breast cancer cells. The study was performed on the MCF-7 tumor cell line. Cell growth, cell cycle perturbation and apoptosis were evaluated by trypan blue dye exclusion assay, flow cytometric analysis and confocal fluorescence microscopy. TRAP assay and Western blot analysis respectively detected levels of telomerase activity and levels of hTERT in intracellular compartments of MCF-7 cells treated with resveratrol. Resveratrol has a direct inhibitory effect on cell proliferation. The results demonstrate that the drug induces apoptosis in MCF-7 cells, in a time-and concentrationrelated manner. Our results also show that the growth-inhibitory effect of resveratrol on malignant cells is mainly due to its ability to induce S-phase arrest and apoptosis in association with reduced levels of telomerase activity. In particular, TRAP assay and Western blot analysis respectively showed that resveratrol treatment down-regulates the telomerase activity of target cells and the nuclear levels of hTERT, the reverse transcriptase subunit of the telomerase complex. In our experimental model of breast cancer, resveratrol shows direct antiproliferative and pro-apoptotic effects. Studies on telomerase function and intracellular hTERT distribution point out that this agent is endowed with additional suppressive functions on critical tumor biological properties. These results speak in favor of a potential role of resveratrol in chemoprevention/chemotherapy of breast cancer.

INTERNATIONAL JOURNAL OF ONCOLOGY, 2009

Altered expression of microRNAs (miRNAs) has been detected in cancer, suggesting that these small... more Altered expression of microRNAs (miRNAs) has been detected in cancer, suggesting that these small non-coding RNAs can act as oncogenes or tumor suppressor genes. In the present study, we investigated the expression of miRNA-17-5p, miRNA-18a, miRNA-20a, miRNA-92a, miRNA-146a, miRNA-146b and miRNA-155 by real-time quantitative RT-PCR in a panel of melanocyte cultures and melanoma cell lines and explored the possible role of miRNA-155 in melanoma cell proliferation and survival. The analyzed miRNAs were selected on the basis of previous studies strongly supporting their involvement in cancer development and/or progression. We found that miRNA-17-5p, miRNA-18a, miRNA-20a, and miRNA-92a were overexpressed, whereas miRNA-146a, miRNA-146b and miRNA-155 were down-regulated in the majority of melanoma cell lines with respect to melanocytes. Ectopic expression of miRNA-155 significantly inhibited proliferation in 12 of 13 melanoma cell lines with reduced levels of this miRNA and induced apoptosis in 4 out of 4 cell lines analyzed. In conclusion, our data further support the finding of altered miRNA expression in melanoma cells and establish for the first time that miRNA-155 is a negative regulator of melanoma cell proliferation and survival.

Proceedings of the National Academy of Sciences, 1970

L1210 leukemia was transplanted serially in CDF 1 mice treated with 5-(3,3-dimethyl-1-triazeno)im... more L1210 leukemia was transplanted serially in CDF 1 mice treated with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC, NSC 45388). After four different lines (C lines) had been treated for several generations, a marked increase in survival time of untreated mice was observed. In contrast, mice treated with DIC or immunosuppressed with cyclophosphamide succumbed earlier with generalized leukemia. Furthermore, a C line showed unusually high sensitivity to chemotherapeutic treatment with 1,3 bis(2-chloroethyl)-1-nitrosourea. The data suggest that C lines acquired strong antigenicity for CDF 1 and DBA/2 hosts. DIC treatment may have selected highly antigenic variants or induced somatic mutations resulting in the appearance of strong new transplantation antigen(s).

Molecular Immunology, 2013

Background: HIV-associated neurocognitive disorders (HAND) exist in approximately 50% of infected... more Background: HIV-associated neurocognitive disorders (HAND) exist in approximately 50% of infected individuals even after the introduction of highly active antiretroviral therapy. HIV-1 Tat has been implicated in HIV-associated neurotoxicity mediated through production of pro-inflammatory cytokines like IL-6 and IL-8 by astrocytes among others as well as oxidative stress. However, the underlying mechanism(s) in the up-regulation of IL-6 and IL-8 are not clearly understood. The present study was designed to determine the mechanism(s) responsible for IL-6 and IL-8 up-regulation by HIV-1 Tat. Methods: SVG astrocytes were transiently transfected with a plasmid encoding HIV-1 Tat. The HIV-1 Tat-mediated mRNA and protein expression levels of both IL-6 and IL-8 in SVG astrocytes were quantified using real time RT-PCR and multiplex cytokine assay respectively. We also employed immunocytochemistry for staining of IL-6 and IL-8. The underlying signaling mechanism(s) were identified using pharmacological inhibitors and siRNA for different intermediate steps involved in PI3K/Akt, p38 MAPK and JNK MAPK pathways. Appropriate controls were used in the experiments and the effect of pharmacological antagonists and siRNA were observed on both mRNA expression and protein levels. Results: Both IL-6/IL-8 mRNA and protein showed peak expressions at 6 hours and 96 hours post-transfection, respectively. Elevated levels of IL-6/IL-8 were also confirmed by immunocytochemistry. Our studies indicated that both NF-kB and AP-1 transcription factors were involved in IL-6 and IL-8 expression mediated by HIV-1 Tat; however, AP-1 was differentially activated for either cytokine. In the case of IL-6, p38δ activated AP-1 whereas JNK but not p38 MAPK was involved in AP-1 activation for IL-8 production. On the other hand both PI3K/Akt and p38 MAPK (β subunit) were found to be involved in activation of NF-κB that led to IL-6 and IL-8 production. Conclusion: Our results demonstrate HIV-1 Tat-mediated induction of both IL-6 and IL-8 in a time-dependent manner in SVG astrocytes. Furthermore, we also showed the involvement of NF-κB and AP-1 transcription factors regulated by PI3/Akt, p38 MAPK and JNK MAPK upstream signaling molecules. These results present new therapeutic targets that could be used in management of HAND.

Journal of Pharmacology and Experimental Therapeutics, 2003

The prognosis of advanced melanoma is generally poor, because this tumor commonly exhibits intrin... more The prognosis of advanced melanoma is generally poor, because this tumor commonly exhibits intrinsic or acquired resistance to chemotherapy. In an attempt to identify the underlying causes of this resistance, we studied the roles played by the DNA repair enzyme O 6-alkylguanine-DNA alkyltransferase (OGAT) and the mismatch repair (MMR) system in the sensitivity of melanoma cells to temozolomide (TMZ), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), or cis-diamminedichloroplatinum(II) (CDDP). To this end, OGAT levels and MMR efficiency of extracts of nine melanoma cell lines and selected clones derived from four of these lines were determined and correlated with the sensitivity of the respective cells to these drugs. The effectiveness of O 6-benzylguanine (BG), a specific OGAT inhib-This work was supported by the Italian Ministry of Health. J.J. and G.M. acknowledge the generous support of the Schweizerischer Nationalfonds zur Förderung der wisseschaftlichen Forschung. Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

Journal of Clinical Oncology, 2005

Purpose Tumor cell killing by anticancer drugs may be supported by their immuno- and pharmacologi... more Purpose Tumor cell killing by anticancer drugs may be supported by their immuno- and pharmacologic effects. Chemotherapy is in fact able to (A) upregulate tumor-associated antigen expression, including carcinoembryonic antigen (CEA) or other target molecules such as thymidylate synthase (TS); and (B) downregulate tumor cell resistance to the death signals induced by tumor antigen–specific cytotoxic T lymphocytes. This provides the rationale for combining chemo- and immunotherapy. Materials and Methods We describe the results of a translational phase II trial designed to evaluate the toxicity, antitumor activity and immunologic effects of gemcitabine + FOLFOX-4 (oxaliplatin, fluorouracil, and folinic acid) polychemotherapy followed by the subcutaneous administration of granulocyte macrophage colony-stimulating factor and low-dose interleukin-2 in colorectal carcinoma patients. The study involved 29 patients (16 males and 13 females with a mean age of 69 years), 21 of whom had receive...

Journal of Chemotherapy, 2001

Non-peptide antigens (e.g. glycolipids of microbial origin) presented by monocyte-associated CD1 ... more Non-peptide antigens (e.g. glycolipids of microbial origin) presented by monocyte-associated CD1 molecules to T cells appear to play an important role in host immunity against tuberculosis and other pathogenic bacteria. Since vaccination with Bacillus Calmette-Guerin (BCG) has limited efficacy, the influence of viable BCG organisms on the induction of CD1b antigen by granulocyte macrophage-colony stimulating factor (GM-CSF) has been tested in adherent mononuclear cells obtained from peripheral blood of healthy donors. The results indicate that the vaccine reduces substantially CD1b induction by GM-CSF. On the other hand, BCG was found to promote a slight increase in the expression of this molecule on target cells not exposed to GM-CSF. Attempts to reverse the antagonistic effects of BCG on GM-CSF with high concentrations of GM-CSF, alone, or associated with IL-4, were unsuccessful. Moreover, mycobacteria suppression by 10 microg/ml of rifampin, did not affect BCG influence on CD1b induction. The present results suggest that mycobacterium-induced impairment of the CD1 system could play a role in the unsatisfactory results obtained with BCG vaccination.

International Journal of Cancer, 1971

Generalized leukemia was observed on day 3 following iritra-peritoneal inoculation of leukemic (L... more Generalized leukemia was observed on day 3 following iritra-peritoneal inoculation of leukemic (L1210) ascites cells in CDF, mice. On day 3 after tumor implantation, residual viable leukemic cells were detected in the peritoneal cavities arid spleens of leukemic mice 6 h following treatment with 180 mglkg of cyclophosphaniide. Mice receiving weekly intraperitoneal injections of X-irradiated leukemic (LI210) cells for 6 weeks were resistant to a challenge of tumor cells. When incubated in vitro, spleen and bone marrow cells of immune mice were able to inactivate viable leukemic cells, as evidenced by failure of tumor growth in mice inoculated with these cells. Leukemic mice injected with immune spleen or bone-marro w cells from isogeneic mice following treatment with cyclophosphaniide survived a 60-day observation period. In one such experiment 90-day survivors were able to resist re-inoculation of tumor cells. Leukemic (D BA/2) mice inoculated with allogeneic spleen cells following cyclophosphamide treatment survived for longer periods than mice injected with isogeneic spleen cells.

Cell Death & Differentiation, 2004