9 results on '"Lucchesi, Alessandro"'
Search Results
2. Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report.
- Author
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Gardini, Andrea Casadei, Chiadini, Elisa, Faloppi, Luca, Marisi, Giorgia, Delmonte, Angelo, Scartozzi, Mario, Loretelli, Cristian, Lucchesi, Alessandro, Oboldi, Devil, Dubini, Alessandra, Frassineti, Giovanni Luca, Ulivi, Paola, and Casadei Gardini, Andrea
- Subjects
SORAFENIB ,LUNG cancer ,CARCINOGENS ,LIVER cancer ,TUMORS ,HEPATOCELLULAR carcinoma ,LIVER tumors ,LUNG tumors ,MULTIPLE tumors ,GENETIC mutation ,TRANSFERASES ,UREA ,TREATMENT effectiveness ,VITAMIN B complex ,VITAMIN therapy ,THERAPEUTICS - Abstract
Background: Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug.Case Presentation: Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity.Conclusions: Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
3. Paraneoplastic lipase and amylase production in a patient with small-cell lung cancer: case report.
- Author
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Gardini, Andrea Casadei, Mariotti, Marita, Lucchesi, Alessandro, Pini, Sara, Valgiusti, Martina, Bravaccini, Sara, Del Monte, Angelo, Burgio, Marco Angelo, Marisi, Giorgia, Amadori, Dino, Frassineti, Giovanni Luca, and Casadei Gardini, Andrea
- Subjects
SMALL cell lung cancer ,CANCER treatment ,LIPASES ,AMYLASES ,EPITHELIUM ,PEPTIDE hormones ,NEURAL crest ,DISEASE complications ,LUNG cancer ,LUNG tumors ,PARANEOPLASTIC syndromes ,TREATMENT effectiveness - Abstract
Background: Small-cell lung cancer (SCLC) is known to express antigens of both the neural crest and epithelium, and to secrete polypeptide hormones and enzymes. Anecdotal reports correlate lung cancer with marked hyperamylasemia, and a review of the literature reveals only one case of metastatic SCLC linked to high paraneoplastic lipase production.Case Presentation: We present the case of a patient with metastatic SCLC who showed both lipase and pancreatic isoamylase elevation in the absence of acute pancreatitis. Chemotherapy resulted in a rapid reduction in serum lipase and in pancreatic isoamylase which was correlated with the radiological response of the tumor to therapy. Lipase and pancreatic isoamylase expression in tumor cells from the lung biopsy was confirmed by immunohistochemical staining.Conclusions: This is a very rare case of paraneoplastic syndrome linked to metastatic SCLC. The enzymes secreted could be used as markers of response to treatment until clonal selection mechanisms and intratumor heterogeneity induce changes in biochemical characteristics and consequently in tumor behavior. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
4. IL-17/IL-10 double-producing T cells: new link between infections, immunosuppression and acute myeloid leukemia.
- Author
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Musuraca, Gerardo, De Matteis, Serena, Napolitano, Roberta, Papayannidis, Cristina, Guadagnuolo, Viviana, Fabbri, Francesco, Cangini, Delia, Ceccolini, Michela, Giannini, Maria Benedetta, Lucchesi, Alessandro, Ronconi, Sonia, Mariotti, Paolo, Savini, Paolo, Tani, Monica, Fattori, Pier Paolo, Guidoboni, Massimo, Martinelli, Giovanni, Zoli, Wainer, Amadori, Dino, and Carloni, Silvia
- Subjects
ACUTE myeloid leukemia ,TUMOR growth ,IMMUNE system ,IMMUNOTHERAPY ,IMMUNOSUPPRESSIVE agents - Abstract
Background: Acute myeloid leukemia (AML) is an incurable disease with fatal infections or relapse being the main causes of death in most cases. In particular, the severe infections occurring in these patients before or during any treatment suggest an intrinsic alteration of the immune system. In this respect, IL-17-producing T helper (Th17) besides playing a key role in regulating inflammatory response, tumor growth and autoimmune diseases, have been shown to protect against bacterial and fungal pathogens. However, the role of Th17 cells in AML has not yet been clarified. Methods: T cell frequencies were assessed by flow cytometry in the peripheral blood of 30 newly diagnosed AML patients and 30 age-matched healthy volunteers. Cytokine production was determined before and after culture of T cells with either Candida Albicans or AML blasts. Statistical analyses were carried out using the paired and unpaired two-tailed Student's t tests and confirmed with the non parametric Wilcoxon signed-rank test. Results: A strong increase of Th17 cells producing immunosuppressive IL-10 was observed in AML patients compared with healthy donors. In addition, stimulation of AML-derived T cells with a Candida albicans antigen induced significantly lower IFN-γ production than that observed in healthy donors; intriguingly, depletion of patient Th17 cells restored IFN-γ production after stimulation. To address the role of AML blasts in inducing Th17 alterations, CD4+ cells from healthy donors were co-cultured with CD33+ blasts: data obtained showed that AML blasts induce in healthy donors levels of IL-10-producing Th17 cells similar to those observed in patients. Conclusions: In AML patients altered Th17 cells actively cause an immunosuppressive state that may promote infections and probably tumor escape. Th17 cells could thus represent a new target to improve AML immunotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
5. Separate episodes of capillary leak syndrome and pulmonary hypertension after adjuvant gemcitabine and three years later after nab-paclitaxel for metastatic disease.
- Author
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Gardini, Andrea Casadei, Aquilina, Michele, Oboldi, Devil, Lucchesi, Alessandro, Carloni, Silvia, Tenti, Elena, Burgio, Marco Angelo, Amadori, Dino, Frassineti, Giovanni Luca, and Casadei Gardini, Andrea
- Subjects
CAPILLARY leak syndrome ,PULMONARY hypertension ,RARE diseases ,CANCER-related mortality ,PACLITAXEL ,BLOOD testing ,PANCREATECTOMY ,DUCTAL carcinoma ,CANCER chemotherapy ,THERAPEUTICS - Abstract
Background: Systemic capillary leak syndrome is a rare disease with a high mortality rate. This syndrome is characterised by generalised edema, hypotension, hemoconcentration, and hypoproteinemia. The cause is the sudden onset of capillary hyperpermeability with extravasations of plasma from the intravascular to the extravascular compartment. We present the case of a patient who experienced two episodes of systemic capillary leak syndrome and pulmonary hypertension; the first after gemcitabine in an adjuvant setting and the second three years later after treatment with nab-paclitaxel for metastatic disease.Case Presentation: A 65-year-old patient underwent a pancreatectomy in January 2010 for ductal carcinoma (pT3 N0 M0, stage IIa), followed by adjuvant chemotherapy. Seven days after the last cycle, she developed dyspnea associated with orthopnea and cough. A transthoracic cardiac ecocolordoppler was performed, with evidence of pulmonary hypertension (58 mmHg). Blood tests showed an increase in creatinine, pro-BNP and D-Dimer. She began high-dose diuretic therapy combined with cortisone. After a month, the patient was eupneic and the anasarca had resolved. We decided gradually to reduce the steroid and diuretic therapy. After ten days of the reduction, the patient began to re-present the same symptoms after treatment with gemcitabine. Corticosteroid therapy was restored with rapid clinical benefit and decreased pro-BNP after a week of treatment. After two years, the disease returned. As a first line treatment, it was decided to use nab-paclitaxel 100 mg/m2 weekly. After two doses, followed by approximately 14 days of treatment, the patient developed acute respiratory distress syndrome. The clinical suspicion was a relapse of capillary leak syndrome and treatment with a high-dose diuretic (furosemide 250 mg daily) was started combined with cortisone (40 mg methylprednisolone). The patient showed a progressive clinical benefit.Conclusions: In patients treated with gemcitabine and nab-paclitaxel who experience a sudden onset of diffuse edema with respiratory distress, capillary leak syndrome should be suspected. Immediate treatment with corticosteroids may be life-saving. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
6. Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients
- Author
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Serena De Matteis, Giovanni Martinelli, Giulia Abbati, Tania Rossi, Roberta Napolitano, Gerardo Musuraca, Daniele Calistri, Chiara Molinari, Pier Paolo Fattori, Andrea Ghelli Luserna di Rorà, Massimiliano Bonafè, Alessandro Lucchesi, Martina Ghetti, Antonio Cuneo, Gian Matteo Rigolin, De Matteis, Serena, Molinari, Chiara, Abbati, Giulia, Rossi, Tania, Napolitano, Roberta, Ghetti, Martina, Di Rorà, Andrea Ghelli Luserna, Musuraca, Gerardo, Lucchesi, Alessandro, Rigolin, Gian Matteo, Cuneo, Antonio, Calistri, Daniele, Fattori, Pier Paolo, Bonafè, Massimiliano, and Martinelli, Giovanni
- Subjects
Genetics and Molecular Biology (all) ,Male ,Chronic lymphocytic leukemia ,lcsh:Medicine ,Adaptive Immunity ,Biochemistry ,Interleukin-23 ,T-Lymphocytes, Regulatory ,0302 clinical medicine ,Candida albicans ,Aged, 80 and over ,medicine.diagnostic_test ,Gene Expression Regulation, Leukemic ,CLL ,Effector-like Tregs ,Plasticity ,Tregs ,Biochemistry, Genetics and Molecular Biology (all) ,General Medicine ,Middle Aged ,Acquired immune system ,Phenotype ,Treg ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Effector-like Treg ,Cytokines ,Female ,Immunosuppressive Agents ,T cell ,chemical and pharmacologic phenomena ,Peripheral blood mononuclear cell ,General Biochemistry, Genetics and Molecular Biology ,NO ,Flow cytometry ,03 medical and health sciences ,Interferon-gamma ,Immune system ,medicine ,Humans ,Aged ,Innate immune system ,business.industry ,Research ,Gene Expression Profiling ,lcsh:R ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Immunity, Innate ,Lymphocyte Subsets ,Immunology ,business ,030215 immunology - Abstract
Background In chronic lymphocytic leukemia (CLL) disease onset and progression are influenced by the behavior of specific CD4+ T cell subsets, such as T regulatory cells (Tregs). Here, we focused on the phenotypic and functional characterization of Tregs in CLL patients to improve our understanding of the putative mechanism by which these cells combine immunosuppressive and effector-like properties. Methods Peripheral blood mononuclear cells were isolated from newly diagnosed CLL patients (n = 25) and healthy volunteers (n = 25). The phenotypic and functional characterization of Tregs and their subsets was assessed by flow cytometry. In vitro analysis of TH1, TH2, TH17 and Tregs cytokines was evaluated by IFN-γ, IL-4, IL-17A and IL-10 secretion assays. The transcriptional profiling of 84 genes panel was evaluated by RT2 Profiler PCR Array. Statistical analysis was carried out using exact non parametric Mann–Whitney U test. Results In all CLL samples, we found a significant increase in the frequency of IL-10-secreting Tregs and Tregs subsets, a significant rise of TH2 IL-4+ and TH17 IL-17A+ cells, and a higher percentage of IFN-γ/IL-10 and IL-4/IL-10 double-releasing CD4+ T cells. In addition, we also observed the up-regulation of innate immunity genes and the down-regulation of adaptive immunity ones. Conclusions Our data show that Tregs switch towards an effector-like phenotype in CLL patients. This multifaceted behavior is accompanied by an altered cytokine profiling and transcriptional program of immune genes, leading to a dysfunction in immune response in the peripheral blood environment of CLL patients. Electronic supplementary material The online version of this article (10.1186/s12967-018-1545-0) contains supplementary material, which is available to authorized users.
- Published
- 2018
7. Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report.
- Author
-
Casadei Gardini A, Chiadini E, Faloppi L, Marisi G, Delmonte A, Scartozzi M, Loretelli C, Lucchesi A, Oboldi D, Dubini A, Frassineti GL, and Ulivi P
- Subjects
- Aged, Carcinoma, Hepatocellular genetics, Carcinoma, Non-Small-Cell Lung genetics, Humans, Liver Neoplasms genetics, Lung Neoplasms genetics, Male, Mutation, Neoplasms, Multiple Primary drug therapy, Neoplasms, Multiple Primary genetics, Niacinamide administration & dosage, Niacinamide therapeutic use, Phenylurea Compounds therapeutic use, Proto-Oncogene Proteins B-raf genetics, Sorafenib, Treatment Outcome, Carcinoma, Hepatocellular drug therapy, Carcinoma, Non-Small-Cell Lung drug therapy, Liver Neoplasms drug therapy, Lung Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds administration & dosage
- Abstract
Background: Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug., Case Presentation: Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity., Conclusions: Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients.
- Published
- 2016
- Full Text
- View/download PDF
8. Paraneoplastic lipase and amylase production in a patient with small-cell lung cancer: case report.
- Author
-
Casadei Gardini A, Mariotti M, Lucchesi A, Pini S, Valgiusti M, Bravaccini S, Del Monte A, Burgio MA, Marisi G, Amadori D, and Frassineti GL
- Subjects
- Fatal Outcome, Humans, Male, Middle Aged, Amylases blood, Lipase blood, Lung Neoplasms enzymology, Paraneoplastic Syndromes enzymology, Small Cell Lung Carcinoma enzymology
- Abstract
Background: Small-cell lung cancer (SCLC) is known to express antigens of both the neural crest and epithelium, and to secrete polypeptide hormones and enzymes. Anecdotal reports correlate lung cancer with marked hyperamylasemia, and a review of the literature reveals only one case of metastatic SCLC linked to high paraneoplastic lipase production., Case Presentation: We present the case of a patient with metastatic SCLC who showed both lipase and pancreatic isoamylase elevation in the absence of acute pancreatitis. Chemotherapy resulted in a rapid reduction in serum lipase and in pancreatic isoamylase which was correlated with the radiological response of the tumor to therapy. Lipase and pancreatic isoamylase expression in tumor cells from the lung biopsy was confirmed by immunohistochemical staining., Conclusions: This is a very rare case of paraneoplastic syndrome linked to metastatic SCLC. The enzymes secreted could be used as markers of response to treatment until clonal selection mechanisms and intratumor heterogeneity induce changes in biochemical characteristics and consequently in tumor behavior.
- Published
- 2016
- Full Text
- View/download PDF
9. Separate episodes of capillary leak syndrome and pulmonary hypertension after adjuvant gemcitabine and three years later after nab-paclitaxel for metastatic disease.
- Author
-
Casadei Gardini A, Aquilina M, Oboldi D, Lucchesi A, Carloni S, Tenti E, Burgio MA, Amadori D, and Frassineti GL
- Subjects
- Aged, Albumins administration & dosage, Albumins therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Capillary Leak Syndrome diagnosis, Chemotherapy, Adjuvant, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Deoxycytidine therapeutic use, Female, Humans, Hypertension, Pulmonary diagnosis, Paclitaxel administration & dosage, Paclitaxel therapeutic use, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Time Factors, Tomography, X-Ray Computed, Ultrasonography, Doppler, Gemcitabine, Albumins adverse effects, Capillary Leak Syndrome etiology, Deoxycytidine analogs & derivatives, Hypertension, Pulmonary etiology, Paclitaxel adverse effects, Pancreatic Neoplasms complications
- Abstract
Background: Systemic capillary leak syndrome is a rare disease with a high mortality rate. This syndrome is characterised by generalised edema, hypotension, hemoconcentration, and hypoproteinemia. The cause is the sudden onset of capillary hyperpermeability with extravasations of plasma from the intravascular to the extravascular compartment. We present the case of a patient who experienced two episodes of systemic capillary leak syndrome and pulmonary hypertension; the first after gemcitabine in an adjuvant setting and the second three years later after treatment with nab-paclitaxel for metastatic disease., Case Presentation: A 65-year-old patient underwent a pancreatectomy in January 2010 for ductal carcinoma (pT3 N0 M0, stage IIa), followed by adjuvant chemotherapy. Seven days after the last cycle, she developed dyspnea associated with orthopnea and cough. A transthoracic cardiac ecocolordoppler was performed, with evidence of pulmonary hypertension (58 mmHg). Blood tests showed an increase in creatinine, pro-BNP and D-Dimer. She began high-dose diuretic therapy combined with cortisone. After a month, the patient was eupneic and the anasarca had resolved. We decided gradually to reduce the steroid and diuretic therapy. After ten days of the reduction, the patient began to re-present the same symptoms after treatment with gemcitabine. Corticosteroid therapy was restored with rapid clinical benefit and decreased pro-BNP after a week of treatment. After two years, the disease returned. As a first line treatment, it was decided to use nab-paclitaxel 100 mg/m2 weekly. After two doses, followed by approximately 14 days of treatment, the patient developed acute respiratory distress syndrome. The clinical suspicion was a relapse of capillary leak syndrome and treatment with a high-dose diuretic (furosemide 250 mg daily) was started combined with cortisone (40 mg methylprednisolone). The patient showed a progressive clinical benefit., Conclusions: In patients treated with gemcitabine and nab-paclitaxel who experience a sudden onset of diffuse edema with respiratory distress, capillary leak syndrome should be suspected. Immediate treatment with corticosteroids may be life-saving.
- Published
- 2013
- Full Text
- View/download PDF
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