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Prophylactic use of mTOR inhibitors and other mmunosuppressive agents in heart transplant patients

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Cellular & Molecular Immunology 2015年第1期12卷 122-124页

作者： Matteo Santoni Francesco Massari Stefano Cascinu clinica di oncologia medica AOU Ospedal Riuniti Universita Politecnica delle Marche Ancona Italy medical Oncology 'G.B Rossi' Academic Hospital University of Verona Verona Italy

Cardiac transplantation is currently the preferred choice of treatment for end-stage cardiac disease. Despite great advances have been made in the prevention and treatment of acute transplant rejection, accelerated cardiac allograft vasculopathy （CAV） still limits the long-term success of heart transplantation. CAV is a rapidly progressive form of atherosclerosis described by vascular remodeling of the graft coronary arteries that occurs uniquely in transplant recipi- ents. In the early stages, CAV is characterized by intimal proliferation, while luminal stenosis of epicardial branches, occlusion of smaller arteries and myocardial infarction occur in the later stages.

关键词： Prophylactic mTOR inhibitors

Activity and safety of pegylated liposomal doxorubicin,5-fluorouracil and folinic acid in inoperable hepatocellular carcinoma:A phase Ⅱ study

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World Journal of Gastroenterology 2007年第48期13卷 6553-6557页

作者： Giuseppe di Lorenzo Antonio Rea Chiara Carlomagno Stefano Pepe Giovannella Palmieri Roberto Labianca Antonio Chirianni Alfonso De Stefano Vincenzo Esposito Sabino De Placido Vincenzo Montesarchio dipartimento di Endocrinologia e oncologia Molecolare e clinica Università degli Studi Federico Ⅱ Naples Italy divisione di oncologia Azienda Ospedaliera Cotugno Naples Italy Oncology Section Ospedali Riuniti Bergamo Italy

AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). METHODS: Thirty-one patients with hystologically- confirmed, inoperable HCC, received combination chemotherapy with PLD 25 mg/mq on d 1, 5FU 1200 mg/mq in 48 h continuous infusion, and oral FA 30 mg on d 1 and 2 every 3 wk until disease progression or intolerable toxicity. RESULTS: The median age was 65 years (range 41-82) and 28 patients were hepatitis C virus seropositive (90%). The majority of patients were Child-Pugh Class B (55%). Two patients showed a partial response (PR), and 16 had stable disease (SD). With a median follow-up of 14 mo, the median time to progression of all evaluable patients was 4 mo (95% CI 1.7-7). Median overall survival was 9 mo (95% CI 3-24 mo). After 1 year, 9 of 18 PR/SD patients were alive. Chemotherapy was well tolerated. CONCLUSION: PLD/FU/FA combination seems capable of achieving durable stabilization of HCC. The manageable toxicity supports a role for combination with other anticancer agents.

关键词： Pegylated liposomal doxorubicin 5-fluorouracil Folinic acid Hepatocellular carcinoma

palliative care and end-stage colorectal cancer management:The surgeon meets the oncologist

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World Journal of Gastroenterology 2014年第24期20卷 7602-7621页

作者： Renato Costi Francesco Leonardi Daniele Zanoni Vincenzo Violi Luigi Roncoroni Istituto di clinica Chirurgica Generale e Terapia Chirurgica Dipartimento di Scienze ChirurgicheUniversità di ParmaAzienda Ospedaliero-Universitaria di Parma43126 ParmaItaly dipartimento Polispecialistico 1 Unità Operativa di Oncologia MedicaAzienda Ospedaliero-Universitaria di Parma43126 ParmaItaly dipartimento di Chirurgia Generale e Specialistica Ospedale di VaioAzienda Unità Sanitaria Locale di Parma43036 Fidenza (Parma)Italy

Colorectal cancer (CRC) is a common neoplasia in the Western countries, with considerable morbidity and mortality. Every fifth patient with CRC presents with metastatic disease, which is not curable with radical intent in roughly 80% of cases. Traditionally approached surgically, by resection of the primitive tumor or stoma, the management to incurable stage IV CRC patients has significantly changed over the last three decades and is nowadays multidisciplinary, with a pivotal role played by chemotherapy (CHT). This latter have allowed for a dramatic increase in survival, whereas the role of colonic and liver surgery is nowadays matter of debate. Although any generalization is difficult, two main situations are considered, asymptomatic (or minimally symptomatic) and severely symptomatic patients needing aggressive management, including emergency cases. In asymptomatic patients, new CHT regimens allow today long survival in selected patients, also exceeding two years. The role of colonic resection in this group has been challenged in recent years, as it is not clear whether the resection of primary CRC may imply a further increase in survival, thus justifying surgery-related morbidity/mortality in such a class of short-living patients. Secondary surgery of liver metastasis is gaining acceptance since, under new generation CHT regimens, an increasing amount of patients with distant metastasis initially considered non resectable become resectable, with a significant increase in long term survival. The management of CRC emergency patients still represents a major issue in Western countries, and is associated to high morbidity/mortality. Obstruction is traditionally approached surgically by colonic resection, stoma or internal by-pass, although nowadays CRC stenting is a feasible option. Nevertheless, CRC stent has peculiar contraindications and complications, and its long-term cost-effectiveness is questionable, especially in the light of recently increased survival. Per

关键词： Colorectal cancer Palliative care Multimodal treatment Chemotherapy Surgery Stenting Radiotherapy

Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea L Inghilesi Donatella Gallori Lorenzo Antonuzzo Paolo Forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani Elena Gianni Luca Boni Giacomo Laffi Francesco di Costanzo Fabio Marra dipartimento di Medicina Sperimentale e clinica Università degli Studi di Firenze oncologia medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM: To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis.

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adverse events Barcelona Clinic Liver Cancer

Treatment of gastric cancer

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World Journal of Gastroenterology 2014年第7期20卷 1635-1649页

作者： Michele Orditura Gennaro Galizia Vincenzo Sforza Valentina Gambardella Alessio Fabozzi Maria Maddalena Laterza Francesca Andreozzi Jole Ventriglia Beatrice Savastano Andrea Mabilia Eva Lieto Fortunato Ciardiello Ferdinando De Vita division of medical Oncology Dipartimento di MedicinaClinica e Sperimentale ‘F. Magrassi-A. Lanzara’Seconda Università degli Studi di Napoli80131 NaplesItaly divisione di Chirurgia oncologia Dipartimento di Scienze AnestesiologicheChirurgiche e delle EmergenzeSeconda Università degli Studi di Napoli80131 NaplesItaly

The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status

关键词： Gastric cancer Surgery Radiotherapy Adjuvant chemotherapy Palliative chemotherapy Chemoradiation

Using organotypic hippocampal slice cultures to gain insight into mechanisms responsible for the neuroprotective effects of meloxicam: a role for gamma aminobutyric and endoplasmic reticulum stress

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Neural Regeneration Research 2019年第1期14卷 65-66页

作者： Elisa Landucci Irene L.Llorente Berta Anuncibay-Soto Domenico E.Pellegrini-Giampietro Arsenio Fernández-López Sezione di Farmacologia clinica e oncologia Dipartimento di Scienze della SaluteUniversità di Firenze Department of Neurology David Geffen School of Medicine University of California área de Biología Celular Instituto de BiomedicinaUniversidad de León Neural Therapies SL Edificio Institutos de Investigación

This perspective aims to put into context the recent article by Landucci et al.(2018)on mechanisms involved in the neuroprotective effects of meloxicam on an organotypic hippocampal slice cultures(OHSCs)*** vitro cell cultures are the main method for studying large quantities of homogeneous cells in an isolated ***,the use of primary dissociated neuron,astrocyte,oligodendrocyte,microglia,or endothelial cell cultures has become a standard

关键词： gamma 文化海马机制应力蜂窝环境学习胃

Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

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World Journal of Gastroenterology 2016年第28期22卷 6345-6361页

作者： Vincenzo Sforza Erika Martinelli Fortunato Ciardiello Valentina Gambardella Stefania Napolitano Giulia Martini Carminia della Corte Claudia Cardone Marianna L Ferrara Alfonso Reginelli Giuseppina Liguori Giulio Belli Teresa Troiani oncologia medica Dipartimento di Medicina Clinica e Sperimentale "F. Magrassi e A. Lanzara" Seconda Università degli Studi di Napoli Department of medical Oncology Biomedical Research Institute INCLIVA University of Valencia Department of Internal and Experimental Medicine Magrassi-Lanzara Institute of Radiology Seconda Università di Napoli Department of Pathology Istituto Nazionale Tumori "Fond. Pascale" - IRCCS Department of General and Hepato-Pancreato-Biliary Surgery S. M. Loreto Nuovo Hospital

The prognosis of patients with metastatic colorectal cancer (mCRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies (moAbs) cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), undoubtedly represent a major step forward in the treatment of mCRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase III clinical trials among different lines of treatment. However, the anti-EGFR moAbs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary (or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR moAbs together with the various strategies evaluated to prevent, overcame or revert them.

关键词： Metastatic colorectal cancer Epidermal growth factor receptor Resistance Mutation KRAS NRAS BRAF PIK3CA MET Monoclonal antibodies

Long lasting response to second-line everolimus in kidney cancer

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World Journal of clinical Cases 2013年第5期1卷 166-168页

作者： Antonella Virtuoso Tania Policastro Michela Izzo Piera Federico Carlo Buonerba Pasquale Rescigno Giuseppe di Lorenzo dipartimento di Endocrinologia e oncologia Molecolare e clinica Università degli Studi Federico Ⅱ80131 NaplesItaly Deparment of clinical Medicine University Federico Ⅱ of Naples80131 Naples Italy

In the case presented here, everolimus was administered after first line therapy with sunitinib in a patient with metastatic renal cell carcinoma. The safety profile was excellent. The prolonged progression-free survival(PFS) obtained with everolimus in this case is of peculiar interest, as it is a multiple of the median PFS obtained in with everolimus in the regulatory trial. Such finding suggests that a subset of patients with renal cell carcinma may particularly benefit from everolimus.

关键词： Metastatic renal cell carcinoma Everolimus(RAD001) Sunitinib Progression-free survival

Tailored therapy in patients treated with fluoropyrimidines: focus on the role of dihydropyrimidine dehydrogenase

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Cancer Drug Resistance 2019年第3期2卷 787-802页

作者： Filippo Merloni Nicoletta Ranallo Laura Scortichini Riccardo Giampieri Rossana Berardi Scuola di Specializzazione in oncologia Universita Politecnica delle MarcheAncona 60121Italy clinica Oncologica UniversitàPolitecnica delle MarcheAOU Ospedali RiunitiAncona 60126Italy

Fluoropyrimidines are widely used in the treatment of solid tumors, mainly gastrointestinal, head and neck and breast cancer. dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for catabolism of 5-FU and it is encoded by DPYD gene. To date, many known polymorphisms cause DPD deficiency and subsequent increase of 5-FU toxicity. In addition, reduced inactivation of 5-FU could lead to increased 5-FU intracellular concentration and augmented efficacy of this drugs. Therefore DPD expression, particularly intratumoral, has been investigated as predictive and prognostic marker in 5-FU treated patients. There also seems to be a tendency to support the correlation between DPD expression and response/survival in patients treated with fluoropyrimidine even if definitive conclusions cannot be drawn considering that some studies are conflicting. Therefore, the debate on intratumoral DPD expression as a potential predictor and prognostic marker in patients treated with fluoropyrimidines is still open. Four DPD-polymorphisms are the most relevant for their frequency in population and clinical relevance. Many studies demonstrate that treating a carrier of one of these polymorphisms with a full dose of fluoropyrimidine can expose patient to a severe, even life-threatening, toxicity. Severe toxicity is reduced if this kind of patients received a dose-adjustment after being genotyped. CPIC (clinical Pharmacogenetics Implementation Consortium) is an International Consortium creating guidelines for facilitating use of pharmacogenetic tests for patient care and helps clinicians ensuring a safer drug delivery to the patient. Using predictive DPD deficiency tests in patients receiving 5FU-based chemotherapy, in particular for colorectal cancer, has proven to be a cost-effective strategy.

关键词： 5-fluorouracil fluoropyrimidines chemotherapy dihydropyrimidine dehydrogenase dihydropyrimidine dehydrogenase DPYD CPIC polymorphisms