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Beersheba, Israel

Besser M.J.,Ella Institute of Melanoma | Besser M.J.,Tel Aviv University
OncoImmunology | Year: 2013

The adoptive transfer of tumor-infiltrating lymphocytes (TILs) can yield durable responses in patients affected by metastatic melanoma. In particular, we have recently reported an 80% 3 year survival rate among patients who responded to this immunotherapeutic regimen. Of note, overall response rates were equal among ipilimumab-naïve and ipilimumabrefractory patients. Thus, the adoptive transfer of TILs, as a standalone therapeutic intervention or combined with other treatment modalities, bears a high clinical potential that must be optimally employed. © 2013 Landes Bioscience.

Besser M.J.,Ella Institute of Melanoma | Besser M.J.,Tel Aviv University | Hershkovitz L.,Ella Institute of Melanoma | Schachter J.,Ella Institute of Melanoma | Treves A.J.,Sheba Cancer Research Center
Clinical and Developmental Immunology | Year: 2010

Adoptive Cell Transfer (ACT) of Tumor-Infiltrating Lymphocytes (TIL) in combination with lymphodepletion has proven to be an effective treatment for metastatic melanoma patients, with an objective response rate in 50%-70% of the patients. It is based on the ex vivo expansion and activation of tumor-specific T lymphocytes extracted from the tumor and their administration back to the patient. Various TIL-ACT trials, which differ in their TIL generation procedures and patient preconditioning, have been reported. In the latest clinical studies, genetically engineered peripheral T cells were utilized instead of TIL. Further improvement of adoptive T cell transfer depends on new investigations which seek higher TIL quality, increased durable response rates, and aim to treat more patients. Simplifying this therapy may encourage cancer centers worldwide to adopt this promising technology. This paper focuses on the latest progress regarding adoptive T cell transfer, comparing the currently available protocols and discussing their advantages, disadvantages, and implication in the future. © 2010 Liat Hershkovitz et al.

Markel G.,Ella Institute of Melanoma | Markel G.,Sheba Medical Center | Markel G.,Tel Aviv University | Imazio M.,Maria Vittoria Hospital | And 4 more authors.
Clinical Cardiology | Year: 2013

The most troublesome complication of acute pericarditis is recurrent pericardial inflammation, which occurs in 15%-32% of cases. The optimal method for prevention has not been fully established; accepted modalities include nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressive agents, and pericardiectomy. Over the last years, objective clinical evidence has matured and clearly indicates the important role and beneficial clinical effect of colchicine therapy in preventing recurrent pericarditis caused by various etiologies. Colchicine-treated patients consistently display significantly fewer recurrences and longer symptom-free periods, and even when attacks occur, they are weaker and shorter in nature. Notably, pretreatment with corticosteroids substantially attenuates the efficacy of colchicine, causing significantly more recurrences and longer therapy periods. The safety profile seems superior to other drugs, such as corticosteroids and immunosuppressive drugs. Colchicine is a safe and effective modality for the treatment and prevention of recurrent pericarditis, especially as an adjunct to other modalities, because it provides a sustained benefit, superior to all current modalities. The authors have no funding, financial relationships, or conflicts of interest to disclose. © 2013 Wiley Periodicals, Inc.

Shoshan E.,University of Houston | Mobley A.K.,University of Houston | Braeuer R.R.,University of Houston | Kamiya T.,University of Houston | And 24 more authors.
Nature Cell Biology | Year: 2015

Although recent studies have shown that adenosine-to-inosine (A-to-I) RNA editing occurs in microRNAs (miRNAs), its effects on tumour growth and metastasis are not well understood. We present evidence of CREB-mediated low expression of ADAR1 in metastatic melanoma cell lines and tumour specimens. Re-expression of ADAR1 resulted in the suppression of melanoma growth and metastasis in vivo. Consequently, we identified three miRNAs undergoing A-to-I editing in the weakly metastatic melanoma but not in strongly metastatic cell lines. One of these miRNAs, miR-455-5p, has two A-to-I RNA-editing sites. The biological function of edited miR-455-5p is different from that of the unedited form, as it recognizes a different set of genes. Indeed, wild-type miR-455-5p promotes melanoma metastasis through inhibition of the tumour suppressor gene CPEB1. Moreover, wild-type miR-455 enhances melanoma growth and metastasis in vivo, whereas the edited form inhibits these features. These results demonstrate a previously unrecognized role for RNA editing in melanoma progression. © 2015 Macmillan Publishers Limited.

Burazor I.,Clinical Center Nis | Imazio M.,Maria Vittoria Hospital | Markel G.,Ella Institute of Melanoma | Markel G.,Sheba Medical Center | And 3 more authors.
Cardiology (Switzerland) | Year: 2013

Malignant pericardial effusion is a common and serious manifestation in malignancies. The origins of the malignant process include solid tumors or hematological malignancies, while primary neoplasms of the pericardium are less common. In the oncological patient, pericardial effusion may develop by several different mechanisms, namely by direct or metastatic spread of the primary process or as a complication of antineoplastic therapies. In some cases, pericardial effusion may be the first manifestation of the disease, and that is why malignancy must be excluded in every case of an acute pericardial disease with cardiac tamponade at presentation, rapidly increasing pericardial effusion and an incessant or recurrent course. Thus, the definite differentiation of malignant pericardial effusion and rapid diagnosis are of particular therapeutic and prognostic importance. Management of these patients is multidisciplinary and requires team work, but at present there is a need for further research. An individual treatment plan should be established, taking into account cancer stage, the patient's prognosis, local availability and experience. In emergency cases with cardiac tamponade or significant effusion, initial relief can be obtained with pericardiocentesis. Despite the magnitude of this serious problem, little progress has been made in the treatment of pericardial effusion secondary to malignant disease. © 2013 S. Karger AG, Basel.

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