Anticancer effects of imatinib via immunostimulation.

the Institut National de la Santé et de la Recherche Médicale (INSERM) U1015, IGR, Villejuif, France
Nature medicine (Impact Factor: 28.05). 09/2011; 17(9):1050-1. DOI: 10.1038/nm.2429
Source: PubMed
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    ABSTRACT: In vitro and in vivo studies have identified that low-frequency ultrasound (US) and microbubbles (MBs) mediate tumor inhibitory effects. However, the application of US in the clinical setting remains unclear. The aim of the present study was to investigate the clinically therapeutic effect of 20 kHz US in combination with MBs for the treatment of hepatic carcinoma. A 71-year-old male with a hepatic malignant tumor was admitted to Nantong University Affiliated Nantong Tumor Hospital (Nantong, China). The patient was subsequently sonicated with 20 kHz US and MBs over a period of five days. The low-frequency US parameters were set at 20 kHz, 2 W/cm(2), duty cycle 40% (on 2 sec, off 3 sec) for a duration of 5 min each day for a total of five days. Computed tomography (CT), contrast-enhanced US (CEUS) and carbohydrate antigen 19-9 (CA19-9) tests were performed to evaluate the therapeutic effects. Although the tumor size increased marginally on CT from 5.4 to 5.6 cm after US treatment, the intensity and enhanced-areas on the CT scans and CEUS decreased. The abdominal lymph node decreased in size, from 2.2 to 1.9 cm, and CA19-9 levels decreased from the pretreatment value of 2,007 to 734 U/ml. Therapy with low-frequency US combined with MBs may exhibit an antivasculature effect and may be used as a palliative treatment for patients with unresectable hepatic malignant tumors.
    Oncology letters 03/2015; 9(3):1249-1253. DOI:10.3892/ol.2014.2812 · 0.99 Impact Factor
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    ABSTRACT: Tumor development requires accomplices among white blood cells. Other than macrophages, mast cells have been observed to support the outgrowth of certain neoplasias because of their proangiogenic properties. In some tumor settings, however, mast cells may have a protective role, exerted by their proinflammatory mediators. In prostate cancer, no conclusive data on mast cell function were available. Here, we discuss recent work on the role of mast cells in mouse and human prostate cancer, showing that mast cells can behave alternatively as dangerous promoters, innocent bystanders, or essential guardians of tumors, according to the stage and origin of transformed cells. In particular, mast cells are essential for the outgrowth of early-stage tumors due to their matrix metalloproteinase-9 production, become dispensable in advanced-stage, post-epithelial-to-mesenchymal transition, and are protective against neuroendocrine prostate tumor variants. The common expression of c-Kit by mast cells and neuroendocrine clones suggests a possible competition for the ligand Stem cell factor and offers the chance of curing early-stage disease while preventing neuroendocrine tumors using c-Kit-targeted therapy. This review discusses the implications of these findings on the advocated mast cell-targeted cancer therapy and considers future directions in the study of mast cells and their interactions with other c-Kit-expressing cells.
    Cancer Research 02/2012; 72(4):831-5. DOI:10.1158/0008-5472.CAN-11-3110 · 9.28 Impact Factor
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    ABSTRACT: Mutations activating the receptor tyrosine kinase c-Kit occur commonly in melanomas arising on mucosal membranes and acral skin. Clinical studies have demonstrated that selective inhibition of c-Kit is effective in treating patients with c-Kit mutant gastrointestinal stromal tumors, but c-Kit inhibitor activity has been disappointing in c-Kit mutant melanoma patients. Activated c-Kit utilises phosphatidylinositol 3-kinase (PI3K) signalling as the dominant effector of cell proliferation and survival with the mitogen-activated protein kinase (MAPK) cascade serving as an ancillary survival pathway. We confirmed that these pathways are re-activated in melanoma cells with acquired resistance to c-Kit inhibitors and that these resistant sublines remain sensitive to the concurrent inhibition of MAPK and PI3K signalling. These findings suggest that durable responses in c-Kit mutant melanoma may require combination therapies that selectively inhibit critical downstream proliferative and survival pathways. We also discuss the interaction between targeted therapies and anti-tumor immune responses and the need to consider immunotherapies in new combinatorial treatment approaches.