Search results for "dacarbazine"

Whole-body MRI radiomics model to predict relapsed/refractory Hodgkin Lymphoma: A preliminary study.

2022

Purpose A strong prognostic score that enables a stratification of newly diagnosed Hodgkin Lymphoma (HL) to identify patients at high risk of refractory/relapsed disease is still needed. Our aim was to investigate the potential value of a radiomics analysis pipeline from whole-body MRI (WB-MRI) exams for clinical outcome prediction in patients with Hodgkin Lymphoma (HL). Materials and methods Index lesions from baseline WB-MRIs of 40 patients (22 females; mean age 31.7 ± 11.4 years) with newly diagnosed HL treated by ABVD chemotherapy regimen were manually segmented on T1-weighted, STIR, and DWI images for texture analysis feature extraction. A machine learning approach based on the Extra T…

Long-term outcome of treatment with dacarbazine, cisplatin, interferon-α and intravenous high dose interleukin-2 in poor risk melanoma patients

1998

Melanoma patients with very advanced disease are usually excluded from chemoimmunotherapy trials; however, the efficacy of intensive treatment regimens needs to be established for this patient population. This study aimed to evaluate the response rate and survival achieved with chemoimmunotherapy in very advanced melanoma patients. Forty-two patients received dacarbazine (250 mg/m2, days 1-3), cisplatin (30mg/m2, days 1-3), interferon-alpha (10 Mio IU/m2 subcutaneously, days 1-5) and intravenous interleukin-2 (18 Mio IU/m2 over 6 h, 12 h then 24 h, followed by 13.5 MioIU/m2 in 72 h). In cases of brain metastases (n = 12) radiation therapy was added. Ten patients (24%) achieved a partial res…

Human Monocytes, but not Dendritic Cells Derived from Them, Are Defective in Base Excision Repair and Hypersensitive to Methylating Agents

2007

Abstract Monocytes and dendritic cells are key players in the immune response. Because dendritic cells drive the tumor host defense, it is important that monocytes and dendritic cells survive cytotoxic tumor therapy. Although most of the anticancer drugs target DNA, the DNA repair capacity of monocytes and dendritic cells has not yet been investigated. We studied the sensitivity of monocytes and monocyte-derived dendritic cells against various genotoxic agents and found monocytes to be more sensitive to overall cell kill and apoptosis upon exposure to methylating agents (e.g., N-methyl-N′-nitro-N-nitrosoguanidine, methyl methanesulfonate, and the anticancer drug temozolomide). On the other …

Pyrrolo[2,1-d][1,2,3,5]tetrazinones deaza analogues of temozolomide with potent antitumor activity

2000

The title compounds, that hold the deaza skeleton of temozolomide, exhibited potent in vitro antiproliferative activity. An evaluation of such a biological activity indicates that the mode of action of these compounds differs from that of temozolomide and is also mechanistically unrelated to that of any known antitumor drug.

Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Pa…

2014

BackgroundThe importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans.MethodsIn this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests.ResultsWe found that chemotherapy induces lymphopenia and that a significantly hig…

A sphingosine kinase inhibitor combined with temozolomide induces glioblastoma cell death through accumulation of dihydrosphingosine and dihydroceram…

2014

AbstractGlioblastomas (GBMs) are very aggressive tumors with low chemosensitivity. The DNA-alkylating agent temozolomide (TMZ) is currently the most efficient chemotoxic drug for GBM therapy; however, many patients develop resistance to TMZ. Combining TMZ with another agent could present an improved treatment option if it could overcome TMZ resistance and avoid side effects. Sphingosine kinase inhibitors (SKIs) have emerged as anticancer agents. Sphingosine kinases are often overexpressed in tumors where their activity of phosphorylating sphingosine (Sph) contributes to tumor growth and migration. They control the levels of the pro-apoptotic ceramide (Cer) and Sph and of the pro-survival sp…

Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover

2020

This study investigated the efficacy and safety of pimasertib (MEK1/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg

Temozolomide- and fotemustine-induced apoptosis in human malignant melanoma cells: response related to MGMT, MMR, DSBs, and p53

2009

Malignant melanomas are highly resistant to chemotherapy. First-line chemotherapeutics used in melanoma therapy are the methylating agents dacarbazine (DTIC) and temozolomide (TMZ) and the chloroethylating agents BCNU and fotemustine. Here, we determined the mode of cell death in 11 melanoma cell lines upon exposure to TMZ and fotemustine. We show for the first time that TMZ induces apoptosis in melanoma cells, using therapeutic doses. For both TMZ and fotemustine apoptosis is the dominant mode of cell death. The contribution of necrosis to total cell death varied between 10 and 40%. The O(6)-methylguanine-DNA methyltransferase (MGMT) activity in the cell lines was between 0 and 1100 fmol m…

The Translesion Polymerase Rev3L in the Tolerance of Alkylating Anticancer Drugs

2009

Temozolomide and fotemustine, representing methylating and chloroethylating agents, respectively, are used in the treatment of glioma and malignant melanoma. Because chemoresistance of these tumors is a common phenomenon, identification of the underlying mechanisms is needed. Here we show that Rev3L, the catalytic subunit of the translesion DNA polymerase zeta, mediates resistance to both temozolomide and fotemustine. Rev3L knockout cells are hypersensitive to both agents. It is remarkable that cells heterozygous for Rev3L showed an intermediate sensitivity. Rev3L is not involved in the tolerance of the toxic O6-methylguanine lesion. However, a possible role of Rev3L in the tolerance of O6-…

Melanoma Clinics and Treatment

2013