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Pituitary Apr 2018Non-functioning pituitary carcinomas (NFPC) are defined as tumours of adenophyseal origin with craniospinal or systemic dissemination, with the absence of a hormonal... (Review)
Review
Non-functioning pituitary carcinomas (NFPC) are defined as tumours of adenophyseal origin with craniospinal or systemic dissemination, with the absence of a hormonal hypersecretion syndrome. These are a histologically heterogenous group of tumours, comprising gonadotroph, null cell, "silent" tumours of corticotroph, somatotroph or lactotroph cell lineages as well as plurihormonal Pit-1 tumours. NFPC are exceedingly rare, and hence few cases have been described. This review has identified 38 patients with NFPC reported in the literature. Recurrent invasive non-functioning pituitary adenomas (NFPA) were observed in a majority of patients. Various factors have been identified as markers of the potential for aggressive behaviour, including rapid tumour growth, growth after radiotherapy, gain or shift of hormone secretion and raised proliferative markers. Typically, there is a latency of several years from the original presentation with an NFPA to identification of metastases and only 5 cases reported with rapidly progressive malignant disease within 1 month of presentation. Therapeutic options include debulking surgery, radiation therapy and chemotherapy with temozolomide recommended as first line systemic treatment. Although long-term survivors are described, prognosis remains generally very poor (median survival 8 months). Improvements in molecular tumour profiling may assist in predicting tumour behaviour, guide therapeutic choices and identify novel therapies.
Topics: Adenoma; Animals; Cell Transformation, Neoplastic; Dacarbazine; Humans; Pituitary Neoplasms; Temozolomide
PubMed: 29299820
DOI: 10.1007/s11102-017-0857-z -
Melanoma Research Aug 2020We observed several cases of hypotension associated with high-dose dacarbazine. We conducted a retrospective observational analysis of all patients treated with...
We observed several cases of hypotension associated with high-dose dacarbazine. We conducted a retrospective observational analysis of all patients treated with high-dose dacarbazine from January 2018 to August 2019 in Oscar Lambret Center, Lille, France. In our study, a total of 23 patients in outpatient care were analyzed, they underwent 57 treatment cycles. We observed 8 episodes of hypotension in 7 of the 23 consecutive treated patients (30.4%). We discuss herein several hypotheses explaining dacarbazine-induced hypotension. Dacarbazine high dose and administration methods seem to be the main causes of hypotension adverse events. Administration methods include administration duration, which should be above 2 hours, concomitant hydration with 500 ml 0.9% sodium chloride, and UV-resistant pump tube downstream the administration tree.
Topics: Acute Disease; Antineoplastic Agents, Alkylating; Dacarbazine; Female; Humans; Hypotension; Male; Retrospective Studies
PubMed: 32141965
DOI: 10.1097/CMR.0000000000000659 -
JCO Oncology Practice Jul 2022
Topics: Dacarbazine; Hodgkin Disease; Humans
PubMed: 35420909
DOI: 10.1200/OP.22.00161 -
Bioorganic Chemistry Mar 2022Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. This study aimed to...
OBJECTIVE
Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. This study aimed to investigate caffeine's ability to enhance the effects of dacarbazine in vitro.
MATERIALS AND METHODS
Murine melanoma B16F10 cells were treated 24 h with 1-40 µM caffeine. We evaluated cytotoxicity, DNA damage, apoptosis, and oxidative lesion induced by dacarbazine associated with caffeine. The metabolization of these drugs, as well as immunocytochemical labeling, were also evaluated.
CONCLUSIONS
The pre-treatment with caffeine showed to be more effective. Caffeine potentiated dacarbazine-induced cytotoxic effects by increasing dacarbazine biotransformation, apoptosis, DNA damage, and malondialdehyde levels; also, caffeine reduced Ki67 and ERK1/2 nuclear labeling and increased p53 labeling in B16F10 cells. In our experiment, caffeine promoted modifications associated with dacarbazine metabolism by viable cells potentiating this antineoplastic drug. These promising results should be further evaluated in experimental models in vivo.
Topics: Animals; Antineoplastic Agents; Apoptosis; Caffeine; Cell Line, Tumor; Dacarbazine; Melanoma; Mice
PubMed: 34979447
DOI: 10.1016/j.bioorg.2021.105576 -
Journal of Experimental & Clinical... Feb 2016Temozolomide (TMZ), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. However, the efficacy of TMZ is often limited by the... (Review)
Review
Temozolomide (TMZ), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. However, the efficacy of TMZ is often limited by the development of resistance. Recently, studies have found that TMZ treatment could induce autophagy, which contributes to therapy resistance in glioma. To enhance the benefit of TMZ in the treatment of glioblastomas, effective combination strategies are needed to sensitize glioblastoma cells to TMZ. In this regard, as autophagy could promote cell survival or autophagic cell death, modulating autophagy using a pharmacological inhibitor, such as chloroquine, or an inducer, such as rapamycin, has received considerably more attention. To understand the effectiveness of regulating autophagy in glioblastoma treatment, this review summarizes reports on glioblastoma treatments with TMZ and autophagic modulators from in vitro and in vivo studies, as well as clinical trials. Additionally, we discuss the possibility of using autophagy regulatory compounds that can sensitive TMZ treatment as a chemotherapy for glioma treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Autophagy; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Chloroquine; Clinical Trials as Topic; Dacarbazine; Drug Resistance, Neoplasm; Drug Synergism; Glioblastoma; Humans; Sirolimus; Temozolomide
PubMed: 26830677
DOI: 10.1186/s13046-016-0303-5 -
Tumour Biology : the Journal of the... Jan 2016Adjuvant temozolomide (TMZ)-based chemoradiation is the standard of care for most glioblastoma patients (GBMs); however, a large proportion of these patients do not... (Review)
Review
Adjuvant temozolomide (TMZ)-based chemoradiation is the standard of care for most glioblastoma patients (GBMs); however, a large proportion of these patients do not respond to TMZ. Silencing of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is thought to induce chemosensitivity, and testing for methylation may allow for patient stratification; however, this has yet to become routine clinical practice despite an abundance of literature on the subject. The databases PubMed, Embase, The Cochrane Library, Science Direct and Medline were searched for relevant articles published between 1999 and 2015. Articles utilising MGMT testing in glioblastomas, and treatment of glioblastomas with temozolomide were assessed. Immunohistochemistry, methylation-specific PCR (MSP), reverse transcriptase PCR, pyrosequencing and bisulphite sequencing were the main testing methods identified. Nested-MSP techniques produced poor correlation with survival, whilst bisulphite sequencing showed no evident benefit over MSP. Testing is limited by sample quality and contamination; however, efforts are made to minimise this. Strong evidence for MGMT-based personalised therapy was presented in the elderly but remains controversial in the entire GBM population. MGMT testing presents many obstacles yet to be overcome, and these warrant attention prior to the routine implementation of MGMT testing to aid decision making in GBMs. However, there is evidence to support its use, particularly in the elderly.
Topics: Aged; DNA Methylation; Dacarbazine; Disease Progression; Disease-Free Survival; Gene Silencing; Humans; Neoplasms; O(6)-Methylguanine-DNA Methyltransferase; Precision Medicine; Promoter Regions, Genetic; Reproducibility of Results; Temozolomide; Treatment Outcome
PubMed: 26518768
DOI: 10.1007/s13277-015-4240-2 -
Experimental Cell Research Dec 2023Metabolic adaptations are central for carcinogenesis and response to therapy, but little is known about the contribution of mitochondrial dynamics to the response of...
Metabolic adaptations are central for carcinogenesis and response to therapy, but little is known about the contribution of mitochondrial dynamics to the response of glioma cells to the standard treatment with temozolomide (TMZ). Glioma cells responded to TMZ with mitochondrial mass increased and the production of round structures of dysfunctional mitochondria. At single-cell level, asymmetric mitosis contributed to the heterogeneity of mitochondrial levels. It affected the fitness of cells in control and treated condition, indicating that the mitochondrial levels are relevant for glioma cell fitness in the presence of TMZ.
Topics: Humans; Temozolomide; Dacarbazine; Apoptosis; Cell Line, Tumor; Glioma; Mitochondria; Antineoplastic Agents, Alkylating; Brain Neoplasms; Drug Resistance, Neoplasm
PubMed: 37866459
DOI: 10.1016/j.yexcr.2023.113825 -
International Journal of Oncology Sep 2017Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain tumor. Despite treatment with surgery, radiotherapy, and chemotherapy with the drug... (Review)
Review
Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain tumor. Despite treatment with surgery, radiotherapy, and chemotherapy with the drug temozolomide, the expected survival after diagnosis remains low. The median survival is only 14.6 months and the two-year survival is a mere 30%. One reason for this is the heterogeneity of GBM including the presence of glioblastoma cancer stem cells (GSCs). GSCs are a subset of cells with the unique ability to proliferate, differentiate, and create tumors. GSCs are resistant to chemotherapy and radiation and thought to play an important role in recurrence. In order to effectively treat GBM, a drug must be identified that can kill GSCs. The ionophore salinomycin has been shown to kill cancer stem cells and is therefore a promising future treatment for GBM. This study focuses on salinomycin's potential to treat GBM including its ability to reduce the CSC population, its toxicity to normal brain cells, its mechanism of action, and its potential for combination treatment.
Topics: Brain; Dacarbazine; Glioblastoma; Humans; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Pyrans; Temozolomide
PubMed: 28766685
DOI: 10.3892/ijo.2017.4082 -
Chinese Clinical Oncology Aug 2017Tumor treating fields (TTF, Optune®), one of the low-intensity alternating electric fields, have been demonstrated to disrupt mitosis and inhibit tumor growth with... (Review)
Review
BACKGROUND
Tumor treating fields (TTF, Optune®), one of the low-intensity alternating electric fields, have been demonstrated to disrupt mitosis and inhibit tumor growth with antimitotic properties in a variety of tumor types. The Food and Drug Administration (FDA) of the United States approved TTF for recurrent GBM and newly diagnosed GBM in 2011 and 2015, respectively.
METHODS
A systematic review was conducted regarding the relevant studies published between January 1, 2000, and May 31, 2017 in PubMed database. The search term included "Tumor Treating Fields", "Optune", "TTF", "Novocure", and "GBM". This review summarizes the mechanism of action, efficacy, and adverse events based on pre-clinical studies and clinical trials for TTF in GBM.
RESULTS
Pre-clinical studies showed that TTF could inhibit tumor growth in vitro and in vivo by disrupting mitosis, inducing cell cycle arrest and apoptosis. Two randomized phase III trials evaluated the efficacy and safety of TTF in GBM patients. It was revealed that the combination of TTF and standard chemotherapy (temozolomide) prolonged the progression-free survival (PFS) and overall survival (OS) without systemic safety issues in newly diagnosed GBM (EF-14 trial). For recurrent GBM, the efficacy of TTF monotherapy was shown to be equivalent in PFS and OS without systemic adverse events when compared to the control group that received best physicians-chosen chemotherapies (EF-11 trial).
CONCLUSIONS
The advantages of TTF in GBM treatment, including non-invasive antitumor effect, superior therapeutic benefit in combination with chemotherapy, and minimal systematic toxicity, have been demonstrated in pre-clinical data and randomized phased III clinical trials. Future investigations will be needed to explore combinations of chemotherapy, radiation therapy, targeted therapy, as well as immunotherapy with this novel anti-tumor treatment modality to achieve additive or synergistic therapeutic benefit for GBM and other solid tumors.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Dacarbazine; Disease-Free Survival; Electric Stimulation Therapy; Glioblastoma; Humans; Randomized Controlled Trials as Topic; Safety; Temozolomide; Treatment Outcome; United States
PubMed: 28841803
DOI: 10.21037/cco.2017.06.29 -
Cancer Chemotherapy and Pharmacology Mar 2018The purpose of this report is to describe, for the first time, the pharmacokinetics of dacarbazine (DTIC) and its metabolites...
PURPOSE
The purpose of this report is to describe, for the first time, the pharmacokinetics of dacarbazine (DTIC) and its metabolites [5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC), 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-aminoimidazole-4-carboxamide (AIC)] during pregnancy (n = 2) and postpartum (n = 1).
METHODS
Non-compartmental DTIC, MTIC, HMMTIC, and AIC pharmacokinetics (PK) were estimated in one case at 29 week gestation and 18 day postpartum and a second case at 32 week gestation, in women receiving DTIC in combination with doxorubicin, bleomycin, and vinblastine for treatment of Hodgkin's lymphoma. Drug concentrations were measured by HPLC.
RESULTS
In the subject who completed both pregnancy and postpartum study days, DTIC area under the concentration-time curve (AUC) was 27% higher and metabolite AUCs were lower by 27% for HMMTIC, 38% for MTIC, and 83% of AIC during pregnancy compared to postpartum. At 7 and 9 year follow-up, both subjects were in remission of their Hodgkin's lymphoma.
CONCLUSIONS
Based on these two case reports, pregnancy appears to decrease the metabolism of the pro-drug dacarbazine, likely through inhibition of CYP1A2 activity. Lower concentrations of active metabolites and decreased efficacy may result, although both these subjects experienced long-term remission of their Hodgkin's lymphoma.
Topics: Administration, Intravenous; Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Bleomycin; Dacarbazine; Doxorubicin; Drug Monitoring; Female; Hodgkin Disease; Humans; Infant, Newborn; Neoplasm Staging; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Treatment Outcome; Vinblastine
PubMed: 29305638
DOI: 10.1007/s00280-017-3511-6