Disease relevance of Chlodithane

• Mitotane therapy of adrenocortical carcinoma [1].
• Mitotane. Spironolactone antagonism in Cushing's syndrome [2].
• This system appears to be useful in elucidating the biochemical mechanism of mitotane action on adrenal cancer [3].
• Mitotane was increased to 2.5 g/d, and the metastasis was removed surgically [4].
• Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer [5].

Psychiatry related information on Chlodithane

• Eighteen months later, however, lethargy and logopathy appeared and the tumor grew again rapidly with the withdrawal of o,p'-DDD performed for the evaluation of these mental disturbances [6].

High impact information on Chlodithane

• Does mitotane reduce endogenous ACTH secretion [7]?
• Because of these reports of good results, a phase II trial that used CDDP with and without mitotane (o,p'DDD) was initiated [8].
• CONCLUSIONS: Mitotane increased SHBG/CBG gene expression and liver production by mechanisms requiring the presence of ERalpha [9].
• Fourteen patients without distant metastases (World Health Organization stage I, one patient; stage II, seven; stage III, three; and stage IV, three) were matched with 14 patients for resection status, adjuvant mitotane treatment, stage, and tumor size [10].
• In the HepG2 cell line, 17beta-estradiol (E2) or o,p'-DDD treatment had no effect on mRNA or SHBG/CBG concentrations [9].

Chemical compound and disease context of Chlodithane

• Pituitary irradiation and mitotane therapy resulted in remission of Cushing's syndrome, with disappearance of the peaks of ACTH and cortisol secretion [11].
• After surgery he was treated with mitotane at a dose of 2 g/d. Six months after surgery 11-deoxycortisol levels increased, and a computed tomography scan showed a pulmonary metastasis [4].
• Serum from a patient with Cushing's syndrome who was being treated with mitotane contained components that interfered with determination of cholesterol in the Du Pont aca [12].
• To investigate the activity of etoposide, doxorubicin, and cisplatin plus mitotane in the management of advanced adrenocortical carcinoma (ACC) patients, 72 patients with measurable disease not amenable to radical surgery were enrolled in a prospective, multicenter phase II trial [13].
• These findings suggest that the expression of P-glycoprotein in adrenocortical carcinoma is not related to clinical manifestations, steroid production, histological index or response to mitotane therapy [14].

Biological context of Chlodithane

• Transient transfection experiments in Hep89 cells showed that E2 or o,p'-DDD treatment did not increase the transcriptional activity of the minimal proximal promoter of human SHBG gene [9].
• Prolonged bleeding time due to mitotane therapy [15].
• In support of a study to develop mitotane analogs as more effective therapeutic agents and as a basis for understanding the toxicity of related compounds in the adrenals, the biotransformations of o,p'-DDD in adrenocortical homogenate preparations have been studied and compared with those of its m,p'- and p,p'-isomers [16].
• 3. Chemical ADX performed with mitotane (a drug that reduces corticosteroid synthesis) produced essentially the same up-regulation of B(1) receptors as that observed in ADX rats [17].
• Before and 1 and 2 or more weeks after starting mitotane we determined the platelet counts, bleeding times and global coagulation parameters [15].

Anatomical context of Chlodithane

• Mitotane, at a concentration achieved in this patient's plasma, completely reversed the Pgp-related resistance both in the Pgp-overexpressing KB8-5 cell line and in the patient's tumor cells [18].
• Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p'-DDD in human adrenal zona fasciculata/reticularis [19].
• Bovine adrenal cortex transformations of mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane; o,p'-DDD] and its p,p'- and m,p'-isomers [16].
• Mitotane (1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane) metabolism in perfusion studies with dog adrenal glands [20].
• The in vitro metabolism of 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane (o,p'-DDD) by dog adrenal mitochondria and metabolite covalent binding to mitochondrial macromolecules: a possible mechanism for the adrenocorticolytic effect [21].

Associations of Chlodithane with other chemical compounds

• The persistence of free steroid secretion with decreased formation of DS suggests that the o,p'-DDD may have altered sulfatase activity before causing tumor necrosis and total decrease in steroidogenesis [22].
• Together, these assays have identified two metabolites of DDT, o,p'-DDD and p,p'-DDD, that have estrogenic activity [23].
• Our results suggest that the cAMP generation step is a target in o,p'-DDD-mediated disruption of ACTH-stimulated adrenal steroidogenesis in rainbow trout but that other downstream targets such as steroidogenic enzymes responsible for cortisol synthesis might also be affected [24].
• Whereas Mitotane strongly suppressed cell growth, Mitometh had a weaker effect [25].
• Dexamethasone levels were measured in the serum by radioimmunoassay and shown to be lowered by o,p'-DDD therapy [26].
• Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS than aldosterone [27].

Gene context of Chlodithane

• Basal plasma ACTH levels were more progressively increased than plasma CT during the postoperative course when the patient was treated with o,p'-DDD, since the tumour was not completely resected [28].
• Methoxychlor, DDT and its metabolites, o,p'-DDD, and o,p'-DDE ranged in potency from 5 to 24 X 10(6) less potent than estradiol [29].
• IGFBP-2 levels did not differ significantly according to tumor secretion or mitotane treatment [30].
• A six month mitotane course induced sustained correction of hypercortisolism in a young woman with PPNAD and Carney complex [31].
• Mitotane toxic effects were nausea, diarrhea, vomiting, neurologic alterations, gynecomastia, a rare case of hypertensive encephalopathy, and CED-related hematologic toxic effects [32].

Analytical, diagnostic and therapeutic context of Chlodithane

• Sustained remission of Cushing's disease with mitotane and pituitary irradiation [33].
• Mitotane enhances cytotoxicity of chemotherapy in cell lines expressing a multidrug resistance gene (mdr-1/P-glycoprotein) which is also expressed by adrenocortical carcinomas [34].
• Extensive hormonal evaluation was performed in a girl with adrenal carcinoma during the primary tumor stage, following adrenalectomy, during the period when metastases were evident and while on treatment with o,p'-DDD [22].
• The following search terms were used in varying combinations: adrenal, adrenocortical, cancer, carcinoma, tumor, diagnosis, imaging, treatment, radiotherapy, mitotane, cytotoxic, surgery [35].
• Adjuvant treatment options after complete tumor removal (e.g. mitotane, radiotherapy) are urgently needed because postoperative disease-free survival at 5 yr is only around 30%, but options have still not been convincingly established [35].

References