Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenocortical carcinoma (AC) is a rare tumor of poor prognosis. Its treatment by o,p'DDD remains a reference after initial surgery. Two galenic forms were recently available in France: Lysodren and Mitotane AP-HP. As Lysodren got a European registration in april 2004, Mitotane is no more produced. O,p'DDD is an adrenolytic and cytotoxic agent. It also reduces the hormonal secretion in AC. Its blood level must reach a therapeutic window (14-20 mg/l) to be effective and to limit toxicity. It is given orally three times a day (3 grams a day for Lysodren and 6-12 grams a day for Mitotane. Its posology is adapted according to serum levels of o,p'DDD and tolerance. Side effects are essentially gastrointestinal (GI), neurologic and hepatic. Five patients (four with AC and one with a metastatic Leydig cell tumor of the testis) were treated by Lysodren. Three patients had early Lysodren discontinuation due to toxicity (skin rash, weight loss, GI toxicity). Studies of combination with other treatments as chemotherapy and targeted drugs are warranted. Surgery is an important part of metastatic disease treatment.
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PMID:[Practical use of o,p'DDD in adrenocortical carcinoma]. 1582 Sep 22

Adrenocortical cancer is one of the most aggressive endocrine malignancies. Growth through the capsule or accidental release of cancer cells during surgery frequently results in metastatic disease. We investigated the antitumoral effect of 2 adrenocorticolytic compounds, O, P'-DDD and MeSO2-DDE, in the adrenocortical cell line H295R both in vitro and as a xenograft model in vivo. H295R cells were injected s. c. in nude mice. O, P'-DDD, MeSO2-DDE, or oil (control) was administered i. p., either simultaneously with cell injection at day 0 (mimicking adjuvant treatment), or at day 48 (established tumors). Accumulation of PET tracers [ (11)C]methionine (MET), [ (11)C] metomidate (MTO), 2-deoxy-2-[ (18)F]fluoro-d-glucose (FDG), and [ (18)F]-l-tyrosine (FLT) in the aggregates were assessed +/- drug treatment in vitro. Tumor growth was significantly inhibited when O, P'-DDD was given at the same time as injection of tumor cells. No significant growth inhibition was observed after treatment with O, P'-DDD at day 48. A significant reduction in FLT uptake and an increased FDG uptake, compared to control, were observed following treatment with 15 microM O, P'-DDD (p<0.01) in vitro. MeSO2-DDE (15 microM) treatment gave rise to a reduced MET and an increased FLT uptake (p<0.01). Both compounds reduced the uptake of MTO compared to control (p<0.01). Treatment with O, P'-DDD simultaneously to inoculation of H295R cells in mice, imitating release of cells during surgery, gave a markedly better effect than treatment of established H295R tumors. We suggest that FLT may be a potential PET biomarker when assessing adrenocortical cancer treatment with O,P'-DDD. Further studies in humans are needed to investigate this.
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PMID:Mitotane effects in a H295R xenograft model of adjuvant treatment of adrenocortical cancer. 2066 29

Adrenal cortical carcinoma is a rare tumor that affects all ages and sexes and has a dismal prognosis. Half are functional, half are not. Early stages are uncommon and are detected by their endocrine effects, usually in females, as incidental findings at surgery or on computed tomography scans. Arteriography, venography, and CT-scan define the local disease. Endocrine evaluations may delay surgery and do not affect the treatment. Radical local surgery with wide exposure is indicated in all adrenal tumors except the radiologically defined small tumor of pure primary hyperaldosteronism. Thoracoabdominal incisions, extra-fascial dissection, nephrectomy, splenectomy, and partial pancreatectomy may be used. Adjunctive chemotherapy or radiation have not been tested. Cures are recorded only in widely-excised, low stage tumors without evidence of metastases (T 1-2 NOMO). Ortho-p-DDD is useful in less than half the cases, functional or not. Phase II studies and collaborative combined chemotherapy treatment studies are badly needed.
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PMID:Carcinoma of the Adrenal Cortex. 2960 71


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