Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the Karnell Cancer Center Grand Rounds, we present a patient who underwent radical prostatectomy with bilateral pelvic lymphadenectomy, but had positive margins and subsequently developed local recurrence and then systemic disease. Pathologic and radiologic aspects of his disease are discussed. Therapeutic options at different stages of the disease are examined from the point of view of the urologist, radiation oncologist, and medical oncologist. The surgical portion of the discussion focuses on the selection of initial therapy. Both the selection of surgical candidates and choice of pre- or post-operative therapy in patients can be aided by prognostic tools looking at several variables, including prostate-specific antigen (PSA) level, Gleason score of the tumor, seminal vesicle invasion, extracapsular invasion, and lymph node involvement. Low-risk patients can be treated with monotherapy, such as radical prostatectomy, external beam radiation therapy, prostate brachytherapy, or cryosurgical ablation of the prostate. Higher risk patients may require adjuvant and possibly neoadjuvant therapy in addition. The radiation portion of the discussion focuses on the use of radiation therapy as salvage for relapsing disease. Of particular importance is the point that treating high-risk patients whose PSA levels have started to rise but are less than 1 ng/ml results in a long-term PSA control rate as high as 75%, but that limiting the use of salvage radiation therapy to patients with high PSA levels or biopsy confirmation of local recurrence in the face of a negative bone scan results in biochemical long-term control of less than 40%. In the medical oncology part of the discussion, the major focus is on the use of chemotherapy to treat patients whose disease has become resistant to hormonal therapy. Mitoxantrone plus a corticosteroid has been found to offer significant palliation for such patients. Combination therapy with estramustine plus taxanes, other microtubule inhibitors, or other agents such as topoisomerase II inhibitors, has been found to cause shrinkage of measurable soft tissue disease and diminution of serum PSA levels. The development of effective hormonal and chemotherapeutic drugs for treatment of metastatic disease has led to new interest in adjuvant and neoadjuvant therapy of high-risk patients.
 ...
PMID:Progressing prostate carcinoma. 1130 30

Extracts from the seeds of milk thistle, Silybum marianum, are known commonly as silibinin and silymarin and possess anticancer actions on human prostate carcinoma in vitro and in vivo. Seven distinct flavonolignan compounds and a flavonoid have been isolated from commercial silymarin extracts. Most notably, two pairs of diastereomers, silybin A and silybin B and isosilybin A and isosilybin B, are among these compounds. In contrast, silibinin is composed only of a 1:1 mixture of silybin A and silybin B. With these isomers now isolated in quantities sufficient for biological studies, each pure compound was assessed for antiproliferative activities against LNCaP, DU145, and PC3 human prostate carcinoma cell lines. Isosilybin B was the most consistently potent suppressor of cell growth relative to either the other pure constituents or the commercial extracts. Isosilybin A and isosilybin B were also the most effective suppressors of prostate-specific antigen secretion by androgen-dependent LNCaP cells. Silymarin and silibinin were shown for the first time to suppress the activity of the DNA topoisomerase IIalpha gene promoter in DU145 cells and, among the pure compounds, isosilybin B was again the most effective. These findings are significant in that isosilybin B composes no more than 5% of silymarin and is absent from silibinin. Whereas several other more abundant flavonolignans do ultimately influence the same end points at higher exposure concentrations, these findings are suggestive that extracts enriched for isosilybin B, or isosilybin B alone, might possess improved potency in prostate cancer prevention and treatment.
 ...
PMID:Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. 1589 38