The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480.

Unlabelled: Interleukin-6 signaling can activate androgen receptor in a ligand-independent manner and may play an important functional role in hormone-refractory prostate cancer (HRCaP) progression and patient survival. Plasma and serum IL-6 levels have been associated with prostate cancer progression in several small studies. In order to evaluate its prognostic significance in metastatic HRCaP patients, we measured IL-6 in plasma collected at baseline from patients in a large cooperative group study [Cancer and Leukemia Group B 9480 (CALGB 9480)].

Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer.

Purpose: To evaluate the antitumor activity and safety of the epothilone B analog, ixabepilone, with or without estramustine phosphate (EMP), in chemotherapy-naive patients with progressive castrate metastatic prostate cancer.

Patients And Methods: Patients were randomly assigned to receive ixabepilone (35 mg/m(2)) by intravenous infusion every 3 weeks with or without EMP 280 mg orally three times daily on days 1 to 5.

Results: Between December 2001 and October 2003, 92 patients were enrolled and randomly assigned to treatment with ixabepilone alone (45 patients) or in combination with EMP (47 patients).

Myocardin is sufficient and necessary for cardiac gene expression in Xenopus.

Myocardin is a cardiac- and smooth muscle-specific cofactor for the ubiquitous transcription factor serum response factor (SRF). Using gain-of-function approaches in the Xenopus embryo, we show that myocardin is sufficient to activate transcription of a wide range of cardiac and smooth muscle differentiation markers in non-muscle cell types. We also demonstrate that, for the myosin light chain 2 gene (MLC2), myocardin cooperates with the zinc-finger transcription factor Gata4 to activate expression.

Bladder cancer. Clinical practice guidelines in oncology.

Urothelial tumors represent a spectrum of diseases with a range of prognosis. After a diagnosis is established at any point within the urothelial tract, the patient remains at risk for developing a new lesion at a different or the same location and at a similar or more advanced stage. Continued monitoring for recurrence is an essential part of management, because most recurrences are superficial and can be managed endoscopically.

A phase I trial of fixed dose rate gemcitabine and capecitabine in metastatic renal cell carcinoma.

Background: Metastatic renal cell carcinoma (RCC) has modest response rates to chemotherapy with gemcitabine and 5-fluorouracil (5-FU). Fixed dose rate gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. To determine the toxicity of this combination therapy in metastatic RCC, a Phase I trial was conducted.

New temperature-sensitive alleles of ftsZ in Escherichia coli.

We isolated five new temperature-sensitive alleles of the essential cell division gene ftsZ in Escherichia coli, using P1-mediated, localized mutagenesis. The five resulting single amino acid changes (Gly109-->Ser109 for ftsZ6460, Ala129-->Thr129 for ftsZ972, Val157-->Met157 for ftsZ2066, Pro203-->Leu203 for ftsZ9124, and Ala239-->Val239 for ftsZ2863) are distributed throughout the FtsZ core region, and all confer a lethal cell division block at the nonpermissive temperature of 42 degrees C. In each case the division block is associated with loss of Z-ring formation such that fewer than 2% of cells show Z rings at 42 degrees C.

Kinetics of development and characteristics of antibodies induced in cancer patients against yeast expressed rDNA derived granulocyte macrophage colony stimulating factor (GM-CSF).

We have determined the presence and kinetics of granulocyte macrophage colony stimulating factor (GM-CSF) antibodies induced after repeated administration of a yeast expressed GM-CSF product in prostate cancer patients with minimal recurrent disease using a panel of assays for detection and characterization of antibodies. Results showed that all 15 prostate cancer patients treated with GM-CSF developed GM-CSF reactive antibodies during the course of therapy. Most patients (87%) developed GM-CSF reactive antibodies within 3 months while in other patients (13%), these antibodies were induced after additional cycles of GM-CSF treatment.

Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma.

Purpose: To review the biology of renal cell carcinoma (RCC) leading to vascular endothelial growth factor (VEGF) overexpression and the clinical results of VEGF blockade in metastatic RCC.

Methods: A review of relevant published literature regarding VEGF, von Hippel-Lindau (VHL) gene inactivation and VEGF overexpression in RCC was performed. Further, a review of the mechanism, toxicity, and clinical development of VEGF-targeted therapy in metastatic RCC was undertaken.

Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480.

Background: Research has suggested that men with hormone-refractory prostate carcinoma have a lower quality of life (QOL) compared with men who have hormone-sensitive prostate carcinoma and that quality of life (QOL) steadily declines over the last year of life for men with prostate carcinoma. The primary purpose of the current study was to evaluate whether there was evidence of palliative effects associated with suramin at any of the three doses administered in the original clinical trial.

Methods: Patients with histologically confirmed advanced hormone-refractory adenocarcinoma of the prostate were randomized to receive suramin at a low dose (n = 129; median age, 69 years), an intermediate dose (n = 129; median age, 71 years), or a high dose (n = 127; median age, 70 years) as part of the Intergroup 0159/Cancer and Leukemia Group B 9480 trial.

Second-line chemotherapy for hormone-refractory prostate cancer: has the time come?

Prostate-specific antigen testing has not only led to an earlier diagnosis of prostate cancer, but also to an earlier identification of hormone-refractory prostate cancer (HRPC). Many patients identified early with HRPC may receive first-line taxane-based chemotherapy. Patients who progress after first-line chemotherapy are still quite healthy and desire further therapy.

Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer.

Background: Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormone-independent prostate cancer.

Methods: We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily.

Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy.

Background: The objective of this study was to assess the biologic activity of rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist that has been approved to treat type 2 diabetes, in men with recurrent prostate carcinoma using change in prostate specific antigen (PSA) doubling time (PSADT) as the primary outcome variable.

Methods: Men with histologically confirmed prostate carcinoma, no recent hormone therapy, a rising serum PSA level after radical prostatectomy and/or radiation therapy, and no radiographic evidence of metastases were assigned randomly to receive either oral rosiglitazone (4 mg twice daily) or placebo. The treatment was continued until the men developed disease progression or adverse effects.

9-Nitrocamptothecin as second line chemotherapy for men with progressive, metastatic, hormone refractory prostate cancer: Results of the CALGB 99901.

Background: Institution of early hormone therapy in the PSA era coupled with demonstration of clinical benefit with chemotherapy in hormone refractory prostate cancer (HRPC) and acceptance of PSA decline as a surrogate for response has resulted in introduction of chemotherapy earlier in the natural history of disease. There now exists a need to identify, effective agents for second line chemotherapy. 9-nitrocamptothecin (9-NC) a novel, oral camptothecin analogue was tested as second line chemotherapy for patients with progressive hormone refractory prostate cancer.

FtsZ fiber bundling is triggered by a conformational change in bound GTP.

Polymer formation by the essential FtsZ protein plays a crucial role in the cytokinesis of most prokaryotes. Lateral associations between these FtsZ polymers to form bundles or sheets are widely predicted to be extremely important for FtsZ function in vivo. We have carried out a study in vitro of FtsZ polymer formation and bundling using linear dichroism (LD) to assess structural properties of the polymers.

Impact of race on survival in men with metastatic hormone-refractory prostate cancer.

Objectives: To determine whether blacks with hormone-refractory prostate cancer have shorter survival compared with whites with the same disease.

Methods: Data from eight multicenter trials (four Phase II and four randomized Phase III studies) conducted by the Cancer and Leukemia Group B were combined. Eligible patients had progressive prostate cancer after androgen deprivation therapy (with documented castration levels of testosterone), an Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate hematologic, renal, and hepatic function.

Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer.

Purpose: To evaluate the herbal combination, PC-SPES, and diethylstilbestrol (DES) in patients with androgen independent prostate cancer (AIPC).

Patients And Methods: A randomized phase II study was conducted with cross-over design. Patients were randomly assigned to receive either three PC-SPES capsules orally three times a day or DES 3 mg orally once a day.

Time to disease progression to evaluate a novel protein kinase C inhibitor, UCN-01, in renal cell carcinoma.

Background: Renal cell carcinoma (RCC) is characterized by von Hippel-Lindau gene inactivation and vascular endothelial growth factor (VEGF) overproduction. The mechanism of VEGF overproduction may involve protein kinase C (PKC) delta and zeta isoforms. UCN-01 (7-hydroxystaurosporine) is a selective inhibitor of PKC.

Convergence across biomes to a common rain-use efficiency.

Water availability limits plant growth and production in almost all terrestrial ecosystems. However, biomes differ substantially in sensitivity of aboveground net primary production (ANPP) to between-year variation in precipitation. Average rain-use efficiency (RUE; ANPP/precipitation) also varies between biomes, supposedly because of differences in vegetation structure and/or biogeochemical constraints.

Practice and progress in kidney cancer: methodology for novel drug development.

Purpose: The minimal efficacy of standard therapy for metastatic renal cell carcinoma (RCC) has resulted in the evaluation of numerous novel agents. Some agents have shown promise in phase II trials and yet none have improved survival over standard therapy in phase III trials. We examined existing data relevant to standard therapy and clinical trial methodology in RCC to understand patient, disease and trial design factors that have impacted clinical trial outcome and drug evaluation.

The selection of hormonal therapy in prostate cancer: who, when, and for how long?

Androgen deprivation is the foundation for the systemic therapy of advanced prostate cancer. Multiple trials have tested combined androgen blockade versus androgen deprivation alone in patients with advanced disease. These studies suggest a slight advantage to the combined approaches that contain flutamide and bicalutamide, but the lack of dramatic differences in outcome makes monotherapy reasonable, especially in patients with more indolent disease.

Cancer and Leukemia Group B 90206: A randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma.

The majority of sporadic clear cell renal cell carcinoma (RCC) is characterized by loss of heterozygosity of the von Hippel-Lindau (VHL) tumor suppressor gene and somatic inactivation of the remaining VHL allele. The resulting VHL gene silencing leads to induction of hypoxia-regulated genes including vascular endothelial growth factor (VEGF). Thus, therapeutic inhibition of VEGF holds promise for treatment of this historically refractory malignancy.

Advances in prostate cancer.

Purpose Of Review: The purpose of this review is to highlight the most important developments in the diagnosis, prevention, and management of prostate cancer reported in the past year that have been published in the medical literature.

Recent Findings: Recent research has yielded important insights into the effects of lowering the serum prostate-specific antigen threshold for prostate biopsy on the incidence of prostate cancer and suggests that a cutoff value of 2.5 ng/mL would double the rate of diagnosis of the disease in young men.

Liposomal doxorubicin for the treatment of hormone-refractory prostate cancer.

There is a pressing need for new agents to treat hormone-refractory prostate cancer (HRPC). Doxorubicin has shown modest activity in this setting, but its use is limited by its toxicities. Liposomal encapsulation of doxorubicin appears to promote enhanced tumor accumulation in some tumor types, and toxicity appears to be reduced.