Induction of AP-1 activity by androgen activation of the androgen receptor in LNCaP human prostate carcinoma cells.

Background: The androgen receptor and activator protein-1 (AP-1) transcription factors affect growth regulation in normal and cancerous prostate cells. Effects of androgen-activated androgen receptor on AP-1 activity were determined in the LNCaP human prostate carcinoma cell model.

Methods: Cells were exposed to 1 nM androgen +/- antiandrogen bicalutamide.

Ursodeoxycholate/Sulindac combination treatment effectively prevents intestinal adenomas in a mouse model of polyposis.

Background & Aims: Preclinical studies in animal models, human epidemiological data, and clinical trials in patients with adenomatous polyposis have consistently indicated that sulindac and other nonsteroidal antiinflammatory drugs or cyclooxygenase inhibitors have the greatest potential efficacy among current candidates for colon tumor chemopreventive agents. However, at highly effective doses they all have some risk of toxicity, and their therapeutic profile might be improved by use at lower, more tolerable doses, in combination with a second agent acting via other mechanisms.

Methods: Sulindac was tested in combination with ursodeoxycholic acid (ursodiol), a naturally occurring 7-B-epimer of the bile component chenodeoxycholic acid, for prevention of adenomas in the Min mouse model of adenomatous polyposis.

A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days.

Purpose: Perillyl alcohol (POH) has been shown to have both chemopreventative and chemotherapeutic activities in preclinical studies. The underlying mechanism(s) of action of POH have yet to be delineated but may involve effects on the transforming growth factor beta (TGFbeta) and/or the Ras signaling pathways. A phase I study of POH for 14 days out of every 28 days in subjects with advanced malignancies was performed to evaluate dose escalation, toxicity, pharmacokinetics, and effects on TGFbeta and Ras.

A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies.

Purpose: To determine the maximum-tolerated dose (MTD) of daily Topotecan with full-dose thoracic radiotherapy (XRT).

Methods And Materials: Patients with advanced thoracic malignancies requiring full dose radiation received daily I.V.

Breast cancer from a public health perspective.

By 2010, the majority of approximately 1.5 million annual new cases of breast cancer will be diagnosed in women in countries with limited resources. Public health approaches to medical problems emphasize the importance of practical, limited toxicity and very inexpensive interventions.

Chemotherapy for advanced non-small cell lung cancer.

Lung cancer is an aggressive disease with poor prognosis after it has advanced. Over the past several years, there has been slow but steady progress in treatment options. Chemotherapy results in a modest improvement in survival, improved quality of life, and decreased pulmonary symptoms.

Combining EGFR inhibitors with radiation or chemotherapy: will preclinical studies predict clinical results?

Purpose: To highlight some of the preclinical data that examine the interaction of epidermal growth factor receptor (EGFR) inhibitors with radiotherapy and chemotherapy.

Methods And Materials: Recognition of the EGFR as an important regulator of tumor cell growth in the early 1980s stimulated the development of a series of molecules specifically designed to inhibit EGFR signaling as anticancer agents. Many of these agents have now matured and are in advanced clinical trial investigations, with tumor response rates on the order of 10-20% identified across a variety of human malignancies.

A Phase II trial of flavopiridol (NSC #649890) in patients with previously untreated metastatic androgen-independent prostate cancer.

Purpose: Flavopiridol is a cyclin-dependent kinase inhibitor with preclinical activity against prostate cancer cell lines. A Phase II trial was conducted to determine the activity of flavopiridol in patients with metastatic hormone-refractory prostate cancer.

Experimental Design: A total of 36 patients was enrolled from several institutions and treated with a 72-h continuous infusion of flavopiridol every 14 days at the eventual starting dose of 40 mg/m(2)/day.

Potential exposure to PCBs, DDT, and PBDEs from sport-caught fish consumption in relation to breast cancer risk in Wisconsin.

In Wisconsin, consumption of Great Lakes fish is an important source of exposure to polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ethers (PBDEs), and other halogenated hydrocarbons, all of which may act as potential risk factors for breast cancer. We examined the association between sport-caught fish consumption and breast cancer incidence as part of an ongoing population-based case-control study. We identified breast cancer cases 20-69 years of age who were diagnosed in 1998-2000 (n = 1,481) from the Wisconsin Cancer Reporting System.

Phase I trial of the polyamine analog N1,N14-diethylhomospermine (DEHSPM) in patients with advanced solid tumors.

Background: This phase I study was conducted to determine maximal tolerated dose (MTD) and dose-limiting toxicities (DLT) in patients with advanced solid tumors treated with the polyamine analog N1, N14-diethylhomospermine (DEHSPM).

Methods: Patients were treated with DEHSPM administered as a subcutaneous (SC) injection daily for five consecutive days repeated every 4 weeks. Three dose levels were examined starting at 12.

Pilot and safety trial of carboplatin, paclitaxel, and thalidomide in advanced non small-cell lung cancer.

We performed a pilot study to assess the safety of thalidomide in combination with standard chemo-therapy in patients with advanced non small-cell lung cancer. Patients with unresectable stage IIIA, IIIB, or IV disease were enrolled starting in July 1999. Patients received paclitaxel 225 mg/m2 over 3 hours and carboplatin area under the curve = 6.

Polo-like kinase (Plk) 1: a novel target for the treatment of prostate cancer.

Second only to skin cancer, cancer of the prostate gland (CaP) is the most commonly occurring cancer in American men. Existing treatment approaches and surgical intervention have been unable to effectively manage this dreaded cancer; therefore, efforts are ongoing to explore novel targets and strategies for the management of CaP. A complete understanding of the genetic control of the processes of cellular proliferation and programmed cell death, or "apoptosis," may provide the basis for the rational design of novel therapeutic strategies against CaP.

Adjuvant therapy in the treatment of non-small-cell lung cancer.

Randomized trials to date have not consistently demonstrated a benefit in overall survival with the use of adjuvant chemotherapy, radiotherapy, or combined modality chemoradiation in patients with resected non-small-cell lung cancer. Subset analyses suggest a reduction in local relapse with adjuvant radiotherapy for patients with completely resected N2 disease. Improvements in patient selection and treatment plans are urgently needed.

The role of human achaete-scute homolog-1 in medullary thyroid cancer cells.

Background: Human achaete-scute homolog-1 (hASH1) is a transcription factor that is expressed highly in neuroendocrine tumors such as medullary thyroid cancer (MTC). Thyroid C-cells do not develop in hASH1 knockout mice, which suggests that hASH1 is essential for normal C-cell development.

Methods: To determine the effect of raf-1 induction on hASH1 and hormone production, we used an estrogen inducible raf-1 construct in MTC cell line (TT) cells (TT-raf cells).

Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer.

Objective: We conducted a phase II multicenter trial of perillyl alcohol in patients with advanced hormone refractory prostate cancer (HRPC). The primary endpoint was to evaluate the 6-month progression-free survival given the potential cytostatic nature of the drug. Secondary objectives included assessing acute and chronic toxicities, as well as measuring objective response rates.

Social networks and quality of life among female long-term colorectal cancer survivors.

Background: The population of long-term colorectal cancer survivors in the United States continues to increase, but little is known about how they fare-physically, mentally, or socially-in the years after diagnosis. The current study examines female long-term colorectal cancer survivors' health-related quality of life (HRQoL) in relation to social networks.

Methods: A population-based sample of female colorectal cancer survivors (n = 726) residing in Wisconsin was recontacted approximately 9 years after the initial diagnosis.

Phase II study of 1alpha-hydroxyvitamin D(2) in the treatment of advanced androgen-independent prostate cancer.

Purpose: In this single institution Phase II trial, we evaluated the efficacy of the vitamin D analogue, 1alpha-OH-D(2), in patients with advanced hormone-refractory prostate cancer.

Experimental Design: The patients initially received 1alpha-OH-D(2) at 12.5 micro g p.

NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy.

We evaluated recurrent NXS2 neuroblastoma tumors that developed following NK- or T-cell-mediated immunotherapy in tumor-bearing mice. Recurrent tumors developed following an NK-dependent antitumor response using a suboptimal dose of hu14.18-IL2, a humanized IL-2 immunocytokine targeted to the GD(2)-ganglioside.

Androgen antagonist activity by the antioxidant moiety of vitamin E, 2,2,5,7,8-pentamethyl-6-chromanol in human prostate carcinoma cells.

Antioxidants, such as vitamin E, are being investigated for efficacy in prostate cancer prevention. In this study, we show that the antioxidant moiety of vitamin E, 2,2,5,7,8-pentamethyl-6-chromanol (PMCol), has antiandrogen activity in prostate carcinoma cells. In the presence of PMCol, the androgen-stimulated biphasic growth curve of LNCaP human prostate carcinoma cells was shifted to the right.

Phase I trial of perillyl alcohol administered four times daily continuously.

Purpose: Previous experience with perillyl alcohol (POH) was with a formulation of 500-mg capsules each containing 250 mg POH and soybean oil. This formulation resulted in the ingestion of large amounts of soybean oil (>10 g/day). Dose-limiting toxicities (DLT) were primarily gastrointestinal.

Preclinical and clinical development of immunocytokines.

Advances in preclinical and clinical development have demonstrated that monoclonal antibodies and immuno-activating cytokines have a beneficial role in certain clinical oncology settings. Genetic engineering has now been used to create 'immunocytokines (ICs)'. These are fusion proteins that consist of an immune-activating cytokine linked to a tumor-reactive monoclonal antibody.

Health-related quality of life in female long-term colorectal cancer survivors.

Although the number of women who survive treatment for colorectal cancer is growing, little is known about the quality of life of long-term survivors. The purpose of analyses presented in this paper is to describe the overall health-related quality of life of female long-term colorectal cancer survivors and the factors that may modify their levels of quality of life. A population-based sample of 726 Wisconsin women diagnosed with colorectal cancer from 1990-1991 was recontacted.

Raf-1 activation suppresses neuroendocrine marker and hormone levels in human gastrointestinal carcinoid cells.

Gastrointestinal carcinoid cells secrete multiple neuroendocrine markers and hormones including 5-HT and chromogranin A. The intracellular signaling pathways that regulate production of bioactive molecules are not completely understood. Our aim was to determine whether activation of the raf-1/MEK/MAPK signal transduction pathway in carcinoid cells could modulate production of neuroendocrine markers and hormones.