Epigenetic Therapy with Panobinostat Combined with Bicalutamide Rechallenge in Castration-Resistant Prostate Cancer.

Purpose: This study assesses the action of panobinostat, a histone deacetylase inhibitor (HDACI), in restoring sensitivity to bicalutamide in a castration-resistant prostate cancer (CRPC) model and the efficacy and safety of the panobinostat/bicalutamide combination in CRPC patients resistant to second-line antiandrogen therapy (2LAARx).

Patients And Methods: The CWR22PC xenograft and isogenic cell line were tested for drug interactions on tumor cell growth and on the androgen receptor (AR), AR-splice variant7, and AR targets. A phase I trial had a 3 × 3 panobinostat dose-escalation design.

KLF6 loss of function in human prostate cancer progression is implicated in resistance to androgen deprivation.

Inactivation of the transcription factor/tumor suppressor Krüppel-like factor 6 (KLF6) has been described in prostate cancer (PC). This study investigated the prevalence and significance of KLF6 exon 2 mutations and splice variants (SVs) in different stages of human PC progression. By using laser-capture microdissection and recombinant clone isolation of DNA sequences to enhance sensitivity, base changes were found in 20 (24.

mTOR signaling pathway and mTOR inhibitors in cancer therapy.

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase. It is ubiquitously expressed in cells and is a therapeutic target for the cancer treatment arsenal. Despite the great responses obtained in tumors addicted to specific mutations or overactivation of key members of the mTOR pathway (HiF1α in RCC, cyclin D1 in MCL, or TSC in SEGA), mTOR inhibitors as single agents have modest activity.

Immunotherapy in the treatment of advanced prostate cancer.

Prostate cancer is a complex disease, and treatment selection is informed by numerous variables depending on the stage of disease. Moreover, patient expectations and the impact of treatment-related adverse events may influence treatment choices. Available treatment options over the course of the disease have included surgery, radiation therapy, hormonal therapy, immunotherapy, and chemotherapy.

Vascular endothelial growth factor (VEGF) serum levels are associated with survival in early stages of lung cancer patients.

Aim: Evaluate the serum vascular endothelial growth factor (VEGF) levels in the prognosis of lung cancer patients.

Methods: Fifty-four serum samples were analyzed for VEGF concentrations (79.3% nonsmall cell lung cancer (NSCLC) and 20.

Induction of bicalutamide sensitivity in prostate cancer cells by an epigenetic Puralpha-mediated decrease in androgen receptor levels.

Background: Increased androgen receptor (AR) levels support resistance to apoptosis and hormone therapy in advanced prostate cancer (PC). We recently linked the overexpression of AR in androgen-independent LNCaP cells (AI-cells) and tissues from castration-resistant patients to decreased nuclear levels of Pur-alpha (Puralpha) and loss from a protein complex bound to repressor sequences (ARS) in the 5'-UTR of AR. Strategies to regain control of increased AR transcription may overcome resistance of AI-cells and improve treatment outcomes.

Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer.

Background: Lung cancer is the leading cause of cancer death in the world. The objective of this study was to investigate the expression of vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) in patients with nonsmall cell lung cancer (NSCLC) and its correlation with the prognosis for patients with lung cancer.

Methods: The expression status of VEGFs and VEGFRs was examined in 48 nonconsecutive specimens of primary lung cancer by immunohistochemistry.