Borealis-1: a randomized, first-line, placebo-controlled, phase II study evaluating apatorsen and chemotherapy for patients with advanced urothelial cancer.

Background: Five-year survival of patients with inoperable, advanced urothelial carcinoma treated with the first-line chemotherapy is 5%-15%. We assessed whether the Hsp27 inhibitor apatorsen combined with gemcitabine plus cisplatin (GC) could improve overall survival (OS) in these patients.

Patients And Methods: This placebo-controlled, double-blind, phase II trial randomized 183 untreated urothelial carcinoma patients (North America and Europe) to receive GC plus either placebo (N = 62), 600 mg apatorsen (N = 60), or 1000 mg apatorsen (N = 61).

Mechanisms of Retinal Damage after Ocular Alkali Burns.

Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments.

Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer.

Background: Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown.

Methods: In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.

Acute and late urinary toxicity following radiation in men with an intact prostate gland or after a radical prostatectomy: A secondary analysis of RTOG 94-08 and 96-01.

Introduction: To estimate the contribution of the prostate gland and prostatic urethral inflammation to urinary symptoms after radiation therapy for prostate cancer, we performed a secondary analysis of urinary toxicity after primary radiation to an intact prostate vs. postprostatectomy radiation to the prostatic fossa in protocols RTOG 94-08 and 96-01, respectively.

Materials And Methods: Patients randomized to the radiation-alone arms (without hormone therapy) of the 2 trials were evaluated, including 104 men receiving primary prostate radiation to 68.

Advancing surgical simulation in gynecologic oncology: robotic dissection of a novel pelvic lymphadenectomy model.

Introduction: Pelvic lymphadenectomy is a key component of the surgical treatment of several gynecologic cancers and involves mastery of complex anatomic relationships. Our aim was to demonstrate that the anatomy relevant to robotic pelvic lymphadenectomy can be modeled using low-cost techniques, thereby enabling simulation focused on surgical dissection, a task that integrates technical skills and anatomic knowledge.

Methods: A model of pelvic lymphadenectomy was constructed through experimentation with several different materials and a number of prototypes.

Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma.

Purpose: Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced.

Patients And Methods: Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models.

CD47 expression on T cell is a self-control negative regulator of type 1 immune response.

The cytokine milieu and dendritic cells (DCs) direct Th1 development. Yet, the control of Th1 polarization by T cell surface molecules remains ill-defined. We here report that CD47 expression on T cells serves as a self-control mechanism to negatively regulate type 1 cellular and humoral immune responses in vivo.

Effect of Baohuoside-1 aglycone and tacrolimus monotherapy and combination therapy on prevention of acute heart allograft rejection in the rat.

Baohuoside-1 (B-1), a recently introduced novel immunosuppressant that was proved to be potent in inhibition of T and B cell proliferation and B-1, also prevents cardiac allograft rejection in rodents. The present study further proved that monotherapy of B-1's analogue B-1 aglycone effectively prolongs cardiac allograft survival and combination therapy of B-1 aglycone with tacrolimus (FK506) produces synergistic effect in prevention acute cardiac allograft rejection in the rat. .

Thrombospondin/CD47 interaction: a pathway to generate regulatory T cells from human CD4+ CD25- T cells in response to inflammation.

Thymus-derived CD4+ CD25+ T regulatory cells (Tregs) are essential for the maintenance of self-tolerance. What critical factors and conditions are required for the extra-thymic development of Tregs remains an important question. In this study, we show that the anti-inflammatory extracellular matrix protein, thrombospondin-1, promoted the generation of human peripheral regulatory T cells through the ligation of one of its receptor, CD47.

Bone-directed treatments for prostate cancer.

Maintaining bone health in men who have advanced prostate cancer is an important goal of therapy. Low bone mass is prevalent in men who have prostate cancer, and long-term androgen deprivation therapy causes additional significant decreases in bone mineral density. The adverse effects of the disease and current treatment modalities on bone health are further compounded when patients develop bone metastases,which cause clinically significant skeletal morbidity.

Human 6-sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes.

Early and high-level production of IL-12 is crucial for effective immune responses against pathogens. Up until now, the cells providing this initial IL-12 have remained elusive. Here we show that a subset of human blood dendritic cells (DC) is the principal and primary source of IL-12p70 when blood leukocytes are stimulated with the TLR4-ligand LPS or with CD40-ligand.

Postoperative cognitive dysfunction after cardiac surgery.

Prolonged postoperative cognitive dysfunction (POCD) is reported to occur frequently after cardiac surgery. However, it is rarely assessed in routine clinical practice and receives little attention. Although the cerebral consequences of cardiopulmonary bypass have been measured clinically, insights into the resulting molecular and pathologic events within the brain have only begun to be investigated.

Thrombospondin 1 is an autocrine negative regulator of human dendritic cell activation.

Thrombospondin 1 (TSP) elicits potent antiinflammatory activities in vivo, as evidenced by persistent, multiorgan inflammation in TSP null mice. Herein, we report that DCs represent an abundant source of TSP at steady state and during activation. Human monocyte-derived immature dendritic cells (iDCs) spontaneously produce TSP, which is strongly enhanced by PGE2 and to a lesser extent by transforming growth factor (TGF) beta, two soluble mediators secreted by macrophages after engulfment of damaged tissues.

Intrasinus administration of topical budesonide to allergic patients with chronic rhinosinusitis following surgery.

Objective: Whether instillation into the maxillary sinus of topical budesonide affected the immune response and improved allergic patients with chronic rhinosinusitis that had persistence of symptoms despite appropriate surgical intervention was assessed.

Study Design: Double-blind placebo-controlled.

Methods: Twenty-six patients with allergy to house dust mites who had previously had surgery and who had persistent symptoms of disabling rhinorrhea or pressure-pain resistant to oral antibiotics and intranasal corticosteroids were recruited.

Cytokines and their role in the pathophysiology of osteoarthritis.

The specific causative agent of the pathological process of osteoarthritis (OA) has not yet been identified, however, episodic inflammation at the clinical stage is now a well documented phenomenon and believed to be involved in the disease progression. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are the predominant proinflammatory cytokines synthesized during the OA process. Other cytokines having proinflammatory properties or catabolic factors could also contribute to this pathological condition, and those having antiinflammatory properties may be able to counteract the negative effects of the former on the disease process.