Cell Death Pathways Associated with Photodynamic Therapy: An Update.

Photodynamic therapy (PDT) has the potential to make a significant impact on cancer treatment. PDT can sensitize malignant tissues to light, leading to a highly selective effect if an appropriate light dose can be delivered. Variations in light distribution and drug delivery, along with impaired efficacy in hypoxic regions, can reduce the overall tumor response.

Disruption of the monocarboxylate transporter-4-basigin interaction inhibits the hypoxic response, proliferation, and tumor progression.

We have previously shown that glioblastoma stem cells (GSCs) are enriched in the hypoxic tumor microenvironment, and that monocarboxylate transporter-4 (MCT4) is critical for mediating GSC signaling in hypoxia. Basigin is involved in many physiological functions during early stages of development and in cancer and is required for functional plasma membrane expression of MCT4. We sought to determine if disruption of the MCT-Basigin interaction may be achieved with a small molecule.

MR Fingerprinting of Adult Brain Tumors: Initial Experience.

Background And Purpose: MR fingerprinting allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assessed the utility of MR fingerprinting in differentiating common types of adult intra-axial brain tumors.

Materials And Methods: MR fingerprinting acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 World Health Organization grade II lower grade gliomas, and 8 metastases.

A national evaluation of a dissemination and implementation initiative to enhance primary care practice capacity and improve cardiovascular disease care: the ESCALATES study protocol.

Background: The Agency for Healthcare Research and Quality (AHRQ) launched the EvidenceNOW Initiative to rapidly disseminate and implement evidence-based cardiovascular disease (CVD) preventive care in smaller primary care practices. AHRQ funded eight grantees (seven regional Cooperatives and one independent national evaluation) to participate in EvidenceNOW. The national evaluation examines quality improvement efforts and outcomes for more than 1500 small primary care practices (restricted to those with fewer than ten physicians per clinic).

Understanding Care Integration from the Ground Up: Five Organizing Constructs that Shape Integrated Practices.

Purpose: To provide empirical evidence on key organizing constructs shaping practical, real-world integration of behavior health and primary care to comprehensively address patients' medical, emotional, and behavioral health needs.

Methods: In a comparative case study using an immersion-crystallization approach, a multidisciplinary team analyzed data from observations of practice operations, interviews, and surveys of practice members, and implementation diaries. Practices were drawn from 2 studies of practices attempting to integrate behavioral health and primary care: Advancing Care Together, a demonstration project of 11 practices located in Colorado, and the Integration Workforce Study, a study of 8 practices across the United States.

Integrating Behavioral Health and Primary Care: Consulting, Coordinating and Collaborating Among Professionals.

Purpose: This paper sought to describe how clinicians from different backgrounds interact to deliver integrated behavioral and primary health care, and the contextual factors that shape such interactions.

Methods: This was a comparative case study in which a multidisciplinary team used an immersion-crystallization approach to analyze data from observations of practice operations, interviews with practice members, and implementation diaries. The observed practices were drawn from 2 studies: Advancing Care Together, a demonstration project of 11 practices located in Colorado; and the Integration Workforce Study, consisting of 8 practices located across the United States.

Progressive proximal-to-distal reduction in expression of the tight junction complex in colonic epithelium of virally-suppressed HIV+ individuals.

Effective antiretroviral therapy (ART) dramatically reduces AIDS-related complications, yet the life expectancy of long-term ART-treated HIV-infected patients remains shortened compared to that of uninfected controls, due to increased risk of non-AIDS related morbidities. Many propose that these complications result from translocated microbial products from the gut that stimulate systemic inflammation--a consequence of increased intestinal paracellular permeability that persists in this population. Concurrent intestinal immunodeficiency and structural barrier deterioration are postulated to drive microbial translocation, and direct evidence of intestinal epithelial breakdown has been reported in untreated pathogenic SIV infection of rhesus macaques.

Risk factors for chronic and recurrent otitis media-a meta-analysis.

Risk factors associated with chronic otitis media (COM) and recurrent otitis media (ROM) have been investigated in previous studies. The objective of this study was to integrate the findings and determine the possible risk factors for COM/ROM based on our meta-analysis. A comprehensive search of electronic bibliographic databases (PubMed, Embase, CNKI and Wanfang database) from 1964 to Dec 2012, as well as a manual search of references of articles, was performed.

Risk of cancer after lumbar fusion surgery with recombinant human bone morphogenic protein-2 (rh-BMP-2).

Study Design: Retrospective cohort study among Medicare beneficiaries with lumbar spinal fusion surgery.

Objective: To determine the risk of subsequent cancer among patients who received recombinant human bone morphogenic protein (rhBMP) at surgery compared with those who did not.

Summary Of Background Data: rhBMP is commonly used to promote bone union after spinal surgery.

Triterpenoid modulation of IL-17 and Nrf-2 expression ameliorates neuroinflammation and promotes remyelination in autoimmune encephalomyelitis.

Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production.

Cyclin-dependent kinase 5 activity is required for T cell activation and induction of experimental autoimmune encephalomyelitis.

Cyclin-dependent kinase 5 (Cdk5) is a ubiquitously expressed serine/threonine kinase. However, a requirement for Cdk5 has been demonstrated only in postmitotic neurons where there is abundant expression of its activating partners p35 and/or p39. Although hyperactivation of the Cdk5-p35 complex has been found in a variety of inflammatory neurodegenerative disorders, the potential contribution of nonneuronal Cdk5-p35 activity has not been explored in this context.

Context for understanding the National Demonstration Project and the patient-centered medical home.

This article introduces a journal supplement evaluating the country's first national demonstration of the patient-centered medical home (PCMH) concept. The PCMH is touted by some as a linchpin for renewing the foundering US health care system and its primary care foundation. The National Demonstration Project (NDP) tested a new model of care and compared facilitated and self-directed implementation approaches in a group-randomized clinical trial.

Racial, ethnic, and socioeconomic differences in the incidence of obesity related to childbirth.

Objectives: We investigated the relationship between childbirth and 5-year incidence of obesity.

Methods: We performed a prospective analysis of data on 2923 nonobese, nonpregnant women aged 14 to 22 years from the 1979 National Longitudinal Survey of Youth Cohort, which was followed from 1980 to 1990. We used multivariable logistic regression analyses to determine the adjusted relative risk of obesity for mothers 5 years after childbirth compared with women who did not have children.

Small Animal Imaging for Early Assessment of Therapeutic Efficacy of Photodynamic Therapy for Prostate Cancer.

We are developing small animal imaging techniques that can measure early effects of photodynamic therapy (PDT) for prostate cancer. PDT is an emerging therapeutic modality that continues to show promise in the treatment of cancer. At our institution, a new second-generation photosensitizing drug, the silicon phthalocyanine Pc 4, has been developed and evaluated at the Case Comprehensive Cancer Center.

Access and equity to cancer care in the USA: a review and assessment.

Cancer represents a serious threat to the health of women and men living in the USA. As the second leading cause of death, it claims about 500,000 lives annually. Health disparities occur when there are differences in the incidence, prevalence, mortality, and burden of disease among specific sub-populations within a specified region.

Photodynamic therapy-induced death of HCT 116 cells: Apoptosis with or without Bax expression.

Cell death following photodynamic therapy (PDT) with the photosensitizer Pc 4 involves the intrinsic pathway of apoptosis. To evaluate the importance of Bax in apoptosis after PDT, we compared the PDT responses of Bax-proficient (Bax(+/-)) and Bax knock-out (BaxKO) HCT116 human colon cancer cells. PDT induced a slow apoptotic process in HCT Bax(+/-) cells following a long delay in the activation of Bax and release of cytochrome c from mitochondria.

Differential responses of Mcl-1 in photosensitized epithelial vs lymphoid-derived human cancer cells.

The antiapoptotic Bcl-2-family proteins, Bcl-2 and Bcl-xL, are recognized phototargets of photodynamic therapy (PDT) with the mitochondrion-targeting phthalocyanine photosensitizer Pc 4. In the present study, we found that myeloid cell leukemia 1 (Mcl-1), another antiapoptotic member of the Bcl-2 family, was not photodamaged in Pc 4-PDT-treated human carcinoma cells MCF-7c3, MDA-MB468, DU145, and A431, although Mcl-1 turnover was observed after exposure of HeLa or MCF-7c3 cells to a supralethal dose of UVC. In contrast, when human lymphoma U937 and Jurkat cells were treated with Pc 4-PDT, staurosporine (STS) or UVC, Mcl-1 was cleaved to generate a 28-kDa fragment over a 2-4 h period.