bluuebunny/crossref_metadata_2025 huggingface dataset:
A Current View of Functional Biomaterials for Wound Care, Molecular and Cellular Therapies
Authors: Piraino Francesco , Selimović Šeila
Published: October 2015

The intricate process of wound healing involves activation of biological pathways that work in concert to regenerate a tissue microenvironment consisting of cells and external cellular matrix (ECM) with enzymes, cytokines, and growth factors. Distinct stages characterize the mammalian response to tissue injury: hemostasis, inflammation, new tissue formation, and tissue remodeling. Hemostasis and inflammation start right after the injury, while the formation of new tissue, along with migration and proliferation of cells within the wound site, occurs during the first week to ten days after the injury. In this review paper, we discuss approaches in tissue engineering and regenerative medicine to address each of these processes through the application of biomaterials, either as support to the native microenvironment or as delivery vehicles for functional hemostatic, antibacterial, or anti-inflammatory agents. Molecular therapies are also discussed with particular attention to drug delivery methods and gene therapies. Finally, cellular treatments are reviewed, and an outlook on the future of drug delivery and wound care biomaterials is provided.
New Delay-Range-Dependent Robust Exponential Stability Criteria of Uncertain Impulsive Switched Linear Systems with Mixed Interval Nondifferentiable Time-Varying Delays and Nonlinear Perturbations
Authors: Niamsup Piyapong , Yotha Narongsak , Mukdasai Kanit
Published: October 2015

We investigate the problem of robust exponential stability analysis for uncertain impulsive switched linear systems with time-varying delays and nonlinear perturbations. The time delays are continuous functions belonging to the given interval delays, which mean that the lower and upper bounds for the time-varying delays are available, but the delay functions are not necessary to be differentiable. The uncertainties under consideration are nonlinear time-varying parameter uncertainties and norm-bounded uncertainties, respectively. Based on the combination of mixed model transformation, Halanay inequality, utilization of zero equations, decomposition technique of coefficient matrices, and a common Lyapunov functional, new delay-range-dependent robust exponential stability criteria are established for the systems in terms of linear matrix inequalities (LMIs). A numerical example is presented to illustrate the effectiveness of the proposed method.
Continuous Curvilinear Capsulorhexis in Cataract Surgery Using a Modified 3-Bend Cystotome
Authors: Zeng Yuan , Gao Jian-hua
Published: October 2015

We modified a 2-bend cystotome for continuous curvilinear capsulorhexis (CCC) in manual or phacoemulsification cataract surgery to improve the safety and ease of performance. A 26G needle was converted into a cystotome with 3 bends. In this retrospective study, the performance of modified 3-bend cystotome was compared with conventional 2-bend cystotome. During cataract surgery, in the 3-bend cystotome group, mean completion time of CCC was shorter, mean times of viscoelastic agent supplement were less, and CCC success rate was higher than that in 2-bend group. Complication incidence, such as postoperative transient corneal edema and irreparable V-shaped tear, was also lower in 3-bend group. No posterior capsular rupture or no other complication was observed in either group. A polymethyl methacrylate intraocular lens or a hydrogel intraocular lens was implanted in the capsular bag in all eyes. We conclude that it is safe and efficient to accomplish a CCC using the 3-bend cystotome due to its ability to sustain the anterior chamber depth (ACD) and keep the posterior lip intact. Using the 3-bend cystotome also allowed for an adequate view into the anterior chamber from lack of wound deformation.
Bone Regeneration from PLGA Micro-Nanoparticles
Authors: Ortega-Oller Inmaculada , Padial-Molina Miguel , Galindo-Moreno Pablo , O’Valle Francisco , Jódar-Reyes Ana Belén , Peula-García Jose Manuel
Published: October 2015

Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.
Increased Anxiety, Akathisia, and Suicidal Thoughts in Patients with Mood Disorder on Aripiprazole and Lamotrigine
Authors: Pondé Milena Pereira , Freire Antonio Carlos Cruz
Published: October 2015

Introduction. Akathisia affects around 18% of patients with bipolar disorder treated with aripiprazole and may worsen when aripiprazole is combined with lamotrigine and antidepressants.Case. This paper reports on two clinical cases involving patients with a diagnosis of mood disorder who developed severe akathisia, anxiety, and suicidal ideation while using a combination of aripiprazole, antidepressants, and lamotrigine.Discussion. We recommend that patients with a mood disorder taking multiple drugs should begin aripiprazole therapy with low doses and be monitored for the development of akathisia, increased anxiety, or suicidal thoughts. The appearance of these limiting side effects requires discontinuation of the drug.
Automatic Recognition of Chinese Personal Name Using Conditional Random Fields and Knowledge Base
Authors: Gu Chuan , Tian Xi-ping , Yu Jiang-de
Published: October 2015

According to the features of Chinese personal name, we present an approach for Chinese personal name recognition based on conditional random fields (CRF) and knowledge base in this paper. The method builds multiple features of CRF model by adopting Chinese character as processing unit, selects useful features based on selection algorithm of knowledge base and incremental feature template, and finally implements the automatic recognition of Chinese personal name from Chinese document. The experimental results on open real corpus demonstrated the effectiveness of our method and obtained high accuracy rate and high recall rate of recognition.
Music Perception Influences Language Acquisition: Melodic and Rhythmic-Melodic Perception in Children with Specific Language Impairment
Authors: Sallat Stephan , Jentschke Sebastian
Published: October 2015

Language and music share many properties, with a particularly strong overlap for prosody. Prosodic cues are generally regarded as crucial for language acquisition. Previous research has indicated that children with SLI fail to make use of these cues. As processing of prosodic information involves similar skills to those required in music perception, we compared music perception skills (melodic and rhythmic-melodic perception and melody recognition) in a group of children with SLI (N=29, five-year-olds) to two groups of controls, either of comparable age (N=39, five-year-olds) or of age closer to the children with SLI in their language skills and about one year younger (N=13, four-year-olds). Children with SLI performed in most tasks below their age level, closer matching the performance level of younger controls with similar language skills. These data strengthen the view of a strong relation between language acquisition and music processing. This might open a perspective for the possible use of musical material in early diagnosis of SLI and of music in SLI therapy.
Block Preconditioners for Complex Symmetric Linear System with Two-by-Two Block Form
Authors: Wu Shi-Liang , Li Cui-Xia
Published: October 2015

Based on the previous work by Zhang and Zheng (A parameterized splitting iteration method for complex symmetric linear systems, Japan J. Indust. Appl. Math., 31 (2014) 265–278), three block preconditioners for complex symmetric linear system with two-by-two block form are presented. Spectral properties of the preconditioned matrices are discussed in detail. It is shown that all the eigenvalues of the preconditioned matrices are well-clustered. Numerical experiments are reported to illustrate the efficiency of the proposed preconditioners.
A Bioinspired Methodology Based on an Artificial Immune System for Damage Detection in Structural Health Monitoring
Authors: Anaya Maribel , Tibaduiza Diego A. , Pozo Francesc
Published: October 2015

Among all the aspects that are linked to a structural health monitoring (SHM) system, algorithms, strategies, or methods for damage detection are currently playing an important role in improving the operational reliability of critical structures in several industrial sectors. This paper introduces a bioinspired strategy for the detection of structural changes using an artificial immune system (AIS) and a statistical data-driven modeling approach by means of a distributed piezoelectric active sensor network at different actuation phases. Damage detection and classification of structural changes using ultrasonic signals are traditionally performed using methods based on the time of flight. The approach followed in this paper is a data-based approach based on AIS, where sensor data fusion, feature extraction, and pattern recognition are evaluated. One of the key advantages of the proposed methodology is that the need to develop and validate a mathematical model is eliminated. The proposed methodology is applied, tested, and validated with data collected from two sections of an aircraft skin panel. The results show that the presented methodology is able to accurately detect damage.
Castleman’s Disease Presenting as a Parotid Mass in the Pediatric Population: A Report of 2 Cases
Authors: Delaney Sean W. , Zhou Shengmei , Maceri Dennis
Published: October 2015

Introduction. Angiofollicular lymph node hyperplasia (Castleman’s disease) is a nonmalignant lymphoproliferative disorder that generally involves the lymph nodes of young adults, most commonly in the mediastinum. Rarely, Castleman’s disease may present in the parotid gland. The disease can be further classified into unicentric or multicentric forms, with considerable differences in presentation, treatment, and prognosis.Case(s). We present cases of two pediatric patients, aged 7 and 11, who both presented with a slow-growing, painless parotid mass. In each case, the mass was excised via a superficial parotidectomy and the diagnosis made postoperatively upon further pathologic examination. At 6 months of follow-up, both had fully intact facial nerve function and no evidence of recurrence.Discussion. Castleman’s disease presents a diagnostic challenge in the head and neck region, as radiographic characteristics and fine needle aspiration results are often inconclusive. Definitive diagnosis requires surgical excision for pathologic examination. The unicentric form generally presents as a painless mass and can be successfully treated with complete excision. The multicentric form is associated with constitutional symptoms and its treatment remains controversial.Conclusion. Although rare, clinicians should be aware of both forms of Castleman’s disease when creating a differential diagnosis for parotid masses.
A Novel WLAN Client Puzzle against DoS Attack Based on Pattern Matching
Authors: Ordi Ali , Zamani Mazdak , Bashah Idris Norbik , Abdul Manaf Azizah , Abdullah Mohd Shahidan
Published: October 2015

Despite the popularity of 802.11 based networks, they suffer several types of DoS attack, launched by an attacker whose aim is to make an access point (AP) unavailable to legitimate users. One of the most common DoS attacks on 802.11 based networks is to deplete the resources of the AP. A serious situation like this can occur when the AP receives a burst of connection requests. This paper addresses this common DoS attack and proposes a lightweight puzzle, based on pattern-matching. Using a pattern-matching technique, this model adequately resists resource-depletion attacks in terms of both puzzle generation and solution verification. Using a sensible series of contextual comparisons, the outcomes were modelled by a simulator, and the security definition and proofs are verified, among other results.
The Influence of Music on Prefrontal Cortex during Episodic Encoding and Retrieval of Verbal Information: A Multichannel fNIRS Study
Authors: Ferreri Laura , Bigand Emmanuel , Bard Patrick , Bugaiska Aurélia
Published: October 2015

Music can be thought of as a complex stimulus able to enrich the encoding of an event thus boosting its subsequent retrieval. However, several findings suggest that music can also interfere with memory performance. A better understanding of the behavioral and neural processes involved can substantially improve knowledge and shed new light on the most efficient music-based interventions. Based on fNIRS studies on music, episodic encoding, and the dorsolateral prefrontal cortex (PFC), this work aims to extend previous findings by monitoring the entire lateral PFC during both encoding and retrieval of verbal material. Nineteen participants were asked to encode lists of words presented with either background music or silence and subsequently tested during a free recall task. Meanwhile, their PFC was monitored using a 48-channel fNIRS system. Behavioral results showed greater chunking of words under the music condition, suggesting the employment of associative strategies for items encoded with music. fNIRS results showed that music provided a less demanding way of modulating both episodic encoding and retrieval, with a general prefrontal decreased activity under the music versus silence condition. This suggests that music-related memory processes rely on specific neural mechanisms and that music can positively influence both episodic encoding and retrieval of verbal information.
Chaotic Tolerant Synchronization Analysis with Propagation Delay and Actuator Faults
Authors: Qunli Zhang
Published: October 2015

The criteria for tolerant synchronization with a constant propagation delay and actuator faults are presented by using matrix analysis techniques. A new algorithm, which constructs the extended error systems in order to make the conservation of the stability lower, is proposed. Based on proper Lyapunov-Krasovskii functional, the novel delay-dependent fault tolerant synchronization analyses are derived. Finally, numerical examples show the effectiveness of the proposed method.
Identification of Human Herpesvirus 8 Sequences in Conjunctiva Intraepithelial Neoplasia and Squamous Cell Carcinoma of Ugandan Patients
Authors: Starita Noemy , Annunziata Clorinda , Waddell Keith M. , Buonaguro Luigi , Buonaguro Franco M. , Tornesello Maria Lina
Published: October 2015

The incidence of squamous cell carcinoma of the conjunctiva is particularly high in sub-Saharan Africa with temporal trends similar to those of Kaposi sarcoma (KS). Human herpesvirus type 8 (HHV8), has not yet been investigated in conjunctiva tumors. In this study biopsies and PBMCs of conjunctiva neoplasia patients along with nonneoplastic conjunctiva tissues have been analyzed for HHV8 sequences by PCR targeting ORF26. All amplimers were subjected to nucleotide sequencing followed by phylogenetic analysis. HHV8 DNA has been identified in 12 out of 48 (25%) HIV-positive, and in 2 out of 24 (8.3%) HIV-negative conjunctiva neoplastic tissues and in 4 out of 33 (12.1%) PBMC samples from conjunctiva neoplasia diseased patients as well as in 4 out of 60 (6.7%) nontumor conjunctiva tissues. The viral load ranged from 1 to 400 copies/105cells. Phylogenetic analysis showed that the majority of HHV8 ORF26 amplimers clustered with subtypes R (n=11) and B2 (n=6). This variant distribution is in agreement with that of HHV8 variants previously identified in Ugandan KS cases. The presence of HHV8 in conjunctiva tumors from HIV-positive patients warrants further studies to test whether HHV8 products released by infected cells may have paracrine effects on the growth of conjunctiva lesions.
Role of Inflammation in Muscle Homeostasis and Myogenesis
Authors: Costamagna Domiziana , Costelli Paola , Sampaolesi Maurilio , Penna Fabio
Published: October 2015

Skeletal muscle mass is subject to rapid changes according to growth stimuli inducing both hypertrophy, through increased protein synthesis, and hyperplasia, activating the myogenic program. Muscle wasting, characteristic of several pathological states associated with local or systemic inflammation, has been for long considered to rely on the alteration of myofiber intracellular pathways regulated by both hormones and cytokines, eventually leading to impaired anabolism and increased protein breakdown. However, there are increasing evidences that even alterations of the myogenic/regenerative program play a role in the onset of muscle wasting, even though the precise mechanisms involved are far from being fully elucidated. The comprehension of the links potentially occurring between impaired myogenesis and increased catabolism would allow the definition of effective strategies aimed at counteracting muscle wasting. The first part of this review gives an overview of skeletal muscle intracellular pathways determining fiber size, while the second part considers the cells and the regulatory pathways involved in the myogenic program. In both parts are discussed the evidences supporting the role of inflammation in impairing muscle homeostasis and myogenesis, potentially determining muscle atrophy.
An Intrusion Tolerance Method Based on Energy Attack for Wireless Sensor Network
Authors: Jiang Yu , Huang Jie
Published: October 2015

Wireless sensor network is vulnerable to malicious attacks because of the broadcast nature of wireless signal. In order to overcome the shortcomings of existing methods, this paper presents an intrusion tolerance method against malicious nodes. Different from the traditional intrusion tolerance methods based on encryption, authentication, and multirouting, the proposed method uses active protection to achieve intrusion tolerance. Small power consumption of many normal nodes is exchanged for large power consumption of relatively small number of malicious nodes to decrease the lifetime of malicious nodes. Theoretical analysis and test results show that the proposed methods not only prolong the lifetime of the sensor network but also achieve the effective protection against malicious nodes. The active protection method provides new ideas for the security in WSN.
The Interaction between Obstructive Sleep Apnea and Parkinson’s Disease: Possible Mechanisms and Implications for Cognitive Function
Authors: Kaminska Marta , Lafontaine Anne-Louise , Kimoff R. John
Published: October 2015

Parkinson’s disease (PD) is a relentlessly progressive neurodegenerative disorder associated with hallmark motor and nonmotor symptoms (NMS) such as sleep disturbances and cognitive dysfunction. While dopaminergic treatments have improved the motor aspects of PD, progression remains inevitable. Research has recently increasingly focused on strategies to modify disease progression and on nonmotor manifestations of PD, given their impact on patients’ quality of life. Obstructive sleep apnea (OSA) is a treatable sleep disorder, common in the general population, associated with excessive daytime sleepiness and neurocognitive deficits. Neuroimaging has demonstrated structural and functional changes in OSA patients; in animal models, OSA causes brain inflammation and oxidative injury, including in key areas involved in PD pathophysiology such as locus coeruleus. The prevalence of OSA in PD has been variable in studies to date, and potential consequences and interrelationship between the two disorders have not been well studied. There is however emerging evidence that OSA is associated with increased NMS in PD, particularly cognitive dysfunction. This review focuses on the possible interrelationship between OSA and PD. Mechanisms promoting OSA in PD will be reviewed, as well as mechanisms whereby OSA can affect the neurodegenerative process in PD.
Catalytic Activity of Co3O4 Nanomaterials with Different Morphologies for the Thermal Decomposition of Ammonium Perchlorate
Authors: Jin Li-Na , Wang Jian-Guo , Qian Xin-Ye , Xia Dan , Dong Ming-Dong
Published: October 2015

Nano‐Co3O4 with different morphologies was successfully synthesized by annealing CoC2O4·2H2O precursors. The as‐obtained samples were characterized by powder X‐ray diffraction (XRD), scanning electron microscopy (SEM), and low‐temperature nitrogen adsorption‐desorption. It was found that the volume ratio of N,N‐dimethylformamide (DMF) and water played an important role in the formation of cobalt oxalate precursors with different morphologies. After calcination in air, cobalt oxalate precursors converted to Co3O4 nanomaterials while their original morphologies were maintained. The catalytic effect was investigated for nano‐Co3O4 with different morphologies on the thermal decomposition of ammonium perchlorate (AP) by differential scanning calorimeter (DSC). The results indicated that all products showed excellent catalytic activity for thermal decomposition of AP and the Co3O4 nanorods with larger BET surface area and pore volume had the highest catalytic activity.
A Review of Computational Methods to Predict the Risk of Rupture of Abdominal Aortic Aneurysms
Authors: Canchi Tejas , Kumar S. D. , Ng E. Y. K. , Narayanan Sriram
Published: October 2015

Computational methods have played an important role in health care in recent years, as determining parameters that affect a certain medical condition is not possible in experimental conditions in many cases. Computational fluid dynamics (CFD) methods have been used to accurately determine the nature of blood flow in the cardiovascular and nervous systems and air flow in the respiratory system, thereby giving the surgeon a diagnostic tool to plan treatment accordingly. Machine learning or data mining (MLD) methods are currently used to develop models that learn from retrospective data to make a prediction regarding factors affecting the progression of a disease. These models have also been successful in incorporating factors such as patient history and occupation. MLD models can be used as a predictive tool to determine rupture potential in patients with abdominal aortic aneurysms (AAA) along with CFD-based prediction of parameters like wall shear stress and pressure distributions. A combination of these computer methods can be pivotal in bridging the gap between translational and outcomes research in medicine. This paper reviews the use of computational methods in the diagnosis and treatment of AAA.
Hybrid Particle Swarm and Differential Evolution Algorithm for Solving Multimode Resource-Constrained Project Scheduling Problem
Authors: Zhang Lieping , Luo Yingxiong , Zhang Yu
Published: October 2015

In order to find a feasible solution for the multimode resource-constrained project scheduling problem (MRCPSP), a hybrid of particle swarm optimization (PSO) and differential evolution (DE) algorithm is proposed in this paper. The proposed algorithm uses a two-level coding structure. The upper-level structure is coded for scheduling sequence, which is optimized by PSO algorithm. The lower-level structure is coded for project execution mode, and DE algorithm is used to solve the optimal scheduling model. The effectiveness and advantages of the proposed algorithm are illustrated by using the test function of project scheduling problem library (PSPLIB) and comparing with other scheduling methods. The results show that the proposed algorithm can well solve MRCPSP.
Synthesis and Characterization of Zinc Borate Nanowhiskers and Their Inflaming Retarding Effect in Polystyrene
Authors: Gao Pingqiang , Zhang Yan
Published: October 2015

Zinc borate nanowhiskers 4ZnO·B2O3·H2O were in situ successfully synthesized via one‐step precipitation reaction. A set of experiments was performed to evaluate the influence of reaction temperature. Increasing the temperature up to 70°C led to the high purity of zinc borate nanowhiskers with a monoclinic crystal structure measuring 50 nm to 100 nm in diameter and approximately 1 µm in length. However, higher temperature decreases the crystallization due to the emergence of other styles of zinc borate. Flame‐resistant nanocomposites of polystyrene and zinc borate nanowhiskers were also successfully synthesized. The samples were investigated by XRD, FESEM, FTIR, and TG. The mechanical properties of the composites were also tested. The incorporation of zinc borate nanowhiskers improved the thermal and mechanical properties for polystyrene. FESEM images show that zinc borate nanowhiskers increased the smoothness of composites. The composites presented good responsive behavior in relation to LOI (limiting oxygen index) allowing them to be suitable for green flame retardants.
Abstract A113: Immunomodulatory properties of bromodomain inhibitors in pancreatic cancer cells
Authors: Leal Ana S. , Williams Charlotte R. , Sporn Michael B. , Liby Karen T.
Published: October 2015

Bromodomain and extra terminal domain (BET) proteins function as epigenetic signaling factors that “read” chromatin modifications, controlling numerous genes involved in cell cycle, cell growth, inflammation and cancer. The BET inhibitors, JQ1 and I-BET-762, occupy selective pockets of bromodomains in BET proteins resulting in a release of the chromatin and consequent suppression of the transduction of targeted genes.

Cell lines developed from a pancreatic carcinoma (Panc 1343) and ascites (PanAsc 2159) of LSL-KrasG12d/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC mouse model) were treated with several concentrations of JQ1 and I-BET-762. JQ1 and I-BET-762 have growth inhibitory properties, with IC50 (48 hr treatment) of 24.5 nM and 94.5 nM, and 1.8 μM and 1.2 μM in PanAsc 2159 and Panc 1343 cells, respectively.

Several cytokines and chemokines, produced by tumor cells, stromal cells or inflammatory infiltrating cells, play important roles in promoting (GM-CSF, IL-6 and CCL2) or suppressing (CCL27, CCL4, IL17A or IL27) tumor progression. RT profiler PCR of PanAsc 2159 cells treated with 300 nM of JQ1 for 24 hr revealed the ability of this compound to upregulate CCL24, IL17a and IL-27 and downregulate CCL7, CXCL1, CCL2, IL16 and IL6. JQ1 and I-BET-762 reduced the protein and RNA levels of CCL2, IL6 and GM-CSF in Panc 1343 and PanAsc 2159 cells, and also in RAW macrophage-like cells stimulated with LPS. JQ1 and I-BET-762 also reduced the protein levels of secreted TNF-α in RAW cells stimulated with LPS.

JQ1 and I-BET-762 appear to have immunomodulatory effects in pancreatic cancer cell lines derived from KPC mice, altering the levels of several chemokines and cytokines. These compounds also have a growth inhibitory effect in these cell lines. Exploring the effects of these compounds in KPC mice is ongoing.

We thank James Bradner for the generous gift of JQ1.

Citation Format: Ana S. Leal, Charlotte R. Williams, Michael B. Sporn, Karen T. Liby. Immunomodulatory properties of bromodomain inhibitors in pancreatic cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A113.
Abstract B76: Targeting Mcl-1 for radiosensitization of pancreatic cancers
Authors: Zhang Qiang , Wei Dongping , Schreiber Jason , Kausar Tasneem , Lawrence Theodore , Sun Yi , Nikolovska-Coleska Zaneta , Morgan Meredith A.
Published: October 2015

In order to identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer and, thus, improve survival in patients with locally advanced pancreatic cancer, we conducted an siRNA library screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1), an anti-apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic cancer cells to gemcitabine-radiation. Thus, we investigated Mcl-1 inhibition by genetic (siRNA) and pharmacological (small molecule) approaches as a radiosensitizing strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA radiosensitized BxPC-3, Panc-1, and MiaPaCa-2 cells with radiation enhancement ratios (RER) of 1.5±0.06, 1.4±0.03, and 1.3±0.01, respectively, and caused Caspase-3 activation and PARP cleavage. We next tested the ability of the recently identified, selective, small molecule inhibitor of Mcl-1, UMI-77 (Abulwerdi F et al., Mol Cancer Ther, 2014), to inhibit the anti-apoptotic functions of Mcl-1 and radiosensitize in pancreatic cancer cells. Consistent with inhibition of Mcl-1 anti-apoptotic function, UMI-77 (1-5uM) caused dissociation of Mcl-1 from the pro-apoptotic protein Bak. Under these same conditions, UMI-77 produced significant radiosensitization in BxPC-3 and Panc-1 cells (RER: 1.5±0.1 and 1.3±0.04, respectively; P<0.05) with minimal radiosensitization of MiaPaCa-2 cells (1.2±0.07). Since Mcl-1 expression levels are highest in BxPC-3 and Panc-1 cells and lowest in MiaPaCa-2 cells, these results suggest that elevated Mcl-1 protein levels may be a biomarker for radiosensitization by Mcl-1 inhibition. In addition, radiosensitization by UMI-77 was associated with Caspase-3 activation, PARP cleavage, and increased sub-G1 DNA content. In contrast, ABT-737, a well-established inhibitor of Bcl-2, Bcl-XL, and Bcl-w, failed to radiosensitize pancreatic cancer cells suggesting the unique importance of Mcl-1 in radiation survival. Taken together, these results validate Mcl-1 as a target for radiosensitization of pancreatic cancer cells and demonstrate the efficacy of small molecules which displace Mcl-1 from Bak/Bax as radiosensitizers in pancreatic cancer. Furthermore, these results support continued investigation of UMI-77 and its analogues in animal models and in combination with gemcitabine-radiation as a strategy for radiation and chemoradiation sensitization of pancreatic cancers.

Citation Format: Qiang Zhang, Dongping Wei, Jason Schreiber, Tasneem Kausar, Theodore Lawrence, Yi Sun, Zaneta Nikolovska-Coleska, Meredith A. Morgan. Targeting Mcl-1 for radiosensitization of pancreatic cancers. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B76.
Abstract IA22: Innate immune cell PI3K gamma as a target for suppression of pancreatic ductal adenocarcinoma
Authors: Kaneda Megan , Hardamon Chanae , Schmid Michael C. , Bouvet Michael , Novelli Franco , Hirsch Emilio , Lowy Andrew , Varner Judith A.
Published: October 2015

Ductal adenocarcinoma of the pancreas (PDAC) is a devastating disease that will afflict greater than 40,000 Americans. Less than 5% of these new pancreatic cancer patients will survive 5 years following diagnosis. PDAC is rarely detected in the early stages, with more than 80% of patients presenting with locally unresectable or metastatic disease at the time of diagnosis. As this form of cancer is also resistant to current cytotoxic therapies and ionizing radiation, novel therapeutic and diagnostic approaches are desperately needed to improve patient outcome. A characteristic feature of PDAC is the presence of an abundant, inflammatory infiltrate. In response to tumor-derived chemoattractants, we found that myeloid cells invade tumors where they promote immunosuppression, resulting in tumor growth and metastasis. We discovered that myeloid cell PI3-kinase gamma (PI3Kgamma) controls tumor immunosuppression, as PI3Kgamma signaling inhibits pro-inflammatory gene expression responses in macrophages, monocytes and granulocytes and promotes anti-inflammatory responses. Suppression of PI3Kgamma in mutant mice and in mice treated with pharmacologic inhibitors of PI3Kgamma promotes CD8+ T cell anti-tumor immune responses, leading to a 50% reduction in tumor growth and metastasis in orthotopic mouse models of pancreatic carcinoma and significant extension of survival in GEM models of PDAC (PDX1-cre; LSL-KrasG12D/+; LSL-Trp53 R172H/+). Furthermore, PI3Kgamma inhibition blocks macrophage stimulation of collagen deposition by fibroblasts in PDAC. We are exploring the combination of PI3kinase gamma inhibition with tumor cell and T cell targeted therapeutics could significantly reduce tumor growth and metastasis of PDAC. These approaches could improve patient outcomes by reducing tumor progression and preserving organ function by inhibiting desmoplasia.

Citation Format: Megan Kaneda, Chanae Hardamon, Michael C. Schmid, Michael Bouvet, Franco Novelli, Emilio Hirsch, Andrew Lowy, Judith A. Varner. Innate immune cell PI3K gamma as a target for suppression of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr IA22.
Abstract A15: Development of a multilevel human papillomavirus (HPV) vaccine intervention
Authors: Katz Mira Lynn , Reiter Paul L. , Ruffin Mack T. , Paskett Electra D.
Published: October 2015

Purpose: New strategies to improve human papillomavirus (HPV) vaccine uptake among minority and underserved adolescents are needed. The purpose of this study is to describe the development of a multi-level HPV vaccine intervention to increase adolescent HPV vaccination rates.

Methods: A community-engaged process was used over a one year period. Caregivers (n=18) and providers (n=27) from a Federally Qualified Health Center participated in: 1) focus groups to better understand knowledge and acceptability of the HPV vaccine, and to generate ideas for the intervention content and format; 2) writing sessions to develop the content and intervention components; and 3) review sessions to obtain initial feedback and make revisions prior to pilot testing the intervention.

Results: Intervention components developed were based on the Protection Motivation Theory and the PACE (Present the issue, Ask questions, Check understanding, and Express concerns) communication system. The intervention components developed (English and Spanish) focus on three levels: 1) Caregivers: a) an interactive computer program tailored for the adolescent's gender, age, race/ethnicity, b) a brochure with information about additional resources, and c) a HPV vaccine comic book to assist caregivers with explaining the HPV vaccine to younger adolescents; 2) Providers: a) an automated PowerPoint presentations including current HPV vaccine initiation and completion rates, suggestions to address common barriers, and video clips demonstrating the teach-back methodology, b) current HPV vaccine scientific literature, and c) “Ask me about the HPV vaccine!” pins; and 3) Health Centers: a) posters, and b) refrigerator magnets that serve as reminders for the second and third dose of the HPV vaccine.

Conclusions: Community members provided valuable input into the development of a multi-level HPV vaccine intervention. The input will make the intervention relatable and more acceptable to the priority population. Using this community-engaged approach is more complex, increases costs, and involves additional time and effort from community members and academic researchers. The value of the partnership is critical and the additional time and energy expended is important to successfully address cancer disparities among minority and underserved populations.

Citation Format: Mira Lynn Katz, Paul L. Reiter, Mack T. Ruffin, IV, Electra D. Paskett. Development of a multilevel human papillomavirus (HPV) vaccine intervention. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A15.
Abstract A20: What's in the cancer biology part of Community Health Worker Curricula: A systematic review
Authors: Offer Nicole , Jeffries Kierstyn , Wilson Danyell S.
Published: October 2015

Background: Disparities in cancer treatment and outcomes mirror socio-economical, racial, ethnic, and educational backgrounds. An important approach for closing health disparities is increasing scientific and health cancer literacy in the community. This can be achieved by Community Health Workers (CHWs). CHWs are thus at the frontline of our efforts to close these health care gap. However, the current status of a standardized cancer-biology training module for CHWs is unknown.

Hypothesis: If we can identify the material covered in the cancer-biology portion of published CHW training curricula, then a standardized cancer-biology module can be developed based on evidence of best practices and recommendations.

Methods: A comprehensive search of the published literature on training of CHWs using Pubmed and following the guidelines established by the Cochrane Collaboration systematic review process was performed. Methods for completing this systematic review included identification of a topic; selection of articles based on specialized criteria; design and implementation of a data extraction form; and systematic data synthesis and appraisal from the selected articles to diminish bias.

Results: Using this methodology, 49 articles were selected from an initial Pubmed search that yielded 228 literature entries using “Cancer Education Curriculum Community Health Workers” as search criteria. Using this strategy, we will produce a systematic and comprehensive review of the science behind cancer training portion of published CHW curriculum in the U.S. This approach will aid in improving CHW training.

Citation Format: Nicole Offer, Kierstyn Jeffries, Danyell S. Wilson. What's in the cancer biology part of Community Health Worker Curricula: A systematic review. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A20.
Abstract A23: Addressing men's health disparities in the District of Columbia
Authors: Dodson Everett
Published: October 2015

The Georgetown University Lombardi Comprehensive Cancer Center Office of Minority Health and Health Disparities Research is a community based center located in Ward 8 of the District of Columbia, which has some of the highest incidence and death from cancer in the city. Programs addressing men's health are very limited in these communities. Our location is easily accessible to the residents in Wards 6, 7, and 8 which are designated by the Department of Health and Human Services as medically underserved. Our mission is to facilitate, stimulate, and to promote synergy in addressing the biological and environmental basis of cancer health disparities via research, training, communication and education. Current programs include breast cancer prevention studies for African American and Hispanic Women, HPV Education, Environmental Justice, exercise studies to relieve the effects of cancer treatments for men and women. The Health Disparities Initiative also conducts community based boot camps, and regular focus groups to engage community support for our programs, and to give the residents the opportunity to let us know what their community needs are. The nearby Capitol Breast Care Center provides women with mammograms and cervical exams and needed follow-up regardless of a woman's ability to pay.

As a Community Health Educator I am a liaison between the residents of these communities and the Health Disparitiess Initiative. I actively participate in community activities that help promote healthy lifestyles and the reduction of chronic diseases. I am actively involved in the recruitment of residents from the community to form our Community Advisory Board and Environmental Justice Advisory Board. And I have accepted the invitation to sit on community boards and committees.

Citation Format: Everett Dodson. Addressing men's health disparities in the District of Columbia. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A23.
Abstract A58: Comorbid conditions among African American breast cancer survivors
Authors: Davis Claudia M. , Myers Hector F.
Published: October 2015

Background: There is compelling evidence that ethnicity is a significant independent risk factor for breast cancer disparity among some racial groups in various geographical locations. In California, African American women carry a disproportionate burden of this disease with a higher mortality rate, when compared to other women. Although the etiology of the burden may be due to multiple factors such as an aggressive phenotype, treatment modalities, etc.., there is growing evidence that the existence and possible interplay of co-morbid conditions may have a negative effect on cancer survivorship outcomes. The aim of our study was to investigate the co-morbid conditions among a cohort of African American breast cancer survivors.

Methods: Via recruitment flyers, support groups, and word-of-mouth, we recruited and screened 169 women from breast cancer support groups and community-dwellers in Southern and Northern California. One hundred and sixty women were eligible and n =155 participated. The inclusion criteria were women who self-identified as African/Black American, age 25 years or older, diagnosed with breast cancer and at least 1 year post-active treatment. As part of a larger study, the breast cancer survivors completed a self-report demographic data questionnaire including, height and weight, cigarette smoking, alcohol intake, breast cancer stage, treatment and the presence of co-morbid conditions.

Results: Our study revealed that over 79% of the survivors reported 1 or more co-morbid conditions inclusive of heart disease, diabetes, high cholesterol, hypothyroidism, and hyperthyroidism. Hypertension was the most prominent (24.5 %) co-morbid condition and 20.6% reported that they did not have any co-morbid conditions.

Conclusion: Our findings suggest the importance of assessing for co-morbid conditions among African American breast cancer survivors as we might have a better understanding of risk and facilitate the need for a collaborative care approach and intervention to manage these co-morbid conditions and thus improve survivorship outcomes.

Citation Format: Claudia M. Davis, Hector F. Myers. Comorbid conditions among African American breast cancer survivors. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A58.
Abstract A70: Mast cells in prostate cancer race disparities: Are the minutemen of the microenvironment the key?
Authors: Hempel Heidi A. , Kulac Ibrahim , Cuka Nathan S. , Cornish Toby C. , Marzo Angelo M. De , Sfanos Karen S.
Published: October 2015

The goal of the current study is to establish the mechanism by which mast cells may serve as a prognostic factor in and possibly explain the racial disparity associated with prostate cancer. There is increasing evidence for a strong association between chronic inflammation and prostate cancer, and the role of mast cells in prostate cancer are of particular interest as they have been suggested to influence cancer progression and immune modulation. It is well established that prostate cancer presents with significant racial disparities, with African American (AA) men being 65% more likely to be diagnosed with prostate cancer than Caucasian American (CA) men and more than two times as likely to die as a result of prostate cancer. In addition, studies have shown AA men to be significantly more likely to present with inflammation in prostate biopsy samples negative for prostate cancer, while microarray data has suggested that inflammatory pathways are highly represented in the differentially expressed mRNA in the tumors of AA vs CA men. Complicating these results, it is probable that inflammatory cells play varied and multiple roles in different regions and grades within the same cancer. With this in mind, we are currently using immunohistochemistry (IHC) and in-situ hybridization techniques to directly visualize and localize mast cells in the prostate microenvironment. These studies are aided by novel digital image analysis using a software framework integrating whole slide imaging, virtual microscopy, and ImageJ based analysis algorithms. Our preliminary results in a 10 case tissue microarray (TMA) are consistent with other reports in the literature indicating that there are higher mast cell densities in better differentiated cancers; however, we are examining this further in a larger full slide cohort in relation to Gleason grade and stage. We are currently utilizing this image analysis technology on a TMA cohort designed to explore differences in mast cell density in AA vs CA men. Furthermore, we aim to examine differences in mast cell subtypes between benign and malignant regions of the prostate and between AA and CA men. Our goal is to establish the mechanism by which mast cells may serve as a prognostic factor in prostate cancer and may help to explain prostate cancer racial disparities.

Citation Format: Heidi A. Hempel, Ibrahim Kulac, Nathan S. Cuka, Toby C. Cornish, Angelo M. De Marzo, Karen S. Sfanos. Mast cells in prostate cancer race disparities: Are the minutemen of the microenvironment the key? [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A70.