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Pericytes: The Role of Multipotent Stem Cells in Vascular Maintenance and Regenerative Medicine.
Authors: Ahmed TA, El-Badri N Abstract Blood vessels consist of an inner endothelial cell layer lining the vessel wall and perivascular pericytes, also known as mural cells, which envelop the vascular tube surface. Pericytes have recently been recognized for their central role in blood vessel formation. Pericytes are multipotent cells that are heterogeneous in their origin, function, morphology and surface markers. Similar to other types of stem cells, pericytes act as a repair system in response to injury by maintaining the structural integrity of blood vessels. Several studies have shown that blood vessels lackin...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Dawning of Translational Breast Cancer: From Bench to Bedside.
Authors: Chen X, Fan S, Song E Abstract Breast cancer is one of the world's leading causes of death in women. Although tumor initiation and progression are predominantly driven by somatic or acquired (epi) genetic alterations that govern signaling abnormalities, growing evidence suggests that the inflammatory microenvironments of cancer also play a role. Molecular characterization of breast cancer biology is essential for high-efficient management of this disease in clinical practice. Translating basic research into clinically valuable biomarkers for diagnosis, prognosis, and prediction of response to treatment and...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Biomarker Studies in Early Detection and Prognosis of Breast Cancer.
Authors: Li G, Hu J, Hu G Abstract Breast cancer is characterized with enormous heterogeneity, which represents the major hurdle for accurate diagnosis and curative therapy. It is generally believed that genome unstability and molecular evolvability underlie the robustness of cancer cells in hostile microenvironment and their resilience to therapeutic intervention. Conventional histopathological classification of breast cancer falls short of providing sufficient prognostic and predictive power, and thus biomarkers indicative of tumor intrinsic features at molecular levels have been actively pursued in biomedical re...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Preventive Intervention of Hereditary Breast Cancer.
Authors: Cao A, Huang L, Shao Z Abstract Approximately 5-10% of breast cancer is considered to be hereditary. Familial breast cancers exhibit a dominant hereditary pattern, which typically have an early age of onset and are accompanied by symptoms of ovarian cancer, bilateral breast cancer, or male breast cancer. BRCA gene mutation carriers should be regarded as high-risk groups for breast cancer, which necessitates early examination of breast cancer. Studies have built up kinds of predictive models and recommended that female BRCA mutation carriers should receive breast self-test training and take monthly breast s...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Predicting and Overcoming Chemotherapeutic Resistance in Breast Cancer.
Authors: Chun KH, Park JH, Fan S Abstract Our understanding of breast cancer and its therapeutic approach has improved greatly due to the advancement of molecular biology in recent years. Clinically, breast cancers are characterized into three basic types based on their immunohistochemical properties. They are triple-negative breast cancer, estrogen receptor (ER) and progesterone receptor (PR)-positive-HR positive breast cancer, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Even though these subtypes have been characterized, assessment of a breast cancer's receptor status is still wide...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Studies on DNA Damage Repair and Precision Radiotherapy for Breast Cancer.
Authors: Jiang Y, Liu Y, Hu H Abstract Radiotherapy acts as an important component of breast cancer management, which significantly decreases local recurrence in patients treated with conservative surgery or with radical mastectomy. On the foundation of technological innovation of radiotherapy setting, precision radiotherapy of cancer has been widely applied in recent years. DNA damage and its repair mechanism are the vital factors which lead to the formation of tumor. Moreover, the status of DNA damage repair in cancer cells has been shown to influence patient response to the therapy, including radiotherapy. Some ...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Targeted Therapies Against Growth Factor Signaling in Breast Cancer.
Authors: Du J, Yu Y, Zhan J, Zhang H Abstract Breast cancer is the most prevalent female malignancy throughout the world. Conventional treatment strategies for breast cancer consist of chemotherapy, radiation, surgery, chemoradiation, hormone therapy, and targeted therapies. Among them, targeted therapies show advantages to reduce cost and toxicity for being possible for individualized treatments based on the intrinsic subtypes of breast cancer. With deeper understanding of key signaling pathways concerning tumor growth and survival, growth factor-controlled signaling pathways are frequently dysregulated in the dev...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Targeting Stemness: Implications for Precision Medicine in Breast Cancer.
Authors: Liang ZM, Chen Y, Luo ML Abstract The genomic landscape of breast cancer has been delineated in recent years. Advances in molecular characterization and targeting strategies are making it feasible to integrate clinical, genome-based and phenotype-based diagnostic and therapeutic methods and apply them to individual patient in the era of precision medicine. Cancer stem cells (CSCs) are a subpopulation in the tumor which have the capability of self-renewal and differentiation. Breast CSCs have important clinical implications as they account for tumor initiation, maintenance, metastasis, therapy resistance, a...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Disrupting Tumor Angiogenesis and "the Hunger Games" for Breast Cancer.
Disrupting Tumor Angiogenesis and "the Hunger Games" for Breast Cancer. Adv Exp Med Biol. 2017;1026:171-195 Authors: Zhou Z, Yao H, Hu H Abstract Angiogenesis, one of the hallmarks of cancers, has become an attractive target for cancer therapy since decades ago. It is broadly thought that upregulation of angiogenesis is involved in tumor progression and metastasis. Though tumor vessels are tortuous, disorganized, and leaky, they deliver oxygen and nutrients for tumor development. Based on this knowledge, many kinds of drugs targeting angiogenesis pathways have been developed, such as bevacizu...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Key Factors in Breast Cancer Dissemination and Establishment at the Bone: Past, Present and Future Perspectives.
Authors: Owen S, Zabkiewicz C, Ye L, Sanders AJ, Gong C, Jiang WG Abstract Bone metastases associated with breast cancer remain a clinical challenge due to their associated morbidity, limited therapeutic intervention and lack of prognostic markers. With a continually evolving understanding of bone biology and its dynamic microenvironment, many potential new targets have been proposed. In this chapter, we discuss the roles of well-established bone markers and how their targeting, in addition to tumour-targeted therapies, might help in the prevention and treatment of bone metastases. There are a vast number of bone m...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Perspectives of Reprogramming Breast Cancer Metabolism.
Authors: Wang YP, Lei QY Abstract Reprogramming of cellular metabolism is one of the hallmarks of breast cancer. Breast cancer cells remodel metabolic network to maintain their transformed state and survive in a harsh tumor microenvironment. Dysregulated metabolism further interacts with cellular signaling and epigenetics to promote breast cancer development. Meanwhile, breast cancer stem cells exhibit unique metabolic features, which are critical for therapeutic resistance and tumor recurrence. Besides, aberrant metabolism of breast cancer cells reshapes tumor microenvironment, such as promoting cancer vasculariza...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Metabolic Changes During Cancer Cachexia Pathogenesis.
Authors: Shyh-Chang N Abstract Wasting of adipose tissue and skeletal muscle is a hallmark of metastatic cancer and a major cause of death. Like patients with cachexia caused by other chronic infections or inflammatory diseases, the cancer subject manifests both malnutrition and metabolic stress. Both carbohydrate utilization and amino acid incorporation are decreased in the muscles of cancer cachexia patients. Cancer cells affect host metabolism in two ways: (a) their own metabolism of nutrients into other metabolites and (b) circulating factors they secrete or induce the host to secrete. Accelerated glycolysis an...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Cell Cycle Regulation in Treatment of Breast Cancer.
Authors: Cai Z, Liu Q Abstract Cell cycle progression and cell proliferation are under precise and orchestrated control in normal cells. However, uncontrolled cell proliferation caused by aberrant cell cycle progression is a crucial characteristic of cancer. Understanding cell cycle progression and its regulation sheds light on cancer treatment. Agents targeting cell cycle regulators (such as CDKs) have been considered as promising candidates in cancer treatment. Although the first-generation pan-CDK inhibitors failed in clinical trials because of their adverse events and low efficacy, new selective CDK 4/6 inhibit...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

BRCA Gene Mutations and Poly(ADP-Ribose) Polymerase Inhibitors in Triple-Negative Breast Cancer.
Authors: Okuma HS, Yonemori K Abstract Breast cancer is the most common cancer in women worldwide. Treatment is chosen according to its hormone receptor status and human epidermal growth factor receptor 2 (HER2) status. Among the four main clinically set subtypes, hormone receptor-negative/HER2-negative subtype, also called triple-negative subtype (TNBC), is the most aggressive type with limited choices of therapy. However, recent research has provided important new insights into effective treatments for this subtype. One molecular target that has gained attention is the BRCA gene. BRCA proteins are involved in the...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Targeting the Epigenome as a Novel Therapeutic Approach for Breast Cancer.
Authors: Oh S, Ko JY, Oh C, Yoo KH Abstract Breast cancer is one of complex diseases that are influenced by environment. Various genetic and epigenetic alterations are provoking causes of breast carcinogenesis. Dynamic epigenetic regulation including DNA methylation and histone modification induces dysregulation of genes related to proliferation, apoptosis, and metastasis in breast cancer. DNA methylation is strongly associated with the repression of transcription through adding to the methyl group by DNA methyltransferases (DNMTs), and tumor suppressor genes such as CCND2 and RUNX3 have been investigated to underg...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Progress in Vaccine Therapies for Breast Cancer.
Authors: Li X, Bu X Abstract Therapeutic cancer vaccines aim to treat pre-existing cancer by boosting the patient's own immune system, which is an attractive strategy for cancer treatment. The cancer vaccines have mainly been designed to elicit antitumor T-cell immune responses that recognize and eradicate cancer. The advantages of cancer immunotherapy with cancer vaccines include a) high specificity of tumor antigen, b) minimal vaccine-related adverse events, and c) long-lasting immunity boosted by cancer vaccine which is important to control tumor relapse. In this chapter, we discuss identification of tumor antig...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Tumor Associated Macrophages as Therapeutic Targets for Breast Cancer.
Authors: Lao L, Fan S, Song E Abstract Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor stroma. TAMs promote tumor growth by suppressing immunocompetent cells, including neovascularization and supporting cancer stem cells. In the chapter, we discuss recent efforts in reprogramming or inhibiting tumor-protecting properties of TAMs, and developing potential strategies to increase the efficacy of breast cancer treatment. PMID: 29282692 [PubMed - in process] (Source: Advances in Experimental Medicine and Biology)
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

New Approaches in CAR-T Cell Immunotherapy for Breast Cancer.
Authors: Wang J, Zhou P Abstract Despite significant advances in surgery, chemotherapy, radiotherapy, endocrine therapy, and molecular-targeted therapy, breast cancer remains the leading cause of death from malignant tumors among women. Immunotherapy has recently become a critical component of breast cancer treatment with encouraging activity and mild safety profiles. CAR-T therapy using genetically modifying T cells with chimeric antigen receptors (CAR) is the most commonly used approach to generate tumor-specific T cells. It has shown good curative effect for a variety of malignant diseases, especially for hemato...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Immune Checkpoint Blockade in Breast Cancer Therapy.
Authors: Bu X, Yao Y, Li X Abstract Cancer immunotherapy is emerging as the most promising novel strategy for cancer treatment. Cancer immunotherapy is broadly categorized into three forms: immune checkpoint modulation, adoptive cell transfer, and cancer vaccine. Immune checkpoint blockade is demonstrated as the most clinically effective treatment with low immune-related adverse events (irAE). Blockade of PD-1/PD-L1 and CTLA-4 has achieved remarkable success in treating various types of tumors, which sparks great interests in this therapeutic strategy and expands the role of immune checkpoint blockade in treating t...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Strategies and Progress of Endocrine Therapy for Patients with Metastatic Breast Cancer.
Authors: Rugo HS, Li H, Gui X Abstract Breast cancer is one of the most prevalent cancers and the leading causes of cancer mortality in women worldwide and in China. For hormone receptor-positive (HR+) breast cancer, accounting for approximately 60-80% of breast cancer, endocrine therapy (ET) is the primary treatment strategy. For patients with HR+ metastatic breast cancer (MBC), there are many endocrine-based treatment options that can improve long-term outcomes and optimize quality of life. With the emergence and availability of new and effective agents, the options for ET have expanded in the last two decades. A...
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Erratum to: The Positive Effects of Exercise in Chemotherapy-Related Cardiomyopathy.
Authors: Cavarretta E, Mastroiacovo G, Lupieri A, Frati G, Peruzzi M PMID: 29285734 [PubMed - in process] (Source: Advances in Experimental Medicine and Biology)
Source: Advances in Experimental Medicine and Biology - December 30, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Efficacy of Tetrasodium EDTA on Biofilms.
In conclusion, these studies show that t-EDTA as a stand-alone agent is an effective anti-biofilm agent in vitro. We have demonstrated that t-EDTA is compatible with numerous wound dressing platforms. EDTA could provide an essential tool to manage biofilm-related infections and should be considered as an anti-biofilm agent alone or in combination with other antimicrobials or technologies for increased antimicrobial performance in recalcitrant wounds. PMID: 29280095 [PubMed - as supplied by publisher] (Source: Advances in Experimental Medicine and Biology)
Source: Advances in Experimental Medicine and Biology - December 29, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Management of Bradyarrhythmias in Heart Failure: A Tailored Approach.
Authors: Masarone D, Ammendola E, Rago A, Gravino R, Salerno G, Rubino M, Marrazzo T, Molino A, Calabrò P, Pacileo G, Limongelli G Abstract Patients with heart failure (HF) may develop a range of bradyarrhythmias including sinus node dysfunction, various degrees of atrioventricular block, and ventricular conduction delay. Device implantation has been recommended in these patients, but the specific etiology should be sought as it may influence the choice of the type of device required (pacemaker vs. implantable cardiac defibrillator). Also, pacing mode must be carefully set in patients with heart failure (HF)...
Source: Advances in Experimental Medicine and Biology - December 29, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Percutaneous Mitral Valve Interventions and Heart Failure.
Authors: Sharma A, Goel S, Agarwal S Abstract Mitral regurgitation (MR) is the most frequent Valvular Heart Disease (VHD) and is an important cause of heart failure. MR can be caused by primary valve abnormality (Degenerative MR/Primary MR) or it can be secondary to cardiomyopathy (Functional MR/Secondary MR). Medical management alleviates symptoms but does not alter the progression of the disease. Current guidelines recommend surgery for moderate-to-severe (Grade > 3) MR in patients with symptoms or evidence of left ventricular dysfunction. Despite current practice guidelines, the majority of patients...
Source: Advances in Experimental Medicine and Biology - December 27, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Tumor Immuno-Environment in Cancer Progression and Therapy.
Authors: Kalinski P, Talmadge JE Abstract The approvals of Provenge (Sipuleucel-T), Ipilimumab (Yervoy/anti-CTLA-4) and blockers of the PD-1 - PD-L1/PD-L2 pathway, such as nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq), have established immunotherapy as a key component of comprehensive cancer care. Further, murine mechanistic studies and studies in immunocompromised patients have documented the critical role of immunity in effectiveness of radio- and chemotherapy. However, in addition to the ability of the immune system to control cancer progression, it can also promote tumor growth, via ...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Cancer Immunotherapy Targets Based on Understanding the T Cell-Inflamed Versus Non-T Cell-Inflamed Tumor Microenvironment.
Authors: Gajewski TF, Corrales L, Williams J, Horton B, Sivan A, Spranger S Abstract Most cancers express tumor antigens that can be recognized by T cells of the host. The fact that cancers become clinically evident nonetheless implies that immune escape must occur. Two major subsets of human melanoma metastases have been identified based on gene expression profiling. One subgroup has a T cell-inflamed phenotype that includes expression of chemokines, T cell markers, and a type I IFN signature. In contrast, the other major subset lacks this phenotype and has been designated as non-T cell-inflamed. The mechanisms of...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Regulation of CTL Infiltration Within the Tumor Microenvironment.
Authors: Church SE, Galon J Abstract The tumor microenvironment consists of a complex milieu of cells and factors that maintain equilibrium between tumor progression and destruction. Characterization of the immune contexture in primary tumors has consistently shown that T lymphocytes are an integral predictor of improved clinical outcome. This is notably true in colorectal carcinoma where high densities of cytotoxic or memory T lymphocytes in the invasive margin and the center of the primary tumor predict better patient survival, a measure termed Immunoscore. Since a high Immunoscore and pre-existing adaptive immun...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Role of Tumor Microenvironment in Cancer Immunotherapy.
Authors: Frankel T, Lanfranca MP, Zou W Abstract The field of tumor immunology and immunotherapy has undergone a renaissance in the past decade do in large part to a better understanding of the tumor immune microenvironment. After suffering countless successes and setbacks in the twentieth century, immunotherapy has now come to the forefront of cancer research and is recognized as an important tool in the anti-tumor armamentarium. The goal of therapy is to aid the immune system in recognition and destruction of tumor cells by enhancing its ability to react to tumor antigens. This traditionally has been accomplished...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Immunogenic and Non-immunogenic Cell Death in the Tumor Microenvironment.
Authors: Pitt JM, Kroemer G, Zitvogel L Abstract The host immune system is continuously exposed to dying cells and has evolved to distinguish between cell death events signaling potential threats and physiological apoptosis that should be tolerated. Tumors can use this distinction to their advantage, promoting apoptotic death of cancer cells to induce tolerance and evasion of immunosurveillance. On the other hand, stimuli that cause immunogenic death of cancer cells can induce an effective anti-tumor immune response. In this chapter we discuss different forms of cell death in the tumor microenvironment, and how the...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Exosomes in Cancer: Another Mechanism of Tumor-Induced Immune Suppression.
Authors: Whiteside TL Abstract Exosomes are the smallest extracellular vesicles (EV) produced under physiological and pathological conditions by all cells and present in all body fluids. They are critical components of the intercellular communication network. Tumor cells release exosomes which are enriched in immunosuppressive molecules as well as biologically-active soluble factors and enzymes. Tumor-derived exosomes (TEX) interact with immune effector cells in the tumor microenvironment and in the circulation, deliver negative signals to these cells and interfere with their anti-tumor functions. By suppressing fu...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Chemo-Immunotherapy: Role of Indoleamine 2,3-Dioxygenase in Defining Immunogenic Versus Tolerogenic Cell Death in the Tumor Microenvironment.
Authors: Johnson TS, Mcgaha T, Munn DH Abstract In certain settings, chemotherapy can trigger an immunogenic form of tumor cell death. More often, however, tumor cell death after chemotherapy is not immunogenic, and may be actively tolerizing. However, even in these settings the dying tumor cells may be much more immunogenic than previously recognized, if key suppressive immune checkpoints such as indoleamine 2,3-dioxygenase (IDO) can be blocked. This is an important question, because a robust immune response to dying tumor cells could potentially augment the efficacy of conventional chemotherapy, or enhance the st...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Targeting Myeloid-Derived Suppressor Cells in Cancer.
Authors: Anani W, Shurin MR Abstract Myeloid derived suppressor cells (MDSC) represent only a minor fraction of circulating blood cells but play an important role in tumor formation and progression. They are a heterogeneous group of cells that influence the tumor microenvironment by depletion of amino acids, oxidative stress, decreased trafficking of antitumor effector cells, and increased regulatory T and regulatory dendritic cell responses. Investigational treatment strategies targeting MDSCs have attempted to inhibit MDSC development and expansion (stem cell factor blockade, modulate of cell signaling, and targe...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Tryptophan Catabolism and Cancer Immunotherapy Targeting IDO Mediated Immune Suppression.
Authors: Amobi A, Qian F, Lugade AA, Odunsi K Abstract Over the last decade, tryptophan catabolism has been firmly established as a powerful mechanism of innate and adaptive immune tolerance. The catabolism of tryptophan is a central pathway maintaining homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. This is driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase 2 (TDO), resulting in local depletion of tryptophan, while tryptophan catabolites accumulate, including kynurenine and ...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Lipid Inflammatory Mediators in Cancer Progression and Therapy.
Authors: Khadge S, Sharp JG, McGuire TR, Thiele GM, Talmadge JE Abstract Rodent and clinical studies have documented that myeloid cell infiltration of tumors is associated with neutrophilia, lymphocytopenia and poor patient outcomes. This contrasts with lymphocyte infiltration of tumors, which is associated with improved outcomes. Lifestyle parameters such as high fat diet s and omega (ω)-6 polyunsaturated fatty acids (PUFA) intake may influence these inflammatory parameters including extramedullary myelopoiesis that can contribute to a metastatic "niche". While, tumor secretion of growth factors (G...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Oncolytic Virotherapy and the Tumor Microenvironment.
Authors: Berkey SE, Thorne SH, Bartlett DL Abstract Oncolytic viral therapy is a promising approach to treat many malignancies, including breast, colorectal, hepatocellular, and melanoma. The best results are seen when using "targeted and armed" viruses. These are viruses that have been genetically modified to selectively replicate within cancer cells and express specific transgenes that alter the tumor microenvironment to inhibit tumor progression. The products of these transgenes induce cell death, make the virus less virulent, compromise tumor vascularity, and are capable of modulating or enhancing the...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Impact of Housing Temperature-Induced Chronic Stress on Preclinical Mouse Tumor Models and Therapeutic Responses: An Important Role for the Nervous System.
Authors: Hylander BL, Eng JW, Repasky EA Abstract In the last 10-15 years, there has been a recognition that the catecholamines (norepinephrine, NE, and epinephrine, Epi) released by the sympathetic nervous system under stressful conditions promote tumor growth through a variety of mechanisms. Tumors recruit autonomic nerves during their development and NE is then released locally in the tumor microenvironment (TME). Acting through adrenergic receptors present on a variety of cells in the TME, NE and Epi induce proliferation, resistance to apoptosis, epithelial to mesenchymal transition, metastasis of tumor ce...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Immunotherapeutic Targeting of Tumor-Associated Blood Vessels.
Authors: Fabian KL, Storkus WJ Abstract Pathological angiogenesis occurs during tumor progression and leads in the formation of an abnormal vasculature in the tumor microenvironment (TME). The tumor vasculature is disorganized, tortuous and leaky, resulting in high interstitial pressure and hypoxia in the TME, all of which are events that support tumor growth and survival. Given the sustaining role of the tumor vasculature, it has become an increasingly attractive target for the development of anti-cancer therapies. Antibodies, tyrosine kinase inhibitors and cancer vaccines that target pro-angiogenic factors, angio...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Adaptive Resistance to Cancer Immunotherapy.
Authors: McGray AJR, Bramson J Abstract Immunosuppressive mechanisms within the tumor microenvironment have emerged as a major impediment to cancer immunotherapy. While a broad range of secreted factors, receptors/ligands, and cell populations have been described that contribute to the immunosuppression, the involvement of these processes in immune evasion by tumors is typically considered to be an intrinsic property of the tumor. Evidence is now emerging that the processes underlying immune suppression within the tumor are, in fact, triggered by immune attack and reflect a dynamic interplay between the tumor and t...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Imaging the Tumor Microenvironment.
Authors: Abadjian MZ, Edwards WB, Anderson CJ Abstract The tumor microenvironment consists of tumor, stromal, and immune cells, as well as extracellular milieu. Changes in numbers of these cell types and their environments have an impact on cancer growth and metastasis. Non-invasive imaging of aspects of the tumor microenvironment can provide important information on the aggressiveness of the cancer, whether or not it is metastatic, and can also help to determine early response to treatment. This chapter provides an overview on non-invasive in vivo imaging in humans and mouse models of various cell types and physio...
Source: Advances in Experimental Medicine and Biology - December 26, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Potency of Induced Pluripotent Stem Cells in Cartilage Regeneration and Osteoarthritis Treatment.
Authors: Murphy C, Mobasheri A, Táncos Z, Kobolák J, Dinnyés A Abstract Osteoarthritis (OA) is the most common chronic disabling condition effecting the elderly, significantly impacting an individual patient's quality of life. Current treatment options for OA are focused on pain management and slowing degradation of cartilage. Some modern surgical techniques aimed at encouraging regeneration at defect sites have met with limited long-term success. Mesenchymal stem cells (MSCs) have been viewed recently as a potential tool in OA repair due to their chondrogenic capacity. Several studies have sho...
Source: Advances in Experimental Medicine and Biology - December 23, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Critical Appraisal of Multivariable Prognostic Scores in Heart Failure: Development, Validation and Clinical Utility.
Authors: Passantino A, Guida P, Parisi G, Iacoviello M, Scrutinio D Abstract Optimal management of heart failure requires accurate risk assessment. Many prognostic risk models have been proposed for patient with chronic and acute heart failure. Methodological critical issues are the data source, the outcome of interest, the choice of variables entering the model, the validation of the model in external population. Up to now, the proposed risk models can be a useful tool to help physician in the clinical decision-making. The availability of big data and of new methods of analysis may lead to developing new models in...
Source: Advances in Experimental Medicine and Biology - December 22, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Introduction to Medication Effects on Male Reproduction.
Authors: Drobnis EZ, Nangia AK Abstract The over-arching goal of this volume is to help infertility practitioners evaluate and manage their patients with poor semen quality. Medications can negatively impact on male reproduction and these effects are of increasing concern. People world-wide are using more medications than in the past, including men of childbearing age. In addition, men are fathering children later in life than previously, which is associated with greater medication use in the reproductive population. Finally, people are experiencing more chronic disease at earlier ages, particularly in developed co...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Challenges of Obtaining Evidence-Based Information Regarding Medications and Male Fertility.
Authors: Drobnis EZ, Nangia AK Abstract In the clinic, the existing literature is insufficient to counsel our infertile men on medication use. Most studies have flaws that limit their application to evidence-based practice. In this chapter, we discuss the limitations of the current literature and the challenges to designing more useful studies. Among the most important weaknesses of existing studies is lack of power; that is, too few men are included to draw conclusions about the existence and size of medication effects. Adequate power is particularly important when confirming an absence of medication effect. Bias ...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Male Reproductive Functions Disrupted by  Pharmacological Agents.
Male Reproductive Functions Disrupted by Pharmacological Agents. Adv Exp Med Biol. 2017;1034:13-24 Authors: Drobnis EZ, Nangia AK Abstract In this chapter, we review the male reproductive functions disrupted by medications. Medications can affect the hypothalamic-pituitary-gonad axis, acting as endocrine disrupting chemicals (EDCs). Disturbances may be directly at androgen receptors, modifying the activity of endogenous androgens at the target tissue, or may disrupt feedback loops at the hypothalamus or pituitary resulting in modification of gonadotropin release. Impaired testosterone production a...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Exogenous Androgens and Male Reproduction.
Authors: Drobnis EZ, Nangia AK Abstract Due in part to aggressive marketing, the prevalence of exogenous androgen use has increased to disturbing levels. Prescribing practitioners are often unaware of the severity of the anti-fertility effects. Exogenous androgens should only be prescribed if hypogonadism has been established by appropriate investigation, and preferably the patient does not intend to father a child. There are alternative medications, or combinations of medications, that can be used if hypogonadism is present and fertility is desired.It is somewhat counterintuitive that testosterone treatment will d...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Phosphodiesterase Inhibitors (PDE Inhibitors) and Male Reproduction.
Authors: Drobnis EZ, Nangia AK Abstract The nonspecific PDE inhibitors, particularly the methylxanthines: caffeine, pentoxifylline (PTX), and theophylline, are known to stimulate sperm motility in vitro and have been used to treat sperm prior to insemination. The in vivo effects are less dramatic. A beneficial effect of caffeine, which is a constituent of some medications, remains controversial. Very high doses of caffeine do have negative effects on fertility endpoints in men and experimental species. The specific PDE5 inhibitors, particularly sildenafil and tadalafil, are prescribed for erectile dysfunction, as w...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Pain Medications and Male Reproduction.
Authors: Drobnis EZ, Nangia AK Abstract The increasing use of opioid medications has become a crisis in developed countries. The profound negative effects of opioids on male reproduction are well known, but this topic is absent from the current conversations about these medications. In the fertility clinic, a significant proportion of our patients are using opioids for pain management, and the options for these men are unclear. Opioids exert their negative effects by a variety of mechanisms. At high doses, testosterone levels fall significantly and hypogonadism is seen. In part, this results from increased prolacti...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

5 ╬▒-Reductase Inhibitors (5ARIs) and Male Reproduction.
5α-Reductase Inhibitors (5ARIs) and Male Reproduction. Adv Exp Med Biol. 2017;1034:59-61 Authors: Drobnis EZ, Nangia AK Abstract The 5ARIs, finasteride and dutasteride, are used to treat benign prostate hyperplasia and lower urinary tract symptoms. At much lower doses, 5ARI treatment reduces male hair loss. These drugs inhibit the conversion of testosterone to the more active dihydrotestosterone (DHT). In men taking these medications, DHT levels are reduced by some 90% while testosterone levels remain relatively stable. Well known for their negative effects on libido and erectile function, 5ARIs ...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Psychotropics and Male Reproduction.
Authors: Drobnis EZ, Nangia AK Abstract Psychotropic drugs, including antidepressants, antipsychotics, and anticonvulsants, all have negative effects on sexual function and semen quality. These adverse events vary among men and are less pronounced for some medications, allowing their effects to be managed to some extent. Use of specific serotonin reuptake inhibitors (SSRIs) is prevalent in men of reproductive age; and application to treat premature ejaculation increases the number of young men on SSRI therapy. Oxidative damage to sperm can result from prolonged residence in the male reproductive tract. The increase...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Cardiovascular/Pulmonary Medications and Male Reproduction.
Authors: Drobnis EZ, Nangia AK Abstract Cardiovascular and respiratory medications are used by men of reproductive age although use of the former is most prevalent in advanced age. Many of these drugs have been associated with sexual dysfunction, including erectile and ejaculatory dysfunction, but for most there is insufficient evidence to link their use with testicular dysfunction, reduced semen quality or infertility. Some exceptions are the irreversible α1-adrenergic antagonist phenoxybenzamine, which carries a high risk of retrograde ejaculation; the specific α1A-adrenergic antagonists silodosin and...
Source: Advances in Experimental Medicine and Biology - December 20, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research