The Memory Activation of NK Cells: New Methods in Cancer Immunotherapy

Cancer remains a main cause of mortality, despite the research efforts to unravel molecular mechanisms and for developing personalized targeted therapies with acceptable side effects. In cancer, both players, the aggressor (tumor cells) and the endogenous defenders (immune cells), are key therapeutic targets. Immunotherapy is nowadays considered the fourth therapeutical approach in cancer, complementing and sometimes replacing surgery and chemo‐ and radiotherapy. Natural killer (NK) cells, generally considered part of the innate immune system, play a critical role in defense against pathogens and tumors. Immunological memory is a hallmark of the adaptive immune system. However, NK cells have been shown to mediate Ag‐specific recall responses and acquire immunological memory in a manner similar to that of T and B cells. This chapter summarizes evidence for NK cell immunotherapy, evidence and characteristics of NK cell memory and mechanisms involved in the generation and survival of these cells. There is no doubt that NK cells have major role in cancer treatments and viral infections, and in the future, NK cell immunotherapy from “a new hope” may become “a reality” for malignant diseases

Schwann Cell Plasticity in Peripheral Nerve Regeneration after Injury

In the normal peripheral nervous system, Schwann cells (SCs) are present in two different states of differentiation: myelinating SCs that surround large-caliber axons, forming myelin sheath, and non-myelinating SCs that surround more small-caliber axons forming Remak bundles. Under pathological conditions (injury or inflammation), SCs, with a remarkable plasticity, undergo phenotypic transformations, downregulating the production of myelin proteins mRNAs, upregulating neurotrophic factors and cytokines, thus promoting the axonal regeneration. Dedifferentiated SCs activate the protein degradation, participating in the demyelination process and clearance of myelin debris; attract macrophages helping wound healing; proliferate to replace lost cells; guide axonal growth; and protect against secondary axonal damage. Thus, SC functions have a critical contribution to regeneration processes that occur in peripheral nerve after injury

The importance of early arthritis in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that manifests predominantly in the synovial joint, where it causes a chronic inflammatory process, leading to early osteoarticular destructions. These destructions are progressive and irreversible, generating a significant functional deficiency. During the last years, the diagnostic approach of RA has focused on early arthritis. Early arthritis can develop into established RA or another established arthropathy, like systemic lupus erythematosus or psoriatic arthritis. It can have a spontaneous resolution or may remain undifferentiated for indefinite periods of time. The management of early arthritis has changed considerably in the past few years, under the influence of new concepts of diagnosis and new effective therapies. The treatment goal of early arthritis should now be the clinical remission and prevention of joint destruction. Methotrexate is the first line of therapy, used to treat early arthralgia and to reverse or limit impending exacerbation to RA. Biological treatment is used as a second line therapy in patients with severe disease who do not respond or have a contraindication to disease-modifying antirheumatic drugs (DMARDs). Patients with early arthritis should usually be identified and directed to rheumatologists to confirm the presence of arthritis, and to establish the correct diagnosis plus to initiate the proper treatment strategies

The importance of early arthritis in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that manifests predominantly in the synovial joint, where it causes a chronic inflammatory process, leading to early osteoarticular destructions. These destructions are progressive and irreversible, generating a significant functional deficiency. During the last years, the diagnostic approach of RA has focused on early arthritis. Early arthritis can develop into established RA or another established arthropathy, like systemic lupus erythematosus or psoriatic arthritis. It can have a spontaneous resolution or may remain undifferentiated for indefinite periods of time. The management of early arthritis has changed considerably in the past few years, under the influence of new concepts of diagnosis and new effective therapies. The treatment goal of early arthritis should now be the clinical remission and prevention of joint destruction. Methotrexate is the first line of therapy, used to treat early arthralgia and to reverse or limit impending exacerbation to RA. Biological treatment is used as a second line therapy in patients with severe disease who do not respond or have a contraindication to disease-modifying antirheumatic drugs (DMARDs). Patients with early arthritis should usually be identified and directed to rheumatologists to confirm the presence of arthritis, and to establish the correct diagnosis plus to initiate the proper treatment strategies

Lymphocyte Updates - Cancer, Autoimmunity and Infection

This book represents a synergic effort of an international team of specialists in immunology to expand the scientific achievements in the field of lymphocytes. It offers important and specific updated information to researchers, students, teachers, and medical professionals. Moreover, considering the remarkable dynamics of immunology and immunotherapy, this book ""Lymphocyte Updates - Cancer, Autoimmunity, and Infection"" aims to represent a significant source of concise scientific data and advancement of knowledge in this field. The chapters offer new insights into the latest scientific progress on lymphocyte roles in protective immunity, as well as their involvement in pathogenesis of various disorders

Exposure of Human Endothelial Progenitors to Sevoflurane Improves Their Survival Abilities

Endothelial progenitor cells (EPCs) have prominent roles in vessel and tissue repair; however, their regenerative efficacy is diminished due to the poor survival in the hostile microenvironment of the injured organs. Recent data suggest a promising potential of volatile anesthetics for improving stem cell biology. Thus, we hypothesized that exposure to sevoflurane could stimulate growth and viability of cultured EPCs

The redox biology network in cancer pathophysiology and therapeutics

The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the hypoxia map in the tumor niche, along with the adjoining and systemic effects of oxidative stress-based therapies. Keywords: Cancer, Tumor niche, Redox signaling, Radiotherapy, Photodynamic therapy, Bystander and abscopal effect

Cardioprotective Mechanisms of Interrupted Anesthetic Preconditioning with Sevoflurane in the Setting of Ischemia/Reperfusion Injury in Rats

Background: Anesthetic preconditioning (AP) is known to mimic ischemic preconditioning. The purpose of this study was to investigate the effects of an interrupted sevoflurane administration protocol on myocardial ischemia/reperfusion (I/R) injury. Methods: Male Wistar rats (n = 60) were ventilated for 30 min with room air (control group, CG) or with a mixture of air and sevoflurane (1 minimum alveolar concentration—MAC) in 5-min cycles, alternating with 5-min wash-out periods (preconditioned groups). Cytokines implicated in the AP response were measured. An (I/R) lesion was produced immediately after the sham intervention (CG) and preconditioning protocol (early AP group, EAPG) or 24 h after the intervention (late AP group, LAPG). The area of fibrosis, the degree of apoptosis and the number of c-kit+ cells was estimated for each group. Results: Cytokine levels were increased post AP. The area of fibrosis decreased in both EAPG and LAPG compared to the CG (p p = 0.006) and EAPG (p = 0.007) and the number of c-kit+ cells was the greatest for the LAPG (p < 0.0001). Conclusions: Sevoflurane preconditioning, using an interrupted anesthesia protocol, is efficient in myocardial protection and could be beneficial to reduce perioperative or periprocedural ischemia in patients with increased cardiovascular risk

Oxidative Stress: A Possible Trigger for Pelvic Organ Prolapse

Pelvic organ prolapse is a frequent health problem in women, encountered worldwide, its physiopathology being still incompletely understood. The integrity of the pelvic-supportive structures is a key element that prevents the prolapse of the pelvic organs. Numerous researchers have underlined the role of connective tissue molecular changes in the pathogenesis of pelvic organ prolapse and have raised the attention upon oxidative stress as an important element involved in its appearance. The advancements made over the years in terms of molecular biology have allowed researchers to investigate how the constituent elements of the pelvic-supportive structures react in conditions of oxidative stress. The purpose of this paper is to underline the importance of oxidative stress in the pathogenesis of pelvic organ prolapse, as well as to highlight the main oxidative stress molecular changes that appear at the level of the pelvic-supportive structures. Sustained mechanical stress is proven to be a key factor in the appearance of pelvic organ prolapse, correlating with increased levels of free radicals production and mitochondrial-induced fibroblasts apoptosis, the rate of cellular apoptosis depending on the intensity of the mechanical stress, and the period of time the mechanical stress is applied. Oxidative stress hinders normal cellular signaling pathways, as well as different important cellular components like proteins, lipids, and cellular DNA, therefore significantly interfering with the process of collagen and elastin synthesis