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The Roles of EDA2R in Ageing and Disease.

Ageing is a complex biological process driven, in part, by inflammaging. Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated EDA2R gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clo

Emerging Role of the Macrophage Migration Inhibitory Factor Family of Cytokines in Neuroblastoma. Pathogenic Effectors and Novel Therapeutic Targets?

Neuroblastoma (NB) is the most frequent extracranial pediatric tumor. Despite the current available multiple therapeutic options, the prognosis for high-risk NB patients remains unsatisfactory and makes the disease a clear unmet medical need. Thus, more tailored therapeutic approaches are warranted to improve both the quality of life and the survival of the patients. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that plays a key role in several diseases, including cancer. Preclinical and clinical studies in NB patients convergently indicate that MIF exerts pro-tumorige

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia.

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemi

Inhibiting of TACC3 Promotes Cell Proliferation, Cell Invasion and the EMT Pathway in Breast Cancer.

Accumulating evidences indicate that transforming acidic coiled-coil 3 (TACC3) is a tumor-related gene, was highly expressed in a variety of human cancers, which is involved in cancer development. However, the potential role of TACC3 in breast cancer remains largely unknown. In the present study, we found that TACC3 was highly-expressed in breast cancer tissues, and its level was positively correlated with the clinical features of breast cancer patients. Specifically, TACC3 expression was significantly associated with the estrogen receptor (ER), progesterone receptor (PR), human epidermal grow

Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called "smoldering" MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TM

The Role of Platelet Dysfunctions in the Pathogenesis of the Hemostatic-Coagulant System Imbalances.

Platelet dysfunction plays a critical role in the pathogenesis of various disorders affecting the hemostatic-coagulant system. This review aims to explore the mechanisms by which platelet dysfunctions contribute to the disruption of hemostasis, leading to an increased risk of both thrombosis and bleeding. Platelets, traditionally known for their role in clot formation, can exhibit altered functionality under pathological conditions such as cardiovascular diseases, metabolic disorders, and autoimmune diseases, impacting their interaction with coagulation factors and vascular endothelium. The re

Mortality patterns and risk among older men and women with intellectual disability: a Swedish national retrospective cohort study.

BackgroundSweden has closed all institutions and imposed legislation to ensure service and support for individuals with intellectual disability (ID). Understanding mortality among older individuals with ID is essential to inform development of health promotion and disease control strategies. We investigated patterns and risk of mortality among older adults with ID in Sweden.MethodsThis retrospective cohort study compared older adults aged 55 years and older with ID with a control population. Participants were followed during 2002-2015 or death, and censored if they moved out of Sweden. Individ

Polyphenols: Chemoprevention and therapeutic potentials in hematological malignancies.

Polyphenols are one of the largest plant-derived natural product and they play an important role in plants' defense as well as in human health and disease. A number of them are pleiotropic molecules and have been shown to regulate signaling pathways, immune response and cell growth and proliferation which all play a role in cancer development. Hematological malignancies on the other hand, are cancers of the blood. While current therapies are efficacious, they are usually expensive and with unwanted side effects. Thus, the search for newer less toxic agents. Polyphenols have been reported to po

Growth differentiation factor-15 may be a novel biomarker in pancreatic cancer: A review.

Pancreatic cancer is a highly malignant and invasive gastrointestinal tumor that is often diagnosed at an advanced stage with a poor prognosis and high mortality. Currently, carbohydrate antigen199(CA199) is the only biomarker approved by the FDA for the diagnosis of pancreatic cancer, but it has great limitations. Growth differentiation factor-15 (GDF-15) is expected to be a novel biomarker for the diagnosis, efficacy prediction, and prognosis assessment of pancreatic cancer patients. In this paper, we searched the keywords GDF-15, macrophage inhibitory cytokine-1 (MIC-1), CA199, pancreatic c

Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma.

Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779), a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21 and v-Raf, and induced autophagy. The first clinical trial in MCL patients was performed using 250 mg of temsirolimus weekly for 6-12 cycles. The overall response rate was 38%; the median time to progression was 6.5 months, median overall survival was 12 months, and the med

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond.

Despite the challenges imposed by the COVID-19 pandemic, exciting therapeutic progress continues to be made in MM. New drug approvals for relapsed/refractory (RR)MM in 2020/2021 include the second CD38 monoclonal antibody, isatuximab, the first BCMA-targeting therapy and first-in-class antibody-drug conjugate (ADC) belantamab mafodotin, the first BCMA-targeting CAR T cell product Idecabtagen-Vicleucel (bb2121, Ide-Cel), the first in-class XPO-1 inhibitor selinexor, as well as the first-in-class anti-tumor peptide-drug conjugate, melflufen. The present introductory article of the Special Issue

Replacement of miR-155 Elicits Tumor Suppressive Activity and Antagonizes Bortezomib Resistance in Multiple Myeloma.

Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given th

Амиотропический латеральный склероз и лобовое дегенерация: сходства в генетическом фоне

Амиотрофический боковой склероз (ALS) — это разрушительное, равномерно смертоносное прогрессивное дегенеративное расстройство моторных нейронов, которое перекликается с клиническим, морфологическим и генетическим дегенерацией лобар (FTLD). Хотя известно, что многие различные мутации в различных генах вызывают амиотрофный боковой склероз, по-прежнему мало что известно о том, как они избирательно влияют на биологию моторных нейронов и сходятся ли они на общих путях, чтобы вызвать нейронное дегенерацию. Многие генные мутации содержатся в белках, которые имеют схожие функции. Их можно сгруппироват

Многофункциональная роль аполипопротеина Е в нейродегенеративных заболеваниях.

Генетическое разнообразие в гене аполипопротеина Е (АпоЭ) было определено в качестве основного фактора риска уязвимости в плане генетического риска для спорадического заболевания Альцгеймера (САД). В частности, аллея АпоЕ4 является важным фактором риска для SAD, в то время как аллея АпоЕ2 обеспечивает защиту по сравнению с более распространенными аллеями АпоЕ3. В настоящем обзоре рассматривается роль АпоЭ в АД и других нейродегенеративных расстройствах. ApoE — белок переноса холестерина — влияет на несколько путей нейродегенерации, особенно в AD. Помимо своей установленной роли в метаболизме и

Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumo

Erythropoiesis: insights into pathophysiology and treatments in 2017.

Erythropoiesis is a tightly-regulated and complex process originating in the bone marrow from a multipotent stem cell and terminating in a mature, enucleated erythrocyte.Altered red cell production can result from the direct impairment of medullary erythropoiesis, as seen in the thalassemia syndromes, inherited bone marrow failure as well as in the anemia of chronic disease. Alternatively, in disorders such as sickle cell disease (SCD) as well as enzymopathies and membrane defects, medullary erythropoiesis is not, or only minimally, directly impaired. Despite these differences in pathophysiolo

Совпадение в полном тексте источника
… The degree of phenotypic correction of murine beta -thalassemia intermedia following lentiviral-mediated transfer of a human gamma-globin gene is influenced by chromosomal position effects and vector copy number. Blood. 2003;101:2175–2183. doi: 10.1182/blood-2002-07-2211. Persons DA, et al. …

Clinical Utility of Selinexor/Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma: A Review of Current Evidence and Patient Selection.

Multiple myeloma (MM) is one the most common hematological malignancies, and despite the survival prolongation offered by proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs) and anti-CD38 monoclonal antibodies, the need for novel agents is prominent. Selinexor is a first-in-class, oral, selective inhibitor of exportin-1 (XPO1), a vital protein for the exportation of more than 200 tumor suppressor proteins from the nucleus. Both in solid tumors and hematologic malignancies, selinexor-mediated inhibition of nucleus export seems to effectively lead to cancer cell death. Selinexor in combi

Получил от "Puff of Domoke"-A Case-Review on the Challenging Discrimination of CNS Demielining Beace and Moyamoya Angiopatia.

Moyamoya aнгиопатия (MMA) — цереброваскулярное заболевание, определяющее хроническое прогрессивное включение надклиноидных внутренних артерий сонной артерии и их основных веток. Патогенез ММА по-прежнему в значительной степени неизвестен. Множественный склероз (MS) является хроническим, подстрекательским и демиелинизирующим заболеванием центральной нервной системы, характеризующимся постепенным накоплением фокусных демиелионирующих повреждений, патофизиология которых была теоретической, но до сих пор не до конца понята. Помимо неправильной диагностики из-за имитирующих эти два расстройства осо

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics.

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly a

Single-cell sequencing reveals MYC targeting gene MAD2L1 is associated with prostate cancer bone metastasis tumor dormancy.

BackgroundAmong malignant tumors, bone metastasis is frequently associated with prostate cancer which is seen in about 80% of patients. During cancer treatments, some tumor cells switch to a "dormant mode" to help tumor cells avoid attack from the immune system and anti-tumor therapies. In this dormant mode, tumor cells can be resuscitated, causing cancer to reoccur. The generally accepted explanation for this phenomenon is that the tumor cells have spread to the bone marrow before treatment and are dormant in the bone marrow. However, the key mechanism for inducing and maintaining the dormanc