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The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins—whose aberrant activities govern the reprogramed state of infected-coronavirus cells—presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to establ

Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies.

Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone marrow. Myeloid-derived suppressor cells (MDSCs) and mesenchymal stromal cells (MSCs) display immunoregulatory properties by controlling the innate and adaptive immune systems that may induce a tolerant and supportive microenvironment for neoplasm

Updates on Therapeutic Strategies in the Treatment of Relapsed/Refractory Multiple Myeloma.

Multiple myeloma is a heterogeneous condition characterized by the proliferation of monoclonal B-cells, for which there is currently no curative treatment available. Relapses are, unfortunately, common after first-line treatment. While the prognosis for relapsed refractory multiple myeloma is generally poor, advances in the treatment of relapsed or refractory multiple myeloma offer hope. However, the expansion of effective options in targeted treatment offers renewed optimism and hope that patients who fail on older therapies may respond to newer modalities, which are often used in combination

The role of proteasomes in tumorigenesis.

Protein homeostasis is the basis of normal life activities, and the proteasome family plays an extremely important function in this process. The proteasome 20S is a concentric circle structure with two α rings and two β rings overlapped. The proteasome 20S can perform both ATP-dependent and non-ATP-dependent ubiquitination proteasome degradation by binding to various subunits (such as 19S, 11S, and 200 PA), which is performed by its active subunit β1, β2, and β5. The proteasome can degrade misfolded, excess proteins to maintain homeostasis. At the same time, it can be utilized by tumors to deg

Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy.

The Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1 (SHP-1), a non-receptor protein tyrosine phosphatase, has been reported as a negative regulator of phosphorylated signal transducer and activator of transcription 3 (STAT3) and linked to tumor development. In this present review, we will discuss the importance and function of SHP-1/p-STAT3 signaling in nonmalignant conditions as well as malignancies, its cross-talk with other pathways, the current clinical development and the potential role of inhibitors of this pathway in anticancer therapy and clinical relevance of SHP

Chemotherapy-induced pulmonary complications in cancer: Significance of clinicoradiological correlation.

Chemotherapy while revolutionizing cancer management by improving survival and quality of life; is also associated with several adverse effects. Lung is the most common organ affected in chemotherapy-related complications, due to either drug toxicity or more commonly due to infections caused by immunosuppression and less commonly due to immune-mediated injury. Radiology, when used in combination with clinical and lab data, can help reach the specific diagnosis or narrow down the differentials. The common radiological patterns of drug toxicity include pulmonary interstitial and airway infiltrat

Генетическое или терапевтическое нарушение траектории подачи сигналов Reelin/Apoer2 улучшает воспалительные результаты артрита.

Ремутатоидный артрит (RA) — хроническое аутоиммунное заболевание, характеризующееся синновальным воспалением, образованием паннуса и постепенным совместным разрушением. Вспыльчивая среда в RA приводит к активации эндотелиальных клеток и к повышению регулирования молекул сцепления, что облегчает проникновение лейкоцитов в синовый. Релин, циркулирующий гликопротеин, ранее связанный с активацией эндотели и вербовкой лейкоцитов для лечения таких заболеваний, как атеросклероз и множественный склероз, стал потенциальным регулятором этих процессов. Однако его роль в патогенезе РА остается слабой. Зде

Potential role of immunotherapy and targeted therapy in the treatment of cancer: A contemporary nursing practice.

Immunotherapy and targeted therapy have emerged as promising therapeutic options for cancer patients. Immunotherapies induce a host immune response that mediates long-lived tumor destruction, while targeted therapies suppress molecular mechanisms that are important for tumor maintenance and growth. In addition, cytotoxic agents and targeted therapies regulate immune responses, which increases the chances that these therapeutic approaches may be efficiently combined with immunotherapy to ameliorate clinical outcomes. Various studies have suggested that combinations of therapies that target diff

Epidemiology of infections in cancer patients.

Although major advances in the care of cancer patients over the past several decades have resulted in improved survival, infectious complications remain a significant cause of morbidity and mortality. To successfully identify, treat, and prevent infections, a comprehensive understanding of risk factors that predispose to infection and of commonly encountered pathogens is necessary. In addition, clinicians must keep abreast of the changing epidemiology of infections in this population. As therapeutic modalities continue to evolve, as established pathogens become increasingly drug resistant, and

Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.

Immune checkpoints are differentially expressed on various immune cells to regulate immune responses in tumor microenvironment. Tumor cells can activate the immune checkpoint pathway to establish an immunosuppressive tumor microenvironment and inhibit the anti-tumor immune response, which may lead to tumor progression by evading immune surveillance. Interrupting co-inhibitory signaling pathways with immune checkpoint inhibitors (ICIs) could reinvigorate the anti-tumor immune response and promote immune-mediated eradication of tumor cells. As a milestone in tumor treatment, ICIs have been first

Therapeutic Targeting of DNA Damage Repair in the Era of Precision Oncology and Immune Checkpoint Inhibitors.

Cancer manifestation is a multistep process involving accumulation of various genetic and epigenetic changes that results in oncogenic "hallmarks of cancer" processes including genomic instability. Exploitation of aberrant DNA-damage response (DDR) mechanisms in cancer is in part a goal of many therapeutic strategies, and recent evidence supports the role of targeting DDR in modulating the tumor immune microenvironment to enhance immunotherapeutic response. Improved cancer profiling, including next-generation and whole-genome mutational sequencing of tumor tissue, as well as circulating nuclei

Development of fever following first administration of zoledronate as a prognostic factor in advanced non-small cell lung cancer patients with bone metastases.

Nitrogen-containing bisphosphonates (N-BPs), which are usually used for the treatment of advanced cancer with bone metastasis, occasionally cause fever following the first administration. However, it is unclear as to how the development of fever following the first administration of N-BP is associated with clinical outcome. The aim of the present study was to determine the prognostic value of the development of fever following the first administration of N-BP in advanced non-small cell lung cancer patients with bone metastases. The present study reviewed the data of 46 patients with advanced n

Infiltrative and inflammatory systemic disorders involving the pituitary gland.

The hypothalamic-pituitary region can be affected by a wide and heterogeneous group of infiltrative and inflammatory disorders, including granulomatous, histiocytic, storage, infectious, non-pituitary neoplastic, and autoimmune or inflammatory conditions collectively grouped as hypophysitis. Although individually rare, these disorders are increasingly recognized due to growing awareness, wider use of pituitary imaging, and the emergence of immune checkpoint inhibitor-induced hypophysitis. They typically present with hypopituitarism (often including arginine vasopressin deficiency, which, parti

Transcriptome Analysis Reveals Altered Inflammatory Pathway in an Inducible Glial Cell Model of Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1), the most frequent inherited muscular dystrophy in adults, is caused by the CTG repeat expansion in the 3'UTR of the DMPK gene. Mutant DMPK RNA accumulates in nuclear foci altering diverse cellular functions including alternative splicing regulation. DM1 is a multisystemic condition, with debilitating central nervous system alterations. Although a defective neuroglia communication has been described as a contributor of the brain pathology in DM1, the specific cellular and molecular events potentially affected in glia cells have not been totally recognized. Thus,

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… Activation of the interferon type I response rather than autophagy contributes to myogenesis inhibition in congenital DM1 myoblasts. Cell Death Dis. 2018;9:1071. doi: 10.1038/s41419-018-1080-1. 55. Todd P.K., Ackall F.Y., Hur J., Sharma K., Paulson H.L., Dowling J.J. …

Стратегии защиты от нейропии в множестве склерозов: обновление статуса и формирующиеся парадигмы.

ВВЕДЕНИЕ: MS представляет собой континуум заболеваний, в котором с момента начала и с течением времени происходит злокачественное воспаление и нейродегенерация. Недавний прогресс в недостатке патобиологии MS создает новые перспективы для новых терапевтических стратегий нейрозащиты. ОБЛАСТЬ ПРИМЕНЕНИЯ: Авторы кратко рассматривают механизмы, лежащие в основе воспаления и нейродегенерации в MS, и обсуждают нынешние и формирующиеся стратегии поощрения нейрозащиты в MS. Данные были получены в значительной степени на основе обширного обзора опубликованной литературы, имеющейся на PubMed (до 5 марта

Unmasking Sapovirus: Chronic Enteritis in an Immunocompromised Adult With Hypogammaglobulinemia.

Sapovirus is a recognized cause of acute viral gastroenteritis, predominantly affecting children and older adults. While typically self-limiting in immunocompetent individuals, sapovirus can result in persistent, severe gastrointestinal illness in immunocompromised patients. Chronic sapovirus enteritis remains underrecognized and lacks standardized treatment guidelines. We report the case of a 69-year-old woman with multiple myeloma and profound hypogammaglobulinemia secondary to chimeric antigen receptor (CAR) T-cell therapy who presented with a 10-month history of chronic watery diarrhea. Im

Improved outcome in patients following autologous stem cell transplantation for multiple myeloma in south eastern Norway 2001-2010: a retrospective, population based analysis.

BackgroundWith the advent of novel drugs improved overall survival in patients with multiple myeloma, including patients who received up-front autologous stem cell transplantation (ASCT), has been reported from several centers. Here we report on overall survival in a population-based cohort of patients receiving ASCT as first line treatment and in whom novel agents were an option for second and later lines of treatment.MethodsPatients with multiple myeloma ≤ 65 years of age who were considered for ASCT from 01.01.2001-31.06.2005 (period 1) and from 01.07.2005 until 31.12.2009 (period 2) at Osl

Эпидемиология, характеристики и лечение пациентов с повторным переносом множественных склерозов и высоким уровнем заболеваемости: Реальные данные по миру, основанные на данных, представленных Германией.

Множественный склероз (MS) является хроническим воспалительным, иммунным средоточием заболевания центральной нервной системы, при этом наиболее распространенным типом является повторное излучение MS (RRMS). В последние годы для принятия клинических решений все более важное значение приобретает состояние высокой заболеваемости (HDA). Тем не менее, мало что известно о частотности, характеристиках и текущем лечении пациентов с RRMS и HDA в Германии. Таким образом, цель данного исследования состоит в том, чтобы оценить распространенность ВИЧ/СПИДа среди немецкой группы пациентов, страдающих ОРМС,

Cytokine release syndrome in solid tumours: mechanism-based therapeutic strategies for prevention and management.

Cytokine release syndrome (CRS) represents a spectrum of immune hyperactivation initiated by rapid T-cell engagement and amplified through innate immune cells, particularly monocytes and macrophages, with downstream cytokine cascades driving endothelial dysfunction, capillary leak and organ impairment. CRS is a frequent, class-associated toxicity of T-cell-engaging immunotherapies and is being observed with increasing regularity as T-cell-redirecting therapies progress through clinical development in solid tumours. Although CRS is typically less severe in patients with solid tumours relative t

Полигенная природа множественного склероза: генетические варианты, иммунологические модуляции и экологические связи.

Множественный склероз (MS) — изнуряющее воспалительное расстройство центральной нервной системы, характеризующееся обезвоживанием, — в значительной степени зависит от полигенных вариаций. Хотя конкретная причина НР остается неясной, считается, что она возникает в результате сложного взаимодействия генетических и экологических факторов. Последние исследования были сосредоточены на полигенном характере генетических изменений, связанных с риском НР. В настоящем обзоре подчеркивается важнейшая роль этих генетических вариантов в формировании восприимчивости к болезням и их развития. Специфические а

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… This association is attributed to TYK2's role in mediating cytokine signaling pathways, including those of Interferon type I (IFN-I) [ 187 , 188 ]. …