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Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation.

The perception that transplantation of hematopoietic stem cells can confer tolerance to any tissue or organ from the same donor is widely accepted but it has not yet become a treatment option in clinical routine. The reasons for this are multifaceted but can generally be classified into safety and efficacy concerns that also became evident from the results of the first clinical pilot trials. In comparison to standard immunosuppressive therapies, the infection risk associated with the cytotoxic pre-conditioning necessary to allow allogeneic bone marrow engraftment and the risk of developing gra

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View.

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding a deep understanding of various mediators' roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage in investigations due to its intricate and context-dependent functions. This review delves into the dual nature of IL-6 in HCC, exploring its seemingly contradictory roles as both a promoter and an inhibitor of disease progression. We dissect the pro-tumorigenic effects of IL-6, including its impact on tumor growth, angiogenesis, and metastasis. Concurrently, we examine its anti-

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenanc

MiR-203a-3p regulates the biological behaviors of ovarian cancer cells through mediating the Akt/GSK-3β/Snail signaling pathway by targeting ATM.

ObjectiveTo investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3β/Snail signaling pathway.MethodsThe expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic,

Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact.

Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic characteristics of HCC and their knowledge would clarify the optimal treatment approach in each patient. Several molecular mechanisms responsible for secondary resistance have been discovered over the last few years; they represent potential targets for new specific drugs. In this light, the advent of checkpoint inhibitors (ICIs) has been a new o

Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients.

Brain cancer and leukemia are the most common cancers diagnosed in the pediatric population and are often treated with lifesaving chemotherapy. However, chemotherapy causes severe adverse effects and chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and debilitating side effect. CIPN can greatly impair quality of life and increases morbidity of pediatric patients with cancer, with the accompanying symptoms frequently remaining underdiagnosed. Little is known about the incidence of CIPN, its impact on the pediatric population, and the underlying pathophysiological mecha

Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications.

Extracellular vesicles (EVs) play an important role in the cellular crosstalk by transferring bioactive molecules through biological barriers from a cell to another, thus influencing recipient cell functions and phenotype. Therefore, EVs are increasingly being explored as biomarkers of disease progression or response to therapy and as potential therapeutic agents in different contexts including in hematological malignancies. Recently, an EV role has emerged in allogeneic hematopoietic cell transplantation (allo-HCT) as well. Allogeneic hematopoietic cell transplantation often represents the on

Myeloma bone disease: pathogenesis and management in the era of new anti-myeloma agents.

IntroductionMultiple myeloma (MM) is a malignancy of plasma cells with characteristic bone disease. Despite recent great strides achieved in MM treatment owing to the implementation of new anti-MM agents, MM is still incurable and bone destruction remains a serious unmet issue in patients with MM.ApproachIn this review, we will summarize and discuss the mechanisms of the formation of bone disease in MM and the available preclinical and clinical evidence on the treatment for MM bone disease.ConclusionsMM cells produce a variety of cytokines to stimulate receptor activator of nuclear factor-κB l

Targeting the BMP Pathway in Prostate Cancer Induced Bone Disease.

From the 33,000 men in the U.S. who die from prostate cancer each year, the majority of these patients exhibit metastatic disease with bone being the most common site of metastasis. Prostate cancer bone metastases are commonly blastic, exhibiting new growth of unhealthy sclerotic bone, which can cause painful skeletal related events. Patient's current care entails androgen deprivation therapy, anti-resorptive agents, radiation, and chemotherapy to help control the spread of the cancer but little intervention is available to treat blastic bone disease. The transforming growth factor beta (TGFβ)

Одноклеточная транскриптомика для иммунного профилирования цереброспинной жидкости в неврологических заболеваниях.

В ходе этого всеобъемлющего обзора мы прорабатываем значительный объем исследований по одноклеточной транскриптомике в цереброспайнальной жидкости (CSF) для понимания неврологических заболеваний с аутоиммунным, нейродегенеративным, инфекционным или онкогенным происхождением. Мы тщательно изучаем все опубликованные исследования в этих областях с особым акцентом на множественный склероз, болезнь Альцгеймера и болезнь Паркинсона. Что касается этих заболеваний, то мы анализируем результаты, связанные с иммунными клетками, проникающими в мозг, на основе вскрытого анализа тканей мозга и с использова

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Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.

In cancer, mutational processes act in concert with epigenetic reprogramming to endow malignant cells with hallmark properties that underpin tumorigenesis. Compared with the relatively rigid and slow processes of genetic evolution, the plastic nature of chromatin enables cells to adapt to a changing environment more rapidly. Multiple myeloma is characterised by high levels of inter- and intra-patient heterogeneity at both the genetic and epigenetic levels. Understanding the many layers of genetic and non-genetic evolution and their interplay is crucial to improve patient outcomes. In this shor

Targeting nuclear import and export in hematological malignancies.

The transport of proteins across the nuclear membrane is a highly regulated process, essential for the cell function. This transport is actively mediated by members of the karyopherin family, termed importins, or exportins, depending on the direction of transport. These proteins play an active part in tumorigenesis, through aberrant localization of their cargoes, which include oncogenes, tumor-suppressor genes and mediators of key signal transduction pathways. Overexpression of importins and exportins is reported in many malignancies, with implications in cell growth and viability, differentia

CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities.

The advent of chimeric antigen receptor (CAR)-T cells has recently changed the prognosis of relapsing/refractory diffuse large B-cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood-brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms,

Совпадение в полном тексте источника
… Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients Front. Immunol. 2023 14 1188818 10.3389/fimmu.2023.1188818 37342332 PMC10277746 139. Shishido S.N. Hart O. Jeong S. …

Последние новости о диагностике и лечении почечных заболеваний в Множественной миеломе.

Множественная миелома (ММ) представляет собой сложно обработанную плазменную порчу клеток и вторую наиболее часто распространенную гематологическую гелингологию у взрослых, что оказывает значительное воздействие на функцию почек. Широкий спектр участия почек в MM включает в себя дисбаланс электролитов, повреждение трубки и даже редкие глумерлуарные заболевания. Эволюция методов лечения MM привела к заметным улучшениям в долгосрочном выживании пациентов, страдающих осложнениями, связанными с почками. За последнее десятилетие появились новейшие терапевтические агенты, включая протеазные ингибито

Многомерное профилирование и модели риска, основанные на клиническом развертывании АИ, в МГУС и миеломе.

Моноклональная гаммопатия неопределённого значения (MGUS), храпающая миелома (SMM) и множественная миелома (MM) образуют континуум расстройств плазменных клеток, причем прогрессировать от MGUS до MM трудно предсказать. Нынешние модели стратификации риска, в значительной степени основанные на клинических, лабораторных и цитогенетических маркерах, не отражают молекулярную сложность, лежащую в основе развития заболеваний, что ограничивает их прогнозную точность. Последние достижения в области мультиомики, включая геномику, транскриптомику, протеомику и метаболомику, позволили глубже понять молеку

Venetoclax Induces Cardiotoxicity through Modulation of Oxidative-Stress-Mediated Cardiac Inflammation and Apoptosis via NF-κB and BCL-2 Pathway.

Cardiovascular damage induced by anticancer therapy has become the main health problem after tumor elimination. Venetoclax (VTX) is a promising novel agent that has been proven to have a high efficacy in multiple hematological diseases, especially acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Considering its mechanism of action, the possibility that VTX may cause cardiotoxicity cannot be ruled out. Therefore, this study was designed to investigate the toxic effect of VTX on the heart. Male Sprague-Dawley rats were randomly divided into three groups: control, low-dose VTX

Implications of regulatory T cells in anti-cancer immunity: from pathogenesis to therapeutics.

Regulatory T cells (Tregs) play an essential role in maintaining immune tolerance and suppressing inflammation. However, Tregs present major hurdle in eliciting potent anti-cancer immune responses. Therefore, curbing the activity of Tregs represents a novel and efficient way towards successful immunotherapy of cancer. Moreover, there is an emerging interest in harnessing Treg-based strategies for augmenting anti-cancer immunity in different types of the disease. This review summarises the crucial mechanisms of Tregs' mediated suppression of anti-cancer immunity and strategies to suppress or to