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The TGF-β/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia.

Natural killer (NK) cells are key components of the innate immune system, providing potent antitumor immunity. Here, we show that the tumor growth factor-β (TGF-β)/SMAD signaling pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia (ALL). We characterized NK cells in 50 consecutive children with B-ALL at diagnosis, end induction and during maintenance therapy compared with age-matched controls. ALL-NK cells at diagnosis had an inhibitory phenotype associated with impaired function, most notably interferon-γ production and cytotoxicity. By mai

Immunologic and clinical effects of targeting PD-1 in lung cancer.

Therapeutic antibodies that block the programmed cell death protein-1 (PD-1) immune checkpoint pathway prevent T-cell downregulation and promote immune responses against cancer. Several PD-1 pathway inhibitors have shown robust activity in initial trials. This article reviews the preclinical evidence, rationale, and clinical pharmacology of blockade of PD-1 or its ligands as therapy for lung cancer and provides an overview of agents in development, clinical evidence to date, and implications for clinical application.

Effect of electronic patient record use on mortality in End Stage Renal Disease, a model chronic disease: retrospective analysis of 9 years of prospectively collected data.

BackgroundIn chronic disease, health information technology promises but has yet to demonstrate improved outcomes and decreased costs. The main aim of the study was to determine the effects on mortality and cost of an electronic patient record used in daily patient care in a model chronic disease, End Stage Renal Disease, treated by chronic maintenance hemodialysis. Dialysis treatment is highly regulated, and near uniform in treatment modalities and drugs used.MethodsThe particular electronic patient record, patient-centered and extensively coded, was used first in patient care in 3 dialysis u

B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.

B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy. To identify the possible mechanisms un

Targeted Therapies in Adult B-Cell Malignancies.

B-lymphocytes are programmed for the production of immunoglobulin (Ig) after antigen presentation, in the context of T-lymphocyte control within lymphoid organs. During this differentiation/activation process, B-lymphocytes exhibit different restricted or common surface markers, activation of cellular pathways that regulate cell cycle, metabolism, proteasome activity, and protein synthesis. All molecules involved in these different cellular mechanisms are potent therapeutic targets. Nowadays, due to the progress of the biology, more and more targeted drugs are identified, a situation that is c

Teams, Tools, Processes and Resources to Manage Oncologic Clinical Decision Support: Lessons Learned from City of Hope's Multistate, Academic, and Community Oncology Enterprise.

Background/Objectives: Clinical decision support systems (CDSSs) consisting of Computerized Physician Order Entry (CPOE) and oncology pathways serve as the foundation of high-quality cancer care. However, the resources needed to develop and maintain these systems have not been characterized for oncology enterprises. Methods: Executive leadership appointed a medical director and clinical pharmacist to develop and lead a Pathways and Protocols Program for the City of Hope (COH) enterprise. This involved developing a program charter and governance committee and a business case for resources to su

Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model.

It is increasingly apparent that cancer cells, in addition to remodelling their metabolism to survive and proliferate, adapt and manipulate the metabolism of other cells. This property may be a telling sign that pre-clinical tumour metabolism studies exclusively utilising in-vitro mono-culture models could prove to be limited for uncovering novel metabolic targets able to translate into clinical therapies. Although this is increasingly recognised, and work towards addressing the issue is becoming routinary much remains poorly understood. For instance, knowledge regarding the biochemical mechan

Recent advances in the management of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting highly heterogeneous clinical manifestations and multi-systemic involvement. Patients are susceptible to relapse- and remission, thus making management challenging. Moreover, a considerable number of side effects may occur with conventional therapies; therefore, there is clearly a need for new therapeutic strategies. Since the pathogenesis of SLE is highly complex, it is far from being fully understood. However, greater understanding of the pathways and of the cellular and molecular mediators involved in SLE is being

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.

In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospita

Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives.

MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease

Multiple Myeloma in 2023 Ways: From Trials to Real Life.

Multiple myeloma is a chronic hematologic malignancy that obstinately tends to relapse. Basic research has made giant strides in better characterizing the molecular mechanisms of the disease. The results have led to the manufacturing of new, revolutionary drugs which have been widely tested in clinical trials. These drugs have been approved and are now part of the therapeutic armamentarium. As a consequence, it is essential to combine what we know from clinical trials with real-world data in order to improve therapeutic strategies. Starting with this premise, our review aims to describe the cu

Combination therapy in combating cancer.

Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival

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… In this review, we discuss some important cellular pathways in cancer whose investigations have produced copious results in the PubMed database search engine. …

A Systematic Review of Laser Photobiomodulation Dosimetry and Treatment Protocols in the Management of Medications-Related Osteonecrosis of the Jaws: A Rationalised Consensus for Future Randomised Controlled Clinical Trials.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or comb

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… Each of the below MeSH Terms used to find the relevant literature from the search engines in Section 2.4 : Photobiomodulation (MeSH Major Topic) OR Low-level laser therapy (MeSH Major Topic) OR LLLT (MeSH Major Topic) OR Osteonecrosis of Jaw (MeSH Major Topic) OR MRONJ (MeSH Major Topic) OR ONJ (Mesh …

Classic Kaposi Sarcoma: Current Treatment Strategies and Emerging Therapeutic Approaches.

Classic Kaposi sarcoma (CKS) is a rare vascular neoplasm driven by infection with Kaposi sarcoma-associated herpesvirus (KSHV) and characterized by a heterogeneous geographic distribution. While the etiology of other Kaposi's sarcoma (KS) variants is well established, the underlying mechanisms of CKS appear multifactorial, with several risk factors, among which advanced age and male sex are most significant. Due to the rarity of CKS and its often indolent clinical course, clinical trials are sparse, and current knowledge of therapeutic approaches remains limited. Most available clinical trials

NUPR1 Promotes Radioresistance in Colorectal Cancer Cells by Inhibiting Ferroptosis.

Radioresistance is a major clinical challenge and the underlying mechanism has not been thoroughly elucidated. In this study, a radioresistant (RR) cell line is established to explore the transcriptomic signatures of radioresistance in colorectal cancer (CRC). KEGG enriched pathway analysis demonstrated that ferroptosis is inactivated in RR cells. Further detection confirmed that radiotherapy can promote ferroptosis, and ferroptosis inactivation is one of the hallmarks of radioresistance in CRC. What's more, induction of ferroptosis can restore the radiosensitivity of CRC cells. Then, we perfo

Central Venous Access Device Complications and Premature Removal in Patients With Haematological Malignancies: A Multi-Site Cohort Study.

BackgroundPatients with haematological malignancies require urgent and reliable venous access for the administration of systemic anticancer therapies (SACTs) commonly via central venous access devices (CVADs). Disease pathophysiology and side effects of SACTs increase the risk of complications during the dwell time and premature removal. CVAD complications are associated with treatment disruption, increased morbidity and mortality. This study aimed to comprehensively describe CVAD performance over a 12-month period in patients with haematological malignancies.MethodsA multi-site cohort study a

Moving Beyond G-CSF Mobilization-Learning From a 15-Year Experience of Different Stem Cell Mobilization Regimens in Multiple Myeloma.

BackgroundStem-cell mobilization in multiple myeloma is usually done with G-CSF with or without Cyclophosphamide (Cy) based chemotherapy/Plerixafor. Pre-clinical data suggest the role of proteasome inhibitors in mobilization. We previously reported that Bortezomib (Bort) when added to a Cy-based regimen had a better stem-cell yield. Consequent to favorable results with Bort + Cy-G-CSF, we used Bortezomib with G-CSF too. Hence, four different mobilization regimens were used-Bort + G-CSF (Group-1); G-CSF + Plerixafor (Group-2); Bort - Cy-G-CSF (Group-3); Cy + G-CSF (Group-4). We report here our

Identification and validation of CKAP2 as a novel biomarker in the development and progression of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic joint disease. However, many patients exhibit inadequate responses to treatment due to disease heterogeneity. Identifying novel biomarkers for RA is crucial for advancing molecular diagnosis and identifying potential therapeutic targets. METHODS: Synovial tissue transcriptome data from RA patients and healthy controls were obtained from the GEO database. Differentially expressed gene (DEG) analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) identified key gene modules in RA. Machine learni

Выбрать первоначальную терапию MS; факторы личного характера, болезни и лекарственные средства.

Инициирование болезни, изменяющей терапию у пациента с недавно поставленным диагнозом повторного склероза, в настоящее время предоставляет наилучшую возможность повлиять на их последующий курс лечения. В этой статье рассматриваются личные факторы, характеристики представления заболеваний и данные о текущих заболеваниях, изменяющих терапию, с точки зрения выбора первоначального лечения в этой среде. Хотя показатели для прогнозирования на индивидуальном уровне остаются ненадежными, особенно для тех, кто имеет мягкие представления, имеющиеся в настоящее время данные об относительной эффективности

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the b