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USP14 inhibition by degrasyn induces YAP1 degradation and suppresses the progression of radioresistant esophageal cancer.

BACKGROUND: Radiotherapy is a major modality for esophageal cancer (ESCA) treatment, yet radioresistance severely hampers its therapeutic efficacy. Ubiquitin-specific peptidase 14 (USP14) is a novel deubiquitinase and can mediate cancer cells' response to irradiation, although the underlying mechanism remains unclear, including in ESCA. METHODS: To evaluate the expression of USP14 in ESCA tissues or cells, we used RNA-Seq, immunoblotting, co-immunoprecipitation (Co-IP), ubiquitination, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence assays in this investigat

Should oncologists trust cannabinoids?

Cannabis enjoyed a "golden age" as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians

Vitamin D in the Prevention and Treatment of Oral Cancer: A Scoping Review.

Introduction: Oral cancer is a serious health problem with an increasing incidence worldwide. Researchers have studied the potential anti-cancerous action of vitamin D and its association with several cancers including oral cancer. The purpose of this scoping review is to synthesize the existing literature on the role of vitamin D on oral cancer. Methods: A scoping review of the literature was conducted using the framework developed by Arkey and O'Malley and the PRISMA-ScR guidelines. Nine databases were searched for peer-reviewed human studies published in English that either investigated the

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review.

Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors

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… SNPs affecting cyclin H and the BCRP were significantly associated with a higher risk of severe oxaliplatin-induced peripheral neuropathy ( Custodio et al., 2014 ). … H | FZD3 | | | BCRP | CYP2C8 | | | Na V channels | CYP3A5 ∗ 3 | | | | CYP3A4 ∗ 22 | | | | ABCB1 | | Demographic variables | Age | Age | Age (children) | – Taxanes Taxane diterpenoids were isolated from the bark of the Pacific yew tree ( Taxus brevifolia and Taxus baccata for paclitaxel …

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

Philadelphia Chromosome-Positive Leukemia in the Lymphoid Lineage-Similarities and Differences with the Myeloid Lineage and Specific Vulnerabilities.

Philadelphia chromosome (Ph) results from a translocation between the breakpoint cluster region (BCR) gene on chromosome 9 and ABL proto-oncogene 1 (ABL1) gene on chromosome 22. The fusion gene, BCR-ABL1, is a constitutively active tyrosine kinase which promotes development of leukemia. Depending on the breakpoint site within the BCR gene, different isoforms of BCR-ABL1 exist, with p210 and p190 being the most prevalent. P210 isoform is the hallmark of chronic myeloid leukemia (CML), while p190 isoform is expressed in majority of Ph-positive B cell acute lymphoblastic leukemia (Ph+ B-ALL) case

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

Association of tumor mutation burden and epidermal growth factor receptor inhibitor history with survival in patients with metastatic stage III/IV non-small-cell lung cancer: A retrospective study.

ObjectivesLung cancer is the leading cause of cancer-related deaths worldwide. However, factors associated with the survival of patients with advanced non-small-cell lung cancer (NSCLC) who received only hospice care are largely unclear. In this study, we aimed to determine the prognostic factors correlated with survival in patients with advanced NSCLC who had undergone hospice care only.MethodsA total of 102 patients with recurrent stage III/IV NSCLC after traditional treatment failure were investigated. Survival was measured from the date of enrollment to December 2019 or the time of death.

IFNIKB: база данных типов I интерферонов для исследований антитуморной иммунности.

Тип I интерферон (ИФН-I) представляет собой важный класс цитокинов, способных ингибировать прогрессирование опухоли через механизмы, такие как иммуномодуляция опухолевого микросреды или воздействие на клеточные компоненты. Несмотря на то, что разработаны различные эндогенные и экзогенные терапевтические стратегии ИФН-I, отчеты о нарушении функции иммунных клеток, вызванных усилением сигнала ИФН-I, указывают на то, что оптимальные стратегии еще не установлены. Однако данные по ИФН-I в настоящее время распределены по нескольким публичным базам данных и отсутствуют систематическая интеграция, что

The Use of Bruton Tyrosine Kinase Inhibitors in Waldenström's Macroglobulinemia.

Waldenström's macroglobulinemia (WM) remains an incurable malignancy. However, a number of treatment options exist for patients with WM, including alkylating agents, anti-CD20 monoclonal antibodies, and small molecule inhibitors such as proteasome inhibitors and Bruton tyrosine kinase inhibitors (BTKi). The focus of this review is to highlight the role of BTKi in the management of WM. The first BTKi to receive US Food and Drug Administration approval for WM was ibrutinib. Ibrutinib has been extensively studied in both treatment-naïve WM patients and in those with relapsed/refractory disease. T

A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest.

BackgroundCurrently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.Methods and findingsAffymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside.

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of num

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

DNA Damaging Drugs

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Polymeric micelles loaded with carfilzomib increase tolerability in a humanized bone marrow-like scaffold mouse model.

Carfilzomib-loaded polymeric micelles (CFZ-PM) based on poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) were prepared with the aim to improve the maximum tolerated dose of carfilzomib in a "humanized" bone marrow-like scaffold model. For this, CFZ-PM were prepared and characterized for their size, carfilzomib loading and cytotoxicity towards multiple myeloma cells. Further, circulation and tumor & tissue distribution of fluorescently labeled micelles were determined. Tolerability of CFZ-PM versus the clinical approved formulation - Kyprolis® - was assessed

Review of the Current Knowledge on the Role of Stem Cell Transplantation in Neurorehabilitation.

The management involving stem cell (SC) therapy along with physiotherapy offers tremendous chance for patients after spinal cord injury (SCI), traumatic brain injury (TBI), stroke, etc. However, there are still only a limited number of reports assessing the impact of stem cells (SCs) on the rehabilitation process and/or the results of the simultaneous use of SC and rehabilitation. Additionally, since there is still not enough convincing evidence about the effect of SCT on humans, e.g., in stroke, there have been no studies conducted concerning rehabilitation program formation and expected outc

Heterogeneity in precision oncology.

Precision oncology is a rapidly evolving concept that holds great promise in cancer treatment. However, a cancer complexity attributed to genomic and acquired tumour heterogeneity limits treatment effectiveness and increases toxicity. These limitations refer to both systemic therapies and radiotherapy, which are two mainstays of non-invasive cancer treatment. By understanding cancer heterogeneity and utilising advanced tools to personalise treatment strategies, precision oncology has the potential to revolutionise cancer care. In this article, we review the current status of precision oncology

A Challenge to Aging Society by microRNA in Extracellular Vesicles: microRNA in Extracellular Vesicles as Promising Biomarkers and Novel Therapeutic Targets in Multiple Myeloma.

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells and is the second most common hematological cancer. MM frequently occurs in the elderly population with the median age as the middle sixties. Over the last 10 years, the prognosis of MM has been dramatically improved by new therapeutic drugs; however, MM is still incurable. The pathogenesis of MM is still unclear, thus greater understanding of the molecular mechanisms of MM malignancy is desirable. Recently, microRNAs (miRNAs) were shown to modulate the expression of genes critical for MM pathogenesis. In addition,

Drug delivery for age-related bone diseases: From therapeutic targets to common and emerging therapeutic strategies.

With the accumulation of knowledge on aging, people have gradually realized that among the many factors that cause individual aging, the accumulation of aging cells is an essential cause of organ degeneration and, ultimately, age-related diseases. Most cells present in the bone microenvironment gradually age over time, leading to an imbalance of osteogenesis, osteoclastogenesis, adipogenesis, and chondrogenesis. This imbalance contributes to age-related bone loss and the development of age-related bone diseases, such as osteoporosis. Bone aging can prolong the lifespan and delay the developmen

Cancer Vaccines for Triple-Negative Breast Cancer: A Systematic Review.

Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the poorest outcomes, and is associated with a high risk of relapse and metastasis. The treatment choices for this malignancy have been confined to conventional chemotherapeutic agents, due to a lack of expression of the canonical molecular targets. Immunotherapy has been recently changing the treatment paradigm for many types of tumors, and the approach of evoking active immune responses in the milieu of breast tumors through cancer vaccines has been introduced as one of the most novel immunotherapeutic approaches. Acco