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Keyword Index for Volume 95

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Selective inhibitors of nuclear export (SINE) in hematological malignancies.

Regulated nucleo-cytoplasmic transport plays a major role in maintaining cellular homeostasis. CRM1 (chromosome region maintenance 1 or exportin 1 or XPO 1) is responsible for the nucleo-cytoplasmic transport of more than 200 proteins, including most of the tumor suppressor proteins (TSP). CRM1 is overexpressed in pancreatic cancer, osteosarcoma, glioma, cervical and hematological malignancies. This inspired the development of novel agents that selectively inhibit nuclear exportins (SINEs). In this review we focus on the significance of CRM1 in carcinogenesis and review the new development of

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… SINEs promoted cell cycle arrest in G1 phase and induced rapid apoptosis in vitro . KPT −330 was studied in mice bearing ALL or AML. KPT-330 demonstrated significant survival benefit in these mice [ 24 ]. …

Advances in Molecular Imaging and Radionuclide Therapy of Neuroendocrine Tumors.

Neuroendocrine neoplasms make up a heterogeneous group of tumors with inter-patient and intra-patient variabilities. Molecular imaging can help to identify and characterize neuroendocrine tumors (NETs). Furthermore, imaging and treatment with novel theranostics agents offers a new, tailored approach to managing NETs. Recent advances in the management of NETs aim to enhance the effectiveness of targeted treatment with either modifications of known substances or the development of new substances with better targeting features. There have been several attempts to increase the detectability of NET

Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives.

Cancer is a type of malignant affliction threatening human health worldwide; however, the molecular mechanism of cancer pathogenesis remains to be elusive. The oncogenic hedgehog (Hh) pathway is a highly evolutionarily conserved signaling pathway in which the hedgehog-Patched complex is internalized to cellular lysosomes for degradation, resulting in the release of Smoothened inhibition and producing downstream intracellular signals. Noncoding RNAs (ncRNAs) with diversified regulatory functions have the potency of controlling cellular processes. Compelling evidence reveals that Hh pathway, ncR

Adverse events of antibody-drug conjugates on the ocular surface in cancer therapy.

Antibody-drug conjugates consist of a monoclonal antibody attached to a cytotoxic therapeutic molecule by a connector. This association allows a highly specific therapy, which increases their effectiveness and decreases their potential toxicity. This new therapy emerged approximately 20 years ago; since then, numerous combinations have appeared in the field of treatment-related neoplasms as an alternative for patients who do not achieve good results with conventional treatment options. Adverse effects of these drugs on the ocular surface are frequent and varied. Their prevalence ranges from 20

Structure, function, and pathology of PHF23.

Plant Homeodomain Finger Protein 23 (PHF23) is a member of the Plant Homeodomain (PHD) finger protein family and has been extensively reported since its discovery. Numerous studies have demonstrated that PHF23 plays a crucial role in various biological processes, such as gene expression regulation, autophagy, and tumorigenesis. Additionally, PHF23 is associated with various diseases including various malignancies, osteoarthritis, and tuberculosis, all of which currently lack effective and targeted treatment options. Therefore, this review systematically summarizes the existing literature on PH

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

The double-edged sword of tumor-targeted treatment: the influence of targeted therapy on the heart.

As an important means of modern cancer treatment, targeted therapy has significant efficacy, but cardiac toxicity cannot be ignored. From subclinical myocardial injury to severe heart failure (HF), it poses significant challenges to the long-term survival and quality of life of patients. This article summarizes the impact of targeted therapy drugs on cardiac function and their mechanisms, including cardiomyocyte damage, myocardial hypertrophy, and HF, and conducts in-depth research into potential molecular mechanisms. These include direct cardiomyocyte damage through targeted pathway inhibitio

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance Stefani Spranger, Thomas F. Gajewski K4 Intra

Decoding multiple myeloma: single-cell insights into tumor heterogeneity, immune dynamics, and disease progression.

BackgroundMultiple myeloma (MM) is a biologically heterogeneous malignancy of clonal plasma cells, often progressing from MGUS or smoldering MM. It causes anemia, bone lesions, and immune dysfunction due to abnormal plasma cell expansion in the bone marrow. Neuroinflammatory and neurotrophic factors may influence MM progression by affecting immune cells and the bone marrow niche. Growing evidence points to a role for neuroimmune regulation in tumor immunity. Despite therapeutic progress, disease heterogeneity and resistance highlight the need for new strategies targeting the tumor microenviron

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigati

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.

BackgroundData on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.MethodsIn this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16

Коллапсирование гломерулопатии в пациенте с малярией и множественной миеломой: доклад по делу.

Коллапсирование гломерулопатии представляет собой серьезную форму сегментального гломерулосклероза (FSGS), который может иметь место в качестве первичного или вторичного заболевания, зачастую в контексте таких инфекций, как ВИЧ. Множественная миэлома может вызывать травму почек с помощью таких механизмов, как нефропатия, в то время как травмы почек, связанные с малярией, чаще всего вызваны острым некрозом трубки. Мы представляем пример 47-летнего мужчины африканского происхождения с хорошо контролируемой ВИЧ-инфекцией, который сильно заболел АКИ и нуждался в интенсивной терапии и почечной тера

Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat.

Epigenetic regulation of gene transcription by small molecule inhibitors of histone deacetylases (HDAC) is a novel cancer therapy. Vorinostat (Zolinza()) is the first FDA approved HDAC-inhibitor for treatment of patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in Phase I development. In two Phase II trials, vorinostat was safe and effective at an oral dose of 400 mg/day with an overall response r

Antibody-based therapies in multiple myeloma.

The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical development of monoclonal antibodies (mAbs) targeting either MM cells or cells of the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic r

A prognostic model for anoikis-related genes in pancreatic cancer.

Anoikis, a distinct form of programmed cell death, is crucial for both organismal development and maintaining tissue equilibrium. Its role extends to the proliferation and progression of cancer cells. This study aimed to establish an anoikis-related prognostic model to predict the prognosis of pancreatic cancer (PC) patients. Gene expression data and patient clinical profiles were sourced from The Cancer Genome Atlas (TCGA-PAAD: Pancreatic Adenocarcinoma) and the International Cancer Genome Consortium (ICGC-PACA: Pancreatic Ductal Adenocarcinoma). Non-cancerous pancreatic tissue gene expressio

Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity-An Isobolographic Analysis.

The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)-valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro.

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… Similarly to SAHA, VPA can suppress the growth of BC cells by inducing apoptosis and arresting them in the G1 phase [ 27 ]. …

Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

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… This reversal of drug resistance was associated with suppressing drug efflux pump activity by downregulating multidrug resistance-associated protein 1 (MRP1), inducing cell G0/G1 phase arrest, increasing the Bax/Bcl-xl ratio to trigger apoptosis, and decreasing TS expression. 84 In the vincristine (VCR …

Advancing cancer therapy: Nanomaterial-based encapsulation strategies for enhanced delivery and efficacy of curcumin.

Curcumin, a polyphenolic compound derived from Curcuma longa, has gained significant attention as a potential anticancer agent due to its anti-inflammatory, antioxidant, and antitumor properties. Despite its therapeutic potential, the clinical application of curcumin is limited by its poor aqueous solubility, rapid metabolism, and limited bioavailability. To address these limitations, various nanomaterial-based encapsulation strategies have been developed, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, micelles, dendrimers, and hybrid nanomaterials. These formulations

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… Cell cycle analysis revealed Cur-SLNs more effectively arrested SKBR3 cells in the G1 phase, suggesting their potential as a promising breast cancer chemotherapy agent ( Fig. 16 ) [ 194 , 195 ]. Fig. 16 Cur-SLNs induced apoptotis in tumor cells and arrested SKBR3 cells in the G1 phase. … Fig. 16 Fig. 16 Cur-SLNs induced apoptotis in tumor cells and arrested SKBR3 cells in the G1 phase. Fig. 16 Dendrimers Dendrimers are highly branched, multifunctional nanocarriers designed for safe and efficient drug delivery to cancer cells. …

Роль фактора транскрипции E2F 1 Протеин в множестве склероза (MS): Сравнительное исследование уровней сериала у пациентов, страдающих синдромом MS, и здоровый контроль.

В этом исследовании изучается роль содержания белков E2F1 у пациентов с множественным склерозом (MS). Генетические и экологические факторы играют определенную роль в патогенезе MS, при этом Т и В лимфоциты способствуют повреждению тканей в результате иммунной реакции. E2F1, коэффициент транскрипции, регулирует клеточный цикл в Т клетках и связан с аутоиммунной реакцией. Методы: Это межсекторальное исследование включало в себя 24 Психиатрические заболевания и 21 Здоровый контроль соответствует возрасту и полу. Уровни сыворотки E2F1 измерялись с использованием иммуносорбента, связанного с фермен