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Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.

IntroductionSmall cell lung cancer (SCLC) initially responds well to cisplatin-based chemotherapy, but rapid development of drug resistance limits long-term efficacy and subsequent treatment options. Understanding the multifactorial mechanisms of cisplatin resistance is essential for improving patient outcomes. This review synthesizes recent preclinical and clinical advances, focusing on seven key resistance mechanisms and emerging therapeutic strategies, including immunotherapy, targeted therapy, and novel chemotherapeutic agents.DiscussionCisplatin resistance in SCLC arises through multiple

Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.

Nucleocytoplasmic transport (NCT) regulates the spatial distribution of proteins and RNA between the nucleus and cytoplasm. NCT dysregulation can mislocalize tumor suppressors, DNA-repair factors, transcription factors, and drug targets in cancer. In this review, we conceptualize NCT-dependent protein mislocalization as a spatial regulatory framework for anticancer drug resistance, rather than as a catalogue of transport components. We systematically discuss how nuclear pore complex (NPC) remodeling, transport-receptor imbalance, post-translational modification (PTM)-regulated cargo routing, s

Influence of gut microbial metabolites on tumor immunotherapy: mechanisms and potential natural products.

In recent years, tumor immunotherapy has made significant breakthroughs in the treatment of malignant tumors. However, individual differences in efficacy have been observed in clinical practice. There is increasing evidence that gut microbial metabolites influence the efficacy of distal tumor immunotherapy via the gut-liver axis, the gut-brain axis and the gut-breast axis, a process that may involve modulating the expression of immune cells and cytokines in the tumor microenvironment (TME). In this review, we systematically explore the relationship between gut microbial metabolites and tumor i

Recent Insights in Multi-Target Drugs in Pharmacology and Medicinal Chemistry.

Many of the drugs used in treatment today have been designed based on the "specificity paradigm". Resistance has developed against drugs designed using this approach, leading to a decrease in their effectiveness. In addition, it is well-documented in the literature that diseases with complex etiologies, such as Alzheimer's, Parkinson's, and cancer are influenced by multiple genetic and/or environmental factors. As a result, specificity paradigm is often insufficient for treating these diseases. Therefore, there is a need to develop drugs that interact with multiple targets simultaneously throu

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… This molecule exhibits the capability to bind concurrently to the allosteric site of type II NADH dehydrogenase and the Qo and Qi sites of cytochrome bc1 in P. falciparum . …

Hypoxia-driven angiogenesis and metabolic reprogramming in vascular tumors.

Hypoxia is a hallmark of the tumor microenvironment (TME), and it plays a crucial role in the occurrence and progression in vascular tumors. Under hypoxic conditions, hypoxia-inducible factor 1-alpha (HIF-1α) is stabilized, inducing changes in the expression of various target genes involved in angiogenesis, metabolism, and cell survival. This includes the upregulation of pro-angiogenic factors like VEGF, which promotes the formation of dysfunctional blood vessels, contributing to the worsening of the hypoxic microenvironment. At the same time, hypoxia induces a metabolic shift toward glycolysi

The Emerging Role of CD8+ T Cells in Shaping Treatment Outcomes of Patients with MDS and AML.

CD8+ T cells are critical players in anti-tumor immunity against solid tumors, targeted by immunotherapies. Emerging evidence suggests that CD8+ T cells also play a crucial role in anti-tumor responses and determining treatment outcomes in hematologic malignancies like myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). In this review, we focus on the implication of CD8+ T cells in the treatment response of patients with MDS and AML. First, we review reported studies of aberrant functionality and clonality of CD8+ T cells in MDS and AML, often driven by the immunosuppressive bone

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… Qi X., Jiang H., Liu P., Xie N., Fu R., Wang H., Liu C., Zhang T., Wang H., Shao Z. Increased Myeloid-Derived Suppressor Cells in Patients with Myelodysplastic Syndromes Suppress CD8+ T Lymphocyte Function through the STAT3-ARG1 Pathway. Leuk. …

Immunotherapy in chronic lymphocytic leukemia: advances and challenges.

Chronic lymphocytic leukemia (CLL) is characterized as a clonal proliferation of mature B lymphocytes with distinct immunophenotypic traits, predominantly affecting the middle-aged and elderly population. This condition is marked by an accumulation of lymphocytes within the peripheral blood, bone marrow, spleen, and lymph nodes. The associated immune dysregulation predisposes CLL patients to a higher risk of secondary malignancies and infections, which significantly contribute to morbidity and mortality rates. The advent of immunotherapy has revolutionized the prognosis of CLL, advancing treat

The broad spectrum of cancer and immunotherapy: achievements and limitations.

Cancer immunotherapy has revolutionized cancer treatment over the past decades, offering renewed hope to patients with previously untreatable malignancies. This therapeutic approach could be categorized into three primary strategies: immune checkpoint blockade, adoptive cell therapy, and cancer vaccines. Immune checkpoint inhibitors have been highly successful in boosting anti-tumour immune responses by blocking the immunosuppressive signals that cancer cells exploit to evade immune surveillance, mainly that exerted by cytotoxic T lymphocytes. Adoptive cell therapy, particularly chimeric antig

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… Lv Qi, Zhang Y, Gao W, Wang J, Hu Y, Yang H, et al. CSF1R inhibition reprograms tumor-associated macrophages to potentiate anti-PD-1 therapy efficacy against colorectal cancer. Pharmacol Res. (2024) 196:107126. doi: 10.1016/j.phrs.2024.107126, PMID: 75. …

Antioxidant Food Supplementation in Cancer: Lessons from Clinical Trials and Insights from Preclinical Studies.

Food antioxidant supplementation has been widely proposed for cancer prevention and adjuvant therapy due to the pleiotropic role of antioxidants. Herein, particular attention is given to recent clinical trials based on the use of dietary supplements in cancer patients, both as monotherapy and in combination with standard treatments, exploring both their potential benefits and risks. This review focuses on the efficacy of the most important food antioxidants, highlighting how their action may change depending on different factors such as cancer type, dose, timing of administration and antioxida

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… Qi Q. Wang J. Kong Y. Feng Z. Chen A. Li W. Zhang Q. Wang J. miR-6858 plays a key role in the process of melatonin inhibition of the malignant biological behavior of glioma J. Clin. Neurosci. 2021 87 137 146 10.1016/j.jocn.2021.02.015 33863521 139. Wang T.H. Hsueh C. Chen C.C. Li W.S. Yeh C.T. …

Метаболомическое исследование синдромов миэлодипластика, множественной миеломы и гомозиговой β-Талассемии.

Хроническая анемия, как правило, диагностируется у пожилых людей и служит важным показателем как реактивных, так и клональных заболеваний. Многие основные заболевания, такие, как миэллодипластические синдромы и множественная миелома, более распространены среди пожилых людей, в то время как новые терапевтические подходы превратили педиатрические расстройства слабого прогноза, такие, как бета-талассемия, в хроническое заболевание пожилых людей. Таким образом, растущая распространенность хронической анемии в пожилом возрасте в значительной степени объясняется более частыми диагностическими и тера

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… Matre P., Velez Lujan J., Jacamo R., Qi Y., Su X., Cai T., Chan S., Lodi A., Sweeney S., Ma H., et al. Inhibiting Glutaminase in Acute Myeloid Leukemia: Metabolic Dependency of Selected AML Subtypes. Oncotarget. 2016;7:79722. doi: 10.18632/oncotarget.12944. 57. …

Role of T cells and cytokines in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a long-term autoimmune disease. It causes persistent joint inflammation, aberrant tissue growth, and progressive joint deterioration. T cells have a key role in the onset of RA. They identify and trigger other immune cells, and produce inflammatory signals such as interleukin-6 (IL-6), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Prolonged inflammation and tissue damage are caused by an imbalance between regulatory T cells (Tregs) and pro-inflammatory T helper 17 (Th17) cells. Additionally, the condition is exacerbated by uncontrolled cytokine netwo

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… Ren C., Chen J., Che Q., Jia Q., Lu H., Qi X., Zhang X., Shu Q. IL-37 alleviates TNF-α-induced pyroptosis of rheumatoid arthritis fibroblast-like synoviocytes by inhibiting the NF-κB/GSDMD signaling pathway. Immunobiology. 2023;228(3) doi: 10.1016/j.imbio.2023.152382. 67. …

Unraveling the link between cardiorespiratory fitness and cancer: a state-of-the-art review.

Cardiorespiratory fitness (CRF) not only reflects an individual's capacity to perform physical activities but also encapsulates broader effects on the basic biology of aging. This review aims to summarize the evidence on the influence of CRF on overall and site-specific cancer risks. It delves into the biological mechanisms through which CRF may exert its effects, explores the clinical implications of these findings, identifies gaps in the current evidence base, and suggests directions for future research. The synthesis of findings reveals that higher CRF levels (general threshold of > 7 METs)

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… Qi C, Song X, Wang H, Yan Y, Liu B. The role of exercise-induced myokines in promoting angiogenesis. Front Physiol. 2022;13:981577. 55. Norling AM, Gerstenecker AT, Buford TW, Khan B, Oparil S, Lazar RM. …

Immune mediated support of metastasis: Implication for bone invasion.

Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we describe

Targeted therapy for multiple myeloma: an overview on CD138-based strategies.

Multiple myeloma (MM) is an incurable hematological disease characterized by the uncontrolled growth of plasma cells primarily in the bone marrow. Although its treatment consists of the administration of combined therapy regimens mainly based on immunomodulators and proteosome inhibitors, MM remains incurable, and most patients suffer from relapsed/refractory disease with poor prognosis and survival. The robust results achieved by immunotherapy targeting MM-associated antigens CD38 and CD319 (also known as SLAMF7) have drawn attention to the development of new immune-based strategies and diffe

The Bone Microenvironment Soil in Prostate Cancer Metastasis: An miRNA Approach.

Bone metastatic prostate cancer (PCa) is associated with a high risk of mortality. Changes in the expression pattern of miRNAs seem to be related to early aspects of prostate cancer, as well as its establishment and proliferation, including the necessary steps for metastasis. Here we compiled, for the first time, the important roles of miRNAs in the development, diagnosis, and treatment of bone metastasis, focusing on recent in vivo and in vitro studies. PCa exosomes are proven to promote metastasis-related events, such as osteoblast and osteoclast differentiation and proliferation. Aberrant m

Chronic stress in solid tumor development: from mechanisms to interventions.

Chronic stress results in disturbances of body hormones through the neuroendocrine system. Cancer patients often experience recurrent anxiety and restlessness during disease progression and treatment, which aggravates disease progression and hinders treatment effects. Recent studies have shown that chronic stress-regulated neuroendocrine systems secret hormones to activate many signaling pathways related to tumor development in tumor cells. The activated neuroendocrine system acts not only on tumor cells but also modulates the survival and metabolic changes of surrounding non-cancerous cells.

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… Zhang H, Fredericks T, Xiong G, Qi Y, Rychahou PG, Li JD, Pihlajaniemi T, Xu W, Xu R. Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance. Breast Cancer Res. 2018;20(1):116. doi: 10.1186/s13058-018-1030-y. 121. Wu Q, Li B, Li Z, Li J, Sun S, Sun S. …

Past, Present, and a Glance into the Future of Multiple Myeloma Treatment.

Multiple myeloma (MM) is a challenging hematological cancer which typically grows in bone marrow. MM accounts for 10% of hematological malignancies and 1.8% of cancers. The recent treatment strategies have significantly improved progression-free survival for MM patients in the last decade; however, a relapse for most MM patients is inevitable. In this review we discuss current treatment, important pathways for proliferation, survival, immune suppression, and resistance that could be targeted for future treatments.

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… Hideshima T., Qi J., Paranal R.M., Tang W., Greenberg E., West N., Colling M.E., Estiu G., Mazitschek R., Perry J.A., et al. Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma. Proc. Natl. Acad. Sci. …

Bispecific Antibodies in Hematological Malignancies: A Scoping Review.

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgk

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… Zhao L., Li S., Wei X., Qi X., Liu D., Liu L., Wen F., Zhang J.S., Wang F., Liu Z.L., et al. A novel CD19/CD22/CD3 trispecific antibody enhances therapeutic efficacy and overcomes immune escape against B-ALL. Blood. 2022;140:1790–1802. doi: 10.1182/blood.2022016243. 15. …

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs hav

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… Qi G., Lu G., Yu J., Zhao Y., Wang C., Zhang H., Xia Q. Up-regulation of TIF1γ by valproic acid inhibits the epithelial mesenchymal transition in prostate carcinoma through TGF-β/Smad signaling pathway. Eur. J. Pharmacol. 2019;860:172551. doi: 10.1016/j.ejphar.2019.172551. 146. …

Retrospective analysis of the preparation and application of immunotherapy in cancer treatment (Review).

Monoclonal antibody technology plays a vital role in biomedical and immunotherapy, which greatly promotes the study of the structure and function of genes and proteins. To date, monoclonal antibodies have gone through four stages: murine monoclonal antibody, chimeric monoclonal antibody, humanised monoclonal antibody and fully human monoclonal antibody; thousands of monoclonal antibodies have been used in the fields of biology and medicine, playing a special role in the pathogenesis, diagnosis and treatment of disease. In this review, we compare the advantages and disadvantages of hybridoma te

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… rheumatic diseases Nat Rev Rheumatol 15 197 207 2019 10.1038/s41584-019-0188-8 30814691 31 Kuramochi T Igawa T Tsunoda H Hattori K Humanization and simultaneous optimization of monoclonal antibody Methods Mol Biol 1904 213 230 2019 10.1007/978-1-4939-8958-4_9 30539472 32 Goydel RS Weber J Peng H Qi …