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Medicinal Plants with Anti-Leukemic Effects: A Review.

Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient's survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half

Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL).

Current intensified chemotherapy regimens have significantly increased survival rates for pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL), but these treatments can result in serious adverse effects; furthermore, patients who are resistant to chemotherapy or who relapse have inferior outcomes, together highlighting the need for improved therapeutic strategies. Despite recent advances in stratifying T-ALL into molecular subtypes with distinct driver mutations, efforts to target the tumor-intrinsic genomic alterations critical for T-ALL progression have yet to translate into m

Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the β-Catenin Signaling Pathway.

Cervical cancer ranks as the fourth most prevalent cancer and cause of cancer-related mortality among women globally. It exhibits a recurrence/metastasis rate of approximately 30% and a dismal 5-year survival of only 17% in metastatic cases. Despite significant advancements in surgical techniques, chemoradiotherapy, and targeted therapies, effective treatment options for metastatic cervical cancer remain limited. This study explored Polyphyllin I (PPI), which is a monomeric compound derived from the Rhizoma of Paris Polyphyllin, as a potential inhibitor of cervical cancer metastasis. Mechanist

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… Polyphyllin I induces autophagy and cell cycle arrest via inhibiting PDK1/Akt/mTOR signal and downregulating cyclin B1 in human gastric carcinoma HGC-27 cells Biomed. Pharmacother. 2019 117 109189 10.1016/j.biopha.2019.109189 31387191 20. Lai L. Shen Q. Wang Y. Chen L. Lai J. Wu Z. Jiang H. …

Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer.

The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-kn

The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.

The well-orchestrated turnover of proteins in cross-striated muscles is one of the fundamental processes required for muscle cell function and survival. Dysfunction of the intricate protein degradation machinery is often associated with development of cardiac and skeletal muscle myopathies. Most muscle proteins are degraded by the ubiquitin-proteasome system (UPS). The UPS involves a number of enzymes, including E3-ligases, which tightly control which protein substrates are marked for degradation by the proteasome. Recent data reveal that E3-ligases of the cullin family play more diverse and c

Von Hippel-Lindau Disease: Current Challenges and Future Prospects.

Understanding of molecular mechanisms of tumor growth has an increasing impact on the development of diagnostics and targeted therapy of human neoplasia. In this review, we summarize the current knowledge on molecular mechanisms and their clinical implications in von Hippel-Lindau (VHL) disease. This autosomal dominant tumor syndrome usually manifests in young adulthood and predisposes affected patients to the development of benign and malignant tumors of different organ systems mainly including the nervous system and internal organs. A consequent screening and timely preventive treatment of l

Apoptotic Pathway as the Therapeutic Target for Anticancer Traditional Chinese Medicines.

Cancer is a leading cause of morbidity and mortality worldwide. Apoptosis is a process of programmed cell death and it plays a vital role in human development and tissue homeostasis. Mounting evidence indicates that apoptosis is closely related to the survival of cancer and it has emerged as a key target for the discovery and development of novel anticancer drugs. Various studies indicate that targeting the apoptotic signaling pathway by anticancer drugs is an important mechanism in cancer therapy. Therefore, numerous novel anticancer agents have been discovered and developed from traditional

Role of Bruton's tyrosine kinase in B cells and malignancies.

Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor a

Circadian clock and cancer.

Circadian rhythms play a critical role in regulating physiological and behavioral processes, such as the sleep-wake cycle, hormone secretion, and metabolism. These rhythms are controlled by endogenous biological clocks, which are synchronized with environmental cues, primarily the light-dark cycle. Notably, disruption or reprogramming of circadian rhythms is closely associated with cancer initiation, progression, and treatment response. At the molecular level, the dysregulation of core clock genes can disturb normal cellular rhythms, leading to aberrant cell proliferation, impaired DNA repair,

Ten tips for an onco-nephrology clinic.

An increasing number of cancer patients are benefiting from long term cancer-directed therapy with an ever-expanding arsenal of novel agents from monoclonal antibodies to small molecules and cellular therapies in addition to the mainstay cytotoxic chemotherapy. All these therapies are accompanied by a unique array of adverse events, which include kidney toxicity. In this context, the need for onco-nephrology expertise continues to grow. Oncologists and hematologists collaborate closely with onco-nephrologists to determine: (i) treatment options for special populations based on accurate assessm

Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance.

BackgroundFollicular thyroid cancer (FTC) is a prevalent form of differentiated thyroid cancer, whereas anaplastic thyroid cancer (ATC) represents a rare, fast-growing, undifferentiated, and highly aggressive tumor, posing significant challenges for eradication. Ferroptosis, an iron-dependent cell death mechanism driven by the excessive production of reactive oxygen species and subsequent lipid peroxidation, emerges as a promising therapeutic strategy for cancer. It has been observed that many cancer cells exhibit sensitivity to ferroptosis, while some other histotypes appear to be resistant,

Identification of a DNA Methylation-Driven Genes-Based Prognostic Model and Drug Targets in Breast Cancer: In silico Screening of Therapeutic Compounds and in vitro Characterization.

DNA methylation is a vital epigenetic change that regulates gene transcription and helps to keep the genome stable. The deregulation hallmark of human cancer is often defined by aberrant DNA methylation which is critical for tumor formation and controls the expression of several tumor-associated genes. In various cancers, methylation changes such as tumor suppressor gene hypermethylation and oncogene hypomethylation are critical in tumor occurrences, especially in breast cancer. Detecting DNA methylation-driven genes and understanding the molecular features of such genes could thus help to enh

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… The Dual Face of Cyclin B1 . JTips ( 2018 ) 23 ( 6 ): 475–8 . doi: 10.1016/j.tplants.2018.03.015 29680634 52 Xia P Zhang H Xu K Jiang X Gao M Wang G . MYC-Targeted WDR4 Promotes Proliferation, Metastasis, and Sorafenib Resistance by Inducing CCNB1 Translation in Hepatocellular Carcinoma . …

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.

The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The

The Herba Patriniae (Caprifoliaceae): A review on traditional uses, phytochemistry, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Patriniae has been used for thousands of years in China as a traditional Chinese medicine with heat-clearing and detoxicating effects. It is applied widly for the treatment of rheumatoid arthritis, diarrhea, acute hepatitis, pelvic inflammatory disease and ulcerative colitis in clinic. Two species, namely Patrinia scabiosaefolia Fisch. (PS) and Patrinia villosa Juss. (PV) from the Caprifoliaceae family, are considered as Herba Patriniae in the pharmaceutical industry. AIM OF THE REVIEW: This paper aims to comprehensively outline the traditional uses, bota

Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.

Compelling evidences have manifested that breast cancer cells prefer to metastasize to certain distant organs, including brain, lung, bone and liver. According to the canonical "seed and soil" theory, this prominent biological behavior, termed as metastatic organotropism, involves intricate interactions between breast cancer cells (the "seeds") and specific residents in the tumor microenvironment (the "soil"), initiating from pre-metastatic niche formation to metastatic outgrowth. Recently, multifaceted heterogeneity of tissue-specific macrophages (TSMs) and their roles played in organotropic

Targeting Oncoproteins for Molecular Cancer Therapy

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Glioblastoma Treatment: State-of-the-Art and Future Perspectives.

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve ove

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… Another in vitro observed effect of RES-529 is a dramatic reduction in cell cycle-associated proteins, such as cyclin B1, cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6. …

Exploring new drug treatment targets for immune related bone diseases using a multi omics joint analysis strategy.

In the field of treatment and prevention of immune-related bone diseases, significant challenges persist, necessitating the urgent exploration of new and effective treatment methods. However, most existing Mendelian randomization (MR) studies are confined to a single analytical approach, which limits the comprehensive understanding of the pathogenesis and potential therapeutic targets of these diseases. In light of this, we propose the hypothesis that genetic variations in specific plasma proteins have a causal relationship with immune-related bone diseases through the MR mechanism, and that k

Enhanced Antitumor Activity and Induction of Immunogenic Cell Death in NUT Carcinoma Cells by Combining Oncolytic Viruses with the Dual Inhibitor NEO2734.

NUT carcinoma (NC) is a rare exceptionally aggressive malignancy, defined by NUTM1 gene translocations, most commonly generating a BRD4::NUTM1 fusion that results in a poor prognosis and limited therapeutic options. Oncolytic virotherapy has emerged as a promising strategy for NC, and the dual bromodomain and extra-terminal domain (BET) and p300/CBP inhibitor NEO2734 has demonstrated potent antiproliferative activity. To investigate multimodal therapeutic approaches that combine epigenetic modulation with immunogenic and cytotoxic effects of oncolytic viruses (OVs), we evaluated two recombinan

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in