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Molecular Inhibitors of Growth Signals

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… PX-866 is a synthetic derivative from the fungal metabolite wortmannin (a product of Penicillium wortmannin). Compared to wortmannin, it has increased stability, reduced toxicity, and stronger drug activity. …

Exploiting Nanomedicine for Cancer Polychemotherapy: Recent Advances and Clinical Applications.

The most important limitations of chemotherapeutic agents are severe side effects and the development of multi-drug resistance. Recently, the clinical successes achieved with immunotherapy have revolutionized the treatment of several advanced-stage malignancies, but most patients do not respond and many of them develop immune-related adverse events. Loading synergistic combinations of different anti-tumor drugs in nanocarriers may enhance their efficacy and reduce life-threatening toxicities. Thereafter, nanomedicines may synergize with pharmacological, immunological, and physical combined tre

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… Nanoparticle Co-Delivery of Wortmannin and Cisplatin Synergistically Enhances Chemoradiotherapy and Reverses Platinum Resistance in Ovarian Cancer Models Biomaterials 2018 169 1 10 10.1016/j.biomaterials.2018.03.055 29631163 PMC5911411 12. Perrelli A. Fatehbasharzad P. Benedetti V. Ferraris C. …

P2X7 Рецептор рентгеновских заболеваний: общие молекулярные механизмы и терапевтические последствия.

Редкие заболевания (РЛ) в индивидуальном порядке редко встречаются, но в совокупности они затрагивают большое число людей во всем мире, и подавляющее большинство из них по-прежнему не имеют эффективных методов лечения, позволяющих вести борьбу с заболеваниями. Благодаря достижениям в области геномики и платформ для обмена данными исследования все чаще переходят от одного заболевания к поиску конвергентных молекулярных путей, которые можно было бы использовать в различных клинически отличных друг от друга структурах. В этом контексте purinergic P2X7 рецептор (P2X7R) превратился в предполагаемую

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… Short-term stimulation decreases SQSTM1/p62, consistent with autophagy activation, whereas prolonged stimulation increases SQSTM1/p62, indicative of impaired autophagic flux; these changes are prevented by the P2X7R antagonist A-804598 and the autophagy inhibitor wortmannin. 107 Treatment with the novel …

Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015.

The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including

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… In particular, AKT inhibition by MK-2206 enhances the anti-tumor therapeutic effect of tumor-specific vaccine; the PI3K inhibitor Wortmannin differentially affects proliferation of human Treg and Tconv cells. …

The Role of IL-33/ST2 Pathway in Tumorigenesis.

Cancer is initiated by mutations in critical regulatory genes; however, its progression to malignancy is aided by non-neoplastic cells and molecules that create a permissive environment known as the tumor stroma or microenvironment (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a nuclear factor. IL-33 typically resides in the nucleus of the cells where it is expressed. However, upon tissue damage, necrosis, or injury, it is quickly released into extracellular space where it binds to its cognate receptor suppression of tumorigenicity 2 (ST2)L found on the membrane o

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… In studies using inhibitors of NF-κB (Bay11–7082), the ERK pathway (U0126), p38 MAPK signaling (SB203580), the JNK pathway (SP600125), and the phosphatidylinositol 3-kinase-Akt pathway (wortmannin), it was shown that IL-1β induced the expression of IL-33 through NF-κB or ERK pathways and partially through …

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for th

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

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… is primary protein clearance system for cellular and organismal homeostasis, and therefore, stimulating autophagy is an effective method to eliminate these intracellular aggregates. 215 , 216 Several life‐prolonging compounds work as autophagy inducers, including VPS34 PI3‐kinase inhibitors (e.g., wortmannin …

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

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… Furthermore, EVO alone or in combination with chemotherapeutic agent wortmannin could inhibit cell growth, migration, and EMT and induce apoptosis by decreasing the levels of Bcl-2, phospho-Akt, and matrix metalloproteinases-2 and -9 proteins and increasing the levels of p21 and p53 proteins in thyroid …

The journey of boswellic acids from synthesis to pharmacological activities.

There has been a lot of interest in using naturally occurring substances to treat a wide variety of chronic disorders in recent years. From the gum resin of Boswellia serrata and Boswellia carteri, the pentacyclic triterpene molecules known as boswellic acid (BA) are extracted. We aimed to provide a detailed overview of the origins, chemistry, synthetic derivatives, pharmacokinetic, and biological activity of numerous Boswellia species and their derivatives. The literature searched for reports of B. serrata and isolated BAs having anti-cancer, anti-microbial, anti-inflammatory, anti-arthritic,

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… Additionally, pre-incubating BA with the phosphatidylinositol-3 kinase (PI3K) inhibitors, LY294002 or wortmannin, significantly increased apoptosis in HT-29 cells (Li et al. 2012 ). …

The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.

One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine parac

Cancer stem cells: advances in knowledge and implications for cancer therapy.

Cancer stem cells (CSCs), a small subset of cells in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, and maintain tumor heterogeneity. Cancer continues to be a significant global disease burden. In the past, surgery, radiotherapy, and chemotherapy were the main cancer treatments. The technology of cancer treatments continues to develop and advance, and the emergence of targeted therapy, and immunotherapy provides more options for patients to a certain extent. However, the limitations of efficacy and treatment resistance are still i

Abstracts of the 28th Annual San Antonio Breast Cancer Symposium, December 8-11, 2005, San Antonio, Texas, USA.

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Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

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

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… GC resistance can also be overcome in Akt-active lymphoma cells by inhibiting Src members (e.g., by PP1), PI3K (e.g., Wortmannin), or an Akt inhibitor [ 67 , 68 ]. …

Current advance of nanotechnology in diagnosis and treatment for malignant tumors.

Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be acc

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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Program-Abstracts

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The Fifth International Meeting of ISEV, ISEV2016, Rotterdam, The Netherlands, 4 - 7 May, 2016.

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ISEV2019 Abstract Book

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… These effects were partially abrogated by wortmannin or U0126, which inhibited AKT and ERK phosphorylation, respectively. The role of exosomal CD73 was confirmed using CD73 inhibitor and theophylline that showed inhibition of exosome-induced AKT and ERK phosphorylation. …