Epithelial-mesenchymal transition (EMT) is a critical process in the development of many tissues and organs in multicellular organisms that its important role in the pathogenesis of metastasis and ...tumor cell migration has been firmly established. Decreased adhesive capacity, cytoskeletal reorganization, and increased mobility are hallmarks of the EMT. Several molecular mechanisms promote EMT, Including regulation of the levels of specific cell-surface proteins, ECM-degrading enzymes, and altering the expression of certain transcription factors and microRNAs. EMT process is modulated through multiple signaling pathways including the AKT/mTOR pathway. AKT is a key component in numerous processes which was recently shown to regulate the EMT through suppression of the expression of E-cadherin via EMT transcription factors. On the other hand, mTOR complexes can also regulate the EMT through the regulation of cell's actin cytoskeleton by altering the PKC phosphorylation state and direct phosphorylation and activation of Akt. Here we review the effect of AKT and mTOR on EMT and consequently metastasis and cell motility.
•The Akt/mTOR pathway induces EMT via transcription factors such as Snail, Zeb, and Twist through down regulation of E-cadherin.•The Akt promotes EMT and migration through the induction of MMPs.•TGF-β-induced activation of mTOR drives EMT and cell invasion.
Effects of statins on brain tumors: a review Afshari, Amir R.; Mollazadeh, Hamid; Henney, Neil C. ...
Seminars in cancer biology,
August 2021, 2021-08-00, 20210801, Letnik:
73
Journal Article
Recenzirano
Odprti dostop
Evidence from preclinical studies suggests that the competitive HMG-CoA reductase (HMGCR) inhibitors universally known as 'statins,' in addition to being powerful drugs that reduce cholesterol and ...improve cardiovascular risk, also have promising antitumor properties. Statins appear to enhance the treatment outcome of various cancers before and concurrent with other cancer treatment interventions. Glioblastoma multiforme (GBM), a particularly invasive cerebral tumor associated with high mortality, holds a poor median overall survival (OS) of around one year after surgical resection followed by concurrent radiation and chemotherapy. Recently, statins have increasingly appeared as potential adjuvant drugs for the treatment of GBM because of their potential to suppress cell growth, survival, migration, metastasis, inflammation, angiogenesis, and promote apoptosis during both in vitro and in vivo studies. However, the clinical outcomes of statins on the survival of patients with GBM are still controversial. This study aims to review and address some of the documented effects of statin drugs when focusing entirely on cancer treatment, especially GBM, including concurrent statin therapy with chemotherapeutic agents.
There are increasing incidences and mortality rates for colorectal cancer in the world. It is common for chemotherapy and radiation given to patients with colorectal cancer to cause toxicities that ...limit their effectiveness and cause cancer cells to become resistant to these treatments. Additional targeted treatments are needed to improve patient's quality of life and outcomes. Immunotherapy has rapidly emerged as an incredibly exciting and promising avenue for cancer treatment in recent years. This innovative approach provides novel options for tackling solid tumors, effectively establishing itself as a new cornerstone in cancer treatment. Specifically, in the realm of colorectal cancer (CRC), there is great promise in developing new drugs that target immune checkpoints, offering a hopeful and potentially transformative solution. While immunotherapy of CRC has made significant advances, there are still obstacles and limitations. CRC patients have a poor response to treatment because of the immune-suppressing function of their tumor microenvironment (TME). In addition to blocking inhibitory immune checkpoints, checkpoint-blocking antibodies may also boost immune responses against tumors. The review summarizes recent advances in immune checkpoint inhibitors (ICIs) for CRC, including CTLA-4, PD-1, PD-L1, LAG-3, and TIM-3.
In the biomedical area, the interdisciplinary field of nanotechnology has the potential to bring numerous unique applications, including better tactics for cancer detection, diagnosis, and therapy. ...Nanoparticles (NPs) have been the topic of many research and material applications throughout the last decade. Unlike small-molecule medications, NPs are defined by distinct physicochemical characteristics, such as a large surface-to-volume ratio, which allows them to permeate live cells with relative ease. The versatility of NPs as both therapeutics and diagnostics makes them ideal for a broad spectrum of illnesses, from infectious diseases to cancer. A significant amount of data has been participated in the current scientific publications, emphasizing the concept that NPs often produce reactive oxygen species (ROS) to a larger degree than micro-sized particles. It is important to note that oxidative stress governs a wide range of cell signaling cascades, many of which are responsible for cancer cell cytotoxicity. Here, we aimed to provide insight into the signaling pathways triggered by oxidative stress in cancer cells in response to several types of nanomaterials, such as metallic and polymeric NPs and quantum dots. We discuss recent advances in developing integrated anticancer medicines based on NPs targeted to destroy malignant cells by increasing their ROS setpoint.
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•Oxidative stress is an inherent player in cancer biology.•ROS has a dual function in cancer suppression and progression.•Augmenting ROS generation pushes cancer cells beyond their oxidative stress limits facilitating programmed death patterns.•ROS-producing engineered NPs have shown promising effects in preclinical anticancer studies.•Recruiting ROS-producing NPs in cancer PDT or cytotoxic anticancer regimens may improve clinical outcomes.
Alzheimer's disease (AD), a type of dementia, is characterized by progressive memory decline and cognition impairment. Despite the considerable body of evidence regarding AD pathophysiology, current ...therapies merely slow down the disease progression, and a comprehensive therapeutic approach is unavailable. Accordingly, finding an efficient multifunctional remedy is necessary to blunt the increasing rate of AD incidence in the upcoming years. AD shares pathophysiological similarities (e.g., impairment of cognitive functions, insulin sensitivity, and brain glucose metabolism) with noninsulin-dependent diabetes mellitus (NIDDM), which offers the utilization of metformin, a biguanide hypoglycemic agent, as an alternative therapeutic approach in AD therapy. Emerging evidence has revealed the impact of metformin in patients suffering from AD. It has been described that metformin employs multiple mechanisms to improve cognition and memory impairment in pre-clinical AD models, including reduction of hippocampal amyloid-beta (Aβ) plaque and neurofibrillary tangles (NFTs) load, suppression of inflammation, amelioration of mitochondrial dysfunction and oxidative stress, restriction of apoptotic neuronal death, and induction of neurogenesis. This review discusses the pre-clinical evidence, which may shed light on the role of metformin in AD and provide a more comprehensive mechanistic insight for future studies in this area of research.
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Glioblastoma Multiforme (GBM) is a poorly curable brain tumor because of its extremely invasive nature. Curcuminoids, as potential phytochemicals extracted from Curcuma Longa L., have been documented ...for their chemopreventive and antitumor activities against several types of malignancies. These compounds exert these effects via modulation of multiple signaling pathways and molecular targets at different stages of tumor progression, proliferation, and metastasis. In experimental studies, curcuminoids have demonstrated promising therapeutic benefits to overcome GBM. Curcuminoids have been shown to exert their anti-GBM effects through regulation of angiogenesis, apoptosis, autophagy, metastasis, invasion, as well as potential molecular targets, including receptor tyrosine kinases, Sonic Hedgehog, and NF-κB. This study reviews the observations regarding the impact of curcumin and its derivatives on GBM and the potential of translating the research findings into the clinic.
The immune system's role in maintaining the health of the gastrointestinal (GI) system is like a double-edged sword. Simultaneously, it could reduce the risk of pathogen invasion by the inflammatory ...response. However, if regulated improperly, it could also propagate oncogenic signaling that transfers a normal cell into the malignant counterpart. Thus, several mechanisms have been proposed, such as the immune system could disturb the GI homeostasis and increase the survival and proliferative capacity of cells, leading to the formation of a wide range of malignancies. Among the endless list of these mechanisms, inflammatory responses are currently fascinating research areas, as this response regulation is by the gut microbiota. Given this, microbiota manipulation might be a convenient and efficient way to prevent GI cancer. Probiotics could potentially achieve this by overturning the milieu in favor of normal gut homeostasis. In addition to the safety of the use of probiotics, along with their potential ability to interact with immune system responses, these bacteria are also being analyzed from the perspective of dietary supplements. In the present review, we aimed to look into the mechanisms through which probiotics modulate immune response to stimulate anti-inflammatory responses and promote immune surveillance against neoplastic cells.
In terms of frequency and aggressiveness, glioblastoma multiforme (GBM) is undoubtedly the most frequent and fatal primary brain tumor. Despite advances in clinical management, the response to ...current treatments is dismal, with a 2-year survival rate varying between 6 and 12 percent. Metformin, a derivative of biguanide widely used in treating type 2 diabetes, has been shown to extend the lifespan of patients with various malignancies. There is limited evidence available on the long-term survival of GBM patients who have taken metformin. This research examined the literature to assess the connection between metformin's anticancer properties and GBM development. Clinical findings, together with the preclinical data from animal models and cell lines, are included in the present review. This comprehensive review covers not only the association of hyperactivation of the AMPK pathway with the anticancer activity of metformin but also other mechanisms underpinning its role in apoptosis, cell proliferation, metastasis, as well as its chemo-radio-sensitizing behavior against GBM. Current challenges and future directions for developments and applications of metformin-based therapeutics are also discussed.
It has become necessary to accept the clinical reality of therapeutic agents targeting the cancer-associated immune system. In recent decades, several investigations have highlighted the role of ...inflammation in cancer development. It has now been recognized that inflammatory cells secrete mediators, including enzymes, chemokines, and cytokines. These secreted substances produce an inflammatory microenvironment that is critically involved in cancer growth. Inflammation may enhance genomic instability leading to DNA damage, activation of oncogenes, or compromised tumor suppressor activity, all of which may promote various phases of carcinogenesis. Conventional cancer treatment includes surgery, radiation, and chemotherapy. However, treatment failure occurs because current strategies are unable to achieve complete local control due to metastasis. Nanoparticles (NPs) are a broad spectrum of drug carriers typically below the size of 100 nm, targeting tumor sites while reducing off-target consequences. More importantly, NPs can stimulate innate and adaptive immune systems in the tumor microenvironment (TME); hence, they induce a cancer-fighting immune response. Strikingly, targeting cancer cells with NPs helps eliminate drug resistance and tumor recurrence, as well as prevents inflammation. Throughout this review, we provide recent data on the role of inflammation in cancer and explore nano-therapeutic initiatives to target significant mediators, for example, nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins (ILs) associated with cancer-related inflammation, to escort the immunomodulators to cancer cells and associated systemic compartments. We also highlight the necessity of better identifying inflammatory pathways in cancer pathophysiology to develop effective treatment plans.
Brain cancers, particularly glioblastoma multiforme (GBM), are challenging health issues with frequent unmet aspects. Today, discovering safe and effective therapeutic modalities for brain tumors is ...among the top research interests. Immunotherapy is an emerging area of investigation in cancer treatment. Since immune checkpoints play fundamental roles in repressing anti-cancer immunity, diverse immune checkpoint inhibitors (ICIs) have been developed, and some monoclonal antibodies have been approved clinically for particular cancers; nevertheless, there are significant concerns regarding their efficacy and safety in brain tumors. Among the various tools to modify the immune checkpoints, phytochemicals show good effectiveness and excellent safety, making them suitable candidates for developing better ICIs. Phytochemicals regulate multiple immunological checkpoint-related signaling pathways in cancer biology; however, their efficacy for clinical cancer immunotherapy remains to be established. Here, we discussed the involvement of immune checkpoints in cancer pathology and summarized recent advancements in applying phytochemicals in modulating immune checkpoints in brain tumors to highlight the state-of-the-art and give constructive prospects for future research.
•Brain cancers, particularly glioblastoma multiforme (GBM) are challenging health issues.•Immunotherapy is an emerging area of investigation in cancer treatment.•Phytochemicals show good effectiveness and making them suitable to develop immune checkpoint inhibitors (ICIs).•We discussed the involvement of immune checkpoints in cancer pathology.•We also summarized the application of phytochemicals in modulating immune checkpoints in brain tumors.
