Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance.

The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors.

Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.

BACKGROUND: Solute carrier (SLC) transporters, a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment (TME). Amino acids are fundamental building blocks of cells and play essential roles in protein synthesis, nutrient sensing, and oncogenic signaling pathways. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. SCOPE OF REVIEW: In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. MAJOR CONCLUSIONS: Amino acids transportation by SLCs plays a critical role in tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although several studies evaluated the function of SLC7A11 and SLC1A5, the role of some SLC proteins in cancer is not studied well. To exert their functions, SLCs mediate metabolic rewiring, regulate the maintenance of redox balance, affect main oncogenic pathways, regulate amino acids bioavailability within the TME, and alter the sensitivity of cancer cells to therapeutics. However, different therapeutic methods that prevent the function of SLCs were able to inhibit tumor progression. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids and their transporters within the SLC superfamily.

Multifunctional and stimuli-responsive liposomes in hepatocellular carcinoma diagnosis and therapy.

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, mainly occurring in Asian countries with an increased incidence rate globally. Currently, several kinds of therapies have been deployed for HCC therapy including surgical resection, chemotherapy, radiotherapy and immunotherapy. However, this tumor is still incurable, requiring novel strategies for its treatment. The nanomedicine has provided the new insights regarding the treatment of cancer that liposomes as lipid-based nanoparticles, have been widely applied in cancer therapy due to their biocompaitiblity, high drug loading and ease of synthesis and modification. The current review evaluates the application of liposomes for the HCC therapy. The drugs and genes lack targeting ability into tumor tissues and cells. Therefore, loading drugs or genes on liposomes can increase their accumulation in tumor site for HCC suppression. Moreover, the stimuli-responsive liposomes including pH-, redox- and light-sensitive liposomes are able to deliver drug into tumor microenvironment to improve therapeutic index. Since a number of receptors upregulate on HCC cells, the functionalization of liposomes with lactoferrin and peptides can promote the targeting ability towards HCC cells. Moreover, phototherapy can be induced by liposomes through loading phtoosensitizers to stimulate photothermal- and photodynamic-driven ablation of HCC cells. Overall, the findings are in line with the fact that liposomes are promising nanocarriers for the treatment of HCC.

NF-ĸB axis in diabetic neuropathy, cardiomyopathy and nephropathy: A roadmap from molecular intervention to therapeutic strategies.

Diabetes mellitus (DM) is a metabolic illness defined by elevated blood glucose levels, mediating various tissue alterations, including the dysfunction of vital organs. Diabetes mellitus (DM) can lead to many consequences that specifically affect the brain, heart, and kidneys. These issues are known as neuropathy, cardiomyopathy, and nephropathy, respectively. Inflammation is acknowledged as a pivotal biological mechanism that contributes to the development of various diabetes consequences. NF-κB modulates inflammation and the immune system at the cellular level. Its abnormal regulation has been identified in several clinical situations, including cancer, inflammatory bowel illnesses, cardiovascular diseases, and Diabetes Mellitus (DM). The purpose of this review is to evaluate the potential impact of NF-κB on complications associated with DM. Enhanced NF-κB activity promotes inflammation, resulting in cellular harm and compromised organ performance. Phytochemicals, which are therapeutic molecules, can potentially decline the NF-κB level, therefore alleviating inflammation and the progression of problems correlated with DM. More importantly, the regulation of NF-κB can be influenced by various factors, such as TLR4 in DM. Highlighting these factors can facilitate the development of novel therapies in the future.

Epigenetic regulation of hepatocellular carcinoma progression: MicroRNAs as therapeutic, diagnostic and prognostic factors.

Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.

Non-coding RNA transcripts, incredible modulators of cisplatin chemo-resistance in bladder cancer through operating a broad spectrum of cellular processes and signaling mechanism.

Bladder cancer (BC) is a highly frequent neoplasm in correlation with significant rate of morbidity, mortality, and cost. The onset of BC is predominantly triggered by environmental and/or occupational exposures to carcinogens, such as tobacco. There are two distinct pathways by which BC can be developed, including non-muscle-invasive papillary tumors (NMIBC) and non-papillary (or solid) muscle-invasive tumors (MIBC). The Cancer Genome Atlas project has further recognized key genetic drivers of MIBC along with its subtypes with particular properties and therapeutic responses; nonetheless, NMIBC is the predominant BC presentation among the suffering individuals. Radical cystoprostatectomy, radiotherapy, and chemotherapy have been verified to be the common therapeutic interventions in metastatic tumors, among which chemotherapeutics are more conventionally utilized. Although multiple chemo drugs have been broadly administered for BC treatment, cisplatin is reportedly the most effective chemo drug against the corresponding malignancy. Notwithstanding, tumor recurrence is usually occurred following the consumption of cisplatin regimens, particularly due to the progression of chemo-resistant trait. In this framework, non-coding RNAs (ncRNAs), as abundant RNA transcripts arise from the human genome, are introduced to serve as crucial contributors to tumor expansion and cisplatin chemo-resistance in bladder neoplasm. In the current review, we first investigated the best-known ncRNAs, i.e. microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), correlated with cisplatin chemo-resistance in BC cells and tissues. We noticed that these ncRNAs could mediate the BC-related cisplatin-resistant phenotype through diverse cellular processes and signaling mechanisms, reviewed here. Eventually, diagnostic and prognostic potential of ncRNAs, as well as their therapeutic capabilities were highlighted in regard to BC management.

Harnessing function of EMT in cancer drug resistance: a metastasis regulator determines chemotherapy response.

Epithelial-mesenchymal transition (EMT) is a complicated molecular process that governs cellular shape and function changes throughout tissue development and embryogenesis. In addition, EMT contributes to the development and spread of tumors. Expanding and degrading the surrounding microenvironment, cells undergoing EMT move away from the main location. On the basis of the expression of fibroblast-specific protein-1 (FSP1), fibroblast growth factor (FGF), collagen, and smooth muscle actin (-SMA), the mesenchymal phenotype exhibited in fibroblasts is crucial for promoting EMT. While EMT is not entirely reliant on its regulators like ZEB1/2, Twist, and Snail proteins, investigation of upstream signaling (like EGF, TGF-ß, Wnt) is required to get a more thorough understanding of tumor EMT. Throughout numerous cancers, connections between tumor epithelial and fibroblast cells that influence tumor growth have been found. The significance of cellular crosstalk stems from the fact that these events affect therapeutic response and disease prognosis. This study examines how classical EMT signals emanating from various cancer cells interfere to tumor metastasis, treatment resistance, and tumor recurrence.

Biological landscape and nanostructural view in development and reversal of oxaliplatin resistance in colorectal cancer.

The treatment of cancer patients has been mainly followed using chemotherapy and it is a gold standard in improving prognosis and survival rate of patients. Oxaliplatin (OXA) is a third-platinum anti-cancer agent that reduces DNA synthesis in cancer cells to interfere with their growth and cell cycle progression. In spite of promising results of using OXA in cancer chemotherapy, the process of drug resistance has made some challenges. OXA is commonly applied in treatment of colorectal cancer (CRC) as a malignancy of gastrointestinal tract and when CRC cells increase their proliferation and metastasis, they can obtain resistance to OXA chemotherapy. A number of molecular factors such as CHK2, SIRT1, c-Myc, LATS2 and FOXC1 have been considered as regulators of OXA response in CRC cells. The non-coding RNAs are able to function as master regulator of other molecular pathways in modulating OXA resistance. There is a close association between molecular mechanisms such as apoptosis, autophagy, glycolysis and EMT with OXA resistance, so that apoptosis inhibition, pro-survival autophagy induction and stimulation of EMT and glycolysis can induce OXA resistance in CRC cells. A number of anti-tumor compounds including astragaloside IV, resveratrol and nobiletin are able to enhance OXA sensitivity in CRC cells. Nanoparticles for increasing potential of OXA in CRC suppression and reversing OXA resistance have been employed in cancer chemotherapy. These subjects are covered in this review article to shed light on molecular factors resulting in OXA resistance.

EZH2 as a potential therapeutic target for gastrointestinal cancers.

Gastrointestinal (GI) cancers continue to be a major cause of mortality and morbidity globally. Understanding the molecular pathways associated with cancer progression and severity is essential for creating effective cancer treatments. In cancer research, there is a notable emphasis on Enhancer of zeste homolog 2 (EZH2), a key player in gene expression influenced by its irregular expression and capacity to attach to promoters and alter methylation status. This review explores the impact of EZH2 signaling on various GI cancers, such as colorectal, gastric, pancreatic, hepatocellular, esophageal, and cholangiocarcinoma. The primary function of EZH2 signaling is to facilitate the accelerated progression of cancer cells. Additionally, EZH2 has the capacity to modulate the reaction of GI cancers to chemotherapy and radiotherapy. Numerous pathways, including long non-coding RNAs and microRNAs, serve as upstream regulators of EZH2 in these types of cancer. EZH2's enzymatic activity enables it to attach to target gene promoters, resulting in methylation that modifies their expression. EZH2 could be considered as an independent prognostic factor, with increased expression correlating with a worse disease prognosis. Additionally, a range of gene therapies including small interfering RNA, and anti-tumor agents are being explored to target EZH2 for cancer treatment. This comprehensive review underscores the current insights into EZH2 signaling in gastrointestinal cancers and examines the prospect of therapies targeting EZH2 to enhance patient outcomes.

Pathological roles of miRNAs and pseudogene-derived lncRNAs in human cancers, and their comparison as prognosis/diagnosis biomarkers.

This review examines and compares the diagnostic and prognostic capabilities of miRNAs and lncRNAs derived from pseudogenes in cancer patients. Additionally, it delves into their roles in cancer pathogenesis. Both miRNAs and pseudogene-derived lncRNAs have undergone thorough investigation as remarkably sensitive and specific cancer biomarkers, offering significant potential for cancer detection and monitoring. . Extensive research is essential to gain a complete understanding of the precise roles these non-coding RNAs play in cancer, allowing the development of novel targeted therapies and biomarkers for improved cancer detection and treatment approaches.

Role of non-coding RNAs in osteoporosis.

Osteoporosis, a prevalent bone disorder influenced by genetic and environmental elements, significantly increases the likelihood of fractures and bone weakness, greatly affecting the lives of those afflicted. Yet, the exact epigenetic processes behind the onset of osteoporosis are still unclear. Growing research indicates that epigenetic changes could act as vital mediators that connect genetic tendencies and environmental influences, thereby increasing the risk of osteoporosis and bone fractures. Within these epigenetic factors, certain types of RNA, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been recognized as key regulatory elements. These RNA types wield significant influence on gene expression through epigenetic regulation, directing various biological functions essential to bone metabolism. This extensive review compiles current research uncovering the complex ways in which miRNAs, lncRNAs, and circRNAs are involved in the development of osteoporosis, especially in osteoblasts and osteoclasts. Gaining a more profound understanding of the roles these three RNA classes play in osteoporosis could reveal new diagnostic methods and treatment approaches for this incapacitating condition. In conclusion, this review delves into the complex domain of epigenetic regulation via non-coding RNA in osteoporosis. It sheds light on the complex interactions and mechanisms involving miRNAs, lncRNAs, and circRNAs within osteoblasts and osteoclasts, offering an in-depth understanding of the less explored aspects of osteoporosis pathogenesis. These insights not only reveal the complexity of the disease but also offer significant potential for developing new diagnostic methods and targeted treatments. Therefore, this review marks a crucial step in deciphering the elusive complexities of osteoporosis, leading towards improved patient care and enhanced quality of life.

New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis.

Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance.

miRNAs and exosomal miRNAs in lung cancer: New emerging players in tumor progression and therapy response.

Non-coding RNAs have shown key roles in cancer and among them, short RNA molecules are known as microRNAs (miRNAs). These molecules have length less than 25 nucleotides and suppress translation and expression. The functional miRNAs are produced in cytoplasm. Lung cancer is a devastating disease that its mortality and morbidity have undergone an increase in recent years. Aggressive behavior leads to undesirable prognosis and tumors demonstrate abnormal proliferation and invasion. In the present review, miRNA functions in lung cancer is described. miRNAs reduce/increase proliferation and metastasis. They modulate cell death and proliferation. Overexpression of oncogenic miRNAs facilitates drug resistance and radio-resistance in lung cancer. Tumor microenvironment components including macrophages and cancer-associated fibroblasts demonstrate interactions with miRNAs in lung cancer. Other factors such as HIF-1α, lncRNAs and circRNAs modulate miRNA expression. miRNAs have also value in the diagnosis of lung cancer. Understanding such interactions can pave the way for developing novel therapeutics in near future for lung cancer patients.

Versatile function of AMPK signaling in osteosarcoma: An old player with new emerging carcinogenic functions.

AMP-activated protein kinase (AMPK) signaling has a versatile role in Osteosarcoma (OS), an aggressive bone malignancy with a poor prognosis, particularly in cases that have metastasized or recurred. This review explores the regulatory mechanisms, functional roles, and therapeutic applications of AMPK signaling in OS. It focuses on the molecular activation of AMPK and its interactions with cellular processes like proliferation, apoptosis, and metabolism. The uncertain role of AMPK in cancer is also discussed, highlighting its potential as both a tumor suppressor and a contributor to carcinogenesis. The therapeutic potential of targeting AMPK signaling in OS treatment is examined, including direct and indirect activators like metformin, A-769662, resveratrol, and salicylate. Further research is needed to determine dosing, toxicities, and molecular mechanisms responsible for the anti-osteosarcoma effects of these compounds. This review underscores the complex involvement of AMPK signaling in OS and emphasizes the need for a comprehensive understanding of its molecular mechanisms. By elucidating the role of AMPK in OS, the aim is to pave the way for innovative therapeutic approaches that target this pathway, ultimately improving the prognosis and quality of life for OS patients.

Semaphorin 3C promotes de novo steroidogenesis in prostate cancer cells.

Intratumoral androgen biosynthesis contributes to castration-resistant prostate cancer progression in patients treated with androgen deprivation therapy. The molecular mechanisms by which castration-resistant prostate cancer acquires the capacity for androgen biosynthesis to bypass androgen deprivation therapy are not entirely known. Here, we show that semaphorin 3C, a secreted signaling protein that is highly expressed in castration-resistant prostate cancer, can promote steroidogenesis by altering the expression profile of key steroidogenic enzymes. Semaphorin 3C not only upregulates enzymes required for androgen synthesis from dehydroepiandrosterone or de novo from cholesterol but also simultaneously downregulates enzymes involved in the androgen inactivation pathway. These changes in gene expression correlate with increased production of androgens induced by semaphorin 3C in prostate cancer model cells. Moreover, semaphorin 3C upregulates androgen synthesis in LNCaP cell-derived xenograft tumors, likely contributing to the enhanced in vivo tumor growth rate post castration. Furthermore, semaphorin 3C activates sterol regulatory element-binding protein, a transcription factor that upregulates enzymes involved in the synthesis of cholesterol, a sole precursor for de novo steroidogenesis. The ability of semaphorin 3C to promote intratumoral androgen synthesis may be a key mechanism contributing to the reactivation of the androgen receptor pathway in castration-resistant prostate cancer, conferring continued growth under androgen deprivation therapy. These findings identify semaphorin 3C as a potential therapeutic target for suppressing intratumoral steroidogenesis.

Multifunctional and theranostic hydrogels for wound healing acceleration: An emphasis on diabetic-related chronic wounds.

Hydrogels represent intricate three-dimensional polymeric structures, renowned for their compatibility with living systems and their ability to naturally degrade. These networks stand as promising and viable foundations for a range of biomedical uses. The practical feasibility of employing hydrogels in clinical trials has been well-demonstrated. Among the prevalent biomedical uses of hydrogels, a significant application arises in the context of wound healing. This intricate progression involves distinct phases of inflammation, proliferation, and remodeling, often triggered by trauma, skin injuries, and various diseases. Metabolic conditions like diabetes have the potential to give rise to persistent wounds, leading to delayed healing processes. This current review consolidates a collection of experiments focused on the utilization of hydrogels to expedite the recovery of wounds. Hydrogels have the capacity to improve the inflammatory conditions at the wound site, and they achieve this by diminishing levels of reactive oxygen species (ROS), thereby exhibiting antioxidant effects. Hydrogels have the potential to enhance the growth of fibroblasts and keratinocytes at the wound site. They also possess the capability to inhibit both Gram-positive and Gram-negative bacteria, effectively managing wounds infected by drug-resistant bacteria. Hydrogels can trigger angiogenesis and neovascularization processes, while also promoting the M2 polarization of macrophages, which in turn mitigates inflammation at the wound site. Intelligent and versatile hydrogels, encompassing features such as pH sensitivity, reactivity to reactive oxygen species (ROS), and responsiveness to light and temperature, have proven advantageous in expediting wound healing. Furthermore, hydrogels synthesized using environmentally friendly methods, characterized by high levels of biocompatibility and biodegradability, hold the potential for enhancing the wound healing process. Hydrogels can facilitate the controlled discharge of bioactive substances. More recently, there has been progress in the creation of conductive hydrogels, which, when subjected to electrical stimulation, contribute to the enhancement of wound healing. Diabetes mellitus, a metabolic disorder, leads to a slowdown in the wound healing process, often resulting in the formation of persistent wounds. Hydrogels have the capability to expedite the healing of diabetic wounds, facilitating the transition from the inflammatory phase to the proliferative stage. The current review sheds light on the biological functionalities of hydrogels, encompassing their role in modulating diverse mechanisms and cell types, including inflammation, oxidative stress, macrophages, and bacteriology. Additionally, this review emphasizes the significance of smart hydrogels with responsiveness to external stimuli, as well as conductive hydrogels for promoting wound healing. Lastly, the discussion delves into the advancement of environmentally friendly hydrogels with high biocompatibility, aimed at accelerating the wound healing process.

Graphene oxide nanoarchitectures in cancer therapy: Drug and gene delivery, phototherapy, immunotherapy, and vaccine development.

The latest advancements in oncology involves the creation of multifunctional nanostructures. The integration of nanoparticles into the realm of cancer therapy has brought about a transformative shift, revolutionizing the approach to addressing existing challenges and limitations in tumor elimination. This is particularly crucial in combating the emergence of resistance, which has significantly undermined the effectiveness of treatments like chemotherapy and radiotherapy. GO stands as a carbon-derived nanoparticle that is increasingly finding utility across diverse domains, notably in the realm of biomedicine. The utilization of GO nanostructures holds promise in the arena of oncology, enabling precise transportation of drugs and genetic material to targeted sites. GO nanomaterials offer the opportunity to enhance the pharmacokinetic behavior and bioavailability of drugs, with documented instances of these nanocarriers elevating drug accumulation at the tumor location. The GO nanostructures encapsulate genes, shielding them from degradation and facilitating their uptake within cancer cells, thereby promoting efficient gene silencing. The capability of GO to facilitate phototherapy has led to notable advancements in reducing tumor progression. By PDT and PTT combination, GO nanomaterials hold the capacity to diminish tumorigenesis. GO nanomaterials have the potential to trigger both cellular and innate immunity, making them promising contenders for vaccine development. Additionally, types of GO nanoparticles that respond to specific stimuli have been applied in cancer eradication, as well as for the purpose of cancer detection and biomarker diagnosis. Endocytosis serves as the mechanism through which GO nanomaterials are internalized. Given these advantages, the utilization of GO nanomaterials for tumor elimination comes highly recommended.

Stimuli-responsive (nano)architectures for phytochemical delivery in cancer therapy.

The use of phytochemicals for purpose of cancer therapy has been accelerated due to resistance of tumor cells to conventional chemotherapy drugs and therefore, monotherapy does not cause significant improvement in the prognosis and survival of patients. Therefore, administration of natural products alone or in combination with chemotherapy drugs due to various mechanisms of action has been suggested. However, cancer therapy using phytochemicals requires more attention because of poor bioavailability of compounds and lack of specific accumulation at tumor site. Hence, nanocarriers for specific delivery of phytochemicals in tumor therapy has been suggested. The pharmacokinetic profile of natural products and their therapeutic indices can be improved. The nanocarriers can improve potential of natural products in crossing over BBB and also, promote internalization in cancer cells through endocytosis. Moreover, (nano)platforms can deliver both natural and synthetic anti-cancer drugs in combination cancer therapy. The surface functionalization of nanostructures with ligands improves ability in internalization in tumor cells and improving cytotoxicity of natural compounds. Interestingly, stimuli-responsive nanostructures that respond to endogenous and exogenous stimuli have been employed for delivery of natural compounds in cancer therapy. The decrease in pH in tumor microenvironment causes degradation of bonds in nanostructures to release cargo and when changes in GSH levels occur, it also mediates drug release from nanocarriers. Moreover, enzymes in the tumor microenvironment such as MMP-2 can mediate drug release from nanocarriers and more progresses in targeted drug delivery obtained by application of nanoparticles that are responsive to exogenous stimulus including light.

PI3K/Akt signaling in urological cancers: Tumorigenesis function, therapeutic potential, and therapy response regulation.

In addition to environmental conditions, lifestyle factors, and chemical exposure, aberrant gene expression and mutations involve in the beginning and development of urological tumors. Even in Western nations, urological malignancies are among the top causes of patient death, and their prevalence appears to be gender dependent. The prognosis for individuals with urological malignancies remains dismal and unfavorable due to the ineffectiveness of conventional treatment methods. PI3K/Akt is a popular biochemical mechanism that is activated in tumor cells as a result of PTEN loss. PI3K/Akt escalates growth and metastasis. Moreover, due to the increase in tumor cell viability caused by PI3K/Akt activation, cancer cells may acquire resistance to treatment. This review article examines the function of PI3K/Akt in major urological tumors including bladder, prostate, and renal tumors. In prostate, bladder, and kidney tumors, the level of PI3K and Akt are notably elevated. In addition, the activation of PI3K/Akt enhances the levels of Bcl-2 and XIAP, hence increasing the tumor cell survival rate. PI3K/Akt ] upregulates EMT pathways and matrix metalloproteinase expression to increase urological cancer metastasis. Furthermore, stimulation of PI3K/Akt results in drug- and radio-resistant cancers, but its suppression by anti-tumor drugs impedes the tumorigenesis.

Epigenetic regulation of temozolomide resistance in human cancers with an emphasis on brain tumors: Function of non-coding RNAs.

Brain tumors, which are highly malignant, pose a significant threat to health and often result in substantial rates of mortality and morbidity worldwide. The brain cancer therapy has been challenging due to obstacles such as the BBB, which hinders effective delivery of therapeutic agents. Additionally, the emergence of drug resistance further complicates the management of brain tumors. TMZ is utilized in brain cancer removal, but resistance is a drawback. ncRNAs are implicated in various diseases, and their involvement in the cancer is particularly noteworthy. The focus of the current manuscript is to explore the involvement of ncRNAs in controlling drug resistance, specifically in the context of resistance to the chemotherapy drug TMZ. The review emphasizes the function of ncRNAs, particularly miRNAs, in modulating the growth and invasion of brain tumors, which significantly influences their response to TMZ treatment. Through their interactions with various molecular pathways, miRNAs are modulators of TMZ response. Similarly, lncRNAs also associate with molecular pathways and miRNAs, affecting the efficacy of TMZ chemotherapy. Given their functional properties, lncRNAs can either induce or suppress TMZ resistance in brain tumors. Furthermore, circRNAs, which are cancer controllers, regulate miRNAs by acting as sponges, thereby impacting the response to TMZ chemotherapy. The review explores the correlation between ncRNAs and TMZ chemotherapy, shedding light on the underlying molecular pathways involved in this process.