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Viruses Jun 2024C-terminal binding protein (CtBP), a transcriptional co-repressor, significantly influences cellular signaling, impacting various biological processes including cell... (Review)
Review
C-terminal binding protein (CtBP), a transcriptional co-repressor, significantly influences cellular signaling, impacting various biological processes including cell proliferation, differentiation, apoptosis, and immune responses. The CtBP family comprises two highly conserved proteins, CtBP1 and CtBP2, which have been shown to play critical roles in both tumorigenesis and the regulation of viral infections. Elevated CtBP expression is noted in various tumor tissues, promoting tumorigenesis, invasiveness, and metastasis through multiple pathways. Additionally, CtBP's role in viral infections varies, exhibiting differing or even opposing effects depending on the virus. This review synthesizes the advances in CtBP's function research in viral infections and virus-associated tumorigenesis, offering new insights into potential antiviral and anticancer strategies.
Topics: Humans; Carcinogenesis; Virus Diseases; Alcohol Oxidoreductases; DNA-Binding Proteins; Animals; Neoplasms
PubMed: 38932279
DOI: 10.3390/v16060988 -
Viruses May 2024Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B... (Review)
Review
Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B patients in whom serum HBV DNA or hepatitis B surface antigen is undetectable. The HBcrAg measurement system was developed based on two concepts. One is a fully-automated and highly-sensitive HBcrAg assay (iTACT-HBcrAg) and the other is a point-of-care testing (POCT) that can be used in in resource-limited areas. iTACT-HBcrAg is an alternative to HBV DNA for monitoring HBV reactivation and predicting the development of hepatocellular carcinoma. This validated biomarker is available in routine clinical practice in Japan. Currently, international guidelines for the prevention of mother-to-child transmission recommend anti-HBV prophylaxis for pregnant women with high viral loads. However, over 95% of HBV-infected individuals live in countries where HBV DNA quantification is widely unavailable. Given this situation, a rapid and simple HBcrAg assay for POCT would be highly effective. Long-term anti-HBV therapy may have potential side effects and appropriate treatment should be provided to eligible patients. Therefore, a simple method of determining the indication for anti-HBV treatment would be ideal. This review provides up-to-date information regarding the clinical value of HBcrAg in HBV management, based on iTACT-HBcrAg or POCT.
Topics: Humans; Hepatitis B Core Antigens; Hepatitis B virus; DNA, Viral; Hepatitis B; Biomarkers; Sensitivity and Specificity; Point-of-Care Testing; Mass Screening; Carcinoma, Hepatocellular; Female; Hepatitis B, Chronic; Infectious Disease Transmission, Vertical; Viral Load; Pregnancy; Liver Neoplasms; Hepatitis B Surface Antigens
PubMed: 38932141
DOI: 10.3390/v16060848 -
Pharmaceutics Jun 2024Potent synthetic drugs, as well as biomolecules extracted from plants, have been investigated for their selectivity toward cancer cells. The main limitation in cancer...
Potent synthetic drugs, as well as biomolecules extracted from plants, have been investigated for their selectivity toward cancer cells. The main limitation in cancer treatment is the ability to bring such molecules within each single cancer cell, which requires accumulation in the peritumoral region followed by homogeneous spreading within the entire tissue. In the last decades, nanotechnology has emerged as a powerful tool due to its ability to protect the drug during blood circulation and allow enhanced accumulation around the leaky regions of the tumor vasculature. However, the ideal size for accumulation of around 100 nm is too large for effective penetration into the dense collagen matrix. Therefore, we propose a multistage system based on graphene oxide nanosheet-based quantum dots (GOQDs) with dimensions that are 12 nm, functionalized with hyaluronic acid (GOQDs-HA), and deposited using the layer-by-layer technique onto an oil-in-water nanoemulsion (O/W NE) template that is around 100 nm in size, previously stabilized by a biodegradable polymer, chitosan. The choice of a biodegradable core for the nanocarrier is to degrade once inside the tumor, thus promoting the release of smaller compounds, GOQDs-HA, carrying the adsorbed anticancer compound, which in this work is represented by curcumin as a model bioactive anticancer molecule. Additionally, modification with HA aims to promote active targeting of stromal and cancer cells. Cell uptake experiments and preliminary penetration experiments in three-dimensional microtissues were performed to assess the proposed multistage nanocarrier.
PubMed: 38931947
DOI: 10.3390/pharmaceutics16060827 -
Pharmaceutics Jun 2024Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in... (Review)
Review
Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy.
PubMed: 38931929
DOI: 10.3390/pharmaceutics16060809 -
Pharmaceutics Jun 2024Pancreatic cancer (PC) is characterized by its notably poor prognosis and high mortality rate, underscoring the critical need for advancements in its diagnosis and... (Review)
Review
Pancreatic cancer (PC) is characterized by its notably poor prognosis and high mortality rate, underscoring the critical need for advancements in its diagnosis and therapy. Gold nanoparticles (AuNPs), with their distinctive physicochemical characteristics, demonstrate significant application potential in cancer therapy. For example, upon exposure to lasers of certain wavelengths, they facilitate localized heating, rendering them extremely effective in photothermal therapy. Additionally, their extensive surface area enables the conjugation of therapeutic agents or targeting molecules, increasing the accuracy of drug delivery systems. Moreover, AuNPs can serve as radiosensitizers, enhancing the efficacy of radiotherapy by boosting the radiation absorption in tumor cells. Here, we systematically reviewed the application and future directions of AuNPs in the diagnosis and treatment of PC. Although AuNPs have advantages in improving diagnostic and therapeutic efficacy, as well as minimizing damage to normal tissues, concerns about their potential toxicity and safety need to be comprehensively evaluated.
PubMed: 38931925
DOI: 10.3390/pharmaceutics16060806 -
Pharmaceutics Jun 2024Breast cancer (BC) poses a significant threat to women's health, with triple-negative breast cancer (TNBC) representing one of the most challenging and aggressive... (Review)
Review
Breast cancer (BC) poses a significant threat to women's health, with triple-negative breast cancer (TNBC) representing one of the most challenging and aggressive subtypes due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Traditional TNBC treatments often encounter issues such as low drug efficiency, limited tumor enrichment, and substantial side effects. Therefore, it is crucial to explore novel diagnostic and treatment systems for TNBC. Multifunctional molecular probes (MMPs), which integrate target recognition as well as diagnostic and therapeutic functions, introduce advanced molecular tools for TNBC theranostics. Using an MMP system, molecular drugs can be precisely delivered to the tumor site through a targeted ligand. Real-time dynamic monitoring of drug release achieved using imaging technology allows for the evaluation of drug enrichment at the tumor site. This approach enables accurate drug release, thereby improving the therapeutic effect. Therefore, this review summarizes the recent advancements in MMPs for TNBC theranostics, encompassing the design and synthesis of MMPs as well as their applications in the field of TNBC theranostics.
PubMed: 38931924
DOI: 10.3390/pharmaceutics16060803 -
Pharmaceutics Jun 2024This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral... (Review)
Review
This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral cancer therapy. By focusing on their core abilities to facilitate targeted and localized drug administration, these systems enhance therapeutic outcomes significantly. Scaffolds, notably those coated with anti-cancer agents such as cisplatin and paclitaxel, have proven effective in inhibiting oral cancer cell proliferation, establishing a promising avenue for site-specific drug delivery. The application of synthetic scaffolds, including Poly Ethylene Glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA), and natural materials, like collagen or silk, in 3D systems has been pivotal for controlled release of therapeutic agents, executing diverse anti-cancer strategies. A key advancement in this field is the advent of smart scaffolds designed for sequential cancer therapy, which strive to refine drug delivery systems, minimizing surgical interventions, accentuating the significance of 3D scaffolds in oral cancer management. These systems, encompassing local drug-coated scaffolds and other scaffold-based platforms, hold the potential to transform oral cancer treatment through precise interventions, yielding improved patient outcomes. Local drug delivery via scaffolds can mitigate systemic side effects typically associated with chemotherapy, such as nausea, alopecia, infections, and gastrointestinal issues. Post-drug release, scaffolds foster a conducive environment for non-cancerous cell growth, adhering and proliferation, demonstrating restorative potential. Strategies for controlled and targeted drug delivery in oral cancer therapy span injectable self-assembling peptide hydrogels, nanocarriers, and dual drug-loaded nanofibrous scaffolds. These systems ensure prolonged release, synergistic effects, and tunable targeting, enhancing drug delivery efficiency while reducing systemic exposure. Smart scaffolds, capable of sequential drug release, transitioning to cell-friendly surfaces, and enabling combinatorial therapy, hold the promise to revolutionize treatment by delivering precise interventions and optimized outcomes. In essence, scaffold-based drug delivery systems, through their varied forms and functionalities, are reshaping oral cancer therapy. They target drug delivery efficiency, diminish side effects, and present avenues for personalization. Challenges like fabrication intricacy, biocompatibility, and scalability call for additional research. Nonetheless, the perspective on scaffold-based systems in oral cancer treatment is optimistic, as ongoing advancements aim to surmount current limitations and fully leverage their potential in cancer therapy.
PubMed: 38931923
DOI: 10.3390/pharmaceutics16060802 -
Pharmaceutics Jun 2024Zastaprazan (JP-1366), a novel potassium-competitive acid blocker, is a new drug for the treatment of erosive esophagitis. JP-1366 is highly metabolized in human, mouse,...
Zastaprazan (JP-1366), a novel potassium-competitive acid blocker, is a new drug for the treatment of erosive esophagitis. JP-1366 is highly metabolized in human, mouse, and dog hepatocytes but moderately metabolized in rat and monkey hepatocytes when estimated from the metabolic stability of this compound in hepatocyte suspension and when 18 phase I metabolites and 5 phase II metabolites [i.e., -dearylation (M6), hydroxylation (M1, M19, M21), dihydroxylation (M7, M8, M14, M22), trihydroxylation (M13, M18), hydroxylation and reduction (M20), dihydroxylation and reduction (M9, M16), hydrolysis (M23), hydroxylation and glucuronidation (M11, M15), hydroxylation and sulfation (M17), dihydroxylation and sulfation (M10, M12), -dearylation and hydroxylation (M3, M4), -dearylation and dihydroxylation (M5), and -dearylation and trihydroxylation (M2)] were identified from JP-1366 incubation with the hepatocytes from humans, mice, rats, dogs, and monkeys. Based on the cytochrome P450 (CYP) screening test and immune-inhibition analysis with CYP antibodies, CYP3A4 and CYP3A5 played major roles in the metabolism of JP-1366 to M1, M3, M4, M6, M8, M9, M13, M14, M16, M18, M19, M21, and M22. CYP1A2, 2C8, 2C9, 2C19, and 2D6 played minor roles in the metabolism of JP-1366. UDP-glucuronosyltransferase (UGT) 2B7 and UGT2B17 were responsible for the glucuronidation of M1 to M15. However, JP-1366 and active metabolite M1 were not substrates for drug transporters such as organic cation transporter (OCT) 1/2, organic anion transporter (OAT) 1/3, organic anion transporting polypeptide (OATP)1B1/1B3, multidrug and toxic compound extrusion (MATE)1/2K, P-glycoprotein (P-gp), and breast cancer-resistant protein (BCRP). Only M1 showed substrate specificity for P-gp. The findings indicated that drug-metabolizing enzymes, particularly CYP3A4/3A5, may have a significant role in determining the pharmacokinetics of zastaprazan while drug transporters may only have a small impact on the absorption, distribution, and excretion of this compound.
PubMed: 38931920
DOI: 10.3390/pharmaceutics16060799 -
Pharmaceutics Jun 2024Cancer immunotherapy has revolutionized oncology by harnessing the patient's immune system to target and eliminate cancer cells. However, immune checkpoint blockades... (Review)
Review
Cancer immunotherapy has revolutionized oncology by harnessing the patient's immune system to target and eliminate cancer cells. However, immune checkpoint blockades (ICBs) face limitations such as low response rates, particularly in immunologically 'cold' tumors. Enhancing tumor immunogenicity through immunogenic cell death (ICD) inducers and advanced drug delivery systems represents a promising solution. This review discusses the development and application of various nanocarriers, including polymeric nanoparticles, liposomes, peptide-based nanoparticles, and inorganic nanoparticles, designed to deliver ICD inducers and ICBs effectively. These nanocarriers improve therapeutic outcomes by converting cold tumors into hot tumors, thus enhancing immune responses and reducing systemic toxicity. By focusing on single-nanoparticle systems that co-deliver both ICD inducers and ICBs, this review highlights their potential in achieving higher drug concentrations at tumor sites, improving pharmacokinetics and pharmacodynamics, and facilitating clinical translation. Future research should aim to optimize these nanocarrier systems for better in vivo performance and clinical applications, ultimately advancing cancer immunotherapy.
PubMed: 38931916
DOI: 10.3390/pharmaceutics16060795 -
Pharmaceutics Jun 2024Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to... (Review)
Review
Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, , and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with supplementation with natural products may confer benefits to cancer patients, by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.
PubMed: 38931908
DOI: 10.3390/pharmaceutics16060787