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1.
Curr Pharm Des ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623972

RESUMO

Due to self-renewal, differentiation, and limitless proliferation properties, Cancer Stem Cells (CSCs) increase the probability of tumor development. These cells are identified by using CSC markers, which are highly expressed proteins on the cell surface of CSCs. Recently, the therapeutic application of CSCs as novel biomarkers improved both the prognosis and diagnosis outcome of colorectal Cancer. In the present review, we focused on a specific panel of colorectal CSC markers, including LGR5, ALDH, CD166, CD133, and CD44, which offers a targeted and comprehensive analysis of their functions. The selection criteria for these markersCancer were based on their established significance in Colorectal Cancer (CRC) pathogenesis and clinical outcomes, providing novel insights into the CSC biology of CRC. Through this approach, we aim to elevate understanding and stimulate further research for developing effective diagnostic and therapeutic strategies in CRC.

2.
Curr Pharm Des ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638053

RESUMO

Hydrogen therapy has emerged as a possible approach for both preventing and treating cancer. Cancers are often associated with oxidative stress and chronic inflammation. Hydrogen, with its unique physiological functions and characteristics, exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties, making it an attractive candidate for cancer treatment. Through its ability to mitigate oxidative damage, modulate inflammatory responses, and sustain cellular viability, hydrogen demonstrates significant potential in preventing cancer recurrence and improving treatment outcomes. Preclinical studies have shown the efficacy of hydrogen therapy in several cancer types, highlighting its ability to enhance the effectiveness of conventional treatments while reducing associated side effects. Furthermore, hydrogen therapy has been found to be safe and well-tolerated in clinical settings. Nonetheless, additional investigations are necessary to improve a comprehensive understanding of the mechanisms underlying hydrogen's therapeutic potential and refine the administration and dosage protocols. However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies.

3.
Mol Genet Genomic Med ; 12(4): e2418, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634215

RESUMO

BACKGROUND: Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). OBJECTIVE: In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. RESULTS: Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. CONCLUSION: We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.


Assuntos
Doenças Cardiovasculares , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/genética , Irã (Geográfico) , Triglicerídeos , Angiopoietinas , Proteína 3 Semelhante a Angiopoietina
4.
Artigo em Inglês | MEDLINE | ID: mdl-38584531

RESUMO

BACKGROUND: Colorectal cancer (CRC) remains a significant contributor to mortality, often exacerbated by metastasis and chemoresistance. Novel therapeutic strategies are imperative to enhance current treatments. The dysregulation of the PI3K/Akt signaling pathway is implicated in CRC progression. This study investigates the therapeutic potential of Wortmannin, combined with 5-fluorouracil (5-FU), to target the PI3K/Akt pathway in CRC. METHODS: Anti-migratory and antiproliferative effects were assessed through wound healing and MTT assays. Apoptosis and cell cycle alterations were evaluated using Annexin V/Propidium Iodide Apoptosis Assay. Wortmannin's impact on the oxidant/antioxidant equilibrium was examined via ROS, SOD, CAT, MDA, and T-SH levels. Downstream target genes of the PI3K/AKT pathway were analyzed at mRNA and protein levels using RTPCR and western blot, respectively. RESULTS: Wortmannin demonstrated a significant inhibitory effect on cell proliferation, modulating survivin, cyclinD1, PI3K, and p-Akt. The PI3K inhibitor attenuated migratory activity, inducing E-cadherin expression. Combined Wortmannin with 5-FU induced apoptosis, increasing cells in sub-G1 via elevated ROS levels. CONCLUSION: This study underscores Wortmannin's potential in inhibiting CRC cell growth and migration through PI3K/Akt pathway modulation. It also highlights its candidacy for further investigation as a promising therapeutic option in colorectal cancer treatment.

5.
Curr Pharm Des ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500284

RESUMO

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal-based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

6.
Haemophilia ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439143

RESUMO

INTRODUCTION: Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. AIMS: We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. METHODS: We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-α were analysed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. RESULTS: In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-α rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. CONCLUSIONS: These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1α, IL1-ß, IL-1R1 and IL-R antagonists might be involved in the GT progression.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38420938

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with limited treatment options, highlighting the urgent need for innovative approaches. A promising target for new anticancer therapies across various tumor types is the receptor tyrosine kinase c-MET. Here, we examined the impact of the c-MET inhibitor tivantinib in combination with gemcitabine on both primary and immortalized PDAC cells, and we investigated the mechanism underlying this combined treatment's effects. Our findings demonstrate that tivantinib is synergistic with gemcitabine, which is not related to cytidine deaminase but to inhibition of the polymerization of tubulin. Moreover, these drugs affected the expression of microRNAs miR-21 and miR-34, which regulate key oncogenic pathways. These findings might have an impact on the selection of patients for future trials.

8.
Mol Biol Rep ; 51(1): 358, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400849

RESUMO

BACKGROUND: Cardiomyocytes form, transport, and metabolize the omnipresent metabolite adenosine. Depending upon the adenosine concentrations and the pharmacological properties of receptor subtypes, adenosine exerts (patho)physiological responses in the cardiovascular system. The objective of this review is to present different protective mechanisms of A1-adenosine receptor inhibitors in cardiovascular diseases. METHODS AND RESULTS: Literature references were collected and sorted using relevant keywords and key phrases as search terms in scientific databases such as Web of Science, PubMed and Google Scholar. A1 adenosine receptor regulates free fatty acid metabolism, lipolysis, heart rate, blood pressure, and cardiovascular toxicity. The evidence clearly supporting the therapeutic potency of pharmacological A1 adenosine receptors agonists and antagonists in modulating cardiovascular risk factor parameters and treatment of cardiovascular diseases. CONCLUSION: This review summarizes the protective role of pharmacological A1-adenosine receptor regulators in the pathogenesis of cardiovascular diseases for a better management of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Antagonistas de Receptores Purinérgicos P1 , Humanos , Antagonistas de Receptores Purinérgicos P1/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Pressão Sanguínea , Adenosina , Receptores Purinérgicos P1
9.
Curr Mol Med ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38243923

RESUMO

Gastrointestinal (GI) cancer is one the most prevalent types of cancer. Despite current chemotherapy's success, patients with GI cancer continue to have a dismal outcome. The onset and progression of cancer are caused by alterations and the abnormal expression of several families of genes, like tumor-suppressor genes, oncogenes, and chemotherapy-resistant genes. The final purpose of tumor therapy is to inhibit cellular development by modifying mutations and editing the irregular expression of genes It has been reported that CDH1, TP53, KRAS, ARID1A, PTEN, and HLA-B are the commonly mutated genes in GI cancer. Gene editing has become one potential approach for cases with advanced or recurrent CRC, who are nonresponsive to conventional treatments and a variety of driver mutations along with progression cause GI progression. CRISPR/Cas9 technique is a reliable tool to edit the genome and understand the functions of mutations driving GI cancer development. CRISPR/Cas9 can be applied to genome therapy for GI cancers, particularly with reference to molecular-targeted medicines and suppressors. Moreover, it can be used as a therapeutic approach by knocking in/out multiple genes. The use of CRISPR/ Cas9 gene editing method for GI cancer therapy has therefore resulted in some improvements. There are several research works on the role of CRISPR/Cas9 in cancer treatment that are summarized in the following separate sections. Here, the use of CRISPR/Cas9-based genome editing in GI and the use of CRISPR/Cas9 is discussed in terms of Targeting Chemotherapy Resistance-related Genes like; KRAS, TP53, PTEN, and ARID1A.

10.
BMC Microbiol ; 24(1): 16, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183010

RESUMO

Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.


Assuntos
Microbiota , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Biomarcadores , Antibacterianos , Disbiose/terapia , Microambiente Tumoral
11.
Curr Cardiol Rev ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38204221

RESUMO

Despite extensive efforts to identify patients with cardiovascular disease (CVD) who could most benefit from the treatment approach, patients vary in their benefit from therapy and propensity for adverse drug events. Genetic variability in individual responses to drugs (pharmacogenetics) is considered an essential determinant in responding to a drug. Thus, understanding these pharmacogenomic relationships has led to a substantial focus on mechanisms of disease and drug response. In turn, understanding the genomic and molecular bases of variables that might be involved in drug response is the main step in personalized medicine. There is a growing body of data evaluating drug-gene interactions in recent years, some of which have led to FDA recommendations and detection of markers to predict drug responses (e.g., genetic variant in VKORC1 and CYP2C9 genes for prediction of drug response in warfarin treatment). Also, statins are widely prescribed drugs for the prevention of CVD. Atorvastatin, fluvastatin, rosuvastatin, simvastatin, and lovastatin are the most common statins used to manage dyslipidemia. This review provides an overview of the current knowledge on the pharmacogenetics of statins, which are being used to treat cardiovascular diseases.

12.
Curr Med Chem ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38275066

RESUMO

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide; however, there is not a convincing treatment for this disease. Limitations of conventional CRC therapies force scientists to develop novel treatment concepts for both primary care alongside adjuvant therapy. Photodynamic therapy (PDT) has been introduced as a promising therapeutic procedure for CRC mediated through theranostic principle in which special dyes, photosensitizers (PSs), are excited by near-infrared (NIR) and visible light. Recent studies showed that PDT has synergistic effects in combination with chemotherapy or immunotherapy in the treatment of CRC patients. Of note, nanoformulation of PS or immunotherapeutic agents could augment the PDT effectiveness. In this review, we summarize PDT application in CRC management with a special focus on the nanoparticles-based delivery system from the perspective of targeting deeper CRC and increased PDT efficiency, which could provide a desirable approach for clinical translation.

13.
Int J Pharm ; 652: 123839, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38266944

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model. METHODS: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests. RESULTS: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group. CONCLUSIONS: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice.


Assuntos
Antineoplásicos , Doenças do Sistema Nervoso Periférico , Ratos , Masculino , Animais , Cisplatino/toxicidade , Lipossomos , Acetona , Antineoplásicos/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/patologia , Polietilenoglicóis/efeitos adversos
14.
Artigo em Inglês | MEDLINE | ID: mdl-38284712

RESUMO

Exosomes are very small (nano-sized) vesicles participating in tumor development by involvement in intercellular communication mediated by transferring biocomponents. Exosomes appear to play vital roles in various cancer development, such as ovarian cancer, a common malignancy in women. Several hallmarks of ovarian cancer are reported to be affected by the exosome-- mediated cellular cross-talk, including modulating peritoneal dissemination and chemoresistance. Since the expression of some biomolecules, such as miRNAs and mRNA, is changed in ovarian cancer, these exo-biomolecules can be applied as prognostic, diagnostic, and therapeutic biomarkers. Also, the selective loading of specific chemotherapeutic agents into exosomes highlights these biocarries as potential delivery devices. Exosomes could be artificially provided and engineered to better target the site of interest in ovarian cancer. In the present review, we summarize the notable achievement of exosome application in ovarian cancer management to gain applicable transitional insight against this cancer.

15.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 899-911, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37530786

RESUMO

The study investigated the use of 5-fluorouracil-loaded ZnO nanocomposites (5-FU/Gd-ZnO NCs) as a potential treatment for cancer. 5-FU is a commonly used drug for cancer treatment but has undesirable side effects. The materials were characterized using various techniques, including PXRD, FTIR, FESEM, TEM, DLS, £-potential, and AFM. The data showed that the nanocomposites had a plate-like agglomeration with particle diameters ranging from 317.6 to 120.1 nm. The IC50 value of 5-FU-ZnO, which inhibits cell growth, was found to be 1.85 ppm. The effects of 5-FU-ZnO on inflammatory markers were also examined. While 5-FU increased the levels of TNF-a and IL-1b, the nanocomposites were able to reduce these levels. Additionally, the 5-FU/Gd-ZnO-NCs group showed an increase in thiol levels and a decrease in catalase and superoxide dismutase levels. Flow cytometry results showed that 5-FU, ZnO-NCs, and 5-FU/Gd-ZnO-NCs did not have any additive or synergistic effects on the suppression or eradication of cancer cells. In vivo, experiments showed that the 5-FU/Gd-ZnO NCs had similar necrotic characteristics and reduced fibrosis and collagen deposition compared to the free medication. The nanocomposites also exhibited higher antioxidative activity and lower inflammatory responses compared to the 5-FU group. It was shown that 5-FU/Gd-ZnO-NCs successfully inhibit cell proliferation. The in vivo results were comparable to those obtained with free 5-FU, suggesting the potential of these nanocomposites as therapeutic agents.


Assuntos
Neoplasias Colorretais , Nanocompostos , Óxido de Zinco , Humanos , Fluoruracila/farmacologia , Antioxidantes , Neoplasias Colorretais/tratamento farmacológico
16.
Cancer Genet ; 282-283: 14-26, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38157692

RESUMO

Gastric cancer (GC), ranking as the third deadliest cancer globally, faces challenges of late diagnosis and limited treatment efficacy. Long non-coding RNAs (lncRNAs) emerge as valuable treasured targets for cancer prognosis, diagnosis, and therapy, given their high specificity, convenient non-invasive detection in body fluids, and crucial roles in diverse physiological and pathological processes. Research indicates the significant involvement of lncRNAs in various aspects of GC pathogenesis, including initiation, metastasis, and recurrence, underscoring their potential as novel diagnostic and prognostic biomarkers, as well as therapeutic targets for GC. Despite existing challenges in the clinical application of lncRNAs in GC, the evolving landscape of lncRNA molecular biology holds promise for advancing the survival and treatment outcomes of gastric cancer patients. This review provides insights into recent studies on lncRNAs in gastric cancer, elucidating their molecular mechanisms and exploring the potential clinical applications in GC.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Prognóstico , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética
17.
Curr Drug Targets ; 24(17): 1335-1345, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053355

RESUMO

Pancreatic cancer (PC) is one the most lethal malignancies worldwide affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Transforming growth factor-beta (TGF-ß) is a multifunctional factor acting as both a tumor promoter in early cancer stages and a tumor suppressor in advanced disease. Programmed death-ligand 1 (PD-L1) is a ligand of programmed death-1 (PD-1), an immune checkpoint receptor, allowing tumor cells to avoid elimination by immune cells. Recently, targeting the TGF-ß signaling and PD-L1 pathways has emerged as a strategy for cancer therapy. In this review, we have summarized the current knowledge regarding these pathways and their contribution to tumor development with a focus on PC. Moreover, we have reviewed the role of TGF-ß and PD-L1 blockade in the treatment of various cancer types, including PC, and discussed the clinical trials evaluating TGF-ß and PD-L1 antagonists in PC patients.


Assuntos
Antígeno B7-H1 , Neoplasias Pancreáticas , Humanos , Fator de Crescimento Transformador beta/metabolismo , Ligantes , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Fatores de Crescimento Transformadores , Microambiente Tumoral
18.
Curr Pharm Des ; 29(34): 2692-2701, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37916491

RESUMO

Ovarian cancer (OC) is one of the most common malignancies in women and is associated with poor outcomes. The treatment for OC is often associated with resistance to therapies and hence this has stimulated the search for alternative therapeutic approaches, including RNA-based therapeutics. However, this approach has some challenges that include RNA degradation. To solve this critical issue, some novel delivery systems have been proposed. In current years, there has been growing interest in the improvement of RNAbased therapeutics as a promising approach to target ovarian cancer and improve patient outcomes. This paper provides a practical insight into the use of RNA-based therapeutics in ovarian cancers, highlighting their potential benefits, challenges, and current research progress. RNA-based therapeutics offer a novel and targeted approach to treat ovarian cancer by exploiting the unique characteristics of RNA molecules. By targeting key oncogenes or genes responsible for drug resistance, siRNAs can effectively inhibit tumor growth and sensitize cancer cells to conventional therapies. Furthermore, messenger RNA (mRNA) vaccines have emerged as a revolutionary tool in cancer immunotherapy. MRNA vaccines can be designed to encode tumor-specific antigens, stimulating the immune system to distinguish and eliminate ovarian cancer cells. A nano-based delivery platform improves the release of loaded RNAs to the target location and reduces the off-target effects. Additionally, off-target effects and immune responses triggered by RNA molecules necessitate careful design and optimization of these therapeutics. Several preclinical and clinical researches have shown promising results in the field of RNA-based therapeutics for ovarian cancer. In a preclinical study, siRNA-mediated silencing of the poly (ADP-ribose) polymerase 1 (PARP1) gene, involved in DNA repair, sensitized ovarian cancer cells to PARP inhibitors, leading to enhanced therapeutic efficacy. In clinical trials, mRNA-based vaccines targeting tumor-associated antigens have demonstrated safety and efficacy in stimulating immune responses in ovarian cancer patients. In aggregate, RNA-based therapeutics represent a promising avenue for the therapy of ovarian cancers. The ability to specifically target oncogenes or stimulate immune responses against tumor cells holds great potential for improving patient outcomes. However, further research is needed to address challenges related to delivery, permanence, and off-target effects. Clinical trials assessing the care and effectiveness of RNAbased therapeutics in larger patient cohorts are warranted. With continued advancements in the field, RNAbased therapeutics have the potential to develop the management of ovarian cancer and provide new hope for patients.


Assuntos
Neoplasias Ovarianas , Vacinas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , RNA Interferente Pequeno , Imunoterapia , RNA Mensageiro
19.
Biochem Genet ; 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37955843

RESUMO

One of the leading causes of mortality worldwide is cardiovascular disease, which is influenced by some variables, including calcium and vitamin D. This study aimed to assess the relationship between Angiopoietin-Like 3 (ANGPTL3) gene polymorphisms with vitamin D and calcium levels in cardiovascular disease (CVD) patients. In this research, 1002 people participated. Participants' anthropometric parameters, and FBG, calcium, and vitamin D were assessed. Blood samples were used to extract DNA. Taqman®-based polymerase chain reaction (PCR) was used to conduct genetic analysis for the rs10789117 and rs17458195. Statistical analysis was applied to determine differences across subgroups and the relationship between polymorphisms and disease. Age, body mass index (BMI), fasting Blood Sugar (FBG), phenylalanine ammonia-lyase (PAL), and smoking history were significantly correlated with CVD. Vitamin D was statistically associated with rs10789117 and rs17458195 in non-CVD individuals. In the moderate group, individuals with the C allele in rs10789117 showed a tenfold increase in vitamin D deficiency compared to those with the A allele. However, in rs11207997, individuals with the T allele had 5 to 6 times higher vitamin D deficiency than those with the C allele in all groups. This research demonstrates the relationship between some ANGPTL3 gene polymorphisms and complement levels in CVD patients. It may be concluded that individuals carrying these variants would likely benefit from using vitamin D and calcium supplements to avoid CVD.

20.
Curr Pharm Des ; 29(39): 3103-3122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37990429

RESUMO

Photodynamic therapy (PDT) is an innovative, non-invasive method of treating cancer that uses light-activated photosensitizers to create reactive oxygen species (ROS). However, challenges associated with the limited penetration depth of light and the need for precise control over photosensitizer activation have hindered its clinical translation. Nanomedicine, particularly gold nanobiostructures, offers promising solutions to overcome these limitations. This paper reviews the advancements in PDT and nanomedicine, focusing on applying antibody-modified gold nanobiostructures as multifunctional platforms for enhanced PDT efficacy and improved cancer treatment outcomes. The size, shape, and composition of gold nanobiostructures can significantly influence their PDT efficacy, making synthetic procedures crucial. Functionalizing the surface of gold nanobiostructures with various molecules, such as antibodies or targeting agents, bonding agents, PDT agents, photothermal therapy (PTT) agents, chemo-agents, immunotherapy agents, and imaging agents, allows composition modification. Integrating gold nanobiostructures with PDT holds immense potential for targeted cancer therapy. Antibody-modified gold nanobiostructures, in particular, have gained significant attention due to their tunable plasmonic characteristics, biocompatibility, and surface functionalization capabilities. These multifunctional nanosystems possess unique properties that enhance the efficacy of PDT, including improved light absorption, targeted delivery, and enhanced ROS generation. Passive and active targeting of gold nanobiostructures can enhance their localization near cancer cells, leading to efficient eradication of tumor tissues upon light irradiation. Future research and clinical studies will continue to explore the potential of gold nanobiostructures in PDT for personalized and effective cancer therapy. The synthesis, functionalization, and characterization of gold nanobiostructures, their interaction with light, and their impact on photosensitizers' photophysical and photochemical properties, are important areas of investigation. Strategies to enhance targeting efficiency and the evaluation of gold nanobiostructures in vitro and in vivo studies will further advance their application in PDT. The integrating antibody-modified gold nanobiostructures in PDT represents a promising strategy for targeted cancer therapy. These multifunctional nanosystems possess unique properties that enhance PDT efficacy, including improved light absorption, targeted delivery, and enhanced ROS generation. Continued research and development in this field will contribute to the advancement of personalized and effective cancer treatment approaches.


Assuntos
Nanopartículas Metálicas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Ouro/química , Espécies Reativas de Oxigênio , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Anticorpos/uso terapêutico , Linhagem Celular Tumoral
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