RESUMO
There has been a surge of interest in recent years in understanding the intricate mechanisms underlying cancer progression and treatment resistance. One molecule that has recently emerged in these mechanisms is MUC13 mucin, a transmembrane glycoprotein. Researchers have begun to unravel the molecular complexity of MUC13 and its impact on cancer biology. Studies have shown that MUC13 overexpression can disrupt normal cellular polarity, leading to the acquisition of malignant traits. Furthermore, MUC13 has been associated with increased cancer plasticity, allowing cells to undergo epithelial-mesenchymal transition (EMT) and metastasize. Notably, MUC13 has also been implicated in the development of chemoresistance, rendering cancer cells less responsive to traditional treatment options. Understanding the precise role of MUC13 in cellular plasticity, and chemoresistance could pave the way for the development of targeted therapies to combat cancer progression and enhance treatment efficacy.
Assuntos
Plasticidade Celular , Resistencia a Medicamentos Antineoplásicos , Mucinas , Neoplasias , Humanos , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Mucinas/metabolismo , Animais , Transição Epitelial-MesenquimalRESUMO
Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are gradually becoming a burden to society. The adverse effects and mortality/morbidity rates associated with these NDDs are a cause of many healthcare concerns. The pathologic alterations of NDDs are related to mitochondrial dysfunction, oxidative stress, and inflammation, which further stimulate the progression of NDDs. Recently, long non-coding RNAs (lncRNAs) have attracted ample attention as critical mediators in the pathology of NDDs. However, there is a significant gap in understanding the biological function, molecular mechanisms, and potential importance of lncRNAs in NDDs. This review documents the current research on lncRNAs and their implications in NDDs. We further summarize the potential implication of lncRNAs to serve as novel therapeutic targets and biomarkers for patients with NDDs.
Assuntos
Doença de Alzheimer , Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Doença de Parkinson , RNA Longo não Codificante , Humanos , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , RNA Longo não Codificante/genética , Doença de Parkinson/genética , Esclerose Lateral Amiotrófica/genéticaRESUMO
Exosomes are nanoscale vesicles generated by cells for intercellular communication. Due to their composition, significant research has been conducted to transform these particles into specific delivery systems for various disease states. In this review, we discuss the common isolation and loading methods of exosomes, some of the major roles of exosomes in the tumor microenvironment, as well as discuss recent applications of exosomes as drug delivery vessels and the resulting clinical implications.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Exossomos/metabolismo , Neoplasias/terapia , Exossomos/patologia , Exossomos/fisiologia , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologiaRESUMO
BACKGROUND: Protein kinase D1 (PKD1) is a serine-threonine kinase that regulates various functions within the cell. Herein, we report the significance of PKD1 expression in glucose metabolism resulting in pancreatic cancer (PanCa) progression and chemo-resistance. METHODS: PKD1 expression in PanCa was investigated by using immunohistochemistry. Functional and metabolic assays were utilised to analyse the effect of PKD1 expression/knockdown on associated cellular/molecular changes. RESULTS: PKD1 expression was detected in human pancreatic intraepithelial neoplasia lesions (MCS = 12.9; P < 0.0001) and pancreatic ductal adenocarcinoma samples (MCS = 15, P < 0.0001) as compared with faint or no expression in normal pancreatic tissues (MCS = 1.54; P < 0.0001). Our results determine that PKD1 enhances glucose metabolism in PanCa cells, by triggering enhanced tumorigenesis and chemo-resistance. We demonstrate that mTORC1 activation by PKD1 regulates metabolic alterations in PanCa cells. siRNA knockdown of Raptor or treatment with rapamycin inhibited PKD1-accelerated lactate production as well as glucose consumption in cells, which confirms the association of mTORC1 with PKD1-induced metabolic alterations. CONCLUSION: This study suggests a novel role of PKD1 as a key modulator of the glucose metabolism in PanCa cells accelerating tumorigenesis and chemo-resistance. The remodelling of PKD1-dysregulated glucose metabolism can be achieved by regulation of mTORC1 for development of novel therapeutic strategies.
Assuntos
Carcinoma in Situ/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Neoplasias Pancreáticas/metabolismo , Pancreatite Crônica/metabolismo , Proteína Quinase C/metabolismo , Carcinogênese/genética , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Técnicas de Silenciamento de Genes , Glucose/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/patologia , Proteína Quinase C/genética , Transdução de Sinais/genética , TransfecçãoRESUMO
The coronavirus disease 2019 (COVID-19) has dramatically challenged the healthcare system of almost all countries. The authorities are struggling to minimize the mortality along with ameliorating the economic downturn. Unfortunately, until now, there has been no promising medicine or vaccine available. Herein, we deliver perspectives of nanotechnology for increasing the specificity and sensitivity of current interventional platforms toward the urgent need of quickly deployable solutions. This review summarizes the recent involvement of nanotechnology from the development of a biosensor to fabrication of a multifunctional nanohybrid system for respiratory and deadly viruses, along with the recent interventions and current understanding about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Nanotecnologia/tendências , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Técnicas Biossensoriais , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pandemias , Tratamento Farmacológico da COVID-19RESUMO
The coronavirus disease 2019 (COVID-19) pandemic, an infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has led to more than 771,000 deaths worldwide. Tobacco smoking is a major known risk factor for severe illness and even death from many respiratory infections. The effects of smoking on COVID-19 are currently controversial. Here, we provide an overview of the current knowledge on the effects of smoking on the clinical manifestations, disease progression, inflammatory responses, immunopathogenesis, racial ethnic disparities, and incidence of COVID-19. This review also documents future directions of smoking related research in COVID-19. The current epidemiological finding suggests that active smoking is associated with an increased severity of disease and death in hospitalized COVID-19 patients. Smoking can upregulate the angiotensin-converting enzyme-2 (ACE-2) receptor utilized by SARS-CoV-2 to enter the host cell and activate a 'cytokine storm' which can lead to worsen outcomes in COVID-19 patients. This receptor can also act as a potential therapeutic target for COVID-19 and other infectious diseases. The COVID-19 pandemic sheds light on a legacy of inequalities regarding gender, racial, and ethnic health disparities associated with active smoking, thus, smoking cessation may help in improving outcomes. In addition, to flatten the COVID-19 curve, staying indoors, avoiding unnecessary social contact, and bolstering the immune defense system by maintaining a healthy diet/living are highly desirable.
Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Fumar/epidemiologia , COVID-19 , Humanos , PandemiasRESUMO
COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19.
Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Doença Hepática Induzida por Substâncias e Drogas , Suplementos Nutricionais , Pandemias , SARS-CoV-2 , Antivirais/efeitos adversos , Antivirais/uso terapêutico , COVID-19/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/dietoterapia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , HumanosRESUMO
Pancreatic cancer (PanCa) is a major cause of cancer-related death due to limited therapeutic options. As pancreatic tumors are highly desmoplastic, they prevent appropriate uptake of therapeutic payloads. Thus, our objective is to develop a next-generation nanoparticle system for treating PanCa. We generated a multi-layered Pluronic F127 and polyvinyl alcohol stabilized and poly-L-lysine coated paclitaxel loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PPNPs). This formulation exhibited optimal size (~160 nm) and negative Zeta potential (-6.02 mV), efficient lipid raft mediated internalization, pronounced inhibition in growth and metastasis in vitro, and in chemo-naïve and chemo-exposed orthotopic xenograft mouse models. Additionally, PPNPs altered nanomechanical properties of PanCa cells as suggested by the increased elastic modulus in nanoindentation analyses. Immunohistochemistry of orthotopic tumors demonstrated decreased expression of tumorigenic and metastasis associated proteins (ki67, vimentin and slug) in PPNPs treated mice. These results suggest that PPNPs represent a viable and robust platform for (PanCa).
Assuntos
Nanopartículas/química , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Endocitose , Humanos , Microdomínios da Membrana/metabolismo , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Paclitaxel/farmacologia , Neoplasias Pancreáticas/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Cancer progression and metastasis is profoundly influenced by protein kinase D1 (PKD1) and metastasis-associated protein 1 (MTA1) in addition to other pathways. However, the nature of regulatory relationship between the PKD1 and MTA1, and its resulting impact on cancer metastasis remains unknown. Here we present evidence to establish that PKD1 is an upstream regulatory kinase of MTA1. METHODS: Protein and mRNA expression of MTA1 in PKD1-overexpressing cells were determined using western blotting and reverse-transcription quantitative real-time PCR. Immunoprecipitation and proximity ligation assay (PLA) were used to determine the interaction between PKD1 and MTA1. PKD1-mediated nucleo-cytoplasmic export and polyubiquitin-dependent proteosomal degradation was determined using immunostaining. The correlation between PKD1 and MTA1 was determined using intra-tibial, subcutaneous xenograft, PTEN-knockout (PTEN-KO) and transgenic adenocarcinoma of mouse prostate (TRAMP) mouse models, as well as human cancer tissues. RESULTS: We found that MTA1 is a PKD1-interacting substrate, and that PKD1 phosphorylates MTA1, supports its nucleus-to-cytoplasmic redistribution and utilises its N-terminal and kinase domains to effectively inhibit the levels of MTA1 via polyubiquitin-dependent proteosomal degradation. PKD1-mediated downregulation of MTA1 was accompanied by a significant suppression of prostate cancer progression and metastasis in physiologically relevant spontaneous tumour models. Accordingly, progression of human prostate tumours to increased invasiveness was also accompanied by decreased and increased levels of PKD1 and MTA1, respectively. CONCLUSIONS: Overall, this study, for the first time, establishes that PKD1 is an upstream regulatory kinase of MTA1 status and its associated metastatic activity, and that the PKD1-MTA1 axis could be targeted for anti-cancer strategies.
Assuntos
Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Neoplasias da Próstata/patologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Técnicas de Inativação de Genes , Humanos , Células MCF-7 , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , PTEN Fosfo-Hidrolase/genética , Fosforilação , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , TransativadoresRESUMO
Tamoxifen administration enhanced overall disease-free survival and diminished mortality rates in cancer patients. However, patients with breast cancer often fail to respond for tamoxifen therapy due to the development of a drug-resistant phenotype. Functional analysis and molecular studies suggest that protein mutation and dysregulation of survival signaling molecules such as epidermal growth factor receptor, vascular endothelial growth factor receptor 2, and Akt contribute to tamoxifen resistance. Various strategies, including combinatorial therapies, show chemosensitize tamoxifen-resistant cancers. Based on chemotoxicity issues, researchers are actively investigating alternative therapeutic strategies. In the current study, we fabricate a mesoporous silica gold cluster nanodrug delivery system that displays exceptional tumor-targeting capability, thus promoting accretion of drug indices at the tumor site. We employ dual drugs, ZD6474, and epigallocatechin gallate (EGCG) that inhibit EGFR2, VEGFR2, and Akt signaling pathways since changes in these signaling pathways confer tamoxifen resistance in MCF 7 and T-47D cells. Mesoporous silica gold cluster nanodrug delivery of ZD6474 and EGCG sensitize tamoxifen-resistant cells to apoptosis. Western and immune-histochemical analyses confirmed the apoptotic inducing properties of the nanoformulation. Overall, results with these silica gold nanoclusters suggest that they may be a potent nanoformulation against chemoresistant cancers.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Engenharia Química , Receptores ErbB/metabolismo , Feminino , Ouro/química , Humanos , Nanopartículas Metálicas/química , Camundongos Nus , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Porosidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Dióxido de Silício/química , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. METHODS: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses. RESULTS: MUC13 expression was detected in 100% pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS = 5.8; AUC >0.8, P < 0.0001), 94.6% of pancreatic ductal adenocarcinoma (PDAC) samples (MCS = 9.7, P < 0.0001) as compared to low expression in tumor adjacent tissues (MCS = 4, P < 0.001) along with faint or no expression in normal pancreatic tissues (MCS = 0.8; AUC >0.8; P < 0.0001). Nuclear MUC13 expression positively correlated with nodal metastasis (P < 0.05), invasion of cancer to peripheral tissues (P < 0.5) and poor patient survival (P < 0.05; prognostic AUC = 0.9). Submicron scale mass density and artificial intelligence based algorithm analyses also elucidated association of MUC13 with greater morphological disorder (P < 0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and poor patient survival. CONCLUSION: This study provides significant information regarding MUC13 expression/subcellular localization in PanCa samples and supporting the use anti-MUC13 MAb for the development of PanCa diagnostic/prognostic test.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Mucinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Biomarcadores Tumorais/genética , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/secundário , Diferenciação Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Humanos , Imuno-Histoquímica , Metástase Linfática , Mucinas/genética , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Análise Serial de TecidosRESUMO
Cytochrome P450 (CYP) enzymes metabolize the majority of xenobiotics and are mainly found in hepatic and some extra-hepatic cells. However, their presence and functional role in exosomes, small extracellular vesicles that are secreted from various cells into extracellular fluids including plasma, is unknown. In this study, we analyzed the expression and biological activity of CYP enzymes in human plasma exosomes. First, we optimized isolation of plasma exosomes and characterized them for their physical properties and quality. The results showed that the purity of exosomes (<200 nm) improved upon prior filtration of plasma using a 0.22 micron filter. We then analyzed the relative level of exosomal CYP mRNAs, proteins, and enzyme activity. The results showed that the relative level of CYP enzymes in exosomes is higher than in plasma, suggesting their specific packaging in exosomes. Of the seven CYP enzymes tested, the mRNA of CYP1B1, CYP2A6, CYP2E1, and CYP3A4 were detectable in exosomes. Interestingly, the relative level of CYP2E1 mRNA was >500-fold higher than the other CYPs. The results from the Western blot showed detectable levels of CYP1A1, CYP1B1, CYP2A6, CYP2E1, and CYP3A4. Our results also demonstrated that exosomal CYP2E1 and CYP3A4 show appreciable activity relative to their respective positive controls (CYP-induced baculosomes). Our results also showed that CYP2E1 is expressed relatively higher in plasma exosomes than hepatic and monocytic cells and exosomes derived from these cells. In conclusion, this is the first evidence of the specific packaging and circulation of CYP enzymes, especially CYP2E1, in human plasma exosomes. The findings have biological and clinical significance in terms of their implications in cellular communications and potential use of plasma exosomal CYPs as biomarkers.
Assuntos
Proteínas Sanguíneas/metabolismo , Comunicação Celular/fisiologia , Citocromo P-450 CYP2E1/metabolismo , Sistema Enzimático do Citocromo P-450/sangue , Exossomos/enzimologia , Ativação Enzimática , HumanosRESUMO
The biomechanical properties of cells and tissues may be instrumental in increasing our understanding of cellular behavior and cellular manifestations of diseases such as cancer. Nanomechanical properties can offer clinical translation of therapies beyond what are currently employed. Nanomechanical properties, often measured by nanoindentation methods using atomic force microscopy, may identify morphological variations, cellular binding forces, and surface adhesion behaviors that efficiently differentiate normal cells and cancer cells. The aim of this review is to examine current research involving the general use of atomic force microscopy/nanoindentation in measuring cellular nanomechanics; various factors and instrumental conditions that influence the nanomechanical properties of cells; and implementation of nanoindentation methods to distinguish cancer cells from normal cells or tissues. Applying these fundamental nanomechanical properties to current discoveries in clinical treatment may result in greater efficiency in diagnosis, treatment, and prevention of cancer, which ultimately can change the lives of patients.
Assuntos
Nanotecnologia , Neoplasias/patologia , Humanos , Microscopia de Força Atômica , Neoplasias/diagnósticoRESUMO
Prostate cancer is the most common non-cutaneous malignancy in American men. Docetaxel is a useful chemotherapeutic agent for prostate cancer that has been available for over a decade, but the length of the treatment and systemic side effects hamper compliance. Additionally, docetaxel resistance invariably emerges, leading to disease relapse. Docetaxel resistance is either intrinsic or acquired by adopting various mechanisms that are highly associated with genetic alterations, decreased influx and increased efflux of drugs. Several combination therapies and small P-glycoprotein inhibitors have been proposed to improve the therapeutic potential of docetaxel in prostate cancer. Novel therapeutic strategies that may allow reversal of docetaxel resistance include alterations of enzymes, improving drug uptake and enhancement of apoptosis. In this review, we provide the most current docetaxel reversal approaches utilizing nanotechnology. Nanotechnology mediated docetaxel delivery is superior to existing therapeutic strategies and a more effective method to induce P-glycoprotein inhibition, enhance cellular uptake, maintain sustained drug release, and improve bioavailability.
Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Nanopartículas/uso terapêutico , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/terapia , Taxoides/uso terapêutico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Transporte Biológico , Docetaxel , Portadores de Fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Terapia de Alvo Molecular , Nanopartículas/química , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
The limitations of conventional therapeutic treatments prevailed in the development of nanotechnology-based medical formulations, termed nanomedicine. Nanomedicine is an advanced medicine that often consists of therapeutic agent(s) embedded in biodegradable or biocompatible nanomaterial-based formulations. Among nanomedicine approaches, tablet (oral) nanomedicine is still under development. In tabletized nanomedicine, the dynamic interplay between nanoformulations and the intricate milieu of the gastrointestinal tract simulates a pivotal role, particularly accentuating the influence exerted upon the luminal, mucosal, and epithelial cells. In this work, we document the perspectives and opportunities of nanoformulations toward the development of tabletized nanomedicine. This review also unveils the notion of integrating nanomedicine within a tablet formulation, which facilitates the controlled release of drugs, biomolecules, and agent(s) from the formulation to achieve a better therapeutic response. Finally, an attempt was made to explore current trends in nanomedicine technology such as bacteriophage, probiotic, and oligonucleotide tabletized nanomedicine and the combination of nanomedicine with imaging agents, i.e., nanotheranostics.
Assuntos
Nanomedicina , Humanos , Comprimidos/química , Sistemas de Liberação de MedicamentosRESUMO
Cancer stands as the second leading cause of death in the United States (US). Most chemotherapeutic agents exhibit severe adverse effects that are attributed to exposure of drugs to off-target tissues, posing a significant challenge in cancer therapy management. In recent years, inulin, a naturally occurring prebiotic fiber has gained substantial attention for its potential in cancer treatment owing to its multitudinous health values. Its distinctive structure, stability, and nutritional properties position it as an effective adjuvant and carrier for drug delivery in cancer therapy. To address some of the above unmet clinical issues, this review summarizes the recent efforts towards the development of inulin-based nanomaterials and nanocomposites for healthcare applications with special emphasis on the multifunctional role of inulin in cancer therapy as a synergist, signaling molecule, immunomodulatory and anticarcinogenic molecule. Furthermore, the review provides a concise overview of ongoing clinical trials and observational studies associated with inulin-based therapy. In conclusion, the current review offers insights on the significant role of inulin interventions in exploring its potential as a therapeutic agent to treat cancer.
Assuntos
Inulina , Neoplasias , Humanos , Inulina/uso terapêutico , Inulina/química , Prebióticos , Preparações Farmacêuticas , Neoplasias/tratamento farmacológico , Sistemas de Liberação de MedicamentosRESUMO
Ovarian cancer stands as the deadliest gynecologic malignancy, responsible for nearly 65% of all gynecologic cancer-related deaths. The challenges in early detection and diagnosis, coupled with the widespread intraperitoneal spread of cancer cells and resistance to chemotherapy, contribute significantly to the high mortality rate of this disease. Due to the absence of specific symptoms and the lack of effective screening methods, most ovarian cancer cases are diagnosed at advanced stages. While chemotherapy is a common treatment, it often leads to tumor recurrence, necessitating further interventions. In recent years, antibody-drug conjugates (ADCs) have emerged as a valuable tool in targeted cancer therapy. These complex biotherapeutics combine an antibody that specifically targets tumor specific/associated antigen(s) with a high potency anti-cancer drug through a linker, offering a promising approach for ovarian cancer treatment. The identification of molecular targets in various human tumors has paved the way for the development of targeted therapies, with ADCs being at the forefront of this innovation. By delivering cytotoxic agents directly to tumors and metastatic lesions, ADCs show potential in managing chemo-resistant ovarian cancers. Mucins such as MUC16, MUC13, and MUC1 have shown significantly higher expression in ovarian tumors as compared to normal and/or benign samples, thus have become promising targets for ADC generation. While traditional markers are limited by their elevated levels in non-cancerous conditions, mucins offer a new possibility for targeted treatment in ovarian cancer. This review comprehensively described the potential of mucins for the generation of ADC therapy, highlighting their importance in the quest to improve the outcome of ovarian cancer patients.
Assuntos
Imunoconjugados , Mucinas , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Mucinas/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , AnimaisRESUMO
BACKGROUND: The trends of pancreatic cancer (PanCa) incidence and mortality are on rising pattern, and it will be a second leading cause of cancer related deaths by 2030. Pancreatic ductal adenocarcinoma (PDAC), major form of PanCa, exhibits a grim prognosis as mortality rate is very close to the incidence rate, due to lack of early detection methods and effective therapeutic regimen. Considering this alarming unmet clinic need, our team has identified a novel oncogenic protein, carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7), that can be useful for spotting early events of PDAC. METHODOLOGY: This study includes bioinformatics pre-screening using publicly available cancer databases followed by molecular biology techniques in PDAC progressive cell line panel and human tissues to evaluate CEACAM7 expression in early events of pancreatic cancer. RESULTS: PanCa gene and protein expression analysis demonstrated the significantly higher expression of CEACAM7 in PDAC, compared to other cancers and normal pancreas. Overall survival analysis demonstrated an association between the higher expression of CEACAM7 and poor patients' prognosis with high hazard ratio. Additionally, in a performance comparison analysis CEACAM7 outperformed S100A4 in relation to PDAC. We also observed an increase of CEACAM7 in PDAC cell line panel model. However, poorly differentiated, and normal cell lines did not show any expression. Human tissue analysis also strengthened our data by showing strong and positive IHC staining in early-stage tumors. CONCLUSION: Our observations clearly cite that CEACAM7 can serve as a potential early diagnostic and/or prognostic marker of PDAC and may also potentiate the sensitivity of the existing biomarker panel of PDAC. However, further studies are warranted to determine its clinical significance.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Prognóstico , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Antígeno Carcinoembrionário , Proteínas Ligadas por GPI/genéticaRESUMO
The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.