169 research outputs found
Mucins in ovarian cancer diagnosis and therapy
Ovarian cancer is the most lethal gynecologic malignancy and the five-year survival rate is only 35% after diagnosis. Epithelial ovarian cancer is a highly metastatic disease characterized by widespread peritoneal dissemination and ascites. The death incidences from ovarian cancer could be significantly lowered by developing new methods for the early diagnosis and treatment of this fatal disease. Several potential markers have been identified recently. However, mucins are the most promising markers for ovarian cancer diagnosis. Mucins are large extracellular, heavily glycosylated proteins and their aberrant expression has been implicated in the pathogenesis of a variety of cancers, including ovarian cancer. This review will summarize known facts about the pathological and molecular characteristics of ovarian cancer, the current status of ovarian cancer markers, as well as general information about mucins, the putative role of mucins in the progression of ovarian cancer and their potential use for the early diagnosis and treatment of this disease
Curcumin nanoformulations: a future nanomedicine for cancer
Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion, apoptosis and cell death, revealing its anticancer potential. In this review, we focus on the design and development of nanoparticles, self-assemblies, nanogels, liposomes and complex fabrication for sustained and efficient curcumin delivery. We also discuss the anticancer applications and clinical benefits of nanocurcumin formulations. Only a few novel multifunctional and composite nanosystem strategies offer simultaneous therapy as well as imaging characteristics. We also summarize the challenges to developing curcumin delivery platforms and up-to-date solutions for improving curcumin bioavailability and anticancer potential for therapy
Scope of nanotechnology in ovarian cancer therapeutics
This review describes the use of polymer micelle nanotechnology based chemotherapies for ovarian cancer. While various chemotherapeutic agents can be utilized to improve the survival rate of patients with ovarian cancer, their distribution throughout the entire body results in high normal organ toxicity. Polymer micelle nanotechnology aims to improve the therapeutic efficacy of anti-cancer drugs while minimizing the side effects. Herein, different types of polymer micelle technology based nanotherapies such as PLGA, polymerosomes, acid cleavable, thermosensitive, pH sensitive, and cross-linked micelles are introduced and structural differences are explained. Additionally, production methods, stability, sustainability, drug incorporation and drug release profiles of various polymer micelle based nanoformulations are discussed. An important feature of polymer micelle nanotechnology is the small size (10-100 nm) of particles which improves circulation and enables superior accumulation of the therapeutic drugs at the tumor sites. This review provides a comprehensive evaluation of different types of polymer micelles and their implications in ovarian cancer therapeutics
Curcumin Attenuates β-catenin Signaling in Prostate Cancer Cells through Activation of Protein Kinase D1
Prostate cancer is the most commonly diagnosed cancer affecting 1 in 6 males in the US. Understanding the molecular basis of prostate cancer progression can serve as a tool for early diagnosis and development of novel treatment strategies for this disease. Protein Kinase D1 (PKD1) is a multifunctional kinase that is highly expressed in normal prostate. The decreased expression of PKD1 has been associated with the progression of prostate cancer. Therefore, synthetic or natural products that regulate this signaling pathway can serve as novel therapeutic modalities for prostate cancer prevention and treatment. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular pathways. Herein, we have demonstrated that curcumin activates PKD1, resulting in changes in β-catenin signaling by inhibiting nuclear β-catenin transcription activity and enhancing the levels of membrane β-catenin in prostate cancer cells. Modulation of these cellular events by curcumin correlated with decreased cell proliferation, colony formation and cell motility and enhanced cell-cell aggregation in prostate cancer cells. In addition, we have also revealed that inhibition of cell motility by curcumin is mediated by decreasing the levels of active cofilin, a downstream target of PKD1. The potent anti-cancer effects of curcumin in vitro were also reflected in a prostate cancer xenograft mouse model. The in vivo inhibition of tumor growth also correlated with enhanced membrane localization of β-catenin. Overall, our findings herein have revealed a novel molecular mechanism of curcumin action via the activation of PKD1 in prostate cancer cells
Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics
The United State Food and Drug Administration has permitted number of therapeutic agents for cancer treatment. Most of them are expensive and have some degree of systemic toxicity which makes overbearing in clinical settings. Although advanced research continuously applied in cancer therapeutics, but drug resistance, metastasis, and recurrence remain unanswerable These accounts to an urgent clinical need to discover natural compounds with precisely safe and highly efficient for the cancer prevention and cancer therapy. Gambogic acid (GA) is the principle bioactive and caged xanthone component, a brownish gamboge resin secreted from the of Garcinia hanburyi tree. This molecule showed a spectrum of biological and clinical benefits against various cancers. In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent. This review also delineates specific molecular mechanism(s) of GA that are involved in anti-cancer, anti-metastasis, anti-angiogenesis, and chemo-/radiation sensitizer activities. Furthermore, recent evidence, development, and implementation of various nanoformulations of gambogic acid (nanomedicine) have been described
Engineered Exosomes for the Multimodal Imaging Directed Photo-Immunotherapy of Colorectal Cancer
Background: Rio Grande Valley experience severe cancer health disparity. A novel therapeutic modality may serve as better therapeutic option. Nanohybrids endowed with multifunctionality, longer circulation time, large surface area have emerged as an active preference for cancer research. However, rising concern of nanomaterials toxicity and scalability issues has slowed their translation to clinics. Exosomes (Exo) are endogenous endocytic origin 40-100 nm vesicles found in various body fluids, which in comparison to synthetic nanoparticles, are biodegradable, highly biocompatible as well as immunocompatible in nature. Although bulk isolation of exosomes from human body fluids is still a problem and engineering of exosomes to harness its potential is still in infancy.
Methods: The Exo were isolated from dairy milk using EDTA precipitation method, and superparamagnetic iron oxide nanoparticles (MNPs) were synthesized by ammonium hydroxide co-precipitation method. The Exo were sonicated (60 sec) with MNPs and near-infrared (NIR) light-absorbing dye indocyanine green (ICG) and then incubated overnight at 37 oC. The characterization of ICG@Exo-MNPs was done using several techniques. The targeting nature of ICG@Exo-MNPs was determined on colorectal cancer cells SW480 and SW680. The phototransduction and in-vitro photothermal therapy were performed using 1W, 808 nm NIR laser.
Results: The ICG@Exo-MNPs nanohybrid found to have size around 100 nm with good dispersity. The coating of exosomes and magnetic field actuation increased the targeting efficacy of ICG@Exo-MNPs in colorectal cancer cells by 10% in SW40 and 30% in SW680. ICG@Exo-MNPs killed the SW480 cells to more than 80% within 2 min. of NIR light irradiation.
Conclusions: This study shows enhanced photothermal therapeutic behavior of ICG@Exo-MNPs for near-infrared fluorescence imaging directing killing of colorectal cancer cells
Biomolecule-functionalized nanoformulations for prostate cancer theranostics
Background Even with the advancement in the areas of cancer nanotechnology, prostate cancer still poses a major threat to men’s health. Nanomaterials and nanomaterial-derived theranostic systems have been explored for diagnosis, imaging, and therapy for different types of cancer still, for prostate cancer they have not delivered at full potential because of the limitations like in vivo biocompatibility, immune responses, precise targetability, and therapeutic outcome associated with the nanostructured system. Aim of Review Functionalizing nanomaterials with different biomolecules and bioactive agents provides advantages specificity towards cancerous tumors, improved circulation time, and modulation of the immune response leading to early diagnosis and targeted delivery of cargo at the site of action.
Key Scientific Concepts of Review In this review, we have emphasized the classification and comparison of various nanomaterials based on biofunctionalization strategy and source of biomolecules such that it can be used for possible translation in clinical settings and future developments. This review highlighted the opportunities for embedding highly specific biological targeting moieties (antibody, aptamer, oligonucleotides, biopolymer, peptides, etc.) on nanoparticles which can improve the detection of prostate cancer-associated biomarkers at a very low limit of detection, direct visualization of prostate tumors and lastly for its therapy. Lastly, special emphasis was given to biomimetic nanomaterials which include functionalization with extracellular vesicles, exosomes and viral particles and their application for prostate cancer early detection and drug delivery. The present review paves a new pathway for next-generation biofunctionalized nanomaterials for prostate cancer theranostic application and their possibility in clinical translation
miR-205: A Potential Biomedicine for Cancer Therapy
microRNAs (miRNAs) are a class of small non-coding RNAs that regulate the expression of their target mRNAs post transcriptionally. miRNAs are known to regulate not just a gene but the whole gene network (signaling pathways). Accumulating evidence(s) suggests that miRNAs can work either as oncogenes or tumor suppressors, but some miRNAs have a dual nature since they can act as both. miRNA 205 (miR-205) is one such highly conserved miRNA that can act as both, oncomiRNA and tumor suppressor. However, most reports confirm its emerging role as a tumor suppressor in many cancers. This review focuses on the downregulated expression of miR-205 and discusses its dysregulation in breast, prostate, skin, liver, gliomas, pancreatic, colorectal and renal cancers. This review also confers its role in tumor initiation, progression, cell proliferation, epithelial to mesenchymal transition, and tumor metastasis. Restoration of miR-205 makes cells more sensitive to drug treatments and mitigates drug resistance. Additionally, the importance of miR-205 in chemosensitization and its utilization as potential biomedicine and nanotherapy is described. Together, this review research article sheds a light on its application as a diagnostic and therapeutic marker, and as a biomedicine in cancer
Developing an assay for easy and rapid detection of ALS biomarker(s): A Hypothesis
Background: Death of motor neurons is the key pathology underlying neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Biomarkers are chemical changes in the biological fluids. Biomarkers serving as a diagnostic tool should be specific to the concerned disease. Biomarkers indicating disease progression should be very sensitive to demonstrate changes during the disease process as well as therapeutics development. Biomarkers proposed for ALS include poly (GP) repeats in C9orf72, neurofilaments, miRNAs, glutathione and 4HNE in CSF, SOD1/TDP43 protein, poly (GP) repeats in C9orf72, neurofilaments, T regulatory cells, CRP, chitotriosidase, creatinine, creatinine kinase, miRNAs, glutamate, albumin, uric acid, glutathione, ferritin, 3-nitrotyrosine and 4HNE in blood, p75ECD, F2-isoprostane, collagen type 4, lucosylgalactosyl hydroxylysine, neoptrin and 8hydroxy-2`-deoxyguanosine in urine. Our hypothesis is to develop a kit-based assay for detection of ALS. Lateral flow immunoassays are one of the rapid, point-of-care diagnostic tests enabling high sensitivity and multiplexing.
Methods: Leftover biological samples of ALS/Non-ALS individuals can be obtained from the clinics, age group 40-90. The samples can be evaluated for the expression of biomarkers and the levels can be compared between ALS and Non-ALS individuals. Using this preliminary data, kit-based assay can be developed that might be based on lateral flow principle.
Result: The assay developed should be chromogenic and the intensity of chromogen should indicate the disease severity when compared to the reference.
Conclusion: Development of a successful kit-based assay will enable its rapid and easy detection and establish a new milestone in the field of ALS
Antibody Mediated Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer
About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in cancers, except pancreatic cancer due to their characteristic fibrotic tumor microenvironment. The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. This makes MUC13 as an excellent protein for specifically targeting pancreatic tumors. In this project, we demonstrate a unique ability of our in-house generated mouse and humanized monoclonal antibody of MUC13 to penetrate and target pancreatic cancer. These antibodies have been conjugated with our recently developed novel patented superparamagnetic iron oxide nanoparticles (SPIONS). The aim of our study is to deliver stroma targeting drugs efficiently to pancreatic tumors that would soften the tumors to improve the response of checkpoint immunotherapies. The stroma targeting drugs used are curcumin and AMD3100, which are both in clinical trials for human use. This study is unique as it will utilize MUC13 antibodies for targeting the pancreatic tumor site and SPION nanoparticle system for delivering the stroma depleting drugs, which would help in improving immunotherapy response. Our results demonstrate that our MUC13 antibody conjugated SPIONS can efficiently internalize the PDAC cells. SPION-MUC13 using Indocyanine dye (ICG) specifically reached to the tumor site in an orthotopic pancreatic cancer model as indicated by ICG fluorescence. MUC13-SPION formulation led to an enhanced uptake in MUC13 positive (MUC13+) PanCa cells, compared with MUC13 null (MUC13-) cells as demonstrated by immunofluorescence, Prussian blue staining and flow cytometry experiments. Interestingly, the formulation resulted in sustained delivery of curcumin (CUR), enhanced inhibition of cell proliferation, migration and invasion in MUC13+ cells as compared with MUC13- cells, which suggests the targeting efficacy of the formulation. Additionally, the treatment of cells with the formulation inhibited the tumor spheroid formation and growth. The formulation softens up the tumors for therapies that can result in improved response to checkpoint immunotherapies. Therefore, this study indicates high significance of MUC13-SPIONS for achieving pancreatic tumor specific delivery of drugs. Efficient MUC13 conjugated SPION-CUR can potentiate checkpoint immunotherapies, inhibit tumor growth and its progression, which will be conducted in continuation in a pancreatic orthotopic mice model. This study has a potential to reduce morbidity and mortality caused by the disease and improve survival in patients
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