Background: The clinicopathological parameters such as residual tumor, grade, the International Federation of Gynecology and Obstetrics (FIGO) score are often used to predict the survival of ovarian cancer patients, but the 5-year survival of high grade serous ovarian cancer (HGSOC) still remains around 30%. Hence, the relentless pursuit of enhanced prognostic tools for HGSOC, this study introduces an unprecedented gene expression-based molecular prognostic score (mPS). Derived from a novel 20-gene signature through Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression, the mPS stands out for its predictive prowess.
View Article and Find Full Text PDFIndia had witnessed unprecedented surge in SARS-CoV-2 infections and its dire consequences during the second wave of COVID-19, but the detailed report of the epidemiological based spatiotemporal incidences of the disease is missing. In the manuscript, we have applied various statistical approaches (correlation, hierarchical clustering) to decipher the pattern of pathogenesis of the circulating VoCs responsible for surge in the incidences. B.
View Article and Find Full Text PDFPurpose: The emergence of highly mutated and transmissible BA variants has caused an unprecedented surge in COVID-19 infections worldwide. Thorough analysis of its genome structure and phylogenomic evolutionary details will serve as scientific reference for future research.
Method: Here, we have analyzed the BA variants from India using whole-genome sequencing, spike protein mutation study, spatio-temporal surveillance, phylogenomic assessment and epitope mapping.
An aptamer is a short sequence of synthetic oligonucleotides which bind to their cognate target, specifically while maintaining similar or higher sensitivity compared to an antibody. The in-vitro selection of an aptamer, applying a conjoining approach of chemistry and molecular biology, is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are further modified chemically in an attempt to make them stable in biofluid, avoiding nuclease digestion and renal clearance.
View Article and Find Full Text PDFOver the last few years, the Transforming growth factor- β (TGF-β) has been significantly considered as an effective and ubiquitous mediator of cell growth. The cytokine, TGF-β is being increasingly recognized as the most potent inducer of cancer cell initiation, differentiation, migration as well as progression through both the SMAD-dependent and independent pathways. There is growing evidence that supports the role of secretory cytokine TGF-β as a crucial mediator of tumor-stroma crosstalk.
View Article and Find Full Text PDFThe majority of ovarian cancer patients are diagnosed in late stages of the disease, in which the tumor cells have leaked into the peritoneum and are present as tumorspheres. These tumorspheres are rich in cancer stem-like cells (CSCs), which are resistant to therapy and are a major source of relapse. The purpose of this research was to identify a safe therapeutic approach that could eradicate the peritoneal CSC-rich tumorspheres and inhibit relapse.
View Article and Find Full Text PDFTamoxifen 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.
View Article and Find Full Text PDFThe therapeutic index of poorly water-soluble drugs is often hampered due to poor pharmacokinetics, reduced blood retention, and lack of effective drug concentrations in the tumor region. In order to overcome these issues, drugs are often delivered by use of delivery vehicles to provide an enhanced therapeutic index. Gold nanoparticles synthesized in micellar networks of amphiphilic block copolymer (AuNM) provide an efficient nanocarrier for tissue- and site-specific drug delivery owing to their low cytotoxicity and immunogenicity.
View Article and Find Full Text PDFThe use of enzyme/prodrug system has gained attention because it could help improve the efficacy and safety of conventional cancer chemotherapies. In this approach, cancer cells are first transfected with a gene that can express an enzyme with ability to convert a non-toxic prodrug into its active cytotoxic form. As a result, the activated prodrug could kill the transfected cancer cells.
View Article and Find Full Text PDFCancer-selective viral replication and delivery of a therapeutic immunomodulating, cancer-selective killing cytokine () by means of a new () combined with a small molecule BH3 mimetic holds promise for treating both primary and metastatic hormone refractory prostate cancer (CaP).
View Article and Find Full Text PDFAbrus agglutinin (AGG), a plant lectin isolated from the seeds of Abrus precatorius, has documented antitumor and immunostimulatory effects in murine models. To examine possible antitumor activity against breast cancer, we established human breast tumor xenografts in athymic nude mice and intraperitoneally administered AGG. AGG inhibited tumor growth and angiogenesis as confirmed by monitoring the expression of Ki-67 and CD-31, respectively.
View Article and Find Full Text PDFAkt overexpression in cancer causes resistance to traditional chemotherapeutics. Silencing Akt through siRNA provides new therapeutic options; however, poor in vivo siRNA pharmacokinetics impede translation. We demonstrate that acidic milieu-sensitive multilamellar gold niosomes (Nio-Au) permit targeted delivery of both Akt-siRNA and thymoquinone (TQ) in tamoxifen-resistant and Akt-overexpressing MCF7 breast cancer cells.
View Article and Find Full Text PDFBackground: Squamous cell carcinoma of the oral cavity (SCCOC) is the dominant origin of cancer associated mortality. Previous findings by our study reported that acquisition of anoikis resistance has a significant role in tumor progression of oral cavity. Several genes were over-expressed in anoikis-resistant cells under detached conditions which we confirmed earlier by microarray.
View Article and Find Full Text PDFLow pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo.
View Article and Find Full Text PDFImproved treatments for pancreatic cancer remain a clinical imperative. Sabutoclax, a small-molecule BH3 mimetic, inhibits the function of antiapoptotic Bcl-2 proteins. Minocycline, a synthetic tetracycline, displays antitumor activity.
View Article and Find Full Text PDFDespite recent advances, treatment options for advanced prostate cancer (CaP) remain limited. We are pioneering approaches to treat advanced CaP that employ conditionally replication-competent oncolytic adenoviruses that simultaneously produce a systemically active cancer-specific therapeutic cytokine, mda-7/IL-24, Cancer Terminator Viruses (CTV). A truncated version of the CCN1/CYR61 gene promoter, tCCN1-Prom, was more active than progression elevated gene-3 promoter (PEG-Prom) in regulating transformation-selective transgene expression in CaP and oncogene-transformed rat embryo cells.
View Article and Find Full Text PDFSingle drug therapies for cancer are often suboptimal and may not provide long term clinical benefits. To overcome this obstacle for effective treatment the applications of two or more drugs are preferable. A limitation of multidrug use is the varying pharmacokinetics of different drugs.
View Article and Find Full Text PDFPancreatic cancer is an aggressive disease with limited therapeutic options. Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), a potent antitumor cytokine, shows cancer-specific toxicity in a vast array of human cancers, inducing endoplasmic reticulum stress and apoptosis, toxic autophagy, an antitumor immune response, an antiangiogenic effect, and a significant "bystander" anticancer effect that leads to enhanced production of this cytokine through autocrine and paracrine loops. Unfortunately, mda-7/IL-24 application in pancreatic cancer has been restricted because of a "translational block" occurring after Ad.
View Article and Find Full Text PDFMolecular-genetic imaging of cancer using nonviral delivery systems has great potential for clinical application as a safe, efficient, noninvasive tool for visualization of various cellular processes including detection of cancer, and its attendant metastases. In recent years, significant effort has been expended in overcoming technical hurdles to enable clinical adoption of molecular-genetic imaging. This chapter will provide an introduction to the components of molecular-genetic imaging and recent advances on each component leading to safe, efficient clinical applications for detecting cancer.
View Article and Find Full Text PDFWe describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through a systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single-photon emission computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity.
View Article and Find Full Text PDFSubtraction hybridization combined with induction of cancer cell terminal differentiation in human melanoma cells identified melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) and SARI (suppressor of AP-1, induced by IFN) that display potent antitumor activity. These genes are not constitutively expressed in cancer cells and forced expression of mda-7/IL-24 (Ad.mda-7) or SARI (Ad.
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