c-Met Antisense Oligodeoxynucleotides as a Novel Therapeutic Agent for Glioma: In Vitro and In Vivo Studies of Uptake, Effects, and Toxicity

Pomegranate (Punica granatum L.) is one of the oldest edible fruits in the Mediterranean area and has been used extensively in the folk medicine. Popularity of pomegranate has increased especially in the last decade because of the health effects of the fruit. Polyphenols, represent the predominant class of phytochemicals of pomegranate, mainly consisting of hydrolysable tannins and ellagic acid. Pomegranate is a rich source of the ellagitannin punicalagin, which has aroused considerable interest in pomegranate fruit as a new therapeutic agent in recent years. Most studies on the effects of pomegranate juice have focused on its ability to cure diabetes and atherosclerosis. The present review summarizes some recent studies on the vasculoprotective and neuroprotective effect of various parts of pomegranate and its main compounds especially hydrolysable tannins ellagitannins, ellagic acid and their metabolites. The in vitro and in vivo studies, showed that the whole parts of pomegranate as well as its main components had a positive influence on blood glucose, lipid levels, oxidation stress and neuro/inflammatory biomarkers. They could be used as a future therapeutic agent towards several vascular and neurodegenerative disorders such as hypertension, coronary heart disease and Alzheimer.

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Valeriana jatamansi Constituent IVHD-valtrate As a Novel Therapeutic Agent to Human Ovarian Cancer: in vitro and in vivo Activities and Mechanisms

Current Cancer Drug Targets ◽

10.2174/1568009611313040009 ◽

2013 ◽

Vol 13 (4) ◽

pp. 472-483 ◽

Cited By ~ 16

Author(s):

Xiaoguang Li ◽

Tao Chen ◽

Sheng Lin ◽

Jing Zhao ◽

Peizhan Chen ◽

...

Keyword(s):

Ovarian Cancer ◽

Therapeutic Agent ◽

Human Ovarian Cancer ◽

Valeriana Jatamansi ◽

Novel Therapeutic

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CSIG-29. TRIBBLES-1 (TRIB1) INCREASES TUMOR FORMATION IN AN ORTHOTOPIC MOUSE MODELS BY PROMOTING SURVIVAL OF GBM CELLS AND TREATMENT RESISTANCE

Neuro-Oncology ◽

10.1093/neuonc/noab196.155 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi39-vi39

Author(s):

Karnika Singh ◽

Chunhua Han ◽

Jessica Fleming ◽

Joseph McElroy ◽

Ashok Kumar ◽

...

Keyword(s):

Overall Survival ◽

Cell Lines ◽

Tumor Volume ◽

Tumor Model ◽

Tumor Formation ◽

In Vivo Studies ◽

Oncogenic Signaling ◽

Novel Therapeutic

Abstract INTRODUCTION Glioblastoma (GBM) is the most aggressive CNS tumor with an average survival of about 15 months after diagnosis. The current gold standard therapy comprises radiation therapy (RT) and concurrent and adjuvant temozolamide (TMZ). Due to poor prognosis, novel therapeutic targets need to be identified for drug development. To this end, we identified TRIB1 through correlative studies using patient derived methylation data from an institutional cohort as a novel therapeutic target. TRIB1 is a Ser/Thr pseudokinase that functions as a scaffold for the degradation of its substrates and activates Akt and MEK oncogenic pathways. In this study, we show that TRIB1 promoted GBM progression by upregulating survival pathways and reducing RT/TMZ-induced cell death. MATERIALS AND METHODS In vitro functional validation was performed by overexpression and knockdown approaches. GBM patient derived (PDX) cell lines overexpressing the TRIB1 transgene were used to create an orthotopic tumor model for in vivo studies. Mice were monitored for changes in tumor volume and overall survival. Stable cell lines were generated by puromycin selection. Western blotting was utilized to detect protein levels. RESULTS Mice inoculated with PDX cells overexpressing TRIB1 transgene had increased tumor volume and worse overall survival compared to the empty vector control. We also observed that TRIB1 overexpression caused decreased apoptosis of PDX cell lines after RT/TMZ treatment. Additionally, an increase in the phosphorylation of ERK and Akt was also noted after TRIB1 overexpression. Consistent with these observations, TRIB1 knockdown sensitized the cells towards radiation and caused decreased Akt phosphorylation/activation as well. CONCLUSION TRIB1 overexpression decreases overall survival of xenograft bearing mice and promotes GBM cell survival by upregulating survival signaling pathways. This compromises the effects of RT/TMZ therapy, which is reversed after TRIB1 knockdown. Targeting of TRIB1 may reduce oncogenic signaling in GBM cells and therefore would sensitize them towards RT/TMZ therapy.

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Synthetic miR-34a Mimics as a Novel Therapeutic Agent for Multiple Myeloma: In Vitro and In Vivo Evidence

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-12-1708 ◽

2012 ◽

Vol 18 (22) ◽

pp. 6260-6270 ◽

Cited By ~ 149

Author(s):

Maria T. Di Martino ◽

Emanuela Leone ◽

Nicola Amodio ◽

Umberto Foresta ◽

Marta Lionetti ◽

...

Keyword(s):

Multiple Myeloma ◽

Therapeutic Agent ◽

Novel Therapeutic

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Oncolytic Vaccinia Virus Expressing Aphrocallistes vastus Lectin as a Cancer Therapeutic Agent

Marine Drugs ◽

10.3390/md17060363 ◽

2019 ◽

Vol 17 (6) ◽

pp. 363 ◽

Cited By ~ 1

Author(s):

Tao Wu ◽

Yulin Xiang ◽

Tingting Liu ◽

Xue Wang ◽

Xiaoyuan Ren ◽

...

Keyword(s):

Vaccinia Virus ◽

Intracellular Signaling ◽

Therapeutic Agent ◽

In Vivo Studies ◽

Antitumor Activities ◽

Gene Encoding ◽

Vaccinia Virus Vector ◽

Erk Activity

Lectins display a variety of biological functions including insecticidal, antimicrobial, as well as antitumor activities. In this report, a gene encoding Aphrocallistes vastus lectin (AVL), a C-type lectin, was inserted into an oncolytic vaccinia virus vector (oncoVV) to form a recombinant virus oncoVV-AVL, which showed significant in vitro antiproliferative activity in a variety of cancer cell lines. Further investigations revealed that oncoVV-AVL replicated faster than oncoVV significantly in cancer cells. Intracellular signaling elements including NF-κB2, NIK, as well as ERK were determined to be altered by oncoVV-AVL. Virus replication upregulated by AVL was completely dependent on ERK activity. Furthermore, in vivo studies showed that oncoVV-AVL elicited significant antitumor effect in colorectal cancer and liver cancer mouse models. Our study might provide insights into a novel way of the utilization of marine lectin AVL in oncolytic viral therapies.

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