Vector-Mediated Cancer Gene Therapy Reduces Toxicity and Inhibition of Lung Carcinoma Growth in Nude Mice.

Replication-competent oncolytic adenovirus (TOA2) gene therapy is a recently introduced anti-tumor treatment regimen with superior results. The biodistribution studies of virus vector-based medicine seem more cautious and have been given much attention recently in terms of its quality and safety in preclinical trials. The current study determined the biodistribution and safety of a replication-competent adenovirus in different organs to predict its toxicity threshold.

Alpha-Momorcharin Inhibits Proinflammatory Cytokine Expression by M1 Macrophages but Not Anti-Inflammatory Cytokine Expression by M2 Macrophages.

Background: Alpha-momorcharin (α-MMC) is a natural medicine derived from bitter melon and has been found to exert immunomodulatory effects. Our previous study indicated that α-MMC can regulate cytokine release from monocytes, but it remains unknown about its regulatory effect on different types of cytokines, such as inflammatory cytokines or anti-inflammatory cytokines.

Methods: LPS-induced M1-type macrophages model and IL-4-induced M2-type macrophages model were established, and the expression of proinflammatory cytokines and anti-inflammatory cytokines were assessed by ELISA after α-MMC was administered.

In-silico analysis of ligand-receptor binding patterns of α-MMC, TCS and MAP30 protein to LRP1 receptor.

Alpha-momorcharin (α-MMC), trichosanthin (TCS), and momordica anti-HIV protein of 30 kD (MAP30) are potential anti-tumor drug candidates but have cytotoxicity to normal cells. The binding of these proteins to LRP1 receptor and the subsequent endocytosis are essential to their cytotoxicity, but this binding process remains largely unknown. This study, in-silico analysis of the binding patterns, was conducted via the protein-protein docking software, ZDOCK 3.

[Alpha-momordicin Regulates Hepatocyte Cytokine Expression].

Objective: To investigate the regulation effect of α-momordicin (α-MMC) on the synthesis and secretion of cytokines in hepatocytes cells.

Methods: Hepatocytes L02 were treated with 189 μg/mL α-MMC with culture supernatant and lysate samples were harvested in different timepoint. Expressions of T-helper 17 (TH17) cytokine profile in samples were detected by the Bio-Plex 200 suspension chip assay system.

Alpha-momorcharin regulates cytokine expression and induces apoptosis in monocytes.

Alpha-momorcharin (α-MMC) is a type I ribosome-inactivating protein (RIP) that is purified from . Despite its strong antitumor activities, α-MMC exerts the undesirable immunotoxicity effects of hypersensitivity or immunosuppression. Since α-MMC is a plant protein, its application can easily induce hypersensitivity, but its immunosuppressive mechanism is still unclear.

LRP1 receptor-mediated immunosuppression of α-MMC on monocytes.

Alpha-MMC is a type I ribosome-inactivating protein purified from bitter gourd that has strong anti-tumour and antiviral activity. Alpha-MMC also has immunosuppressive effects, but the mechanism of these immunosuppressive effects remains unclear. It is reported that the binding of α-MMC to its specific cell membrane LRP1 receptor is key to its biological effects.

Cytotoxicity mechanism of α-MMC in normal liver cells through LRP1 mediated endocytosis and JNK activation.

Alpha-momorcharin (α-MMC), a type I ribosome-inactivating protein isolated from Momordica charantia, is a potential drug candidate with strong anti-tumor activity. However, α-MMC has a severe hepatotoxicity when applied in vivo, which may greatly hinders its use in clinic in the future. The biological mechanism of hepatotoxicity induced by α-MMC is largely unknown, especially the mechanism by which α-MMC enters the hepatocytes.

[Research on Molecular Biological Characteristics of Proto-oncogene pim-2].

The purpose of this paper is to present the research on the molecular biological characteristics of proto-oncogene pim-2 and to analyze the related mechanism. Proto-oncogene pim-2 was studied and analyzed by the bioinformatics method and technology. With an online server, the chromosomal localization of pim-2 gene was analyzed, and the exon, open reading frame, CpG island and miRNAs complementary fragments and the like were predicted.

TOA02, a recombinant adenovirus with tumor-specific granulocyte macrophage colony-stimulating factor expression, has limited biodistribution and low toxicity in rhesus monkeys.

TOA02 is a genetically modified oncolytic adenovirus that contains human granulocyte macrophage colony-stimulating factor (hGM-CSF). It has been verified in vitro that TOA02 can specifically replicate in tumor cells that possess high telomerase reverse transcriptase activity and Rb pathway deficiency. However, the replication specificity, hGM-CSF expression, and toxicity of TOA02 in vivo are still unknown.

Alpha-momorcharin (α-MMC) exerts effective anti-human breast tumor activities but has a narrow therapeutic window in vivo.

Alpha-momorcharin (α-MMC), a ribosome inactivating protein (RIP) extracted from the seeds of Momordica charantia, exerts anti-tumor, antiviral, and anti-fungal activities. However, α-MMC has an obvious toxicity that limits its clinical application. We examined the effect of α-MMC on the inhibition of human breast cancer and assessed its general toxicity to find the therapeutic window in vivo for its potential clinical use.

PEGylation alleviates the non-specific toxicities of Alpha-Momorcharin and preserves its antitumor efficacy in vivo.

Alpha-Momorcharin (α-MMC) is a ribosome inactivating protein from Momordica charantia with anti-tumor activity. Previously, we had observed that modification of α-MMC with polyethylene glycol (PEG) could reduce toxicity, but it also reduces its anti-tumor activity in vitro. This study aims to investigate whether the metabolism-extended properties of α-MMC resulting from PEGylation could preserve its anti-tumor efficacy in vivo through pharmacokinetics and antitumor experiments.

[Effect of PEGylation of alpha-Momorcharin against its hepatotoxicity in rats].

Objective: To explore the effect of PEGylation of alpha-Momorcharin (alpha-MMC), one of ribosome-inactivating proteins from bitter melon seed, against its hepatotoxicity in rats.

Methods: SD rats were randomized into NS group, alpha-MMC treated groups, and alpha-MMC-PEG treated groups. The doses of alpha-MMC and alpha-MMC-PEG were high, middle, and low dose (6.

PEGylation is effective in reducing immunogenicity, immunotoxicity, and hepatotoxicity of α-momorcharin in vivo.

Background And Aim: α-momorcharin (α-MMC), a type I ribosome-inactivating protein (RIP) from Momordica charantia, is well known for its antitumor and antivirus activities. However, the immunotoxicity and hepatotoxicity hampers its potential therapeutic usage. In order to reduce its toxicity, we had modified the α-MMC with polyethylene glycol (PEG), and detected the toxicity of the PEGylated α-MMC conjugates (α-MMC-PEG) in vivo.

Alpha-momorcharin possessing high immunogenicity, immunotoxicity and hepatotoxicity in SD rats.

Unlabelled: Momordica charantia L., a genus of Momordica Linn. of the family Cucurbitaceae, commonly known as bitter melon, has been widely planted in China, Southeast Asia, Turkey and other areas, and has been used as a medicine for a long time.

Immunoaffinity purification of α-momorcharin from bitter melon seeds (Momordica charantia).

α-Momorcharin (α-MMC), a type I ribosome-inactivating protein (RIP), has shown therapeutic potential such as anti-tumor and anti-viral agent. Traditional process of α-MMC purification from bitter melon seeds was time consuming and low efficient. To take this challenge, we made an affinity matrix by coupling the monoclonal antibody (McAb) with Sepharose 4B.

PEGylation of alpha-momorcharin: synthesis and characterization of novel anti-tumor conjugates with therapeutic potential.

Alpha-momorcharin (alpha-MMC) is a ribosome-inactivating protein (RIP) with excellent cytotoxicity to tumor cells. However, its strong immunogenicity and short plasma half-life limit its clinical applications. To overcome this, we have to PEGylated alpha-MMC using a branched 20 kDa (mPEG) (2)-Lys-NHS.

[Study on the immunotoxicity of ribosome inhibiting protein of Momordica charantia].

Objective: To separate and purify ribosome inhibiting protein (RIP) from Momordica charantia (bitter melon) seeds and to evaluate its acute toxicity and immunotoxicity in animal.

Methods: Ion exchange chromatography and gel filtration chromatography were applied in the separating and purifying of RIP from Momordica charantia seeds. Then the acute toxicity testing of RIP in mice was conducted to obtain its half lethal dose (LD50).

Anti-tumor activity and immunological modification of ribosome-inactivating protein (RIP) from Momordica charantia by covalent attachment of polyethylene glycol.

Ribosome-inactivating proteins (RIPs) are a family of enzymes that depurinate rRNA and inhibit protein biosynthesis. Here we report the purification, apoptosis-inducing activity, and polyethylene glycol (PEG) modification of RIP from the bitter melon seeds. The protein has a homogenous N-terminal sequence of NAsp- Val-Ser-Phe-Arg.

[Effects of KH901, a tumor-specific oncolytic recombinant adenovirus, on antitumor and expressing GM-CSF in xenograft tumor models].

Objective: Conditionally replicating oncolytic adenovirus KH901 was engineered with a genetically modified telomerase reverse transcriptase promoter and a cDNA of human granulocyte macrophage colony stimulating factor (GM-CSF). The objective of this study was to evaluate the anti-tumor efficacy and the selective GM-CSF expression of KH901 in xenograft tumor models.

Methods: After intratumoral administration of KH901, the rates of Relative Tumor Growth (T/C%) and inhibition in Hep3B and LNcap xenograft models were measured for observing the KH901 antitumor efficacy.

[Tumor-selective replication, cytotoxicity and GM-CSF production of oncolytic recombinant adenovirus in KH901 injection].

Objective: To study the tumor-selective replication, cytotoxicity and GM-CSF production of the recombinant virus in KH901 injection used to infect the cells cultured in vitro.

Methods: A panel of tumor and normal cells was infected with recombinant adenovirus in KH901 and wild-type adenovirus type 5 at a MOI of 2 PPC, the cells were harvested at 72 hours after infection and made a titer after three cycles of freeze/thaw; A panel of tumor and normal cells was infected with recombinant adenovirus KH901 at MOI of 1 or 10 PPC. For 24 hours after infection the medium was harvested to determine the biological activity of GM-CSF; A panel of tumor and normal cells was infected with KH901 of recombinant adenovirus and wild-type adenovirus type 5 at MOIs of 0, 0.