scholarly journals Yb3+-containing chitosan hydrogels induce B-16 melanoma cell anoikis via a Fak-dependent pathway

2019 ◽  
Vol 8 (1) ◽  
pp. 645-660 ◽  
Author(s):  
Yu Miao ◽  
Jiawei Lu ◽  
Junhui Yin ◽  
Changchun Zhou ◽  
Yaping Guo ◽  
...  

AbstractMelanoma is the most lethal dermal tumor, and a high recurrence rate and skin defects are two main serious problems. An antimelanoma material,which effectively inhibits tumor recurrence and possesses excellent biocompatibility, is urgently needed to treat melanoma. In this study, we developed a novel antitumor Yb3+ [Yb(NO3)3]containing chitosan hydrogel (Yb-CS hydrogel) by dissolving Yb(NO3)3 and chitosan in acetic acid solution and forming composite hydrogels by a freeze-drying process after adding NaOH to the mixed solution. In vitro studies demonstrated that the Yb3+ produces effect of inducing cell death in Yb-CS hydrogel. Moreover, we found that the Yb-CS hydrogel inhibited a focal adhesion kinase (FAK)-dependent signaling pathway and induced B-16 cell anoikis. However, the Yb-CS hydrogel was less effective on L929 normal mouse dermal cells. In vivo studies showed that the Yb-CS hydrogel inhibited the recurrence of melanoma in a mouse bare xenograft tumor model. We concluded that the Yb-CS hydrogel could potentially be used in the antimelanoma field, especially in the inhibition of melanoma recurrence.

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi39-vi39
Author(s):  
Karnika Singh ◽  
Chunhua Han ◽  
Jessica Fleming ◽  
Joseph McElroy ◽  
Ashok Kumar ◽  
...  

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.


2020 ◽  
Vol 11 (2) ◽  
pp. 1793-1797
Author(s):  
Madesh T ◽  
Abhinav Raj Ghosh ◽  
Krishna K L ◽  
Seema Mehdi ◽  
Nandini H S ◽  
...  

Momordica dioicaRoxb. (Cucurbitaceae) is commonly known as spiny gourd and traditionally used as astringent, febrifuge, antiseptic, anthelmintic, spermicidal and also used in bleeding piles, urinary infection and as a sedative. Studies indicate that it possesses antioxidant, hepatoprotective, antibacterial, anti-inflammatory, anti-lipid peroxidative, hypoglycaemic and analgesic properties. In this study, the anticancer efficacy of Cucurbitacins obtained from Momordica dioicaRoxb. (MDR) has been evaluated. Based on previous in-vitro studies performed, in-vivo studies were carried out on mice model.  Ehrlich ascites carcinoma (EAC) cells were inoculated into swiss albino mice intraperitoneally to form a liquid tumor and then treated with oral administration of 50, 100, 200mg/kg. Evaluation parameters involved the mean survival time (MST), body weight, hematological parameters, Percentage increase in life span were measured in normal control, EAC control and Cucurbitacintreated groups (n = 6). Treatment with Cucurbitacins enriched fraction has shown anti-tumor effects against liquid tumor as indicated by a significant (P < 0.05) reduction in body weight. Interestingly, the enriched bio fraction restored the altered hematological parameters of tumor-bearing animals and significantly increased their life span. These data indicate the cytotoxic potential effects of MDRon tumor cells opening new opportunities for further studies on the anti-cancer effects of this agent.


Author(s):  
Robert Love ◽  
Eliza Ranjit ◽  
Ajay Sharma ◽  
Stephen Hamlet ◽  
Roy George ◽  
...  

Purpose: This systematic review was carried out to investigate the effects of keratin and chitosan hydrogel preparations on dental implant osseointegration. Materials and Methods: The electronic search was conducted on five databases: Scopus, EBSCOhost MEDLINE, EBSCOhost Dentistry and Oral Science, PubMed, and Web of Science. Studies that determined the in vitro or in vivo efficacy of keratin and chitosan hydrogel on osseointegration were included in the review. Results: Of the 760 studies initially gathered, nine met the inclusion criteria. These studies demonstrated that dental implants coated with keratin and chitosan hydrogels resulted in improved biological properties. It was also concluded that the inclusion of chitosan in keratin hydrogels improves the mechanical strength and helps increase durability through ameliorating degradation and swelling characters. Both the polymers increased bone-implant contact and new bone formation in animal models. Conclusion: This systematic review demonstrates that keratin and chitosan hydrogel, is effective in initiating osteogenesis, reinforcing the currently available evidence that these polymers could be a substrate in dental implant treatment.


2001 ◽  
Vol 5 (8) ◽  
pp. 645-651
Author(s):  
M. Peeva ◽  
M. Shopova ◽  
U. Michelsen ◽  
D. Wöhrle ◽  
G. Petrov ◽  
...  
Keyword(s):  

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S198-S198
Author(s):  
Joseph R Meno ◽  
Thien-son K Nguyen ◽  
Elise M Jensen ◽  
G Alexander West ◽  
Leonid Groysman ◽  
...  

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.


2020 ◽  
Vol 72 (5) ◽  
Author(s):  
Mario Fadin ◽  
Maria C. Nicoletti ◽  
Marzia Pellizzato ◽  
Manuela Accardi ◽  
Maria G. Baietti ◽  
...  
Keyword(s):  

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