Role of CTGF in Sensitivity to Hyperthermia in Ovarian and Uterine Cancers

Hatakeyama, Hiroto; Wu, Sherry Y.; Lyons, Yasmin; Pradeep, Sunila; Wang, Wanqin; Huang, Qian; Court, Karem A.; Liu, Tao; Nie, Song; Rodríguez-Aguayo, Cristian; Shen, Fu‐Ming; Huang, Yan; Hisamatsu, Takeshi; Mitamura, Takashi; Jennings, Nicholas B.; Shim, Jeajun; Dorniak, Piotr L.; Mangala, Lingegowda S.; Petrillo, Marco; Petyuk, Vladislav; Schepmoes, Athena; Shukla, Anil; Torres‐Lugo, Madeline; Lee, Ju Seog; Rodland, Karin D.; Fagotti, Anna; López-Berestein, Gabriel; Li, Chun; Sood, Anil K.

doi:10.1016/j.celrep.2016.10.020

Cited by 22 publications

(32 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As for MFH, evidence supports that HeyA8 cells exposed to AMF are only minimally affected at 41°C. 11,33 At higher temperatures (i.e., 43°C and 45°C) this work showed that ovarian cancer cell viability is strongly affected in a celldependent fashion ( Figure SI-5-b). The effects of various individual and combination treatments are depicted in Figure 4 comparing mild and moderate hyperthermia conditions.…”

Section: Us/mfh/pes Combination Treatmentsmentioning

confidence: 83%

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

Mérida¹,

Rinaldi²,

Juan³

et al. 2020

IJN

Self Cite

View full text Add to dashboard Cite

Background: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments. Purpose: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer. Methods: The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity ® microbubbles and polyethylene glycol (PEG)-coated iron oxide nanoparticles were used to induce cell sonoporation and MFH, respectively. Assessment of cell membrane permeabilization was evaluated via fluorescence microscopy, iron uptake by cells was quantified by UV-Vis spectroscopy, and cell viability was determined using automatic cell counting. Results: Notable reductions in cancer cell viability were observed when ultrasound was incorporated. For example, the treatment US+PES reduced cell viability by 37% compared to the non-toxic effect of the drug. Similarly, the treatment US+MFH using mild hyperthermia (41°C), reduced cell viability by an additional 18% when compared to the effect of MH alone. Significant improvements were observed for the combination of US+PES+MFH with cell viability reduced by an additional 26% compared to the PES+MFH group. The improved cytotoxicity was attributed to enhanced drug/nanoparticle intracellular delivery, with iron uptake values nearly twice those achieved without ultrasound. Various treatment schedules were examined, and all of them showed substantial cell death, indicating that the time elapsed between sonoporation and magnetic field exposure was not significant. Conclusion: Superior cancer cell-killing patterns took place when ultrasound was incorporated thus demonstrating the in vitro ultrasonic potentiation of PES and mild MFH. This work demonstrated that ultrasound is a promising non-invasive enhancer of PES/MFH combination treatments, aiming to establish a sono-thermo-chemotherapy in the treatment of ovarian cancer.

show abstract

Section: Us/mfh/pes Combination Treatmentsmentioning

confidence: 83%

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

Mérida¹,

Rinaldi²,

Juan³

et al. 2020

IJN

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, in vitro experiments reveal that CTGF can suppress cell proliferation in the clear cell and endometrioid subtypes of human ovarian cancer cells and ovarian granulosa cells [ 23 , 24 ]. In contrast, previous studies have demonstrated that CTGF promotes cell migration and proliferation, and patients with higher CTGF expression levels are associated with poor survival in HGSC [ 11 – 13 , 25 ]. Taken together, these results indicate that the role of CTGF in human ovarian cancer progression is complicated and its biological effects may depend on the subtype of the disease.…”

Section: Discussionmentioning

confidence: 84%

Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis

Cheng

Chang

2017

Oncotarget

View full text Add to dashboard Cite

Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression. Transforming growth factor-β1 (TGF-β1) is a well-known molecule that can strongly up-regulate CTGF expression in different types of normal and cancer cells. Our previous study demonstrated that TGF-β1 induces apoptosis of LGSC cells. However, the effect of TGF-β1 on CTGF expression in LGSC needs to be defined. In addition, whether CTGF mediates TGF-β1-induced LGSC cell apoptosis remains unknown. In the present study, we show that TGF-β1 treatment up-regulates CTGF expression by activating SMAD3 signaling in two human LGSC cell lines. Additionally, siRNA-mediated CTGF knockdown attenuates TGF-β1-induced cell apoptosis. Moreover, our results show that the inhibitory effect of the CTGF knockdown on TGF-β1-induced cell apoptosis is mediated by down-regulating SMAD3 expression. This study demonstrates an important role for CTGF in mediating the pro-apoptotic effects of TGF-β1 on LGCS.

show abstract

“…Through integrative analyses of static gene signatures and dynamic changes in protein expression between hyperthermiasensitive and -resistant cells, we identified that connective tissue growth factor (CTGF) regulates hyperthermia resistance by manipulating glucose metabolism under heat stress in ovarian and uterine cancer cells. 87) Therefore, for efficient hyperthermia therapy of ovarian cancers, we examined the combination of inhibiting CTGF and hyperthermia. The silencing of CTGF was achieved by treatment with 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) liposomal siRNA, which is currently undergoing testing in clinical trials.…”

Section: Improved Efficacy Of Hyperthermia By Inhibiting a Hyperthermmentioning

confidence: 99%

Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics

Hatakeyama

2017

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

Significant progress has been achieved in the development of stimuli-responsive nanocarriers for drug delivery, diagnosis, and therapy. Various types of triggers are utilized in the development of nanocarrier delivery. Endogenous factors such as changes in pH, redox, gradient, and enzyme concentration which are linked to disease progression have been utilized for controlling biodistribution and releasing drugs from nanocarriers, as well as increasing subsequent pharmacological activity at the disease site. Nanocarriers which respond to artificially-induced exogenous factors (such as temperature, light, magnetic field, and ultrasound) have also been developed. This review aims to discuss recent advances in the design of stimuliresponsive nanocarriers which appear to have a promising future in medicine.

show abstract

Role of CTGF in Sensitivity to Hyperthermia in Ovarian and Uterine Cancers

Cited by 22 publications

References 31 publications

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis

Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics

Contact Info

Product

Resources

About