scholarly journals Focused Ultrasound-Induced Cavitation Sensitizes Cancer Cells to Radiation Therapy and Hyperthermia

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2595
Author(s):  
Shaonan Hu ◽  
Xinrui Zhang ◽  
Michael Unger ◽  
Ina Patties ◽  
Andreas Melzer ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cancer Cells ◽  
Focused Ultrasound ◽  
Clonogenic Survival ◽  
Non Invasive ◽  
Cavitation Effect ◽  
Good Potential ◽  
C 30

Focused ultrasound (FUS) has become an important non-invasive therapy for solid tumor ablation via thermal effects. The cavitation effect induced by FUS is thereby avoided but applied for lithotripsy, support drug delivery and the induction of blood vessel destruction for cancer therapy. In this study, head and neck cancer (FaDu), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS by using an in vitro FUS system followed by single-dose X-ray radiation therapy (RT) or water bath hyperthermia (HT). Sensitization effects of short FUS shots with cavitation (FUS-Cav) or without cavitation (FUS) to RT or HT (45 °C, 30 min) were evaluated. FUS-Cav significantly increases the sensitivity of cancer cells to RT and HT by reducing long-term clonogenic survival, short-term cell metabolic activity, cell invasion, and induction of sonoporation. Our results demonstrated that short FUS treatment with cavitation has good potential to sensitize cancer cells to RT and HT non-invasively.

scholarly journals Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage

2021 ◽  
Author(s):  
Xinrui Zhang ◽  
Mariana Bobeica ◽  
Michael Unger ◽  
Anastasia Bednarz ◽  
Bjoern Gerold ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Metabolic Activity ◽  
Focused Ultrasound ◽  
Double Strand Breaks ◽  
High Intensity Focused Ultrasound ◽  
Dna Double Strand Breaks ◽  
Strand Breaks

Abstract Purpose High-intensity focused ultrasound (HIFU/FUS) has expanded as a noninvasive quantifiable option for hyperthermia (HT). HT in a temperature range of 40–47 °C (thermal dose CEM43 ≥ 25) could work as a sensitizer to radiation therapy (RT). Here, we attempted to understand the tumor radiosensitization effect at the cellular level after a combination treatment of FUS+RT. Methods An in vitro FUS system was developed to induce HT at frequencies of 1.147 and 1.467 MHz. Human head and neck cancer (FaDU), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS in ultrasound-penetrable 96-well plates followed by single-dose X‑ray irradiation (10 Gy). Radiosensitizing effects of FUS were investigated by cell metabolic activity (WST‑1 assay), apoptosis (annexin V assay, sub-G1 assay), cell cycle phases (propidium iodide staining), and DNA double-strand breaks (γH2A.X assay). Results The FUS intensities of 213 (1.147 MHz) and 225 W/cm2 (1.467 MHz) induced HT for 30 min at mean temperatures of 45.20 ± 2.29 °C (CEM43 = 436 ± 88) and 45.59 ± 1.65 °C (CEM43 = 447 ± 79), respectively. FUS improves the effect of RT significantly by reducing metabolic activity in T98G cells 48 h (RT: 96.47 ± 8.29%; FUS+RT: 79.38 ± 14.93%; p = 0.012) and in PC-3 cells 72 h (54.20 ± 10.85%; 41.01 ± 11.17%; p = 0.016) after therapy, but not in FaDu cells. Mechanistically, FUS+RT leads to increased apoptosis and enhancement of DNA double-strand breaks compared to RT alone in T98G and PC-3 cells. Conclusion Our in vitro findings demonstrate that FUS has good potential to sensitize glioblastoma and prostate cancer cells to RT by mainly enhancing DNA damage.

scholarly journals Low Intensity Focused Ultrasound Augmented Multifunctional Nanoparticles for Integrating Ultrasound Imaging and Synergistic Therapy of Metastatic Breast Cancer

2021 ◽  
Author(s):  
Qian Zhang ◽  
Wen Wang ◽  
Hongyuan Shen ◽  
Hongyu Tao ◽  
Yating Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ultrasound Imaging ◽  
Focused Ultrasound ◽  
Metastatic Breast ◽  
Sonodynamic Therapy ◽  
Non Invasive ◽  
Low Intensity ◽  
Negative Effect

Abstract The metastasis of breast cancer is believed to have a negative effect on its prognosis. Benefiting from the remarkable deep-penetrating and non-invasive characteristics, sonodynamic therapy (SDT) demonstrates a whole series of potential leading to cancer treatment. To relieve the limitation of monotherapy, a multifunctional nanoplatform has been explored to realize the synergistic treatment efficiency. Herein, we establish a novel multifunctional nano-system which encapsulates chlorin e6 (Ce6, for SDT), perfluoropentane (PFP, for ultrasound imaging), and docetaxel (DTX, for chemotherapy) in a well-designed PLGA core-shell structure. The synergistic nanoparticle (CPDP NPs) featured with excellent biocompatibility and stability primarily enables its further application. Upon low intensity focused ultrasound (LIFU) irradiation, the enhanced ultrasound imaging could be revealed both in vitro and in vivo. More importantly, combined with LIFU, the nanoparticle exhibits intriguing antitumor capability through Ce6 induced cytotoxic reactive oxygen species as well as DTX releasing to generate a concerted therapeutic efficiency. Furthermore, this treating strategy actives a strong anti-metastasis capability by which lung metastatic nodules have been significantly reduced. The results indicate that the SDT-oriented nanoplatform combined with chemotherapy could be provided as a promising approach in elevating effective synergistic therapy and suppressing lung metastasis of breast cancer.

P5990In vivo tracking of long-term survival of xenogeneic porcine mesenchymal stem cells seeded on tissue-engineered heart valve implanted in sheep

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Gyongyosi ◽  
D Lukovic ◽  
N Pavo ◽  
A Gugerell ◽  
J Winkler ◽  
...  
Keyword(s):  
Reporter Gene ◽  
Insertional Mutagenesis ◽  
Term Survival ◽  
Long Term Survival ◽  
Non Invasive ◽  
Pet Ct ◽  
Valve Implantation

Abstract Background Long-term survival of xenogeneic transplanted cells in adults requires strong immunosuppression and/or encapsulation of the cells to achieve peripheral transplant tolerance. Purpose The aim of our project was to seed decellularized tissue engineered heart valves (TEHV) with xenogeneic (porcine) mesenchymal stem cells (pMSCs) transfected transiently (Lipofectamine) with a positron emission tomography (PET)-reporter gene (pMSC-PETr), followed by implantation as pulmonary valve replacement into sheep without immunosuppression. The fate of the seeded pMSC-PETr was tracked via serial in-vivo non-invasive PET-computed tomography (PET-CT). Methods Static cultivation of TEHV scaffold led to successful ingrowth of the pMSC-PETr. For enabling quantitative assessment of viable pMSC-PETr in the TEHV scaffold after in vivo implantation, vials containing 5x104, 2x105, and 4x105 pMSC-PETr were in vitro mixed with the [18F]-FHBG PET tracer for 1 hr, then the non-bound tracer was washed out and vials were in vitro PET-CT imaged, giving reference values. TEHV-pMSC-PETr were then implanted percutaneously into the pulmonary valve position of sheep (n=4) under general anesthesia, while an additional sheep with no valve implantation served as a control. Ten mCi of [18F]-FHBGPET radiotracer was produced for each procedure and serial PET-CT imaging of the sheep was performed at 3 hr, 24 hr, 2 or 3 weeks, and 5 and 6 months after valve implantation. The study followed the Principles of laboratory animal care. Results PET-CT of vials containing increasing number of pMSC-PETr showed dose-dependent tracer uptake in the transfected cells in vitro (Figure). PET-CT images of the sheep 3 hr after implantation of the TEHV-pMSC-PETr showed a clear signal of transfected cells, with a mean estimated number of viable pMSC-PETr of 5.18±1.19x106. No meaningful decrease of the amount of living cells occurred at 24 hr or 2 or 3 weeks. Interestingly, 5- and 6-month follow-up PET-CT images showed clear in vivo and in vitro (after explantation) PET signals of the pMSC-PETr on TEHV, indicating spontaneous stable transfection of the PET reporter plasmid (insertional mutagenesis). Histology confirmed the survival of the pMSC-PETr at 5 and 6-month after xenogeneic transplantation. Merged immunohistochemistry and fluorescence imaging of anti-pig SLA I and anti-sheep MHC I antibodies and PET-reporter gene (HSV1-tk) suggested in vivo inter-species lateral jump gene transfer between pig MSCs and host sheep cells. Figure 1 Conclusions This is the first report on serial non-invasive in vivo tracking of long-term survival of xenogeneic pMSCs-PETr seeded on TEHVs and percutaneously implanted into the pulmonary position of sheep. Long-term follow-up revealed spontaneous stable transfection of the plasmid PET-reporter gene, which suggests the risk of insertional mutagenesis induced by the plasmid (transposon), and PET-reporter gene shuttle from xenogeneic pig MSCs to sheep cells. Acknowledgement/Funding LifeValve EU project (grant number: 242008)

Contribution of microRNA-200b-3p to radiation therapy resistance in 22RV1 prostate cancer cells.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 89-89
Author(s):  
John Thoms ◽  
Satoko Aoki ◽  
Lourdes Pena Castillo
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Cancer Cells ◽  
Cell Lines ◽  
Clonogenic Survival ◽  
Negative Control ◽  
Differentially Expressed ◽  
Prostate Cancer Cells ◽  
Altered Expression ◽  
Resistant Phenotype

89 Background: Radiation therapy (RT) is a standard treatment option for men with localized prostate cancer. Despite having well-established treatment regimens, such men still fail RT at a rate of up to 30-50%. RT resistant phenotype is a key component leading to treatment failure. MicroRNAs (miRNAs) can influence the response to RT, and the abundance or lack of certain miRNAs can induce a RT resistant phenotype through alteration of survival pathways. We show that altered expression of miR-200b-3p plays an important role in contributing to RT resistance. Methods: RT resistant subline from the parental 22RV1 prostate cancer cell line was generated by exposure to fractionated RT – 22RV1-RT. The global expression level of miRNAs and mRNA was determined, using the Affymetrix GeneChip®: miRNA 4.0 and Human Gene 2.0 ST Arrays. Parental and 22RV1-RT cells were transfected with miR-200b-3p mimics or negative control. The influence of miR-200b-3p on cellular proliferation, morphology, migration, clonogenic survival and response to RT was determined by standard assays. Results: MiR-200b-3p was the only miRNA that was statistically differentially expressed between the two cell lines. There were 39 differentially expressed genes. Of the 65 genes predicted to be regulated by miR-200b-3p as identified from miRTarBase, only Fibronectin 1 (FN1) was in common. FN1 was up-regulated in 22RV1- RT cells. MiR-200b-3p mimics; in comparison to negative control mimics, suppressed cell proliferation in both cell lines. Both cell lines with negative control mimics have fibroblastic-type morphology and display a stretched shape following RT. While, cells transfected with miR-200b-3p mimics demonstrated a round morphology and formed clusters following RT. Over-expression of miR-200b-3p mimics inhibited cell migration synergically with RT and demonstrated a lower degree of clonogenic survival following RT in 22RV1-RT cells compared to negative control mimics. Surprisingly, miR-200b-3p mimics reversed the observed RT resistance and the sensitivity to RT was to the same degree as the parental 22RV1 cells. Conclusions: Together, these data suggest that miR-200b-3p independently contributes to RT resistance in 22RV1 prostate cancer cells.

Diameter and Pulsatile Oscillations of the Femoral Artery Recorded by Ultrasound

1984 ◽  
Vol 25 (4) ◽  
pp. 313-316 ◽  
Author(s):  
T. Christensen ◽  
J. Jørgensen ◽  
B. Neubauer
Keyword(s):  
Arterial Wall ◽  
External Iliac Artery ◽  
Non Invasive ◽  
Time Motion ◽  
Invasive Method ◽  
Inner Diameter ◽  
In Vitro Examination

A new non-invasive method for in vivo investigations of the inner diameter and pulsatile oscillations of large muscular arteries by means of an ultrasound time-motion technique is presented. Each histologic layer of the arterial wall is identified at in vitro examination of the external iliac artery. The method has been used for in vivo investigations of 16 long term diabetics and of 16 non-diabetics. A reduction of the lumen and decrement in pulse deflections were found in the diabetics when compared with those of the normal group.

scholarly journals PARP Inhibitor Olaparib Enhances the Efficacy of Radiotherapy on Xrcc2-deficient Colorectal Cancer Cells

2021 ◽  
Author(s):  
changjiang Qin ◽  
Zhi-Yu Ji ◽  
Er-Tao Zhai ◽  
Kai-Wu Xu ◽  
Quan-Ying Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Parp Inhibitor ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Clonogenic Survival ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Abstract Background: Loss of XRCC2 compromises DNA damage repairs, and induced DNA damage burdens may increase the reliance on PARP-dependent DNA repairs of cancer cells to render cell susceptibility to PARP inhibitor therapy. Here, we study if XRCC2 loss sensitizes colorectal cancer(CRC) to PARP inhibitor in combination with radiotherapy (RT).Methods: The relationships between the expression of XRCC2 and PARP with patient outcome were investigated in 167 patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (neoCRT). The in vitro radiosensitizing effects of olaparib were tested in XRCC2-deficient CRC using a clonogenic survival assay, determination of γH2AX foci, and measurement of β-galactosidase activity. An in vivo mouse xenograft model was used to determine the effect of olaparib on sensitization of tumors to ionizing radiation (IR).Results: High levels of XRCC2 or PARP1 were significantly associated with poor overall survival (OS) in patients with LARC who received neoCRT, co-expression analyses found low PARP1 and low XRCC2 expression have better OS. Our in vitro experiments indicated that olaparib+IR reduced clonogenic survival, increased persistent DNA damage, and prolonged cell cycle arrest and senescence in XRCC2-deficient cells relative to wild-type cells. Furthermore, our mouse xenograft experiments indicated that RT+olaparib had greater anti-tumor effects and led to long-term remission in mice with XRCC2-deficient tumors.Conclusions: XRCC2-deficient CRC acquire high sensitivity to PARP inhibition after IR treatment. Our preclinical findings provide a rationale for the use of Olaparib as a radiosensitizer for treatment of XRCC2-deficient CRC.

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