Correction to: Evaluation of Two Optical Probes for Imaging the Integrin αvβ6− In Vitro and In Vivo in Tumor-Bearing Mice

Abstract As a cancer therapy, hypothermia has been used at sub-zero temperatures to cryosurgically ablate tumors. However, these temperatures can indiscriminately damage both tumorous and healthy cells. Additionally, strategies designed to kill tumor typically accelerate their evolution and recurrence can be inevitable in cancers such as glioblastoma (GBM). To bypass these limitations, here we studied the use of hypothermia as a cytostatic tool against cancer and deployed it against an aggressive rodent model of GBM. To identify the minimal dosage of ‘cytostatic hypothermia’, we cultured at least 4 GBM lines at 4 continuous or intermittent degrees of hypothermia and evaluated their growth rates through a custom imaging-based assay. This revealed cell-specific sensitivities to hypothermia. Subsequently, we examined the effects of cytostatic hypothermia on these cells by a cursory study of their cell-cycle, energy metabolism, and protein synthesis. Next, we investigated the use of cytostatic hypothermia as an adjuvant to chemotherapy and CAR T immunotherapy. Our studies demonstrated that cytostatic hypothermia did not interfere with Temozolomide in vitro and may have been synergistic against at least 1 GBM line. Interestingly, we also demonstrated that CAR T immunotherapy can function under cytostatic hypothermia. To assess the efficacy of hypothermia in vivo, we report the design of an implantable device to focally administer cytostatic hypothermia in an aggressive rodent model of F98 GBM. Cytostatic hypothermia significantly doubled the median survival of tumor-bearing rats with no obvious signs of distress. The absence of gross behavioral alterations is in concurrence with literature suggesting the brain is naturally resilient to focal hypothermia. Based on these findings, we anticipate that focally administered cytostatic hypothermia alone has the potential to delay tumor recurrence or increase progression-free survival in patients. Additionally, it could also provide more time to evaluate concomitant, curative cytotoxic treatments.

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Preclinical Pharmacokinetics of C118P, a Novel Prodrug of Microtubules Inhibitor and Its Metabolite C118 in Mice, Rats, and Dogs

Molecules ◽

10.3390/molecules23112883 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2883 ◽

Cited By ~ 3

Author(s):

Cang Zhang ◽

Xiaolan Zhang ◽

Guangji Wang ◽

Ying Peng ◽

Xueyuan Zhang ◽

...

Keyword(s):

Clinical Development ◽

High Dose ◽

Protein Inhibitor ◽

Promising Candidate ◽

Preclinical Pharmacokinetics ◽

Tumor Bearing ◽

Microtubule Protein ◽

Further Development

C118P, a phosphate prodrug of C118, which is a novel microtubule protein inhibitor, is currently under Phase I clinical development in China for treating ovarian cancer and lung cancer. The preclinical pharmacokinetics of prodrug C118P and its metabolite C118 were extensively characterized in vivo in mice, rats, and dogs and in vitro to support the further development of C118P. The preclinical tissue distribution and excretion were investigated in rats. Plasma protein binding in mice, rat, and human, and hepatic microsomal metabolic stability in mice, rat, dog, monkey, and human, were also evaluated. The (AUC0-inf) and C30s of C118P at 50 mg/kg in rats and 6 mg/kg in dogs, and the C2min of C118 at 6 mg/kg in dogs increased less than the dosage increase, suggested nonlinear pharmacokinetic occurred at high dose. As a prodrug, C118P can be quickly hydrolyzed into C118 after an intravenous administration. The unbound C118 in plasma is slightly higher than C118P. C118P can hardly penetrate the tissue, while C118 can distribute widely into tissues. In tumor-bearing nude mice, the concentration of C118 is high in lung, ovary, and tumor, with an extended half-life in tumor. C118P is a promising candidate prodrug for further clinical development.

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pH-Sensitive Hydrazone-Linked Doxorubicin Nanogels via Polymeric-Activated Ester Scaffolds: Synthesis, Assembly, and In Vitro and In Vivo Evaluation in Tumor-Bearing Zebrafish

Chemistry of Materials ◽

10.1021/acs.chemmater.8b03702 ◽

2018 ◽

Vol 30 (23) ◽

pp. 8587-8596 ◽

Cited By ~ 13

Author(s):

Alexandra Van Driessche ◽

Agnese Kocere ◽

Hannelien Everaert ◽

Lutz Nuhn ◽

Simon Van Herck ◽

...

Keyword(s):

Ph Sensitive ◽

In Vivo Evaluation ◽

Tumor Bearing

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Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging

Frontiers in Pharmacology ◽

10.3389/fphar.2021.778396 ◽

2022 ◽

Vol 12 ◽

Author(s):

Leanne De Silva ◽

Ju-Yen Fu ◽

Thet Thet Htar ◽

Wan Hamirul Bahrin Wan Kamal ◽

Azahari Kasbollah ◽

...

Keyword(s):

Intravenous Injection ◽

Gamma Scintigraphy ◽

Biodistribution Study ◽

Scintigraphic Imaging ◽

Tumor Bearing ◽

Tumor Accumulation ◽

Tumor Area

The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.

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Quercetin inhibits intrahepatic cholangiocarcinoma by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation via the NF-κB pathway

10.21203/rs.3.rs-947377/v1 ◽

2021 ◽

Author(s):

Yinghui Song ◽

Zhihua Zhang ◽

Qin Chai ◽

GuoYi Xia ◽

Zhangtao Yu ◽

...

Keyword(s):

Intrahepatic Cholangiocarcinoma ◽

Clonogenic Assay ◽

Direct Interaction ◽

Rna Seq ◽

Wound Healing Assay ◽

Tumor Bearing ◽

Mesenchymal Transformation ◽

First Time

Abstract Intrahepatic cholangiocarcinoma (ICC) is a rare high-fatal hepatobiliary malignancy, the treatment option of ICC is very limited, and the prognosis is also poor. Recently, emerging evidence has shown the potential of quercetin (QE) for cancer therapy. We explored the effect and mechanism of QE on ICC in vitro and in vivo. CCK-8 assay and Clonogenic assay showed that QE could inhibit ICC cells proliferation and survival. PI staining suggested QE could induce ICC cells arrest in G1 phase. AV/PI staining suggested QE could promote ICC cells apoptosis. Wound Healing Assay and Transwell chamber experiment suggested QE could inhibit ICC cells EMT. RNA-seq, the changes in the structure of mitochondria by electron microscopy and the key markers of ferroptosis (free iron ions, MDA, SOD, GPX4) were supported QE could promote ferroptosis in ICC cells. Molecular docking showed that QE had direct interaction with NF-κB and GPX4. In vivo, treatment with QE inhibited tumor growth and prolonged survival time of tumor-bearing nude mice. Our data for the first time suggest that QE is a new ferroptosis inducer and combinative treatment of inhibiting NF-κB in ICC cells by inducing ferroptosis and inhibiting EMT, which will hopefully provide a prospective strategy for ICC patients.

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Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

10.21203/rs.3.rs-19911/v1 ◽

2020 ◽

Author(s):

Sheng Zhao ◽

Wen-Bin Pan ◽

Hui-Jie Jiang ◽

Rong-Jun Zhang ◽

Hao Jiang ◽

...

Keyword(s):

Colorectal Cancer ◽

Monoclonal Antibody ◽

Competitive Inhibition ◽

Specific Binding ◽

Luminescence Imaging ◽

Tumor Bearing ◽

Cerenkov Luminescence Imaging ◽

The Status

Abstract Background : Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131 I-labeled anti-PD-L1 monoclonal antibody tracer, 131 I-PD-L1-Mab, was developed to study the target ability of non-invasive Cerenkov luminescence imaging in colorectal cancer xenograft mice.Method: Anti-PD-L1 monoclonal antibody labeled with 131 I( 131 I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131 I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, western blot analysis, and immunofluorescence staining. The clinical application value of 131 I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.Results: 131 I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069×10 -9 M. The competitive inhibition assay further confirmed the specific binding ability of 131 I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131 I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% ID/g at 120 h.Conclusions: There is a great potential for 131 I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.

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Comparison of hepatic protein synthesis in vivo versus in vitro in the tumor-bearing rat

Journal of Surgical Research ◽

10.1016/0022-4804(87)90063-1 ◽

1987 ◽

Vol 42 (1) ◽

pp. 43-50 ◽

Cited By ~ 18

Author(s):

Robert S. Warren ◽

M. Jeevanandam ◽

Murray F. Brennan

Keyword(s):

Protein Synthesis ◽

Tumor Bearing ◽

Hepatic Protein Synthesis

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Trimeric Small Interfering RNAs and Their Cholesterol-Containing Conjugates Exhibit Improved Accumulation in Tumors, but Dramatically Reduced Silencing Activity

Molecules ◽

10.3390/molecules25081877 ◽

2020 ◽

Vol 25 (8) ◽

pp. 1877

Author(s):

Ivan V. Chernikov ◽

Daniil V. Gladkikh ◽

Ulyana A. Karelina ◽

Mariya I. Meschaninova ◽

Alya G. Ven’yaminova ◽

...

Keyword(s):

Target Gene ◽

Drug Resistant ◽

Small Interfering Rnas ◽

Tumor Bearing ◽

Carrier Free ◽

Free Mode ◽

Derivatives Of ◽

Transfection Agent

Cholesterol derivatives of nuclease-resistant, anti-MDR1 small-interfering RNAs were designed to contain a 2’-OMe-modified 21-bp siRNA and a 63-bp TsiRNA in order to investigate their accumulation and silencing activity in vitro and in vivo. The results showed that increasing the length of the RNA duplex in such a conjugate increases its biological activity when delivered using a transfection agent. However, the efficiency of accumulation in human drug-resistant KB-8-5 cells during delivery in vitro in a carrier-free mode was reduced as well as efficiency of target gene silencing. TsiRNAs demonstrated a similar biodistribution in KB-8-5 xenograft tumor-bearing SCID mice with more efficient accumulation in organs and tumors than cholesterol-conjugated canonical siRNAs; however, this accumulation did not provide a silencing effect. The lack of correlation between the accumulation in the organ and the silencing activity of cholesterol conjugates of siRNAs of different lengths can be attributed to the fact that trimeric Ch-TsiRNA lags mainly in the intercellular space and does not penetrate sufficiently into the cytoplasm of the cell. Increased accumulation in the organs and in the tumor, by itself, shows that using siRNA with increased molecular weight is an effective approach to control biodistribution and delivery to the target organ.

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Effect of Plasmonic Gold Nanoparticles on Benign and Malignant Cellular Autofluorescence: A Novel Probe for Fluorescence Based Detection of Cancer

Technology in Cancer Research & Treatment ◽

10.1177/153303460700600505 ◽

2007 ◽

Vol 6 (5) ◽

pp. 403-412 ◽

Cited By ~ 21

Author(s):

Ivan El-Sayed ◽

Xiaohua Huang ◽

Fima Macheret ◽

Joseph Oren Humstoe ◽

Randall Kramer ◽

...

Keyword(s):

Gold Nanoparticles ◽

Metallic Nanoparticles ◽

Noble Metal Nanoparticles ◽

Live Cells ◽

Epithelial Cell Line ◽

Optical Probes ◽

Oral Squamous Carcinoma ◽

Absorption Of Light

Due to the strong surface fields of noble metal nanoparticles, absorption and scattering of electromagnetic radiation is greatly enhanced. Noble metallic nanoparticles represent potential novel optical probes for simultaneous molecular imaging and photothermal cancer therapy using the enhanced scattering and absorption of light. Further, gold nanoparticles can affect molecular fluorescence via chemical, electronic, or photonic interactions. Live cells generate fluorescence due to intracellular and extracellular molecules. Differences in the biochemical composition between healthy and malignant cells can be exploited in vivo to help identify cancer spectroscopically. The interaction of gold nanoparticles with cellular autofluorescence has not yet been characterized. We hypothesized that gold nanoparticles delivered to live cells in vitro would alter cellular autofluorescence and may be useful as a novel class of contrast agent for fluorescence based detection of cancer. The fluorescence of two fluorophores that are responsible for tissue autofluorescence, NADH and collagen, and of two oral squamous carcinoma cell lines and one immortalized benign epithelial cell line were measured in vitro. Gold nanoparticles of different shapes, both spheres and rods, quenched the fluorescence of the soluble NADH and collagen. Reduction of NADH fluorescence was due to oxidation of NADH to NAD+ catalyzed by gold nanoparticles (results we previously published). Reduction of collagen fluorescence appears due to photonic absorption of light. Furthermore, a mean quenching of 12/8% (p<0.00050) of the tissue autofluorescence of cell suspensions was achieved in this model when nanospheres were incubated with the live cells. Gold nanospheres significantly decrease cellular autofluorescence of live cells under physiological conditions when excited at 280nm. This is the first report to our knowledge to suggest the potential of developing targeted gold nanoparticles optical probes as contrast agents for fluorescence based diagnoses of cancer.

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