scholarly journals Brachytherapy Approach Using 177Lu Conjugated Gold Nanostars and Evaluation of Biodistribution, Tumor Retention, Dosimetry and Therapeutic Efficacy in Head and Neck Tumor Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1903
Author(s):  
Min-Ying Lin ◽  
Hsin-Hua Hsieh ◽  
Jyh-Cheng Chen ◽  
Chuan-Lin Chen ◽  
Nin-Chu Sheu ◽  
...  
Keyword(s):  
Head And Neck ◽  
Therapeutic Efficacy ◽  
Absorbed Dose ◽  
Tumor Model ◽  
Normal Tissues ◽  
Gold Nanostars ◽  
Biodistribution Studies ◽  
Surface Enhanced Raman ◽  
Tumor Viability ◽  
Minimal Damage

Brachytherapy can provide sufficient doses to head and neck squamous cell carcinoma (HNSCC) with minimal damage to nearby normal tissues. In this study, the β−-emitter 177Lu was conjugated to DTPA-polyethylene glycol (PEG) decorated gold nanostars (177Lu-DTPA-pAuNS) used in surface-enhanced Raman scattering and photothermal therapy (PTT). The accumulation and therapeutic efficacy of 177Lu-DTPA-pAuNS were compared with those of 177Lu-DTPA on an orthotopic HNSCC tumor model. The SPECT/CT imaging and biodistribution studies showed that 177Lu-DTPA-pAuNS can be accumulated in the tumor up to 15 days, but 177Lu-DTPA could not be detected at 24 h after injection. The tumor viability and growth were suppressed by injected 177Lu-DTPA-pAuNS but not nonconjugated 177Lu-DTPA, as evaluated by bioluminescent imaging. The radiation-absorbed dose of the normal organ was the highest in the liver (0.33 mSv/MBq) estimated in a 73 kg adult, but that of tumorsphere (0.5 g) was 3.55 mGy/MBq, while intravenous injection of 177Lu-DTPA-pAuNS resulted in 1.97 mSv/MBq and 0.13 mGy/MBq for liver and tumorsphere, respectively. We also observed further enhancement of tumor-suppressive effects by a combination of 177Lu-DTPA-pAuNS and PTT compared to 177Lu-DTPA-pAuNS alone. In conclusion, 177Lu-DTPA-pAuNS may be considered as a potential radiopharmaceutical agent for HNSCC brachytherapy.

scholarly journals A Modified Tyrosinase-Related Protein 2 Epitope Generates High-Affinity Tumor-Specific T Cells but Does Not Mediate Therapeutic Efficacy in an Intradermal Tumor Model

2006 ◽  
Vol 177 (1) ◽  
pp. 155-161 ◽  
Author(s):  
Jennifer A. McWilliams ◽  
Sean M. McGurran ◽  
Steven W. Dow ◽  
Jill E. Slansky ◽  
Ross M. Kedl
Keyword(s):  
T Cells ◽  
Therapeutic Efficacy ◽  
Tumor Model ◽  
Related Protein ◽  
High Affinity ◽  
Tyrosinase Related Protein

The Expression of Glutaminases and their Association with Clinicopathological Parameters in the Head and Neck Cancers

2021 ◽  
Vol 22 ◽  
Author(s):  
Haneen A . Basheer ◽  
Lina Elsalem ◽  
Anwar Salem ◽  
Artysha Tailor ◽  
Keith Hunter ◽  
...  
Keyword(s):  
Head And Neck ◽  
Tumor Grade ◽  
Head And Neck Cancers ◽  
Glutamine Metabolism ◽  
Clinicopathological Parameters ◽  
Normal Tissues ◽  
Enzyme Isoforms ◽  
Cd147 Expression ◽  
New Treatment ◽  
First Time

Background: The increased glutamine metabolism is a characteristic feature of cancer cells. The interconversion between glutamine and glutamate is catalyzed by two glutaminase isoforms, GLS1 and GLS2, which appear to have different roles in different types of cancer. We investigated for the first time the protein expression of GLS1 and GLS2, and their correlation with advanced clinicopathological parameters in head and neck cancers. Method: Consecutive slides from a tissue microarray comprised of 80 samples ranging from normal to metastatic, were stained immunohistochemically for GLS1, GLS2, HIF-1α or CD147. Following analysis by two expert pathologists we carried out statistical analysis of the scores. Results: GLS1 and GLS2 are upregulated at protein level in head and neck tumours compared to normal tissues and this increased expression correlated positively (GLS1) and negatively (GLS2) with tumor grade, indicating a shift of expression between GLS enzyme isoforms based on tumor differentiation. Increased expression of GLS1 was associated with high CD147 expression; and elevated GLS2 expression was associated with both high CD147 and high HIF-1α expressions. The correlation of the GLS1 and GLS2 with HIF-1α or CD147 was strongly associated with more advanced clinicopathological parameters. Conclusion: The increased expression of GLS1 and GLS2 may be explored as a new treatment for head and neck cancers.

Ionizing radiation and its considerations in imaging diagnosis: comparison of absorbed dose between cone beam computed tomography and multi-detector computed tomography in the head and neck

2021 ◽  
Author(s):  
P.L.E. Oliveira ◽  
C.R. Starling ◽  
C.L.P. Maurício ◽  
F.R. Guedes ◽  
M.A. Visconti ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Head And Neck ◽  
Cone Beam Computed Tomography ◽  
Absorbed Dose ◽  
Cone Beam ◽  
Thermoluminescent Dosimeters ◽  
Organ Tissue ◽  
The Mean ◽  
Average Adult ◽  
Multi Detector Computed Tomography

Introduction: The objective of this study was to compare the mean absorbed dose in patients undergoing head and neck examinations using two cone beam computed tomography (CBCT, Kodak and i-CAT) and one multi-detector computed tomography (MDCT). Methods: Three thermoluminescent dosimeters (TLDs), calibrated in air kerma, were positioned in 24 regions of the head and neck of a phantom simulating an average adult. The mean absorbed dose (mGy) values in these positions, for different organs and tissues, were obtained using correction factors, considering the ratio between the mass energy absorption coefficients of organ/tissue and air. Comparison between radiation doses in the most radiosensitive regions was done by calculating the ratio of these dose values, with propagated uncertainty. Results: The dose in all regions was significantly higher for MDCT when compared to CBCT. Concerning CBCT equipment, the Kodak device had a higher absorbed dose than the i-CAT for most of the regions tested. The uncertainty of the i-CAT was greater than that of the Kodak. Conclusion: Due to the considerable difference between absorbed doses, emphasizing the higher dose values obtained in MDCT, the dissemination of CBCT application in medicine is recommended, as well as further studies to broaden the criteria for use.

Oral Sequelae of Head and Neck Radiotherapy

2003 ◽  
Vol 14 (3) ◽  
pp. 199-212 ◽  
Author(s):  
A. Vissink ◽  
J. Jansma ◽  
F.K.L. Spijkervet ◽  
F.R. Burlage ◽  
R.P. Coppes
Keyword(s):  
Head And Neck ◽  
Neck Region ◽  
Normal Tissues ◽  
Radiation Caries ◽  
Temporomandibular Joints ◽  
Clinical Consequences ◽  
Radiation Induced ◽  
Heavy Burden ◽  
Effects Of Radiation ◽  
Induced Changes

In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed.

scholarly journals Targeting UCP2 Suppresses the FAK Signaling and Progression of Human Head and Neck Cancer Cells

2020 ◽  
pp. 1-8
Author(s):  
Yunfeng Zhao ◽  
Cherie Ann Nathan ◽  
Chunjing Zhang ◽  
Hongyan Du ◽  
Manikandan Panchatcharam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Uncoupling Protein ◽  
Human Head ◽  
Atp Production ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Lactate Formation

Background: New adjuvant therapies for human head and neck (H&N) cancer to improve the quality of life of the patients are in great demand. Our early studies have demonstrated that uncoupling protein 2 (UCP2) is upregulated in the tumor tissues of H&N cancer compared to the adjacent normal tissues; however, the role of UCP2 in H&N cancer has not been studied. Objective: In this manuscript, we aim to examine whether UCP2 contributes to H&N cancer progression in vitro. Methods: We generated UCP2 stable knockdown H&N cancer cells and detected the effects of UCP2 inhibition on cell proliferation, migration, invasion, 3D spheroid formation, and the sensitivity to a chemodrug treatment. Results: Knockdown of UCP2 suppressed the progression of H&N cancer in vitro, which might be mediated via the following mechanism: 1) increased the G1 phase whereas decreased the S phase of the cell cycle, which could be mediated by suppression of the G1/S regulators including CDK4/6 and cyclin D1. 2) Decreased mitochondrial oxygen consumption, ATP production, and lactate formation, which is consistent with the downregulation of c-Myc. 3) FAK may serve as the upstream signaling molecule, and its action was mediated by Akt and ERK. Conclusions: Our studies first demonstrate that targeting UCP2 may suppress H&N cancer progression in vitro.

scholarly journals Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1666
Author(s):  
Zijing Liu ◽  
Lihua Dong ◽  
Zhuangzhuang Zheng ◽  
Shiyu Liu ◽  
Shouliang Gong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Serious Adverse Event ◽  
Oral Infections ◽  
Normal Tissues ◽  
Radiation Induced ◽  
Swallowing Muscles

Radiation therapy is a common treatment for head and neck cancers. However, because of the presence of nerve structures (brain stem, spinal cord, and brachial plexus), salivary glands (SGs), mucous membranes, and swallowing muscles in the head and neck regions, radiotherapy inevitably causes damage to these normal tissues. Among them, SG injury is a serious adverse event, and its clinical manifestations include changes in taste, difficulty chewing and swallowing, oral infections, and dental caries. These clinical symptoms seriously reduce a patient’s quality of life. Therefore, it is important to clarify the mechanism of SG injury caused by radiotherapy. Although the mechanism of radiation-induced SG injury has not yet been determined, recent studies have shown that the mechanisms of calcium signaling, microvascular injury, cellular senescence, and apoptosis are closely related to oxidative stress. In this article, we review the mechanism by which radiotherapy causes oxidative stress and damages the SGs. In addition, we discuss effective methods to prevent and treat radiation-induced SG damage.

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