scholarly journals Modulation of nanoparticle uptake, intracellular distribution, and retention with docetaxel to enhance radiotherapy

2020 ◽  
Vol 93 (1106) ◽  
pp. 20190742 ◽  
Author(s):  
Aaron Henry Bannister ◽  
Kyle Bromma ◽  
Wonmo Sung ◽  
Mesa Monica ◽  
Leah Cicon ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Linear Accelerator ◽  
Normal Tissue ◽  
Healthy Tissue ◽  
Triple Combination ◽  
Concurrent Treatment ◽  
Important Target ◽  
Normal Tissue Toxicity ◽  
Therapeutic Results ◽  
Surrounding Healthy Tissue

Objective: One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizing the damage to healthy tissue surrounding the tumor. We chose gold nanoparticles (GNPs) and docetaxel (DTX) as our choice of two radiosensitizing agents. They have a different mechanism of action which could lead to a synergistic effect. Our first goal was to assess the variation in GNP uptake, distribution, and retention in the presence of DTX. Our second goal was to assess the therapeutic results of the triple combination, RT/GNPs/DTX. Methods: We used HeLa and MDA-MB-231 cells for our study. Cells were incubated with GNPs (0.2 nM) in the absence and presence of DTX (50 nM) for 24 h to determine uptake, distribution, and retention of NPs. For RT experiments, treated cells were given a 2 Gy dose of 6 MV photons using a linear accelerator. Results: Concurrent treatment of DTX and GNPs resulted in over 85% retention of GNPs in tumor cells. DTX treatment also forced GNPs to be closer to the most important target, the nucleus, resulting in a decrease in cell survival and increase in DNA damage with the triple combination of RT/ GNPs/DTX vs RT/DTX. Our experimental therapeutic results were supported by Monte Carlo simulations. Conclusion: The ability to not only trap GNPs at clinically feasible doses but also to retain them within the cells could lead to meaningful fractionated treatments in future combined cancer therapy. Furthermore, the suggested triple combination of RT/GNPs/DTX may allow lowering the RT dose to spare surrounding healthy tissue. Advances in knowledge: This is the first study to show intracellular GNP transport disruption by DTX, and its advantage in radiosensitization.

Modulation of the Rho/ROCK Pathway in Heart and Lung after Thorax Irradiation Reveals Targets to Improve Normal Tissue Toxicity

2010 ◽  
Vol 11 (11) ◽  
pp. 1395-1404 ◽  
Author(s):  
Virginie Monceau ◽  
Nadia Pasinetti ◽  
Charlotte Schupp ◽  
Fred Pouzoulet ◽  
Paule Opolon ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Normal Tissue Toxicity

Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization

2020 ◽  
Vol 20 (2) ◽  
pp. 130-145 ◽  
Author(s):  
Keywan Mortezaee ◽  
Masoud Najafi ◽  
Bagher Farhood ◽  
Amirhossein Ahmadi ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Normal Tissue ◽  
Medical Science ◽  
Treatment Modalities ◽  
Radiation Toxicity ◽  
Normal Tissues ◽  
Normal Tissue Toxicity

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.

scholarly journals Nanoparticles in enhancing microwave imaging and microwave Hyperthermia effect for liver cancer treatment

2021 ◽  
Vol 60 (1) ◽  
pp. 223-236
Author(s):  
Walaa Maamoun ◽  
Mohamed I. Badawi ◽  
Ayman A Aly ◽  
Y. Khedr
Keyword(s):  
Silver Nanoparticles ◽  
Liver Cancer ◽  
Cancer Treatment ◽  
Electromagnetic Waves ◽  
Microwave Imaging ◽  
Healthy Tissue ◽  
Cancer Tissue ◽  
Hyperthermia Treatment ◽  
Hyperthermia Therapy ◽  
Surrounding Healthy Tissue

Abstract Hyperthermia therapy is a promising therapy for liver cancer treatment that utilizes external electromagnetic waves to heat the tumor zone to preferentially kill or minimize cancer cells. Nevertheless, it’s a challenge to realize localized heating of the cancer tissue without harming the surrounding healthy tissue. This research proposes to utilize nanoparticles as microwave absorbers to enhance microwave imaging and achieve localized hyperthermia therapy. A realistic 3D abdomen model has been segmented using 3D Slicer segmentation software, and then the obtained segmented CAD model exported to Computer Simulation Technology (CST STUDIO) for applying the Finite Element Modeling (FEM). Next investigating both imaging and treatment capability. Finally, the specific absorption rate (SAR) and temperature distribution were computed without nanoparticles and with different types of nanoparticles such as gold (GNPs) and silver nanoparticles at frequency 915 MHz. By comparing the achived results, it was seen that Silver nanoparticles can make a great enhancement in raising the temperature. However, this result was unsatisfactory but, after adding gold nanoparticles the temperature exceed 42°C, at frequency 915 MHz which is achieving the hyperthermia treatment without harming the nearby healthy tissue, GNPs also can achieve a great enhancement in SAR result

scholarly journals Radioimmunotherapy of PANC-1 human pancreatic cancer xenografts in NOD/SCID or NRG mice with Panitumumab labeled with Auger electron emitting, 111In or β-particle emitting, 177Lu

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Sadaf Aghevlian ◽  
Zhongli Cai ◽  
David Hedley ◽  
Mitchell A. Winnik ◽  
Raymond M. Reilly
Keyword(s):  
Normal Saline ◽  
Normal Tissue ◽  
Auger Electron ◽  
Absorbed Dose ◽  
Clonogenic Survival ◽  
Scid Mice ◽  
Human Pancreatic Cancer ◽  
Cell Counts ◽  
Normal Tissue Toxicity

Abstract Background Epidermal growth factor receptors (EGFR) are overexpressed on > 90% of pancreatic cancers (PnCa) and represent an attractive target for the development of novel therapies, including radioimmunotherapy (RIT). Our aim was to study RIT of subcutaneous (s.c.) PANC-1 human PnCa xenografts in mice using the anti-EGFR monoclonal antibody, panitumumab labeled with Auger electron (AE)-emitting, 111In or β-particle emitting, 177Lu at amounts that were non-toxic to normal tissues. Results Panitumumab was conjugated to DOTA chelators for complexing 111In or 177Lu (panitumumab-DOTA-[111In]In and panitumumab-DOTA-[177Lu]Lu) or to a metal-chelating polymer (MCP) with multiple DOTA to bind 111In (panitumumab-MCP-[111In]In). Panitumumab-DOTA-[177Lu]Lu was more effective per MBq exposure at reducing the clonogenic survival in vitro of PANC-1 cells than panitumumab-DOTA-[111In]In or panitumumab-MCP-[111In]In. Panitumumab-DOTA-[177Lu]Lu caused the greatest density of DNA double-strand breaks (DSBs) in the nucleus measured by immunofluorescence for γ-H2AX. The absorbed dose in the nucleus was 3.9-fold higher for panitumumab-DOTA-[177Lu]Lu than panitumumab-DOTA-[111In]In and 7.7-fold greater than panitumumab-MCP-[111In]In. No normal tissue toxicity was observed in NOD/SCID mice injected intravenously (i.v.) with 10.0 MBq (10 μg; ~ 0.07 nmoles) of panitumumab-DOTA-[111In]In or panitumumab-MCP-[111In]In or in NRG mice injected i.v. with 6.0 MBq (10 μg; ~ 0.07 nmoles) of panitumumab-DOTA-[177Lu]Lu. There was no decrease in complete blood cell counts (CBC) or increased serum alanine aminotransferase (ALT) or creatinine (Cr) or decreased body weight. RIT inhibited the growth of PANC-1 tumours but a 5-fold greater total amount of panitumumab-DOTA-[111In]In or panitumumab-MCP-[111In]In (30 MBq; 30 μg; ~ 0.21 nmoles) administered in three fractionated amounts every three weeks was required to achieve greater or equivalent tumour growth inhibition, respectively, compared to a single amount of panitumumab-DOTA-[177Lu]Lu (6 MBq; 10 μg; ~ 0.07 nmoles). The tumour doubling time (TDT) for NOD/SCID mice with s.c. PANC-1 tumours treated with panitumumab-DOTA-[111In]In or panitumumab-MCP-[111In]In was 51.8 days and 28.1 days, respectively. Panitumumab was ineffective yielding a TDT of 15.3 days vs. 15.6 days for normal saline treated mice. RIT of NRG mice with s.c. PANC-1 tumours with 6.0 MBq (10 μg; ~ 0.07 nmoles) of panitumumab-DOTA-[177Lu]Lu increased the TDT to 20.9 days vs. 11.5 days for panitumumab and 9.1 days for normal saline. The absorbed doses in PANC-1 tumours were 8.8 ± 3.0 Gy and 2.6 ± 0.3 Gy for panitumumab-DOTA-[111In]In and panitumumab-MCP-[111In]In, respectively, and 11.6 ± 4.9 Gy for panitumumab-DOTA-[177Lu]Lu. Conclusion RIT with panitumumab labeled with Auger electron-emitting, 111In or β-particle-emitting, 177Lu inhibited the growth of s.c. PANC-1 tumours in NOD/SCID or NRG mice, at administered amounts that caused no normal tissue toxicity. We conclude that EGFR-targeted RIT is a promising approach to treatment of PnCa.

scholarly journals Anti-oxidant vitamins reduce normal tissue toxicity induced by radio-immunotherapy

2000 ◽  
Vol 86 (2) ◽  
pp. 276-280 ◽  
Author(s):  
Rosalyn D. Blumenthal ◽  
Walter Lew ◽  
Albert Reising ◽  
Danielle Soyne ◽  
Lou Osorio ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Normal Tissue Toxicity ◽  
Anti Oxidant

scholarly journals Neoadjuvant Radiotherapy-Related Wound Morbidity in Soft Tissue Sarcoma: Perspectives for Radioprotective Agents

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2258
Author(s):  
Cameron M. Callaghan ◽  
M. M. Hasibuzzaman ◽  
Samuel N. Rodman ◽  
Jessica E. Goetz ◽  
Kranti A. Mapuskar ◽  
...  
Keyword(s):  
Wound Healing ◽  
Soft Tissue ◽  
Adjuvant Radiotherapy ◽  
Normal Tissue ◽  
Soft Tissue Sarcomas ◽  
Limb Amputation ◽  
Neoadjuvant Radiotherapy ◽  
Normal Tissue Toxicity ◽  
Radiation Induced ◽  
Intensity Radiation

Historically, patients with localized soft tissue sarcomas (STS) of the extremities would undergo limb amputation. It was subsequently determined that the addition of radiation therapy (RT) delivered prior to (neoadjuvant) or after (adjuvant) a limb-sparing surgical resection yielded equivalent survival outcomes to amputation in appropriate patients. Generally, neoadjuvant radiation offers decreased volume and dose of high-intensity radiation to normal tissue and increased chance of achieving negative surgical margins—but also increases wound healing complications when compared to adjuvant radiotherapy. This review elaborates on the current neoadjuvant/adjuvant RT approaches, wound healing complications in STS, and the potential application of novel radioprotective agents to minimize radiation-induced normal tissue toxicity.

Sign in / Sign up

Export Citation Format

Share Document