WordNet

a substance that exerts some force or effect
a businessman who buys or sells for another in exchange for a commission (同)factor, broker
any agent or representative of a federal agency or bureau (同)federal agent
a representative who acts on behalf of other persons or organizations
an active and efficient cause; capable of producing a certain effect; "their research uncovered new disease agents"
how long something has existed; "it was replaced because of its age"
a time of life (usually defined in years) at which some particular qualification or power arises; "she was now of school age"; "tall for his eld" (同)eld
begin to seem older; get older; "The death of his wife caused him to age fast"
make older; "The death of his child aged him tremendously"

PrepTutorEJDIC

『代理人』;周旋人 / 働き(作用)を起こすもの;作用物,薬剤 / (政府機関,特にFBI,CIAなどの)部員,機関員
〈U〉(一般に)『年齢』,寿命;〈C〉(個々の)『年齢』,年 / 〈U〉成年(おとなとしての資格・権利を得る年齢;通例18または21歳) / 〈U〉『老齢』;《集合的に》老人たち / 〈U〉(人生の)『一時期』;〈C〉世代(generation) / 〈U〉〈C〉《しばしばA-》(歴史上の)『時代』 / 〈C〉《話》長い間 / 年をとる,ふける;〈物が〉古くなる / 〈年〉'を'とらせる;〈物〉'を'古びさせる

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2018/05/22 10:56:55」(JST)

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Cisplatin, a platinum-based chemotherapeutic and radio sensitizer

A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer.

Mechanism of action

Conventional chemotherapeutics are currently being used in conjunction with radiation therapy to increase its effectiveness. Examples include the fluoropyrimidines, gemcitabine and platinum analogs; fluoropyrimidines increase sensitivity by dysregulating S-phase cell cycle checkpoints in tumor cells. Gemcitabine progresses through a similar mechanism, causing cells in the S-phase to disrepair DNA damage caused by the radiation. Platinum analogs such as cisplatin inhibit DNA repair by cross linking strands, and so exacerbate the effects of DNA damage induced by radiation.^[1]

Limitations

One of the major limitations of radiotherapy is that the cells of solid tumors become deficient in oxygen. Solid tumors can outgrow their blood supply, causing a low-oxygen state known as hypoxia. Oxygen is a potent radiosensitizer, increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. Tumor cells in a hypoxic environment may be as much as 2 to 3 times more resistant to radiation damage than those in a normal oxygen environment.^[2] Much research has been devoted to overcoming this problem including the use of high pressure oxygen tanks, blood substitutes that carry increased oxygen, hypoxic cell radiosensitizers such as misonidazole and metronidazole, and hypoxic cytotoxins, such as tirapazamine.

Drug development

As of September 2016, there are a number of radiosensitizers in clinical trials.

Name	Sponsor	Description
NBTXR3	Nanobiotix	Also known as PEP503, NBTXR3 is injected via syringe directly into tumors by a surgeon.^[3]^[4] The drug then creates free radicals when exposed to x-rays.^[4] It is composed of hafnium oxide nanoparticles.^[3]^[5] The company is running four trials on the drug simultaneously. The four trials are a Phase II/III in soft tissue sarcoma of the extremity and trunk wall,^[6] a Phase I/II for hepatocellular carcinoma,^[7] a Phase I/II for prostate cancer,^[8] and a Phase I for squamous cell carcinoma of the oral cavity.^[9]
Nimoral	Azanta	This compound increases the yield of DNA damage from irradiation under hypoxic conditions. Nimoral is in Phase III in Europe as a first-line therapy for squamous cell carcinoma of the head and neck.^[10]
Trans Sodium Crocetinate (TSC)	Diffusion Pharmaceuticals	TSC is meant to increase the diffusion of oxygen through tissue. It was tested in a Phase II clinical trial in glioblastoma (GBM) patients.^[11] The results of the Phase II showed that 36% of the full-dose TSC patients were alive at 2 years, compared with historical survival values ranging from 27% to 30% for the standard of care.^[12]
NVX-108	NuvOx Pharma	NVX-108 is an oxygen therapeutic that is injected intravenously, picks up oxygen in the lungs, and delivers oxygen to hypoxic tissue. It is a Phase Ib/II clinical trial where it raises tumor oxygen levels prior to radiation therapy in order to radiosensitize them.^[13]

References

^ "The mechanism of action of radiosensitization of conventional chemotherapeutic agents". Seminars in Radiation Oncology. 13 (1): 13–21. doi:10.1053/srao.2003.50002. Retrieved 2016-08-10.
^ Harrison LB, Chadha M, Hill RJ, Hu K, Shasha D (2002). "Impact of tumor hypoxia and anemia on radiation therapy outcomes". Oncologist. 7 (6): 492–508. doi:10.1634/theoncologist.7-6-492. PMID 12490737.
^ ^a ^b "PharmaEngine, Nanobiotix Enter Global Pivotal Trial of PEP503 (NBTXR3) in Soft Tissue Sarcoma". businesswire.com. 8 October 2014.
^ ^a ^b "NanoXray video". nanobiotix.
^ [1]
^ "NBTXR3 Crystalline Nanoparticles and Radiation Therapy in Treating and Randomized Patients in Two Arms With Soft Tissue Sarcoma of the Extremity and Trunk Wall". ClinicalTrials.gov.
^ "NBTXR3 Crystalline Nanoparticles and Stereotactic Body Radiation Therapy in the Treatment of Liver Cancers". ClinicalTrials.gov.
^ "NBTXR3 Nanoparticles and EBRT or EBRT With Brachytherapy in the Treatment of Prostate Adenocarcinoma". ClinicalTrials.gov.
^ "NBTXR3 Crystalline Nanoparticles and Radiation Therapy in Treating Patients With Locally Advanced Squamous Cell Carcinoma of the Oral Cavity or Oropharynx". ClinicalTrials.gov.
^ "AF CRT +/- Nimorazole in HNSCC".
^ "Safety and Efficacy Study of Trans Sodium Crocetinate (TSC) With Concomitant Radiation Therapy and Temozolomide in Newly Diagnosed Glioblastoma (GBM)". ClinicalTrials.gov. November 2011.
^ Gainer JL, Sheehan JP, Larner JM, Jones DR (2016). "Trans sodium crocetinate with temozolomide and radiation therapy for glioblastoma multiforme". Journal of Neurosurgery. 126 (2): 460–466. doi:10.3171/2016.3.JNS152693.
^ "The Effects of NVX-108 as a Radiation Sensitizer in Glioblastoma (GBM)".

This article incorporates public domain material from the U.S. National Cancer Institute document "Dictionary of Cancer Terms".

External links

Radiosensitizer entry in the public domain NCI Dictionary of Cancer Terms

UpToDate Contents

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1. 頭頚部癌の放射線抵抗性を克服するための方法 methods to overcome radiation resistance in head and neck cancer
2. 高グレードの神経膠腫に対する補助放射線療法 adjuvant radiation therapy for high grade gliomas
3. 限局進行性および切除可能境界膵外分泌癌に対する初回化学療法および放射線治療 initial chemotherapy and radiation for nonmetastatic locally advanced unresectable borderline resectable and potentially resectable exocrine pancreatic cancer
4. 従来の癌の化学療法による皮膚合併症 cutaneous complications of conventional chemotherapy agents
5. 局所再発性頭頸部癌に対する再照射 reirradiation for locally recurrent head and neck cancer

English Journal

Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E inhibition.

Mayes PA, Degenhardt YY, Wood A, Toporovskya Y, Diskin SJ, Haglund E, Moy C, Wooster R, Maris JM.SourceDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA.
International journal of cancer. Journal international du cancer.Int J Cancer.2013 Feb 1;132(3):E149-57. doi: 10.1002/ijc.27781. Epub 2012 Sep 28.
Inhibition of centromere-associated protein-E (CENP-E) has demonstrated preclinical anti-tumor activity in a number of tumor types including neuroblastoma. A potent small molecule inhibitor of the kinesin motor activity of CENP-E has recently been developed (GSK923295). To identify an effective drug
PMID 22948716

Nuclear EGFRvIII-STAT5b complex contributes to glioblastoma cell survival by direct activation of the Bcl-XL promoter.

Latha K, Li M, Chumbalkar V, Gururaj A, Hwang Y, Dakeng S, Sawaya R, Aldape K, Cavenee WK, Bogler O, Furnari FB.SourceDepartment of Neurosurgery, University of Texas MD Anderson Cancer Center, TX, USA. klatha@mdanderson.org
International journal of cancer. Journal international du cancer.Int J Cancer.2013 Feb 1;132(3):509-20. doi: 10.1002/ijc.27690. Epub 2012 Jul 9.
Aberrant EGFR signaling strongly promotes glioma malignancy and treatment resistance. The most prevalent mutation, ΔEGFR/EGFRvIII, is an in-frame deletion of the extracellular domain, which occurs in more than 25% of glioblastomas and enhances growth and survival of tumor cells. Paradoxically, the
PMID 22729867

Japanese Journal

AN IODINE LABELED PORPHYRIN AS A NEW RADIATION SENSITIZER IN HUMAN BLADDER CANCER CELLS IN VITRO AND IN VIVO, COMBINING PHOTODYMAMIC THERAPY (PDT) WITH PHOTON ACTIVATION THERAPY (PAT)