Mechanism and research progress of cancer treatment by α-therapy combined with immunotherapy / 中华核医学与分子影像杂志

Alpha-particles, which have strong cytotoxicity, could reduce radiation damage to surrounding tissues, and stimulate anti-tumor immune response, so they have good development prospect in cancer treatment. The current researches show that α-emitting radionuclides increase the presentation of major histocompatibility complex-I (MHC-Ⅰ) on tumor cells and induce immunogenic cell death (ICD) to activate immune response mediated by CD8 + T cells. As two methods of α-therapy, α radioimmunotherapy and diffusing α-emitters radiation therapy (DART) further enhance the anti-cancer effect when combined with immunotherapy. The methods of immunotherapy include adoptive cell therapy (ACT), immune checkpoint blockade, neutralization of immunosuppressive cells and immunoadjuvant. This article reviews the characteristics of α-particles for cancer treatment, the mechanism of immune response induced by ionizing radiation (including α-radionuclides) and the related research of α-therapy combined with immunotherapy.

Progress of α ray labeled probes in tumor targeted radionuclide therapy / 中华核医学与分子影像杂志

As an effective treatment for tumor, the radionuclide targeting therapy is developing rapidly. Radionuclides produced β ray or α ray can be used for labeling tumor targeting probes. Compared with β ray, α ray has higher linear energy transfer, which can destroy DNA more effectively and kill tumor cells thoroughly. Besides, the tissue penetration distance of α ray is short, which can reduce the damage to normal tissue. In recent years, α ray radionuclides are more and more used in tumor targeted therapy. A variety of probes have been labeled with different α ray radionuclides and used in the treatment of hematological malignancies, neuroendocrine neoplasms, prostate cancer, melanoma, etc. This article summarizes the progress of α ray radionuclides and their labeled probes in tumor treatment.

Health effects and consultations about radon exposure

Radon is a naturally occurring radioactive material classified as a carcinogen by the World Health Organization, and is known to be the factor with the second-greatest impact on lung cancer after smoking. An association between radon and lung cancer has consistently been reported in epidemiological studies on mine workers and residents of homes with indoor radon exposure. However, associations between radon and other diseases, such as leukemia and thyroid cancer, have yet to be confirmed due to a lack of consistent research findings and biological relevance. Such associations are unlikely because there is a very low likelihood that organs other than the lungs are exposed to radon upon inhalation due to the short half-life of radon and its progeny and the low permeability of alpha rays. In spring 2018, the radon bed mattress incident occurred, leading to a spike of concern and interest among the public regarding the health effects of radiation exposure. This paper presents a description of radon exposure and its health effects based on the current literature and provides practical information based on health consultations experienced following the 2018 radon mattress incident.

Radon and environmental diseases

People are generally exposed to radiation from natural sources. Radon is the most important radiation source among natural sources. Radon is a naturally occurring, radioactive noble gas that is odorless and tasteless. Radon is normally found at very low levels in outdoor air and in drinking water from rivers and lakes but higher levels in indoor air in homes, schools, and office buildings, and in well water. When radon undergoes radioactive decay, it expels high-energy alpha particles. The alpha particle radiation dose from long-term exposure increases the chance of developing lung cancer. Radon is the second most important cause of lung cancer after smoking. There is no known threshold concentration below which radon exposure presents no risk. Even low concentrations of radon can result in a small increase in the risk of lung cancer. No study of the radon exposure-lung cancer association has been performed in Korea. What is needed is a large-scale prospective study of the association between residential radon exposure and lung cancer. The cumulative indoor radon exposure is an important environmental health hazard (carcinogen).

Low energy proton beam induces tumor cell apoptosis through reactive oxygen species and activation of caspases

Proton beam is useful to target tumor tissue sparing normal cells by allowing precise dose only into tumor cells. However, the cellular and molecular mechanisms by which proton beam induces tumor cell death are still undefined. We irradiated three different tumor cells (LLC, HepG2, and Molt-4) with low energy proton beam (35 MeV) with spread out Bragg peak (SOBP) in vitro, and investigated cell death by MTT or CCK-8 assay at 24 h after irradiation. LLC and HepG2 cells were sensitive to proton beam at over 10 Gy to induce apoptosis whereas Molt-4 showed rather low sensitivity. Relative biological effectiveness (RBE) values for the death rate relative to gamma-ray were ranged from 1.1 to 2.3 in LLC and HepG2 but from 0.3 to 0.7 in Molt-4 at 11 d after irradiation by colony formation assay. The typical apoptotic nuclear DNA morphological pattern was observed by staining with 4'-6-diamidino-2-phenylindole (DAPI). Tiny fragmented DNA was observed in HepG2 but not in Molt-4 by the treatment of proton in apoptotic DNA fragment assay. By FACS analysis after stained with FITC-Annexin-V, early as well as median apoptotic fractions were clearly increased by proton treatment. Proton beam-irradiated tumor cells induced a cleavage of poly (ADP-ribose) polymerase-1 (PARP-1) and procaspases-3 and -9. Activity of caspases was highly enhanced after proton beam irradiation. Reactive oxygen species (ROS) were significantly increased and N-acetyl cysteine pretreatment restored the apoptotic cell death induced by proton beam. Furthermore, p38 and JNK but not ERK were activated by proton and dominant negative mutants of p38 and JNK revived proton-induced apoptosis, suggesting that p38 and JNK pathway may be activated through ROS to activate apoptosis. In conclusion, our data clearly showed that single treatment of low energy proton beam with SOBP increased ROS and induced cell death of solid tumor cells (LLC and HepG2) in an apoptotic cell death program by the induction of caspases activities.