Objective： To observe the influence of connexin 43 （Cx43） on the bystander effect induced by cytosine deaminase （CD） and herpes simplex virus thymidine kinase （HSV-tk） coexpression suicide genes system in human...Objective： To observe the influence of connexin 43 （Cx43） on the bystander effect induced by cytosine deaminase （CD） and herpes simplex virus thymidine kinase （HSV-tk） coexpression suicide genes system in human cholangiocarcinoma QBC939 cells and transplantation tumors in nude mice. Methods： In vitro, the CD＋tk＋ and CD＋tk＋Cx＋ cells were respectively treated with 5-fluorocytosine （5-Fc） and Ganciclovir （GCV）. The cytotoxic effect was evaluated by MTT method. In order to investigate the influence of Cx43 on the bystander effect, the size of transplantation tumors of the CD＋tk＋ and CD＋tk＋Cx＋ cells was measured before and after application of 5-Fc and GCV. Results： CD and tk genes were stably expressed in transfected QBC939 cells. The increased expression of Cx43 was determined by testing for the presence of Cx43 mRNA by RT-PCR and the presence of Cx43 protein by Western Blot in CD＋tk＋Cx＋ cells. The killing effect of 5-Fc and GCV on CD＋tk＋Cx＋ cells was more effective than that on CD＋tk＋ cells both in vitro and in vivo. Conclusion： Double suicide genes system CD/5-Fc＋tk/GCV could induce remarkable killing effect on cholangiocarcinoma cells in vitro and transplantation tumors in vivo. The cotransfection of Cx43 gene could enhance the bystander effect and hence the inhibition of carcinoma cells.展开更多
Objective Since most reports on bystander effect have been only concerned with radiation-induced damage, the present paper aimed at disclosing whether low dose radiation could induce a stimulatory or beneficial bystan...Objective Since most reports on bystander effect have been only concerned with radiation-induced damage, the present paper aimed at disclosing whether low dose radiation could induce a stimulatory or beneficial bystander effect. Methods A co-culture system containing irradiated antigen presenting cells (J774A.1) and unirradiated T lymphocytes (EL-4) was established to observe the effect of J774A.1 cells exposed to both low and high doses of X-rays on the unirradiated EL-4 cells. Incorporation of 3H-TdR was used to assess the proliferation of the EL-4 cells, expression of CD80/86 and CD48 on J774A.1 cells was measured with immunohistochemistry and flow cytometry, respectively. NO release from J774A.1 cells was estimated with nitrate reduction method. Results Low dose-irradiated J774A.1 cells could stimulate the proliferation of the unirradiated EL-4 cells while the high dose-irradiated J774A.1 cells exerted an inhibitory effect on the proliferation of the unirradiated EL-4 cells. Preliminary mechanistic studies illustrated that the differential changes in CD48 expression and NO production by the irradiated J774A.1 cells after high and low dose radiation might be important factors underlying the differential bystander effect elicited by different doses of radiation. Conclusion Stimulatory bystander effect can be induced in immune cells by low dose radiation.展开更多
Niigata University Hospital is a regional center institution of cancer therapy where many patients with gastrointestinal stromal tumors （GISTs） are visiting to seek the latest treatment.During the time Ⅰ was treati...Niigata University Hospital is a regional center institution of cancer therapy where many patients with gastrointestinal stromal tumors （GISTs） are visiting to seek the latest treatment.During the time Ⅰ was treating GIST patients there with imatinib,a tyrosine kinase inhibitor,a small concern was raised：Ⅰ successively encountered patients who were newly diagnosed as having malignant neoplasms during the course of their treatment.Of the 70 GIST patients who were enrolled in our prospective study of imatinib therapy,seven suffered from second primary malignancies （SPMs）.One female GIST patient who suffered from advanced esophageal cancer died of the SPM,whereas the remaining six patients continued with their imatinib therapy and their prognoses were not affected by their SPMs.I reported on the risk of SPMs in GIST patients under imatinib therapy to an international journal of clinical oncology （1）.As the patient cohort of our study was so small in number to apply to statistical analysis,our observation was no more than a clinical alert.展开更多
BACKGROUND: Understanding bystander reactions to an emergency is an important component of effective training. Four stages of bystander intervention (BI) have been previously described: noticing the situation as a pro...BACKGROUND: Understanding bystander reactions to an emergency is an important component of effective training. Four stages of bystander intervention (BI) have been previously described: noticing the situation as a problem, interpreting when it is appropriate to intervene, recognizing personal responsibility to intervene, and knowing how to intervene. Using virtual reality (VR) to simulate emergencies such as sudden cardiac arrest (SCA) can be used to study these stages. METHODS: In a secondary analysis of an observational cohort study, we analyzed bystander self-effi cacy for stages of BI before and after simulated SCA. Each subject participated in a singleplayer, immersive, VR SCA scenario. Subjects interacted with simulated bystanders through voice commands (“call 911”,“get an AED”). Actions taken in scenario, like performing CPR, were documented. Scenario BI actions were compared based on dichotomized comfort/discomfort. RESULTS: From June 2016 to June 2017, 119 subjects participated. Average age was 37±14 years, 44% were female and 46% reported CPR training within 2 years. During the scenario, 98%“noticed the event” and “interpreted it as a problem”, 78%“took responsibility”, and 54%“possessed the necessary skills”. Self-effi cacy increased from pre- to post-scenario: noticing the event increased from 80% to 96%;interpreting as a problem increased from 86% to 97%;taking responsibility increased from 56% to 93%;possessing necessary skills increased from 47% to 63%(P<0.001). CONCLUSION: Self-efficacy to respond to an SCA event increased pre- to post-scenario. Bystanders who reported feeling comfortable “taking responsibility to intervene” during an emergency were more likely to take action during a simulated emergency.展开更多
BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect a...BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma.CASE SUMMARY A 44-year-old female presented with shortness of breath.Eleven years prior,she was diagnosed with athymic tumor located in the anterosuperior mediastinum.She underwent extensive tumor resection,and the postoperative pathologic diagnosis was thymic carcinoma.She was administered 50 Gy/25 Fx of postoperative radiation.In 2019,she was diagnosed with a recurrence of thymic carcinoma,with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity,the largest of which was in the diaphragm pleura proximal to the pericardium,with a size of 6.7 cm×5.3 cm×4.8 cm.She received carbonion radiotherapy.After carbon-ion radiotherapy treatment,the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging.We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case.CONCLUSION This report is the first of obvious abscopal and bystander effects following carbonion irradiation in a human patient,and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.展开更多
In the past 20 years, the classic paradigm in radiobiology recognizing DNA as the main target for the action of radiation has changed. The new paradigm assumes that both targeted and non-targeted effects of radiation ...In the past 20 years, the classic paradigm in radiobiology recognizing DNA as the main target for the action of radiation has changed. The new paradigm assumes that both targeted and non-targeted effects of radiation determine the final outcome of irradiation. Radiotherapy is one of the main modality treatments of neoplastic diseases with intent to cure, or sometimes to palliate only, thus radiation-induced non-targeted effect, commonly referred to as the radiation-induced bystander effect (RIBE) may have a share in cancer treatment. RIBE is mediated by molecular signaling from radiation targeted cells to their non-irradiated neighbors, and comprises such phenomena as bystander effect, genomic instability, adaptive response and abscopal effect. Whereas first three phenomena may appear both in vitro and in vivo, an abscopal effect is closely related to partial body irradiation and is a systemic effect mediated by immunologic system which synergizes with radiotherapy. From the clinical point of view abscopal effect is particularly interesting due to both its possible valuable contribution to the treatment of metastases, and the potential harmful effects as induction of genetic instability and carcinogenesis. This review summarized the main results of investigations of non-targeted effects coming from in vitro monolayer cultures, 3-dimentional models of tissues, preclinical studies on rodents and clinically observed beneficial abscopal effects with particular emphasis on participation of immunotherapy in the creation of abscopal effects.展开更多
We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient ...We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments,with each recurrence occurring 7-8 wk from a GCP.After his third recurrence,he was prescribed successive treatment with rifampicin,berberine,and monthly administered GCP for 4 mo,and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy,and eventually died of septic shock.Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis.From the treatment process and laboratory investigations,it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state.Incorporation of rifampicin,berberine,and monthly GCP into cyclosporine can enhance the immunosuppressive effect.In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure,the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.展开更多
Mammalian cells respond to ionization radiation by sending out extracellular signals to affect non-irradiated neighboring cells, which is referred to as radiation bystander effect. In
Purpose: Ionizing radiation is a well known human carcinogen. It has been generally accepted that direct damage to nuclear DNA is the main caused to induce genotoxicity
Objective： To find out whether ultraviolet ray, a kind of non-ionic ray, could cause the bystander effect, the UV exposed MOLT-4 cells had been investigated. Methods： Two experiment groups were carried out, in which...Objective： To find out whether ultraviolet ray, a kind of non-ionic ray, could cause the bystander effect, the UV exposed MOLT-4 cells had been investigated. Methods： Two experiment groups were carried out, in which cells were culture and treated at two concentrations： 2 × 10^5/mL and 5 × 10^5/mL. All other treatments were the same. Part of the cells was labeled with DID and exposed to UV ray for 40 s as effect cells; other cells was untreated as bystander cells. Then, the cells were co-cultured and harvested at 4 h interval over a period of 24 h. Annexin V-FITC/PI assay was used to evaluate the bystander effect in bystander cells co-cultured with effected cells. Laser confocal microscope method was used to observe the morphologic changes of the bystander cells. Results： The percentage of cells undergoing apoptosis in the bystander cells was increased over time compared with the control group. They were 6.84%, 8.09%, 9.88%, 17.64%, 17.43%, 30.99% and 37.93% respectively in 0 h, 4 h, 8 h, 12 h, 16 h, 20 h and 24 h. When observed by laser scanning confocal microscope, the bystander cells show some classic character of apoptosis such as chromosome condense, phosphatidylsedne transfer and formation of apoptotic bodies. Conclusion： Bystander effect is significant in un-irradiated bystander MOLT-4 cells when co-cultured with UV exposed cells.展开更多
This work aims to theoretically show the development of a nonequilibrium of radiation-induced bystander effect (RIBE) under steep dose gradient regions that typically occur in the field edges of a beam. We applied the...This work aims to theoretically show the development of a nonequilibrium of radiation-induced bystander effect (RIBE) under steep dose gradient regions that typically occur in the field edges of a beam. We applied the kinetics model proposed by (McMahon et al. 2013) for in vivo conditions coupled with a hypothesis called “Layer-limited bystander signaling (LLBS)” to demonstrate 1) an enhancement in TCP (i.e. Enhanced TCP or ETCP) due to bystander signals, 2) the development of nonequilibrium of RIBE under steep dose gradient regions and 3) the reduction in ETCP in the surface of Clinical Target Volume (CTV) due to the non-equilibrium of RIBE. We incorporated the elements of RIBE directly in the existing Poisson LQ model available in Pinnacle3 TPS (Version 9.10.0) to compute the percentage reduction of ETCP in the tumor surface due to nonequilibrium of RIBE. The percentage improvement in TCP obtained in tumor surface by accounting for RIBE is about 46% lower than that obtained in the interior of the tumor. This suggests that relatively more number of cancerous cells might survive in the vicinity of tumor surface. The result obtained from the study is indicative of an additional uncertainty component associated with radiation treatment. Hence, this paper suggests that the radiation treatments employing steep dose gradients could be biophysically different in many ways.展开更多
Radiation-induced bystander effect is the phenomenon that the cells which are not directly exposed to radiation have identical or similar biological reactions with the cells of direct exposure to radiation. It is a co...Radiation-induced bystander effect is the phenomenon that the cells which are not directly exposed to radiation have identical or similar biological reactions with the cells of direct exposure to radiation. It is a common second reaction of radiotherapy and has a strong impact on cancer patients. Here we review and synthesize its studies in vitro and in vivo, its time effect and the mechanism. And the existing problems and its research significance are also discussed.展开更多
Genomic instability after radiation is the main reason of the increase of malignancy degree and normal tissuetransformation[1]. Previous study indicated that bystander cells show more long-term genomic instability aft...Genomic instability after radiation is the main reason of the increase of malignancy degree and normal tissuetransformation[1]. Previous study indicated that bystander cells show more long-term genomic instability afterradiation[2].In this study, non-small cell lung cancer cell line (A549) was radiated with X-rays (30 kV of 2 Gy), and theconditioned medium was transferred to bystander cells. The fast and slowly proliferating populations in bystandercells were isolated by the colony formation assay. After one month, the chromosome number (Table 1, Fig. 1),drug resistance ability (Fig. 2) and cancer stem-like cell enrichment (Fig. 3) were investigated in fast and slowlyproliferating cells, respectively.展开更多
Since the first report by Nagasawa et al.[1] in 1992, which demonstrates evidences that non-irradiated bystandercells also showed damage of sister chromatid exchange in samples irradiated with low-dose α particles, r...Since the first report by Nagasawa et al.[1] in 1992, which demonstrates evidences that non-irradiated bystandercells also showed damage of sister chromatid exchange in samples irradiated with low-dose α particles, radiationinduced bystander effect (RIBE) has been studied for more than decades and many publications showed that RIBEswere found after treatment of both low and high-LET radiations. However, there are also some reports showingcontrary facts that no obvious bystander effects can be found, for example Fournier et al.[2] reported that theyobserved no early cytogenetic damage in the bystander cells after heavy ion microbeam irradiation. RIBE is ofgreat interest in radiotherapy using X-ray radiation or high-LET heavy ions because of RIBE-related cell killing andcarcinogenesis in neighboring normal cells[3]. In this work, we investigated the damage in bystander cells exposedto medium from cells irradiated with X-ray and carbon beam.展开更多
Background Cytosine deaminase （CD） converts 5-fluorocytosine （5-FC） to 5-fluorouracil （5-FU） in CD/5-FC gene therapy, 5-FU will be mostly converted into nontoxic 13-alanine without uracil phosphoribosyltransfera...Background Cytosine deaminase （CD） converts 5-fluorocytosine （5-FC） to 5-fluorouracil （5-FU） in CD/5-FC gene therapy, 5-FU will be mostly converted into nontoxic 13-alanine without uracil phosphoribosyltransferase （UPRT）. UPRT catalyzes the conversion of 5-FU to 5-fluorouridine monophosphate, which directly kills CD：：UPRT-expressing cells and surrounding cells via the bystander effect. But the pharmacokinetics and the bystander effect of CD：：UPRT/5-FC has not been verified in vivo and in vitro. Before the CD：：UPRT/5-FC bi-gene therapy system is used in clinical trial, it is essential to monitor the transgene expression and function in vivo. Thus, we developed a preclinical tumor model to investigate the feasibility of using ^19F-magnetic resonance spectroscopy （^19F-MRS） and optical imaging to measure non-invasive CD and UPRT expression and its bystander effect. Methods C6 and C6-CD：：UPRT cells were cultured with 5-FC. The medium, cells and their mixture were analyzed by ^19F-MRS. Rats with intracranial xenografted encephalic C6-CD：：UPRT glioma were injected intraperitoneally with 5-FC and their ^19F-MRS spectra recorded. Then the pharmacokinetics of 5-FC was proved. Mixtures of C6 and C6-CD：：UPRT cells at different ratios were cultured with 5-FC and the cytotoxic efficacy and survival rate of cells recorded. To determine the mechanism of the bystander effect, the culture media from cell comprising 25% and 75% C6-CD：：UPRT cells were examined by ^19F-MRS. A comparative study of mean was performed using analysis of variance （ANOVA）. Results ^19F-MRS on samples from C6-CD：：UPRT cells cultured with 5-FC showed three broad resonance signals corresponding to 5-FC, 5-FU and fluorinated nucleotides （F-Nuctd）. For the C6 mixture, only the 5-FC peak was detected. In vivo serial ^19F-MRS spectra showed a strong 5-FC peak and a weak 5-FU peak at 20 minutes after 5-FC injection. The 5-FU concentration reached a maximum at about 50 minutes. The F-Nuctd signal appeared after about 1 hour, reached a maximum at around 160 minutes, and was detectable for several hours. At a 10% ratio of C6-CD：：UPRT cells, the survival rate was （79.55±0.88）% （P 〈0.01）. As the C6-CD：：UPRT ratio increased, the survival rate of the cells decreased. ^19F-MRS showed that the signals for 5-FU and F-Nuctd in the culture medium increased as the ratio of C6-CD：：UPRT in the mixture increased. Conclusions ^19F-MRS studies indicated that C6-CD：：UPRT cells could effectively express CD and UPRT enzymes. The CD：：UPRT/5-FC system showed an obvious bystander effect. This study demonstrated that CD：：UPRT/5-FC gene therapy is suitable for 5-FC to F-Nuctd metabolism; and ^19F-MRS can monitor transferred CD：：UPRT gene expression and catalysis of substrates noninvasively, dynamically and quantitatively.展开更多
Radiation-induced bystander effect(RIBE)and abscopal effect(RIAE)are non-target cellular responses outside the radiation field.It has been recognized that these effects are of great significance to both radiation prot...Radiation-induced bystander effect(RIBE)and abscopal effect(RIAE)are non-target cellular responses outside the radiation field.It has been recognized that these effects are of great significance to both radiation protection of environmental low-dose radiation and clinical radiotherapy in which the anti-tumor abscopal effect is even beneficial to patients.However,the mechanisms of them are still obscure.This review briefly introduced the inflammatory signaling factors and immune regulation in RIBE in vitro and RIAE on normal tissues and organisms,and emphasized the genetic consequences of RIAE.Based on a large number of investigation results,we suggest that it’s time to incorporate RIBE and RIAE into the concept of“classic”radiation biology.展开更多
Aim:We aimed to investigate the association between bystander cardiopulmonary resuscitation(CPR)and survival of patients with out-of-hospital cardiac arrests(OHCA)in Beiing.Methods:This observational study analyzed ad...Aim:We aimed to investigate the association between bystander cardiopulmonary resuscitation(CPR)and survival of patients with out-of-hospital cardiac arrests(OHCA)in Beiing.Methods:This observational study analyzed adult patients with OHCA treated by the Beiing emergency medical service(EMS)from January 2013 to December 2017.Data were collected in a Utstein style with a 1-year follow-up and a primary outcome 01 survival to hospital discharge.Secondary outcomes were return of spontaneous circulation(ROSC),survival to admission,favorable neurological outcome at hospital discharge,and survival and favorable neurological outcomes of up to 1 year.Results:A total of 5016 patients with OHCA from Beiing's urban area were recorded by EMS,wherein 765 patients(15.25%)underwent bystander CPR.The data were propensity score-matched forage,sex,location,witness,aetiology,initial rhythm,and call to EMS arrival to compare the difference between the occurrence and nonoccurrence of bystander CPR.The survival upon the discharge of patients who experienced bystander CPR was superior to that of patients who did not receive bystander CPR(3.7%vs 1.2%,respectively;P<0.001).Moreover,patients with OHCA resuscitated with bystander CPR achieved better outcomes of ROSC,survival to admission,favorable neurological outcome at hospital discharge,survival and favorable neurological outcome after 1 year compared with those who were not resuscitated with bystander CPR.Conclusion:Survival and neu rological outcome of patients who underwent bystander CPR was better than those who underwent nonbystander CPR in Beiing.However,the rate of bystander CPR was low.展开更多
This paper presents a comprehensive overview of the historical trajectory and development in biophoton studies over the past 100 years,with a particular focus on the recent progress regarding the pivotal role of bioph...This paper presents a comprehensive overview of the historical trajectory and development in biophoton studies over the past 100 years,with a particular focus on the recent progress regarding the pivotal role of biophoton in mediating radiation-induced bystander effects(RIBE).The exploration of biophoton mystery starts from the initial observation of mitogenetic radiation and continues to develop to the contemporary science of biophotonics.The properties and underlying mechanisms of biophoton emission are described with illustrative examples from diverse biological systems such as plants,animals and humans.The conclusive evidence of cell-to-cell commu-nication facilitated by biophoton signaling is presented,followed by an elaborate interpretation of potential mechanisms through which biophoton mediates RIBE.The engagement of mitochondria and exosomes in this process is extensively clarified,by highlighting their significant roles in biophoton-mediated RIBE.The advances in biophoton research in respect of bystander response to ionizing radiation may offer profound insights into radiobiology and provide for possible future applications as well in radiation medicine and protection.展开更多
We report resuscitation of a near-drowning child by a bystander in a rural south China township.Resuscitation was performed on a 6-year-old,otherwise healthy boy who was witnessed drowning in a river,with submersion f...We report resuscitation of a near-drowning child by a bystander in a rural south China township.Resuscitation was performed on a 6-year-old,otherwise healthy boy who was witnessed drowning in a river,with submersion for approximately 12 min.Following several resuscitation attempts,spontaneous breathing was established at the scene and the boy was transferred to a nearby hospital.He developed pneumonia but recovered completely on the ward and was discharged without any neurologic disabilities.This case shows that early bystander resuscitation is an important factor for survival after submersion.The search for an ideal approach to resuscitation must continue,and all members of society must work together towards this goal.展开更多
A public debate on the bystander effect,prompted by a viral video of a fatal traffic accident,has highlighted continued gaps in China’s'Good Samaritan'laws—legal protections for those who volunteer to help v...A public debate on the bystander effect,prompted by a viral video of a fatal traffic accident,has highlighted continued gaps in China’s'Good Samaritan'laws—legal protections for those who volunteer to help victims.The 94-second video from Zhumadian,Henan,recorded in April but circulated in mid-June,showed a展开更多
基金The National High Technology Research and Development Program of China (863 Program) (No. 2002AA214061).
文摘Objective： To observe the influence of connexin 43 （Cx43） on the bystander effect induced by cytosine deaminase （CD） and herpes simplex virus thymidine kinase （HSV-tk） coexpression suicide genes system in human cholangiocarcinoma QBC939 cells and transplantation tumors in nude mice. Methods： In vitro, the CD＋tk＋ and CD＋tk＋Cx＋ cells were respectively treated with 5-fluorocytosine （5-Fc） and Ganciclovir （GCV）. The cytotoxic effect was evaluated by MTT method. In order to investigate the influence of Cx43 on the bystander effect, the size of transplantation tumors of the CD＋tk＋ and CD＋tk＋Cx＋ cells was measured before and after application of 5-Fc and GCV. Results： CD and tk genes were stably expressed in transfected QBC939 cells. The increased expression of Cx43 was determined by testing for the presence of Cx43 mRNA by RT-PCR and the presence of Cx43 protein by Western Blot in CD＋tk＋Cx＋ cells. The killing effect of 5-Fc and GCV on CD＋tk＋Cx＋ cells was more effective than that on CD＋tk＋ cells both in vitro and in vivo. Conclusion： Double suicide genes system CD/5-Fc＋tk/GCV could induce remarkable killing effect on cholangiocarcinoma cells in vitro and transplantation tumors in vivo. The cotransfection of Cx43 gene could enhance the bystander effect and hence the inhibition of carcinoma cells.
基金This work was supported by grants from NSFC (No. 39270207, No. 39570188).
文摘Objective Since most reports on bystander effect have been only concerned with radiation-induced damage, the present paper aimed at disclosing whether low dose radiation could induce a stimulatory or beneficial bystander effect. Methods A co-culture system containing irradiated antigen presenting cells (J774A.1) and unirradiated T lymphocytes (EL-4) was established to observe the effect of J774A.1 cells exposed to both low and high doses of X-rays on the unirradiated EL-4 cells. Incorporation of 3H-TdR was used to assess the proliferation of the EL-4 cells, expression of CD80/86 and CD48 on J774A.1 cells was measured with immunohistochemistry and flow cytometry, respectively. NO release from J774A.1 cells was estimated with nitrate reduction method. Results Low dose-irradiated J774A.1 cells could stimulate the proliferation of the unirradiated EL-4 cells while the high dose-irradiated J774A.1 cells exerted an inhibitory effect on the proliferation of the unirradiated EL-4 cells. Preliminary mechanistic studies illustrated that the differential changes in CD48 expression and NO production by the irradiated J774A.1 cells after high and low dose radiation might be important factors underlying the differential bystander effect elicited by different doses of radiation. Conclusion Stimulatory bystander effect can be induced in immune cells by low dose radiation.
文摘Niigata University Hospital is a regional center institution of cancer therapy where many patients with gastrointestinal stromal tumors （GISTs） are visiting to seek the latest treatment.During the time Ⅰ was treating GIST patients there with imatinib,a tyrosine kinase inhibitor,a small concern was raised：Ⅰ successively encountered patients who were newly diagnosed as having malignant neoplasms during the course of their treatment.Of the 70 GIST patients who were enrolled in our prospective study of imatinib therapy,seven suffered from second primary malignancies （SPMs）.One female GIST patient who suffered from advanced esophageal cancer died of the SPM,whereas the remaining six patients continued with their imatinib therapy and their prognoses were not affected by their SPMs.I reported on the risk of SPMs in GIST patients under imatinib therapy to an international journal of clinical oncology （1）.As the patient cohort of our study was so small in number to apply to statistical analysis,our observation was no more than a clinical alert.
基金supported by the Medtronic Foundationthe Laerdal Foundation
文摘BACKGROUND: Understanding bystander reactions to an emergency is an important component of effective training. Four stages of bystander intervention (BI) have been previously described: noticing the situation as a problem, interpreting when it is appropriate to intervene, recognizing personal responsibility to intervene, and knowing how to intervene. Using virtual reality (VR) to simulate emergencies such as sudden cardiac arrest (SCA) can be used to study these stages. METHODS: In a secondary analysis of an observational cohort study, we analyzed bystander self-effi cacy for stages of BI before and after simulated SCA. Each subject participated in a singleplayer, immersive, VR SCA scenario. Subjects interacted with simulated bystanders through voice commands (“call 911”,“get an AED”). Actions taken in scenario, like performing CPR, were documented. Scenario BI actions were compared based on dichotomized comfort/discomfort. RESULTS: From June 2016 to June 2017, 119 subjects participated. Average age was 37±14 years, 44% were female and 46% reported CPR training within 2 years. During the scenario, 98%“noticed the event” and “interpreted it as a problem”, 78%“took responsibility”, and 54%“possessed the necessary skills”. Self-effi cacy increased from pre- to post-scenario: noticing the event increased from 80% to 96%;interpreting as a problem increased from 86% to 97%;taking responsibility increased from 56% to 93%;possessing necessary skills increased from 47% to 63%(P<0.001). CONCLUSION: Self-efficacy to respond to an SCA event increased pre- to post-scenario. Bystanders who reported feeling comfortable “taking responsibility to intervene” during an emergency were more likely to take action during a simulated emergency.
基金Supported by Key R&D Plan of Science and Technology Program of Gansu Province,China,No.19YF3FH001.
文摘BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma.CASE SUMMARY A 44-year-old female presented with shortness of breath.Eleven years prior,she was diagnosed with athymic tumor located in the anterosuperior mediastinum.She underwent extensive tumor resection,and the postoperative pathologic diagnosis was thymic carcinoma.She was administered 50 Gy/25 Fx of postoperative radiation.In 2019,she was diagnosed with a recurrence of thymic carcinoma,with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity,the largest of which was in the diaphragm pleura proximal to the pericardium,with a size of 6.7 cm×5.3 cm×4.8 cm.She received carbonion radiotherapy.After carbon-ion radiotherapy treatment,the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging.We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case.CONCLUSION This report is the first of obvious abscopal and bystander effects following carbonion irradiation in a human patient,and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.
文摘In the past 20 years, the classic paradigm in radiobiology recognizing DNA as the main target for the action of radiation has changed. The new paradigm assumes that both targeted and non-targeted effects of radiation determine the final outcome of irradiation. Radiotherapy is one of the main modality treatments of neoplastic diseases with intent to cure, or sometimes to palliate only, thus radiation-induced non-targeted effect, commonly referred to as the radiation-induced bystander effect (RIBE) may have a share in cancer treatment. RIBE is mediated by molecular signaling from radiation targeted cells to their non-irradiated neighbors, and comprises such phenomena as bystander effect, genomic instability, adaptive response and abscopal effect. Whereas first three phenomena may appear both in vitro and in vivo, an abscopal effect is closely related to partial body irradiation and is a systemic effect mediated by immunologic system which synergizes with radiotherapy. From the clinical point of view abscopal effect is particularly interesting due to both its possible valuable contribution to the treatment of metastases, and the potential harmful effects as induction of genetic instability and carcinogenesis. This review summarized the main results of investigations of non-targeted effects coming from in vitro monolayer cultures, 3-dimentional models of tissues, preclinical studies on rodents and clinically observed beneficial abscopal effects with particular emphasis on participation of immunotherapy in the creation of abscopal effects.
文摘We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments,with each recurrence occurring 7-8 wk from a GCP.After his third recurrence,he was prescribed successive treatment with rifampicin,berberine,and monthly administered GCP for 4 mo,and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy,and eventually died of septic shock.Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis.From the treatment process and laboratory investigations,it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state.Incorporation of rifampicin,berberine,and monthly GCP into cyclosporine can enhance the immunosuppressive effect.In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure,the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.
文摘Mammalian cells respond to ionization radiation by sending out extracellular signals to affect non-irradiated neighboring cells, which is referred to as radiation bystander effect. In
文摘Purpose: Ionizing radiation is a well known human carcinogen. It has been generally accepted that direct damage to nuclear DNA is the main caused to induce genotoxicity
基金the Clinical Key Subject Foundation of HealthMinistry of China [Diagnosis and analysis of clinical tumor cell cycle (3)] and Life science Ministry Director Foundation (No.30440024)
文摘Objective： To find out whether ultraviolet ray, a kind of non-ionic ray, could cause the bystander effect, the UV exposed MOLT-4 cells had been investigated. Methods： Two experiment groups were carried out, in which cells were culture and treated at two concentrations： 2 × 10^5/mL and 5 × 10^5/mL. All other treatments were the same. Part of the cells was labeled with DID and exposed to UV ray for 40 s as effect cells; other cells was untreated as bystander cells. Then, the cells were co-cultured and harvested at 4 h interval over a period of 24 h. Annexin V-FITC/PI assay was used to evaluate the bystander effect in bystander cells co-cultured with effected cells. Laser confocal microscope method was used to observe the morphologic changes of the bystander cells. Results： The percentage of cells undergoing apoptosis in the bystander cells was increased over time compared with the control group. They were 6.84%, 8.09%, 9.88%, 17.64%, 17.43%, 30.99% and 37.93% respectively in 0 h, 4 h, 8 h, 12 h, 16 h, 20 h and 24 h. When observed by laser scanning confocal microscope, the bystander cells show some classic character of apoptosis such as chromosome condense, phosphatidylsedne transfer and formation of apoptotic bodies. Conclusion： Bystander effect is significant in un-irradiated bystander MOLT-4 cells when co-cultured with UV exposed cells.
文摘This work aims to theoretically show the development of a nonequilibrium of radiation-induced bystander effect (RIBE) under steep dose gradient regions that typically occur in the field edges of a beam. We applied the kinetics model proposed by (McMahon et al. 2013) for in vivo conditions coupled with a hypothesis called “Layer-limited bystander signaling (LLBS)” to demonstrate 1) an enhancement in TCP (i.e. Enhanced TCP or ETCP) due to bystander signals, 2) the development of nonequilibrium of RIBE under steep dose gradient regions and 3) the reduction in ETCP in the surface of Clinical Target Volume (CTV) due to the non-equilibrium of RIBE. We incorporated the elements of RIBE directly in the existing Poisson LQ model available in Pinnacle3 TPS (Version 9.10.0) to compute the percentage reduction of ETCP in the tumor surface due to nonequilibrium of RIBE. The percentage improvement in TCP obtained in tumor surface by accounting for RIBE is about 46% lower than that obtained in the interior of the tumor. This suggests that relatively more number of cancerous cells might survive in the vicinity of tumor surface. The result obtained from the study is indicative of an additional uncertainty component associated with radiation treatment. Hence, this paper suggests that the radiation treatments employing steep dose gradients could be biophysically different in many ways.
基金the National Natural Science Foundation of China (81460695, 81760836).
文摘Radiation-induced bystander effect is the phenomenon that the cells which are not directly exposed to radiation have identical or similar biological reactions with the cells of direct exposure to radiation. It is a common second reaction of radiotherapy and has a strong impact on cancer patients. Here we review and synthesize its studies in vitro and in vivo, its time effect and the mechanism. And the existing problems and its research significance are also discussed.
文摘Genomic instability after radiation is the main reason of the increase of malignancy degree and normal tissuetransformation[1]. Previous study indicated that bystander cells show more long-term genomic instability afterradiation[2].In this study, non-small cell lung cancer cell line (A549) was radiated with X-rays (30 kV of 2 Gy), and theconditioned medium was transferred to bystander cells. The fast and slowly proliferating populations in bystandercells were isolated by the colony formation assay. After one month, the chromosome number (Table 1, Fig. 1),drug resistance ability (Fig. 2) and cancer stem-like cell enrichment (Fig. 3) were investigated in fast and slowlyproliferating cells, respectively.
文摘Since the first report by Nagasawa et al.[1] in 1992, which demonstrates evidences that non-irradiated bystandercells also showed damage of sister chromatid exchange in samples irradiated with low-dose α particles, radiationinduced bystander effect (RIBE) has been studied for more than decades and many publications showed that RIBEswere found after treatment of both low and high-LET radiations. However, there are also some reports showingcontrary facts that no obvious bystander effects can be found, for example Fournier et al.[2] reported that theyobserved no early cytogenetic damage in the bystander cells after heavy ion microbeam irradiation. RIBE is ofgreat interest in radiotherapy using X-ray radiation or high-LET heavy ions because of RIBE-related cell killing andcarcinogenesis in neighboring normal cells[3]. In this work, we investigated the damage in bystander cells exposedto medium from cells irradiated with X-ray and carbon beam.
基金This study was supported by grants from Jiangsu Provincial Health Department （No. RC2002075） and Natural Science Foundation of Jiangsu Province （No. BK2007257）.
文摘Background Cytosine deaminase （CD） converts 5-fluorocytosine （5-FC） to 5-fluorouracil （5-FU） in CD/5-FC gene therapy, 5-FU will be mostly converted into nontoxic 13-alanine without uracil phosphoribosyltransferase （UPRT）. UPRT catalyzes the conversion of 5-FU to 5-fluorouridine monophosphate, which directly kills CD：：UPRT-expressing cells and surrounding cells via the bystander effect. But the pharmacokinetics and the bystander effect of CD：：UPRT/5-FC has not been verified in vivo and in vitro. Before the CD：：UPRT/5-FC bi-gene therapy system is used in clinical trial, it is essential to monitor the transgene expression and function in vivo. Thus, we developed a preclinical tumor model to investigate the feasibility of using ^19F-magnetic resonance spectroscopy （^19F-MRS） and optical imaging to measure non-invasive CD and UPRT expression and its bystander effect. Methods C6 and C6-CD：：UPRT cells were cultured with 5-FC. The medium, cells and their mixture were analyzed by ^19F-MRS. Rats with intracranial xenografted encephalic C6-CD：：UPRT glioma were injected intraperitoneally with 5-FC and their ^19F-MRS spectra recorded. Then the pharmacokinetics of 5-FC was proved. Mixtures of C6 and C6-CD：：UPRT cells at different ratios were cultured with 5-FC and the cytotoxic efficacy and survival rate of cells recorded. To determine the mechanism of the bystander effect, the culture media from cell comprising 25% and 75% C6-CD：：UPRT cells were examined by ^19F-MRS. A comparative study of mean was performed using analysis of variance （ANOVA）. Results ^19F-MRS on samples from C6-CD：：UPRT cells cultured with 5-FC showed three broad resonance signals corresponding to 5-FC, 5-FU and fluorinated nucleotides （F-Nuctd）. For the C6 mixture, only the 5-FC peak was detected. In vivo serial ^19F-MRS spectra showed a strong 5-FC peak and a weak 5-FU peak at 20 minutes after 5-FC injection. The 5-FU concentration reached a maximum at about 50 minutes. The F-Nuctd signal appeared after about 1 hour, reached a maximum at around 160 minutes, and was detectable for several hours. At a 10% ratio of C6-CD：：UPRT cells, the survival rate was （79.55±0.88）% （P 〈0.01）. As the C6-CD：：UPRT ratio increased, the survival rate of the cells decreased. ^19F-MRS showed that the signals for 5-FU and F-Nuctd in the culture medium increased as the ratio of C6-CD：：UPRT in the mixture increased. Conclusions ^19F-MRS studies indicated that C6-CD：：UPRT cells could effectively express CD and UPRT enzymes. The CD：：UPRT/5-FC system showed an obvious bystander effect. This study demonstrated that CD：：UPRT/5-FC gene therapy is suitable for 5-FC to F-Nuctd metabolism; and ^19F-MRS can monitor transferred CD：：UPRT gene expression and catalysis of substrates noninvasively, dynamically and quantitatively.
文摘Radiation-induced bystander effect(RIBE)and abscopal effect(RIAE)are non-target cellular responses outside the radiation field.It has been recognized that these effects are of great significance to both radiation protection of environmental low-dose radiation and clinical radiotherapy in which the anti-tumor abscopal effect is even beneficial to patients.However,the mechanisms of them are still obscure.This review briefly introduced the inflammatory signaling factors and immune regulation in RIBE in vitro and RIAE on normal tissues and organisms,and emphasized the genetic consequences of RIAE.Based on a large number of investigation results,we suggest that it’s time to incorporate RIBE and RIAE into the concept of“classic”radiation biology.
基金the Beiing Municipal Administration of Hospitals Clinical Medicine Development(XMLX201313)National Science&Technology Fundamental Resource Investigation Programme of China(No.2018FY 100600,2018FY 100602)。
文摘Aim:We aimed to investigate the association between bystander cardiopulmonary resuscitation(CPR)and survival of patients with out-of-hospital cardiac arrests(OHCA)in Beiing.Methods:This observational study analyzed adult patients with OHCA treated by the Beiing emergency medical service(EMS)from January 2013 to December 2017.Data were collected in a Utstein style with a 1-year follow-up and a primary outcome 01 survival to hospital discharge.Secondary outcomes were return of spontaneous circulation(ROSC),survival to admission,favorable neurological outcome at hospital discharge,and survival and favorable neurological outcomes of up to 1 year.Results:A total of 5016 patients with OHCA from Beiing's urban area were recorded by EMS,wherein 765 patients(15.25%)underwent bystander CPR.The data were propensity score-matched forage,sex,location,witness,aetiology,initial rhythm,and call to EMS arrival to compare the difference between the occurrence and nonoccurrence of bystander CPR.The survival upon the discharge of patients who experienced bystander CPR was superior to that of patients who did not receive bystander CPR(3.7%vs 1.2%,respectively;P<0.001).Moreover,patients with OHCA resuscitated with bystander CPR achieved better outcomes of ROSC,survival to admission,favorable neurological outcome at hospital discharge,survival and favorable neurological outcome after 1 year compared with those who were not resuscitated with bystander CPR.Conclusion:Survival and neu rological outcome of patients who underwent bystander CPR was better than those who underwent nonbystander CPR in Beiing.However,the rate of bystander CPR was low.
文摘This paper presents a comprehensive overview of the historical trajectory and development in biophoton studies over the past 100 years,with a particular focus on the recent progress regarding the pivotal role of biophoton in mediating radiation-induced bystander effects(RIBE).The exploration of biophoton mystery starts from the initial observation of mitogenetic radiation and continues to develop to the contemporary science of biophotonics.The properties and underlying mechanisms of biophoton emission are described with illustrative examples from diverse biological systems such as plants,animals and humans.The conclusive evidence of cell-to-cell commu-nication facilitated by biophoton signaling is presented,followed by an elaborate interpretation of potential mechanisms through which biophoton mediates RIBE.The engagement of mitochondria and exosomes in this process is extensively clarified,by highlighting their significant roles in biophoton-mediated RIBE.The advances in biophoton research in respect of bystander response to ionizing radiation may offer profound insights into radiobiology and provide for possible future applications as well in radiation medicine and protection.
文摘We report resuscitation of a near-drowning child by a bystander in a rural south China township.Resuscitation was performed on a 6-year-old,otherwise healthy boy who was witnessed drowning in a river,with submersion for approximately 12 min.Following several resuscitation attempts,spontaneous breathing was established at the scene and the boy was transferred to a nearby hospital.He developed pneumonia but recovered completely on the ward and was discharged without any neurologic disabilities.This case shows that early bystander resuscitation is an important factor for survival after submersion.The search for an ideal approach to resuscitation must continue,and all members of society must work together towards this goal.
文摘A public debate on the bystander effect,prompted by a viral video of a fatal traffic accident,has highlighted continued gaps in China’s'Good Samaritan'laws—legal protections for those who volunteer to help victims.The 94-second video from Zhumadian,Henan,recorded in April but circulated in mid-June,showed a
