Enhancement of radiosensitivity of MCF-7 breast cancer cells subjected to X-ray or carbon-ion irradiations

The sensitivity of cancer cells to radiation therapy varies based on cell cycle phase. Here we evaluated the differences between X-ray and carbon-ion irradiation with respect to cellular radiosensitivity and cancer cycle arrest in the breast cancer cell line, MCF-7. The cell survival rate, cell cycle distribution and the presence of apoptosis were measured by clonogenic assay and flow cytometry. BRCA1 and p21 protein levels were analyzed by Western blot, and the levels of human telomerase reverse transcriptase(h TERT) m RNA expression and telomere length were detected with real-time polymerase chain reaction. The results show a significant dose-dependent effects on survival rate, apoptosis and protein levels in the carbon-ion group of MCF-7 cells. Decreased proliferation was not observed at 2 Gy X-ray irradiation. There were significant differences in cellular cycle arrest, apoptosis percentages and BRCA1 and p21 protein expression between X-ray and heavy-ion groups. The results indicatedthat increasing in BRCA1 and p21 expression, and attenuation of h TERT gene expression induced by heavy-ion irradiation in MCF-7 cells might relate to mechanism of cellular radiosensitivity in G2/M arrested phase.

Induction of adaptive response in utero by ionizing radiation:A radiation quality dependent phenomenon

Investigation on possible induction of adaptive response(AR)by high-liner energy transfer(LET)particle radiation for protection against low-LET photon radiation-induced detrimental effects has not yet been performed in utero.This study verified if an AR could be induced by high-LET particle radiation from accelerated heavy ions against low-LET X-ray radiation-induced detrimental effects on fetal mice.Total body irradiation of pregnant C57BL/6J mice were performed by delivering a priming dose ranging from 10 mGy to 320 mGy of particle radiation on gestation day 11 followed one day later by a challenge dose at 3500 mGy from X-ray radiation.The monoenergetic beams of carbon,silicon and iron with the LET values of about 15,55,and 200 KeV/μm,respectively,were examined.Significant suppression by the priming radiation of the detrimental effects(fetal death,malformation,or low body weight)was used as the endpoints for judgment of a successful AR induction on gestation day 18.Existence of AR was not observed.On the other hand,the priming dose of high-LET particle radiation,in some cases,even increased the detrimental effects induced by the challenge dose from low-LET X-ray radiation.Although existence of AR induced by high-LET radiation in cultured mammalian cells in vitro and in certain tissues of laboratory mice in vivo was demonstrated,the present study did not suggest that low dose of high-LET particle radiation could induce an AR in fetal mice in utero under the setup of our experimental system.

Exercise-induced torsades de pointes as an unusual presentation of cardiac sarcoidosis: A case report and review of literature

BACKGROUND Sarcoidosis is a rare multisystem disease characterized histologically by noncaseating granuloma formation in the affected organ.While cardiac sarcoidosis is found on autopsy in up to 25%of sarcoidosis cases,it is still underdiagnosed and is associated with a poor prognosis.Although the etiology of sarcoidosis remains unclear,an antigen triggered exaggerated immune response has been hypothesized.Early detection and prompt management of cardiac sarcoidosis remains pivotal.CASE SUMMARY A 60-year-old female,with pulmonary sarcoidosis in remission,presented to the cardiology outpatient clinic for evaluation of weeks-long dyspnea on moderate exertion(New York Heart Association class II)that was relieved by rest.Submaximal exercise stress test showed multifocal ventricular extrasystoles,followed by a self-limiting torsades de pointes.Cardiac magnetic resonance imaging showed nondilated and normotrophic left ventricle with basoseptal and mid-septal dyskinesis.The magnetic resonance imaging-derived left ventricular ejection fraction was 45%.Delayed enhancement showed patchy transmural fibrosis of the septum and hyperenhancement of the papillary muscles,all in favor of extensive cardiac involvement of sarcoidosis.A double-chamber implantable cardiac defibrillator was implanted,and methylprednisolone(12 mg/d)and methotrexate(12.5 mg/wk)treatment was initiated.Follow-up and implantable cardiac defibrillator interrogation showed episodes of asymptomatic nonsustained ventricular tachycardia and an asymptomatic episode of nonsustained ventricular tachycardia ending by the first antitachycardia pacing run.CONCLUSION Along an extensive review of the literature,this unusual case report highlights the importance of early detection of cardiac involvement of sarcoidosis,in order to avoid potential complications and increase survival.

A Surgical Case of Primary Cardiac Osteosarcoma Arising from Mitral Posterior Leaflet

Little is reported about primary cardiac osteosarcoma from mitral valve. We report a surgical case of primary cardiac osteosarcoma arising from mitral valve. The patient was a 54-year-old woman with congestive heart failure caused by mitral regurgitation due to a tumor (30 × 20 mm) from the posterior leaflet. We performed complete resection of the tumor combined with the mitral valve and replaced it to a mechanical valve. Histopathological examination showed evidence of complete excision of cardiac osteosarcoma. Sixteen months after the initial surgery, the mechanical valve has a trouble with its opening of leaflets due to local recurrence in the mitral annulus, and 2nd mitral valve replacement following tumor excision was performed. Eighteen months after the 2nd surgery, the patient finally died by recurrence as well as invasion of osteosarcoma from mitral annulus to left ventricular myocardium. We discussed about the management and treatments of primary cardiac osteosarcoma in this case.

More efficient induction of genotoxicity by high-LET Fe-particle radiation than low-LET X-ray radiation at low doses

Objective:To understand differential effects on induction of genotoxicity and genomic instability(GI)by high-LET particle radiation and low-LET photon radiation,based on ground-based experiments using total body irradiation(TBI)of mice with Fe-particle radiation and X-ray radiation.Methods:TBI was delivered to C57BL/6J Jms strain female mice of 8 weeks old at a dose ranging from 0.1 to 3.0 Gy of Fe-particle radiation or at a dose ranging from 0.1 to 5.0 Gy of X-ray radiation.Induction of genotoxicity and GI by TBI was determined respectively at 1 and 2 months after exposure using frequency of micronuclei in bone marrow erythrocytes as the endpoint.Inhibition of bone marrow cell proliferation by TBI was measured as reduced erythropoiesis.Physiological conditions were also investigated.Results:TBI,regardless of the type of radiation,caused statistically significant increase in genotoxicity at 1 month after exposure,but did not induce GI at 2 months after exposure even at higher doses(>1.0 Gy).The doseresponse curve for the frequency of micronucleated polychromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y=0.7798 t 1.7889x–0.5978x^(2)(R^(2)=0.8109)and y=0.7421 t 1.3792x–0.2588 x^(2)(R^(2)=0.8081),respectively.The dose-response curve for the frequency of micronucleated normochromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y=0.7191 t 1.4545x–0.4978x^(2)(R^(2)=0.7047)and y=0.658 t 1.344x–0.2531x^(2)(R^(2)=0.7853),respectively.In general,high-LET Fe-particle radiation was more efficient in inducing genotoxicity than low-LET X-ray radiation at lower doses(<0.5 Gy).Conclusions:These results further confirm that exposure to TBI,even at higher doses and regardless the type of radiation,does not induce GI in C57BL/6J strain mice measured as increased micronuclei in bone marrow erythrocytes.These findings indicate that radiation-induced GI is mouse strain dependent and suggest that more comprehensive studies should be done to explore the late health consequences from exposure to high-LET radiation at low doses.