E2F is involved in radioresistance of carbon ion induced apoptosis via Bax/caspase 3 signal pathway in human hepatoma cell.

Deletion of p53, most common genetic alteration, is observed in human tumors and reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR) could induce p53-/- cancer cells apoptosis. However, little is known regarding the molecular mechanism in this type of cell apoptosis. The present studies have focused on mechanisms state of signaling pathways as an activator of the cell fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up-regulation of E2F1 expression in cancer cells. This phenomenon was not observed in X-ray IR group. Up-regulation of E2F1 could cause a higher reduction in clonogenic survival, low level of cellular activity, G2 /M phase arrest, promotion of apoptosis rate, up-regulation of phosphor-Rb, Bax, and cleaved-caspase 3 proteins expressions without p53. Changes of E2F1 expressions could partly alter radioresistance in cancer cells. The results were suggested that heavy ion IR could induce p53-/- cancer cells apoptosis via E2F1 signal pathway. Our study provides a scientific rationale for the clinical use of heavy ion as radiotherapy in patients with p53-deficient tumors, which are often resistant to radiotherapy.

Empirical modeling of the percent depth dose for megavoltage photon beams.

INTRODUCTION: This study presents an empirical method to model the high-energy photon beam percent depth dose (PDD) curve by using the home-generated buildup function and tail function (buildup-tail function) in radiation therapy. The modeling parameters n and µ of buildup-tail function can be used to characterize the Collimator Scatter Factor (Sc) either in a square field or in the different individual upper jaw and lower jaw setting separately for individual monitor unit check. METHODS AND MATERIALS: The PDD curves for four high-energy photon beams were modeled by the buildup and tail function in this study. The buildup function was a quadratic function in the form of [Formula: see text] with the main parameter of d (depth in water) and n, while the tail function was in the form of e-µd and was composed by an exponential function with the main parameter of d and µ. The PDD was the product of buildup and tail function, PDD = [Formula: see text]. The PDD of four-photon energies was characterized by the buildup-tail function by adjusting the parameters n and µ. The Sc of 6 MV and 10 MV can then be expressed simply by the modeling parameters n and µ. RESULTS: The main parameters n increases in buildup-tail function when photon energy increased. The physical meaning of the parameter n expresses the beam hardening of photon energy in PDD. The fitting results of parameters n in the buildup function are 0.17, 0.208, 0.495, 1.2 of four-photon energies, 4 MV, 6 MV, 10 MV, 18 MV, respectively. The parameter µ can be treated as attenuation coefficient in tail function and decreases when photon energy increased. The fitting results of parameters µ in the tail function are 0.065, 0.0515, 0.0458, 0.0422 of four-photon energies, 4 MV, 6 MV, 10 MV, 18 MV, respectively. The values of n and µ obtained from the fitted buildup-tail function were applied into an analytical formula of Sc = nE(S)0.63µE to get the collimator to scatter factor Sc for 6 and 10 MV photon beam, while nE, µE, S denotes n, µ at photon energy E of field size S, respectively. The calculated Sc were compared with the measured data and showed agreement at different field sizes to within ±1.5%. CONCLUSIONS: We proposed a model incorporating a two-parameter formula which can improve the fitting accuracy to be better than 1.5% maximum error for describing the PDD in different photon energies used in clinical setting. This model can be used to parameterize the Sc factors for some clinical requirements. The modeling parameters n and µ can be used to predict the Sc in either square field or individual jaws opening asymmetrically for treatment monitor unit double-check in dose calculation. The technique developed in this study can also be used for systematic or random errors in the QA program, thus improves the clinical dose computation accuracy for patient treatment.

A Mathematical Method to Adjust MLC Leaf End Position for Accurate Dose Calculation in Carbon Ion Beam Radiation Therapy Treatment Planning System.

INTRODUCTION: We present a mathematical method to adjust the leaf end position for dose calculation correction in the carbon ion radiation therapy treatment planning system. METHODS AND MATERIALS: A straggling range algorism of 400 MeV/n carbon ion beam in nine different multileaf collimator (MLC) materials was conducted to calculate the dose 50% point to derive the offset corrections in the carbon ion treatment planning system (ciPlan). The visualized light field edge position in the treatment planning system is denoted as X tang.p, and MLC position (X mlc.p) is defined as the source to leaf end midpoint projection on axis for monitor unit calculation. The virtual source position of energy at 400 MeV/n and straggling range in MLC at different field sizes were used to calculate the dose 50% position on axis. On-axis MLC offset (correction) could then be obtained from the position corresponding to 50% of the central axis dose minus the X mlc.p. RESULTS: The exact MLC position in the carbon ion treatment planning system can be used as an offset to do the correction. The offset correction of pure tungsten is the smallest among the others due to its shortest straggling range of carbon ion beam in MLC. The positions of 50% dose of all MLC materials are always located in between X tang.p and X mlc.p under the largest field of 12 cm by 12 cm. CONCLUSIONS: MLC offset should be adjusted carefully at different field sizes in the treatment planning systems especially of its small penumbra characteristic in the carbon ion beam. It is necessary to find out the dose 50% position for adjusting MLC leaf edge on-axis location in the treatment planning system to reduce dose calculation error.

The Study of Field Equivalence Determined by the Modeled Percentage Depth Dose in Electron Beam Radiation Therapy.

INTRODUCTION: This study presents an empirical method to model the curve of electron beam percent depth dose (PDD) by using the primary-tail function in electron beam radiation therapy. The modeling parameters N and n can be used to predict the minimal side length when the field size is reduced below that required for lateral scatter equilibrium (LSE) in electron radiation therapy. METHODS AND MATERIALS: The electrons' PDD curves were modeled by the primary-tail function in this study. The primary function included the exponential function and the main parameters of N and µ, while the tail function was composed of a sigmoid function with the main parameter of n. The PDD of five electron energies was modeled by the primary and tail function by adjusting the parameters of N, µ, and n. The R 50 and R p can be derived from the modeled straight line of 80% to 20% region of PDD. The same electron energy with different cone sizes was also modeled by the primary-tail function. The stopping power of different electron energies in different depths can also be derived from the parameters N, µ, and n. RESULTS: The main parameters N and n increase but µ decreases in the primary-tail function for characterizing the electron beam PDD when the electron energy increased. The relationship of parameter n, N, and ln(-µ) with electron energy are n = 31.667E 0 - 88, N = 0.9975E 0 - 2.8535, and ln(-µ) = -0.1355E 0 - 6.0986, respectively. Percent depth dose was derived from the percent reading curve by multiplying the stopping power relevant to the depth in water at a certain electron energy. The stopping power of different electron energies can be derived from n and N with the following equation: stopping power = (-0.042ln(N E 0 ) + 1.072)e (-nE0 · 5 · 10-5 + 0.0381)·x , where x is the depth in water. The lateral scatter equivalence (LSE) of the clinical electron beam can be described by the parameters E 0, n, and N in the equation of Seq = (n E 0 - N E 0 )0.288/(E 0/n E 0 )0.0195. The LSE was compared with the root mean square scatter angular distribution method and shows the agreement of depth dose distributions within ±2%. CONCLUSIONS: The PDD of the electron beam at different energies and cone sizes can be modeled with an empirical model to deal with what is the minimal field size without changing the percent depth dose when approximate LSE is given in centimeters of water.

Energy-Related Scatter Analysis for Determining the Effective Point of Measurement of Cylindrical Ion Chamber in Heavy Charged Particle Carbon Ion Beam.

PURPOSE: An experimental and mathematical study for determining the effective point of measurement (P eff) for a Farmer-type cylindrical chamber in a carbon ion passive scatter beam is presented. METHODS: The ionization depth curves measured by the Bragg peak chamber were plotted according to the position of the inner surface of the entrance window, while the Farmer chamber was plotted at the tip of the cylindrical geometric center. The ionization depth curves measured by a cylindrical chamber in the 3D water phantom were then compared with a high-precision parallel-plate PTW Bragg peak chamber for inspecting the upstream shift correction of the cylindrical chamber in the carbon ion beam. A component of the vertical and horizontal integration method and the barrier model, cosφ = 1 - [2αR L /(1 + α - R L )], for analyzing the shift of effective point of measurement in different carbon ion energies and various field sizes, were studied. RESULTS: The shift between the maximum peak of the Bragg peak chamber and the Farmer chamber in a field size of 10 cm × 10 cm with an energy of 330 MeV/u of carbon ion is 2.3 mm. This upstream shift corresponds to (0.744 ± 0.07)r, where r is the Farmer chamber inner radius of 3.05 mm. Carbon ion energy from 120 MeV/u to 400 MeV/u with different field sizes show different shifts of effective point of measurement in a range of (0.649 ± 0.02)r to (0.843 ± 0.06)r of 3 cm × 3 cm at an energy of 400 MeV/u and 10 cm × 10 cm at an energy of 120 MeV/u, respectively. The vertical and horizontal scatter analysis by the barrier model can precisely describe the shift of the effective point of measurement at different carbon ion energies with various field sizes. CONCLUSIONS: We conclude that the Farmer chamber can be used for a patient-specific dose verification check in carbon ion beam treatment if P eff is well calibrated.

Carbon ion radiotherapy for bladder cancer: A case report.

BACKGROUND: Radical cystectomy is considered the first choice for the treatment of muscle-invasive bladder cancer. However, for some patients who have lost the indications for surgery, external beam radiotherapy is a non-invasive and effective treatment. CASE SUMMARY: A 76-year-old patient with bladder cancer who had serious comorbidities and could not tolerate surgery or chemotherapy came to the Wuwei Heavy Ion Center. He received carbon ion radiotherapy (CIRT) with a whole-bladder dose of 44 GyE and tumor boost of 20 GyE. When he finished CIRT, his bladder cancer-related hematuria completely disappeared, and computed tomography examination showed that the tumor had obviously decreased in size. At the 3-mo follow-up, the tumor disappeared, and there were no acute or late adverse events. CIRT was well tolerated in this patient. CONCLUSION: CIRT may allow for avoiding resection and was well tolerated with curative outcomes.

Carbon ion radiotherapy for synchronous choroidal melanoma and lung cancer: A case report.

BACKGROUND: Despite being the most common intraocular malignancy among adults, choroidal melanoma is a rare cancer type, even more so when accompanied by lung cancer. We report a patient with synchronous choroid melanoma and lung cancer treated with carbon ion radiotherapy (CIRT). CASE SUMMARY: A 41-year-old woman was transferred to our center with a diagnosis of choroidal melanoma in her right eye. During the examination, we found a right lung tumor that was histologically diagnosed as lung cancer. The patient was treated with CIRT for both malignant neoplasms. The CIRT dose was 70 photon equivalent doses (GyE) in five fractions for the right eye choroidal melanoma and 72 GyE in 16 fractions for the right lung cancer. At 3 mo after CIRT, the choroidal melanoma completely disappeared, as did the right lung cancer 7 mo after; the patient was in complete remission. CONCLUSION: CIRT may be an effective treatment for double primary lung cancer and choroid melanoma.

Bystander effect and abscopal effect in recurrent thymic carcinoma treated with carbon-ion radiation therapy: A case report.

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 carbon-ion 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 carbon-ion irradiation in a human patient, and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.

Evaluation of the toxicity of iron-ion irradiation in murine bone marrow dendritic cells via increasing the expression of indoleamine 2,3-dioxygenase 1.

High linear energy transfer radiation is known to deposit higher energy in tissues and cause greater toxicity compared to low-LET irradiation. Local immunosuppression is frequently observed after irradiation (IR). Dendritic cells (DCs) play important roles in the initiation and maintenance of the immune response. The dysfunction of DCs contributes to tumor evasion and growth. However, molecular mechanisms underlying the establishment of immune tolerance induced by heavy ion IR through this DC population are poorly understood. Therefore, here we report our findings on the dysfunction of bone marrow-derived dendritic cells (BMDCs) induced by 1 Gy iron ion radiation and promotions of expressions of JNK1/2/3, indoleamine 2,3-dioxygenase 1 (IDO1), p-ERK1/2 and p38/MAPK; and decrease of IDO2, MHC class II, CD40, CD80 expressions and IFN-γ and TNF-α secretion after total-body IR in mice. JNK+IDO1+ BMDCs showed up-expression of p-ERK1/2 and p-p38/MAPK, reduced expression of MHC class II and CD80, and were not able to effectively stimulate allogeneic spleen T cells. The inhibition of IDO1 expressions could partly restore the function of BMDCs. In all, our study shows that elevated JNK and IDO1 expression induced by Fe ion IR could result in dysfunction of BMDCs via p-p38/MAPK and p-ERK1/2 signal pathway, and it may represent a new mechanism in radiation-induced immune tolerance.

Cryptotanshinone inhibits lung tumorigenesis and induces apoptosis in cancer cells in vitro and in vivo.

Cryptotanshinone is one of the compounds extracted from the root of Salvia miltiorrhiza Bunge. Unlike other tanshinones, only a small number of studies have focused on cryptotanshinone for medical treatment. In the present study, the A549 lung cancer cell line and xenograft models of human lung tumors were used to assess the anti-cancer effect of cryptotanshinone. The effect of cryptotanshinone on human lung cancer, including growth inhibition, cell cycle arrest and apoptosis factors, were identified in vitro, and inhibition of tumor formation, improvement of body condition as well as pathological apoptotic effects were detected in vivo. These results suggested that cryptotanshinone is a potential drug for the treatment and prevention of human lung cancer.