Carbon-ion radiotherapy alone vs. standard dose photon radiation with carbon-ion radiotherapy boost for high-grade gliomas: a retrospective study.

BACKGROUND: This study aimed to compare the survival outcome and side effects in patients with primary high-grade glioma (HGG) who received carbon ion radiotherapy (CIRT) alone or as a boost strategy after photon radiation (photon + CIRTboost). PATIENTS AND METHODS: Thirty-four (34) patients with histologically confirmed HGG and received CIRT alone or Photon + CIRTboost, with concurrent temozolomide between 2020.03-2023.08 in Wuwei Cancer Hospital & Institute, China were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and acute and late toxicities were analyzed and compared. RESULTS: Eight WHO grade 3 and 26 grade 4 patients were included in the analysis. The median PFS in the CIRT alone and Photon + CIRTboost groups were 15 and 19 months respectively for all HGG cases, and 15 and 17.5 months respectively for grade 4 cases. The median OS in the CIRT alone and Photon + CIRTboost groups were 28 and 31 months respectively for all HGG cases, and 21 and 19 months respectively for grade 4 cases. No significant difference in these survival outcomes was observed between the CIRT alone and Photon + CIRTboost groups. Only grade 1 acute toxicities were observed in CIRT alone and Photon + CIRTboost groups. CIRT alone group had a significantly lower ratio of acute toxicities compared to Photon + CIRTboost (3/18 vs. 9/16, p = 0.03). No significant difference in late toxicities was observed. CONCLUSION: Both CIRT alone and Photon + CIRTboost with concurrent temozolomide are safe, without significant differences in PFS and OS in HGG patients. It is meaningful to explore whether dose escalation of CIRTboost might improve survival outcomes of HGG patients in future randomized trials.

Gas-sensing properties of Ti, Zr, V, and Nb-modified Ti3C2O2 for decomposed gases in locomotive electric transformers: a DFT study.

This study investigated the adsorption properties of the decomposed gases in locomotive electric transformers: C2H2, CH4, and CO on metal atoms (Ti, Zr, V, and Nb) modified Ti3C2O2 by DFT calculations. The optimal modification structures of metal atoms on Ti3C2O2 were calculated and band structure, adsorption energy, charge transfer, density of states, charge density diagrams, and recovery time were used to analyze the adsorption properties. The results showed that metal atom modifications could enhance the conductivity and surface activity. In the adsorption systems, gas received electrons, and the conductivity was changed after gas adsorption. The adsorption processes of CH4 on modified systems were physical and had an extremely short recovery time. However, new bonds were formed in the adsorption of C2H2 and CO resulting in long recovery times. In essence, Ti, Zr, V, and Nb-doped Ti3C2O2 can be used as gas-sensing materials for CH4 and as adsorbents for C2H2 and CO gases in locomotive electric transformers.

Increased DNA methylation of the splicing regulator SR45 suppresses seed abortion in litchi.

The gene regulatory networks that govern seed development are complex, yet very little is known about the genes and processes that are controlled by DNA methylation. Here, we performed single-base resolution DNA methylome analysis and found that CHH methylation increased significantly throughout seed development in litchi. Based on the association analysis of differentially methylated regions and weighted gene co-expression network analysis (WGCNA), 46 genes were identified as essential DNA methylation-regulated candidate genes involved in litchi seed development, including LcSR45, a homolog of the serine/arginine-rich (SR) splicing regulator SR45. LcSR45 is predominately expressed in the funicle, embryo, and seed integument, and displayed increased CHH methylation in the promoter during seed development. Notably, silencing of LcSR45 in a seed-aborted litchi cultivar significantly improved normal seed development, whereas the ectopic expression of LcSR45 in Arabidopsis caused seed abortion. Furthermore, LcSR45-dependent alternative splicing events were found to regulate genes involved in seed development. Together, our findings demonstrate that LcSR45 is hypermethylated, and plays a detrimental role in litchi seed development, indicating a global increase in DNA methylation at this stage.

Adsorption Properties of Ptn (n = 1-3) Cluster-Doped SnS2 and MoTe2 toward Vehicle Emissions: CO, CO2, and NO.

The interaction mechanism between CO, CO2, and NO gas molecules and Ptn-SnS2 (n = 1-3) and Ptn-MoTe2 (n = 1-3) is analyzed based on density functional theory calculations. For Pt2-SnS2, the structure of Pt2-SnS2 is deformed during CO2 adsorption. For Pt3-SnS2, its structure is also significantly deformed when the gas is adsorbed. Pt2-SnS2 is not suitable for the detection and adsorption of CO2 gas, while Pt3-SnS2 is not suitable for the detection and adsorption of these three gases. According to the density of states and molecular orbital analysis, the conductivity of the adsorption system of Pt-SnS2 remains almost unchanged after the adsorption of CO, so Pt-SnS2 is not suitable for the detection of CO gases. The adsorption of gases on intrinsic MoTe2 is a weakly interacting physical adsorption. Doping with one to three Pt atoms all resulted in different degrees of enhancement of the adsorption capacity of the substrates for these three target gases. However, for Pt2-MoTe2 and Pt3-MoTe2, the structure of these two materials undergoes significant deformation upon NO adsorption. In addition, the interaction between Pt3-MoTe2 and CO2 is weak, and the conductivity of this system is almost unaffected by CO2 adsorption. In addition, all other constructions are suitable for the detection of the corresponding gases. This paper provides a theoretical basis for the development of gas sensors for the detection of automotive and industrial emission gases.

Non-invasive high frequency oscillatory ventilation inhibiting respiratory motion in healthy volunteers.

Precision radiotherapy needs to manage organ movements to prevent critical organ injury. The purpose of this study is to examine the feasibility of motion control of the lung by suppressing respiratory motion. The non-invasive high frequency oscillatory ventilation (NIHFOV) is a technique commonly used in the protection of lung for patients with acute lung disease. By using a very high respiratory frequency and a low tidal volume, NIHFOV allows gas exchange, maintains a constant mean airway pressure and minimizes the respiratory movements. We tested healthy volunteers NIHFOV to explore the optimal operational parameter setting and the best possible motion suppression achievable. This study was conducted with the approval of Institutional Review Boards of the Wuwei Cancer hospital (approval number: 2021-39) and carried out in accordance with Declaration of Helsinki. The study comprises two parts. Twenty three healthy volunteers participated in the first part of the study. They had 7 sessions of training with the NIHFOV. The duration of uninterrupted, continuous breathing under the NIHFOV and the optimal operational machine settings were defined. Eight healthy volunteers took part in the second part of the study and underwent 4-dimensional CT (4DCT) scanning with and without NIHFOV. Their respiratory waveform under free breathing (FB) and NIHFOV were recorded. The maximum range of motion of the diaphragm from the two scannings was compared, and the variation of bilateral lung volume was obtained to evaluate the impact of NIHFOV technique on lung volume. The following data were collected: comfort score, transcutaneous partial pressure of oxygen (PtcO2), transcutaneous partial pressure of carbon dioxide (PtcCO2), and pulse rate. Data with and without NIHFOV were compared to evaluate its safety, physiological impacts and effect of lung movement suppression. All the volunteers completed the training sessions eventlessly, demonstrating a good tolerability of the procedure. The median NIHFOV-on time was 32 min (22-45 min), and the maximum range of motion in the cephalic-caudal direction was significantly reduced on NIHFOV compared with FB (1.8 ± 0.8 cm vs 0.3 ± 0.1 cm, t = - 3.650, P = 0.003); the median range of motion was only 0.3 ± 0.1 cm on NIHFOV with a good reproducibility. The variation coefficient under NIHFOV of the right lung volume was 2.4% and the left lung volume was 9.2%. The PtcO2 and PtcCO2 were constantly monitored during NIHFOV. The medium PtcCO2 under NIHFOV increased lightly by 4.1 mmHg (interquartile range [IQR], 4-6 mmHg) compared with FB (t = 17.676, P < 0.001). No hypercapnia was found, PtcO2 increased significantly in all volunteers during NIHFOV (t = 25.453, P < 0.001). There was no significant difference in pulse rate between the two data sets (t = 1.257, P = 0.233). NIHFOV is easy to master in healthy volunteers to minimize respiratory movement with good tolerability and reproducibility. It is a feasible approach for lung motion control and could potentially be applied in accurate radiotherapy including carbon-ion radiotherapy through suppression of respiratory movement.

Carbon ion radiotherapy for recurrent ameloblastoma: A case report.

Ameloblastoma is a kind of benign, odontogenic tumor of epithelial origin, and surgery is mainstay treatment method; however, recurrence is common, and usually the treatment for recurrence is still surgery. We report on a patient of recurrent ameloblastoma treated with carbon ion radiation therapy and achieved a good efficacy. A 25-year-old female with relapse of an ameloblastoma was referred to the Wuwei Heavy Ion Center for carbon ion therapy. She had been initially diagnosed with ameloblastoma 8 years ago and underwent operation of right mandible ameloblastoma. After she transferred to our center, she accepted a dose of 60 GyE carbon ion radiation therapy, and the efficacy is good. Carbon ion radiation therapy can be an effective treatment option for ameloblastoma.

Carbon ion radiotherapy with complete tumor regression for primary malignant melanoma of female urethra orifice: a case report.

Primary malignant melanoma of the female urethra (PMMFU) is extremely rare, accounting for 0.2% of all melanomas, and fewer than 200 cases have been reported worldwide. Because of the small number of clinical cases and unclear biological characteristics, there is no uniform and standard treatment protocol. We herein describe the treatment of PMMFU using carbon ion radiotherapy. The radiotherapy was delivered at 60.8 Gy (RBE) in 16 fractions, once daily, five times per week. The patient achieved complete tumor disappearance within 1 year after carbon ion radiotherapy and remained disease-free thereafter. She developed acute grade 1 radiation dermatitis and urethritis, which resolved quickly; no other toxic effects were observed. At the time of this writing, her survival duration was 33 months. This case demonstrates that carbon ion radiotherapy may be a good option for primary genitourinary mucosal malignancies.

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.

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.

Analysis of the Dose Drop at the Edge of the Target Area in Heavy Ion Radiotherapy.

BACKGROUND: The dose distribution of heavy ions at the edge of the target region will have a steep decay during radiotherapy, which can better protect the surrounding organs at risk. OBJECTIVE: To analyze the dose decay gradient at the back edge of the target region during heavy ion radiotherapy. METHODS: Treatment planning system (TPS) was employed to analyze the dose decay at the edge of the beam under different incident modes and multiple dose segmentation conditions during fixed beam irradiation. The dose decay data of each plan was collected based on the position where the rear edge of the beam began to fall rapidly. Uniform scanning mode was selected in heavy ion TPS. Dose decay curves under different beam setup modes were drawn and compared. RESULTS: The dose decay data analysis showed that in the case of single beam irradiation, the posterior edge of the beam was 5 mm away, and the posterior dose could drop to about 20%. While irradiation in opposite direction, the posterior edge of the beam was 5 mm away, and the dose could drop to about 50%. In orthogonal irradiation of two beams, the posterior edge of the beam could drop to about 30-38% in a distance of 5 mm. Through the data analysis in the TPS, the sharpness of the dose at the back edge of the heavy ion beam is better than that at the lateral edge, but the generated X-ray contamination cannot be ignored. CONCLUSIONS: The effect of uneven CT value on the dose decay of heavy ion beam should also be considered in clinical 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.

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.

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.

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.

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.

Carbon ion radiotherapy for recurrent calf myxoid liposarcoma: a case report.

Liposarcoma (LPS) is the most common soft tissue sarcoma. Myxoid LPS (MLPS) is the second most common subtype of LPS and accounts for 25% to 50% of all LPSs. Like most other soft tissue sarcomas, the mainstay of treatment for LPS is inevitably surgery. Multidisciplinary approaches, including surgery, chemotherapy, and radiotherapy, have been successful in the treatment of LPS during the last three decades. Even so, recurrence of LPS remains challenging. Carbon ion beams produce increased energy deposition at the end of their range to form a Bragg peak while minimizing irradiation damage to surrounding tissues, which facilitates more precise dosage and localization than that achieved with photon beams. Furthermore, carbon ion beams have high relative biologic effectiveness. We herein describe a patient who developed recurrent MLPS in the right calf after two surgeries and underwent carbon ion radiotherapy (CIRT), achieving complete disappearance of the tumor. The patient developed Grade 1 radiation dermatitis 30 days after CIRT, but no other acute toxicities were observed. The tumor had completely disappeared by 120 days after CIRT, and the patient remained disease-free for 27 months after CIRT. The CARE guidelines were followed in the reporting of this case.

Upregulation of miR-519 enhances radiosensitivity of esophageal squamous cell carcinoma trough targeting PI3K/AKT/mTOR signaling pathway.

PURPOSE: MicroRNA-519 (miR-519) has been previously reported to function as a tumor suppressor in several types of malignancies. This study aimed to probe the biological role of miR-519 in esophageal squamous cell carcinoma (ESCC). METHODS: qRT-PCR was utilized to test the miR-519 expression level in ESCC tissues and cells. Clinical value of miR-519 was investigated by Kaplan-Meier method. Function assays were conducted to determine the role of miR-519 in radioresistance of ESCC cells. The miR-519-regulated pathways were determined by Kyoto Encyclopedia of Genes and Genomes pathway analysis. RESULTS: Low expression level of miR-519 was closely correlated with the poor prognosis for overall survival of ESCC patients or patients who received radiotherapy. Functional assays indicated that upregulation of miR-519 made ESCC cells more sensitive to γ-ray radiation and facilitated ESCC cell apoptosis triggered by irradiation treatment via regulating DNA response. Ectopic expression of miR-519 decreased the level of p-AKT and p-mTOR, thus inactivating PI3K/AKT/mTOR signaling pathway after irradiation. CONCLUSION: These observations elucidated that upregulated miR-519 is closely correlated with the radiosensitivity of ESCC cells, which may contribute to finding a new promising target for improving the efficiency of radiotherapy in patients with ESCC.

Cryptotanshinone inhibits lung cancer invasion via microRNA-133a/matrix metalloproteinase 14 regulation.

Cryptotanshinone inhibits the proliferative and colony formation abilities of human non-small cell lung cancer cells (NSCLCs). The present study reported that signal transducer and activator of transcription 3 is not the only target of cryptotanshinone during the inhibition of human NSCLCs. It was identified that cryptotanshinone upregulates the expression levels of microRNA (miR)-30d-5p, miR-126-3p, miR-133a, miR-338-3p and miR-451a, and downregulates miR-21-5p, miR-96-5p, miR-182-5p and miR-205-5p. Among these, miR-133a was the most significantly upregulated. miR-133a targets and downregulates the expression of matrix metalloproteinase (MMP)14; however, MMP15, MMP16 and MMP24 were determined to be unaffected. This process was identified to be independent of tissue inhibitor of metalloproteinases 2. Cryptotanshinone also suppresses the invasion of human NSCLCs, which may be due to the inhibited expression of MMP14. In conclusion, cryptotanshinone may serve as a potential therapeutic agent in the treatment of lung cancer.

LINC00473/miR-374a-5p regulates esophageal squamous cell carcinoma via targeting SPIN1 to weaken the effect of radiotherapy.

Esophageal squamous cell carcinoma (ESCC) is the most prevalent type in esophageal cancers. Despite accumulating achievements in treatments of ESCC, patients still suffer from recurrence because of the treatment failures, one of the reasons for which is radioresistance. Therefore, it is a necessity to explore the molecular mechanism underlying ESCC radioresistance. Long intergenic noncoding RNA 473 (LINC00473) has been reported to be aberrantly expressed in several human malignancies. However, its biological function in radiosensitivity of ESCC remains to be fully understood. This study explored the role of LINC00473 in radiosensitivity of ESCC cells and whether LINC00473 acted as a competing endogenous RNA to realize its modulation on radioresistance. We found that LINC00473 was markedly upregulated in ESCC tissues and cell lines, and its expression was remarkably related to cellular response to irradiation. In addition, knockdown of LINC00473 could sensitize ESCC cells to radiation in vitro. As for the underlying mechanism, we uncovered that there was a mutual inhibition between LINC00473 and miR-374a-5p. Spindlin1 (SPIN1) was verified as a downstream target of miR-374a-5p, and LINC00473 upregulated SPIN1 expression through negatively modulating miR-374a-5p expression. Furthermore, we revealed that SPIN1 could aggravate the radioresistance of ESCC cells. Finally, overexpression of SPIN1 reversed the LINC00473 silencing-enhanced radiosensitivity in ESCC cells. To sum up, we demonstrated that LINC00473 facilitated radioresistance by regulating the miR-374a-5p/SPIN1 axis in ESCC.

LBX2-AS1 is activated by ZEB1 and promotes the development of esophageal squamous cell carcinoma by interacting with HNRNPC to enhance the stability of ZEB1 and ZEB2 mRNAs.

Long non-coding RNAs (lncRNAs) are a group of transcripts, which can regulate the progression of esophageal squamous cell carcinoma (ESCC). According to the data of TCGA, Ladybird homeobox 2 antisense RNA 1 (LBX2-AS1) is a highly expressed lncRNA in ESCC samples. Herein, we chose it for further study. Furtherly, dysregulation of LBX2-AS1 was identified in ESCC tissues with metastasis. Loss-of function assays were conducted and revealed that LBX2-AS1 knockdown suppressed ESCC cell migration and epithelial-mesenchymal transition (EMT). Zinc finger E-box binding homeobox 1 (ZEB1) and zinc finger E-box binding homeobox 2 (ZEB2) are two EMT-related transcription factors. Since LBX2-AS1 promoted the EMT progress and simultaneously enhanced the level of ZEB1 and ZEB2, we further investigated whether LBX2-AS1 promoted cell migration and EMT in ESCC by regulating ZEB1 and ZEB2. Mechanism investigations revealed that RNA binding protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) could interact with LBX2-AS1, ZEB1 and ZEB2, simultaneously. The similar function of HNRNPC in regulating migration and EMT process was demonstrated. ZEB1 has been reported as a positive transcriptional regulator of lncRNA. Therefore, further mechanism analysis was made to demonstrate whether ZEB1 could regulate the transcription of LBX2-AS1. Collectively, our data showed that ZEB1-induced upregulation of LBX2-AS1 promoted cell migration and EMT process in ESCC via enhancing the stability of ZEB1 and ZEB2.