Up modulation of dose-averaged linear energy transfer by simultaneous integrated boost in carbon-ion radiotherapy for pancreatic carcinoma.

BACKGROUND: Local recurrence in locally advanced pancreatic cancer (LAPC) after carbon-ion radiotherapy (CIRT) may partly attribute to low dose-averaged linear energy transfer (LETd ), despite high CIRT dose. PURPOSE: This study aimed to investigate the approaches to up-modulate the CIRT LETd and to evaluate the corresponding oxygen enhancement ratio (OER) reduction. METHODS: 10 LAPCs that had been irradiated by CIRT with 67.5 Gy (RBE) in 15 fractions were selected. Their original plans were taken as the control plan for the LETd and OER investigations. Our considerations for up-modulating LETd were: (1) to deliver high doses to gross tumor volume core (GTVcore), while keeping dose constraints of the gastrointestinal (GI) tract in tolerance; (2) to put more Bragg-peak (BP) within the modulated targets; (3) to increase the BP density, high doses were necessary; (4) CIRT LETd could be effectively increased to small volumes; and (5) simultaneous integrated boost technique (SIB) could achieve the aforementioned tasks. The LETd and the corresponding OER distributions of each type of SIB plan were evaluated. RESULTS: We delivered up to 100 Gy (RBE) to GTVcore using SIB. The mean LETd of GTV increased significantly by 21.3% from 47.8 to 58.0 keV/µm (p < 0.05). Meanwhile, the mean OER of GTVcore decreased by 6.6%, from 1.51 to 1.41 (p < 0.05). The GI LETd S in all modulated plans were not more than those in the original plans. CONCLUSIONS: SIB could effectively increase CIRT LETd to LAPC, thus producing reduced OER, which may effectively overcome the radioresistance of LAPCs.

Regulation of Cellular Signaling with an Aptamer Inhibitor to Impede Cancer Metastasis.

Tumor invasion and metastasis are the main causes of tumor progression and are the leading causes of death among cancer patients. In the present study, we propose a strategy to regulate cellular signaling with a tumor metastasis-relevant cytoskeleton-associated protein 4 (CKAP4) specific aptamer for the achievement of tumor metastasis inhibition. The designed aptamer could specifically bind to CKAP4 in the cell membranes and cytoplasm to block the internalization and recycling of α5ß1 integrin, resulting in the disruption of the fibronectin-dependent cell adhesion and the weakening of the cell traction force. Moreover, the aptamer is able to impede the interaction between CKAP4 and Dickkopf1 (DKK1) to further block the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which subsequently reduces AKT phosphorylation and inhibits the reorganization of the actin cytoskeleton in cell migration. The synergetic function of the designed aptamer in inhibiting cancer cell adhesion and blocking the PI3K signaling pathway enables efficient tumor cell metastasis suppression. The aptamer with specific targeting ability in regulating cellular signaling paves the way for cancer treatment and further provides a guiding ideology for inhibiting tumor metastasis.

Definitive carbon ion re-irradiation with pencil beam scanning in the treatment of unresectable locally recurrent rectal cancer.

This study aimed to evaluate the oncological outcomes and safety of carbon ion re-irradiation with pencil beam scanning (PBS) delivery technique for previously irradiated and unresectable locally recurrent rectal cancer (LRRC). Between June 2017 and September 2021, 24 patients of unresectable LRRC with prior pelvic photon radiotherapy who underwent carbon ion re-irradiation at our institute were retrospectively analyzed. Carbon ion radiotherapy was delivered by raster scanning with a median relative biological effectiveness-weighted dose of 72 Gy in 20 fractions. Weekly CT reviews were carried out, and offline adaptive replanning was performed whenever required. The median follow-up duration was 23.8 months (range, 6.2-47.1 months). At the last follow-up, two patients had a local disease progression, and 11 patients developed distant metastases. The 1- and 2-year local control, progression-free survival and overall survival rates were 100 and 93.3%, 70.8 and 45.0% and 86.7 and 81.3%, respectively. There were no Grade 3 or higher acute toxicities observed. Three patients developed Grade 3 late toxicities, one each with gastrointestinal toxicity, skin reaction and pelvic infection. In conclusion, definitive carbon ion re-irradiation with PBS provided superior oncologic results with tolerable toxicities and may be served as a curative treatment strategy in unresectable LRRC.

Validation of the relative biological effectiveness of active-energy scanning carbon-ion radiotherapy on a commercial treatment planning system with a microdosimetic kinetic model.

BACKGROUND: The study objective was to validate the relative biological effectiveness (RBE) calculated by the modified microdosimetric kinetic model in RayStation (Ray-MKM) for active-energy scanning carbon-ion radiotherapy. METHODS: The Ray-MKM was benchmarked using a spread-out Bragg-peak (SOBP) plan, which was suggested in literature from the National Institute of Radiobiological Science (NIRS) in Japan. The residual RBE differences from the MKM at NIRS (NIRS-MKM) were derived using several SOBP plans with different ranges, SOBP widths, and prescriptions. To investigate the origins of the differences, we compared the saturation-corrected dose-mean specific energy [Formula: see text] of the aforementioned SOBPs. Furthermore, we converted the RBE-weighted doses with the Ray-MKM to those with local effect model I (LEM doses). The purpose was to investigate whether the Ray-MKM could reproduce the RBE-weighted conversion study. RESULTS: The benchmark determined the value of the clinical dose scaling factor, [Formula: see text], as 2.40. The target mean RBE deviations between the Ray-MKM and NIRS-MKM were median: 0.6 (minimum: 0.0 to maximum: 1.69) %. The [Formula: see text] difference in-depth led to the RBE difference in-depth and was remarkable at the distal end. The converted LEM doses from the Ray-MKM doses were comparable (the deviation being - 1.8-0.7%) to existing literature. CONCLUSION: This study validated the Ray-MKM based on our active-energy scanning carbon-ion beam via phantom studies. The Ray-MKM could generate similar RBEs as the NIRS-MKM after benchmarking. Analysis based on [Formula: see text] indicated that the different beam qualities and fragment spectra caused the RBE differences. Since the absolute dose differences at the distal end were small, we neglected them. Furthermore, each centre may determine its centre-specific [Formula: see text] based on this approach.

Efficacy and safety of apatinib and transcatheter arterial chemoembolization as second-line therapy for advanced hepatocellular carcinoma: A retrospective cohort study.

Background: Transarterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) have demonstrated clinical efficacy against hepatocellular carcinoma (HCC) as first-line therapy. However, there is limited evidence on the efficacy and safety of apatinib plus TACE as second-line treatment for advanced HCC. Aim: To evaluate the efficacy and safety of apatinib in combination with TACE for advanced HCC patients with disease progression or intolerant to first-line treatment. Patients and Methods: Between May 2019 and January 2022, 72 advanced HCC patients received apatinib plus TACE as second-line treatment. Clinical parameters, efficacy, and safety were assessed. The primary endpoint was progression-free survival (PFS) and the secondary the objective response rate (ORR) and disease control rate (DCR). Results: The median follow-up duration was 14.7 months (range, 4.5-26.0). The median PFS from the beginning of treatment was 7.1 months (1.0-15.2) and its 95% CI was 6.6-8.2 according to Kaplan-Meier analysis. The ORR and DCR were 34.7% (95% CI: 23.9%-46.9%) and 48.6% (95% CI: 36.7%-60.7%), respectively. By the cutoff date, 33 patients (45.8%) had died and 39 (54.2%) were undergoing survival follow-up. The estimated median overall survival (mOS) was 22.3 months (95% CI: 20.6-24.0) by Kaplan-Meier analysis. The most common apatinib-related adverse events of any grade were hypertension [35 (48.6%)], appetite loss [30 (41.6%)], and hand-foot syndrome [21 (29.2%)]. Conclusion: The combination of apatinib and TACE as second-line therapy demonstrated promising clinical efficacy and tolerable adverse effects for advanced HCC patients.

Calculating dose-averaged linear energy transfer in an analytical treatment planning system for carbon-ion radiotherapy.

BACKGROUND: Compelling evidence shows the association between the relative biological effectiveness (RBE) of carbon-ion radiotherapy (CIRT) and the dose averaged linear energy transfer (LETd). However, the ability to calculate the LETd in commercially available treatment planning systems (TPS) is lacking. PURPOSE: This study aims to develop a method of calculating the LETd of CIRT plans that could be robustly carried out in RayStation (V10B, Raysearch, Sweden). METHODS: The calculation used the fragment spectra in RayStation for the CIRT treatment planning. The dose-weighted averaging procedure was supported by the microdosimetric kinetic model (MKM). The MKM-based pencil beam dose engine (PBA, v4.2) for calculating RBE-weighted doses was reformulated to become a LET-weighted calculating engine. A separate module was then configured to inversely calculate the LETd from the absorbed dose of a plan and the associated fragment spectra. In this study, the ion and energy-specific LET table in the LETd module was further matched with the values decoded from the baseline data of the Syngo TPS (V13C, Siemens, Germany). The LETd distributions of several monoenergetic and modulated beams were calculated and validated against the values derived from the Syngo TPS and the published data. RESULTS: The differences in LETds of the monoenergetic beams between the new method and the traditional method were within 3% in the entrance and Bragg-peak regions. However, a larger difference was observed in the distal region. The results of the modulated beams were in good agreement with the works from the published literature. CONCLUSIONS: The method presented herein reformulates the MKM dose engine in the RayStation TPS to inversely calculate LETds. The robustness and accuracy were demonstrated.

Carbon ion radiotherapy with pencil beam scanning for hepatocellular carcinoma: Long-term outcomes from a phase I trial.

This study evaluates the feasibility of the pencil beam scanning technique of carbon ion radiotherapy (CIRT) in the setting of hepatocellular carcinoma (HCC) and establishes the maximum tolerated dose (MTD) calculated by the Local Effect Model version I (LEM-I) with a dose escalation plan. The escalated relative biological effectiveness-weighted dose levels included 55, 60, 65, and 70 Gy in 10 fractions. Active motion management techniques were employed, and several measures were applied to mitigate the interplay effect induced by a moving target. CIRT was planned with the LEM-I-based treatment planning system and delivered by raster scanning. Offline PET/CT imaging was used to verify the beam range. Offline adaptive replanning was performed whenever required. Twenty-three patients with a median tumor size of 4.3 cm (range, 1.7-8.5 cm) were enrolled in the present study. The median follow-up time was 56.1 months (range, 5.7-74.4 months). No dose limiting toxicity was observed until 70 Gy, and MTD had not been reached. No patients experienced radiation-induced liver disease within 6 months after the completion of CIRT. The overall survival rates at 1, 3, and 5 years were 91.3%, 81.9%, and 67.1% after CIRT, respectively. The local progression-free survival and progression-free survival rates at 1, 3 and 5 years were 100%, 94.4%, and 94.4% and 73.6%, 59.2%, and 37.0%, respectively. The raster scanning technique could be used to treat HCC. However, caution should be exercised to mitigate the interplay effect. CIRT up to 70 Gy in 10 fractions over 2 weeks was safe and effective for HCC.

Pencil Beam Scanning Carbon Ion Radiotherapy for Hepatocellular Carcinoma.

Purpose: Carbon ion radiotherapy (CIRT) has emerged as a promising treatment modality for hepatocellular carcinoma (HCC). However, evidence of using the pencil beam scanning (PBS) technique to treat moving liver tumors remains lacking. The present study investigated the efficacy and toxicity of PBS CIRT in patients with HCC. Methods: Between January 2016 and October 2021, 90 consecutive HCC patients treated with definitive CIRT in our center were retrospectively analyzed. Fifty-eight patients received relative biological effectiveness-weighted doses of 50-70 Gy in 10 fractions, and 32 received 60-67.5 Gy in 15 fractions, which were determined by the tumor location and normal tissue constraints. Active motion-management techniques and necessary strategies were adopted to mitigate interplay effects efficiently. Oncologic outcomes and toxicities were evaluated. Results: The median follow-up time was 28.6 months (range 5.7-74.6 months). The objective response rate was 75.0% for all 90 patients with 100 treated lesions. The overall survival rates at 1-, 2- and 3-years were 97.8%, 83.3% and 75.4%, respectively. The local control rates at 1-, 2- and 3-years were 96.4%, 96.4% and 93.1%, respectively. Radiation-induced liver disease was not documented, and 4 patients (4.4%) had their Child-Pugh score elevated by 1 point after CIRT. No grade 3 or higher acute non-hematological toxicities were observed. Six patients (6.7%) experienced grade 3 or higher late toxicities. Conclusion: The active scanning technique was clinically feasible to treat HCC by applying necessary mitigation measures for interplay effects. The desirable oncologic outcomes as well as favorable toxicity profiles presented in this study will be a valuable reference for other carbon-ion centers using the PBS technique and local effect model-based system, and add to a growing body of evidence about the role of CIRT in the management of HCC.

Calibration and evaluation of the relative biological effectiveness for carbon-ion radiotherapy in a new relative to a clinically applied treatment planning system.

BACKGROUND: The study objective was to validate the relative biological effectiveness (RBE) in RayStation for carbon-ion radiotherapy (CIRT) using the Syngo treatment planning system as reference. METHODS: Local effect model I was established in RayStation (Ray-LEM) with the same parameters as in LEM I in Syngo (Syngo-LEM). Three cube plans covering most of the tumors treated at our center were generated with Syngo-LEM. Ray-LEM re-calculated the Syngo plans and compared the RBEs to the Syngo counterparts. The results showed that RayStation RBE was smaller than Syngo RBE. To ensure that Ray-LEM reproduced Syngo RBE, the observed deviations were used to scale the maximum RBE (RBEmax) in Ray-LEM. After this calibration, we further compared the RayStation RBE to Syngo RBE using additional plans in both homogeneous phantoms and patients, to ensure that the calibrated Ray-LEM reproduced Syngo RBE even with more complex planning features. RESULTS: The calibration increased the RBEmax by 2.3% to raise the Ray-LEM RBE. The target mean RBE deviations in the phantom evaluation plans were median: 0.0 (minimum: - 1.1 to maximum: 0.7) %, and the target mean RBE deviations of the clinical target volumes of 16 patient cases were - 0.4 (- 1.5 to 0.2) %. CONCLUSIONS: The residual RBE difference between RayStation and Syngo was found to be ≤ 1.0%. Thus, we can propose to use RayStation for clinical CIRT treatment planning. However, the potential differences due to the absorbed beam model warrants further exploration.

Changes of the linear energy transfer (LET) and beam width of therapeutic carbon ion beam in density heterogeneous phantoms.

This work aims to investigate the changes in the linear energy transfer (LET) spectra distribution and the beam spot width of a therapeutic carbon ion beam in density heterogeneous phantoms. Three different heterogeneous phantoms were fabricated using a combination of solid water, lung, and bone tissue slabs and irradiated by a single energy carbon beam (276.5 MeV u-1). CR-39 detectors were used for experimental measurements and the Monte Carlo toolkit Geant4 was employed for theoretical simulations. The results demonstrated that the measured LET spectra agree well with the simulation results. The lung and bone tissues displayed no obvious effect on the spectral distribution of LET. The dose-average LET was invariant and showed no obvious difference in the different materials, while the track-average LET increased in the lung and decreased in the bone materials. Similarly, the beam spot size increased in the lung, and decreased in the bone materials. Additionally, the fluence of the secondary fragments varied in different tissues. These findings are expected to provide cross-validation data for the quality assurance of carbon ion therapy and to be beneficial for validating the base data in treatment planning systems.

Adaptive carbon ion radiotherapy for locally advanced non-small cell lung cancer: Organ-sparing potential and target coverage.

BACKGROUND: The dose distribution of carbon ion radiotherapy (CIRT) for locally advanced non-small cell lung cancer (LANSCLC) is highly sensitive to anatomical changes. PURPOSE: To demonstrate the dosimetric benefits of adaptive CIRT for LANSCLC and compare the differences between patients with and without adaptive plans based on dosimetry and clinical effect factors. MATERIALS AND METHODS: Of the 98 patients with LANSCLC receiving CIRT, 31 patients underwent replanning following re-evaluations that revealed changes that would have compromised the dose coverage of the target volume or violated dose constraints. Dosimetric parameters and clinical factors were compared between patients with and without adaptive plans. Multivariate analysis identified factors influencing the adaptive planning. RESULTS: The median number of fractions delivered using adaptive plans was eight (range: 2-18). Adaptive plans ensured target coverage, and the maximum spinal cord dose was significantly decreased (p = 0.02). The median reduction in the maximum spinal cord dose was 10.4 Gy (relative biological effectiveness). Patients with adaptive plans had larger tumor volumes (p < 0.001); the median initial internal gross tumor volumes (iGTVs) of patients with adaptive and nonadaptive plans were 125.9 and 49.79 cm3 , respectively. Tumor volumes of patients with adaptive plans were altered to a greater extent (p < 0.001); the median absolute percentage of volume changes in patients in the adaptive and in nonadaptive groups were 20.76% and 3.63%, respectively, while the median movements of iGTV centers were 5.75 and 2.44 mm, respectively. Binary logistic regression analysis revealed that the iGTV volume change and iGTV center movements were significantly different between the groups. CONCLUSIONS: An adaptive plan can effectively ensure target area coverage and protect normal tissues, especially in patients with large tumor volumes and substantial changes. iGTV volume changes and iGTV center movements are the main factors influencing adaptive planning. Weekly simulation computed tomography scans are necessary for treatment evaluation in patients with LANSCLC treated with CIRT.

Dosimetric impact of using a commercial metal artifact reduction tool in carbon ion therapy in patients with hip prostheses.

The study investigated the dosimetric impact of an iterative metal artifact reduction (iMAR) tool on carbon ion therapy for pelvic cancer patients with hip prostheses. An anthropomorphic pelvic phantom with unilateral and bilateral hip prostheses was used to simulate pelvic cancer patients with metal implants. The raw data obtained from phantom CT scanning were reconstructed with a regular filtered back projection (FBP) algorithm and then corrected with iMAR. The phantom without hip prosthesis was also scanned and used as a reference ground truth (GT). The CT images of three prostate and four sarcoma patients with unilateral hip prosthesis were also reconstructed by FBP and iMAR algorithm and compared. iMAR algorithm reduced the metal artifacts and the maximum WEPL deviation in phantom images from -19.1 to -0.4 mm. However, the CT numbers cannot be retrieved using iMAR for periprosthetic bone materials, eventually leading to a WEPL deviation of -3.6 mm. The use of iMAR improved large discrepancies in DVHs of PTVs and the gamma index between FBP and GT images but increased the difference in the bladder DVH for bilateral hip prostheses due to newly introduced artifacts. In the patient study, the discrepancies of dose distribution were small on iMAR images when compared with FBP images for most cases, except for two sarcoma cases where gamma analysis failed and dose coverage in 98% of the PTV maximally reduced due to large volume of dark metal artifacts. iMAR reduced the metal artifacts and improved dose distribution accuracy in carbon ion radiotherapy for pelvic cancer. However, the residual and newly introduced artifacts, especially with bilateral hip prostheses, may potentially increase WEPL inaccuracy and dose uncertainty. The use of iMAR has the potential to improve carbon ion treatment planning of pelvic cancer but should be used with caution.

Conversion and validation of rectal constraints for prostate carcinoma receiving hypofractionated carbon-ion radiotherapy with a local effect model.

BACKGROUND: The study objective was to establish the local effect model (LEM) rectum constraints for 12-, 8-, and 4-fraction carbon-ion radiotherapy (CIRT) in patients with localized prostate carcinoma (PCA) using microdosimetric kinetic model (MKM)-defined and LEM-defined constraints for 16-fraction CIRT. METHODS: We analyzed 40 patients with PCA who received 16- or 12-fraction CIRT at our center. Linear-quadratic (LQ) and RBE-conversion models were employed to convert the constraints into various fractionations and biophysical models. Based on them, the MKM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to 12-, 8-, and 4-fraction CIRT using the LQ model. Then, MKM constraints were converted to LEM using the RBE-conversion model. Meanwhile the LEM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to LEM using the RBE-conversion model. Then, LEM constraints were converted from 16-fraction constraints to the rectum constraints for 12-, 8-, and 4-fraction CIRT using the LQ model. The LEM constraints for 16- and 12-fraction CIRT were evaluated using rectum doses and clinical follow-up. To adapt them for the MKM LQ strategy, CNAO LEM constraints were first converted to MKM constraints using the RBE-conversion model. RESULTS: The NIRS (i.e. DMKM|v, V-20%, 10%, 5%, and 0%) and CNAO rectum constraints (i.e. DLEM|v, V-10 cc, 5 cc, and 1 cc) were converted for 12-fraction CIRT using the MKM LQ strategy to LEM 37.60, 49.74, 55.27, and 58.01 Gy (RBE), and 45.97, 51.70, and 55.97 Gy (RBE), and using the LEM LQ strategy to 39.55, 53.08, 58.91, and 61.73 Gy (RBE), and 49.14, 55.30, and 59.69 Gy (RBE). We also established LEM constraints for 8- and 4-fraction CIRT. The 10-patient RBE-conversion model was comparable to 30-patient model. Eight patients who received 16-fraction CIRT exceeded the corresponding rectum constraints; the others were within the constraints. After a median follow-up of 10.8 months (7.1-20.8), No ≥ G1 late rectum toxicities were observed. CONCLUSIONS: The LEM rectum constraints from the MKM LQ strategy were more conservative and might serve as the reference for hypofractionated CIRT. However, Long-term follow-up plus additional patients is necessary.

A highly selective switch-on fluorescence sensor targeting telomeric dimeric G-quadruplex.

The fluorescence probes with high selectivity and sensitivity for telomeric multimeric G-quadruplexes have attracted much attention. Nevertheless, few small molecules have exhibited telomeric multimeric G-quadruplexes recognition specificity. Thus, there is an urgent demand to develop specific fluorescence probes for telomeric multimeric G-quadruplexes. We reported herein the specific sensing of telomeric dimeric G-quadruplex TTA45 via a fluorescence light-up response using a commercially available triazine derivative HPTA-1 as a probe. HPTA-1 could discriminate the telomeric dimeric G-quadruplex TTA45 against other types of DNA structures accompanied by a drastic enhancement of the emission intensity without compromising the conformation and stability. Compared with most multimeric G-quadruplex recognition ligands, HPTA-1 had much simpler structure and lower molecular weight. The binding mechanism studies suggested that the distinct fluorescence response was caused by electrostatic and π-π stacking interactions of HPTA-1 with the pocket between two G-quadruplex units of telomeric dimeric G-quadruplex TTA45..

Measurement of therapeutic12C beam in a water phantom using CR-39.

The motivation for this study was to explore a new method to test the particle spatial distribution for a therapeutic carbon beam. CR-39 plastic nuclear track detectors were irradiated to a 276.5 MeV u-1mono-energy carbon beam at the heavy ion facility in the Shanghai Proton and Heavy Ion Center. The spatial distribution of the primary carbon beam and secondary fragments in a water phantom were systematically analyzed both in the transverse direction (perpendicular to the projection direction of the primary beam) and at different depths in the longitudinal direction (along the projection direction of the primary beam) with measured tracks on the CR-39 detectors. Meanwhile, the theoretically spatial distribution and linear energy transfer (LET) spectra of the primary beam and secondary fragments were calculated using the Monte Carlo (MC) toolkit Geant4. The results showed that the CR-39 detectors are capable of providing high lateral resolution of carbon ion at different depths. In the range of the primary carbon beam, the beam width simulated with MC is in good agreement with that of experimental measurement. The track size registered in the CR-39 has a good correlation with the particle LET. These findings indicate that the CR-39 can be used for measuring both the particle flux and its spatial distribution of carbon ions.

Effect of storage time on biochemical characteristics and antioxidant activity of hawk tea (Litsea coreana) processed by boiling water fixation.

This study investigated the effect of storage time on biochemical characteristics of hawk tea (Litsea coreana) and explored the correlation between the content of flavonoids and polyphenols and antioxidant activity. The antioxidant activity and the content of inclusions, amino acid, and mineral elements in hawk tea processed by boiling water fixation and packed in airtight polypropylene bags and stored in 0°C refrigerator under different storage time (one year, three years, and six years) were analyzed. Results indicated that the biochemical characteristics of hawk tea changed less within 12 months. The total content and types of amino acids in hawk tea reached the maximum in the third year, as well as the content of total trace elements. The water extracts, tea polyphenol, caffeine, lysine, valine, isoleucine, glycine, proline, Ca, and Zn decreased continuously in the storage period of 6 years, but the total flavonoids, Mg, and Ni changed just the opposite. Total polyphenol is the main antioxidant material in hawk tea. Results of the present study provided useful information for people to systematically understand the changes of tea in the storage process and to reasonably develop hawk tea product.

The Impacts of Different Types of Radiation on the CRT and PDL1 Expression in Tumor Cells Under Normoxia and Hypoxia.

INTRODUCTION: Hypoxia is a hallmark of cancer that may contribute to an immunosuppressive microenvironment and promote radioresistance. High linear energy transfer (LET) radiation is considered to be able to overcome the negative effects of hypoxia. However, the anti-tumorigenic effects induced by low or high LET radiation have not been fully elucidated. This study aimed to compare the effects of different types of radiation on the immune response, particularly the impact on calreticulin (CRT), and programmed cell death ligand 1 (PDL1) expression. METHODS: Four human tumor cell lines were investigated in this study. Cells in normoxic and hypoxic groups were irradiated with 4Gy (physical dose) photon, proton, and carbon-ion radiation, respectively. The expression of CRT and PDL1 was detected 48 h after irradiation, and the median fluorescence intensities (MFIs) were compared by flow cytometry. Meanwhile, the radiosensitivity of tumor cells in each group was also compared by colony formation assays and flow cytometry. RESULTS: All types of radiation could significantly inhibit the colony formation of tumor cells under normoxia. However, the efficacy of photon and proton radiation was impaired under hypoxia. Carbon-ion radiation could still inhibit colony formation. The percentage of viable cells after irradiation was higher under hypoxia compared with those under normoxia. The CRT expression under normoxia was significantly increased after radiation. Carbon-ion radiation enhanced CRT expression compared to photon and proton radiation. Conversely, under hypoxia, the CRT expression level was significantly upregulated at baseline (0Gy). Radiation could not increase the expression further. PDL1 expression was also significantly increased by radiation under normoxia in all cell lines except the Ln18 cell line. Carbon-ion radiation induced the most significant increase. Under hypoxia, the PDL1 expression level was also upregulated at baseline and radiation could not increase expression further. CONCLUSION: Tumor cells were resistant to photon and proton but sensitive to carbon-ion radiation under hypoxia. Carbon-ion radiation could induce the highest CRT and PDL1 expression under normoxia. However, under hypoxia, radiation could not further enhance the high baseline expression of CRT and PDL1.

Specific recognition of telomeric multimeric G-quadruplexes by a simple-structure quinoline derivative.

The development of highly sensitive fluorescence probes for telomeric multimeric G-quadruplexes has attracted extensive attention. However, few probes reported have exhibited selectivity for telomeric multimeric G-quadruplexes. Thus, it is challenging to design fluorescence probes with high specificity and selectivity for telomeric multimeric G-quadruplexes. This study employed a commercially available quinoline derivative BEPQ-1 as an effective switch-on sensor for telomeric multimeric G-quadruplexes. The fluorescence intensity enhanced more than 20 folds upon the addition of telomeric multimeric G-quadruplexes. This probe exhibited good selectivity and sensitivity for telomeric multimeric G-quadruplexes. And the detection limit of BEPQ-1 for the telomeric multimeric G-quadruplex TTA45 was calculated to be 0.11 µM. The distinctive feature of BEPQ-1 is the simple structure and small size. In the light of binding mode, BEPQ-1 could even simultaneously bind to the end two G-quartets of the two adjacent G-quadruplex units in telomeric multimeric G-quadruplex by π-π stacking. To our knowledge, this is the first simple-structure fluorescence probe for telomeric multimeric G-quadruplex. This finding might provide a strategy to design specific probes for telomeric multimeric G-quadruplexes and contribute to understand the structures and functions of G-quadruplexes in the telomere region.

Recent advances in the development of ligands specifically targeting telomeric multimeric G-quadruplexes.

Long human telomeric DNA sequence could form higher-order G-quadruplex structures, namely telomeric multimeric G-quadruplexes. The formation of telomeric multimeric G-quadruplexes has been demonstrated. Several efforts have been devoted to the development of ligands targeting telomeric multimeric G-quadruplexes in recent years. The reported ligands specifically targeting telomeric multimeric G-quadruplexes exhibited either high anticancer activity with effective stabilization ability or distinct fluorescence responses to telomeric multimeric G-quadruplexes. In this review, the ligands including three types of small molecules are discussed which focus on their structural features and binding modes. Furthermore, we put forward the promising prospects and current challenges. This presented review might provide new strategies to exploit more sophisticated ligands targeting telomeric multimeric G-quadruplexes.

Development of a Monte Carlo beam model for raster scanning proton beams and dosimetric comparison.

PURPOSE: To develop a Monte Carlo (MC) beam model for raster scanning proton beams for dose verification purposes. METHODS AND MATERIALS: MC program FLUKA was used in the model. The nominal energy, momentum spread and beam angular distribution in the model were determined by matching the simulation profiles with the measured integral depth dose (IDD) and in air spot size. Dosimetric comparison was done by comparing the measured and simulated dose distributions. The 1 D dose profile of cubic Spread Out Bragg Peak (SOBP) plans, and the 2 D dose distribution of previously treated breast cancer patients' clinical plans were measured by using Pinpoint chambers and 2 D array ionization chambers, respectively. Corresponding DICOM plan information was utilized for MC simulation. RESULTS: The MC results showed good agreement with measurements for the SOBP plans. The absolute comparison of the absorbed dose difference between the MC and the measurement was 0.93%±0.88%. For the patient plans, the overall passing rate of the gamma index analysis (γ-PR) between the MC simulation and measurement with the 2%-2 mm criteria was 97.78%, and only 1 case had a γ-PR less than 90%. With the 3%-3 mm criteria, γ-PR was never below 99% for all cases with and without the range shifter. CONCLUSIONS: This work described a method for adapting a MC simulation model for a raster scanning proton beam. The good concordance between the simulations and measurements shows that the MC model is an accurate and reliable method. It has the potential to be used for patient specific quality assurance (PSQA) to reduce the beam time for the measurements in water.