Evaluating the response of anaerobic ammonium-oxidizing bacteria to heavy metal spill in freshwater sediment.

Anaerobic ammonium-oxidizing (anammox) bacteria can play an important role in nitrogen elimination in the environment. However, the effect of heavy metals on anammox bacteria in aquatic ecosystem remains largely unknown. The present study investigated the variability of anammox bacterial community in a freshwater reservoir after a severe heavy metal spill. The richness (Chao1 richness estimator = 2-18), diversity (Shannon index = 0.26-2.04) and community structure of anammox bacteria changed considerably with sampling date, while anammox bacterial abundance (from 1.38 × 105 to 3.09 × 105 anammox bacterial 16S rRNA gene copies per gram dry sediment) was less responsive to metal spill. Anammox bacterial communities were mainly composed of Brocadia- and Anammoxoglobus-like bacteria as well as novel phylotype, however, there relative abundance varied among sampling dates. This work could add the knowledge of the response of anammox bacteria to heavy metal contamination.

Response of ammonia-oxidizing archaea to heavy metal contamination in freshwater sediment.

It has been well-documented that the distribution of ammonia-oxidizing bacteria (AOB) and archaea (AOA) in soils can be affected by heavy metal contamination, whereas information about the impact of heavy metal on these ammonia-oxidizing microorganisms in freshwater sediment is still lacking. The present study explored the change of sediment ammonia-oxidizing microorganisms in a freshwater reservoir after being accidentally contaminated by industrial discharge containing high levels of metals. Bacterial amoA gene was found to be below the quantitative PCR detection and was not successfully amplified by conventional PCR. The number of archaeal amoA gene in reservoir sediments were 9.62 × 102-1.35 × 107 copies per gram dry sediment. AOA abundance continuously decreased, and AOA richness, diversity and community structure also considerably varied with time. Therefore, heavy metal pollution could have a profound impact on freshwater sediment AOA community. This work could expand our knowledge of the effect of heavy metal contamination on nitrification in natural ecosystems.

Aerobic and anaerobic methanotrophic communities in urban landscape wetland.

Both aerobic methane-oxidizing bacteria (MOB) and nitrite-dependent anaerobic methane oxidation (n-damo) organisms can be important methane sinks in a wetland. However, the influences of the vegetation type on aerobic MOB and n-damo communities in wetland, especially in constructed wetland, remain poorly understood. The present study investigated the influences of the vegetation type on both aerobic MOB and n-damo organisms in a constructed urban landscape wetland. Sediments were collected from eight sites vegetated with different plant species. The abundance (1.19-3.27 × 107 pmoA gene copies per gram dry sediment), richness (Chao1 estimator = 16.3-81.5), diversity (Shannon index = 2.10-3.15), and structure of the sediment aerobic MOB community were found to vary considerably with sampling site. In contrast, n-damo community abundance (8.74 × 105-4.80 × 106 NC10 16S rRNA gene copies per gram dry sediment) changed slightly with the sampling site. The richness (Chao1 estimator = 1-11), diversity (Shannon index = 0-0.78), and structure of the NC10 16S rRNA gene-based n-damo community illustrated slight site-related changes, while the spatial changes of the pmoA gene-based n-damo community richness (Chao1 estimator = 1-8), diversity (Shannon index = 0-0.99), and structure were considerable. The vegetation type could have a profound impact on the wetland aerobic MOB community and had a stronger influence on the pmoA-based n-damo community than on the NC10 16S-based one in urban wetland. Moreover, the aerobic MOB community had greater abundance and higher richness and diversity than the n-damo community. Methylocystis (type II MOB) predominated in urban wetland, while no known type I MOB species was detected. In addition, the ratio of total organic carbon to total nitrogen (C/N) might be a determinant of sediment n-damo community diversity and aerobic MOB richness.

The Design and Rationale of a Clinical Trial Evaluating Limb Postconditioning in Young Patients with Intracranial Arterial Stenosis.

OBJECTIVES: To examine the effectiveness of bilateral arm remote ischemic postconditioning (RIPC) on the rehabilitation of nerve function and collateral circulation in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). SETTING: Open, controlled, prospective trial (EPIC-sICAS trial) in Xi'an, Shaanxi, China. PARTICIPANTS: Up to 100 sICAS patients (age: 18-45 years, gender balance) who fulfill the inclusion and exclusion criteria will be enrolled and randomized to intervention group and control group (n ~ 50/group). INTERVENTIONS: The intervention group will undergo ischemia and reperfusion on both arms twice a day for 6 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Mean changes in collateral circulation from baseline to the end of the 6-month RIPC treatment period, measured by dynamic contrast-enhanced magnetic resonance imaging, will be the primary outcome. Clinical symptoms, serum levels of vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) will be compared as secondary outcome. RESULTS: A safety evaluation and preliminary experiment of the EPIC-sICAS trial were completed in November 2014 and March 2015, respectively. Overall and regional brain hemodynamics remained stable throughout RIPC. Activities of daily living score and serum VEGF and bFGF levels were significantly higher (P < .05) in the intervention group. CONCLUSIONS: Repetitive bilateral arm RIPC appears to have protective effects in the brain related to angiogenesis promotion and neuroprotection in the acute phase of sICAS. Assessment of the role of RIPC in collateral circulation requires imaging tests and longer follow-up, as planned in the EPIC-sICAS trial.

Dosimetric effect due to the motion during deep inspiration breath hold for left-sided breast cancer radiotherapy.

Deep inspiration breath-hold (DIBH) radiotherapy for left-sided breast cancer can reduce cardiac exposure and internal motion. We modified our in-house treatment planning system (TPS) to retrospectively analyze breath-hold motion log files to calculate the dosimetric effect of the motion during breath hold. Thirty left-sided supine DIBH breast patients treated using AlignRT were studied. Breath-hold motion was recorded ­ three translational and three rotational displacements of the treatment surface ­ the Real Time Deltas (RTD). The corresponding delivered dose was estimated using the beam-on portions of the RTDs. Each motion was used to calculate dose, and the final estimated dose was the equally weighted average of the multiple resultant doses. Ten of thirty patients had internal mammary nodes (IMN) purposefully included in the tangential fields, and we evaluated the percentage of IMN covered by 40 Gy. The planned and delivered heart mean dose, lungs V20 (volume of the lungs receiving > 20 Gy), percentage of IMN covered by 40 Gy, and IMN mean dose were compared. The averaged mean and standard deviation of the beam-on portions of the absolute RTDs were 0.81 ± 1.29 mm, 0.68 ± 0.85mm, 0.76 ± 0.85 mm, 0.96° ± 0.49°, 0.93° ± 0.43°, and 1.03° ± 0.50°, for vertical, longitudinal, lateral, yaw, roll, and pitch, respectively. The averaged planned and delivered mean heart dose were 99 and 101 cGy. Lungs V20 were 6.59% and 6.74%. IMN 40 Gy coverage was 83% and 77%, and mean IMN dose was 4642 and 4518 cGy. The averaged mean motion during DIBH was smaller than 1 mm and 1°, which reflects the relative reproducibility of the patient breath hold. On average, the mean heart dose and lungs V20 were reasonably close to what have been planned. IMN 40 Gy coverage might be modestly reduced for certain cases.

Tonic activation of Bax primes neural progenitors for rapid apoptosis through a mechanism preserved in medulloblastoma.

Commitment to survival or apoptosis within expanding progenitor populations poses distinct risks and benefits to the organism. We investigated whether specialized mechanisms regulate apoptosis in mouse neural progenitors and in the progenitor-derived brain tumor medulloblastoma. Here, we identified constitutive activation of proapoptotic Bax, maintained in check by Bcl-xL, as a mechanism for rapid cell death, common to postnatal neural progenitors and medulloblastoma. We found that tonic activation of Bax in cerebellar progenitors, along with sensitivity to DNA damage, was linked to differentiation state. In cerebellar progenitors, active Bax localized to mitochondria, where it was bound to Bcl-xL. Disruption of Bax:Bcl-xL binding by BH3-mimetic ABT 737 caused rapid apoptosis of cerebellar progenitors and primary murine medulloblastoma cells. Conditional deletion of Mcl-1, in contrast, did not cause death of cerebellar progenitors. Our findings identify a mechanism for the sensitivity of brain progenitors to typical anticancer therapies and reveal that this mechanism persists in medulloblastoma, a malignant brain tumor markedly sensitive to radiation and chemotherapy.

Direct aperture optimization using an inverse form of back-projection.

Direct aperture optimization (DAO) has been used to produce high dosimetric quality intensity-modulated radiotherapy (IMRT) treatment plans with fast treatment delivery by directly modeling the multileaf collimator segment shapes and weights. To improve plan quality and reduce treatment time for our in-house treatment planning system, we implemented a new DAO approach without using a global objective function (GFO). An index concept is introduced as an inverse form of back-projection used in the CT multiplicative algebraic reconstruction technique (MART). The index, introduced for IMRT optimization in this work, is analogous to the multiplicand in MART. The index is defined as the ratio of the optima over the current. It is assigned to each voxel and beamlet to optimize the fluence map. The indices for beamlets and segments are used to optimize multileaf collimator (MLC) segment shapes and segment weights, respectively. Preliminary data show that without sacrificing dosimetric quality, the implementation of the DAO reduced average IMRT treatment time from 13 min to 8 min for the prostate, and from 15 min to 9 min for the head and neck using our in-house treatment planning system PlanUNC. The DAO approach has also shown promise in optimizing rotational IMRT with burst mode in a head and neck test case.

Spatially fractionated radiation therapy: a critical review on current status of clinical and preclinical studies and knowledge gaps.

Spatially fractionated radiation therapy (SFRT) is a therapeutic approach with the potential to disrupt the classical paradigms of conventional radiation therapy. The high spatial dose modulation in SFRT activates distinct radiobiological mechanisms which lead to a remarkable increase in normal tissue tolerances. Several decades of clinical use and numerous preclinical experiments suggest that SFRT has the potential to increase the therapeutic index, especially in bulky and radioresistant tumors. To unleash the full potential of SFRT a deeper understanding of the underlying biology and its relationship with the complex dosimetry of SFRT is needed. This review provides a critical analysis of the field, discussing not only the main clinical and preclinical findings but also analyzing the main knowledge gaps in a holistic way.

[Analysis of imaging features of rare tumors in nasal cavity and paranasal sinus].

Objective:To explore the imaging features of rare tumors of nasal cavity and sinuses, and to improve the understanding of these diseases, thereby aiding clinical diagnosis and treatment. Methods:The CT and MRI findings of 79 cases of rare neoplasm of nasal cavity and sinuses confirmed by pathology were retrospectively analyzed, and the imaging features were summarized. Results:Among the 79 cases, there were 16 cases of neuroendocrine carcinoma, most showing expansive and infiltrative bone destruction without hyperosteogeny and sclerosis. The sphenoid sinus exhibited a "pigeon" shape. In 28 cases of malignant melanoma, MRI signals were diverse, typical signals were rare, but mixed signals were more common. In 12 cases of rhabdomyosarcoma, MRI enhancement mostly showed "grape-like" enhancement and partial ring enhancement; There were 10 cases of olfactory neuroblastoma, the lesions were consistent with the distribution area of olfactory mucosa, most of them were lobulated, marginal nodules, and "flower ring" enhancement, and 2 cases grew across intracranial and external, with multiple cystic lesions and surrounding flaky edema bands. In 5 cases of solitary fibrous tumor, Benign tumors had regular shape and uniform density, while malignant tumors had irregular shape and uneven density, The enhancement was obviously uneven and showed a "pattern" change. There were 2 cases of sarcomatoid carcinoma, both with lobed appearance, uneven density, lamellar low-density shadow, and osteolytic bone destruction. In 4 cases of schwannoma, the enhancement showed obvious inhomogeneous enhancement. One case showed cystic necrosis, one case showed calcification, and the surrounding structure was compressed without damage. There was 1 case of neurofibroma, with many cystic components, low signal separation and compartmentalized enhancement. One case of paraganglioma showed moderate enhancement in the arterial phase and progressive enhancement in the venous phase, accompanied by significant swelling bone destruction. Conclusion:Rare tumors of nasal cavity and paranasal sinuses have distinctive imaging features. CT and MRI can effectively show the extent of the lesions and the degree of infiltration into adjacent tissues and organs, which is helpful for early clinical diagnosis and staging. However, definitive diagnosis still depends on pathology and immunohistochemistry.

Overview and Recommendations for Prospective Multi-institutional Spatially Fractionated Radiation Therapy Clinical Trials.

PURPOSE: The highly heterogeneous dose delivery of spatially fractionated radiation therapy (SFRT) is a profound departure from standard radiation planning and reporting approaches. Early SFRT studies have shown excellent clinical outcomes. However, prospective multi-institutional clinical trials of SFRT are still lacking. This NRG Oncology/American Association of Physicists in Medicine working group consensus aimed to develop recommendations on dosimetric planning, delivery, and SFRT dose reporting to address this current obstacle toward the design of SFRT clinical trials. METHODS AND MATERIALS: Working groups consisting of radiation oncologists, radiobiologists, and medical physicists with expertise in SFRT were formed in NRG Oncology and the American Association of Physicists in Medicine to investigate the needs and barriers in SFRT clinical trials. RESULTS: Upon reviewing the SFRT technologies and methods, this group identified challenges in several areas, including the availability of SFRT, the lack of treatment planning system support for SFRT, the lack of guidance in the physics and dosimetry of SFRT, the approximated radiobiological modeling of SFRT, and the prescription and combination of SFRT with conventional radiation therapy. CONCLUSIONS: Recognizing these challenges, the group further recommended several areas of improvement for the application of SFRT in cancer treatment, including the creation of clinical practice guidance documents, the improvement of treatment planning system support, the generation of treatment planning and dosimetric index reporting templates, and the development of better radiobiological models through preclinical studies and through conducting multi-institution clinical trials.

High-quality haplotype-resolved genome assembly for ring-cup oak (Quercus glauca) provides insight into oaks demographic dynamics.

Quercus section Cyclobalanopsis represents a dominant woody lineage in East Asian evergreen broadleaved forests. Regardless of its ecological and economic importance, little is known about the genomes of species in this unique oak lineage. Quercus glauca is one of the most widespread tree species in the section Cyclobalanopsis. In this study, a high-quality haplotype-resolved reference genome was assembled for Q. glauca from PacBio HiFi and Hi-C reads. The genome size, contig N50, and scaffold N50 measured 902.88, 7.60, and 69.28 Mb, respectively, for haplotype1, and 913.28, 7.20, and 71.53 Mb, respectively, for haplotype2. A total of 37,457 and 38,311 protein-coding genes were predicted in haplotype1 and haplotype2, respectively. Homologous chromosomes in the Q. glauca genome had excellent gene pair collinearity. The number of R-genes in Q. glauca was similar to most East Asian oaks but less than oak species from Europe and America. Abundant structural variation in the Q. glauca genome could contribute to environmental stress tolerance in Q. glauca. Sections Cyclobalanopsis and Cerris diverged in the Oligocene, in agreement with fossil records for section Cyclobalanopsis, which document its presence in East Asia since the early Miocene. The demographic dynamics of closely related oak species were largely similar. The high-quality reference genome provided here for the most widespread species in section Cyclobalanopsis will serve as an essential genomic resource for evolutionary studies of key oak lineages while also supporting studies of interspecific introgression, local adaptation, and speciation in oaks.

A journey to understand SFRT.

This article tells the story of a medical physicist's journey to understand SFRT which started by accident more than 15 years ago. For decades, clinical application and preclinical research have shown that spatially fractionated radiation therapy (SFRT) can achieve a magically high therapeutic index. However, only recently, SFRT received well-deserved attention from mainstream radiation oncology. Today, our understanding of SFRT remains limited, which significantly hinders the advancement of SFRT for patient care. In this article, the author intends to shed some light on several important but unanswered SFRT research questions, including what is the essence of SFRT, which dosimetric parameters have clinical relevance and which do not, how does SFRT spare normal tissue but not tumor, and why radiobiological models developed for conventional radiation therapy may not be suitable for SFRT.

Exercise preconditioning attenuates cerebral ischemia-induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway.

BACKGROUND: Exercise preconditioning (EP) is essential for preventing ischemic stroke. Recent studies have shown that EP exerts neuroprotective effects in the cerebral ischemia-reperfusion injury model. Nonetheless, there have been few reports on the relationship between EP and the Th17/Treg balance. Moreover, it is unclear whether the JAK2/STAT3 pathway is responsible for the neuroprotective effect of EP. Therefore, we aimed to explore the impact of EP, other than the anti-inflammatory and antiapoptotic functions, on the Th17/Treg balance via the JAK2/STAT3 pathway in a middle cerebral artery occlusion (MCAO)-induced model. RESULTS: Fifty rats were randomly allocated into five groups, including the sham group (n = 10), EP+sham group (n = 10), MCAO group (n = 10), EP+MCAO group (n = 10), and EP+MCAO+JAK2/STAT3 pathway agonist (coumermycin A1, CA1) group (n = 10). The results indicated that EP alleviated neurological deficits, reduced infarct volume, and ameliorated neuronal apoptosis induced by MCAO. Additionally, the MCAO-induced Th17/Treg imbalance could be rectified by EP. The decreased levels of IL-10 and Foxp3 and increased IL-17 and RORα in the MCAO group were reversed by EP treatment. Regarding inflammation, EP reduced the concentrations of IL-6 and IL-17 and elevated those of IL-10 and TGF-ß. The neuroprotective effects of EP were accompanied by decreased phosphorylation of JAK2 and STAT3. Furthermore, CA1 pretreatment diminished all the beneficial effects of EP partially. CONCLUSION: Our findings suggest that EP contributes to attenuating neuronal apoptosis, Th17/Treg imbalance, and inflammation induced by MCAO via inhibiting the JAK2/STAT3 pathway, indicating its therapeutic potential in ischemic stroke.

Monte Carlo simulation of a compact microbeam radiotherapy system based on carbon nanotube field emission technology.

PURPOSE: Microbeam radiation therapy (MRT) is an experimental radiotherapy technique that has shown potent antitumor effects with minimal damage to normal tissue in animal studies. This unique form of radiation is currently only produced in a few large synchrotron accelerator research facilities in the world. To promote widespread translational research on this promising treatment technology we have proposed and are in the initial development stages of a compact MRT system that is based on carbon nanotube field emission x-ray technology. We report on a Monte Carlo based feasibility study of the compact MRT system design. METHODS: Monte Carlo calculations were performed using EGSnrc-based codes. The proposed small animal research MRT device design includes carbon nanotube cathodes shaped to match the corresponding MRT collimator apertures, a common reflection anode with filter, and a MRT collimator. Each collimator aperture is sized to deliver a beam width ranging from 30 to 200 µm at 18.6 cm source-to-axis distance. Design parameters studied with Monte Carlo include electron energy, cathode design, anode angle, filtration, and collimator design. Calculations were performed for single and multibeam configurations. RESULTS: Increasing the energy from 100 kVp to 160 kVp increased the photon fluence through the collimator by a factor of 1.7. Both energies produced a largely uniform fluence along the long dimension of the microbeam, with 5% decreases in intensity near the edges. The isocentric dose rate for 160 kVp was calculated to be 700 Gy∕min∕A in the center of a 3 cm diameter target. Scatter contributions resulting from collimator size were found to produce only small (<7%) changes in the dose rate for field widths greater than 50 µm. Dose vs depth was weakly dependent on filtration material. The peak-to-valley ratio varied from 10 to 100 as the separation between adjacent microbeams varies from 150 to 1000 µm. CONCLUSIONS: Monte Carlo simulations demonstrate that the proposed compact MRT system design is capable of delivering a sufficient dose rate and peak-to-valley ratio for small animal MRT studies.

Should Peak Dose Be Used to Prescribe Spatially Fractionated Radiation Therapy?-A Review of Preclinical Studies.

Spatially fractionated radiotherapy (SFRT) is characterized by the coexistence of multiple hot and cold dose subregions throughout the treatment volume. In preclinical studies using single-fraction treatment, SFRT can achieve a significantly higher therapeutic index than conventional radiotherapy (RT). Published clinical studies of SFRT followed by RT have reported promising results for bulky tumors. Several clinical trials are currently underway to further explore the clinical benefits of SFRT. However, we lack the important understanding of the correlation between dosimetric parameters and treatment response that we have in RT. In this work, we reviewed and analyzed this important correlation from previous preclinical SFRT studies. We reviewed studies prior to 2022 that treated animal-bearing tumors with minibeam radiotherapy (MBRT) or microbeam radiotherapy (MRT). Eighteen studies met our selection criteria. Increased lifespan (ILS) relative to control was used as the treatment response. The preclinical SFRT dosimetric parameters analyzed were peak dose, valley dose, average dose, beam width, and beam spacing. We found that valley dose was the dosimetric parameter with the strongest correlation with ILS (p-value < 0.01). For studies using MRT, average dose and peak dose were also significantly correlated with ILS (p-value < 0.05). This first comprehensive review of preclinical SFRT studies shows that the valley dose (rather than the peak dose) correlates best with treatment outcome (ILS).

MRI Feature-Based Nomogram Model for Discrimination Between Non-Hypervascular Pancreatic Neuroendocrine Tumors and Pancreatic Ductal Adenocarcinomas.

This study aimed to investigate whether magnetic resonance imaging (MRI) features could differentiate non-hypervascular pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal adenocarcinomas (PDACs). In this study, 131 patients with surgically and pathologically proven non-hypervascular PNETs (n = 44) or PDACs (n = 87) were enrolled. Two radiologists independently analyzed MRI imaging findings and clinical features. Relevant features in differentiating non-hypervascular PNETs from PDACs were identified via univariate and multivariate logistic regression models. The MRI feature-based nomogram was constructed based on multivariable logistic analysis and the reliability of the constructed nomogram was further validated. The results showed that tumor margin (P = 0.012; OR: 6.622; 95% CI: 1.510, 29.028), MPD dilation (P = 0.047; OR: 4.309; 95% CI: 1.019, 18.227), and signal in the portal phase (P < 0.001; OR: 53.486; 95% CI: 10.690, 267.618) were independent discriminative MRI features between non-hypervascular PNETs and PDACs. The discriminative performance of the developed nomogram was optimized compared with single imaging features. The calibration curve, C-index, and DCA validated the superior practicality and usefulness of the MRI-based nomogram. In conclusion, the radiologically discriminative model integrating various MRI features could be preoperatively and easily utilized to differentiate non-hypervascular PNETs from PDACs.

LncRNA FGD5-AS1 accelerates intracerebral hemorrhage injury in mice by adsorbing miR-6838-5p to target VEGFA.

Intracerebral hemorrhage (ICH) can usually cause severe neuroinflammation and blood-brain barrier (BBB) damage. Previous studies supported the important role of long non-coding RNAs (lncRNAs) in ICH treatment. This study aimed to explore the effect of lncRNA FGD5 antisense RNA 1 (FGD5-AS1) on ICH and its potential molecular mechanisms. C57BL/6 mice were injected with collagenase VII to establish an ICH mice model. In addition, brain cerebral microvascular endothelial cells (BMVECs) were treated by oxygen-glucose deprivation (OGD)/hemin to simulate ICH. RT-qPCR revealed that FGD5-AS1 was upregulated in serum of ICH patients and mice and in OGD/hemin-treated BMVECs. Luciferase reporter gene and pull-down assays predicted and verified that FGD5-AS1 bound to miR-6838-5p, and VEGFA was a target of miR-6838-5p. FGD5-AS1 knockdown decreased the inflammatory factor contents in brain tissues and BMVECs. FGD5-AS1 overexpression inhibited cell proliferation, invasion and tight junction protein levels, and promoted apoptosis, increased the permeability of BBB and secretion of pro-inflammatory factors. In addition, miR-6838-5p knockdown reversed the inhibitory effect of FGD5-AS1 knockdown on the PI3K/Akt signaling pathway. In conclusion, FGD5-AS1 may act as an important regulator to promote apoptosis, cell permeability and inflammatory response of BMVECs via the miR-6838-5p/VEGFA axis in ICH mice.

Dosimetric evaluation of high-Z inhomogeneity used for hip prosthesis: A multi-institutional collaborative study.

PURPOSE: A multi-institutional investigation for dosimetric evaluation of high-Z hip prosthetic device in photon beam. METHODS: A bilateral hip prosthetic case was chosen. An in-house phantom was built to replicate the human pelvis with two different prostheses. Dosimetric parameters: dose to the target and organs at risk (OARs) were compared for the clinical case generated by various treatment planning system (TPS) with varied algorithms. Single beam plans with different TPS for phantom using 6 MV and 15 MV photon beams with and without density correction were compared with measurement. RESULTS: Wide variations in target and OAR dosimetry were recorded for different TPS. For clinical case ideal PTV coverage was noted for plans generated with Corvus and Prowess TPS only. However, none of the TPS were able to meet plan objective for the bladder. Good correlation was noticed for the measured and the Pinnacle TPS for corrected dose calculation at the interfaces as well as the dose ratio in elsewhere. On comparing measured and calculated dose, the difference across the TPS varied from -20% to 60% for 6 MV and 3% to 50% for the 15 MV, respectively. CONCLUSION: Most TPS do not provide accurate dosimetry with high-Z prosthesis. It is important to check the TPS under extreme conditions of beams passing through the high-Z region. Metal artifact reduction algorithms may reduce the difference between the measured and calculated dose but still significant differences exist. Further studies are required to validate the calculational accuracy.

MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases.

Hepatocellular carcinomas (HCCs) are aggressive tumors with a poor prognosis. Approved first-line treatments include sorafenib, lenvatinib, and a combination of atezolizumab and bevacizumab; however, they do not cure HCC. We investigated MBP-11901 as a drug candidate for HCC. Cell proliferation and cytotoxicity were evaluated using normal and cancer human liver cell lines, while Western blotting and flow cytometry evaluated apoptosis. The anticancer effect of MBP-11901 was verified in vitro through migration, invasion, colony formation, and JC-1 MMP assays. In mouse models, the tumor volume, tumor weight, and bodyweight were measured, and cancer cell proliferation and apoptosis were analyzed. The toxicity of MBP-11901 was investigated through GOT/GPT and histological analyses in the liver and kidney. The signaling mechanism of MBP-11901 was investigated through kinase assays, phosphorylation analysis, and in silico docking simulations. Results. MBP-11901 was effective against various human HCC cell lines, leading to the disappearance of most tumors when administered orally in animal models. This effect was dose-dependent, with no differences in efficacy according to administration intervals. MBP-11901 induced anticancer effects by targeting the signaling mechanisms of FLT3, VEGFR2, c-KIT, and PDGFRß. MBP-11901 is suggested as a novel therapeutic agent for the treatment of advanced or unresectable liver cancer.