A cloud-based consultation and collaboration system for radiotherapy: Remote decision support services for community radiotherapy centers.

PURPOSE: This study aimed to establish a cloud-based radiotherapy consultation and collaboration system, then investigated the practicability of remote decision support for community radiotherapy centers using the system. METHODS AND MATERIALS: A cloud-based consultation and collaboration system for radiotherapy, OncoEvidance®, was developed to provide remote services of LINAC modeling, simulation CT data import/export, target volume and organ-at-risk delineation, prescription, and treatment planning. The system was deployed on a hybrid cloud. A federate of public nodes, each corresponding to a medical institution, are managed by a central node where a group of consultants have registered. Users can access the system through network using computing devices. The system has been tested at three community radiotherapy centers. One accelerator was modeled. 12 consultants participated the remote radiotherapy decision support and 77 radiation treatment plans had been evaluated remotely. RESULTS: All the passing rates of per-beam dose verification are > 94% and all the passing rates of composite beam dose verification are > 99%. The average downloading time for one set of simulation CT data for one patient from Internet was within 1 min under the cloud download bandwidth of 8 Mbps and local network bandwidth of 100 Mbps. The average response time for one consultant to contour target volumes and make prescription was about 24 h. And that for one consultant to design and optimize a IMRT treatment plan was about 36 h. 100% of the remote plans passed the dosimetric criteria and could be imported into the local TPS for further verification. CONCLUSION: The cloud-based consultation and collaboration system saved the travel time for consultants and provided high quality radiotherapy to patients in community centers. The under-staffed community radiotherapy centers could benefit from the remote system with lower cost and better treatment quality control.

Anti-silencing function 1B knockdown suppresses the malignant phenotype of colorectal cancer by inactivating the phosphatidylinositol 3-kinase/AKT pathway.

BACKGROUND: Mounting studies have highlighted the pivotal influence of anti-silencing function 1B (ASF1B) on the malignancy of cancers. AIM: To explore the influence and mechanism of ASF1B in colorectal cancer (CRC). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect mRNA expression of ASF1B. Immunohistochemical staining was performed to detect protein expression of ASF1B and Ki67 in tumor tissues. Western blot analysis was used to determine levels of ASF1B and proliferation/epithelial mesenchymal transition (EMT)/stemness-related proteins. In addition, the proliferation of CRC cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2'-Deoxyuridine assays. The migration and invasion of CRC cells were evaluated using transwell assays. Stemness of CRC cells was tested using the sphere formation assay. To construct a xenograft tumor model, HCT116 cells were introduced into mouse flanks via subcutaneous injection. RESULTS: ASF1B expression was markedly increased in CRC tissues and cells, and it was inversely correlated with overall survival of CRC patients and was positively associated with the tumor node metastasis (TNM) stage of CRC patients. Silencing of ASF1B suppressed proliferation, migration, invasion, stemness and EMT of CRC cells as well as tumorigenesis of xenograft mice. Furthermore, protein levels of P-phosphatidylinositol 3-kinase (p-PI3K) and p-AKT were decreased after silencing of ASF1B in CRC cells. The inhibitory effects of ASF1B knockdown on cell proliferation, stemness and EMT were partly abolished by PI3K activator in CRC cells. CONCLUSION: Silencing of ASF1B inactivated the PI3K/AKT pathway to suppress CRC malignancy in vitro.

Severe Radiation-Induced Lymphopenia Affects the Outcomes of Esophageal Cancer: A Comprehensive Systematic Review and Meta-Analysis.

The aim of the current study was to evaluate the influence of severe radiation-induced lymphopenia (RIL) on the outcomes of esophageal cancer (EC). A systematic review and meta-analysis was performed through the PRISMA guideline. Seventeen studies were included in the current systematic review, with eight included in the meta-analyses. Meta-analyses found that severe RIL was associated with lower pathologic complete response (pCR) rate (odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.30-0.66, I2 = 0%), inferior overall survival (OS) (hazard ratio (HR) = 1.50, 95% CI = 1.29-1.75, I2 = 6%), and worse progression-free survival (PFS) (HR = 1.70, 95% CI = 1.39-2.07, I2 = 0%) of EC patients. The lymphocyte nadir was found during 4-6 weeks after the start of radiotherapy. The leading dosimetric factors associated with severe RIL included larger PTV, higher dose to heart and body, and higher effective dose to the immune cells (EDIC). Clinical risk factors for RIL mainly comprised lower baseline ALC, higher tumor length and clinical stage, and distal EC. In conclusion, severe RIL might be associated with a lower pCR rate and worse OS and PFS of EC patients. Minimizing the dosimetric risk factors, especially in patients with clinical risk factors, might benefit their outcomes.

Secondary myelodysplastic syndromes identified via next-generation sequencing in a non-small cell lung cancer patient.

BACKGROUND: Myelodysplastic syndrome (MDS) is a group of clonal disorders characterized by ineffective and dysplastic hematopoiesis in the bone marrow with a high risk of progression to leukemia. Many studies have demonstrated that chemo-radiotherapy for cancer patients and exposure to certain chemicals may increase the risk of secondary MDS, which is characterized by specific chromosomal abnormalities and genomic alterations. Since next-generation sequencing (NGS) has been widely used for the diagnosis of cancer patients, advanced analysis of the sequencing data may provide supplementary information for secondary MDS. CASE PRESENTATION: A male patient with non-small cell lung cancer (NSCLC) and bone metastases has presented distal obstructive inflammation, the enlargement of the left hilar, mediastinal lymph node metastases, and multiple bone metastases. This patient has undergone long-term exposures to certain chemicals. Moreover, the deletion of chromosome 7 and 5q is detected in his peripheral blood sequencing, indicating secondary MDS, subsequently confirmed by bone marrow examination. CONCLUSION: In this case, an NSCLC patient was diagnosed with secondary MDS via NGS analysis, indicating that the NGS analysis may serve as supplementary for diagnosis of secondary MDS and provide useful information of therapeutic regimens for subsequent-line treatment of EGFR-mutated lung cancer. To the best of our knowledge, this is the first report of acquired MDS in a lung adenocarcinoma patient.

PD-1 expression is elevated in monocytes from hepatocellular carcinoma patients and contributes to CD8 T cell suppression.

It is recently shown that PD-1 expression by immune cells of the myeloid lineage contributes to the suppression of antitumor immunity. The expression of PD-1 by antigen-presenting cells in hepatocellular carcinoma (HCC), a malignancy with high intratumoral PD-L1 expression, remained understudied. Here, we found that circulating monocytes from HBV-associated HCC patients upregulated PD-1 in a severity-dependent manner. Monocyte stimulation using IFN-γ or high levels of IL-10 could slightly increase PD-1 expression, while LPS could markedly increase PD-1 expression. Interestingly, LPS in combination with IL-4 or IL-10 presented stronger stimulation of PD-1 expression than LPS in combination with IFN-γ or LPS alone. At resting state, PD-1+ monocytes presented comparable MHC-I and IL-12 expression and higher MHC-II, CD86, iNOS, arginase I, and IL-10 expression than PD-1- monocytes. Upon LPS stimulation, PD-1+ monocytes presented lower iNOS and higher arginase I and IL-10 expression than PD-1- monocytes, indicating an M2-polarization bias in PD-1+ monocytes. CD8 T cells following coculture with PD-1+ monocytes presented lower IFN-γ and lower TNF-α expression, together with lower proliferation capacity, than CD8 T cells following coculture with PD-1- monocytes, suggesting that PD-1+ monocytes were less capable of supporting CD8 T cell activation. Overall, these data indicated that PD-1 expression was elevated in monocytes from hepatocellular carcinoma patients. In addition, PD-1+ monocytes presented a preference toward M2 polarization and had a deficiency in supporting CD8 T cells.

Patients with radiation enteritis present regulatory T cell impairment associated with CTLA-4.

Radiation enteritis is one of the most common side effects of ionizing radiation in patients with pelvic cancers. Increasing amounts of evidence indicate that pro-inflammatory responses significantly contribute to the development of radiation enteritis. In this study, we investigated the association between T regulatory (Treg) cells and the risk of developing radiation enteritis in cervical cancer patients. The following observations were made. First, the frequencies of CD25hiFoxp3+ Treg cells were significantly lower in patients with radiation enteritis than in both healthy subjects and cervical cancer patients without radiation enteritis. Also, patients with the more severe grade 3 enteritis presented significantly lower Treg levels than patients with the more common grade 1 enteritis. Second, the expression of several molecules associated with Treg function, including CTLA-4, IL-10, TGF-ß, and perforin, was significantly lower in patients with radiation enteritis than in healthy subjects. In patients without radiation enteritis, however, only CTLA-4, but not other Treg-associated suppressive molecules, was reduced in Treg cells. Third, Treg cells can markedly suppress CD8 T cell proliferation, but in patients with radiation enteritis, this function of Treg cells was significantly impaired, in a manner that was associated with lower CTLA-4 expression. Overall, these data suggest that the frequency and function of Treg cells is negatively associated with the risk of developing enteritis following radiation. In clinical practice, the characteristics of Treg cells may be considered to evaluate the risk of developing enteritis if the cancer patient is receiving ionizing radiation.

Definitive chemoradiotherapy and salvage chemotherapy for patients with isolated locoregional recurrence after radical resection of primary pancreatic cancer.

Purpose: The objective of this study was to analyze the safety and efficacy of definitive chemoradiotherapy and salvage chemotherapy in pancreatic cancer (PC) patients with isolated locoregional recurrence after radical resection and assess the factors associated with tumor response. Patients and methods: A retrospective study of isolated locoregional recurrent PC patients who were treated with definitive chemoradiotherapy and salvage chemotherapy at our institution between 2012 and 2017 was conducted. Medium dose of 56.0 Gy (range: 54.0 Gy - 60.2 Gy) in 1.8 Gy to 2.15 Gy daily fractions was prescribed to the PTV-G and 50.4 Gy was prescribed to the PTV-C. Patients received chemotherapy before, at the same time with or after radiotherapy. The overall survival (OS) and freedom from locoregional progression (FFLP) rates were estimated by the Kaplan-Meier method, and the log-rank test was performed to compare survival curves. The Cox regression was used to identify factors affecting response to treatment and survival. Results: Thirty-one patients were included. The median interval from the resection of primary PC to the diagnosis of the locoregional recurrence (DFI) was 7.4 months (range 0.2-44.6). Within a median follow-up from the start of radiotherapy (RT) of 31.7 months (95% CI: 20.0-43.5 months), the medium OS and FFLP rates from the start of RT were 23.6 and 12.0 months, respectively. DFI >6 months was shown to be a significant factor associated with favorable OS. Acute and late toxicity of grade 3 occurred in 3 patients (9.7%) and 1 patient (3.2%) respectively. No grade 4 toxicity or higher occurred. Conclusions: This single-institution retrospective analysis identified definitive chemoradiotherapy and salvage chemotherapy to be a feasible and tolerable treatment strategy for patients with isolated locoregional recurrence after radical resection of primary PC.

Preparation and Properties of Polyvinylidene Fluoride Nanocomposited Membranes based on Poly(N-Isopropylacrylamide) Modified Graphene Oxide Nanosheets.

The nanomaterial of graphene oxide grafting poly (N-isopropylacrylamide) (GO-g-PNIPAAm) was synthesized and PVDF/GO-g-PNIPAAm blended membranes were fabricated by wet phase inversion. In this work, a hydrophilic nanomaterial GO-g-PNIPAAm with poly(N-isopropylacrylamide) (PNIPAAm) grafted on GO, was synthesized by the atom transfer radical polymerization (ATRP) method. The resulting nanomaterial was confirmed by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectrum, and X-ray photoelectron spectroscopy (XPS) analysis. The synthesized GO-g-PNIPAAm was incorporated with polyvinylidene fluoride (PVDF) via phase inversion, and investigated for its temperature sensitivity, porosity, contact angle, scanning electron microscopy, and permeate properties. The water contact angle measurements confirmed that GO-g-PNIPAAm nanomaterial-endowed PVDF membranes with better hydrophilicity and thermo-responsive properties compared with those of the pristine PVDF membranes. Bovine serum albumin (BSA) adsorption experiments suggested that excellent antifouling properties of membranes were acquired after adding GO-g-PNIPAAm. The modified membranes showed good performance when the doping amount of GO-g-PNIPAAm was 0.2 wt %.

The proliferation of colorectal cancer cells is suppressed by silencing of EIF3H.

Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Eukaryotic translation initiation factor 3, subunit H (EIF3H) is a subunit of EIF3, which is involved in mRNA recruitment and ribosomal complex disassembly and is known to be a driver of cell proliferation and survival in cancer. To investigate its function in colorectal cancer, the Oncomine database was used to evaluate the expression of EIF3H in human colorectal cancer and normal tissues. Then, we constructed a Lentivirus shorthair EIF3H vector (Lv-shEIF3H) to silence EIF3H expression in the colorectal cancer cell lines HCT116 and SW1116. We observed impaired cell growth and colony formation in these silenced cell lines. In addition, we showed that EIF3H knock-down led to cell apoptosis. In conclusion, EIF3H plays key roles in the apoptosis in colorectal cancer cells, which suggests EIF3H as a potential diagnostic biomarker in colorectal cancer.

Tr1 responses are elevated in asymptomatic H. pylori-infected individuals and are functionally impaired in H. pylori-gastric cancer patients.

Gastric cancer is one of the most lethal malignancies worldwide. Chronic Helicobacter pylori (H. pylori) infection can induce an inflammatory response that promotes atrophic gastritis, a preceding event to cancer development. The type 1 regulatory T (Tr1) cells have recently emerged as a critical participant in maintaining self-tolerance. In this study, we examined Tr1 cells in H. pylori infection and gastric cancer development. While H. pylori-uninfected (uninfected) subjects presented low Tr1 frequency in the peripheral blood, H. pylori-infected asymptomatic (infected) individuals and H. pylori-infected gastric cancer (cancer) individuals both presented elevated Tr1 frequency. Although the Tr1 cells from infected asymptomatic subjects were functionally more potent than those from uninfected healthy subjects, the Tr1 cells in cancer individuals demonstrated several functional impairments, such as reduced interleukin 10 (IL-10) expression, lower secretion of cytolytic factors including granzyme B and perforin, and lower capacity to suppress CD4+CD25- T cell and CD8+ T cell proliferation. In addition, the frequency and function of Tr1 cells were positively correlated with the disease-free survival of the gastric cancer patients. These results suggest that Tr1 cells might be involved in the regulating immune responses in H. pylori infection and gastric cancer development. The fact that Tr1 cells could suppress inflammation and produce cytotoxic molecules at the same time has made them attractive potential candidates for future immunotherapies.

The recommended treatment strategy for locally advanced gastric cancer in elderly patients aged 75 years and older: a Surveillance, Epidemiology, and End Results database analysis.

BACKGROUND: As patients aged 75 years and older are often underrepresented in randomized clinical trials, the external validity of clinical trials-based recommendations in older gastric patients was still controversial. The aim of this study is to explore the recommended treatment strategy for locally advanced gastric cancer in elderly patients. METHODS: We designed our study to specifically evaluate the cancer-specific survival (CSS) of four subgroups of patients according to four different treatment modalities: adjuvant radiation (RT), surgery only, RT only and no surgery/no RT by analyzing the Surveillance, Epidemiology, and End Results (SEER)-registered database. Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. RESULTS: The 5-year CSS was 43.8 % in adjuvant RT, 28.5 % in surgery only, 14.9 % in RT only and 1.4 % in no surgery/no RT, which had significant difference in univariate log-rank test (P < 0.001) and multivariate Cox regression (P < 0.001). Moreover, we observed significant survival benefits in adjuvant RT group in all age categories, including age 75-79 years, age 80-84 years and age ≥85 years (all P < 0.001). CONCLUSIONS: Surgery and adjuvant RT may be the recommended treatment strategy in elderly patients with locally advanced gastric cancer, especially for patients medically fit for the combined modality therapy.

Response of magnetic properties to heavy metal pollution in dust from three industrial cities in China.

Magnetic method is a reliable and powerful technique for identification of the relative contribution of industrial pollutants. However, it has not been fully applied in urban area impacted by non-ferrous metal (NFM) smelting/processing activities. The aim of this study is to explore the applicability of magnetic methods for detecting heavy metal contamination in dust from three NFM smelting/processing industrial cities (Ezhou, Zhuzhou, and Hezhang) in China. The enhancements of magnetic susceptibility (MS) and saturation isothermal remanent magnetization (SIRM) together with heavy metals were significant in the studied areas in comparison with the background values. Scanning electron microscope (SEM) analysis revealed that magnetic particles in dust from Ezhou were dominated by spherules, while those from Zhuzhou and Hezhang were mainly consisted of irregular-shaped particles. κ-T curves and X-ray diffraction (XRD) analyses indicated that the magnetic particles from Ezhou were dominated by magnetite and metallic iron, whereas those from Zhuzhou and Hezhang were consisted of magnetite and hematite. Our study indicates that magnetic properties of the dust are sensitive to the NFM smelting/processing related heavy metal pollutants. However, the relationship between magnetic parameters and heavy metals was influenced by the presence of metallic iron particles and multi-sources of metal pollutants.