Induction of Hepatocellular Carcinoma in Conventional Domestic Swine Using N-Diethylnitrosamine and Phenobarbital.

Purpose: Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs, generally bred for meat production, can be used to generate hepatocellular carcinoma (HCC) animal models. The goal of this study was to investigate how N-diethylnitrosamine (DENA) and phenobarbital (PB) together can generate HCC in ordinary farmed pigs. Materials and Methods: Conventional domestic swine (Sus scrofa domesticus) were used. DENA 15 mg/kg was intraperitoneally injected weekly for 12 weeks, while PB tablets (4 mg/kg) were also administered through food for 16 weeks. Blood testing and ultrasonography evaluation were performed to monitor the progress. Subsequently, computed tomography was conducted in cases with suspected nodules, followed by histopathological examination to confirm the diagnosis. Results: Ten swine (seven males, three females; age: 2 months; weight: 9-15 kg) were included in the study and followed up for 25 months; nine were experimental, and one was control for ethical considerations. The maximum weight of animals during this study reached 162-228 kg. The weight gain seen in the intervention swine was predominantly lower than that documented in the control. The laboratory analysis revealed no notable abnormalities in liver function markers but did demonstrate statistically significant changes in urea (p = 0.028) and creatinine (p = 0.003) levels. Ultrasonography and computed tomography showed multiple liver nodules with characteristics resembling HCC. Serial imaging screening and more extended observations revealed that all animals eventually developed tumors. Histopathological confirmation at 15-22 weeks post-induction revealed that all intervened swine developed multiple nodules of well-differentiated HCC and some with hepatic angiosarcoma. Conclusion: This study successfully generated HCC in conventional domestic swine with a DENA and PB combination. This investigation required at least 15 months to develop tumors. This model will be beneficial for future investigations of HCC in large animals.

Cold Tumour Phenotype Explained Through Whole Genome Sequencing in Clinical Nasopharyngeal Cancer: A Preliminary Study.

Introduction: Nasopharyngeal cancer (NPC) is a complex cancer due to its unique genomic features and association with the Epstein-Barr virus (EBV). Despite therapeutic advancements, NPC prognosis remains poor, necessitating a deeper understanding of its genomics. Here, we present a comprehensive whole genome sequencing (WGS) view of NPC genomics and its correlation with the phenotype. Methods: This study involved WGS of a clinical NPC biopsy specimen. Sequencing was carried out using a long read sequencer from Oxford Nanopore. Analysis of the variants involved correlation with the phenotype of NPC. Results: A loss of genes within chromosome 6 from copy number variation (CNV) was found. The lost genes included HLA-A, HLA-B, and HLA-C, which work in the antigen presentation process. This loss of the major histocompatibility complex (MHC) apparatus resulted in the tumour's ability to evade immune recognition. The tumour exhibited an immunologically "cold" phenotype, with mild tumour-infiltrating lymphocytes, supporting the possible etiology of loss of antigen presentation capability. Furthermore, the driver mutation PIK3CA gene was identified along with various other gene variants affecting numerous signaling pathways. Discussion: Comprehensive WGS was able to detect various mutations and genomic losses, which could explain tumour progression and immune evasion ability. Furthermore, the study identified the loss of other genes related to cancer and immune pathways, emphasizing the complexity of NPC genomics. In conclusion, this study underscores the significance of MHC class I gene loss and its probable correlation with the cold tumour phenotype observed in NPC.

Relapsed isolated CNS lymphoma treated with radiotherapy and intrathecal methotrexate followed by high-dose intravenous methotrexate, rituximab, and temozolomide: A case report.

Key Clinical Message: Optimized treatments for relapsed isolated CNS lymphoma (RI-SCNSL) remains under investigation. Temozolomide combination-based therapy, which is often used in glioblastoma may be used as potential treatment in RI-SCNSL. Abstract: One of the most common types of non-Hodgkin lymphoma (NHL) is diffuse large B-cell lymphoma (DLBCL). Despite advances in treatment, relapsed isolated CNS lymphoma (RI-SCNSL) from DLBCL remains an issue. The optimal approach in RI-SCNSL remains an area of active investigation as currently there is no high level of evidence for the treatments due to lack of randomized studies. In this case report, we present a DLBCL patient with CNS recurrence treated radiotherapy and intrathecal methotrexate (MTX) followed by intravenous high-dose MTX, rituximab, and temozolomide. To the best of our knowledge, this is the first case report describing RI-SCNSL treated with the regiments above which also include temozolomide which is used for glioblastoma.

The association of prognostic awareness with quality of life, spiritual well-being, psychological distress, and pain severity in patients with advanced cancer: Results from the APPROACH Study in Indonesia.

BACKGROUND AND OBJECTIVES: Advanced cancer patients' understanding of their illness is key for making informed treatment decisions. Despite the known importance of patients' awareness of their disease prognosis, it is debatable whether this awareness is positively, negatively, or not associated with clinical and psychological outcomes among patients with advanced cancer. This paper aims to determine the prevalence of and factors associated with prognostic awareness and its association with quality of life (QoL), spiritual well-being, pain control, and psychological distress in patients with advanced cancer in Indonesia. METHODS: This cross-sectional questionnaire-based survey was part of a multicountry study titled "Asian Patient Perspectives Regarding Oncology Awareness, Care and Health (APPROACH)." Patients were asked what they knew about their cancer and treatment. QoL and spiritual well-being were measured using the Functional Assessment of Cancer Therapy - General (FACT-G) and Functional Assessment of Chronic Illness Therapy - Spiritual Well-being (FACIT-Sp) questionnaire. Psychological distress experienced by patients was recorded via the Hospital Anxiety and Depression Scale. Pain severity was also assessed. Data from 160 patients were analyzed using descriptive statistics and multivariable regression models. RESULTS: Of the 160 patients who participated, 55 (34.4%) were unaware of their cancer stage. Those who were aware of their stage of cancer were younger than those who were not aware (45.7 years vs 50.4 years, p = .015). There was no significant difference in spiritual well-being and other domains of QoL between those who were aware and those who were not aware of their advanced cancer stage. There was also no significant difference in anxiety depression or pain severity, even after adjustment for demographic and clinical characteristics. SIGNIFICANT OF RESULTS: Given the high prevalence of patients who wrongly thought their cancer was curable, more could be done to improve disease and prognostic understanding among patients with advanced cancer in Indonesia. Those who were aware of their advanced cancer stage did not have a poorer QoL, nor did they have more anxiety or depression than those who were unaware. This finding suggests that concerns about the negative impact of prognostic disclosure may be unfounded.

Current and projected gaps in the availability of radiotherapy in the Asia-Pacific region: a country income-group analysis.

BACKGROUND: Cancer incidence and mortality is increasing rapidly worldwide, with a higher cancer burden observed in the Asia-Pacific region than in other regions. To date, evidence-based modelling of radiotherapy demand has been based on stage data from high-income countries (HIC) that do not account for the later stage at presentation seen in many low-income and middle-income countries (LMICs). We aimed to estimate the current and projected demand and supply in megavoltage radiotherapy machines in the Asia-Pacific region, using a national income-group adjusted model. METHODS: Novel LMIC radiotherapy demand and outcome models were created by adjusting previously developed models that used HIC cancer staging data. These models were applied to the cancer case mix (ie, the incidence of each different cancer) in each LMIC in the Asia-Pacific region to estimate the current and projected optimal radiotherapy utilisation rate (ie, the proportion of cancer cases that would require radiotherapy on the basis of guideline recommendations), and to estimate the number of megavoltage machines needed in each country to meet this demand. Information on the number of megavoltage machines available in each country was retrieved from the Directory of Radiotherapy Centres. Gaps were determined by comparing the projected number of megavoltage machines needed with the number of machines available in each region. Megavoltage machine numbers, local control, and overall survival benefits were compared with previous data from 2012 and projected data for 2040. FINDINGS: 57 countries within the Asia-Pacific region were included in the analysis with 9·48 million new cases of cancer in 2020, an increase of 2·66 million from 2012. Local control was 7·42% and overall survival was 3·05%. Across the Asia-Pacific overall, the current optimal radiotherapy utilisation rate is 49·10%, which means that 4·66 million people will need radiotherapy in 2020, an increase of 1·38 million (42%) from 2012. The number of megavoltage machines increased by 1261 (31%) between 2012 and 2020, but the demand for these machines increased by 3584 (42%). The Asia-Pacific region only has 43·9% of the megavoltage machines needed to meet demand, ranging from 9·9-40·5% in LMICs compared with 67·9% in HICs. 12 000 additional megavoltage machines will be needed to meet the projected demand for 2040. INTERPRETATION: The difference between supply and demand with regard to megavoltage machine availability has continued to widen in LMICs over the past decade and is projected to worsen by 2040. The data from this study can be used to provide evidence for the need to incorporate radiotherapy in national cancer control plans and to inform governments and policy makers within the Asia-Pacific region regarding the urgent need for investment in this sector. FUNDING: The Regional Cooperative Agreement for Research, Development and Training Related to Nuclear Science and Technology for Asia and the Pacific (RCA) Regional Office (RCARP03).

Calreticulin Upregulation in Cervical Cancer Tissues From Patients After 10 Gy Radiation Therapy.

Purpose: Understanding the immune response during radiation therapy (RT) in a clinical setting is imperative for maximizing the efficacy of combined RT and immunotherapy. Calreticulin, a major damage-associated molecular pattern that is exposed on the cell surface after RT, is presumed to be associated with the tumor-specific immune response. Here, we examined changes in calreticulin expression in clinical specimens obtained before and during RT and analyzed its relationship with the density of CD8+ T cells in the same patient set. Methods and Materials: This retrospective analysis evaluated 67 patients with cervical squamous cell carcinoma who were treated with definitive RT. Tumor biopsy specimens were collected before RT and after 10 Gy irradiation. Calreticulin expression in tumor cells was evaluated via immunohistochemical staining. Subsequently, the patients were divided into 2 groups according to the level of calreticulin expression, and the clinical outcomes were compared. Finally, the correlation between calreticulin levels and density of stromal CD8+ T cells was evaluated. Results: The calreticulin expression significantly increased after 10 Gy (82% of patients showed an increase; P < .01). Patients with increased calreticulin levels tended to show better progression-free survival, but this was not statistically significant (P = .09). In patients with high expression of calreticulin, a positive trend was observed between calreticulin and CD8+ T cell density, but the association was not statistically significant (P = .06). Conclusions: Calreticulin expression increased after 10 Gy irradiation in tissue biopsies of patients with cervical cancer. Higher calreticulin expression levels are potentially associated with better progression-free survival and greater T cell positivity, but there was no statistically significant relationship between calreticulin upregulation and clinical outcomes or CD8+ T cell density. Further analysis will be required to clarify mechanisms underlying the immune response to RT and to optimize the RT and immunotherapy combination approach.

Quality of life in children with brain tumors post radiotherapy in a lower-middle income country.

Indonesia is a rapidly growing lower-middle-income country (LMIC) located in Southeast Asia. It has 267.3 million inhabitants, with 31.6% (84.4 million) children. According to GLOBOCAN 2020, Indonesia had the highest prevalence of pediatric cancer cases in Southeast Asia (43.5%), and brain tumors had the third-highest incidence in Indonesia. Treating children with brain tumors with radiotherapy is challenging, especially the late treatment effects that can affect their quality of life (QoL). This study aimed to show the QoL in children with brain tumors after radiotherapy in Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia, based on PedsQL™ 4.0 generic core scale and the possible affecting factors. In this cross-sectional study, 26 of 88 children with brain tumors after radiotherapy were assessed by the PedsQL™ 4.0 generic core scale. Of the 88 patients who had brain tumor radiotherapy in 2014-2019, 31 patients were lost to follow-up, 28 were confirmed dead, and 29 were assured alive. One-year, three-year, and five-year overall survival were 71.6%, 43.2%, and 5.7%, respectively. The mean of children's QoL was 70.686 and 70.152 based on child self-report and parent proxy-report. Family income > 290 USD (regional minimum wage) was a factor that improved the QoL in children with brain tumors after radiotherapy (p = 0.008). QoL in children with brain tumors after radiotherapy could be influenced by family income.

Treatment acceptance and its associated determinants in cancer patients: A systematic review.

Treatment recommendations for cancer patients are carried out according to clinical assessment, type and stage of cancer and treatment guidelines. However, many patients do not accept the recommendations. This raises obstacles in managing of cancers, which not only affects the patients, but also the family and people around the patients. This problem could increase morbidity, mortality and recurrence rate, which might result in lower quality of life. Since this condition is a complex problem, there is necessity to explore and determine various determinants from different levels. The aim of this systematic review was to explore the acceptances of cancer treatments among cancer patients and its associated determinants. Articles published from 2010 to 2023 were searched in four databases: ScienceDirect, Medline, Google Scholar and PubMed. Articles written in English and focussing on three main cancer treatments (surgery, chemotherapy and radiotherapy) were eligible. A narrative approach was used and the data were analysed into selected themes. Data suggest that several factors influence patient acceptance for cancer therapy including sociodemographic, economic and spiritual cultural backgrounds; patient knowledge and perceptions; community support, as well as policy and availability of health facilities. The determinants consist of individual, interpersonal, institutional, community and public policy level and interaction between levels are contributing to cancer treatment acceptance. In conclusion, cancer treatment acceptance remains a problem in particular in low middle income countries. In addition, the data on radiotherapy referral acceptance were limited and needed further study.

Deciphering Driver of Nasopharyngeal Cancer Development.

A great deal of progress has been made on understanding nasopharyngeal cancer in recent decades. Genomic, transcriptomic, and proteomic studies have enabled us to gain a deeper understanding on the biology of nasopharyngeal cancer, and though this new information is elaborate and detailed, an overall picture of the driver of nasopharyngeal cancer that includes all this information is lacking. This review will focus on providing a broad overview, with plausible and simple language, on nasopharyngeal carcinogenesis based on current updated information. This will help readers to gain a broad understanding, which may be necessary to provide common ground for further research on nasopharyngeal cancer.

Correlation of Ki-67 with Radiation Response and Grade in Meningiomas: A Systematic Review.

PURPOSE: This systematic review aimed to identify the role of Ki-67 as a prognostic factor in estimating tumor grade and the radiation response in meningiomas. METHODS: A systematic search of the literature on meningiomas was carried out through the PubMed, Scopus, and EBSCOhost databases according to the PRISMA guidelines. RESULTS: Our search resulted in 465 collected articles, 15 of which satisfied the eligibility criteria. Twelve studies reported the correlation between Ki-67 and meningioma grade. Two other investigations reported the relationship between Ki-67 and the radiation response in meningioma, and one failed to capture the association between Ki-67 and the radiation response in meningioma. CONCLUSION: The Ki-67 proliferation index has a uniform correlation with meningioma grade. Two of the 3 studies on the correlation of Ki-67 with the radiation response in meningioma patients reported that patients with a higher Ki-67 responded better to radiation therapy.

Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer.

INTRODUCTION: EBV infection in nasopharyngeal cancer ensued in latent infection mode. In this latent infection various EBV oncoproteins such as EBNA1 and LMP1 was expressed. EBV oncoproteins could theoretically recruit immune cells, which might help to control cancer. Therefore, this study was aimed to elucidate the association with EBV oncoproteins (EBNA1 and LMP1), immune markers (CD4, CD8, and FOXP3) from nasopharyngeal cancer microenvironment with tumor progression. METHOD: Nasopharyngeal biopsy was obtained from patients suspected to have nasopharyngeal cancer. Those samples with microscopically confirmed nasopharyngeal cancer were tested for EBNA1, LMP1, CD4, CD8, and FOXP3 concentration with ELISA, then verified with IHC. Each patient tumor volume was assessed for primary nasopharyngeal tumor volume (GTVp) and neck nodal metastases tumor volume (GTVn). Correlation test with Spearman correlation and scatterplot were carried out. RESULT: Total 23 samples with nasopharyngeal cancer were analyzed. There was moderate correlation (ρ = 0.45; p value = 0.032) between LMP1 and GTVp. There was strong correlation (ρ = 0.81; p value < 0.001) between CD8 and GTVp. There was also moderate correlation (ρ = 0.6; p value = 0.002) between FOXP3 and GTVp. The CD8 concentration has moderate correlation with both EBNA1 (ρ = 0.46; p value = 0.026) and LMP1 (ρ = 0.47; p value = 0.023). While FOXP3 has moderate correlation with only LMP1 (ρ = 0.58; p value = 0.004). No correlation was found between all the markers tested here with GTVn. DISCUSSION: We found larger primary nasopharyngeal tumor was associated with higher CD8 marker. This was thought due to the presence of abundance CD8 T cells in the nasopharynx, but those abundance CD8 T cells were suspected to be dysfunctional. The nasopharyngeal cancer was also known to upregulate chemokines that could recruit T regulatory FOXP3 cells. Furthermore, T regulatory FOXP3 cells differentiation was induced through several pathways which was triggered by EBNA1. The correlation found in this study could guide further study to understand nasopharyngeal carcinogenesis and the relationship with our immune system.

Modern Radiotherapy Technology: Obstacles and Opportunities to Access in Low- and Middle-Income Countries.

Low- and middle-income countries (LMICs) have a large burden of cancer with differential population needs and outcomes compared to high-income countries. Access to radiotherapy, especially modern technology, is a major challenge. Modern radiotherapy has been demonstrated with better utility in overall cancer outcomes. We deliberate various challenges and opportunities unique to LMICs' set up for access to modern radiotherapy technology in the light of discussions and deliberations made during the recently concluded annual meeting of Tata Memorial Centre, India. We take examples available from various LMICs in this direction in our manuscript.

Planning human resources and facilities to achieve Sustainable Development Goals: a decision-analytical modelling approach to predict cancer control requirements in Indonesia.

OBJECTIVES: Indonesia aims to achieve universal health coverage (UHC) and Sustainable Development Goals (SDGs), including SDG 3 target 4, which focuses on cancer control, by 2030. This study aimed to forecast the human resources for health (HRH) and facilities required for cancer control in Indonesia over an 11-year period to support these goals. DESIGN: A two-stage Markov model was developed to forecast the demand side of facilities and HRH requirements for cancer control in Indonesia over an 11-year period. SETTING: Data sources used include the Indonesia Health Profile Report (2019), the Indonesian Radiation Oncology Society Database and National Cancer Control Committee documents (2019). METHODS: The study involved modelling the current availability of HRH and healthcare facilities in Indonesia and predicting future requirements. The gap between the current and the required HRH and facilities related to oncology, and the costs associated with meeting these requirements, were analysed. RESULTS: Results indicate the need to increase the number of healthcare facilities and HRH to achieve SDG targets. However, UHC for cancer care still may not be achieved, as eastern Indonesia is predicted to have no tertiary hospital until 2030. The forecast shows that Indonesia had a median of only 39% of the HRH requirements in 2019. Closing the HRH gap requires around a 47.6% increase in salary expenditure. CONCLUSION: This study demonstrates the application of decision-analytical modelling approach to planning HRH and facilities in the context of a low-to-middle-income country. Scaling up oncology services in Indonesia to attain the SDG targets will require expansion of the number and capability of healthcare facilities and HRH. This work allows an in-depth understanding of the resources needed to achieve UHC and SDGs and could be utilised in other disease areas and contexts.

DNA damage promotes HLA class I presentation by stimulating a pioneer round of translation-associated antigen production.

Antigen presentation by the human leukocyte antigen (HLA) on the cell surface is critical for the transduction of the immune signal toward cytotoxic T lymphocytes. DNA damage upregulates HLA class I presentation; however, the mechanism is unclear. Here, we show that DNA-damage-induced HLA (di-HLA) presentation requires an immunoproteasome, PSMB8/9/10, and antigen-transporter, TAP1/2, demonstrating that antigen production is essential. Furthermore, we show that di-HLA presentation requires ATR, AKT, mTORC1, and p70-S6K signaling. Notably, the depletion of CBP20, a factor initiating the pioneer round of translation (PRT) that precedes nonsense-mediated mRNA decay (NMD), abolishes di-HLA presentation, suggesting that di-antigen production requires PRT. RNA-seq analysis demonstrates that DNA damage reduces NMD transcripts in an ATR-dependent manner, consistent with the requirement for ATR in the initiation of PRT/NMD. Finally, bioinformatics analysis identifies that PRT-derived 9-mer peptides bind to HLA and are potentially immunogenic. Therefore, DNA damage signaling produces immunogenic antigens by utilizing the machinery of PRT/NMD.

Expression of non-homologous end joining factor, Ku80, is negatively correlated with PD-L1 expression in cancer cells after X-ray irradiation.

The growing importance of antitumour immunity by cancer immunotherapy has prompted studies on radiotherapy-induced immune response. Previous studies have indicated that programmed cell death-1 ligand (PD-L1) expression is regulated by DNA damage signalling. However, PD-L1 up-regulation after radiotherapy has not been fully investigated at the clinical level, particularly in the context of expression of DNA repair factors. The present study examined the correlation of mRNA expression between PD-L1 and non-homologous end joining (NHEJ) factors using The Cancer Genome Atlas database analysis. Among NHEJ factors, Ku80 mRNA expression was negatively correlated with PD-L1 mRNA expression levels in several types of cancer (colon adenocarcinoma, breast invasive carcinoma, skin cutaneous melanoma, lung adenocarcinoma, head and neck squamous cell carcinoma, uterine corpus endometrial carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma). To verify the negative correlation in clinical samples, the present study analysed whether Ku80 expression levels affected PD-L1 up-regulation after radiotherapy using cervical squamous cell carcinoma samples. Quantitative evaluation using software analysis of immunohistochemically stained slides revealed that patients with low Ku80 positivity in biopsy specimens demonstrated increased PD-L1 expression levels after 10 Gy irradiation (Spearman's rank correlation coefficient=-0.274; P=0.017). Furthermore, PD-L1 induction levels in tumour cells after 10 Gy of irradiation were significantly inversely correlated with Ku80 expression levels (Spearman's rank correlation coefficient=-0.379; P<0.001). The present study also confirmed that short interfering RNA-mediated Ku80 depletion was associated with greater X-ray-induced PD-L1 up-regulation in HeLa cells. These results indicated that radiotherapy could enhance PD-L1 induction in tumour cells with low Ku80 expression in a clinical setting. Furthermore, these data highlighted Ku80 as a potential predictive biomarker for immune checkpoint therapy combined with radiotherapy.

Role of CD4+CD25+FOXP3+ TReg cells on tumor immunity.

Not all T cells are effector cells of the anti-tumor immune system. One of the subpopulations of CD4+ T cells that express CD25+ and the transcription factor FOXP3, known as Regulator T cells (TReg), plays an essential role in maintaining tolerance and immune homeostasis preventing autoimmune diseases, minimalize chronic inflammatory diseases by enlisting various immunoregulatory mechanisms. The balance between effector T cells (Teff) and regulator T cells is crucial in determining the outcome of an immune response. Regarding tumors, activation or expansion of TReg cells reduces anti-tumor immunity. TReg cells inhibit the activation of CD4+ and CD8+ T cells and suppress anti-tumor activity in the tumor microenvironment. In addition, TReg cells also promote tumor angiogenesis both directly and indirectly to ensure oxygen and nutrient transport to the tumor. There is accumulating evidence showing a positive result that removing or suppressing TReg cells increases anti-tumor immune response. However, depletion of TReg cells will cause autoimmunity. One strategy to improve or restore tumor immunity is targeted therapy on the dominant effector TReg cells in tumor tissue. Various molecules such as CTLA-4, CD4, CD25, GITR, PD-1, OX40, ICOS are in clinical trials to assess their role in attenuating TReg cells' function.

Overexpression of c-Met is Associated with Poor Prognosis in Glioblastoma Multiforme: A Systematic Review and Meta-Analyses.

OBJECTIVE: The aim of this study is to evaluate the association of c-Met overexpression with survival of glioblastoma multiforme (GBM) patients. METHODS: A systematic review with meta-analyses was conducted on related articles from PubMed, EBSCOhost, Scopus, and Cochrane databases with last updated search on October 31, 2020. A total of 7 studies regarding c-Met overexpression and overall survival (OS) and/or progression free survival (PFS) are included in this study. RESULTS: All studies used immunohistochemistry to examine the expression of c-Met protein. The results showed that the positive rate of c-Met overexpression was detected in approximately 33,9% - 60,5% of GBM patients. c-Met overexpression was related to worse OS (HR: 1,74; 95% CI: 1,482-2,043; Z=6,756; p<0,001) and PFS (HR: 1,66; 95% CI: 1,327-2,066; Z=4,464; p<0,001) in GBM patients. Low heterogeneity of subjects was found in both OS and PFS analyses, I2 values were 7,8% and 0,0%, respectively. CONCLUSION: In conclusion, c-Met overexpression is significantly related to shorter OS and PFS in GBM patients, so c-Met can be considered as a potential prognostic indicator in GBM.

Dosimetric analysis of three-dimensional conformal radiotherapy, intensity-modulated radiotherapy-step and shoot, helical tomotherapy, and volumetric modulated arc therapy in prostate cancer radiotherapy.

INTRODUCTION: There is limited study comparing dosimetry parameters in detail. In regard to prostate cancer, there are four different techniques, namely three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy-step and shoot (IMRT-SS), IMRT-helical tomotherapy (HT), and volumetric-modulated arc therapy (VMAT). MATERIALS AND METHODS: Experimental study with intervention on ten prostate cancer patients' computed tomography planning data. 78 Gy dose in 39 fractions was given for planning target volume.Experimental study with intervention on ten prostate cancer patients' computed tomography planning data. 78 Gy dose in 39 fractions was given for planning target volume. RESULTS: The mean V75 Gy rectum and bladder between 3D-CRT and the other three abovementioned techniques all showed significant results (P < 0.05). V5 Gy remaining volume at risk (RVR) between 3D-CRT versus VMAT and HT, IMRT-SS versus HT, and VMAT versus HT is statistically significant (P < 0.0001). The longest radiation time was done with HT (mean 4.70 ± 0.84 min). CONCLUSION: V75 Gy rectum bladder between 3D-CRT techniques differ significantly compared to the three other techniques and may not be suitable to the implementation of escalation doses. The HT technique produced the highest V5 Gy RVR and needed the highest monitor unit amount and the longest radiation duration. The VMAT technique was considered capable of realizing dose escalation in prostate cancer radiotherapy by minimizing toxicity in the rectum and bladder with the shortest radiation duration.

High linear energy transfer carbon-ion irradiation upregulates PD-L1 expression more significantly than X-rays in human osteosarcoma U2OS cells.

Programmed death ligand 1 (PD-L1) expression on the surface of cancer cells affects the efficacy of anti-PD-1/PD-L1 immune checkpoint therapy. However, the mechanism underlying PD-L1 expression in cancer cells is not fully understood, particularly after ionizing radiation (IR). Here, we examined the impact of high linear energy transfer (LET) carbon-ion irradiation on the expression of PD-L1 in human osteosarcoma U2OS cells. We found that the upregulation of PD-L1 expression after high LET carbon-ion irradiation was greater than that induced by X-rays at the same physical and relative biological effectiveness (RBE) dose, and that the upregulation of PD-L1 induced by high LET carbon-ion irradiation was predominantly dependent on ataxia telangiectasia and Rad3-related (ATR) kinase activity. Moreover, we showed that the downstream signaling, e.g. STAT1 phosphorylation and IRF1 expression, was upregulated to a greater extent after high LET carbon-ion irradiation than X-rays, and that IRF1 upregulation was also ATR dependent. Finally, to visualize PD-L1 molecules on the cell surface in 3D, we applied immunofluorescence-based super-resolution imaging. The three-dimensional structured illumination microscopy (3D-SIM) analyses revealed substantial increases in the number of presented PD-L1 molecules on the cell surface after high LET carbon-ion irradiation compared with X-ray irradiation.