COL8A1 Regulates Esophageal Squamous Carcinoma Proliferation and Invasion Through PI3K/AKT Pathway.

PURPOSE: Esophageal squamous carcinoma (ESCC) is a gastrointestinal malignancy with a high mortality, but the tumorigenesis is still unclear, restricting the target therapy development of ESCC. We explored the role of COL8A1 in ESCC development. METHODS: Tissue microarrays were used to investigate the expression level of COL8A1 in ESCC tissues. The association between COL8A1 and the overall survival of ESCC patients was assessed. The effect of differential COL8A1 expression on tumor growth was investigated by the xenograft model. The regulation of COL8A1 on tumor growth, migration, and invasion was studied by using ESCC cell lines. The signal transduction pathways involved in COL8A1 were bioinformatically profiled and validated. RESULTS: The COL8A1 was significantly expressed in cancerous tissues and was associated with poor prognosis in patients with ESCC. In vivo, the tumor growth obviously declined after inhibition of the COL8A1 expression. The abilities of cell proliferation and invasion were both decreased when the expression of COL8A1 was knockdown in ESCC cell line. Furthermore, we found the inactivation of the PI3K/AKT pathway that was mediated by knockdown of COL8A1 in ESCC cells, which was reversed with COL8A1 overexpression, whereas the cell proliferation and invasion ability were restored. CONCLUSIONS: This is the first report that COL8A1 promote ESCC progression, which hopefully will provide a theoretical basis for clinical targeting of ESCC.

microRNA-15a-5p suppresses hypoxia-induced tumor growth and chemoresistance in bladder cancer by binding to eIF5A2.

In various malignant tumors (including bladder cancer) poor prognosis is associated with hypoxia and therapeutic resistance. Evidence indicates that in bladder cancer, microRNAs (miRNAs) have vital functions in acquired drug resistance. However, the involvement of miRNAs in hypoxia-mediated bladder cancer doxorubicin (Dox) resistance is unknown. Herein, we showed that hypoxia and Dox treatment downregulated miR-15a-5p expression. Using UM-UC-3 and J82 bladder cancer cell lines and in vivo mouse models of bladder cancer, we confirmed that miR-15a-5p arrests tumor cell growth and Dox resistance in vitro and in vivo. Furthermore, we determined the interaction between miR-15a-5p and eukaryotic translation initiation factor 5A-2 (eIF5A2) using dual luciferase reporters and quantitative real-time reverse transcription polymerase chain reaction assays. We also showed that a miR-15a-5p agomir repressed EIF5A2 expression in bladder cancer cells, thereby inhibiting the epithelial-mesenchymal transition (EMT) induced by Dox or hypoxia. Moreover, ectopic expression of miR-15a-5p abrogated eIF5A2-mediated Dox resistance in bladder cancer cells. Collectively, these data indicated that hypoxia promotes tumor growth and chemoresistance through the HIF-1α/miR-15a-5p/eIFTA2/EMT pathway. This new finding not only has implications for improving our understanding of the Dox resistance process during bladder cancer progression but also indicates that the miR-15a-5p agomir is a promising tool to prevent Dox resistance in patients with bladder cancer.

Nimotuzumab plus concurrent chemo-radiotherapy in unresectable locally advanced oesophageal squamous cell carcinoma (ESCC): interim analysis from a Phase 3 clinical trial.

BACKGROUND: This prospectively randomised, double-blinded, placebo-controlled, multicenter Phase 3 clinical trial was conducted to assess the efficacy and safety profile of nimotuzumab (nimo) plus concurrent chemo-radiotherapy (CCRT) in patients with unresectable locally advanced ESCC. METHODS: Patients were randomly assigned (1:1) to receive CCRT plus nimotuzumab or placebo. The primary endpoint was overall survival (OS). In addition, interim analysis for short-term response rate was pre-defined. RESULTS: A total of 201 patients were randomised into two groups. Eighty patients in the nimo group and eighty-two in the placebo group were evaluable. Three to six months after treatment, 26 (32.5%) patients achieved complete response (CR) in the nimo group, and 10 (12.2%) in the placebo group (P = 0.002). The ORR of the nimo group was significantly higher than the placebo group (93.8% vs. 72.0%, P < 0.001). The two groups' grade 3-5 adverse drug reactions were 11.1% vs. 10.9% (P > 0.05). CONCLUSIONS: Nimotuzumab, in combination with chemo-radiotherapy, increased the CRR and ORR with a good safety profile. The OS is needed to be followed and finally analysed. CLINICAL TRIAL REGISTRATION: NCT02409186.

Radical Resection Combined With Intestinal Autotransplantation for Locally Advanced Pancreatic Cancer After Neoadjuvant Therapy: A Report of 36 Consecutive Cases.

OBJECTIVE: To achieve radical resection of locally advanced pancreatic ductal adenocarcinoma (PDAC), and tested the safety and benefits of intestinal autotransplantation in pancreatic surgery. BACKGROUND: PDAC has an extremely dismal prognosis. Radical resection was proved to improve the prognosis of patients with PDAC; however, the locally advanced disease had a very low resection rate currently. We explored and evaluated whether the combination of modern advances in systemic treatment and this macroinvasive surgery was feasible in clinical practice. METHODS: Patients diagnosed as PDAC with superior mesenteric artery involvement and with or without celiac trunk involvement were included. Patients were treated with modified-FOLFIRINOX chemotherapy with or without anti-PD-1 antibodies and were applied to tumor resection combined with intestinal autotransplantation. Data on operative parameters, pathologic results, mortality, morbidity, and survival were analyzed. RESULTS: A total of 36 consecutive cases were applied to this strategy and underwent radical resection combined with intestinal autotransplantation. Among these patients, 24 of them received the Whipple procedure, 11 patients received total pancreatectomy, and the other 1 patient received distal pancreatectomy. The median operation time was 539 minutes. Postoperative pathology showed an R0 resection rate of 94.4%, and tumor invasion of a superior mesenteric artery or superior mesenteric vein was confirmed in 32 patients. The median number of dissected lymph nodes was 43, and 25 patients were positive for lymph node metastasis. The median time of intensive care unit stay was 4 days. Two patients died within 30 days after surgery due to multiorgan failure. The severe postoperative adverse events (equal to or higher than grade 3) were observed in 12 out of 36 patients, and diarrhea, gastroparesis, and abdominal infection were the most frequent adverse events. Postoperative hospital stay was averagely of 34 days. The recurrence-free survival is 13.6 months. The median overall survival of patients after diagnosis and after surgery was 21.4 months and 14.5 months, respectively. CONCLUSIONS: Our attempt suggests the safety of this modality and may be clinically beneficial for highly selected patients with PDAC. However, the experience in multidisciplinary pancreatic cancer care and intestinal transplantation is warranted.

The global burden of nasopharyngeal carcinoma from 2009 to 2019: an observational study based on the Global Burden of Disease Study 2019.

PURPOSE: The incidence and mortality rate of nasopharyngeal carcinoma (NPC) has changed in recent years. Our goal is to determine the epidemiological pattern of NPC to help policymakers allocate limited medical resources. METHODS: Detailed information about NPC from 2009 to 2019 was collected from the Global Burden of Disease 2019 database. Age-standardized rates (ASRs) and corresponding estimated annual percentage changes (EAPCs) were calculated to assess NPC's incidence and mortality trends. RESULTS: Globally, there was a consistent increase in the NPC incidence cases from 2009 to 2019 (from 121.65 × 103 cases in 2009 to 176.50 × 103 cases in 2019, increasing by 45.09%). The age-standardized incidence rate (ASIR) of NPC increased from 1.81 in 2009 to 2.12 in 2019 (EAPC = 1.59, 95% CI 1.36-1.81). On the contrary, the mortality of NPC showed a downward trend (ASDR: 0.93 in 2009 and 0.86 in 2019; EAPC = - 0.63, 95% CI - 0.78 to - 0.48), and it was negatively correlated with the social demographic index (SDI) in most regions. Both incidence and mortality rates of high-incidence territories tended to be stable or decline. Males had significantly higher incidence and mortality of NPC than females. The number of patients with onset age greater than 50 years old accounted for the highest proportion. We found that smoking, occupational exposure to formaldehyde, and alcohol use were the main risk factors for NPC-related mortality. CONCLUSION: Globally, the incidence rate of NPC has been slightly increasing, while the mortality and disability-adjusted life years (DALYs) have been decreasing. NPC burden in high-middle and middle SDI areas was the heaviest. The current prevention strategy should be repositioned, and some countries should formulate more targeted approaches to reduce the current burden of NPC.

CHI3L1 promotes proliferation and improves sensitivity to cetuximab in colon cancer cells by down-regulating p53.

BACKGROUND: Chitinase 3-like protein 1 (CHI3L1) is most likely a malignant tumor metastasis-associated gene. However, the functions of CHI3L1 in colon cancer cell proliferation and its cetuximab sensitivity are still unclear. We aimed to investigate the mechanism of CHI3L1 in promoting colon cancer cell proliferation and its sensitivity to cetuximab. METHODS: The expression of CHI3L1 in colon cancer and adjacent tissues were detected by immunohistochemistry. CHI3L1 was overexpressed in colon cancer cell lines by lentiviral technology. Cell proliferation and sensitivity to cetuximab were measured by MTT assay, cell cycle was analyzed by flow cytometry, and expression of cell cycle-related proteins was analyzed by immunoblotting. RESULTS: The results showed that the level of CHI3L1 in colon cancer tissue was significantly higher than that in adjacent tissue, which was also correlated with overall survival. The cell proliferation rate was significantly increased after overexpression of CHI3L1, and the sensitivity to cetuximab was significantly increased. The expression of p53 was down-regulated while the EGFR was up-regulated significantly in CHI3L1 overexpressed cells. When rescued the expression of p53 in HCT116-CHI3L1 cells, the cell proliferation and sensitivity to cetuximab could be restored. CONCLUSION: High levels of CHI3L1 are associated with poor prognosis and accelerate the proliferation of colon cancer cells and increase the sensitivity to cetuximab. Its mechanism of increasing the cell proliferation and sensitivity to cetuximab may be explained by down-regulating p53 expression and then, up-regulating the expression of EGFR.

The benefits evaluation of abdominal deep inspiration breath hold based on knowledge-based radiotherapy treatment planning for left-sided breast cancer.

PURPOSE: To study the impact of abdominal deep inspiration breath hold (DIBH) technique on knowledge-based radiotherapy treatment planning for left-sided breast cancer to guide the application of DIBH technology. MATERIALS AND METHODS: Two kernel density estimation (KDE) models were developed based on 40 left-sided breast cancer patients with two CT acquisitions of free breathing (FB-CT) and DIBH (DIBH-CT). Each KDE model was used to predict dose volume histograms (DVHs) based on DIBH-CT and FB-CT for another 10 new patients similar to our training datasets. The predicted DVHs were taken as a substitute for dose constraints and objective functions in the Eclipse treatment planning system, with the same requirements for the planning target volume (PTV). The mean doses to the heart, the left anterior descending coronary artery (LADCA) and the ipsilateral lung were evaluated and compared using the T-test among clinical plans, KDE predictions, and KDE plans. RESULTS: Our study demonstrated that the KDE model can generate deliverable simulations equivalent to clinically applicable plans. The T-test was applied to test the consistency hypothesis on another ten left-sided breast cancer patients. In cases of the same breathing status, there was no statistically significant difference between the predicted and the clinical plans for all clinically relevant DVH indices (P > 0.05), and all predicted DVHs can be transferred into deliverable plans. For DIBH-CT images, significant differences were observed between FB model predictions and clinical plans (P < 0.05). DIBH model prediction cannot be optimized to a deliverable plan based on FB-CT, with a counsel of perfection. CONCLUSION: KDE models can predict DVHs well for the same breathing conditions but degrade with different breathing conditions. The benefits of DIBH for a given patient can be evaluated with a quick comparison of prediction results of the two models before treatment planning.

Prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The efficacy of prophylactic cranial irradiation (PCI) in treating patients with small cell lung cancer (SCLC) has not been clear, and recent randomized studies have demonstrated conflicting results from previously published findings. The purpose of this study was to reevaluate the efficacy of PCI in patients with SCLC and to assess factors associated with its efficacy. METHODS: We conducted a quantitative meta-analysis to explore the efficacy of PCI in patients with SCLC. A literature search was performed using EMBASE, MEDLINE, Cochrane and ClinicalTrials.gov databases. We pooled the data and compared overall survival (OS) and brain metastasis (BM) between patients treated with PCI (PCI group) and patients without PCI treatment (observation group). RESULTS: Of the 1074 studies identified in our analysis, we selected seven studies including 2114 patients for the current meta-analysis. Our results showed that the PCI group showed decreased BM (HR = 0.45, 95% CI: 0.38-0.55, P < 0.001) and prolonged OS (HR = 0.81, 95% CI: 0.67-0.99, P < 0.001). However, in terms of OS, the pooled analysis showed a high heterogeneity (I2 = 74.1%, P = 0.001). In subgroup analyses of OS, we found that the heterogeneity mainly came from patients with brain imaging after initial chemoradiotherapy (HR = 0.94, 95% CI: 0.74-1.18, P = 0.59). CONCLUSIONS: The results of this study showed that PCI has a significant effect on decreasing BM but little benefit in prolonging OS when brain imaging was introduced to confirm lack of BM after initial chemoradiotherapy and before irradiation.

The prognostic value of pretreatment tumor apparent diffusion coefficient values in nasopharyngeal carcinoma.

BACKGROUND: Diffusion-weighted MR imaging (DWI) has increasingly contributed to the management of nasopharyngeal carcinoma (NPC) patients. The objective of this paper was to explore the prognostic significance of apparent diffusion coefficient (ADC) values in 93 NPC patients. METHODS: This retrospective study included 93 newly diagnosed NPC patients. Pretreatment ADC values were determined and compared with patients' age, gender, alcohol intake, smoking, tumor volume, pathological type, tumor stage, and nodal stage. Using the Kaplan-Meier method, overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated and the values compared between the low and high ADC groups. Multivariate analysis of ADC values and other 9 clinical parameters was performed using a Cox proportional hazards model to test the independent significance for OS, LRFS and DMFS. RESULTS: The mean ADC value for the initial nasopharyngeal tumors was 0.72 × 10-3 mm2/s (range: 0.48-0.97 × 10-3 mm2/s). There was no significant difference between pretreatment ADCs and patient' gender, age, smoking, alcohol intake, or tumor stage. A significant difference in the ADCs for different N stages (P = 0.022) and correlation with initial tumor volume (r = -0.26, P = 0.012) were observed. In comparison, the ADC value for undifferentiated carcinoma was lower than that for other 3 pathological types. With a median follow-up period of 50 months, the 3-year and 5-year OS rates were 88.2% and 83.3%, respectively, 3-year and 5-year LRFS rates were 93.5% and 93.3%, respectively, and 3-year and 5-year DMFS rates were 83.9% and 83.3%, respectively. Patients with tumor ADC values ≥0.72 × 10-3 mm2/s exhibited longer OS and LRFS periods compared with tumor ADC values <0.72 × 10-3 mm2/s, with P values 0.036 and 0.018, respectively. In addition, patients with deaths or recurrences or distant metastasis had significant lower ADC values than those without disease failures. According to a multivariate analysis using the Cox proportional hazard test, ADC values showed a significant correlation with OS (P = 0.0004), LRFS (P = 0.0009), and DMFS (P < 0.0001), respectively. CONCLUSIONS: Pretreatment tumor ADC values supposed to be a noninvasive important prognostic parameter for NPC.

Association between the MTHFR A1298C polymorphism and risk of cancer: evidence from 265 case-control studies.

Many molecular, epidemiological studies have been performed to explore the association between MTHFR A1298C polymorphism and cancer risk. However, the results were inconsistent or even contradictory. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR A1298C (81,040 cases and 114,975 controls from 265 studies) polymorphism. Overall, significant association was observed between MTHFR A1298C polymorphism and cancer risk when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly increased cervical cancer (dominant model: OR 1.46, 95 % CI 1.13-1.90; AC vs. AA: OR 1.48, 95 % CI 1.13-1.92) and lymphoma (dominant model: OR 1.22, 95 % CI 1.04-1.44; recessive model: OR 1.66, 95 % CI 1.15-2.39; CC vs. AA: OR 1.75, 95 % CI 1.21-2.53) risk were observed in Asians, and significantly decreased colorectal cancer risk was found in Asians (recessive model: OR 0.75, 95 % CI 0.59-0.96; CC vs. AA: OR 0.77, 95 % CI 0.60-1.00). In summary, this meta-analysis suggests that MTHFR A1298C polymorphism is associated with increased cervical cancer and lymphoma risk in Asians, and MTHFR A1298C polymorphism is associated with decreased colorectal cancer risk in Asians. Moreover, this meta-analysis also points out the importance of new studies, such as oral cancer and chronic myeloid leukemia, because they had high heterogeneity in this meta-analysis (I (2) > 75 %).

Association between the CYP2E1 polymorphisms and lung cancer risk: a meta-analysis.

The previous, published data on the association between CYP2E1 RsaI (rs2031920), DraI (rs6413432) polymorphisms and lung cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between lung cancer and CYP2E1 RsaI (5,074 cases and 6,828 controls from 34 studies), and CYP2E1 DraI (2,093 cases and 2,508 controls from 16 studies) in different inheritance models. Overall, significantly decreased lung cancer risk was observed (dominant model: odds ratio (OR) 0.80, 95 % confidence interval (95 % CI) 0.71-0.90; heterozygote model: OR 0.80, 95 % CI 0.70-0.90; additive model: OR 0.82, 95 % CI 0.72-0.94) when all the eligible studies were pooled into the meta-analysis of CYP2E1 RsaI polymorphism. In further stratified and sensitivity analyses, significantly decreased lung cancer risk was found among Asians (dominant model: OR 0.81, 95 % CI 0.71-0.93; heterozygous model: OR 0.81, 95 % CI 0.69-0.95), population-based studies (dominant model: OR 0.69, 95 % CI 0.54-0.88; recessive model: OR 0.39, 95 % CI 0.16-0.91; additive model: OR 0.67, 95 % CI 0.53-0.84; homozygous model: OR 0.34, 95 % CI 0.14-0.80; heterozygous model: OR 0.70, 95 % CI 0.54-0.91), hospital-based studies (dominant model: OR 0.80, 95 % CI 0.69-0.93; additive model: OR 0.84, 95 % CI 0.70-1.00; heterozygous model: OR 0.80, 95 % CI 0.68-0.95), lung AC (heterozygous model: OR 0.84, 95 % CI 0.71-1.00), smokers (dominant model: OR 0.72, 95 % CI 0.55-0.94), and non-smokers (dominant model: OR 0.74, 95 % CI 0.61-0.91). There was no significant association between CYP2E1 DraI polymorphism and the risk of lung cancer when all the eligible studies were pooled into the meta-analysis. However, in further stratified and sensitivity analyses, significant association was observed among smokers (dominant model: OR 0.49, 95 % CI 0.35-0.69). In summary, this meta-analysis indicates that CYP2E1 RsaI polymorphism is associated with lung cancer risk among Asians, CYP2E1 RsaI polymorphism may be associated with lung adenocarcinoma risk, and CYP2E1 RsaI and DraI polymorphisms may be associated with decreased lung cancer risk in smokers.

Association between the TP53 polymorphisms and lung cancer risk: a meta-analysis.

The previous published data on the association between TP53 codon 72, intron 6, and intron 3 16 bp polymorphisms and lung cancer risk remained controversial. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. 38 publications with 51 studies were selected for this meta-analysis, including 17,337 cases and 16,127 controls for TP53 codon 72 (from 43 studies), 2,201 cases and 2,399 controls for TP53 intron 6 (from four studies), and 4,322 cases and 4,558 controls for TP53 intron 3 16 bp (from four studies). When all the eligible studies were pooled into the meta-analysis of codon 72 polymorphism, there was significant association between lung cancer risk and codon 72 polymorphism in any genetic model (dominant model: OR = 1.13, 95 % CI 1.05-1.21; recessive model: OR = 1.14, 95 % CI 1.02-1.27; additive model: OR = 1.19, 95 % CI 1.05-1.33). In the subgroup analysis by ethnicity, histological type, source of control, and smoking status, significantly increased risks were observed in subgroups such as Asians, Caucasians, lung squamous cell carcinoma patients for Asians, population-based study, hospital-based study, non-smokers, and smokers. When all the eligible studies were pooled into the meta-analysis of intron 6 polymorphism, there was significant association between lung cancer risk and intron 6 polymorphism in dominant model (OR = 1.27, 95 % CI 1.11-1.44). When all the eligible studies were pooled into the meta-analysis of intron 3 16 bp polymorphism, there was significant association between lung cancer risk and intron 3 16 bp polymorphism in dominant model (OR = 1.12, 95 % CI 1.02-1.23) and additive model (OR = 1.41, 95 % CI 1.04-1.90). Additionally, when one study was deleted in the sensitive analysis, the results of TP53 intron 3 16 bp duplication polymorphism were changed in the dominant model (OR = 1.11, 95 % CI 0.87-1.42) and additive model (OR = 1.01, 95 % CI 0.65-1.56). In summary, this meta-analysis indicates that codon 72 and intron 6 polymorphisms show an increased lung cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on TP53 codon 72, intron 6, and intron 3 16 bp polymorphisms and lung cancer risk.

A Population-Based and Propensity Score-Matched Investigation of the Occurrence, Management, and Prognosis of Anal Mucinous Adenocarcinoma Patients.

BACKGROUND: Anal mucinous adenocarcinoma (AMAC) is an extremely rare form of anal cancer. Our objective was to examine the incidence, management, and prognostic factors of AMAC. MATERIALS AND METHODS: We analyzed age-adjusted incidence rates (AAI) over time and compared the prognosis of AMAC with anal squamous cell carcinoma (ASCC) and adenocarcinoma (AAC) using propensity score matching (PSM) and Kaplan-Meier analysis. Patients were classified based on summary stage and treatments to determine cancer-specific survival (CSS). RESULTS: AAI of AMAC fluctuated within a narrow range (0.082-0.237 per million person-years) from 2000 to 2018. AMAC had a slight non-significant trend of worse prognosis than ASCC (p=0.348) and a better prognosis than AAC (p<0.01). Females made up a larger proportion of patients diagnosed with the distant disease (p<0.05) and unmarried (p<0.05), and somewhat less probably to need surgical removal (p<0.01) and radiotherapy (p<0.01). Elderly patients, with regional stage, distant-stage disease, no surgery tended to have lower rates of survival (all p<0.05). Localized stage was associated with better prognosis (p<0.05). Surgery was associated with a tendency towards better survival (p=0.095). CONCLUSIONS: The incidence of AMAC is consistently low. AMAC demonstrates a more favorable prognosis compared to typical AAC and a slightly worse prognosis compared to ASCC. Females with AMAC were less likely to undergo surgical removal or receive radiotherapy. AMAC exhibits a low incidence yet favorable prognosis compared to typical AAC and slightly worse compared to ASCC. Elderly age is associated with poorer prognosis, while localized stage indicates better prognosis. Surgery demonstrates a trend towards improved survival.

Dynamic change of gut microbiota in head and neck concurrent chemoradiotherapy patients and its potential value in the prediction of acute oral mucositis grade as well as quality of life.

PURPOSE: Radiotherapy is the major therapy for head and neck squamous cell carcinoma (HNSCC). However, whether gut microbiota changes in HNSCC patients who received concurrent chemoradiotherapy remains unclear. This study aimed to investigate the dynamic change of gut microbiota composition, construct the first radiotherapy-related gut microbiota database in these patients and identify the potential value of the gut microbiota changing in the prediction of acute oral mucositis grade as well as patients' life quality. METHODS: We enrolled 47 HNSCC patients who scheduled with concurrent chemoradiotherapy. The field was irradiated with a total dose of 66-70 Gy in 33-35 fractions. All the patients received 2-3 cycles of platinum-based chemotherapy. After feces specimens collected, bacterial genomic DNA was isolated using magnetic beads and then analyzed by the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene. RESULTS: 194 genera which belonged to 27 phyla were found in 141 samples. Increased abundance of microbiota in diversity and richness was observed in mid-radiotherapy group. Bacteroides, Blautia, Phascolarctobacterium were three main genera in all three groups and the mid-radiotherapy group had the highest relative abundance of Phascolarctobacterium. What is more, most significantly altered bacteria shared the same variation pattern which was increased in mid-radiotherapy while decreased to the almost same level of as pre-radiotherapy in post-radiotherapy group. Further analysis indicated that Bacteroidetes showing an upward trend while Proteobacteria declining in higher grade of acute mucositis. Moreover, relatively low abundant Proteobacteria was significantly correlated with high-grade acute oral mucositis. As for the quality of life, Lactobacillales and Actinomycetales were specifically found in better life quality group. However, Clostridia_UCG_014, Eubacteriaceae, UCG_010 and Moraxellaceae were unique abundantly present in worse life quality group. CONCLUSION: Chemoradiotherapy can affect the composition of the gut microbiota in HNSCC patients during the mid-term of treatment. Yet self-stabilized ability maintained the gut microbiota homeostasis. Dynamic change of specific species could help predict acute oral mucositis grade and characterize different quality of life group in these patients.

A Convenient and Effective Preoxygenation Technique for Prolonging Deep Inspiration Breath-Hold Duration With a Venturi Mask With a 50% Oxygen Concentration.

PURPOSE: Voluntary deep inspiration breath-hold (DIBH) is commonly used in radiation therapy (RT), but the short duration of a single breath-hold, estimated to be around 20 to 40 seconds, is a limitation. This prospective study aimed to assess the feasibility and safety of using a simple preoxygenation technique with a Venturi mask to prolong voluntary DIBH. METHODS AND MATERIALS: The study included 33 healthy volunteers and 21 RT patients. Preoxygenation was performed using a Venturi mask with a 50% oxygen concentration. Paired t tests compared the duration of a single DIBH in room air and after 5, 15, and 30 minutes of preoxygenation in healthy volunteers. Sustainability of breath-hold and tolerability of heart rate and blood pressure were assessed for multiple DIBH durations in both volunteers and patients. RESULTS: In healthy volunteers, a 15-minute preoxygenation significantly prolonged the duration of a single DIBH by 24.95 seconds compared with 5-minute preoxygenation (89 ± 27.76 vs 113.95 ± 30.63 seconds; P < .001); although there was a statistically significant increase in DIBH duration after 30-minute preoxygenation, it was only extended by 4.95 seconds compared with 15-minute preoxygenation (113.95 ± 30.63 vs 118.9 ± 29.77 seconds; P < .01). After 15-minute preoxygenation, a single DIBH lasted over 100 seconds in healthy volunteers and over 80 seconds in RT patients, with no significant differences among 6 consecutive cycles of DIBH. Furthermore, there were no significant differences in heart rate or blood pressure after DIBHs, including DIBH in room air and 6 consecutive DIBHs after 15-minute preoxygenation (all P > .05). CONCLUSIONS: Preoxygenation with a 50% oxygen concentration for 15 minutes effectively prolongs the duration of 6 cycles of DIBH both in healthy volunteers and RT patients. The utilization of a Venturi mask to deliver 50% oxygen concentration provides a solution characterized by its convenience, good tolerability, and effectiveness.

Radiotherapy-Induced Astrocyte Senescence Promotes an Immunosuppressive Microenvironment in Glioblastoma to Facilitate Tumor Regrowth.

Accumulating evidence suggests that changes in the tumor microenvironment caused by radiotherapy are closely related to the recurrence of glioma. However, the mechanisms by which such radiation-induced changes are involved in tumor regrowth have not yet been fully investigated. In the present study, how cranial irradiation-induced senescence in non-neoplastic brain cells contributes to glioma progression is explored. It is observed that senescent brain cells facilitated tumor regrowth by enhancing the peripheral recruitment of myeloid inflammatory cells in glioblastoma. Further, it is identified that astrocytes are one of the most susceptible senescent populations and that they promoted chemokine secretion in glioma cells via the senescence-associated secretory phenotype. By using senolytic agents after radiotherapy to eliminate these senescent cells substantially prolonged survival time in preclinical models. The findings suggest the tumor-promoting role of senescent astrocytes in the irradiated glioma microenvironment and emphasize the translational relevance of senolytic agents for enhancing the efficacy of radiotherapy in gliomas.

Predictors for replanning in loco-regionally advanced nasopharyngeal carcinoma patients undergoing intensity-modulated radiation therapy: a prospective observational study.

BACKGROUND: Replanning in intensity-modulated radiotherapy (IMRT) has been reported to improve quality of life and loco-regional control in patients with nasopharyngeal cancer (NPC). Determination of the criteria for replanning is, however, urgently needed. We conducted a prospective study to determine when and for what type of patients is replanning preferred through weekly repeat computed tomography (CT) imaging during the course of IMRT. METHODS: We recruited 20 patients who were diagnosed as having loco-regionally advanced, non-metastatic stage III or IVa NPC and treated with concurrent platinum-based chemoradiotherapy (CRT) using IMRT. Patients received CT simulation (sim-CT) and plain magnetic resonance imaging (MRI) plus diffusion-weighted imaging (DWI) weekly for five consecutive weeks. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated and recorded weekly based on the CT-CT fusion. The relationship between GTV/CTV reduction and clinical characteristics of the patients were assessed using Pearson correlation test. RESULTS: GTV and CTV decreased during the treatment by 36.03 mL (range, 10.91-98.82 mL) and 76.79 mL (range, 33.94-125.14 mL), respectively, after 25 fractions of treatment. The percentage reductions from their initial volume were 38.4% (range, 25.3-50.7%) and 11.8% (range, 6.7-18.3%), respectively. The greatest reductions in GTV and CTV were observed at the fourth week (i.e., upon completion of 20 fractions), compared to pre-treatment sim-CT. Weight loss and CTV reduction were significantly correlated with pre-treatment body mass index (BMI ) (r =0.58, P =0.012, and r =0.48, P =0.046, respectively). However, no significant correlation was observed between CTV reduction and initial tumor volume. In addition, GTV reduction was not significantly correlated with pre-treatment tumor volume (P =0.65), but negatively correlated with pre-treatment tumor apparent diffusion coefficient (ADC) values (r = -0.46, P =0.042). CONCLUSIONS: Our results indicate that the most appropriate replanning time is after 20 fractions of treatment, and pre-treatment BMI and ADC are potential predictive factors for the determination of replanning during IMRT.

Effect of antisense oligodeoxynucleotides glucose transporter-1 on enhancement of radiosensitivity of laryngeal carcinoma.

PURPOSE: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngeal carcinoma. METHODS: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vitro and in vivo. RESULTS: After transfection of GLUT-1 AS-ODNs: MTS assay showed the survival rates of radiation groups were reduced with the prolongation of culture time (p<0.05); Cell survival rates were significantly reduced along with the increasing of radiation dose (p<0.05). There was significant difference in the expression of GLUT-1mRNA and protein in the same X-ray dose between before and after X-ray radiation (p<0.05). In vivo, the expressions of GLUT-1 mRNA and protein after 8Gy radiation plus transfection of GLUT-1 AS-ODNs were significant decreased compared to 8Gy radiation alone (p<0.001). CONCLUSION: Radioresistance of laryngeal carcinoma may be associated with increased expression of GLUT-1 mRNA and protein. GLUT-1 AS-ODNs may enhance the radiosensitivity of laryngeal carcinoma mainly by inhibiting the expression of GLUT-1.

The Natural History of Parapharyngeal Solitary Fibrous Tumor/Hemangiopericytoma: A Case Report.

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is extremely rare, and most of them are immediately treated for radical resection. However, the information concerning its natural history remains unclear. In this report, we presented a patient with parapharyngeal SFT/HPC, who was not immediately treated with surgical resection at first diagnosis. After approximately 3 years, the tumor volume doubling time (TVDT) and specific growth rate (SGR) could be measured through 3 serial magnetic resonance imagings. The TVDTs in the early and late pretreatment stages were 350 and 180 days, respectively, while the SGRs were 0.002 and 0.003, respectively. The growth rate of this disease entity is generally slow and may accelerate in the disease process.