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.

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.

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.

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.

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.

Suicide rates among patients with first and second primary cancer.

AIMS: With advancements in cancer treatments, the survival rates of patients with their first primary cancer (FPC) have increased, resulting in a rise in the number of patients with second primary cancer (SPC). However, there has been no assessment on the incidence of suicide among patients with SPC. This study assessed the occurrence of suicide among patients with SPC and compared them with that in patients with FPC. METHODS: This was a retrospective, population-based cohort study that followed patients with FPC and SPC diagnosed from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 17 registries database between 1 January 2000 and 31 December 2019. RESULTS: For patients with SPC, an age of 85+ years at diagnosis was associated with a higher incidence of suicide death (HR, 1.727; 95% CI, 1.075-2.774), while the suicide death was not considerably different in the chemotherapy group (P > 0.05). Female genital system cancers (HR, 3.042; 95% CI, 1.819-6.361) accounted for the highest suicide death among patients with SPC. The suicide death distribution of patients with SPC over time indicated that suicide events mainly occurred within 5 to 15 years of diagnosis. Compared with patients with FPC, patients with SPC in general had a lower risk of suicide, but increased year by year. CONCLUSION: The risk of suicide was reduced in patients with SPC compared with patients with FPC, but increased year by year. Therefore, oncologists and related health professionals need to provide continuous psychological support to reduce the incidence of suicide. The highest suicide death was found among patients with female genital system cancer.

Induction chemotherapy reduces target volume drift in patients with locoregionally advanced nasopharyngeal carcinoma undergoing adaptive intensity-modulated radiotherapy: a retrospective cohort study.

Background: Adaptive radiotherapy (ART) provides real-time correction of the target and dose of radiation based on repeat computed tomography (CT) imaging and replanning during intensity-modulated radiation therapy (IMRT) and is important for locoregionally advanced nasopharyngeal carcinoma (NPC). However, repeat CT imaging and replanning are time-consuming and hinder the broader application of ART. The optimum dose and frequency of replanning time have been published in previous reports. The purpose of this study was to determine whether induction chemotherapy (IC) reduces target volume drift during IMRT, potentially reducing the replanning workload. Methods: From January 2012 to December 2017, 40 patients with locoregionally advanced, nonmetastatic stage III-IVa NPC treated in the Department of Radiation Oncology in the First Affiliated Hospital, College of Medicine, Zhejiang University, were enrolled into this study. Of the 40 patients, 20 received 2-3 cycles of IC before concurrent chemoradiotherapy (IC + CCRT), and the other 20 patients were treated with CCRT plus adjuvant chemotherapy (CCRT + AC). During CCRT, all patients underwent weekly simulated CT for 6 weeks. The gross tumor volume (GTV), clinical target volume (CTV), and body weight were measured weekly and compared between the 2 groups. Results: Compared with the baseline, the mean weight loss after 25 fractions was 7.0 kg (13.6%; range, 3.9-25.5%) in the CCRT + AC group and 5.7 kg (8.3%; range, 3.6-20%) in the IC + CCRT group. The mean GTV and CTV decreased by 16.55 mL (15.7%; range, 6.1-33.7%) and 61.25 mL (9.33%; range, 4.4-17.0%), respectively, in the IC + CCRT group, and by 39.86 mL (38.79%; range, 25.3-50.7%) and 87.72 mL (12.7%; range, 6.7-22.9%), respectively, in the CCRT + AC group. The degree of weekly reduction in the GTV of the IC + CCRT group was not significantly higher than that of the CCRT + AC group, with the following P values of each percentage reduction in comparison with the previous week over 5 weeks, respectively: P<0.001, P=0.015, P=0.01, P=0.01, and P<0.001. The weekly CTV reduction only significantly correlated with weight loss (P=0.005) in the IC + CCRT group. Conclusions: IC significantly decreased the degree of weight loss, GTV shrinkage, and CTV reduction during CCRT, consequently decreasing the anatomical and target dose drift during the adaptive replanning of IMRT. This may lead to a reduction in the recurrence of locoregionally advanced NPC, especially among patients with large metastatic cervical lymph nodes, potentially improving survival. This result provides favorable evidence that IC improves locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with locoregionally advanced NPC.

Protective Role of Shenmai Injection on Radiation-Induced Heart Injury.

Radiation-induced heart injury (RIHI) limits the dose delivery of radiotherapy for thoracic cancer. Shenmai injection (SMI) is reported to have potential cytoprotective properties and is commonly used in cardiovascular diseases. So, we aimed to investigate the potential protective effects of SMI treatment on RIHI. In this study, we established the RIHI model using Sprague-Dawley rats and H9c2 cell line. In vivo, the biochemical assay was used to measure serum cardiac injury-related biomarkers and echocardiography to evaluate heart function. The pathological analysis was also applied to observe the myocardial structural changes. In vitro, we further measured the cell viability and reactive oxygen species (ROS) levels after irradiation with or without SMI treatment. Our data showed the administration of SMI reduced the level of serum cardiac injury biomarkers and ameliorated cardiac dysfunction after irradiation in rats. Pathological analysis revealed that SMI mitigated cardiac structural damage, fibrosis, and macrophage infiltration. Besides, treatment with SMI increased cell viability and decreased excess ROS production after irradiation in vitro. Taken together, our study demonstrated the protective role of SMI treatment on RIHI by inhibiting oxidative stress and decreasing structural remodeling.

STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma.

Radioresistance is the major reason for the failure of radiotherapy in esophageal squamous cell carcinoma (ESCC). Previous evidence indicated that stanniocalcin 2 (STC2) participates in various biological processes of malignant tumors. However, researches on its effect on radioresistance in cancers are limited. In this study, STC2 was screened out by RNA-sequencing and bioinformatics analyses as a potential prognosis predictor of ESCC radiosensitivity and then was determined to facilitate radioresistance. We found that STC2 expression is increased in ESCC tissues compared to adjacent normal tissues, and a higher level of STC2 is associated with poor prognosis. Also, STC2 mRNA and protein expression levels were higher in radioresistant cells than in their parental cells. Further investigation revealed that STC2 could interact with protein methyltransferase 5 (PRMT5) and activate PRMT5, thus leading to the increased expression of symmetric dimethylation of histone H4 on Arg 3 (H4R3me2s). Mechanistically, STC2 can promote DDR through the homologous recombination and non-homologous end joining pathways by activating PRMT5. Meanwhile, STC2 can participate in SLC7A11-mediated ferroptosis in a PRMT5-dependent manner. Finally, these results were validated through in vivo experiments. These findings uncovered that STC2 might be an attractive therapeutic target to overcome ESCC radioresistance.

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.

Alternating Expiration and Inspiration Breath-Hold Spares the Chest Wall During Stereotactic Body Radiation Therapy for Peripheral Lung Malignancies.

PURPOSE: The proximity of tumors to the chest wall brings additional risks of chest wall pain during stereotactic body radiation therapy. Herein, we dosimetrically compared alternated breath-hold (ABH) plans with single BH plans and determined the common characteristics of eligible patients who may obtain better chest wall sparing using this technique. METHODS AND MATERIALS: Twenty patients with lung lesions adjacent to the chest wall were enrolled and received respiratory training. Their half-fraction end expiration BH and deep inspiration BH plans were summed to generate the ABH plans. Dosimetric parameters of the chest wall were compared between single and alternated BH plans, and the correlation between tumor location and the outcome of chest wall sparing was quantitatively evaluated. Pretreatment cone beam computed tomography variations in eligible patients were recorded as well. RESULTS: Compared with the end expiration BH and deep inspiration BH plans, the ABH plans reduced chest wall dosimetric results with median reductions of 2.0% and 3.9% (Dmax: maximum point dose), 15.4% and 14.8% (D1cc: dose to a volume of 1 cm3), and 48.8% and 63% (V30: volume receiving 30 Gy or more), respectively. Relative tumor displacements (ratio of tumor displacement in the superior-inferior direction to planning target volume diameter) were greater in the lower lobe than in the upper and middle lobes (1.17 vs 0.18). Meanwhile, better median reductions of 44% (Dmax), 46% (D1cc), and 98% (V30) were obtained in the lower lobe cohort using the ABH technique. Pretreatment variations for all BHs met the 5-mm threshold. CONCLUSIONS: The ABH technique can significantly spare the adjacent chest wall without compromising planning target volume coverage in comparison with the single BH, and patients with tumors in the lower lobes can obtain better chest wall sparing than in the upper and middle lobes. Further investigation is warranted to validate these findings.

Prognostic Value of a CT Radiomics-Based Nomogram for the Overall Survival of Patients with Nonmetastatic BCLC Stage C Hepatocellular Carcinoma after Stereotactic Body Radiotherapy.

Purpose: This study aimed to investigatie the feasibility of pretherapeutic CT radiomics-based nomograms to predict the overall survival (OS) of patients with nondistant metastatic Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) undergoing stereotactic body radiotherapy (SBRT). Methods: A retrospective review of 137 patients with nondistant metastatic BCLC-C HCC who underwent SBRT was made. Radiomics features distilled from pretherapeutic CT images were selected by the method of LASSO regression for radiomics signature construction. Then, the clinical model was constructed based on clinical characteristics. A radiomics nomogram was constructed using the radiomics score (Rad-score) and clinical characteristics to predict post-SBRT OS in BCLC-C HCC patients. An analysis of discriminatory ability and calibration was performed to confirm the efficacy of the radiomics nomogram. Results: In order to construct the radiomic signature, seven significant features were selected. Patients were divided into low-risk (Rad-score < -0.03) and high-risk (Rad-score ≥ -0.03) groups based on the best Rad-score cutoff value. There were statistically significant differences in OS both in the training set (p < 0.0001) and the validation set (p=0.03) after stratification. The C-indexes of the radiomics nomogram were 0.77 (95% CI: 0.72-0.82) in the training set and 0.71 (95% CI: 0.61-0.81) in the validation set, which outperformed the clinical model and radiomics signature. An AUC of 0.76, 0.79, and 0.84 was reached for 6-, 12-, and 18-month survival predictions, respectively. Conclusions: The predictive nomogram that combines radiomic features with clinical characteristics has great prospects for application in the prediction of post-SBRT OS in nondistant metastatic BCLC-C HCC patients.

A powerful antitumor "trident": the combination of radio-, immuno- and anti-angiogenesis therapy based on mesoporous silica single coated gold nanoparticles.

Although immunotherapy in combination with anti-angiogenesis therapy has made a breakthrough in the first-line treatment of cancer, considering the low responder rate and the adverse events, it is vital to propose a new combination modality. In this study, we report single encapsulated mesoporous silica coated gold nanoparticles that synergize sensitizing radiotherapy with the current combination therapy. Distinguished from simply combining two treatments, the nanoparticle-mediated "trident" therapy resolved the problem of matching the dose between radiation and drug, which determines the outcome since drug demand rises with immunosuppression from increased sensitivity to radiotherapy. The nanomedicine produced energy depositions when radiation was introduced, and released the loaded toripalimab and bevacizumab, exhibiting significant anti-tumor properties. In vitro tumor cell viability results indicated the highest inhibition by the "trident" therapy and in vivo animal models also revealed the earliest decrease in tumor tissue volume. As a result, the "trident" therapy is expected to further improve the anti-tumor benefits of the combination of immunotherapy and anti-angiogenesis therapy and provides a versatile perspective on cancer treatment.

Prognostic and Immunological Potential of Ribonucleotide Reductase Subunits in Liver Cancer.

Background: Ribonucleotide reductase (RR) consists of two subunits, the large subunit RRM1 and the small subunit (RRM2 or RRM2B), which is essential for DNA replication. Dysregulations of RR were implicated in multiple types of cancer. However, the abnormal expressions and biologic functions of RR subunits in liver cancer remain to be elucidated. Methods: TCGA, HCCDB, CCLE, HPA, cBioPortal, and GeneMANIA were utilized to perform bioinformatics analysis of RR subunits in the liver cancer. GO, KEGG, and GSEA were used for enrichment analysis. Results: The expressions of RRM1, RRM2, and RRM2B were remarkably upregulated among liver cancer tissue both in mRNA and protein levels. High expression of RRM1 and RRM2 was notably associated with high tumor grade, high stage, short overall survival, and disease-specific survival. Enrichment analyses indicated that RRM1 and RRM2 were related to DNA replication, cell cycle, regulation of nuclear division, DNA repair, and DNA recombination. Correlation analysis indicated that RRM1 and RRM2 were significantly associated with several subsets of immune cell, including Th2 cells, cytotoxic cells, and neutrophils. RRM2B expression was positively associated with immune score and stromal score. Chemosensitivity analysis revealed that sensitivity of nelarabine was positively associated with high expressions of RRM1 and RRM2. The sensitivity of rapamycin was positively associated with high expressions of RRM2B. Conclusion: Our findings demonstrated high expression profiles of RR subunits in liver cancer, which may provide novel insights for predicting the poor prognosis and increased chemosensitivity of liver cancer in clinic.

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.

MsVRL: Self-Supervised Multiscale Visual Representation Learning via Cross-Level Consistency for Medical Image Segmentation.

Automated medical image segmentation for organs or lesions plays an essential role in clinical diagnoses and treatment plannings. However, training an accurate and robust segmentation model is still a long-standing challenge due to the time-consuming and expertise-intensive annotations for training data, especially 3-D medical images. Recently, self-supervised learning emerges as a promising approach for unsupervised visual representation learning, showing great potential to alleviate the expertise annotations for medical images. Although global representation learning has attained remarkable results on iconic datasets, such as ImageNet, it can not be applied directly to medical image segmentation, because the segmentation task is non-iconic, and the targets always vary in physical scales. To address these problems, we propose a Multi-scale Visual Representation self-supervised Learning (MsVRL) model, to perform finer-grained representation and deal with different target scales. Specifically, a multi-scale representation conception, a canvas matching method, an embedding pre-sampling module, a center-ness branch, and a cross-level consistent loss are introduced to improve the performance. After pre-trained on unlabeled datasets (RibFrac and part of MSD), MsVRL performs downstream segmentation tasks on labeled datasets (BCV, spleen of MSD, and KiTS). Results of the experiments show that MsVRL outperforms other state-of-the-art works on these medical image segmentation tasks.

Prognostic implications of necroptosis-related long noncoding RNA signatures in muscle-invasive bladder cancer.

Background: Bladder cancer (BLCA) is the sixth most common cancer in men, with an increasing incidence of morbidity and mortality. Necroptosis is a type of programmed cell death and plays a critical role in the biological processes of bladder cancer (BLCA). However, current studies focusing on long noncoding RNA (lncRNA) and necroptosis in cancer are limited, and there is no research about necroptosis-related lncRNAs (NRLs) in BLCA. Methods: We obtained the RNA-seq data and corresponding clinical information of BLCA from The Cancer Genome Atlas (TCGA) database. The seven determined prognostic NLRs were analyzed by several methods and verified by RT-qPCR. Then, a risk signature was established based on the aforementioned prognostic NLRs. To identify it, we evaluated its prognostic value by Kaplan-Meier (K-M) survival curve and receiver operating characteristics (ROC) curve analysis. Moreover, the relationships between risk signature and clinical features, functional enrichment, immune landscape, and drug resistance were explored as well. Results: We constructed a signature based on seven defined NLRs (HMGA2-AS1, LINC02489, ETV7-AS1, EMSLR, AC005954.1, STAG3L5P-PVRIG2P-PILRB, and LINC02178). Patients in the low-risk cohort had longer survival times than those in the high-risk cohort, and the area under the ROC curve (AUC) value of risk signature was higher than other clinical variables. Functional analyses, the infiltrating level of immune cells and functions, ESTIMATE score, and immune checkpoint analysis all indicated that the high-risk group was in a relatively immune-activated state. In terms of treatments, patients in the high-risk group were more sensitive to immunotherapy, especially anti-PD1/PD-L1 immunotherapy and conventional chemotherapy. Conclusion: The novel NLR signature acts as an invaluable tool for predicting prognosis, immune microenvironment, and drug resistance in muscle-invasive bladder cancer (MIBC) patients.

Impact of marital status on overall survival in patients with early-stage hepatocellular carcinoma.

The purpose of the present research was to assess the prognostic impact of marital status in hepatocellular carcinoma (HCC) patients with tumors ≤ 2 cm (stage Ia) based on the data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received a histopathologic HCC diagnosis between 2004 and 2016 were recruited. Overall survival (OS) was the major outcome measure. The Cox regression model and the Fine-Gray regression model were used for the purpose of comparing and examining the prognostic value of marital status for OS. The data for a total of 2446 stage Ia HCC patients were extracted from the database. The median overall survival time was 96.0 months, with 5-year and 10-year overall survival rates of 58.2% and 45.8%, respectively. In both the Fine-Gray regression model and Cox regression model, marital status [married vs. unmarried and others, both P < 0.001, hazard ratio (HR) = 1.389 for Cox and HR = 1.378 for Fine-Gray], age at diagnosis, tumor grade, and surgery at the primary site independently served as prognostic indicators associated with OS. In conclusion, positive marital status was independently associated with better OS for stage Ia HCC patients, and its prognostic influence should be validated in the near future.

Comprehensive and clinically accurate head and neck cancer organs-at-risk delineation on a multi-institutional study.

Accurate organ-at-risk (OAR) segmentation is critical to reduce radiotherapy complications. Consensus guidelines recommend delineating over 40 OARs in the head-and-neck (H&N). However, prohibitive labor costs cause most institutions to delineate a substantially smaller subset of OARs, neglecting the dose distributions of other OARs. Here, we present an automated and highly effective stratified OAR segmentation (SOARS) system using deep learning that precisely delineates a comprehensive set of 42 H&N OARs. We train SOARS using 176 patients from an internal institution and independently evaluate it on 1327 external patients across six different institutions. It consistently outperforms other state-of-the-art methods by at least 3-5% in Dice score for each institutional evaluation (up to 36% relative distance error reduction). Crucially, multi-user studies demonstrate that 98% of SOARS predictions need only minor or no revisions to achieve clinical acceptance (reducing workloads by 90%). Moreover, segmentation and dosimetric accuracy are within or smaller than the inter-user variation.