RSPO3 regulates the radioresistance of Non-Small cell lung cancer cells via NLRP3 Inflammasome-Mediated pyroptosis.

PURPOSE: Radioresistance is a significant challenge in the radiotherapy of non-small cell lung cancer (NSCLC). This study aimed to investigate the role of R-spondin 3 (RSPO3) in regulating NSCLC radioresistance. METHODS AND MATERIALS: RNA sequencing was performed to analyze genes that are differentially expressed in radioresistant NSCLC cell lines. RSPO3 overexpression and knockdown experiments were conducted to assess its impact on radiosensitivity. The involvement of the ß-catenin-NF-κB signaling pathway and the NLRP3 inflammasome in RSPO3-mediated radiosensitivity was also evaluated. In vivo experiments were conducted using a clinical-grade anti-RSPO3 antibody (OMP-131R10/rosmantuzumab) to assess its impact on radiation-induced pyroptosis and subsequent anti-tumor immunity. RESULTS: RSPO3 expression was downregulated in radioresistant NSCLC cells. Overexpression of RSPO3 increased NSCLC radiosensitivity through the induction of pyroptosis, which was mediated by the ß-catenin-NF-κB signaling pathway and the NLRP3 inflammasome. The anti-RSPO3 antibody effectively blocked radiation-induced pyroptosis and anti-tumor immunity in vivo. Conversely, upregulation of RSPO3 enhanced NSCLC tumor radiosensitivity. CONCLUSIONS: The findings demonstrated that RSPO3 plays a crucial role in regulating NSCLC radioresistance via NLRP3 mediated pyroptosis. Targeting the RSPO3-NLRP3 inflammasome axis may offer a potential therapeutic strategy to enhance the efficacy of radiotherapy for NSCLC patients.

Spontaneous rupture and hemorrhage of renal epithelioid angiomyolipoma misdiagnosed to renal carcinoma: a case report.

BACKGROUND: Renal epithelioid angiomyolipoma is a rare and unique subtype of classic angiomyolipoma, characterized by the presence of epithelioid cells. It often presents with nonspecific symptoms and can be easily misdiagnosed due to its similarity to renal cell carcinoma and classic angiomyolipoma in clinical and radiological features. This case report is significant for its demonstration of the challenges in diagnosing epithelioid angiomyolipoma and its emphasis on the importance of accurate differentiation from renal cell carcinoma and classic angiomyolipoma. CASE PRESENTATION: A 58-year-old Asian female presented with sudden left flank pain and was initially diagnosed with a malignant renal tumor based on imaging studies. She underwent laparoscopic radical nephrectomy, and postoperative histopathology confirmed the diagnosis of epithelioid angiomyolipoma. The patient recovered well and is currently in good health with regular follow-ups. This case highlights the diagnostic challenges, with a focus on the clinical, radiological, and histopathological features that eventually led to the identification of epithelioid angiomyolipoma. CONCLUSIONS: Epithelioid angiomyolipoma is easily misdiagnosed in clinical work. When dealing with these patients, it is necessary to make a comprehensive diagnosis based on clinical symptoms, imaging manifestations, and pathological characteristics.

Role of LncRNA H19 in tumor progression and treatment.

As one of the earliest discovered lncRNA molecules, lncRNA H19 is usually expressed in large quantities during embryonic development and is involved in cell differentiation and tissue formation. In recent years, the role of lncRNA H19 in tumors has been gradually recognized. Increasing evidence suggests that its aberrant expression is closely related to cancer development. LncRNA H19 as an oncogene not only promotes the growth, proliferation, invasion and metastasis of many tumors, but also develops resistance to treatment, affecting patients' prognosis and survival. Therefore, in this review, we summarise the extensive research on the involvement of lncRNA H19 in tumor progression and discuss how lncRNA H19, as a key target gene, affects tumor sensitivity to radiotherapy, chemotherapy and immunotherapy by participating in multiple cellular processes and regulating multiple signaling pathways, which provides a promising prospect for further research into the treatment of cancer.

Killing two birds with one stone: Abscopal effect mechanism and its application prospect in radiotherapy.

Abscopal effects are characterized by the emergence of neoplasms in regions unrelated to the primary radiation therapy site, displaying a gradual attenuation or regression throughout the progression of radiation therapy, which have been of interest to scientists since Mole's proposal in 1953. The incidence of abscopal effects in radiation therapy is intricately linked to the immune system, with both innate and adaptive immune responses playing crucial roles. Biological factors impacting abscopal effects ultimately exert their influence on the intricate workings of the immune system. Although abscopal effects are rarely observed in clinical cases, the underlying mechanism remains uncertain. This article examines the biological and physical factors influencing abscopal effects of radiotherapy. Through a review of preclinical and clinical studies, this article aims to offer a comprehensive understanding of abscopal effects and proposes new avenues for future research in this field. The findings presented in this article serve as a valuable reference for researchers seeking to explore this topic in greater depth.

Carrier systems of radiopharmaceuticals and the application in cancer therapy.

Radiopharmaceuticals play a vital role in cancer therapy. The carrier of radiopharmaceuticals can precisely locate and guide radionuclides to the target, where radionuclides kill surrounding tumor cells. Effective application of radiopharmaceuticals depends on the selection of an appropriate carrier. Herein, different types of carriers of radiopharmaceuticals and the characteristics are briefly described. Subsequently, we review radiolabeled monoclonal antibodies (mAbs) and their derivatives, and novel strategies of radiolabeled mAbs and their derivatives in the treatment of lymphoma and colorectal cancer. Furthermore, this review outlines radiolabeled peptides, and novel strategies of radiolabeled peptides in the treatment of neuroendocrine neoplasms, prostate cancer, and gliomas. The emphasis is given to heterodimers, bicyclic peptides, and peptide-modified nanoparticles. Last, the latest developments and applications of radiolabeled nucleic acids and small molecules in cancer therapy are discussed. Thus, this review will contribute to a better understanding of the carrier of radiopharmaceuticals and the application in cancer therapy.

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy.

Pyroptotic cell death, an inflammatory form of programmed cell death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT is commonly used for cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized by cell swelling, membrane rupture, and release of pro-inflammatory cytokines, has been shown to enhance the immune response against cancer cells. By inducing pyroptotic cell death in tumor cells, RT has the potential to enhance treatment outcomes by stimulating anti-tumor immune responses and improving the overall efficacy of RT. Furthermore, the release of danger signals from pyroptotic cells can promote the recruitment and activation of immune cells, leading to a systemic immune response that may target distant metastases. Although further research is needed to fully understand the mechanisms and optimize the use of pyroptotic cell death in RT, it holds promise as a novel therapeutic strategy for improving cancer treatment outcomes. This review aims to synthesize recent research on the regulatory mechanisms underlying radiation-induced pyroptosis and to elucidate the potential significance of this process in RT. The insights gained from this analysis may inform strategies to enhance the efficacy of RT for tumors.

Gadolinium Oxide Nanoparticles Reinforce the Fractionated Radiotherapy-Induced Immune Response in Tri-Negative Breast Cancer via cGAS-STING Pathway.

Introduction: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo. Methods: 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization. Results: GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway. Discussion: Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway.

Associations of the Geriatric Nutritional Risk Index with high risk for prostate cancer: A cross-sectional study.

OBJECTIVES: The geriatric Nutritional Risk Index (GNRI) is an effective tool to assess the nutritional status of the elderly. However, the relationship between the GNRI and the risk for prostate cancer (PCa) remains uncertain in middle-aged and older men. The aim of this study was to investigate the association between the GNRI and the risk for PCa by analyzing the serum total (tPSA) and free prostate-specific antigen (fPSA) levels (including percent fPSA [%fPSA]). METHODS: Data for this study were obtained from 7396 men ≥40 y of age from the 2001-2010 National Health and Nutrition Survey (NHANES). We obtained the tPSA and fPSA and calculated the %fPSA and the GNRI. Participants with %fPSA >25% and tPSA <4 ng/mL were defined as high PCa risk. The relationship between the GNRI and serum PSA levels was investigated using a linear regression model. The odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the GNRI and PCa risk were estimated by a logistic regression model. The non-linear relationship was also characterized by a restricted cubic spline regression model. RESULTS: The median of tPSA, fPSA, and %fPSA was 0.90, 0.26, and 29%, respectively. The mean of the GNRI was 29. The proportion of participants in the low PCa- and high PCa-risk groups was 93% and 7%, respectively. There was a negative and linear correlation between the GNRI and serum tPSA and fPSA levels in all models. However, no association between the GNRI and the %fPSA was observed. In the adjusted model, lower GNRI was associated with higher PCa risk (OR, 0.570; 95% CI, 0.415-0.784; Ptrend = 0.001). The restricted cubic spline regression model showed a non-linear and negative association between the GNRI and PCa risk (Pnon-linearity = 0.020), with inflection points of 109.148. CONCLUSION: The results of this study suggest that nutritional status, as represented by the GNRI, is associated with the risk for PCa.

Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy.

BACKGROUND: Ferroptosis is a regulated cell death mode triggered by iron-dependent toxic membrane lipid peroxidation. As a novel cell death modality that is morphologically and mechanistically different from other forms of cell death, such as apoptosis and necrosis, ferroptosis has attracted extensive attention due to its association with various diseases. Evidence on ferroptosis as a potential therapeutic strategy has accumulated with the rapid growth of research on targeting ferroptosis for tumor suppression in recent years. METHODS: We summarize the currently known characteristics and major regulatory mechanisms of ferroptosis and present the role of ferroptosis in cellular stress responses, including ER stress and autophagy. Furthermore, we elucidate the potential applications of ferroptosis in radiotherapy and immunotherapy, which will be beneficial in exploring new strategies for clinical tumor treatment. RESULT AND CONCLUSION: Based on specific biomarkers and precise patient-specific assessment, targeting ferroptosis has great potential to be translated into practical new approaches for clinical cancer therapy, significantly contributing to the prevention, diagnosis, prognosis, and treatment of cancer.

Management of urinary incontinence after radical cystectomy and orthotopic neobladder: A scoping review of international practices.

OBJECTIVES: To identify and describe international practice in incontinence management after radical cystectomy and orthotopic neobladder. MATERIALS AND METHODS: A systematic scoping review following the methodology of the Joanne Briggs Institute was conducted in which the application searched 15 data sources to identify papers published in English, from 1979 to 2022. RESULTS: Of the 16 papers that met the eligibility criteria, articles in Eastern countries mainly focus on the effect of conservative treatment, while in Western countries, more attention is paid to the effect of surgical treatment. Clinical characteristics of patients included conservative treatment failure, duration of post-operative intervention and unique differential treatment of male and female patients. Reported factors influencing the achievement of urinary incontinence (UI) include lack of evidence to guide management practice, limited value of conservative treatment, high risk of surgical treatment and uncertainty of efficacy; currently, early behavioural research and multimodal rehabilitation training have good results. CONCLUSIONS: UI in neobladder patients is a distressing condition that is difficult to treat and often requires high-quality rehabilitation guidance and surgical intervention. Further research to address current knowledge gaps is important to inform practice.

Comparison of laparoscopic, robotic, and open retroperitoneal lymph node dissection for non-seminomatous germ cell tumor: a single-center retrospective cohort study.

PURPOSE: To compare the perioperative outcomes of L-RPLND, R-RPLND and O-RPLND, and determine which one can be the mainstream option. METHODS: We retrospectively reviewed medical records of 47 patients undergoing primary RPLND by three different surgical techniques for stage I-II NSGCT between July 2011 and April 2022 at our center. Standard open and laparoscopic RPLND was performed with usual equipment, and robotic RPLND was operated with da Vinci Si system. RESULTS: Forty-seven patients underwent RPLND during 2011-2022, and 26 (55.3%) of them received L-RPLND, 14 (29.8%) were operated with robot, while 7 (14.9%) were performed O-RPLND. The median follow-up was 48.0 months, 48.0 months, and 60.0 months, respectively. The oncological outcomes were comparable among all groups. In L-RPLND group, there were 8 (30.8%) cases of low grade (Clavien I-II) complications, and 3 (11.5%) cases of high-grade (Clavien III-IV) complications. In R-RPLND group, one (7.1%) low-grade complication and four (28.6%) high-grade complications were observed. In O-RPLND group, there were 2 (28.5%) cases of low-grade complications and one case (14.2%) of high-grade one. The operation duration of L-RPLND was the shortest. In O-RPLND group, the number of positive lymph nodes were higher than other two groups. Patients undergoing open surgery had lower (p < 0.05) red blood cell count, hemoglobin level, and higher (p < 0.05) estimated blood loss, white blood cell count than those receiving either laparoscopic or robotic surgery. CONCLUSION: All three surgical techniques are comparable in safety, oncological, andrological, and reproductive outcomes under the circumstance of not using primary chemotherapy. L-RPLND might be the most cost-effective option.

R-spondin family biology and emerging linkages to cancer.

The R-spondin protein family comprises four members (RSPO1-4), which are agonists of the canonical Wnt/ß-catenin pathway. Emerging evidence revealed that RSPOs should not only be viewed as agonists of the Wnt/ß-catenin pathway but also as regulators for tumor development and progression. Aberrant expression of RSPOs is related to tumorigenesis and tumor development in multiple cancers and their expression of RSPOs has also been correlated with anticancer immune cell signatures. More importantly, the role of RSPOs as potential target therapies and their implication in cancer progressions has been studied in the preclinical and clinical settings. These findings highlight the possible therapeutic value of RSPOs in cancer medicine. However, the expression pattern, effects, and mechanisms of RSPO proteins in cancer remain elusive. Investigating the many roles of RSPOs is likely to expand and improve our understanding of the oncogenic mechanisms mediated by RSPOs. Here, we reviewed the recent advances in the functions and underlying molecular mechanisms of RSPOs in tumor development, cancer microenvironment regulation, and immunity, and discussed the therapeutic potential of targeting RSPOs for cancer treatment. In addition, we also explored the biological feature and clinical relevance of RSPOs in cancer mutagenesis, transcriptional regulation, and immune correlation by bioinformatics analysis.KEY MESSAGESAberrant expressions of RSPOs are detected in various human malignancies and are always correlated with oncogenesis.Although extensive studies of RSPOs have been conducted, their precise molecular mechanism remains poorly understood.Bioinformatic analysis revealed that RSPOs may play a part in the development of the immune composition of the tumor microenvironment.

Mutant p53 in cancer: from molecular mechanism to therapeutic modulation.

TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed "gain-of-function". Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor prognosis, which makes it a target for development of novel cancer therapies. Herein, we provide a summary of our knowledge of the mutp53 types and mutp53 spectrum in cancers. The mechanisms of mutp53 accumulation and gain-of-function are also summarized. Furthermore, we discuss the gain-of-function of mutp53 in cancers: genetic instability, ferroptosis, microenvironment, and stemness. Importantly, the role of mutp53 in the clinic is also discussed, particularly with regard to chemotherapy and radiotherapy. Last, emphasis is given to emerging strategies on how to target mutp53 for tumor therapy. Thus, this review will contribute to better understanding of the significance of mutp53 as a target for therapeutic strategies.

Increased diaphragm echodensity correlates with postoperative pulmonary complications in patients after major abdominal surgery: a prospective observational study.

BACKGROUND: Associated with increased morbidity and mortality, postoperative pulmonary complications (PPCs) often occur after major abdominal surgery. Diaphragmatic dysfunction is suggested to play an important role in the development of PPCs and diaphragm echodensity can be used as an indicator of diaphragm function. This study aimed to determine whether diaphragm echodensity could predict the occurrence of PPCs in patients after major abdominal surgery. METHODS: Diaphragm ultrasound images of patients after major abdominal surgery were collected during spontaneous breathing trials. Echodensity was quantified based on the right-skewed distribution of grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean). Intra- and inter-analyzer measurement reproducibility was determined. Outcomes including occurrence of PPCs, reintubation rate, duration of ventilation, and length of ICU stay were recorded. RESULTS: Diaphragm echodensity was measured serially in 117 patients. Patients who developed PPCs exhibited a higher ED50 (35.00 vs. 26.00, p < 0.001), higher ED85 (64.00 vs. 55.00, p < 0.001) and higher EDmean (39.32 vs. 33.98, p < 0.001). In ROC curve analysis, the area under the curve of ED50 for predicting PPCs was 0.611. The optimal ED50 cutoff value for predicting the occurrence of PPCs was 36. According to this optimal ED50 cutoff value, patients were further divided into a high-risk group (ED50 > 36, n = 35) and low-risk group (ED50 ≤ 36, n = 82). Compared with the low-risk group, the high-risk group had a higher incidence of PPCs (unadjusted p = 0.003; multivariate-adjusted p < 0.001). CONCLUSION: Diaphragm echodensity can be feasibly and reproducibly measured in mechanically ventilated patients. The increase in diaphragm echodensity during spontaneous breathing trials was related to an increased risk of PPCs in patients after major abdominal surgery.

Circular RNA-regulated autophagy is involved in cancer progression.

Circular RNAs (circRNAs) are a sort of long, non-coding RNA molecules with a covalently closed continuous ring structure without 5'-3' polarity and poly-A tail. The modulative role of circRNAs in malignant diseases has been elucidated by many studies in recent years via bioinformatics and high-throughput sequencing technologies. Generally, circRNA affects the proliferative, invasive, and migrative capacity of malignant cells via various mechanisms, exhibiting great potential as novel biomarkers in the diagnoses or treatments of malignancies. Meanwhile, autophagy preserves cellular homeostasis, serving as a vital molecular process in tumor progression. Mounting studies have demonstrated that autophagy can not only contribute to cancer cell survival but can also induce autophagic cell death in specific conditions. A growing number of research studies have indicated that there existed abundant associations between circRNAs and autophagy. Herein, we systemically reviewed and discussed recent studies on this topic in different malignancies and concluded that the circRNA-autophagy axis played crucial roles in the proliferation, metastasis, invasion, and drug or radiation resistance of different tumor cells.

Lumican is elevated in the lung in human and experimental acute respiratory distress syndrome and promotes early fibrotic responses to lung injury.

BACKGROUND: Fibroproliferative repair starts early in the inflammatory phase of acute respiratory distress syndrome (ARDS) and indicates a poor prognosis. Lumican, a small leucine-rich proteoglycan, is implicated in homeostasis and fibrogenesis, but its role in ARDS is unclear. METHODS: Bronchoalveolar lavage fluid (BALF) samples were obtained from ARDS patients (n = 55) enrolled within 24 h of diagnosis and mechanically ventilated (n = 20) and spontaneously breathing (n = 29) control subjects. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse models were intratracheally administered an adeno-associated virus (AAV) vector expressing lumican shRNA. Primary human lung fibroblasts (HLF) and small airway epithelial cells (SAECs) were cultured with tumour necrosis factor (TNF)-α or lumican. Luminex/ELISA, histochemistry/immunohistochemistry, immunofluorescence microscopy, quantitative real-time PCR, and western blotting were performed. RESULTS: Lumican levels were significantly higher in the BALF of ARDS patients than in that of ventilated or spontaneously breathing controls (both p < 0.0001); they were correlated with the PaO2/FiO2 ratio and levels of proinflammatory cytokines (interleukin-6, interleukin-8, and TNF-α) and profibrotic factors (fibronectin, alpha-1 type I collagen [COL1A1], and alpha-1 type III collagen [COL3A1]). Lumican expression was enhanced in the alveolar walls and airway epithelium in the ALI mouse model. Murine lumican levels were also linked to proinflammatory and profibrotic cytokine levels in the BALF. In vitro, TNF-α induced the synthesis and secretion of lumican in HLF. In turn, lumican increased the expression of alpha-smooth muscle actin (α-SMA), COL1A1, and COL3A1 in HLF, upregulated α-SMA and COL3A1, downregulated E-cadherin, and caused spindle-shaped morphological changes in SAECs. Moreover, increased ERK phosphorylation and Slug were noted in both HLF and SAECs treated with lumican. In vivo, AAV-mediated knockdown of lumican inhibited the pulmonary production of fibronectin and COL3A1 and alleviated lung fibrotic lesions in LPS-challenged mice. CONCLUSIONS: Pulmonary lumican levels were increased early in human and experimental ARDS and linked to disease severity and inflammatory fibrotic processes. Lumican triggers the transdifferentiation of lung fibroblasts into myofibroblasts and epithelial-mesenchymal transition in SAECs, possibly via the ERK/Slug pathway. Knockdown of pulmonary lumican attenuated extracellular matrix deposition in ALI mice. Overall, lumican promotes fibrotic responses in the early phase of ARDS, suggesting its potential as a therapeutic target.

Isolated dysarthria as the sole manifestation of myasthenia gravis: a case report.

Myasthenia gravis (MG) is an acquired autoimmune disease. Its clinical manifestations comprise ptosis, diplopia, dysarthria, dysphagia, limb weakness, and in severe cases, respiratory muscle involvement. Dysarthria as an exclusive initial and primary complaint in MG is rare and seldom reported. In this paper, we report a case of type IIIb MG with isolated dysarthria as the only clinical manifestation and we review the relevant literature. The patient was a 62-year-old man who presented with episodes of slurred speech for 20 days that had worsened in the previous 9 days. His medical history comprised hypertension, diabetes mellitus, and coronary heart disease. The initial diagnosis on admission was transient ischemic attack. Careful re-examination of the patient's history revealed that his symptoms mainly involved increasingly worse slurred speech episodes without drinking or swallowing difficulties, and no significant improvement with rest was observed. Electromyography and autoantibody profiling led to a diagnosis of type IIIb MG. His symptoms improved after the oral administration of pyridostigmine bromide 60 mg. Laryngeal MG is important to differentiate from stroke. It is necessary to perform a computerized voice analysis when encountering patients with atypical symptoms of MG.

[Retracted] MicroRNA­186 targets IGF­1R and exerts tumor-suppressing functions in glioma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration assay data shown in Fig. 2C were strikingly similar to data that had appeared in different form in another article by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 7821­7828, 2017; DOI: 10.3892/mmr.2017.7586].

Artificial Intelligence Radiotherapy Planning: Automatic Segmentation of Human Organs in CT Images Based on a Modified Convolutional Neural Network.

Objective: Precise segmentation of human organs and anatomic structures (especially organs at risk, OARs) is the basis and prerequisite for the treatment planning of radiation therapy. In order to ensure rapid and accurate design of radiotherapy treatment planning, an automatic organ segmentation technique was investigated based on deep learning convolutional neural network. Method: A deep learning convolutional neural network (CNN) algorithm called BCDU-Net has been modified and developed further by us. Twenty two thousand CT images and the corresponding organ contours of 17 types delineated manually by experienced physicians from 329 patients were used to train and validate the algorithm. The CT images randomly selected were employed to test the modified BCDU-Net algorithm. The weight parameters of the algorithm model were acquired from the training of the convolutional neural network. Result: The average Dice similarity coefficient (DSC) of the automatic segmentation and manual segmentation of the human organs of 17 types reached 0.8376, and the best coefficient reached up to 0.9676. It took 1.5-2 s and about 1 h to automatically segment the contours of an organ in an image of the CT dataset for a patient and the 17 organs for the CT dataset with the method developed by us, respectively. Conclusion: The modified deep neural network algorithm could be used to automatically segment human organs of 17 types quickly and accurately. The accuracy and speed of the method meet the requirements of its application in radiotherapy.

A positive feedback circuit comprising p21 and HIF-1α aggravates hypoxia-induced radioresistance of glioblastoma by promoting Glut1/LDHA-mediated glycolysis.

The radioresistance induced by hypoxia is the major obstacle in the successful treatment of cancer radiotherapy. p21 was initially identified as a widespread inhibitor of cyclin-dependent kinases, through which mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. In this study, we discovered a novel function of p21, which participated in the regulation of metabolic pathways under hypoxia. We found that p21 was upregulated in glioblastoma (GBM) cells under hypoxic conditions, which enhanced the radioresistance of GBM cells. In principle, HIF-1α is bound directly to the hypoxia response elements (HREs) of the p21 promoter to enhance its transcription activity, in turn, p21 also promoted the transcription of HIF-1α at the mRNA level and maintained HIF-1α function under oxygen deficiency. The positive correlation between p21 and HIF-1α augmented Glut1/LDHA-mediated glycolysis and aggravated the radioresistance of GBM cells. Thus, our results constructed a positive feedback circuit comprising p21/HIF-1α that might play a key role in enhancing the radioresistance of GBM under hypoxia.