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In the original publication [...].
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OBJECTIVE: This study aims to analyze setup errors in pelvic Volumetric Modulated Arc Therapy (VMAT) for patients with non-surgical primary cervical cancer, utilizing the onboard iterative kV cone beam CT (iCBCT) imaging system on the Varian Halcyon 2.0 ring gantry structure accelerator to enhance radiotherapy precision. METHOD: We selected 132 cervical cancer patients who underwent VMAT with daily iCBCT imaging guidance. Before each treatment session, a registration method based on the bony structure was employed to acquire iCBCT images with the corresponding planning CT images. Following verification and adjustment of image registration results along the three axes (but not rotational), setup errors in the lateral (X-axis), longitudinal (Y-axis), and vertical (Z-axis) directions were recorded for each patient. Subsequently, we analyzed 3642 iCBCT image setup errors. RESULTS: The mean setup errors for the X, Y, and Z axes were 4.50 ± 3.79 mm, 6.08 ± 6.30 mm, and 1.48 ± 2.23 mm, respectively. Before correction with iCBCT, setup margins based on the Van Herk formula for the X, Y, and Z axes were 6.28, 12.52, and 3.26 mm, respectively. In individuals aged 60 years and older, setup errors in the X and Y axes were significantly larger than those in the younger group (p < 0.05). Additionally, there is no significant linear correlation between setup errors and treatment fraction numbers. CONCLUSION: Data analysis underscores the importance of precise Y-axis setup for cervical cancer patients undergoing VMAT. Radiotherapy centers without daily iCBCT should appropriately extend the planning target volume (PTV) along the Y-axis for cervical cancer patients receiving pelvic VMAT. Elderly patients exhibit significantly larger setup errors compared to younger counterparts. In conclusion, iCBCT-guided radiotherapy is recommended for cervical cancer patients undergoing VMAT to improve setup precision.
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Tomografia Computadorizada de Feixe Cônico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Erros de Configuração em Radioterapia , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/diagnóstico por imagem , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Pessoa de Meia-Idade , Erros de Configuração em Radioterapia/prevenção & controle , Idoso , Adulto , Processamento de Imagem Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Idoso de 80 Anos ou mais , Órgãos em Risco/efeitos da radiação , Aceleradores de Partículas/instrumentação , PrognósticoRESUMO
Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening clinical syndrome characterized by immune hyperactivation. Unlike primary HLH, immune checkpoint inhibitor (ICI)-triggered HLH is not well described, and there is a lack of theranostic guidelines. Herein, we first reported the successful management of PD-1 inhibitor-associated HLH in locally advanced cervical cancer. Case presentation: We report a case of HLH in a 47-year-old patient with International Federation of Gynecology and Obstetrics (FIGO) IIIC1r cervical cancer who received toripalimab, a programmed cell death-1 receptor inhibitor, combined with chemoradiotherapy. The patient developed pyrexia, splenomegaly, leukopenia, anemia, thrombocytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, reduced NK cell activity, elevated sCD25 levels, and hemophagocytosis in a bone marrow aspirate. Our patient was successfully treated with methylprednisolone, indicating that immune-induced HLH might respond to glucocorticoids, and is still alive with a complete response of the tumor. Conclusion: Considering the possibility of HLH is needed in patients receiving ICIs to detect rare toxicities at an early stage when the patient develops uncontrollable fever, cytopenia, and splenomegaly, our multidisciplinary treatment modality contributed to the early diagnosis and successful management of HLH, avoiding progressive tissue damage and organ failure. Whether glucocorticoids are used alone or not for immune-associated HLH needs further investigation.
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The origin of breast cancer (BC) has traditionally been a focus of medical research. It is widely acknowledged that BC originates from immortal mammary stem cells and that these stem cells participate in two division modes: symmetric cell division (SCD) and asymmetrical cell division (ACD). Although both of these modes are key to the process of breast development and their imbalance is closely associated with the onset of BC, the molecular mechanisms underlying these phenomena deserve in-depth exploration. In this review, we first outline the molecular mechanisms governing ACD/SCD and analyze the role of ACD/SCD in various stages of breast development. We describe that the changes in telomerase activity, the role of polar proteins, and the stimulation of ovarian hormones subsequently lead to two distinct consequences: breast development or carcinogenesis. Finally, gene mutations, abnormalities in polar proteins, modulation of signal-transduction pathways, and alterations in the microenvironment disrupt the balance of BC stem cell division modes and cause BC. Important regulatory factors such as mammalian Inscuteable mInsc, Numb, Eya1, PKCα, PKCθ, p53, and IL-6 also play significant roles in regulating pathways of ACD/SCD and may constitute key targets for future research on stem cell division, breast development, and tumor therapy.
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Neoplasias da Mama , Carcinogênese , Glândulas Mamárias Humanas , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Animais , Glândulas Mamárias Humanas/crescimento & desenvolvimento , Glândulas Mamárias Humanas/patologia , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/metabolismo , Carcinogênese/patologia , Carcinogênese/metabolismo , Carcinogênese/genética , Células-Tronco/metabolismo , Células-Tronco/citologia , Divisão Celular , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/patologia , Glândulas Mamárias Animais/metabolismo , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Transdução de SinaisRESUMO
Circular RNAs (circRNAs) represent an emerging category of endogenous transcripts characterized by long half-life time, covalently closed structures, and cell-/tissue-specific expression patterns, making them potential disease biomarkers. Herein, we demonstrate the construction of fluorescent G-quadruplex nanowires for label-free and accurate monitoring of circular RNAs in breast cancer cells and tissues by integrating proximity ligation-rolling circle amplification cascade with lighting up G-quadruplex. The presence of target circRNA facilitates the SplintR ligase-mediated ligation of the padlock probe. Upon the addition of primers, the ligated padlock probe can serve as a template to initiate subsequent rolling circle amplification (RCA), generating numerous long G-quadruplex nanowires that can incorporate with thioflavin T (ThT) to generate a remarkably improved fluorescence signal. Benefiting from good specificity of SplintR ligase-mediated ligation reaction and exponential amplification efficiency of RCA, this strategy can sensitively detect target circRNA with a limit of detection of 4.65 × 10-18 M. Furthermore, this method can accurately measure cellular circRNA expression with single-cell sensitivity and discriminate the circRNA expression between healthy para-carcinoma tissues and breast cancer tissues, holding great potential in studying the pathological roles of circRNA and clinic diagnostics.
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Neoplasias da Mama , Nanofios , Humanos , Feminino , RNA Circular , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Corantes Fluorescentes/química , Ligases , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
Pyroptosis, an inflammatory programmed cell death, distinguishes itself from apoptosis and necroptosis and has drawn increasing attention. Recent studies have revealed a correlation between the expression levels of many pyroptosis-related genes and both tumorigenesis and progression. Despite advancements in cancer treatments such as surgery, radiotherapy, chemotherapy, and immunotherapy, the persistent hallmark of cancer enables malignant cells to elude cell death and develop resistance to therapy. Recent findings indicate that pyroptosis can overcome apoptosis resistance amplify treatment-induced tumor cell death. Moreover, pyroptosis triggers antitumor immunity by releasing pro-inflammatory cytokines, augmenting macrophage phagocytosis, and activating cytotoxic T cells and natural killer cells. Additionally, it transforms "cold" tumors into "hot" tumors, thereby enhancing the antitumor effects of various treatments. Consequently, pyroptosis is intricately linked to tumor development and holds promise as an effective strategy for boosting therapeutic efficacy. As the principal executive protein of pyroptosis, the gasdermin family plays a pivotal role in influencing pyroptosis-associated outcomes in tumors and can serve as a regulatory target. This review provides a comprehensive summary of the relationship between pyroptosis and gasdermin family members, discusses their roles in tumor progression and the tumor immune microenvironment, and analyses the underlying therapeutic strategies for tumor treatment based on pyroptotic cell death.
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Acute kidney injury (AKI) is a frequently occurring severe disease with high mortality. Cystatin C (Cys-C), as a biomarker of early kidney failure, can be used to detect and prevent acute renal injury. In this paper, a biosensor based on a silicon nanowire field-effect transistor (SiNW FET) was studied for the quantitative detection of Cys-C. Based on the spacer image transfer (SIT) processes and channel doping optimization for higher sensitivity, a wafer-scale, highly controllable SiNW FET was designed and fabricated with a 13.5 nm SiNW. In order to improve the specificity, Cys-C antibodies were modified on the oxide layer of the SiNW surface by oxygen plasma treatment and silanization. Furthermore, a polydimethylsiloxane (PDMS) microchannel was involved in improving the effectiveness and stability of detection. The experimental results show that the SiNW FET sensors realize the lower limit of detection (LOD) of 0.25 ag/mL and have a good linear correlation in the range of Cys-C concentration from 1 ag/mL to 10 pg/mL, exhibiting its great potential in the future real-time application.
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Técnicas Biossensoriais , Nanofios , Insuficiência Renal , Humanos , Silício , Cistatina C , Transistores Eletrônicos , Biomarcadores , Técnicas Biossensoriais/métodosRESUMO
BACKGROUND: Understanding the molecular mechanisms driving oncogenic processes in glioma is important in order to develop efficient treatments. Recent studies have proposed gasdermin D (GSDMD) as a newly discovered pyroptosis executive protein associated with tumorigenesis. However, the precise effect of GSDMD on glioma progression remains unknown. METHODS: The expression levels of GSDMD in 931 glioma and 1157 normal control tissues were collected. A series of bioinformatic approaches and in vivo and in vitro experiments were used to investigate the roles and mechanisms of GDSMD in glioma. RESULTS: Significant upregulation of GSDMD was detected in glioma tissues compared to normal brain tissues. Patients with glioma and higher GSDMD levels had shorter overall survival, and the Cox regression analysis revealed that GSDMD was an independent risk factor. In addition, upregulation of GSDMD was associated with higher tumor mutation burden and PD-1/PD-L1 expression. Immune infiltration and single-cell analyses indicated that GSDMD was positively associated with an immunosuppressive microenvironment with more infiltrated macrophages and cancer-associated fibroblasts. Furthermore, the in vitro and in vivo experiments revealed that GSDMD knockdown inhibited glioma proliferation, migration, and growth in vivo. CONCLUSION: Our analyses revealed a relatively comprehensive understanding of the oncogenic role of GSDMD in glioma. GSDMD is a promising prognostic biomarker and a potential target for glioma treatment.
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Gasderminas , Glioma , Microambiente Tumoral , Humanos , Gasderminas/genética , Gasderminas/imunologia , Glioma/genética , Glioma/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Macrófagos/imunologia , Piroptose/genética , Piroptose/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
OBJECTIVE: To evaluate the clinical outcomes of volumetric modulated arc therapy (VMAT) followed by brachytherapy (BT), combined with chemotherapy, and local hyperthermia (HT) on locally advanced cervical cancer (LACC). METHODS: In total, 40 patients with FIGO stage IB1-IVB cervical cancer from January 2016 to December 2018 were selectively enrolled in this study. All patients were treated with VMAT (50.4â Gy/1.8â Gy/28â f) concurrent with cisplatin-based chemotherapy (40â mg/m2, q1w, 6 cycles) and local HT (40.5-41°C for 60â min, BIW). BT (30-36 y/5-6 f, 2 f/w) was conducted after VMAT. Objective response rate (ORR), local control (LC) time, LC rate, progression-free survival (PFS) rate, cancer-specific survival (CSS) rate, overall survival (OS), median time to tumor progression and treatment-related toxicity were evaluated. RESULTS: The median follow-up time was 31 months (8-48). The ORR was 100% at 3 months after treatment and 92.1% at 6 months, respectively. The 1-year, 2-year, and 3-year LC rates were 87.4%, 81.9%, and 70.9%, respectively. The average LC time was 31.50 ± 1.89 months (95% CI 27.79-35.21). The 1-year, 2-year, and 3-year PFS rates were 75.85%, 61.2%, and 51.3%, respectively, while the median PFS was 27.07 months. The 1-year, 2-year, and 3-year OS rates were 95%, 84%, and 79.6%, respectively. In total, 12(30%) patients had grade 3/4 bone marrow suppression. One patient had grade 4 leukopenia. In total, 17 patients had grade 1/2 bone marrow suppression. Two patients had grade 3 nausea and grade 3 vomiting reaction, respectively. No grade 3/4 proctitis and bladder reaction were observed. In the late period of treatment, 1 patient had a rectal hemorrhage. In total, 13 patients had vaginal stenosis. CONCLUSION: VMAT concurrent with chemotherapy, BT, and local HT had a favorable short-term efficacy and acceptable toxicity on cervical cancer, which was an alternative option for LACC.
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Braquiterapia , Hipertermia Induzida , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Humanos , Feminino , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Braquiterapia/efeitos adversos , Constrição Patológica/tratamento farmacológico , Constrição Patológica/etiologia , Quimiorradioterapia/efeitos adversos , Vagina , Cisplatino , Resultado do TratamentoRESUMO
Natural killer cells play crucial roles in tumor immunosurveillance and serve as first responders to recognize abnormal cells. Radiotherapy is the mainstay of cancer treatment. However, the effect of high-dose radiotherapy on NK cells remains elusive. Here, we used tumor-bearing mice in the murine colorectal cancer cell line, MC38. The function of NK cells in tumor-draining lymph nodes and tumors was explored after the mice were treated using radiotherapy with 20 Gy and/or blocking antibody αTIGIT at the indicated time. High-dose radiotherapy shaped an immunosuppressive tumor microenvironment to support tumor growth, showing a decreased anti-tumor immunity phenotype in which effector T cells were reduced significantly. Furthermore, the production of functional cytokines and markers in NK cells, including CD107a, granzyme B, and IFN-γ, also remarkably decreased after radiotherapy, while the inhibitory receptor TIGIT was significantly upregulated by FACS analysis. The effect of radiotherapy was significantly elevated after treatment with the combination of radiotherapy and TIGIT inhibition. Moreover, this combination significantly decreased tumor recurrence. Our findings reported that local single high-dose radiotherapy shaped the immunosuppressive microenvironment and inhibited the function of NK cells. Our study revealed compelling evidence suggesting that the enhancement of NK cell function through TIGIT targeting is an effective strategy to mitigate immune suppression caused by high-dose radiotherapy, thereby promoting the inhibition of tumor recurrence.
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Células Matadoras Naturais , Recidiva Local de Neoplasia , Animais , Camundongos , Recidiva Local de Neoplasia/radioterapia , Receptores Imunológicos/metabolismo , Linhagem Celular , Imunoterapia , Microambiente TumoralRESUMO
Sorafenib, a multi-kinase inhibitor, has been approved for cancer treatment for decades, especially hepatocellular carcinoma (HCC). Although sorafenib produced substantial clinical benefits in the initial stage, a large proportion of cancer patients acquired drug resistance in subsequent treatment, which always disturbs clinical physicians. Cumulative evidence unraveled the underlying mechanism of sorafenib, but few reports focused on the role of immune subpopulations, since the immunological rationale of sorafenib resistance has not yet been defined. Here, we reviewed the immunoregulatory effects of sorafenib on the tumor microenvironment and emphasized the potential immunological mechanisms of therapeutic resistance to sorafenib. Moreover, we also summarized the clinical outcomes and ongoing trials in combination of sorafenib with immunotherapy, highlighted the immunotherapeutic strategies to improve sorafenib efficacy, and put forward several prospective questions aimed at guiding future research in overcoming sorafenib resistance in HCC.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Prospectivos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Microambiente TumoralRESUMO
Recent studies have revealed that tumor-associated macrophages are the most abundant stromal cells in the tumor microenvironment and play an important role in tumor initiation and progression. Furthermore, the proportion of macrophages in the tumor microenvironment is associated with the prognosis of patients with cancer. Tumor-associated macrophages can polarize into anti-tumorigenic phenotype (M1) and pro-tumorigenic phenotype (M2) by the stimulation of T-helper 1 and T-helper 2 cells respectively, and then exert opposite effects on tumor progression. Besides, there also is wide communication between tumor-associated macrophages and other immune compositions, such as cytotoxic T cells, regulatory T cells, cancer-associated fibroblasts, neutrophils and so on. Furthermore, the crosstalk between tumor-associated macrophages and other immune cells greatly influences tumor development and treatment outcomes. Notably, many functional molecules and signaling pathways have been found to participate in the interactions between tumor-associated macrophages and other immune cells and can be targeted to regulate tumor progression. Therefore, regulating these interactions and CAR-M therapy are considered to be novel immunotherapeutic pathways for the treatment of malignant tumors. In this review, we summarized the interactions between tumor-associated macrophages and other immune compositions in the tumor microenvironment and the underlying molecular mechanisms and analyzed the possibility to block or eradicate cancer by regulating tumor-associated macrophage-related tumor immune microenvironment.
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Neoplasias , Microambiente Tumoral , Humanos , Macrófagos , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Reguladores/metabolismoRESUMO
OBJECTIVE: To investigate predictive value of CT-based radiomics features on visceral pleural invasion (VPI) in ≤3.0âcm peripheral type early non-small cell lung cancer (NSCLC). METHODS: A total of 221 NSCLC cases were collected. Among them, 115 are VPI-positive and 106 are VPI-negative. Using a stratified random sampling method, 70% cases were assigned to training dataset (nâ=â155) and 30% cases (nâ=â66) were assigned to validation dataset. First, CT findings, imaging features, clinical data and pathological findings were retrospectively analyzed, the size, location and density characteristics of nodules and lymph node status, the relationship between lesions and pleura (RAP) were assessed, and their mean CT value and the shortest distance between lesions and pleura (DLP) were measured. Next, the minimum redundancy-maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) features were extracted from the imaging features. Then, CT imaging prediction model, texture feature prediction model and joint prediction model were built using multifactorial logistic regression analysis method, and the area under the ROC curve (AUC) was applied to evaluate model performance in predicting VPI. RESULTS: Mean diameter, density, fractal relationship with pleura, and presence of lymph node metastasis were all independent predictors of VPI. When applying to the validation dataset, the CT imaging model, texture feature model, and joint prediction model yielded AUCâ=â0.882, 0.824 and 0.894, respectively, indicating that AUC of the joint prediction model was the highest (pâ<â0.05). CONCLUSION: The study demonstrates that the joint prediction model containing CT morphological features and texture features enables to predict the presence of VPI in early NSCLC preoperatively at the highest level.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Pleura/diagnóstico por imagem , Pleura/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X/métodosRESUMO
Exosomes are highly important in clinical diagnosis due to their high homology with their parental cells. However, conventional exosome detection methods still face the challenges of expensive equipment, low sensitivity, and complex procedures. Field effect transistors (FETs) are not only the most essential electronic component in the modern microelectronics industry but also show great potential for biomolecule detection owing to the advantages of rapid response, high sensitivity, and label-free detection. In this study, we proposed a Si nanowire field-effect transistor (Si-NW Bio-FET) device chemically modified with specific antibodies for the electrical and label-free detection of exosomes. The Si-NW FETs were fabricated by standard microelectronic processes with 45 nm width nanowires and packaged in a polydimethylsiloxane (PDMS) microfluidic channel. The nanowires were further modified with the specific CD63 antibody to form a Si-NW Bio-FET. The use of the developed Si-NW Bio-FET for the electrical and label-free detection of exosomes was successfully demonstrated with a limit of detection (LOD) of 2159 particles/mL. In contrast to other technologies, in this study, Si-NW Bio-FET provides a unique strategy for directly quantifying and real-time detecting exosomes without labeling, indicating its potential as a tool for the early diagnosis of cancer.
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Circular ribonucleic acids (circRNAs) are a type of RNA that originates through back-splicing events from linear primary transcripts. CircRNAs display high structural resistance and tissue specificity. Accurate quantification of the circRNA expression level is of vital importance to disease diagnosis. Herein, we construct a label-free fluorescent biosensor for ultrasensitive analysis of circRNAs based on the integration of target-initiated cascade signal amplification strategy with a light-up G-quadruplex. This assay involves only one assistant probe that targets the circRNA-specific back-splice junction. When circRNA is present, it hybridizes with the assistant probe to initiate the duplex-specific nuclease (DSN)-catalyzed cyclic cleavage reaction, producing abundant triggers with 3'OH termini. Then, terminal deoxynucleotidyl transferase (TdT) catalyzes the addition of dGTP and dATP at the 3'-OH termini of the resultant triggers to obtain abundant long G-rich DNA sequences that can form efficient G-quadruplex products. The addition of Thioflavin T (ThT) can light up G-quadruplex, generating an enhanced fluorescence. This assay may be performed isothermally without the involvement of any nucleic acid templates, exogenous primers, and specific labeled probes. Importantly, this biosensor can discriminate target circRNA from one-base mismatched circRNA and exhibits good performance in human serum. Moreover, it can accurately detect circRNA in cancer cells at a single-cell level and even differentiate the circRNA levels in the tissues of healthy persons and nonsmall cell lung cancer (NSCLC) patients, with promising applications in circRNA-related cancer diagnosis and therapeutics.
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Técnicas Biossensoriais , Carcinoma Pulmonar de Células não Pequenas , Quadruplex G , Neoplasias Pulmonares , DNA Nucleotidilexotransferase/química , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Técnicas de Amplificação de Ácido Nucleico , RNA , RNA CircularRESUMO
A systematic literature review to validate the conclusions with regard to stranded seeds versus loose seeds. Published data for this review were identified by searching the PubMed databases. PD90, PV100, PV150, UD30, and RV100 acquired during the perioperative period and the postoperative period were analyzed by meta-analysis. Based on these studies, in addition to the reduction of migration and displacement, stranded seeds had some dosimetric advantages, especially in dose homogeneity and coverage of target area due to its connection characteristics. We also noticed implanted seeds usually excessive both in stranded seeds group and loose seed group. Intraoperatively built custom links will prolong operation time, with the proficiency of technology, the prolonged time gradually decreases.
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Braquiterapia , Neoplasias da Próstata , Humanos , Masculino , Próstata , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radiometria , Dosagem RadioterapêuticaRESUMO
The treatment modality for recurrent cervical cancer (rCC) is limited, and the prognosis of these patients is poor. Seed implantation could be an important component of rCC management in the context of dose boost or salvage therapy after surgery or radiotherapy, which is characterized by a minimally invasive, high local dose, and rapidly does fall, sparing normal tissue. For patients with good performance status and lateral pelvic wall recurrence with an available puncture path, seed implantation was recommended, as well as for selected central pelvic recurrence and extra-pelvic recurrence. The combination of brachytherapy treatment planning system and CT guidance was needed, and three-dimensional printing templates could greatly improve the accuracy, efficiency, and quality of seed implantation to achieve a potential ablative effect and provide an efficient treatment for rCC. However, the recommendations of seed implantation were mainly based on retrospective articles and lack high-quality evidence, and multicenter prospective randomized studies are needed. In this consensus on iodine125 seed implantation for rCC, indication selection, technical process and requirements, dosimetry criteria, radiation protection, combined systemic therapy, and outcomes of seed implantation for rCC are discussed.
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Radioactive iodine-125 (I-125) is the most widely used radioactive sealed source for interstitial permanent brachytherapy (BT). BT has the exceptional ability to deliver extremely high doses that external beam radiotherapy (EBRT) could never achieve within treated lesions, with the added benefit that doses drop off rapidly outside the target lesion by minimizing the exposure of uninvolved surrounding normal tissue. Spurred by multiple biological and technological advances, BT application has experienced substantial alteration over the past few decades. The procedure of I-125 radioactive seed implantation evolved from ultrasound guidance to computed tomography guidance. Compellingly, the creative introduction of 3D-printed individual templates, BT treatment planning systems, and artificial intelligence navigator systems remarkably increased the accuracy of I-125 BT and individualized I-125 ablative radiotherapy. Of note, utilizing I-125 to treat carcinoma in hollow cavity organs was enabled by the utility of self-expandable metal stents (SEMSs). Initially, I-125 BT was only used in the treatment of rare tumors. However, an increasing number of clinical trials upheld the efficacy and safety of I-125 BT in almost all tumors. Therefore, this study aims to summarize the recent advances of I-125 BT in cancer therapy, which cover experimental research to clinical investigations, including the development of novel techniques. This review also raises unanswered questions that may prompt future clinical trials and experimental work.
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PURPOSE: To investigate the accuracy of needle distribution and dosimetric parameter differences of 3D-printing non-coplanar template (3D-PNCT)-assisted computed tomography (CT)-guided iodine-125 seed ablative brachytherapy (125I-SAB) in gynecological cancer patients with non-central pelvic recurrence between pre-operative plan and post-operative plan. MATERIAL AND METHODS: Thirty-eight patients with forty-one non-central pelvic recurrent gynecological carcinomas after radiotherapy were enrolled in this study. All patients received 3D-PNCT-assisted CT-guided 125I-SAB from January 2016 to January 2019. The position, angle, and depth of seed needles were measured in both pre-operative plan and intra-operative real-time plan in brachytherapy treatment planning system (B-TPS). Dosimetric parameters of D90, D100, V100, V150, and V200 as well as quality parameters of conformal index (CI), external index (EI), and homogeneity index (HI) were compared between pre-operative plan and post-operative plan. Peri-operation complications and radiation-related toxicity were assessed. RESULTS: Median follow-up time was 12 months (range, 5-34 months). Prescribed dose was 100-170 Gy (median, 120 Gy). Radioactivity of 125I seed was 0.4-0.7 mCi (median, 0.55 mCi). Mean depth deviation for 499 needles was 0.8 ±1.0 cm. Mean angular deviation was 2.2 ±2.1 degrees. Mean tip distance deviation of needles was 0.4 ±0.3 cm. There were significant differences between pre-operative and post-operative plans in CI (p = 0.001) and EI (p = 0.005). No significant differences were shown in D90, D100, V100, V150, V200, and HI between pre-operative and post-operative plans. Only few patients suffered from ≤ grade 2 toxicities. CONCLUSIONS: 3D-PNCT-assisted CT-guided 125I-SAB is safe and feasible for non-central pelvic recurrence of gynecological cancer. All complications are tolerable and mild.
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Macrophages are the most important phagocytes in vivo. However, the tumor microenvironment can affect the function and polarization of macrophages and form tumor-associated macrophages (TAMs). Usually, the abundance of TAMs in tumors is closely associated with poor prognosis. Preclinical studies have identified important pathways regulating the infiltration and polarization of TAMs during tumor progression. Furthermore, potential therapeutic strategies targeting TAMs in tumors have been studied, including inhibition of macrophage recruitment to tumors, functional repolarization of TAMs toward an antitumor phenotype, and other therapeutic strategies that elicit macrophage-mediated extracellular phagocytosis and intracellular destruction of cancer cells. Therefore, with the increasing impact of tumor immunotherapy, new antitumor strategies to target TAMs are now being discussed.