T cell receptor clonotype in tumor microenvironment contributes to intratumoral signaling network in patients with colorectal cancer.

Single-cell RNA sequencing (scRNA-seq) has contributed to understanding cellular heterogeneity and immune profiling in cancer. The aim of the study was to investigate gene expression and immune profiling in colorectal cancer (CRC) using scRNA-seq. We analyzed single-cell gene expression and T cell receptor (TCR) sequences in 30 pairs of CRC and matched normal tissue. Intratumoral lymphocytes were measured with digital image analysis. CRC had more T cells, epithelial cells, and myeloid cells than normal colorectal tissue. CRCs with microsatellite instability had more abundant T cells than those without microsatellite instability. Immune cell compositions of CRC and normal colorectal tissue were inversely correlated. CD4 + or CD8 + proliferating T cells, CD4 + effector memory T cells, CD8 + naïve T cells, and regulatory T cells of CRC showed higher TCR clonal expansion. Tumor epithelial cells interacted with immune cells more strongly than normal. T cells, myeloid cells, and fibroblasts from CRCs of expanded T cell clonotypes showed increased expression of genes related to TNF and NFKB signaling and T cell activation. CRCs of expanded T cell clonotypes also showed stronger cellular interactions among immune cells, fibroblasts, and endothelial cells. Pro-inflammatory CXCL and TNF signaling were activated in CRCs of expanded T cell clonotype. In conclusion, scRNA-seq analysis revealed different immune cell compositions, differential gene expression, and diverse TCR clonotype dynamics in CRC. TCR clonality expansion is associated with immune activation through T cell signaling and chemokine signaling. Patients with CRCs of expanded clonotype can be promising candidates for immunotherapy.

Reliability and Validity of the Martin Vigorimeter for Grip Strength Measurement in Korean Adults.

Background: Grip strength is important for fine motor skills, and one of the measurement tools for grip strength is the Martin Vigorimeter (MV) dynamometer. Studies on establishing the reliability and validity of the MV in Koreans are limited. We aimed to establish the reliability and validity of the MV for grip strength measurement in healthy Korean adults by comparing it with the Jamar dynamometer, the standard tool used by the American Society of Hand Therapists. Methods: In total, 99 healthy participants (50 men and 49 women) were enrolled. Grip strength was measured using the Jamar dynamometer and MV. Reliability and validity were assessed using the intraclass correlation coefficient (ICC) and minimal detectable change (MDC). The correlation between the measurements of the instruments was analyzed using Pearson's correlation. The effect of hand anthropometry was evaluated, and the conversion equation between the instruments was calculated. Results: MV showed excellent reliability (ICC > 0.90, p < 0.001) and validity with a high correlation (0.7 ≤ r < 0.9) with the Jamar dynamometer. The MDC was acceptable for detecting minimal clinically important differences (< 19.5%) in both instruments (Jamar: 3.4%-6.7%, MV: 3.8% to 6.3%). The grip strength measured using the MV was independent of hand anthropometry, unlike that using the Jamar dynamometer. Conclusions: This study provides insights into the relationship between the Jamar and MV instruments for measuring grip strength in Koreans. The MV is a viable alternative to the Jamar dynamometer in Koreans, offering not only reproducible and reliable measurements of grip strength but also the advantage of being unaffected by variations in hand anthropometry.

Effects of body mass index on mortality in elderly patients with hip fractures.

Hip fractures remain a substantial health concern, particularly among elderly individuals with osteoporosis, leading to high global mortality rates. This study aimed to analyze the association between body mass index (BMI) and postoperative mortality in patients who underwent surgery for hip fractures. A total of 680 patients treated at a single institution between January 2018 and December 2022 were included. Factors such as age, BMI, sex, Charlson Comorbidity Index (CCI), preoperative hemoglobin levels, American Society of Anesthesiologists score, anesthesia method, duration of surgery, and time from injury to surgery were assessed. Underweight status, male sex, higher CCI, and general anesthesia were significantly associated with 1-year and in-hospital mortality. Notably, underweight individuals exhibited a higher risk of mortality than normal-weight individuals, and female patients had lower mortality rates. This study underscores the importance of considering BMI, along with other demographic and clinical factors, in predicting postoperative mortality among patients with hip fractures, aiding the development of tailored management strategies to improve outcomes and reduce complications in this vulnerable patient population.

The expression of PD-L1 on tumor-derived exosomes enhances infiltration and anti-tumor activity of αCD3 × αPD-L1 bispecific antibody-armed T cells.

Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44highCD62Llow effector memory CD8+ T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T.

Comparative analysis of molecular and histological glioblastomas: insights into prognostic variance.

PURPOSE: Whether molecular glioblastomas (GBMs) identify with a similar dismal prognosis as a "classical" histological GBM is controversial. This study aimed to compare the clinical, molecular, imaging, surgical factors, and prognosis between molecular GBMs and histological GBMs. METHODS: Retrospective chart and imaging review was performed in 983 IDH-wildtype GBM patients (52 molecular GBMs and 931 histological GBMs) from a single institution between 2005 and 2023. Propensity score-matched analysis was additionally performed to adjust for differences in baseline variables between molecular GBMs and histological GBMs. RESULTS: Molecular GBM patients were substantially younger (58.1 vs. 62.4, P = 0.014) with higher rate of TERTp mutation (84.6% vs. 50.3%, P < 0.001) compared with histological GBM patients. Imaging showed higher incidence of gliomatosis cerebri pattern (32.7% vs. 9.2%, P < 0.001) in molecular GBM compared with histological GBM, which resulted in lesser extent of resection (P < 0.001) in these patients. The survival was significantly better in molecular GBM compared to histological GBM (median OS 30.2 vs. 18.4 months, P = 0.001). The superior outcome was confirmed in propensity score analyses by matching histological GBM to molecular GBM (P < 0.001). CONCLUSION: There are distinct clinical, molecular, and imaging differences between molecular GBMs and histological GBMs. Our results suggest that molecular GBMs have a more favorable prognosis than histological GBMs.

Prediction for Perioperative Stroke Using Intraoperative Parameters.

BACKGROUND: Perioperative stroke is a severe complication following surgery. To identify patients at risk for perioperative stroke, several prediction models based on the preoperative factors were suggested. Prediction models often focus on preoperative patient characteristics to assess stroke risk. However, most existing models primarily base their predictions on the patient's baseline characteristics before surgery. We aimed to develop a machine-learning model incorporating both pre- and intraoperative variables to predict perioperative stroke. METHODS AND RESULTS: This study included patients who underwent noncardiac surgery at 2 hospitals with the data of 15 752 patients from Seoul National University Hospital used for development and temporal internal validation, and the data of 449 patients from Boramae Medical Center used for external validation. Perioperative stroke was defined as a newly developed ischemic lesion on diffusion-weighted imaging within 30 days of surgery. We developed a prediction model composed of pre- and intraoperative factors (integrated model) and compared it with a model consisting of preoperative features alone (preoperative model). Perioperative stroke developed in 109 (0.69%) patients in the Seoul National University Hospital group and 11 patients (2.45%) in the Boramae Medical Center group. The integrated model demonstrated superior predictive performance with area under the curve values of 0.824 (95% CI, 0.762-0.880) versus 0.584 (95% CI, 0.499-0.667; P<0.001) in the internal validation; and 0.716 (95% CI, 0.560-0.859) versus 0.505 (95% CI, 0.343-0.654; P=0.018) in the external validation, compared to the preoperative model. CONCLUSIONS: We suggest that incorporating intraoperative factors into perioperative stroke prediction models can improve their accuracy.

Hydrophobic, ultraviolet radiation-shielding, and antioxidant functionalities of TEMPO-oxidized cellulose nanofibril film coated with modified lignin nanoparticles.

In this study, lignin nanoparticles (LN) and octadecylamine-modified LN (LN-ODA) were utilized as coating materials to enhance the hydrophobic, antioxidant, and ultraviolet radiation-shielding (UV-shielding) properties of a TEMPO-oxidized nanocellulose film (TOCNF). The water contact angle (WCA) of the TOCNF was approximately 53° and remained stable for 1 min, while the modified LN-ODA-coated TOCNF reached over 130° and maintained approximately 85° for an hour. Pure TOCNF exhibited low antioxidant properties (4.7 %), which were significantly enhanced in TOCNF-LN (81.6 %) and modified LN-ODA (10.3 % to 27.5 %). Modified LN-ODA-coated TOCNF exhibited antioxidant properties two to six times higher than those of pure TOCNF. Modified LN-ODA exhibited thermal degradation max (Tmax) at 421 °C, while pure LN showed the main degradation temperature at approximately Tmax 330 °C. The thermal stability of TOCNF-LN-ODA-coated materials remained consistent with that of pure TOCNF, while the crystallinity index of the sample showed a slight decrease due to the amorphous nature of the lignin structure. The tensile strength of TOCNF was approximately 114.1 MPa and decreased to 80.1, 51.3, and 30.3 MPa for LN-ODA coating at 5, 10, and 15 g/m2, respectively.

Recent deep learning-based brain tumor segmentation models using multi-modality magnetic resonance imaging: a prospective survey.

Radiologists encounter significant challenges when segmenting and determining brain tumors in patients because this information assists in treatment planning. The utilization of artificial intelligence (AI), especially deep learning (DL), has emerged as a useful tool in healthcare, aiding radiologists in their diagnostic processes. This empowers radiologists to understand the biology of tumors better and provide personalized care to patients with brain tumors. The segmentation of brain tumors using multi-modal magnetic resonance imaging (MRI) images has received considerable attention. In this survey, we first discuss multi-modal and available magnetic resonance imaging modalities and their properties. Subsequently, we discuss the most recent DL-based models for brain tumor segmentation using multi-modal MRI. We divide this section into three parts based on the architecture: the first is for models that use the backbone of convolutional neural networks (CNN), the second is for vision transformer-based models, and the third is for hybrid models that use both convolutional neural networks and transformer in the architecture. In addition, in-depth statistical analysis is performed of the recent publication, frequently used datasets, and evaluation metrics for segmentation tasks. Finally, open research challenges are identified and suggested promising future directions for brain tumor segmentation to improve diagnostic accuracy and treatment outcomes for patients with brain tumors. This aligns with public health goals to use health technologies for better healthcare delivery and population health management.

Revisiting oligodendroglioma grading in the 2021 WHO classification: calcification and larger contrast-enhancing tumor volume may predict higher oligodendroglioma grade.

PURPOSE: To investigate whether qualitative and quantitative imaging phenotypes can predict the grade of oligodendroglioma. METHODS: Retrospective chart and imaging reviews were conducted on 180 adults with oligodendroglioma (IDH-mutant and 1p/19q codeleted) between 2005 and 2021. Qualitative imaging characteristics including tumor location, calcification, gliomatosis cerebri, cystic change, necrosis, and infiltrative pattern were analyzed. Quantitative imaging assessment was performed from the tumor mask via automatic segmentation to calculate total, contrast-enhancing (CE), non-enhancing (NE), and necrotic tumor volumes. Logistic analyses were conducted to determine predictors of oligodendroglioma grade. RESULTS: This study included 180 patients (84 [46.7%] with grade 2 and 96 [53.3%] with grade 3 oligodendrogliomas), with a median age of 42 years (range 23-76 years), comprising 91 females and 89 males. On univariable analysis, calcification (odds ratio [OR] = 6.00, P < 0.001), necrosis (OR = 21.84, P = 0.003), presence of CE tumor (OR = 7.86, P < 0.001), larger total (OR = 1.01, P < 0.001), larger CE (OR = 2.22, P = 0.010), and larger NE (OR = 1.01, P < 0.001) tumor volumes were predictors of grade 3 oligodendroglioma. On multivariable analysis, calcification (OR = 3.79, P < 0.001) and larger CE tumor volume (OR = 2.70, P = 0.043) remained as independent predictors of grade 3 oligodendroglioma. The multivariable model exhibited an AUC, accuracy, sensitivity, specificity of 0.78 (95% confidence interval 0.72-0.84), 72.8%, 79.2%, 69.1%, respectively. CONCLUSION: Presence of calcification and larger CE tumor volume may serve as useful imaging biomarkers for prediction of oligodendroglioma grade. CLINICAL RELEVANCE STATEMENT: Assessment of intratumoral calcification and CE tumor volume may facilitate accurate preoperative estimation of oligodendroglioma grade. Presence of intratumoral calcification and larger contrast-enhancing tumor volume were the significant predictors of higher grade oligodendroglioma based on the 2021 WHO classification.

Robotic versus open mini-incision living donor nephrectomy: Single centre experience.

BACKGROUND: Robotic surgery is associated with less tissue manipulation and earlier recovery with minimal incision. The aim of this study was to compare the short-term clinical outcomes between robotic-assisted donor nephrectomy (RDN) and open mini-incision donor nephrectomy (ODN). METHODS: From 2016 to 2019, 141 cases involving RDN were analysed. Patient outcomes were compared with those of 191 patients who underwent ODN from 2010 to 2015. Demographics, operation factors, perioperative outcomes, and complications were retrospectively reviewed. RESULTS: The RDN group presented with less blood loss than the ODN group (p = 0.023). The length of hospital stay was significantly shorter in the RDN group than in the ODN group (p < 0.005). The overall rate of complications was low and there was no significant difference in complication rates between the groups. CONCLUSION: The robotic approach has benefits over the traditional open approach, including shorter length of hospital stay and reduced intraoperative blood loss.

Risk Factors for the Recurrence of Chronic Subdural Hematoma.

Objective: Chronic subdural hematoma (CSDH) is commonly encountered in neurosurgery, and often occurs in elderly patients following a head injury. Despite favorable postoperative prognosis, recurrence remains common. Herein, we retrospectively analyzed the clinical and radiological data of patients at our institute to identify the risk factors for CSDH recurrence. Methods: We investigated 370 patients who underwent surgery for CSDH at our institute. The following data were analyzed: sex, age, antiplatelet/anticoagulant use, preexisting diseases, radiological parameters, and surgical techniques. A univariate analysis was subsequently performed to examine the association between these variables and CSDH recurrence. Variables with a p-value of <0.05 in univariate analysis were further subjected to a multivariate logistic regression model to identify independent risk factors of CSDH. Results: Of the 370 patients, 345 (93.2%) had no recurrence and 25 (6.8%) had recurrence. Univariate and multivariate analyses revealed that male sex, advanced age, bilateral hematoma, moderate or severe brain atrophy, separation type, gradation type, and burr hole trephination were independent risk factors for CSDH recurrence. Conclusion: Sex, age, bilateral hematoma, brain atrophy, hematoma density and architecture, and surgical techniques are all associated with CSDH recurrence.

Evaluation of resazurin phenoxazine dye as a highly sensitive cell viability potency assay for natural killer cell-derived extracellular vesicle-based cancer biotherapeutics.

Natural killer cell-derived extracellular vesicles (NK-EVs) are candidate biotherapeutics against various cancers. However, standardised potency assays are necessary for a reliable assessment of NK-EVs' cytotoxicity. This study aims to thoroughly evaluate a highly sensitive resazurin phenoxazine-based cell viability potency assay (measurement of the cellular redox metabolism) for quantifying the cytotoxicity of NK-EVs against leukaemia K562 cells (suspension model) and breast cancer MDA-MB-231 cells (adherent model) in vitro. The assay was evaluated based on common analytical parameters setforth by regulatory guidelines, including specificity, selectivity,accuracy, precision, linearity, range and stability. Our results revealed that this resazurin-based cell viability potency assay reliably and reproducibly measured a dose-response of NK-EVs' cytotoxic activity against both cancer models. The assay showed precision with 5% and 20% variation for intra-run and inter-run variability. The assay signal showed specificity and selectivity of NK-EVs against cancer target cells, as evidenced by the diminished viability of cancer cells following a 5-hour treatment with NK-EVs, without any detectable interference or background. The linearity analysis of target cancer cells revealed strong linearity for densities of 5000 K562 and 1000 MDA-MB-231 cells per test with a consistent range. Importantly, NK-EVs' dose-response for cytotoxicity showed a strong correlation (|ρ| ∼ 0.8) with the levels of known cytotoxic factors associated with the NK-EVs' corona (FasL, GNLY, GzmB, PFN and IFN-γ), thereby validating the accuracy of the assay. The assay also distinguished cytotoxicity changes in degraded NK-EVs, indicating the ability of the assay to detect the potential loss of sample integrity. Compared to other commonly reported bioassays (i.e., flow cytometry, cell counting, lactate dehydrogenase release assay, DNA-binding reporter assay and confluence assay), our results support this highly sensitive resazurin-based viability potency assay as a high-throughput and quantitative method for assessing NK-EVs' cytotoxicity against both suspension and adherent cancer models for evaluating NK-EVs' biotherapeutics.

Overexpression of Hypermethylated Homeobox A11 (HOXA11) Inhibits Tumor Cell Growth and Induces Apoptosis in Cervical Cancer.

This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment.

Metabolic Profiling Changes Induced by Fermented Blackberries in High-Fat-Diet-Fed Mice Utilizing Gas Chromatography-Mass Spectrometry Analysis.

The aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet.

Real-World Clinical Utility of Targeted RNA Sequencing in Leukemia Diagnosis and Management.

Gene fusions are key drivers in acute leukemia, impacting diagnosis and treatment decisions. We analyzed 264 leukemia patients using targeted RNA sequencing with conventional karyotyping and reverse transcription polymerase chain reaction (RT-PCR). Leukemic fusions were detected in 127 patients (48.1%). The new guidelines introduced additional diagnostic criteria, expanding the spectrum of gene fusions. We discovered three novel fusions (RUNX1::DOPEY2, RUNX1::MACROD2, and ZCCHC7::LRP1B). We analyzed recurrent breakpoints for the KMT2A and NUP98 rearrangements. Targeted RNA sequencing showed consistent results with RT-PCR in all tested samples. However, when compared to conventional karyotyping, we observed an 83.3% concordance rate, with 29 cases found only in targeted RNA sequencing, 7 cases with discordant results, and 5 cases found only in conventional karyotyping. For the five cases where known leukemic gene rearrangements were suspected only in conventional karyotyping, we conducted additional messenger RNA sequencing in four cases and proved no pathogenic gene rearrangements. Targeted RNA sequencing proved advantageous for the rapid and accurate interpretation of gene rearrangements. The concurrent use of multiple methods was essential for a comprehensive evaluation. Comprehensive molecular analysis enhances our understanding of leukemia's genetic basis, aiding diagnosis and classification. Advanced molecular techniques improve clinical decision-making, offering potential benefits.

Tumor phagocytosis-driven STING activation invigorates antitumor immunity and reprograms the tumor micro-environment.

Immunogenic cell death (ICD) holds the potential for in situ tumor vaccination while concurrently eradicating tumors and stimulating adaptive immunity. Most ICD inducers, however, elicit insufficient immune responses due to negative feedback against ICD biomarkers, limited infiltration of antitumoral immune cells, and the immunosuppressive tumor micro-environment (TME). Recent findings highlight the pivotal roles of stimulators of interferon gene (STING) activation, particularly in stimulating antigen-presenting cells (APCs) and TME reprogramming, addressing ICD limitations. Herein, we introduced 'tumor phagocytosis-driven STING activation', which involves the activation of STING in APCs during the recognition of ICD-induced cancer cells. We developed a polypeptide-based nanocarrier encapsulating both doxorubicin (DOX) and diABZI STING agonist 3 (dSA3) to facilitate this hypothesis in vitro and in vivo. After systemic administration, nanoparticles predominantly accumulated in tumor tissue and significantly enhanced anticancer efficacy by activating tumor phagocytosis-driven STING activation in MC38 and TC1 tumor models. Immunological activation of APCs occurred within 12 h, subsequently leading to the activation of T cells within 7 days, observed in both the TME and spleen. Furthermore, surface modification of nanoparticles with cyclic RGD (cRGD) moieties, which actively target integrin αvß3, enhances tumor accumulation and eradication, thereby verifying the establishment of systemic immune memory. Collectively, this study proposes the concept of tumor phagocytosis-driven STING activation and its effectiveness in generating short-term and long-term immune responses.

Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): study protocol for a multi-center, prospective, randomized trial.

BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. METHODS: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. DISCUSSION: This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.

Facile synthesis of elastin nanogels encapsulated decursin for castrated resistance prostate cancer therapy.

Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/ßcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.