PKCα Induced the Generation of Extracellular Vesicles in Activated Platelets to Promote Breast Cancer Metastasis.

Platelet extracellular vesicles (PEVs) play an important role in tumor development. However, the mechanisms underlying their biogenesis have not been fully elucidated. Protein kinase Cα (PKCα) is an important regulator of platelet activation, but the effect of PKCα on EV generation is unclear. We used small-particle flow cytometry and found that the number of PEVs was increased in patients with breast cancer compared to those with benign breast disease. This was accompanied by increased levels of activated PKCα in breast cancer platelets. Treating platelets with the PKCα agonist phorbol 12-myristate 13-acetate (PMA) increased the phosphorylation PKCα and induced PEV production, while the PKCα inhibitor GÖ6976 showed the opposite effects. Notably, incubating platelets from patients with benign tumors with the culture supernatant of MDA-MB-231 cells induced PKCα phosphorylation in the platelets. Mass spectrometry and coimmunoprecipitation assays showed that Dynamin 2 (DNM2), a member of the guanosine-triphosphate-binding protein family, might cooperate with activated PKCα to regulate PEV production by breast cancer platelets. Similar results were observed in a mouse model of lung metastasis. In addition, PEVs were engulfed by breast cancer cells and promoted cancer cell migration and invasion via miR-1297 delivery. These findings suggested that PKCα cooperates with DNM2 to induce PEV generation, and PEV release might triggered by factors in the breast cancer environment.

Effects of Acute High-Altitude Exposure on Morphology and Function of Retinal Ganglion Cell in Mice.

Purpose: High altitude retinopathy (HAR) is a retinal functional disorder caused by inadequate adaptation after exposure to high altitude. However, the cellular and molecular mechanisms underlying retinal dysfunction remain elusive. Retinal ganglion cell (RGC) injury is the most important pathological basis for most retinal and optic nerve diseases. Studies focusing on RGC injury after high-altitude exposure (HAE) are scanty. Therefore, the present study sought to explore both functional and morphological alterations of RGCs after HAE. Methods: A mouse model of acute hypobaric hypoxia was established by mimicking the conditions of a high altitude of 5000 m. After HAE for 2, 4, 6, 10, 24, and 72 hours, the functional and morphological alterations of RGCs were assessed using retinal hematoxylin and eosin (H&E) sections, retinal whole mounts, transmission electron microscopy (TEM), and the photopic negative response (PhNR) of the electroretinogram. Results: Compared with the control group, the thickness of the ganglion cell layer and retinal nerve fiber layer increased significantly, RGC loss remained significant, and the amplitudes of a-wave, b-wave, and PhNR were significantly reduced after HAE. In addition, RGCs and their axons exhibited an abnormal ultrastructure after HAE, including nuclear membrane abnormalities, uneven distribution of chromatin in the nucleus, decreased cytoplasmic electron density, widening and vacuolization of the gap between axons, loosening and disorder of myelin sheath structure, widening of the gap between myelin sheath and axon membrane, decreased axoplasmic density, unclear microtubule and nerve fiber structure, and abnormal mitochondrial structure (mostly swollen, with widened membrane gaps and reduced cristae and vacuolization). Conclusions: The study findings confirm that the morphology and function of RGCs are damaged after HAE. These findings lay the foundation for further study of the specific molecular mechanisms of HAR and promote the effective prevention.

Effect of carboxyl group on photoelectrochemical performance of TiO2 nanowire arrays for water splitting.

TiO2 is one of the most studied semiconductor materials for the photoelectrochemical water splitting to hydrogen production, but it only responds to ultraviolet light. The introduction of organic compound is one of the common means to expand the visible light response of TiO2. In this work, rutile TiO2 nanowire arrays (NWs) were grown on conductive glass by a modified solvothermal method using oleic acid as the key additive. The obtained TiO2 NWs are characterized using X-ray diffraction, X-ray photoelectron spectroscopy, infrared spectroscopy and electrochemical characterization. The results show that the carboxyl groups arising from oleic acid are chemically bonded with the TiO2 NWs in the form of chelating bidentate, which increases the visible light absorption range and active sites of TiO2, and reduces the transfer resistance between the photoelectrode and the electrolyte. The photocurrent density is doubled to 0.17 mA cm-2 at 1.23 V vs. RHE. This work provides a novel idea for the design of metal oxide semiconductor photoanodes by adsorbing organic compounds.

Cobb syndrome effectively treated with trametinib.

Cobb syndrome is a rare neurocutaneous disease characterized by vascular anomalies involving the skin and spinal cord at the same metamere. The most common initial symptoms are neurological manifestations such as pain, monoparesis, headache, scoliosis, and motor damage. We present two patients with Cobb syndrome and severe disease burden harboring somatic mutations in KRAS. The two patients were subsequently treated with the MEK inhibitor trametinib, indicating the potential therapeutic benefit of this treatment for patients with life-threatening Cobb syndrome who are currently considered incurable.

Biocompatibility and osteogenic capacity of additively manufactured biodegradable porous WE43 scaffolds: An in vivo study in a canine model.

Magnesium is the most promising absorbable metallic implant material for bone regeneration and alloy WE43 is already FDA approved for cardiovascular applications. This study investigates the cyto- and biocompatibility of novel additively manufactured (AM) porous WE43 scaffolds as well as their osteogenic potential and degradation characteristics in an orthotopic canine bone defect model. The cytocompatibility was demonstrated using modified ISO 10993-conform extract-based indirect and direct assays, respectively. Additionally, degradation rates of WE43 scaffolds were quantified in vitro prior to absorption tests in vivo. Complete blood cell counts, blood biomarker analyses, blood trace element analyses as well as multi-organ histopathology demonstrated excellent biocompatibility of porous y WE43 scaffolds for bone defect repair. Micro-CT analyses further showed a relatively higher absorption rate during the initial four weeks upon implantation (i.e., 36 % ± 19 %) than between four and 12 weeks (41 % ± 14 %), respectively. Of note, the porous WE43 implants were surrounded by newly formed bony tissue as early as four weeks after implantation when unmineralized trabecular ingrowth was detected. After 12 weeks, a substantial amount of mineralized bone was detected inside and around the gradually disappearing implants. This first study on AM porous WE43 implants in canine bone defects demonstrates the potential of this alloy for in vivo applications in humans. Our data further underscore the need to control initial bulk absorption kinetics through surface modifications.

Radix Isatidis polysaccharide (RIP) alleviates QX-genotype infectious bronchitis virus-induced interstitial nephritis through the Nrf2/NLRP3/Caspase-3 signaling pathway.

Interstitial nephritis is the primary cause of mortality in IBV-infected chickens. Our previous research has demonstrated that Radix Isatidis polysaccharide (RIP) could alleviate this form of interstitial nephritis. To explore the mechanism, SPF chickens and chicken embryonic kidney cells (CEKs) were pre-treated with RIP and subsequently infected with QX-genotype IBV strain. Kidneys were sampled for transcriptomic and metabolomic analyses, and the cecum contents were collected for 16S rRNA gene sequencing. Results showed that pre-treatment with RIP led to a 50 % morbidity reduction in infected-chickens, along with decreased tissue lesion and viral load in the kidneys. Multi-omics analysis indicated three possible pathways (including antioxidant, anti-inflammatory and anti-apoptosis) which associated with RIP's efficacy against interstitial nephritis. Following further validation both in vivo and in vitro, the results showed that pre-treatment with RIP could activate the antioxidant transcription factor Nrf2, stimulate antioxidant enzyme expression, and consequently inhibit oxidative stress. Pre-treatment with RIP could also significantly reduce the expression of NLRP3 inflammasome and apoptosis-associated proteins (including Bax, Caspase-3, and Caspase-9). Additionally, RIP was also observed to promote the growth of beneficial bacteria in the intestine. Overall, pretreatment with RIP can alleviate QX-genotype IBV-induced interstitial nephritis via the Nrf2/NLRP3/Caspase-3 signaling pathway. This study lays the groundwork for the potential use of RIP in controlling avian infectious bronchitis (IB).

Nerve Regeneration Potential of Antioxidant-Modified Black Phosphorus Quantum Dots in Peripheral Nerve Injury.

Peripheral nerve injury is a major societal concern. Black phosphorus (BP) has inherent advantages over cell-based therapies in regenerative medicine. However, controlling spontaneous degradation and size-dependent cytotoxicity remains challenging and poses difficulties for clinical translation. In this study, we constructed zero-dimensional BP quantum dots (QDs) modified with antioxidant ß-carotene and comprehensively investigated them in Schwann cells (SCs) to elucidate their potential for peripheral nerve repair. In vitro experiments demonstrated that BPQD@ß-carotene has an inappreciable toxicity and good biocompatibility, favoring neural regrowth, angiogenesis, and inflammatory regulation of SCs. Furthermore, the PI3K/Akt and Ras/ERK1/2 signaling pathways were activated in SCs at the genetic, protein, and metabolite levels. The BPQD@ß-carotene-embedded GelMA/PEGDA scaffold enhanced functional recovery by promoting axon remyelination and regeneration and facilitating intraneural angiogenesis in peripheral nerve injury models of rats and beagle dogs. These results contribute to advancing knowledge of BP nanomaterials in tissue regeneration and show significant potential for application in translational medicine.

The activities of daily living partially mediate the relationship between rapid eye movement sleep behavior disorder and depressive symptoms in Parkinson's disease.

Objective: A longitudinal study was conducted to investigate whether rapid eye movement sleep behavior disorder affect depression in patients with Parkinson's disease through activities of daily living. Methods: A total of 387 Parkinson's disease patients' six-year follow-up data (one follow-up per year) were obtained from the Parkinson's Progression Markers Initiative. To allow causal effects to manifest, this study increased the lag period and divided the data from the six follow-ups into two groups: wave 1 (wave refers to time points), wave 3, and wave 5 as one group, and wave 2, wave 4, and wave6 as the other group. The time interval between two time points in each group was two years. To comprehensively and deeply analyze the dynamic relationships between variables, accurately infer causal relationships, control for individual differences, and detect the stability of these relationships, this study constructed the fixed effects cross-lagged panel model (CLPM), the random effects CLPM (RE-CLPM) model, and the Equating CLPM and Equating RE-CLPM models with applied restriction conditions. Additionally, a reverse path was added to verify the reverse prediction effect. The most suitable data analysis model was selected to explore the relationships between the study variables. Furthermore, the longitudinal mediating effect of daily living activities between rapid eye movement sleep behavior disorder and depression was investigated. Results: In the models, Equating cross-lagged panel model was the best. The lag effect was positive and significant. In wave 1, 3, 5, activities of daily living mediated 11.82% on the path from rapid eye movement sleep behavior disorder to depression; in wave 2, 4, 6, it mediated 13.13%. Therefore, attention should be paid to the treatment of activities of daily living. Conclusion: Longitudinal changes in activities of daily living have indirect effects on the relationship between rapid eye movement sleep behavior disorder and depression, which highlights the importance of changes in activities of daily living ability in Parkinson's disease patients with rapid eye movement sleep behavior disorder.

DNA methylation profiling deciphers three EMT subtypes with distinct prognoses and therapeutic vulnerabilities in breast cancer.

Background: Epithelial-mesenchymal transition (EMT), deemed a pivotal hallmark of tumours, is intricately regulated by DNA methylation and encompasses multiple states along tumour progression. The potential mechanisms that drive the intrinsic heterogeneity of breast cancer (BC) via EMT transformation have not been identified, presenting a significant obstacle in clinical diagnosis and treatment. Methods: A total of 7,602 patients have been included in this study. We leveraged integrated multiomics data (epigenomic, genomic, and transcriptomic data) to delineate the comprehensive landscape of EMT in BC. Subsequently, a subtyping classifier was developed through a machine learning framework proposed by us. Results: We classified the BC samples into three methylation-driven EMT subtypes with distinct features, namely, C1 (the mammary duct development subtype with TP53 activation), C2 (the immune infiltration subtype with high TP53 mutation), and C3 (the ERBB2 amplification subtype with an unfavorable prognosis). Specifically, patients with the C1 subtype might respond to endocrine therapy or the p53-MDM2 antagonist nutlin-3. Patients with the C2 subtype might benefit from combined therapeutic regimens involving radiotherapy, PARP inhibitors, and immune checkpoint blockade therapy. Patients with the C3 subtype might benefit from anti-HER2 agents such as lapatinib. Notably, to increase the clinical applicability of the EMT subtypes, we devised a 96-gene panel-based classifier via a machine learning framework. Conclusions: Our study identified three methylation-driven EMT subtypes with distinct prognoses and biological traits to capture heterogeneity in BC and provided a rationale for the use of this classification as a powerful tool for developing new strategies for clinical trials.

Application of genome tagging technology in elucidating the function of sperm-specific protein 411 (Ssp411).

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.

Research on Division of Labor Decision and System Stability of Swarm Robots Based on Mutual Information.

In rational decision-making processes, the information interaction among individual robots is a critical factor influencing system stability. We establish a game-theoretic model based on mutual information to address division of labor decision-making and stability issues arising from differential information interaction among swarm robots. Firstly, a mutual information model is employed to measure the information interaction among robots and analyze its influence on the behavior of individual robots. Secondly, employing the Cournot model and the Stackelberg model, we model the diverse decision-making behaviors of swarm robots influenced by discrepancies in mutual information. The intricate decision dynamics exhibited by the system under the disparity mutual information values during the game process, along with the stability of Nash equilibrium points, are analyzed. Finally, dynamic complexity simulations of the game models are simulated under the disparity mutual information values: (1) When ν1 of the game model varies within a certain range, the Nash equilibrium point loses stability and enters a chaotic state. (2) As I(X;Y) increases, the decision-making pattern of robots transitions gradually from the Cournot game to the Stackelberg game. Concurrently, the sensitivity of swarm robotics systems to changes in decision parameter decreases, reducing the likelihood of the system entering a chaotic state.

Study on the Tribological Properties of Multilayer Concentric Hexagonal Laser Texturing on Rubber Surfaces of Screw Pumps.

Given the friction and drag reduction effects observed in various biological hexagonal structures in nature, a new design was implemented on the rubber surface of the stator of a submersible screw pump. This design featured a multilayer concentric hexagonal groove structure. Furthermore, a composite multilayer hexagonal structure integrating grooves and pits was also developed and applied. This study investigated the influence of groove layer number, groove depth, pit depth, and multilayer hexagonal groove texture arrangement on the rubber surface flow characteristics. Additionally, the pressure field state, the degree of influence on the oil film-bearing capacity, and the biomimetic and hydrodynamic lubrication theories were tested using the finite element analysis method. Tribological experiments were conducted on nanosecond laser-processed rubber textures under simulated liquid lubrication conditions, reflecting actual shale oil well experiments. These experiments aimed to investigate the influence of multilayer hexagonal shape parameters on the tribological characteristics of the stator-rotor friction pair of a submersible screw pump. The results indicated that with a constant overall size, a multilayer hexagonal structure with ~0.1 mm groove depth enhanced the oil film-bearing capacity, providing significant friction and drag reduction. For composite textures, a deeper pit depth within the study area enhanced the oil film-bearing capacity. Furthermore, a gradient arrangement of groove textures featuring wider outer grooves and shallower depth exhibited superior performance in terms of bearing capacity.

Quantitative Analysis of White Matter Hyperintensities as a Predictor of 1-Year Risk for Ischemic Stroke Recurrence.

INTRODUCTION: This study evaluates the role of quantitative characteristics of white matter hyperintensities (WMHs) in predicting the 1-year recurrence risk of ischemic stroke. METHODS: We conducted a retrospective analysis of 1061 patients with ischemic stroke from January 2018 to April 2021. WMHs were automatically segmented using a cluster-based method to quantify their volume and number of clusters (NoC). Additionally, two radiologists independently rated periventricular and deep WMHs using the Fazekas scale. The cohort was divided into a training set (70%) and a testing set (30%). We employed Cox proportional hazards models to develop predictors based on quantitative WMH characteristics, Fazekas scores, and clinical factors, and compared their performance using the concordance index (C-index). RESULTS: A total of 180 quantitative variables related to WMHs were extracted. A higher NoC in deep white matter and brainstem, advanced age (> 90 years old), specific stroke subtypes, and absence of discharge antiplatelets showed stronger associations with the risk of ischemic stroke recurrence within 1 year. The nomogram incorporating quantitative WMHs data showed superior discrimination compared to those based on the Fazekas scale or clinical factors alone, with C-index values of 0.709 versus 0.647 and 0.648, respectively, in the testing set. Notably, a combined model including both WMHs and clinical factors achieved the highest predictive accuracy, with a C-index of 0.735 in the testing set. CONCLUSION: Quantitative assessment of WMHs provides a valuable neuro-imaging tool for enhancing the prediction of ischemic stroke recurrence risk.

Prediction of lateral lymph node metastasis in rectal cancer patients based on MRI using clinical, deep transfer learning, radiomic, and fusion models.

Introduction: Lateral lymph node (LLN) metastasis in rectal cancer significantly affects patient treatment and prognosis. This study aimed to comprehensively compare the performance of various predictive models in predicting LLN metastasis. Methods: In this retrospective study, data from 152 rectal cancer patients who underwent lateral lymph node (LLN) dissection were collected. The cohort was divided into a training set (n=86) from Tianjin Union Medical Center (TUMC), and two testing cohorts: testing cohort (TUMC) (n=37) and testing cohort from Gansu Provincial Hospital (GSPH) (n=29). A clinical model was established using clinical data; deep transfer learning models and radiomics models were developed using MRI images of the primary tumor (PT) and largest short-axis LLN (LLLN), visible LLN (VLLN) areas, along with a fusion model that integrates features from both deep transfer learning and radiomics. The diagnostic value of these models for LLN metastasis was analyzed based on postoperative LLN pathology. Results: Models based on LLLN image information generally outperformed those based on PT image information. Rradiomics models based on LLLN demonstrated improved robustness on external testing cohorts compared to those based on VLLN. Specifically, the radiomics model based on LLLN imaging achieved an AUC of 0.741 in the testing cohort (TUMC) and 0.713 in the testing cohort (GSPH) with the extra trees algorithm. Conclusion: Data from LLLN is a more reliable basis for predicting LLN metastasis in rectal cancer patients with suspicious LLN metastasis than data from PT. Among models performing adequately on the internal test set, all showed declines on the external test set, with LLLN_Rad_Models being less affected by scanning parameters and data sources.

Revealing and reconstructing the 3D Li-ion transportation network for superionic poly(ethylene) oxide conductor.

Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.

Surgical management of a temporal meningoencephalocele with a patient-specific combined craniofossa prosthesis: illustrative case.

BACKGROUND: Meningoencephaloceles can originate through any defect in the cranial bones, including the skull base. They can be completely asymptomatic or present with typical symptoms such as headaches, seizures, or meningitis. OBSERVATIONS: The authors present the case of a 54-year-old female who presented with right-sided ear and temporomandibular joint (TMJ) pain. Computed tomography showed a large lytic lesion of the squamous part of the temporal bone with cortical bone destruction, extending to the mandibular fossa. Magnetic resonance imaging demonstrated a temporal bone meningoencephalocele. The patient underwent resection, dural repair, and multilayer reconstruction with a patient-specific three-dimensional-printed titanium combined craniofossa prosthesis. LESSONS: To the authors' knowledge, this is the first case report of TMJ pain associated with a temporal meningoencephalocele. The exact location and extension of the lesion determine the surgical approach and need for reconstruction in temporal bone meningoencephaloceles. In cases of destruction of the mandibular fossa, a patient-specific combined craniofossa prosthesis is recommended to reconstruct the bone defect. https://thejns.org/doi/10.3171/CASE24132.

Laparoscopic partial splenectomy for a giant splenic pseudocyst with elevated CA19-9: a case report.

Introduction and importance: Currently, there is a lack of reliable evidence on the management of splenic cysts, which are rare. Exploring the efficacy of laparoscopic partial splenectomy can aid in the accumulation of treatment-related evidence. Case presentation: Here, we report the case of a 31-year-old female who was diagnosed with a giant splenic cyst with elevated serum CA19-9 and subsequently underwent laparoscopic partial splenectomy. Clinical discussion: The effects of most treatment options for splenic cysts, including percutaneous aspiration and drainage, fenestration, and partial splenectomy, have not been confirmed by high-level evidence. With the development of minimally invasive surgery, laparoscopic partial splenectomy has drawn increasing attention. Additionally, the relationships between tumor markers and splenic cysts need to be further elucidated. Conclusions: Laparoscopic partial splenectomy might be recommended for patients with splenic cysts, especially when the cysts are not completely covered by the splenic parenchyma.

miR-16-5p specifically inhibits IFN-γ-regulated memory T helper cell differentiation in malignant pleural effusion of non-small cell lung cancer.

Background: The mechanism for memory T helper (Th) cell differentiation in malignant pleural effusion (MPE) of non-small cell lung cancer (NSCLC) is poorly understood. MicroRNAs (miRNAs), as small non-coding RNA that regulate gene expression, play a crucial role in the regulation of memory Th cell differentiation. However, whether miRNAs can inhibit the differentiation of memory Th cells in MPE of NSCLC has not been reported. This study aimed to explore miR-16-5p specifically inhibits interferon-gamma (IFN-γ)-regulated memory Th cell differentiation in MPE of NSCLC. Methods: A total of 30 patients with NSCLC and 30 age- and sex-matched patients, who were clinically diagnosed as benign pleural effusion (BPE) of lung disease and had not received any intervention, were collected. The expression of nucleic acids, miRNAs, and cytokines was detected by polymerase chain reaction (PCR), miRNA microarray, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and western blotting. Results: The expression of CD4+CD69+ T cells in NSCLC with MPE was lower than that in lung disease BPE. CD4+CD69+ T cells highly express CD45RO+ and mainly secrete anti-tumor cytokines IFN-γ, interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α). The expression of miR-16-5p in CD4+CD69+ CD45RO+ T cells in MPE was higher than that in BPE. Moreover, miR-16-5p can bind to both IFN-γ promoter and its 5'untranslated region (5'-UTR), suggesting that IFN-γ may be the target gene directly affected by miR-16-5p. IFN-γ also affects the differentiation of memory CD4+ T cells by regulating T-bet. Conclusions: We believe that miR-16-5p may regulate the decrease of differentiation of naïve CD4+ T cells into memory CD4+CD69+ T cells through its target gene IFN-γ in MPE, thus reducing the number of cytokines that produce anti-tumor effects. It may be the main reason for the low response rate of lung cancer with MPE immunotherapy.

Hypofractionated radiotherapy plus PD-1 antibody and SOX chemotherapy as second-line therapy in metastatic pancreatic cancer: a single-arm, phase II clinical trial.

PURPOSE: To assess the efficacy and safety of concurrent hypofractionated radiotherapy plus anti-PD-1 antibody and SOX chemotherapy in the treatment of metastatic pancreatic cancer (mPC) after failure of first-line chemotherapy. METHODS: Patients with pathologically confirmed mPC who failed standard first-line chemotherapy were enrolled. The patients were treated with a regimen of hypofractionated radiotherapy, SOX chemotherapy, and immune checkpoint inhibitors at our institution. We collected the patients' clinical information and outcome measurements. The median progression-free survival (mPFS) was the primary endpoint of the study, followed by disease control rate (DCR), objective response rate (ORR), median overall survival (mOS) and safety. Exploratory analyses included biomarkers related to the benefits. RESULTS: Between February 24, 2021, and August 30, 2023, twenty-five patients were enrolled in the study, and twenty-three patients who received at least one dose of the study agent had objective efficacy evaluation. The mPFS was 5.48 months, the mOS was 6.57 months, and the DCR and ORR were 69.5% and 30.4%, respectively. Among the seven patients who achieved a PR, the median duration of the response was 7.41 months. On-treatment decreased serum CA19-9 levels were associated with better overall survival. Besides, pretreatment inflammatory markers were associated with tumor response and survival. CONCLUSIONS: Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with these combination therapies in patients with refractory mPC. On-treatment decreased serum CA19-9 levels and pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) might be biomarkers related to clinical benefits. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=130211 , identifier: ChiCTR2100049799, date of registration: 2021-08-09.