ABSTRACT
The sialic acid binding Ig like lectin 15 (Siglec-15) was previously identified as tumor immune suppressor gene in some human cancers with elusive molecular mechanism to be elucidated. The continuous focus on both clinical and basic biology of bladder cancer leads us to characterize aberrant abundance of BACH1-IT2 associating with stabilization of Siglec-15, which eventually contributes to local immune suppressive microenvironment and therefore tumor advance. This effect was evidently mediated by miR-4786-5p. BACH1-IT2 functions in this scenario as microRNA sponge, and competitively conceals miR-4786 and up-regulates cancer cell surface Siglec-15. The BACH1-IT2-miR-4786-Siglec-15 axis significantly influences activation of immune cell co-culture. In summary, our data highlights the critical involvements of BACH1-IT2 and miR-4786 in immune evasion in bladder cancer, which hints the potential for both therapeutic and prognostic exploitation.
Subject(s)
MicroRNAs , Urinary Bladder Neoplasms , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Urinary Bladder Neoplasms/genetics , Sialic Acid Binding Immunoglobulin-like Lectins/metabolism , Tumor Microenvironment/genetics , Basic-Leucine Zipper Transcription Factors/geneticsABSTRACT
BACKGROUNDS: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with those of TACE alone . METHODS: A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. RESULTS: After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P < 0.001), disease control rate (DCR) (94.3%% vs. 72.9%, P < 0.001), and conversion rates before and after propensity matching were 44.1% and 41.4%, respectively, compared with the TACE group. The median progression free survival (PFS) was longer in the TLC group than in the TACE group (12.7 vs. 6.1 months, P = 0.005). The median overall survival (OS) was longer in the TLC group than in the TACE group (19.4 vs. 13.0 months, P = 0.023). Cox multivariate analysis with different modes of adjustment showed that treatment was an independent influencing factor of PFS and OS. The interaction analysis showed that cirrhosis and Child-Pugh stage an interactive role in the PFS of different treatment. Decreased AFP after treatment portends higher ORR and DCR. CONCLUSION: TACE combined Lenvatinib plus Camrelizumab regimen was safe and superior to TACE alone in improving PFS, OS, and tumor response rates for unresectable recurrent HCC patients.
Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Phenylurea Compounds , Propensity Score , Quinolines , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/therapy , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Quinolines/therapeutic use , Quinolines/administration & dosage , Quinolines/adverse effects , Male , Female , Chemoembolization, Therapeutic/methods , Chemoembolization, Therapeutic/adverse effects , Middle Aged , Retrospective Studies , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/adverse effects , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Treatment Outcome , Combined Modality Therapy , AdultABSTRACT
BACKGROUND: Macrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs. RESULTS: Naïve murine bone marrow-derived macrophages were treated with lipopolysaccharide or interlukin-4 to induce M1 or M2 macrophages, respectively. The proteins of EVs and their parental macrophages were subjected to quantitative proteomics analyses, followed by bioinformatic analyses. The enriched proteins of M1-EVs were involved in proinflammatory pathways and those of M2-EVs were associated with immunomodulation and tissue remodeling. The signature proteins of EVs shared a limited subset of the proteins of their respective progenitor macrophages, but they covered many of the typical pathways and functions of their parental cells, suggesting their respective M1-like and M2-like phenotypes and functions. Experimental examination validated that protein cargos in M1- or M2-EVs induced M1 or M2 polarization, respectively. More importantly, proteins in M1-EVs promoted viability, proliferation, and activation of T lymphocytes, whereas proteins in M2-EVs potently protected the tight junction structure and barrier integrity of epithelial cells from disruption. Intravenous administration of M2-EVs in colitis mice led to their accumulation in the colon, alleviation of colonic inflammation, promotion of M2 macrophage polarization, and improvement of gut barrier functions. Protein cargos in M2-EVs played a key role in their protective function in colitis. CONCLUSION: This study has yielded a comprehensive unbiased dataset of protein cargos in macrophage-derived EVs, provided a systemic view of their potential functions, and highlighted the important engagement of protein cargos in the pathophysiological functions of these EVs.
Subject(s)
Colitis , Extracellular Vesicles , Animals , Mice , Macrophages/metabolism , Phagocytosis , Extracellular Vesicles/metabolism , Colitis/metabolism , Inflammation/metabolismABSTRACT
The clinical success of immune checkpoint blockade against diverse human cancers highlights the critical importance of insightful understanding into mechanisms underlying PD-L1 regulation. IFN-γ released by intratumoral lymphocytes regulates PD-L1 expression in tumor cells through JAK-STAT-IRF1 pathway, while the molecular events prime IRF1 to translocate into nucleus are still obscure. Here we identified STXBP6, previously recognized involving in SNARE complex assembly, negatively regulates PD-L1 transcription via retention of IRF1 in cytoplasm. IFN-γ exposure stimulates accumulation of cytosolic IRF1, which eventually saturates STXBP6 and triggers nuclear translocation of IRF1. Nuclear IRF1 in turn inhibits STXBP6 expression and thereby liberates more IRF1 to migrate to nucleus. Therefore, we identified a novel positive feedback loop between STXBP6 and IRF1 in regulation of PD-L1 expression in cancer. Furthermore, we demonstrate STXBP6 overexpression significantly inhibits T cell activation both in vitro and in vivo. These findings offer new insight into the complexity of PD-L1 expression in cancer and suggest a valuable measure to predict the response to PD-1/PD-L1-based immunotherapy.
Subject(s)
B7-H1 Antigen/metabolism , Carrier Proteins/metabolism , Interferon Regulatory Factor-1/metabolism , Neoplasms/metabolism , Animals , B7-H1 Antigen/biosynthesis , Carrier Proteins/genetics , Cell Line, Tumor , Feedback , Female , HCT116 Cells , HeLa Cells , Hep G2 Cells , Heterografts , Humans , Jurkat Cells , MCF-7 Cells , Mice , Mice, Inbred BALB C , TransfectionABSTRACT
The pioneering work from Lieping Chen's laboratory identified Siglec-15 as a novel tumor immune suppressor, while the regulatory mechanisms underlying the broad upregulation of Siglec-15 in human cancers remain obscure. Here we found that long non-coding RNA (lncRNA) LINC00973 was higher in Siglec-15-positive clear-cell renal cell carcinoma (ccRCC), and LINC00973 positively regulated Siglec-15 expression at transcriptional level. This effect was evidently dependent on miR-7109-3p (designated as miR-7109 hereafter), and we provided evidence that Siglec-15 is a direct target of miR-7109. Through sponging miR-7109, LINC00973 functioned as competing endogenous RNA (ceRNA) to control cell surface abundance of Siglec-15, and, consequently, was involved in cancer immune suppression. We further demonstrated that LINC00973 and miR-7109 expression in ccRCC antagonistically influenced immune activation of co-cultured Jurkat cells. Our study highlighted the importance of LINC00973-miR-7109-Siglec-15 in immune evasion in ccRCC, which offers significant opportunity for both therapeutic intervention and diagnostic/prognostic exploitations.
Subject(s)
Carcinoma, Renal Cell/genetics , Cell Proliferation/genetics , Immunoglobulins/genetics , Membrane Proteins/genetics , Prognosis , RNA, Long Noncoding/genetics , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Movement/genetics , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , MicroRNAs/genetics , Middle AgedABSTRACT
BACKGROUND: To characterize the MIAT expression in cervical cancer and elucidate its mechanistic involvement in the tumor biology of this disease. METHODS: The relative expression of MIAT and miR-150 was determined by real-time PCR. Cell proliferation was measured by the CCK-8 and clonogenic assay. The anchorage-independent growth was evaluated by soft agar assay. The in vivo tumor progression was assayed with xenograft mice model. The regulatory effect of miR-150 on MIAT was interrogated by luciferase reporter assay. The endogenous CNKD1B protein was detected by western blotting. RESULTS: The low expression of MIAT was characterized in cervical cancer, which associated with relatively poor prognosis. Ectopic expression of MIAT inhibited malignant growth of cervical cancer both in vitro and in vivo. Mechanistically, MIAT regulated CDKN1B expression via competition with miR-150, and miR-150-inhibition directly suppressed cervical cancer cell growth. CONCLUSIONS: Our study characterized the anti-tumor property of MIAT in cervical cancer and elucidated its competitively regulation of CDKN1B with miR-150. Our data highlighted the critical role of MIAT-miR-150-CDKN1B signaling axis in cervical cancer.
ABSTRACT
Enterovirus 71 (EV71) is a human pathogen that induces hand, foot, and mouth disease (HFMD) and fatal neurological diseases in young children and infants. Pathogenicity of EV71 is likely related to its ability to evade host innate immunity through inhibiting cellular type I interferon signaling. However, it is less well understood the molecular events governing this process. In this study, we found that EV71 infection suppressed the induction of antiviral immunity by inhibiting the expression levels of IFN-ß and IFN-stimulated genes (ISGs), such as ISG54 and ISG56, at the late stage of viral infection. At the same time, our results showed that EV71 infection significantly inhibited ubiquitination of RIG-I. In contrast, up-regulation of RIG-I ubiquitination promoted expression of IFN-ß and ISGs, suggesting that inhibition of cellular type I interferon signaling was caused by down-regulation of RIG-I ubiquitination during EV71 infection. These results suggest that inhibition of RIG-I-mediated type I IFN responses by EV71 may contribute to the pathogenesis of viral infection.
Subject(s)
DEAD Box Protein 58/antagonists & inhibitors , Enterovirus A, Human/physiology , Host-Pathogen Interactions , Immune Evasion , Interferon Type I/antagonists & inhibitors , Signal Transduction , Ubiquitination , Cell Line, Tumor , DEAD Box Protein 58/metabolism , Enterovirus A, Human/pathogenicity , Humans , Protein Processing, Post-Translational , Receptors, ImmunologicABSTRACT
Stellate ganglion blockade (SGB) protects patients from focal cerebral ischemic injury, and transection of the cervical sympathetic trunk (TCST) in a rat model can mimic SGB in humans. The purpose of this study was to investigate the mechanisms underlying the neuroprotective effects of TCST on neuronal damage in the hippocampus in a rat model of middle cerebral artery occlusion (MCAO) in an attempt to elucidate the neuroprotective effects of SGB. The modified method of Zea Longa was used to establish the permanent MCAO model. Male Wistar rats were randomly divided into three groups: sham-operated group, MCAO group, and TCST group. The animals in TCST group were sacrificed 48 h after TCST which was performed after the establishment of the MCAO model. Proteins were extracted from the ipsilateral hippocampus and analyzed by two-dimensional difference gel electrophoresis (2D-DIGE) and peptide mass fingerprinting (PMF). The levels of N-ethylmaleimide-sensitive factor (NSF) were measured as well. The results showed that 11 types of proteins were identified by 2D-DIGE. The expressions of eight proteins were changed both in the sham-operated and TCST groups, and the expressions of the other three proteins were changed in all three groups. Moreover, the expression of NSF was higher in the TCST group than in the MCAO group but lower in the MCAO group than in sham-operated group. The ratio of NSF expression between the MCAO group and shamoperated group was -1.37 (P<0.05), whereas that between the TCST group and MCAO group was 1.35 (P<0.05). Our results imply that TCST increases the expression of NSF in the hippocampus of adult rats with focal cerebral ischemia, which may contribute to the protection of the injured brain. Our study provides a theoretical basis for the therapeutic application of SGB to patients with permanent cerebral ischemia.
Subject(s)
Brain Injuries/metabolism , Brain Ischemia/metabolism , Gene Expression Regulation , N-Ethylmaleimide-Sensitive Proteins/biosynthesis , Stellate Ganglion/metabolism , Transfection , Animals , Brain Injuries/genetics , Brain Injuries/pathology , Brain Ischemia/genetics , Brain Ischemia/pathology , Hippocampus/metabolism , Hippocampus/pathology , Male , N-Ethylmaleimide-Sensitive Proteins/genetics , Rats , Rats, Wistar , Stellate Ganglion/pathologyABSTRACT
OBJECTIVE: To compare the incidence rates of postoperative urinary incontinence between transurethral bipolar plasmakinetic enucleation and resection of the prostate (PKERP) and transurethral bipolar plasmakinetic resection of the prostate (PKRP), and provide evidence for the clinical application of PKERP. METHODS: Totally, 180 BPH patients were equally and randomly assigned to undergo PKERP and PKRP, respectively. We measured the urinary incontinence of the patients by pad test at 24 hours after extubation and every week after surgery for 4 weeks. Meanwhile, we recorded and compared the PSA level, prostate volume, Qmax, residual urine, IPSS, QOL, and the results of pad test between the two groups before and after surgery. RESULTS: The incidence rates of urinary incontinence in the PKERP and PKRP groups were 35.56% and 18.89% (P < 0.01) at 24 hours after extubation, 20.00% and 7.78% at 1 week after surgery (P < 0.05), and 3.33% and 2.22% at 2 weeks. There was no significant difference in the severity of urinary incontinence between the two groups at any time point (P > 0.05). No permanent urinary incontinence was observed in either group. CONCLUSION: Compared with PKRP, PKERP has a higher incidence rate of short-term urinary incontinence in the treatment of BPH, but not that of genuine incontinence, with similar severity and recovery time.
Subject(s)
Postoperative Complications/epidemiology , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/adverse effects , Transurethral Resection of Prostate/methods , Urinary Incontinence/epidemiology , Aged , Humans , Incidence , Male , Single-Blind MethodABSTRACT
Artificial skins with functions such as sensing, variable stiffness, actuation, self-healing, display, adhesion, and camouflage have been developed and widely used, but artificial skins with escape function are still a research gap. In nature, every species of animal can use its innate skills and functions to escape capture. Inspired by the behavior of fish-scale geckoes escaping predation by shedding scales when grasped or touched, we propose a flexible escape skin by attaching artificial scales to a flexible film. Experiments demonstrate that the escape skin has significant effects in reducing escape force, escaping from harmful force environments, and resisting mechanical damage. Furthermore, we enabled active control of escape force and skin hardness by changing temperature, increasing the adaptability of the escape skin to the surrounding. Our study helps lay the foundation for engineering systems that depend on escape skin to improve robustness.
Subject(s)
Skin , Touch Perception , Animals , Mechanical Phenomena , Touch , HardnessABSTRACT
The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1-4 (L1-L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P < 0.05), and the probability of major osteoporotic fracture in the next 10 years (PMOF) was significantly higher than that in T2DM group (P < 0.001). However, with the prolongation of the course of T2DM, the BMD significantly decreased, while fracture risk and the prevalence of osteoporosis significantly increased (P < 0.05). We also found that the BMD of L1-4, LFN and LHJ were negatively correlated with homeostatic model assessment-insulin resistance (HOMA-IR) (P = 0.028, P = 0.01 and P = 0.047, respectively). The results also showed that the BMD of LHJ was positively correlated with indirect bilirubin (IBIL) (P = 0.018). Although the BMD was lower in the non-T2DM group than in the T2DM group, the prolongation of the course of T2DM associated with the lower BMD. And the higher prevalence of osteoporosis and fracture risk significantly associated with the prolongation of the course of T2DM. In addition, BMD was significantly associated with insulin resistance (IR) and bilirubin levels in T2DM patients.Registration number: China Clinical Trials Registry: MR-51-23-051741; https://www.medicalresearch.org.cn/search/research/researchView?id=c0e5f868-eca9-4c68-af58-d73460c34028 .
Subject(s)
Bone Density , Diabetes Mellitus, Type 2 , Postmenopause , Humans , Diabetes Mellitus, Type 2/complications , Female , Male , Aged , Middle Aged , Lumbar Vertebrae/diagnostic imaging , Osteoporosis/epidemiology , Osteoporosis/etiology , Femur Neck/diagnostic imaging , Risk Factors , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , PrevalenceABSTRACT
Background: The prognosis of initially unresectable hepatocellular carcinoma (iuHCC) has been improved by TACE with TKIs and PD-1 inhibitors (TTP). However, the role of timing of tumor progression and and early salvage surgery during TTP therapy remains unclear. Patients and Methods: The data of 151 patients who received TTP for iuHCC consecutively between November 2019 and December 2022 were retrospectively analyzed. The X-Tile software was used to determine the optimal threshold of progression timing to differentiate the post-progression survival (PPS) for patients with tumor progression, ultimately yielding 9 months as the optimal cut-off time. Early tumor progression was defined as patients with tumor recurrence (surgical patients) or progressive disease by mRECIST (nonsurgical patients) within 9 months of initial treatment. Accordingly, early salvage surgery was defined as salvage surgery performed within 9 months of the initial treatment. Results: Out of all the patients, 55 (36.4%) patients showed early tumor progression, 33 (34.4%) showed late tumor progression, and 63 (41.7%) showed non-progression. Patients who experienced early tumor progression had a median PPS of 5.2 months, while those with late tumor progression had a median PPS of 16.8 months (P < 0.001). Multivariable analysis revealed a robust independent correlation between early tumor progression and PPS (HR = 3.279, 95% CI: 1.591-6.756; P = 0.001). Patients who received early salvage surgery showed a considerably lower early tumor progression rate when compared with patients who did not receive early surgery (12.5% vs 42.9%, P = 0.002). The multivariable analysis revealed that early salvage surgery was an independent factor influencing early tumor progression (OR = 0.246; 95% CI: 0.078-0.773; P = 0.016). Conclusion: Early tumor progression is associated with worse PPS in patients with iuHCC receiving TTP therapy. Early salvage surgery can further improve patient outcomes by lowering the incidence of early progression.
ABSTRACT
Fully absorbable meshes can repair abdominal wall defects and effectively reduce the incidence of complications, but different types of fully absorbable meshes have different remodeling and regeneration effects. In order to investigate and compare the effects of different fully absorbable meshes on remodeling and regeneration in animals and reduce the biological risk of clinical translation, SYRCLE was adopted to evaluate the methodological quality of the included studies, and GRADE and ConQual were used to evaluate the quality of evidence. According to the inclusion and exclusion criteria, a total of 22 studies related to fully absorbable meshes were included in this systematic review. These results showed that fiber-based synthetic materials and fiber-based natural materials exhibited better restorative and regenerative effects indicated by infiltration and neovascularization, when compared with a porcine acellular dermal matrix. In addition, the human acellular dermal matrix was found to have a similar regenerative effect on the host extracellular matrix and scaffold degradation compared to the porcine acellular dermal matrix, porcine intestinal submucosa, and fiber-based natural materials, but it offered higher tensile strength than the other three. The quality of the evidence in this field was found to be poor. The reasons for downgrading were analyzed, and recommendations for future research included more rigor in study design, more transparency in result reporting, more standardization of animal models and follow-up time for better evaluation of the remodeling and regenerative performance of abdominal wall hernia repair meshes, and less biological risk in clinical translation.
Subject(s)
Abdominal Wall , Surgical Mesh , Animals , Abdominal Wall/surgery , Humans , Swine , Absorbable Implants , Regeneration , Acellular Dermis/metabolism , Tensile Strength , Wound Healing , Biocompatible Materials/therapeutic useABSTRACT
BACKGROUND: Conversion therapy for initially unresectable hepatocellular carcinoma (iuHCC) using lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus a PD-1 inhibitor (LTP) has achieved promising results. However, further comparative research is necessary to evaluate the effectiveness and safety of conversion surgery (CS) for iuHCC. METHODS: Data for 32 consecutive patients with iuHCC receiving CS and 419 consecutive patients with resectable HCC receiving initial surgery (IS) between November 2019 and September 2022 were collected retrospectively. After propensity score matching (PSM), 65 patients were selected. RESULTS: Before matching, the CS group had longer EFS (not reached vs. 12.9 months, P < 0.001) and similar OS (not reached vs. not reached, P = 0.510) compared with the IS group. Similar results for EFS (P = 0.001) and OS (P = 0.190) were obtained after matching. The multivariable Cox model (HR = 0.231, 95% CI: 0.105-0.504; P < 0.001) and subgroup analyses confirmed that CS could improve EFS. The CS group had significantly lower incidence of microvascular invasion (MVI) than the IS group (3.1% vs. 50.4%, P < 0.001). Moreover, the two groups had similar safety profiles. CONCLUSIONS: CS is effective and safe for patients with iuHCC receiving LTP. LTP has the potential to reduce risk factors for postoperative recurrence, especially MVI, which may influence surgical decision-making.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Phenylurea Compounds , Quinolines , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/therapy , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Male , Female , Chemoembolization, Therapeutic/methods , Middle Aged , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/administration & dosage , Retrospective Studies , Quinolines/therapeutic use , Quinolines/administration & dosage , Aged , Hepatectomy , Propensity Score , Immune Checkpoint Inhibitors/therapeutic use , Treatment OutcomeABSTRACT
Non-alcoholic steatohepatitis (NASH), an advanced form of non-alcoholic fatty liver disease (NAFLD), has emerged as the leading cause of liver failure and related death. Currently, no medication is specifically approved to treat NAFLD or NASH. Here we report that oral administration of honey vesicle-like nanoparticles (H-VLNs) to naturally aged mice protects the liver from NASH development. H-VLNs are dominantly taken up by Kupffer cells in the liver and suppress hepatic chronic inflammation and further development of fibrosis and nodule formation in aged mice. Besides their reported anti-inflammasome function, H-VLNs are found to inhibit the transcriptional activities of C-JUN and nuclear factor-kappa B (NF-κB). MicroRNAs miR5119 and miR5108 and phenolic compound luteolin in H-VLNs are identified in suppressing both the C-JUN and NF-κB pathways. Collectively, oral intake of H-VLNs represents a promising new user-friendly modality to prevent the development of NASH.
ABSTRACT
Purpose: To evaluate the outcomes and prognostic factors for patients using conversion therapy with lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus programmed cell death protein-1 (PD-1) inhibitors (LTP) for initially unresectable hepatocellular carcinoma (iuHCC). Methods: Data on 94 consecutive patients with iuHCC who received LTP conversion therapy from November 2019 to September 2022 were retrospectively analyzed. Early tumor response was reported when patients showed complete or partial response at the time of their first follow-up (4-6 weeks) after initial treatment, in accordance with mRECIST. The endpoints consisted of conversion surgery rate, overall survival (OS), and progression-free survival (PFS). Results: Early tumor response was found in 68 patients (72.3%) and not in the remaining 26 patients (27.7%) in the entire cohort. Early responders had a significantly higher conversion surgery rate than non-early responders (44.1% vs. 7.7%, p=0.001). Early tumor response was the only factor independently associated with successful conversion resection, as indicated by multivariate analysis (OR=10.296; 95% CI: 2.076-51.063; p=0.004). Survival analysis showed that early responders had longer PFS (15.4 vs. 7.8 months, p=0.005) and OS (23.1 vs. 12.5 months, p=0.004) than non-early responders. Early responders who underwent conversion surgery also had significantly longer median PFS and OS (not reached, not reached) than those who did not (11.2 months, p=0.004; 19.4 months, p<0.001). In multivariate analyses, early tumor response was identified as an independent prognostic factor for longer OS (HR=0.404, 95% CI: 0.171-0.954; p=0.039). Successful conversion surgery was also an independent predictive factor for longer PFS (HR=0.248, 95% CI: 0.099-0.622; p=0.003) and OS (HR=0.147, 95% CI: 0.039-0.554; p=0.005). Conclusions: Early tumor response is an important predictive marker for successful conversion surgery and prolonged survival in patients with iuHCC treated using LTP conversion therapy. Conversion surgery is necessary to improve survival during conversion therapy, particularly for early responders.
ABSTRACT
BACKGROUND: Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. AIM: To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS: PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS: This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. CONCLUSION: This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.
ABSTRACT
In this work, we propose a signal selection procedure for determination of hemoglobin (Hb) concentration in whole blood using near infrared (NIR) transmission spectral signals. A dataset of 190 whole blood NIR transmission spectra with reference Hb concentrations was used to evaluate the method. Spectral signals were selected based on the squared correlation coefficient (R(2)) between the signal and the Hb concentration. An improved uninformative variable elimination (UVE) procedure was performed to remove redundant signals from the primary selected signal set. A partial least squares (PLS) regression model was built with the final selected signals and the corresponding Hb concentrations. The results indicate that the proposed method is effective at increasing the predictive power of the NIR-PLS spectral model for determining Hb concentration in whole blood samples.
Subject(s)
Blood Chemical Analysis/statistics & numerical data , Hemoglobins/analysis , Spectroscopy, Near-Infrared/methods , Spectroscopy, Near-Infrared/statistics & numerical data , Humans , Least-Squares AnalysisABSTRACT
We report a case of inflammatory myofibroblastic tumor of the bladder (IMTB) that arises from left posterior bladder wall. The IMTB usually demonstrates slight hypointensity on T1WI, heterogeneous bright hyperintensity on T2WI, hyperintensity on DWI, and no restricted diffusion on ADC map. IMTB exhibits irregular ring enhancement and scatters stripe-like enhancement in central area with progressive and persistent enhancement pattern on CE-MRI. High-contrast multisequence MRI may be a potential technique to distinguish IMTB from other bladder tumors.
ABSTRACT
Despite the well-established role of CMTM6 in the stabilization of cell surface PD-L1 in cancer cells, the mechanisms underlying CMTM6 expression and regulation are still largely unknown. Here we unexpectedly find a strikingly positive correlation between CMTM6 and Hu-Antigen R (HuR) expression in most types of cancer. Mechanistically, we elucidate HuR stabilizes CMTM6 mRNA via direct association with AU-rich elements (AREs) in its 3'UTR and predominantly up-regulates CMTM6, which is readily abolished by HuR-specific inhibitor, MS-444. Phenotypically, we notice abundant cell surface PD-L1 in HuR-high cancer cells, which significantly inhibits immune activation of co-cultured T cells as indicated by IL-2 production. Treatment with MS-444 completely relieves immune suppression imposed by HuR-overexpression and further stimulates immune responses. Ectopic HuR accelerates allograft tumor progression in vivo, which is greatly compromised by simultaneous administration with MS-444. Our study uncovers a novel mechanism in control of CMTM6 and therefore PD-L1 expression, and suggests the potential of combining HuR inhibitor with PD-1/PD-L1 antibodies for cancer immunotherapy.