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1.
Adv Mater ; : e2407010, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39011780

ABSTRACT

Miniaturized polarimetric photodetectors based on anisotropic two-dimensional materials attract potential applications in ultra-compact polarimeters. However, these photodetectors are hindered by the small polarization ratio values and complicated artificial structures. Here, a novel polarization photodetector based on in-sublattice carrier transition in the CdSb2Se3Br2/WSe2 heterostructure, with a giant and reconfigurable PR value, is demonstrated. The unique periodic sublattice structure of CdSb2Se3Br2 features an in-sublattice carrier transition preferred along Sb2Se3 chains. Leveraging on the in-sublattice carrier transition in the CdSb2Se3Br2/WSe2 heterostructure, gate voltage has an anisotropic modulation effect on the band alignment of heterostructure along sublattice. Consequently, the heterostructure exhibits a polarization-tunable photo-induced threshold voltage shift, which provides reconfigurable PR values from positive (unipolar regime) to negative (bipolar regime), covering all possible numbers (1→+∞/-∞→-1). Using this anisotropic photovoltaic effect, gate-tunable polarimetric imaging is successfully implemented. This work provides a new platform for developing next-generation highly polarimetric optoelectronics.

2.
Blood Adv ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38865708

ABSTRACT

The identification and targeting of B cell maturation antigen (BCMA) through immunotherapeutic strategies such as antibody-drug conjugates (ADC), chimeric antigen receptor T-cells (CAR T-cells), and T-cell engagers (TCE) have revolutionized the care of patients with multiple myeloma (MM). These treatment modalities have improved survival outcomes of relapsed and/or refractory (R/R) MM patients compared to previously established strategies and are moving into earlier lines of therapy (LOT). Despite their efficacy, the majority of patients eventually relapse, necessitating additional therapeutic targets for salvage. G-protein-coupled receptor class 5 member D (GPRC5D), Fc receptor-homolog 5 (FcRH5), and SLAMF7 are some examples of novel targets in development. This expanding armamentarium of immunotherapeutic agents will be crucial to address the unmet need for relapses following BCMA-targeting therapies, particularly antigen-negative relapses. The utilization of sequential T-cell redirective therapies including agents targeting different tumor-associated antigens and combination therapies appears feasible paves the way for effective chemotherapy-free regimes. Deliberate consideration of treatment timing, preserving T-cell health, overcoming antigenic loss, and comprehension of the complex tumor microenvironment would be key to maximizing therapeutic benefits and minimizing adverse effects. This review summarizes novel targets in development for myeloma beyond BCMA, presenting pivotal safety and efficacy data derived from clinical trials where available and the considerations vital for navigating this expanding landscape of immunotherapeutic options.

3.
Nat Commun ; 15(1): 4368, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778090

ABSTRACT

Two-dimensional (2D) AMX2 compounds are a family of mixed ionic and electronic conductors (where A is a monovalent metal ion, M is a trivalent metal, and X is a chalcogen) that offer a fascinating platform to explore intrinsic coupled ionic-electronic properties. However, the synthesis of 2D AMX2 compounds remains challenging due to their multielement characteristics and various by-products. Here, we report a separated-precursor-supply chemical vapor deposition strategy to manipulate the chemical reactions and evaporation of precursors, facilitating the successful fabrication of 20 types of 2D AMX2 flakes. Notably, a 10.4 nm-thick AgCrS2 flake shows superionic behavior at room temperature, with an ionic conductivity of 192.8 mS/cm. Room temperature ferroelectricity and reconfigurable positive/negative photovoltaic currents have been observed in CuScS2 flakes. This study not only provides an effective approach for the synthesis of multielement 2D materials with unique properties, but also lays the foundation for the exploration of 2D AMX2 compounds in electronic, optoelectronic, and neuromorphic devices.

4.
Eur J Haematol ; 112(2): 144-152, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36987995

ABSTRACT

Although chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in patients with chemo-refractory B-cell lymphoma, a significant portion is refractory or relapse. Resistance is a major barrier to improving treatment efficacy and long-term survival in CAR T-cell therapy, and clinicians have very limited tools to discriminate a priori patients who will or will not respond to treatment. While CD19-negative relapses due to loss of target antigen is well described, it accounts for only about 30% of cases with treatment failure. Recent efforts have shed light on mechanisms of CD19-positive relapse due to tumor intrinsic resistance, T-cell quality/manufacturing, or CAR T-cell exhaustion mediated by hostile tumor microenvironment. Here, we review the latest updates of preclinical and clinical trials to investigate the mechanisms of resistance and relapse post CAR T-cell therapy in B cell lymphoma and discuss novel treatment strategies to overcome resistance as well as advances that are useful for a CAR T therapist to optimize and personalize CAR T-cell therapy.


Subject(s)
Lymphoma, B-Cell , Receptors, Chimeric Antigen , Humans , Immunotherapy, Adoptive/adverse effects , Receptors, Chimeric Antigen/genetics , Receptors, Antigen, T-Cell/genetics , Antigens, CD19 , Lymphoma, B-Cell/therapy , Recurrence , Cell- and Tissue-Based Therapy , Tumor Microenvironment
5.
JCO Oncol Pract ; 19(12): 1168-1178, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37844267

ABSTRACT

PURPOSE: Treatment options for myeloma and indolent lymphoma are increasing exponentially, with distinct efficacy, side effects, and cost. We aim to determine the factors influencing patient and caregiver treatment preferences. METHODS: Patients and caregivers of patients with myeloma and indolent lymphoma were recruited from two cancer centers in Singapore. Preferences were elicited using a discrete choice experiment. Attributes and levels were selected based on a previous qualitative study. The relative preference for levels within each attribute (part worth utility values) and the extent to which an attribute would influence decision making (relative importance) were calculated. Patient and caregiver participation in the treatment plan selection process were assessed using the Control Preference Scale. RESULTS: One hundred ninety-nine patients and 169 caregivers were recruited. Patients placed the highest importance on out-of-pocket costs (relative importance = 35%), followed by efficacy (25%), persistent side effects (19%), administration route (8%), treatment duration (7%), and short-term side effects (5%). Caregivers ranked efficacy (27%) as the most important attribute, over out-of-pocket costs (24%). Most patients preferred a collaborative role in the shared decision-making process, while similar proportions of caregivers favored active and collaborative roles. CONCLUSION: Our study demonstrates that both patients and caregivers consider cost seriously when making treatment decisions. Furthermore, as patient and caregiver preferences may differ, there are implications for treatment selection and counseling, especially in cultures where caregivers have more prominent roles in treatment planning.


Subject(s)
Lymphoma , Multiple Myeloma , Humans , Multiple Myeloma/therapy , Caregivers/psychology , Health Expenditures , Lymphoma/therapy , Singapore
6.
Curr Hematol Malig Rep ; 18(5): 190-200, 2023 10.
Article in English | MEDLINE | ID: mdl-37400631

ABSTRACT

PURPOSE OF REVIEW: The development of potent novel agents has improved outcomes for patients with multiple myeloma (MM). Heterogeneity of response to therapy, an expanding arsenal of treatment options, and cost are however major challenges for physicians making treatment decisions. Response-adapted therapy is hence an attractive strategy for sequencing of therapy in MM. Despite its successful application in other haematologic malignancies, response-adapted therapy is yet to become a standard of care for MM. We provide our perspective on response-adapted therapeutic strategies evaluated thus far and how they may be implemented and improved on in treatment algorithms of the future. RECENT FINDINGS: While older studies suggested that early response based on International Myeloma Working Group response criteria could impact long-term outcomes, recent data have contradicted these findings. The advent of minimal residual disease (MRD) as a powerful prognostic factor in MM has raised the promise of MRD-adapted treatment strategies. The development of more sensitive techniques for paraprotein quantification as well as imaging modalities to detect extramedullary disease is likely to change response assessment in MM. These techniques combined with MRD assessment may provide sensitive and holistic response assessments which could be evaluated in clinical trials. Response-adapted treatment algorithms have the potential to allow an individualised treatment strategy, maximising efficacy, while minimising toxicities and cost. Standardisation of MRD methodology, incorporation of imaging into response assessment, and the optimal management of MRD positive patients are key questions to be addressed in future trials.


Subject(s)
Hematologic Neoplasms , Multiple Myeloma , Humans , Multiple Myeloma/therapy , Multiple Myeloma/drug therapy , Disease-Free Survival , Neoplasm, Residual/diagnosis
8.
J Am Chem Soc ; 145(18): 10355-10363, 2023 May 10.
Article in English | MEDLINE | ID: mdl-37104621

ABSTRACT

Owing to the inherent instability caused by the low Cu(I)/Cu(0) half-cell reduction potential, Cu(0)-containing copper nanoclusters are quite uncommon in comparison to their Ag and Au congeners. Here, a novel eight-electron superatomic copper nanocluster [Cu31(4-MeO-PhC≡C)21(dppe)3](ClO4)2 (Cu31, dppe = 1,2-bis(diphenylphosphino)ethane) is presented with total structural characterization. The structural determination reveals that Cu31 features an inherent chiral metal core arising from the helical arrangement of two sets of three Cu2 units encircling the icosahedral Cu13 core, which is further shielded by 4-MeO-PhC≡C- and dppe ligands. Cu31 is the first copper nanocluster carrying eight free electrons, which is further corroborated by electrospray ionization mass spectrometry, X-ray photoelectron spectroscopy and density functional theory calculations. Interestingly, Cu31 demonstrates the first near-infrared (750-950 nm, NIR-I) window absorption and the second near-infrared (1000-1700 nm, NIR-II) window emission, which is exceptional in the copper nanocluster family and endows it with great potential in biological applications. Of note, the 4-methoxy groups providing close contacts with neighboring clusters are crucial for the cluster formation and crystallization, while 2-methoxyphenylacetylene leads only to copper hydride clusters, Cu6H or Cu32H14. This research not only showcases a new member of copper superatoms but also exemplifies that copper nanoclusters, which are nonluminous in the visible range may emit luminescence in the deep NIR region.

10.
Horm Metab Res ; 55(2): 142-148, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36630972

ABSTRACT

Diabetic retinopathy is one of the common microvascular complications of diabetes, and it is the main cause of vision loss among working-age people. This study interpreted the roles of miR-99a-5p in DR patients and human retinal microvascular endothelial cell (hRMECs) injury induced by high glucose. The expression of miR-99a-5p was detected in patients with NDR, NPDR, and PDR. The indictive impacts of miR-99a-5p were tested by the ROC curve, and the link between miR-99a-5p and clinical information was verified by the Pearson test. HG was used to instruct cell models. The CCK-8 and transwell methods were performed to detect the proliferative and migrated cells. The targeted relationship was explained by luciferase activity. The content of miR-99a-5p was gradually lessened in NPDR and PDR patients. MiR-99a-5p might differentiate DR patients from NDR patients and PDR patients from NPDR patients. The interconnection between miR-99a-5p and clinical factors was endorsed in all DR patients. Overexpression of miR-99a-5p assuaged the abnormality of cell migration and proliferation of hRMECs triggered by HG. NOX4 was a downstream signaling component of miR-99a-5p. In conclusion, MiR-99a-5p protected hRMECs against HG damage, and the miR-99a-5p might be a novel target for diagnosis of DR.


Subject(s)
Diabetic Retinopathy , MicroRNAs , Retinal Diseases , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Endothelial Cells/metabolism , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Signal Transduction , Cell Proliferation/genetics , NADPH Oxidase 4/genetics , NADPH Oxidase 4/metabolism
11.
Transpl Infect Dis ; 25(3): e14024, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36715661

ABSTRACT

INTRODUCTION: A high incidence of mortality and severe COVID-19 infection was reported in hematopoietic stem cell transplant (HSCT) recipients during the early phases of the COVID-19 pandemic; however, outcomes with subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as the omicron variant, have yet to be reported. Additionally, rollout of COVID-19 vaccinations in subsequent pandemic waves may modify COVID-19 disease severity and mortality in this immunocompromised population. We describe COVID-19 outcomes among a highly vaccinated population of HSCT recipients at a single center during successive waves of community transmission arising from the SARS-CoV-2 delta and omicron variants. METHODS: We retrospectively reviewed medical records of all HSCT recipients at our institution who tested positive for SARS-CoV-2 from May 2021 to May 2022. Descriptive statistics were reported; the chi-square test was utilized to identify factors associated with 90-day all-cause mortality and severity of COVID-19 infection. RESULTS: Over the 1-year study period, 77 HSCT recipients at our center contracted COVID-19 (43 allogenic; 34 autologous). Twenty-six (33.8%) patients were infected with the SARS-CoV-2 delta variant, while 51 (66.2%) had the SARS-CoV-2 omicron variant. Thirty-nine (50.6%) patients required hospitalization. More than 80% had received prior COVID-19 vaccination (57.1% with two doses, 27.3% with three doses). The majority (90.9%) had mild disease; only one (1.3%) patient required mechanical ventilation. Active hematological disease at time of COVID-19 infection was associated with increased odds of mortality [odds ratio (OR) = 6.90, 95% confidence interval (CI) = 1.20-40]. The 90-day all-cause mortality was 7.8% (six patients). Infection with the omicron variant (vs. delta) was associated with less severe illness (OR = 0.05, 95% CI = 0.01-0.47) and decreased odds of mortality (OR = 0.08, 95% CI = 0.01-0.76). Being on immunosuppression (OR = 5.10, 95% CI = 1.10-23.60) and being unvaccinated at disease onset (OR = 14.76, 95% CI = 2.89-75.4) were associated with greater severity of COVID-19 infection. CONCLUSION: We observed favorable outcomes with COVID-19 infection in a cohort of vaccinated HSCT patients. The SARS-CoV-2 omicron variant was associated with both less severe illness and decreased odds of mortality. As COVID-19 moves toward endemicity, early access to treatment and encouraging vaccination uptake is crucial in mitigating the challenge of COVID-19 management among HSCT recipients. Surveillance and assessment of clinical outcomes with new SARS-CoV-2 variants also remains important in this immunocompromised population.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , COVID-19 Vaccines , Pandemics , Retrospective Studies , Transplant Recipients , Hematopoietic Stem Cell Transplantation/adverse effects
12.
J Adv Res ; 50: 55-68, 2023 08.
Article in English | MEDLINE | ID: mdl-36243399

ABSTRACT

INTRODUCTION: Serum amyloid P component (SAP) regulates the innate immune system and microbial diseases. Periodontitis is an inflammatory oral disease developed by the host immune system's interaction with the dysbiotic oral microbiome, thereby SAP could play a role in periodontitis pathogenicity. OBJECTIVES: To investigate the role of SAP in oral microbiome modulation and peridontitis pathogenicity. METHODS: In this study, wildtype and SAP-knockout (KO) mice were used. Ligature-based periodontitis was developed in mice. Oral microbiome diversity was analyzed by 16 s rRNA sequencing. Macrophages and Porphyromonas gingivalis (P. gingivalis) co-culture system analyzed the effect of SAP in macrophage phagocytosis of P. gingivalis. RESULTS: The level of SAP was upregulated in the periodontitis-affected periodontium of humans and mice but not in the liver and blood circulation. Periodontal macrophages were the key source of upregulated SAP in periodontitis. SAP-KO aggravated periodontal inflammation, periodontitis, and a higher number of M1-type inflammatory macrophage infiltration in the periodontium. The oral microbiome of SAP-KO periodontitis mice was altered with a higher abundance of Porphyromonas at the genus level. SAP-KO macrophages showed compromised phagocytosis of P. gingivalis in the co-culture system. Co-culture of SAP-KO macrophages and P. gingivalis induced the C5a expression and exogenous SAP treatment nullified this effect. Exogenous recombinant SAP treatment did not affect P. gingivalis growth and opsonization. PMX205, an antagonist of C5a, treatment robustly enhanced P. gingivalis phagocytosis by SAP-KO macrophages, indicating the involvement of the C5a-C5aR signaling in the compromised P. gingivalis phagocytosis by SAP-KO macrophages. CONCLUSION: SAP deficiency aggravates periodontitis possibly via C5a-C5aR signaling-mediated defective macrophage phagocytosis of P. gingivalis. A higher abundance of P. gingivalis during SAP deficiency could promote M1 macrophage polarization and periodontitis. This finding suggests the possible protecting role of elevated levels of periodontal SAP against periodontitis progression.


Subject(s)
Periodontitis , Porphyromonas gingivalis , Animals , Humans , Mice , Macrophages/metabolism , Mice, Knockout , Periodontitis/metabolism , Phagocytosis , Porphyromonas gingivalis/physiology , Signal Transduction , Serum Amyloid P-Component/metabolism
13.
Ann Acad Med Singap ; 52(11): 601-624, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38920149

ABSTRACT

AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical suspicion to detect unexplained manifestations in the appropriate clinical setting. Early detection and treatment are crucial as the degree of cardiac involvement emerges as a primary prognostic predictor of survival in a patient with AL amyloidosis. Following the diagnosis of AL amyloidosis with appropriate tissue biopsies, prompt treatment with a bortezomib, cyclophosphamide and dexamethasone-based first-line induction with or without daratumumab should be initiated. The goal of treatment is to achieve the best haematologic response possible, ideally with involved free light chain <20 mg/L, as it offers the best chance of organ function improvement. Treatment should be changed if patients do not achieve a partial response within 2 cycles of treatment or very good partial response after 4 cycles or after autologous stem cell transplant, as achievement of profound and prolonged clonal responses translates to better organ response and long-term outcomes. Early involvement of multidisciplinary subspecialists such as renal physicians, cardiologists, neurologists, and gastroenterologists for optimal maintenance and support of involved organs is recommended for optimal management of patients with AL amyloidosis.


Subject(s)
Dexamethasone , Immunoglobulin Light-chain Amyloidosis , Humans , Immunoglobulin Light-chain Amyloidosis/diagnosis , Immunoglobulin Light-chain Amyloidosis/therapy , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Singapore , Bortezomib/therapeutic use , Bortezomib/administration & dosage , Cyclophosphamide/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Consensus , Antibodies, Monoclonal/therapeutic use , Hematopoietic Stem Cell Transplantation , Stem Cell Transplantation
14.
BMC Ophthalmol ; 22(1): 450, 2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36418980

ABSTRACT

BACKGROUND: This study was to assess the diagnostic value of PCED1B-AS1 for proliferative diabetic retinopathy (PDR) and investigate the involvement of PCED1B-AS1 in PDR. METHODS: The vitreous and blood specimens from 37 subjects with PDR and 21 non-diabetics were examined by reverse transcription quantitative PCR to determine the PCED1B-AS1 level. The two groups were age- and gender-matched. Receiver operating characteristic (ROC) curves were plotted to visually illustrate the diagnostic ability of PCED1B-AS1. Human retinal Müller glial cells were studied by ELISA. Proliferation and migration of human retinal microvascular endothelial cells (HRMECs) were assessed in vitro. RESULTS: Significant increases of PCED1B-AS1 levels were observed in the vitreous samples and CD34 + VEGFR-2 + cells from blood samples of diabetic subjects with PDR, compared with those of non-diabetics. The ROC curve based on the vitreous PCED1B-AS1 levels revealed an AUC of 0.812, while the ROC curve based on the PCED1B-AS1 levels in CD34 + VEGFR-2 + cells from blood samples revealed an AUC of 0.870. In Müller cell cultures, PCED1B-AS1 siRNA significantly attenuated VEGF and MCP-1 upregulation which were induced by CoCl2 and TNF-α. Additionally, PCED1B-AS1 siRNA attenuated VEGF-induced proliferation and migration in HRMECs. CONCLUSION: This study revealed the potential of PCED1B-AS1 as a diagnostic biomarker for PDR. In vitro data point to the anti-angiogenic and anti-proliferation effects of PCED1B-AS1.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnosis , Up-Regulation , Vascular Endothelial Growth Factor Receptor-2 , Vascular Endothelial Growth Factor A/metabolism , Vitreous Body/metabolism , Endothelial Cells/metabolism , RNA, Small Interfering
15.
Adv Mater ; 34(39): e2206122, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35953088

ABSTRACT

2D transition metal dichalcogenides (TMDs) are promising candidates for realizing ultrathin and high-performance photovoltaic devices. However, the external quantum efficiency (EQE) and power conversion efficiency (PCE) of most 2D photovoltaic devices face great challenges in exceeding 50% and 3%, respectively, due to the low efficiency of photocarrier separation and collection. Here, this study demonstrates photovoltaic devices with defect-free interface and recombination-free channel based on 2D WS2 , showing high EQE of 92% approaching the theoretical limit and high PCE of 5.0%. The high performances are attributed to the van der Waals metal contact without interface defects and Fermi-level pinning, and the fully depleted channel without photocarrier recombination, leading to intrinsic photocarrier separation and collection with high efficiency. Furthermore, this study demonstrates that the strategy can be extended to other TMDs such as MoSe2 and WSe2 with EQE of 92% and 94%, respectively. This work proposes a universal strategy for building high-performance 2D photovoltaic devices. The nearly ideal EQE provides great potential for PCE approaching the Shockley-Queisser limit.

16.
Int J Mol Sci ; 23(13)2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35805933

ABSTRACT

Chimeric antigen receptor (CAR) T cell therapy has ushered in a new era in cancer treatment. Remarkable outcomes have been demonstrated in patients with previously untreatable relapsed/refractory hematological malignancies. However, optimizing efficacy and reducing the risk of toxicities have posed major challenges, limiting the success of this therapy. The tumor microenvironment (TME) plays an important role in CAR T cell therapy's effectiveness and the risk of toxicities. Increasing research studies have also identified various biomarkers that can predict its effectiveness and risk of toxicities. In this review, we discuss the various aspects of the TME and biomarkers that have been implicated thus far and discuss the role of creating scoring systems that can aid in further refining clinical applications of CAR T cell therapy and establishing a safe and efficacious personalised medicine for individuals.


Subject(s)
Hematologic Neoplasms , Neoplasms , Receptors, Chimeric Antigen , Biomarkers , Hematologic Neoplasms/etiology , Hematologic Neoplasms/therapy , Humans , Immunotherapy, Adoptive/adverse effects , Neoplasm Recurrence, Local/etiology , Neoplasms/pathology , Receptors, Chimeric Antigen/genetics , Tumor Microenvironment
17.
Horm Metab Res ; 54(2): 119-125, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35130573

ABSTRACT

This paper aims to discuss the possibility of lncRNA PVT1 as a diagnostic biomarker for diabetic retinopathy (DR) and explore the underlying mechanism. Real-time quantitative polymerase chain reaction (RT-qPCR) was selected to determine the expression level of lncRNA PVT1 in the serum of all subjects. The receiver operating characteristic (ROC) curve reflected the diagnostic significance of PVT1 for DR patients. The Cell Counting Kit-8 (CCK-8) and Transwell assays were used to evaluate the effect of PVT1 expression on the proliferation and migration of human retinal microvascular endothelial cells (HRMECs). The luciferase reporter gene was selected to verify the interaction between PVT1 and miR-128-3p. The relative expression level of PVT1 in serum was higher in both the DB and DR group than in the healthy controls group (HC), and it was highest in the DR group. ROC curve indicated that serum PVT1 could distinguish between HC and DB patients, DB patients and DR patients, respectively. In vitro, high glucose induction significantly increased the proliferation and migration capabilities of HRMECs, but silencing PVT1 (si-PVT1) downregulated the proliferation and migration capabilities of HRMECs. The detection of luciferase reporter gene showed that lncRNA PVT1 targeted miR-128-3p, and there was a negative correlation in the serum of DR patients. In conclusion, this study confirmed that lncRNA PVT1 might regulate the process of DR by targeting miR-128-3p, and has the potential as a biomarker for the diagnosis of DR.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Apoptosis , Cell Proliferation/genetics , Endothelial Cells/metabolism , Glucose/metabolism , Glucose/pharmacology , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Signal Transduction/genetics
19.
Blood Cancer J ; 11(8): 143, 2021 08 12.
Article in English | MEDLINE | ID: mdl-34385415

ABSTRACT

The role of central nervous system (CNS) prophylaxis with high-dose methotrexate (HDMTX) in DLBCL is controversial. In this retrospective study, we evaluated the efficacy of prophylactic HDMTX on isolated CNS relapse, concomitant CNS and systemic relapse, systemic relapse, and survival outcomes in 226 patients with newly diagnosed DLBCL and high-risk CNS International Prognostic Index (CNS-IPI) score treated with RCHOP. The three-year risk of isolated CNS relapse was significantly lower in patients who received HDMTX, at 3.1% compared to 14.6% (P = 0.032) in those who did not. However, neither concomitant CNS-systemic relapse rates, systemic relapse rates, nor three-year PFS and OS were significantly different between treatment groups in multivariable analysis. Among propensity score-matched patients (N = 102), HDMTX was also associated with significantly lower isolated CNS relapse rates (HR 0.06, 95% CI 0.004-0.946, P = 0.046). HDMTX was well tolerated with manageable toxicities when given at a dose of 3 g/m2 by day 3 of RCHOP chemotherapy. Using propensity score matching and multivariable regression to yield treatment groups with well-balanced covariates, we showed that prophylactic HDMTX improved isolated CNS relapse rates but did not decrease concomitant CNS-systemic relapse rates, systemic relapse rates, or improve survival outcomes.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Central Nervous System Neoplasms/prevention & control , Central Nervous System Neoplasms/secondary , Lymphoma, Large B-Cell, Diffuse/prevention & control , Methotrexate/therapeutic use , Neoplasm Recurrence, Local/prevention & control , Aged , Antimetabolites, Antineoplastic/administration & dosage , Female , Humans , Male , Methotrexate/administration & dosage , Middle Aged , Retrospective Studies
20.
Adv Ther ; 38(6): 3342-3361, 2021 06.
Article in English | MEDLINE | ID: mdl-34014550

ABSTRACT

INTRODUCTION: NOP58 ribonucleoprotein, a core component of box C/D small nucleolar ribonucleoproteins, is involved in various cell physiological processes. However, its role in hepatocellular carcinoma (HCC) remains very unclear. We aim to investigate NOP58 expression and its probable prognostic value in patients with HCC based on The Cancer Genome Atlas (TCGA) database. METHODS: RNA sequencing data and clinicopathological characteristics of patients with HCC were collected from TCGA database. Expression of NOP58 in HCC tissues and normal tissues was analyzed by Wilcoxon rank-sum test. Patients were divided into high and low subgroups according to median expression of NOP58. Logistic regression, gene set enrichment analysis (GSEA), and single-sample gene set enrichment analysis (ssGSEA) were conducted to annotate biological function and immune infiltration of NOP58. RESULTS: NOP58 was significantly overexpressed in HCC tissues and correlated with significantly high tumor stage [odds ratio (OR) 10.01, 95% confidence interval (CI) 10.01-10.03; P = 0.003], advanced pathologic stage (OR 10.02, 95% CI 10.01-10.03; P < 0.001), advanced histologic stage (OR 10.03, 95% CI 10.02-10.04; P < 0.001), vascular invasion (OR 10.02, 95% CI 10.01-10.03; P = 0.003), poor performance status (OR 10.01, 95% CI 10.01-10.03; P = 0.003), and Mut-TP53 status (OR 10.02, 95% CI 10.01-10.03; P < 0.001). Elevated NOP58 expression had poor disease-specific survival (DSS; P < 0.001), progression-free interval (P = 0.006), and overall survival (OS; P < 0.001). NOP58 expression was independently correlated with OS (HR 1.731, 95% CI 10.037-2.890; P = 0.036). GSEA demonstrated that various cell cycle pathways along with RB-1 pathway, interleukin-10 signaling, regulation of TP53 activity, and P53 downstream pathway were differentially enriched in NOP58 high expression phenotype. NOP58 expression was positively correlated with infiltrating the levels of T helper type 2 (Th2) cells. CONCLUSIONS: Overexpression of NOP58 is negatively correlated with overall survival in patients with HCC and might be a potential biomarker for prognosis of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Data Analysis , Humans , Liver Neoplasms/genetics , Nuclear Proteins , Prognosis , Ribonucleoproteins, Small Nucleolar
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