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1.
Nature ; 560(7718): 382-386, 2018 08.
Article in English | MEDLINE | ID: mdl-30089911

ABSTRACT

Tumour cells evade immune surveillance by upregulating the surface expression of programmed death-ligand 1 (PD-L1), which interacts with programmed death-1 (PD-1) receptor on T cells to elicit the immune checkpoint response1,2. Anti-PD-1 antibodies have shown remarkable promise in treating tumours, including metastatic melanoma2-4. However, the patient response rate is low4,5. A better understanding of PD-L1-mediated immune evasion is needed to predict patient response and improve treatment efficacy. Here we report that metastatic melanomas release extracellular vesicles, mostly in the form of exosomes, that carry PD-L1 on their surface. Stimulation with interferon-γ (IFN-γ) increases the amount of PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumour growth. In patients with metastatic melanoma, the level of circulating exosomal PD-L1 positively correlates with that of IFN-γ, and varies during the course of anti-PD-1 therapy. The magnitudes of the increase in circulating exosomal PD-L1 during early stages of treatment, as an indicator of the adaptive response of the tumour cells to T cell reinvigoration, stratifies clinical responders from non-responders. Our study unveils a mechanism by which tumour cells systemically suppress the immune system, and provides a rationale for the application of exosomal PD-L1 as a predictor for anti-PD-1 therapy.


Subject(s)
B7-H1 Antigen/immunology , Exosomes/metabolism , Immune Tolerance/immunology , Melanoma/immunology , Programmed Cell Death 1 Receptor/immunology , Tumor Escape/immunology , Animals , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/pharmacology , Antineoplastic Agents, Immunological/therapeutic use , B7-H1 Antigen/blood , B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Case-Control Studies , Cell Line, Tumor , Disease Progression , Female , Humans , Immune Tolerance/drug effects , Interferon-gamma/blood , Interferon-gamma/immunology , Melanoma/drug therapy , Melanoma/pathology , Mice , Mice, Nude , Neoplasm Metastasis , Prognosis , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Tumor Escape/drug effects , Xenograft Model Antitumor Assays
2.
World J Surg ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955808

ABSTRACT

BACKGROUND: The superiority between remimazolam and propofol for anesthesia is controversial in elderly patients (≥60 years). This meta-analysis aimed to systematically compare anesthetic effect and safety profile between remimazolam and propofol in elderly patients under any surgery. METHODS: Cochrane Library, Web of Science, and PubMed were searched until December 25, 2023 for relevant randomized controlled trials. RESULTS: Ten studies with 806 patients receiving remimazolam (experimental group) and 813 patients receiving propofol (control group) were included. Time to loss of consciousness [standard mean difference (SMD) (95% confidence interval (CI): 1.347 (-0.362, 3.055), p = 0.122] and recovery time [SMD (95% CI): -0.022 (-0.300, 0.257), p = 0.879] were similar between experimental and control groups. Mean arterial pressure at baseline minus 1 min after induction [SMD (95% CI): -1.800 (-3.250, -0.349), p = 0.015], heart rate at baseline minus 1 min after induction [SMD (95% CI): -1.041 (-1.537, -0.545), p < 0.001], incidences of hypoxemia [relative risk (RR) (95% CI): 0.247 (0.138, 0.444), p < 0.001], respiratory depression [RR (95% CI): 0.458 (0.300, 0.700), p < 0.001], bradycardia [RR (95% CI): 0.409 (0.176, 0.954), p = 0.043], hypotension [RR (95% CI): 0.415 (0.241, 0.714), p = 0.007], and injection pain [RR (95% CI): 0.172 (0.113, 0.263), p < 0.001] were lower in the experimental group compared to the control group. Postoperative nausea and vomiting was not different between groups [RR (95% CI): 1.194 (0.829, 1.718), p = 0.341]. Moreover, this meta-analysis displayed a low risk of bias, minimal publication bias, and good robustness. CONCLUSION: Remimazolam shows comparative anesthetic effect and better safety profile than propofol in elderly patients under any surgery.

3.
AAPS PharmSciTech ; 25(5): 135, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862657

ABSTRACT

Lutein (Lut) is a recognized nutritional supplement known for its antioxidative and anti-inflammatory properties, crucial in mitigating ocular disease. However, enhancements to Lut stability and solubility remain challenges to be addressed in the healthcare industry. Herein, we fabricated and evaluated a food-grade highly porous ß-cyclodextrin metal-organic framework (ß-CD-MOF) for its ability to encapsulate Lut. Lut stability considerably improved when loaded into ß-CD-MOF to form a Lut@ß-CD-MOF complex, which exhibited better stability than Lut loaded into the γ-cyclodextrin metal-organic framework (Lut@γ-CD-MOF), Lut@ß-CD, and commercial product (Blackmores™) at 40°C, 60°C, and 70°C, respectively. The solubility of Lut@ß-CD-MOF in water increased by 26.8-fold compared to raw Lut at 37°C. Lut@ß-CD-MOF exhibited greater hydrophilicity, as determined by measuring the water contact angle. Molecular docking and other characterizations of Fourier transform infrared spectroscopy and powder X-ray diffraction confirmed that Lut was successfully encapsulated in the chamber formed by the three cyclodextrins in ß-CD-MOF. Thermogravimetric analysis and Raman spectroscopy demonstrated that Lut distributed in the ß-CD-MOF cavity deeply improved Lut stability and solubility. In conclusion, our findings underscored the function of ß-CD-MOF in enhancing Lut stability and solubility for formulation applications.


Subject(s)
Lutein , Metal-Organic Frameworks , Solubility , beta-Cyclodextrins , Metal-Organic Frameworks/chemistry , beta-Cyclodextrins/chemistry , Lutein/chemistry , Drug Stability , X-Ray Diffraction/methods , Molecular Docking Simulation/methods , Spectroscopy, Fourier Transform Infrared/methods , Hydrophobic and Hydrophilic Interactions , Porosity
4.
Dermatol Ther ; 33(4): e13310, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32170800

ABSTRACT

Health professions preventing and controlling Coronavirus Disease 2019 are prone to skin and mucous membrane injury, which may cause acute and chronic dermatitis, secondary infection and aggravation of underlying skin diseases. This is a consensus of Chinese experts on protective measures and advice on hand-cleaning- and medical-glove-related hand protection, mask- and goggles-related face protection, UV-related protection, eye protection, nasal and oral mucosa protection, outer ear, and hair protection. It is necessary to strictly follow standards of wearing protective equipment and specification of sterilizing and cleaning. Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.


Subject(s)
Coronavirus Infections/therapy , Health Personnel , Mucous Membrane/pathology , Occupational Diseases/prevention & control , Pneumonia, Viral/therapy , Skin/pathology , COVID-19 , China , Consensus , Emollients/administration & dosage , Gloves, Protective , Hand Disinfection/methods , Humans , Masks , Pandemics , Personal Protective Equipment
5.
Lasers Surg Med ; 51(3): 268-277, 2019 03.
Article in English | MEDLINE | ID: mdl-30592537

ABSTRACT

OBJECTIVES: Although transdermal drug delivery system (TDDS) has been successfully used for delivering small molecules, its application in the delivery of diagnostic antibodies has been limited due to their large size. In this study, we aim to obtain a broad insight in the dynamics of TRITC-conjugated Goat Anti-Mouse IgG (T-IgG) uptake in fractional Er:YAG laser pretreated skin and provide a new technical option for detecting lupus erythematosus (LE) in mice. METHODS: The skins of SD and MRL/lpr mice were treated by fractional Er:YAG laser followed by external application of T-IgG. The classic Franz diffusion method was used to observe the effects of different fractional fluences, densities and antibody concentrations on transdermal delivery of T-IgG at different time points (2, 4, 6, 8, 20, and 24 hours). Frozen tissue sections and confocal microscopy were used to observe the distribution of T-IgG on the sagittal and coronal planes of murine skin. RESULTS: Increased laser fluence (12.5 J/cm2 to 37.5 J/cm2 ) within 24 hours resulted in the obvious increase in transdermal amounts of T-IgG during the early stage (before 8 hours). However, increasing laser density (100 pores/cm2 to 200 pores/cm2 ) produced a significant increase in T-IgG permeation during the late stage (20 and 24 hours). Unlike fluence and density, increase in T-IgG loading concentration (0.5 to 2 µg/µl) led to continuous increase in the whole process of transdermal delivery. T-IgG appeared in the micro-pores of SD mice skin within 4 hours after treatment in vivo. After 24 hours, it was observed in the skin. In MRL/lpr mice, positive lupus band testing (LBT) could be found on the skin lesion after laser and T-IgG external application. CONCLUSIONS: Fractional Er:YAG laser can help antibodies (150 kDa) to implement effective and controllable transdermal delivery. LBT can be achieved in MRL/lpr mice using TDDS in vivo, which may contribute to the minimally invasive diagnosis of LE. Lasers Surg. Med. 51:268-277, 2019. © 2018 Wiley Periodicals, Inc.


Subject(s)
Immunoglobulin G/administration & dosage , Lasers, Solid-State , Lupus Erythematosus, Cutaneous/diagnosis , Administration, Cutaneous , Animals , Disease Models, Animal , Drug Delivery Systems , Fluorescent Antibody Technique , Mice , Mice, Inbred MRL lpr , Rats, Sprague-Dawley
6.
Lasers Med Sci ; 31(6): 1251-60, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27272747

ABSTRACT

The fractional erbium:yttrium aluminum garnet (Er:YAG) laser is widely applied. Microstructural changes after laser treatment have been observed with histopathology. Epidermal and dermal microstructures have also been analyzed using reflectance confocal microscopy (RCM). However, no studies have compared these two types of microstructural changes in the same subject at multiple time points after irradiation, and it is unclear if these two types of changes are consistent. We use RCM to observe the effect of different laser energies on skin healing and collagen changes in the skin of Sprague-Dawley rats that had been irradiated by fractional Er:YAG lasering at different energies. RCM was used to observe skin healing and detect collagen changes at different time points. Collagen changes were observed using hematoxylin and eosin (H&E) staining and quantitatively analyzed by western blot. RCM showed that, irrespective of laser energy, microscopic treatment zones (MTZs) were larger at 1 day after irradiation. The MTZs then reduced in size from 3 to 7 days after irradiation. The higher the energy, the larger the MTZ area. The amount of collagen also increased with time from 1 day to 8 weeks. However, the increase in the collagen amount on both RCM and H&E staining was not influenced by the laser energy. Western blotting confirmed that the amount of type I and type III collagens increased over time, but there were no significant differences between the different energy groups (p > 0.05). In conclusion, RCM is a reliable technique for observing and evaluating skin healing and collagen expression after laser irradiation.


Subject(s)
Collagen/radiation effects , Lasers, Solid-State/therapeutic use , Low-Level Light Therapy/methods , Wound Healing/radiation effects , Aluminum , Animals , Collagen/metabolism , Epidermis , Erbium , Male , Microscopy, Confocal , Rats , Rats, Sprague-Dawley , Skin/pathology , Yttrium
7.
Small ; 11(21): 2571-81, 2015 Jun 03.
Article in English | MEDLINE | ID: mdl-25630756

ABSTRACT

Gold nanoclusters (Au NCs) are one of the most promising fluorescent nanomaterials for bioimaging, targeting, and cancer therapy due to their tunable optical properties, yet their biocompatibility still remains unclear. Herein, the cytotoxicity of bovine serum albumin (BSA)-stabilized Au NCs is studied by using three tumor cell lines and two normal cell lines. The results indicate that Au NCs induce the decline of cell viabilities of different cell lines to varying degrees in a dose- and time-dependent manner, and umbilical vein endothelial cells which had a higher intake of Au NCs than melanoma cells show more toxicity. Addition of free BSA to BSA-Au NCs solutions can relieve the cytotoxicity, implying that BSA can prevent cell damage. Moreover, Au NCs increase intracellular reactive oxygen species (ROS) production, further causing cell apoptosis. Furthermore, N-acetylcysteine, a ROS scavenger, partially reverses Au NCs-induced cell apoptosis and cytotoxicity, indicating that ROS might be one of the primary reasons for the toxicity of BSA-Au NCs. Surprisingly, Au NCs with concentrations of 5 and 20 nM significantly inhibit tumor growth in the xenograft mice model of human liver cancer, which might provide a new avenue for the design of anti-cancer drug delivery vehicles.


Subject(s)
Gold/toxicity , Metal Nanoparticles/toxicity , Animals , Apoptosis/drug effects , Biological Transport, Active , Cattle , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Drug Stability , Gold/administration & dosage , HeLa Cells , Hep G2 Cells , Human Umbilical Vein Endothelial Cells , Humans , In Vitro Techniques , Metal Nanoparticles/administration & dosage , Mice , Reactive Oxygen Species/metabolism , Serum Albumin, Bovine/administration & dosage , Xenograft Model Antitumor Assays
11.
Ann Ital Chir ; 95(4): 699-707, 2024.
Article in English | MEDLINE | ID: mdl-39186342

ABSTRACT

AIM: Patients with permanent colostomy need continuous nursing management measures. Therefore, this study aimed to investigate the impact of discharge planning combined with "Internet home ostomy care platform'' on post-discharge complications, self-management abilities, quality of life, and satisfaction of patients with permanent colostomy after rectal cancer surgery. METHODS: This retrospective analysis included 72 rectal cancer patients who underwent permanent colostomy in Zhejiang Provincial People's Hospital between January 2021 and December 2021. Patients receiving routine nursing management were included in the control group (n = 36), and those receiving discharge planning combined with "Internet home ostomy care platform'' were included in the study group (n = 36). We collected baseline data, complication rate, self-management behavior questionnaire for Chinese enterostomy patients (SBQ-CEP), and Chinese version of the City of Hope Quality of Life-Ostomy Questionnaire (COH-QOL-OQ) and Medical Experience Scale for Outpatient Care of Enterostomy (MES-OCE) score. The complication rate, self-management ability, quality of life, and satisfaction of the two groups were statistically compared and analyzed. RESULTS: The study group demonstrated significantly higher medical compliance behavior, dietary behavior, symptom management behavior, psychosocial behavior, information management behavior scores, and SBQ-CEP total scores compared to the control group six months after discharge (p < 0.05). However, the study group showed a significantly lower incidence of complications than the control group at 1 week, 2 weeks, 1 month, 3 months, and 6 months after discharge (p < 0.05). Furthermore, the study group demonstrated significantly lower psychological well-being, physical well-being, spiritual well-being, social well-being scores, and COH-QOL-OQ total scores compared to the control group 6 months after discharge (p < 0.05). Additionally, the study group indicated significantly higher environment and process, service attitude, health guidance, diagnosis and treatment effect, overall evaluation of treatment experience scores, and MES-OCE total scores compared to the control group 6 months after discharge (p < 0.05). CONCLUSIONS: Discharge planning combined with "Internet home ostomy care platform'' can effectively reduce the risk of complications in patients with permanent colostomy after rectal cancer surgery. It improves patients' self-management abilities, quality of life, and satisfaction. This finding provides an ongoing guarantee for the quality of rehabilitation at home for patients with permanent colostomy.


Subject(s)
Colostomy , Patient Discharge , Quality of Life , Rectal Neoplasms , Humans , Female , Male , Retrospective Studies , Middle Aged , Rectal Neoplasms/surgery , Aged , Patient Satisfaction , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Surveys and Questionnaires , Home Care Services
12.
Article in English | MEDLINE | ID: mdl-39115044

ABSTRACT

Cutaneous melanoma is the most lethal of all skin tumors. Recently, cuproptosis, a novel form of cell death linked to oxidative phosphorylation, has emerged as an important factor. However, the precise role of cuproptosis in melanoma remains unclear. Our research explored the potential links between cuproptosis-related genes, prognosis, immune microenvironments, and melanoma treatments. Significantly, cuproptosis regulators showed remarkable differences between melanoma and normal tissues, establishing their relevance to melanoma. The newly developed cuproptosis-related gene signature (CGS) demonstrated a robust ability to predict overall survival (OS) in melanoma. We constructed a novel nomogram that combined clinical features with CGS to improve predictive accuracy. In addition, the study revealed correlations between CGS and immune cell populations, including CD8+T cells, Tfh cells, B cells, and myeloid-derived suppressor cells. Within the CGS, Peptidylprolyl isomerase C (PPIC) emerged as the most strongly associated with poor prognosis and drug resistance in melanoma. PPIC was identified as a promoter of melanoma progression, enhancing cell invasiveness while concurrently suppressing CD8+T cell activation. This comprehensive study not only elucidated the intricate connections between CGS, melanoma prognosis, immune microenvironment, and drug resistance but also provided compelling evidence supporting PPIC as a promising biomarker for predicting OS in melanoma treatment.

13.
J Pharm Sci ; 113(9): 2786-2794, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38986870

ABSTRACT

Topical ocular sustained-release drug delivery systems represent an effective strategy for the treatment of ocular diseases, for which a suitable carrier has yet to be sufficiently developed. Herein, an eye-compatible sodium polystyrene sulfonate resin (SPSR) was synthesized with a uniform particle size of about 3 µm. Ligustrazine phosphate (LP) was adsorbed to SPSR by cation exchange to form LP@SPSR. LP@SPSR suspension eye drops were further developed using the combination of Carbopol 934P and xanthan gum as suspending agents. The LP@SPSR suspension showed a sustained release in vitro, which was consistent with the observed porcine corneal penetration ex vivo. Pharmacokinetics in tear fluid of rabits indicated that LP@SPSR suspension led to prolonged ocular retention of LP and a 2-fold improved the area under the drug concentration-time curve (AUC0-t). Pharmacokinetics in the aqueous humor of rabbits showed 2.8-fold enhancement in the AUC0-t compared to LP solution. The LP@SPSR suspension exhibited no cytotoxicity to human corneal epithelial cells, nor irritation was observed in rabbit eyes. Thus, the LP@SPSR suspension has been validated as a safe and sustained release system leading to enhanced ophthalmic bioavailability for treating ocular diseases.


Subject(s)
Biological Availability , Delayed-Action Preparations , Drug Carriers , Polystyrenes , Pyrazines , Animals , Rabbits , Pyrazines/pharmacokinetics , Pyrazines/administration & dosage , Pyrazines/chemistry , Delayed-Action Preparations/pharmacokinetics , Polystyrenes/chemistry , Polystyrenes/pharmacokinetics , Humans , Drug Carriers/chemistry , Ophthalmic Solutions/pharmacokinetics , Ophthalmic Solutions/administration & dosage , Swine , Male , Administration, Ophthalmic , Drug Delivery Systems/methods , Drug Liberation , Cornea/metabolism , Cornea/drug effects
14.
Int J Pharm ; 659: 124279, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38806096

ABSTRACT

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment.


Subject(s)
Delayed-Action Preparations , Drug Carriers , Drug Liberation , Dry Eye Syndromes , Retinyl Esters , Vitamin A , Animals , Rabbits , Vitamin A/administration & dosage , Vitamin A/chemistry , Vitamin A/analogs & derivatives , Dry Eye Syndromes/drug therapy , Humans , Drug Carriers/chemistry , Cyclodextrins/chemistry , Ophthalmic Solutions/administration & dosage , Particle Size , Male , Cell Line , Cross-Linking Reagents/chemistry , Administration, Ophthalmic , Disease Models, Animal , Drug Delivery Systems/methods , Diterpenes
15.
Int J Pharm ; 660: 124294, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38823467

ABSTRACT

Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration-time curve (AUC0-12h) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.


Subject(s)
Atropine , Biological Availability , Delayed-Action Preparations , Drug Stability , Ophthalmic Solutions , Polystyrenes , Animals , Rabbits , Delayed-Action Preparations/pharmacokinetics , Polystyrenes/chemistry , Polystyrenes/pharmacokinetics , Ophthalmic Solutions/pharmacokinetics , Ophthalmic Solutions/administration & dosage , Atropine/pharmacokinetics , Atropine/administration & dosage , Atropine/chemistry , Male , Hypromellose Derivatives/chemistry , Tears/metabolism , Drug Liberation , Aqueous Humor/metabolism , Polysaccharides, Bacterial/chemistry , Administration, Ophthalmic
16.
Nanotechnology ; 24(45): 455302, 2013 Nov 15.
Article in English | MEDLINE | ID: mdl-24145641

ABSTRACT

We present a simple, yet versatile strategy for the fabrication of uniform biodegradable polymer nanoparticles (NPs) with controllable sizes by a hand-driven membrane-extrusion emulsification approach. The size and size distribution of the NPs can be easily tuned by varying the experimental parameters, including initial polymer concentration, surfactant concentration, number of extrusion passes, membrane pore size, and polymer molecular weight. Moreover, hydrophobic drugs (e.g., paclitaxel (PTX)) and inorganic NPs (e.g., quantum dots (QDs) and magnetic NPs (MNPs)) can be effectively and simultaneously encapsulated into the polymer NPs to form the multifunctional hybrid NPs through this facile route. These PTX-loaded NPs exhibit high encapsulation efficiency and drug loading density as well as excellent drug sustained release performance. As a proof of concept, the A875 cell (melanoma cell line) experiment in vitro, including cellular uptake analysis by fluorescence microscope, cytotoxicity analysis of NPs, and magnetic resonance imaging (MRI) studies, indicates that the PTX-loaded hybrid NPs produced by this technique could be potentially applied as a multifunctional delivery system for drug delivery, bio-imaging, and tumor therapy, including malignant melanoma therapy.


Subject(s)
Biocompatible Materials/chemistry , Magnetite Nanoparticles/chemistry , Melanoma/pathology , Particle Size , Polymers/chemistry , Biodegradation, Environmental , Cell Death/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Endocytosis/drug effects , Humans , Inhibitory Concentration 50 , Lactic Acid/chemistry , Light , Magnetic Resonance Imaging , Magnetite Nanoparticles/ultrastructure , Melanoma/drug therapy , Microscopy, Fluorescence , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Phantoms, Imaging , Polyesters , Polyvinyl Alcohol/chemistry , Quantum Dots , Scattering, Radiation
17.
Discov Med ; 35(176): 283-292, 2023 06.
Article in English | MEDLINE | ID: mdl-37272095

ABSTRACT

BACKGROUND: Breast cancer with low human epidermal growth factor receptor (HER2) expression is increasingly considered as a distinct subtype which consists of types of HER2 immunohistochemistry (IHC) 1+ and HER2 IHC 2+/in-situ hybridization (ISH)-negative. We aim to assess the survival difference between HER2 IHC 1+ and HER2 IHC 2+/ISH-negative breast cancer patients with metastasis at presentation and construct a prognostic nomogram for HER2-low patients. METHOD: Patients diagnosed with de novo metastatic HER2-low breast cancer from 2010 to 2015 were included and analyzed using the National Cancer Database (NCDB). Cox proportional hazards regression model and Kaplan-Meier (KM) method were used for survival analysis. Nomograms were built to predict survival. RESULT: A total of 7897 patients were included in the final analysis, among which 5458 (69.1%) patients were HER2 IHC 1+ and 2439 (30.9%) were HER2 IHC 2+/ISH-negative. Although the Kaplan-Meier survival analysis showed difference in survival, this survival difference was lost in the multivariate Cox analysis (multivariate: HR (hazard ratio) = 0.97; 95% CI (confidence interval) [0.92-1.03]). A prognostic nomogram was successfully constructed for individually predicting the long-term survival rate of HER2-low patients, which exhibited an acceptable predictive capability in training (C index: 0.719) and validation cohort (C index: 0.706). This nomogram could easily divide patients into high and low-risk subgroups with distinct prognoses. CONCLUSIONS: Our data suggest no statistical survival differences between HER2 1+ and HER2 2+ breast cancer. Additionally, a nomogram was constructed with an acceptable capacity to individually predict the long-term outcome of HER2-low metastatic breast cancer patients.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/metabolism , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Prognosis , Immunohistochemistry
18.
Bioact Mater ; 21: 253-266, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36157249

ABSTRACT

Many skin diseases, such as atopic dermatitis (AD), are featured with the dysbiosis of skin microbiota. The clinically recommended options for AD treatments suffer from poor outcomes and high side-effects, leading to severe quality-of-life impairment. To deal with this long-term challenge, we develop a living bacterial formulation (Hy@Rm) that integrates skin symbiotic bacteria of Roseomonas mucosa with poly(vinyl pyrrolidone), poly(vinyl alcohol) and sodium alginate into a skin dressing by virtue of the Ca2+-mediated cross-linking and the freezing-thawing (F-T) cycle method. Hy@Rm dressing creates a favorable condition to not only serve as extrinsic culture harbors but also as nutrient suppliers to support R. mucosa survival in the harsh microenvironment of AD sites to defeat S. aureus, which predominantly colonizes AD skins as an indigenous pathogen, mainly through the secretion of sphingolipids metabolites by R. mucosa like a therapeutics bio-factory. Meanwhile, this elaborately designed skin dressing could accelerate wound healing, normalize aberrant skin characters, recover skin barrier functions, alleviate AD-associated immune/inflammation responses, functioning like a combinational therapy. This study offers a promising means for the topical bacteria transplant to realize effective microbe biotherapy toward the skin diseases feature with microbe milieu disorders, including but not limited to AD disease.

19.
Front Bioeng Biotechnol ; 10: 1039154, 2022.
Article in English | MEDLINE | ID: mdl-36304892

ABSTRACT

Nanomedicine has demonstrated great potential in enhancing cancer immunotherapy. However, nanoparticle (NP)-based immunotherapy still has limitations in inducing effective antitumor responses and inhibiting tumor metastasis. Herein, polyethylenimine (PEI) hybrid thin shell hollow mesoporous silica NPs (THMSNs) were applied as adjuvant-nanocarriers and encapsulated with very small dose of photosensitizer chlorine e6 (Ce6) to realize the synergy of photodynamic therapy (PDT)/immunotherapy. Through PEI etching, the obtained Ce6@THMSNs exhibited enhanced cellular internalization and endosome/lysosome escape, which further improved the PDT efficacy of Ce6@THMSNs in destroying tumor cells. After PDT treatment, the released tumor-associated antigens with the help of THMSNs as adjuvants promoted dendritic cells maturation, which further boosted CD8+ cytotoxic T lymphocytes activation and triggered antitumor immune responses. The in vivo experiments demonstrated the significant potency of Ce6@THMSNs-based PDT in obliterating primary tumors and inducing persistent tumor-specific immune responses, thus preventing distant metastasis. Therefore, we offer a THMSNs-mediated and PDT-triggered nanotherapeutic system with immunogenic property, which can elicit robust antitumor immunity and is promising for future clinical development of immunotherapy.

20.
J Dermatol ; 49(6): 661-665, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35384058

ABSTRACT

Pulsed-dye laser (PDL), as an effective and frequently-used treatment modality for infantile hemangiomas (IH), could render patients at risk of developing long-term alopecia. Data on alopecia caused by PDL treatment remain scant and the contributing factors are not clear. Our objective was to identify the risk factors associated with long-term alopecia resulting from PDL treatment for scalp IH. We conducted a retrospective study incorporating patients with IH diagnosis and PDL intervention via thoroughly reviewing the clinical database of the dermatology department. Scalp IH patients were further screened and their medical records were collected. Long-term alopecia was defined as no signs of terminal hair regrowth for at least 2 years in this study. Of the 1293 IH patients, 47 (14 boys and 33 girls) with a mean age of 4.5 months (standard deviation, 3.2) were diagnosed as scalp IH and had subsequently undergone PDL treatments. Hair growth in the treatment area of 18 patients (38.3%) nearly returned to normal, 22 patients (46.8%) had varying degrees of hair loss, and seven patients (14.9%) had no hair regrowth (long-term alopecia). Compared with the older patients receiving treatment, IH patients younger than 3 months who started PDL treatment had a higher risk of developing long-term alopecia (odds ratio, 30.833; 95% confidence interval, 4.079-232.025; p = 0.01). The total number of PDL sessions, post-treatment blisters, and location of IH were not shown to be significantly associated with the development of long-term alopecia. Collectively, our study provides an important insight into curating treatments for IH in infants younger than 3 months. PDL treatments for scalp IH may perhaps be avoided or delayed to prevent the development of treatment-associated long-term alopecia.


Subject(s)
Hemangioma , Lasers, Dye , Alopecia/etiology , Female , Hemangioma/drug therapy , Humans , Infant , Lasers, Dye/adverse effects , Male , Retrospective Studies , Risk Factors , Scalp , Treatment Outcome
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