Common Type Research Articles

Uveal metastasis arising from thyroid neoplasms: A case study synthesis.

We systematically reviewed the case report literature to identify cases of uveal metastases originating from thyroid cancer (TC), evaluate factors and indications in uveal metastases from TC, and provide clinical insights through recent case studies. Web of Science, Medline, and Scopus databases were searched for case reports or series reporting uveal metastasis from a thyroid neoplasm. Articles published in any language from inception through November 2022 were searched and screened independently by two reviewers. The quality of the included studies was assessed using the JBI Critical Appraisal Checklist for Case Reports. A total of 1049 records were screened, resulting in the identification of 46 cases from 43 studies. The mean (SD) age at uveal metastases diagnosis was 58.44 (±17.99) years with the median (interquartile range) of 56.5 (29.75) (range, 20-83 years), with 34.8% of cases (16/46) cases reported in elderly patients (>64 years). The sample consisted of 56.5% (26/46) male patients. Uveal metastases were observed in the right eye in 16 cases, the left eye in 19 cases, and both eyes in 11 cases. Choroidal involvement was present in 84.8% of cases (39/46) cases. Papillary carcinoma was the most common thyroid cancer type (34.8%, 16/46), followed by follicular carcinoma (32.6%, 15/46), and medullary carcinoma (21.7%, 10/46). Uveal metastases have been observed to appear in metastatic TC, and physicians should approach ocular symptoms cautiously in cases that accompany a neck mass or a history of previous TC.

Analysis of pharmaceutical interventions in chemotherapy prescriptions of adult and pediatric patients at an oncology reference institute.

Chemotherapy, one of the primary cancer treatments, has a high risk of causing significant harm in cases of its misuse. Pharmaceutical intervention is one of the strategies used to prevent medication errors from reaching the patient by identifying drug-related problems or other discrepancies related to patient data or medical progress. The primary objective of this study was to analyze the profile of the pharmaceutical intervention made in chemotherapy prescriptions for adult and pediatric patients in order to measure its impact on patient safety. A retrospective cross-sectional and observational study was conducted at a reference center for cancer treatment in Rio de Janeiro, Brazil. Pharmaceutical interventions performed in chemotherapy prescriptions from January to October 2022 were quantified, classified, and analyzed by their type, most common medicine, and acceptability. From the patients treated in the period, 220 (14.8%) adults and 64 (23.4%) children and teenagers received at least one pharmaceutical intervention. The most common types for adults were dose adjustments: overdose (22.5%) and underdose (22.5%). However, in pediatry, incompleteness of supporting drug protocol (22.1%) was the most registered. The most common medicines involved in pharmaceutical intervention were carboplatin (for adults) and electrolytes/hydration (for pediatric patients). Pharmaceutical intervention acceptability by prescriptors was very similar, reaching 80.4% for adults and 77.9% for pediatrics. The pharmaceutical intervention profile was quite distinct by virtue of the singularities of each population. The pharmacists' role was shown to be paramount in intercepting medication errors in the prescription of chemotherapy protocols, contributing to patient safety.

ANALYSIS AND ALGORITHM FOR STRENGTHENING ARCHED STRUCTURES OF END-TO-END COMPOSITE CROSS-SECTION

As a result of the increase in snow load, which affects the reliability of arched structures, in accordance with changes No. 2, 3, 4 SP20.13330.2016 (russ. Set of rules), there is a need to strengthen these structures.The aim of the work is to develop reinforcement of arched structures and to develop a typical technical solution to increase the margin of safety for the most common type of structure.

4-{3-[(Pyridin-4-ylmethyl)amino]-[1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl}phenol: An improved anticancer agent in hepatocellular carcinoma and a selective MDR1/MRP modulator.

Hepatocellular carcinoma is the most common type of primary liver cancer. However, multidrug resistance (MDR) is a major obstacle to the effective chemotherapy of cancer cells. This report documents the rational design, synthesis, and biological evaluation of a novel series of triazolotriazines substituted with CH2 NH-linked pyridine for use as dual c-Met/MDR inhibitors. Compound 12g with IC50 of 3.06 μM on HepG2 cells showed more potency than crizotinib (IC50 = 5.15 μM) in the MTT assay. In addition, 12g inhibited c-Met kinase at a low micromolar level (IC50 = 0.052 μM). 12g significantly inhibited P-gp and MRP1/2 efflux pumps in both cancerous HepG2 and BxPC3 cells starting from the lower concentrations of 3 and 0.3 µM, respectively. 12g did not inhibit MDR1 and MRP1/2 in noncancerous H69 cholangiocytes up to the concentration of 30 and 60 µM, respectively. Current results highlighted that cancerous cells were more susceptible to the effect of 12g than normal cells, in which the inhibition occurred only at the highest concentrations, suggesting a further interest in 12g as a selective anticancer agent. Overall, 12g, as a dual c-Met and P-gp/MRP inhibitor, is a promising lead compound for developing a new generation of anticancer agents.

A hospital-based cross-sectional study on parental self‑medication among children in a tertiary care hospital in Kolkata

Introduction: Self-medication/self-prescription, the practice of using measures to treat and handle diseases, without consulting appropriate authority, has been significantly inculcated in modern society. Parental self-medication is today a significant paediatric public health problem contributing to global rise of antimicrobial resistance.Objectives: To assess the magnitude and determinants of parental self-medication among children attending a tertiary care hospital in Kolkata. Method: This cross-sectional study was conducted on parents of 105 children attending the paediatric clinic of a tertiary care hospital in Kolkata. Universal sampling was employed. Parents were surveyed by face-to-face interview using a pre-tested semi-structured interview schedule validated by subject experts. Information on pattern, reasons, and perception of parental self-medication were elicited from the schedule. Microsoft Excel and STATA MP16 were used for statistical analysis. Results: Mean ages of the parents and their children were 31.79±5.6 years, and 5.3±2.9 years respectively. Prevalence of parental self-medication was 78.1% (95% CI: 69-85%). Analgesic-antipyretics were the most common type of medicine used during self-medication (77.1%), whereas prior experience in dealing with similar illness was the most common reason (42%) for practising self-medication. Higher educational levelof respondent parent and increased age of child (>3 years) were significantly associated with the practice of self-medication in bivariate analysis.Conclusions: Prevalence of parental self-medication was 78.1%. Analgesic-antipyretics were used during self-medication in 77.1% cases. Prior experience in dealing with similar illness was the reason for practising self-medication in 42% cases. Higher educational level of the respondent parent and increased age of child (>3 years) were significantly associated with the practice of self-medication.

The complex etiology of autism spectrum disorder due to missense mutations of CHD8.

CHD8 is an ATP-dependent chromatin-remodeling factor encoded by the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Although many studies have examined the consequences of CHD8 haploinsufficiency in cells and mice, few have focused on missense mutations, the most common type of CHD8 alteration in ASD patients. We here characterized CHD8 missense mutations in ASD patients according to six prediction scores and experimentally examined the effects of such mutations on the biochemical activities of CHD8, neural differentiation of embryonic stem cells, and mouse behavior. Only mutations with high prediction scores gave rise to ASD-like phenotypes in mice, suggesting that not all CHD8 missense mutations detected in ASD patients are directly responsible for the development of ASD. Furthermore, we found that mutations with high scores cause ASD by mechanisms either dependent on or independent of loss of chromatin-remodeling function. Our results thus provide insight into the molecular underpinnings of ASD pathogenesis caused by missense mutations of CHD8.

The Role of Fingernails in Death Investigation.

In forensic pathology, forensic onychology studies fingernails and toenails for medicolegal purposes. It mainly deals with DNA profiling from nails, toxicological analysis for detecting poisons, and the collection of trace evidence present under the nails. Injuries to fingernails and their interpretation for medicolegal purposes are the neglected areas of this study. We have discussed the most common types of fingernail injuries and their significance. We found that their notification has significant value in drowning cases, defense wounds on the palm, self-inflicted cuts, burns, electrocution, blunt trauma, physical assault, sexual offenses, and other issues like torture. We emphasize the examination of fingernails in the autopsy and medicolegal clinical examination for better administration of law and justice.

Non-medical interventions to enhance return to work for people with cancer.

Non-medical interventions to enhance return to work for people with cancer.

Clinical characteristics of adult cases with urolithiasis from Türkiye: A regional epidemiological study.

To evaluate the metabolic and clinical characteristics of adult cases with stone disease from a regional part of Türkiye. The study included 2348 adult patients with sonography and/or computed tomography-proven urinary stones. All cases were given a questionnaire about the epidemiological features of urolithiasis. Aside from the type and severity of stoneforming risk factors, both patient (age, gender, BMI, associated comorbidities, first onset of stone disease, positive family history, educational level) and stone-related (size, number, location, chemical composition, previous stone attacks) factors have been thoroughly assessed. The data were evaluated in multiple aspects to outline the epidemiological features. The overall mean age value of the cases was 43.3 years, and the M/F ratio was 1.34. The first onset of the disease was found to vary between 15-57 years, with a mean value of 32.4 years. While most of the stones were located in kidney and ureter, calcium-containing stones constituted the most common type (CaOx 69%, CaOxPO4 7%). More than 42% of the cases suffered from multiple stone attacks; positive family history waspresent in 31.6%. Among the associated comorbidities, hypertension was the most common pathology (45.8%), and the BMI index value was > 30 in 31.3% of the cases. 57.7% of the patients had just one stone attack, and 42.2% had recurrent stone formation. Our findings clearly show that important implications may be extracted from epidemiologic data acquired from local scale research to implement an effective preventative program and closely monitor the patients.

PENGETAHUAN SISWA SEKOLAH MAN 4 BALANGAN TENTANG TUMBUHAN OBAT DI KECAMATAN HALONG KABUPATEN BALANGAN PADA PELESTARIAN TUMBUHAN OBAT TRADISIONAL

The Meratus Dayak people still believe that traditional medicine using medicinal plants can cure diseases and still often use it as needed. This traditional medicine has become extinct because the system of inheritance of knowledge is only through oral without any written records from generation to generation. This has led to a decrease in the number of individuals who have knowledge and skills in traditional medicine, especially in the younger generation who are less interested in learning traditional medicine. The purpose of this study was to analyze the knowledge of Madrasah Aliyah Negeri 4 Balangan students on medicinal plants, their use as daily or traditional customs and efforts to preserve traditional medicines in Halong Subdistrict, Balangan District. Students from class X IPA and X IPS at Madrasah Aliyah Negeri 4 Balangan have low knowledge about medicinal plants caused by several factors, including curriculum, teaching methods that are less interactive, the influence of parents who have limited knowledge, and modernization make modern medicines easier to obtain. Students have basic knowledge of medicinal plants, but limited to a few common types, there is a desire to expand their knowledge. The application of medicinal plants in everyday life is still low due to lack of practical knowledge and limited access.

Haploinsufficiency of Adenomatous Polyposis Coli Coupled with Kirsten Rat Sarcoma Viral Oncogene Homologue Activation and P53 Loss Provokes High-Grade Glioblastoma Formation in Mice.

Glioblastoma multiforme (GBM) is the most common and deadly type of brain tumor originating from glial cells. Despite decades of clinical trials and research, there has been limited success in improving survival rates. However, molecular pathology studies have provided a detailed understanding of the genetic alterations associated with the formation and progression of glioblastoma-such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling activation (5%), P53 mutations (25%), and adenomatous polyposis coli (APC) alterations (2%)-laying the groundwork for further investigation into the biological and biochemical basis of this malignancy. These analyses have been crucial in revealing the sequential appearance of specific genetic lesions at distinct histopathological stages during the development of GBM. To further explore the pathogenesis and progression of glioblastoma, here, we developed the glial-fibrillary-acidic-protein (GFAP)-Cre-driven mouse model and demonstrated that activated KRAS and p53 deficiencies play distinct and cooperative roles in initiating glioma tumorigenesis. Additionally, the combination of APC haploinsufficiency with mutant Kras activation and p53 deletion resulted in the rapid progression of GBM, characterized by perivascular inflammation, large necrotic areas, and multinucleated giant cells. Consequently, our GBM models have proven to be invaluable resources for identifying early disease biomarkers in glioblastoma, as they closely mimic the human disease. The insights gained from these models may pave the way for potential advancements in the diagnosis and treatment of this challenging brain tumor.

Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use.

Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy. Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time-stamped medical records. The study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrialdimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow-up, arrhythmia-free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56). Use of forward-solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications.

Abstract B069: Bone marrow-derived adipocytes promote ovarian cancer progression and metastasis

Abstract B069: Bone marrow-derived adipocytes promote ovarian cancer progression and metastasis

New MoS2/Tegafur-Containing Pharmaceutical Formulations for Selective LED-Based Skin Cancer Photo-Chemotherapy.

Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic to healthy tissues; therefore, new, alternative, selective treatments are needed. In this work, a combined photothermal and chemotherapeutic approach is proposed. MoS2 was used as photothermal agent. It was prepared by a liquid-phase exfoliation and intercalation method using polyvinylpyrrolidone (PVP), followed by recirculation through a custom-built high-power ultrasonication probe. After 6 h of ultrasonication treatment, the average particle size was 165 ± 170 nm. Near-infrared (NIR) irradiation assays (810 nm, 0.1 W/cm2, 30 min, 180 J/cm2) confirmed that MoS2 nanosheets can efficiently convert NIR light into heat and reach 52 °C. The therapeutic doses of MoS2 (125 µg/mL) and Tegafur (50 µg/mL) were optimized and both were simultaneously incorporated into a Carbopol hydrogel. The cells were brought into contact with the hydrogel and irradiated with a custom-built NIR LED system. In HFF-1 cells (normal human fibroblasts), the metabolic activity was 78% (above the 70% toxicity limit-ISO 10993-5:2009(E)), while in A-431 skin cancer cells, it was 28%. In addition, the MoS2 + Tegafur hydrogels led to a 1.9-fold decrease in A-431 cancer cell metabolic activity, 72 h after irradiation, in comparison to MoS2 hydrogels, indicating a combined effect of photothermal and chemotherapy.

Abstract PR-004: Targeting EPHB2/ABL1 restores anti-tumor immunity in a preclinical model of ependymoma

Abstract Purpose: Ependymoma (EPN) is a common type of brain tumor in children and is often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of unique EPN subtypes and revealed a critical role of EPHB2. However, the immune system's role in tumor progression and treatment response remains poorly understood. New treatments for EPN are desperately needed and should be developed in a molecular subtype-specific fashion. Experimental Design: We developed a syngeneic mouse model using subtype-specific EPHB2-driven genetically engineered EPN tumor cells. Druggable targets were identified by matching transcriptomic signatures with the target spectrum of FDA-approved drugs. After identifying dasatinib as a potentially effective agent, we measured the changes in the immune microenvironment during EPN growth and after dasatinib treatment. Results: Transcriptomic profiling of EPHB2-driven EPN and analysis of a human EPN dataset revealed multiple protein kinases as potential druggable targets. We found that the multikinase inhibitor dasatinib potently inhibited the growth of EPN both in vitro and in vivo, mainly through blocking EPHB2 and ABL1 signaling. We found an increased frequency of immunosuppressive M2-like tumor-associated macrophages (TAMs), which proportionally increased with tumor size during tumor progression. However, treatment with dasatinib reprogrammed the EPN immune microenvironment by polarizing the TAMs toward an anti-tumor M1-like phenotype and increasing CD8 T cell activation. Furthermore, dasatinib treatment induced complete regression of established EPN tumors in 78% of the animals and protected survivors against tumor recurrence. Depletion of CD8 T cells compromised the durability of EPN responses and reduced overall survival. Conclusions: These data indicate that dasatinib may be an effective therapy for EPHB2-driven molecular subgroup of EPNs by activating the anti-tumor immune response and support further investigations of dasatinib in clinical trials. Citation Format: Taylor P. Uccello, Jun Ren, Zohreh Amoozgar, Yuhui Zhao, Pin-Ji Lei, William W. Ho, Sylvie Roberge, Peigen Huang, Dan G. Duda, Lei Xu, Rakesh K. Jain. Targeting EPHB2/ABL1 restores anti-tumor immunity in a preclinical model of ependymoma [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr PR-004.

Effective refractive error coverage and spectacle coverage among school children in Telangana, South India.

Uncorrected refractive error (URE) is one of the leading causes of childhood vision impairment. Increasing effective refractive error coverage (e-REC) is one of the main indicators of WHO's 2030 global eye health targets. The aim of this study is to estimate the e-REC and spectacle coverage among school children in Telangana, South India. School children aged 4-15 years in the study locations underwent vision screening using 6/12 tumbling E optotype by trained community eye health workers in the schools. Those failing the initial vision screening and/or found to be having eye conditions were referred to a nearby referral centre appropriately, where they underwent detailed eye examination. A total of 774,184 children were screened in schools of which 51.49% were boys. The mean age was 9.40 ± 3.27 years. The prevalence of URE was 1.44% (95%CI:1.41-1.46) of which myopia was 1.38% (95%CI: 1.35-1.41). In multivariate analysis, the risk of myopia was higher among older children (Adj.OR: 17.04; 95%CI: 14.64-19.85), those residing in urban areas (Adj.OR:3.05, 95%CI:2.60-3.57), those with disabilities (Adj.OR:2.61, 95%CI:2.00-3.39) and among girls (Adj.OR:1.30, 95%CI:1.25-1.35) (P < 0.001). The overall e-REC was 56.97% and the spectacle coverage was 62.83%. The need for interventions to improve e-REC to achieve 2030 global eye health target is eminent among children in this region. Improving refractive services through school eye health programs could aid in accelerating this process to achieve the target. Myopia being the most common type of RE, the risk factors included increasing age, urban location, and presence of disability.

Analysis of Research Activity Among Ophthalmology Fellows

ABSTRACT Purpose The academic success of ophthalmology fellows may be significantly impacted by their research engagement. Evaluating the research activity of fellows by subspecialty may provide insight into trends useful for prospective applicants. The objective of this study was to assess the research activity of ophthalmology fellows in the year 2023. Methods Ophthalmology fellowship programs were compiled using the Association of University Professors of Ophthalmology and the American Society of Ophthalmic Plastic and Reconstructive Surgery websites. Program subspecialties were categorized as: Cornea and External Disease [CED]; Cornea, External Disease, and Refractive Surgery [CEDRS]; Glaucoma; Medical Retina [MR]; Neuro-Ophthalmology [NO]; Oculoplastics; Pediatric Ophthalmology [PO]; Surgical Retina [SR]; Uveitis; and Other. “Other” consisted of Oncology, Pathology, combined Oncology and Pathology fellowships. We identified current fellows using publicly available online information. Programs and fellows that did not have information available were excluded. Total publications, Hirsch index (h-index), and weighted-relative citation ration (w-RCR) were utilized as measures of research output, while total citations and mean-RCR (m-RCR) served as proxies for research impact. Duration of publishing was calculated using the years of the oldest and most recent publications. Statistical analysis was performed using Kruskal–Wallis H tests with an alpha value of .05. Results A total of 373 fellows from 229 programs met our inclusion criteria. More than half of fellows were men (54.4%), and the most common degree type was MD (93.0%). Across all subspecialties, the median h-index was 3.0 (IQR = 4), m-RCR was .9 (IQR = 1.2) and w-RCR was 3.2 (IQR = 9.8). The median number of publications was six (IQR = 10, with 34 citations (IQR = 110) and 4 years of publishing (IQR = 6). We observed significant differences in h-index (p = .038), total publications (p < .001), and w-RCR (p = .028) by subspecialty. Conclusion We observed significant differences in research output, but no differences in research impact by subspecialty. Overall, Uveitis and Oculoplastics fellows had higher research activity, while Medical Retina and Other fellows had the lowest. This data is pertinent to better understand the landscape of ophthalmology fellowship applications.

Analysis of following vehicle driver injury severity in rear-end collision on straight road based on LightGBM and SHAP

Rear-end accidents, as one of the common accident types, may cause serious injuries to the driver and passengers. There are mutual coupling effects among causal features of rear-end accidents, and traditional analytical methods may lead to modeling distortion due to assumption constraints. In this study, the Light Gradient Boosting Machine (LightGBM), a machine learning algorithm, is used to model the injury severity of the following vehicle driver in a rear-end crash accident on a straight road, based on the data from the China In-depth Accident Study data. The Shapley Additive Explanations (SHAP) method was used to interpret the results of the LightGBM model and to analyze the relationship between factors and driver injury severity. The results show that location familiarity, willingness to take risks, and driving time have a significant impact on the injury severity for following vehicle drivers involved in rear-end crashes. Cloudy conditions increase a driver’s risk of being involved in a fatal or injured rear-end collision. In rain, snow, hail, and foggy conditions, have a higher propensity to cause driver fatalities in the crash event. The rear-end crash of passenger cars resulted in a higher death probability of the following vehicle driver compared to sedan and truck, and female drivers are more likely to be involved in uninjured accidents compared to males. These results are informative for preventing rear-end accidents and reducing the extent of accidental injuries.

Novel method of image analysis that combines Radon and Fourier image transformations for the purpose of differentiating between malignant and benign colonic biopsies.

Colorectal cancer is the third most common type of cancer. It develops slowly as a polyp that can turn into a cancerous tumor. This study aimed to develop a decision-making algorithm of microscopic images using texture analysis that is orientation free, to be used for automated classification of normal and neoplastic (malignant or premalignant) colonic biopsies. Forty-nine colonic adenocarcinomas, 41 adenomas and a control group of adjacent normal colonic mucosa were included in the texture analysis. Radon transform followed by the Fast Fourier transform were applied to the images. Subsequently, the gray level co-occurrence matrix (GLCM) transform was applied allowing the extraction of four textural variables (homogeneity, contrast, correlation, and entropy). For classification and prediction of the diagnosis, a statistical multivariate regression model and a neural network (NNET) model were used and compared. The statistical model provided a sensitivity of 71.3% and a specificity of 50% (Area under the ROC curve: 0.67) for classifying the neoplastic and the normal images, respectively. The NNET model was superior to the statistical model and produced a sensitivity of 97.9% and specificity of 88% (Area under the ROC curve: 0.92). To our knowledge, this is the first study that used a combination of Radon, FFT, and GLCM transformations in order to overcome the tissue orientation problem in texture analysis of microscopic images of colonic biopsies. The NNET classifier trained by the extracted textural features proved to be superior to the statistical classifier, thus predicting colonic neoplasia with high accuracy. RESEARCH HIGHLIGHTS: We propose a novel decision-making algorithm of orientation invariant image texture analysis, fast and easily implemented for automated differentiation between benign and neoplastic epithelial tumors of the colon. This method can reduce the turnaround time allowing to prioritize the biopsies during their examination and diagnosis by the pathologist.

Nanoparticle‐Mediated Tumor Microenvironment Remodeling Favors the Communication with the Immune Cells for Tumor Killing

AbstractMelanoma is one of the most common types of skin cancer with a bad prognosis and limited treatment options in advanced stages. Immunotherapy has changed the landscape of oncology. Cancer cells can activate various mechanisms to suppress immune responses, such as the immunological checkpoint programmed cell death‐1 (PD‐1)/programmed cell death‐ligand 1 (PD‐L1), whose blockage reactivates immune killing of melanoma cells. Moreover, exposure to inhibitory cytokines such as transforming growth factor‐beta (TGF‐β) induces T regulatory cell differentiation, which promotes cancer immunosuppression. These advances provided exciting outcomes in the clinical treatment of melanoma, however, there are still limitations, and a combination of several treatments is usually needed. Based on the above, inhibition of the TGF‐β production and the PD‐1/PD‐L1 checkpoint may be a feasible strategy to increase T cell infiltration and cytotoxicity and thus overcome tumor immune escape. Here, mesoporous silica nanoparticles loaded with a PD‐L1 inhibitor (JQ1, a thienotriazolodiazepine and a potent bromodomain family inhibitor) and capped with polyethyleneimine and a small interfering RNA targeting TGF‐β are reported. An efficient PD‐L1 downregulation and TGF‐β silencing are achieved using the nanoparticles, along with the promotion of cancer death. This system demonstrates to be a specific and innovative therapeutic approach for the treatment of melanoma.