Volume 25, Issue 5

Many dermatological diseases still do not have an adequate treatment, such as melanoma. The treatments are usually lengthy, complex, with low cure rates and with severe side effects. This leads to low patient compliance, generating recurrence and/or worsening of the disease. Ethosomes, which are phospholipid-based vesicles containing ethanol, have shown great potential as drug delivery systems for the treatment of melanoma and other skin diseases. The unique structure of ethosomes allows for enhanced skin penetration and efficient delivery of therapeutic agents to the target site, improving the efficacy of treatment. The use of ethosomes in melanoma treatment holds promise for overcoming the limitations of conventional therapies, offering the potential for improved patient outcomes, reduced treatment duration, and minimized side effects. In this mini-review we present the advances, challenges, limitations and advantages, and future perspectives of the use of ethosomes in the treatment of the melanoma.

Objectives This study aimed to identify high-risk factors for high cardiac radiation exposure, based on anatomical measurements taken from planning CT images of patients with left-sided breast cancer who underwent breast-conserving surgery and received radiotherapy. Methods We retrospectively analyzed 45 patients with left-sided breast cancer who underwent whole-breast radiotherapy, either under free breathing (27/45) or deep inspiratory breath-holding (DIBH) (18/45), after breast-conserving surgery. Six anatomical parameters were measured from planning CT images, including treatment planning target volume (PTV), cardiopulmonary volume ratio (CVR), maximum cardiac margin distance, the relative distance between inferior boundaries of heart and PTV (DBIB(H2P)), axial cardiac contact distance, and para-sagittal cardiac contact distance (CCDps). Multiple linear regression analysis was performed using SPSS software to explore the correlation between the six parameters, body mass index (BMI), and the mean heart dose (MHD). Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive power of the selected predictor of cardiac dose exposure. Results Significant correlations were observed between the MHD of patients and the CVR, DBIB(H2P), and CCDps parameters. Among them, the CVR was the most important predictor of cardiac dose exposure, with an area under the curve of 0.915 and a cut-off value of 0.17. Conclusions The study results indicated that CVR, DBIB(H2P), and CCDps are the primary parameters associated with the risk of cardiac dose exposure, with CVR being the most significant predictor. Further prospective studies are required to determine whether these parameters can be used to identify patients who would benefit from the DIBH technique.

Objectives Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world with a high incidence and it lacks effective biomarkers for early-stage detection. In this investigation, we aimed to investigate the alterations in plasma glycans related to NSCLC and assess the possibility of plasma glycopatterns as potential biomarkers for the diagnosis of NSCLC. Methods First, plasma samples from 16 patients with early-stage lung adenocarcinoma (LUAD), 16 patients with early-stage Lung squamous cell carcinoma (LUSC), and 16 healthy volunteers, were selected for inclusion in this study to probe the difference in plasma glycopatterns using lectin microarrays. Then, the diagnostic effectiveness of the candidate lectins was evaluated using ROC. Results In contrast to the NL group, seven candidate lectins offered potential diagnostic utility in the NSCLC (LUAD and LUSC) group. F17AG was significantly altered in LUSC with an AUC of 0.818 (adj.P.Val<0.05) compared to NL samples. There were 20 differentially expressed lectins in the LUAD group compared to the NL group. Based on the AUC values (AUC>0.800) and the normalized fluorescence intensities of the lectins, we selected eight lectins, GAL2, PTL-1, GNA, SSA, LENTIL, CA, PHA-E, and MAA to perform logistic regression analysis, and found that the combination of these eight candidate lectins had high diagnostic potential. Conclusions The results of this study should help to distinguish between NSCLC and NL based on changes in plasma glycopatterns, which have a great deal of potential to be biomarkers for diagnosing NSCLC.

Objectives Previous studies have shown that tripartite motif-containing 28 (TRIM28) might be a latent target for cancer therapy. However, the detailed roles and mechanisms of TRIM28 in hepatocellular carcinoma (HCC) remain ambiguous. Methods We systematically analyzed TRIM28 mRNA expression and protein levels in HCC tissues based on large-scale data and publicly available immunohistochemistry images. We estimated the prognostic capacity of TRIM28 in HCC. Additionally, we performed gene enrichment, immune infiltration, and drug sensitivity analyses to further explore the roles of TRIM28 in HCC. To determine the effect of TRIM28 expression on HCC cell proliferation and migration, successful transfection of siRNAs was conducted in MHCC97-L and Huh7 cells, followed by cell functional assays. Results We verified the overexpression of TRIM28 in HCC at the mRNA and protein levels. The summary receiver operating characteristics curve with the area under curve of 0.84 (95 % CI: 0.81–0.87) indicated the high accuracy of increasing TRIM28 expression for discriminating HCC from non-HCC tissues. According to The Cancer Genome Atlas datasets, TRIM28 mRNA expression was significantly related to age, grade, stage, and pathologic T (p<0.05). Increased TRIM28 expression levels were significant correlated to poor survival in HCC patients. An enrichment analysis suggested that TRIM28-reated genes primarily participated in the spliceosome signaling pathway, with hub genes including SNRPA1, SNRPF, SNRPD1, SF3B2, SNRPB, SNRPE, and EFTUD2. TRIM28 expression was correlated with the infiltration of five immune cells. Higher TRIM28 expression was linked to better sensitivity of tumor cells to pluripotin. Molecular docking showed that pluripotin could bind to TRIM28. Further, knockdown of TRIM28 inhibited the proliferation and migration of HCC cells. Conclusions TRIM28 is highly expressed in HCC and contribute to the proliferation and migration of HCC cells, leading to unfavorable outcomes. These findings indicate TRIM28 promise as a novel prognostic indicator.

Objective Worldwide, gastric cancer (GC) is one of primary reasons for cancer-related deaths. However, the pathogenic mechanism underlying GC remains to be fully understood. MicroRNAs are momentous regulators of diverse biological progression in cancer. Even though the ability of miR-219a-1-3p to inhibit malignant progression in pancreatic cancer have been previously reported, its role in GC remains to be elucidated. Methods Quantitative real-time PCR (qRT-PCR) was performed to measure miR-219a-1-3p expression levels in collected GC samples (n=98) and paired nearby non-tumor tissues. Cell proliferation, migration, and invasion assays were then conducted to explain the biological influences of miR-219a-1-3p in vitro . In vivo effects were confirmed by subcutaneously injecting miR-219a-1-3p overexpressing MGC-803 cells into nude mice. Methylation-specific PCR was employed to evaluate the CpG island upstream methylation condition of miR-219a-1-3p in collected clinical tissues (n=22), GC cell lines and GES-1 cells. GC cells were supplemented with 5-aza-2′-deoxycytidine to identify the miR-219a-1-3p expression changes using qRT-PCR. Results The miR-219a-1-3p expression was obviously suppressed in GC tissues relation to nearby non-tumor tissues, along with in GC cell lines in comparison to GES-1. Moreover, in vivo and in vitro functional evaluations indicated the function of miR-219a-1-3p in inhibiting the malignant characteristics of GC cells. Mechanistically, MiR-219a-1-3p expression was partly regulated utilizing DNA hypermethylation in GCs. In addition, overexpression of miR-219a-1-3p inhibited PI3K/AKT signaling. Conclusions MiR-219a-1-3p might function as a tumor suppressor in GC, and our investigation creates a foundation to diagnose of GC.

Objectives Although ubiquitin-specific peptidase 21 (USP21) has been shown to promote the development of various cancers, its role in prostate cancer has been poorly reported. Therefore, this study attempted to investigate the involvement of USP21 in prostate adenocarcinoma (PRAD) progression. Methods Information from public databases was used to evaluate the pattern of USP21 expression in PRAD tissues and its effect on patient prognosis. Subsequently, we either upregulated or knocked down USP21 expression in the human PRAD cell line DU145 to assess cell growth, migration, invasiveness, and apoptosis. Results The transcript levels of USP21 in PRAD tissues were low, indicating a poor prognosis. In DU145 cells, USP21 silencing impaired cell proliferation, colony formation, cell cycle progression, migratory capacity, and invasiveness, while it increased rates of apoptosis. Furthermore, cell proliferation, migration, and invasion were all induced by upregulating USP21. In addition, gene enrichment analysis revealed that USP21 had the potential to regulate cell adhesion and the cell cycle. This observation was further validated by the detection of expression of related genes in cells with either knockdown or increased USP21 expression levels. The expression and copy numbers of USP21 were significantly correlated with the infiltration levels of immune cells. Conclusions Expression level of USP21 is associated with PRAD progression and poor prognosis, and may have a role in potential therapeutic strategies for patients with PRAD.

Objectives Bone is the most common site of metastasis in prostate cancer (PCa) patients and is correlated with poor prognosis and increasing economic burden. Few studies have analyzed the prognostic prediction for metastatic PCa patients with the assistance of neural networks. Methods Four convolutional neural network (CNN) models are developed and evaluated to predict the overall survival (OS) of PCa patients with bone metastasis. All the CNN models are first trained with 64 samples and evaluated with 10 samples; two models use only bone scan images and two models use both bone scan images and clinical parameters (CPs). The predictions of the best models are compared with those by two urology surgeons on 20 test samples. Results Our best models can predict OS of PCa patients with bone metastasis with AUC=0.8022 by using only bone scan images and AUC=0.8132 by using both bone scan images and CPs on 20 test samples. The best Youden indexes of the two models are 0.6263 and 0.7142, respectively, which are 0.3077 and 0.3131 higher than that of the urologists’ average Youden index, which indicate that CNN models exhibit significant advantages. Conclusions CNN models are suitable to predict OS in PCa patients with bone metastasis using bone scan images and CPs. Our models show better performance in terms of accuracy and stability than urology surgeons.

Objectives Most researches have shown that neutrophils are closely related to bladder urothelial carcinoma (BLCA), especially its occurrence and development. Although tumor microenvironment (TME) related genes have an impact on prognosis, the role of neutrophil related genes in BLCA adjuvant therapy is not clear. Methods We used sample information from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. And we utilized the CIBERSORT algorithm to obtain the tumor immune microenvironment (TIME) landscape and weighted gene co-expression network analysis (WCGNA) to detect neutrophil-related gene modules. We used univariate Cox regression, multivariate Cox regression, and lasso regression analyses to identify genes that have a relationship with BLCA prognosis. Using the median risk score (RS), we classified the cohort into a high-risk group (HRG) and low-risk group (LRG). External validation of RS was performed via GEO data feeds. Prognostic nomograms were constructed with reference to RS and clinically relevant information and validated using calibration curves. We analyzed the latent connections between RS and tumor mutational burden. Finally, the latent associations between risk markers and chemotherapy prognosis were explored using the pRRophetic algorithm. Results In this study, 10 TME-related genes with important prognostic value were screened. Then, by deriving the RS, we constructed a prognostic risk prediction nomogram using parameters such as sex, age, TNM stage, clinical stage, and RS. The area under the receiver operating characteristic curve showed that the predictive accuracy of the constructed nomogram was high. We found that using immunotherapy with new immune checkpoint inhibitors (ICIs) was more beneficial for patients in the LRG. In addition, we can learn from the chemotherapeutic drug model that patients with LRG are more sensitive to cisplatin and imatinib. Conclusions In short, the prognostic prediction model based on neutrophil-related genes will help to predict the prognosis and guide the precise treatment of BLCA.

Objectives Forkhead Box P4 (FOXP4) is a transcription factor that promotes tumor formation and progression. However, studies on its roles in colorectal adenocarcinoma (CRAC) and cell proliferation regulation are few to date. This work investigates the expression of FOXP4 in CRAC, explores the characteristic of FOXP4 in different clinicopathological features, and analyzes its regulation of cell proliferation. Methods The GEPIA database was used to predict the trend of FOXP4 expression in colon cancer and normal mucosa. Tumor tissue and normal paracancerous mucosal tissue were sampled from 64 cases diagnosed with CRAC and who were receiving radical surgery at Tianjin Hospital from January 2017 and December 2022. FOXP4 and proliferating cell nuclear antigen (PCNA) were detected by the immunohistochemistry EnVision method. The colon cancer cell lines SW480, HCT15, and SW620 and the normal colon cell line NCM460 were selected, and expression of FOXP4 was detected by the Western blot method. The siRNA-FOXP4 plasmid was synthesized and transfected with SW480 and HCT15 cell lines, respectively, to establish si-FOXP4 groups, and empty vector transfection group (NC-FOXP4) and blank control group (NC) was set up. The expression levels of FOXP4 and PCNA were detected by the Western blot method, while the cell proliferation activity was assessed using CCK-8. Normally distributed quantitative data were compared between two and more groups with ANOVA (SNK-based pairwise comparison), while intergroup enumeration data comparisons were performed through χ 2 test and assessed through linear correlation analysis. Results GEPIA-based prediction shows a potential rise in FOXP4 expression in colon cancer. The rate of positive FOXP4 expression is significantly higher in CRAC tissue than in normal mucosa (p<0.05). The difference in FOXP4 is statistically significant in the comparison of maximum tumor diameter and depth of invasion in CRAC (p<0.05) but not in the comparison of gender, age, degree of differentiation, tumor focus, tumor embolism, and lymph node metastasis (p>0.05). The expression levels of FOXP4 and PCNA in CRAC are positively correlated (p<0.05). FOXP4 expression is significantly higher in cell lines SW480, HCT15, and SW620 than in cell line NCM460. The cell proliferation activity and PCNA expression are significantly lower in si-FOXP4 group than in NC-FOXP4 and NC groups for cell lines SW480 and HCT15. Conclusions FOXP4 is highly expressed and has a proliferative effect on tumor cells in CRAC.

Objectives To evaluate the anti-tumor activities of CD20/HLA-DR Crossmab CH1-CL through cell and animal models. Methods Based on “knobs-into-holes” and “crossover” technology, CrossMab, targeting CD20 and HLA-DR, was constructed. A binding assay and a competitive inhibition assay were performed to confirm its specificity. The effects of CrossMab on antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity were measured. Cell apoptosis, lysosome-mediated cell death, and lysosomal permeability were quantified. In addition, the effects of CrossMab on peripheral blood leukocytes were tested. The pharmacokinetics were determined with a noncompartmental analysis model. Human malignant lymphoma xenograft models in CB17-SCID mice were established for an in-vivo efficacy study. Results The antitumor activities of CrossMab were shown both in vitro and in vivo . CrossMab exhibited strong binding to CD20 and HLA-DR at the same time in Raji cells. CrossMab also demonstrated antilymphoma effects by inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Furthermore, CrossMab altered the lysosomal membrane permeability. The toxicity of CrossMab on normal peripheral blood lymphocytes (PBLs) was specific to B cells. A mouse xenograft model demonstrated the antitumor activities of CrossMab in vivo . Conclusions CrossMab exhibited an enhanced antigen recognition ability and antitumor activities in lymphoma without evident toxicity. CrossMab could be an effective immunotherapeutic strategy for non-Hodgkin lymphoma.

Objectives Gastric glomus tumor (GGT) is a rare mesenchymal tumor, mostly located in the gastric antrum region, and occasionally displays malignant behavior. Due to the lack of typical endoscopic or clinical features that distinguish GGT from other gastric submucosal tumors, the diagnosis is based primarily on postoperative histopathological and immunohistochemical findings. The first-line treatment is either local laparoscopic resection or open surgical intervention. Endoscopic resection techniques can also be used to successfully treat such lesions. Case presentation This case report presented a 39-year-old woman suffering from anorexia for the past 15 days. Barium upper gastrointestinal radiography suggested a benign space-occupying lesion in the antrum region. Endoscopically, a non-ulcerative, smooth submucosal lesion was observed in the greater curvature of the antrum. Endoscopic ultrasound (EUS) examination revealed a hypoechoic lesion with an anechoic zone in the center, originating from the muscularis propria layer of the stomach wall, which could be a gastrointestinal stromal tumor (GIST). Conclusions The lesion was successfully removed via submucosal tunneling endoscopic resection (STER). Based on histopathological and immunohistochemical findings, the patient was diagnosed with GGT.

Objectives This article analyzed the imaging features of 18 long bone metastasis (LBM) of renal cell carcinoma (RCC) confirmed by pathology and reviewed the available literature. Case presentation Patients who underwent radiographic examinations at our hospital between January 2015 and December 2021 with pathology-confirmed bone metastases were evaluated. The clinical and radiographs and CT, and MR images features of the patients were analyzed. Eighteen patients with pathology-confirmed LBM from RCC were collected. All the patients had X-ray examinations, 15 had computed tomography (CT), 13 had magnetic resonance (MR) imaging, and six had MR enhancement. The clinical and imaging features of the lesions were analyzed, including morphological and signal intensity characteristics. Ten patients were found with metastases after nephrectomy, and eight patients were admitted to the hospital with skeletal-related events (SREs). Eighteen cases originated from clear cell RCC. Fourteen lesions were located in the epiphysis and four in the diaphysis. The height-to-width ratio of the lesions ranged from 1.11 to 3.41 (mean, 1.84). All lesions showed osteolytic destruction, with 16 lesions showing expansile destruction. Seven lesions demonstrated soap bubble hyperintensity and hypointense separation on T2-weighted images. Six lesions demonstrated a flow-void sign, and six showed marked marginal enhancement. Conclusions The LBM of RCC mainly occurred in the proximal epiphysis and tended to spread along the long bone axis with expansile osteolytic destruction. In some cases, soap bubble hyperintensity, hypointense separation, and the flow-void sign were seen.

Obejectives Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, comparising various subtypes including classical PTC (accounting for approximately 55–65 % of cases) and several variants. The identified variants include papillary microcarcinoma, encapsulated variant, follicular variant, diffuse sclerosing variant, tall cell variant, columnar cell variant, cribriform-morular variant, and Warthin-like variant (WLV-PTC). WLV-PTC is a rare malignant neoplasm. Case presentation The present study introduced two cases of WLV-PTC from Affiliated Hospital of Chengde Medical College in retrospect. The macroscopic characteristics, histological feature, immunophenotyping, gene mutations, local invasion, and distant metastasis of the tumors were observed, and the relevant literature on WLV-PTC was reviewed. The tumor cells exhibited nuclear the characteristics similar to those of classic papillary thyroid carcinoma. Immunohistochemical analysis showed strong positivity for thyroid transcription factor 1, cytokeratin 19, Galectin-3, and CK, weak positivity for thyroglobulin, and the Ki-67 proliferation index ranging from 5 to 10 %. Gene mutation analysis revealed that Case 1 had a BRAF V600E mutation, whereas Case 2 had a wild-type mutation. WLV-PTC has histological features similar to those of Warthin tumor originating from salivary gland. Conclusions The prognosis of WLV-PTC is similar to that of conventional PTC of comparable size and stage.