A bibliometric and visualization analysis of research trends and hotspots on targeted therapy for breast cancer from 2003 to 2022.

Background: Breast cancer is a significant public health issue, exhibiting the most pronounced occurrence and fatality rates among malignant neoplasms globally. Targeted therapy is a medical intervention that focuses on specific molecular markers. This study aims to investigate and evaluate the current research trends and directions in the field of targeted therapy for breast cancer using bibliometric analysis. Method: The Web of Science database was utilized to retrieve relevant articles published between 2003 and 2022. The VOSviewer software and Bibliometrix package in the R language were employed to conduct co-occurrence and clustering analyses of authors, countries, institutions, journals, references, and the CiteSpace tool was utilized for keyword burst detection. Results: A total of 2,258 articles were included and the annual number of publications increased rapidly. The most prolific country on this topic was the USA (n=898, 39.77%) and the University of Texas MD Anderson Cancer Center published most papers (n=93). Dennis J. Slamon and Gabriel N. Hortobagyi stood out in the field, with Dennis J. Slamon leading in terms of co-citations(n=653) and Gabriel N. Hortobagyi topping the list in terms of published articles(n=18). The most productive journal was Breast Cancer Research and Treatment and the most cited journal was Journal of Clinical Oncology. The clustering of keywords indicated that the primary focus of researches in the past two decades was on the development and clinical evaluation of tumor-targeted drugs associated with the epidermal growth factor receptor (EGFR) family signaling pathway, and explored mechanisms related to biological behavior of breast cancer. Keywords co-occurrence and burst analysis identified current research hotspots and potential research trends. Conclusion: This study employed bibliometric analysis to examine research on targeted therapy for breast cancer over a span of 20 years, and identified development trends of research and elucidated potential research trajectories in the domain of this topic. This study helps in the identification of prospective collaborators and partner institutions for researchers.

A Two-Stage End-to-End Deep Learning Framework for Pathologic Examination in Skin Tumor Diagnosis.

Neurofibromas (NFs), Bowen disease (BD), and seborrheic keratosis (SK) are common skin tumors. Pathologic examination is the gold standard for diagnosis of these tumors. Current pathologic diagnosis is primarily based on microscopic observation, which is laborious and time-consuming. With digitization, artificial intelligence can be used to improve the efficiency of pathologic diagnosis. This research aims to develop an end-to-end extendable framework for the diagnosis of skin tumor based on pathologic slide images. NF, BD, and SK were selected as target skin tumors. A two-stage skin cancer diagnosis framework is proposed in this article, which consists of two parts: patches-wise diagnosis, and slide-wise diagnosis. Patches-wise diagnosis compares different convolutional neural networks to extract features and distinguish categories from patches generated in whole slide images. Slide-wise diagnosis combines attention graph gated network model prediction with post-processing algorithm. This approach can fuse information from feature-embedding learning and domain knowledge to draw conclusions. Training, validation, and testing were performed on NF, BD, SK, and negative samples. Accuracy and receiver operating characteristic curves were used to evaluate the classification performance. This study investigated the feasibility of skin tumor diagnosis from pathologic images and may be the first instance of applying deep learning to address these three types of tumor diagnoses in skin pathology.

Comparative analysis of nutritional and transcriptional regulation of hacd1 in large yellow croaker (Larimichthys crocea) and rainbow trout (Oncorhynchus mykiss).

3-hydroxyacyl-CoA dehydratases 1 (Hacd1) is a critical enzyme in long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The difference in expression of hacd1 might account for the stronger capacity of LC-PUFA biosynthesis in freshwater fish than in marine fish, but little is known about fish hacd1. Therefore, this study compared the responses of large yellow croaker and rainbow trout hacd1 to different oil sources or fatty acids, and also examined transcriptional regulation of this gene. In this study, hacd1 was highly expressed in the liver of large yellow croaker and rainbow trout, which is the main organ for LC-PUFA biosynthesis. Therefore, we cloned the hacd1 coding sequence, with a phylogenetic analysis showing that this gene is evolutionarily conserved. Its localization to the endoplasmic reticulum (ER), likely also indicates a conserved structure and function. The expression of hacd1 in the liver was significantly decreased after the substitution of soybean oil (SO) for fish oil but was not significantly affected after palm oil (PO) substitution. Linoleic acid (LA) incubation significantly promoted hacd1 expression in primary hepatocytes of large yellow croaker and eicosapentaenoic acid (EPA) incubation significantly promoted hacd1 expression in primary hepatocytes of rainbow trout. Transcription factors STAT4, C/EBPα, C/EBPß, HNF1, HSF3 and FOXP3 were identified in both large yellow croaker and rainbow trout. HNF1 had a stronger activation effect in rainbow trout than in large yellow croaker. FOXP3 inhibited hacd1 promoter activity in large yellow croaker but had no effect in rainbow trout. Therefore, the differences between HNF1 and FOXP3 affected the expression of hacd1 in the liver thus being responsible for the high capacity of LC-PUFA biosynthesis in rainbow trout.

HMGB3 Targeted by miR-145-5p Impacts Proliferation, Migration, Invasion, and Apoptosis of Breast Cancer Cells.

This study focused on the investigation into how HMGB3 works in breast cancer (BC) progression. Firstly, we analyzed the relationship between HMGB3 and BC patients through the TCGA database. We performed qRT-PCR for determining the HMGB3 mRNA level and Western blot for detecting the protein level of HMGB3 in BC cell lines. CCK-8, flow cytometry, transwell, and wound healing assays were utilized to detect the effect of HMGB3 on BC cell phenotypes. Next, the prediction of the binding site shared by miR-145-5p and HMGB3 was performed by the bioinformatics method. The targeting relationship between miR-145-5p and HMGB3 was validated by using dual-luciferase assay. Finally, rescue experiments were employed for assessing the effect of the miR-145-5p/HMGB3 axis on BC cells. HMGB3 was demonstrated to have a high-level expression in BC cell lines and facilitated BC progression. On the contrary, miR-145-5p was shown a low-level expression in BC cell lines, which could target HMGB3. miR-145-5p restrained the proliferation, migration, and invasion of BC cells via inhibiting HMGB3.

Circ_0008035 promotes the progression of gastric cancer via the regulation of miR-1256/CEACAM6 axis.

Gastric cancer (GC) is one of the most common malignant tumors. Circular RNA (circRNA) has been shown to be involved in the progression of GC. However, the function of circ_0008035 in GC has not been studied. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0008035, microRNA-1256 (miR-1256) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and transwell assay were used to detect cell function. Western blot examined the protein levels of Ki67, Bax, MMP-2, and CEACAM6. The relationship between miR-1256 and circ_0008035 or CEACAM6 was verified by dual-luciferase reporter assays and RNA pull down. The xenotransplantation model was established in BALB/c nude mice to study the role of circ_0008035 in vivo. Circ_0008035 and CEACAM6 were significantly high-expressed in GC tissues and cells. Silencing of circ_0008035 reduced GC cell proliferation, migration, and invasion while enhancing apoptosis. MiR-1256 was a target of circ_0008035. The inhibition effect of circ_0008035 knockdown on the malignant behavior of GC cells could be reversed by miR-1256 inhibitor. In addition, CEACAM6 was a target of miR-1256. Overexpression of CEACAM6 partially restored the inhibitory effect of miR-1256 on cell progression. Animal experiments confirmed the anti-tumor effect of circ_0008035 knockdown in vivo. Collectively, circ_0008035 regulated the expression of CEACAM6 by sponging miR-1256, thereby promoting the development of GC. Our data provided a novel targeted therapy for GC.

Research on the effect of interfering with miRNA-155 on triple-negative breast cancer cells.

BACKGROUND: Triple negative breast cancer (TNBC) is a poor prognosis breast cancer with the highest mutation rate and limited treatment options. MiR-155 is highly expressed in TNBC, but its role and potential mechanism in TNBC remain to be elucidated. OBJECTIVE: The aim of this study is to examine the effect of interfering with miRNA-155 on the inflammatory pathway of NLRP 3 in TNBC (MDA-MB-231). METHODS: MiRNA-155-specific interference (Si-miR-155) on MDA-MB-231 cell was manifested by transfection of miRNA-155 inhibitor. Meanwhile, blank control (Blank) and negative control (NC) were set. Cell growth and proliferation rate were detected by MTT; apoptosis rate were detected by flow cytometry; colony forming test was used to detected cell viability; cell migration ability was detected by Wound healing assay; TNF-α, IL-18, IL-6 and IL-1ß levels were detected by ELISA. The mRNA of miRNA-155, NLRP3, ASC, caspase-1 and Ki67 were detected by qRT-PCR. The expression levels of NLRP3, caspase-1, ASC and Ki67 were detected by Western blotting. RESULTS: The proliferation rate of Si-miRNA-155 group decreased, while the apoptosis rate increased significantly. After interfering with miRNA-155, the number of cancer cell colonies and the migration ability was decreased, and the secretion levels of IL-18, TNF-α, IL-6 and IL-1ß were also inhibited. Moreover the mRNA and protein expression of NLRP3, caspase-1, ASC and Ki67 were significantly suppressed. CONCLUSIONS: Interference with miRNA-155 can inhibit the NLRP3 pathway of MDA-MB-231 cells, as well as the proliferation, migration and inflammatory factor secretion of MDA-MB-231 cell, and can accelerate its apoptosis.

Development and Validation of an Artificial Intelligence-Based Image Classification Method for Pathological Diagnosis in Patients With Extramammary Paget's Disease.

Extramammary Paget's disease (EMPD) is a rare, malignant cutaneous adenocarcinoma with a high recurrence rate after surgical resection. Early diagnosis of EMPD is critical as 15%-40% of cases progress into an invasive form and resulting in a dismal prognosis. However, EMPD can be a diagnostic challenge to pathologists, especially in the grassroots hospital, because of its low incidence and nonspecific clinical presentation. Although AI-enabled computer-aided diagnosis solutions have been extensively used in dermatological pathological image analysis to diagnose common skin cancers such as melanoma and basal cell carcinoma, these techniques have yet been applied to diagnose EMPD. Here, we developed and verified a deep learning method with five different deep convolutional neural networks, named ResNet34, ResNet50, MobileNetV2, GoogLeNet, and VGG16, in Asian EMPD pathological image screening to distinguish between Paget's and normal cells. We further demonstrated that the results of the proposed method are quantitative, fast, and repeatable by a retrospective single-center study. The ResNet34 model achieved the best performance with an accuracy of 95.522% in pathological images collected at a magnification of ×40. We envision this method can potentially empower grassroots pathologists' efficiency and accuracy as well as to ultimately provide better patient care.

Analysis of apolipoprotein multigene family in spotted sea bass (Lateolabrax maculatus) and their expression profiles in response to Vibrio harveyi infection.

Apolipoproteins (Apos), which are the protein components of plasma lipoproteins, play important roles in lipid transport in vertebrates. It has been demonstrated that in teleosts, several Apos display antimicrobial activity and play crucial roles in innate immunity. Despite their importance, apo genes have not been systematically characterized in many aquaculture fish species. In our study, a complete set of 23 apo genes was identified and annotated from spotted sea bass (Lateolabrax maculatus). Phylogenetic and homology analyses provided evidence for their annotation and evolutionary relationships. To investigate their potential roles in the immune response, the expression patterns of 23 apo genes were determined in the liver and intestine by qRT-PCR after Vibrio harveyi infection. After infection, a total of 20 differentially expressed apo genes were observed, and their expression profiles varied among the genes and tissues. 5 apo genes (apoA1, apoA4a.1, apoC2, apoF and apoO) were dramatically induced or suppressed (log2 fold change >4, P < 0.05), suggesting their involvement in the immune response of spotted sea bass. Our study provides a valuable foundation for future studies aimed at uncovering the specific roles of each apo gene during bacterial infection in spotted sea bass and other teleost species.

Prognostic value of the Glasgow prognostic score in colorectal cancer: a meta-analysis of 9,839 patients.

PURPOSE: The aim of this study was to perform a systematic review and meta-analysis to evaluate the value of the Glasgow prognostic score (GPS) or modified Glasgow prognostic score (mGPS) in patients with colorectal cancer (CRC). METHODS: A comprehensive medical literature search was performed using the online databases PubMed, Embase, Web of Science, and the Cochrane Library. After extracting basic characteristics and prognostic data from the included studies, overall survival (OS) and cancer-specific survival (CSS) were pooled as primary outcomes. Subgroup analyses were performed according to therapeutic strategies, models, cutoff values, regions, tumor, node, metastasis stages, sample size, and ages. RESULTS: Forty-three independent cohorts from 41 studies with 9,839 CRC patients were included in the present study. Correlation between GPS or mGPS and OS was analyzed in 32 cohorts of 7,714 patients, and 23 independent cohorts of 5,375 patients focused on the correlation between GPS or mGPS and CSS. The overall outcomes showed that patients with elevated GPS or mGPS were associated with poor OS (HR: 2.20, 95% CI: 1.88-2.57, P<0.001). Elevated GPS or mGPS also resulted in worse CSS (HR: 1.86, 95% CI: 1.59-2.17, P<0.001). The results of the subgroup analyses confirmed the overall outcomes. CONCLUSION: GPS or mGPS is an accurate prognostic predictor in patients with CRC. Patients with elevated pretreatment GPS or mGPS have a poor prognosis. Subgroup analyses confirmed the overall outcomes. Pretreatment GPS is a useful biomarker in the management of CRC.

Lack of association between the risk of prostate cancer and vitamin D receptor Bsm I polymorphism: a meta-analysis of 27 published studies.

BACKGROUND: The association between vitamin D receptor gene Bsm I (rs1544410) polymorphism and prostate cancer (PCa) risk has been investigated by numerous previous studies, which yielded inconsistent results. We conducted this meta-analysis to derive a relatively precise description of this association. METHODS: All studies published up to December 2017 were identified via a systematic search of PubMed, Embase, and China National Knowledge Infrastructure databases. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to describe the strength of the relationship between Bsm I and PCa risk. RESULTS: In this meta-analysis, 27 studies with 9,993 cases and 9,345 controls were included. The pooled results revealed that Bsm I polymorphism was not associated with PCa risk in the overall analysis. Moreover, no significant relationship was found in the subgroup analyses by ethnicities, genotyping methods, Hardy-Weinberg equilibrium status, and Gleason score. In the stratified analysis by the source of controls and clinical stages, controls of benign prostatic hyperplasia (BPH) seemed to be in the particular groups in which the association of PCa risk with Bsm I polymorphism was significant (Bb vs. bb: OR=0.643, 95% CI=0.436-0.949, p=0.026; BB/Bb vs. bb: OR=0.627, 95% CI=0.411-0.954, p=0.029; B vs. b: OR=0.715, 95% CI=0.530-0.965, p=0.029). CONCLUSION: Our results suggest that Bsm I polymorphism is weakly associated with PCa risk, and hence, it cannot be considered as a predictor of the occurrence and development of PCa in clinical practice. Future studies with a larger number of samples are needed to verify our results.

Vitamin D receptor Taq I polymorphism and the risk of prostate cancer: a meta-analysis.

Numerous previous studies reported the association of Vitamin D receptor gene Taq Ipolymorphism with prostate cancer risk, however these results were controversial. In order to provide a relatively comprehensive description of this relationship, we conducted this meta-analysis by searching PubMed, Embase, and China National Knowledge Infrastructure. Finally, 36 studies with 8,423 cases and 8,887 controls were included. Taq I polymorphism was found to marginally increase the prostate cancer risk in recessive genetic model (tt/Tt vs. TT: Odds Ratio (OR) = 0.89, 95% Confidence Interval (CI) = 0.80-1.00, p = 0.05) and allele genetic model (t vs. T allele: OR = 0.91, 95% CI = 0.84-0.99, p = 0.003) in the overall analysis. Subgroup analyses showed that significant increased risk was found in Asians in homozygote model (tt vs. TT: OR = 0.63, 95% CI = 0.41-0.95, p = 0.029) and allele genetic model (t vs. T: OR = 0.78, 95% CI = 0.67-0.90, p = 0.002), and in the subgroup of population-based controls in all the genetic models. These results suggest that Taq Ipolymorphism might be a risk factor of prostate cancer risk, especially in Asians. It could be considered as a promising target to predict the prostate cancer risk for clinical practice.

Excellent surface-enhanced Raman scattering (SERS) based on AgFeO2 semiconductor nanoparticles.

A simple hydrothermal method was employed to synthesize AgFeO2 nanoparticles, which were utilized as substrates in SERS detection of Rhodamine 6G and 4-mercaptobenzoic acid. The magnetic properties of the products provided the capability of concentrating analyte molecules under an external magnetic field. The detection in aqueous solution has ensured the uniformity of the SERS signals and the reproducibility of the substrates. It was interesting that the substrates exhibited high SERS activity at Rhodamine 6G concentration of 1 × 10(-7) M with an enhancement factor of 5.1 × 10(5), showing the highest SERS effect for semiconductor substrates, which might be ascribed to the orderly orientation of AgFeO2 nanoparticles under external magnetic field.