Pathology, research and practice最新文献

The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to multiple waves of infections globally. As the virus continues to evolve, new variants have emerged, some with concerning changes in transmissibility and virulence. Among these variants, the "FLiRT Variants" have recently gained attention due to their potential to alter the dynamics of transmission and disease severity. According to the Infectious Disease Society of America, the nickname ‘FLiRT’ is based on the technical names for their mutations. The FLiRT variants, particularly KP.2, seem to exhibit heightened transmissibility in comparison to earlier Omicron sub-variants. Additionally, they demonstrate a capacity to evade immunity conferred by prior infection and vaccines, although the full extent of this evasion is still being investigated. In this article, we review the characteristics of the FLiRT variants, including their genetic mutations, epidemiological features, potential impact on public health measures, and implications for vaccine efficacy. We also discuss strategies for surveillance, prevention, and mitigation efforts to control the spread of this variant and mitigate its impact on global health.

Cancer remains a current active problem of modern medicine, a process during which cell growth and proliferation become uncontrolled. However, the role of autophagy in the oncological processes is counterintuitive and, at the same time, increasingly influential on the formation, development, and response to therapy of oncological diseases. Autophagy is a vital cellular process that removes defective proteins and organelles and supports cellular homeostasis. Autophagy can enhance the ability to form new tumors and suppress this formation in cancer. The dual potential of apoptosis may be the reason for this duality in either promoting or impeding the survival of cancer cells, depending on the situation, including starvation or treatment stress. Furthermore, long non-coding RNA NEAT1, which has been linked to several stages of carcinogenesis and in all forms of the illness, has drawn attention as a major player in cancer biology. NEAT1 is a structural portion of nuclear paraspeckles and has roles in deactivating expression in both transcriptional and post-transcriptional levels. NEAT1 acts in carcinogenesis in numerous ways, comprising interactions with microRNAs, the influence of gene articulation, regulation of epigenetics, and engagement in signalling cascades. In addition, the complexity of NEAT1’s role in cancer occurrence is amplified by its place in regulating cancer stem cells and the tumor microenvironment. NEAT1’s interaction with autophagy further complicates the already complicated function of this RNA in cancer biology. NEAT1 has been linked to autophagy in several types of cancer, influencing autophagy pathways and altering its stress response and tumor cell viability. Understanding the interrelation between NEAT1, autophagy, and cancer will enable practitioners to identify novel treatment targets and approaches to disrupt oncogenic processes, reduce the occurrence of treatment resistance, and increase patient survival rates. Specialized treatment strategies and regimens are thus achievable. In the present review, the authors analyze sophisticated relationship schemes in cancer: The NEAT1 pathway and the process of autophagy.

Background

Several studies on biomarker properties of microRNAs from liquid biopsy in prostate cancer (PCa) identified miR-146a-5p as a potential novel diagnostic marker. However, other studies with the same or similar topic failed to confirm the supposed discriminatory ability of miR-146a-5p, for which reason we aimed at elucidating the potential biomarker role of circulatory/urinary miR-146a-5p in PCa by conducting a qualitative and quantitative data synthesis.

Methods

Eligible articles were identified by searching PubMed, Scopus and Web of Science databases. Open MetaAnalyst software was used for pooling data on sensitivity, specificity, likelihood ratio and diagnostic odds ratio (OR) of miR-146a-5p.

Results

A total of 15 articles were eligible for qualitative data synthesis, while the results from 13 studies with 2080 participants were included in the meta-analysis. The established between-study heterogeneity was high, while the expression of hsa-miR-146a was associated with a diagnostic OR of 3.544 (P < 0.001; 95 %CI 2.186–5.747). Pooled sensitivity was found to be lower than 70 % (0.655, 95 %CI 0.573–0.729, P < 0.001), while the obtained value for specificity was 65 % (95 %CI 0.583–0.709, P < 0.001). Segregating studies according to ethnicity, sample type or the type of controls did not result in significantly higher sensitivity and specificity in subgroups, compared to the overall pooled data.

Conclusions

The resulting pooled sensitivity, specificity and diagnostic OR do not qualify miR-146a-5p for a reliable diagnostic biomarker of PCa.

Aims

In this proof-of-concept study, we propose a new method for automated digital quantification of PRAME (PReferentially expressed Antigen of MElanoma) as a diagnostic aid to distinguish between benign and malignant melanocytic lesions. The proposed method utilizes immunohistochemical virtual double nuclear staining for PRAME and SOX10 to precisely identify the melanocytic cells of interest, which is combined with digital image analyse to quantify a PRAME-index.

Methods

Our study included 10 compound nevi, 3 halo nevi, and 10 melanomas. Tissue slides were stained with PRAME, scanned, the cover glass removed, stained with SOX10, scanned again, and finally analysed digitally. The digitally quantified PRAME-index was compared with a manual qualitative assessment by a dermatopathologist using the standard PRAME-scoring system.

Results

The digitally quantified PRAME-index showed a sensitivity of 70 % and a specificity of 100 % for separating melanomas from benign lesions. The manual qualitative PRAME-score showed a sensitivity of 60 % and a specificity of 100 %. Comparing the two methods using ROC-analyses, our digital quantitative method (AUC: 0.931, 95 % CI: 0.834;1.00, SD: 0.050) remains on par with the manual qualitative method (AUC: 0.877, 95 % CI: 0.725;1.00, SD: 0.078).

Conclusion

We found our novel digital quantitative method was at least as precise at classifying lesions as benign or malignant as the current manual qualitative assessment. Our method has the advantages of being operator-independent, objective, and replicable. Furthermore, our method can easily be implemented in an already digitalized pathology department. Given the small cohort size, more studies are to be done to validate our findings.

The purpose of this review is to present a comprehensive overview of the literature published up to February 2024 on the PubMed database regarding the development of mitral valve disease, with detailed reference to mitral valve prolapse, from embryology to a genetic profile. Out of the 3291 publications that deal with mitral valve embryology, 215 refer to mitral valve genetics and 83 were selected for further analysis. After reviewing these data, we advocate for the importance of a gene-based therapy that should be available soon, to prevent or treat non-invasively the valvular degeneration.

Background

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of three receptors commonly targeted in breast cancer treatment. In this study, the research focused on investigating the role of centrosomal protein 55 (CEP55) in TNBC progression and its interaction with the transcription factor Spi-1 proto-oncogene (SPI1).

Methods

Various techniques including qRT-PCR, western blotting, and immunohistochemistry assays were utilized to examine gene expression patterns. Functional assays such as wound-healing assay, transwell invasion assay, 5-Ethynyl-2’-deoxyuridine assay, and metabolic assays were conducted to assess the impact of CEP55 on the behaviors of TNBC cells. CD163-positive macrophages were quantified by flow cytometry. The chromatin immunoprecipitation assay and dual-luciferase reporter assay were performed to assess the association of SPI1 with CEP55. A xenograft mouse model experiment was used to analyze the impact of SPI1 on tumor development in vivo.

Results

CEP55 and SPI1 expression levels were significantly upregulated in TNBC tissues and cells. The depletion of CEP55 led to decreased TNBC cell migration, invasion, proliferation, glucose metabolism, and M2 macrophage polarization, indicating its crucial role in promoting TNBC progression. Moreover, SPI1 transcriptionally activated CEP55 in TNBC cells, and its overexpression was associated with accelerated tumor growth in vivo. Further, CEP55 overexpression relieved SPI1 silencing-induced inhibitory effects on TNBC cell migration, invasion, proliferation, glucose metabolism, and M2 macrophage polarization.

Conclusion

SPI1-mediated transcriptional activation of CEP55 plays a key role in enhancing TNBC cell migration, invasion, proliferation, glucose metabolism, and M2 macrophage polarization. These insights provide valuable information for potential targeted therapies to combat TNBC progression by modulating the SPI1-CEP55 axis.

Background

microRNAs (miRNAs) are crucial regulators of various biological processes and molecular functions. Aberrant miRNA expression has been linked in many studies to neoplastic transformation. Among these miRNAs, dysregulation of miR-301b-5p was associated with different types of cancer including breast cancer. Although many research works have investigated the function of miR-301b in carcinogenesis, few have examined its expression, biological, and clinical implications in breast cancer.

Methods

we examined the expression levels of miR-301b-5p in human cancerous breast tissue compared to normal breast controls using different bioinformatic tools and RT-qPCR analyses.

Results

we detected that miR-301b-5p was differentially expressed in cancerous breast tissue when compared to normal controls. MiR-301b-5p was detected to be upregulated in high-grade (Grade 3) and triple-negative breast cancers. A significant strong positive correlation was detected between miR-301b and Ki-67, the commonly used proliferative marker in breast cancer. Bioinformatics analyses using the KM plotter revealed that miR-301b has significant prognostic power in assessing the OS of patients with breast cancer. The study also identified many fundamental biological processes and regulatory pathways associated with the investigated miR-301b-related hub genes. Interestingly, the expression pattern and prognostic significance of PTEN, the top hub gene regulated by miR-301b, highlighted the prognostic significance of PTEN in breast cancer.

Conclusion

The current study findings suggest the potential use of miR-301b-5p as a possible diagnostic and prognostic biomarker in breast cancer. Moreover, this study emphasized the clinical and biological relevance of miR-301b-5p in breast cancer.

The PI3K/Akt pathway plays a critical role in the progression and treatment of oral squamous cell carcinoma (OSCC). Recent research has uncovered the involvement of long non-coding RNAs (lncRNAs) in regulating this pathway, influencing OSCC cell proliferation, survival, and metastasis. This review explores the latest findings on how certain lncRNAs act as either cancer promoters or cancer inhibitors within the PI3K/Akt signaling pathway. Certain lncRNAs act as oncogenic or tumor-suppressive agents, making them potential diagnostic and prognostic markers. Targeting these lncRNAs may lead to novel therapeutic strategies. The evolving fields of precision medicine and artificial intelligence promise advancements in OSCC diagnosis and treatment, enabling more personalized and effective patient care.

Multidisciplinary team (MDT) meetings have emerged as a promising approach for the treatment of cancer patients. These meetings involve a team of healthcare professionals from different disciplines working together to develop a holistic, patient-centered treatment. Although MDT meetings are well established in oncology, they play a minor role in other diseases. Recent evidence suggests that the implementation of MDT meetings can improve patient outcomes in musculoskeletal infections.

The aim of this retrospective, observational study was to present the agenda of our multidisciplinary limb board including live microscopy with a special focus on the pathologist’s role. The descriptive analysis of the limb board included 66 cases receiving live microscopy at the meeting and a total of 124 histopathological findings and 181 stainings. We could elucidate that pathologists seem to play an important role especially in clarifying the correct diagnosis. In 80.3 % of the findings, the pathologist specified the clinical diagnosis of the requesting physician leading to a consensus-based treatment plan for each patient.

The implementation of MDT meetings including live microscopy in patients with musculoskeletal infections holds potential benefits, such as improved communication, scientific collaboration, and raising clinicians' awareness and understanding of histopathology findings. However, potential challenges, such as organizational effort and technical prerequisites should be considered.

Cadherin 17 (CDH17) and claudin 18.2 (CLDN18.2) are highly selective markers of intestinal and gastric lineages and are expressed in adenocarcinomas of various organs. They have also been identified as potential targets for immunotherapy. Expression of CDH17 and CLDN18.2 has been observed in a subset of pancreatic neuroendocrine tumours (PanNETs). This study investigates the immunohistochemical expression of CDH17 and CLDN18 in PanNETs in comparison with hormonal expression profiles to provide baseline data for determining candidate indications for targeted therapy with CDH17 and CLDN18.2 in PanNETs, including insulinomas (n = 22), glucagonomas (n = 13), gastrinomas (n = 3), serotoninomas (n = 2) and PanNETs not otherwise specified (NOS) (n = 17). In the normal pancreas, CDH17 was expressed in the lateral membrane of ducts and some islet cells, whereas CLDN18 was occasionally expressed in the intercalated ducts and centroacinar cells. In PanNETs, CDH17 and CLDN18 was detected by membranous staining. CDH17 expression was observed in 9 to 17 (58.8 %) PanNETs NOS, 3 of 13 (23.1 %) glucagonomas, 1 of 3 (33.3 %,) gastrinomas, 1 of 2 (50 %) serotoninomas, and none of the insulinomas. According to predefined criteria, 7 of 17 (41.2 %) PanNETs NOS, 1 of 3 (33.3 %) gastrinomas, and 1 of 2 (50 %) serotoninomas were classified as CDH17-positive. There were no significant differences in clinicopathological features between CDH17-positive and CDH17-negative PanNETs, except for a higher tumour grade in the former (p<0.05). For CLDN18, expression was noted in 2 out of 3 (66.7 %) gastrinomas, one with focal staining and the other with diffuse staining. One of three (33.3 %) gastrinomas was classified as CLDN18-positive using predefined criteria. These findings suggest that a particular subset of PanNETs, including PanNET NOS, gastrinoma, and serotoninoma, may be potential candidates for CDH17-targeted immunotherapy. Additionally, gastrinoma may be a potential candidate for immunotherapy targeting CLDN18.2.