Pathology, research and practice最新文献

Long non-coding RNAs (lncRNAs) have been identified as important participants in several biological functions, particularly their complex interactions with the KRAS pathway, which provide insights into the significant roles lncRNAs play in cancer development. The KRAS pathway, a central signaling cascade crucial for cell proliferation, survival, and differentiation, stands out as a key therapeutic target due to its aberrant activation in many human cancers. Recent investigations have unveiled a myriad of lncRNAs, such as H19, ANRIL, and MEG3, intricately modulating the KRAS pathway, influencing both its activation and repression through various mechanisms, including epigenetic modifications, transcriptional regulation, and post-transcriptional control. These lncRNAs function as fine-tuners, delicately orchestrating the balance required for normal cellular function. Their dysregulation has been linked to the development and progression of multiple malignancies, including lung, pancreatic, and colorectal carcinomas, which frequently harbor KRAS mutations. This scrutiny delves into the functional diversity of specific lncRNAs within the KRAS pathway, elucidating their molecular mechanisms and downstream effects on cancer phenotypes. Additionally, it underscores the diagnostic and prognostic potential of these lncRNAs as indicators for cancer detection and assessment. The complex regulatory network that lncRNAs construct within the context of the KRAS pathway offers important insights for the creation of focused therapeutic approaches, opening new possibilities for precision medicine in oncology. However, challenges such as the dual roles of lncRNAs in different cancer types and the difficulty in therapeutically targeting these molecules highlight the ongoing debates and need for further research. As ongoing studies unveil the complexities of lncRNA-mediated KRAS pathway modulation, the potential for innovative cancer interventions becomes increasingly promising.

The fast spread and severe consequences of novel coronavirus disease 2019 (COVID-19) have once again underscored the critical necessity of early detection of viral infections. Several serology-based techniques, including as point-of-care assays and high-throughput enzyme immunoassays that support the diagnosis of COVID-19 are utilized in the detection and identification of coronaviruses. A rapid, precise, simple, affordable, and adaptable diagnostic tool is required for controlling COVID-19 as well as for outbreak management, since the calculation and monitoring of viral loads are crucial for predicting the infection stage and recovery time. Nowadays, the most popular method for diagnosing COVID-19 is reverse transcription polymerase chain reaction (RT-PCR) testing, and chest computed tomography (CT) scans are also used to determine the disease's phases. This is all because of the fact that RT-PCR method caries with itself a number of downsides comprising of being immovable, expensive, and laborious. RT-PCR has not well proven to be capable of detection on the very early infection stages. Nanomaterial-based diagnostics, together with traditional clinical procedures, have a lot of promise against COVID-19. It is worthy of attention that nanotechnology has the mainstay capacity for purposes of developing even more modern stratagems fighting COVID-19 by means of focusing on state-of-the-art diagnostics. What we have centered on in this review, is bringing out even more efficient detection techniques whereby nanobiosensors are employed so that we might obstruct any further development and spreading of SARS-CoV-2.

Modern cancer research depends heavily on the identification and validation of biomarkers because they provide important information about the diagnosis, prognosis, and response to treatment of the cancer. This review will provide a comprehensive overview of cancer biomarkers, including their development phases and recent breakthroughs in transcriptomics and computational techniques for detecting these biomarkers. Blood-based biomarkers have great potential for non-invasive tumor dynamics and treatment response monitoring. These include circulating tumor DNA, exosomes, and microRNAs. Comprehensive molecular profiles are provided by multi-omic technologies, which combine proteomics, metabolomics, and genomes to support the identification of biomarkers and the targeting of therapeutic interventions. Genetic changes are detected by next-generation sequencing, and patterns of protein expression are found by protein arrays and mass spectrometry. Tumor heterogeneity and clonal evolution can be understood using metabolic profiling and single-cell studies. It is projected that the use of several biomarkers-genetic, protein, mRNA, microRNA, and DNA profiles, among others-will rise, enabling multi-biomarker analysis and improving individualised treatment plans. Biomarker identification and patient outcome prediction are further improved by developments in AI algorithms and imaging techniques. Robust biomarker validation and reproducibility require cooperation between industry, academia, and doctors. Biomarkers can provide individualized care, meet unmet clinical needs, and enhance patient outcomes despite some obstacles. Precision medicine will continue to take shape as scientific research advances and the integration of biomarkers with cutting-edge technologies continues to offer a more promising future for personalized cancer care.

Breast cancer (BC) is the most common cancer among women, characterized by significant heterogeneity. Diagnosis of the disease in the early stages and appropriate treatment plays a crucial role for these patients. Despite the available treatments, many patients due to drug resistance do not receive proper treatments. Recently, circular RNAs (circRNAs), a type of non-coding RNAs (ncRNAs), have been discovered to be involved in the progression and resistance to drugs in BC. CircRNAs can promote or inhibit malignant cells by their function. Numerous circRNAs have been discovered to be involved in the proliferation, invasion, and migration of tumor cells, as well as the progression, pathogenesis, tumor metastasis, and drug resistance of BC. Circular RNAs can also serve as a biomarker for diagnosing, predicting prognosis, and targeting therapy. In this review, we present an outline of the variations in circRNAs expression in various BCs, the functional pathways, their impact on the condition, and their uses in clinical applications.

Warthin tumor (WT) is the second most common benign parotid gland tumor after pleomorphic adenoma. WT is characterized by cystic and papillary proliferation of a two-layered oncocytic epithelium supported by lymphoid tissue. Heterotopic salivary duct inclusions (SDIs) are frequently observed in lymph nodes (LNs) of WT (SDI/LNs), and are thought to be the origin of WT. If this is true, SDIs should also persist in the lymphoid tissue of WT itself (SDI/WT), as a missing link between SDIs and WTs, but studies of this issue are limited. From 2008–2023, 138 WT cases were surgically excised at our hospital. SDI/LNs and SDI/WTs were histologically examined. Of 100 WT cases with LNs, SDI/LNs were observed in 67 cases (67 %). SDI/WTs were detected in 114 of 138 cases (82.6 %), including 107 of 127 smokers (84.3 %) and 7 of 11 never-smokers (63.6 %). SDI/WTs were located mainly in the subcapsular lymphoid tissue and often surrounded by a fibrous coat resembling salivary excretory ducts. This study revealed a high incidence of SDIs in WT itself, strongly supporting the theory that WT develops from heterotopic salivary ducts.

Purpose

The management of indeterminate thyroid nodules remains a topic of ongoing debate, particularly regarding the differentiation of malignancy. Somatic mutation analysis offers crucial insights into tumor characteristics. This study aimed to assist the clinical management of indeterminate nodules with somatic mutation analysis. Methods: Aspiration samples from 20 indeterminate thyroid nodules were included in the study. A next-generation sequencing panel containing 67 genes was used for molecular profiling. The results were compared with pathology data from surgical material, which is considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: Variants in six genes (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) were detected in 10 out of 20 samples. We identified nine Tier 1 or 2 variants in 10 (67 %) out of 15 malignant nodules (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) and one Tier 2 (PIK3CA) variant in one out of five benign nodules. The study demonstrated an NPV of 40 %, a PPV of 90 %, a specificity of 80 %, and a sensitivity of 60 %. Conclusion: Based on the detected molecular markers, at least nine patients (45 %) could be managed correctly without needing a repeat FNAB attempt. This study underscores the clinical practicality of molecular tests in managing nodules with indeterminate cytology. Additionally, this study emphasizes the importance of considering the patient's age when determining the DNA- or RNA-based genetic testing method. Finally, we discussed the significance of the somatic mutation profile and its impact on the current pathological classification.

Colorectal cancer (CRC) remains a significant global health challenge, marked by increasing incidence and mortality rates in recent years. The pathogenesis of CRC is complex, involving chronic inflammation of the intestinal mucosa, heightened immunoinflammatory responses, and resistance to apoptosis. The suppressor of cytokine signaling (SOCS) family, comprised of key negative regulators within cytokine signaling pathways, plays a crucial role in cell proliferation, growth, and metabolic regulation. Deficiencies in various SOCS proteins can trigger the activation of the Janus kinase (JAK) and signal transducers and activators of transcription (STAT) pathways, following the binding of cytokines and growth factors to their receptors. Mounting evidence indicates that SOCS proteins are integral to the development and progression of CRC, positioning them as promising targets for novel anticancer therapies. This review delves into the structure, function, and molecular mechanisms of SOCS family members, examining their roles in cell proliferation, apoptosis, migration, epithelial-mesenchymal transition (EMT), and immune modulation. Additionally, it explores their potential impact on the regulation of CRC immunotherapy, offering new insights and perspectives that may inform the development of innovative therapeutic strategies for CRC.

Objectives

Alcohol drinking is a major risk factor for head and neck cancer (HNC), and this risk may be modified by alcohol dehydrogenase (ADH) genes. The first systematic review and meta-analysis was designed with more studies and added trial sequential analysis and functional analysis for a better understanding of the role of ADH3 polymorphism in HNC patients.

Methods

A search was performed across several databases, including PubMed/Medline, Web of Science, Scopus, and Cochrane Library, up to May 5, 2024, without any restrictions to find pertinent studies. The RevMan 5.3 software was used to calculate the effect sizes. These were expressed as the odds ratio (OR) with a 95 % confidence interval.

Results

Twenty-seven articles were included in the meta-analysis. The frequency of *1/*1, *1/*2, and *2/*2 genotypes in cases with HNC was 47.14 %, 41.06 %, and 11.80 %, respectively, and in controls was 50.56 %, 38.29 %, and 11.15 %, respectively. The pooled OR for the allelic model is 1.11 (p = 0.18), for the homozygous model is 0.95 (p = 0.64), for the heterozygous model is 0.99 (p = 0.90), for the dominant model is 1.11 (p = 0.14), and for the recessive model is 0.98 (p = 0.78). In the Asians, the three models showed an increased significant association. In the cancer subtype subgroup, a protective significant association was found in the pharyngeal cancer subtype.

Conclusions

The current analysis suggests that ADH3 polymorphism may not have a significant impact on the risk of HNC, but the polymorphism had an increased risk in Asians and a protective role in pharyngeal cancers.

Different types of cytokines, growth factors, or hormones present within the tumor microenvironment that can activate the JAK-STAT signaling pathway by binding to their specific cell surface receptors. The constitutive activation of the JAK-STAT pathway can promote uncontrolled cell proliferation and prevent apoptosis contributing to tumor development. Activation of the JAK-STAT pathway is controlled by several regulatory molecules, particularly the suppressor of cytokine signaling (SOCS) family consisting of eight members, which include SOCS1-SOCS7 and the cytokine-inducible SH2-containing (CIS) proteins. In prostate cancer cells, the irregular expression of the SOCS1-SOCS3, SOCS5-SOCS7 as well as CIS can similarly and differentially result in the initiation of various cellular signaling pathways (in particular JAK-STAT3, MAPK, ERK) that promote cell proliferation, migration, invasion and viability; cell cycle progression; epithelial-mesenchymal transition; angiogenesis; resistance to therapy; immune evasion; and chronic inflammation within the tumor microenvironment which lead to tumor progression, metastasis and poor prognosis. Epigenetic modifications, mainly due to DNA methylation, microRNAs, pro-inflammatory cytokines, growth factors and androgens can influence the expression of the SOCS molecules in prostate cancer cells. Using strategies to modulate, restore or enhance the expression of SOCS proteins, may help overcome treatment resistance and improve the efficacy of existing therapies. In this review, we provide a comprehensive explanation regarding SOCS dysregulation in prostate cancer to provide insights into the mechanisms underlying the dysregulation of SOCS proteins. This knowledge may pave the way for the development of novel therapeutic strategies to manage prostate cancer by restoring and modulating the expression of SOCS molecules.