Pathology, research and practice最新文献

T cells are essential to the immune system's reaction. The major job of the immune system is to identify and get rid of any abnormal or malignant cells in the body. White blood cells called T cells coordinate and carry out immunological responses, including identifying and eliminating cancer cells. It mostly consists of two types called helper T-cells and cytotoxic T-cells. Together, they create an efficient reaction against cancer. Both the primary T cell subtype – CD4+ and CD8+ Tcells have specific role to play in our immune system.CD4+ T cells are limited to MHC-II molecules and acts as helper cell by activating and enhancing other immune cells. On the other side CD8+ T cells are called the killer cells as they eradicate the abnormal and contaminated cells and are limited to MHC-I molecules. The malignant cells are destroyed when cytotoxic T cells come into direct contact with them. This happens via number of processes, including TCR recognition, the release of cytotoxic chemicals, and finally the activation of the immune system. T cell receptors on the surface of cytotoxic T cells allow them to identify tumour cells and these T cells release harmful chemicals like perforins and granzymes when they connect to malignant cells. T-cells that have been stimulated release cytokines such as gamma interferon. T-cells can also acquire memory responses that improve their capacity for recognition and response. Helper T-cells contribute to the development of an immune response. It entails coordination and activation as well as the enlistment of additional immune cells, including macrophages and natural killer cells, to assist in the eradication of cancer cells. Despite the fact that the cancer frequently creates defence systems to circumvent their immune response. Together, these activities support the immune surveillance and T-cell-mediated regulation of cancer cells. Treatments like chemotherapy, radiation, and surgery are main ways to treat cancer but immunotherapy has been emerging since last few decades. These immune specific treatments have shown huge positive result. CAR T cell therapy is a promising weapon to fight again blood cancer and it works by focusing on our immune system to fight and eliminate cancer.

Colorectal cancer (CRC) is a major global health concern, with rising incidence and mortality rates. Conventional treatments often come with significant complications, prompting the exploration of natural compounds like curcumin as potential therapeutic agents. Using bioinformatic tools, this study investigated the role of curcumin in CRC treatment. Significant protein interactions between curcumin and target proteins were identified in the STITCH database. Differentially expressed genes (DEGs) associated with CRC were then analyzed from GEO databases. Comparing curcumin targets and CRC-related DEGs, nine significant common targets were identified: DNMT1, PCNA, CCND1, PLAU, MMP3, SOX9, FOXM1, CXCL2, and SERPINB5. Pathway enrichment analyses revealed that curcumin-targeted pathways were primarily related to p53, IL-17, NF-kappa B, TNF, and cell cycle signaling, all crucial in CRC development and progression. Further analyses using DAID and EnrichR algorithms showed that the curcumin targets exhibited greater specificity to bronchial epithelial cells and colorectal adenocarcinoma than other diseases. Analyses via the DSigDB database indicated that curcumin ranks highly among other drugs targeting the identified CRC-related genes. Docking studies revealed favorable binding interactions between curcumin and the key CRC-related proteins, suggesting potential molecular mechanisms by which curcumin may exert its effects. In summary, this study provides bioinformatic and docking evidence that curcumin may exert beneficial effects on CRC by modulating the expression or activity of multiple CRC-susceptibility genes involved in critical signaling pathways. These findings warrant further experimental validation and support the potential of curcumin as a therapeutic agent for CRC.

Background and Aims

Oral squamous cell carcinoma (OSCC) is among the most malignant cancers in the world and has a high mortality rate. MicroRNAs (miRNAs) have progressively gained attention due to their roles in the pathogenesis and maintenance of various kinds of cancers, including OSCC. In this research, we carried out a scoping review to analyze the role of miRNA and therapeutic response in OSCC and focus on target axes associated with miRNA that inhibit metastasis and cell proliferation in OSCC.

Methods

This review adhered to a six-stage methodology framework and PRISMA guidelines. Three databases were systematically searched to find eligible articles until July 2024. Two reviewers conducted publication screening and data extraction independently. 54 articles meeting the predefined inclusion criteria were successfully identified. Quality assessment was done using the QUIN checklist specified for dental in vitro studies.

Results

Studies with different designs reported 53 miRNAs that were experimentally validated to act as therapeutic targets in OSCC in vivo and in vitro studies. The study found that 25 miRNAs were up-regulated in OSCC patients and cell lines, while another 25 were down-regulated. Mir-186 was also found to be up- and down-regulated in two different investigations. The study highlights the potential of six microRNAs (miR-32–5p, miR-195–5p, miR-3529–3p, miR-191, miR-146b-5p, and miR-377–3p) as anti-proliferation, migration, and invasion therapeutics for OSCC treatment. Two miRNAs (miR-302b and miR-18a) are identified as anti-metastatic therapeutics, while four miRNAs (miR-617, miR-23a-3p, miR-105, miR-101) are anti-proliferation therapeutics.

Conclusion

The study recommends that restoring the expression of tumor suppressor miRNAs may be a suitable cancer therapy. Utilizing this technology does present certain difficulties, and resolving them will improve the methods for miRNA transfer to target cells. With more research and the resolution of associated issues, miRNA can be employed as an efficient therapeutic method for OSCC.

Currently, CAR-T cell therapy relies on an individualized manufacturing process in which patient's own T cells are infused back into patients after being engineered and expanded ex vivo. Despite the astonishing outcomes of autologous CAR-T cell therapy, this approach is endowed with several limitations and drawbacks, such as high cost and time-consuming manufacturing process. Switching the armature of CAR-T cell therapy from autologous settings to allogeneic can overcome several bottlenecks of the current approach. Nevertheless, the use of allogeneic CAR-T cells is limited by the risk of life-threatening GvHD. Thus, in recent years, developing a method to move CAR-T cell therapy to allogeneic settings without the risk of GvHD has become a hot research topic in this field. Since the alloreactivity of αβ T-cell receptor (TCR) accounts for developing GvHD, several efforts have been made to disrupt endogenous TCR of allogeneic CAR-T cells using gene editing tools to prevent GvHD. Nonetheless, the off-target activity of gene editing tools and their associated genotoxicities, as well as the negative consequences of endogenous TCR disruption, are the main concerns of using this approach. As an alternative, CAR αβ-T cells can be replaced with other types of CAR-engineered cells that are capable of recognizing and killing malignant cells through CAR while avoiding the induction of GvHD. These alternatives include T cell subsets with restricted TCR repertoire (γδ-T, iNKT, virus-specific T, double negative T cells, and MAIT cells), killer cells (NK and CIK cells), non-lymphocytic cells (neutrophils and macrophages), stem/progenitor cells, and cell-free extracellular vesicles. In this review, we discuss how these alternatives can move CAR-based immunotherapy to allogeneic settings to overcome the bottlenecks of autologous manner without the risk of GvHD. We comprehensively discuss the pros and cons of these alternatives over the traditional CAR αβ-T cells in light of their preclinical studies and clinical trials.

Aim

The objective of this study was to investigate the pooled prevalence and possible association between polyomavirus infection and lung cancer.

Methods

A systematic publication search was conducted by identifying relevant cross-sectional and case-control studies from major online databases. Heterogeneity, OR, and corresponding 95 % CI were applied to all studies through meta-analysis and forest plot. Random effects models were used to calculate the overall pooled prevalence. Visual inspection of a funnel plot plotting the log-transformed OR and its associated standard error of the log (OR) was combined with the Begg and Egger test to examine the presence and influence of publication bias. Analyzes were performed using Stata software v.14.1.

Results

23 articles (33 datasets) were included in the meta-analysis, of which 14 datasets were case/control and the rest were cross-sectional studies. The pooled polyomavirus infection rate in lung cancer patients was 0.06 % (0.02–0.11 %). In subgroup analysis, the pooled prevalence of JCV, MCPyV, KI, SV40, BKV, WU, MU, and STL was 21 %, 7 %, 6 %, 2 %, 0 %, 0 %, 0 %, and 0 % respectively. An association has been found between polyomavirus infection and lung cancer [summary OR 6.33 (95 % CI (1.76–22.77); I2=67.45 %)]. The subgroup analysis, based on the virus type, showed a strong association between MCPyV and lung cancer [summary OR 13.61 (95 % CI 2.41–76.59; I2=40.0 %)]. despite the high prevalence of JCV DNA in lung cancer tissue, analysis of case-control studies showed that JCV is not associated with lung cancer and does not increase the risk of lung cancer.

Conclusion

This study showed a significant association between polyomaviruses infection with lung cancer. The results also revealed a pooled prevalence of 6 % for polyomaviruses in lung tumor patients. Altogether, the findings of the present work suggest that Merkel cell polyomavirus infection is a potential risk factor for lung cancer.

Background

Mutations of the TP53 oncosuppressor gene are frequent events in patients with malignant tumors including IDH-wildtype GBM (GBM IDH wt). However, the effective impact of TP53 mutations on prognosis has been poorly evaluated.

Methods

We performed a retrospective study investigating the impact of TP53 mutations on patients with GBM IDH wt. Only patients with PS=0–1, treated with temozolomide concurrent with and adjuvant to radiotherapy, and younger than 70 years assessed with NGS were included in the analysis.

Results

97 GBM IDH wt have been selected. The median follow-up was 34.5 months (95 %CI, 30.6 – NA). Overall, 20 patients (19.4 %) presented a TP53 mutation. There were no significant differences in terms of TERT mutation (75 % vs 79.2 %) between TP53 mutated and TP53 wild-type (wt) patients. We detected 6 TP53 mutations not previously described within GBM IDH wt patients. The overall survival (OS) did not significantly differ between TP53 mutated and wt patients (HR 0.69, 95 %CI 0.37–1.27, p = 0.24). Considering only patients with an OS longer than 36 months (n = 10), the presence of a TP53 mutation was significantly associated with prolonged survival (45.6 months vs Not Reached, p = 0.037).

Conclusion

The presence of a TP53 mutation does not appear to be correlated with overall survival in this patient cohort. While there is an association with survival for patients with an OS of 36 months or longer, the number of patients is low and there is no available evidence correlating TP53 mutations to long-term survivors.

Melanoma can pose a significant diagnostic challenge due to the high variability in histological morphology and expression of non-melanocytic immunomarkers. We present a case of a 47-year-old male with an aggressive mediastinal neoplasm and disseminated disease posing several diagnostic challenges. Multiple biopsies were submitted from different anatomic locations and during multiple time points showing an undifferentiated round cell tumor (URCT) with synovial sarcoma-like immunophenotype. SS18::SSX fusion was sought through NGS study for diagnostic confirmation. NGS results revealed NRAS and CDKN2A mutations and absence of fusions, resulting in a new review of the histologic material with a broader immunohistochemical panel, finding strong positivity to melanic antibodies. This case is an illustrative example of a malignant melanoma with small round cell morphology showing aberrant expression of CD99, BCL2, TLE1 and SS18-SSX antibodies exposing a potentially hazardous pitfall highlighting the importance of a wide differential diagnosis and the role of confirmational studies with molecular tests.

Background

The human cytochrome P450 (CYP) superfamily encompasses different categories of isoenzymes that contribute to multiple metabolic processes involving drug detoxification, cellular signaling, and the proliferation of malignant tissues. Using genetic technology, customized bioinformatic analysis, and meta-analysis design, the main goal of this study was to identify the association between the CYP1A2*rs762551 variant and the susceptibility to breast carcinoma (BRCA).

Methods

The case-control study was conducted based on 104 BRCA women and 102 healthy controls. Using the TaqMan allelic discrimination assay, the CYP1A2 (rs762551; c.–9–154 C>A) variant was genotyped. Bioinformatic frameworks and logistic regression analysis were used to assess the involvement of this genetic variant in BRCA development. A meta-analysis design was accomplished based on our case-control study and other previously published records. Publication bias, heterogeneity between studies, and trial sequential analysis (TSA) were analyzed.

Results

The CYP1A2*rs762551 variant conferred protection against BRCA development under allelic (OR = 0.48, p-value < 0.001), dominant (OR = 0.34, p-value < 0.001), and recessive (OR = 0.44, p-value = 0.011) models. However, this intronic variant was correlated with a decreased risk of BRCA among late-onset menopause women compared to other cases. Bioinformatic analysis confirmed that this genetic variant has a functional impact on the progression of tumorgenesis. Moreover, this meta-analysis design included 12922 BRCA women and 15603 healthy controls. Our findings disclosed the contribution of the CYP1A2*rs762551 variant with protection against cancer development among Caucasian females under allelic (OR = 0.75, p-value = 0.025), and dominant (OR = 0.58, p-value = 0.015) models.

Conclusions

This case-control study confirmed the contribution of the CYP1A2*rs762551 variant with decreased risk of BRCA development among Egyptian subjects. Moreover, BRCA women with late-onset menopause conferred protection against cancer progression compared to other subjects. Our findings identified that this meta-analysis design achieved protection against BRCA development among Caucasian women compared to other ethnicities.

One of the mainstays of cancer treatment is chemotherapy. Drug resistance, however, continues to be the primary factor behind clinical treatment failure. Gene expression is regulated by long non-coding RNAs (lncRNAs) in several ways, including chromatin remodeling, translation, epigenetic, and transcriptional levels. Cancer hallmarks such as DNA damage, metastasis, immunological evasion, cell stemness, drug resistance, metabolic reprogramming, and angiogenesis are all influenced by LncRNAs. Numerous studies have been conducted on LncRNA-driven mechanisms of resistance to different antineoplastic drugs. Diverse medication kinds elicit diverse resistance mechanisms, and each mechanism may have multiple contributing factors. As a result, several lncRNAs have been identified as new biomarkers and therapeutic targets for identifying and managing cancers. This compels us to thoroughly outline the crucial roles that lncRNAs play in drug resistance. In this regard, this article provides an in-depth analysis of the recently discovered functions of lncRNAs in the pathogenesis and chemoresistance of cancer. As a result, the current research might offer a substantial foundation for future drug resistance-conquering strategies that target lncRNAs in cancer therapies.