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Pathology Oncology Research : POR 2024Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the... (Review)
Review
Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the gradual cut of smoking prevalence. Consequently, the relative frequency of adenocarcinoma increased while that of squamous and small cell carcinomas declined. During the last two decades a plethora of targeted drug therapies have appeared for the treatment of metastasizing non-small cell lung carcinomas (NSCLC). Personalized oncology aims to precisely match patients to treatments with the highest potential of success. Extensive research is done to introduce biomarkers which can predict the effectiveness of a specific targeted therapeutic approach. The EGFR signaling pathway includes several sufficient targets for the treatment of human cancers including NSCLC. Lung adenocarcinoma may harbor both activating and resistance mutations of the EGFR gene, and further, mutations of KRAS and BRAF oncogenes. Less frequent but targetable genetic alterations include ALK, ROS1, RET gene rearrangements, and various alterations of MET proto-oncogene. In addition, the importance of anti-tumor immunity and of tumor microenvironment has become evident recently. Accumulation of mutations generally trigger tumor specific immune defense, but immune protection may be upregulated as an aggressive feature. The blockade of immune checkpoints results in potential reactivation of tumor cell killing and induces significant tumor regression in various tumor types, such as lung carcinoma. Therapeutic responses to anti PD1-PD-L1 treatment may correlate with the expression of PD-L1 by tumor cells. Due to the wide range of diagnostic and predictive features in lung cancer a plenty of tests are required from a single small biopsy or cytology specimen, which is challenged by major issues of sample quantity and quality. Thus, the efficacy of biomarker testing should be warranted by standardized policy and optimal material usage. In this review we aim to discuss major targeted therapy-related biomarkers in NSCLC and testing possibilities comprehensively.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Biomarkers, Tumor; Proto-Oncogene Mas
PubMed: 38953007
DOI: 10.3389/pore.2024.1611733 -
Frontiers in Public Health 2024The need for health surveillance of former workers exposed to asbestos was provided by law in Italy after the asbestos ban in 1992.
BACKGROUND
The need for health surveillance of former workers exposed to asbestos was provided by law in Italy after the asbestos ban in 1992.
OBJECTIVES
We describe the results of the health surveillance of former workers exposed to asbestos, conducted over 27 years, from 1994 to 2020, at the Operative Unit of Occupational Medicine of the University Hospital of Bari.
MATERIALS AND METHODS
We adopted the health surveillance protocol, which was validated at the national level in 2018.
RESULTS
A total of 1,405 former workers exposed to asbestos were examined. We proceeded with diagnosing pathologies in 339 cases (24% of the cohort subjected to surveillance), with diagnoses of some cases involving multiple pathologies. Specifically, pleural plaques were diagnosed in 49.2% of the 339 cases, asbestosis in 35.9%, malignant pleural mesothelioma (MPM) in 20.3%, mesothelioma of the vaginal tunic of the testis (MTVT) in 9.1%, lung cancer in 5.8%, and laryngeal cancer in 0.8%.
CONCLUSION
Despite the 1992 asbestos ban, asbestos-related diseases remain a serious public health issue. It is important to establish criteria that ensure the health surveillance of formerly exposed workers minimizes costs, reduces the number of invasive examinations, and optimizes achievable results.
Topics: Humans; Italy; Occupational Exposure; Male; Asbestos; Hospitals, University; Female; Middle Aged; Asbestosis; Aged; Mesothelioma, Malignant; Adult; Lung Neoplasms; Population Surveillance; Pleural Neoplasms; Mesothelioma
PubMed: 38952736
DOI: 10.3389/fpubh.2024.1411910 -
Oncoimmunology 2024The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal... (Randomized Controlled Trial)
Randomized Controlled Trial
The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal cancer (CRC) might benefit from potentially immunogenic, short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade (ICB). Three of 38 patients assigned to this experimental treatment had metastases from -mutant MSS-CRC, in general a poor-prognostic subgroup explored here. The ≥70-year-old females presented with ascending colon adenocarcinomas with intermediate tumor mutational burden (6.2-11.8 mutations per megabase). All experienced early disappearance of the primary tumor followed by complete response of all overt metastatic disease, resulting in progression-free survival as long as 20-35 months. However, they encountered recurrence at previously unaffected sites and ultimately sanctuary organs, or as intrahepatic tumor evolution reflected in the terminal loss of initially induced T-cell clonality in liver metastases. Yet, the remarkable first-line responses to short-course oxaliplatin-based chemotherapy alternating with ICB may offer a novel therapeutic option to a particularly hard-to-treat MSS-CRC subgroup.
Topics: Humans; Oxaliplatin; Female; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Immune Checkpoint Inhibitors; Aged; Antineoplastic Combined Chemotherapy Protocols; Mutation; Microsatellite Instability; Treatment Outcome; Aged, 80 and over
PubMed: 38952672
DOI: 10.1080/2162402X.2024.2372886 -
Pakistan Journal of Medical Sciences Jul 2024Mixed-phenotype acute leukemia (MPAL) is rare in the clinic, accounting for approximately 2%-5% of acute leukemia cases. (Review)
Review
OBJECTIVES
Mixed-phenotype acute leukemia (MPAL) is rare in the clinic, accounting for approximately 2%-5% of acute leukemia cases.
METHODS
In this study the cohort included 126 patients, of which 125 cases were from re-examined published data and current patients from Shenzhen Longhua District Central Hospital, carrying an ETV6-ABL1 rearrangement from April 15, 2020 to December 19, 2020. The ETS variant transcription factor 6-Abelson proto-oncogene 1 (ETV6-ABL1) fusion gene is mainly seen in malignant hematological diseases such as acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myeloproliferative neoplasms (MPNs). Positivity of both MPAL and ETV6-ABL1 suggest a poor prognosis. This is the first report of B lymphocytic/myeloid mixed-phenotype acute leukemia with ETV6-ABL1 fusion gene positivity. Complete remission was achieved with chemotherapy for lymphoid and myeloid leukemia and targeted therapy with tyrosine kinase inhibitors (TKIs).
RESULTS
The level of ETV6-ABL1/ABL decreased from 23.056% to 11.165%. After consolidation chemotherapy, the patient underwent allogeneic hematopoietic stem cell transplantation but died due to intestinal rejection. There are 126 cases of ETV6-ABL1 fusion gene transcript expression in numerous hematologic malignancies reported to date, including 48 cases of ALL, 12 of AML, and 65 of MPN. Eosinophilia is a common characteristic, especially in MPN patients.
CONCLUSION
Survival analysis suggests that the survival time of ALL and MPN patients receiving TKI treatment is better than that of patients not receiving this treatment. Dasatinib or nilotinib, especially the former, is more effective than imatinib for MPN.
PubMed: 38952502
DOI: 10.12669/pjms.40.6.8497 -
Pediatric Blood & Cancer Jul 2024The objective of this study is to assess the concordance and added value of combined comparative genomic hybridization plus single-nucleotide polymorphism microarray...
BACKGROUND
The objective of this study is to assess the concordance and added value of combined comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH/SNP) analyses in pediatric acute lymphoblastic leukemia (ALL) risk stratification compared to conventional cytogenetic methods.
PROCEDURE
This is a retrospective study that included patients aged 1-18 years diagnosed with de novo ALL at Sainte-Justine Hospital between 2016 and 2021. Results from conventional cytogenetic and molecular analyses were collected and compared to those of CGH/SNP.
RESULTS
A total of 135 ALL patients were included. Sample failures or non-diagnostic analyses occurred in 17.8% cases with G-banding karyotypes versus 1.5% cases with CGH/SNP. The mean turnaround time for results was significantly faster for CGH/SNP than karyotype with 5.8 versus 10.7 days, respectively. The comparison of ploidy assessment by CGH/SNP and G-banding karyotype showed strong concordance (r = .82, p < .001, r= .68). Furthermore, G-banding karyotype did not detect additional clinically relevant aberrations that were missed by the combined analysis of CGH/SNP and fluorescence in situ hybridization. The most common gene alterations detected by CGH/SNP were deletions involving CDKN2A (35.8%), ETV6 (31.3%), CDKN2B (28.4%), PAX5 (20.1%), IKZF1 (12.7%), and copy-neutral loss of heterozygosity (CN-LOH) of 9p (9.0%). Among these, only ETV6 deletion was found to have a significant prognostic impact with superior event-free survival in both univariate and multivariate analyses (adjusted hazard ratio 0.08, 95% confidence interval: 0.01-0.50, p = .02).
CONCLUSION
CGH/SNP provided faster, reliable, and highly concordant results than those obtained by conventional cytogenetics. CGH/SNP identified recurrent gene deletions in pediatric ALL, of which ETV6 deletion conferred a favorable prognosis.
PubMed: 38952259
DOI: 10.1002/pbc.31129 -
MicroRNA (Shariqah, United Arab... Jun 2024This study aims to investigate the potential role of lncRNA NR2F2-AS1 in the development of gastric cancer by affecting the levels of miR-320b and BMI1.
Investigating the Association between LncRNA NR2F2-AS1, miR-320b, and BMI1 in Gastric Cancer: Insights into Expression Profiles as Potential Biomarkers for Disease Management.
AIM
This study aims to investigate the potential role of lncRNA NR2F2-AS1 in the development of gastric cancer by affecting the levels of miR-320b and BMI1.
BACKGROUND
Gastric cancer is a high-mortality malignancy, and understanding the underlying molecular mechanisms is crucial. Non-coding RNAs play an important role in gene expression, and their dysregulation can lead to tumor initiation and progression.
OBJECTIVE
This study aims to determine the pathological role of LncRNA NR2F2-AS1 in gastric cancer progression and its association with the clinicopathological characteristics of patients.
METHODS
Bioinformatics databases were used to predict the expression levels and interactions between the studied factors to achieve this objective. The expression pattern of NR2F2-AS1/miR- 320b/BMI1 in 40 pairs of tumor and adjacent normal tissues was examined using RT-PCR, IHC, and western blot. The correlation, ROC curve, and survival analyses were also conducted for the aforementioned factors.
RESULTS
The results showed an increase of more than 2-fold for BMI-1 and lncRNA NR2F2-AS1 in lower stages, and the elevation continued with the increasing stage of the disease. This correlated with significant downregulation of miR-320b and PTEN, indicating their association with gastric cancer progression and decreased patient survival. LncRNA NR2F2-AS1 acts as an oncogene by influencing the level of miR-320b, altering the amount of BMI1. A reduction in the amount of miR-320b against lncRNA NR2F2-AS1 and BMI1 directly correlates with a reduced overall survival rate of patients, especially if this disproportion is more than 3.0. ROC curve analysis indicated that alteration in the lncRNA NR2F2-AS1 level showed more than 98.0% sensitivity and specificity to differentiate the lower from higher stages of GC and predict the early onset of metastasis.
CONCLUSION
In conclusion, these results suggest that NR2F2-AS1/miR-320b/BMI1 has the potential to be a prognostic as well as diagnostic biomarker for gastric cancer.
PubMed: 38952161
DOI: 10.2174/0122115366291818240606112725 -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Macrophage migration inhibitor factor (MIF), as a pro-inflammatory and oncogenic cytokine, is highly expressed in a variety of malignant tumors and recruits tumor cells... (Review)
Review
Macrophage migration inhibitor factor (MIF), as a pro-inflammatory and oncogenic cytokine, is highly expressed in a variety of malignant tumors and recruits tumor cells or immune cells into the tumor microenvironment. MIF affects the development of tumor by altering the tumor microenvironment. In the process of tumor, MIF not only plays an anti-inflammatory role, but also promotes tumorigenesis by immune escape and immune tolerance.This is closely related to immune cells that play a role in the tumor immune response, mainly including natural killer (NK) cells, macrophages, dendritic cells, B cells, T cells and myeloid-derived suppressor cells. The article summarizes the role of MIF in tumor immune and the relationship between MIF and the development of malignant tumors, in order to provide new ideas and possible therapy for tumor treatment.
Topics: Macrophage Migration-Inhibitory Factors; Humans; Neoplasms; Animals; Tumor Microenvironment; Killer Cells, Natural; Macrophages; Dendritic Cells; T-Lymphocytes
PubMed: 38952097
DOI: No ID Found -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To verify the anti-tumor effect of the mesenchymal-epithelial transition single-chain antibody (Met scFv) on subcutaneously transplanted tumors in nude mice....
Objective To verify the anti-tumor effect of the mesenchymal-epithelial transition single-chain antibody (Met scFv) on subcutaneously transplanted tumors in nude mice. Methods A tumor model was established in nude mice by subcutaneous injection of A549 lung adenocarcinoma cells. Once the tumors were formed, IRDye680 LT N-hydroxysuccinimide (NHS) ester-labeled Met scFv was administered intraperitoneally. Real-time monitoring was conducted using a small animal imager to observe the dynamic distribution of the antibody in tumor-bearing mice. The affinity between c-Met and the antibody in tumor cells was detected. Tumor volume changes were observed and the tumor growth curve were plotted following regular tail vein injections of Met scFv. Immunohistochemical staining was employed to determine whether Met scFv could effectively bind to the c-Met antigen in tumor tissues. Results The distribution of Met scFv in nude mice showed that it was primarily located in the peritoneal cavity within the first 3 hours. After approximately 48 hours, fluorescent signals began to accumulate in the tumor tissue. Immunohistochemical staining of the tumors revealed high expression of c-Met in the tumor tissues; regular tail vein injections of Met scFv significantly slowed down the growth of tumors in mice. Conclusion Met scFv specifically recognizes tumor cells in vivo and exhibites significant anti-tumor activity.
Topics: Animals; Humans; Proto-Oncogene Proteins c-met; Mice, Nude; Single-Chain Antibodies; Lung Neoplasms; A549 Cells; Mice; Adenocarcinoma of Lung; Injections, Intraperitoneal; Adenocarcinoma; Xenograft Model Antitumor Assays; Mice, Inbred BALB C; Cell Line, Tumor
PubMed: 38952095
DOI: No ID Found -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To identify immune-related transcription factors (TFs) in renal glomeruli and tubules from diabetic kidney disease (DKD) patients by bioinformatics analysis....
Objective To identify immune-related transcription factors (TFs) in renal glomeruli and tubules from diabetic kidney disease (DKD) patients by bioinformatics analysis. Methods Gene expression datasets from GEO (GSE30528, GSE30529) and RNA sequencing (RNA-seq) data from the Karolinska Kidney Research Center were used. Gene set enrichment analysis (GSEA) was conducted to examine differences in immune-related gene expression in the glomeruli and tubules (DKD) patients. To identify immune-related genes (IRGs) and TFs, differential expression analysis was carried out using the Limma and DESeq2 software packages. Key immune-related TFs were pinpointed through co-expression analysis. The interaction network between TFs and IRGs was constructed using the STRING database and Cytoscape software. Furthermore, the Nephroseq database was employed to investigate the correlation between the identified TFs and clinical-pathological features. Results When compared to normal control tissues, significant differences in the expression of immune genes were observed in both the glomeruli and tubules of individuals with Diabetic Kidney Disease (DKD). Through differential and co-expression analysis, 50 immune genes and 9 immune-related transcription factors (TFs) were identified in the glomeruli. In contrast, 131 immune response genes (IRGs) and 41 immune-related TFs were discovered in the renal tubules. The protein-protein interaction (PPI) network highlighted four key immune-related TFs for the glomeruli: Interferon regulatory factor 8 (IRF8), lactotransferrin (LTF), CCAAT/enhancer binding protein alpha (CEBPA), and Runt-related transcription factor 3 (RUNX3). For the renal tubules, the key immune-related TFs were FBJ murine osteosarcoma viral oncogene homolog B (FOSB), nuclear receptor subfamily 4 group A member 1 (NR4A1), IRF8, and signal transducer and activator of transcription 1 (STAT1). These identified TFs demonstrated a significant correlation with the glomerular filtration rate (GFR), highlighting their potential importance in the pathology of DKD. Conclusion Bioinformatics analysis identifies potential genes associated with DKD pathogenesis and immune dysregulation. Further validation of the expression and function of these genes may contribute to immune-based therapeutic research for DKD.
Topics: Humans; Diabetic Nephropathies; Transcription Factors; Computational Biology; Gene Expression Profiling; Kidney Glomerulus; Gene Regulatory Networks; Kidney Tubules
PubMed: 38952087
DOI: No ID Found -
Thoracic Cancer Jul 2024Phosphoribosyl pyrophosphate synthetase 2 (PRPS2) is known as an oncogene in many types of cancers, including lung cancer. However, its role in regulating...
BACKGROUND
Phosphoribosyl pyrophosphate synthetase 2 (PRPS2) is known as an oncogene in many types of cancers, including lung cancer. However, its role in regulating tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) remains unclear. Our study aimed to explore the involvement of PRPS2 in TAM and MDSC regulation.
METHODS
Stable Lewis lung cancer (LLC) cell lines were established using a lentivirus system. These LLC lines were then used to establish tumor model in mice. The levels of target genes were determined using qPCR, western blotting, and ELISA assays. The percentage of different immune cell types was analyzed using fluorescence-activated cell sorting. The chemotaxis ability of TAM and MDSC was evaluated using an in vitro transwell chemotaxis assay.
RESULTS
Notably, PRPS2 was found to regulate the chemotaxis of TAM and MDSC in tumor cells, as evidenced by the positive correlation of PRPS2 expression levels and abundance of TAM and MDSC populations. In addition, the expression of CCL2, mediated by PRPS2, was identified as a key factor in the chemotaxis of TAM and MDSC, as evidenced by a significant reduction in macrophages and MDSC numbers in the presence of the CCL2 antibody. Furthermore, in vivo experiments confirmed the involvement of PRPS2 in mediating CCL2 expression. PRPS2 was also found to regulate immune cell infiltration into tumors, whereas knockdown of CCL2 reversed the phenotype induced by PRPS2 overexpression. In tumor tissues from mice implanted with LLC-PRPS2-shCCL2 cells, a notable increase in CD4+ and CD8+ T cell percentages, alongside a marked decrease in TAMs, M-MDSC, and PMN-MDSC, was observed.
CONCLUSION
Taken together, PRPS2 plays a crucial role in modulating the antitumor immune response by reprogramming CCL2-mediated TAM and MDSC.
PubMed: 38952044
DOI: 10.1111/1759-7714.15398