International journal of clinical and experimental pathology最新文献

Objective: Although the combination of atezolizumab and bevacizumab (A+B) shows promise for advanced hepatocellular carcinoma (HCC), its response rate is still inadequate. Previous studies indicate that the integration of FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) with transarterial chemoembolization (TACE) is advantageous for the management of HCC. This meta-analysis aims to assess the safety and efficacy of the A+B+TACE or HAIC therapy protocol in patients with advanced HCC.

Method: We collected pertinent studies from databases such as PubMed, Cochrane Library, Web of Science, and Embase, all published prior to August 1, 2024. We used Stata MP 14.0 software for data analysis, incorporating data extraction and quality assessment procedures.

Results: Data synthesis employed a fixed-effects model in certain contexts and a random-effects model where significant variability was present. A total of 405 patients were involved over ten trials. The overall objective response rate (ORR) was 57.2% (95% CI, 46.9-67.6%), and the disease control rate (DCR) was 85.9% (95% CI, 82.0-89.7%), as determined by the modified response assessment criteria in solid tumors (mRECIST). The rates for complete response (CR) and partial response (PR) were 10.8% (95% CI, 5.0-16.6%) and 45.5% (95% CI, 38.0-53.0%), respectively. The median progression-free survival (mPFS) was 10.9 months, with a 95% confidence interval (CI) of 8.0 to 13.8. 91.0% (95% CI: 84.9-97.1%) of patients experienced adverse events (AEs) of any severity during therapy, with 24.8% (95% CI: 8.8-40.9%) reporting AEs of grade 3 or higher.

Conclusion: The A+B+TACE-HAIC therapy demonstrates promising efficacy and tolerance for the management of advanced HCC.

Background: Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder in which the immune system mistakenly attacks the myelin sheath, affecting the communication between the brain and the rest of the body.

Objective: This study investigated the prophylactic use of peptide inhibitor of trans-endothelial migration (PEPITEM), a novel peptide, in alleviating experimental autoimmune encephalomyelitis (EAE), a mouse model for Multiple Sclerosis (MS).

Methods: Female C57BL/6 female mice were assigned to the control, untreated EAE, or PEPITEM group. EAE was induced in mice in the untreated EAE and PEPITEM groups through immunization by injecting an emulsion containing myelin oligodendrocyte glycoprotein 35-55 in complete Freund's adjuvant. Mice in these groups subsequently received PEPITEM or scramble peptide injections daily for 21 days. Then, all mice were euthanized to obtain samples for histologic and immunohistochemical analyses of central nervous system lymphocytic infiltrate. Levels of biomarkers, including myelin basic protein, microtubule-associated protein 2 (MAP-2), interleukin-17 (IL-17), and forkhead box P3 (Foxp3), were evaluated in both serum and spinal cord lysates using western blotting and enzyme-linked immunosorbent assay.

Results: In the PEPITEM group, EAE onset was significantly delayed and disease severity was reduced compared to the untreated EAE group. Analysis of spinal cord tissues revealed a marked reduction in inflammatory cell infiltration following PEPITEM administration. Furthermore, PEPITEM treatment led to significantly reduced IL-17 and Foxp3 levels, highlighting its potential in mitigating inflammatory responses.

Conclusion: PEPITEM has potent prophylactic potential against MS, providing a robust foundation for further exploration.

Background: B-cell specific Moloney MLV insertion site-1 (Bmi-1) belongs to the polycomb group (PcG) gene and is a transcriptional suppressor to maintain appropriate gene expression patterns during development. To investigate whether the Bmi-1 gene has a corrective effect on bone senescence induced in Bmi-1^-/- mice through regulating the bone microenvironment.

Methods: Littermate heterozygous male and female mice (Bmi-1^+/-) were used in this study. Related experiments were performed in wild type mice (10 mice, WT group) and Bmi-1 knock out mice (10 mice, BKO group) for analysis of phenotype, skeletal radiography, micro-computed tomography, histology, immunohistochemical staining, western blot analysis, and detection of ROS levels.

Results: Our results indicated that the Bmi-1 gene could proportionally rescued mice suffering from bone aging induced by Bmi-1 gene defects. Bmi-1 plays an anti-aging effect in bone through multiple aspects, such as increasing osteoblast bone formation and decreascing osteoclast bone absorption, stimulating proliferation, reducing apoptosis, inhibiting reactive oxygen species (ROS) and delaying DNA damage.

Conclusions: Our results suggested that Bmi-1 may play a fundamental and important role in correcting bone senescence in BKO mice. At the same time, it may provide theoretical basis for the clinical application of Bmi-1 in anti-aging in bone.

Objectives: Ovarian cancer is a gynecologic tumor with the highest mortality rate worldwide. Nonetheless, chemoresistance remains a significant obstacle in treating ovarian cancer. PARP inhibitors (PARPis) are effective drugs approved for maintenance therapy in ovarian cancer. However, the development of natural or acquired resistance to PARPis poses a major challenge for ovarian cancer treatment.

Methods: Public database analysis of cGAS expression in relation to PARPi resistance. cCK-8 assay was used to determine cell survival. qPCR assay with Western Blot was implemented to determine gene expression and protein activation status.

Results: Analysis of public databases revealed significantly higher cGAS expression in Olaparib-resistant cells and in recurrent ovarian tumors. Furthermore, high cGAS expression significantly promoted Olaparib tolerance in ovarian cancer cells. Our findings demonstrate that Olaparib treatment induces activation of the TBK1-IRF3 signaling axis downstream of cGAS, leading to the production of type I interferon. This, in turn, activates NF-κB and IL-6-STAT3 signaling, contributing to inflammation and PARPi resistance. Consequently, targeting cGAS effectively counteracts Olaparib resistance and enhances its efficacy in suppressing cancer cell growth, ultimately leading to cell death.

Conclusions: Our study highlights the crucial function of cGAS signaling in mediating PARPi resistance in ovarian cancer cells. These findings provide valuable novel therapeutic strategies targeting cGAS to improve the efficacy of PARPi-based treatments for ovarian cancer.

[This corrects the article on p. 11076 in vol. 8, PMID: 26617826.].

Background: This study looked at the efficacy of combining the phytochemical resveratrol with the anticancer drugs cisplatin and carboplatin on lung adenocarcinoma cell lines.

Materials and methods: We used MTT assay and generation of Reactive Oxygen Species levels using molecular fluorogenic probe 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) to investigate the effects of resveratrol in combination with cisplatin and carboplatin on the proliferation and viability of cells and levels of reactive oxygen species (ROS).

Results: Resveratrol has an anti-proliferative effect on A549 lung cancer cells, inhibiting cell proliferation in a dose and time-dependent manner. Resveratrol in conjunction with cisplatin and carboplatin inhibited cell proliferation synergistically. The combination therapy of cisplatin and carboplatin with Resveratrol showed enhanced growth inhibition of lung cancer cells in in-vitro with IC50 values of 15.09 ± 0.71 µM and IC50 values of 21.72 ± 1.9 µM, respectively. The present investigation also revealed the significant dose-dependent ROS generation in A549 cells by cisplatin, carboplatin, and their combination with resveratrol. Carboplatin treatment in combination with Resveratrol induced a higher generation of ROS (3.4-fold) when compared to carboplatin treatment (2.4-fold) at the highest concentration.

Conclusions: Our findings offered a basis for further research for assessing the potential of Resveratrol as a therapeutic agent to treat lung adenocarcinoma and whether it can be used as an adjuvant with drugs like cisplatin and carboplatin for improving their efficacies. However, the underlying processes of cell inhibition and cell death should be thoroughly investigated.

Introduction: EpCAM (epithelial cell adhesion molecule) protein expression was detected in 45 to 90% of breast cancers in different studies, and high expression levels were associated with poor outcomes in several retrospective analyses. This study aims to investigate the relationship between EpCAM and clinicopathological parameters and survival in breast cancer.

Methodology: This study was conducted as a Quasi-Experimental Cohort Study to explore 100 breast cancer patients. After the surgical excision of breast cancer, pathology blocks were deparaffinized and subjected to IHC (immunohistochemistry) for EpCAM examination. Using a Roche VENTANA Benchmark GX automated staining instrument and a well-established IHC staining protocol, the expression of EpCAM in breast cancer tissue was assessed. Independent sample T-test and Chi squared and Logistic Regression test with STATA version 17 software were used for data analysis.

Results: The difference in the distribution of the negative state of biomarkers (ER = estrogen receptor, PR = Progesterone receptor) and EPCAM positive group was significant (P-value = 0.002) (P-value = 0.006). A statistically insignificant distinction was observed in the distribution of the HER2 (human epidermal growth factor receptor) and EPCAM groups (P-value = 0.198). With 30.95% of those in the EPCAM-positive cohort experienced metastasis or recurrence. ER+ and PR+ decreased the chance of EPCAM positive by 0.25 and 0.29, respectively. HER2+ and Basal like breast cancer increase the chances of EPCAM being positive by 1.9 and 2.08, respectively. Basal like breast cancer increases the odds of EpCAM positive 2.19 times. Similarly, N2 and stage 3 increase the odds of EpCAM positive by 1.95 and 0.5 times, respectively.

Conclusion: We found that Basal like breast cancer, HER2+, and stage 3 increase the chance of EpCAM positivity. It seems that EPCAM positive cancer has more chance for recurrence and metastasis.

[This corrects the article on p. 1224 in vol. 12, PMID: 31933937.].

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a five-year survival rate of 13%, the lowest among all malignant tumors. The work aims to use bioinformatics methods to mine Nerve-cancer crosstalk-related genes (NCCGs) in pancreatic cancer and evaluate their correlation with tumor stage and prognosis, thereby providing a new direction of development and experimental basis for pancreatic cancer treatment. This study included 185 individuals with PDAC from the TCGA database, together with clinical and RNA sequencing data. A review of prior studies revealed the mechanism of neural-cancer crosstalk and identified 42 neural-cancer crosstalk-related genes (NCCGs). Multivariate logistic regression analysis showed that NGFR (OR=39.076, 95% CI; P<0.05), CHRNB2 (OR=41.076, 95% CI; P<0.05), and CHRNA10 (OR=39.038, 95% CI; P<0.05) were identified as independent risk factors for PNI development. Pearson correlation analysis revealed that CHRNA10 was negatively connected with PDAC microsatellite instability, whereas CHRNA10, CHRNB2, and NGFR were negatively correlated with PDAC tumor mutation burden. The GEPIA database revealed that CHRNB2 expression was higher in stage I PDAC. The pancreatic cancer single-cell dataset PAAD_CRA001160 revealed that malignant tumor cells, ductal cells, endothelial cells and fibroblasts accounted for a large proportion in the tumor microenvironment of pancreatic cancer. Furthermore, the NGFR gene was shown to be more significantly expressed in various pancreatic cancer cells. Bioinformatics analysis was used to create a validated prognostic model of pancreatic cancer, which explored the critical mechanisms of neural-tumor interactions and revealed the potential of cancer-neural crosstalk-related genes as prognostic biomarkers and anti-tumor therapy targets.

The hepatocarcinoma (HCC) is the most important liver tumor. It represents 90% of liver cancer cases. One of the main problems is the limited prompt cancer diagnosis and the advanced stages where the chances of treatment are limited. The main diagnostic methods for HCC are imaging techniques and liver biopsy. With advances in technology, proteins as significant diagnostic biomarkers have increased. The objective of this review is to describe the role of Alpha-fetoprotein (AFP), Glipican 3 (GPC-3), and Kininogen 1 (KNG-1) as biomarkers for the diagnosis of hepatocellular carcinoma. A systematic search of studies was carried out in the literature and the diagnostic values of these proteins were compared. The results showed that the combined use of biomarkers increases the diagnostic capacity for the detection of hepatocellular carcinoma.