Ovarian cancer (OC) poses a significant global health challenge with high mortality rates, emphasizing the need for improved treatment strategies. The immune system’s role in OC progression and ...treatment response is increasingly recognized, particularly regarding peripheral blood mononuclear cells (PBMCs) and cytokine production. This study aimed to investigate PBMC subpopulations (T and B lymphocytes, natural killer cells, monocytes) and cytokine production, specifically interleukin-1 beta (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNFα), in monocytes of OC patients both preoperatively and during the early postoperative period. Thirteen OC patients and 23 controls were enrolled. Preoperatively, OC patients exhibited changes in PBMC subpopulations, including decreased cytotoxic T cells, increased M2 monocytes, and the disbalance of monocyte cytokine production. These alterations persisted after surgery with subtle additional changes observed in PBMC subpopulations and cytokine expression in monocytes. Considering the pivotal role of these altered cells and cytokines in OC progression, our findings suggest that OC patients experience an enhanced pro-tumorigenic environment, which persists into the early postoperative period. These findings highlight the impact of surgery on the complex interaction between the immune system and OC progression. Further investigation is needed to clarify the underlying mechanisms during this early postoperative period, which may hold potential for interventions aimed at improving OC management.
Pancreatic diseases, especially acute pancreatitis and pancreatic cancer, are associated with high rates of complications, difficult treatment that may not always be effective, and high mortality in ...complex cases ....
Background: Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including anastomotic ...strictures, recurrent cholangitis, and secondary biliary cirrhosis. Methods: We provide a comprehensive overview of current literature on the long-term outcome of BDI. Considering the availability of only limited data regarding treatment of anastomotic strictures in literature, we also retrospectively analyzed patients with anastomotic strictures following a hepaticojejunostomy (HJ) from a prospectively maintained database of 836 BDI patients. Results: Although clinical outcomes of endoscopic, radiologic, and surgical treatment of BDI are good with success rates of around 90%, quality of life (QoL) may be impaired even after “clinically successful” treatment. Following surgical treatment, the incidence of anastomotic strictures varies from 5 to 69%, with most studies reporting incidences around 10–20%. The median time to stricture formation varies between 11 and 30 months. Long-term BDI-related mortality varies between 1.8 and 4.6%. Of 91 patients treated in our center for anastomotic strictures after HJ, 81 (89%) were treated by percutaneous balloon dilatation, with a long-term success rate of 77%. Twenty-four patients primarily or secondarily underwent surgical revision, with recurrent strictures occurring in 21%. Conclusions: The long-term impact of BDI is considerable, both in terms of clinical outcomes and QoL. Treatment should be performed in tertiary expert centers to optimize outcomes. Patients require a long-term follow-up to detect anastomotic strictures. Strictures should initially be managed by percutaneous dilatation, with surgical revision as a next step in treatment.
The aryl hydrocarbon receptor (AHR) is a transcription factor that is commonly upregulated in pancreatic ductal adenocarcinoma (PDAC). AHR hinders the shuttling of human antigen R (ELAVL1) from the ...nucleus to the cytoplasm, where it stabilises its target messenger RNAs (mRNAs) and enhances protein expression. Among these target mRNAs are those induced by gemcitabine. Increased AHR expression leads to the sequestration of ELAVL1 in the nucleus, resulting in chemoresistance. This study aimed to investigate the interaction between AHR and ELAVL1 in the pathogenesis of PDAC in vitro.
and
genes were silenced by siRNA transfection. The RNA and protein were extracted for quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Direct binding between the ELAVL1 protein and
mRNA was examined through immunoprecipitation (IP) assay. Cell viability, clonogenicity, and migration assays were performed. Our study revealed that both AHR and ELAVL1 inter-regulate each other, while also having a role in cell proliferation, migration, and chemoresistance in PDAC cell lines. Notably, both proteins function through distinct mechanisms. The silencing of ELAVL1 disrupts the stability of its target mRNAs, resulting in the decreased expression of numerous cytoprotective proteins. In contrast, the silencing of
diminishes cell migration and proliferation and enhances cell sensitivity to gemcitabine through the AHR-ELAVL1-deoxycytidine kinase (DCK) molecular pathway. In conclusion, AHR and ELAVL1 interaction can form a negative feedback loop. By inhibiting AHR expression, PDAC cells become more susceptible to gemcitabine through the ELAVL1-DCK pathway.
Surgical treatment is a cornerstone of ovarian cancer (OC) therapy and exerts a substantial influence on the immune system. Immune responses also play a pivotal and intricate role in OC progression. ...The aim of this study was to investigate the dynamics of immune-related protein expression and the activity of peripheral blood mononuclear cells (PBMCs) in OC patients, both before surgery and during the early postoperative phase. The study cohort comprised 23 OC patients and 20 non-cancer controls. A comprehensive analysis of PBMCs revealed significant pre-operative downregulation in the mRNA expression of multiple immune-related proteins, including interleukins, PD-1, PD-L1, and HO-1. This was followed by further dysregulation during the first 5 post-operative days. Although most serum interleukin concentrations showed only minor changes, a distinct increase in IL-6 and HO-1 levels was observed post-operatively. Reduced metabolic and phagocytic activity and increased production of reactive oxygen species (ROS) were observed on day 1 post-surgery. These findings suggest a shift towards immune tolerance during the early post-operative phase of OC, potentially creating a window for treatment. Further research into post-operative PBMC activity could lead to the development of new or improved treatment strategies for OC.
AIM: To investigate the expression of Hu R in pancreatic ductal adenocarcinoma(PDA) and to assess the effects of Hu R silencing on the expression of cyclooxygenase-2(COX-2) and heme oxygenase-1(HO-1) ...and the in vitro response to gemcitabine(GEM) treatment in pancreatic cell lines.METHODS: We compared the expression of Hu R,COX-2,and HO-1 in PDA and normal pancreatic tissueusing quantitative reverse transcription polymerase chain reaction(q RT-PCR) and western blot. In addition,the Hu R,COX-2 and HO-1 were analyzed in four types of cancer cell lines(Mia Paca2,Su.86.86,Capan-1,and Capan-2) with and without GEM treatment. Immunocytofluorescence analysis was used to investigate Hu R localization in cells. Cell viability and response to GEM after Hu R silencing were determined with the 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide test and the crystal violet clonogenic assay,respectively. To measure apoptosis,activation of caspases 3/7 was evaluated using immunofluorescence. RESULTS: In PDA tissue obtained from patients not treated with GEM,Hu R m RNA expression was 3.2 times lower(P < 0.05) and COX-2 and HO-1 m RNAexpression was 2.3-fold and 7.2-fold higher(P < 0.05),respectively,than normal pancreatic tissue(from organ donor). q RT-PCR analysis showed that Hu R,COX-2,and HO-1 m RNA were overexpressed in all cancer cell lines treated with the half maximal inhibitory concentration(IC50) dose of GEM compared with control cells(P < 0.05). Western blot analysis revealed that COX-2 and HO-1 levels were significantly decreased in cancer cells after Hu R silencing. Furthermore,HuR silencing in creased the response to GEM treatmentand decreased cell viability by 11.6%-53.7% compared to control cell lines. Caspases 3 and 7 were activated after Hu R silencing and GEM treatment in all pancreatic cancer cell lines. In comparison,treatment with GEM alone did not activate caspases 3 and 7 in the same cell lines. CONCLUSION: Hu R mediated post-transcriptional upregulation of COX-2 and HO-1 expression after GEM treatment in pancreatic cancer cells. Hu R silencing significantly increased the effectiveness of GEM treatment in vitro.
Thyroid surgeries are among the most common operations performed in the world. Hypocalcemia following total thyroidectomy is a common complication that is sometimes difficult to correct. The aim of ...this study is to determine the risk factors for hypocalcemia following total thyroidectomy and their clinical value.
From January 2015 through to April 2017, 400 patients were included in this prospective multicenter study. All patients underwent total thyroidectomy due to various thyroid diseases. The following risk factors were analyzed: pre-operative and post-operative biochemical blood parameters, clinical effects and factors related to surgery, the patient, and the disease.
Post-operative hypocalcemia developed in 257 patients (64.2%). Of them, 197 patients (76.7%) were diagnosed with asymptomatic hypocalcemia. Clinical symptoms were present in 60 of the 257 patients with hypocalcemia (23.3%). The statistically significant predictors of hypocalcemia were decreased calcium and ionized calcium pre-operatively (p < 0.001), parathyroid hormone on day one following surgery (p < 0.001), thyrotoxicosis <10 years before surgery (odds ratio 1.65, 95% CI 1.01-2.70, p = 0.046), the number of parathyroid glands found during surgery (odds ratio 0.52, 95% CI 0.38-0.70, p < 0.001), ligation of the trunk of the left inferior thyroid artery (odds ratio 2.04, 95% CI 1.27-3.29, p = 0.003), ligation of the trunk of the right inferior thyroid artery (odds ratio 2.37, 95% CI 1.47-3.81, p < 0.001), and the number of transplanted parathyroid glands (odds ratio 1.87, 95% CI 1.12-2.97, p = 0.015). In the multivariate analysis, age (odds ratio 1.05, 95% CI 1.01-1.09, p = 0.029) and gender (odds ratio 5.94, 95% CI 1.13-31.26, p = 0.035) were statistically significant predictors.
This study demonstrates that there is a number of different patient (gender, age, and duration of thyrotoxicosis <10 years before surgery) and surgical (number of parathyroid glands found during surgery, decreased calcium and ionized calcium before surgery, parathyroid hormone on day one following surgery, and ligation of the trunk of the left and right inferior thyroid artery) risk factors predictive of hypocalcemia following total thyroidectomy. Optimization of the surgical technique could possibly prevent the occurrence of hypocalcemia after total thyroidectomy in some cases; in other cases, identification of known risk factors post-operatively could permit early detection and effective treatment of these patients.
AIM:To study secretion patterns of proand anti-in-flammatory cytokines, and activation of various cellular subsets of leukocytes in peripheral blood.METHODS: We have conducted a prospective ...obser-vational study. One hundred and eight patients with a diagnosis of acute pancreatitis and onset of the disease within last 72 h were included in this study. The mRNA expression of 25 different types of cytokines in white blood cells was determined by quantitative real time polymerase chain reaction. Levels of 8 dif...
This systematic review and meta-analysis evaluates surgical outcome and safety results of conventional (OT) versus endoscopic transaxillary gasless thyroidectomies (ET).
A systematic literature ...search was performed. The weighted mean differences or the odd ratios with corresponding 95% CIs were examined for surgical outcomes and complications. The results were analysed using fixed- or random-effects models. The heterogeneity was checked by the Cochran Q test and the extent of inconsistency was evaluated by the I
statistic.
Ten studies and 1597 patients were included. All studies found that ET required longer operative time. Postoperative pain was significantly lower after ET on day 1 and day 7. No statistical difference was found in complication rates.
ET has disadvantages such as longer surgery time, but it is a feasible and safe procedure with lower postoperative pain and comparable complication rates to OT. However, good quality prospective randomised studies are necessary to draw firmer conclusions.
Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), has an immune suppressive environment that allows tumour cells to evade the immune system. The aryl-hydrocarbon receptor (AHR) ...is a transcription factor that can be activated by certain exo/endo ligands, including kynurenine (KYN) and other tryptophan metabolites. Once activated, AHR regulates the expression of various genes involved in immune responses and inflammation. Previous studies have shown that AHR activation in PDAC can have both pro-tumorigenic and anti-tumorigenic effects, depending on the context. It can promote tumour growth and immune evasion by suppressing anti-tumour immune responses or induce anti-tumour effects by enhancing immune cell function. In this study involving 30 PDAC patients and 30 healthy individuals, peripheral blood samples were analysed. PDAC patients were categorized into Low (12 patients) and High/Medium (18 patients) AHR groups based on gene expression in peripheral blood mononuclear cells (PBMCs). The Low AHR group showed distinct immune characteristics, including increased levels of immune-suppressive proteins such as PDL1, as well as alterations in lymphocyte and monocyte subtypes. Functional assays demonstrated changes in phagocytosis, nitric oxide production, and the expression of cytokines IL-1, IL-6, and IL-10. These findings indicate that AHR’s expression level has a crucial role in immune dysregulation in PDAC and could be a potential target for early diagnostics and personalised therapeutics.
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