Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.KEY WORDS: Immune checkpoint, Pancreatic cancer, Tumor microenvironment, Immunotherapy, Clinical development     

Correction: Synthesis and characterization of AFe2O4 (A: Ni,Co, Mg)–silica nanocomposites and their application for the removal of dibenzothiophene (DBT) by an adsorption process: kinetics,isotherms and experimental design

Correction for ‘Synthesis and characterization of AFe₂O₄ (A: Ni, Co, Mg)–silica nanocomposites and their application for the removal of dibenzothiophene (DBT) by an adsorption process: kinetics, isotherms and experimental design’ by Fahimeh Vafaee et al., RSC Adv., 2021, 11, 22661–22676, https://doi.org/10.1039/D1RA02780H.

The authors regret an error in Fig. 4 where a section of the XRD for 4(a) and (b) is identical.Open in a separate windowFig. 4(a) The XRD pattern of sample 3 after adsorption of DBT. (b) The XRD pattern of sample 3 before adsorption of DBT.The authors have repeated the experiment and provided new data for Fig. 4. An independent expert has viewed the new data and has concluded that it is consistent with the discussions and conclusions presented. The correct Fig. 4 is shown below:The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neu^hi), but low levels of CD8⁺ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neu^hi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.     

Primary malignant epithelioid hemangioendothelioma of the pleura: A review and report of a novel case

Epithelioid hemangioendothelioma is considered an uncommon tumor originating from vascular tissues. Although this disease is an extremely rare malignant cancer, its pleural subtype is even less common. We discuss a 68‐year‐old man with isolated pleural epithelioid hemangioendothelioma, along with a literature review of all similar cases.     

Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors

Cyclooxygenase-2 (COX-2) is an enzyme expressed primarily in pathologic states, such as inflammatory disorders and cancer, where it mediates prostaglandin production. Its overexpression is associated with more aggressive biologic tumor behavior and adverse patient outcome. Increasing evidence shows that agents that selectively inhibit COX-2 enhance tumor response to radiation or chemotherapeutic agents. This article gives an overview of some of this evidence. In addition, we describe new results showing that celecoxib, a selective COX-2 inhibitor, enhanced response of A431 human tumor xenografts in nude mice to radiation by an enhancement factor (EF) of 1.43 and to the chemotherapeutic agent docetaxel by an EF of 2.07. Celecoxib also enhanced tumor response when added to the combined docetaxel plus radiation treatment (EF = 2.13). Further experiments showed that selective COX-2 inhibitors enhanced tumor cell sensitivity to ionizing radiation, involving inhibition of cellular repair from radiation damage and cell cycle redistribution as mechanisms for some cell types. The results show that selective COX-2 inhibitors have the potential to improve tumor radiotherapy or radiochemotherapy, and this therapeutic strategy is currently under clinical testing.     

A prospective randomized controlled trial of Wallace and Rocket embryo transfer catheters

The aim of this study was to compare the efficacy of two embryo transfer catheters: Wallace and Rocket Embryon in an IVF programme of a tertiary referral university centre. A total of 308 patients undergoing embryo transfer were prospectively randomized to either a transfer with the Wallace catheter or a transfer with the Rocket catheter. The main outcome measure in this study was the clinical pregnancy rate, and secondary outcome measures included implantation rate, visibility of the catheter under ultrasound, number of retained embryos post transfer, and whether change of catheter was required. In addition, patient discomfort during the procedure was recorded. Pregnancy and implantation rates were similar when Wallace or Rocket catheters were used. However, for the Rocket catheter, the tip was more often clearly seen on ultrasound and it had a lower rate of retained embryos in the catheter after transfer (P < 0.05). Experience with different transfer catheters is recommended for difficult cases.     

Immobilization effect of Ruta graveolens L. on human sperm: a new hope for male contraception

AIM OF THE STUDY: Contraceptive plants which were introduced by folk in traditional remedies are investigated worldwide. In this study, the contraceptive effects of Ruta graveolens L., which has been mentioned for male contraceptive in Iranian traditional folk medicine, was experimented on human sperm. MATERIALS AND METHODS: Different doses of lyophilized aqueous extract of Ruta graveolens L. were added to an amount of fresh semen, containing 10(6) cells in a 1:1 volumic ratio. Motility and viability of cells, DNA status, mitochondrial activity and sperm revival tests were carried out. RESULTS: The sperm immobilization effects of the extract appeared immediately in a does-dependent manner and 100% of the sperms became immotile at a concentration of 100mg/ml but other parameters were intact. After washing the sperms, motility was returned in 30.8+/-3.2% of the sperms, besides coiled tails in 38.6+/-5.5% of the treated cells, in comparison to 12.5+/-2.0% of the control group (p=0.001). The part of the extract, responsible for immobilization of the sperms was stable upon boiling. CONCLUSIONS: As the cells were alive and immotile, probably some ionic currents are blocked by a thermostable component of the plant which can be promising as a new male channel blocker contraceptive.     

Down syndrome due to partial trisomy 21q

A patient is reported with a typical Down syndrome phenotype, caused by patrial trisomy of chromosome 21. Based on the present case and data from the literature, it is suggested that the Down phenotype is due to the trisomy of the distal portion of the band (q22) of chromosome 21.