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Over the course of the last decade, immunotherapy has revolutionised the management of a great number of cancer types. The treatment of pleural mesothelioma, a rare and highly aggressive cancer, is also being transformed by immunotherapy. The recent combination of ipilimumab and nivolumab improved overall survival compared with platinum-based chemotherapy, irrespective of the histology, establishing immunotherapy as a front-line standard of care in advanced pleural mesothelioma. Yet, most patients do not derive long-term benefit from any of the available therapies, and we note a significant lack of predictive and prognostic biomarkers. After progressing on first-line therapy, patients have limited therapeutic options, and data are scarce about optimal sequencing. In this perspective, we discuss the current management of pleural mesothelioma, defining what we consider to be the therapeutic sequence based on performance status and tumour histology. We also highlight promising ongoing trials that could further shape the management of this rare disease.

Abstract Introduction: Lung cancer is the second most common cancer; however, synchronous lung cancer is rare and challenging to treat. Case Presentation: We report the case of an 80-year-old female patient who presented with two lung lesions with primary tumor characteristics, which revealed squamous cell carcinoma and synchronous adenocarcinoma after histological sampling. Next-generation sequencing (NGS) analysis revealed a MET Exon 14 skipping mutation in squamous cell carcinoma and an epidermal growth factor receptor mutation in adenocarcinoma. Capmatinib and stereotactic radiotherapy were initiated for the adenocarcinoma with a good clinical response. Capmatinib treatment had to be discontinued because of stage 3 edema of the lower limbs, after which a left lobectomy was performed. Currently, the patient is considered to be in remission. Conclusion: This case highlights the need for histological analysis of every lung lesion with primary tumor characteristics, as well as for NGS analysis in search of specific mutations enabling the introduction of targeted therapies. mesenchymal-epithelial transition.

Bone is a frequent site of metastases in advanced cancers including lung, breast, prostate, kidney, or myeloma. Lesions are commonly located on the spine. Neoplastic invasion of the vertebral body can result in painful vertebral fractures, leading to disability and substantial morbidity. Percutaneous vertebroplasty is a minimally invasive surgical procedure used to treat spinal fractures due to osteolytic tumors. It could result in pain reduction or resolution in 80–90% of patients with fractures, and it improves stability. Although considered safe, vertebroplasty has been associated over the years with life-threatening complications. We have reported the case of a 55-year-old patient with lung adenocarcinoma, who underwent vertebroplasty for a pathological neoplastic fracture of L2. The procedure was complicated by a leak of cement into the systemic venous circulation, characterized by an 11-cm filament in the right heart chambers and multiple pulmonary emboli. To our knowledge, only one similar case was previously reported, involving an intracardiac cement filament longer than 10 cm. The data are scant, hence the importance of collecting and reporting possible complications about what is perceived as a rather safe procedure. The case highlights the need for a robust postprocedure imaging plan to detect complications, which can impact patients’ morbidity and survival.

Background A short-term randomized controlled trial shows that the one anastomosis gastric bypass (OAGB) is a safe and effective alternative to the Roux-en-Y gastric bypass (RYGB). Objective The aim of this study is to evaluate the OAGB at our University Hospital between 2006 and 2013. Patients One thousand patients have undergone an OAGB. Data were collected on all consecutive patients. The mean follow-up period was 31 months (SD, 26.3; range, 12–82.9), and complete follow-up was available in 126 of 175 patients (72 %) at 5 years after surgery. Results Mortality rate was 0.2 %. Overall morbidity was 5.5 %; 34 required reoperations: i.e., 6 leaks, 5 obstructions, 5 incisional hernias, 7 biliary refluxes, 2 perforated ulcers, 2 bleeds, 2 abscesses, and 1 anastomotic stricture. Four patients were reoperated for weight regain. Overall rate of marginal ulcers was 2 % ( n  = 20), all in heavy smokers. Conversion from an OAGB to a RYGB was required in nine cases (0.9 %): seven for intractable biliary reflux, two for a marginal ulcer. At 5 years, percent excess body mass index loss was 71.6 ± 27 %. One hundred patients with type-2 diabetes, with a mean preoperative HbA1C of 7.7 ± 1.9 %, were followed for >2 years; the total resolution rate was 85.7 %. Conclusion This study confirms that the OAGB is an effective procedure for morbid obesity with comparable outcomes to RYGB; in addition, it seems to be safer with lower morbidity. Its technical simplicity represents a real advantage and makes it an option that should be considered by all bariatric surgeons.

Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class I gene complex, as well as increased selection for diversity at these genes is associated with sharply decreasing cancer mortality risk across mammals. This suggests that the efficient presentation of diverse peptides in somatic cells is important for cancer suppression across mammals, providing pioneering evidence that supports the cancer immunosurveillance hypothesis across species. Here, the authors find that mammals with more diverse immune genes (MHC I) face lower cancer risk, suggesting that immune surveillance could be a widespread natural defense against cancer.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in xenobiotic metabolism. Plexiform neurofibromas (PNFs) can transform into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to existing therapies. These tumors are primarily composed of Schwann cells. In addition to neurofibromatosis type 1 (NF1) gene inactivation, further genetic lesions are required for malignant transformation. We have quantified the mRNA expression levels of AHR and its associated genes in 38 human samples. We report that AHR and the biosynthetic enzymes of its endogenous ligand are overexpressed in human biopsies of PNFs and MPNSTs. We also detect a strong nuclear AHR staining in MPNSTs. The inhibition of AHR by siRNA or antagonists, CH-223191 and trimethoxyflavone, induces apoptosis in human MPNST cells. Since AHR dysregulation is observed in these tumors, we investigate AHR involvement in Schwann cell physiology. Hence, we studied the role of AHR in myelin structure and myelin gene regulation in Ahr −/− mice during myelin development. AHR ablation leads to locomotion defects and provokes thinner myelin sheaths around the axons. We observe a dysregulation of myelin gene expression and myelin developmental markers in Ahr −/− mice. Interestingly, AHR does not directly bind to myelin gene promoters. The inhibition of AHR in vitro and in vivo increased β-catenin levels and stimulated the binding of β-catenin on myelin gene promoters. Taken together, our findings reveal an endogenous role of AHR in peripheral myelination and in peripheral nerve sheath tumors. Finally, we suggest a potential therapeutic approach by targeting AHR in nerve tumors.

This paper presents the impact of overhead pressure (constant pressure and pressure modulation) during mixing on important mixing parameters (maximal power level and the corresponding time (t PEAK )), dough properties after mixing and fermentation (dough voidage and growth rate), and bread characteristics (such as specific volume, void fraction, and crumb microstructure). The overhead pressure during mixing, which was done with air as overhead pressure, did not significantly affect the maximal power level and t PEAK , but significantly impacted dough and bread characteristics. Mixing at high pressure, i.e., 0.5 bar above atmospheric pressure, led to higher dough voidage at the end of mixing, resting, and sheeting. Moreover, high-pressure mixing led to higher dough growth, resulting in the attainment of desired expansion ratio of 3.5 much early (after 70 min fermentation). The bread obtained from this condition had the largest specific volume of 4.29 ml/g and void fraction of 82.98% and possessed one of the largest crumb cell sizes. On the other hand, mixing under atmospheric pressure (1 bar) and step decrease to partial vacuum (i.e., 0.2 bar below atmospheric pressure) from atmospheric pressure and high pressure led to dough with relatively low void fraction and slow dough growth rate during fermentation. For the same fermentation time (i.e., 70 min), these conditions resulted in bread with similar characteristics but had significantly smaller measured parameters than other conditions. Moreover, dough mixed under these conditions had to be fermented for an additional 10 min (i.e., total of 80 min) to attain bread with specific volume and void fraction similar to that of other studied conditions. Overall, it was found that overhead pressure during mixing mainly impacted the dough void fraction which, in turn, impacts the dough growth rate during fermentation and the final bread characteristics.

The Aryl hydrocarbon Receptor or AhR, a ligand-activated transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Recent studies in Caenorhabditis elegans and Drosophila melanogaster show that the orthologs of the AhR are expressed exclusively in certain types of neurons and are implicated in the development and the homeostasis of the central nervous system. While physiological roles of the AhR were demonstrated in the mammalian heart, liver and gametogenesis, its ontogenic expression and putative neural functions remain elusive. Here, we report that the constitutive absence of the AhR in adult mice (AhR-/-) leads to abnormal eye movements in the form of a spontaneous pendular horizontal nystagmus. To determine if the nystagmus is of vestibular, visual, or cerebellar origin, gaze stabilizing reflexes, namely vestibulo-ocular and optokinetic reflexes (VOR and OKR), were investigated. The OKR is less effective in the AhR-/- mice suggesting a deficit in the visuo-motor circuitry, while the VOR is mildly affected. Furthermore, the AhR is expressed in the retinal ganglion cells during the development, however electroretinograms revealed no impairment of retinal cell function. The structure of the cerebellum of the AhR-/- mice is normal which is compatible with the preserved VOR adaptation, a plastic process dependent on cerebellar integrity. Finally, intoxication with TCDD of control adults did not lead to any abnormality of the oculomotor control. These results demonstrate that the absence of the AhR leads to acquired central nervous system deficits in the adults. Given the many common features between both AhR mouse and human infantile nystagmus syndromes, the AhR-/- mice might give insights into the developmental mechanisms which lead to congenital eye disorders.

The Aryl hydrocarbon Receptor(AhR) is among the most important receptors which bind pollutants; however it also regulates signaling pathways independently of such exposure. We previously demonstrated that AhR is expressed during development of the central nervous system(CNS) and that its deletion leads to the occurrence of a congenital nystagmus. Objectives of the present study are to decipher the origin of these deficits, and to identify the role of the AhR in the development of the CNS. We show that the AhR-knockout phenotype develops during early infancy together with deficits in visual-information-processing which are associated with an altered optic nerve myelin sheath, which exhibits modifications in its lipid composition and in the expression of myelin-associated-glycoprotein(MAG), a cell adhesion molecule involved in myelin-maintenance and glia-axon interaction. In addition, we show that the expression of pro-inflammatory cytokines is increased in the impaired optic nerve and confirm that inflammation is causally related with an AhR-dependent decreased expression of MAG. Overall, our findings demonstrate the role of the AhR as a physiological regulator of myelination and inflammatory processes in the developing CNS. It identifies a mechanism by which environmental pollutants might influence CNS myelination and suggest AhR as a relevant drug target for demyelinating diseases.

Indoor air pollution is one of the leading causes of morbidity and mortality worldwide, but its sources and impacts are largely misunderstood by the public. In a randomised controlled trial including 281 households in France, we test two interventions aimed at changing indoor polluting behaviour by raising households’ awareness of health risks associated with indoor air pollution. While both generic and personalised information increased knowledge, only personalised information including social comparison feedback changed behaviour, leading to a reduction of indoor PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 µm) emissions by 20% on average. Heterogeneous treatment effects show that this effect is concentrated on the most polluted households at baseline, for whom the reduction reaches 40%.