Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos‐exposed individuals and rapidly leads to death. MPM harbors loss‐of‐function mutations in ...BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM‐like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.
Synopsis
Human malignant pleural mesothelioma (MPM) is a devastating occupational cancer that kills more than 200,000 individuals annually. Some MPM harbor mutations of the KRAS proto‐oncogene, but their functional significance is unknown and experimental models for these MPM are not available.
Activating mutations, amplifications, and transcriptional activation of KRAS alone or in combination with inactivating alterations of TP53 are found in 20% of 86 MPM patients from the TCGA dataset.
KRAS mutations alone or in combination with TP53 loss are corroborated in 40–50% of 35 newly reported MPM patients and of 33 established MPM cell lines.
Mesothelial‐restricted ectopic expression of KRASG12D alone or in combination with deletion of the murine TP53 genes are shown to trigger epithelioid or biphasic MPM, respectively, with 100% penetrance.
Three MPM cell lines are provided, which feature the causative KRAS and TP53 mutations but also secondary mutations in the mouse BAP1 gene, as well as a human MPM‐like transcriptome.
Transgenic and transplantable MPM models for hypothesis testing and drug triage are provided and the prototype KRAS inhibitor deltarasin is shown to block MPM development in mice by 76%.
Human malignant pleural mesothelioma (MPM) is a devastating occupational cancer that kills more than 200,000 individuals annually. Some MPM harbor mutations of the KRAS proto‐oncogene, but their functional significance is unknown and experimental models for these MPM are not available.
Aim: Fine-needle aspiration plays a significant role in the evaluation
of solitary thyroid nodules. Several cytological criteria are defined and
these primarily aim to distinguish papillary carcinoma ...(PC), the most
common thyroid malignancy, from other benign diseases. In our study,
we aimed to determine which cytologic criteria are more valuable in
diagnosing PC.
Methods: Patients, who had undergone thyroidectomy operation
between January 2013 and December 2014 and had preoperative
fine-needle aspiration cytology, were screened. Among cases that
were postoperatively diagnosed as benign, 62 cases and among
those diagnosed as PC and papillary microcarcinoma, 24 cases were
included in this study. The cytologic criteria were reassessed. In the
linear regression analysis, the variables associated with the diagnosis
of malignancy at the level of p<0.05 were considered significant for
predicting the diagnosis of PC.
Results: The variables that remained as predictive for the diagnosis of
cancer as the result of the Backward analysis following the multivariate
analysis performed with the variables with a p value of less than 0.1
were cellular pleomorphism, nuclear atypia, papillary structures with
fibrovascular cores, and intranuclear pseudoinclusion.
Conclusion: Although every cytological feature is characteristic for PC,
none of them alone is specific; they should be evaluated together with
all nuclear and structural features during the diagnostic approach.
Abstract Objectives This study investigates the usefulness of glutathione-S-transferases (GST) isoenzymes and p53 immunostaining as a marker of malignancy in urinary cytology, and evaluates their ...potential effect in increasing diagnostic accuracy in a series of urine cytologic samples. They are also correlated with cytopathology diagnosis and histopathologic diagnosis. Materials and methods In this study, the slides from 124 bladder carcinoma patients prepared by the cytocentrifugation method were observed. The cytomorphologic properties of these cancer cells were determined. Moreover, the immunocytochemical distributions of GST alpha (GSTA), pi (GSTP), mu (GSTM4), theta (GSTT1) isoenzymes and p53 protein were studied for the patients. Results The urothelial cancer cells had small cytoplasm and rough nuclear membrane. The chromatin granules were heterogeneously distributed in each malignant cell's nucleus. There was a pleomorphism of the malignant cells' nuclei. According to immunocytopathologic observations, the urothelial cancer cells had stronger staining intensity than the benign cells had in 48% of cases for GSTA, 46% of cases for GSTP, 38% of cases for GSTM4, and 42% of cases for GSTT1. For all papillary cases, the malignant cells were stained negative, while the benign cells were positive. For 83% of patients, the malignant cells were stained positive for p53. There was a significant difference in GSTA ( P = 0.006), GSTT1 ( P = 0.004), GSTP ( P = 0.000) and p53 ( P = 0.000) expressions for benign cells whereas, a non-statistical difference in the malignant cells for GSTA, GSTT1, GSTP, GSTM4, and p53 expressions ( P > 0.05). Conclusions GST isoenzymes and p53 immunostaining were not found to be markers of malignancy in urinary cytology.
Background
The term radiologic subsolid lung nodule (SLN) represents a heterogeneous group of non‐neoplastic and neoplastic lesions. Intraoperative evaluation (IO) is often required to differentiate ...and diagnose. The current study aims to investigate the feasibility and reliability of scrape cytology (SC) and radiologic solid size correlation for the IO diagnosis of SLNs.
Methods
Sixty‐eight patients with SLN signs were eligible to take part in the study due to intraoperatively prepared SC slides. We managed to complete the blind radiologic solid size measurement and cytologic evaluation retrospectively. Cases were grouped into three categories based on their cytological features: Group‐0 (Benign), Group‐1 (mild atypical features), and Group‐2 (severe atypical features/unequivocally carcinoma). IO diagnoses were given by combining the radiologic solid size and cytological findings.
Results
Cytological features of Group‐1 were observed in 100%, 93%, 32.5%, and 17% of the AIS, MIA, IA, and benign lesions, respectively. Cytological features of Group‐2 were observed in 67.5%, and 7% of the IA and MIA, respectively. By combining cytology with radiologic solid size, 100%, 85%, 71%, and 83% of the AIS, IA, MIA, and benign lesions respectively were diagnosed correctly. Fifteen (15%) percent of the IA cases were underdiagnosed as MIA since their radiological solid sizes were less than 0.5 cm with cytological features of Group‐1. Conversely, 29% of the MIA cases were overdiagnosed as IA since their radiological solid sizes were greater than 0.5 cm.
Conclusion
SLNs should be handled with caution in terms of IO management. SC and radiologic solid size correlation both provide a practical and tissue‐protecting approach for the IO evaluation of SLNs, ensuring a high consistency between IO and definitive diagnosis.
Peripheral nerves with defective segments can only be repaired using nerve grafts. Among the various nerve graft options, the outcome of vascularized grafts has been shown to be better, especially ...when used in the hypovascular and scarred recipient bed. The purpose of this study was to compare the regeneration capacities of various types of venous nerve grafts in a rat model. Forty adult male Wistar albino rats were divided into four groups. A 2-cm-long segment of femoral sheath was isolated from the surrounding tissue without disturbing the unity of the femoral sheath contents. Four different nerve graft models were applied: flow-through venous, arterialized venous, prefabricated venous, and conventional nerve graft (control). All nerve grafts were closed with silicone sheets. These neurovascular segments were reopened in postoperative week 10 to determine the viability of the grafted nerves and to assess the degree of nerve healing. Histopathologic examinations, morphometric analysis, and electrophysiological measurements were performed. The degree of nerve healing in the flow-through venous nerve grafts was similar to that observed in the arterialized nerve grafts. Prefabricated flow-through venous grafts were not as successful as flow-through venous grafts or arterialized nerve grafts. All of the vascularized nerve grafts showed better results than the conventional nerve grafts.
Mediastinal lymphadenopathy is rare in Coronavirus Disease-2019 (COVID-19) patients with mild clinical course. The frequency of lymphadenopathy increases in COVID-19 patients who develop Acute ...Respiratory Distress Syndrome (ARDS). In a 38-year-old male patient, mediastinal lymphadenopathy and asymptomatic pulmonary embolism were detected during the third week of COVID-19 infection at home. Sarcoidosis was diagnosed with a finding of non-caseating granulomas. Even if it is asymptomatic, pulmonary embolism should be considered, especially in COVID-19 patients with high C - Reactive Protein (CRP) and D-dimer levels. If mediastinal lymphadenopathy is detected in mild COVID-19 cases, systemic diseases should be investigated. In severe COVID-19 cases, if lymphadenopathy continues despite a COVID-19 recovery, further investigation is required.
Extracellular matrix (ECM)-derived hydrogels are in demand for use in lung tissue engineering to mimic the native microenvironment of cells in vitro. Decellularization of native tissues has been ...pursued for preserving organotypic ECM while eliminating cellular content and reconstitution into scaffolds which allows re-cellularization for modeling homeostasis, regeneration, or diseases. Achieving mechanical stability and understanding the effects of the decellularization process on mechanical parameters of the reconstituted ECM hydrogels present a challenge in the field. Stiffness and viscoelasticity are important characteristics of tissue mechanics that regulate crucial cellular processes and their in vitro representation in engineered models is a current aspiration. The effect of decellularization on viscoelastic properties of resulting ECM hydrogels has not yet been addressed. The aim of this study was to establish bovine lung tissue decellularization for the first time via pursuing four different protocols and characterization of reconstituted decellularized lung ECM hydrogels for biochemical and mechanical properties. Our data reveal that bovine lungs provide a reproducible alternative to human lungs for disease modeling with optimal retention of ECM components upon decellularization. We demonstrate that the decellularization method significantly affects ECM content, stiffness, and viscoelastic properties of resulting hydrogels. Lastly, we examined the impact of these aspects on viability, morphology, and growth of lung cancer cells, healthy bronchial epithelial cells, and patient-derived lung organoids.
Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos ...exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.
20 yıl içerisinde azot döngüsünün kayıp halkası olarak keşfedilen yeni bir bakteri türü, Anaerobik Amonyum Oksidasyonu (Anammox) bakterisi, atıksudan azot giderimini biyolojik atıksu arıtmasında önem ...kazanmıştır. Anammox prosesi çamur oluşumunu azaltmakta, havalandırma ve organik karbon ihtiyacını elimine etmekte, sera gazı oluşumuna katkısı bulunmamaktadır. Düşük maliyetli bir proses olmasına rağmen Anammox bakterisinin çoğalma hızının düşük olması ve aşı çamurunun henüz çoğu ülkede lokal olarak bulunmaması sebebiyle gerçek ölçekli tercih edilmemektedir. Anammox bakterilerinin Anammoksozom departmanları içerisinde bulunan demir nano parçacıkları bakterilerin metabolizmik demir kullanımlarının bulunduğuna işaret etmektedir. Yapılan çalışmalar, Anammox bakterilerinin ortamına enjekte edilen demir parçacıklarının Anammox aktivitesinde artışa, granüler yapılaşmaya ve hücre dışı polimerik madde salgısında artışa sebep olduklarını ortaya çıkartmıştır. Bu çalışma kapsamında, sıfır değerlikli nano boyutlu demir parçacıklarının (nSDD) Anammox prosesi üzerine etkileri incelenmiştir. Bu kapsamda, ardışık kesikli bir reaktör sistemi sürekli olarak amonyak ve nitrit içeren sentetik atıksu ile beslenmiş ve reaktör haftada 1 ila 3 arası değişen sıklıklar ile 250- 5000 ppb aralığında nSDD ile dozlanmıştır. Demirin Anammox üzerine etkileri amonyak tüketim hızı, nitrit tüketim hızı, N₂ gazı üretim hızı, hücre dışı polimerik madde salgılanması mikroskobik ve moleküler analizler ile takip edilmiştir.
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