Authentication of processed meat products by peptidomic analysis using rapid ambient mass spectrometry

We present the application of a novel ambient LESA-MS method for the authentication of processed meat products. A set of 25 species and protein-specific heat stable peptide markers has been detected in processed samples manufactured from beef, pork, horse, chicken and turkey meat. We demonstrate that several peptides derived from myofibrillar and sarcoplasmic proteins are sufficiently resistant to processing to serve as specific markers of processed products. The LESA-MS technique required minimal sample preparation without fractionation and enabled the unambiguous and simultaneous identification of skeletal muscle proteins and peptides as well as other components of animal origin, including the milk protein such as casein alpha-S1, in whole meat product digests. We have identified, for the first time, six fast type II and five slow/cardiac type I MHC peptide markers in various processed meat products. The study demonstrates that complex mixtures of processed proteins/peptides can be examined effectively using this approach

Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration

Rapid detection of peptide markers for authentication purposes in raw and cooked meat using ambient liquid extraction surface analysis mass spectrometry

In this paper, our previously developed ambient LESA-MS methodology is implemented to analyze five types of thermally treated meat species, namely beef, pork, horse, chicken, and turkey meat, in order to select and identify heat-stable and species-specific peptide markers. In-solution tryptic digests of cooked meats were deposited onto a polymer surface, followed by LESA-MS analysis and evaluation using multivariate data analysis and tandem electrospray MS. The five types of cooked meat were clearly discriminated using principal component analysis and orthogonal partial least squares discriminant analysis. A number of 23 heat stable peptide markers unique to species and muscle protein were identified following data-dependent tandem LESA-MS analysis. Surface extraction and direct ambient MS analysis of mixtures of cooked meat species was performed for the first time and enabled detection of 10% (w/w) of pork, horse, and turkey meat, and 5% (w/w) of chicken meat in beef, using the developed LESA-MS/MS analysis. The study shows, for the first time, that ambient LESA-MS methodology displays specificity sufficient to be implemented effectively for the analysis of processed and complex peptide digests. The proposed approach is much faster and simpler than other measurement tools for meat speciation; it has potential for application in other areas of meat science or food production

First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer

Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens

Determination of Levels cytokeratin 18 in chronic pancreatitis

Giriş ve Amaç: Kronik pankreatit (KP), endokrin ve ekzokrin fonksiyonel bozukluk ile giden, pankreasta morfolojik değişikliklerin gözlendiği, kalıcı yıkım, fibrozis, fonksiyon bozukluğu oluşturan inflamatuvar bir hastalıktır. Patogenezinde inflamasyon , fibrozis , apoptozis rol oynar .Sitokeratinler epitelyal hücre iskeletini yapan ara flamentlerdir.Hücrenin şeklini koruma,motilite ve hücreler arası etkileşim gibi birçok işlevleri vardır. .Sitokeratin 18 mesane epiteli, kolon mukozası, hepatosit, pankreas asiner hücresi gibi çeşitli dokulardan sentezlenir ve apoptozisin belirlenmesinde bir marker olarak rol oynayabildiği çeşitli çalışmalarda gösterilmiştir. Bu çalışmanın amacı kronik pankreatitin sitokeratin 18 düzeyi ile ilişkisi olup olmadığını saptamaktır. Gereç ve Yöntem: Kronik pankreatit tanısı ile izlenen 35 hasta ve sağlıklı 35 kontrol grubu çalışmaya dahil edildi. Hastaların 12 saat açlık sonrası açlık serum sitokeratin 18 düzeyleri ölçüldü. Kronik pankreatit ve sitokeratin 18 düzeyleri arasındaki ilişki değerlendirildi. Bulgular: Kronik pankreatli hastaların serum sitokeratin 18 düzeyleri 0,45 ±1,40 g/ml, sağlıklı erişkinlerin değerlendirildiği kontrol grubunda ise sitokeratin düzeyi 0,16 ± 0,16 ng/mL saptandı. Çalışma grubunda ve kontrol grubunda sitokeratin 18 düzeyleri arasında istatiksel olarak anlamlı ilişki saptanmadı. (p:0,23) Tartışma ve Sonuç: Kronik pankreatit patogenezinde apoptozisin rolü bilinmesine karşın biz yaptığımız çalışmada apoptozis belirteci olan sitokeratin 18 düzeyi ile kronik pankreatit arasında ilişki saptayamadık. Sitokeratin 18 in kronik pankreatit tanı ve takibinde kullanılmak için uygun bir marker olmadığını gösterdik. Kronik pankreatit tanı ve progresyonu gösterecek yeni markerların bulunması amacıyla ek çalışmalara ihtiyaç vardırIntroduction and aims: Chronic pancreatitis (CP) is a inflammatory disease that leading to morphological changes, , permanent destruction, fibrosis in pancreas with endocrine and exocrine functional impairment. İnflammation, fibrosis and apoptosis plays role in the pathogenesis of the disease. Cytokeratins compose the intermediate filament cytoskeleton of epithelial cells. Cytokeratin functions are maintain cell shape, motility, and cell-cell interactions. Cytokeratin 18 is synthesized bladder epithelium, colonic mucosa, hepatocytes, pancreatic acinar cells of various tissues. Several studies showed that cytokeratin 18 have a role in apoptosis and can be use as a marker of apoptosis. The aim of this study is to determine relationship between chronic pancreatitsn and cytokeratin 18 . Materials and Methods: 35 chronic pancreatitis patients and 35 healthy volunteers were enrolled for the study. Blood samples for cytokeratin 18 tests were taken after 12 h fasting. Relationship between chronic pancreatin and cytokeratin 18 were evaluated. Results: The mean levels of cytokeratin 18 were 0.45 ± 1.40 ng / ml in patients with chronic pankreatits and the mean levels of cytokeratin 18 were 0.16 ± 0.16 ng / ml in the control group. There was no statistically association between chronic pancreatits and cytokeratin 18 . Discussion and Conclution:. The role of apoptosis in the pathogenesis of chronic pankreatitis well known situation but in this study there was no statistically association between chronic pancreatitis and cytokeratin 18 which is the marker of apoptosis. We showed that cytokeratin is not a reliable marker for the diagnosis and fallow up of chronic pancreatitis and additional studies are needed to show new markers for diagnosis and fallow up of chronic pancreatiti

MUSICAL TRACES IN KAHRAMANMARAS IN THE LIGHT OF DOCUMENTS IN THE BEGINING OF THE 20TH CENTURY OTTOMAN EMPIRE

In the period from Tanzimat to the Republic, many innovations in the field of music are encountered along with westernization movements in the Ottoman Empire. In this period, which is also called as the process of modernization in the literature, European music took its place in Ottoman music, many composers and musicians from abroad were invited to the palace, and works were written for the sultans. Among the musical innovations made since the reign of Sultan II. Abdülhamid; music venues, instrument supply centers, note printing houses, music broadcasts, associations and schools are seen to be widespread. As a result of this researches we have done in this way, the document with the sketch plan and the facade sections of the construction of a two-storey music building adjacent to the American Girls’ School, was reached during the reign of V. Mehmed Reşad. In the light of the document obtained within the scope of this research, the current location of the relevant music building in Kahramanmaraş has been determined and examined within the framework of Ottoman, American and British relations. It is understood that the Maras Music School continued its function until the missionary schools were closed. We do not know when the building that does not exist today destroyed. Keywords