Brain Metastases, Large Cell Neuroendocrine Carcinomas and Prognosis

Objective: Pulmonary large cell neuroendocrine carcinomas (LNECs) are not common but brain metastases are common in LNEC patients. Because of their rarity, there are no randomized controlled trials on optimal treatment. Generally available data are based on case reports and retrospective studies. For this reason, we retrospectively analyzed patients with LNEC that we followed up for brain metastases to contribute to the literature. Methods: Between 2009 and 2020, 38 patients with brain metastases diagnosed with LNEC in our center were reviewed retrospectively. Results: 38 patients were evaluated. The mean survival time was 5.17 months (95% confidence interval (CI) : 3.17-7.13). In multivariate analysis showed us that; shorter overal survival is associated with age (p=0.001), uncontrol of primary cancer (p=0.014), presence of metachronous metastases (p=0.003), poor Eastern Cooperative Oncology Group (ECOG) performance score (p=0.025), and high uric acid level (p=0.001) and high lactate dehydrogenase (LDH) levels (p=0.009). Conclusion: LNECs are rare but aggressive cancers. LNECs often metastasize to the brain. According to our study, high LDH, high uric acid, poor ECOG performance score, ≥65 years, metachronous metastasis, uncontrolled primary tumor are associated poor prognosis. LDH, uric acid, age, presence of metachron metastasis, controbility of primary tumor can be used as easy and inexpensive biomarkers to determine the prognosis and in the follow-up and treatment of patients with LNECs with brain metastases as metastases seen of other cancers

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

Relationship between brain metastasis and thyroid transcription factor 1

Abstract Brain metastases (BMs) are common in lung adenocarcinomas (ACs). Thyroid transcription factor 1 (TTF-1) is important in the diagnosis of AC. This study aimed to examine the relationship between TTF-1 and BM for the first time in literature. The data of 137 patients with AC that developed BM between 2009 and 2020 were retrospectively analyzed. A total of 137 patients, 120 (87.6%) male, and 17 (12.4%) female were examined. Their mean age was 59.78 ± 0.82 years. The Eastern Cooperative Oncology Group (ECOG) performance score was 0–1 (< 2) for 39 (28.5%) patients and 2–4 (≤ 2) for 98 (71.5%). TTF-1 was positive in 100 (73%) patients and negative in 37 (27%). More than five BMs were present in 102 (74.4%) patients and less than five in 35 (25.6%). All the patients received whole-brain radiotherapy. None of the patients was suitable for surgery or radiosurgery. The median survival time was 6.4 [95% confidence interval (CI), 5.67–7.1] months. The survival time was 7 (95% CI, 5.91–8.09) months for the TTF-1 (+) patients and 5.8 (95% CI, 4.1–7.5) months for the TTF-1 (−) patients. In the univariate analysis, there was a significant relationship between survival time and age (p = 0.047), TTF-1 (p = 0.024), and ECOG performance score (p = 0.002). The multivariance analysis revealed a significant relationship between survival and TTF-1 (p = 0.034) and ECOG score (p = 0.007). We found a correlation between survival time and ECOG performance score and TTF-1. TTF-1 can be used as a biomarker to monitor prognosis in the follow-up and treatment of patients with AC that develop BM

ELEŞTİREL DÜŞÜNME BECERİLERİNİ GELİŞTİRMEYE YÖNELİK TASARLANAN TEKNOLOJİ DESTEKLİ ÖĞRETİM UYGULAMALARININ ÖĞRETMEN ADAYLARI GÖRÜŞLERİ AÇISINDAN DEĞERLENDİRİLMESİ

Bu araştırmada, ilköğretim matematik öğretmeni adaylarının, Facione (1990) tarafından belirlenen eleştirel düşünme becerilerinin gelişimine katkı sağlayabilmek için tasarlanan teknoloji destekli öğretim modeli uygulamaları ile ilgili görüşleri incelenmiştir. Araştırma, 2019-2020 eğitim-öğretim yılı güz döneminde, Marmara Bölgesindeki bir devlet üniversitesinin Eğitim Fakültesi İlköğretim Matematik Öğretmenliği 4. sınıf öğrencileriyle gerçekleştirilmiştir. Araştırmada nitel araştırma yöntemlerinden durum çalışması deseni kullanılmıştır. Veri toplama aracı olarak toplam beş sorunun yer aldığı yarı yapılandırılmış görüşme formu kullanılmıştır. Görüşmeler uygulama sürecine katılmış 14 öğretmen adayı ile gerçekleştirilmiştir. Elde edilen veriler betimsel analiz tekniği ile incelenmiştir. Analiz sonucunda tasarlanan öğretim modeli uygulamalarının etkisi, öğretmen adaylarının görüşlerinden yola çıkarak beş tema altında sunulmuştur. Bu temalar, (1) derslerde uygulanan yöntem, (2) derslerin içeriği, (3) GeoGebra kullanımının ders ortamına etkisi, (4) ders planlarının etkinliği ve (5) derslerin eleştirel düşünme becerilerine etkisi şeklindedir. Temalar, olumlu ve olumsuz iki kategori olacak şekilde 40 koddan oluşmuştur. Temalarda en sık ifade edilen kodlardan araştırmanın sonuçları elde edilmiştir. Araştırmanın sonucunda, tasarlanan öğretim modeli uygulamalarının Facione’nin belirlediği eleştirel düşünme alt becerileri ile uyumlu olduğu tespit edilmiştir. Ayrıca, öğretmen adaylarının, tasarlanan modülün eleştirel düşünme farkındalığının oluşmasına katkı sağladığı yönünde görüş bildirdikleri sonucuna ulaşılmıştır

Prognostic significance of the baseline serum uric acid level in non-small cell lung cancer patients treated with first-line chemotherapy: a study of the Turkish Descriptive Oncological Researches Group

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Non-small cell lung cancer (NSCLC) is one of the most common cancers. Most of the patients are inoperable at the time of diagnosis, and the prognosis is poor. Many prognostic factors have been identified in prior studies. However, it is not clear which factor is more useful. In this study, we investigated whether uric acid, the last breakdown product of purine metabolism in humans, has a prognostic significance in advanced NSCLC. A total of 384 NSCLC patients at stage IIIB/IV and who did not meet exclusion criteria were included in this retrospective cross-sectional study. The patients’ serum uric acid levels before first-line chemotherapy and demographic (age, gender, smoking), clinical (performance status, weight loss, disease stage, first-line treatment regimen), laboratory (hemoglobin, lactate dehydrogenase), and histologic (histologic type, tumor grade) characteristics were recorded. First, a cut-off value was determined for serum uric acid level. Then, the patients were stratified into four groups (quartiles) based on their serum uric acid levels. Descriptive statistics, univariate and multivariate analyses, and survival analyses were used. Majority of the patients were males, smokers and metastatic at time of diagnosis and had history of weight loss and adenocarcinoma upon pathological examination. The serum uric acid levels of all patients were determined as 4.9 ± 2.9 (range 1.9–11.3). The patients were stratified according to quartiles of serum uric acid concentration with cutoff values defined as 7.49 mg/dL (highest quartile, Group 4). Among the patients who had serum uric acid levels over 7.49, it was observed that those who also had squamous cell carcinoma had a greater rate of brain metastasis, a shorter time lapse until brain metastasis, and lower overall survival rate. It can be assumed that NSCLC patients who had histologically shown squamous cell carcinoma display brain metastasis and poor prognosis. It can be recommended to repeat this study with larger patient series including immunohistochemical, molecular, and wider laboratory investigations

The Effects of Vitamin E on Antioxidant Enzyme Activity in HepG2 Cells

Sayiner, Serkan/0000-0002-3297-5369; SALMANOGLU, BERRIN/0000-0003-4344-5782WOS: 000382113800009It is aimed to investigate the effect of vitamin E, powerful antioxidant (alpha-tocopherol succinate) on antioxidant enzyme activities in hepatocellular carcinoma (HepG2) cells. The hepatocellular carcinoma cell line HepG2 was used and the cells were cultured in the absence (control) or presence of different dose of vitamin E (50 mM, 50 mu M and 10 mu M vitamin E) for 24 h. The effect of vitamin E (alpha-tocopherol succinate) on catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities in hepatocarcinoma cells were measured by spectrophotometry. A significant decrease in GPx activity was detected in 50 mM vitamin E treated HepG2 cells. However a significant decrease occurred in 10 mu M and 50 mu M vitamin E applied HepG2 cells. SOD activity in study groups were lower than in control cells. In addition to this, the decrease in SOD activity in 50 mM vitamin E applied cells was significant. CAT enzyme activity in 50 mu m vitamin E applied HepG2 cells was higher and, in 10 mu M and 50 mM vitamin E applied HepG2 cells were lower than in control group. It was determined that vitamin E has a dose-dependent effect on antioxidant enzyme activity in HepG2 cells

Vitamin E'nin HepG2 Hücrelerinde Antioksidan Enzim AktivitesiÜzerine Etkileri

Güçlü bir antioksidan olan vitamin E'nin (alfa-tokoferolsüksinat) HepG2 hücrelerinde antioksidan enzim aktiviteleri üzerine etkisinin araştırılması amaçlanmıştır. Çalışma materyali olarak HepG2 hücre hattı kullanılmıştır. Vitamin E uygulanan hücreler çalışma grubunu vitamin E uygulaması yapılmayan hücreler kontrol grubunu oluşturmuştur. Çalışma grubu hücrelerine 10 µM, 50 µM, 50 mM dozlarda vitamin E uygulaması yapılarak, 24 saat sonunda HepG2 hücrelerinde antioksidan enzimlerden katalaz (CAT), süperoksitdismutaz (SOD) ve glutasyonperoksidaz (GPx) aktiviteleri spektrofotometrik olarak ölçülmüştür. 50 mM vitamin E uygulanan HepG2 hücrelerinde GPx enzim aktivitesinde anlamlı bir artış saptanmıştır. Ancak, 10 µM ve 50 µM vitamin E uygulanan HepG2 hücrelerinde ise anlamlı bir azalma meydana gelmiştir. Vitamin E uygulaması yapılan hücrelerdeki SOD aktivitesi vitamin E uygulaması yapılmayan kontrol grubuna göre daha düşük ölçülürken, 50 µM vitamin E uygulanan HepG2 hücrelerinde SOD aktivitesinde anlamlı azalma tespit edilmiştir. 50 µM vitamin E uygulanan HepG2 hücrelerindeki CAT enzim aktivitesi kontrol grubuna göre daha yüksek bulunurken, 10 ?M ve 50 mM vitamin E uygulanan hücrelerdeki CAT enzim aktivitesi kontrol grubuna göre daha düşük tespit edilmiştir. Vitamin E'nin HepG2 hücrelerinde antioksidan enzim aktiviteleri üzerinde doz-bağımlı etkisinin olduğu belirlenmiştirIt is aimed to investigate the effect of vitamin E, powerful antioxidant (alpha-tocopherol succinate) on antioxidant enzyme activities in hepatocellular carcinoma (HepG2) cells. The hepatocellular carcinoma cell line HepG2 was used and the cells were cultured in the absence (control) or presence of different dose of vitamin E (50 mM, 50 ?M and 10 ?M vitamin E) for 24 h. The effect of vitamin E (alpha-tocopherol succinate) on catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities in hepatocarcinoma cells were measured by spectrophotometry. A significant decrease in GPx activity was detected in 50 mM vitamin E treated HepG2 cells. However a significant decrease occurred in 10 µM and 50µM vitamin E applied HepG2 cells. SOD activity in study groups were lower than in control cells. In addition to this, the decrease in SOD activity in 50 mM vitamin E applied cells was significant. CAT enzyme activity in 50 ?m vitamin E applied HepG2 cells was higher and, in 10 ?M and 50 mM vitamin E applied HepG2 cells were lower than in control group. It was determined that vitamin E has a dose-dependent effect on antioxidant enzyme activity in HepG2 cell

Are pretreatment inflammation-based prognostic scores useful in predicting the outcomes of patients with ALK-positive NSCLC?

Background: Approximately 5% of all diagnosed non-small cell lung cancer (NSCLC) patients harbor a genetic rearrangement between the ALK and EML4 genes, representing a specific molecular and clinical subgroup (ALK+ NSCLC). To date, upfront treatment with ALK-tyrosine-kinase inhibitors (ALK-TKIs) has replaced chemotherapy in the first line setting for this subset of patients with excellent results, but reliable prognostic markers are lacking. An increased systemic inflammatory response has been shown to be associated with a poor prognosis, and some of the parameters used to characterize this response can easily be measured in clinical practice in several tumor types, but have not been analyzed extensively in ALK+ lung cancer in the era of crizotinib. Method: We reviewed the medical records of all patients with previously treated advanced ALK-positive NSCLC who received crizotinib between January 2013 and March 2018 outside of a clinical trial. Pre-treatment modified Glasgow prognostic score (mGPS), Prognostic Nutritional Index (PNI) and Systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI and SII on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Result: 82 patients were treated. Median age was 52.5 years (range; 20e77 years); 42.7% were female. Eighty-four point two percent of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1; 17.1% had received 2 prior systemic therapies. The objective response rate was 77.2% (CR+PR). The optimal cutoff levels were 0.09 for mGPS and PNI, 934.7 for SII by ROC curves analysis. Patients in the SII 934.7 grous was significantly correlated with worse PFS and OS by univariate analysis (Figure 1). In multivariate analyses, pretreatment prognostic nutritional index (PNI) 0.09 was independently associated with inferior OS (1 year OS rates, 90.2% vs. 73.7%; HR 2.46, 95% CI 0.88- 4.85; p ¼ 0.035). Additionally, we evaluated the effects of these markers on response prediction. The logistic regression analysis of the predictive factors for the response to crizotinib demonstrated that the mGPS and PNI were associated with inferior ORR (OR: 0.1, 95% CI 0.16-1.04; p ¼ 0.009 and OR: 0.16, 95% CI 0.02-0.55; p ¼ 0.035, respectively). Conclusion: In a cohort of patients with ALK positive NSCLC treated with crizotinib in routine practice, elevated pre-treatment SII was associated with shorter OS and PFS in univariate analysis and PNI was associated with shorter OS in multivariate analyses. Moreover the mGPS and PNI were associated with lower response rates

Systemic inflammatory markers as a predictors of response to crizotinib in patients with ALK-positive non-small-cell lung cancer

The significance of the presence of a systemic inflammatory response (SIR) in predicting survival has been demonstrated in patients with cancer. Moreover, neutrophil-to-lymphocyte ratio (NLR), lymphocyteratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) have been also investigated in patients with both early and advanced non-small-cell lung cancer (NSCLC). However, determination of SIR predicting outcomes of patients who are likely to response to crizotinib in ALK-positive NSCLC patients has not been clearly demonstrated