The interaction of glucose transporter 1 and mast cell tryptase levels with prognostic and predictive factors in early stage breast cancer

Amaç ve Hipotez: Erken evre meme kanserinde uygulanan tedavilerle kür şansının artması nedeniyle prognostik ve prediktif faktörlerin iyi tanımlanması büyük önem taşımaktadır. Başlıca prognostik ve/veya prediktif faktörler arasında lenf nodu tutulumu, tümör boyutu, tümör dokusunda östrojen reseptörü (ER), progesteron reseptörü (PR) ve insan epidermal büyüme faktör reseptörü-2 (HER2/neu), Ki-67 ve p53 düzeyleri, hastanın yaşı, performansı ve menapozal durumu sayılabilir. Mast hücre triptazı (MHT) tripsin benzeri serin peptidaz (proteinaz) aktivitesine sahip bir enzimdir. Bu enzimin aktivitesinin tümöral kan akımı, dolayısıyla da oksijenizasyonu düzenlediği, anjiyogenezi destekleyerek tümöral gelişim ve metastazı indüklediği düşünülmektedir. Glikoz taşıyıcısı (GLUT) ailesi glikozun ortamdan hücre içine alımında rol oynayan membranda yerleşik proteinlerdir. Bu ailenin en sık çalışılan ve yaygın alt tiplerinden biri olan GLUT-1, özellikle hücrenin bazal glikoz ihtiyacı yönünden önem taşımaktadır. Malin hücrelerin akselere metabolizmaları sonucu glikoz ihtiyaçları artmaktadır. Erken evre meme kanserinde gerek MHT gerekse GLUT-1 ekspresyonunun prognostik önemi iyi bilinmemektedir. Bu çalışmanın amacı hastanemizde tanı alarak opere edilmiş erken evre meme kanseri olgularında MHT ve GLUT-1 ekspresyon düzeylerini belirlemek ve bilinen histopatolojik ve klinik prognostik ve prediktif faktörler ile ilişkisini değerlendirmektir. Yöntem: Bu çalışmada, 2003'2008 yılları arasında Adnan Menderes Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı'na incelenmek üzere gönderilen meme kanseri tanısıyla opere edilmiş olgular arasından çalışma kriterlerine uyan 35 postmenapozal kadın hastaya ait dosyalar ve mastektomi veya lumpektomi materyalleri incelendi. Çalışma parametreleri ile etkileşme potansiyeli taşıyan ilaç ve alışkanlık öyküleri, neoadjuvan tedavi alımı veya komorbid hastalıkları bulunan olgular çalışma dışı bırakıldı. Meme kanseri materyalleri hematoksilen-eozin (H.E.) boyaları ve ER, PR, HER2/neu, GLUT-1 ve MHT düzeyleri de immünohistokimyasal çalışmalar ile değerlendirildi. Verilerin istatistiksel olarak değerlendirilmesinde SPSS Windows version 14.0 bilgisayar paket programı kullanılarak gereğine göre Fisher's Exact test, Mann Whitney U testi, Kruskal Wallis testi ve Pearson's ve Spearman korelasyon analizleri kullanıldı. İstatistiksel olarak p<0.05 anlamlı kabul edildi. Bulgular: Hastaların ortalama tanı yaşı 64±11 yıldı. Lenf nodu tutulumu 19 (%54) olguda pozitif, 16 (%46) olguda negatifti, tümör boyutu %80 T1 ve T2 düzeyindeydi. Hücre tipi 24 (%69) olguda invaziv duktal karsinomdu, ER ve/veya PR 28 (%80) olguda pozitif, HER2/neu ise 11 (%31) olguda pozitif (3+) bulundu. Prognostik ve prediktif faktörlerden lenf nodu tutulumu ile tümör boyutu, patolojik evre ve nükleer derece, tümör boyutu ile patolojik evre ve nükleer derece, patolojik evre ile nükleer derece, nükleer derece ile histolojik derece ve ER ile PR arasındaki ilişkiler anlamlı bulundu. Sadece invaziv duktal karsinom olgularını içeren alt grup analizinde de bu sonuçlar değişmedi. Çalışmada MHT aktivitesi ve GLUT-1 düzeyleri sırasıyla 5 (%14) ve 11 (%31) hastada negatif iken, 30 (%86) ve 24 (%69) olguda değişen derecelerde pozitif değerler gösterdiler. Mast hücre triptazı aktivitesi pozitif olgularda fibrozis derecesi ile MHT düzeyleri arasında pozitif korelasyon tespit edildi. Ayrıca, MHT aktivitesi, histolojik derece ile de anlamlı (negatif) korelasyon gösterdi. Hastaların GLUT-1 ekspresyonu ile prognostik ve prediktif faktörler, ayrıca vücut kitle indeksi ve diabetes mellitus varlığı gibi olası ilişki gösterebilecek parametreler arasında anlamlı korelasyon bulunmadı. Lenf nodu tutulumu negatif 16 (%46) düşük riskli olgunun alt grup analizinde, GLUT-1 düzeyi ile tümör boyutu arasında pozitif korelasyon tespit edildi, ancak istatistiksel olarak anlamlı bulunmadı. Sonuç: Bu çalışmada tüm olgularda MHT aktivitesi ile tümöral fibrozis ve histolojik derece arasında, nod negatif olgularda da GLUT-1 düzeyi ile tümör boyutu arasında korelasyon tespit edilmiş olması, erken evre meme kanserinde MHT aktivitesi ve GLUT-1 ekspresyonunun prognostik önem taşıyabileceğini ve her ikisinin de daha geniş olgu sayıları içeren, uzun takip süreli prospektif çalışmalarla değerlendirilmesinin uygun olacağını düşündürmüştür.Purpose: Identification of prognostic and predictive factors is critically important in early stage breast cancer due to the chance of achieving cure with appropriate adjuvant treatments. Major prognostic and/or predictive factors include lymph node metastasis, size and estrogen receptor (ER) and progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2/neu), Ki-67 and p53 status of the primary tumor, the age, performance and menopausal status of the patient. Mast cell tryptase (MCT) is a trypsin like enzyme with serine peptidase (proteinase) activity. This enzyme's activity regulates tumor blood flow as well as oxygenization and supports tumor growth and metastasis by promoting angiogenesis. Glucose transporters (GLUT) family, represent a group of trans-membrane proteins that have a role on internalizing glucose in the cells. GLUT-1 is one of the most common and widely studied subtype of the GLUT family. Consumption of glucose increases in malignant cells due to the accelerated cell metabolism. The prognostic value of both MCT and GLUT-1 expressions in early stage breast cancer has not been established well. The purpose of this study was to measure the levels of MCT and GLUT-1 expressions in early stage breast cancer patients operated in our hospital and to determine the interaction of these parameters with established clinical and pathological prognostic and predictive factors. Methods: We studied the hospital registries and mastectomy or lumpectomy materials of 35 postmenopausal women that have been operated in-between the years 2003-2008 for breast cancer and referred to the Department of Pathology of Adnan Menderes University, Medical Faculty. The patients with histories of addiction and use of medicine, neoadjuvant treatments or co-morbid diseases to interact with the study parameters were excluded. The breast tumor materials stained with routine hematoxylin & eosin (H.E.) were also analyzed by immunohistochemical methods for ER, PR, HER2/neu, GLUT-1, and MCT expressions. The statistical analyzes were performed by SPSS Windows version 14.0 PC packet program and Fisher's Exact, Mann Whitney U, and Kruskal Wallis tests and Pearson's and Spearman correlation analyzes were used as needed. Statistical value of p<0.05 was accepted as significant. Results: The patients' mean age of diagnosis was 64±11 years. Lymph node metastases was positive in 19 (54%), and negative in 16 (46%) patients and the tumor size was at T1 and T2 stages in 80%. The cell type was invasive ductal carcinoma in 24 (69%), ER and/or PR was positive in 28 (80%), and HER2/neu was positive (3+) in 11 (%31) patients. The correlations were positive in-between the prognostic and predictive factors such as; lymph node status and tumor size, pathological stage and nuclear grade; tumor size and pathological stage and nuclear grade; pathological stage and nuclear grade; nuclear grade and histological grade; and ER and PR. These results did not also differ in the subgroup analyzes of the invasive ductal carcinoma cases. The MCT levels and GLUT-1 expressions were negative in 5 (14%) and 11 (31%) patients, showed varying degrees of positivity in 30 (86%) and 24 (69%) patients, respectively. In study patients with positive MCT activity there was a positive correlation in between the grade of fibrosis and MCT activity. Also, the MCT activity had a significant negative correlation with histological grade. There was no significant correlation in-between the GLUT-1 expression level and the prognostic and predictive factors as well as the existence of diabetes mellitus and the body mass index of the patients. In the subgroup analyzes of the 16 (46%) low risk patients with negative lymph node metastases, GLUT-1 expression level showed positive correlation with primary tumor size, however, this correlation did not reach to significant levels. Conclusion: The determination of correlations in-between MCT activity levels and tumor fibrozis and histological grade in the overall study group; and in-between GLUT-1 expression levels and primary tumor size in the node negative patients subgroup in this study suggest that, both MCT activity and GLUT-1 expression levels might have prognostic values in early stage breast cancer patients and should be further researched in extended prospective studies with longer follow-up periods

Assessment of sprinkler irrigation systems used for peanut irrigation in Mediterranean zone, Turkey

This study was conducted to evaluate irrigation practices of sprinkler-irrigated peanut farms at Kadirli-Osmaniye province of Turkey. The seasonal number of irrigation in the examined farms varied from 3 to 5. Sprinklers with double nozzle had flow rates ranging from 1.5 to 2.2 m3 /h. The average rate of sprinkler precipitation was found as 13 mm/h with a 20 h of water application under four irrigation events to the peanut during whole growth cycles, and seasonal applied irrigation water was around 314 mm. Average net grain yield was between 3.15 and 3.50 t/ha. Total labor and irrigation energy costs were 200 USD/ha and 158 USD/ha, respectively. The sprinkler irrigation system was found well suited for peanut irrigation. High quality management of irrigation water resources is necessarily prerequisites for sustainable agro-production particularly at water shortage agro-zones

Watering uniformity of drip irrigation systems using in irrigation of maize for Konya-Çumra province, Turkey

This study was conducted to determine water distribution uniformity of emitters at different drip irrigation systems using at maize farms in Çumra region of Konya, Turkey. Watering performance of drippers was classified by using two criteria namely Uniformity Coefficient, UC, and Emission Uniformity, EU. In results, UC varied from 68% to 84% with an average of 75% and water delivery class was ‘Moderate’ in accordance of such a mean value. EU varied from 44% to 71% with an average of 55%, and watering performance was ‘Poor’ or ‘Unacceptable’ in regard to average of EU value. Variations in emitter discharge rates in all examined drip irrigation systems were found higher than 10%. Drip irrigation system should be designated in accordance of hydraulic principles, installed by experienced people and timely maintenance-repair works are needed for maximizing water distribution uniformity consequently improvement grain/ silage yields as well as more economical returns

Production performance of caged layers in evaporative cooling and mechanical ventilated housing

The study was designed to investigate effect of evaporative cooling and mechanical systems on the performance of caged layers for Konya province of Turkey. Two different treatments were analyzed- evaporative cooling, house - 1 and mechanical ventilation, house - 2 during the summer season of 2005. Inside temperature reduced effectively in house - 1 while higher inside temperatures in house - 2 created a stressful environment for caged layers. The average temperature in house - 1 was as 24.4ºC while it was 27.1ºC in house - 2. The average relative humidity was 52.7% and 40.1% in house - 1 and house - 2, respectively. Average egg production of layers was 1.03% higher in house - 1 than house - 2. The mortality rate in house - 1 and house - 2 was determined to be 0.18% and 0.23%, respectively. The average percentages of cracked eggs in houses - 1 and house - 2 were 1.41% and 0.89%, respectively. The average egg weights were 65.1g and 60.2g in houses 1 and 2, respectively. Daily feed intake of layers in houses - 1 and house - 2 was found as 116.5 g/hen and 103.4 g/hen, respectively

Losartanın yeni tanı hipertansiyon hastalarının hematolojik parametrelerine ve trombosit agregasyonuna etkisi

Objective: Hypertension is associated with increased platelet function. Some antihypertensive drugs have antiplatelet activity. In this study, we aimed to investigate the effects of losartan on platelet aggregation induced by adenosine diphosphate (ADP), collagen, epinephrine, ristocetin, other hematological and, inflammatory parameters. Materials and Methods: Twenty-five patients (19 female, 6 male; mean age: 54±8 years) with newly diagnosed hypertension were included in the study. All patients were with stage 1-2 essential hypertension according to the seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Initial blood pressure measurement was performed in all patients and losartan 100 mg/daily together with life style changes, such as diet and exercise was started. Platelet aggregation was evaluated with the use of ristocetin, epinephrine, collagen, and ADP. Complete blood count was also done. Platelet aggregation tests and blood pressure measurements were repeated after 8 weeks of therapy. Results: Systolic and diastolic blood pressure significantly decreased with losartan after 8 weeks (p<0.001). After treatment, there was no significant difference in platelet aggregation with ADP, collagen, and epinephrine (p>0.05). The aggregation with ristocetin significantly decreased (p=0.027). Besides, significantly lower hemoglobin and hematocrit levels were observed (p=0.034, p=0.039, respectively). Conclusion: Losartan may produce independent activities apart from its antihypertensive effects by providing significant reductions in platelet aggregation with ristocetin, and in hematocrit levels with hemoglobin. Therefore, it may be beneficial in the prevention of atherosclerosis and thrombosis.Amaç: Hipertansiyon artmış trombosit fonksiyonu ile ilişkilidir. Bazı antihipertansif ilaçların anti-trombosit aktiviteleri vardır. Biz bu çalışmada, losartanın adenozin difosfat (ADP), kollajen, epinefrin, ristosetin ile trombosit agregasyonuna, diğer hematolojik ve enflamatuvar parametreler üzerine etkilerinin araştırılmasını amaçladık.Gereç ve Yöntem: Çalışmaya yeni tanı hipertansiyonlu ortalama yaşı 54±8 yıl olan 19’u kadın, 6’sı erkek 25 hasta alındı. Yüksek kan basıncını önleme, saptama, değerlendirme ve tedavi üzerine Birleşik Komite’nin yedinci raporuna göre tüm hastaların, evre 1-2 esansiyel hipertansiyon tanısı mevcuttu. Başlangıç kan basınçları ölçüldü ve her bir hastaya diyet, egzersiz gibi yaşam tarzı değişikliği ile birlikte losartan 100 mg/gün tedavisi başlandı. Tedavi öncesi ristosetin, epinefrin, kollagen ve ADP ile trombosit agregasyonu değerlendirildi. Ayrıca tam kan sayımları ölçüldü. Trombosit agregasyon testleri ve kan basıncı ölçümleri tedaviden 8 hafta sonra tekrar değerlendirildi. Bulgular: Losartan ile 8 haftanın sonunda sistolik ve diyastolik kan basıncında anlamlı düşüş saptandı (p<0,001). Tedavi sonrası, ADP, kollajen ve epinefrin seviyeleri ile trombosit agregasyonunda anlamlı farklılık saptanmadı (p>0,05). Ristosetin ile agregasyon önemli ölçüde azaldı (p=0,027). Aynı zamanda, önemli ölçüde düşük hemoglobin ve hematokrit seviyeleri gözlemlendi (p=0,034 ve 0,039, sırasıyla). Sonuç: Losartan, hemoglobin ile hematokrit seviyelerinde ve ristosetinle trombosit agregasyonunda önemli ölçüde düşüş sağlayarak antihipertansif etkisinden bağımsız aktiviteler ortaya koyabilir. Bu sayede aterosklerozun ve trombozun önlenmesinde faydalı olabilir

Forage yield and lodging traits in peas (Pisum sativum L.) with different leaf types

Two semi-leafless and four leafed pea (Pisum sativum L.) genotypes were evaluated for plant height, lodging scores, and forage yield in eight diverse locations with typical Mediterranean or Mediterranean-type climate in the 2001-2002 and 2002-2003 growing seasons. The genotypes used in this study were forage type with indeterminate growing habit. Significant differences among pea genotypes were found for all traits over years and locations. All interactions which related to G x E interaction showed significance (P>0.01) for all traits. The forage yield of the pea genotypes averaged 26605 kg ha(-1) and the highest yield was obtained from the leafed genotype Urunlu. Its forage yield reached to 35970 kg ha(-1) yield level at Samsun location

Genotype x nvironment interaction and stability analysis for dry matter and seed yield in field pea (Pisum sativum L.)

The objectives of this study were to evaluate dry matter (DM) yield and seed yield of six leafed and semi-leafless pea (Pisum sativum L.) genotypes, and to compare them for these traits. Evaluation of genotype x environment (G x E) interaction, stability and cluster analysis were also carried out at eight diverse locations with typical Mediterranean and Mediterranean-type climate during the 2001-2002 and 2002-2003 growing seasons. Significant differences were found among the pea genotypes for DM and seed yield on individual years and combined over years, and in all locations. All interactions which related to G x E interaction showed significance (P>0.001) for DM and seed yield. The highest yield (4789 kg ha(-1)) was obtained from the leafed genotype 'Urunlu'. However, stability analysis indicated that for DM yield, the leafed genotypes 'Golyazi' and 'Urunlu' should be grown in low yielding and high yielding environments, respectively. Cluster analysis, based on grouping locations, showed that P101 was the preferred variety in low yielding environments, and P98, in high yielding ones. It was suggested that the use of both stability and cluster analyses might give better results. Comparison of cluster and stability analyses showed that the stability analysis fails to recommend cultivars to different regions where yield potential showed significant differences. It seems, however, that cluster analysis could be a powerful tool to examine G x E interaction. If the number of environments was sufficient, a separate stability analysis could be run in each cluster

Monocyte-to-HDL-cholesterol ratio is associated with Ascending Aorta Dilatation in Patients with Bicuspid Aortic Valve

Background: The importance of monocyte count-to-HDL-cholesterol ratio (MHR) in cardio- vascular diseases has been shown in various studies. Ascending aortic dilatation (AAD) is a common complication in the patients with bicuspid aortic valve. In this study, we aimed to investigate the relationship between MHR and the presence of aortic dilatation in the patients with bicuspid aortic valve. Methods: The study population included totally 347 patients with bicuspid aortic valve.169 patients with aortic dilatation (ascending aorta diameter 65 4.0 cm) and 178 patients with no aortic dilatation. Echocardiographic and laboratory measurement was done and compared between groups. Results: The mean age of the participants was 44.7 \ub1 15.4 years and average ascending aorta diameter was 3.2 \ub1 0.3 cm in dilatation negative group and 4.4 \ub1 0.4 cm in positive group. MHR was significantly increased in in patients with aortic dilatation. MHR and uric acid level was independently associated with the presence of aortic dilatation in the patients with bicuspid aortic valve. Conclusion: We found a significant relationship between MHR and aortic dilatation in the patients with bicuspid aortic valve

The genetic history of the Southern Arc: a bridge between West Asia and Europe

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra–West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe