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Evaluation of BCL-2 and survivin expression in lung adenocarcinoma, squamous cell carcinoma and pleural mesothelioma
Tıp Fakültesi, Tıbbi Patoloji Ana Bilim DalıAmaç: Dünyada, akciğer karsinomu ve plevral mezotelyoma sıklığı giderek artmakta ve yılda yaklaşık 2,2 milyon yeni akciğer karsinomu vakası ile 14.200 yeni plevral mezotelyoma vakasının olduğu bildirilmektedir. Programlanmış hücre ölümünde ortaya çıkan anormallikler karsinomların oluşumunda ve progresyonunda önemli rol oynar. Genetik yolaklarla düzenlenen programlı hücre ölümünde yolakların çalışma ve kontrol edilme süreçlerinde oluşacak bozulmalar kontrolsüz hücre büyümesine ve tümör gelişimine neden olur. Söz konusu süreçlerde görev alan bcl-2, apopitozu inhibe ederek programlı hücre ölümüne engel olduğu tespit edilmiş ilk proteindir. Survivin ise apopitozu düzenleyen öneml b r prote n ailesinin mensubu olup, belirlenen ilk inhibitörlerden biridir. Çalışmamızda, akciğer adenokarsinomu, skuamöz hücreli karsinom (SHK) ve plevral mezotelyomalarda, survivin ve bcl-2 ekspresyonları ve tümörü infiltre eden lenfositlerin (TIL) progresyondaki rollerinin incelenmesi amaçlandı. Ayrıca, klinikopatolojik parametrelerle söz konusu belirteçlerin karşılaştırılması da hedeflenmiştir. Metod: Bu çalışmada akciğer adenokarsinomu, SHK ve plevral mezotelyomada immunohistokimyasal bcl-2 ve survivin ekspresyonları, TIL varlığı ve TIL'lerde bcl-2 ekspresyonu araştırıldı. Elde edilen verilerin klinikopatolojik parametrelerle karşılaştırılması ve immun belirteçlerin korelasyonları değerlendirilmiştir. Bulgular: Çalışma grupları; 29 akciğer adenokarsinomu, 18 SHK, 10 plevral mezotelyoma ve kontrol grubu olarak 12 normal akciğer parankiminden oluşmaktadır. Solid tip adenokarsinomlarda asiner tipe göre LVİ, plevral invazyon ve lenf nodu metastazı yüksek saptandı (sırasıyla p=0,001, p<0,001, p=0,039). Adenokarsinom grubunda, plevra invazyonu bulunmayan olgularda invazyon bulunanlara göre daha yüksek TIL varlığı tespit edilmiştir (p=0,013). SHK grubunda, adenokarsinom grubuna göre anlamlı şekilde daha yüksek TIL varlığı saptandı (p=0,04). İleri evredeki SHK'da TIL'lerin anlamlı ölçüde azaldığı izlenmiştir (p=0,004). SHK'da TIL'lerdeki bcl-2 ekspresyonu, evre I olan olgularda evre II-III'e göre daha fazla saptandı (p=0,045). SHK'da survivin ile TIL'lerdeki bcl-2 ekspresyonu arasında pozitif korelasyon tespit edilmiştir (p=0,001, rho=0,693). SHK'da survivin ile TIL'lerde bcl-2 koekspresyonu bulunan olguların, daha düşük pT (p=0,025) ve daha düşük klinik evrede (p=0,019) bulundukları saptanmıştır. TIL'lerdeki bcl-2 ekspresyonu adenokarsinom grubunda 70 yaş üzeri olgularda daha az (p=0,01) ve erkeklerde daha fazla (p=0,04) olarak bulundu. Adenokarsinom ve plevral mezotelyoma arasında survivin ile TIL'lerdeki bcl-2 ekspresyonu arasında korelasyon saptanmamıştır. Gruplar arasında, tümörde survivin ile bcl-2 ekspresyonu bakımından anlamlı fark saptanmamıştır. Normal akciğer parankiminde her iki belirteç ile ekspresyon izlenmemiştir. Sonuç: Elde ettiğimiz bulgular bir arada değerlendirildiğinde, erken evre SHK olgularında bcl-2 bakımından pozitif TIL varlığının yüksek düzeyde saptanmış olması ayrıca tümörde survivin ve TIL'de bcl-2 koekspresyonlarının tespit edilmiş olmaları söz konusu belirteçlerin SHK'da iyi bir prognostik faktör olabileceğini düşündürmektedir.Objective: The incidence of lung carcinoma and pleural mesothelioma is increasing in the world, and it is reported that there are approximately 2.2 million new lung carcinoma cases and 14,200 new pleural mesothelioma cases annually. Abnormalities that occur in programmed cell death play an important role in the formation and progression of carcinomas. In programmed cell death, which is regulated by genetic pathways, disruptions in the working and controlling processes of pathways cause uncontrolled cell growth and tumor development. Bcl-2, which is involved in these processes, is the first protein found to prevent apoptosis by inhibiting programmed cell death. Survivin, on the other hand, is a member of an important protein family that regulates apoptosis and is one of the first inhibitors identified. In our study, it was aimed to examine the roles of survivin and bcl-2 expressions and tumor-infiltrating lymphocytes (TIL) in progression in lung adenocarcinoma, squamous cell carcinoma (SCC) and pleural mesotheliomas. In addition, it was aimed to compare the clinicopathological parameters with the aforementioned markers. Methods: In this study, the expression of bcl-2 and survivin in lung adenocarcinoma, squamous cell carcinoma (SHC) and pleural mesothelioma was examined, as well as the presence of tumor-infiltrating lymphocytes (TIL) and bcl-2 expression in TILs were investigated. Comparison of the obtained data with clinicopathological parameters and correlations of immune markers were evaluated. Results: Working groups; 29 lung adenocarcinomas, 18 SCCs, 10 pleural mesotheliomas and 12 normal lung parenchyma as the control group. LVI, pleural invasion and lymph node metastasis were higher in solid type adenocarcinomas compared to acinar type (p=0.001, p<0.001, p=0.039, respectively). TIL was found to be higher in the adenocarcinoma group than in the cases without pleural invasion (p=0.013). We found significantly higher TIL in the SCC group than in the adenocarcinoma group (p=0.04). TIL was significantly lower in advanced tumors in the SCC group (p=0.004). Bcl-2 expression in TILs in SCC was found to be higher in patients with stage I than stage II-III (p=0.045). A positive correlation was found between survivin and bcl-2 expression in TILs in SCC (p=0.001, rho=0.693). In addition, cases with simultaneous expression of survivin in SCC and bcl-2 in TILs had lower pT (p=0.025) and lower clinical stage (p=0.019). Bcl-2 expression in TILs was found to be lower in the adenocarcinoma group in cases over 70 years of age (p=0.01) and higher in males (p=0.04). No correlation was found between survivin and bcl-2 expression in TILs between adenocarcinoma and pleural mesothelioma. In addition, no significant difference was found between the groups in terms of survivin and bcl-2 expression in the tumor. Expression of both markers was not observed in normal lung parenchyma. Conclusion: When our findings were evaluated together, the high level of bcl-2 positive TIL in SCC cases and the detection of survivin in the tumor and bcl-2 coexpression in TIL made us think that these markers may be a good prognostic factor in early stage SCC
Evaluation of P27, CD10,amacr and tmprss2-ERG protein expressions among different gleason grades prostatic adenocarcinoma on needle biopsy samples
Amaç: Prostat karsinomu erkeklerde en sık görülen visseral malignitedir ve erkeklerde kanser ile ilişkili ölümlerde ikinci sırada yer almaktadır. Prostat karsinomu değişken bir klinik gidişe sahip olup, indolan ile agresiflik arasında heterojen bir seyir gösterir. Bu hastalığın tedavisinde karşılaşılan en büyük zorluklardan biri agresif tümörleri, hastaya daha az zarar vermesi muhtemel yavaş seyirli formlarından ayırt etmektir. Son dekatlar içerisinde, prostat adenokarsinomunun tanısı ve yönetimi, büyük oranda prostat karsinogenezisinde yer alan biyobelirteçlere dayanır. Çalışmamızda, p27, CD10, AMACR ve TMPRSS2-ERG antikorlarının ekspresyon derecelerini, farklı Gleason büyüme paternlerine sahip prostat adenokarsinom olguları ile benign prostat hiperplazisi, atrofi olgu grubunda kıyaslamak ve bu belirteçlerin karsinogenezisteki rollerini aydınlatmak amaçlanmıştır. Gereç ve Yöntem: Çalışmaya, farklı Gleason derecelerinive benign prostat hiperplazisi ve atrofi olgularını içeren toplam 80 arşiv iğne biyopsi örneği dahil edilmiştir. Çalışma grupları; benign hiperplazi ve atrofi(20), grade 3 (20), grade 4 (20) ve grade 5 (20) büyüme paternlerinden oluşturulmuştur. İmmünskorlama, p27, CD10, AMACR ve TMPRSS2-ERG ile boyanan hücrelerin yüzdesi ile boyanma yoğunluğunun çarpımının hesaplanmasına dayanılarak değerlendirilmiştir. Kruskal Wallis testi kullanılarak ortalama değerler ve anlamlılık testi elde edilmiş olup 0.05'ten düşük olasılık değerleri, anlamlı kabul edilmiştir. Bulgular: P27, benign hiperplastik dokuların çoğunda, karsinom vakalarına kıyasla, daha yaygın ve yoğun boyanma göstermiştir(p<0.001).CD10, AMACR ve ERG, karsinom vakalarında, benign prostat hiperplazisi ve atrofi içeren vakalara kıyasla,daha yaygın ve yoğun boyanma göstermiştir(p<0.001). P27, AMACR ve ERG immünohistokimyasal boyanma skorunda, pattern 3, 4 ve 5 arasında istatistiksel olarak anlamlı bir fark bulunmamıştır. CD10 boyanmasının pattern 3 ve pattern 4 arasında, pattern 4 ve pattern 5 arasında, kontrol grubu ve pattern 4 arasında, kontrol grubu ve pattern 5 arasında anlamlı fark göstermediği bulunmuştur. Öte yandan pattern 3'teki CD10 boyanmasının pattern 5'ten ve kontrol grubundan anlamlı düzeyde daha düşük olduğu bulunmuştur.(p<0,008). Sonuç: Çalışmamızda CD10, AMACR ve ERG ile karsinom odaklarında benign prostat dokusuna göre yu¨ksek ekspresyon, P27 ile düşük ekspresyon izlenmektedir. Buna göre bu immünohistokimyasal boyaların prostat adenokarsinomunda prognostik belirteç olabileceğini ve prostat adenokarsinomunun hedefe yönelik immu¨noterapisinde kullanılabileceğini du¨şu¨nmekteyiz. Fakat rutin tedaviye girmeleri ve prognostik belirteç olarak kullanılabilmeleri için daha geniş serilerle yapılan çalışmalara ihtiyaç vardır.Objective: Prostate cancer is the most commonly diagnosed visceral malignancy in men and the second leading cause of cancer–related death in men. The clinical course of prostate carcinoma is heterogenous with a variable natural history that ranges from indolent to aggressive. One of the more difficult challenges in treating this disease involves identifying and distinguishing aggressive more tumors from those likely to remain indolent with little detriment to the patient. During the last decades, the diagnosis and management of prostate adenocarcinoma has hugely relied on biomarkers involved in prostate carcinogenesis. We aim to this study the immunohistochemical expression of p27, CD10, AMACR and TMPRSS2-ERG fusion in prostatic acinar adenocarcinoma cases with different Gleason growth patterns in comparison to their expression benign prostatic hyperplasia to elucidate their roles in prostatic carcinogenesis. Material and Methods: A total of 80 archival core biopsy tissues who were diagnosed prostate carcinoma harboring different Gleason grade and benign prostate hyperplasia and atrophy cases were included. The study groups consisted of benign hyperplasia and atrophy(20), grade 3 (20), grade 4 (20) and grade 5 (20) growth patterns. The immunoreaction with p27, CD10, AMACR and TMPRSS2-ERG were evaluated in each case based on calculating the percentage positive-stained cells and the staining intensity of the cells. The mean values and test of significance were obtained using the Kruskal–Wallis test. Probability values less than 0.05 were considered significant. Results: P27 staining was more diffuse and intense in most of benign hyperplastic and atrophic tissues compared to carcinoma cases(p<0.001).CD10, AMACR and ERG staining was more diffuse and intense in most of carcinoma cases compared to benign hyperplastic and atrophic tissues(p<0.001).There was no statistically significant difference in the staining score between grade3, 4 and 5 with p27, AMACR and ERG. CD10 staining was not found to be significantly different between pattern 3 and pattern 4, between pattern 4 and pattern 5, between the control group and the pattern 4, between the control group and the pattern 5. On the otherhand, CD10 staining in pattern 3 was found to be significantly lower than pattern 5 and control group. Conclusion: In our study, CD10, AMACR and ERG expressions were higher in carcinoma foci than benign prostate tissue. P27 expression was lower in carcinoma foci than benign prostate tissue. So we suggest that these stains may be prognostic markers in prostate adenocarcinoma and can be used in targeted immunotherapy in prostate adenocarcinoma
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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