Ali Veral

Introduction/Objective: CAR-T therapy has transformed haematological oncology but faces major obstacles in solid tumours, notably a shortage of suitable surface antigens and on-target off-tumour toxicity. We present STRIVE, an in silico workflow coupling structure-guided de novo scFv design with homolog cross-reactivity risk prioritization, applied to Claudin-4 (CLDN4) in Non-Small Cell Lung Cancer (NSCLC). Methods: CLDN4 expression was characterised using TCGA, the LuCA single-cell atlas, immunohistochemistry in 45 matched tumour/adjacent non-tumour lung pairs, and a pan-normal-tissue survey. RFdiffusion and ProteinMPNN within RFantibody generated 1,000 scFvs against the CLDN4 extracellular loops; RoseTTAFold2 filtering retained 39, screened by AlphaFold3 against CLDN4 and 24 claudin homologues and scored with STRIVE. STRIVE was benchmarked against solved complexes and non-cognate decoys, and the lead complex was simulated for 500 ns in a membrane. Results: CLDN4 was elevated in NSCLC relative to adjacent non-tumour lung (45/45 pairs concordant; p = 5.7 × 10^-14) but is also expressed in gastrointestinal, renal, pancreatic, urothelial and cutaneous epithelium. The screen prioritized scFv-73-0, whose worst-case margin against CLDN18.2 was 1.061-fold. On the independent benchmark, STRIVE discriminated cognate from non-cognate pairs only marginally better than chance (AUROC 0.606, 95% CI 0.348-0.846). Discussion: CLDN4 is therefore tumour-associated, not tumour-specific, and the 1.061-fold margin lies within the predictor's run-to-run variability, an unresolved liability. STRIVE is a triage heuristic and cannot exclude an off-target. Conclusion: The workflow reduces a large design library to a ranked shortlist and surfaces testable liabilities. scFv-73-0 is a computationally prioritized candidate requiring experimental validation, not a validated binder.

Introduction: Cancers of the lip and tongue are the sixteenth most common malignancy worldwide, with 377,713 new cases per year. Despite the decrease in smoking, early diagnosis, and advances in adjuvant treatment methods, significant increases in tongue cancers incidence are observed in western society, especially in young adults. This study aims to investigate the effect of LOX and LOXL-2 expression in tumor cells of patients operated on for early-stage T1-T2 tongue cancer on neck metastasis and prognosis. Methods: A total of 43 patients, 22 N(+) and 21 N(-) operated for T1-T2 tongue cancer were included in the study. He sought to discover cytoplasmic level LOX and LOXL-2 in the paraffin sections of subjects. The relationship of LOX and LOXL-2 cases with tumor T stage, N stage, recurrence, and survival outcomes were analyzed. Results: A total of 43 patients, 22 N(+) and 21 N(-) operated for T1-T2 tongue cancer were included in the study. LOX expression was observed in 16 patients (n=43, 37.2%) (12 N(+) and 4 N(-)) and in 15 patients (n=43, 34.8%) (12N(+) and 3 N(-) )) LOXL-2 expression was detected. In the analysis performed according to LOX and LOXL-2 expression, it was determined that LOX and LOXL-2 expression was statistically significantly higher in the group with tumor stage T1 than in those with T2 and in the N(+) group with pathological lymph nodes in the neck compared to those with N(-) (p

Introduction: The global elderly population is increasing and becoming more susceptible to oral and systemic diseases. Therefore, comprehensive clinical and histopathological examinations of the oral and maxillofacial area to assess the oral health of this population are crucial. This study aimed to increase the knowledge base regarding the prevalence of biopsied oral and maxillofacial lesions among a sample of the elderly Turkish population (≥ 65 years of age). Materials and Method: The clinical records of geriatric patients ≥ 65 years of age, who underwent biopsy for a pathological formation(s) in the oral region between January 2017 and January 2020 at Ege University School of Dentistry, Department of Oral and Maxillofacial Surgery (İzmir, Türkiye), were reviewed. Clinical follow-up data including demographic information, anatomical localization of the pathological mass, preliminary diagnosis, and biopsy results were evaluated. In order to ascertain the relationship between lesion formation and the independent variables, univariate analysis was employed. Results: Data were collected from 353 of 400 patients over a threeyear period. There was a high prevalence of odontogenic lesions (42.5%), and pathological diagnosis revealed an increased number of cases (43.1%). Pathological lesions were reported mostly in the posterior mandible (33.4%), followed by the anterior maxilla (21%), anterior mandible (13.3%), and posterior maxilla (7.1%). Conclusion: These findings are in accordance with those of previous studies based on histopathological data, emphasizing their importance in guiding public health policies for this patient population. Keywords: Biopsy; Pathology, Oral; Epidemiology; Geriatrics.

Objectives: The aim of the present study was to evaluate any conjunctival metaplastic changes by impression cytology in patients who underwent topical 1% voriconazole treatment for severe fungal keratitis. Materials and Methods: The study was conducted at Ege University Faculty of Medicine, Departments of Ophthalmology and Medical Pathology. Patients who were treated with 1% topical voriconazole for fungal keratitis for at least 3 months were included. The used topical voriconazole treatment was initiated as one drop every hour and was tapered according to clinical improvement in all patients. Treatment was continued 4 times a day for at least 3 months. Impression cytology samples were collected at least 3 months after cessation of topical voriconazole from the affected eyes and from the fellow eyes as a control group. Collected specimens were transferred to the pathology department for evaluation and grading (Nelson's grading system). Results: The mean age of the patients was 57.68 +/- 17.32 years (range, 22-87 years). The impression cytology grade of the inferior bulbar conjunctiva was 1.73 +/- 0.77 (range, 0-3) in the study group and 1.19 +/- 0.98 (range, 0-3) in the control group (p=0.03). The impression cytology grade of the temporal bulbar conjunctiva was 1.69 +/- 0.73 (range, 0-3) in the study group and 1.15 +/- 0.88 (range, 0-3) in the control group (p=0.02). The impression cytology grades of the nasal and superior bulbar conjunctiva did not differ statistically (p values 0.13 and 0.17, respectively). Conclusion: Topical voriconazole is an effective broad-spectrum antifungal drug, but it induces conjunctival squamous metaplasia. Clinicians should be aware of this possible side effect of topical voriconazole and should carefully evaluate the conjunctiva of treated patients at each visit to detect possible metaplastic changes.

Aim: To determine adiponectin and leptin expression levels in samples from healthy, dysplastic and cancerous oral lesions and to investigate the potential role of these biomarkers in oral cancer development. Methods: Tissue samples from the archives which were histologically diagnosed as oral squamous cell carcinoma (OSCC) (n=24), oral dysplasia (n=12) and healthy tissue (n=16) were included. The concentration and purity of samples were determined after total RNA extraction. Thereafter, cDNA synthesis was performed. The differences between expression levels were evaluated with qPCR. Expression levels related to OSCC were performed according to normalizing gene ACTB. 2-ΔΔCT method was used for comparison of expression levels. Student t-test was used to compare the differences in gene expression levels between groups, using 2-ΔΔCT value for each gene. Results: Adiponectin and leptin expression levels were decreased by 1.09 (p = 0.49) and 10.3 (p = 0.22), respectively, in OSCC group, however differences were not statistically significant. The level of adiponectin expression decreased by 1.65 times (p = 0.62) and leptin expression increased by 3 times (p = 0.30) in the dysplasia group. When OSCC and dysplasia groups were compared, it was found that the level of adiponectin expression increased by 1.52 times (p = 0.99) and the level of leptin expression decreased by 30.94 times (p = 0.16) in the OSCC group. The samples were re-grouped as increased risk (OSCC+dysplasia) (n=36) and healthy (n=16) and a decrease by 16.5 (p= 0.3) in leptin expression and an increase by 1.14 (p= 0.6) in adiponectin expression was observed in the increased risk group compared to the healthy group. Conclusion: In tissue samples diagnosed as healthy, dysplastic and OSCC, expression levels for leptin and adiponectin have not been compared before. The results revealed a significant decrease in leptin expression and an increase in adiponectin expression in increased risk group.

Tr en Amaç: Bu çalışmada Ege Üniversitesi Kanserle Savaş Uygulama ve Araştırma Merkezi (EÜKAM) sisteminde kayıtlı olan larinks kanseri tanısı alan hastaların demografik özellikleri ile birlikte malignite kliniğine göre genel sağkalımlarının araştırılması amaçlanmıştır. Gereç ve Yöntem: EÜKAM’da görevli kanser kayıt teknik ekibi tarafından kaydedilen 1992-2016 yılları arasında Ege Üniversitesi’nde tanı, tedavi ve takip sürecinde yer alan 3144 olgunun yaşı,cinsiyeti, histopatolojisi, tümör evresi, uygulanan tedavi şekli, takip süresi ve sağkalım durumu retrospektif olarak analiz edilmiştir. Bulgular: 3144 olgunun ortalama yaşı 59.4±10.5 saptanmıştır. En sık histopatolojik tip %97.4 ile karsinom olarak, en sık gözlenen evre durumu %47.1 ile lokal sınırlı evre olarak saptanmıştır. Tüm olgu serisinin 5, 10, 15 ve 20 yıllık genel sağkalımları ise sırasıyla %67, %48.6, %33.8 ve %23.5 olarak bulunmuştur. Sonuç: Larinks kanserleri genel sağkalımında tümör evresi, yaş gibi faktörlerin anlamlı olarak etkili olduğu saptanırken cinsiyetin sağkalım üzerinde anlamlı etkisinin olmadığı görülmüştür. Ayrıca son yıllarda organ koruyucu tedavi modellerindeki alternatif seçenek ve başarı oranlarında artış olduğu, bunun yanında larinks kanseri insidansında artışın günümüze kadar devam ettiği saptanmıştır. Aim: The scope of this study was to investigate the demographic characteristics of laryngeal cancer and the factors that may effect the overall survival of laryngeal cancer in patients recorded in Ege University Cancer and Research Center (EUKAM) database. Materials and Methods: Data of 3144 laryngeal cancer patients registered at EUKAM between 1992-2016; diagnosis, age, gender, histopathology, tumor stage, treatment modalities, follow-up period and latest status were retrospectively evaluated. Results: The average age of 3144 patients was 59.4±10.5 years. 94.9% of the cases were male and 5.1% were female. The most common histopathological type was carcinoma with the percentage of 97.4%, and the most common stage was locally limited with the percentage of 47.1%. The 5, 10, 15 and 20-year overall survival rates were 67%, 48.6%, 33.8% and 23.5%, respectively. Conclusion: Tumor stage and age were found to be significantly effective on survival of laryngeal cancers, on the other hand gender did not have a significant effect on survival. In last decades there has been an increase in alternative options and success rates in larynx preservation treatment modalities in recent years, as well as an increase in the incidence of laryngeal cancer.

Amaç: Ege Üniversitesi Kanserle Savaş Uygulama ve Araştırma Merkezi’nde (EÜKAM) kayıtlı olan, baş-boyun bölgesi yerleşimli tümör tanısı alan hastaların, genel demografik özellikleri, tümör yerleşim sıklığı, kanser yerleşimlerine göre genel sağ kalımları araştırılmıştır. Gereç ve Yöntem: EÜKAM’nin kanser kayıt elemanları tarafından kaydedilen 1992-2016 yılları arasında, Ege Üniversitesinde kayıtlı 6951 Baş-Boyun kanserli hasta topografi koduna göre; tanı yaşı, tümör yerleşimi, histopatolojileri, cinsiyetleri, uygulanan tedavi yöntemleri, son durumları, takip süreleri değerlendirilmiştir. Bulgular: Olgularımızın 6549’u (%94,2) karsinom, larinks %45,3 oranıyla en sık yerleşim yeridir. Olguların %80’i erkektir. Cinsiyetlere göre tümör yerleşim yeri, erkeklerde sıklıkla larinkse (%57,3), kadınlarda oral kavite bölgesine (%40,6) olmuştur. Olguların çoğunlukla lokal sınırlı evrede tanı almışlardır (%47,9). Tüm olgularda beş ve 10 yıllık genel sağ kalım sırasıyla %56, %48’dir. Larinks ve nazofarinks yerleşiminde beş yıllık sağ kalım sırasıyla %61 ve %57 bulunmuştur. Sonuç: Larinks kanseri en sık görülen tümör olup ve beş yıllık genel sağ kalım %61’dir. Yıllar içinde baş-boyun tümörlü olgu sayısında artış devam etmiştir.

The aim of this study was to evaluate the effects of topical voriconazole with histopathological and immunohistochemical analysis of the conjunctiva in rats. Twenty-eight Sprague Dawley rats were divided into four groups as two study (S1, S2) and two control (C1, C2). Voriconazole was instilled four times daily to S1, S2 rats. Physiologic saline (0.9%) was instilled four times daily in C1 and C2 rats. S1 and C1 were followed in a dark room; S2 and C2 were held in a room with sunlight. Impression cytology was performed at 0, 15, 30, 45 and 60th d after instillations. After 2 months of treatment conjunctival tissue was removed for histological and immunohistochemical analysis. In impression cytology evaluation, there was no difference between S1 and S2. At 60 d the difference between S1 and C1 was significant. In other comparisons, there was no difference between S1 and C1, C2. The scores of S2 was higher than C1 and C2 for all comparisons except 15th day scores of S2 and C2. In study groups, epithelial and gland degeneration were higher in S2, but inflammation scores were similar. The comparison of immunreactivity of ERK, TGFβ and E-cadherin were different in the study groups than the control groups for all comparisons. In conclusion, voriconazole has side effects due to phototoxicity including squamous cell carcinoma. Clinicians should particularly be careful with the long-term use of topical voriconazole and should follow-up patients strictly in terms of ocular surface alterations.

Aim: The aim of this study was to present the sonographic characteristics of follicular variant of papillary thyroid carcinoma (FVPTC) related to different forms of the thyroid nodules, including those without a capsule. Another purpose was to analyze the color Doppler ultrasonography (CDUS) features of this unique tumor, which have not been intensively studied in previous works.Materials and Methods: Twenty-two thyroid nodules (male/female: 17/5; mean age±SD: 42±16 years; range: 17-70) diagnosed with FVPTC were included in this study. The sonographic and Doppler features of the nodules were analyzed retrospectively. The intranodular pattern of vascularity was categorized with regard to the presence of perinodular and/or intranodular vascular signals, as well as a “spoke-and-wheel” appearance.Results: The length of the nodules varied from 6 to 55 mm. Most of nodules were purely solid (77.3%), isoechoic (59.1%) or hypoechoic (31.8%) and had an oval shape (72.7%), well-defined margins (68.2%) and a peripheral hypoechoic halo (68.2%). Thirty-one percent of the nodules had a lobulated shape with microlobulated margins or an irregular configuration with ill-defined margins. Encapsulated FVPTCs had a peripheral hypoechoic halo and well-defined margins, whereas infiltrative cases exhibited the opposite characteristics. No calcification was observed in 72.7% of the nodules. Perinodular and predominantly peripheral intranodular hypervascularity was observed in 14 nodules (66.7%) and was the dominant pattern of vascularity in most of the encapsulated FVPTCs, unlike the infiltrative FVPTCs.Conclusion: Diagnosis of FVPTC should always be considered when large thyroid nodules with predominantly solid echo-texture and other sonographic features that suggest benignity and nodular hypervascularity are observe.