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Background: Pancreatic cancer is mostly diagnosed in advanced stages, and treatment results are not satisfactory. L3 skeletal muscle index (SMI) has emerged as a prognostic factor in pancreatic cancer patients. We aimed to assess the association between sarcopenia and overall survival in patients with pancreatic cancer in this study. Methods: Patients who were admitted to the Department of Oncology between March 2012 and December 2019 and diagnosed with pancreatic cancer were evaluated. The computerized tomography images and laboratory parameters of a total of 115 patients were included in this retrospective singlecenter study. We defined sarcopenia as an SMI Results: 70% of the patients were male, and the mean age was 64.9±9.9 years (mean ± SD). 70.6% of female patients and 67.9% of male patients were diagnosed with stage 4 cancer. The prevalence of sarcopenia in the whole patient group was 29.6%. By multivariate analysis, SMI (p=0.009) and advanced stage (p=0.003) were found as poor prognostic factors for overall survival (OS). The neutrophil to lymphocyte ratio (NLR) was statistically significantly higher in sarcopenic patients than in nonsarcopenic patients (p=0.031). Conclusion: Patients having sarcopenia at the time of diagnosis may demonstrate poorer overall survival of pancreatic cancer, and SMI may be considered as a potential prognostic factor.

Background Chlorine dioxide (ClO2) is an effective disinfectant consisting of oxygen, chloride, and potassium. Because of its high oxidative capacity, ClO2 exerts antimicrobial, antiviral, and antifungal effects. However, its anticancer effects remain to be elucidated. Methodology The anticancer activity of ClO2 was assessed on DMS114 small-cell lung cancer (SCLC) cells and human umbilical vein endothelial cells (HUVEC) as control by WST-1, Annexin V, cell cycle analysis, and acridine orange staining. We for the first time investigated the possible therapeutic effects of long-term stabilized ClO2 solution (LTSCD). Results Our preliminary findings showed that LTSCD significantly inhibited the proliferation of SCLC cells (p < 0.01) with less toxicity in HUVEC cells. Additionally, LTSCD induced apoptotic cell death in SCLC cells through nuclear blehhing and vacuolar formation. However, LTSCD treatment did not induce cell cycle arrest in both cell lines. Conclusions LTSCD can be a therapeutic potential for the treatment of SCLC. However, further investigations are required to assess the LTSCD-induced cell death in SCLC both in vitro and in vivo. WOS:000877509600032

Purpose: Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females. Methods: After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR. Results: Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT. Conclusion: Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population. WOS:000862536300001 Q3

Objectives: This research aims to identify the effects of premenstrual syndrome (PMS) symptoms on the school exam scores in medical students. Methods: This cross-sectional study was designed at Sakarya University School of Medicine The study included medical students who were in the first, second, and third year of class. In this study, there were 193 male and 100 female students. The study investigated how PMS symptoms affected medical student’s exam scores and school success. All exam scores were recorded during the two-consecutive semester so duration of study was one year. Results: There were 100 female students, and they had five different committee exams for one year. Female student’s exam scores were significantly higher for four committees and an average score of all year. The mean age of female students was 19.9 ±1.5. Acne, nausea/vomiting, sleeping, abdominal bloating, and prurience change had significantly different exam scores compared to the group without these symptoms. Students with acne had substantially higher exam scores than without acne; inversely, the other four symptoms negatively affected exam scores. Conclusion: Some of the PMS symptoms can be more annoying and should change the quality of life more than the other symptoms, so we should define these symptoms to improve our student’s quality of life and school success. doi: https://doi.org/10.12669/pjms.37.4.3931 How to cite this:Bilir F, Akdemir R, Bilir C. Some, but not all of the premenstrual syndrome symptoms affect the medical exam scores in medical students. Pak J Med Sci. 2021;37(4):1190-1195. doi: https://doi.org/10.12669/pjms.37.4.3931 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

OBJECTIVE: To evaluate the mortality rates in patients receiving anticancer therapy in the coronavirus disease-19 (COVID-19) pandemic period. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Sakarya University Training and Research Hospital, Sakarya, Turkey, from December 2017 to May 2020. METHODOLOGY: Only patients who received chemotherapy and immunotherapy were selected and enrolled in the study. All patients (n=3,204) were divided into three groups, namely the first group (1st December 2017-31st May 2018, n=918), second group (1st December 2018-31st May 2019, n=1,147), and the pandemic period group (PPG) (1st December 2019-31st May 2020, n=1,139), according to the period during which they received anticancer treatment. The clinical and demographic characteristics and mortality rates of these three groups of patients were compared. RESULTS: The median age of the total of 3,204 patients was 61 (53-69). In this study, 51.1% (n=1,636) were females and 48.9% were males. The mortality rates were 13.5% (n=124) in the first group, 13.4% (n=154) in the second group, and 13.0% (n=148) in the PPG, respectively. Overall mortality rates did not differ among patients with cancer in the three different six-month periods analysed (p = 0.931). CONCLUSION: There was no unexpected increased in mortality rate among patients undergoing cancer therapy during the COVID-19 pandemic as compared to the previous years of the same timeline. No increase in monthly mortality rates among patients receiving anti-cancer treatment were demonstrated during the pandemic period.

In colorectal cancer (CRC), the mutation of the K(N)RAS gene has a significant impact on the clinical course, and is associated with a negative prognosis. We aim to present the morbidity and long-term results in patients with wild/mut-K(N)RAS, undergoing CRC surgery.A total of 116 patients who underwent surgery for colorectal cancers with wild/mut-K(N)RAS were included in this retrospective study. The patients were divided into two groups: wild-K(N)RAS patients (Group 1) and mutant- K(N)RAS patients (Group 2). Results were evaluated for clinical, operative, morbidity and long-term survival outcomes.The highest surgical site infection (SSI) rate (OR=140.339)(4.303-4581.307)(P=0.005) was seen in patients given Bevacizumab during neoadjuvant treatment. Meanwhile, the SSI site infection rate was at its lowest in cases where minimally invasive surgery was preferred (OR=0.062)(0.006-0.628)(P=0.019). In addition, the overall median survival rate for the total cohort was 38±3.1 (31-44) months. Multivariate analysis showed that CEA (5ng/mL)(HR 2.94)(1.337-6.492))(P=0.007); tumor stage (P=0.034), T(T4) stage (HR 1.91)(1.605-252.6)(P=0.02); metastasectomy/ablation (HR 0.19)(0.077-0.520)(P=0.001); the number of removed metastatic lymph nodes (HR 1.08)(1.010-1.155)(P=0.025); tumor implant or nodule (HR 2.71)(1.102-6.706)(P=0.03); curative resection (HR 2.40)(0.878-6.580)(P=0.042) to be factors affecting the overall survival rate.Treatment with Bevacizumab during the neoadjuvant period in mut-K(N)RAS cases, surgical technique and complications of Grade 3 or higher are risk factors for SSI on morbidity in patients with mut/wild-K(N)RAS undergoing colorectal cancer surgery. Moreover, CEA (5ng/mL), tumor stage, T stage, metastasectomy/ablation, the number of removed metastatic lymph nodes, tumor implant/nodule and curative resection are risk factors on the overall survival rate.Bevacizumab, Colorectal cancer, K(N)RAS mutation, Morbidity, Mortality.CONTESTO: nel cancro del colon-retto (CRC), la mutazione del gene K(N)RAS ha un impatto significativo sul decorso clinico ed è associata a una prognosi negativa. Il nostro obiettivo è presentare la morbilità e i risultati a lungo termine in pazienti con wild/mut- K(N)RAS, sottoposti a chirurgia CRC.In questo studio retrospettivo sono stati inclusi un totale di 116 pazienti sottoposti a intervento chirurgico per tumori del colon-retto con wild/mut-K(N)RAS. I pazienti sono stati divisi in due gruppi: pazienti con K(N)RAS non mutato (Gruppo 1) e pazienti con K(N)RAS mutato (Gruppo 2). I risultati sono stati valutati per gli esiti clinici, operativi, di morbilità e di sopravvivenza a lungo termine.Il più alto tasso di infezione del sito chirurgico (SSI) (OR=140,339) (4,303-4581,307) (P=0,005) è stato osservato nei pazienti trattati con Bevacizumab durante il trattamento neoadiuvante. Nel frattempo, il tasso di infezione del sito SSI era al minimo nei casi in cui si preferiva la chirurgia minimamente invasiva (OR=0.062)(0.006-0.628)(P=0.019). Inoltre, il tasso di sopravvivenza mediano complessivo per la coorte totale è stato di 38±3,1 (31-44) mesi. L’analisi multivariata ha mostrato che CEA (5 ng/mL) (HR 2,94) (1,337-6,492)) (P=0,007); stadio del tumore (P=0,034), stadio T(T4) (HR 1,91) (1,605-252,6) (P=0,02); metastasectomia/ ablazione (HR 0,19) (0,077-0,520) (P=0,001); il numero di linfonodi metastatici rimossi (HR 1,08) (1,010-1,155) (P=0,025); impianto o nodulo tumorale (HR 2,71) (1,102-6,706) (P=0,03); resezione curativa (HR 2,40)(0,878-6,580)(P=0,042) come fattori che influenzano il tasso di sopravvivenza globale.Il trattamento con Bevacizumab durante il periodo neoadiuvante nei casi mut-K(N)RAS, la tecnica chirurgica e le complicanze di grado 3 o superiore sono fattori di rischio per SSI sulla morbilità in pazienti con mut/wild-K(N)RAS sottoposti a cancro del colon-retto chirurgia. Inoltre, CEA (5ng/mL), stadio del tumore, stadio T, metastasectomia/ablazione, numero di linfonodi metastatici rimossi, impianto/nodulo del tumore e resezione curativa sono fattori di rischio sul tasso di sopravvivenza globale.

Canine mammary gland tumors (CMGTs) are heterogeneous disease and subclassified [sarcomas (S), carcinomas (C), and carcinosarcomas (CS)] according to histopathological differentiation. Photodynamic therapy (PDT) is a promising treatment strategy based on the use of a photosensitizer (PS) activated by light. However, the therapeutic potential of PDT in the treatment of CMGTs has not been investigated, yet. Therefore, the aim of this study was to determine the in vitro protocol of 5-ALA-based-PDT for the treatment of three subtypes of CMGTs, for the first time. The intracellular PpIX florescence intensity was measured for 5-ALA (0.5 and 1 mM). After irradiation with different light doses (6, 9, 12, 18, and 24 J/cm(2)) for two different modes [continuous wave (CW) and pulse radiation (PR)], the cytotoxic effects of 5-ALA (0.5 and 1 mM) on the subtypes (C, S, and CS) of CMGTs were analyzed by WST-1. Finally, the optimal PDT treatment protocol was validated through Annexin V and AO/EtBr staining. Our results showed that 1 mM 5-ALA for 4-h incubation was the best treatment condition in all subtypes of CMGTs due to higher intracellular PpIX level. After irradiation with different light doses, PR mode was more effective in S primary cells at 9 J/cm(2). However, a significant decrease in the viability of C and CS cells was detected at 12 /cm(2) in CW mode (p < 0.05). Additionally, 1 mM 5-ALA induced apoptotic cell death in each subtype of CMGTs. Our preliminary findings suggest that (i) each subtype of CMGTs differentially responds to PDT and (ii) the light dose and mode could play an important role in the effective PDT treatment. However, further studies are needed to investigate the role of the different light sources and PDT-based apoptotic cell death in CMGTs cells.

Background: Indoleamine 2,3-dioxygenase (IDO) inhibition has received much attention in cancer immunotherapy due to its role in immune escape in cancer cells. Additionally, changes in the pro-inflammatory cytokine levels can affect tumor growth and metastasis as well as the effectiveness of immunotherapy. The purpose of this study was for the first time to determine the effects of indoximod as an IDO inhibitor on triple-negative breast cancer (TNBC) and to assess the link between the efficacy of indoximod and IFN-γ or TNF-α stimulation. Methods: The cytotoxic and apoptotic effects of indoximod alone or IFN-γ or TNF-α induction to mimic an inflammatory environment were evaluated by WST-1, Annexin V, cell cycle analysis, and acridine orange (AO)/ethidium bromide (EtBr) staining. Furthermore, the expression levels of IDO1 and PD-L1 expression were analyzed by RT-PCR. Results: Our results demonstrated that indoximod significantly decreased the TNBC cell viability through apoptotic cell death (p < .05). The combination of indoximod and TNF-α was more effective than indoximod and IFN-γ stimulation or indoximod alone in TNBC cells. Additionally, PD-L1 expression level was significantly up-regulated after treatment with indoximod and TNF-α or IFN-γ combinations (p < .05). Conclusions: Indoximod exhibited a therapeutic potential in TNBC cells and pro-inflammatory cytokines could affect the effectiveness of indoximod. However, further studies are required to identify the role of the IDO-associated signaling pathways, the molecular mechanisms of indoximod induced apoptotic cell death, and the relationship between IDO inhibition by IDO inhibitors and pro-inflammatory cytokine levels. WOS:000677935300001 34314307 Q3

To compare enzalutamide (E) and abiraterone acetate (AA) in terms of efficacy, survival and to characterize prognostic factors affecting survival in metastatic castration-resistant prostate cancer (mCRPC) patients. A total of 250 patients treated with E or AA in 5 centers were included. The number of patients with no prostate specific antigen (PSA) decline was higher in the AA group than that in the E group, and the proportion of patients with a PSA decline of ≥ 50% was higher in the E group (p = 0.020). Radiological progression free survival (rPFS) and overall survival (OS) were significantly longer in the E group when compared to that in the AA group (p

Amac: Meme kanseri kadinlarda en sik gorulen ve farkli alt tiplere ayrilan heterojen bir kanser turudur. Bu nedenle, meme kanseri alt tiplerine ozgu tedavi yaklasimlari dikkat cekmektedir. Mevcut calismada, kemik metastazi gorulen kanser tiplerinin tedavisinde klinikte kullanilan ve anti-proliferatif, ve anti-metastatik etkiye sahip oldugu bilinen bir bifosfonat inhibitoru zoledronik asitin (ZOL)’un, iki farkli meme kanseri alt tipinde [MCF-7 (ER+, PR+, HER2-) ve MDA-MB-231 (ER-, PR-, HER2-)] ve HUVEC kontrol hucrelerinde terapotik etkisinin arastirilmasi amaclanmistir. Gerec ve Yontem: ZOL’un (10-100 µM) 24 ve 48 saat boyunca sitotoksik ve apoptotik etkisi WST-1, Annexin V ve hucre siklusu analizleri ile belirlenmistir. Ayrica ZOL’un, hucrelerde ve nukleusda neden oldugu morfolojik degisimler sirasiyla akridin oranj (AO) ve DAPI boyamasi ile goruntulenmistir. Bulgular: ZOL’un MCF-7 hucrelerine gore, MDA-MB-231 hucrelerinde daha fazla anti-proliferatif etkiye ve erken ve gec apoptotik olume neden oldugu analiz edilmistir (p

Small cell lung cancer (SCLC) patients unresponsive or relapsing within 90 days following frontline chemotherapy have poor prognosis and they should be treated with different chemotherapy regimens other than those used in the first-line regimen. Currently there is no globally accepted standard chemotherapeutic regimen for the treatment of these patients. This retrospective study was designed to compare CAV (Cyclophosphamide, Doxorubicin, Vincristine), weekly topotecan and weekly irinotecan regimens and to evaluate the efficacy of the three regimens in patients with chemotherapy resistant/refractory (CRR) SCLC.A total of 67 CRR-SCLC patients, who were treated with CAV, weekly topotecan and weekly irinotecan were reviewed for weekly irinotecan (27 for 60 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle,24 for CAV (Cyclophosphamide 750 mg/m² on day 1, Doxorubicin 50 mg/m² on day 1 and Vincristine 1.4mg/m2 on day 1 every 3 weeks), 16 for weekly topotecan (4 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle).The median follow-up time was 12.45 months, there was no difference about disease control rates (DCR) between three chemotherapy regimens (DCR; 25.9% with irinotecan, 29.2% with CAV and 31.3% with topotecan, p=0.92). Objective response rates (ORR) for irinotecan, CAV and topotecan groups were 3,7%, 8,8%, and 0%, respectively (p=0.63). Median progression free survival (PFS) and overall survival (OS) were similar according to irinotecan, CAV, and topotecan (PFS: 1.93 months, 2.30 months and 3.45 months; OS: 2.89 months, 4.79 months and 5.81 months, respectively). The adverse events were generally mild and manageable for both hematological and nonhematological toxicities in all three arms.Weekly irinotecan, CAV and weekly topotecan are similarly effective and safe chemotherapy protocols for the treatment of CRR-SCLC patients.

Background: To compare enzalutamide (E) and abiraterone acetate (AA) in terms of efficacy, survival and prognostic factors affecting survival in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: A total of 250 patients treated with E or AA in 5 centers were included.Results: The number of patients with no prostate specific antigen (PSA) decline was higher in the AA group than that in the E group, and the proportion of patients with a PSA decline of ≥50% was higher in the E group (p = 0.020). The rate of progression in the AA group (82.2%) was significantly higher than that in the E group (p Conclusion: With longer OS and PFS, E seems to be more suitable for mCRPC patients in the post-docetaxel setting than AA.

Amaç: Bu çalışmanın amacı baş boyun kanserli (BBK) hastalarımızın genel özelliklerini, risk faktörlerini, tedavi modalitelerini gözden geçirmek ve sağkalımlarını hesaplayıp sağkalımı ve tedavi sonuçlarını etkileyen faktörleri değerlendirmekti.Gereç ve Yöntemler: Altmış yedi BBK tanılı hasta değerlendirildi. Çalışmanın verileri Sakarya Üniversitesi Eğitim ve Araştırma Hastanesinde 2011-2020 yılları arasında takipli hastaların dosyalarından elde edildi.Bulgular: Tanı anındaki medyan yaş erkekler 62, kadınlar 50 olmak üzere tüm hastalarda 62 ± 11,42 (aralık: 19-82) idi. En sık yerleşim yeri %55 oranla larinks idi. Sigara ve alkol kullanım oranları sırasıyla %69 ve %18 idi. Sekonder malignite oranı %18 olup en sık görüleni akciğer kanseriydi (%9, n = 6). Hastaların tanı anındaki evreleri 1,2,3 ve 4 sırasıyla %13,45 (n = 9), %22,47 (n = 15), %50,77(n = 34) ve %11,93 (n = 8) idi. Hastaların tanı anında ya da takibi sırasında olmak üzere toplam %42’si metastatikti. Metastaz bölgeleri 13 hastada (%19,45) akciğer, 10 hastada (%15) lenf nodu, 7 hastada (%10,56) kemik, ve 1 hastada (%1,50) karaciğerdi. Lokal rekürrens %27 (n = 18) oranındaydı. Evre 1,2 ve 3 58 hastanın %50’sinde lokal rekürrens ve/veya metastaz gelişmişti. Bu hastaların çoğunluğu evre 3 hastalardı (n = 17 (%59)). Evre 1-2 hastalarda medyan hastalıksız sağkalım 49 ± 29,65 ay (aralık: 0-107 ay) iken evre 3 hastalarda medyan hastalıksız sağkalım 19 ± 10,95 ay (aralık: 0-40 ay) idi. Metastatik birinci seri kemoterapi sonrası medyan progresyonsuz sağkalım 8±3 ay (aralık: 2-14 ay) ve tüm hastalarda medyan genel sağkalım 192±83 ay idi. Sonuç: Çalışmamızda sekonder malignite gelişme oranı hafif yüksekti. Radyoterapi eş zamanlı sisplatin total dozları literatürdeki benzer diğer çalışmalara göre hafifçe düşüktü. En çok tercih edilen metastatik birinci seri kemoterapi kombinasyonu sisplatin/5Fluorourasil/setuximab’tı. Progresyonsuz sağkalım sonuçları literatüre göre hafif yüksekti.

COVID-19 hayatimiza girdigi tarihten beri sosyal hayatimizi, calisma hayatimizi, yasayisimizi, hastabakim hizmetlerini, arastirmalarimizi ve hatta davranis tarzimizi etkiledi. Ustelik bu oyle bir salgin kisadece bir ulkede degil, butun dunya ulkelerinde ayni zamanda ve benzer yogunlukta etkilendi. Adetaulkelerin saglik sistemleri bircok sorunla sinanmistir. Salgin sirasinda bircok bilinmeyen denklem ic iceidi. Salgin basinda o kadar cok bilinmeyenimiz vardi ki hastalara nasil yaklastigimizi, nasil tedavi verecegimizive hangi ilaclarin verilmesi gerektigini henuz net bir sekilde bilmiyorduk. Gecen sure zarfindabircok arastirma ve bircok deneyim bizim hastaliga karsi nasil davranmamiz gerektigini ogretti.Salgin sirasinda bilgi kirliliginin ne kadar zarar verebilir oldugunu yasayarak ogrendik. Ayrica, salginbize asi savaslarini gosterdi. Salgindan kurtulmak icin kullandigimiz asilarin ne kadar degerli oldugunu,gelismis ulkelerin nasil asi savaslarina girdigini ve asilama ile beraber salgin dinamiklerinin nasil degistiginigorduk.2020 ve 2021 yillari salgin yillari olarak tanimlanacaktir. Bu salgin sirasinda saglik calisanlarinindogru bilgilere ulasmasinin cok degerli oldugunu gorduk. Elinizdeki bu kaynak, salgini bizzat yasayarakelde edilen tecrubelerini paylasip olusturulmaya calisilmistir. Kitabin olusturulmasinda emegi olan tumarkadaslarimiza icten tesekkurlerimizi arz ediyoruz. Bu kitabin okuyuculara fayda getirmesini diliyoruz.Bu kitabi, cani pahasina COVID-19 ile savasan ve hayatini kaybeden tum saglik calisanlarina armaganediyoruz.Saglicakla kalin. Prof. Dr. Oguz KARABAYDoc. Dr. Hamad DHEIRDoc. Dr. Selcuk YAYLACI

[No Abstract Available], Amgen Ilac Tic Ltd Sti, Turkey

Highlights • ABE treatment may be a promising treatment strategy in especially mCRPC. • ABE treatment significantly inhibited PC cell growth through apoptosis, depolarization of mitochondria membrane potential, the generation of ROS 2. ABE treatment induced depolarization of mitochondria membrane potential. • ABE caused many cytoplasmic vacuoles in PC cells and these effects were more profound in LNCaP cells than PC-3 cells., The therapeutic effects of abemaciclib (ABE), an inhibitor of cyclin- dependent kinases (CDK) 4/6, on the proliferation of two types of prostate cancer (PC) cells were revealed. In this study, in vitro cytotoxic and apoptotic effects of ABE on metastatic castration-resistant prostate cancer (mCRPC) androgen receptor (AR) negative PC-3 and AR mutant LNCaP PC cells were analyzed with WST-1, Annexin V, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential, RT-PCR, western blot, and apoptosis protein array. ABE considerably inhibited the growth of PC cells in a dose-dependent manner (p

Although positron emission tomography–computed tomography (PET/CT) is widely used for staging, there are limited data available to describe exactly the role of PET/CT metabolic and quantitative parameters for the prediction of disease outcome. A total of 145 patients diagnosed with histology-proven lung carcinoma in the advanced stage were included. According to the exclusion criteria remaining 76 patients (41 of them were adenocarcinoma EGFR wild-type, 35 were squamous non-small cell lung cancer (NSCLC)) were analyzed. Maximum standardized uptake value (SUV(max)) of a primary lesion was only statistically significant parameter with progression-free survival (PFS) in regression analyses in the whole study population as well as for overall survival (OS). According to the tumor histology, squamous cell carcinoma group did not have any significant PET CT parameters for PFS and OS, but adenocarcinoma group had significant PET CT parameters which were primary lesion of SUV max, SUV mean, total lesion glycolysis (TLG), mediastinal TLG and whole body TLG. In adenocarcinoma group, patients with lower than median TLG values had significantly increased overall survival than patients having higher median whole body TLG values (median OS was 11 vs 6.5 months, P = 0.031, HR 2.1), also they had more PFS without statistical significance (median PFS 6.5 vs 4 months, P = 0.3 HR 1.2). The present study showed that PET/CT metabolic parameters give some prognostic information other than staging of NSCLC, but this information was only significant in EGFR-wild type adenocarcinoma. For squamous cell carcinoma, we need to find any driver targets.

Tryptophan (Trp) is one of the important essential amino acids and Kynurenine pathway (KP) is the first and rate limiting step of degrading Trp to active metabolites. Recent studies showed that KP metabolites have antimicrobial and immunosuppressive roles. The main controller enzyme of this pathway is indoleamine-2,3-dioxygenase (IDO). IDO is an intracellular monomeric, heme-containing enzyme that controls the Trp breakdown in the KP. In this review, we discuss IDO functions on cancer progression and prognosis, and possible therapeutic aspects of inhibition of IDO on cancer immunotherapy.

Purpose: Toll-like receptor 4 (TLR4) is over-expressed in breast tumors and thus contributing to the tumor progression and metastasis. Natural products have drawn attention in cancer immunotherapy due to their various biological activities. Curcumin is well investigated in different types of cancer. However, the mechanisms underlying its anti-inflammatory actions have not been extensively elucidated. For this purpose, we explored the inhibitory effects of curcumin on lipopolysaccharide (LPS)-induced TLR4 dependent TRIF signaling pathway in two subtypes of breast cancer cell lines (MCF-7 and MDA-MB-231) in this study. Methods: In this context, the cytotoxicity of curcumin and LPS alone and the combination of curcumin with LPS on these cells was evaluated by WST-1 assay. The expression level of TLR4 and the release of type I interferon (IFN) levels were determined after treatment with curcumin and/or LPS by RT-PCR and ELISA analysis, respectively. Furthermore, the subcellular localization of TLR4 and interferon regulatory factor 3 (IRF3) were detected by immunofluorescence analysis. Results: Curcumin treatment suppressed breast cancer cells viabilities and the activation of TLR4-mediated TRIF signaling pathway by the downregulation of TLR4 and IRF3 expression levels and the inhibition of type I IFN (IFN-α/β) levels induced by LPS. However, curcumin was more efficient in MDA-MB-231 cells than MCF-7 cells owing to its greater inhibitory efficacy in the LPS- enhanced TLR4 signaling pathway. Furthermore, IFN-α/β levels induced by TLR4 and IRF3 were decreased in these cells following curcumin treatment. Conclusions: Consequently, these results demonstrated that the activation of LPS stimulated TLR4/TRIF/IRF3 signaling pathway was mediated by curcumin in breast cancer cells, in vitro. However, more studies are necessary to examine the curcumin’s anti-inflammatory activities on TLR4/MyD88/NF-κB as well as other signaling pathways downstream of TLRs in breast cancer.

Objective: Herein we, for the first time, investigated a potential synergistic effect of nobiletin (NOB) and sorafenib (SOR) on PC-3 prostate cancer and HUVEC control cell lines. Methods: In order to determine the cytotoxic and apoptotic effects of the combination of NOB and SOR, WST-1, Annexin V, and cell cycle analysis were performed. The potential molecular mechanism of apoptotic cell death was assessed by Bax, Bcl-2, CCDN1, Rb1, and CDKN1A gene expression and acridine orange (AO) and DAPI staining. Results: Our results indicated that NOB and SOR combination had a significant inhibitory effect on the viability of PC-3 cells with less toxicity on HUVEC cells than SOR alone (P

Introduction Plusieurs etudes de phase II non comparatives ont evalue la vinorelbine orale metronomique (VOM) dans le cancer bronchique metastatique non a petites cellules (CBNPC), mais la petite taille de chaque etude limite leurs conclusions. Objectif Realiser une meta-analyse sur donnees individuelles des patients inclus dans les etudes evaluant la VOM dans les cas de CBNPC metastatique afin de mesurer la survie et la securite du traitement avec ce schema therapeutique. Methodes Les etudes ont ete selectionnees si : – l’administration de vinorelbine par voie orale etait donnee trois fois par semaine ; – avec une dose quotidienne fixe comprise entre 30 et 50 mg ; – la publication etait anterieure au 4 octobre 2018. La base de donnees comprenait 8 variables caracterisant la maladie et la demographie, 3 variables informant sur le schema therapeutique et 12 variables decrivant la survie et la toxicite. Resultats Neuf etudes portant sur 418 patients remplissaient les criteres de selection, 80 % des patients presentaient des criteres de fragilite tel qu’un âge de 75 ans ou plus, ou un indice de performance ECOG (PS) = 2. La survie globale (SG) mediane etait de 8,7 mois (IC95 % : 7,6 a 9,5). Les taux de SG a six mois, un an et deux ans apres le debut du traitement par la vinorelbine etaient respectivement de 64 %, 30,3 % et 8,9 %. Dans le modele de Cox, un PS = 2 et l’anemie quel qu’en soit le grade etaient des determinants significatifs d’une SG plus breve. La survie sans progression mediane etait de 4,2 mois (IC95 % : 3,9–5). A 6 mois et a un an, les taux de SSP etaient respectivement de 35 % et 11,9 %. Dans le modele de Cox stratifie pour la variable « etude », un PS = 2 et un stade IV (vs IIIb) etaient des determinants significatifs d’une PFS plus breve. Pour 40 % des patients, aucune toxicite n’a ete rapportee, alors que 66 autres patients (15,8 %) ont presente une toxicite de grade 3–4. La toxicite la plus frequente etait une anemie de tout grade (35,8 %) qui etait la plus severe avec la dose de 50 mg. Conclusion La vinorelbine orale metronomique est une chimiotherapie active et bien toleree pour le CBNPC metastatique et constitue une option de traitement gerable pour les patients fragiles.

Background: Glomerular filtration rate (GFR) measurements are critical in patients with cancer. A variety of methods are used to calculate the estimated GFR. The aim of this study is to investigate whether there is a correlation between these methods and oncologic outcomes according to the stage and treatment agents.Methods: A total of 153 patients were retrospectively recruited. All GFR measurement methods was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations.Results: In the study population 40% of whom received platinum-based chemotherapy. In this group, overall survival was statistically significant in patients with a CKD-EPI creatinine value of 65 or greater (p:0.023). When we separated the arms according to the stage, there was no relationship between CKD-EPI Cystatin C and progression-free survival in metastatic patients (p: 0.13). In the non-metastatic group, median DFS was 7 months and OS was 13.9 months in patients with CKD-EPI Cystatine C level above 45 (p:0.005).Conclusions: Both CKD-EPI creatinine and CKD-EPI cystatin C were significantly associated with overall survival and disease-free survival in patients receiving platinum-based chemotherapy. When assessed according to the stage, there was a general survival relationship with CKD-EPI cystatin C in the non-metastatic group and in the other groups there was no significant correlation with the estimated GFR measurements., Amaç: Glomerüler filtrasyon hızı (GFR) ölçümleri kanser hastalarında kritiktir. Tahmini GFR’yi hesaplamak için çeşitli yöntemler kullanılır. Bu çalışmanın amacı, bu yöntemler arasında bir korelasyon olup olmadığını araştırmak ve onkolojik sonuçların evre ve tedavi ajanlarına göre değişip değişmediğini araştırmaktır.Metot: Toplam 153 hasta retrospektif olarak tarandı. Tüm hastalarda kemoterapi tedavisinin 1. Siklusu öncesi ve sonraki kemoterapi sikluslarından önce tüm GFR ölçüm metodları hesaplanarak kaydedildi.Sonuçlar: Çalışma populasyonundaki hastaların %40’ı platin bazlı kemoterapi aldı. Bu grupta CKD-EPI kreatinin değeri 65 ve üzerinde olan hastalarda genel sağkalım istatistiksel olarak anlamlıydı (p:0,023). Kolları evreye göre ayırdığımızda metastatik hastalarda CKD-EPI sistatin C ve progresyonsuz sağkalım arasında istatistiksel olarak anlamlı ilişki bulunamadı (p:0,13). Metastatik olmayan grupta CKD-EPI sistatin C seviyesi 45’in üzerinde olan hastalarda ortanca DFS 7 ay ve ortanca OS 13,9 ay olarak bulundu (p:0,005).Tartışma: Platin bazlı kemoterapi alan hastalarda hem CKD-EPI kreatinin hem de CKD-EPI sistatin C genel sağkalım ve hastalıksız sağkalım ile anlamlı olarak ilişkili bulundu. Evrelere göre değerlendirildiğinde, metastatik olmayan grupta CKD-EPI sistatin C ile genel sağkalım arasında anlamlı ilişki bulunmuş olup, diğer gruplarda tahmini GFR ölçüm metotları ile anlamlı korelasyon bulunmadı.

WOS: 000438245400018, Background: PET imaging involves several parameters. However, it is not well known which parameters in each measurable site of tumors may have a greater effect on oncologic outcomes. Method: This study included a total of 42 patients diagnosed with histology-proven NSCLC. Baseline and consecutive FDG-PET scans were carried out 3 weeks before and at least 3 months after treatment, respectively. Results: According to the PERCIST, 9 (21%) patients had Complete Response (CR), and 3 of them underwent surgical resection. Sixteen patients (38%) had Partial Response (PR), and 4 (9.5%) had Stable Disease (SD), the remaining 15 (35%) had Progressive Disease (PD). Patients who responded to the treatment had significantly higher Overall Survival (OS) and Progression Free Survival (PFS), 15 versus 9.5 months and 10 versus 6 months, respectively. The SUVmax values decreased from 12.2 to 3.7 (P=

Amac: Erken ve gec evre mide kanserli hastalarin klinikopatolojik, demografik ozelliklerini karsilastirmak ve ileri evre hastalarda evreye ozel prognostoik faktorleri belirlemek. Hastalar ve yontemler: Zonguldak Karaelmas Universitesi Tip Fakultesi Uygulama ve Arastirma Hastanesinde mide adenokarsinomu tanisi konulmus ve ameliyat edilmis 145 hastanin dosyalari retrospektif olarak incelendi. Bulgular: Calismamizda 19 erken evre hasta vardi. Iki hastada lenf nodu tutulumu pozitifti. Uc hasta kanser disi nedenlerden dolayi kaybedildi. Diger 16 hastada ortalama takip suresi 58.7 aydi. Ileri evre mide kanserli hastalarin ortalama sagkalimi 26.10 aydi. Regresyon analizinde sagkalima istatistiksel olarak anlamli duzeyde etki eden faktorler; yas, T-N skoru ve cikarilan lenf nodu sayisi idi. Evrelere ozel prognostik faktorler incelendiginde ise evre 2’de yas, cikarilan lenf nodu sayisi, evre 3’de yas, makroskopik gorunum, kemoradyoterapi almak, boyut ve diferansiyasyon derecesi, evre 4’de tumor boyutu sagkalima etki eden faktorlerdi. Sonuc: Calismamizda erken evrede lenf nodu pozitifligi ile invazyon derinligi iliskiliydi. Ileri evrede cikarilan lenf nodu sayisinin prognostik faktor olarak saptanmasinin nedeni 126 hastanin 46’sina yetersiz lenf nodu diseksiyonu yapilmasi olabilir. Evre 3-4 arasinda sagkalim acisindan istatistiksel fark olmamasi evre 3’de cikarilan lenf nodu ortalamasinin evre 4’e gore dusuk kalmasindan dolayi yanlis evrelemeden, evre 4’de daha fazla lenf nodu cikarilmasinin sagkalimi uzatmasindan kaynaklanabilir.

Obesity appears to be associated with an increased risk of breast cancer (BC) and an inferior oncological outcome at the time of diagnosis, with poor outcomes most prominent in cases of triple-negative BC (TNBC). The present study analyzed serum tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and TNF receptor associated factor-6 (TRAF) protein expression levels in 48 patients with non-metastatic BC and 26 obese control patients (without BC). The mean age of the cohort was 52.5 years (range, 35-78 years) and the patients had a median body mass index of 33.5 kg/m2 (range, 30-47 kg/m2). In the study population, 27.1% of BC patients were triple negative and 70.8% were hormone receptor (HR)-positive. Median serum TRAF6 expression was 0.90 ng/ml (range, 0.55-1.53 ng/ml) in the 13 TNBC patients and 0.63 ng/ml (range, 0.49-1.22 ng/ml) in the 35 HR-positive BC patients; thus, TRAF6 expression was significantly higher in the TNBC patients compared with the obese control group (0.90 vs. 0.73 ng/ml; P=0.033). Furthermore, median serum TRAF6 expression levels were significantly higher in HR-negative patients compared with HR-positive patients (0.83 vs. 0.62 ng/ml; P=0.002). The present study demonstrated that serum TRAF6 expression levels were increased in TNBC and HR-negative patients with non-metastatic BC compared with HR- and human epidermal growth factor receptor 2-positive cases or the obese healthy control group. Therefore, elevated TRAF6 expression may be a poor prognostic factor in non-metastatic BC. In addition, we propose that progesterone (PR) negativity may be a more useful poor prognosis factor than estrogen receptor (ER) negativity, as TRAF6 expression levels were higher in the PR-negative patients compared with the ER-negative patients. © 2015, Spandidos Publications. All Rights Reserved., National Natural Science Foundation of China: 30850004

Metronomic chemotherapy&mdash, administration of low-dose chemotherapy&mdash, allows for a prolonged treatment duration and minimizes toxicity for unfit patients diagnosed with advanced non-small-cell lung cancer (nsclc). Oral metronomic vinorelbine at 30 mg thrice weekly was given to 35 chemotherapy-na&iuml, ve patients who were elderly and vulnerable to toxicity and who had been diagnosed with advanced nsclc. Median age in this male-predominant cohort (29:6) was 76 years (range: 65&ndash, 86 years). Histology was squamous cell carcinoma in 21 patients and adenocarcinoma in 14. There were no complete responses and 9 partial responses, for an overall response rate of 26%. Stable disease was seen in 15 patients (43%), and 11 patients (31%) had progressive disease. The 1-year survival rate was 34%, and the 2-year survival rate was 8%. The survival analysis showed a median progression-free survival duration of 4 months (range: 2&ndash, 15 months) and an overall survival duration of 7 months (range: 3&ndash, 24 months). Metronomic vinorelbine had an acceptable efficacy and safety profile in elderly patients with multiple comorbidities who had been diagnosed with advanced nsclc. Metronomic vinorelbine could be a treatment option for elderly patients with poor performance status who are unfit for platinum-based chemotherapy and intravenous single-agent chemotherapy, and who are not candidates for combination modalities.

WOS: 000399505100004 PubMed ID: 28333566 Background: There are insufficient predictive markers for renal cell carcinoma (RCC). Methods: A total of 308 metastatic RCC patients were analyzed retrospectively. Results: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35months (p < .001) and 21.0 versus 11.36months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. Conclusions: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

Demirtaş, Abdullah Orhan (Balikesir Author), "Introduction. There are controversial results in the risk of atrial fibrillation as well as arrhythmogenic potential of bis-phosphonates. Method. 37 patients and 40 healthy controls were evaluated prospectively with regard to the cardiac side effects related to the use of zoledronic acid (ZA) and its effects on electrocardiography (ECG) parameters. Result. As the basal ECG results of the patients diagnosed with cancer compared with the control group, it was determined that QT maximum was significantly lower, QT minimum was significantly higher. However; it was determined that QT disp, P max, P min, and P disp values were not significantly different. There was no statistically significant difference in P max, P min, P disp, QT max, QT min, QT disp values of the ECG parameters measured from cancer patients, before and 60 minutes after ZA therapy. Conclusion. There were no significant alterations in ECG in the acute period, indicated that ZA had no arrhythmia potential in the early period in patients with no underlying cardiac disease. However: patients receiving ZA should be monitored more closely because of the risk of arrhythmia which may ensue due to hypocalcemia, hypomagnesemia, or other chemotherapeutics. Weywords"

Parathyroid cancers (PTC) are very rare and have a poor prognosis. A 48 year old case with locally invasive PTC that was positive for close surgical removal margin was treated with chemo radiotherapy after surgery. Even though this required bimodal chemo and radio adjuvant therapy, the patient was treated by chemo radiotherapy with some modifications, including oral administration of capestabine. These treatments were well tolerated with minimal side effects, which have proven to be very effective in freeing the patient from the invasive tumor for the following twenty six months of monitoring. This treatment method could be adopted in place of the widely preferred surgical therapy. We believe that this case report will guide future studies concerning with similar cases.

Anahtar kelimeler: Mide kanseri, kemoradyoterapi SUMMARY The Results of Postoperative Chemoradiotheapy in Gastric Carcinoma Patients: Bulent Ecevit University Experience Objective: The treatment results of postopeative chemoradiotherapy in patients with gastric carcinoma were evaluated. Material and Methods: A total of 77 patients with gastric carcinoma, treated with postoperative chemoradiotherapy between 2007-2011, were evaluated retrospectively. Chemoradiotherapy was applied in accordance with the Integroup-0116 study protocol. Total 45 Gy radiotherapy was delivered to the gastric bed and regional lymphatic nodes and 50.4 Gy was given to patients with positive surgical margins after 3-dimensional conformal planning. Results: Forty-six of the patients were male (59.7 %), and 31 of the patients were female (40.3 %) with a median age of 59 (31-78). Median overall survival and disease-fee survival were 28.3, and 21 months, respectively. The 3-year overall and disease-free survival rates were 43.8 % and 41.7 %, respectively. Locoregional recurrence was detected in 10 (13 %), distant metastasis was detected in 22 (28.6 %) and both locoregional and distant metastasis were detected in 3 (3.9 %) of patients. During chemoradiotherapy grade 1-2 hematological toxicity was seen in 23 (30 %) patients, grade 3-4 hematological toxicity in 46 (59.7 %) patients, grade 1-2 gastrointestinal toxicity in 30 (39 %) patients, and grade 3-4 gastrointestinal toxicity in 11 (14.3 %) patients. While in the univariate analysis lymph node stage and percentage of positive lymph nodes were found to be prognostic factors for overall and disease-free survival, in the multivariate analysis type of lymph node dissection and percentage of positive lymph nodes were found to be prognostic factors that are correlated with overall and diseasefree survival.

Over ablasyonu meme kanserinin temel hedeflerinden biridir. Premenopozal kadinlarda overler ostrojen sentezinin ana kaynagidir ve bu nedenle tedavi secenekleri olarak ooferektomi, over radyoterapisi veya hipotalamik- pituiter-overyan aksin baskilayici luteinize hormone analoglari (loprolid asetat, goseralin asetat gibi) bilinmektedir. Cok nadiren bu ajanlar etkili olmayarak LHRH analoglari kullananlarda gebelik gozlenebilir. Biz loprolid asetat (LA) kullanirken gebe kalan meme kanserli bir vaka sunduk. Otuz dort yasinda kadin hasta kemik metastatik meme kanser tanili tamoksifen 10 mg gunde 2 kez ve 28 gunde bir LA 3.75 mg cilt alti ve zolendronik asit 4 mg intravenoz uygulama ile takip edilmekteydi. MAyis 2013'te 7 aydir LA asit kullanmakta iken hastada 3-4 kg kilo artisi, karninda hareket hissi tarifledi ve gebelik tanisi konuldu. Bugune kadar LHRH analoglari ile tedavi altinda iken toplam 4 gebelik vakasi bildirilmistir ancak bu vakalarin hepsi GA kullanmakta idi. Tum vakalar en az 15 aydir GA kullanmakta olup bizim vakamiz en erken donemde LHRH kullanirken gozlenen gebelik vakasiydi. Klinisyenler LHRH kullanan hastalarda gebelik acisindan dikkatli olmali ve hastalari olasi riskler icin bilgilendirmeliler.

Background: Venous thromboembolism (VTE) including the pulmonary embolism and / or deep vein thrombosis is an important cause of morbidity and mortality. Many risk factors had been investigated for VTE and still under investigation. Blood group antigen is one of these factor.Methods: Patients who followed and treated between 2004-2012 in the oncology clinic of Bülent Ecevit University School of Medicine were retrospectively studied.Results: There was no statistically significant difference between the two groups for age, gender and laboratory parameters. The most common type of cancers were colorectal, gynecological and breast cancer. We detected 52% of blood group A in the DVT group and there was no significant difference with the control group (OR 1.3, CI 95%, P 0.37). 0 blood group had detected fewer than control but there was no statistical significance between the groups (OR 0.6 CI 95%, P 0.2).In conclusion, our study showed that, ABO blood group did not have an additional risk factor for the development of DVT in cancer patients. The difference from the other studies is our stud population had only cancer patients. Also, many factors can increase tendency to thrombosis in cancer patients due to cancer., Amaç: Venöz tromboembolizm (VTE) pulmoner embolizm ve/veya derin ven trombozundan oluşan önemli bir morbidite ve mortalite sebebidir. VTE için birçok risk faktörü araştırılma konusu olmuştur ve halen araştırılmaktadır. Kan grubu antijenleri de bu konulardan biridir.Metod: Bülent Ecevit Üniversitesi Tıp Fakültesi Onkoloji kliniğinde 2004-2012 yılları arasında tedavi alan ve takipleri yapılan hasta dosyaları retrospektif olarak incelendi.Bulgular: Her iki grup arasında yaş, cinsiyet ve laboratuar özellikleri arasında istatiksel olarak anlamlı fark saptanmadı. En çok görülen kanser türleri kolorektal, jinekolojik maligniteler ve meme kanseriydi. A kan grubu DVT grubunda %52 oranında saptanmış olup kontrol grubu ile anlamlı fark izlenmedi (OR 1.3, CI %95, P 0.37). 0 kan grubu olanlarda DVT daha az saptanmakla birlikte istatiksel anlam yoktu (OR 0.6 CI%95, P 0.2). Sonuç olarak bizim hasta grubumuzda kan grubunun DVT gelişimi için ek bir risk faktörü katmadığı ortaya konulmuş olup diğer çalışmalardakinden faklı olması da bizim hasta grubunun sadece kanser hastalarından oluşmasına bağlı olabilirdi. Ayrıca kanser hastalarında birçok faktöre bağlı olarak tromboz eğiliminde artış olabilmektedir.