Wos Açık Erişimli Yayınlar

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    Clinical characteristics of relapsed ovarian cancer patients with striking response to the bevacizumab at first relapse
    (2020) Kose, Fatih; Alemdaroglu, Songul; Mertsoylu, Huseyin; Besen, Ali Ayberk; Guler, Ozan Cem; Simsek, Seda Yuksel; Erbay, Gurcan; Onal, Cem; Celik, Husnu; 0000-0002-2742-9021; 0000-0003-4335-6659; 0000-0001-6908-3412; 0000-0002-0156-5973; 0000-0002-7862-0192; 0000-0002-1932-9784; D-5195-2014; AAI-8400-2021; AAC-5654-2020; G-4827-2016; AAD-6910-2021; M-9530-2014
    Background: Ovarian cancer is fifth leading cause of the cancer related death in women. Platin based doublet regimen plus bevacizumab is standard treatment in relapse. The primary aim of this study is to define clinicopathological characteristics of the relapsed ovarian cancer who derived unexpectedly long benefit from bevacizumab treatment. Methods: Total number of 106 patients with relapsed ovarian cancer and treated with bevacizumab (bevacizumab is not reimbursed as a part of adjuvant treatment in Turkey) on their first relapse were included. For the purpose of the study, the patients were placed into two groups, Group A and B, selected on the basis of the rate of PFS 1 (time between first day of adjuvant chemotherapy and first radiological progression) to PFS 2 (time between first day of second line treatment and second radiological progression). The patients included into Group A if PFS 1 greater than PFS 2 and Group B vice versa. Results: Group A and B were consisted of 67 (63%) and 39 (37%) patients. At a median follow-up of 32.1 months (5.3-110.8), 56 (52.8%) patients were died. Significant number of patients (78.4%) treated with primary surgery without neoadjuvant treatment and 59 (57.8%) out of the 102 patients had debulking surgery when their cancer relapsed. PFS 1 and 2 were estimated as 16.5 mo (14.1-18.9) vs. 13.7 mo (9.9-17.5) and 13.4 mo (8.0-18.6) vs. 29.7 mo (21.5-38.0) in group A and B, respectively (p < 0.001 and p < 0.001). Only parameter that show significant difference between groups was the rate of platin resistant patients; Group A: 13 (19.4%) out of 67 patients vs. Group B: 15 (38.6%) out of 39 patients with ap value of 0.041. Binary logistic regression indicates PFS1 is significant inverse predictor (shorter PFS-1 means greater chance of being in group B) of entering Group B [Chi-Square = 16.5, df = 6 and p = 0.011 (< 0.05)]. PFS1 is significant at the 5% level [ PFS1 wald = 4.33,p = 0.038 (p < 0.05)]. In multivariate analysis, cox-regression proportional hazard, cytoreductive surgery at second relapse (yes or no) (p: 0.028; HR: 0.3, 0.02-0.7, 95% CI) showed significant effect on PFS-2. On the other hand, platin resistance (< 6 mos; yes or no) (p: 0.04; HR: 4.0, 1.1-14.4, 95% CI) and secondary surgery outcome (no visible vs. visible) (p: 0.003; HR: 0.2, 0.07-0.58, 95% CI) showed significant effect on OS. Bevacizumab related adverse effects with greater than grad 3 detected in 13 (15%) and 10 (25%) in group A and B (p: 0.77). Conclusions: Our findings indicate that bevacizumab produced strikingly high PFS (over 24 months) in significant portion of relapsed ovarian cancer patients whom were mostly platin resistant cases with short PFS-1. This gain specifically achieved in patients who had aggressive secondary surgery with no-visible surgical outcome.
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    Can serial monitoring of serum Vascular Endothelial Growth Factor (VEGF), Nitric Oxide (NO), and Angiotensin II (ANGII) levels have predictive role during Bevacizumab treatment?
    (2014) Sumbul, Ahmet Taner; Disel, Umut; Sezgin, Nurzen; Sezer, Ahmet; Kose, Fatih; Besen, Ali Ayberk; Sumbul, Zehra; Abali, Huseyin; Ozyilkan, Ozgur
    Background: Standard treatment of colorectal cancer includes both cytostatic chemotherapy and targeted therapies. Bevacizumab, targeting the VEGF receptor, is one of the primary targeted therapies that achieve better response rate and survival rate as compared to combination chemotherapy. To the best of our knowledge, there is no established single marker that can be used as a predictive marker in bevacizumab therapy. Material/Methods: We enrolled 24 patients with the diagnosis of metastatic colorectal cancer in our study. During the study, 2 blood samples were drawn from patients before the first cycle and after the sixth cycle of bevacizumab therapy. Serum levels of VEGF, ANG II, and NO were recorded. Results: While the change across VEGF levels was found to be a statistically significant decreasing trend (p=0.009), this decrease was not found to be correlated with treatment response and hypertension development. Additionally, no statistically significant difference was found in terms of NO and ANG II levels. Conclusions: This study showed a significant decrease in serum VEGF, but failed to show a significant change in NO and ANG II levels during bevacizumab treatment. Although no significant correlation was found between the presence of hypertension and markers, most patients (83%) had an increase in their blood pressure. Our results suggest that dynamic monitoring of NO and ANG II, along with VEGF, may not be useful as predictive markers for bevacizumab treatment in colorectal cancer.
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    Comparison of the inhibitory effect of different doses of subconjunctival bevacizumab application in an experimental model of corneal neovascularization
    (2018) Ulas, Burak; Altan-Yaycioglu, Rana; Bal, Nebil; 30046522; AAG-3306-2019; AAL-4440-2020
    AIM: To evaluate the inhibitory effect of subconjunctival bevacizumab as single- and multiple-dose application, and compare their effects on corneal neovascularization in a rat model. METHODS: Thirty adult Sprague-Dawley rats were used in this experimental study. The central cornea of the rats was cauterized chemically. The rats were randomly enrolled into three groups. All groups received subconjunctival injections. In Group 1 (control group, n=10), 0.05 mL 0.9% NaCl solution was injected on the first day. In Group 2 (single-dose group, n=10), 0.05 mL bevacizumab (1.25 mg) was injected on the first day. In Group 3 (multiple-dose group, n=10), four doses of 0.05 mL bevacizumab (1.25 mg) were injected on the first, third, fifth and seventh day. Slit-lamp examination of all rats was performed at the third and ninth day. Digital images of the corneas were taken and analyzed using image analysis software to calculate corneal neovascularization area. All rats were sacrificed on the tenth day. In corneal sections, the number of blood vessels, state of inflammation and collagen formation was evaluated histopathologically. RESULTS: In Group 3, corneal edema grades were significantly lower than Group 1 and Group 2 (P=0.02, and P=0.035, respectively). The mean percentage of neovascularized corneal area in Group 3 was significantly lower than Group 2 (P=0.005). On histopathological examination, Group 2 and Group 3 showed significantly less number of blood vessels than Group 1 (P=0.005, and P=0.001, respectively). Additionally, Group 3 showed significantly less number of blood vessels compared to Group 2 (P=0.019). Inflammation and edema grades were significantly lower in Group 3 compared to Group 1 (P=0.001). CONCLUSION: Subconjunctival bevacizumab injection is effective in inhibition of newly formed corneal neovascularization. The multiple-dose bevacizumab treatment seems to be more effective compared to single-dose treatment.