Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study

Uncu, Dogan,Bayoglu, Ibrahim Vedat,Arslan, Ulku Yalcintas,Kucukoner, Mehmet,Artac, Mehmet,Koca, Dogan,Oguz, Arzu,Demirci, Umut,Arpaci, Erkan,Dogan, Mutlu,Kucukzeybek, Yuksel,Turker, Ibrahim,Isikdogan, Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.

Clinicopathological Characteristics of Hepatocellular Carcinoma in Turkey

Dogan, Erkan,Yalcin, Suayib,Koca, Dogan,Olmez, Aydemir Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Background: Hepatocellular carcinoma (HCC), the main malignant tumor of the liver, is very common and highly lethal. The aim of this study was to determine its clinicopathologic characteristics and risk factors in Turkey. Materials and methods: In this study, patients who were diagnosed as suffering from HCC in the period between August 2004 and December 2011 were evaluated retrospectively. Results: A total of 98 patients were included, with a median age 61 (range: 16 to 82). Seventy nine (80.6%) were male 59 (60.2%) were infected with hepatitis B virus (HBV) and 15 (15.3%) with HCV, another 15 (15.3%) being alcohol abusers. Seventy two (73.5%) were at advanced stage and 54 (55.1%) had elevated serum alpha-fetoprotein (AFP). Surgery, chemoembolization, systemic chemotherapy and application of the tyrosine kinase inhibitor sorafenib were the major treatment options. Conclusions: According to our findings HCC is mostly diagnosed in advanced stage and age, being five times more common in males than females. Main risk factors of HCC are HBV infection, HCV infection and alcohol abuse. Elevation in AFP may facilitate early diagnosis of HCC in high risk groups.

The role of serum lipoxin A4 levels in the association between periodontal disease and metabolic syndrome

Dogan, Esra Sinem Kemer,Dogan, Burak,Fentoglu, Ozlem,Kirzioglu, Fatma Yesim Korean Academy of Periodontology 2019 Journal of Periodontal & Implant Science Vol.49 No.2

Purpose: An unresolved inflammatory state contributes to the pathogenesis of periodontal disease and metabolic syndrome (MetS). Therefore, the purpose of this study was to evaluate the role of lipoxin A4 (LXA4), a proresolving lipid mediator, in the association between periodontal disease and MetS. Methods: Sixty-seven patients with MetS and 65 patients without MetS were included in the study. Sociodemographic information was obtained via a questionnaire, and detailed medical diagnoses were made. Periodontal parameters (plaque index [PI], gingival index [GI], probing pocket depth [PD], and clinical attachment level [CAL]) and metabolic parameters were measured, and serum LXA4 levels were determined. The associations among MetS, periodontal parameters, and serum LX levels were evaluated by adjusted multivariate linear regression analyses. Results: Patients with MetS were older and had a higher body mass index than patients without MetS. Periodontal parameters (PI, GI, PD, and CAL) were higher in patients with MetS than in those without MetS. Serum LXA4 levels were higher in patients without MetS. Multivariate linear regression analysis indicated a positive association between MetS and periodontal parameters (PD and CAL). Negative associations were established between MetS and LXA4 levels, and between LXA4 and periodontal parameters (PI, PD, and CAL). Conclusions: The presence of higher values of periodontal parameters in patients with MetS and the negative relationship of LXA4 with MetS and periodontal disease may support the protective role of proresolving lipid mediators in the association between periodontal disease and MetS.

Effects of anisotropy and curvature on free vibration characteristics of laminated composite cylindrical shallow shells

Dogan, Ali,Arslan, H. Murat,Yerli, Huseyin R. Techno-Press 2010 Structural Engineering and Mechanics, An Int'l Jou Vol.35 No.4

This paper presents effects of anisotropy and curvature on free vibration characteristics of cross-ply laminated composite cylindrical shallow shells. Shallow shells have been considered for different lamination thickness, radius of curvature and elasticity ratio. First, kinematic relations of strains and deformation have been showed. Then, using Hamilton's principle, governing differential equations have been obtained for a general curved shell. In the next step, stress-strain relation for laminated, cross-ply composite shells has been given. By using some simplifications and assuming Fourier series as a displacement field, differential equations are solved by matrix algebra for shallow shells. The results obtained by this solution have been given tables and graphs. The comparisons made with the literature and finite element program (ANSYS).

Assessment of Tissue Perfusion Following Conventional Liposuction of Perforator-Based Abdominal Flaps

Dogan, Zeynep Deniz Akdeniz,Sacak, Bulent,Yalcin, Dogus,Pilanci, Ozgur,Tuncer, Fatma Betul,Celebiler, Ozhan Korean Society of Plastic and Reconstructive Surge 2017 Archives of Plastic Surgery Vol.44 No.2

Background The effect of liposuction on the perforators of the lower abdominal wall has been investigated in several studies. There are controversial results in the literature that have primarily demonstrated the number and patency of the perforators. The aim of this study was to determine the effect of liposuction on the perfusion of perforator-based abdominal flaps using a combined laser-Doppler spectrophotometer (O2C, Oxygen to See, LEA Medizintechnik). Methods Nine female patients undergoing classical abdominoplasty were included in the study. Perforators and the perfusion zones of the deep inferior epigastric artery flap were marked on the patient's abdominal wall. Flap perfusion was quantitatively assessed by measuring blood flow, velocity, capillary oxygen saturation, and relative amount of hemoglobin for each zone preoperatively, after tumescent solution infiltration, following elevation of the flap on a single perforator, and after deep and superficial liposuction, respectively. Results The measurements taken after elevation of the flap were not significantly different than measurements taken after the liposuction procedures. Conclusions The liposuction procedure does not significantly alter the perfusion of perforator-based abdominal flaps in the early period. The abdominal tissue discarded in a classic abdominoplasty operation can be raised as a perforator flap and has been demonstrated to be a unique model for clinical research.

Relationship Between Antimetabolite Toxicity and Pharmacogenetics in Turkish Cancer Patients

Dogan, Mutlu,Karabulut, Halil G.,Tukun, Ajlan,Demirkazik, Ahmet,Utkan, Gungor,Yalcin, Bulent,Dincol, Dilek,Akbulut, Hakan,Icli, Fikri Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.

Is it Time to Change the Control Placebo Arms in Phase III Trials of Metastatic Castration Resistant Prostate Cancer?

Dogan, Mutlu,Erdem, Gokmen Umut,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Prostate cancer is common all around the world. Hormonal therapy is the mainstay of therapy, however castration-resistant prostate cancer (CRPC) becomes a serious problem and needs further clinical trials with novel agents. Novel agents like cabazitaxel, abireterone acetate or enzalutamide are encouraging but we do not know which one is the best in metastatic CRPC. In here, treatment modalities for metastatic CRPC are discussed witha mini-review of the literature.

A generative sampling system for profile designs with shape constraints and user evaluation

Dogan, Kemal Mert,Suzuki, Hiromasa,Gunpinar, Erkan,Kim, Myung-Soo Elsevier 2019 Computer aided design Vol.111 No.-

<P><B>Abstract</B></P> <P>A sampling approach is proposed for deriving profiles of an existing product design using profile similarities and primitive shapes, such as circles, triangles, and ellipses, as constraints. A common approach for a designer is to generate or collect sketches to create a design space. The design space can be explored to retrieve the samples directly based on requirements or crossing over them to obtain new design variations. In this stage, the proposed method can be used to derive a large number of samples from a design image to work with. First, the user clicks on the image to define each design feature as cubic Bézier curve segment. The primitive shapes are then constructed for each segment and used as constraints, such that the control points can move only to where these shapes allow. Moreover, the design similarities are computed using the triangles based on their anisotropy ratios, which are measures of the deformation between corresponding triangles and which are used to ensure that they are highly related samples in the example design. Modified Hausdorff distances are also computed between the biarc approximations of the samples. There is diversity provided that these distances are large enough. A customized sampling algorithm that fulfills our constraints is executed several times synchronously via parallel programming to create a design space. Finally, the user-specified number of distinct samples is retrieved from the design space by minimizing the Audze–Eglais potential energy. We provide an additional tool with which the users can adjust the weights for each control point to guide the sampling process and record the chosen samples. The main goal of this study is to generate samples, which are diverse but still convey the key features of the supplied shape. Using the settings related to similarity, a designer can derive samples sticking to their initial idea to explore its better version or more creative results that they could not imagine on their own. The proposed system offers simplicity automating every step that must be done by the user. Thus even inexperienced users without needing any programming skill can vary shapes defined using a set of points in a matter of seconds, and experienced users can even focus on specific shape features weighting them without dealing any constraint or rule definition requirements. Besides, the proposed system allows partial modifications, in which users can select a specific region to modify while the rest of the shape maintains the original appearance and functionality of the exemplary design.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Diverse sampling of profile curves using similarity measures. </LI> <LI> Efficient sampling from single image using parallel chain algorithm. </LI> <LI> Comprehensive representation of constraints using primitive geometries. </LI> <LI> Easy to use prototype system for inexperienced users. </LI> </UL> </P>

Direct Access to Primary Amines and Particle Morphology Control in Nanoporous CO₂ Sorbents

Dogan, Nesibe A.,Ozdemir, Ercan,Yavuz, Cafer T. Wiley (John WileySons) 2017 CHEM SUS CHEM Vol.10 No.10

<P>Chemical tuning of nanoporous, solid sorbents for ideal CO2 binding requires unhindered amine functional groups on the pore walls. Although common for soluble organics, post-synthetic reduction of nitriles in porous networks often fails due to insufficient and irreversible metal hydride penetration. In this study, a nanoporous network with pendant nitrile groups, microsphere morphology was synthesized in large scale. The hollow microspheres were easily decorated with primary amines through in situ reduction by widely available boranes. The CO2 capture capacity of the modified sorbent was increased to up to four times that of the starting nanoporous network with a high heat of adsorption (98 kJ mol(-1)). The surface area can be easily tuned between 1 and 354 m(2)g(-1). The average particle size (ca. 50 mu m) is also quite suitable for CO2 capture applications, such as those with fluidized beds requiring spheres of micron sizes.</P>

Free vibration of an axially functionally graded pile with pinned ends embedded in Winkler-Pasternak elastic medium

Dogan Çetin,Mesut Simsek 국제구조공학회 2011 Structural Engineering and Mechanics, An Int'l Jou Vol.40 No.4

In the present study, free vibration of an axially functionally graded (AFG) pile embedded in Winkler-Pasternak elastic foundation is analyzed within the framework of the Euler-Bernoulli beam theory. The material properties of the pile vary continuously in the axial direction according to the power-law form. The frequency equation is obtained by using Lagrange’s equations. The unknown functions denoting the transverse deflections of the AFG pile is expressed in modal form. In this study, the effects of material variations, the parameters of the elastic foundation on the fundamental frequencies are examined. It is believed that the tabulated results will be a reference with which other researchers can compare their results.