bluuebunny/crossref_metadata_2025_split huggingface dataset:
DPP-4 inhibition resembles exercise in preventing type 2 diabetes development by inhibiting hepatic protein kinase Cε expression in a mouse model of hyperinsulinemia
Authors: Li Yu-peng , Xiao Jing , Liang Xu , Pei Yu , Han Xiao-fei , Li Chen-xi , Tian Hui 
Published: June 2020

Objective Interventions for hyperinsulinemia (HINS), an early indicator of type 2 diabetes mellitus (T2DM), can significantly reduce the T2DM risk. This study aims to determine how dipeptidyl peptidase-4 (DPP-4) inhibition prevents HINS progression to T2DM through ameliorating hepatic steatosis. Methods KKay mice were used as a HINS model and they underwent exercise or received a DPP-4 inhibitor, MK0626. Hepatic steatosis was examined and liver diacylglycerol levels were determined. Human hepatic cells (LO2) were treated with MK0626 or transfected with DPP-4 siRNA. Protein kinase C ε isoform (PKCε) and DPP-4 expression and insulin receptor substrate 1 (IRS-1) phosphorylation were assessed using immunohistochemistry and western blot. Results KKay mice developed HINS spontaneously at 7 weeks of age. Similar to exercise, MK0626 ameliorated hepatic steatosis and reduced the liver triglyceride and diacylglycerol content. Both exercise and MK0626 suppressed diacylglycerol-induced PKCε expression and restored insulin signaling, which was shown by tyrosine phosphorylation of IRS-1, in the livers of KKay mice. Additionally, silencing DPP-4 or MK0626 treatment decreased PKCε expression in LO2 cells. Conclusions Our data demonstrate that DPP-4 inhibition resembles exercise and effectively delays T2DM onset by suppressing hepatic PKCε expression in the HINS mouse model.
Comparative study of assisted reproductive outcomes between young patients with occult premature ovarian insufficiency and advanced-age patients
Authors: Yao Ling-nv , Lin Wen-qin , Jiang Nan , Li Chuyan , Cao Hai-feng , Li Hong , Qian Jian-hua 
Published: June 2020

Objective The purpose of this study was to compare the pregnancy outcomes among young patients with occult premature ovarian insufficiency (OPOI), advanced-age patients with diminished ovarian reserve (DOR), and advanced-age patients with normal ovarian reserve. Methods We retrospectively reviewed 324 women who underwent their first cycles of in vitro fertilization/intracytoplasmic sperm injection. The women were divided into the following groups: young women with OPOI, advanced-age women with DOR, and advanced-age women with normal ovarian reserve. The outcomes were compared among the different groups: Results The rates of live birth and embryo implantation in the young OPOI group were significantly higher than in the advanced-age DOR group, but comparable to those in the advanced-age normal ovarian reserve group. Moreover, the abortion rate was significantly lower in young OPOI patients compared with advanced-age patients with or without DOR. Conclusion Higher embryo implantation and live birth rates and a lower abortion rate can be achieved in young patients with OPOI compared with older patients. The better outcomes in advanced-age patients with normal ovarian reserve compared with DOR may be related to egg quantity rather than quality.
Circulating Micro RNA 181A as Biomarker in Breast Cancer, Its Possible Association with Metastasis & Epithelial Mesenchymal Transformation
Authors: Rashed LA , Faiz SH , Hassan MA , Elsebaie MM , Saad AE 
Published: June 2020

Background: Recent studies have reported the involvement of micro RNA 181a in diverse cellular functions. Though some studies have shown that miR-181a expression is downregulated in several human solid tumors, others have demonstrated that upregulation of miR-181a may promote metastasis and invasion of human cancers. Aim of the Study: The aim of this work is to detect the level of circulating miRNA-181a in breast cancer cases at different stages and to study its role in metastasis & epithelial mesenchymal transformation (EMT) through the possible association between miRNA 181a and transforming growth factor beta (TGFβ) signaling pathway. Subjects and Methods: The present work included 70 female patients, with breast cancer at different stages 30 patients with metastatic disease and 40 patients with non-metastatic disease 20 healthy subjects were taken as a control group. We detected miRNA-181a expression in peripheral blood with qRT PCR, and TGF-beta, SMAD-4, SNAIL-1 and Bim expression by quantitative PCR. Results: miRNA-181a, TGF-beta, SNAIL-1 and SMAD-4 were significantly upregulated in patients with metastatic breast cancer compared to patients with non-metastatic disease while Bim is significantly downregulated in metastatic versus non-metastatic group. Also, miRNA-181a was a prognostic marker for disease progression and overall survival. Conclusion: signaling pathway of TGFβ-SMAD, regulate miRNA-181a which in turn play role in stabilizing SNAIL transcription factor that promote tumor aggressiveness and metastasis through epithelial mesenchymal transition, as well as down-regulation of Bim.
Risk Factors of Venous Thromboembolic Events after Breast Cancer Surgeries; A Meta-Analysis of 166929 Patients
Authors: Elkholy A.M.E. , Awadeen A. , Kabeil I.H. , Sokar A. 
Published: June 2020

Introduction: Venous thromboembolism (VTE) is the second most common cause of death among patients with breast cancer. In particular, VTE accounted for 20% of deaths after radical mastectomy. Owing to the devastating sequels associated with VTE and its financial impact, the current study was conducted to reveal the possible risk factors of VTE after breast cancer surgeries. Materials and Methods: Extensive systematic literature review, from inception up to 1 October 2019, was performed throughout 12 databases to reveal all clinical studies reported the risk factors of VTE after breast cancer surgeries. Pooled analysis was implemented using Review Manager. Results: This meta-analysis included 8 articles that encompassed an overall 166929 patients. There was no statistically significant difference between patients developed VTE and those not developed such condition regarding Caprini total score (SMD0.5;95%CI-0.58,1.57; P=0.36). Subsequently, patients developed VTE were elder than patients did not develop such complications (MD1.21;95%CI 1.06,1.35; P<0.001). Patients had pre-operative diabetes mellitus (OR 0.69;95%CI0.49,0.98; P=0.04) or pulmonary disease (OR1.43;95%CI1.09,1.88; P=0.01) were more susceptible to experience post-operative VTE, relative to other patients. Besides that, post-operative hospitalization stays were significantly longer among patients experienced VTE, relative to patients did not experience such complications (MD 2.6;95%CI 2.54,2.66; P<0.001). Patients subjected to radical mastectomy and primary reconstruction were more vulnerable to have VTE post-operatively (OR 2.66;95%CI 1.90,3.71; P<0.001). Similarly, patients received concurrent venous catheterization were more susceptible to develop VTE post-operatively (OR 2.13;95%CI 1.22,3.73; P<0.00=0.008). On the contrary, post-operative hormonal therapy, radiotherapy, or chemotherapy were not statistically significant risk factors of VTE after breast cancer surgeries. Conclusions: Elderly patients and those with pre-operative diabetes mellitus or pulmonary diseases and patients subordinated to primary reconstruction after radical mastectomy were more susceptible to develop VTE. Understanding these factors will aid health care providers to optimize the optimal preventive strategies of VTE after breast cancer surgeries.
Non-Epithelial Ovarian Cancer; NCI Study
Authors: Sobhy Ashraf , Gamil Mohammed , Youssef Omar , Mebed Ali Hassan 
Published: June 2020

Background: Non-epithelial cancers of the ovary are uncommon. They include malignancies of germ cell origin, sex cord-stromal cell origin, metastatic carcinomas to the ovary, and a variety of extremely rare ovarian cancers, such as sarcomas and lipoid cell tumors. Nonepithelial malignancies account for about 10% of all ovarian cancers. Objective: To review the management of Non-epithelial ovarian cancer in the NCI Cairo university during a period of 5 years (2005 till 2010). Material and Methods: Retrospective study including 114 patients who were diagnosed and treated with Non-epithelial ovarian cancer (2005 to 2010). Data were collected from the biostatistics and cancer epidemiology department. Results: Out of 114 patients; 25(21.9%) were benign and 25 (21.9%) were borderline malignant; 55 (48.2%) were malignant and 9 (7.89%) of them were unpredicted biologic behavior; the median age of the study population was 49.7 years (range 14_83years). Panhysterectomy was done in 77(67.5%) of the patients; ovariectomy and debulking were done in 22(19.3%; salpingooophorectomy was done in 10(8.8%) 0f patients and cystectomy was done in 3(2.6%) and 2 cases underwent biopsy. Conclusion: Sex cord-stromal tumors and malignant germ cell tumors are the most common nonepithelial ovarian cancers. These tumors often, but not always, present with the sequelae of overproduction of either androgens or estrogens. It is important to diagnose these masses early, as overall prognosis is typically very good for early stage disease in all histological subtypes. Both sex cord-stromal tumors and malignant germ cell tumors of the ovary are treated with initial surgical resection. Fertility sparing surgery can be considered for both sex cord-stromal and malignant germ cell tumors of the ovary. Depending on the pathological diagnosis and disease stage, postoperative management consists of either expectant management or adjuvant chemotherapy. It is recommended that all patients with nonepithelial ovarian cancer be monitored for evidence of disease recurrence on a standardized schedule.
Variability of Medial and Lateral Borders Delineation in Guidelines for Post-Mastectomy Irradiation Significantly Affects Radiation Dose Received by Left Lung and Heart
Authors: Alsherif Wessam A. , Mousa Ranya M. 
Published: June 2020

Background: Delineation of Clinical Target Volume (CTV) is a basic step in 3 Dimensional Conformal (3DCRT). A notable variation however exists among different guidelines in delineation of chest wall (CW) CTV specially for the lateral margin. Some authors used wire localization for the anatomical insertion of the presumed breast It is expected that lateral margin delineation will affect the standard tangential fields and therefore the ipsilateral lung & heart (in left side) volumes irradiated to high dose. Aim of work: Evaluation of the effect of using various guidelines for chest wall CTV delineation on outcome regarding doses received by heart and left lung (in post left mastectomy irradiation) and compare these outcomes to that of wire based delineation (WBD). Methodology: Ten patients with T3/4 &/or N+ left breast cancer were planned for post mastectomy CW-3DCRT. Delineation of CW by one radiation oncologist followed 2 different guidelines namely RTOG & ESTRO in addition to a 3rd anatomical based wire delineation of chest wall underlying the presumed breast. Three CRT plans for the 3 CTVs were compared regarding coverage, homogenity & toxic dose to heart & lt. lung. Results: CTV was a highly significantly smaller when delineated using WBD vs RTOG or ESTRO guidelines. There was no statistically significant difference between the 3 delineated volumes regarding coverage & homogeneity parameters. A highly statistically significant better (lesser) V20Gy & V30Gy received by lt. lung for plans based on WBD (16.0 +/- 4.1% &12.75 +/- 2% respectively) vs those based on ESTRO (19.1 +/- 1.73 & 15.2 +/- 5.1 respectively) or RTOG guidelines (18.22 ± 1.6 & 14.52 ± 5.3 respectively), p=0.001 for V20Gy & 0.01 for V30Gy. For cardiac dose, a statistically significant lower D50% received by the heart in plans based on WBM delineation (101.6 ± 41.2 Gy) compared to plans based on ESTRO & RTOG guidelines based CTV (141 +/- 81cGy & 132 +/- 93 cGy respectively, p= 0-00001). Conclusion: WBD of post lt. mastectomy chest wall CTV delineation significantly reduced toxic dose received by heart & lt. lung. Larger trial with clinical follow up to test for being not inferior to ESMO &/or ESRTO guidelines based treatment regarding local recurrence.
Interval Debulking Surgery After Neodjuvant Chemotherapy Vs Primary Debulking Surgery For Stage Iii Epithelial Ovarian Carcinoma
Authors: Ahmed BM , Amin AT , Khallaf MK , Ahmed Refaat A , Sileem SA 
Published: June 2020

Introduction: Ovarian cancer is the most lethal gynecologic malignancy and is the fifth most common cause of cancer-related death among women. Approach to FIGO stage III epithelial ovarian cancer remains challengeable. This study aims to evaluate the outcome of interval debulking surgery (IDS) vs. primary debulking surgery (PDS) for FIGO stage III epithelial ovarian cancer. Materials and Methods: During a period of six years (January 2014 to December 2019), we analyzed the patients for eligibility criteria, which were: (1) FIGO stage III epithelial ovarian cancer. (2) The age of 18 years or more (3) Patients underwent either PDS or IDS and received chemotherapy at South Egypt Cancer Institute. We divided them into two groups: (1) Those received three cycles of neoadjuvant chemotherapy and then underwent IDS plus three additional cycles of adjuvant chemotherapy and (2) Those who have PDS followed by six cycles of chemotherapy. Results: This study includes 380 eligible patients. The first group included 226 patients (59.47%) underwent PDS then 6 cycles of chemotherapy, while the group of IDS included 154 patients (40.53%). The treatment modality was not significant for overall survival (OS); however disease-free survival (DFS) was significantly reduced after IDS when compared to PDS (median DFS: 33 months; 95% CI 30.23-35.77 vs. 45 months; 95% CI 41.25-48.75 respectively; p= .000). Moreover, in subgroup analysis, OS and DFS were significantly dropped after IDS in elderly patients, patients with bad performance status, sub-optimal cytoreduction as well as high grade and undifferentiated tumors when compared to those who underwent PDS. Conclusion: Although treatment modality may not impact overall survival (OS), however, PDS results in a better disease-free survival than IDS. Moreover, IDS results in a significant drop in OS and DFS in special patients subgroups when compared to PDS. Therefore patients selection should be considered.
Incidence of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors, Case Series from Two Tertiary Care Centeers in Dubai, UAE
Authors: Omara M , Abdelgadir Elamin , Khan F , Latif M F , Alawadi Fatheya , Koury M , Elshourbagy D. , Hamza Dina , Kumar S. , Das K. , Malik Quayom , Tirmazy S H 
Published: June 2020

Introduction: Immune checkpoint inhibitors (ICI) represent a major component of systemic therapy in advanced malignancy. Studies have reported unique spectrum of toxicity profile of ICI as compared to systemic chemotherapy. Aim of this study is to evaluate toxicities of ICI in our population and to compare this with published data. Material and Methods: We retrospectively reviewed medical records of patients treated with ICI at Dubai hospital and American hospital Dubai from November 2015 to April 2019. After patient identification from hospitals cancer registry, data regarding patients’ demographics, cancer type, type of ICI, adverse events, and duration of treatment were collected. Results: Forty-Five patients were identified with median age of 60 (27-80) years. 27 (60%) patients were male and 18 (40%) were female. Underlying diagnosis was lung cancer (n=25), renal cell cancer (n=6), melanoma (n=5), bladder cancer (n=3), Hodgkins lymphoma (n=3) and other malignancies (n=3). Majority of patients received Nivolumab (n=20, 44%) followed by Pembrolizumab (n=19, 42%), Atezolizumab (n=4, 9%) and Durvalumab (n=2, 5%) respectively. Thyroid dysfunction was the most common side effect observed in 17 (38%) patients including hypothyroidism (n=12, 27%) and hyperthyroidism (n=5, 11%). 53 % patients treated with Nivolumab developed thyroid dysfunction as compared to Pembrolizumab (22%). 7 patients (16%) had elevated liver enzymes. Grade II and III hepatotoxicity was noted in 1 patient (2.2 %) each. One patient (2.2 %) developed grade II skin toxicity. One patient (2.2 %) developed grade III colitis. Grade II, III and IV pneumonitis was observed in 2 (4.4 %), 1 (2.2%) and 1 (2.2%) patient respectively. Immune mediated adverse events were managed according to standard guidelines and 2 patients (4.4 %) had treatment discontinuation due to grade IV Pneumonitis and grade III Colitis. Conclusion: Our study reports relatively higher incidence of thyroid adverse events in patients treated with ICI. The incidence of grade III-IV immune related toxicity remains low. Overall treatment with ICI was tolerated reasonably well and toxicity was manageable.
Changes in Perceived Social Support after Starting Treatment in Egyptian Patients with Operable Breast Cancer: A Longitudinal Observational Study
Authors: Saleh Mariam A. , Kassem Loay , Atteya Hanaa , Mousa Mohamed , Alsirafy Samy 
Published: June 2020

Background: Social support (SS) has been proven to be associated with improved outcome of early breast cancer. Little is known about the magnitude of social support available for Egyptian breast cancer patient and much less is known about the changes that occur in such support after the diagnosis of breast cancer and starting treatment. Methods: We designed a longitudinal questionnaire based prospective cohort study using the six item form of the Medical Outcomes Study- Social Support Survey (MOS-SSS) questionnaire and included patients with pathologically proven non-metastatic breast cancer 18-70 years of age. Patients completed the self administered questionnaire at 2 time points: at first diagnosis of breast cancer and after 3-6 months of starting treatment. Comparison of the pre and post treatment questionnaires was done using paired sample T test. Results: A total of 48 patients completed the 2 questionnaires. Median age was 48 years (range: 24-65 years). Seventy percent of our patients were married, 67% had more than 2 children and 77.8% were housewives. Around half of the patients (45.2%) had monthly income below 1200 EGP. Patients who had higher education level (p=0.002) and those who were living in Cairo (p=0.033) reported higher SS at baseline. Mean MOS-SSS score at baseline was 64.4 (±24.8) while after treatment was 76.4 (±22.3); p<0.001. The increase in SS was consistent in most of the patient subgroups but was more prominent in illiterate patients compared to educated (p=0.033), those who work a handy job compared to housewife (p=0.04), and those who lived in Upper Egypt compared to Cairo residents (p=0.029). Conclusion: The majority of Egyptian breast cancer patients had a supportive environment after the diagnosis of breast cancer. A special attention should be paid to the at-risk groups with no sufficient SS during that period.
A Dosimetrical Analysis of the Magnitude of Isocenter Shifts Using CT-on-Rails Guided Online Adaptive Planning for Left Breast Cancer Patients Treated by Intensity Modulated Radiation Therapy
Authors: Mashhour K , Eliteo S , Hashem W 
Published: June 2020

Introduction: This study was conducted to check the accuracy and validity of an automated adaptive planning (AAP) method which combines automated re-contouring and re-planning to check for inter-fractional anatomical changes in breast cancer patients receiving intensity modulated radiation therapy (IMRT) based on a weekly computed tomography (CT)-on rails images dosimetrically viewing the magnitude of difference in isocenter shifts and the degree of dose deviations regarding target coverage and dose received by organs at risk. Methods and Materials: Twenty left sided conservative breast cancer patients were selected for IMRT treatment. Automatic generation of the contours on each repeat CT image was performed by mapping the contours from the planning CT image using deformable image registration. 3D- CRT and IMRT plans were automatically recalculated for each patient. The magnitude of isocenter shifts in postero-anterior (PA), cranio-caudal (CC) and right-left (RL) directions was calculated and the degree of dose deviations regarding target coverage and dose received by organs at risk. Results: In the PA,CC and RL directions, 9.2%, 11.4% and 6.4% of the 100 CT scans didn’t require any position adjustments. The mean isocenter shifts and standard deviation (SD) were 0.5 & 0.6 +/- 1.1mm, 0.3 &0.4 +/- 0.5mm and 0.2 & 0.4+/- 0.6mm for the IMRT and 3D-CRT plans in the PA,CC and RL directions, respectively. 74.1%, 65.1%, and 55.8% required a shift of 1 - 3 mm; 10.5%, 23.9%, and 33.2% required a shift of 3 - 5mm; and 1.5%, 3.3%, and 5.4% required a shift of more than 5 mm, respectively. With respect to target coverage, the D90[Gy] for the breast CTV was 46.2 Gy and 45.6 for the IMRT and 3D-CRT plans. The mean doses to the heart and left lung were reduced by 5.5 %, 3.7 Gy and 4.1%, 2.6 Gy using the AAP method. Conclusions: The fully automated AAP method using CT on rails for online re-planning was effective in reducing the magnitude of isocenter shifts and compensating for target volume coverage underdosing and higher doses perceived by risk organs caused by anatomical inter-fractional changes in breast cancer patients.
Results of Genetic Screening of Germinal Mutations in BRCA 1 And BRCA 2 Genes in Patients with Breast Cancer in the Aktobe Region of West Kazakhstan
Authors: Aitmagambetova M.A. , Smagulova G.A. , E.Zh. Bekmukhambetov , Kokhreidze I. , Tulyaeva A.B. , Bakytzhanov G.B. 
Published: June 2020

Introduction: Breast cancer (BC) is the most common malignant disease affecting women around the world. Clinically, the most important BC susceptibility genes are BRCA1 and BRCA2. The objective of our study was to establish the frequencies of 8 mutations in the BRCA1 genes (185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T> G (Cys61Gly), 2080delA mutations) and BRCA2 (6174delT mutation) in patients with BC in the Aktobe region of Western Kazakhstan. Materials and research methods: This study involved 300 women with a confirmed diagnosis of BC, who were observed at the Medical Center of the West Kazakhstan Medical University named after Marat Ospanov in the period 2018-2019. Prior to sampling the material (peripheral whole blood), patients received informed consent to conduct the study. Genotyping was carried out by real-time PCR using the Oncogenetics BRCA kit (NPO DNA Technology) according to the manufacturer's instructions. Results: A total of 300 patients were identified 3 cases. Patient No. 1, 31 years old, Asian race (kazakh), a mutation in the BRCA1 5382insC gene was detected, the hereditary history was burdened. Given the patient’s mutation (5382incS), a family history (father died of lung cancer, sibling died of ovarian cancer), work was done on genetic counseling for relatives (mother, brother, sisters and their adult children). Based on the analysis, we revealed a similar mutation of 5382incS in a sibling (42 years old) and his own daughter (17 years old), a second sibling (37 years old). Patient No. 2, 68 years old, Caucasian race, a mutation in the BRCA1 300T> G gene (Cys61Gly) was detected, the hereditary history is not burdened. Patient No. 3, 59 years old, Caucasian race, burdened by heredity. Also, given the patient’s mutation (5382incS), a family history (mother and grandmother died of BC), a study was conducted (daughters). According to the result of the analysis, we revealed a similar mutation of 5382incS in the daughter. Thus, the case presented shows the need for a large-scale, in-depth study of this population for further personification of treatment and prophylactic examination of patient families.