bluuebunny/crossref_metadata_2025_split huggingface dataset:
ID2018 Radioisotope Enzymes And Cancer Study
Authors: Tran Luyen Van 
Published: September 2017

Cancer is a pathological symptom, when abnormal cells appear in certain human tissues or organs. These cells can reproduce beyond the control of normal biological protection mechanism. Because they multiply themselves rapidly, the metabolic process is accelerated, which causes an extreme need for energy, substrate material and catalyzing enzyme. Bases on these needs, we can control the metabolic process by: • Stopping the supply of energy. • Stopping the supply of substrate materials to build up the cell’s structure. • Stopping the catalysis process by breaking out the enzyme’s structure and/or deactivating the catalytic function of existing enzymes. • Destroying the tumor cells by extraneous agents such as radiations and chemicals. All of these methods have been studied for a long time, with a lot of resources to be spent. Although we obtained some positive result, it is nowhere closed to satisfactory. There are many reasons for this situation but the main issue is the lack of information of the processes taking place in human’s cells and body. In this paper, we, however, would like to propose a method to break the structure and/or to deactivate the catalytic function of the enzyme by nuclear decay process.
ID:2025 Cancer Molecular Medicine: Targeting C-Myc and USP37 Interactions
Authors: Shakir Saadia , Hussain Mushtaq 
Published: September 2017

Background: C-Myc is master transcriptional regulator found to be dysregulated in variety of cancers. One major ubiquitin specific protease that regulate the turnover of C-Myc is USP37. The present work aims to explore molecular interaction points between C-MYC and USP37. Secondarily, a peptide disruptor is designed for this interaction.
Methods: A composite molecular model of USP37 was generated by Modeller v9.17 using atomic coordinates of C19 domain of USP46, pleckstrin domain and atomic coordinates of USP37 generated using iterative threading modeling. After thermodynamic and structural refinement, finally selected model of USP37 was docked against atomic coordinates of C-Myc (PDBid 5I4Z) under static and dynamic state. The disruptor peptide was designed de novo and based on the hotspots of interactions between USP37 and C-Myc. Finally, the potential activity of disruptor peptide was assessed by undertaking molecular docking of peptide with USP37.
Results: Structurally, USP37 molecule resemble with a bowl shape where both C19 and pleckstrin domain were found in the central region. Near N-terminal the un annotated region was found to adopt structure homologous to the Zn finger. This denotes the possibility of USP37 interaction with DNA alone or along with c-Myc. The interaction points of USP37 and c-Myc lies at region which is exterior to both pleckstrin and C-19 domain. This binding interface contains both polar and no polar residues, taken this and sequence permutation into account a peptidyl disruptor is designed and docked against USP37. Most docking simulation results in the congregation of designed peptidyl disruptor to the targeted spatial position on USP37 molecule, suggesting its potential effectiveness.
Conclusion: The findings could be exploited in designing small molecular and peptidyl disruptor that could be used as a chemotherapeutic agent in cancers where C-Myc-USP37 interactions plays an important role in pathogenesis.
ID:2026 Investigating Molecular Interactions of EBV Oncogene, EBNA1, by Heterologous Cloning and Peptide Array System
Authors: Hussain Mushtaq , Wilson Joanna B 
Published: September 2017

Background: EBNA1 is an important latent genes that is involved in the oncogenesis associated with Epstein Barr Virus. The protein is highly promiscuous in terms of its interaction with the several proteins including EBP2 and USP7, a p53 stabilizer. Herein, we aim to investigate the interactions points of molecular complexes of EBNA1, an EBV oncogene, in order to design potential therapeutic peptides.
Methods: Full length EBNA1, EBP2 and USP7 models were constructed employing iterative threading. After proper refinements of models, EBNA1 dimer was constructed employing geometrical and structural constraints. Disruptor peptide was designed and its efficiency was assessed by molecular docking and confocal microscopy. In parallel, USP7 and EBP2 molecules were expressed in pET28c expression vector and after purification by affinity chromatography, the purified proteins were probed over EBNA1 peptide array (wild type and alanine substitution array) to resolve the fine interaction details. Finally, structural conformations of intermolecular complexes were examined by molecular docking.
Results: EBNA1 forms a dimer by engaging its C-terminal DNA binding domain where a proline loop of one molecule penetrated the C-terminal tail of another monomer. A disruptor peptide designed accordingly tend to bind in that region and found to inhibit EBNA1 dimerization resulting in the cellular apoptosis as observed in confocal microscopy and MTT assay. Peptide array systems showed the binding EBNA1 at the glycine and arginine rich regions especially ranging between 325 to 375 amino acids. Similarly, USP7 interactions were noticed between 441 to 450 amino acids where Ser447 holds a key position. Interestingly, phosphorylation of this serine completely inhibits the interaction. Molecular docking analysis further verify the binding sites and their draggability.
Conclusion: The present data shows molecular interactions of EBNA1 molecules at molecular resolution. The findings can be exploited to design inhibitors to curtail molecular interactions that leads to pathological consequences.
ID:2028 PLASMA LEVELS OF MMPs AND TIMP-1 IN BLADDER CANCER PATIENTS
Authors: Yakovlev Pavel , Tetiana Ishchuk , Diana Glavachek , Olexsiy Savchuk , Tetiana Falaleeva , Ludmila Ostapchenko 
Published: September 2017

Background: Urinary bladder cancer (UBC) is a common disease worldwide with high mortality rate [1]. UBC is the ninth most frequently diagnosed cancer worldwide, with highest incidence rates observed in developed countries. About 75% of bladder cancer patients are men [2]. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are diagnostic tools in oncology, liver diseases, and rheumatoid arthritis, which may prove to be a valuable prognostic tool in clinical setting [3]. The aim of the present study was to assess the prognostic power of plasma MMPs and TIMP-1 in patients with UBC of different stages.

Methods: This study enrolled 29 patients with UBC (27 males, 2 females), aged 52-76 years. Preoperative study for all patients included blood test, blood chemistry, urine analysis, immunogram, computer tomography, tumor biopsy. The spread of cancer was characterized based on TNM clinical classification 7th review (2009). Stage distribution of patients were as following: Stage I – 6 patients; Stage II - 5; Stage III - 7; Stage IV - 8 patients). The control group consisted of 15 healthy individuals (8 females and 22 males; aged 30-35 years). Plasma levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and TIMP-1 were determined by ELISA before the curative procedure and correlated afterwards with clinical parameters of the patient. Data analysis was conducted using Microsoft Excel 2010.

Results: Plasma levels of MMP-9 were significantly higher (by 1.5-2.0 times) in all patients with UBC compared to controls. Plasma level of MMP-8 in Stage III UBC patients was 1.2 times higher than in control group. The levels of MMP-1 and MMP-2 were increased compared to controls, and their elevation correlated with increase in cancer stage. Plasma level of MMP-3 in patients with bladder cancer Stage I, II and III were higher compared to controls by 1.3, 1.2 and 1.2 times respectively. High plasma levels of TIMP-1 were determined in patients with Stages III and IV, which raises question as to its role and function in advanced stage disease, as it may have a protective role in the mechanism of invasion by inhibiting extracellular matrix degradation.
Conclusion: In patients with urinary bladder cancer the plasma levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and TIMP-1 are elevated. We demonstrated that elevation pattern of MMP-1, MMP-2 and MMP-9 could serve as potential plasma marker for monitoring the cancer progression.
ID2033 Precision-cut tissue slices as a novel ex-vivo model for evaluating the efficacy of potential drugs
Authors: Iswandana Raditya , Pham Bao Tung , Luangmonkon Theerut , Mutsaers Henricus A.M. , Olinga Peter 
Published: September 2017

Background: Recently, we developed a novel model for drug screening by culturing ex-vivo precision-cut tissue slices (PCTS). The tissue slice consists of multiple cell types still in their normal matrix environment and structure provides numerous advantages compare to other models. Our objective was to use this model to investigate the effect of various potential compounds. In this study precision-cut intestinal slices (PCIS) were used to evaluate some transforming growth factor (TGF- β) and platelet-derived growth factor (PDGF) pathway inhibitors. TGF-β and PDGF are key cytokines in fibrotic and cancer diseases and are the main targets for treatment.
Methods: Murine PCIS were cultured for 48 h in the presence of profibrotic and/or antifibrotic compounds. The fibrotic process was studied on gene and protein level using a variety of markers including (pro)collagen 1a1 (Col1a1), heat shock protein 47 (Hsp47), fibronectin (Fn2) and plasminogen activator inhibitor-1 (PAI-1). The effects of potential drugs mainly inhibiting the TGFb pathway i.e. valproic acid, tetrandrine, pirfenidone, SB203580 and LY2109761 as well as compounds mainly acting on the PDGF pathway i.e. imatinib, sorafenib and sunitinib were assessed in the model at maximum non-toxic concentrations.
Results: Murine PCIS remained viable for 48 h and the onset of fibrosis was observed during culture, as demonstrated by an increased expression of, amongst others, Hsp47, Fn2 and Pai-1. Furthermore, TGFb1 stimulated fibrogenesis while PDGF had no effect. Regarding the tested antifibrotics, pirfenidone, LY2109761 and sunitinib had the most pronounced impact on fibrogenesis, both in the absence and presence of profibrotic factors, as illustrated by reduced levels of Col1a1, Hsp47, Fn2 and Pai-1 following treatment. Moreover, LY2109761 significantly reduced fibronectin protein expression in the presence of TGFb1.
Conclusion: PCIS can successfully be used to test drug efficacy. Using the model we demonstrated that tetrandrine, pirfenidone, LY2109761 and sunitinib showed potential antifibrotic effects on a gene level, warranting further evaluation of these compounds for the treatment of fibrosis disease. By using tissue extracted from patient, PCIS could also be a promising model to screen drug for personalized treatment in fibrotic and cancer disease.
ID:2034 Structural and Functional Polymorphism in Hepatitis B Virus Oncogene, HBx
Authors: Jabeen Nusrat , Hussain Mushtaq 
Published: September 2017

Background: HBV is now firmly associated with the incidence of Hepatocellular Carcinoma. This oncogenic potential of HBV is primarily due to an oncogene referred to as HBx. The present study deals with the sequential and structural variations found in the HBx protein encoded by the genomes of different HBV genotypes.

Methods: In total 5991 sequences of HBx belonging to different genotypes of HBV were aligned to procure consensus sequences of each genotype. The sequence was than used to construct molecular structure of HBx employing iterative threading alignment. The models were optimized and refined for the structural and thermodynamic parameters. The selected models were used to develop structures of HBx of each genotype which were in turn compared for their structural attributes, dimer formation and molecular interactions with p53.

Results: The sequence alignment reveals considerable conservation in the HBx sequences of different genotypes. The strongly conserved C-terminal region is a component of p53 interaction region of HBx. The most diverged region was found to be dimerization region spanning 25 to 50 aa. Structurally, HBx molecule has found to be nearly disordered except the C-terminal p53 binding region that adopts helical conformation. This in turn may explain in part the promiscuous nature of HBx in terms of binding with multiple binding partners. These observations have been further verified by GlobPlot analysis. The disordered region potentially rendered variations in the intra and inter molecular complexes of HBx as observed by molecular docking analysis.

Conclusion: The data highlights the variations in the structural characteristics of HBx that underscores the variations in the pathological and oncogenic consequences of HBV infections rendered by different HBV genotypes.
ID:2043 Response to a 2-Indolinones laboratory based regimen analogous in cancerous-infected cells
Authors: Hajare Rahul 
Published: September 2017

2-Indolinone is multifunctional expressed by drug discovery series of novel 97 compounds were synthesized for anticancer and cytotoxic activity against different 60 cell line cultures [1]. 07 compounds were selected on molecular recognition and screened for anticancer study [2]. Among those is screened compounds RH8, RH 42, RH84, RH89, RH90, RH 94, RH97 found good quality of anticancer activity against most of the cancer cell line with ranges from -77.23 to 55.85% growth. Target compound 5-Flouro-1-benzyl isatin -2, 3-b-quinoxaline (RH-89) display -77.23 to 7.31% growth & another target compound RH 94 display -64.78 to 65.14% growth against most of the leukemic cell lines, while RH-08 has shown very good activity against CCRF-CEM cell line with -31.85% growths and weak anticancer activity against breast cancer cell line with 53.47% growth, but failed to respond against other leukemic cell lines. RH-89 has also shown moderate activity against non-small cell-lung cancer (HOP-62) with 34.69% growth. RH-90 has shown good anticancer activity against leukemic cell line SR with 18.70% growth and weak activity against Non small cell lung cancer HOP-92 and NCL-H322M with 57.14 and 57.20% growth respectively. The cytotoxic property [3] of 2-indolinone analogs, among 3-benzohydrazide (RH 06-64) series, RH-22 and 28 were found to be most cytotoxic against L-1210 cell line (9 and 6 µg/ml). RH-33 was found to be cytotoxic against CEM/0 cell line (6.9 µg/ml). Among 3-isonicotinohydrazide derivatives (RH 65-72), RH-70 was found to have better cytotoxic property against all three types of cell lines (6.1-6.7 µg/ml).
From 3-quinazolin-4(3H)-one series (RH 74-82), RH-75 was found to be better cytotoxic against Molt4/8 cell line (6.0 µg/ml) and RH-77 was found to have better cytotoxicity against L1210 cell line (9µg/ml) remaining compounds RH-79, 80, 82 have shown moderate to weak cytotoxic property. Among 6H-indolo [2,3-b]quinoxaline derivatives (RH 83-96), RH-92 have shown better cytotoxic property against L1210 cell line(7.2 µg/ml).
ID: 1015 Taraxacum officinale (dandelion) extract efficiently inhibited the breast cancer stem cell proliferation
Authors: Trinh Ngu Van , Dang Nghi Doan-Phuong , Tran Diem Hong , Pham Phuc Van 
Published: September 2017

Introduction:
Breast cancer stem cells (BCSCs) play an important role in breast cancer initiation, metastasis, recurrence, and drug resistance. Therefore, targeting BCSCs is an essential strategy to suppress cancer growth. This study aimed to evaluate the effects of dandelion Taraxacum officinale extracts on BCSC proliferation in vitro in 2D and 3D cell culture platforms.
Methods:
The BCSCs were maintained understandard conditions, verified for expression of CD44 and CD24 surface markers, and transfected with GFP before use in experiments. In the 2D model, the BCSCs were cultured as adherent cells in standard culture plates; in the 3D model, the BCSCs were cultured on low-adherent plates to form spheroids. The effect of Dandelion extracts on proliferation of BCSC was assessed by evaluating induction of cell death, expression of genes of death receptor signaling pathways, and production of reactive oxygen species (ROS) by BCSCs.
Results:
BCSCs formed spheroids as microtumors in vitro and exhibited some in vivo characteristics of tumors, such as increased expression of N-cadherin and Slug, decreased expression of E-cadherin, capacity to invade into the extracellular matrix (ECM), and presence of a hypoxic environment at the core of tumor spheroids. The dandelion extracts significantly inhibited BCSC proliferation in both two-dimensional (2D) and three-dimensional (3D) models of BCSCs. However, the IC50 value of dandelion extracts in BCSCs in the 3D model was much higher than that in the 2D model. The results also demonstrated that BCSCs treated with Dandelion extracts showed increased expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor 2 (TRAILR2; i.e. death receptor 5;DR5). Moreover, treatment induced expression of DR4. Treatment with methanol dandelion extract enhanced production of ROS in BCSCs.
Conclusion:
Dandelion extracts are promising extracts for the treatment of breast tumors. The effect of methanol dandelion extract was better than that for ethanol extract. Importantly, BCSCs in 3D exhibited stronger drug resistance than those in 2D. In summary, our results indicate the strong potential of dandelion extracts as anti-cancer agents and rational use for drug development.
ID: 1023 All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth
Authors: Nguyen P H , Giraud J , Staedel C , Chambonnier L , Dubus P , Chevret E , Boeuf H , Gauthereau X , Rousseau B , Fevre M , Soubeyran I , Belleannée G , Evrad S , Collet D , Mégraud F , Varon C 
Published: September 2017

Gastric carcinoma is the third leading cause of cancer-related death worldwide. This cancer, most of the time metastatic, is essentially treated by surgery associated with conventional chemotherapy, and has a poor prognosis. The existence of cancer stem cells (CSC) expressing CD44 and a high aldehyde dehydrogenase (ALDH) activity has recently been demonstrated in gastric carcinoma and has opened new perspectives to develop targeted therapy. In this study, we evaluated the effects of all-transretinoic acid (ATRA) on CSCs in human gastric carcinoma. ATRA effects were evaluated on the proliferation and tumorigenic properties of gastric carcinoma cells from patient-derived tumors and cell lines in conventional 2D cultures, in 3D culture systems (tumorsphere assay) and in mouse xenograft models. ATRA inhibited both tumorspheres initiation and growth in vitro, which was associated with a cell-cycle arrest through the upregulation of cyclin-dependent kinase (CDK) inhibitors and the downregulation of
cell-cycle progression activators. More importantly, ATRA downregulated the expression of the CSC markers CD44 and ALDH as well as stemness genes such as Klf4 and Sox2 and induced differentiation of tumorspheres. Finally, 2 weeks of daily ATRA treatment were sufficient to inhibit gastric tumor progression in vivo, which was associated with a decrease in CD44, ALDH1, Ki67 and PCNA expression in the remaining tumor cells. Administration of ATRA appears to be a potent strategy to efficiently inhibit tumor growth and more importantly to target gastric CSCs in both intestinal and diffuse types of gastric carcinoma.
ID: 1026 Reconstruction of the major defects of the tissue scalp
Authors: Muradov M.I. , Mukhamedkerim K.B. , ABaiguzeva A. , Kazantaev K.E. , Koshkarbaev D.Zh. 
Published: September 2017

Background: To provide quantitative objective data demonstrating the longevity and amount of volume augmentation in the fatty dystrophy of the facial tissue obtained with autologous lipofilling.

Methods: In our clinic had been operated 8 patients for last 2 years with fatty dystrophy of the facial tissue. A prospective analysis of all patients who underwent at our private practice and were followed up for at least 1,5 year. Surgery was performed under general anesthesia it is necessary for clear results tissue correction. We based on the literature has seen numerous clinical reports highlighting the benefits of autologous fat transfer for face from that areas, fat was collected from the abdomen (most frequently used donor site), hips, outer thighs (saddle-bags), internal knee or thigh, with quantitative volume measurements evaluating the amount of postoperative volume change.

Results: Twenty eight patients were included in the study. The mean follow-up time was 18 months. The mean amount of autologous fat injected into each face region was 10-70 mL. Hypercorrection was performed after 3 months and it was 20-50% of the initial injected fat volume. Overall, the mean absolute volume augmentation measured at their last (after 6 month) post operative visit was 10-25%. There was variability between patients in the volume amount and percentage that remained. The resorption process was observed in two patients after 6 month. We made correction with hyaluronic acid and silicone implants.

Conclusion: To our knowledge, this study is the first clinical quantification in our practise of autologous fat transfer and/or grafting in the literature that provides definitive evidence on the amount as well as the resultant longevity in the face. Autologous fat transfer to the face has definite long-term volume augmentation results. On average, approximately 25-35% of the injected volume remains at 18 months. However, some variability exists in the percentage of volume that remains that may require a touch-up procedure.
ID: 1029 Effects of carnosine on regulation of migration and invasion in human colorectal cancer cells
Authors: Lai Po-Yu , Hsieh Shu-Chen , Wu Chih-Chung , Hsieh Shu-Ling 
Published: September 2017

Colorectal cancer is the third most commonly diagnosed cancer in the word. Carnosine is an endogenous dipeptide found in vertebrate skeletal muscles. It is known to have anti-fatigue, antioxidative, antihypertensive, antidiabetic, and cancer inhibiting effects. However, little research has been done regarding its influence on the metastasis of colon cancer. This study cultivated HCT-116 human colon cancer cells as a test model in order to investigate the impact of carnosine on the migration and invasion of human colon cancer cells. The results showed that 48-hour treatments of HCT-116 cells with 0.5, 1, or 5 mM carnosine each significantly inhibited the migration ability of the cells (P < 0.05). The 48-hour treatments with 0.5, 1, or 5 mM carnosine were also found to significantly reduce MMP-9 activity (P < 0.05), but not MMP-2 expression. Furthermore, when HCT-116 cells treated with 1 or 5 mM carnosine, invasion ability are significantly decreased and significantly increased E-cadherin expression (P < 0.05). On the other hand, the protein of TIMP-1, an inhibitor of MMP-9, is signification increased after 1 or 5 mM carnosine treatment (P<0.05). In addition, the u-PA protein level are significantly decreased after carnosine treatment.
The results indicate that carnosine can regulate the migration and invasion by regulating MMPs and its regulator molecular expression in HCT-116 cells.