Pub Date : 2020-07-31DOI: 10.2174/1574362413666180724134204
E. Osaki, S. Mizuno
Poly-(ADP-Ribose) Polymerase (PARP) plays a central role in recovery from single-strand DNA (ssDNA) damage via base excision repair. When PARP activity is inhibited by a NAD+ mimetic analog, ssDNA is converted into a Double-Strand Break (DSB) during the S-phase in a cell cycle. However, the DSB site is repaired in a process of Homologous Recombination (HR) that is derived by genes such as BRCA1/2, PALB2, and RAD51. Under conditions of HR dysfunction, including mutations of BRCA1/2 (called BRCAness), PARP inhibitor (PARPi) induces “synthetic lethality” in BRCAness-specific cancer cells. Indeed, clinical trials using forms of PARPi that include olaparib, veliparib and rucaparib, have revealed that PARP inhibition produces a dramatic effect that actually arrests cancer progression. Its clinical efficiency is limited, however, due to the acquisition of PARPi resistance during long-term use of this inhibitor. Thus, it is important to elucidate the mechanisms of PARPi resistance. We searched the scientific literature published in PubMed, with a special focus on kinase phosphorylation that is involved in acquiring PARPi resistance. We also summarized the possible molecular events for recovering HR system, a key event for acquiring PARPi resistance. CDK1 is a critical kinase for 5’-3’ DNA end resection, which is important for generating ssDNA for recruiting HR-priming factors. CDK12 is necessary for the transcription of HR-driver genes, such as BRCA1, BRCA2, RAD51 and ATR via the phosphorylation of RNA Pol-II. PLK-1 participates in driving HR via the phosphorylation of RAD51. The PI3K-AKT-mTOR signaling cascade is involved in BRCA1 induction via an ETS1 transcriptional pathway. Even under ATMdeficient conditions, the ATR-CHK1 axis compensates for loss in the DNA damage response, which results in HR recovery. The HGF receptor Met tyrosine kinase is responsible for promoting DNA repair by activating the PARP catalytic domain. These kinase-based signaling pathways are biologically important for understanding the compensatory system of HR, whereas inactivation of these kinases has shown promise for the release of PARPi resistance. Several lines of preclinical studies have demonstrated the potential use of kinase inhibitors to enhance PARPi sensitivity. We emphasize the clinical importance of chemical inhibitors as adjuvant drugs to block critical kinase activities and prevent the possible PARPi resistance.
聚ADP核糖聚合酶（PARP）通过碱基切除修复在单链DNA（ssDNA）损伤的恢复中起着核心作用。当PARP活性被NAD+模拟类似物抑制时，ssDNA在细胞周期的S期转化为双链断裂（DSB）。然而，DSB位点在同源重组（HR）过程中被修复，该过程由BRCA1/2、PALB2和RAD51等基因衍生。HR功能障碍的病症，包括BRCA1/2（称为BRCAness）、PARP抑制剂（PARPi）的突变，在BRCAness特异性癌症细胞中诱导“合成致死性”。事实上，使用包括奥拉帕尼、韦利帕利和鲁卡帕利在内的PARP形式的临床试验表明，PARP抑制产生了显著的效果，实际上阻止了癌症的进展。然而，由于长期使用该抑制剂会产生PARPi耐药性，其临床疗效有限。因此，阐明PARPi抵抗的机制是很重要的。我们检索了发表在PubMed上的科学文献，特别关注与获得PARPi耐药性有关的激酶磷酸化。我们还总结了恢复HR系统的可能分子事件，这是获得PARPi抗性的关键事件。CDK1是5’-3’DNA末端切除的关键激酶，对产生DNA以募集HR启动因子很重要。CDK12对于通过RNA Pol II的磷酸化转录HR驱动基因如BRCA1、BRCA2、RAD51和ATR是必需的。PLK-1通过RAD51的磷酸化参与驱动HR。PI3K-AKT-mTOR信号级联通过ETS1转录途径参与BRCA1的诱导。即使在ATM不足的条件下，ATR-CHK1轴也能补偿DNA损伤反应的损失，从而导致HR恢复。HGF受体Met酪氨酸激酶负责通过激活PARP催化结构域来促进DNA修复。这些基于激酶的信号通路在理解HR的补偿系统方面具有重要的生物学意义，而这些激酶的失活已显示出缓解PARPi耐药性的前景。几项临床前研究表明，激酶抑制剂有增强PARPi敏感性的潜力。我们强调化学抑制剂作为辅助药物在阻断关键激酶活性和预防可能的PARPi耐药性方面的临床重要性。
{"title":"Kinase Phosphorylation-based Mechanisms of PARP Inhibitor Resistance During Synthetic Lethal Oncotherapy","authors":"E. Osaki, S. Mizuno","doi":"10.2174/1574362413666180724134204","DOIUrl":"https://doi.org/10.2174/1574362413666180724134204","url":null,"abstract":"\u0000\u0000Poly-(ADP-Ribose) Polymerase (PARP) plays a central role in recovery\u0000from single-strand DNA (ssDNA) damage via base excision repair. When PARP activity is\u0000inhibited by a NAD+ mimetic analog, ssDNA is converted into a Double-Strand Break (DSB)\u0000during the S-phase in a cell cycle. However, the DSB site is repaired in a process of Homologous\u0000Recombination (HR) that is derived by genes such as BRCA1/2, PALB2, and RAD51. Under\u0000conditions of HR dysfunction, including mutations of BRCA1/2 (called BRCAness), PARP\u0000inhibitor (PARPi) induces “synthetic lethality” in BRCAness-specific cancer cells. Indeed, clinical\u0000trials using forms of PARPi that include olaparib, veliparib and rucaparib, have revealed that\u0000PARP inhibition produces a dramatic effect that actually arrests cancer progression. Its clinical\u0000efficiency is limited, however, due to the acquisition of PARPi resistance during long-term use of\u0000this inhibitor. Thus, it is important to elucidate the mechanisms of PARPi resistance.\u0000\u0000\u0000\u0000 We searched the scientific literature published in PubMed, with a special focus on\u0000kinase phosphorylation that is involved in acquiring PARPi resistance. We also summarized the\u0000possible molecular events for recovering HR system, a key event for acquiring PARPi resistance.\u0000\u0000\u0000\u0000CDK1 is a critical kinase for 5’-3’ DNA end resection, which is important for generating\u0000ssDNA for recruiting HR-priming factors. CDK12 is necessary for the transcription of HR-driver\u0000genes, such as BRCA1, BRCA2, RAD51 and ATR via the phosphorylation of RNA Pol-II. PLK-1\u0000participates in driving HR via the phosphorylation of RAD51. The PI3K-AKT-mTOR signaling\u0000cascade is involved in BRCA1 induction via an ETS1 transcriptional pathway. Even under ATMdeficient\u0000conditions, the ATR-CHK1 axis compensates for loss in the DNA damage response,\u0000which results in HR recovery. The HGF receptor Met tyrosine kinase is responsible for promoting\u0000DNA repair by activating the PARP catalytic domain.\u0000\u0000\u0000\u0000These kinase-based signaling pathways are biologically important for understanding\u0000the compensatory system of HR, whereas inactivation of these kinases has shown promise for the\u0000release of PARPi resistance. Several lines of preclinical studies have demonstrated the potential\u0000use of kinase inhibitors to enhance PARPi sensitivity. We emphasize the clinical importance of\u0000chemical inhibitors as adjuvant drugs to block critical kinase activities and prevent the possible\u0000PARPi resistance.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"12-23"},"PeriodicalIF":0.0,"publicationDate":"2020-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46990396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-07-31DOI: 10.2174/1574362413666180724105508
Ankita Sharma, S. Nandi
Existing cancer chemotherapeutics can kill normal as well as malignant cells. To solve these issues, scientists are now more concerned about the design and discovery of potential anticancer, least toxic leads, which can promote apoptosis process and inhibition of abnormal signal transduction via hyperactivation of protein kinases such as Pim-1 due to overexpression or mutation of proto-oncogenes and tumor suppressor genes related to molecular mechanisms of senescence, cell cycle, apoptosis and metastatic invasion, thus leading to anticancer activities. Natural scaffolds play a great role in this aspect. Sea is full of biodiverse natural resources of medicinal compounds derived from marine plants, sponges, actinomycetes, cynobacteria, fungi, corals and animals. Many anticancer compounds were successfully discovered. But there are few potent compounds developed against abnormal signal transduction mechanism. Therefore, an attempt has been made in the present review to focus on molecular mechanisms of various targets in connection with the over-expression of Pim-1 mediated senescence, cell cycle, apoptosis and metastatic invasion and their potent inhibitors. Biochemical mechanisms of the potent marine sourced inhibitors keeping activities against abnormal signal transduction were discussed in this study. It gives great attention to expand the capabilities in these upcoming areas to remain globally relevant. Existed marine sourced anticancer compounds tabulated in this study could be used as a template for further design and synthesis of promising congeneric synthetic compounds against another disease by the application of in silico high throughput screening through drug repositioning.
{"title":"Abnormal Signal Transduction via Over-expression of Pim-1 Regulated Senescence, Cell Cycle, Apoptosis and Metastatic Invasion: Novel Anticancer Targets and Their Potent Inhibitors from Marine Sources","authors":"Ankita Sharma, S. Nandi","doi":"10.2174/1574362413666180724105508","DOIUrl":"https://doi.org/10.2174/1574362413666180724105508","url":null,"abstract":"\u0000\u0000Existing cancer chemotherapeutics can kill normal as well as malignant\u0000cells. To solve these issues, scientists are now more concerned about the design and discovery of\u0000potential anticancer, least toxic leads, which can promote apoptosis process and inhibition of abnormal\u0000signal transduction via hyperactivation of protein kinases such as Pim-1 due to overexpression\u0000or mutation of proto-oncogenes and tumor suppressor genes related to molecular\u0000mechanisms of senescence, cell cycle, apoptosis and metastatic invasion, thus leading to anticancer\u0000activities. Natural scaffolds play a great role in this aspect.\u0000\u0000\u0000\u0000Sea is full of biodiverse natural resources of medicinal compounds derived from marine\u0000plants, sponges, actinomycetes, cynobacteria, fungi, corals and animals. Many anticancer\u0000compounds were successfully discovered. But there are few potent compounds developed against\u0000abnormal signal transduction mechanism.\u0000\u0000\u0000\u0000 Therefore, an attempt has been made in the present review to focus on\u0000molecular mechanisms of various targets in connection with the over-expression of Pim-1 mediated\u0000senescence, cell cycle, apoptosis and metastatic invasion and their potent inhibitors.\u0000\u0000\u0000\u0000Biochemical mechanisms of the potent marine sourced inhibitors keeping activities\u0000against abnormal signal transduction were discussed in this study. It gives great attention to expand\u0000the capabilities in these upcoming areas to remain globally relevant.\u0000\u0000\u0000\u0000Existed marine sourced anticancer compounds tabulated in this study could be used\u0000as a template for further design and synthesis of promising congeneric synthetic compounds\u0000against another disease by the application of in silico high throughput screening through drug repositioning.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"3-11"},"PeriodicalIF":0.0,"publicationDate":"2020-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42184394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-07-31DOI: 10.2174/1574362413666181109111518
Sethu Selvi
Dedicated wavelength utilization and the isolation of control plane from the data plane are the important features in the design of Optical Burst Switching (OBS). The contention in bursts, link congestion and the reservation cause the burst dropping in optical networks. The slotted time and the burst assembly models incorporate the wavelength assignment and the channel reservation schemes to reduce the dropping probability. The reservation of resources prior to burst arrival and the additional delay due to the burst assembly and the offset time are the major issues in the reduction of probability. Besides, the traditional one-to-one packet transmission consumes more time due to a large number of packets handling. This paper proposes the novel OBS model that incorporates the three processes such as Open-Flow (OF)-based Orchestrator Live Node (OLN) modeling, fuzzy logic based ranking and the offset time-based reservation (without/with void filling) to overcome the issues in the traditional methods. Initially, the OLN modeling based on OF analysis includes the Flow Information Base (FIB) table for the periodical update of the link information. The fuzzy logic- based ranking of channels followed by OF-OLN predicts the status of the wavelength such as free, used and conversion. Based on the status, the channels are reserved without and with void filling to schedule the bursts effectively. The reservation scheme employs the Offset-Time Burst Assembly algorithm to allow the resource reservation prior to burst arrival. Through these processes, the reuse of wavelength and the reallocation of resources are possible in OBS. The controlling of maximum burst transfer delay by the OTBA efficiently reduces the end-to-end delay for data traffic. The comparative analysis between the proposed OLN-WR with the existing Hybrid Burst Assembly (HBA), Fuzzy-based Adaptive Threshold (FAT) and Fuzzy-based Adaptive Hybrid Burst Assembly (FAHBA) in terms of end-to-end delay and transmitted amount of bursts assures the applicability of OLN-WR in scheduling and communication activities in OBS networks.
光突发交换(OBS)设计的重要特点是专用波长的利用和控制平面与数据平面的隔离。争用突发、链路拥塞和预留是造成光网络突发下降的主要原因。狭缝时间和突发装配模型结合了波长分配和信道保留方案，以降低跌落概率。突发到达前的资源预留、突发集合造成的额外延迟和偏移时间是降低概率的主要问题。此外，传统的一对一的数据包传输由于处理大量的数据包而消耗更多的时间。本文提出了一种新的OBS模型，该模型结合了基于Open-Flow (OF)的Orchestrator Live Node (OLN)建模、基于模糊逻辑的排序和基于偏移时间的预约(无/有空隙填充)三个过程，克服了传统OBS模型存在的问题。最初，基于OF分析的OLN建模包括流量信息库(flow Information Base, FIB)表，用于定期更新链路信息。基于模糊逻辑的信道排序，然后是of - oln，预测波长的状态，如空闲、使用和转换。根据信道的状态，对信道进行无填充和有填充的保留，有效地调度突发。预留方案采用Offset-Time BurstAssembly算法，允许在突发到达之前预留资源。通过这些过程，可以实现光存储系统中波长的重复利用和资源的重新分配。OTBA对最大突发传输延迟的控制有效地降低了数据流量的端到端延迟。通过与现有的混合突发组合(Hybrid Burst Assembly, HBA)、基于模糊自适应阈值(FAT)和基于模糊自适应混合突发组合(FAHBA)在端到端延迟和突发传输量方面的比较分析，保证了OLN-WR在OBS网络调度和通信活动中的适用性。
{"title":"Channel Scheduling Based on Orchestrator Live Node-Wavelength Reservation for Optical Burst Switching Networks","authors":"Sethu Selvi","doi":"10.2174/1574362413666181109111518","DOIUrl":"https://doi.org/10.2174/1574362413666181109111518","url":null,"abstract":"\u0000\u0000 Dedicated wavelength utilization and the isolation of control plane from\u0000the data plane are the important features in the design of Optical Burst Switching (OBS). The contention\u0000in bursts, link congestion and the reservation cause the burst dropping in optical networks.\u0000The slotted time and the burst assembly models incorporate the wavelength assignment and the\u0000channel reservation schemes to reduce the dropping probability. The reservation of resources prior\u0000to burst arrival and the additional delay due to the burst assembly and the offset time are the major\u0000issues in the reduction of probability. Besides, the traditional one-to-one packet transmission consumes\u0000more time due to a large number of packets handling.\u0000\u0000\u0000\u0000This paper proposes the novel OBS model that incorporates the three\u0000processes such as Open-Flow (OF)-based Orchestrator Live Node (OLN) modeling, fuzzy logic\u0000based ranking and the offset time-based reservation (without/with void filling) to overcome the issues\u0000in the traditional methods. Initially, the OLN modeling based on OF analysis includes the\u0000Flow Information Base (FIB) table for the periodical update of the link information. The fuzzy logic-\u0000based ranking of channels followed by OF-OLN predicts the status of the wavelength such as\u0000free, used and conversion. Based on the status, the channels are reserved without and with void\u0000filling to schedule the bursts effectively. The reservation scheme employs the Offset-Time Burst\u0000Assembly algorithm to allow the resource reservation prior to burst arrival. Through these processes,\u0000the reuse of wavelength and the reallocation of resources are possible in OBS.\u0000\u0000\u0000\u0000The controlling of maximum burst transfer delay by the OTBA efficiently\u0000reduces the end-to-end delay for data traffic. The comparative analysis between the proposed\u0000OLN-WR with the existing Hybrid Burst Assembly (HBA), Fuzzy-based Adaptive Threshold\u0000(FAT) and Fuzzy-based Adaptive Hybrid Burst Assembly (FAHBA) in terms of end-to-end delay\u0000and transmitted amount of bursts assures the applicability of OLN-WR in scheduling and communication\u0000activities in OBS networks.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"13 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2020-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41846841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-30DOI: 10.2174/1574362414666190131105731
M. Khosravi
Some interpolators cannot be used in an image magnification problem in a freely scalable form. For instance, when we want to magnify an image to a 16-time bigger scale, some interpolators have to do this process in two steps including two 4-time magnification steps, however, some are able to do it directly. For generating data of this study, MATLAB as a simulator has been used. Bi-; Linear (BL) and Cubic Convolution (CC) interpolators are the two applied re-samplers in the reconstruction of digital images. Data shows that the performance of both free-size interpolators (BL and CC) is obviously different in both direct and indirect pixel reconstruction. The acquired data shows a less error in the condition of direct interpolation. The relative results of experiments are different from the type of core interpolators (BL and CC).
{"title":"Single- and Multi-Step Image Enlargement for Medical Image Coding","authors":"M. Khosravi","doi":"10.2174/1574362414666190131105731","DOIUrl":"https://doi.org/10.2174/1574362414666190131105731","url":null,"abstract":"\u0000\u0000Some interpolators cannot be used in an image magnification problem in a freely scalable form.\u0000For instance, when we want to magnify an image to a 16-time bigger scale, some interpolators have to do this process in\u0000two steps including two 4-time magnification steps, however, some are able to do it directly.\u0000\u0000\u0000\u0000 For generating data of this study, MATLAB as a simulator has been used. Bi-; Linear (BL) and\u0000Cubic Convolution (CC) interpolators are the two applied re-samplers in the reconstruction of digital images.\u0000\u0000\u0000\u0000 Data shows that the performance of both free-size interpolators (BL and CC) is obviously different in both direct\u0000and indirect pixel reconstruction.\u0000\u0000\u0000\u0000The acquired data shows a less error in the condition of direct interpolation. The relative results of experiments\u0000are different from the type of core interpolators (BL and CC).\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"86-87"},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574362414666190131105731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43101258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-30DOI: 10.2174/1574362413666180412142930
S. Lai, A. Sciarra, Federico Pierella, S. Pastore, L. Piloni, S. Salciccia, A. Perrotta, P. Protopapa, G. Pintus, G. P. Ricciuti, Mauro Ciccariello, M. V. Heland
Chronic Kidney Disease (CKD) is a highly prevalent condition and it is a major risk factor for End-Stage Renal Disease (ESRD), cardiovascular disease, and premature death. Some congenital and acquired anomalies of the kidneys and lower urinary tract (CAKUT and CALUT) are well-known causes of CKD and ESRD, but often remain undiagnosed and their prevalence is underestimated. This study aims to provide an overview that considered mainly some of the major congenital and acquired urological diseases that could lead to renal clinical manifestations common even to the most widespread renal pathologies, for which often underdiagnosed. PubMed search was conducted for available English literature describing the actual knowledge on congenital and acquired urological disorders determining acute and chronic kidney disease. Prospective and retrospective studies as well as meta-analyses and latest systematic reviews were included. Most of the studies examined and reviewed were discarded for wrong population or intervention or deemed unfit, and only 87 met the inclusion criteria for the review. The studies included in the review related to urological disorders that may determine chronic and acute kidney disease. Some urological diseases, as CAKUT and CALUT, especially in adults, show symptoms, as renal failure, proteinuria and hypertension, very common to other kidney diseases, for this reason may remain undiagnosed and their prevalence is not completely known. Therefore, in doubtful cases, non-invasive and inexpensive tests, as cystourethrogram, should be made, to rule out urological disorders and if necessary, ultrasonography, urography and scintigraphy, might allow a correct and early diagnosis of these defects and thus adequate therapy, preventing or at least slowing down an evolution toward CKD and ESRD.
{"title":"Chronic Kidney Disease and Urological Disorders: An Overview","authors":"S. Lai, A. Sciarra, Federico Pierella, S. Pastore, L. Piloni, S. Salciccia, A. Perrotta, P. Protopapa, G. Pintus, G. P. Ricciuti, Mauro Ciccariello, M. V. Heland","doi":"10.2174/1574362413666180412142930","DOIUrl":"https://doi.org/10.2174/1574362413666180412142930","url":null,"abstract":"\u0000\u0000Chronic Kidney Disease (CKD) is a highly prevalent condition and it is a\u0000major risk factor for End-Stage Renal Disease (ESRD), cardiovascular disease, and premature\u0000death. Some congenital and acquired anomalies of the kidneys and lower urinary tract (CAKUT\u0000and CALUT) are well-known causes of CKD and ESRD, but often remain undiagnosed and their\u0000prevalence is underestimated. This study aims to provide an overview that considered mainly\u0000some of the major congenital and acquired urological diseases that could lead to renal clinical\u0000manifestations common even to the most widespread renal pathologies, for which often underdiagnosed.\u0000\u0000\u0000\u0000 PubMed search was conducted for available English literature describing\u0000the actual knowledge on congenital and acquired urological disorders determining acute and\u0000chronic kidney disease. Prospective and retrospective studies as well as meta-analyses and latest\u0000systematic reviews were included.\u0000\u0000\u0000\u0000 Most of the studies examined and reviewed were discarded for wrong population or intervention\u0000or deemed unfit, and only 87 met the inclusion criteria for the review. The studies included\u0000in the review related to urological disorders that may determine chronic and acute kidney\u0000disease.\u0000\u0000\u0000\u0000Some urological diseases, as CAKUT and CALUT, especially in adults, show symptoms,\u0000as renal failure, proteinuria and hypertension, very common to other kidney diseases, for\u0000this reason may remain undiagnosed and their prevalence is not completely known. Therefore, in\u0000doubtful cases, non-invasive and inexpensive tests, as cystourethrogram, should be made, to rule\u0000out urological disorders and if necessary, ultrasonography, urography and scintigraphy, might allow\u0000a correct and early diagnosis of these defects and thus adequate therapy, preventing or at least\u0000slowing down an evolution toward CKD and ESRD.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"224-231"},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47006961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-30DOI: 10.2174/1574362413666180912113856
Supriatno
3,4-Dihydro-6-[4-3,4-dimethoxybenzoyl-1-piperazinyl]-2(1H)-quinolinone (vesnarinone), a novel inotropic drug with unique and complex mechanisms of action, is known to show antitumor activity against several human malignancies. In the present study, vesnarinone-induced signal transduction of S-phase kinase-associated protein 2 (Skp2) and Nuclear Factor-kappa Beta (NF-κB) as molecular targets of oral malignant Burkitt’s lymphoma (Raji cells) was evaluated. Raji cells were incubated with vesnarinone at concentrations of 0, 1.25x10-2, 2.50x10-2, or 5.0x10-2 Molar. After 24 h, chemotactic cell migration was examined by a Boyden chamber kit. Apoptosis induction was observed by caspase-9 colorimetric assay. To evaluate levels of Skp2, NF-kB, and α-tubulin, Western blot analysis was performed. Vesnarinone markedly suppressed chemotactic cell migration and significantly induced apoptosis by increasing the caspase-9 activity of Raji cells through down regulation of Skp2 and NF-κB. Vesnarinone decreased the expression of Skp2 and NF-κB indicating these molecules may be targeted for the treatment of oral malignant Burkitt’s lymphoma (BL). The results of this work offer a promising therapeutic approach for BL tumors.
{"title":"S-Phase Kinase-Associated Protein-2 and Nuclear Factor-kappa Beta as Molecular Targets of Oral Burkitt’s Lymphoma Cell Induced by Quinolinone Derivate-Vesnarinone","authors":"Supriatno","doi":"10.2174/1574362413666180912113856","DOIUrl":"https://doi.org/10.2174/1574362413666180912113856","url":null,"abstract":"\u0000\u00003,4-Dihydro-6-[4-3,4-dimethoxybenzoyl-1-piperazinyl]-2(1H)-quinolinone\u0000(vesnarinone), a novel inotropic drug with unique and complex mechanisms of action, is\u0000known to show antitumor activity against several human malignancies. In the present study,\u0000vesnarinone-induced signal transduction of S-phase kinase-associated protein 2 (Skp2) and\u0000Nuclear Factor-kappa Beta (NF-κB) as molecular targets of oral malignant Burkitt’s lymphoma\u0000(Raji cells) was evaluated.\u0000\u0000\u0000\u0000Raji cells were incubated with vesnarinone at concentrations of 0,\u00001.25x10-2, 2.50x10-2, or 5.0x10-2 Molar. After 24 h, chemotactic cell migration was examined by\u0000a Boyden chamber kit. Apoptosis induction was observed by caspase-9 colorimetric assay. To\u0000evaluate levels of Skp2, NF-kB, and α-tubulin, Western blot analysis was performed.\u0000\u0000\u0000\u0000Vesnarinone markedly suppressed chemotactic cell migration and significantly induced\u0000apoptosis by increasing the caspase-9 activity of Raji cells through down regulation of Skp2\u0000and NF-κB.\u0000\u0000\u0000\u0000 Vesnarinone decreased the expression of Skp2 and NF-κB indicating these molecules\u0000may be targeted for the treatment of oral malignant Burkitt’s lymphoma (BL). The results\u0000of this work offer a promising therapeutic approach for BL tumors.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"88-93"},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46600352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-30DOI: 10.2174/1574362413666181113124958
Himanshi Khera, Anupam Awasthi, S. Mehan
Hedgehog pathway plays a crucial role in the neovascularisation and angiogenesis during the embryonic stage in humans. Three genes of hedgehog protein isolated from humans are Sonic hedgehog, Desert hedgehog and Indian hedgehog gene. Two G-protein coupled receptors identified in the sonic hedgehog pathway served as patched receptor and smoothened receptor. Particularly, sonic hedgehog gene plays a versatile role in cellular homeostasis and can be a novel therapeutic target in the prevention of cardiovascular disorders. Further various sonic hedgehog modulators have been reported working as futuristic drug molecules in the modulation of cardiovascular dysfunctions. However, there was limited literature availability that has summarized the possible mechanism of targeting Sonic hedgehog signaling pathway. Thus, the present review is aimed at exploring the role of targeting sonic hedgehog protein signaling and modulators as well as to enlighten that how targeting sonic hedgehog protein involves in the amelioration of atherosclerosis, ischemic heart diseases, vascular endothelial dysfunction, heart failure and congenital heart diseases.
{"title":"Sonic Hedgehog Signaling Activation Promotes Cardioprotective Strategies","authors":"Himanshi Khera, Anupam Awasthi, S. Mehan","doi":"10.2174/1574362413666181113124958","DOIUrl":"https://doi.org/10.2174/1574362413666181113124958","url":null,"abstract":"\u0000\u0000Hedgehog pathway plays a crucial role in the neovascularisation and angiogenesis\u0000during the embryonic stage in humans. Three genes of hedgehog protein isolated from\u0000humans are Sonic hedgehog, Desert hedgehog and Indian hedgehog gene. Two G-protein coupled\u0000receptors identified in the sonic hedgehog pathway served as patched receptor and smoothened receptor.\u0000\u0000\u0000\u0000 Particularly, sonic hedgehog gene plays a versatile role in cellular homeostasis\u0000and can be a novel therapeutic target in the prevention of cardiovascular disorders. Further\u0000various sonic hedgehog modulators have been reported working as futuristic drug molecules\u0000in the modulation of cardiovascular dysfunctions.\u0000\u0000\u0000\u0000 However, there was limited literature availability that has summarized the possible\u0000mechanism of targeting Sonic hedgehog signaling pathway.\u0000\u0000\u0000\u0000 Thus, the present review is aimed at exploring the role of targeting sonic hedgehog\u0000protein signaling and modulators as well as to enlighten that how targeting sonic hedgehog protein\u0000involves in the amelioration of atherosclerosis, ischemic heart diseases, vascular endothelial dysfunction,\u0000heart failure and congenital heart diseases.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"189-196"},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48281598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-30DOI: 10.2174/1574362414666181220105908
R. Kala, P. Deepa
Accurate detection of brain tumor and its severity is a challenging task in the medical field. So there is a need for developing brain tumor detecting algorithms and it is an emerging one for diagnosis, planning the treatment and outcome evaluation. Brain tumor segmentation method using deep learning classification and multi-modal composition has been developed using the deep convolutional neural networks. The different modalities of MRI such as T1, flair, T1C and T2 are given as input for the proposed method. The MR images from the different modalities are used in proportion to the information contents in the particular modality. The weights for the different modalities are calculated blockwise and the standard deviation of the block is taken as a proxy for the information content of the block. Then the convolution is performed between the input image of the T1, flair, T1C and T2 MR images and corresponding to the weight of the T1, flair, T1C, and T2 images. The convolution is summed between the different modalities of the MR images and its corresponding weight of the different modalities of the MR images to obtain a new composite image which is given as an input image to the deep convolutional neural network. The deep convolutional neural network performs segmentation through the different layers of CNN and different filter operations are performed in each layer to obtain the enhanced classification and segmented spatial consistency results. The analysis of the proposed method shows that the discriminatory information from the different modalities is effectively combined to increase the overall accuracy of segmentation. The proposed deep convolutional neural network for brain tumor segmentation method has been analysed by using the Brain Tumor Segmentation Challenge 2013 database (BRATS 2013). The complete, core and enhancing regions are validated with Dice Similarity Coefficient and Jaccard similarity index metric for the Challenge, Leaderboard, and Synthetic data set. To evaluate the classification rates, the metrics such as accuracy, precision, sensitivity, specificity, under-segmentation, incorrect segmentation and over segmentation also evaluated and compared with the existing methods. Experimental results exhibit a higher degree of precision in the segmentation compared to existing methods. In this work, deep convolution neural network with different modalities of MR image are used to detect the brain tumor. The new input image was created by convoluting the input image of the different modalities and their weights. The weights are determined using the standard deviation of the block. Segmentation accuracy is high with efficient appearance and spatial consistency. The assessment of segmented images is completely evaluated by using well-established metrics. In future, the proposed method will be considered and evaluated with other databases and the segmentation accuracy results should be analysed with the presence of different
{"title":"Segmentation of Brain Magnetic Resonance Images using Deep Learning Classification and Multi-modal Composition","authors":"R. Kala, P. Deepa","doi":"10.2174/1574362414666181220105908","DOIUrl":"https://doi.org/10.2174/1574362414666181220105908","url":null,"abstract":"\u0000\u0000Accurate detection of brain tumor and its severity is a challenging task in\u0000the medical field. So there is a need for developing brain tumor detecting algorithms and it is an\u0000emerging one for diagnosis, planning the treatment and outcome evaluation.\u0000\u0000\u0000\u0000Brain tumor segmentation method using deep learning classification and\u0000multi-modal composition has been developed using the deep convolutional neural networks. The\u0000different modalities of MRI such as T1, flair, T1C and T2 are given as input for the proposed\u0000method. The MR images from the different modalities are used in proportion to the information\u0000contents in the particular modality. The weights for the different modalities are calculated blockwise\u0000and the standard deviation of the block is taken as a proxy for the information content of the\u0000block. Then the convolution is performed between the input image of the T1, flair, T1C and T2\u0000MR images and corresponding to the weight of the T1, flair, T1C, and T2 images. The convolution\u0000is summed between the different modalities of the MR images and its corresponding weight\u0000of the different modalities of the MR images to obtain a new composite image which is given as\u0000an input image to the deep convolutional neural network. The deep convolutional neural network\u0000performs segmentation through the different layers of CNN and different filter operations are performed\u0000in each layer to obtain the enhanced classification and segmented spatial consistency results.\u0000The analysis of the proposed method shows that the discriminatory information from the different\u0000modalities is effectively combined to increase the overall accuracy of segmentation.\u0000\u0000\u0000\u0000The proposed deep convolutional neural network for brain tumor segmentation method\u0000has been analysed by using the Brain Tumor Segmentation Challenge 2013 database (BRATS\u00002013). The complete, core and enhancing regions are validated with Dice Similarity Coefficient\u0000and Jaccard similarity index metric for the Challenge, Leaderboard, and Synthetic data set. To\u0000evaluate the classification rates, the metrics such as accuracy, precision, sensitivity, specificity,\u0000under-segmentation, incorrect segmentation and over segmentation also evaluated and compared\u0000with the existing methods. Experimental results exhibit a higher degree of precision in the segmentation\u0000compared to existing methods.\u0000\u0000\u0000\u0000 In this work, deep convolution neural network with different modalities of MR image\u0000are used to detect the brain tumor. The new input image was created by convoluting the input\u0000image of the different modalities and their weights. The weights are determined using the standard\u0000deviation of the block. Segmentation accuracy is high with efficient appearance and spatial consistency.\u0000The assessment of segmented images is completely evaluated by using well-established\u0000metrics. In future, the proposed method will be considered and evaluated with other databases and\u0000the segmentation accuracy results should be analysed with the presence of different ","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"94-108"},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574362414666181220105908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44818955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-30DOI: 10.2174/1574362414666190204124731
Laijun Xu, Lingzhi Li, Shouliang Zhao, Shangfeng Liu
Salivary Adenoid Cystic Carcinoma (ACC) is a malignant tumor located at oral and maxillofacial regions, and its conventional treatments are surgery, chemotherapy and radiotherapy. However, its poor survival rates and prognosis resulting from the molecular mechanisms underlying the carcinogenesis remain obscure. To date, there are insufficient reviews to summarize the genes and molecular pathways for ACC. Therefore, it is required for us to highlight the main oncogenes, tumor suppressor genes and genetic signal transduction pathways associated with ACC in this review. A literature review based on PubMed for the genetic characteristics and molecular transduction pathways for ACC was conducted. Ninety articles were selected as references using the search terms or keywords such as “genes, molecular pathways, salivary adenoid cystic carcinoma or ACC”. We have briefly described histopathology, current treatments and main clinical features in ACC. Besides, we have also elaborated the associated genes and pathways in this review according to the searched articles in recent years. We have summarized vital genes and proteins targeting or mechanism-based on proliferation, apoptosis, invasion and metastasis. Although there are few kinds of research on ACC currently exist, we expect that better detailed genetic studies would pave the way for promising advancement in our understanding of the molecular biology and pathogenesis mechanisms underlying tumors.
{"title":"Recent Advances and Molecular Pathway in Salivary Adenoid Cystic Carcinoma (Review)","authors":"Laijun Xu, Lingzhi Li, Shouliang Zhao, Shangfeng Liu","doi":"10.2174/1574362414666190204124731","DOIUrl":"https://doi.org/10.2174/1574362414666190204124731","url":null,"abstract":"\u0000\u0000Salivary Adenoid Cystic Carcinoma (ACC) is a malignant tumor located\u0000at oral and maxillofacial regions, and its conventional treatments are surgery, chemotherapy and\u0000radiotherapy. However, its poor survival rates and prognosis resulting from the molecular mechanisms\u0000underlying the carcinogenesis remain obscure. To date, there are insufficient reviews to\u0000summarize the genes and molecular pathways for ACC. Therefore, it is required for us to highlight\u0000the main oncogenes, tumor suppressor genes and genetic signal transduction pathways associated\u0000with ACC in this review.\u0000\u0000\u0000\u0000A literature review based on PubMed for the genetic characteristics and\u0000molecular transduction pathways for ACC was conducted. Ninety articles were selected as references\u0000using the search terms or keywords such as “genes, molecular pathways, salivary adenoid\u0000cystic carcinoma or ACC”.\u0000\u0000\u0000\u0000We have briefly described histopathology, current treatments and main clinical features\u0000in ACC. Besides, we have also elaborated the associated genes and pathways in this review according\u0000to the searched articles in recent years.\u0000\u0000\u0000\u0000 We have summarized vital genes and proteins targeting or mechanism-based on proliferation,\u0000apoptosis, invasion and metastasis. Although there are few kinds of research on ACC\u0000currently exist, we expect that better detailed genetic studies would pave the way for promising\u0000advancement in our understanding of the molecular biology and pathogenesis mechanisms underlying\u0000tumors.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"197-207"},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574362414666190204124731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41604994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-30DOI: 10.2174/1574362413666181005101315
M. Khosravi, Babak Bahri-Aliabadi, Seyed Reza Salari, S. Samadi, H. Rostami, Vahid Karimi
The presence of speckle noise in synthetic aperture radar (SAR) images makes the images of low quality in terms of textural features and spatial resolution which are required for processing issues such as image classification and clustering. Already, there are many adaptive filters to remove noise in SAR images. ENVI software is a fully applicable tool for this purpose which has a good library including several filters in the classes of adaptive, orderstatistics and non-linear filters. In this study, the toolbox of ENVI is reviewed, analyzed and then numerically evaluated based on several single-band images along with multi-band polarimetric SAR (Pol-SAR) images achieved from SAR sensors such as TerraSAR-X. For evaluation, two metrics including Equivalent Number of Looks (ENL) and Edge Preservation Index (EPI) are used which show the ability of the filters in preserving jointly spatial/textural features based on general information and edges quality, respectively. It is notable that both metrics illustrate that some classic filters are better in comparison to newer filters. The experiments can help us in selecting a better filter towards our aims. In this respect, attention to the results of commercial filters of ENVI software and their analysis can guide us to find the best case in order to process commercial data of SAR sensors in the applications of environmental monitoring, geo-science studies, industrial usages and so on.
{"title":"A Tutorial and Performance Analysis on ENVI Tools for SAR Image Despeckling","authors":"M. Khosravi, Babak Bahri-Aliabadi, Seyed Reza Salari, S. Samadi, H. Rostami, Vahid Karimi","doi":"10.2174/1574362413666181005101315","DOIUrl":"https://doi.org/10.2174/1574362413666181005101315","url":null,"abstract":"\u0000\u0000The presence of speckle noise in synthetic aperture radar (SAR) images\u0000makes the images of low quality in terms of textural features and spatial resolution which are\u0000required for processing issues such as image classification and clustering. Already, there are many\u0000adaptive filters to remove noise in SAR images. ENVI software is a fully applicable tool for this\u0000purpose which has a good library including several filters in the classes of adaptive, orderstatistics\u0000and non-linear filters.\u0000\u0000\u0000\u0000In this study, the toolbox of ENVI is reviewed, analyzed and then\u0000numerically evaluated based on several single-band images along with multi-band polarimetric\u0000SAR (Pol-SAR) images achieved from SAR sensors such as TerraSAR-X. For evaluation, two\u0000metrics including Equivalent Number of Looks (ENL) and Edge Preservation Index (EPI) are used\u0000which show the ability of the filters in preserving jointly spatial/textural features based on general\u0000information and edges quality, respectively.\u0000\u0000\u0000\u0000 It is notable that both metrics illustrate that some classic filters are better in comparison\u0000to newer filters.\u0000\u0000\u0000\u0000The experiments can help us in selecting a better filter towards our aims. In this\u0000respect, attention to the results of commercial filters of ENVI software and their analysis can\u0000guide us to find the best case in order to process commercial data of SAR sensors in the\u0000applications of environmental monitoring, geo-science studies, industrial usages and so on.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"15 1","pages":"215-222"},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44473291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：