scholarly journals Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Cheng-Wei Li ◽  
Bor-Sen Chen
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Side Effects ◽  
Regulatory Networks ◽  
Multiple Drug ◽  
Genome Wide ◽  
Stage 4 ◽  
Network Biomarkers ◽  
Stage 1 ◽  
Generation Sequencing

Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.

scholarly journals Understanding the Acceptability of Subdermal Implants as a Possible New HIV Prevention Method: Multi-Stage Mixed Methods Study

10.2196/16904 ◽  
2020 ◽  
Vol 22 (7) ◽  
pp. e16904
Author(s):  
Christine Tagliaferri Rael ◽  
Cody Lentz ◽  
Alex Carballo-Diéguez ◽  
Rebecca Giguere ◽  
Curtis Dolezal ◽  
...  
Keyword(s):  
Side Effects ◽  
Literature Review ◽  
Scientific Literature ◽  
Mixed Methods Study ◽  
Web Based ◽  
Stage 4 ◽  
Subdermal Implants ◽  
Contraceptive Implants ◽  
Stage 1 ◽  
Oral Prep

Background A long-acting implant for HIV pre-exposure prophylaxis (PrEP) is in development in the Sustained Long-Action Prevention Against HIV (SLAP-HIV) trial. This could provide an alternative to oral PrEP. Objective Our mixed methods study aimed to understand (1) users’ experiences with a similar subdermal implant for contraception and (2) factors influencing the likelihood that gay and bisexual men (GBM) would use a proposed PrEP implant. Methods Work was completed in 4 stages. In stage 1, we conducted a scientific literature review on existing subdermal implants, focusing on users’ experiences with implant devices. In stage 2, we reviewed videos on YouTube, focusing on the experiences of current or former contraceptive implant users (as these implants are similar to those in development in SLAP-HIV). In stage 3, individuals who indicated use of a subdermal implant for contraception in the last 5 years were recruited via a web-based questionnaire. Eligible participants (n=12 individuals who liked implants a lot and n=12 individuals who disliked implants a lot) completed in-depth phone interviews (IDIs) about their experiences. In stage 4, results from IDIs were used to develop a web-based survey for HIV-negative GBM to rate their likelihood of using a PrEP implant on a scale (1=very unlikely and 5=very likely) based on likely device characteristics and implant concerns identified in the IDIs. Results In the scientific literature review (stage 1), concerns about contraceptive implants that could apply to the PrEP implants in development included potential side effects (eg, headache), anticipated high cost of the device, misconceptions about PrEP implants (eg, specific contraindications), and difficulty accessing PrEP implants. In the stage 2 YouTube review, individuals who had used contraceptive implants reported mild side effects related to their device. In stage 3, implant users reported that devices were comfortable, unintrusive, and presented only minor discomfort (eg, bruising) before or after insertion and removal. They mainly reported removing or disliking the device due to contraceptive-related side effects (eg, prolonged menstruation). Participants in the stage 4 quantitative survey (N=304) were mainly gay (204/238, 85.7%), white (125/238, 52.5%), cisgender men (231/238, 97.1%), and 42.0% (73/174) of them were on oral PrEP. Not having to take a daily pill increased the likelihood of using PrEP implants (mean 4.13). Requiring >1 device to achieve 1 year of protection (mean range 1.79-2.94) mildly discouraged PrEP implant use. Participants did not mind moderate bruising, a small scar, tenderness, or bleeding after insertion or removal, and an implant with a size slightly larger than a matchstick (mean ratings 3.18-3.69). Conclusions PrEP implants are promising among GBM. Implant features and insertion or removal-related concerns do not seem to discourage potential users. To ensure acceptability, PrEP implants should require the fewest possible implants for the greatest protection duration.

scholarly journals KIF5A Promotes Bladder Cancer Proliferation In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Da-Wei Tian ◽  
Zhou-Liang Wu ◽  
Li-Ming Jiang ◽  
Jie Gao ◽  
Chang-Li Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Regulatory Networks ◽  
Migration And Invasion ◽  
Bladder Tissue ◽  
Tissue Samples ◽  
Normal Bladder ◽  
Tumor Tissues

Background. Bladder cancer is a common malignancy with uncontrolled and rapid growth. Although lots of the important regulatory networks in bladder cancer have been found, the cancer-relevant genes remain to be further identified. Methods. We examined the KIF5A expression levels in bladder cancer and normal bladder tissue samples via immunohistochemistry and observed the effect of KIF5A on bladder tumor cell proliferation in vitro and in vivo. Additionally, a coexpression between KIF5A and KIF20B in tumor tissues was explored. Results. KIF5A expression level was higher in the bladder cancer tissues than in the adjacent nontumor tissues. Patients with higher KIF5A expression displayed advanced clinical features and shorter survival time than those with lower KIF5A expression. Moreover, KIF5A knockdown inhibited bladder cancer cell proliferation, migration, and invasion demonstrated in vivo and in vitro. In addition, coexpression was found between KIF5A and KIF20B in tumor tissues. Conclusion. The results demonstrated that KIF5A is a critical regulator in bladder cancer development and progression, as well as a potential target in the treatment of bladder cancer.

Effect of the patient's age on radiotherapy-based adverse effect.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19575-e19575
Author(s):  
Yillar Okur ◽  
Birsen Yucel ◽  
Ebru Atasever Akkas ◽  
Mehmet Fuat Eren ◽  
Nalan Akgul Babacan ◽  
...  
Keyword(s):  
Side Effects ◽  
Radiation Oncology ◽  
Radiation Therapy Oncology Group ◽  
Eastern Cooperative Oncology Group ◽  
Significant Other ◽  
Oncology Group ◽  
Number Of Patients ◽  
Stage 4 ◽  
Acute Side Effects ◽  
Stage 1

e19575 Background: We aim to determine the acute side effects of radiotherapy and the contribution of age to side effect occurrence in patients treated with radiotherapy. Methods: The data of 346 patients having treatment at Cumhuriyet University Radiation Oncology Department in 2010 and 2011 were analyzed. The patients were evaluated according to Radiation Therapy Oncology Group (RTOG) one a week after starting to radiotherapy. Results: There were 167 women (48%) and 179 men (52%). Two-hundred-forty-seven (71%) of the patients were under the age of 65, 99 (29) were above the age of 65. Eastern Cooperative Oncology Group (ECOG) performance situation was 0, 1 and 2 in 278 (80%), 51 (15%) and 19 (5%) patients. Stage 1, 2, 3 and without metastasis stage 4 were found in 30 (9%), 105 (30%), 172 (50%) and 39 (11%) patients. Radiotherapy was applied to 55 head and neck regions (16%), 31 brains (9%), 86 breasts (25%), 30 thoraxes (9%), 52 abdomens (15%) and 90 pelvises (26%). Fifty-four patients (55%) of above the age of 65 received radiotherapy, 45 patients (45%) received chemoradiotherapy. One-hundred-twenty-six patients (51%) of under the age of 65, received radiotherapy and 121 patients (49%) received chemoradiotherapy. For all the patients, the ratio of radiotherapy dependent side effects was 89% (307). The verage time for occurrence was two weeks. When the treatment was over, the number of patients who lost more than five kg was 42 (12%). ECOG difference was seen in 70 (18%) patients. Twelve of them (4%) showed recovery in ECOG performance, 50 (16%) patients showed disruption. Seventy-nine patients (23%) had a interruption in treatment because of the side effects. The occurrence of dermal side effects was higher in the group of patients below the age of 65 and the occurrence of genitourinary side effects was higher in patients above the age of 65. Thedifferences for both of the side effects were statistically significant. Other side effects and time showed no difference between the patients under 65 and patients above 65. Conclusions: The age does not affect the acute side effects of radiotherapy or chemoradiotherapy, so that both groups can tolerate radiotherapy and chemoradiotherapy.

scholarly journals Understanding the Acceptability of Subdermal Implants as a Possible New HIV Prevention Method: Multi-Stage Mixed Methods Study (Preprint)

2019 ◽  
Author(s):  
Christine Tagliaferri Rael ◽  
Cody Lentz ◽  
Alex Carballo-Diéguez ◽  
Rebecca Giguere ◽  
Curtis Dolezal ◽  
...  
Keyword(s):  
Side Effects ◽  
Literature Review ◽  
Scientific Literature ◽  
Mixed Methods Study ◽  
Web Based ◽  
Stage 4 ◽  
Subdermal Implants ◽  
Contraceptive Implants ◽  
Stage 1 ◽  
Oral Prep

BACKGROUND A long-acting implant for HIV pre-exposure prophylaxis (PrEP) is in development in the Sustained Long-Action Prevention Against HIV (SLAP-HIV) trial. This could provide an alternative to oral PrEP. OBJECTIVE Our mixed methods study aimed to understand (1) users’ experiences with a similar subdermal implant for contraception and (2) factors influencing the likelihood that gay and bisexual men (GBM) would use a proposed PrEP implant. METHODS Work was completed in 4 stages. In stage 1, we conducted a scientific literature review on existing subdermal implants, focusing on users’ experiences with implant devices. In stage 2, we reviewed videos on YouTube, focusing on the experiences of current or former contraceptive implant users (as these implants are similar to those in development in SLAP-HIV). In stage 3, individuals who indicated use of a subdermal implant for contraception in the last 5 years were recruited via a web-based questionnaire. Eligible participants (n=12 individuals who liked implants a lot and n=12 individuals who disliked implants a lot) completed in-depth phone interviews (IDIs) about their experiences. In stage 4, results from IDIs were used to develop a web-based survey for HIV-negative GBM to rate their likelihood of using a PrEP implant on a scale (1=very unlikely and 5=very likely) based on likely device characteristics and implant concerns identified in the IDIs. RESULTS In the scientific literature review (stage 1), concerns about contraceptive implants that could apply to the PrEP implants in development included potential side effects (eg, headache), anticipated high cost of the device, misconceptions about PrEP implants (eg, specific contraindications), and difficulty accessing PrEP implants. In the stage 2 YouTube review, individuals who had used contraceptive implants reported mild side effects related to their device. In stage 3, implant users reported that devices were comfortable, unintrusive, and presented only minor discomfort (eg, bruising) before or after insertion and removal. They mainly reported removing or disliking the device due to contraceptive-related side effects (eg, prolonged menstruation). Participants in the stage 4 quantitative survey (N=304) were mainly gay (204/238, 85.7%), white (125/238, 52.5%), cisgender men (231/238, 97.1%), and 42.0% (73/174) of them were on oral PrEP. Not having to take a daily pill increased the likelihood of using PrEP implants (mean 4.13). Requiring >1 device to achieve 1 year of protection (mean range 1.79-2.94) mildly discouraged PrEP implant use. Participants did not mind moderate bruising, a small scar, tenderness, or bleeding after insertion or removal, and an implant with a size slightly larger than a matchstick (mean ratings 3.18-3.69). CONCLUSIONS PrEP implants are promising among GBM. Implant features and insertion or removal-related concerns do not seem to discourage potential users. To ensure acceptability, PrEP implants should require the fewest possible implants for the greatest protection duration.

Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

1995 ◽  
Vol 53 ◽  
pp. 970-971
Author(s):  
L. Vacca-Galloway ◽  
Y.Q. Zhang ◽  
P. Bose ◽  
S.H. Zhang
Keyword(s):  
Spinal Cord ◽  
Early Stage ◽  
Cervical Spinal Cord ◽  
Wild Type Mouse ◽  
Reflex Response ◽  
Mouse Strains ◽  
Behavioral Tests ◽  
Wobbler Mouse ◽  
Stage 4 ◽  
Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

SARS-CoV-2 Biology Insights, Part I. Genome-wide structure and druggability: literature review (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes
Keyword(s):  
Side Effects ◽  
Literature Review ◽  
Host Cell ◽  
Nucleoside Analogs ◽  
Viral Proteins ◽  
Therapeutic Strategies ◽  
Adverse Side Effects ◽  
Viral Proteases ◽  
Genome Wide ◽  
Therapeutic Alternatives

BACKGROUND COVID-19 pandemic prompts the study of coronavirus biology and search of putative therapeutic strategies. OBJECTIVE To compare SARS-CoV-2 genome-wide structure and proteins with other coronaviruses, focusing on putative coronavirus-specific or SARS-CoV-2 specific therapeutic designs. METHODS The genome-wide structure of SARS-CoV-2 was compared to that of SARS and other coronaviruses in order to gain insights, doing a literature review through Google searches. RESULTS There are promising therapeutic alternatives. Host cell targets could be modulated to hamper viral replication, but targeting viral proteins directly would be a better therapeutic design, since fewer adverse side effects would be expected. CONCLUSIONS Therapeutic strategies (Figure 1) could include the modulation of host targets (PARPs, kinases) , competition with G-quadruplexes or nucleoside analogs to hamper RDRP. The nicest anti-CoV options include inhibitors of the conserved essential viral proteases and drugs that interfere ribosome slippage at the -1 PRF site.

scholarly journals X chromosome-dependent disruption of placental regulatory networks in hybrid dwarf hamsters

Genetics ◽  
2021 ◽  
Author(s):  
Thomas D Brekke ◽  
Emily C Moore ◽  
Shane C Campbell-Staton ◽  
Colin M Callahan ◽  
Zachary A Cheviron ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Regulatory Networks ◽  
Mammalian Species ◽  
Strongly Correlated ◽  
Placental Development ◽  
Substitution Lines ◽  
Genome Wide ◽  
Highly Sensitive ◽  
First And Second Generation

AbstractEmbryonic development in mammals is highly sensitive to changes in gene expression within the placenta. The placenta is also highly enriched for genes showing parent-of-origin or imprinted expression, which is predicted to evolve rapidly in response to parental conflict. However, little is known about the evolution of placental gene expression, or if divergence of placental gene expression plays an important role in mammalian speciation. We used crosses between two species of dwarf hamsters (Phodopus sungorus and Phodopus campbelli) to examine the genetic and regulatory underpinnings of severe placental overgrowth in their hybrids. Using quantitative genetic mapping and mitochondrial substitution lines, we show that overgrowth of hybrid placentas was primarily caused by genetic differences on the maternally inherited P. sungorus X chromosome. Mitochondrial interactions did not contribute to abnormal hybrid placental development, and there was only weak correspondence between placental disruption and embryonic growth. Genome-wide analyses of placental transcriptomes from the parental species and first- and second-generation hybrids revealed a central group of co-expressed X-linked and autosomal genes that were highly enriched for maternally biased expression. Expression of this gene network was strongly correlated with placental size and showed widespread misexpression dependent on epistatic interactions with X-linked hybrid incompatibilities. Collectively, our results indicate that the X chromosome is likely to play a prominent role in the evolution of placental gene expression and the accumulation of hybrid developmental barriers between mammalian species.

Genome-Wide Association Studies Identify Two Novel Loci Conferring Susceptibility to Diabetic Retinopathy in Japanese Patients with Type 2 Diabetes

2021 ◽  
Author(s):  
Minako Imamura ◽  
Atsushi Takahashi ◽  
Masatoshi Matsunami ◽  
Momoko Horikoshi ◽  
Minoru Iwata ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Association Studies ◽  
Meta Analysis ◽  
Japanese Patients ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Stage 1

Abstract Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p < 1.0 × 10−4) in an independent case–control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10−9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11–1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10−8, OR = 1.61, 95% CI 1.36–1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10−6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.

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