scholarly journals Radiation Therapy in Patients With Brain Cancer: Post-proteomics Interpretation

2019 ◽  
Vol 10 (5) ◽  
pp. S59-S63
Author(s):  
Hamid Asadzadeh-Aghdaei ◽  
Farshad Okhovatian ◽  
Zahra Razzaghi ◽  
Mohammadhossein Heidari ◽  
Reza Vafaee ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Skin Lesions ◽  
Network Stability ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Complementary Study

Introduction: Radiation therapy (RT) as a common method for cancer treatment could result in some side effects. The molecular investigation is one of the approaches that could assist in decrypting the molecular mechanisms of this incident. For this aim, protein-protein interaction (PPI) network analysis as a complementary study of the proteome is conducted to explore the RT effect on brain cancer after the early stage of exposure prior to the appearance of the skin lesion. Methods: Cytoscape 3.7.2 and its plug-ins were used to analyze the network of differential expression of proteins (DEPs) in the treatment condition, and the centrality and pathway enrichment was conducted by the use of NetworkAnalyzer and ClueGO+CluePedia. Results: A network of 15 DEPs indicated that 6 nodes were key players in the network stability and SERPINC1 and F5 were from the query proteins. The pathways of post-translational protein phosphorylation, platelet degranulation, and complement and coagulation cascades were the most highlighted ones for the central nodes that could be affected in RT. Conclusion: The central proteins of the network of early-stage treatments could have additional importance in the mechanisms of radiotherapy response prior to skin lesions. Introduced biomarkers can be used for the patients’ follow-up. These candidates are worth precise attention for this type of therapy after approving by validation studies.

scholarly journals Intraoperative radiation therapy for early stage breast cancer: experiences from Iran

2020 ◽  
Author(s):  
Vahid Zangouri ◽  
Hamid Nasrollahi ◽  
Ali Taheri ◽  
Majid Akrami ◽  
Peyman Arasteh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Patient Selection ◽  
Tumor Size ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Intraoperative Radiation Therapy ◽  
Study Patient ◽  
Intraoperative Radiation

Abstract Background and objective Currently no definite guideline exists on the use of intraoperative radiation therapy (IORT) among patients with early stage BC. We report our experiences with IORT among breast cancer (BC) patients in our region.Methods All patient who received radical IORT from April 2014 on to March 2020 were included in the study. Patient selection criteria were as followed: age equal or older than 45 years old; all cases of invasive carcinomas, moreover in lobular carcinomas only after MRI and confirmation, and in cases with ductal carcinoma in-situ (DCIS) only those with low, intermediate grade, tumor size of equal or less than 2.5cm and a margin of 2-3mm; those between 45 and 50 years old with a tumor size of 0-2cm, those between 50 and 55 years old with a tumor size of 2-2.5cm, and those ≥55 years old with a tumor size of 2.5-3cm; those with invasive tumors a negative margin and in cases of DCIS a margin of 3mm; a negative nodal status (exception in patients with micrometastasis); and a positive estrogen receptor status. Results Overall, 252 patients entered the study. Mean (SD) age of patients was 56.43±7.79 years. In total, 32.9% of patients had a family history of BC. Mean tumor size was 1.56±0.55 cm. Median (IQR) follow-up of patients was 24 (13, 36) months. Overall, 6 patients (2.4%) experienced recurrence in follow-up visits, among which three (1.2%) were local recurrence, two (0.8%) were regional recurrence and one patients (0.4%) had metastasis.Median (IQR) time to recurrence was 23 (13, 36) among the six patient who had recurrence. Overall, 11 patients (4.3%) with DCIS in our study received IORT. All these patients had free margins in histopathology examination. None of these patients experience recurrence.Conclusion For the first time, we categorized patients according to age and tumor size and older patients with larger tumor sizes were considered appropriate candidates for IORT. Our series showed a successful experience with the use of IORT in a region where facilities for IORT are limited using our modified criteria for patient selection.

Surgical and Oncologic Outcomes With Intraoperative Radiation Therapy for Early Breast Cancer

2021 ◽  
pp. 000313482110474
Author(s):  
Orli Friedman-Eldar ◽  
Christina Layton ◽  
Iago De Castro Silva ◽  
Mecker G Moller ◽  
Ahkeel Allen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Early Stage ◽  
Oncologic Outcomes ◽  
Intraoperative Radiation Therapy ◽  
Perioperative Outcomes ◽  
Wound Complications ◽  
Intraoperative Radiation ◽  
Areola Complex

Background For selected patients with early-stage breast cancer (BC), intraoperative radiation therapy (IORT) has emerged as a convenient alternative to standard whole breast irradiation (WBI). We report a single institution experience with IORT in terms of oncologic outcomes, toxicities, and cosmesis. Methods Clinicopathological and perioperative outcomes of patients who underwent IORT for early-stage BC at a public hospital from 2017 to 2020 were retrospectively retrieved. Toxicity was categorized to acute or chronic based on 6 months post-IORT cutoff. Results 85 patients underwent IORT and had complete data, aged 49‐85 years (mean 62). Intraoperative radiation therapy added 23 minutes on average to the total operative time. Final stage was 0, I, and II in 40%, 58.9%, and 1.1% of patients, respectively. Mean tumor size was 0.8 cm (range .1-2.1), with ductal histology comprising 94% of cases. Surgical margins were positive in 2 patients, and adjuvant WBI was required in 5 patients. After a median follow‐up of 17 months (range 3-41), none of the patients had local recurrence and no mortality was recorded. Early wound complications included wound dehiscence (n = 1), seroma/hematoma (n = 15), and re-operation with loss of nipple-areola complex (n = 1). Chronic skin toxicities were reported in 10 (12%) patients and good or excellent cosmetic outcome was reported in 93% of patients. Conclusions Utilizing IORT among low-risk early BC patients may be a safe and more convenient alternative to traditional WBI, with low toxicity rate, acceptable cosmetic results, and good oncologic outcomes at 17 months. Longer follow-up and further prospective controlled studies are needed to confirm these findings.

Changes In The Use Of Radiation Therapy Among Adolescents and Young Adults With Early Stage Classical Hodgkin Lymphoma: Implications For Survival and Risk Of Secondary Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 722-722
Author(s):  
Ana Xavier ◽  
Luciano J Costa
Keyword(s):  
Young Adults ◽  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
Early Stage ◽  
Stage I ◽  
Secondary Malignancies ◽  
Classical Hodgkin Lymphoma

Abstract Background Early stage classical Hodgkin lymphoma (HL) is a highly curable disease with the combined use of chemotherapy and radiation therapy (RT). There has been a recent trend to abandon RT, driven mostly by concerns of development of secondary malignancies (SMN). However, it is unknown whether the omission of RT in adolescents and young adults (AYA) with early stage HL affects survival and the risk of developing SMN. Methods We used data from the National Cancer Institute's Surveillance Epidemiology and End Results program (SEER-13) to determine the overall survival (OS) and the risk of SMN among AYA with early stage HL treated or not with radiation therapy. Inclusion criterion was the diagnosis of stage I or II HL in the period of 1995-2010 as first malignant neoplasm among patients age 13 to 40 years. Patients with less than 6 months of follow up and patients with unknown use of RT were excluded. Follow up was updated to the end of 2012 (November 2012 submission). Cases were divided in two “eras”, 1995-2002 and 2003-2010, with the latter being expected to reflect changes in the use of RT. The impact of the era, RT, age, race, gender, and stage on survival were accessed utilizing multivariate analysis. Cumulative incidence of SMN among early stage HL survivors was calculated using a competing risk model, treating death from any cause in absence of SMN as the competing risk. Results A total of 5,336 early stage HL cases were included in the analysis with median follow up of 89 months (range 7-191). Median age of patients was 27 years, 2,459 (46%) were male, 1,327 (24.8%) had stage I, 512 (9.7%) had classical HL non otherwise specified, 4,231 (79.2%) had nodular sclerosing HL, 442 (8.3%), had mixed-cellularity HL, 130 (2.4%) had lymphocyte-rich HL, and 21 (0.4%) had lymphocyte depleted HL. Most patients were white (4,438; 83.2%), 513 (9.6%) black, 337 (6.4%) other ethnicity, and 44 (0.8%) unknown. There where 2,793 patients in the 1995-2002 era and 2,542 patients in the 2003-2010 era. Radiation was included in the initial treatment of 1,659 (59.4%) patients in the former and 1,351 (53%) patients in the latter era (P<0.001). Factors associated with use of RT were earlier era, white race and stage II HL. Within the 1995-2002 era, there was a trend towards better survival among patients treated with RT (5-year survival 95.0% vs. 93.6%, P=0.058). In the 2003-2010 cohort survival was superior among patients treated with RT (5-year survival 97.3% vs. 95.9%, P=0.008). In multivariate analysis, diagnosis of HL in the 1995-2002 era (HR=1.73, 95% C.I. 1.31-2.28, P < 0.001), black race (HR= 2.18, 95% C.I. 1.63-2.91, P <0.001), male sex (HR=1.55, 97% C.I. 1.24-1.93, P < 0.001), and omission of RT (HR=1.31, 95% C.I. 1.05-1.64, P=0.017) were associated with higher mortality. The cumulative incidence of SMN was not significantly different between patients treated or not with radiation, while the risk of death was higher among patients not treated with RT (Figure). Conclusion There has been a reduction in utilization of RT among AYA with early stage HL in the US. Omission of RT was associated with increased overall mortality but no reduction in incidence of SMN and should not be adopted outside clinical trials. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-Term Follow-Up of CALGB 9343

2013 ◽  
Vol 31 (19) ◽  
pp. 2382-2387 ◽  
Author(s):  
Kevin S. Hughes ◽  
Lauren A. Schnaper ◽  
Jennifer R. Bellon ◽  
Constance T. Cirrincione ◽  
Donald A. Berry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Distant Metastasis ◽  
Early Stage ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Er Positive ◽  
Long Term Follow Up

Purpose To determine whether there is a benefit to adjuvant radiation therapy after breast-conserving surgery and tamoxifen in women age ≥ 70 years with early-stage breast cancer. Patients and Methods Between July 1994 and February 1999, 636 women (age ≥ 70 years) who had clinical stage I (T1N0M0 according to TNM classification) estrogen receptor (ER) –positive breast carcinoma treated by lumpectomy were randomly assigned to receive tamoxifen plus radiation therapy (TamRT; 317 women) or tamoxifen alone (Tam; 319 women). Primary end points were time to local or regional recurrence, frequency of mastectomy, breast cancer–specific survival, time to distant metastasis, and overall survival (OS). Results Median follow-up for treated patients is now 12.6 years. At 10 years, 98% of patients receiving TamRT (95% CI, 96% to 99%) compared with 90% of those receiving Tam (95% CI, 85% to 93%) were free from local and regional recurrences. There were no significant differences in time to mastectomy, time to distant metastasis, breast cancer–specific survival, or OS between the two groups. Ten-year OS was 67% (95% CI, 62% to 72%) and 66% (95% CI, 61% to 71%) in the TamRT and Tam groups, respectively. Conclusion With long-term follow-up, the previously observed small improvement in locoregional recurrence with the addition of radiation therapy remains. However, this does not translate into an advantage in OS, distant disease-free survival, or breast preservation. Depending on the value placed on local recurrence, Tam remains a reasonable option for women age ≥ 70 years with ER-positive early-stage breast cancer.

scholarly journals Comprehensive Analysis of Common Different Gene Expression Signatures in the Neutrophils of Sepsis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhaojun Liu ◽  
Yang Chen ◽  
Tingting Pan ◽  
Jialin Liu ◽  
Rui Tian ◽  
...  
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Clinical Samples ◽  
Central Component ◽  
Inflammatory Disorder ◽  
Rt Pcr ◽  
Hub Gene ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Pathogenic Factors

The central component of sepsis pathogenesis is inflammatory disorder, which is related to dysfunction of the immune system. However, the specific molecular mechanism of sepsis has not yet been fully elucidated. The aim of our study was to identify genes that are significantly changed during sepsis development, for the identification of potential pathogenic factors. Differentially expressed genes (DEGs) were identified in 88 control and 214 septic patient samples. Gene ontology (GO) and pathway enrichment analyses were performed using David. A protein-protein interaction (PPI) network was established using STRING and Cytoscape. Further validation was performed using real-time polymerase chain reaction (RT-PCR). We identified 37 common DEGs. GO and pathway enrichment indicated that enzymes and transcription factors accounted for a large proportion of DEGs; immune system and inflammation signaling demonstrated the most significant changes. Furthermore, eight hub genes were identified via PPI analysis. Interestingly, four of the top five upregulated and all downregulated DEGs were involved in immune and inflammation signaling. In addition, the most intensive hub gene AKT1 and the top DEGs in human clinical samples were validated using RT-PCR. This study explored the possible molecular mechanisms underpinning the inflammatory, immune, and PI3K/AKT pathways related to sepsis development.

scholarly journals Radical treachelectomy in treatment of early stages of cervical cancer

2008 ◽  
Vol 55 (4) ◽  
pp. 93-97
Author(s):  
K. Jeremic ◽  
S. Petkovic ◽  
A. Stefanovic ◽  
M. Gojnic ◽  
M. Maksimovic ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Radiation Therapy ◽  
Radical Hysterectomy ◽  
Diagnostic Method ◽  
Early Stage ◽  
Radical Trachelectomy ◽  
Residual Cancer ◽  
Early Stage Cervical Cancer ◽  
Early Cervical Cancer

The aim of the study was to determine if radical trachelectomy with pelvic lymphonodectomy could be a method for treatment of early cervical cancer to preserve fertility. We examined 12 patients who were operatively treated from 1996. to 2006. year. Diagnostic method for cervical cancer was histologic examination, cone or biopsy. Histologic condition was planocelular carcinoma well differenced. Two of the patients had Ia1 stage, seven had Ia2, and three of them had Ib1. We performed abdominal radical trachelectomy with pelvic lymphonodectomy. Resectional edges were patohistologically analyzed ex tempore, as well as lymphonodi, selectively. According to ex tempore analysis we determined if the radical trachelectomy should be done. In one patient resectional edges were positive, so she underwent radical hysterectomy. Postoperatively we found a positive lymphonodus in one patient, so we continued radiation therapy. In twoyear follow-up period we did not find any sign of residual cancer. We concluded that radical trachelectomy with pelvic lymphonodectomy could be appropriate method for treatment of early stage cervical cancer.

scholarly journals Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis

2020 ◽  
Author(s):  
Xiaoqin Wang ◽  
Ming Chen ◽  
Liuzhi Zeng ◽  
Longqian Liu
Keyword(s):  
Gene Expression ◽  
Aqueous Humor ◽  
Molecular Mechanisms ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Gene Expression Omnibus ◽  
Open Angle ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Non Coding Rnas

AbstractPrimary open-angle glaucoma (POAG) is the leading cause of blindness globally, which develops through complex and poorly understood biological mechanisms. Herein, we conducted an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and regulatory mechanisms governing POAG progression. We downloaded AH gene expression datasets (GSE101727 and GSE105269) corresponding to healthy controls and POAG patients from the Gene Expression Omnibus. We then identified mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were differentially expressed (DE) between control and POAG patients. DEmRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein-protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA-miRNA-mRNA and miRNA-transcription factor(TF)-mRNA networks. In total, the GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 37, 5, and 14 of these lncRNAs, miRNAs and mRNAs, respectively. The proteins encoded by these 14 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA-TF-mRNA regulatory network containing 2 miRNAs (miR-135a-5p and miR-139-5p), 5 TFs (TGIF2, TBX5, HNF1A, TCF3, and FOS) and 5 mRNAs (SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2). The SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2 genes that may be viable therapeutic targets for the prevention or treatment of POAG, and regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).

scholarly journals Weighted gene co-expression network analysis to identify key modules and hub genes related to hyperlipidaemia

2021 ◽  
Author(s):  
Fu Jun Liao ◽  
Peng-Fei Zheng ◽  
Yao-Zong Guan ◽  
Hong Wei Pan ◽  
Wei Li
Keyword(s):  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Unsaturated Fatty Acids ◽  
Microarray Dataset ◽  
Hub Genes ◽  
Online Tool ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Qpcr Analysis ◽  
Blue Module

Abstract Background: The purpose of this study was to explore the potential molecular targets of hyperlipidaemia and the related molecular mechanisms.Methods: The microarray dataset of GSE66676 obtained from patients with hyperlipidaemia was downloaded. Weighted gene co-expression network (WGCNA) analysis was used to analyse the gene expression profile, and the royal blue module was considered to have the highest correlation. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were implemented for the identification of genes in the royal blue module using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool (version 6.8; http://david.abcc.ncifcrf.gov). A protein-protein interaction (PPI) network was established by using the online STRING tool. Then, several hub genes were identified by the MCODE and cytoHubba plug-ins in Cytoscape software.Results: The significant module (royal blue) identified was associated with TC, TG and non-HDL-C. GO and KEGG enrichment analyses revealed that the genes in the royal blue module were associated with carbon metabolism, steroid biosynthesis, fatty acid metabolism and biosynthesis pathways of unsaturated fatty acids. SQLE (degree = 17) was revealed as a key molecule associated with hypercholesterolaemia (HCH), and SCD was revealed as a key molecule associated with hypertriglyceridaemia (HTG). RT-qPCR analysis also confirmed the above results based on our HCH/HTG samples.Conclusions: SQLE and SCD are related to hyperlipidaemia, and SQLE/SCD may be new targets for cholesterol-lowering or triglyceride-lowering therapy, respectively.

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