scholarly journals Molecular Features and Clinical Management of Hereditary Gynecological Cancers

2020 ◽  
Vol 21 (24) ◽  
pp. 9504
Author(s):  
Arisa Ueki ◽  
Akira Hirasawa
Keyword(s):  
Clinical Management ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Gynecological Cancers ◽  
Hereditary Cancers ◽  
Nccn Guidelines ◽  
Molecular Features ◽  
Methods Of Evaluation ◽  
Cancer Network ◽  
Tumor Profiling

Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li–Fraumeni, Cowden, and Peutz–Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests.

Subcapsular prostate cancer: Identification with mpMRI and MRI/TRUS fusion-guided biopsy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 52-52
Author(s):  
Anna Mary Brown ◽  
Sandeep Sankineni ◽  
Arvin Koruthu George ◽  
Soroush Rais-Bahrami ◽  
Bradford J. Wood ◽  
...  
Keyword(s):  
Clinical Management ◽  
Transrectal Ultrasound ◽  
Risk Scores ◽  
Nccn Guidelines ◽  
Trus Biopsy ◽  
Guided Biopsy ◽  
Aggressive Cancer ◽  
Prostate Cancers ◽  
Cancer Network ◽  
Prostate Capsule

52 Background: The subcapsular region is often under-sampled by standard 12-core transrectal ultrasound (TRUS) prostate biopsy. We retrospectively evaluated multi-parametric MRI (mpMRI) features of subcapsular prostate cancers (PCa) and their detection on MRI/TRUS fusion-guided biopsy (FgBx). Methods: All patients referred for 3T mpMRI and subsequent FgBx under an IRB-approved protocol from Jan 2010 to July 2014 were reviewed. Histologically confirmed subcapsular lesions (just inside the prostate capsule with capsular border length >> width) were identified. Impact of the FgBx on clinical management according to current National Comprehensive Cancer Network (NCCN) guidelines was evaluated, with prior status based on outside TRUS biopsy results. Results: Of 992 eligible patients, 33 had subcapsular prostate lesions on mpMRI. In this subpopulation, mean age, PSA, and prostate volume were 63 years (range 52-76), 8.4ng/mL (1.2-63), and 53 mL (12-125). The FgBx, consisting of targeted (TBx) and systematic (SBx) portions, confirmed PCa in 24 of 33 patients. Five cancers (21%) were only detected by TBx. The remaining 19 were diagnosed on both TBx and SBx, but in 5 of these 19 (26%), higher Gleason scores were found on TBx cores. The FgBx results more accurately classified patients’ NCCN risk scores, with 17 prior unknown or low risk PCa upgraded to higher risk scores (Table). Conclusions: Subcapsular lesions on mpMRI are rare but largely malignant. Most are found on 12-core SBx, but ~20% require TBx for diagnosis, and TBx more accurately grades >25% of the lesions. The FgBx may improve clinical management of patients with subcapsular PCa, since more aggressive cancer was found in 17 of 24 patients. [Table: see text] [Table: see text] [Table: see text]

scholarly journals Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2878
Author(s):  
Claudia Maria Hattinger ◽  
Maria Pia Patrizio ◽  
Leonardo Fantoni ◽  
Chiara Casotti ◽  
Chiara Riganti ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Cure Rate ◽  
Acquired Drug Resistance ◽  
Unselected Patient ◽  
Dismal Prognosis ◽  
Non Coding Rnas ◽  
High Grade Osteosarcoma

High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed.

Does thyroid-sparing total laryngectomy decrease the risk of hypothyroidism?

2020 ◽  
pp. 1-4
Author(s):  
G Viljoen ◽  
J K McGuire ◽  
A Alhadad ◽  
S Dalvie ◽  
J J Fagan
Keyword(s):  
South Africa ◽  
Retrospective Study ◽  
Laryngeal Carcinoma ◽  
Adjuvant Radiotherapy ◽  
Total Laryngectomy ◽  
Inclusion Criteria ◽  
Nccn Guidelines ◽  
Thyroid Lobectomy ◽  
Cancer Network ◽  
Advanced Laryngeal Carcinoma

Abstract Background Thyroid lobectomy is recommended with total laryngectomy for laryngeal cancer in the National Comprehensive Cancer Network (‘NCCN’) guidelines. However, it is associated with a 32–89 per cent risk of hypothyroidism, with or without adjuvant radiotherapy. Objective The study aimed to determine whether preserving the whole thyroid, compared to a single lobe, does indeed significantly lower the incidence of hypothyroidism in the setting of total laryngectomy. Method A retrospective study was conducted at Groote Schuur Hospital in Cape Town, South Africa. Results Eighty-four patients met the inclusion criteria. The overall incidence of hypothyroidism was 45.2 per cent. The incidence of hypothyroidism was significantly reduced in patients who underwent thyroid-sparing total laryngectomy compared to hemithyroidectomy (p = 0.037). Adjuvant radiotherapy was associated with a higher incidence of hypothyroidism (p = 0.001). Conclusion Thyroid-preserving laryngectomy should be advocated in carefully selected patients with advanced laryngeal carcinoma, as it reduces the incidence of hypothyroidism.

scholarly journals Different Therapeutic Strategies to Tackle the Infection Associated with COVID-19

2021 ◽  
Author(s):  
Meemansha Sharma ◽  
Thakur Uttam Singh ◽  
Madhu Cholenahalli Lingaraju ◽  
Subhashree Parida
Keyword(s):  
Human Resources ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Morbidity And Mortality ◽  
The Novel ◽  
Present Book ◽  
Short Period

Covid-19 is a pandemic and the whole world is facing the loss in terms of morbidity and mortality of the human resources. Therefore, there is an urgent need for various therapeutic agents or drugs to treat the covid-19 patients. Although, vaccination process is under way, it is not possible to provide the vaccination to whole world in a short period. Therefore, it is an essential strategy to work on the various therapeutic aspects of covid-19 treatment. The present book chapter will discuss and review the various aspects of the treatment strategies of the covid-19. Further, we will provide an overview of the virus and host based potential therapeutic targets along with existing therapeutics which are effective against SARS-CoV-2 virus. Also, the novel vaccines are being developed against covid-19 deadly virus will be discussed.

scholarly journals Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

2021 ◽  
Vol 19 (9) ◽  
pp. 1079-1109
Author(s):  
Patrick A. Brown ◽  
Bijal Shah ◽  
Anjali Advani ◽  
Patricia Aoun ◽  
Michael W. Boyer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Supportive Care ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Treatment Strategies ◽  
Adolescent And Young Adult ◽  
Cancer Center ◽  
Nccn Guidelines ◽  
Treatment Regimens

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.

Abstract 17402: Single Nuclei RNA-sequencing of Human Hypertrophic Cardiomyopathy Myectomy Samples Reveals Common Novel Mechanisms of Pathogenesis and Potential Therapeutic Targets Regardless of Genotype

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Amy Larson ◽  
Hassan Rastegar ◽  
Gordon S Huggins ◽  
Ethan J Rowin ◽  
Martin S Maron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hypertrophic Cardiomyopathy ◽  
Rna Sequencing ◽  
Alternative Treatment ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Surgical Myectomy

Introduction: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease, often resulting in left ventricular outflow tract obstruction, relieved by surgical myectomy. Current treatments are largely palliative and do not target the root causes. Understanding the molecular drivers of the disease could lead to alternative treatment strategies through identification of novel therapeutic targets. Methods: We performed single nuclei RNA-sequencing (snRNA-seq) on thousands of nuclei from 9 patient myectomy samples and septal tissue from 4 unused donor hearts selected randomly without regard to genotype to identify the cell populations and determine the gene expression patterns in individual cells. Each sample was processed individually using Seurat v3 for quality control and normalization. Next, all 13 samples were integrated into a combined dataset for clustering and differential gene expression analysis to identify markers specific to each cluster and to assign cell identities. Results: Our results revealed several clusters of cardiomyocytes with differences in sarcomeric and metabolic gene expression. Several fibroblast populations were also observed. Numerous genes were differentially expressed between the HCM and normal samples. For example, RARRES1 expression was observed in many of the fibroblast populations in the normal samples, but was absent in the HCM samples. RARRES1 is involved in regulating fatty acid metabolism and autophagy, both of which are altered in HCM. Additionally, expression of PLA2G2A was absent in the HCM samples but was present in almost every cell type in the normal controls. PLA2G2A is involved in suppression of RTK mediated hypertrophic signaling, impacts lipid signaling, and has tumor suppressor properties. Thus, both RARRES1 and PLA2G2A may represent novel targets in HCM. Conclusions: This approach reveals novel potential therapeutic targets within common final HCM pathological pathways independent of genotype that have the potential to guide development of alternative treatment strategies. Further analysis of larger datasets using this approach will likely identify even more common pathway targets and identify additional common mechanisms in the pathogenesis of obstructive HCM.

Level of Scientific Evidence Underlying Recommendations from the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Aakash Desai ◽  
Harry E Fuentes ◽  
Sri Harsha Tella ◽  
Caleb J Scheckel ◽  
Thejaswi Poonacha ◽  
...  
Keyword(s):  
Clinical Practice ◽  
National Comprehensive Cancer Network ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Scientific Evidence ◽  
Hematologic Malignancies ◽  
Level Of Evidence ◽  
Nccn Guidelines ◽  
Therapeutic Recommendations ◽  
Cancer Network

Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in malignant hematology by clinicians and payers in the US. The level of scientific evidence in NCCN guidelines for malignant hematological conditions has not been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are: category I, high level of evidence such as randomized controlled trials with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. We compared our results with previously published results from 2011 guidelines. Results: Total recommendations increased by 16.6% from 1160 (2011) to 1353 (2020). Of the 1353 recommendations, Category 1, 2A, 2B and 3 EC were 5%, 91%, 4%, 1% while in 2011 they were 3%, 93%, 4% and 0% respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt's Lymphoma. 6.3% of therapeutic recommendations were category 1 EC with the majority (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were Multiple Myeloma (12.4%), CLL/SLL (6.9%) and AML (5.6%). Between 2011 and 2020, the proportion of category I recommendations increased significantly only in Follicular lymphoma and CLL/SLL. No category 1 EC recommendations existed in staging or surveillance. Conclusion: Recommendations issued in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Despite the major advances in hematology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders which forms the platform for clinical practice guidelines. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Network-based characterization of disease–disease relationships in terms of drugs and therapeutic targets

2020 ◽  
Vol 36 (Supplement_1) ◽  
pp. i516-i524
Author(s):  
Midori Iida ◽  
Michio Iwata ◽  
Yoshihiro Yamanishi
Keyword(s):  
Large Scale ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Molecular Networks ◽  
Supplementary Information ◽  
New Associations ◽  
Disease States ◽  
Molecular Features ◽  
Novel Approach

Abstract Motivation Disease states are distinguished from each other in terms of differing clinical phenotypes, but characteristic molecular features are often common to various diseases. Similarities between diseases can be explained by characteristic gene expression patterns. However, most disease–disease relationships remain uncharacterized. Results In this study, we proposed a novel approach for network-based characterization of disease–disease relationships in terms of drugs and therapeutic targets. We performed large-scale analyses of omics data and molecular interaction networks for 79 diseases, including adrenoleukodystrophy, leukaemia, Alzheimer's disease, asthma, atopic dermatitis, breast cancer, cystic fibrosis and inflammatory bowel disease. We quantified disease–disease similarities based on proximities of abnormally expressed genes in various molecular networks, and showed that similarities between diseases could be explained by characteristic molecular network topologies. Furthermore, we developed a kernel matrix regression algorithm to predict the commonalities of drugs and therapeutic targets among diseases. Our comprehensive prediction strategy indicated many new associations among phenotypically diverse diseases. Supplementary information Supplementary data are available at Bioinformatics online.

Uterine serous carcinoma: Molecular features, clinical management, and new and future therapies

2021 ◽  
Vol 160 (1) ◽  
pp. 322-332
Author(s):  
Elizabeth K. Lee ◽  
Amanda N. Fader ◽  
Alessandro D. Santin ◽  
Joyce F. Liu
Keyword(s):  
Clinical Management ◽  
Serous Carcinoma ◽  
Molecular Features ◽  
Uterine Serous Carcinoma
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