scholarly journals Targeting autophagy in thyroid cancers

2019 ◽  
Vol 26 (4) ◽  
pp. R181-R194 ◽  
Author(s):  
Weijun Wei ◽  
Heather Hardin ◽  
Quan-Yong Luo
Keyword(s):  
Drug Resistance ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Future Research ◽  
Thyroid Cancers ◽  
Acquired Drug Resistance ◽  
Research Perspectives ◽  
Molecular Therapeutics ◽  
Dedifferentiation Process

Thyroid cancer is one of the most common endocrine malignancies. Although the prognosis for the majority of thyroid cancers is relatively good, patients with metastatic, radioiodine-refractory or anaplastic thyroid cancers have an unfavorable outcome. With the gradual understanding of the oncogenic events in thyroid cancers, molecularly targeted therapy using tyrosine kinase inhibitors (TKIs) is greatly changing the therapeutic landscape of radioiodine-refractory differentiated thyroid cancers (RR-DTCs), but intrinsic and acquired drug resistance, as well as adverse effects, may limit their clinical efficacy and use. In this setting, development of synergistic treatment options is of clinical significance, which may enhance the therapeutic effect of current TKIs and further overcome the resultant drug resistance. Autophagy is a critical cellular process involved not only in protecting cells and organisms from stressors but also in the maintenance and development of various kinds of cancers. Substantial studies have explored the complex role of autophagy in thyroid cancers. Specifically, autophagy plays important roles in mediating the drug resistance of small-molecular therapeutics, in regulating the dedifferentiation process of thyroid cancers and also in affecting the treatment outcome of radioiodine therapy. Exploring how autophagy intertwines in the development and dedifferentiation process of thyroid cancers is essential, which will enable a more profound understanding of the physiopathology of thyroid cancers. More importantly, these advances may fuel future development of autophagy-targeted therapeutic strategies for patients with thyroid cancers. Herein, we summarize the most recent evidence uncovering the role of autophagy in thyroid cancers and highlight future research perspectives in this regard.

Non-coding RNAs in Lung Cancer Chemoresistance

2020 ◽  
Vol 20 (13) ◽  
pp. 1023-1032 ◽  
Author(s):  
Priya Mondal ◽  
Jagadish Natesh ◽  
Mohammad Amjad Kamal ◽  
Syed Musthapa Meeran
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Gene Expressions ◽  
Intrinsic Factors ◽  
Non Coding Rnas ◽  
Altered Gene

Background: Lung cancer is the leading cause of cancer-associated death worldwide with limited treatment options. The major available treatment options are surgery, radiotherapy, chemotherapy and combinations of these treatments. In chemotherapy, tyrosine kinase inhibitors and taxol are the first lines of chemotherapeutics used for the treatment of lung cancer. Often drug resistance in the clinical settings hinders the efficiency of the treatment and intrigues the tumor relapse. Drug-resistance is triggered either by intrinsic factors or due to the prolonged cycles of chemotherapy as an acquired-resistance. There is an emerging role of non-coding RNAs (ncRNAs), including notorious microRNAs (miRNAs), proposed to be actively involved in the regulations of various tumor-suppressor genes and oncogenes. Result: The altered gene expression by miRNA is largely mediated either by the degradation or by interfering with the translation of targeted mRNA. Unlike miRNA, other type of ncRNAs, such as long non-coding RNAs (lncRNAs), can target the transcriptional activator or the repressor, RNA polymerase, and even DNA-duplex to regulate the gene expressions. Many studies have confirmed the crucial role of ncRNAs in lung adenocarcinoma progression and importantly, in the acquisition of chemoresistance. Recently, ncRNAs have become early biomarkers and therapeutic targets for lung cancer. Conclusion: Targeting ncRNAs could be an effective approach for the development of novel therapeutics against lung cancer and to overcome the chemoresistance.

scholarly journals Decision Making from the Experience of Orthognathic Surgery Patients: A Grounded Theory Approach

2021 ◽  
pp. 238008442110144
Author(s):  
N.R. Paul ◽  
S.R. Baker ◽  
B.J. Gibson
Keyword(s):  
Decision Making ◽  
Grounded Theory ◽  
Treatment Options ◽  
Study Data ◽  
Primary Objective ◽  
Major Surgery ◽  
Future Research ◽  
Decision Making Process ◽  
Theory Approach

Introduction: Patients’ decisions to undergo major surgery such as orthognathic treatment are not just about how the decision is made but what influences the decision. Objectives: The primary objective of the study was to identify the key processes involved in patients’ experience of decision making for orthognathic treatment. Methods: This study reports some of the findings of a larger grounded theory study. Data were collected through face-to-face interviews of patients who were seen for orthognathic treatment at a teaching hospital in the United Kingdom. Twenty-two participants were recruited (age range 18–66 y), of whom 12 (male = 2, female = 10) were 6 to 8 wk postsurgery, 6 (male = 2, female = 4) were in the decision-making stage, and 4 (male = 0, female = 4) were 1 to 2 y postsurgery. Additional data were also collected from online blogs and forums on jaw surgery. The data analysis stages of grounded theory methodology were undertaken, including open and selective coding. Results: The study identified the central role of dental care professionals (DCPs) in several underlying processes associated with decision making, including legitimating, mediating, scheduling, projecting, and supporting patients’ decisions. Six categories were related to key aspects of decision making. These were awareness about their underlying dentofacial problems and treatment options available, the information available about the treatment, the temporality of when surgery would be undertaken, the motivations and expectation of patients, social support, and fear of the surgery, hospitalization, and potentially disliking their new face. Conclusion: The decision-making process for orthognathic treatment is complex, multifactorial, and heavily influenced by the role of DCPs in patient care. Understanding the magnitude of this role will enable DCPs to more clearly participate in improving patients’ decision-making process. The findings of this study can inform future quantitative studies. Knowledge Transfer Statement: The results of this study can be used both for informing clinical practice around enabling decision making for orthognathic treatment and also for designing future research. The findings can better inform clinicians about the importance of their role in the patients’ decision-making process for orthognathic treatment and the means to improve the patient experience. It is suggested that further research could be conducted to measure some of the key constructs identified within our grounded theory and assess how these change during the treatment process.

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.

The approach to patients with cognitive impairment and hip fracture: the role of orthogeriatric care

2014 ◽  
Vol 24 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Francisco J Tarazona-Santabalbina ◽  
Juan R Doménech-Pascual ◽  
Ángel Belenguer-Varea A ◽  
Eduardo Rovira Daudi
Keyword(s):  
Cognitive Impairment ◽  
Hip Fracture ◽  
Functional Recovery ◽  
Functional Outcomes ◽  
Older Patients ◽  
Future Research ◽  
Research Perspectives ◽  
Increased Risk ◽  
Risk Of Falls

SummaryHip fracture is very common among older patients, who are characterized by increased co-morbidities, including cognitive impairment. These patients have an increased risk of falls and fractures, poorer functional recovery and lower survival both in hospital and 12 months after discharge. We review the survival and functional outcomes of older patients with cognitive impairment and hip fracture managed in orthogeriatric units, and highlight the gaps in our knowledge of the efficacy and efficiency of specific orthogeriatric programmes for such patients and the future research perspectives in this field.

scholarly journals The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Carolina Soekmadji ◽  
Colleen C. Nelson
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Advanced Prostate Cancer ◽  
Control Cell ◽  
Extracellular Vesicle ◽  
Multidrug Resistance Proteins ◽  
Acquired Drug Resistance ◽  
Resistance Proteins

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

scholarly journals Autocrine IL-6/STAT3 signaling aids development of acquired drug resistance in Group 3 medulloblastoma

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Lakshana Sreenivasan ◽  
Hui Wang ◽  
Shyong Quin Yap ◽  
Pascal Leclair ◽  
Anthony Tam ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance ◽  
Acquired Drug Resistance ◽  
Stat3 Signaling ◽  
Therapeutic Benefits ◽  
Signaling Axis ◽  
Neuronal Precursors ◽  
Cranial Fossa ◽  
Group 3

AbstractMedulloblastoma (MB) is a high-grade pediatric brain malignancy that originates from neuronal precursors located in the posterior cranial fossa. In this study, we evaluated the role of STAT3 and IL-6 in a tumor microenvironment mediated drug resistance in human MBs. We established that the Group 3 MB cell line, Med8A, is chemosensitive (hence Med8A-S), and this is correlated with a basal low phosphorylated state of STAT3, while treatment with IL-6 induced robust increases in pY705-STAT3. Via incremental selection with vincristine, we derived the stably chemoresistant variant, Med8A-R, that exhibited multi-drug resistance, enhanced IL-6 induced pY705-STAT3 levels, and increased IL6R expression. Consequently, abrogation of STAT3 or IL6R expression in Med8A-R led to restored chemosensitivity to vincristine, highlighting a prominent role for canonical IL-6/STAT3 signaling in acquired drug resistance. Furthermore, Med8A-S subjected to conditioning exposure with IL-6, termed Med8A-IL6+ cells, exhibited enhanced vincristine resistance, increased expression of pY705-STAT3 and IL6R, and increased secretion of IL-6. When cocultured with Med8A-IL6+ cells, Med8A-S cells exhibited increased pY705-STAT3 and increased IL-6 secretion, suggesting a cytokine feedback loop responsible for amplifying STAT3 activity. Similar IL-6 induced phenomena were also observed in the Group 3 MB cell lines, D283 and D341, including increased pY705-STAT3, drug resistance, IL-6 secretion and IL6R expression. Our study unveiled autocrine IL-6 as a promoter of STAT3 signaling in development of drug resistance, and suggests therapeutic benefits for targeting the IL-6/STAT3 signaling axis in Group 3 MBs.

scholarly journals Emerging Role of Immune Therapy in HCC

2021 ◽  
Author(s):  
Stacey M. Stein
Keyword(s):  
Kinase Inhibitors ◽  
Immune Therapy ◽  
Treatment Options ◽  
Single Agent ◽  
Small Subset ◽  
Vascular Endothelial ◽  
Number Of Patients ◽  
Endothelial Growth Factor ◽  
Expected Increase

AbstractHepatocellular carcinoma (HCC) remains a prevalent cancer diagnosis with an expected increase in incidence in the next decade. Treatment options for advanced disease have expanded significantly in the last decade since sorafenib was first approved in 2007. There have been approvals for multiple tyrosine kinase inhibitors (TKIs) with modest improvements in survival. Single-agent PD-1 inhibition has shown responses in ∼15% of patients, with a tail of the curve that is very beneficial to a small subset of patients. Most recently, studies of combination therapy with immune therapy drugs are showing more durable responses in a larger number of patients with unprecedented response rates over 30%. Different strategies have been pursued, including PD-1 and PD-L1 combinations with vascular endothelial growth factor inhibition, TKIs, and anti-CTLA-4 antibodies. This article provides a review of studies both completed and ongoing with immune therapy in advanced HCC.

Endometriosis

2019 ◽  
Author(s):  
Valerie A Flores ◽  
Hugh S Taylor
Keyword(s):  
Pelvic Pain ◽  
Treatment Options ◽  
Reproductive Age ◽  
Fertility Treatment ◽  
Future Research ◽  
Retrograde Menstruation ◽  
Reproductive Age Women ◽  
Aberrant Gene Expression ◽  
Aberrant Gene

Endometriosis is a chronic, gynecologic disease affecting 6 to 10% of reproductive age women. Pelvic pain, dyspareunia, and infertility are the most common symptoms of endometriosis that can have a significant impact on patients’ lives. Although the etiology remains largely unknown, the role of estrogens in the development and growth of endometriosis is well characterized. Medical and surgical therapies are the two cornerstones of endometriosis management. Following diagnosis of endometriosis, treatment options will be dependent on patient preference (ie, seeking pain relief versus fertility treatment). Future research aimed at targeting altered molecular pathways in patients with endometriosis will hopefully help mitigate the burden of this debilitating disease. This review contains 5 figures, 7 tables, and 75 references. Key Words: aberrant gene expression, altered immunity, endometriosis, infertility, medical and surgical therapy, pelvic pain, retrograde menstruation, stem cells

Fundamentals of Electrostatic Spraying

2015 ◽  
pp. 461-490 ◽  
Author(s):  
Manoj Kumar Patel ◽  
Chirravoori Ghanshyam
Keyword(s):  
Cost Effective ◽  
Future Research ◽  
Electrostatic Spraying ◽  
Research Perspectives ◽  
The People ◽  
Agricultural Applications ◽  
Engineering Practices ◽  
Agriculture And Food ◽  
Uniform Deposition

The desired attributes of electrostatic spraying are uniform deposition onto both directly exposed or obscured crop surfaces which minimize the off-target losses of active ingredients to soil, water, atmosphere and provide more effective and economical pest control. This chapter presents an overview of electrostatic spraying technologies in the field of agriculture emphasizing the key role of advanced electrostatic instrumentation and chronicles the scientific innovations in the parlance of providing cost effective and reliable commercial systems along with an insight on the needs of future research perspectives and directives. It is aimed primarily at a familiarization with spraying concepts and engineering practices. This text is to bridge the knowledge and experience gap among researchers and technology developers and the people involved in electrostatic processes applied to agriculture and food processing. It will also introduce the engineering aspects of design and development of an electrostatic spraying nozzle for agricultural applications.

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