scholarly journals Liquid Biopsy for the Detection of Resistance Mechanisms in NSCLC: Comparison of Different Blood Biomarkers

2019 ◽  
Vol 8 (7) ◽  
pp. 998 ◽  
Author(s):  
Luigi Pasini ◽  
Paola Ulivi
Keyword(s):  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Specific Resistance ◽  
Extracellular Vesicle ◽  
Resistance Mechanisms ◽  
Blood Biomarkers ◽  
Different Types ◽  
Pros And Cons ◽  
Tumor Material

The use of targeted agents and immunotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC) has made it mandatory to characterize tumor tissue for patient selection. Moreover, the development of agents that are active against specific resistance mechanisms arising during treatment make it equally important to characterize the tumor tissue at progression by performing tissue re-biopsy. Given that tumor tissue is not always available for molecular characterization due to the paucity of diagnostic specimens or problems relating to the carrying out of invasive procedures, the use of liquid biopsy represents a valid approach to overcoming these difficulties. The most common material used for liquid biopsy in this setting is plasma-derived cell free DNA (cfDNA), which originates from cells undergoing apoptosis or necrosis. However, other sources of tumor material can be considered, such as extracellular vesicle (EV)-derived nucleic acids, which are actively secreted from living cells and closely correspond to tumor dynamics. In this review, we discuss the role of liquid biopsy in the therapeutic management of NSCLC with particular regard to targeted therapy and immunotherapy, and analyze the pros and cons of the different types of samples used in this context.

scholarly journals Cancer, Retrogenes, and Evolution

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 72
Author(s):  
Klaudia Staszak ◽  
Izabela Makałowska
Keyword(s):  
Specific Resistance ◽  
Neoplastic Transformation ◽  
Resistance Mechanisms ◽  
Response To Therapy ◽  
Additional Gene ◽  
Cancer Subtypes ◽  
Gene Copies ◽  
Specific Cancer ◽  
Evolution Of Genomes

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis.

scholarly journals Evaluation Methods for the Impacts of Shared Mobility: Classification and Critical Review

2020 ◽  
Vol 12 (24) ◽  
pp. 10504
Author(s):  
Anastasia Roukouni ◽  
Gonçalo Homem de Almeida Correia
Keyword(s):  
State Of The Art ◽  
The State ◽  
Added Value ◽  
Research And Practice ◽  
Shared Mobility ◽  
The World ◽  
Different Types ◽  
Pros And Cons

In recent years, shared mobility services have had a growing presence in cities all over the world. Developing methodologies to measure and evaluate the impacts of shared mobility has therefore become of critical importance for city authorities. This paper conducts a thorough review of the different types of methods that can be used for this evaluation and suggests a classification of them. The pros and cons of each method are also discussed. The added value of the paper is twofold; first, we provide a systematic recording of the state of the art and the state of the practice regarding the evaluation of the impacts of shared mobility, from the perspective of city authorities, reflecting on their role, needs, and expectations. Second, by identifying the existing gaps in the literature, we highlight the specific needs for research and practice in this field that can help society figure out the role of urban shared mobility.

Expression of hepatoma-derived growth factor in early-stage cervical adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16002-16002
Author(s):  
C. Tsai ◽  
M. Tai ◽  
T. Hu ◽  
S. Huang ◽  
J. Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Tissue ◽  
Early Stage ◽  
Cervical Adenocarcinoma ◽  
Clinical Samples ◽  
Tissue Samples ◽  
Vascular Space ◽  
Different Types ◽  
Spss Software

16002 Background: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and plays an important role in the progression of different types of cancer. The current study was designed to elucidate the role of HDGF expression during the development of. early-stage cervical adenocarcinoma. Methods: A total of 63 patients with early-stage cervical adenocarcinoma were enrolled in this retrospective study. The HDGF expression in cervical adenocarcinoma was determined by immunohistochemistry. The HDGF immunostaining in the nuclei and cytoplasm of clinical samples was scored and expressed as labeling index to correlate with the clinical parameters of patients with early-stage cervical adenocarcinoma using SPSS software. Results: HDGF immunostaining was detected in both cytoplasm and nucleus of cervical adenocarcinoma. Compared with adjacent non-tumor tissue samples, HDGF expression was significantly increased in either nuclear or cytoplasmic compartment in cervical adenocarcinoma samples (P < 0.001). Moreover, elevated nuclear HDGF levels were correlated with lymph-vascular space invasion (P < 0.05), lymph node metastasis (P < 0.001), recurrence (P < 0.001), advaced grade(P < 0.001). Conclusions: HDGF overexpression is involved in the carcinogenesis of cervical adenocarcinoma. [Table: see text] No significant financial relationships to disclose.

Unravelling how adjuvants work, and what their roles are in vaccination and allergy

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 44-46
Author(s):  
Etsushi Kuroda
Keyword(s):  
Immune System ◽  
Allergic Inflammation ◽  
Adaptive Immune System ◽  
Adaptive Immune ◽  
Different Types ◽  
Pros And Cons ◽  
Disease Agent ◽  
The Difference ◽  
Excessive Activation

The development of safe and effective vaccines is essential to tackling a variety of infectious diseases. Vaccines fall into a variety of different types, depending on how they are produced. The inclusions of live attenuated, inactivated, toxoid, subunit or conjugate vaccines contain key antigens which are used in the vaccines to encourage the immune system to mount an immune response. This response will eventually trigger the creation of targeted memory B cells that persist and can quickly multiple and tackle future interactions with the disease agent. This is the cornerstone of our adaptive immune system, protecting us against getting many diseases more than once. Vaccines often contain more than just the antigen. They also commonly contain a facilitating agent known as an adjuvant. Adjuvants enhance the effect of the vaccine, making it more likely to work and to work well, however, it has long been thought that they themselves confer no immunity if presented to the immune system without the antigen. One of the biggest mysteries in immunology is how exactly adjuvants function. They certainly do function, often making the difference between an ineffectual vaccine and one that can help tackle a disease. However, answering the question of 'how?' may well prove key to the development of better vaccines and even treatments in other fields of human disease. Investigating the mode of action of adjuvants is Dr Etsushi Kuroda, Senior Researcher at NIBIOHN, Japan. He works in the Center for Vaccine and Adjuvant Research under Dr Ken J. Ishii in a large lab with multiple researchers focussing on a different aspect of adjuvants. Kuroda's field of interest is the role of pollution particulates as adjuvants to allergy and asthma. Kuroda explains his area of research in greater detail: 'Particle pollutants that we focused on are also thought to be adjuvants and induce inflammation when they are inhaled. There are pros and cons in adjuvants, and excessive activation of immune cells by adjuvant might induce immune-related diseases such as allergic inflammation.'

scholarly journals Inflammation and Inflammasomes: Pros and Cons in Tumorigenesis

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Liliana R. Balahura ◽  
Aida Selaru ◽  
Sorina Dinescu ◽  
Marieta Costache
Keyword(s):  
Proinflammatory Cytokines ◽  
Tumor Development ◽  
The Past ◽  
Persistent Inflammation ◽  
Gene And Protein Expression ◽  
Different Types ◽  
Pros And Cons ◽  
Promote Cell Death ◽  
Made In

Over the past decade, it has been well established that tumorigenesis is affected by chronic inflammation. During this event, proinflammatory cytokines are produced by numerous types of cells, such as fibroblasts, endothelial cells, macrophages, and tumor cells, and are able to promote the initiation, progression, and metastasis of different types of cancer. When persistent inflammation occurs, activation of inflammasome complexes is initiated, leading to its assembly and further activation of caspase, production of proinflammatory cytokines, and pyroptosis induction. The function of this multiprotein complex is not only to reassure inflammation and to promote cell death, through caspase activity, but also has been identified to have significant contributions during tumorigenesis and cancer development. So far, many efforts have been made in order to extend the knowledge of inflammasome implications and how its components could be targeted as therapeutic agents. Additionally, microRNAs (miRNAs), evolutionary conserved noncoding molecules, have emerged as pivotal players during numerous biological events by regulating gene and protein expression. Therefore, dysregulations of miRNA expressions have been correlated with inflammation during tumor development. In this review, we aim to highlight the dual role of inflammasomes and proinflammatory cytokines during carcinogenesis paired with the distinguished effects of miRNAs upon inflammation cascades during tumor growth and progression.

scholarly journals Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130505 ◽  
Author(s):  
Luigi F. Agnati ◽  
Kjell Fuxe
Keyword(s):  
Synaptic Transmission ◽  
Intercellular Communication ◽  
Cortical Neurons ◽  
Extracellular Fluid ◽  
Extracellular Vesicle ◽  
Volume Transmission ◽  
Different Types ◽  
Point To Point

Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (WT; point-to-point communication via private channels, e.g. synaptic transmission) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid). Volume and synaptic transmission become integrated because their chemical signals activate different types of interacting receptors in heteroreceptor complexes located synaptically and extrasynaptically in the plasma membrane. In VT, we focus on the role of the extracellular-vesicle type of VT, and in WT, on the potential role of the tunnelling-nanotube (TNT) type of WT. The so-called exosomes appear to be the major vesicular carrier for intercellular communication but the larger microvesicles also participate. Extracellular vesicles are released from cultured cortical neurons and different types of glial cells and modulate the signalling of the neuronal–glial networks of the CNS. This type of VT has pathological relevance, and epigenetic mechanisms may participate in the modulation of extracellular-vesicle-mediated VT. Gerdes and co-workers proposed the existence of a novel type of WT based on TNTs, which are straight transcellular channels leading to the formation in vitro of syncytial cellular networks found also in neuronal and glial cultures.

scholarly journals Extracellular Vesicle-Derived DNA vs. CfDNA as a Biomarker for the Detection of Colon Cancer

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1171
Author(s):  
Kavita Thakur ◽  
Manu Smriti Singh ◽  
Sara Feldstein-Davydova ◽  
Victoria Hannes ◽  
Dov Hershkovitz ◽  
...  
Keyword(s):  
Colon Carcinoma ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Mutation Detection ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
P Value ◽  
Liquid Biopsies ◽  
Targeted Ngs ◽  
Tumor Dna

Liquid biopsy has emerged as a promising non-invasive way to diagnose tumor and monitor its progression. Different types of liquid biopsies have different advantages and limitations. In the present research, we compared the use of two types of liquid biopsy, extracellular vesicle-derived DNA (EV-DNA) and cell-free DNA (cfDNA) for identifying tumor mutations in patients with colon carcinoma. Method: DNA was extracted from the tumor tissue of 33 patients diagnosed with colon carcinoma. Targeted NGS panel, based on the hotspots panel, was used to identify tumor mutations. Pre-surgery serum and plasma were taken from the patients in which mutation was found in the tumor tissue. Extracellular vesicles were isolated from the serum followed by the extraction of EV-DNA. CfDNA was extracted from the plasma. The mutations found in the tumor were used to detect the circulating tumor DNA using ultra-deep sequencing. We compared the sensitivity of mutation detection and allele frequency obtained in EV-DNA and cfDNA. Results: The sensitivity of mutation detection in EV-DNA and cfDNA was 61.90% and 66.67%, respectively. We obtained almost identical sensitivity of mutation detection in EV-DNA and cfDNA in each of the four stages of colon carcinoma. The total DNA concentration and number mutant copies were higher in cfDNA vs. EV-DNA (p value = 0.002 and 0.003, respectively). Conclusion: Both cfDNA and EV-DNA can serve as tumor biomarkers. The use of EV-DNA did not lead to improved sensitivity or better detection of tumor DNA in the circulation.

scholarly journals miRNAs as Key Players in the Management of Cutaneous Melanoma

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 415 ◽  
Author(s):  
Celeste Lorusso ◽  
Simona De Summa ◽  
Rosamaria Pinto ◽  
Katia Danza ◽  
Stefania Tommasi
Keyword(s):  
Biological Networks ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Mirna Gene ◽  
Progression Free Survival ◽  
Extracellular Vesicle ◽  
Resistance Mechanisms ◽  
Melanoma Patients ◽  
New Biomarkers

The number of treatment options for melanoma patients has grown in the past few years, leading to considerable improvements in both overall and progression-free survival. Targeted therapies and immune checkpoint inhibitors have opened a new era in the management of melanoma patients. Despite the clinical advances, further research efforts are needed to identify other “druggable” targets and new biomarkers to improve the stratification of melanoma patients who could really benefit from targeted and immunotherapies. To this end, many studies have focused on the role of microRNAs (miRNAs) that are small non-coding RNAs (18-25 nucleotides in length), which post-transcriptionally regulate the expression of their targets. In cancer, they can behave either as oncogenes or oncosuppressive genes and play a central role in many intracellular pathways involved in proliferation and invasion. Given their modulating activity on the transcriptional landscape, their biological role is under investigation to study resistance mechanisms. They are able to mediate the communication between tumor cells and their microenvironment and regulate tumor immunity through direct regulation of the genes involved in immune activation or suppression. To date, a very promising miRNA-based strategy is to use them as prognosis and diagnosis biomarkers both as cell-free miRNAs and extracellular-vesicle miRNAs. However, miRNAs have a complex role since they target different genes in different cellular conditions. Thus, the ultimate aim of studies has been to recapitulate their role in melanoma in biological networks that account for miRNA/gene expression and mutational state. In this review, we will provide an overview of current scientific knowledge regarding the oncogenic or oncosuppressive role of miRNAs in melanoma and their use as biomarkers, with respect to approved therapies for melanoma treatment.

Potential Uses of Vinegar as a Medicine and Related in vivo Mechanisms

2016 ◽  
Vol 86 (3-4) ◽  
pp. 127-151 ◽  
Author(s):  
Zeshan Ali ◽  
Zhenbin Wang ◽  
Rai Muhammad Amir ◽  
Shoaib Younas ◽  
Asif Wali ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Review Paper ◽  
Heart Diseases ◽  
Folk Medicine ◽  
Active Role ◽  
Current Review ◽  
Different Types ◽  
Positive Effect

While the use of vinegar to fi ght against infections and other crucial conditions dates back to Hippocrates, recent research has found that vinegar consumption has a positive effect on biomarkers for diabetes, cancer, and heart diseases. Different types of vinegar have been used in the world during different time periods. Vinegar is produced by a fermentation process. Foods with a high content of carbohydrates are a good source of vinegar. Review of the results of different studies performed on vinegar components reveals that the daily use of these components has a healthy impact on the physiological and chemical structure of the human body. During the era of Hippocrates, people used vinegar as a medicine to treat wounds, which means that vinegar is one of the ancient foods used as folk medicine. The purpose of the current review paper is to provide a detailed summary of the outcome of previous studies emphasizing the role of vinegar in treatment of different diseases both in acute and chronic conditions, its in vivo mechanism and the active role of different bacteria.

The Diagnosis of Lupus Anticoagulants by the Activated Partial Thromboplastin Time - The Central Role of Phosphatidyl Serine

1984 ◽  
Vol 52 (02) ◽  
pp. 172-175 ◽  
Author(s):  
P R Kelsey ◽  
K J Stevenson ◽  
L Poller
Keyword(s):  
Screening Method ◽  
Coagulation Factors ◽  
Phosphatidyl Serine ◽  
Test System ◽  
Specific Factor ◽  
Marginal Effect ◽  
Constant Composition ◽  
Lupus Anticoagulants ◽  
Different Types

SummaryLiposomes of pure phospholipids were used in a modified APTT test system and the role of phosphatidyl serine (PS) in determining the sensitivity of the test system to the presence of lupus anticoagulants was assessed. Six consecutive patients with lupus anticoagulants and seven haemophiliacs with anticoagulants directed at specific coagulation factors, were studied. Increasing the concentration of phospholipid in the test system markedly reduced the sensitivity to lupus anticoagulants but had marginal effect on the specific factor inhibitors. The same effect was achieved when the content of PS alone was increased in a vehicle liposome of constant composition.The results suggest that the lupus anticoagulants can best be detected by a screening method using an APTT test with a reagent of low PS content. The use of a reagent rich in PS will largely abolish the lupus anticoagulant’s effect on the APTT. An approach using the two different types of reagent may facilitate differentiation of lupus inhibitors from other types of anticoagulant.

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