Circulating tumor DNA (ctDNA) has potential as a biomarker for prostate cancer (PC) diagnosis and management. ctDNA is DNA released from tumor cells into the bloodstream and makes up a small fraction of total cell-free DNA. Recent studies show ctDNA levels can distinguish between PC patients and those with benign prostate diseases. Advanced techniques like digital PCR and next-generation sequencing allow sensitive detection and characterization of genetic alterations in ctDNA. Ongoing research aims to validate ctDNA analysis for early cancer detection, predicting tumor behavior, and monitoring treatment response in PC.
Molecular characterization of a patient’s tumor to guide treatment decisions is increasingly being
applied in clinical care and can have a significant impact on disease outcome. These molecular analyses,
including mutation characterization, are typically performed on tissue acquired through a biopsy at diagnosis.
However, tumors are highly heterogeneous and sampling in its entirety is challenging. Furthermore, tumors
evolve over time and can alter their molecular genotype, making clinical decisions based on historical biopsy
data suboptimal. Personalized medicine for cancer patients aims to tailor the best treatment options for the
individual at diagnosis and during treatment. To fully enable personalized medicine it is desirable to have an
easily accessible, minimally invasive way to determine and follow the molecular makeup of a patient’s tumor
longitudinally. One such approach is through a liquid biopsy, where the genetic makeup of the tumor can be
assessed through a bio fluid sample. Liquid biopsies have the potential to help clinicians screen for disease,
stratify patients to the best treatment and monitor treatment response and resistance mechanisms in the tumor. A liquid biopsy can be used for molecular characterization of the tumor and its non-invasive nature
allows repeat sampling to monitor genetic changes over time without the need for a tissue biopsy. This review will summarize three approaches in the liquid biopsy field: circulating tumor cells (CTCs), cell free DNA (cfDNA) and exosomes. We also outline some of the analytical challenges encountered using liquid biopsy techniques to detect rare mutations in a background of wild-type sequences.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...daranisaha
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...AnonIshanvi
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...JohnJulie1
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most
aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively,
therefore subjecting a patient to unnecessary surgical intervention,
and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...EditorSara
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...EditorSara
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most
aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy
Molecular characterization of a patient’s tumor to guide treatment decisions is increasingly being
applied in clinical care and can have a significant impact on disease outcome. These molecular analyses,
including mutation characterization, are typically performed on tissue acquired through a biopsy at diagnosis.
However, tumors are highly heterogeneous and sampling in its entirety is challenging. Furthermore, tumors
evolve over time and can alter their molecular genotype, making clinical decisions based on historical biopsy
data suboptimal. Personalized medicine for cancer patients aims to tailor the best treatment options for the
individual at diagnosis and during treatment. To fully enable personalized medicine it is desirable to have an
easily accessible, minimally invasive way to determine and follow the molecular makeup of a patient’s tumor
longitudinally. One such approach is through a liquid biopsy, where the genetic makeup of the tumor can be
assessed through a bio fluid sample. Liquid biopsies have the potential to help clinicians screen for disease,
stratify patients to the best treatment and monitor treatment response and resistance mechanisms in the tumor. A liquid biopsy can be used for molecular characterization of the tumor and its non-invasive nature
allows repeat sampling to monitor genetic changes over time without the need for a tissue biopsy. This review will summarize three approaches in the liquid biopsy field: circulating tumor cells (CTCs), cell free DNA (cfDNA) and exosomes. We also outline some of the analytical challenges encountered using liquid biopsy techniques to detect rare mutations in a background of wild-type sequences.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...daranisaha
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...AnonIshanvi
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...JohnJulie1
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most
aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively,
therefore subjecting a patient to unnecessary surgical intervention,
and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...EditorSara
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...EditorSara
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most
aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...NainaAnon
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most
aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy
Construction and Validation of Prognostic Signature Model Based on Metastatic...daranisaha
Colorectal Cancer (CRC) is a common malignant cancer with a poor prognosis. Liver metastasis is the dominant cause of death in CRC patients, and it often involves changes in various gene expression profiling. This study proposed to construct and validate a risk model based on differentially expressed genes between the primary and liver metastatic tumors from CRC for prognostic prediction.
Colorectal cancer is one of the leading causes of death in the United States. Recent advances of understandings in anatomical patterns and molecular mechanisms may bring better therapeutical options and treatment plan. This article reviews the different outcomes of colorectal cancer associated with anatomical pattern: left-sided or right-sided; and the recently discoveries of colorectal cancer related miRNA.
Cancer recognition from dna microarray gene expression data using averaged on...IJCI JOURNAL
Cancer is a major leading cause of death and responsible for around 13% of all deaths world-wide. Cancer
incidence rate is growing at an alarming rate in the world. Despite the fact that cancer is preventable and
curable in early stages, the vast majority of patients are diagnosed with cancer very late. Therefore, it is of
paramount importance to prevent and detect cancer early. Nonetheless, conventional methods of detecting
and diagnosing cancer rely solely on skilled physicians, with the help of medical imaging, to detect certain
symptoms that usually appear in the late stages of cancer. The microarray gene expression technology is a
promising technology that can detect cancerous cells in early stages of cancer by analyzing gene
expression of tissue samples. The microarray technology allows researchers to examine the expression of
thousands of genes simultaneously. This paper describes a state-of-the-art machine learning based
approach called averaged one-dependence estimators with subsumption resolution to tackle the problem of
recognizing cancer from DNA microarray gene expression data. To lower the computational complexity
and to increase the generalization capability of the system, we employ an entropy-based geneselection
approach to select relevant gene that are directly responsible for cancer discrimination. This proposed
system has achieved an average accuracy of 98.94% in recognizing and classifyingcancer over 11
benchmark cancer datasets. The experimental results demonstrate the efficacy of our framework.
Enhanced convolutional neural network for non-small cell lung cancer classif...IJECEIAES
Lung cancer is a common type of cancer that causes death if not detected early enough. Doctors use computed tomography (CT) images to diagnose lung cancer. The accuracy of the diagnosis relies highly on the doctor's expertise. Recently, clinical decision support systems based on deep learning valuable recommendations to doctors in their diagnoses. In this paper, we present several deep learning models to detect non-small cell lung cancer in CT images and differentiate its main subtypes namely adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. We adopted standard convolutional neural networks (CNN), visual geometry group-16 (VGG16), and VGG19. Besides, we introduce a variant of the CNN that is augmented with convolutional block attention modules (CBAM). CBAM aims to extract informative features by combining cross-channel and spatial information. We also propose variants of VGG16 and VGG19 that utilize a support vector machine (SVM) at the classification layer instead of SoftMax. We validated all models in this study through extensive experiments on a CT lung cancer dataset. Experimental results show that supplementing CNN with CBAM leads to consistent improvements over vanilla CNN. Results also show that the VGG variants that use the SVM classifier outperform the original VGGs by a significant margin.
Cancer is one of the deadliest diseases in the world and is responsible for around 13% of all deaths worldwide.
Cancer incidence rate is growing at an alarming rate in the world. Despite the fact that cancer is
preventable and curable in early stages, the vast majority of patients are diagnosed with cancer very late.
Furthermore, cancer commonly comes back after years of treatment. Therefore, it is of paramount
importance to predict cancer recurrence so that specific treatments can be sought. Nonetheless,
conventional methods of predicting cancer recurrence rely solely on histopathology and the results are not
very reliable. The microarray gene expression technology is a promising technology that couldpredict
cancer recurrence by analyzing the gene expression of sample cells. The microarray technology allows
researchers to examine the expression of thousands of genes simultaneously. This paper describes a stateof-
the-art machine learning based approach called averaged one-dependence estimators with subsumption
resolution to tackle the problem of predicting, from DNA microarray gene expression data, whether a
particular cancer will recur within a specific timeframe, which is usually 5 years. To lower the
computational complexity, we employ an entropy-based geneselection approach to select relevant
prognosticgenes that are directly responsible for recurrence prediction. This proposed system has achieved
an average accuracy of 98.9% in predicting cancer recurrence over 3 datasets. The experimental results
demonstrate the efficacy of our framework.
Research Progress in Chronic Lymphocytic LeukemiaAnonIshanvi
Cancer is an uncontrolled division of cell occurs due to genetic alterations and mutation. Chronic lymphocytic leukemia is the heterogeneous lymphocytic malignancy worldwide that leads to death.
Genetics of Breast and Ovary Cancers Associated with Hereditary Cancers and t...AnonIshanvi
Carriers of the BRCA-1/2 mutation have increased and variable risks of Breast Cancer (BC) and ovarian cancer and vary or are modified by common genetic variants and their incidence genetic testing and risk-reducing surgery has increased, they should receive advice and evaluation by the physician with experience in genetics.
Increased of Protein O-Fucosyl Transferase 1 and 2 Genes Expression in Gastri...AnonIshanvi
Gastric cancer is one of the most common cancers in the world. Gastric cancer usually occurs at an advanced age (average ≥ 65 years) and has symptoms similar to gastric ulcers and other gastric infections, its early diagnosis is one of the major problems of this type of cancer. Molecular mechanisms initiate cancer and the molecular changes of normal cells compared to cancer cells are very important. dysfunction of Fucosyl transferase enzymes is associated with gastric cancer.
The impact of the SARS-CoV-2 infection in all areas at the national and international level is undeniable, the aftermath of this “tornado” will be visible for a long time, even when the infection manages to be controlled. Two aspects of great interest to those of us who work in the area of oncology must be considered: on the one hand, the need to contain and control the devastating effects of the disease forced a reorganization in the operation of services, giving priority to COVID, conversion of medical units to hospitals COVID created a high-risk scenario for patients with other types of pathologies; This reorganization includes the allocation of large amounts of budget to COVID areas to the detriment of patients with other types of equally serious diseases - such as cancer, among others - who cannot wait for care in better times.
Meta-Analysis of Lateral Lymph Node Dissection for Mid Lower Rectal Cancer: I...AnonIshanvi
Presence of lateral lymph node metastasis in rectal cancer was originally reported in the 1950s.Lateral lymph node metastasis occurs in 15 to 20% of patients with locally advanced low rectal cancer which escalates likelihood of local recurrence and reduced survival following neoadjuvant chemoradiotherapy (nCRT) and Total Mesolectal Excision (TME).
Analyzing Speech Outcomes in Hemiglossectomy Patients Using Telecare PlatformAnonIshanvi
Dysarthria is a common postoperative sequela of glossectomy and can greatly impact daily function and Quality of Life (QOL). It is important to study the anatomic and physiological factors that influence speech function, even with the challenges of conducting clinical research during the COVID pandemic. Therefore, our study aims to 1) display the feasibility of using a telecare platform to conduct clinical research; 2) analyze speech outcomes of patients who underwent hemiglossectomy with radial forearm free flap (RFFF) tongue reconstruction.
Uterine Myoma, Risk Factor and Pathophysiology: A Review ArticleAnonIshanvi
Uterine myoma is a benign neoplasm composed of uterine smooth muscle and connective tissue that supports it and is often referred to as fibromyoma, leiomyoma, fibroids. Can be single or multiple and reach large sizes (100 pounds). It has a tough consistency, with a clear cap boundary so that it can be removed from the surroundings. Uterine myoma, also known as leiomyoma or fibroid is a benign tumor that is often found in women of reproductive age (20-25%). At age> 35 years the incidence is higher, that is, closer to 40%. The high incidence of uterine myomas between the ages of 35 and the ages of 50 indicates a relationship between the incidence of uterine myomas and estrogen.
Functional Disparity of Carcinoma Associated Fibroblasts in Different Stages ...AnonIshanvi
Carcinoma associated fibroblasts (CAFs) are known responsible for immune evasion and growth of cancer and the crosstalk between CAFs and the immune system is still unidentified.
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aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy
Construction and Validation of Prognostic Signature Model Based on Metastatic...daranisaha
Colorectal Cancer (CRC) is a common malignant cancer with a poor prognosis. Liver metastasis is the dominant cause of death in CRC patients, and it often involves changes in various gene expression profiling. This study proposed to construct and validate a risk model based on differentially expressed genes between the primary and liver metastatic tumors from CRC for prognostic prediction.
Colorectal cancer is one of the leading causes of death in the United States. Recent advances of understandings in anatomical patterns and molecular mechanisms may bring better therapeutical options and treatment plan. This article reviews the different outcomes of colorectal cancer associated with anatomical pattern: left-sided or right-sided; and the recently discoveries of colorectal cancer related miRNA.
Cancer recognition from dna microarray gene expression data using averaged on...IJCI JOURNAL
Cancer is a major leading cause of death and responsible for around 13% of all deaths world-wide. Cancer
incidence rate is growing at an alarming rate in the world. Despite the fact that cancer is preventable and
curable in early stages, the vast majority of patients are diagnosed with cancer very late. Therefore, it is of
paramount importance to prevent and detect cancer early. Nonetheless, conventional methods of detecting
and diagnosing cancer rely solely on skilled physicians, with the help of medical imaging, to detect certain
symptoms that usually appear in the late stages of cancer. The microarray gene expression technology is a
promising technology that can detect cancerous cells in early stages of cancer by analyzing gene
expression of tissue samples. The microarray technology allows researchers to examine the expression of
thousands of genes simultaneously. This paper describes a state-of-the-art machine learning based
approach called averaged one-dependence estimators with subsumption resolution to tackle the problem of
recognizing cancer from DNA microarray gene expression data. To lower the computational complexity
and to increase the generalization capability of the system, we employ an entropy-based geneselection
approach to select relevant gene that are directly responsible for cancer discrimination. This proposed
system has achieved an average accuracy of 98.94% in recognizing and classifyingcancer over 11
benchmark cancer datasets. The experimental results demonstrate the efficacy of our framework.
Enhanced convolutional neural network for non-small cell lung cancer classif...IJECEIAES
Lung cancer is a common type of cancer that causes death if not detected early enough. Doctors use computed tomography (CT) images to diagnose lung cancer. The accuracy of the diagnosis relies highly on the doctor's expertise. Recently, clinical decision support systems based on deep learning valuable recommendations to doctors in their diagnoses. In this paper, we present several deep learning models to detect non-small cell lung cancer in CT images and differentiate its main subtypes namely adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. We adopted standard convolutional neural networks (CNN), visual geometry group-16 (VGG16), and VGG19. Besides, we introduce a variant of the CNN that is augmented with convolutional block attention modules (CBAM). CBAM aims to extract informative features by combining cross-channel and spatial information. We also propose variants of VGG16 and VGG19 that utilize a support vector machine (SVM) at the classification layer instead of SoftMax. We validated all models in this study through extensive experiments on a CT lung cancer dataset. Experimental results show that supplementing CNN with CBAM leads to consistent improvements over vanilla CNN. Results also show that the VGG variants that use the SVM classifier outperform the original VGGs by a significant margin.
Cancer is one of the deadliest diseases in the world and is responsible for around 13% of all deaths worldwide.
Cancer incidence rate is growing at an alarming rate in the world. Despite the fact that cancer is
preventable and curable in early stages, the vast majority of patients are diagnosed with cancer very late.
Furthermore, cancer commonly comes back after years of treatment. Therefore, it is of paramount
importance to predict cancer recurrence so that specific treatments can be sought. Nonetheless,
conventional methods of predicting cancer recurrence rely solely on histopathology and the results are not
very reliable. The microarray gene expression technology is a promising technology that couldpredict
cancer recurrence by analyzing the gene expression of sample cells. The microarray technology allows
researchers to examine the expression of thousands of genes simultaneously. This paper describes a stateof-
the-art machine learning based approach called averaged one-dependence estimators with subsumption
resolution to tackle the problem of predicting, from DNA microarray gene expression data, whether a
particular cancer will recur within a specific timeframe, which is usually 5 years. To lower the
computational complexity, we employ an entropy-based geneselection approach to select relevant
prognosticgenes that are directly responsible for recurrence prediction. This proposed system has achieved
an average accuracy of 98.9% in predicting cancer recurrence over 3 datasets. The experimental results
demonstrate the efficacy of our framework.
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Cancer is an uncontrolled division of cell occurs due to genetic alterations and mutation. Chronic lymphocytic leukemia is the heterogeneous lymphocytic malignancy worldwide that leads to death.
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The impact of the SARS-CoV-2 infection in all areas at the national and international level is undeniable, the aftermath of this “tornado” will be visible for a long time, even when the infection manages to be controlled. Two aspects of great interest to those of us who work in the area of oncology must be considered: on the one hand, the need to contain and control the devastating effects of the disease forced a reorganization in the operation of services, giving priority to COVID, conversion of medical units to hospitals COVID created a high-risk scenario for patients with other types of pathologies; This reorganization includes the allocation of large amounts of budget to COVID areas to the detriment of patients with other types of equally serious diseases - such as cancer, among others - who cannot wait for care in better times.
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Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...AnonIshanvi
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies
Myelomastocytic leukemia is a very rare variant of myeloid leukemia, behaves clinically very aggressive and belongs to the group of so-called metachromatic leukemias. Metachromatic leu- kemias comprise leukemias with at least 10 to 20% tumor cells exhibiting metachromatic gran- ules: mast cell leukemia
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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Circulatingtumordna (Ctdna) in Prostate Cancer: Current Insights and New Perspectives
1. Circulatingtumordna (Ctdna) in Prostate Cancer: Current In-
sights and New Perspectives
Conteduca V*
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Italy
Volume 1 Issue 1 - 2018
Received Date: 20 May 2018
Accepted Date: 05 June 2018
Published Date: 07 June 2018
1. Abstract
Prostate Cancer (PC) is the common tumor in men, which represents one of leading
cause of cancer death throughout the world. Most patients were diagnosed too late for cura-
tive treatment. So, it is necessary to develop a minimal invasive method to identify novel bio-
markers. Currently, plasma DNA has attracted increasing attention as a potential tumor marker.
However, to date its origin remains still unknown. Recent findings showed that a fraction of the
plasma DNA is derived from the tumor itself, and genetic and epigenetic alterations are regu-
larly detected in PC patients. Many studies have evidenced an association among the plasma
DNA analysis, Gleason score, tumor stage, lymph node status, clinical progression, develop-
ment of metastasis, and clinical outcome, concluding that plasma DNA levels could serve as
a viable tool for diagnostic and prognostic information in prostate tumor. In addition, several
genetic and epigenetic changes, identified by recent genotyping and sequencing technologies,
such as copy number variation, point mutation, loss of heterozygosity, microsatellite instabil-
ity, and gene methylation were correlated with treatment response and resistance mechanisms.
Here, we reviewed the evidence of plasma DNA in PC and consider current and possible future
applications in patient management.
3. Introduction
Prostate Cancer (PC) is one of the three most common
cancer type for the estimated new cancer cases and deaths, respec-
tively, among men in worldwide [1]. PC is highly heterogeneous in
terms of the clinical behavior and molecular pathogenesis. There
is a plethora of clinical situations between indolent and aggressive
tumors and within the same setting, particularly in the Castration-
Resistant Prostate Cancer (CRPC). In addition, tumors with the
same histopathologic grade are often biologically heterogeneous
with different outcome. The remarkable variation in PC clinical
behaviour reflects the broad landscape of molecular alterations
among various prostate tumors and within the same tumor at dif-
ferent stages of disease progression [2-4].
On the basis of wide heterogeneity of prostate tumor, more pre-
cise biomarkers are needed to help accurately the identification
of indolent or aggressive PC, a better knowledge of the genetic
Clinics of Oncology
Citation: Vincenza Conteduca. Circulatingtumordna (Ctdna) in Prostate Cancer: Current Insights and New
Perspectives Clinics of Oncology. 2018; 1(1): 1-12
united Prime Publications: http://unitedprimepub.com
mechanisms of tumor progression and the optimization of PC
management.
Over the years, the use of serum Prostate-Specific Antigen (PSA),
the only routine test approved for the PC screening, detection and
treatment response has become a highly debated question for the
lack of specificity leading often to the over detection and over-
treatment of prostate tumors [5-8]. Consequently, the identifica-
tion of novel biomarkers is one of the most important issue for PC
management and further studies for their validation and intro-
duction into clinical practice are warranted the identification of
novel biomarkers is one of the most important issue for PC man-
agement and further studies for their validation and introduction
into clinical practice are warranted [9,10].
With advances in genotyping and sequencing technologies, the
development of non-invasive methods to detect and monitor tu-
mors continues to be a major challenge in oncology. New molecu-
2. Keywords
Plasma DNA; Prostate cancer; Bio-
marker; PCR; Sequencing
*Corresponding Author (s): Vincenza Conteduca, Department of Medical Oncology,
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Italy,
Tel: +39-0543-739100; Fax: +39-0543-739151; Email: vincenza.conteduca@irst.emr.it
Research article
3. possible to subdivide the approaches for ctDNA analysis into three
groups: a) Polymerase Chain Reaction (PCR) based methods, b)
targeted deep sequencing, and c) whole sequencing [43]. The PCR
based approaches are usually used for the evaluation of a low num-
ber of loci, even digital PCR is considered as a sensitive analysis
tool for the identification of mutations at low allele fraction [44].
Methods involving the use of digital PCR include droplet-based
systems [45,46], microfluidic devices [22,47], and the use of Beads,
Emulsions, Amplification and Magnetics (BEAMing) [48,49]. An
example of the utility of PCR based approaches for ctDNA analysis
is showed by a work evaluating the prognostic utility of circulating
plasma testing in 85 patients with different advanced solid tumors.
Specifically, the presence of NRAS, PIK3CA and AKT1 was dem-
onstrated in 3 of 11 (27.3%) circulating DNA specimens of CRPC
patients and PIK3CA and AKT1 were found in the corresponding
formalin-fixed paraffin-embedded tumor tissue pointing up that
circulating plasma DNA in advanced cancer patients is largely de-
rived from tumor [21].
Next Generation Sequencing (NSG) methods are characterized
by more complete detection of mutations across larger genomic
regions. They revolutionized the field of genomics, allowing rapid
and cost-effective generation of genome-scale sequence data with
excellent resolution and accuracy.
Targeted deep sequencing using PCR-based (e.g. TAm-Seq
[22,50,51], Safe-Seq [52], Ion AmpliSeq™ [4,53] or capture-based
(e.g. CAPP-seq [54]) approaches have been used to sequence spec-
ified genomic regions in plasma DNA. The utility of targeted deep
sequencing in PC is showed in a recent study describing the clonal
architectural heterogeneity at different stages of disease progres-
sion.This work evaluated genomic aberrations by sequencing se-
rial plasma and tumor samples from 16 ERG-positive PC patients
treated with abiraterone, achieving high coverage with lower in-
put DNA (approximately 6 ng) and allowing applicability across a
larger range of patients, including those with lower tumor burden.
In addition, combining targeted deep sequencing and read based
clonality computations provided timely non-invasive biomarkers
for CRPC clinical management [4].
Whole-genome analysis of plasma DNA permits the complete
characterization of mutation profiles, without focusing on pre-
defined mutations [51]. Among these methods, there is personal-
ized analysis of rearrangement ends, which allows to identify spe-
cific somatic rearrangements in human tumors and, subsequently,
to design of PCR-based assays to detect these alterations in plasma
DNA, using these alterations for development of tumor biomark-
ers [39,40]. Some studies have used whole genome sequencing to
detect directly somatic chromosomal alterations and copy num-
ber aberrations in ctDNA genome-wide [38,40]. The first whole-
genome sequencing analysis from plasma DNA of 13 patients with
prostate cancer revealed multiple copy number aberrations and
chromosomal aberrations [55].
With continued developments in the sensitivity of genomic ap-
proaches, NGS techniques will be increasingly able in ctDNA
analysis for future management of many tumors, including PC
at different disease stages, advancing precision medicine for PC
through genomics clinical applications.
6. Application of Circulating DNA in Prostate Cancer
6.1. Early detection: The 2012 recommendations of the United
States Preventive Services Task Force [8] and the National Com-
prehensive Cancer Network (NCCN) Guidelines for Prostate
Cancer Early Detection Panel [56] show a decreased mortality in
populations screened with PSA, stressing benefits from PC screen-
ing and early detection. However, many improvements are being
made to enhance powerful tests that maximize early diagnosis
of aggressive, but often curable disease, whereas diminishing the
identification and treatment of indolent disease. cfDNA could be
useful to discriminate between patients with PC and no malig-
nant prostate disease. Many studies have explorated the utility of
cfDNA as a marker of tumor dynamics in addition to conventional
PSA or imaging techniques. However, the results have been often
conflicting according to different cfDNA isolation and detection
methods and various clinical setting.
Quantitative and qualitative alterations between patients with
diagnosis of PC and nonmalignant lesions, including Prostatic
Intraepithelial Neoplasia (PIN) and Benign Prostate Hyperplasia
(BPH), have evaluated the role of cfDNA in screening and early
detection. Many studies have demonstrated that higher cfDNA
levels in PC patients are able to identify patients with malignant
disease; however, contrasting results have emerged from other
studies making the use of cfDNA a topic of much debate in oncol-
ogy [25-27,36,57-62] (Table 1).
The first study [27], published in 2004, did not demonstrate signif-
icant differences between patients with clinically localized PC and
BPH; on the contrary, it showed a significant increase of plasma
DNA levels in patients with metastatic PC compared to controls.
Another study failed to detect significant differences between pa-
tients with PC and benign prostate diseases [26]. Seventy-eight PC
patients had a significantly higher level of DNA compared with
the control group, but they had significantly lower level of DNA
than 74 patients with benign diseases (P = 0.02).Consequently,
this study suggested that elevated cfDNA levels could not be used
as a new non-invasive approach for PC early detection. These data
have been confirmed in a subsequent study [25] showing a ma-
jor cfDNA concentration in BPH patients than PC patients and,
a lower cfDNA in healthy donors compared to PC patients (P <
0.01), most likely due to the reduced DNase activity in the blood
plasma of PC patients
united Prime Publications: http://unitedprimepub.com 3
volume 1 Issue 1-2018 Research article
4. The failure to distinguish BPH and localized PC may have differ-
ent causes, including the use of a less sensitive fluorometric assay,
or the presence of other diseases within the prostate gland, such as
prostatitis, which may be elevating the cell-free DNA level perhaps
to a greater degree than that of PC.
Recent studies employed a real-time PCR and demonstrated sig-
nificant higher DNA levels in PC then in BPH patients and healthy
donors with good values of sensitivity and specificity (more than
united Prime Publications: http://unitedprimepub.com 4
volume 1 Issue 1-2018 Research article
UTILITY OF QUANTITATIVE ALTERATIONS
YES NO
Study
PC
(number
setting)
Control
(number,
setting)
Source,
Method
Results Study
PC
(number,
setting)
Control
(number,
setting)
Method Results
Allen et al. [57]
27 (12 high
grade PIN,
15 PC)
10 (BPH) Plasma, PCR
S: 85%
Jung et al. [14]
91 (32
pNoMo, 30
pN1M0 29
M1)
93 (30
female
controls,
29 HD, 34
BPH)
Plasma,
Flurome-
tric assay
S:n.s.
Sp: 73% Sp:n.s.
AUC:n.r. AUC:n.s.
P:0.04
(PIN vs
HD);
P: 0.140*
P:0.01 (PC
vs HD)
Papadopoulou et
al. [58]
12 13 Plasma, PCR
S: 58%
Boddy et al.
[26]
78
99 (74
benign, 15
low-risk
benign, 10
HD)
Plasma,
PCR
S: n.s.
Sp: 92% Sp: n.s.
AUC:
0.708
AUC: n.s.
P: n.r.
P (benign
vs. PC):
0.0001;
P (PBH vs.
PC): 0.02
Chun et al. [59]
142 (local-
ized PC)
19 (BPH)
Plasma,
Spectropho-
tometry
S: n.r.
Cherepanova
et al. [25]
5
52 (22
BPH, 30
HD)
Flurome-
tric assay
S: n.r.
Sp: n.r. Sp: n.r.
AUC: n.r. AUC: n.r
P: 0.032 P: n.s. **
Altimari et al. [60] 64 45 (HD) Plasma, PCR
S: 80%
Sp: 82%
AUC:
0.881
P <0.001
Ellinger et al.
[33,34]
173
53 (42
BPH, 11
HD)
Serum, PCR
S: 88%
Sp: 64%
AUC:
0.824
P <0.001
Schwarzenbach
et al. [36]
69 (PC M1) 12 (PC M0) Plasma, PCR
S: n.r.
Sp: n.r.
AUC: n.r
P: 0.03
Wroclawsky et
al. [37]
133 33
Plasma,
Spectropho-
tometry
S: 66.2%
Sp: 87.9%
AUC:
0.824
P<0.05
Feng et al. [61] 96 112 (BPH) Plasma, PCR
S: 73.2%
Sp: 72.7%
AUC:
0.864
P<0.001
Table 1. Role of circulating free DNA levels for early detection of prostate cancer.
58% and 64%, respectively) [34,36,57,58,60,61]. Among PCR-
based studies, the largest one [34] included 216 patients, whose
173 with PC and 53 controls (11 healthy individuals and 42 with
BPH) and had by a sensitivity of 88% and a specificity of 64%. In
this study, the analysis of PTGS2 DNA fragment, that biochemi-
cally characterizes apoptosis, showed DNA fragment levels in se-
rum of patients with PC significantly increased in comparison to
BPH patients and healthy individuals (both P<0.0001). Another
important study [60], quantifying by real-time PCR assessment
5. cfDNA in plasma samples from 64 patients with localized PC and
45 healthy males, showed a better discrimination between PC and
healthy subjects with a sensitivity of 80% and a specificity of 82%.
It concluded that ctDNA quantification could be a candidate bio-
marker for early diagnosis correlating with pathologic tumor stage.
A prospective study [59] also detected increased DNA levels in 161
PC patients using spectrophotometry. The median plasma concen-
tration of cfDNA was 267 ng/mL in men with BPH and 709 ng/mL
in men with PC. Uni-and multivariate analyses (after controlling
for age, total PSA, free/total PSA, prostate volume) suggested that
cfDNA was highly accurate and informative predictor (P=0.032
and predictive accuracy 0.643) for the presence of PC on needle
biopsy. A recent study [62] of 133 patients affected by PC and 33
controls used also spectrophotometry that confirmed cfDNA as a
potential tool for PC diagnosis with sensitivity of 66.2% and speci-
ficity of 87.9% and the additional role of cfDNA during follow-up
of PC patients.
For the discrimination between PC and benign conditions, the
identification of genetic and epigenetic alterations in cfDNA may
be also an interesting tool for molecular screening of PC patients.
The presence of allelic imbalance, including loss of heterozygos-
ity and microsatellite DNA, has been investigated on circulat-
ing DNA of PC patients in PCR-based studies, characterized by
a sensitivity ranging from 34% to 57% and specificity from 70%
to 100% [35,36,63-65]. Diagnostic information derives also from
cell-free DNA hypermethylation, especially the hypermethylation
of GSTP1 (Glutathione S-Transferase 1 Pi gene), a detoxifying
enzyme present in about 30% of PC patients. Many studies us in
gmethylation-specific PCR tests, characterized by a high speci-
ficity nearly 100% for the presence of prostatic neoplasia, but by
a variable sensitivity ranging from 11% to 100%, suggested that
measurement of GSTP1 promoter methylation in plasma, serum,
or other samples may complement PSA screening and early detec-
tion for PC diagnosis [58,60,64,66-75].
Finally, some studies [34,76] showed also the utility of the DNA
Integrity Assay (DIA) as a plasma-based screening tool for the PC
detection.In 2006, Hanley et al. [76]evaluatedblood samples pa-
tients with biopsy-proven PC prior to prostatectomy (n = 123). He
studied three control groups including young men with no his-
tory of cancer (group 1, n = 20); cancer-free post-prostatectomy
patients (group 2, n = 25), and patients with a negative prostate
biopsy (group 3, n = 22). A baseline cutoff was used for individual
DNA fragment lengths to fix a DIA score for each patient sample.
PC patients (86 of 123; 69.9%) had a strongly positive DIA score.
The DIA results from control groups 1, 2, and 3 showed specifici-
ties of 90%, 92%, and 68.2%, respectively. So this study concluded
that DIA could detect approximately 70% of PC patients with a
specificity of 68.2% to 92%, a range similar to that currently ac-
cepted for PSA (60-70%).
6.2. Prognostic role: Recent evidences highlighted the clinical
importance of increased levels of cfDNA and presence of genetic
and epigenetic alterations as an adverse prognostic marker in PC
patients. In 2004, Jung et al. [27] published the first study that em-
phasized cfDNA concentration as a survival predictor in PC pa-
tients. It showed survival curves of 91 PC patients (stage pN0M0,
n=32; stage pN1M0, n=30; stage M1, n=29) according to the plas-
matic concentrations of DNA, total PSA, and osteoprotegerin as a
marker for bone metastases. The association between plasma DNA
and the survival was similarly strong as with PSA but only in pa-
tients with distant metastases.
Lately, a retrospective study of 59 taxane-based chemotherapy
treated PC men [77] showed the role of cfDNA level as a prognos-
tic marker according to PSA response and survival. Patients with a
PSA decline of more than 80 % had a lower cfDNA concentration
compared to patients with the least PSA decline of less than 30%.
In addition, cfDNA level was associated with a significantly longer
survival rate (31 months in patients with cfDNA levels of less than
55ng/μl compared to 17 months in patients with higher concen-
trations) (p=0.03). Another recent work [78] aimed to clinically
qualify baseline and on-treatment cfDNA levels as biomarkers of
patient outcome treated with taxane chemotherapy. The authors
analyzed blood samples prospectively collected from 571 mCRPC
patients participating in two phase III clinical trials, FIRSTANA
(NCT01308567) and PROSELICA (NCT01308580). They iden-
tified that baseline log10 cfDNA concentration correlated with
shorter radiographic PFS (HR 1.54; 95% CI 1.15–2.08; P=0.004),
and shorter OS on taxane therapy (HR 1.53; 95% CI1.18–1.97;
P=0.001), and cfDNA concentration before starting docetaxel or
cabazitaxel was an independent prognostic variable on multivari-
able analyses for PFS and OS in both first- and second-line che-
motherapy settings. Patients with a PSA response experienced a
decline in log10 cfDNA levels during the first four cycles of treat-
ment.
Survival analysis from a phase I exploratory cohort of 75 men
with CRPC and a phase II independent validation cohort of 51
CRPC men [74] demonstrated that detection of plasma methyl-
ated GSTP1 in CRPC patients was associated with a shorter OS
(HR 4.2, 95% CI 2.1-8.2; P<0.0001). The 2-year survival for men
with no detectable plasma mGSTP1 was 71% compared with 23%
for men with detectable plasma methylated GSTP1 levels.
The prognostic value of cfDNA and circulating DNA fragments
of apoptotic origin (i.e., PTGS2 DNA fragment that biochemically
characterizes apoptosis) has also been showed in PC men as pre-
dictor of PSA recurrence after radical prostatectomy [34,79] and of
biochemical recurrence free survival during follow-up in plasma
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volume 1 Issue 1-2018 Research article
6. samples of 133 PC patients collected prospectively every 3 months
for 2 years (P = 0.048) [62].
In addition, cell-free DNA hypermethylation of GSTP1, Ras as-
sociation [RalGDS/AF-6] domain family member 1 (RASSF1A)
and retinoic acid receptor β, variant 2 (RARB2) was also corre-
lated with the Gleason score, tumor stage, extent of metastasis
[64,69,74].
Currently, the identification of genetic aberrations in cfDNA has
emerged as a promising prognostic biomarker. Recent studies
[4,80-86] demonstrated a significant correlation between aberra-
tions (copy number variations and point somatic mutations) of
Androgen Receptor (AR) detected in blood and treatment out-
come in CRPC patients treated with second generation hormonal
drugs, abiraterone or enzalutamide. One of the most recent bio-
markers studies [83] was aimed to clinically qualify AR status
measurement in plasma DNA from 265 CRPC patients (191 in
the primary cohort and 94 in the secondary cohort), using an op-
timized multiplex droplet digital PCR (ddPCR) assay in pre- and
post-chemotherapy CRPC.AR gain was observed in 10 (14%) che-
motherapy-naïve and 33 (34%) post-docetaxel patients and was
associated with a worse OS (HR 3.98; 95% CI, 1.74-9.10; P<0.001
and HR 3.81; 95% CI, 2.28-6.37; P<0.001 respectively), PFS (HR,
2.18; 95% CI, 1.08-4.39; P = .03, and HR, 1.95; 95% CI 1.23-3.11;
P=0.01, respectively) and rate of PSA decline ≥50% (Odds ratio
(OR) 4.7; 95% CI, 1.17-19.17; P=0.035 and OR 5.0; 95% CI 1.70-
14.91; P=0.003 respectively). AR mutations (2105T>A (p.L702H)
and 2632A>G (p.T878A)) were observed in 8 (11%) post-docetax-
el but no chemotherapy-naïve abiraterone-treated patients and
were also associated with worse OS (HR 3.26; 95% CI, 1.47-not
reached; P=0.004). These data were confirmed in the secondary
cohort of the study and plasma AR resulted an independent pre-
dictor of outcome on multivariate analyses in both cohorts.
6.3. Predictive role and treatment resistance: Treatment resis-
tance may develop mainly for an incessant evolving spectrum of
genetic and epigenetic alterations within the tumor under the se-
lective pressure of therapy. The analysis of ctDNAcould integrate
invasive biopsy approaches to evaluate noninvasively from plasma
DNAgenomic alterations related to acquired drug resistance in
advanced cancers [51]. Beyond the prognostic role, recent stud-
ies [4,79,83] have demonstrated the association between clinical,
biochemical and radiographic response and genomic aberrations,
especially involving AR, in ctDNA of CRPC patients treated with
novel hormonal therapies, as abiraterone and enzalutamide [4,80-
86]. Carreira et al. [4] sequenced serial plasma and tumor samples
from 16 ERG-positive lethal PC patients and identified genomic
lesions, including common tumor deletions, AR copy number
gain, functionally active AR mutations. This study demonstrated
a temporal association between clinical progression and emer-
gence of AR mutations activated by glucocorticoids in about
20% of patients progressing on abiraterone and prednisolone
or dexamethasone. A subsequently study [80] of 53 consecu-
tive CRPC patients treated with abiraterone after chemother-
apy showed that AR or CYP17A1 amplification in cfDNA led
to early progression disease that occurred within 4 months of
the start of abiraterone treatment. So, the authors concluded
that CNVs of AR and CYP17A1 genes were predictive of early
resistance to therapy. Azad et al. [84] confirmed the utility of
cfDNA to identify therapeutic resistance to novel hormonal
drugs. They used array Comparative Genomic Hybridization
(aCGH) for chromosome copy number analysis and NGS of
exon 8 of the AR in cfDNA samples from 62 metastatic CRPC
patients stopping abiraterone (n=29), enzalutamide (n=19) or
other agents (n=14) due to disease progression. The results
from aCGH showed that AR amplification was significantly
more frequent in patients progressing on enzalutamide than
on abiraterone or other agents (53% vs. 17% vs. 21%, P=0.02).
Missense AR exon 8 mutations were detected in 11/62 patients
(18%), including enzalutamide- and abiraterone-resistant pa-
tients.
In addition, a recent prospective study [74] showed the asso-
ciations between detectable plasma mGSTP1 prior to chemo-
therapy and no response to chemotherapy (docetaxel or mito-
xantrone) and so epigenetic alteration could be also a potential
surrogate therapeutic efficacy marker for chemotherapy.
6.4. Role in follow-up: In this era of survival prolonging drugs
in the treatment of PC patients, the identification of noninva-
sive biomarkers for monitoring patients during follow-up is
essential. Wroclawsky et al. [62] showed a significant shorter
biochemical recurrence free survival for patients with at least
one value of cfDNA greater than140 ng/mL during a mean fol-
low-up of 13.5 months (P=0.048).
The utility of cfDNA in follow-up of PC patients has emerged
also from the relation between the measurement of cfDNA and
radiographic imaging. Kwee et al. [87] explored cfDNA content
in relation to fluorine-18 Fluorocholine (FCH) positron emis-
sion tomography/computed tomography (PET/CT) in 8 CRPC
patients receiving docetaxel-based chemotherapy. Serial cfDNA
samples were assessed by microfluidic electrophoresis, quanti-
fied by real-time PCR, and compared with results from FCH
PET/CT scans, used for whole-body measurement of tumor
activity results. Promoter methylation of two PC-associated
genes, GSTP1 and RARB2, was evaluated by methylation-spe-
cific PCR. Plasma cfDNA concentrations increased significant-
ly after one and three treatment cycles, respectively (P=0.001).
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volume 1 Issue 1-2018 Research article
7. GSTP1 and/or RARB2 promoter methylation was identified in
all pretreatment samples. The appearance of large (200 bp-10.4
kb) cfDNA fragments and loss of methylation at GSTP1 and/or
RARB were observed after treatment. Tumor activity on PET/CT
correlated significantly with cfDNA levels and PET/CT tumor re-
sponse had significantly lower before therapy cfDNA levels than
those who did not (P=0.03). These preliminary data exploratory
examinated the translational significance of cfDNA as therapeutic
response marker, but larger studied are warranted.
7. Comparison between Circulating DNA in Plasma and
in Other Body Fluids
Like blood, urine and semen represent a source of cfDNA which
can be gained in a more noninvasive manner and could therefore
be useful as an easy substrate for biomarker measurement in PC
patients. In 2013, the pilot study [88] investigating the potential
role of urinary cfDNA in early PC diagnosis. The authors analyzed
urinary cfDNA fragments longer than 250 bp in three regions fre-
quently amplified in solid tumors, including PC: c-Myc (8q24.21,
HER2 (17q12.1), and BCAS1 (20q13.2) and concluded that urine
DNA integrity could distinguishing between PC patients and
healthy individuals with an accuracy of about 80%, similar to that
observed previously for bladder cancer [89,90]. However, this
finding of longer cfDNA fragments in urine of PC patients was
apparently in contrast to the presence of short DNA fragments in
blood, as shown in previous work [34]. Conversely, the same pro-
file of GSTP1 gene promoter methylation has been demonstrated
in the pool of circulating and extracellular DNA from the blood
and urine of PC patients. This profile differs from those charac-
teristic of healthy donors and BPH patients, confirming that the
quantification of cfDNA in different body fluids from blood, such
as urine and ejaculates, could represent a diagnostic tool charac-
terized by the ability to detect PC and lower the rate of unneces-
sary biopsies [66,91].
7.1. Comparison between cfDNA and other circulating bio-
markers: Over cfDNA, other cell-free nucleic acids, including
mRNA and microRNA (miRNA) are released and circulate in the
blood of PC patients, probably from the same apoptotic or necrot-
ic cells originating cfDNA. Changes in the levels of other circu-
lating nucleic acids have been associated also with tumor burden
and malignant progression. RNA released into the blood stream is
more stable in spite of the increased amounts of circulating RNas-
es. Consequently, RNA may be protected from degradation by its
packaging into exosomes, such as microparticles, microvesiclesor
multivesicles, which are shed from cellular surfaces into the cir-
culation. For the detection and identification of RNA microarray
technologies or reverse transcription quantitative real-time PCR
are used [13] (Figure1).
Figure 1. Current and future potential applications of circulating DNA in pros-
tate cancer patients.
Prostate-derived exosomes (also called prostatosome) are endo-
some-derived vesicles with a diameter between 50 and 150 nm
that contain cytoplasmic content (proteins and RNAs) encapsu-
lated by a cholesterol rich phospholipid membrane. It is possible
to detect exosomes in blood, urine and semen [92]. Some studies
suggested the diagnostic and prognostic role of prostatosomes, re-
vealing a higher number of exosomes in blood of PC patient com-
pared to men with no disease and correlating exosome number
with Gleason score [93,94]. In addition, recent studies revealed
that the detection of a splice variant of AR (AR-V7) in plasma-
derived exosomal RNA strongly predicted resistance to hormonal
therapy in metastatic CRPC patients, making exosomes a poten-
tial source of clinically relevant biomarkers [94].
Among circulating biomarkers of PC, one area of expanding in-
vestigation is CTCs, rare cells that are shed from primary and
metastatic tumor deposits into the peripheral circulation [95].
Enumeration of CTCs before and after therapy has shown that
CTC burden correlates with outcome in CRPC patients [96-98].
Moreover, studies have demonstrated the potential of molecular
analysis of CTCs in monitoring and predicting response to thera-
py in patients [99].
Both CTCs and ctDNA offer snapshots of genomic alterations in
primary tumors and metastases at various stages during the course
of disease. However, there are yet some limits for the use of CTC
and ctDNA as liquid biopsies. Because CTCs are very rare cells,
capturing them depends on rather sophisticated equipment, while
plasma DNA is easily obtained, even tumor DNA fragments are
diluted with various amounts of DNA from normal cells, which
may hinder analysis [100]. Despite these limitations, combining
both ctDNA and CTC analyses as a blood biomarker panel results
in a higher diagnostic accuracy compared to the use of a single
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volume 1 Issue 1-2018 Research article
8. marker. Concerning the heterogeneity of the disease, the future
prospect will have to be focused on the combination of differ-
ent circulating biomarkers to improve PC management.
Recently, it has emerged that detection of AR-V7 in CTCs
may represent one such treatments election marker in men
with metastatic CRPC associated with a lack of benefit of abi-
raterone and enzalutamide [101], but no with taxane chemo-
therapy [102,103].
8. Conclusions and Future Perspectives
Despite some limitations of using cfDNA related mainly to the
sensitivity of measuring ctDNA using plasma versus serum
[34] and the different detection methods [76], and lower con-
centration of ctDNA in early disease, plasma DNA is a clini-
cally relevant marker offering new chances for management of
PC patients adding a new helpful tool for diagnosis, staging and
prognosis (Figure 2).
Figure 2. Circulating tumor DNA and other circulating biomarkers in
prostate cancer.
All mCRPC have tumor lesions to detect in plasma matching per-
fectly with tumor tissue.
Future studies are also aimed at the improvement of cancer screen-
ing or as diagnostic biomarkers in early stage disease. In fact, there
are ongoing some clinical trials carried out on early stages of PC.
One study has main objective to evaluate genetic testing in pre-
dicting biomarkers of recurrence in PC patients undergoing sur-
gery (NCT00977457) and two phase 3 trials performing plasma
DNA analysis in PC patients after radiotherapy (NCT01411332
and NCT01411345). Moreover, next studies could also include
patients with localized PC patients receiving neoadjuvant chemo-
therapy predicting pathological residual disease that usually cor-
relates with poor prognosis, as already shown in other tumors. In
the complex scenario of prostate tumor, the detection of ctDNA
may become readily available for routine clinical decision making.
Nowadays, circulating biomarkers are correlated with new imag-
ing techniques, that do not only evaluate tumor extent and distri-
bution, but it can also detect biologic characteristics of all lesions
rather than those of a single biopsy or blood draw. A recent work
[104] made a direct comparison between circulating AR CNV
and 18F-Fluorocholine (FCH) uptake on PET/CT in patients with
metastatic CRPC. AR CNV was determined by digital droplet
PCR and Taqman on pre-treatment plasma from 80 patients with
metastatic CRPC progressing after docetaxel treated with abi-
raterone (n=47) or enzalutamide (n=33). For all patients, an FCH
PET/CT scans was performed. Plasma AR gain was significantly
correlated with tumor metabolic activity. In addition, multivariate
analysis revealed that AR CNV and FCH PET/CT values were as-
sociated with both shorter PFS and OS. These evidences suggested
that choline uptake is higher in AR gained cancers, introducing
the possibility of identifying this molecularly distinct group us-
ing non-invasive imaging, also obtaining further biologic tumor
information performing new tracers, such as Prostate-Specific
Membrane Antigen (PSMA).
In conclusion, the utility of plasma DNA derives from preclinical
and clinical observations and from the integration of circulating
and imaging markers that require, however, larger prospective tri-
als with a clinically meaningful impact in PC patients.
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