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Archive for the ‘Nanotechnology for Drug Delivery’ Category


Ferritin Cage Enzyme Encapsulation as a New Platform for Nanotechnology

 Reporter: Irina Robu, PhD

In bionanotechnology, biological systems such as viruses, protein complexes, lipid vesicles and artificial cells, are being developed for applications in medicine and materials science.  However, the paper published by Stephan Tetter and Donald Hilvert in Angewandte Chemie International Edition show that it is possible to encapsulate proteins such as ferritin by manipulating electrostatic interactions with the negatively charged interior of the cage.The primary role of ferritin is to protect cells from the damage caused by the Fenton reaction; where, in oxidizing conditions, free Fe(II) produces harmful reactive oxygen species that can damage the cellular machinery.

The ferritin family proteins are protein nanocages that evolved to safely store iron in an oxidizing world. Since ferritin family proteins are able to mineralize and store metal ions, they have been the focus of much research for the production of metal nanoparticles and as prototypes for semiconductor production. The ferritin cage itself is highly symmetrical, and is made up of 24 subunits arranged in an octahedral symmetry. Ferritins are smaller than other protein used for protein   encapsulation.   Their  outer  diameter is only 12 nm, whereas engineered lumazine synthase variants form cages with diameters ranging from about 20 to 60 nm.The ferritin cage displays remarkable thermal and chemical stability it is likely to modify the surface of the ferritin cage through the addition of peptide and protein tags. These characteristics have made ferritins attractive vectors for the delivery of drug molecules and as scaffolds for vaccine design.

In summary, the paper published in Angewandte Chemie International Edition is the first example of protein incorporation by a ferritin.  Dr. Donald Hilvert and colleagues have shown that AfFtn not only complexes positively charged guest proteins within its naturally negatively charged luminal cavity, but that the in vitro mixing technique can be extended to the encapsulation and protection of other functional  fusion proteins.

Hence, the recent discovery of encapsulated ferritins has identified an exciting new platform for use in bio nanotechnology. The use of synthetic biology tools will allow their rapid implementation in materials science, bio-nanotechnology and medical applications.

SOURCE

https://www.readbyqxmd.com/read/28902449/enzyme-encapsulation-by-a-ferritin-cage

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Novel Blood Substitute – ErythroMer

Reporter: Irina Robu, PhD

For years, scientists have tried ineffectively to create an artificial molecule that emulates the oxygen-carrying function of human red blood cell but the efforts failed because of oxygen delivery and safety issues. Now, a group of researchers led by Dr. Alan Doctor at Washington University in Saint Louis, are trying to resuscitate blood substitutes with a new nanotechnology-based, artificial red blood cell may overcome the problems that killed products designed by a team of companies such as BiopureAlliance PharmaceuticalsNorthfield Labs and even Baxter. Dr. Alan Doctor’s new company, Kalocyte is advancing the development of the

The donut-shaped artificial cells, ErythroMer are one-fiftieth the size of human red blood cells. ErythroMer is a novel blood substitute composed of a patented nanobialys nanoparticle. A special lining and control system tied to changes in blood Ph allows Erythromer to grab onto oxygen in the lungs and then dispense the oxygen in tissues where it is needed. The new artificial cells are intended to sidestep problems with vasoconstriction or narrowing of blood vessels.

Erythromer is stored freeze dried and reconstituted with water when needed but it can also be stored at room temperature which makes it for military and civilian trauma.

Trials have been successful in rats, mice, and rabbits, and human trials are planned. However, moving Erythromer into human clinical trials is still 8-10 years away.

SOURCE

https://www.thestreet.com/story/13913099/1/human-blood-substitutes-once-dead-now-resuscitated.html

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Walking DNA Nanorobot

Reporter: Irina Robu, PhD

New research from California Institute of Technology headed by Anupama Thubagere and Lulu Qian built robots from DNA and programmed them to sort and deliver molecules to a specified location. These robots can potentially transform the drug delivery field to how body fights infections to how microscopic measurements are made. The dominant premise of DNA robots is that rather than creating molecular devices from scratch, we can use the power of molecular machinery by building microscopic-size robots and send them to places that are then impossible to reach, such as a cell or a hard-to-reach cancerous tumor. These robots demonstrated the ability to perform simple tasks, however this latest effort ramped up a path by programming DNA robots to perform a cargo‐sorting task and possibly many other tasks.

Each robot was built from a single-stranded DNA molecule of just 53 nucleotides equipped with “legs” for walking and “arms” for picking up objects. The robot are 20 nanometers tall and their walking strides measures six nanometers long, where one nanometer is a billionth of a meter. For the cargo, the researchers used two types of molecules, each being a distinct single-stranded piece of DNA. For the tests, the researchers placed the cargo onto a random location along the surface of a two-dimensional origami DNA test platform. The walking DNA robots moved in parallel along this surface, hunting for their cargo.

To see if a robot successfully picked up and dropped off the right cargo at the right location, the researchers used two fluorescent dyes to differentiate the molecules.

The researchers guess that each DNA robot took around 300 steps to complete its task, or roughly ten times more than in previous efforts. Though, more work is needed to figure out how these DNA robots perform under different environmental conditions. This new study suggests a worthwhile methodology for scientists to continue pursuing.

SOURCE

http://science.sciencemag.org/content/357/6356/eaan6558

 

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Nanostraws Developed at Stanford Sample a Cell’s Contents without Damage

Reporter: Irina Robu, PhD

Cells within our bodies change over time and divide, with thousands of chemical reactions happening within cell daily. Nicholas Melosh, Associate Professor of Materials Science and Engineering, developed a new, non-destructive system for sampling cells with nanoscale straws which could help uncover mysteries about how cells function.

Currently, cells are sampled via lysing which ruptures the cell membrane which means that it can’t ever be sampled again. The sample system that Dr. Melosh invented banks on, on tiny tubes 600 times smaller than a strand of hair that allow researchers to sample a single cell at a time. The nanostraws penetrate a cell’s outer membrane, without damaging it, and draw out proteins and genetic material from the cell’s salty interior.

The Nanostraw sampling technique, according to Melosh, will knowingly impact our understanding of cell development and could result to much safer and operational medical therapies because the technique allows for long term, non-destructive monitoring. The sampling technique could also inform cancer treatments and answer questions about why some cancer cells are resistant to chemotherapy while others are not. The sampling platform on which the nanostraws are grown is tiny, similar to the size of a gumball. It’s called the Nanostraw Extraction (NEX) sampling system, and it was designed to mimic biology itself.

The goal of developing this technology was to make an impact in medical biology by providing a platform that any lab could build.

SOURCE

http://news.stanford.edu/2017/02/20/minuscule-nanostraws-sample-cells-contents-without-damage

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cancerandoncologyseriesccover

Series C: e-Books on Cancer & Oncology

Series C Content Consultant: Larry H. Bernstein, MD, FCAP

 

VOLUME ONE 

Cancer Biology and Genomics

for

Disease Diagnosis

2015

http://www.amazon.com/dp/B013RVYR2K

Stephen J. Williams, PhD, Senior Editor

sjwilliamspa@comcast.net

Tilda Barliya, PhD, Editor

tildabarliya@gmail.com

Ritu Saxena, PhD, Editor

ritu.uab@gmail.com

Leaders in Pharmaceutical Business Intelligence 

Part I

Historical Perspective of Cancer Demographics, Etiology, and Progress in Research

Chapter 1:  The Occurrence of Cancer in World Populations

1.1   Understanding Cancer

Prabodh Kandala, PhD

1.2  Cancer Metastasis

Tilda Barliya, PhD

1.3      2013 Perspective on “War on Cancer” on December 23, 1971

Aviva Lev-Ari, PhD, RN

1.4   Global Burden of Cancer Treatment & Women Health: Market Access & Cost Concerns

Aviva Lev-Ari, PhD, RN

1.5    The Importance of Cancer Prevention Programs: New Perspectives for Fighting Cancer

Ziv Raviv, PhD

1.6      The “Cancer establishments” examined by James Watson, co-discoverer of DNA w/Crick, 4/1953,  

Larry H Bernstein, MD, FCAP

1.7      New Ecosystem of Cancer Research: Cross Institutional Team Science

Aviva Lev-Ari, PhD, RN

1.8       Cancer Innovations from across the Web

Larry H Bernstein, MD, FCAP

1.9         Exploring the role of vitamin C in Cancer therapy

Ritu Saxena PhD

1.10        Relation of Diet and Cancer

Sudipta Saha, PhD

1.11      Association between Non-melanoma Skin Cancer and subsequent Primary Cancers in White Population 

Aviva Lev-Ari, PhD, RN

1.12       Men With Prostate Cancer More Likely to Die from Other Causes

Prabodh Kandala, PhD

1.13      Battle of Steve Jobs and Ralph Steinman with Pancreatic Cancer: How we Lost

Ritu Saxena, PhD

Chapter 2.  Rapid Scientific Advances Changes Our View on How Cancer Forms

2.1     All Cancer Cells Are Not Created Equal: Some Cell Types Control Continued Tumor Growth, Others Prepare the Way for Metastasis 

Prabodh Kandala, PhD

2.2      Hold on. Mutations in Cancer do Good

Prabodh Kandala, PhD

2.3       Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

Larry H Bernstein, MD, FCAP

2.4          Naked Mole Rats Cancer-Free

Larry H Bernstein, MD, FCAP

2.5           Zebrafish—Susceptible to Cancer

Larry H Bernstein, MD, FCAP

2.6         Demythologizing Sharks, Cancer, and Shark Fins,

Larry H Bernstein, MD, FCAP

2.7       Tumor Cells’ Inner Workings Predict Cancer Progression

Prabodh Kandala, PhD

2.8      In Focus: Identity of Cancer Stem Cells

Ritu Saxena, PhD

2.9      In Focus: Circulating Tumor Cells

Ritu Saxena, PhD

2.10     Rewriting the Mathematics of Tumor Growth; Teams Use Math Models to Sort Drivers from Passengers 

Stephen J. Williams, PhD

2.11     Role of Primary Cilia in Ovarian Cancer

Aashir Awan, PhD

Chapter 3:  A Genetic Basis and Genetic Complexity of Cancer Emerges

3.1       The Binding of Oligonucleotides in DNA and 3-D Lattice Structures

Larry H Bernstein, MD, FCAP

3.2      How Mobile Elements in “Junk” DNA Promote Cancer. Part 1: Transposon-mediated Tumorigenesis. 

Stephen J. Williams, PhD

3.3      DNA: One Man’s Trash is another Man’s Treasure, but there is no JUNK after all

Demet Sag, PhD

3.4 Issues of Tumor Heterogeneity

3.4.1    Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

Stephen J. Williams, PhD

3.4.2       Issues in Personalized Medicine: Discussions of Intratumor Heterogeneity from the Oncology Pharma forum on LinkedIn

Stephen J. Williams, PhD

3.5        arrayMap: Genomic Feature Mining of Cancer Entities of Copy Number Abnormalities (CNAs) Data

Aviva Lev-Ari, PhD, RN

3.6        HBV and HCV-associated Liver Cancer: Important Insights from the Genome

Ritu Saxena, PhD

3.7      Salivary Gland Cancer – Adenoid Cystic Carcinoma: Mutation Patterns: Exome- and Genome-Sequencing @ Memorial Sloan-Kettering Cancer Center

Aviva Lev-Ari, PhD, RN

3.8         Gastric Cancer: Whole-genome Reconstruction and Mutational Signatures

Aviva Lev-Ari, PhD, RN

3.9        Missing Gene may Drive more than a quarter of Breast Cancers

Aviva Lev-Ari, PhD, RN

3.10     Critical Gene in Calcium Reabsorption: Variants in the KCNJ and SLC12A1 genes – Calcium Intake and Cancer Protection

Aviva Lev-Ari,PhD, RN

Chapter 4: How Epigenetic and Metabolic Factors Affect Tumor Growth

4.1    Epigenetics

4.1.1     The Magic of the Pandora’s Box : Epigenetics and Stemness with Long non-coding RNAs (lincRNA)

Demet Sag, PhD, CRA, GCP

4.1.2     Stomach Cancer Subtypes Methylation-based identified by Singapore-Led Team

Aviva Lev-Ari, PhD, RN

4.1.3     The Underappreciated EpiGenome

Demet Sag, Ph.D., CRA, GCP

4.1.4     Differentiation Therapy – Epigenetics Tackles Solid Tumors

Stephen J. Williams, PhD

4.1.5      “The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

Demet Sag, Ph.D., CRA, GCP

4.1.6      DNA Methyltransferases – Implications to Epigenetic Regulation and Cancer Therapy Targeting: James Shen, PhD

Aviva Lev-Ari, PhD, RN

4.2   Metabolism

4.2.1      Mitochondria and Cancer: An overview of mechanisms

Ritu Saxena, PhD

4.2.2     Bioenergetic Mechanism: The Inverse Association of Cancer and Alzheimer’s

Aviva Lev-Ari, PhD, RN

4.2.3      Crucial role of Nitric Oxide in Cancer

Ritu Saxena, PhD

4.2.4      Nitric Oxide Mitigates Sensitivity of Melanoma Cells to Cisplatin

Stephen J. Williams, PhD

4.2.5      Increased risks of obesity and cancer, Decreased risk of type 2 diabetes: The role of Tumor-suppressor phosphatase and tensin homologue (PTEN)

Aviva Lev-Ari, PhD, RN

4.2.6      Lipid Profile, Saturated Fats, Raman Spectrosopy, Cancer Cytology

Larry H Bernstein, MD, FCAP

4.3     Other Factors Affecting Tumor Growth

4.3.1      Squeezing Ovarian Cancer Cells to Predict Metastatic Potential: Cell Stiffness as Possible Biomarker

Prabodh Kandala, PhD

4.3.2      Prostate Cancer: Androgen-driven “Pathomechanism” in Early-onset Forms of the Disease

Aviva Lev-Ari, PhD, RN

Chapter 5: Advances in Breast and Gastrointestinal Cancer Research Supports Hope for Cure

5.1 Breast Cancer

5.1.1      Cell Movement Provides Clues to Aggressive Breast Cancer

Prabodh Kandala, PhD

5.1.2    Identifying Aggressive Breast Cancers by Interpreting the Mathematical Patterns in the Cancer Genome

Prabodh Kandala, PhD

5.1.3  Mechanism involved in Breast Cancer Cell Growth: Function in Early Detection & Treatment

Aviva Lev-Ari, PhD, RN

5.1.4       BRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair

Sudipta Saha, PhD

5.1.5      Breast Cancer and Mitochondrial Mutations

Larry H Bernstein, MD, FCAP

5.1.6      MIT Scientists Identified Gene that Controls Aggressiveness in Breast Cancer Cells

Aviva Lev-Ari PhD RN

5.1.7       “The Molecular pathology of Breast Cancer Progression”

Tilda Barliya, PhD

5.1.8       In focus: Triple Negative Breast Cancer

Ritu Saxena, PhD

5.1.9       Automated Breast Ultrasound System (‘ABUS’) for full breast scanning: The beginning of structuring a solution for an acute need!

Dror Nir, PhD

5.1.10       State of the art in oncologic imaging of breast.

Dror Nir, PhD

 

5.2 Gastrointestinal Cancer

5.2.1         Colon Cancer

Tilda Barliya, PhD

5.2.2      PIK3CA mutation in Colorectal Cancer may serve as a Predictive Molecular Biomarker for adjuvant Aspirin therapy

Aviva Lev-Ari, PhD, RN

5.2.3     State of the art in oncologic imaging of colorectal cancers.

Dror Nir, PhD

5.2.4     Pancreatic Cancer: Genetics, Genomics and Immunotherapy

Tilda Barliya, PhD

5.2.5     Pancreatic cancer genomes: Axon guidance pathway genes – aberrations revealed

Aviva Lev-Ari, PhD, RN

Part II

Advent of Translational Medicine, “omics”, and Personalized Medicine Ushers in New Paradigms in Cancer Treatment and Advances in Drug Development

Chapter 6:  Treatment Strategies

6.1 Marketed and Novel Drugs

Breast Cancer                                   

6.1.1     Treatment for Metastatic HER2 Breast Cancer

Larry H Bernstein MD, FCAP

6.1.2          Aspirin a Day Tied to Lower Cancer Mortality

Aviva Lev-Ari, PhD, RN

6.1.3       New Anti-Cancer Drug Developed

Prabodh Kandala, Ph.D.

6.1.4         Pfizer’s Kidney Cancer Drug Sutent Effectively caused REMISSION to Adult Acute Lymphoblastic Leukemia (ALL)

Aviva Lev-Ari ,PhD, RN

6.1.5     “To Die or Not To Die” – Time and Order of Combination drugs for Triple Negative Breast Cancer cells: A Systems Level Analysis

Anamika Sarkar, PhD. and Ritu Saxena, PhD

Melanoma

6.1.6    “Thymosin alpha1 and melanoma”

Tilda Barliya, PhD

Leukemia

6.1.7    Acute Lymphoblastic Leukemia and Bone Marrow Transplantation

Tilda Barliya PhD

6.2 Natural agents

Prostate Cancer                 

6.2.1      Scientists use natural agents for prostate cancer bone metastasis treatment

Ritu Saxena, PhD

Breast Cancer

6.2.2        Marijuana Compound Shows Promise In Fighting Breast Cancer

Prabodh Kandala, PhD

Ovarian Cancer                  

6.2.3        Dimming ovarian cancer growth

Prabodh Kandala, PhD

6.3 Potential Therapeutic Agents

Gastric Cancer                 

6.3.1       β Integrin emerges as an important player in mitochondrial dysfunction associated Gastric Cancer

Ritu Saxena, PhD

6.3.2      Arthritis, Cancer: New Screening Technique Yields Elusive Compounds to Block Immune-Regulating Enzyme

Prabodh Kandala, PhD

Pancreatic Cancer                                   

6.3.3    Usp9x: Promising therapeutic target for pancreatic cancer

Ritu Saxena, PhD

Breast Cancer                 

6.3.4       Breast Cancer, drug resistance, and biopharmaceutical targets

Larry H Bernstein, MD, FCAP

Prostate Cancer

6.3.5        Prostate Cancer Cells: Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition

Stephen J. Williams, PhD

Glioblastoma

6.3.6      Gamma Linolenic Acid (GLA) as a Therapeutic tool in the Management of Glioblastoma

Raphael Nir, PhD, MSM, MSc

6.3.7   Akt inhibition for cancer treatment, where do we stand today?

Ziv Raviv, PhD

Chapter 7:  Personalized Medicine and Targeted Therapy

7.1.1        Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders

Aviva Lev-Ari, PhD, RN

7.1.2      Personalized medicine-based cure for cancer might not be far away

Ritu Saxena, PhD

7.1.3      Personalized medicine gearing up to tackle cancer

Ritu Saxena, PhD

7.1.4       Cancer Screening at Sourasky Medical Center Cancer Prevention Center in Tel-Aviv

Ziv Raviv, PhD

7.1.5       Inspiration From Dr. Maureen Cronin’s Achievements in Applying Genomic Sequencing to Cancer Diagnostics

Aviva Lev-Ari, PhD, RN

7.1.6       Personalized Medicine: Cancer Cell Biology and Minimally Invasive Surgery (MIS)

Aviva Lev-Ari, PhD, RN

7.2 Personalized Medicine and Genomics

7.2.1       Cancer Genomics – Leading the Way by Cancer Genomics Program at UC Santa Cruz

Aviva Lev-Ari, PhD, RN

7.2.2       Whole exome somatic mutations analysis of malignant melanoma contributes to the development of personalized cancer therapy for this disease

Ziv Raviv, PhD

7.2.3       Genotype-based Analysis for Cancer Therapy using Large-scale Data Modeling: Nayoung Kim, PhD(c)

Aviva Lev-Ari, PhD, RN

7.2.4         Cancer Genomic Precision Therapy: Digitized Tumor’s Genome (WGSA) Compared with Genome-native Germ Line: Flash-frozen specimen and Formalin-fixed paraffin-embedded Specimen Needed

Aviva Lev-Ari, PhD, RN

7.2.5         LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2

Aviva Lev-Ari, PhD, RN

7.2.6       Ethical Concerns in Personalized Medicine: BRCA1/2 Testing in Minors and Communication of Breast Cancer Risk

Stephen J. Williams, PhD

7.3  Personalized Medicine and Targeted Therapy

7.3.1     The Development of siRNA-Based Therapies for Cancer

Ziv Raviv, PhD

7.3.2       mRNA interference with cancer expression

Larry H Bernstein, MD, FCAP

7.3.3       CD47: Target Therapy for Cancer

Tilda Barliya, PhD

7.3.4      Targeting Mitochondrial-bound Hexokinase for Cancer Therapy

Ziv Raviv, PhD

7.3.5       GSK for Personalized Medicine using Cancer Drugs needs Alacris systems biology model to determine the in silico effect of the inhibitor in its “virtual clinical trial”

Aviva Lev-Ari, PhD, RN

7.3.6         Personalized Pancreatic Cancer Treatment Option

Aviva Lev-Ari, PhD, RN

7.3.7        New scheme to routinely test patients for inherited cancer genes

Stephen J. Williams, PhD

7.3.8        Targeting Untargetable Proto-Oncogenes

Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

7.3.9        The Future of Translational Medicine with Smart Diagnostics and Therapies: PharmacoGenomics 

Demet Sag, PhD

7.4 Personalized Medicine in Specific Cancers

7.4.1      Personalized medicine and Colon cancer

Tilda Barliya, PhD

7.4.2      Comprehensive Genomic Characterization of Squamous Cell Lung Cancers

Aviva Lev-Ari, PhD, RN

7.4.3        Targeted Tumor-Penetrating siRNA Nanocomplexes for Credentialing the Ovarian Cancer Oncogene ID4

Sudipta Saha, PhD

7.4.4        Cancer and Bone: low magnitude vibrations help mitigate bone loss

Ritu Saxena, PhD

7.4.5         New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

Prabodh Kandala, PhD

Part III

Translational Medicine, Genomics, and New Technologies Converge to Improve Early Detection

Diagnosis, Detection And Biomarkers

Chapter 8:  Diagnosis Diagnosis: Prostate Cancer

8.1        Prostate Cancer Molecular Diagnostic Market – the Players are: SRI Int’l, Genomic Health w/Cleveland Clinic, Myriad Genetics w/UCSF, GenomeDx and BioTheranostics

Aviva Lev-Ari PhD RN

8.2         Today’s fundamental challenge in Prostate cancer screening

Dror Nir, PhD

Diagnosis & Guidance: Prostate Cancer

8.3      Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?

Aviva Lev-Ari, PhD, RN

Diagnosis, Guidance and Market Aspects: Prostate Cancer

8.4       New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

Prabodh Kandala, PhD

Diagnossis: Lung Cancer

8.5      Diagnosing lung cancer in exhaled breath using gold nanoparticles

Tilda Barliya PhD

Chapter 9:  Detection

Detection: Prostate Cancer

9.1     Early Detection of Prostate Cancer: American Urological Association (AUA) Guideline

Dror Nir, PhD

Detection: Breast & Ovarian Cancer

9.2       Testing for Multiple Genetic Mutations via NGS for Patients: Very Strong Family History of Breast & Ovarian Cancer, Diagnosed at Young Ages, & Negative on BRCA Test

Aviva Lev-Ari, PhD, RN

Detection: Aggressive Prostate Cancer

9.3     A Blood Test to Identify Aggressive Prostate Cancer: a Discovery @ SRI International, Menlo Park, CA

Aviva Lev-Ari, PhD, RN

Diagnostic Markers & Screening as Diagnosis Method

9.4      Combining Nanotube Technology and Genetically Engineered Antibodies to Detect Prostate Cancer Biomarkers

Stephen J. Williams, PhD

Detection: Ovarian Cancer

9.5      Warning signs may lead to better early detection of ovarian cancer

Prabodh Kandala, PhD

9.6       Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-guided intervention?

Dror Nir, PhD

Chapter 10:  Biomarkers

                                                Biomarkers: Pancreatic Cancer

10.1        Mesothelin: An early detection biomarker for cancer (By Jack Andraka)

Tilda Barliya, PhD

Biomarkers: All Types of Cancer, Genomics and Histology

10.2                  Stanniocalcin: A Cancer Biomarker

Aashir Awan, PhD

10.3         Breast Cancer: Genomic Profiling to Predict Survival: Combination of Histopathology and Gene Expression Analysis

Aviva Lev-Ari, PhD, RN

Biomarkers: Pancreatic Cancer

10.4         Biomarker tool development for Early Diagnosis of Pancreatic Cancer: Van Andel Institute and Emory University

Aviva Lev-Ari, PhD, RN

10.5     Early Biomarker for Pancreatic Cancer Identified

Prabodh Kandala, PhD

Biomarkers: Head and Neck Cancer

10.6        Head and Neck Cancer Studies Suggest Alternative Markers More Prognostically Useful than HPV DNA Testing

Aviva Lev-Ari, PhD, RN

10.7      Opens Exome Service for Rare Diseases & Advanced Cancer @Mayo Clinic’s OncoSpire

Aviva Lev-Ari, PhD, RN

Diagnostic Markers and Screening as Diagnosis Methods

10.8         In Search of Clarity on Prostate Cancer Screening, Post-Surgical Followup, and Prediction of Long Term Remission

Larry H Bernstein, MD, FCAP

Chapter 11  Imaging In Cancer

11.1  Introduction by Dror Nir, PhD

11.2  Ultrasound

11.2.1        2013 – YEAR OF THE ULTRASOUND

Dror Nir, PhD

11.2.2      Imaging: seeing or imagining? (Part 1)

Dror Nir, PhD

11.2.3        Early Detection of Prostate Cancer: American Urological Association (AUA) Guideline

Dror Nir, PhD

11.2.4        Today’s fundamental challenge in Prostate cancer screening

Dror Nir, PhD

11.2.5       State of the art in oncologic imaging of Prostate

Dror Nir, PhD

11.2.6        From AUA 2013: “HistoScanning”- aided template biopsies for patients with previous negative TRUS biopsies

Dror Nir, PhD

11.2.7     On the road to improve prostate biopsy

Dror Nir, PhD

11.2.8       Ultrasound imaging as an instrument for measuring tissue elasticity: “Shear-wave Elastography” VS. “Strain-Imaging”

Dror Nir, PhD

11.2.9       What could transform an underdog into a winner?

Dror Nir, PhD

11.2.10        Ultrasound-based Screening for Ovarian Cancer

Dror Nir, PhD

11.2.11        Imaging Guided Cancer-Therapy – a Discipline in Need of Guidance

Dror Nir, PhD

11.3   MRI & PET/MRI

11.3.1     Introducing smart-imaging into radiologists’ daily practice

Dror Nir, PhD

11.3.2     Imaging: seeing or imagining? (Part 2)

[Part 1 is included in the ultrasound section above]

Dror Nir, PhD

11.3.3    Imaging-guided biopsies: Is there a preferred strategy to choose?

Dror Nir, PhD

11.3.4     New clinical results support Imaging-guidance for targeted prostate biopsy

Dror Nir, PhD

11.3.5      Whole-body imaging as cancer screening tool; answering an unmet clinical need?

Dror Nir, PhD

11.3.6        State of the art in oncologic imaging of Lymphoma

Dror Nir, PhD

11.3.7      A corner in the medical imaging’s ECO system

Dror Nir, PhD

11.4  CT, Mammography & PET/CT 

11.4.1      Causes and imaging features of false positives and false negatives on 18F-PET/CT in oncologic imaging

Dror Nir, PhD

11.4.2     Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma

Dror Nir, PhD

11.4.3        Improving Mammography-based imaging for better treatment planning

Dror Nir, PhD

11.4.4       Closing the Mammography gap

Dror Nir, PhD

11.4.5       State of the art in oncologic imaging of lungs

Dror Nir, PhD

11.4.6       Ovarian Cancer and fluorescence-guided surgery: A report

Tilda Barliya, PhD

11.5  Optical Coherent Tomography (OCT)

11.5.1       Optical Coherent Tomography – emerging technology in cancer patient management

Dror Nir, PhD

11.5.2     New Imaging device bears a promise for better quality control of breast-cancer lumpectomies – considering the cost impact

Dror Nir, PhD

11.5.3        Virtual Biopsy – is it possible?

Dror Nir, PhD

11.5.4      New development in measuring mechanical properties of tissue

Dror Nir, PhD

Chapter 12. Nanotechnology Imparts New Advances in Cancer Treatment,  Detection, and Imaging  

12.1     DNA Nanotechnology

Tilda Barliya, PhD

12.2     Nanotechnology, personalized medicine and DNA sequencing

Tilda Barliya, PhD       

12.3     Nanotech Therapy for Breast Cancer

Tilda Barliya, PhD

12.4     Prostate Cancer and Nanotecnology

Tilda Barliya, PhD

12.5     Nanotechnology: Detecting and Treating metastatic cancer in the lymph node

Tilda Barliya, PhD

12.6     Nanotechnology Tackles Brain Cancer

Tilda Barliya, PhD

12.7     Lung Cancer (NSCLC), drug administration and nanotechnology

Tilda Barliya, PhD

Volume Epilogue by Larry H. Bernstein, MD, FACP

Epilogue: Envisioning New Insights in Cancer Translational Biology

Larry H. Berstein, MD, FACP

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Topical Solution for Combination Oncology Drug Therapy: Patch that delivers Drug, Gene, and Light-based Therapy to Tumor

Reporter: Aviva Lev-Ari, PhD, RN

 

Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment

Affiliations

  1. Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts 02139, USA
    • João Conde,
    • Nuria Oliva,
    • Mariana Atilano,
    • Hyun Seok Song &
    • Natalie Artzi
  2. School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK
    • João Conde
  3. Grup dEnginyeria de Materials, Institut Químic de Sarrià-Universitat Ramon Llull, Barcelona 08017, Spain
    • Mariana Atilano
  4. Division of Bioconvergence Analysis, Korea Basic Science Institute, Yuseong, Daejeon 169-148, Republic of Korea
    • Hyun Seok Song
  5. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    • Natalie Artzi
  6. Department of Medicine, Biomedical Engineering Division, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    • Natalie Artzi

Contributions

J.C. and N.A. conceived the project and designed the experiments. J.C., N.O., H.S.S. and M.A. performed the experiments, collected and analysed the data. J.C. and N.A. co-wrote the manuscript. All authors discussed the results and reviewed the manuscript.

Nature Materials
15,
353–363
(2016)
doi:10.1038/nmat4497
Received
22 April 2015
Accepted
26 October 2015
Published online
07 December 2015

The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs—a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)—provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional in vitro and in vivo, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.

SOURCE

http://www.nature.com/nmat/journal/v15/n3/abs/nmat4497.html#author-information

 

 

Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results

In mice, device destroyed colorectal tumors and prevented remission after surgery.

Helen Knight | MIT News Office
July 25, 2016

Approximately one in 20 people will develop colorectal cancer in their lifetime, making it the third-most prevalent form of the disease in the U.S. In Europe, it is the second-most common form of cancer.

The most widely used first line of treatment is surgery, but this can result in incomplete removal of the tumor. Cancer cells can be left behind, potentially leading to recurrence and increased risk of metastasis. Indeed, while many patients remain cancer-free for months or even years after surgery, tumors are known to recur in up to 50 percent of cases.

Conventional therapies used to prevent tumors recurring after surgery do not sufficiently differentiate between healthy and cancerous cells, leading to serious side effects.

In a paper published today in the journal Nature Materials, researchers at MIT describe an adhesive patch that can stick to the tumor site, either before or after surgery, to deliver a triple-combination of drug, gene, and photo (light-based) therapy.

Releasing this triple combination therapy locally, at the tumor site, may increase the efficacy of the treatment, according to Natalie Artzi, a principal research scientist at MIT’s Institute for Medical Engineering and Science (IMES) and an assistant professor of medicine at Brigham and Women’s Hospital, who led the research.

The general approach to cancer treatment today is the use of systemic, or whole-body, therapies such as chemotherapy drugs. But the lack of specificity of anticancer drugs means they produce undesired side effects when systemically administered.

What’s more, only a small portion of the drug reaches the tumor site itself, meaning the primary tumor is not treated as effectively as it should be.

Indeed, recent research in mice has found that only 0.7 percent of nanoparticles administered systemically actually found their way to the target tumor.

“This means that we are treating both the source of the cancer — the tumor — and the metastases resulting from that source, in a suboptimal manner,” Artzi says. “That is what prompted us to think a little bit differently, to look at how we can leverage advancements in materials science, and in particular nanotechnology, to treat the primary tumor in a local and sustained manner.”

The researchers have developed a triple-therapy hydrogel patch, which can be used to treat tumors locally. This is particularly effective as it can treat not only the tumor itself but any cells left at the site after surgery, preventing the cancer from recurring or metastasizing in the future.

Firstly, the patch contains gold nanorods, which heat up when near-infrared radiation is applied to the local area. This is used to thermally ablate, or destroy, the tumor.

These nanorods are also equipped with a chemotherapy drug, which is released when they are heated, to target the tumor and its surrounding cells.

Finally, gold nanospheres that do not heat up in response to the near-infrared radiation are used to deliver RNA, or gene therapy to the site, in order to silence an important oncogene in colorectal cancer. Oncogenes are genes that can cause healthy cells to transform into tumor cells.

The researchers envision that a clinician could remove the tumor, and then apply the patch to the inner surface of the colon, to ensure that no cells that are likely to cause cancer recurrence remain at the site. As the patch degrades, it will gradually release the various therapies.

The patch can also serve as a neoadjuvant, a therapy designed to shrink tumors prior to their resection, Artzi says.

When the researchers tested the treatment in mice, they found that in 40 percent of cases where the patch was not applied after tumor removal, the cancer returned.

But when the patch was applied after surgery, the treatment resulted in complete remission.

Indeed, even when the tumor was not removed, the triple-combination therapy alone was enough to destroy it.

The technology is an extraordinary and unprecedented synergy of three concurrent modalities of treatment, according to Mauro Ferrari, president and CEO of the Houston Methodist Research Institute, who was not involved in the research.

“What is particularly intriguing is that by delivering the treatment locally, multimodal therapy may be better than systemic therapy, at least in certain clinical situations,” Ferrari says.

Unlike existing colorectal cancer surgery, this treatment can also be applied in a minimally invasive manner. In the next phase of their work, the researchers hope to move to experiments in larger models, in order to use colonoscopy equipment not only for cancer diagnosis but also to inject the patch to the site of a tumor, when detected.

“This administration modality would enable, at least in early-stage cancer patients, the avoidance of open field surgery and colon resection,” Artzi says. “Local application of the triple therapy could thus improve patients’ quality of life and therapeutic outcome.”

Artzi is joined on the paper by João Conde, Nuria Oliva, and Yi Zhang, of IMES. Conde is also at Queen Mary University in London.

SOURCE

http://news.mit.edu/2016/patch-delivers-drug-gene-light-based-therapy-tumor-0725

Other related articles published in thie Open Access Online Scientific Journal include the following:

The Development of siRNA-Based Therapies for Cancer

Author: Ziv Raviv, PhD

https://pharmaceuticalintelligence.com/2013/05/09/the-development-of-sirna-based-therapies-for-cancer/

 

Targeted Liposome Based Delivery System to Present HLA Class I Antigens to Tumor Cells: Two papers

Reporter: Stephen J. Williams, Ph.D.

https://pharmaceuticalintelligence.com/2016/07/20/targeted-liposome-based-delivery-system-to-present-hla-class-i-antigens-to-tumor-cells-two-papers/

 

Blast Crisis in Myeloid Leukemia and the Activation of a microRNA-editing Enzyme called ADAR1

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/06/10/blast-crisis-in-myeloid-leukemia-and-the-activation-of-a-microrna-editing-enzyme-called-adar1/

 

First challenge to make use of the new NCI Cloud Pilots – Somatic Mutation Challenge – RNA: Best algorithms for detecting all of the abnormal RNA molecules in a cancer cell

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/17/first-challenge-to-make-use-of-the-new-nci-cloud-pilots-somatic-mutation-challenge-rna-best-algorithms-for-detecting-all-of-the-abnormal-rna-molecules-in-a-cancer-cell/

 

miRNA Therapeutic Promise

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/05/01/mirna-therapeutic-promise/

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Targeted Liposome Based Delivery System to Present HLA Class I Antigens to Tumor Cells: Two papers

Reporter: Stephen J. Williams, Ph.D.

 

Abstract

Cell-mediated immunotherapies have potential as stand-alone and adjuvant therapies for cancer. However, most current protocols suffer from one or more of three major issues: cost, safety, or efficacy. Here we present a nanoparticle delivery system that facilitates presentation of an immunogenic measles antigen specifically in cancer cells. The delivery system does not contain viral particles, toxins, or biologically derived material. Treatment with this system facilitates activation of a secondary immune response against cancer cells, bypassing the need to identify tumor-associated antigens or educate the immune system through a primary immune response. The delivery system consists of a stealth liposome displaying a cancer-specific targeting peptide, named H1299.3, on its exterior surface and encapsulating H250, an immunogenic human leukocyte antigen class 1 restricted peptide. This targeted-nanoparticle facilitates presentation of the H250 peptide in major histocompatibility complex class I molecules. Activation is dependent on the targeting peptide, previous antigen exposure, and utilizes a novel autophagy-mediated mechanism to facilitate presentation. Treatment with this liposome results in a significant reduction of tumor growth using an aggressive LLC1 model in vaccinated C57BL/6 mice. These data provide proof-of-principle for a novel cell-mediated immunotherapy that is scalable, contains no biologically derived material, and is an efficacious cancer therapy.

Introduction

Cell-mediated (CM) immunotherapies for cancer treatment are designed to activate the body’s adaptive immune responses against a malignant growth.1,2 Generally, the goal of a CM response is to activate a cytotoxic T-cell response against a tumor to eliminate cancer cells. The principle of these treatments is straightforward, yet current work studying the complexity of the tumor micro-environment2,3 as well as methods that attempt to directly activate T cells against tumor antigens4,5,6 demonstrate the difficulty associated generating an immune response against a tumor.

Several CM cancer immunotherapies exist today. Major examples include PD-1 inhibitors, injection of live virus or viral particles into tumors, and adoptive T-cell therapies.1,6,7,8 However, concerns regarding efficacy, safety, and/or cost have limited the use of many of these treatments. To address these concerns, we sought to develop a novel treatment based on developing a fully synthetic, minimal delivery system that facilitates presentation of human leukocyte antigen (HLA) class I restricted immunogenic peptides specifically on cancer cells without using live virus, viral subunits, or biologically derived material.

Based on these requirements, we developed a liposomal based agent consisting of a neutral, stealth liposome that encapsulates a synthetically manufactured immunogenic HLA class I restricted peptide derived from measles virus.1,2,9 In addition, the liposome has a targeting peptide on the external surface that both specifically accumulates in cancer cells and facilitates presentation of the immunogenic peptide in HLA class I molecules (Figure 1a). Thus, this treatment is designed to generate a secondary CM immune response specifically against the tumor if the patient was previously vaccinated against or infected with measles.

Figure 1

The minimal antigen delivery system consists of three components. (a) PEGylated stealth liposomes are loaded with an immunogenic human leukocyte antigen (HLA) class 1 restricted peptide derived from measles virus, named H250. The surface of the liposome

In this proof-of-concept study, we synthesized a liposome that encapsulates H250,1 an immunogenic HLA class 1 restricted peptide identified from measles hemagglutinin protein. The liposome is designed to specifically internalize in cancer cells by displaying the recently identified targeting peptide H1299.3 on the exterior surface (Figure 1b).10 H1299.3 is a 20mer, cancer-specific targeting peptide that was recently identified by our group. The peptide was identified using a novel phage display technique that allows for selection of cancer-specific targeting peptides that preferentially internalize in cancer cells via a defined mechanism of endocytosis. This peptide was dimerized on a lysine core and is fully functional outside the context of the phage particle. The H1299.3 peptide accumulates specifically in a panel of non-small cell lung cancer (NSCLC) cell lines compared to a normal bronchial epithelial cell control cell line via a clathrin-dependent mechanism of endocytosis. In this study, we demonstrate that H1299.3 facilitates functional presentation of an immunogenic antigen in both major histocompatibility complex (MHC) and HLA class I molecules as indicated by CD8+-specific interferon (IFN)γ secretion. In addition, H1299.3 facilitated presentation utilizes an autophagy-dependent mechanism. Finally, treatment with H1299.3 targeted liposomes containing H250 substantially reduces the growth rate of subcutaneous LLC1 tumors implanted in vaccinated C57BL/6 mice compared to treatment with vehicle control.

Result summarized:

  1. The H1299.3 targeting ligand specifically accumulates in cancer and facilitates HLA class I presentation: H250 is an immunogenic peptide identified from sequencing peptides present in HLA A*0201 molecules following measles infection. identified two donors that were HLA A*02 positive and had previously been vaccinated against measles virus (the human NSCLC cell line, H1993, which we determined to be HLA A*02 positive)
  2. identified three different cancer-specific targeting peptides that internalize into H1993 that have been previously published: H1299.2, H2009.1, and H1299.3. Each of these peptides specifically internalize in NSCLC cell lines compared to normal bronchial epithelial cells
  3. H1299.3 facilitated HLA class I presentation requires autophagy. H1299.3 peptide colocalizes with Lamp-1 which is a marker of both lysosomes and autolysosomes, therefore it was possible autophagy involved and shown that H1299.3 colocalizes with autophagosomes.  Chlorpromazine, which inhibits clathrin coated mediatated endocytosis, decreased the HLA1 presentation of H250.
  4. H1299.3-targeted liposomes encapsulating H250 reduce tumor burden in vivo. Mice were first vaccinated against H250.  The J1299.3 targeted liposome encapsulation H250 reduced tumor growth of LLC1 s.c. xenograpfts  by 50%.
J Transl Med. 2011 Mar 31;9:34. doi: 10.1186/1479-5876-9-34.

Enhanced presentation of MHC class Ia, Ib and class II-restricted peptides encapsulated in biodegradable nanoparticles: a promising strategy for tumor immunotherapy.

Abstract

BACKGROUND:

Many peptide-based cancer vaccines have been tested in clinical trials with a limited success, mostly due to difficulties associated with peptide stability and delivery, resulting in inefficient antigen presentation. Therefore, the development of suitable and efficient vaccine carrier systems remains a major challenge.

METHODS:

To address this issue, we have engineered polylactic-co-glycolic acid (PLGA) nanoparticles incorporating: (i) two MHC class I-restricted clinically-relevant peptides, (ii) a MHC class II-binding peptide, and (iii) a non-classical MHC class I-binding peptide. We formulated the nanoparticles utilizing a double emulsion-solvent evaporation technique and characterized their surface morphology, size, zeta potential and peptide content. We also loaded human and murine dendritic cells (DC) with the peptide-containing nanoparticles and determined their ability to present the encapsulated peptide antigens and to induce tumor-specific cytotoxic T lymphocytes (CTL) in vitro.

RESULTS:

We confirmed that the nanoparticles are not toxic to either mouse or human dendritic cells, and do not have any effect on the DC maturation. We also demonstrated a significantly enhanced presentation of the encapsulated peptides upon internalization of the nanoparticles by DC, and confirmed that the improved peptide presentation is actually associated with more efficient generation of peptide-specific CTL and T helper cell responses.

CONCLUSION:

Encapsulating antigens in PLGA nanoparticles offers unique advantages such as higher efficiency of antigen loading, prolonged presentation of the antigens, prevention of peptide degradation, specific targeting of antigens to antigen presenting cells, improved shelf life of the antigens, and easy scale up for pharmaceutical production. Therefore, these findings are highly significant to the development of synthetic vaccines, and the induction of CTL for adoptive immunotherapy.

[PubMed – indexed for MEDLINE]

Free PMC Article

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