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Original Tweets Re-Tweets and Likes by @pharma_BI and @AVIVA1950 at #kisymposium for 17th annual Summer Symposium: Breakthrough Cancer Nanotechnologies: Koch Institute, MIT Kresge Auditorium, June 15, 2018, 9AM-4PM

 

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SYNOPSIS – 17th annual Summer Symposium: Breakthrough Cancer Nanotechnologies: Koch Institute, MIT Kresge Auditorium, June 15, 2018, 9AM-4PM

 

 

https://kochinstituteevents.cvent.com/events/Registrations/MyAgenda.aspx?i=c46642c6-abb0-4f3b-97b7-ae1bb167f304&sw=1

Announcement

Aviva Lev-Ari, PhD, RN,

Founder and Director of LPBI Group will be in attendance covering the event in

REAL TIME

@pharma_BI

@AVIVA1950

 

All TWEETS from LPBI’s Twitter.com handles at

 

  • Friday, June 15, 2018
8:00 AM – 9:00 AM Registration/Check-In

 

9:00 AM – 9:10 AM Introductory Remarks: Tyler Jacks and Sangeeta Bhatia

Speakers:

o   Sangeeta Bhatia,

  • Challenge meet Opportunity – Future Cancer Research Priorities
  • Prevention and early detection of Cancer for improved outcomes
  • Global cancer burden – Cancer diagnosis in Low-resources settings
  • 2000 microchip became nanoscale – other materials in nanoscale: 1994 – Present advancement in material and devices

o   Tyler Jacks

  • Nanotech, Diagnostics, Therapeutics, Cancer Care, Cancer Biology
  • New Center for NanoMedicine @MIT aka, @MIT.NANO
  • Sponsored: J&J, Sanofi, Thermo Scientific

 

9:10 AM – 10:40 AM Session I: Imaging and Diagnostics

·       Sanjiv Sam Gambhir, MD, PhD, Stanford University

Bubble Based Nanodiagnostics

  • Companies involved: Endra Inc, Bracco, Visualsonics
  • Canary Center Vision: Imaging: identify, isolate, Intervene
  • Value of early cancer detection: Survival is high ONLY in very very early vs tail of the distribution where 90% of funds goes for therapy: Prostate and Breast cancers — ARE detected early
  • Technology: Ultrasound Imaging ($1500 – low cost solution, for molecular level
  • Bubble based Nanodiognostics: Molecular level, gas pore shell made of lipids or albomin – provide information on location of cancer – molecular events, atomical modelity
  • Bubble size nanobubbles vs microbubbles targeted for Vascular Endothilium In vivo
  • Angiogenesis: KDR (molecule)/VEGFR2 (receptor)- over expressed only in neovascularized: Molecular targer is KDR – over expressed in ovarian and breast cancers
  • ability of bubbles to identify cancer, toxicity monitored , bubble arrive, bind, cleared
  • blind to histology – examine the binding, blind pathology
  • bubbles well correlated
  • histological diagnosis few mm to few cm — correlation of lesions benign
  • 1 cm lesion targeted present in KDR, normal tissue clears more rapidly vs in malignant tissue: ductal adenocarcenoma – 11 minutes after injection
  • Duration of US Molecular Imaging Signal
  • First-in-man – Bubble Transrectal US Photoaccustic detection modality
  • Enzyme activation nanobubbles – nano microbubbles to aggregate and create mass impact vs nanobubbles that are weak in signal potential
  • Synthesis of PA/US nanosize RF-acoustic imaging  – target Saline nanodroplets

·       Ralph Weissleder Developing Next Generation Diagnostics for Cancer @MGH

  • translational diagnostics: Precision oncology (1) Imaging (2) Tumor biopsy (3) Liquid biopsy
  • Enable earlier detection
  • Visualization for affordable cost
  • NEW Technologies at MGH with use of AI
  1. Rapid cellular protein profiling – Fine needle aspirates (FNA): DNA Barcode: Epitope – monoclonal antibodies: Sampling, Barcoding, Imaging, Analysis with AI: Pathways in single cells – protein level in different patient:

x axis patient number

y-axis: Protein type

Vesicles from Host vs from Tumor

2, Exosome

surface – Label-free detection and molecualr profiling of exosome : Pancreatic cancer detection – vesicle express  – they are heteroginous micro vesicles

3. POC testing (AI- Defraction Analysis)

Remote diagnosis:

  • Molecular diagnosis – 2015 (PNAS) – nano bids defract patterns – smart phone vs proprietary box – BioMed Eng
  • Algorithms – identify molecules and decision tree Clinical Trial at MGH: 24 Lymphoma patients, rest no-Lymphoma, higher precision than microspectrometry
  • Automated diagnosis – aspirate – subject to dioagnosis in the Box
  • From tissue to single cell
  • multiplex pathways
  • early detection
  • affordability
  • visualization/connectivity for interpretation

·       Angela Belcher New Approaches for Finding Tiny Tumors: Towards Early Detection and Treatment of Ovarian Cancer

  • Nano material and Biomaterial the intersection of
  • Genetic control of materials
  • Carbon nano tubes – Using Bacteriophage or phage – A virus that infect bacteria
  • from DNA to devices
  • Lincoln Labs + MGH + MIT – Carbon Nanotubes used in inexpensive diagnostics: Biomedical imaging: MI, PET: Optical imaging in vivo: Trade-fee: Resolution vs Depth
  • Ovarian Cancer: Minimal increase in overall survival over 30 years : Fallopian tubesmaximum reduction in tumor better survival rate
  • submillimiter detection: Carbon nanotube multiple tubes
  • Pre-surgical planning locates hard-to-detect ovarian tumor – find tumors that are hidden
  • Detection od Optically Luminescent – RT tracking T-cells in Cancer Immmunotherapy – following injection in mice remain for 2 days

Speakers:

·       Angela Belcher,

·       Sanjiv Sam Gambhir,

·       Ralph Weissleder

10:40 AM – 11:00 AM Coffee Break

 

11:00 AM – 12:30 PM Session II: Therapeutics

·       Mark Davis Designing Nanoparticles to Safely Cross the Blood-Brain Barrier for Treating Brain Cancers

  • Engineer particles for treating solid tumors
  • Intracellular drug delivery
  • 30-50nm
  • Improve PK properties
  • Limit Toxicity
  • Cyclodex
  • Interspecies translation – Nanoparticles can function to design in Humans
  • Combination of Avastin and nanoparticle component
  • PARP Inhibitor + CRLX101 – in clinical trial by AstraZeneka
  • PK in human been presicted if PK known in non-humans
  • Therapeutic escape from the exosome polymer end group chemistry
  • Tumor localization of Nanoparticles
  • Nanoparticles can function in Human NOT in the brain
  • better clinical trial design and combination drugs in small clinical trials
  • Brain primary vs mestasis in th ebrain
  • 50% HER2 positive will have metastesis in the brain
  • BBB TfP Receptor-mediate Transcytosis : Antibody affinity, monodenriate
  • Nanoparticles behave similarity to antibodies in the brain Nanoparticles characteristics: decreased
  • Improved Uptake of Nanoparticles  – fast release of NP during transcytosis
  • bring nanoparticles in combination therapy to the brain using transcytosis

·       Suzie Pun Modulating Tumor-Associated Macrophage

  • TAM – Targeting Tumor-associated macrophages
  • blood monocytes, immunosuppression, metastasis, invasion
  • Can we potentiated therapeutics delivery using TAM
  • wiin tumors, M2pep is internalized by TAMs
  • Cytotoxic KLA peptide – reduce inflammatory of the tumor – M2pepKLA reduces tumor growth rate and improves survival
  • increase avidity binding
  • Immunomodulation – Marophage targeting for
  • Targeting TAM for translation to Humans
  • improve drug potency
  • synthetic Nucleocapsids  —
  • Biomaterials for modulating tumor extracellular matrix
  • FSP integrates into fibrin, increasing its half-life – delay degradation of FSP-fibrin
  • Polymer cross linking – fibrin deposition in brain metastases
  • Fibrin stabilization by FSP alters TAM chronic FSP treatment increases brain metastasis

·       Daniel Anderson Nanoparticle Formulations for RNA Therapy and Gene Editing

  • can we make drugs to repair our DNA for therapy
  • barriers for systemic delivery of nanaoparticles
  • RNA THERAPEUTICS sIRNA – interference: Turning Genes Off: Modular Pharmacology: sequence Selection, Chemical Modification, Encapsulation (like artificial viruses)
  • What material can be used for RNA delivery? – How can we increase diversity?
  • combinatorial synthesis of lipid-like materials
  • RNA Interference – RNA Tx for Liver: Transthyretin-(TTR)
  • TTR in primates, in Humans – Delivery of sRNAi – new class of machines
  • Chylomicron metabolism: The rate of dietary : Mechanism of APoE mediated iLNP delivery
  • sRNAi are not limited for hypatocytes
  • One injection – 5 genes silencing in lung endothelial cells
  • IMMUNE CELLS AS A TARGET FOR siRNA
  • Repaired liver cells in mouth: repopulation of the liver
  • How do we deliver Cas9 in vivo?
  • Modular Pharmacology: Deliver mRNA to inside cells? using nanoparticles
  • chemistry of nanoparticles will delivery to lungs not to liver or to liver not to lungs
  • inhaled nanoparticles for mRNA delivery
  • Cas9 – for gene editing – – Inject AAV-Virus — >> AAV +Cas( mRNA
  • Chemical modification for siRNA: guiding siRNA delivery
  • Guide RNA improve Genome editing
  • Full modification abolishes the function of sgRNA: Cas9-sgRNA
  • e-sgRNA – edited
  • PCKS9- hyperlipidemia — Nanoparticle for in vivo  Genome Editing
  • RNA NANOTHERAPEUTICS AND CANCER
  • Delivery to Immune system – Genome editing in vivo of CAR-Ts

Speakers:

·       Daniel Anderson,

·       Mark Davis,

·       Suzie Pun

 

12:30 PM – 2:00 PM Lunch Break

 

2:00 PM – 3:00 PM Panel ‘Translation of Nanomedicine to Patients’

Noubar Afeyan, John Maraganore, Bob Langer, Paula Hammond, Michelle Bradbury, Cristianne Rijcken

Moderated by Rebecca Spalding

Noubar Afeyan,

John Maraganore,

Bob Langer,

Paula Hammond,

Michelle Bradbury,

Cristianne Rijcken

 

 

3:00 PM – 4:30 PM Session III: Nanosystems and Devices

Sangeeta Bhatia Activity-based biomarkers for non invasive Cancer Detection, Classification and Monitoring

    • Biomarker paradigm for clinical decisions – Endogenous, singular, blood
    • Synthetic Biomarker paradigm for clinical decisions – Exogenous, multiples, urine
    • Endoprotease in Cancer: MMP9, MMP4
    • Synthetic Biomarkers: Sensitivity
    • Enzyme-responsive nanosensors and PK switch [acitvation fluorescence]
    • Benchmarking synthetic biomarkers against a blood biomarker: Urinary synthetic biomarkers outperform CEA
    • multi-compartment modeling for predicting PK
    • Enhancing sensitivity by nanosensor engineering for ovarian cancer detection
    • Mass barcodes enable multiplexing
    • Mass encoded synthetic biomarkers
    • Differentiating similar diseases with protease activity
    • Paper-based microfluidics in urine biomarker
    • synthetic breath biomarkers for lung disease
    • Protease-Responsive Imaging Sensor for Metastasis (PRISM) – localization of Tumor
    • In vivo Enzyme Profiling by Syntahtic Biomarkers

Rashid Bashir Micro and Nanotechnologies for Analysis of Tissues and Molecules

  • liquid biopsy, molecualar analysis of the tumor
  • spatial map of nuclei acids in tissue – Intra tumor heterogeniety
  • subclonal genetic diversity is important
  • laser capture microdissection
  • fluoresence in situ hybridization
  • Cryo-section on microwell array, pixelate and fix tissue inside wells amplification reagents loaded on chip – amplification reaction: Advantages over PCR
  • procees flow on chip
  • On-chip RT-LAMP: Spatial fluorescence analysis
  • ON CHIP RT-LAMP CONTROL: CANCER (red) VS NON-CANCER (blue)  – FTIR control same section
  • Single cell spatial RNA Seq
  • Hematology Analyzer – complete blood celll count  vs FLow cytometry
  • Cells and Proteins from a Drop of Blood

Convergence : The Future of Health – Cancer Center at Illinois

    • Medical Schools MUST Change  CurrentCurriculum vs Future Curriculum
    • NOW: Yr 1: Basic Science Yr 2: Basic Science Yr 3: Clinical Science +  Required rotation Yr 4: Clinical Science +  elective rotation
    • FUTURE: ALL GENOMICS +BIOENGINEERING to be integrated

Jim Heath A Molecular View of Immuno-Oncology, Institute of System Biology

  • Analytical Chemistry challenge:
  • Fundamental Immunology
  • Challenge CRISPR knocking out genes not for knocking in genes
  • Mutated proteins and NEO antiagens: mostly a computational task

Speakers:

·       Rashid Bashir,

·       Sangeeta Bhatia,

·       James Heath

  • Personalized Immuno-Oncology

 

4:30 PM – 4:50 PM Vladimir Bulović: MIT.nano Nanoscale Discoveries for Transformative Breakthroughs

Speakers:

·       Vladimir Bulović

    • MIT.nano
    • color depend on the size of the molecule
    • Drugs & Vitamins are nano-sized:
    • Scents are nano-sized – a fraction of an atom – ethylene – plant hormone – Pheromones – are nanosized
    • Nanoscale will define many future discoveries
    • 51% of the recently tenured SOS faculty – use nano
    • 67% of the recently tenured SOE faculty with benefits – use nano

 

4:50 PM – 5:00 PM Closing Remarks

Speakers:

·       Sangeeta Bhatia

 

Speakers


Daniel Anderson

Nanoparticle Formulations for RNA Therapy and Gene Editing

Daniel Anderson, PhD
Samuel A. Goldblith Professor of Applied Biology, MIT
Associate Professor, Chemical Engineering and Institute for Medical Engineering and Science, MIT
Member, Koch Institute, MIT

Rashid Bashir

Micro and Nanotechnologies for Analysis of Tissues and Molecules

Rashid Bashir, PhD
Executive Associate Dean and Chief Diversity Officer, Carle Illinois College of Medicine
Grainger Distinguished Chair in Engineering, Professor of Bioengineering, Electrical and Computer Engineering, Mechanical Science and Engineering, Materials Science and Engineering, and Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign

Angela Belcher

New Approaches for Finding Tiny Tumors: Towards Early Detection and Treatment of Ovarian Cancer

Angela Belcher, PhD
James Mason Crafts Professor and Professor of Biological Engineering, MIT
Member, Koch Institute, MIT

Sangeeta Bhatia

Protease Nanosensors for Cancer Detection, Classification and Monitoring

Sangeeta Bhatia, MD, PhD
Director, Marble Center for Cancer Nanomedicine
John J. and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science, MIT
Member, Koch Institute, MIT
Investigator, Howard Hughes Medical Institute

Vladimir Bulović, PhD

Nanoscale Discoveries for Transformative Breakthroughs

Vladimir Bulović, PhD
Director, MIT.nano
Associate Dean for Innovation, MIT School of Engineering
Fariborz Maseeh (1990) Professor of Emerging Technology, Department of Electrical Engineering and Computer Science (EECS), MIT

Mark E. Davis, PhD

Designing Nanoparticles to Safely Cross the Blood-Brain Barrier for Treating Brain Cancers

Mark E. DavisPhD  
Warren and Katharine Schlinger Professor of Chemical Engineering, California Institute of Technology
Member of the City of Hope Comprehensive Cancer Center
Member of the UCLA Jonsson Comprehensive Cancer Center

Sanjiv Sam Gambhir, MD, PhD

Bubble Based Nanodiagnostics

Sanjiv Sam GambhirMD, PhD  
Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research, Professor of Bioengineering, Professor of Materials Science and Engineering, Stanford University

James R. Heath

A Molecular View of Immuno-Oncology

James R. Heath, PhD
President and Professor, Institute for Systems Biology
Professor of Molecular and Medical Pharmacology, UCLA

Suzie H. Pun

Modulating Tumor-Associated Macrophage

Suzie H. Pun, PhD
Robert F. Rushmer Professor of Bioengineering, Adjunct Professor of Chemical Engineering, University of Washington

Ralph Weissleder

Developing Next Generation Diagnostics for Cancer

Ralph Weissleder, MD, PhD
Thrall Professor of Radiology and Professor of Systems Biology, Harvard Medical School
Director of the Center for Systems Biology at Massachusetts General Hospital

 

Panelists: Translation of Nanomedicine to Patients


Noubar Afeyan

Noubar Afeyan, PhD
Founder and CEO, Flagship Pioneering

Michelle S. Bradbury, MD, PhD

Michelle S. Bradbury, MD, PhD
Co-Director, MSK-Cornell Center for Translation of Cancer Nanomedicines & Director, Intraoperative Imaging Program
Member, Molecular Pharmacology Program, Sloan Kettering Institute
Attending, Radiology, Memorial Sloan Kettering Cancer Center
Professor, Gerstner Sloan Kettering Graduate School of Biomedical Sciences & Weill Medical College of Cornell University

Paula Hammond

Paula Hammond, PhD
Head, Department of Chemical Engineering, MIT
David H. Koch Professor of Engineering, MIT
Member, Koch Institute, MIT

Robert Langer

Robert Langer, ScD
David H. Koch Institute Professor
Member, Koch Institute, MIT

John Maraganore

John Maraganore, PhD
CEO and Director, Alnylam

Cristianne Rijcken

Cristianne Rijcken, PhD
Founder and Chief Scientific Officer, Cristal Therapeutics

Rebecca Spalding

Moderator

Rebecca Spalding
Biotech Reporter, Bloomberg

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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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