This document describes a lentiviral vector called AJS2001 that can selectively silence the Cdc6 gene in cancer cells. Cdc6 is essential for initiating DNA replication, and silencing it blocks cancer cell proliferation. The vector was shown to inhibit growth of several cancer cell lines through Cdc6 knockdown, inducing senescence. Case studies are presented of cancer patients who recovered after treatment with injections of AJS2001 lentivirus, including patients with gastric carcinoma, brain and liver metastases from ovarian cancer, lung and larynx metastases from parotid carcinoma, and breast cancer.
ADCC Reporter Bioassay - V and F Variants: Novel, Bioluminescent Cell-Based A...Neal Cosby
The ADCC Reporter Bioassay from Promega is now available in both V158 and F158 variant formats. Use this functional, sister bioassay approach to better characterize Ab drugs with MOA directed through FcgammaRIIIa (CD16a) receptor. Not yet familiar with this novel bioassay that is becoming the industry standard? This slidedoc introduces the reporter-based ADCC technology. Contact me for any questions.
Carbonic Anhydrase IX: regulation and role in cancerMAASTRO clinic
Lecture by Prof. Silvia Pastorekova in the course: "Tumour Hypoxia: From Biology to Therapy III". For the complete e-Course see http://www.myhaikuclass.com/MaastroClinic/metoxia
Analysis of mutant parasites that have a defect in adhésion - Conférence du 6e édition du Cours international « Atelier Paludisme » - MATTEI Denise - France - dmm@pasteur.fr
GeneChrome, two biochemist joined hand & started this concept on the basis of 11 year experience in diagnostics segment with exposure of various technology.
We decided to focus on niche area where most of the laboratory does not focus & to provide quality services in health care segments like…
Autoimmunity
Allergy
Hormones
Vitamins
Genetics
Electrophoresis
Special biochemistry & many more profile ……………….
We have a team of technically sound professional in diagnostics to drive our mission without compromising our values.
An approach to describing and analysing bulk biological annotation quality: a...Michael Bell
Motivation:
Annotations are a key feature of many biological databases, used to convey our knowledge of a sequence to the reader. Ideally, annotations are curated manually, however manual curation is costly, time consuming and requires expert knowledge and training. Given these issues and the exponential increase of data, many databases implement automated annotation pipelines in an attempt to avoid un-annotated entries. Both manual and automated annotations vary in quality between databases and annotators, making assessment of annotation reliability problematic for users. The community lacks a generic measure for determining annotation quality and correctness, which we look at addressing within this work. Specifically we investigate word reuse within bulk textual annotations and relate this to Zipf's Principle of Least Effort. We use UniProt Knowledge Base (UniProtKB) as a case study to demonstrate this approach since it allows us to compare annotation change, both over time and between automated and manually curated annotations.
Results:
By applying power-law distributions to word reuse in annotation, we show clear trends in UniProtKB over time, which are consistent with existing studies of quality on free text English. Further, we show a clear distinction between manual and automated analysis and investigate cohorts of protein records as they mature. These results suggest that this approach holds distinct promise as a mechanism for judging annotation quality.
For more information available at the authors website: www.michaeljbell.co.uk
Poster - RNAi Therapeutics by Silence Therapeutics - American Society of Cli...Silence Therapeutics
A poster detailing the results from the first-in-human Phase I study of Atu027, novel RNAi therapeutic. Atu027 is a liposomal siRNA formulation that targets protein kinase N3 (PKN3) in patients with advanced solid tumors. Find out more here:
http://silence-therapeutics.com/content/pipeline/internalprograms.htm
ADCC Reporter Bioassay - V and F Variants: Novel, Bioluminescent Cell-Based A...Neal Cosby
The ADCC Reporter Bioassay from Promega is now available in both V158 and F158 variant formats. Use this functional, sister bioassay approach to better characterize Ab drugs with MOA directed through FcgammaRIIIa (CD16a) receptor. Not yet familiar with this novel bioassay that is becoming the industry standard? This slidedoc introduces the reporter-based ADCC technology. Contact me for any questions.
Carbonic Anhydrase IX: regulation and role in cancerMAASTRO clinic
Lecture by Prof. Silvia Pastorekova in the course: "Tumour Hypoxia: From Biology to Therapy III". For the complete e-Course see http://www.myhaikuclass.com/MaastroClinic/metoxia
Analysis of mutant parasites that have a defect in adhésion - Conférence du 6e édition du Cours international « Atelier Paludisme » - MATTEI Denise - France - dmm@pasteur.fr
GeneChrome, two biochemist joined hand & started this concept on the basis of 11 year experience in diagnostics segment with exposure of various technology.
We decided to focus on niche area where most of the laboratory does not focus & to provide quality services in health care segments like…
Autoimmunity
Allergy
Hormones
Vitamins
Genetics
Electrophoresis
Special biochemistry & many more profile ……………….
We have a team of technically sound professional in diagnostics to drive our mission without compromising our values.
An approach to describing and analysing bulk biological annotation quality: a...Michael Bell
Motivation:
Annotations are a key feature of many biological databases, used to convey our knowledge of a sequence to the reader. Ideally, annotations are curated manually, however manual curation is costly, time consuming and requires expert knowledge and training. Given these issues and the exponential increase of data, many databases implement automated annotation pipelines in an attempt to avoid un-annotated entries. Both manual and automated annotations vary in quality between databases and annotators, making assessment of annotation reliability problematic for users. The community lacks a generic measure for determining annotation quality and correctness, which we look at addressing within this work. Specifically we investigate word reuse within bulk textual annotations and relate this to Zipf's Principle of Least Effort. We use UniProt Knowledge Base (UniProtKB) as a case study to demonstrate this approach since it allows us to compare annotation change, both over time and between automated and manually curated annotations.
Results:
By applying power-law distributions to word reuse in annotation, we show clear trends in UniProtKB over time, which are consistent with existing studies of quality on free text English. Further, we show a clear distinction between manual and automated analysis and investigate cohorts of protein records as they mature. These results suggest that this approach holds distinct promise as a mechanism for judging annotation quality.
For more information available at the authors website: www.michaeljbell.co.uk
Poster - RNAi Therapeutics by Silence Therapeutics - American Society of Cli...Silence Therapeutics
A poster detailing the results from the first-in-human Phase I study of Atu027, novel RNAi therapeutic. Atu027 is a liposomal siRNA formulation that targets protein kinase N3 (PKN3) in patients with advanced solid tumors. Find out more here:
http://silence-therapeutics.com/content/pipeline/internalprograms.htm
Cdc6 Knockdown Renders p16INK4a Re-Activation, Leading to Senescence Human Br...gan-navi
Luo Feng, Jerry R. Barnhart, Lingtao Wu, Greg Shackleford,
Sheng-he Huang and Ambrose Jong
Department of Hematology and Oncology
Childrens Hospital Los Angeles
University of Southern California, Los Angeles
USA
Rho kinase(ROCK) are a family of small signalling G-proteins and subfamily of Ras super family.
It forms signalling pathway for varios agonists like AT-ll,5-HT, ET-1,Histamine,TXA2.
Current Chemotherapy and the
Future of Targeted Therapies presented by Lee Krug, MD, of Memorial Sloan-Kettering Cancer Center at the Mesothelioma Applied Research Foundation's conference in New York, NY on September 28, 2012. www.curemeso.org
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2QIAGEN
Advanced prostate cancer is highly heterogeneous but this inter-patient heterogeneity has until recently not been understood. We have through an international research effort dissected the molecular landscape of advanced castration resistant prostate, elucidating key molecular targets in this group of diseases. We have also shown that PARP inhibitors have antitumor activity against a significant proportion of these cancers, mainly in men whose cancers harbor DNA repair defects.
Making genome edits in mammalian cellsChris Thorne
Looking at the kind of modifications that can be made in mammalian cells, and how at Horizon moving to a haploid model system has significantly improved efficiency of both editing and validation
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...
AJS: a lethal weapon to combat with cancers Treatment of Human Cancers Using Mechanism-Based Lentivirus
1. AJS: a lethal weapon to combat with cancers
Treatment of Human Cancers Using Mechanism-Based Lentivirus
Luo Feng
Takeshi Hirota
Tsuyoshi Takara
RNtein Biotech Co., LtD
Tokyo, Japan
RNTein Biotech. Lab.
Dedicated to human cancer gene therapy
San Gabriel, California, USA
2. Self-sufficiency Sustained
in growth signals angiogenesis Insensitivity to
anti-growth signals
Limitless replicative Evading apoptosis Tissue invasion
potential & metastasis
The development of human cancer cells
3. Cdc6 is essential in the initiation of DNA replication:
A). Assembling pre-replication complex (pre-RC) with ORC,
and loading MCMs to replication origins;
B). Licensing DNA replication to ensure one round
DNA replication per cell cycle.
4. The novel function of AJSFL1 is the silencing of human Cdc6,
the specific genes for cell proliferation:
Specific Cdc6 shRNAs produced from the viral vector Inhibit Cdc6 and block
Cancer cell proliferation, but not normal cells.
LA-N-2 MCF7 CHLA255
Cdc6 shRNA
THTD6Ai
THTD6Ai
THTD6Ai
THTP
Mock
Mock
THTP
THTP
Cdc6
Cdc6 knockdown
-actin
1 2 3 4 5 6 7 8
6. Cdc6
Telomere Oncogene
dysfunction activation
? Rb-E2F
Cyclin D1
Cdk4/Cdk6
DNA damage p16INK4a P Rb-E2F
response
p53 p21 P Rb E2F
Rb
Apoptosis
Senescence G1 S
Adapted from J. M. Sedivy, Cancer Cell, 11:389-391, 2007
9. The formation of senescence associated heterochromatic foci via
Cdc6 knockdown
Anti-H3K9me3/me2
indirect fluorescent
staining
Mock THTD6Ai
Confocal fluorescent
microscopy
Mock THTD6Ai
10. A male patient age 55, with advanced gastric carcinoma found in April 2006 is first survivor by
GFL1(AJS). After second injection since 07/06/2006, he gained weight with good appetite, and left
hospital on 27/06/2006. After 4th injection, his gastric carcinoma disappeared without side effect.
Now, 2 years and 8 month has passed since recovery, and he leads normal life with good appetite
and feeling.
He and his wife filled with joy • • • has become active for social work
Speech about his own recovery experience at Cancer Control Association. He is now doing
volunteer activity for many other cancer patient.
An advanced gastric carcinoma patient shows
his recovery after receiving AJS injections.
11. Multiple gastric scirrhous carcinoma of the male patient age 55
Emergency medical admission on 10/04/2006
First injection
on
24/04/2006
2 weeks after 4 times of weekly
injection on 05/06/2006
Effect of AJS treatment shown by endoscope
12. A female patient age 52, who had major operation for uterus carcinoma metastated to liver and brain
resulted in 14 days life expectancy because brain carcinoma remain, has amazingly recovered by
continuous AJS injection for 3 month. Now, she leads pleasant normal life
CT of brain before injection CT of brain after recovery
MRI of liver before injection Healthy expression after recovery
The treatment of a patient with brain metastatic ovary tumour
13. A male patient age 64, recovered from parotid carcinoma metastated to lung and larynx. He
had the therapy by day return to keep his office work. He has been nominated to chairman of
I (AJS) patient association. He has now 6 grandchild, and is doing volunteer activity to
promote AJS.
Before injection After injection
14. A female patient age 52, has recovered from breast cancer metastated to lymph node by only 4 times
injection without surgery. In addition, her hair returned deep black. She is now doing volunteer activity
for many other breast cancer patient by saying “do not need surgery, do not give up hope, breast
cancer can be cured by injection only”.
Before injection After 1st injection After 2nd injection After 3rd injection
After 4th injection Current recovery Her black hair
A breast carcinoma patient voluntarily wants to have AJS treatment, not surgery.