This document discusses treating cancer through targeting telomeres and telomerase. It begins by explaining that cancer results from changes in DNA that alter gene expression. It then describes telomeres, the protective caps on chromosome ends, and telomerase, the enzyme that replenishes telomeres. Cancer cells are able to proliferate indefinitely due to their active telomerase. The document outlines two strategies for inhibiting telomerase in cancer cells: directly targeting telomerase components or indirectly blocking telomerase access to telomeres. It provides examples of specific telomerase inhibitors, including GRN163L and G-quadruplex stabilizing agents.
This oral presentation made at ESOC Marbella 2016 by Eric Raymond describes the role of bromodomain proteins in transcription and updates data on drugs inhibiting bromodomain functions in cancer cells. Data on NUT moline carcinoma, lymphoma, leukemia, prostate, breast, lung carcinomas and neuroblastoma are recapitulated using JQ1 and 0TX-015.
This oral presentation made at ESOC Marbella 2016 by Eric Raymond describes the role of bromodomain proteins in transcription and updates data on drugs inhibiting bromodomain functions in cancer cells. Data on NUT moline carcinoma, lymphoma, leukemia, prostate, breast, lung carcinomas and neuroblastoma are recapitulated using JQ1 and 0TX-015.
Different researches shows that, g-quadruplex- kind of tandem repeats are present in vivo,
Telomeres having tandem repeats of d(TTAGGG) , herein G is either anti or sync.
5’- UTR (untranslated region) of mRNA (U–U–U–U tetrads, as well as G- and U-containing octads)
Promoter region of c-myc , c-kit and variant bcl-2 oncogenes.
inferior oncogenic expression & veiled binding target of telomere associated proteins ( TRF1, POT1) may help to combat the uncontrolled cellular growth by inducing apoptosis & inhibit the telomerase overactivity.
A methyl group from S-adenosyl-methionine (SAM) is transferred to the C5 position of the pyrimidine ring of cytosine residues by DNMTs in genomic CpG dinucleotides.
https://www.creative-biogene.com/Services/Drug-Discovery-Services/DNA-Methyltransferase-Screening-and-Profiling.html
P53 Tumor Suppressor Gene: Understanding P53 Based Dietary Anti Cancer Thera...Sheldon Stein
The P53 tumor suppressor gene which has been dubbed both the “Guardian of the Genome” (Lane 1992) and Science “Molecule of the Year”, is directly involved in the initiation of apoptosis and programmed cell death, to prevent an accumulation of abnormal cells. However apoptosis evasion is a characteristic feature of human cancers that promote tumor formation and progression (1). Presently, P53 is known to play a key role in practically all types of human cancers, and the mutation or loss of P53 gene function, can be identified in more than 50% of all human cancer cases worldwide.
This paper was uploaded on behalf of Professor Serge Jurasunas of Lisbon Portugal, www.sergejurasunas.com
The paper goes on to explain the role of the P53 gene and its relationship to Cancer and Apoptosis. It then elaborates on the importance of dietary agents can have a beneficial impact in cancer treatment, and provides a number of case studies. He addresses the importance of the P53 gene and DNA repair, as well as his use of Molecular Markers testing.
Professor Jurasunas believes:
We urgently need to put into clinical practice what we have discovered and learned. Targeting P53 and other genes remain one of the greatest challenges in the treatment of cancer. We have been working now for over 8 years with molecular markers as a diagnostic, prognosis, and follow up to treatment, selected the appropriate bioactive dietary compounds or anticancer agents, exceeding 1000 cases, blood tests, and successes. This may be an incentive for more doctors to venture into this new direction in order to achieve more beneficial results with their patient treatment, especially in cases where we can verify the ones who would be refractory to chemotherapy and have a poor response. It is always best to first check through patient testing, to determine whether or not chemotherapy would be beneficial.
Telomere structure stability, function in plant breedingSachin Dharwad
TELOMERE, TELOMERE STRUCTURE, ITS FUNCTION AND USE IN PLANT BREEDING. Telomere in plant breeding perspective. Case studies related to telomere in case of plant breeding. telomeres can be made use as markers in plant breeding.
Currently, around 11 million people are living with a tumour that contains an inactivating mutation of TP53 (the human gene that encodes p53) and another 11 million have tumours in which the p53 pathway is partially abrogated through the inactivation of other signalling or effector components. The p53 pathway is therefore a prime target for new cancer drug development, and several original approaches to drug discovery that could have wide applications to drug development are being used. In one approach, molecules that activate p53 by blocking protein–protein interactions with MDM2 are in early clinical development. Remarkable progress has also been made in the development of p53-binding molecules that can rescue the function of certain p53 mutants.
p53 has been described as “GUARDIAN ANGEL OF THE GENOME”
because it performs following mechanism:
DNA Repair
Cell growth arrest
Apoptosis (programmed cell death)
P53 is also known as cellular tumour antigen Ag, phosphoprotein
P53 or tumour suppressor p53.
P53 protein is encoded by TP53.
This presentation describes the structure and function of telomeres ,their role in various disease.The structure and function of telomerase is also described ,together with its possible role in therapy .
Different researches shows that, g-quadruplex- kind of tandem repeats are present in vivo,
Telomeres having tandem repeats of d(TTAGGG) , herein G is either anti or sync.
5’- UTR (untranslated region) of mRNA (U–U–U–U tetrads, as well as G- and U-containing octads)
Promoter region of c-myc , c-kit and variant bcl-2 oncogenes.
inferior oncogenic expression & veiled binding target of telomere associated proteins ( TRF1, POT1) may help to combat the uncontrolled cellular growth by inducing apoptosis & inhibit the telomerase overactivity.
A methyl group from S-adenosyl-methionine (SAM) is transferred to the C5 position of the pyrimidine ring of cytosine residues by DNMTs in genomic CpG dinucleotides.
https://www.creative-biogene.com/Services/Drug-Discovery-Services/DNA-Methyltransferase-Screening-and-Profiling.html
P53 Tumor Suppressor Gene: Understanding P53 Based Dietary Anti Cancer Thera...Sheldon Stein
The P53 tumor suppressor gene which has been dubbed both the “Guardian of the Genome” (Lane 1992) and Science “Molecule of the Year”, is directly involved in the initiation of apoptosis and programmed cell death, to prevent an accumulation of abnormal cells. However apoptosis evasion is a characteristic feature of human cancers that promote tumor formation and progression (1). Presently, P53 is known to play a key role in practically all types of human cancers, and the mutation or loss of P53 gene function, can be identified in more than 50% of all human cancer cases worldwide.
This paper was uploaded on behalf of Professor Serge Jurasunas of Lisbon Portugal, www.sergejurasunas.com
The paper goes on to explain the role of the P53 gene and its relationship to Cancer and Apoptosis. It then elaborates on the importance of dietary agents can have a beneficial impact in cancer treatment, and provides a number of case studies. He addresses the importance of the P53 gene and DNA repair, as well as his use of Molecular Markers testing.
Professor Jurasunas believes:
We urgently need to put into clinical practice what we have discovered and learned. Targeting P53 and other genes remain one of the greatest challenges in the treatment of cancer. We have been working now for over 8 years with molecular markers as a diagnostic, prognosis, and follow up to treatment, selected the appropriate bioactive dietary compounds or anticancer agents, exceeding 1000 cases, blood tests, and successes. This may be an incentive for more doctors to venture into this new direction in order to achieve more beneficial results with their patient treatment, especially in cases where we can verify the ones who would be refractory to chemotherapy and have a poor response. It is always best to first check through patient testing, to determine whether or not chemotherapy would be beneficial.
Telomere structure stability, function in plant breedingSachin Dharwad
TELOMERE, TELOMERE STRUCTURE, ITS FUNCTION AND USE IN PLANT BREEDING. Telomere in plant breeding perspective. Case studies related to telomere in case of plant breeding. telomeres can be made use as markers in plant breeding.
Currently, around 11 million people are living with a tumour that contains an inactivating mutation of TP53 (the human gene that encodes p53) and another 11 million have tumours in which the p53 pathway is partially abrogated through the inactivation of other signalling or effector components. The p53 pathway is therefore a prime target for new cancer drug development, and several original approaches to drug discovery that could have wide applications to drug development are being used. In one approach, molecules that activate p53 by blocking protein–protein interactions with MDM2 are in early clinical development. Remarkable progress has also been made in the development of p53-binding molecules that can rescue the function of certain p53 mutants.
p53 has been described as “GUARDIAN ANGEL OF THE GENOME”
because it performs following mechanism:
DNA Repair
Cell growth arrest
Apoptosis (programmed cell death)
P53 is also known as cellular tumour antigen Ag, phosphoprotein
P53 or tumour suppressor p53.
P53 protein is encoded by TP53.
This presentation describes the structure and function of telomeres ,their role in various disease.The structure and function of telomerase is also described ,together with its possible role in therapy .
Telomere is the end part of a chromosome.its length is maintained by na enzyme called telomerase.if telomerase is lacking,many genetic diseases may result( like progeria)
Telomere, Functions & Role in Aging & CancerZohaib HUSSAIN
Why senescence occurs in eukaryotic organisms?
The major function of telomere is to cap the ends of chromosomes and protect the chromosomes from RED mechanism. As cells divide, telomeres continuously shorten with each successive cell division. Telomerase provides the necessary enzymatic activity to restore and maintain the telomere length. The vast majority of tumour's activate telomerase , and only few maintain telomeres by ALT mechanism relying on recombination. Telomere and telomerase are the attractive targets for anti-cancer therapeutics
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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2. Cancer:
On the cellular and molecular levels, Cancer
is only a few diseases that result from faulty
or abnormal genetic expression caused by
changes in deoxyribonucleic acid (DNA).
a) The transcription of DNA into a single
strand of messenger ribonucleic acid
(mRNA) may be changed.
b) When abnormal mRNA exists, the
sequence of amino acids is changed,
resulting in abnormal protein synthesis
3. Telomeres :
Region in each end of chromosome,
composed of large noncoding
sequences of approximately 1000–
2000 (5’TTAGGG 3’) tandem base pair
and maintained by an enzyme called
telomerase, protect chromosome
ends from fusion.
4. Sheltering
• Human telomeres are bound
by a six-protein complex
called sheltering, comprised
of TRF1, TRF2, POT1, RAP1,
TIN2 and TPP1.
• Telomere-associated proteins
have a conserved function,
which is to assemble a
protective cap that ensures
telomeres are maintained at
an appropriate length and are
protected from being
recognized and processed as
broken DNA.
5. While replicating DNA, the eukaryotic
DNA replication enzymes cannot replicate
the sequences present at the ends of the
chromosomes these sequences and the
information they carry may get lost.
But the cell has an enzyme called
telomerase, which carries out the task of
adding repetitive nucleotide sequences to
the ends of the DNA. Telomerase
"replenishes" the telomere "cap.“ In
most multicellular eukaryotic organisms.
The steady shortening of telomeres with
each replication in somatic (body) cells
may have a role in senescence and in the
prevention of cancer.
6. Telomerase
Contains tow main composed :
1- Catalytic protein subunit (hTERT).
2- RNA subunit (hTR), RNA sequence in building repetitive
sequences of telomere.
7. • Note: Telomerase is inactive in normal somatic
cells. These cells, therefore, lose telomeres
over time and when telomere length reaches
below a critical limit, cells either senesce or
die.
• Several studies indicate that shorter telomeres
are a risk factor for cancer.
9. There are two general strategies to inhibit
telomerase activity in cancer cells:
1- Direct mechanism:
using compounds that directly cause telomerase
inhibition by inhibiting the activity of the catalytic
subunit (hTERT), the RNA template (hTR) or the
telomere structure.
2- Indirect mechanism:
blocking telomerase access to telomeres by using
G-quadruplexes stabilizers, or by inhibiting
binding of telomerase-associated proteins leading
to telomere uncapping and cell apoptosis.
10. GRN163L
• Which is known as IMETELSTAT and is a 13-nucleotide
sequence .
• The sequence of GRN163L
• (5’-palmitate TAGGGTTAGACAA- NH2-3’) targets the 13-
nucleotide region of the (hTR), preventing it from
forming an active complex with (hTERT). Because
telomerase inhibitors may require a period of
treatment to produce telomeres short enough to
trigger cancer cell death, telomerase inhibition therapy
may be most effective when used in conjunction with
conventional chemotherapies, radiation or other
targeted therapeutics.
11.
12. G-quadruplex
• Indirectly inhibit telomerase activity by blocking hTR binding.
• If telomeres could be stabilized using a G-quadruplex structure,
the cells could be prevented from infinite proliferation
characteristic of cancer inhibit telomerase activity.
• The three most commonly studied G-quadruplex stabilizing
agents are telomestatin, BRACO-19 and RHPS4
