This seminar presentation evaluated the association between metformin and/or statin treatment and key tumor parameters in prostate cancer. Biguanides like metformin and statins lower blood glucose and cholesterol. Treatment with these drugs has been linked to lower cancer risk and mortality. The objective was to analyze the direct effects of metformin, different statins, and their combination on cancer cell proliferation, viability, tumorsphere formation, and associated molecular pathways. Various experiments assessed these endpoints in prostate cancer cell lines treated with the drugs. The results showed that metformin and simvastatin alone and in combination inhibited cell proliferation and viability, and reduced tumorsphere formation and size. Analysis of gene and protein expression provided insights into the molecular mechanisms affected by the treatments. The conclusion
define the cancer, types of tumor cells, TNM classification, staging, cancer cells in different area, etiology, carcinogenesis, sign of cancer, diagnosis, prevention - radiation therapy, chemotherapy, surgical management
define the cancer, types of tumor cells, TNM classification, staging, cancer cells in different area, etiology, carcinogenesis, sign of cancer, diagnosis, prevention - radiation therapy, chemotherapy, surgical management
TNBC has had the bearings of a protagonist for Immuno oncology in breast ever since the discovery of its molecular subtypes. Recent FDA approvals of Immunotherapies and some of the ASCO 2020 highlights hold the promise of an more optimistic outlook for drug development for this cancer. Finally I close with some thoughts on ensuring patient safety and centricity in the changed circumstances of the post Covid times.
Cancer chemoprevention with dietary phytochemicalsdegarden
Young-Joon Surh
Chemoprevention refers to the use of agents to inhibit, reverse or retard tumorigenesis.
Numerous phytochemicals derived from edible plants have been reported to interfere with a
specific stage of the carcinogenic process. Many mechanisms have been shown to account
for the anticarcinogenic actions of dietary constituents, but attention has recently been
focused on intracellular-signalling cascades as common molecular targets for various
chemopreventive phytochemicals.
How to Understand and Treat Cancer with Molecular MarkersSheldon Stein
How to Understand and Treat Cancer with Molecular Markers by Professor Serge Jurasunas, N.D., M.D. (Hom)
This is the first in a series of presentations on Naturopathic Oncology.
For More Information Visit: www.sergejurasunas.com
TNBC has had the bearings of a protagonist for Immuno oncology in breast ever since the discovery of its molecular subtypes. Recent FDA approvals of Immunotherapies and some of the ASCO 2020 highlights hold the promise of an more optimistic outlook for drug development for this cancer. Finally I close with some thoughts on ensuring patient safety and centricity in the changed circumstances of the post Covid times.
Cancer chemoprevention with dietary phytochemicalsdegarden
Young-Joon Surh
Chemoprevention refers to the use of agents to inhibit, reverse or retard tumorigenesis.
Numerous phytochemicals derived from edible plants have been reported to interfere with a
specific stage of the carcinogenic process. Many mechanisms have been shown to account
for the anticarcinogenic actions of dietary constituents, but attention has recently been
focused on intracellular-signalling cascades as common molecular targets for various
chemopreventive phytochemicals.
How to Understand and Treat Cancer with Molecular MarkersSheldon Stein
How to Understand and Treat Cancer with Molecular Markers by Professor Serge Jurasunas, N.D., M.D. (Hom)
This is the first in a series of presentations on Naturopathic Oncology.
For More Information Visit: www.sergejurasunas.com
Protocol for the Treatment of Prostate CancerSheldon Stein
Professor of Naturopathic Oncology, Serge Jurasunas explains the nature of prostate cancer and outlines the unique protocols he utilizes at his Lisbon clinic. Additional information is available on his website: www.sergejurasunas.com
In this webinar, Dr. Azad discusses colorectal cancer recurrence. She addresses things to do to help reduce the risk of recurrence, in addition to what steps should be taken if colon or rectal cancer returns.
A Review on Protein and Cancer ; Etiology, Metabolism and ManagementAbdulrahman Ragab
Altered metabolism is one of the hallmarks of cancer cells. Cell cycling and protein synthesis are both key
physiological tasks for cancer cells. In recent years, interest has been renewed as clear that many of the signaling
pathways that are affected by genetic mutations and the tumor microenvironment have a profound effect on core
metabolism of cancer cells. Metabolic alterations in cancer cells are numerous and include aerobic glycolysis,
reduced oxidative phosphorylation and the increased generation of biosynthetic intermediates needed for cell
growth and proliferation. Furthermore, accelerated protein turnover seen in many cancer patients and whole body
protein turnover is increased with advancing stage of disease. Cancer cells alter their consumption and the way
they process sugars, fats, amino acids and other energy sources to satisfy the demands of continuous proliferation.
The possible effects of specific amino acid, methionine, asparagine, arginine, tyrosine and glutamine, etc. on
protein cancer metabolism are discussed. Evidences confirm a contribution of proteins in all cancer stages and
describe metabolism of protein in cancer and how amino acids can be targeted to management or initially prevent
different types of cancer. Several studies suggest that people who eat more red meat have higher risk for
developing colorectal cancer than those who eat less red meat, but avoiding processed meats is even more
important for cancer prevention. In this review we summarize the role of proteins in cancer etiology, metabolism,
its complication, prevention and treatments.
Bill Faloon on Anti-Aging Drugs at DaVinci 50 Conference, 2021maximuspeto
In this presentation, Bill Faloon gives an update on the prospects of anti-aging drugs at the DaVinci 50 Masters Conference in Key Largo, Florida on April 29th, 2021.
BREAST CANCER DRUG DISCOVERY & RESEARCH FROM VARIOUS WELL KNOWN ETHNOMEDICINAL PLANTS. ESTABLISHED PHYTOMOLECULES WITH CHEMOPREVENTIVE, ANTICANCER ACTIVITIES WITH MINIMAL TOXICITY.
Protocol for the Treatment Prostate Cancer - Dr Serge JurasunasSheldon Stein
Dr. Serge Jurasunas shares his Prostate Cancer Protocol in this paper, explaining the nature and treatment of Prostate Cancer from a Naturopathic Oncology Perspective. Professor Jurasunas is located in Lisbon Portugal and has lectured worldwide throughout his 50 years as a clinician.
He explains what can be done about the #1 cause of death in males even before lung cancer and what can be done, from the new perspective of Naturopathic Oncology.He offers an example, explains diagnostic procedures with Molecular markers and addresses detox, supplements and treatment.
Further information may be found in his new book, Health and Disease Begin in the Colon" and in his Blog: Naturopathiconcology.blogspot.com .
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Clinical, cellular and molecular evidence of the additive antitumor effects of biguanides and statins in Prostate cancer
1. Presented by Luis Feria Prado and Isabel Cristina Escobar Franco
Molecular Biology Seminar
UPB – Third semester
2. PROSTATE CANCER
u Prostate is a glandular organ of the male reproductive system,
responsible to produce most of the seminal fluid.
u Benign and malignant changes increase with age.
u Prostate cancer is one of the leading causes of death among the
male population throughout the world. It is caused by the
uncontrolled growth of prostate cells.
3. BIGUANIDES AND STATINS
u Biguanides are a group of oral type 2 diabetes drugs that work by preventing the
production of glucose in the liver, improving the body’s sensitivity towards insulin and
reducing the amount of glucose absorbed by the intestines.
u Statins are a group of drugs that help lower the amount of cholesterol and triglycerides in
the blood.
u Treatment of patients with drugs as biguanides and statins has been associated to a lower
cancer-specific death and even lower risk to develop different cancer types.
4. OBJECTIVE
u To evaluate:
1. The putative in vivo asociation bewteen metformin and/or statins treatment and key
tumor and clinical parameters
2. The direct effects of different biguanides (metformin/buformin/phenformin), statins
(atorvastatin/simvastatin/lovastatin), and their combination, on key funtional
endpoints and associated signalling mechanisms.
5. Materials and Methods
CELL PROLIFERATION AND CELL VIABILITY
u Cells were seed in 96-well plates at a density of 3000 to 5000 cell/well and serum-
starved for 24 hours. Then, cell proliferation/viability was evaluted every 24 hours
until 72 hours.
6. Materials and Methods
TUMORSPHERES
FORMATION
u In this study, 2000 cells were
seeded per well in 24-well fixation
plates, metformin, simvastatin, and
combined treatment were added
while the cells were being plated
and refreshed every three days, the
tumorphere formation assay was
carried out.
u Carried out in representative cell
lines of cells with androgen-
dependent prostate cancer (LNCaP)
and a hormone-refractory
biomarker (PCa-3) where the
number and size of the
tumorspheres were determined
after 14 days of incubation.
7. Materials and Methods
RNA EXTRACTION, RETROTRANSCRIPTION, AND
QUANTITIVE PCR
u RNA from PCa Cells
was isolated after 24
hours of incubation
with metformin,
simvastatin, and
combined treatment.
Total RNA was
retrotranscribed. After,
the quantitive RT-PCR
was used to measure
expression levels of
the transcripts of
interest.
8. Materials and Methods
WESTERN BLOT ANALYSIS
Proteins of interest were extracted after 12 hours of incubation with metformin,
simvastatin, and combined treatment, then they were separated into
10% polyacrylamide gels and transferred to nitrocellulose membranes, which
were previously incubated with specific primary antibodies.
13. DISCUSSION
Author What they said Agree or not?
Danzing Mr, et al Synergism between metformin
and statins to modify the risk
of biochemical reccurrence
after radical prostatectomy in
men with diabetes.
Agree
Sarmento Cabral Metformin reduces prostates
tumor growth in a diet-
dependent manner,
modulating multiple signalling
pathways.
Agree
Wang ZS, et al Combination of metformin and
atorvastatin caused stronger
inhibition on tumor growth.
Agree
14. CONCLUSIONS
u The department of molecular biology is both multidisciplinary and interdisciplinary, through
which it is possible to do multiple investigations on fundamental aspects of diseases that affect
our society, this is fundamental in medicine due to the impact that molecular biology has both
at the level of developing therapies that will generally improve the state of health of society as
well as education and sustainability of a country by improving job expectations.
u The use of molecular biology techniques allows a detailed and comparative analysis of the
parameters of a clinical study to be carried out, which facilitates the rapid obtaining of results,
allowing significant advances in medical practice.
u In this study, molecular biology allows the knowledge of new alternatives to prostate cancer and
the verification of possible recurrences to the disease, through genetic and molecular analysis.
