Neoplasia refers to abnormal cell growth or tumors. There are two main types of neoplasia - benign and malignant. Benign tumors remain localized and are non-invasive, while malignant tumors can invade surrounding tissues and spread to distant sites through lymphatic vessels or blood vessels in a process called metastasis. The development of cancer is a multistep process that involves genetic mutations that activate oncogenes and inactivate tumor suppressor genes, resulting in uncontrolled cell growth and division. Key hallmarks of cancer include self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and ability to invade and metastasize.
Dear all, Pathologybasics is out with a new series of power point presentations on general Pathology.. Following is link presentation on seventh and the most difficult to understand chapter of robbins.. chapter 7,neoplasia. Any suggestions/feedback/constructive criticism are welcome on facebook.com/pathologybasics or pathologybasics@gmail.com
Dear all, Pathologybasics is out with a new series of power point presentations on general Pathology.. Following is link presentation on seventh and the most difficult to understand chapter of robbins.. chapter 7,neoplasia. Any suggestions/feedback/constructive criticism are welcome on facebook.com/pathologybasics or pathologybasics@gmail.com
UNDERSTANDING OF CHEMICAL CARCINOGENESIS:CURRENT AND FUTURE PERSPECTIVES
Carcinogenesis refers to the process by which a normal cell is transformed into a malignant cell and repeatedly divides to become a cancer
Chemicals which initiate this process is called chemical carcinogens
Chemicals which increase the effectiveness of carcinogens is called co-carcinogens
CLASSIFICATION OF CHEMICAL CARCINOGENS
MECHANISM OF ACTION
STAGES OF CARCINOGENESIS
ROLE OF PROTO-ONCOGENES AND TUMOR SUPPRESSOR GENES
ACTIVATION OF PROTO ONCOGENES
INACTIVATION OF TUMOR SUPPRESSOR GENE
OXIDATIVE STRESS IN CARCINOGENESIS
ROS can be produced from both endogenous and exogenous sources
Attack both purine and pyrimidine bases, as well as the deoxyribose backbone
Induces DNA damage which includes single or double-strand breakage, deoxyribose modification, and DNA cross-link
If DNA damage is not properly repaired it may result in mutation which leads to cancer
BIOMARKERS
REGULATORY BACKGROUND
OECD guidelines
451- Carcinogenecity studies
453- Combined chronic toxicity/carcinogenecity
ICH guidelines
S1A- Guideline on the need for carcinogenicity studies of
pharmaceuticals
S1B- Testing for carcinogenicity of pharmaceuticals
S1C- Dose selection for carcinogenicity studies of pharmaceuticals
A brief description on cancer.Cancer – a large group of diseases characterized by the uncontrolled growth and spread of abnormal cells,Some topics are genesis of cancer,types of cancer,causes of cancer like Heredity,Immunity,Chemical,Physical,Viral Bacterial,Lifestyle.
,sign&symptom:*Change in bowel habits or bladder function,*Sores that do not heal,*Unusual bleeding or discharge,*Thickening or lump in breast or other parts of the body,Indigestion or trouble swallowing,*Recent change in a wart or mole,Nagging cough or hoarseness,
diagnosis and staging,treatment:Surgery,Radiation,Chemotherapy,Immunotherapy,Hormone therapy, Gene therapy,side effect of cancer treatment,prevention of cancer
The study of disease transmission
By and large, the frequency of disease is higher in men than in ladies and higher in industrialized areas and countries.
Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body. Here in this presentation cancer and its characteristics are discussed along with anti-cancer drugs, in brief.
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
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.
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
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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- 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
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
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
2. DEFINITION
• Neo = New ; Plasia= growth
• Abnormal mass of tissue as a result of abnormal growth
or multiplication of cell.
• Growth of neoplastic cell persist in excessive manner
even after the stimulus that evoked the changes stop.
3. CLASSIFICATION OF NEOPLASIA
2 types :
BENIGN MALIGNANT
- Suffix = –oma to cell type which the tumor arise
- Eg: fibrous tissue – fibroma
Bone tissue – Osteoma etc.
- Suffix: –Sarcoma =
Malignant tumor (Cancer) that arises from
transformed cells of mesenchymal origin
Eg: Chondrosarcoma
–Carcinoma= Malignant tumor from epithelial origin
Eg: Adenocarcinoma
- Microscopic and gross characteristic relatively inoncent - Invade and destroyed adjacent structure and spread to distant
site.(metastasize).
- Remain localized • Will invade other neighbouring tissues & m etastasize (Lymph &
BV)
- Amendable to local surgical removal • Lower prognosis than benign tumors
5. TYPE BENIGN MALIGNANT
DIFFERENTI
ATION @
ANAPLASIA
- Well differentiated
- Closely resemble their normal
counterpart.
- Mitosis usually rare
- Nuclei remain at basal layer
but usually enlarged.
- Poor differentiate@anaplastic
- Loss of structure and function
- Plemorphism, hyperchromatic,
increase nuclear-cytoplasmic
ration, giant cell.
- Mitosis often numerous.
- Loss of polarity
6. LOCAL
INVASION
- Remain localized at site of
origin
- Does not have the capacity
to infiltrate,invade or
metastasize.
- Encapsulated.
- Grow by progressive
infiltration,invasion,
destraction and penetration of
surrounding tissue.
- Do not develop well of define
capsule.
- Hemmorhage and necrosis.
- Ulceration.
7. METASTASIS - Absent - Metastasize
- Factor increase of metastasis
• Larger of tumor
• Older of tumor
• Poorly differentiated
- Disseminate by 3 pathways
• Seeding body cavity
• Lymphatic spread
• Hematogenous spread
9. Method Explanation
History and physical
examination
What the health care worker learns from talking to the patient and
through direct examination may give clues to the presence of a
neoplasm. Signs and symptoms such as weight loss, fatigue, and
pain may be present. A mass may be palpable or visible.
Radiographic
technique
The use of plain films (x-rays), computed tomography (CT),
magnetic resonance imaging (MRI), mammography, and
ultrasonography (US) may be very helpful to detect the presence
and location of mass lesions. The findings from these methods
may aid in staging and determination of therapy.
Genetic
Testing
Genetic markers include chromosomal alterations (translocations,
deletions, duplication, etc.); specific gene defects; single
nucleotide polymorphisms, and gene rearrangements. Detection
of specific genes (such as BRCA-1 for breast cancer) may
suggest an increased risk for some malignancies.
10. Cytology Methods that sample cells can be simple and cost-effective and
minimally invasive. A good example is the Pap smear for diagnosis of
cervical dysplasias and neoplasms. Cells exfoliated into body fluids may
also be examined. Fine needle aspiration (FNA) can be used to sample a
variety of mass lesions.
Tissue
biopsy and
surgery
Methods that sample small pieces of tissue (biopsy) from a particular
site, often via endoscopic techniques (such as colonoscopy, upper
endoscopy, or bronchoscopy) can often yield a specific diagnosis of
malignancy. At surgery, portions of an organ or tissue can be sampled, or
the diseased tissue(s) removed and examined in surgical pathology to
determine the stage and grade of the neoplasm.
Autopsy Sometimes neoplasms are not detected or completely diagnosed during
life. The autopsy serves as a means of quality assurance for clinical
diagnostic methods, as a way of confirming diagnoses helpful in
establishing risks for family members, as a means for gathering statistics
for decision making about how to approach diagnosis and treatment of
neoplasms, and to provide material for future research.
11. Laboratory
analyses
General findings such as anemia, enzyme abnormalities (such as an
increased alkaline phosphatase), and hematuria or positive stool
occult blood are helpful to suggest further workup. Tumor markers in
serum such as carcinoembryonic antigen (CEA), alpha-fetoprotein
(AFP), or human chorionic gonadotropin (HCG) can be performed.
Unfortunately, they are not all that specific or sensitive, particularly
when applied as screening tests to a general population. More specific
testing, such as measurement of prostate specific antigen (PSA)
levels, may help to determine the presence of specific neoplasms, but
such tests are not perfect screening tools in a general population.
12. Spread of tumour:
Direct spread Distant spread
-means tumour spreading and involving the
tissues around the tumour.
- As example,if the primary tumours arises
from the bronchus,this tumour can spread
to the lung tissue.
-means the tumour from one site (primary)
is now transferred to a distant site
(secondary).
-This process called metastasis.
-There are three ways on how tumour can
metastasise to distant sites. (refer table in
next slide)
13. Distant spread
By Invasion of
lymphatic
-Lymphatic are channels lined by endothelium-drain lymph from
tissues to lymph nodes (regional lymphnodes)
-Ex : Breast carcinoma-enlarged axillary lymph nodes
-Usually cancers that spread via lymphatic are *CARCINOMAS.
14. Hematogenous
spread
-Spread via blood channels.
-VEINS are more frequently invaded than arteries because:
a-thinner walls
b-lower pressure
c-slower blood flow
-Neoplasm that spread via blood channels usually *SARCOMAS
15. Through body cavity It can either spread via:
1-coelomic cavity
-tumours seeding over surfaces in peritoneal,pleural and
pericardial spaces.
-Ex:Carcinoma in ovary of one side spreading to the other ovary
or to other organs in peritoneum
2-Cerebral spinal fluid
-occurs for cancers in the brain and spinal cord.
16.
17. Grading
(Differentiation)
• Made by Pathologist
• Microscopic appearance
• Assesment depends on :
Mitotic activity
Nuclear size &
pleomorphism
The differentition
• Degree of diff. indicates :
Prognosis
Appropiate treatment
Grading of Malignant Neoplasms
Grade Definition
I Well differentiated
II
Moderately
differentiated
III Poorly differentiated
IV Nearly anaplastic
Eg :
Adenocarcinoma
18. Staging
(Spreading)
• Made by Surgeon
• Gross anatomical appearance
Eg : lung carcinoma
Staging of Malignant Neoplasms
Tis In situ, non-invasive
T Refers to Primary tumors
T1
Small, minimally invasive within primary
organ site
T2
Larger, more invasive within the primary
organ site
T3
Larger and/or invasive beyond margins of
primary organ site
T4
Very large and/or very invasive, spread to
adjacent organs
N Refers to Lymph Nodes
N0 No lymph node involvement
N1 Nearby lymph node involvement
N2 Regional lymph node involvement
N3 More distant lymph node involvement
M Refers to anatomical distance metastases
M0 No distant metastases
M1 Distant metastases present
19. Although benign tumours are confined
to their site of origin, they may cause
clinical problems due to:
Pressure on adjacent tissues
(e.g. benign meningeal tumours
causing epilepsy)
Obstruction to the flow of fluid
(e.g. benign epithelial tumour
blocking a duct)
Production of a hormone (e.g.
benign thyroid tumour causing
thyrotoxicosis)
Transformation into a
malignant neoplasm (e.g.
adenormatous polyp progressing
to an adenocarcinoma)
anxiety
20.
21. Morbidity and mortality associated with
malignant tumours:
Pressure on and destruction of
adjacent tissue
Formation of secondary tumours
(metastases)
Blood loss from ulcerated
surfaces
Obstruction of flow (e.g.
malignant tumour of the colon
causing intestinal obstruction)
Production of a hormone (e.g.
ACTH and ADH from some lung
tumours)
Other paraneoplastic effects
causing weight loss and debility
22. Cachexia (wasting syndrome)
• Progressive loss of body fat and lean body mass
accompanied by profound weakness, anorexia, and
anemia.
• The origins of cancer cachexia are obscure.
• Cachexia is not caused by the nutritional demands of the
tumor.
• Results from the action of soluble factors such as
cytokines produced by the tumor or host
• Cachexia- the loss of
1.skeletal muscle,
2.adipose tissue
3.immunological competence.
23. Paraneoplastic Syndrome
• Symptoms complexes in cancer-bearing
patients that cannot be explained by :-
• local or metastatic spread
• elaboration of hormones indigenous to tissue
• May represent early manifestations of tumor
• May represent significant clinical problems
• May even be fatal
• Occurs in about. in 10% of patients with cancer
• They are syndromes involving nonmetastatic
systemic effects that accompany malignant
disease.
24. Paraneoplastic syndromes
Syndrome Mechanism Example
Cushing
Syndrome
Secretion of ACTH-
like substance
Lung small cell anaplastic
(oat cell) carcinoma
Hypercalcemia
Parathyroid hormone-
like substance
Lung (squamous cell)
carcinoma
Hyponatremia
Inappropriate ADH
secretion
Lung small cell anaplastic
(oat cell) carcinoma
Polycythemia
Erythropoietin-like
substance
Renal cell carcinoma
Trousseau
Syndrome
Hypercoagulable state Various carcinomas
Hypoglycemia Insulin-like substance
Various carcinomas and
sarcomas
Carcinoid
Syndrome
5-hydroxy-
indoleacetic acid (5-
HIAA)
Metastatic malignant
carcinoid tumors
25. • From team Omega
It is a process by which normal cells are transformed into cancer cells
27. Carcinogenesis:Amultiple step process
• Carcinogenesis= A multistep process resulting from the accumulation of
multiple genetic alteration , give rise to transform phenotype .
MUTATION
• Mutation provide cells of precursor lesion with a selective advantage
(Darwinin Selection) . Once initiate, cancer continue undergoes darwinian
selection.
• Over period of time, tumors become more aggressive and acquire greater
malignant potential (Tumor Progression, not represent simply by an
increase in tumor size) .
Non neoplastic
precursor
lesion
Cancer
28. •Some mutation may lethal. Others may spur cell growth by affecting proto-oncogenes or
cancer suppressor genes.
29. Hallmarks of cancer
• Self sufficiency in growth signals
• Insensitivity to growth inhibitory signals
• Evasion (Immortalization) of cell death
• Limitless replicative potential
• Development of sustained angiogenesis
• Ability to invade and metastasize
30.
31. SELF SUFFICIENCY IN GROWTH FACTORS
1.Growth factors:
Normal cells require growth stimulation by growth factors to undergo proliferation.
•Many cancer cells acquire growth self-sufficiency by acquiring ability to synthesize the
same growth factors which they are responsive.
•Another mechanism by which cancer cells acquire growth self-sufficiency is by
interaction with stroma. In some cases, tumor cells send signals to activate normal cells in
the supporting stroma which in turn produce growth factors that promote tumor growth .
2. Growth factor receptors and non-Receptor Tyrosine Kinases
•Mutant receptor proteins deliver continuous mitogenic signals to cells even in the absent
of growth factor in the environment .
•Mutation is overexpression of growth factor to level which growth factor receptor which
render cancer cells hyperresponsive to level of the growth factor that would not normally
trigger proliferation.
32. *** RAS
•Most commonly mutated proto-oncogene in human tumor.
•Normal RAS protein flip back and forth between an excited signal-transmitting state and not active
state.
•Activated RAS stimulates downstream regulators of proliferation by two distinct pathway that
converge on the nucleus and flood it with signal for cell proliferation.
•Mutational activation of these massengers to the nucleus can mimic growth promoting effect of
activation RAS .
•Activating mutation RAS as well as it downstream signaling molecules are very common in wide
variety of tumor .
•Also mutation in RAS mimicked by loss-of—function mutations in the GTPase-activating
proteins with a failure to stimulate GTP hydrolysis and thereby restrain normal RAS protein.
33.
34. INSENSITIVITYTO GROWTH INHIBITORYSIGNALS
• Products of tumor suppresor genes apply brakes to cell proliferation. Disruption of such
genes renders cells refractory to growth inhibition and mimics the growth-promoting
effect on oncogenes .
RB GENES: Governor of the cell cycle
o RB gene product is a DNA-binding protein that expressed in every cell type examined ,
exists in active hypophosphorylated state and an inactive hyperphosphorylated stated.
o RB exerts antiproliferative effect by controlling regulations of G1/S checkpoint (mitosis
cycle) , the portal through which cell must pass before DNA replication commences .
35. o RB in active form, hypophosphorylation bind to E2F transcription factors. This
interaction prevents transcription of genes like cyclin E that are needed for DNA
replication, and so the cell arrested in G1.
o Growth factor signaling leads to cyclin D expression, activation of the cyclin D-CDK4/6
complexes, inactivation of RB by phosphorylation , and thus release E2F .
o Loss of cell cycle control is fundamental to malignant transformation.
o All cancers have disabled G1 checkpoint due to mutation either RB or genes that affect
RB function such as cyclin D, CDK4, and CDKIs
36. TP53 GENE: Guardian of the genome
• The p53-encoding tumor suppressor gene, TP53 , one of the most commonly mutated
genes in human cancers.
• The p53 proteins prevents neoplastic transformation by three interlocking mechanisms :
• Activation of temporary cell cycle arrest (quiescence ) when DNA damage and assist DNA repair
genes.
• Induction of permanent cell cycle arrest (Senescence) when DNA damage genes cannot be
repaired
• Or triggering of programmed death (apoptosis)
• Rb sense external signal, p53 is central monitor of internal stress, directing stress to one
of the three mechanism .
• Example of stresses that trigger the p53 responses pathway including anoxia,
inappropriate oncoprotein activity and damage to integrity of DNA .
43. • Metastatic cascade subdivided into :
Invasion of ECM
Vascular dissemination and homing of tumor
cell
• 2 types of ECM :
basement membrane both are composed
Interstitial connective tissue of collagen, glycoprotein
and proteoglycans
44.
45. Loosening of intracellular junctions occurred because
of E-cadherin lost its function (keep cells together &
transmit antigrowth signal) by :
• mutational inactivation of E-cadherin gene
• activation of β-catenin gene
(regulating the coordination of cell–cell adhesion and gene
transcription.)
• inappropriate expression of SNAIL & TWIST
transcription factors (Give Metastatic Ability)
Degradation of basement membrane & interstitial
connective tissue
Tumor cells secrete proteolytic enzymes / induce stromal
cells elaborate proteases (cathepsin D, urokinase
plasminogen activator, MMPs) tumor cell invasion
remodel insoluble components of
basement membrane & interstitial
matrix + release ECM-sequestered GF
46. Changes in attachment of tumor cells to ECM
Loss in adhesion in normal cells apoptosis ; but
tumor cells are resistant to apoptosis, instead caused
matrix modification by cleaving of basement membrane
proteins (collagen IV, laminin) by MMP generates
novel sites (bind to tumor cells’ receptors) migration
Migration is directed by tumor cell-derived cytokines
(autocrine motility factors) + cleaved products (collagen &
laminin) + some growth factors + stormal cells (HGF/SCF)
47. • In circulation, tumor cells vulnerable to destruction by host immune cells – it will form emboli & adhere to
the circulating leukocytes = protection
• Site of extravasation & the organ distribution of metastases based on location of primary tumor and its
vascular or lymphatic drainage. This tropism influences by :
i. Expression of adhesion molecules by tumor cells are preferential to the ligand on endothelium of
target organ
ii. Expression of chemokines (participate in chemotaxis of leukocytes) & their receptors – tumor cells use
similar tricks to home in on tissue
iii. When reach the target colonize the site (tumor cells dependent on a receptive stroma for growth)
• Tumor cells are inefficient in colonizing of distant organs and concept of dormancy refer to prolonged
survival of micrometastases w/o progression
48. Etiology of cancer: carcinogenic events
• Chemical carcinogens
- direct-acting
- Indirect-acting
• Radiation carcinogens
• Viral and microbial oncogenesis
49. CHEMICAL
Direct-acting agents Indirect-acting agents
• Does not require metabolic
conversion to become carcinogenic
• Require metabolic conversion to
become active carcinogenic
• Weak carcinogens • E.g: polycyclic hydrocarbons,
aromatic amines, azo dyes
• E.g: alkylating agents
50. Chemical carcinogens and the tumours
with which they are associated:
Chemical Tumor Comments
Polycyclic hydrocarbon Lung cancer Present on fossil fuels
Aromatic amines Skin cancer
Bladder cancer
Rubber and dye workers
Nitrosamines Gut cancer Proven in animals
Azo dyes Bladder n liver cancer Proven in animals
Alkylating agents
e.g: cyclophosphamide
Leukemia Small risk in human
Other organic chemicals
e.g: vinyl chloride
Liver angiosarcoma PVC manufactures
Arsenic compounds Skin cancer No longer a common
event
51. RADIATION
UV light, x rays, nuclear fission
• Ionizing radiation
- cause chromosome breakage, translocation, less
frequency, point mutation
- Lead to genetic damage n carcinogenesis
- E.g: chronic lymphocytic leukemia , Thyroid carcinoma
(children)
• UV radiation
- Damage DNA by forming pyrimidine dimer
- Cause skin cancer (melanoma, SCC, BCC)
- Risk factor: fair-skinned people
52. •Initiation
- May cause the mutational activation of an oncogen (RAS)
•Promoter
- non-mutagenic, non-tumorigenic
- Induces cell proliferation
- E.g: phorbol esters, hormones, phenols, certain drugs
59. Xeroderma Pigmentosum
• Autosomal recessive
• Defects in NER genes = (DNA repair mechanism )
• Due to inability to repair DNA damage induced by UV
• 200 X increase risk of skin cancer
60. VIRAL and MICROBIAL
RNA virus:
•Cause by Retrovirus: Human T Cell Lymphotropic Virus-1
(HTLV-1)
•a/w T cell leukemia/lymphoma
•Has tropism for CD4 Tcells target for neoplastic
transformation
•Transmission: sexual intercourse, blood products or
breastfeedin
61. DNA viruses:
• Human papilloma virus
• Epstein-Barr virus
• Hepatitis B virus
• Kaposi Sarcoma herpes virus