Malignant disease 17/10/22 Flashcards

Question

What is angiogenesis?

Answer 1

Angiogenesis is how the body forms new blood vessels. This is a normal part of growth and healing.

Answer 2

1) Cancer cells need oxygen and nutrients to grow. 2) Tumours will send signals (pro-angiogenic factors such as VEGF/FGF) that exceed the anti-angiogenic factors. 3) This results in the angiogenic process proceeding which means more blood vessels develop around the tumour to sustain growth.

Answer 3

The spread of cancer cells from the place where they first formed to another part of the body.

Answer 4

1) Direct 2) Lymphatic 3) Venous 4) Transcoelomic 5) Cerebrospinal fluid 6) Arterial routes Direct - tumour grows into structures and tissues surround it. For example, mediastinal tumour surrounding and compressing the superior vena cava. Lymphatics - tumours spread through the lymphatic system. For example, carcinoma of breast first spreads to the local axillary lymph nodes. Venous - tumours spread through the veins. For example, sarcomas commonly spread this way and some tumours can grow in a vein causing its obstruction (renal cell carcinoma). Arteries - spread of tumours through arteries. This is not common as they are difficult to penetrate but can occur in later stages of metasistic spread. Transcoelomic - spread of a tumour through a body cavity. For example, gastric carcinoma cells seeding through the peritoneal cavity to cause ovarian cancer. CSF - spread of a tumour through the CFS fluid in the nervous system. This can cause brain cancer.

Answer 5

1) The cancer will grow at the primary site and infiltrate the surrounding connective tissue; this may necessitate breaking through a basement membrane and the connective tissues nearby. It may also have to overcome inhibitor substances to the enzymes that it produces to break down these connective tissue proteins. 2) It is only then that it can reach the lymphatic and blood vascular channels, which are an important route for dissemination. The vessel wall is traversed and the tumour cells must detach to float in the blood or lymph and hope to evade any immune cells that might destroy them. 3) They must lodge in the capillaries at their destination, attach to the endothelium again, and penetrate the vessel wall to enter the perivascular connective tissue where they finally proliferate to produce a tumour deposit and angiogenesis can occur. Even here, the local environment is important in dictating whether the cells will grow.

Answer 6

The tumour edge is irregular, due to infiltrative growth. The cut surface is variegated, due to haemorrhage and necrosis within tumour. Evidence of secondary spread in the draining of lymph nodes or adjacent structures may obviously be infiltrated.

Answer 7

The tumour edge is smooth, due to expansile growth, may be encapsulated. The cut surface is bland and homogeneous. No sign of secondary spread.

Answer 8

Resemblance to original tissue is often poor. Cell shape and size is highly variable (pleomorphic). Mitotic figures are often numerous and frequently abnormal, e.g., tripolar mitoses. Invasion of blood vessels/lymphatics/perineural space often present. Dysplasia in adjacent tissues is sometimes present (e.g., cervix, skin, stomach).

Answer 9

Resemblance to original tissue is good. The cell shape and size are fairly uniform. Mitotic figures are often very few and all normal. No invasion of blood vessels/lymphatics/perineural space. No dysplasia in adjacent tissues.

Answer 10

The type of tumour - this can impact how easily the tumour can be treated or not The grade of tumour - this can determine how severe the tumour is based on histological appearance The stage of the disease - if the disease has metastasised this can result in a worse prognosis and how large the tumour is Tumour markers - can diagnosis a cancer

Answer 11

This cancer begins in the skin or in tissues that line or cover internal organs.

Answer 12

This is the general term for a broad group of cancers that begin in the bones and in the soft tissues.

Answer 13

This is a type of cancer that affects the lymphatic system, a network of vessels and glands found throughout your body.

Answer 14

Myeloid leukaemia, lymphocytic leukaemia, lymphomas, and myeloma.

Answer 15

Germ cells - malignant teratoma, seminoma/dysgerminoma Placenta - choriocarcinoma Embryonal - Embryonal cell tumours

Answer 16

The cause of something.

Answer 17

Genetic material Age Geographical and racial factors Environmental factors Carcinogens

Answer 18

1) Some cancers can be inheritable (breast cancer/ovarian cancer - BRCA1 and BRCA2) 2) An inability of the body to repair DNA 3) Chromosomal abnormalities 4) Carcinogens can cause mutations 5) DNA from cancerous cells when injected into healthy cells can make those cells cancerous

Answer 19

People are living longer than ever and are alive longer to be exposed to more carcinogens. This exposure and the fact replication has occurred more and age-related hormone and metabolic changes have occurred there is a higher chance of cancer developing.

Answer 20

There is a higher incidence of melanoma in white Australians due to the lack of pigment in their sin and therefore increased UV light damage. This is both a geographical and racial factor which has contributed towards the cancer.

Answer 21

Exposure to asbestos and smoking can cause lung cancer, even in a bystander. Exposure to B-naphthylamine, which may occur in the rubber and dye industries, increases the risk of transitional cell tumours of the bladder. Exposure to vinyl chloride in the plastic industry enhances the development of liver angiosarcoma (malignant tumour of blood vessels). Other environmental factors such as diet, lifestyle, and weight can also cause cancer. Diets high in red meat can increase risk of stomach cancer. Being overweight can increase the risk of colon and breast cancer and around 17,000 cases of cancer a year in the UK is linked to excess weight. Lifestyle factors such as smoking, drinking alcohol, occupational hazards, sunbeds and sun exposure.

Answer 22

Cancer caused by carcinogens can sometimes be in development for 10-15 years therefore giving a direct aetiological factor can be hard. 1) Chemical carcinogens - chemicals can act like initiators or promotors. Certain chemicals can be both a promotor and initiator and this would result in a cancer, some chemicals are only an initiator or a promotor and therefore two chemicals may be needed to cause cancer and there could be years between these. For example, (initiation) B-Naphthylamine enters the body mainly via the respiratory system and is inactivated by conjugation with glucuronic acid. After excretion in the urine, it is activated again due to the action of urinary glucuronidase (promotor), which splits the conjugate releasing the active molecule. Its carcinogenic effects are hence confined to the urinary tract where it causes transitional cell tumours. 2) Radiation - ionising radiation includes electromagnetic rays, such as UV light, X-rays and y-rays, and particulate radiation, such as a particles, B particles, neutrons and protons. All of these are carcinogenic. As ionising radiation passes through tissue, it interacts with atoms in its path to destabilise them. This disturbance in the electron shell of atoms may lead to chemical changes. Radiation causes chromosomal breakage, translocations and mutations. For example, XP and thyroid cancer. 3) Infectious agents - a large number of viruses, bacteria and parasites have been implicated in the aetiology of cancer. For example, human papillomavirus (HPV), patients with HPV have defective cell-mediated immunity and numerous skin papillomas. These papillomas may transform into squamous cell carcinomas, which frequently contain the genome of HPV-5, -8 or -1.

Answer 23

An oncogene is a mutated gene that has the potential to cause cancer.

Answer 24

Benign or malignant tumour.

Answer 25

The cell of origin.

Answer 26

Nausea/vomiting Poor appetite Fever Pain Fatigue Weight loss (cachexia)

Answer 27

This is characterised as progressive loss of skeletal muscle mass (sarcopenia), adipose tissue wasting, systemic inflammation, and metabolic abnormalities leading to functional impairment. Cachexia can increase with the tumour type, for example gastric or pancreatic cancer patients have an incidence of 80%. Chemotherapy and radiotherapy may exacerbate cachexia.

Answer 28

Compression Obstruction Ulceration Haemorrhage Rupture Perforation Infarction

Answer 29

Symptoms in cancer patients that are not readily explained by local or metastatic disease. These are: * hypercalcaemia * endocrine effects * Cushing’s syndrome * clubbing of the fingers * skin rashes * hypertrophic osteoarthropathy * peripheral neuropathy * cerebellar degeneration

Answer 30

The exogenous sources include viral oncogenes (v-onc), which may be introduced into cells by tumour viruses.

Answer 31

Endogenous genes are called cellular oncogenes (c-onc), and these are genes that are normally present in the cell but have been altered to produce the oncogene.

Answer 32

They are a group of genes (before they become mutated) that cause normal cells to become cancerous when they are mutated.

Answer 33

By mutations such as: Deletion Insertion Amplification Point mutations Gene rearrangements/translocation Altered expression

Answer 34

Increased growth factor production Increase in growth factor receptors on the cell’s surface Abnormal growth factor receptors Abnormal signalling through the cascade of signal transduction pathways in the cytoplasm Abnormalities in the nuclear acting molecules Alterations to the control of the cell cycle

Answer 35

Substances found in blood, urine or tissue that can be associated with the presence of malignancy.

Answer 36

Sensitive, specific, easily detected, marker levels correlate with the extend of the disease.

Answer 37

AFP - hepatocellular carcinoma, teratoma of testis CA153 - breast cancer CA19-9 - pancreatic cancer CA-125 - ovarian cancer Calcitonin - medullary thyroid carcinoma PSA - prostate cancer

Answer 38

Determined by: how aggressive a tumour is predictability of its spread mortality of patients from treatment procedure cure rate for procedure

Answer 39

Surgery Radiotherapy Chemotherapy Bone marrow transplant Immuno therapy Proton beam therapy Targeted cancer therapy Gene therapy Hormone therapy

Answer 40

Measured as a 5-year survival with no recurrence.

Answer 41

Alkylating agents (e.g., busulfan) Anti-metabolites (e.g., methotrexate) Rosy periwinkles (e.g., vinblastine -leukaemia and vincristine - Hodgkin's disease) Cyclophosphamide - (e.g., from mustard gas to cancer treatment) Pacific Yew (e.g., taxol) These were introduced and proved useful in the management of disseminated cancers. The main problem with such agents is that all of the body’s normal tissues are also exposed to the drug, and so the challenge is to deliver enough drug to kill the tumour without killing the patient.

Answer 42

Frequent infections Diarrhoea Nausea and loss of appetite Hair loss Anaemia

Answer 43

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumour growth and progression, tumour blood vessel development, and promotion of specific death of cancer cells. Treatments based on the unique set of molecular targets produced by the patient’s tumour.

Answer 44

Proton therapy is a type of radiation treatment that uses protons rather than x-rays to treat cancer. A proton is a positively charged particle. Doctors may use proton therapy alone, or they may combine it with standard treatments.

Answer 45

p53 is a regulatory protein that is often mutated in human cancers as it normally prevents cancer formation. It is classified as a tumour suppressor gene.

Answer 46

Aflatoxins are various poisonous carcinogens and mutagens that are produced by certain molds, particularly Aspergillus species.

Answer 47

Benzo[a]pyrene is a polycyclic aromatic hydrocarbon and the result of incomplete combustion of organic matter at temperatures between 300 °C and 600 °C. The ubiquitous compound can be found in coal tar, tobacco smoke and many foods, especially grilled meats. It is a carcinogen.

Answer 48

It is a natural constituent of coal tar and is a carcinogen.

Answer 49

Asbestos is a naturally occurring mineral composed of flexible fibres that are resistant to heat, electricity and corrosion. These qualities make the mineral useful, but they also make asbestos exposure highly toxic. Asbestos was widely used in construction as an effective insulator, and it can be added to cloth, paper, cement, plastic and other materials to make them stronger. But when asbestos dust is inhaled or ingested, the fibres can become permanently trapped in the body. Over decades, trapped asbestos fibres can cause inflammation, scarring and eventually genetic damage, it is a carcinogen.

Answer 50

Vitamin C, it is not a carcinogen.

Answer 51

Paraneoplastic syndromes are a group of rare disorders that are triggered by an abnormal immune system response to a cancerous tumour known as a "neoplasm." Typical symptoms are skin rashes, endocrine effects, hypercalcemia, and Cushing's syndrome.