Deze bundel bevat uitwerkingen van alle hoorcolleges, patientdemonstraties en eventuele (proef)tentamens van het blok Mechanisms of Disease 2 van de studie Geneeskunde aan de universiteit Leiden.
A normal epithelial cell has to go through several stages to be transformed into a metastasizing tumor. There is a progressive development from normal to neoplastic tissue, with many non-malignant intermediate stages.
Cancer development is driven by the accumulation of mutations:
There are 10 hallmarks of cancer which distinguish epithelial cells from carcinomas:
Tumor promoting inflammation and genome instability and mutation are enabling
........Read moreThere are multiple risk factors for cancer. The most important ones are:
The chance of getting cancer increases with age:
If someone has a sibling with breast cancer and is 40-50 years old, the chance of developing breast cancer is 2x as
........Read moreMany cell divisions are required in embryonic development and during human life. Daughter cells inherit identical DNA. Cell division requires accurate DNA duplication and takes approximately 5 hours. 6 x 109base pairs are copied almost flawlessly → there is less than 1 error per division.
If not repaired,
........Read moreBRCA and Lynch syndrome occur very frequently in the population. Both syndromes are caused by DNA repair genes.
Even though germline mutations are equally distributed through the genome, hereditary cancer cases associate with syndromes caused by mutations in DNA repair genes. On the other hand, cancers related to inherited APC-mutations are
........Read moreA spiculated mass is a mass with spikes going into the surrounding tissue. Benign lesions generally don’t grow in this type of fashion → a biopsy needs to be taken.
FNAC stands for fine needle aspiration cytology:
There are many kinds of mesenchymal tumors:
These tumors can be benign of malignant:
Metastasis is Greek word, which in medical use describes the shift of disease from one part of the body to another. It is mainly used in context of cancer.
In the 19th century, Jean Claude Recamier recognized that cancer can spread from a primary tumor.
Stephan Paget came up
........Read moreMolecular diagnostics is a subspecialty of pathology that utilizes molecular biology techniques to:
Molecular biology techniques utilize DNA, RNA and enzymes that interact with nucleic acids to understand biology at a molecular level:
Cancer is the emperor of all maladies, the king of all terrors. The attention to and visibility of cancer is growing:
In cancer, there are 3 types of heterogeneity:
Examples are:
The incidence peak of cancer is around the 6th decade of life. Therefore, it isn’t important in the evolution or in shaping the immune system → mainly occurs after reproductive age.
In the beginning of the 20th century, a number of scientists proposed a theory of immune surveillance, which later was further
........Read moreA tumor grade reflects intrinsic biological behavior of tumors. In general, a low grade is less aggressive. It is necessary to grade a tumor for treatment and prognosis:
Tumors are graded based on the microscopic appearance of cancer cells. Dependent
........Read moreTo determine what therapy is effective, it is necessary to make a therapeutic plan. This can be done according to the WHO 6STEPS method:
Cancer can be diagnosed based on:
A biomarker refers to a measurable indicator of some biological state or condition. Humans shed particles into the bloodstream or environment as evidence of their presence in a particular location:
In 2012, there where 14 million new cancer cases, 8 million cancer deaths and 33 million people living with cancer. These numbers will only increase. Even though surgeons aren’t the only doctors involved in cancer therapy, 80% of all solid cancers need surgery.
Surgical oncology has several challenges which need to be taken
........Read moreRadiation oncology is a separate discipline in oncology where ionizing radiation is used to treat cancer. It is not the same as radiology or nuclear medicine:
An oncologist is a doctor who treats cancer and provides medical care for a person diagnosed with cancer. The field of oncology has 3 major areas:
A medical oncologist treats cancer using hormonal therapy, chemotherapy or other medications such as targeted therapy or immunotherapy.
Drug treatments can
........Read moreThe therapeutic window can be increased by:
The sensitivity can be enhanced via:
Blood forms 8% of the total body weight, the other 92% consists of fluids and tissues. Blood is made up for 55% of blood plasma and for 45% of formed elements. Plasma is mostly made up of water, formed elements of red blood cells, white blood cells and platelets.
A 40-year-old man visits the GP with complaints of fatigue and pallor. The GP thinks the most likely clinical problem is anemia.
The GP requests a complete blood count (CBC) → a differential count of Hb, leukocytes, and thrombocytes. Blood goes through an automatic hematology analyzer, a laser which gets scattered
........Read moreMyeloid malignancies are divided into 3 categories:
Chronic myeloid leukemia is a disorder of proliferation → it is a
........Read moreThere are 2 types of malignant lymphomas:
Pluripotent hematopoietic stem cells (HSC) differentiate into:
Hematopoietic stem cell transplantation (SCT) is performed because:
There are 2 ways of doing an allogeneic SCT:
While patients experience cancer treatment as a unique life-changing series of events, to medical professionals it constitutes routine work practice.
Joanna Baines wrote an article containing 3 stories of 3 generations of breast cancer:
CD20 is an IgG isotype expressed antigen on normal and malignant B-cells. It is used for treatment of many B-cell lymphomas → by targeting CD20 antigens, both malignant and normal B-cells are depleted.
Chemotherapy combined with CHOP monoclonal antibodies leads to a significant increase of survival
........Read moreThrombophlebtis is thrombosis due to infected vessels. Thrombotic events are the second leading cause of death in cancer patients, after death from cancer itself. The Trousseau syndrome describes the presence of thrombosis in relationship to cancer. Fibrin clots may be induced by cancerous processes:
Blood flows as a fluid through the blood vessels to all the organ systems. Upon injury, blood vessel loss has to be prevented. This is done via blood coagulation. Under normal conditions, blood coagulation is a tightly regulated process:
At some point, the platelet plug needs to be removed to return the normal blood flow.
Fibrinolysis is part of the normal hemostasis. It enables repair of the injured vessel wall and is important in resolving an unwanted clot such as a thrombus.
Fibrinolysis consists of the conversion of earlier formed fibrin, which is
........Read moreCancer leads to coagulation, which leads to thrombosis. Coagulation itself also leads to cancer, and thrombosis may as well. The link between cancer and thrombosis was established almost 200 years ago by Jean-Baptiste Bouillaud and Armand Trousseau. Trousseau diagnosed himself with thrombosis and predicted he suffered of cancer.
........Read moreA bleeding disorder can roughly have 3 different causes:
Bleeding disorders can be congenital or acquired:
Thrombosis is caused by a decrease in anticoagulant factors. Deep vein thrombosis (DVT) has the following symptoms:
In 40% of cases with suspected DVT, the clinical diagnosis is correct. Ultrasounds of the vessels in the leg are primarily used to diagnose DVT. In
........Read moreIn deze bundel zijn samenvattingen, oefenmaterialen en aantekeningen samengevoegd voor het vak Mechanisms of Disease 1 en Mechanisms of Disease 2 (MOD 1 & 2) voor de opleiding Geneeskunde, jaar 2 aan de Universiteit van Leiden
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