ISCM2_ Cancer Week_ Dev and Ca Flashcards
Name the four type of tumor affecting development.
1) WILMS’ TUMORS
2) SACROCOCCYGEAL TERATOMAS
3) PRIMORDIAL GERM CELL MIGRATION ERROR
4) HYDATIFORM MOLE
What is Wilms’ Tumour?
Renal Cancer (nephroblastoma)
*Tumour caused by the failure of immature cells in the kidney to differentiate, mesenchymal cells don’t convert to epithelium.
- Affects fetus and/or children <5 yo
- 80-85 children per year in the UK
> One of the genes responsible: WT1 (Wilms’ Tumour 1)- Wt1 involved in mesenchymal-epithelial transition
Development of the urogenital system
Regulates cell growth and survival by binding to DNA (transcription factor)
Tumour suppressor and oncogenic role
What are the other associated congenital symptoms of Wilms’ Tumour?
Associated with other congenital symptoms: aniridia, hemihypertrophy and other genitourinary disorders
What gene is involved in Wilms’ Tumour?
Wt1 involved in mesenchymal-epithelial transition
What is SACROCOCCYGEAL TERATOMAS?
Sacrococcygeal teratoma (SCT) is a tumor that develops before birth and grows from a baby’s coccyx
- Solid and fluid filled
- Often highly vascularised: risk of cardiac failure pre and post-operation
- affecting females more than boys (~4:1)
Teratomas have tissue from all three germ layers. Name the three layers.
Epiderm, mesoderm, endoderm
What is Primordial Germ Cells (PGC) tumour?
Primordial Germ Cells (PGC) migrate to the kidney to the gonads, failure to migrate to the right place can cause tumours: extragonadal germ cell tumours*
In ovaries, they differentiate.
In testis, they continue to proliferate. This can lead to tumour development
Teratoma: benign
Carcinoma: malignant
What are the prevalence and effects of Hydatiform mole?
Quite common: 1-3 :1000 pregnancies
- ↑ levels of hCG
- Pregnancy bigger than for age expectations
- May have vaginal bleeding
- Higher BP
- Early pre-eclampsia
What may Hydatiform mole develop into? And its risk factors.
Benign growth, but may develop into Gestational Trophoblastic Neoplasia
> Trophoblast: the presumptive placenta develops normally, but rapidly.
The epiblast: the presumptive embryonic tissue does not form
risk factors: under 16s / over 50s
Asian ethnicity
Name the type of Hydatiform mole.
1) Complete mole:
Spermatazoan fertilises an ovum with no genetic component. Male chromatids duplicate. No fetus forms.
2) Partial mole:
Two spermatazoa fertilise a single ovum. Triploid. Fetus does begin to develop, but unviable.
What are the treatment for Hydatiform mole?
Treatment: - Removal of the tissue - Regular monitoring of **hCG** post pregnancies - Elevated hCG indicative of: >GTN >Invasive mole >Choriocarcinoma
- Chemotherapy: 100% success rate
Does Cancer recapitulates Development?
1) Context dependent
2) Cell-Cell Communication
3) Paracrine defects
4) Cancer Stem Cells
Explain what is Context dependent in cancer development.
Melanomas: Melanocytes- derived from Neural Crest Cells
Melanomas:
If surrounded by normal melanocytes, secrete Nodal and affect the surrounding cells to become cancerous
If surrounded by Embryonic Stem Cells (ESC): secrete Nodal Inhibitors, Melanoma will become a normal melanocyte
Explain Cell-Cell Communication in cancer development.
Neighbouring tissue types influence each other
Signals from surrounding cells influences cell behaviour and differentiation
i.e. WILM’S TUMOR
Name the Signalling pathways in cancer.
Signalling pathways in cancer:
Shh (Sonic Hedgehog)
Nodal ( TGF-β)
Wnt
Affecting cell regulation through auto and paracrine signalling
Name the Key developmental signalling pathways in cancer
Key developmental signalling pathways:
Hedgehog, Notch, Wnt and BMP/TGF-β
SHH appears to have two modes of action:
SHH appears to have two modes of action:
1) Autocrine:
Shh promotes cell growth and may increase invasion. Shh release by Purkinje cells increase replication of granular precursor
i.e. Medulloblastomas
2) Paracrine
Therapy for Autocrine control of Cancer.
Therapy: Surgery, Smoothened (SMO) inhibitors, radiotherapy- age dependent
Describe the Paracrine control of SHH
Paracrine control
Shh often acts as a long-range signalling molecule too. Limb patterning model:
Shh stimulates growth, prevents apoptosis and activates gene expression
eg. Drugs affecting Shh: Cyclopamine
> Acts on *stromal cells to stimulate gene expression
i.e. Insulin-like Growth Factor
Pancreatic cancer
> Paracrine effect:
Supports tumour cell growth: increases angiogenesis, contributes to spread of disease
i.e. Lymphangiogenesis
Describe the Autocrine control of SHH
Autocrine control
Shh promotes cell growth and may increase invasion. Shh release by Purkinje cells increase replication of granular precursor
i.e. Medulloblastomas
