ISCM2_ Cancer Week_ Dev and Ca Flashcards

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1
Q

Name the four type of tumor affecting development.

A

1) WILMS’ TUMORS
2) SACROCOCCYGEAL TERATOMAS
3) PRIMORDIAL GERM CELL MIGRATION ERROR
4) HYDATIFORM MOLE

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2
Q

What is Wilms’ Tumour?

A

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

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3
Q

What are the other associated congenital symptoms of Wilms’ Tumour?

A

Associated with other congenital symptoms: aniridia, hemihypertrophy and other genitourinary disorders

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4
Q

What gene is involved in Wilms’ Tumour?

A

Wt1 involved in mesenchymal-epithelial transition

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5
Q

What is SACROCOCCYGEAL TERATOMAS?

A

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)
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6
Q

Teratomas have tissue from all three germ layers. Name the three layers.

A

Epiderm, mesoderm, endoderm

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7
Q

What is Primordial Germ Cells (PGC) tumour?

A

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

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8
Q

What are the prevalence and effects of Hydatiform mole?

A

Quite common: 1-3 :1000 pregnancies

  • ↑ levels of hCG
  • Pregnancy bigger than for age expectations
  • May have vaginal bleeding
  • Higher BP
  • Early pre-eclampsia
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9
Q

What may Hydatiform mole develop into? And its risk factors.

A

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

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10
Q

Name the type of Hydatiform mole.

A

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.

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11
Q

What are the treatment for Hydatiform mole?

A
Treatment:
- Removal of the tissue
- Regular monitoring of **hCG** post pregnancies
- Elevated hCG indicative of:
>GTN
>Invasive mole               
>Choriocarcinoma
  • Chemotherapy: 100% success rate
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12
Q

Does Cancer recapitulates Development?

A

1) Context dependent
2) Cell-Cell Communication
3) Paracrine defects
4) Cancer Stem Cells

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13
Q

Explain what is Context dependent in cancer development.

A

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

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14
Q

Explain Cell-Cell Communication in cancer development.

A

Neighbouring tissue types influence each other

Signals from surrounding cells influences cell behaviour and differentiation

i.e. WILM’S TUMOR

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15
Q

Name the Signalling pathways in cancer.

A

Signalling pathways in cancer:
Shh (Sonic Hedgehog)
Nodal ( TGF-β)
Wnt

Affecting cell regulation through auto and paracrine signalling

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16
Q

Name the Key developmental signalling pathways in cancer

A

Key developmental signalling pathways:

Hedgehog, Notch, Wnt and BMP/TGF-β

17
Q

SHH appears to have two modes of action:

A

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

18
Q

Therapy for Autocrine control of Cancer.

A

Therapy: Surgery, Smoothened (SMO) inhibitors, radiotherapy- age dependent

19
Q

Describe the Paracrine control of SHH

A

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

20
Q

Describe the Autocrine control of SHH

A

Autocrine control
Shh promotes cell growth and may increase invasion. Shh release by Purkinje cells increase replication of granular precursor
i.e. Medulloblastomas