Possible Reasons Why Nausea And Vomiting Does Not Occur In Choriocarcinoma

Possible Reasons Why Nausea And Vomiting Does Not Occur In Choriocarcinoma

Human Chorionic Gonadotrophin (hCG) in Choriocarcinoma 

Very raised serum and cerebrospinal fluid levels of hCG occur in choriocarcinoma in the absence
of nausea and vomiting provided there are no gastrointestinal or cerebral matestases (personal
communication Bagshawe KD 1997). As in choriocarcinoma high maternal serum levels of hCG
did not cause nausea and vomiting it seemed unlikely that the maternal serum hCG did cause
nausea and vomiting in pregnancy.
However it is now known that there are major changes in the hCG beta sub unit secreted in
choriocarcinoma particularly significant to this is that it is 100% nicked at the B47-48 level (1). A
macrophage or circulating leukocyte elastase proteus cleaves hCG beta subunit at Val residue 44
(residue 44-45 cleavage) or glyresidue 47 (residue 47-48 cleavage) generating nicked hCG. Both
nicking and dissociation eliminates hCG hormone activity (2). The combination of nicking of beta
subunit and dissociation of alpha and beta units in either order leads to a rapid deactivation and
clearance of hyperglycosylated hCG (2). Therefore the fact that hCG produced by choriocarcinoma
cells lacks hormone activity due to being 100% nicked at residue 47-48 will explain why high
levels of hCG which occur with choriocarcinoma are not associated with nausea and vomiting.
It is therefore possible that regular hCG can be associated with nausea and vomiting in pregnancy.

PGE2 is not or is only minimally synthesised by choriocarcinoma cells. The authors were unable to demonstrate the presence or synthesis of prostaglandins in human malignant choriocarcinoma cells (four lines BEWO, JAR, 2 and Omega 2) growing in continuous culture (3).

To determine the production of PGE2 and PGF2 by JEG-3 choriocarcinoma cells, the cells were incubated in either (a) control media or (b) media containing TNF- (1-20ng/ml). After 15 mins - 23 hours media were collected and analysed directly for PGF2 and derivisited for the determination of PGE2 as the methyloxinate derivative. TNF (1-20ng/ml) appeared to have no effect on the viability of JEG-3 cells. The effect of TNF on the formation of PGE2 and PGF2 was studied at 15 mins and 24 hours. Levels of PGE2 and PGF2 were below the limit of assay sensitivity in all cultures (1.25 and 3.1pg respectively). We were unable to demonstrate any effect of TNF- on the production of either PGE2 or PGF2 (4).

Decrease in Nicotinamide Adenine Dinucleotide-dependent 15-Hydroxyprostaglandin Dehydrogenase Activity (PGDH) may be important in the accumulation of PGs in neoplastic tissues. The activity of PGDH in neoplastic trophoblast tissue, namely hydatidiform mole tissues and in choriocarcinoma cells grown in monolayer culture and the activity of PGDH in term placenta which is known to be high, was compared at the same time. The specific activity of PGDH in hydatidiform mole tissue (0 to 1.2nmol 15 ketoprostaglandin E2 formed x min-1 x mg-1 cytosolic protein) and in choriocarcinoma cells (BEWOline) (1.0nmol 15-ketoprostaglandin E2 x min-1 x mg-1 protein) was strikingly less than that found in normal term placental tissue (11.4 ± 2.3 (SE) nmol ketoprostaglandin x min-1 x mg-1 protein).  PGDH activity in neoplastic tissues was found to be one tenth or less of that in normal term human placentae (5). If choriocarcinoma cells were able to synthesise prostaglandin E2 or PGF2a then the very limited amounts of PGDH in these cells would allow considerable quantities of these prostaglandins to be produced. The lack of PGDH in these cells suggests that very little or no PGE2 is synthesised in choriocarcinoma cells (5).

REFERENCES

1. ELLIOT MM, KARDANA A, LUSTBADER JW, COLE LA
Carbohydrate and Peptide structure of the alpha and beta subunit of Human Chrionic Gonadotrophin for normal and aberrant pregnancy and choriocarcinoma Endrocrine
1997 7:15-32

2. COLE L.A .
New discoveries on the biology and detection of Human Chorionic Gonadotrophin reproductive biology and endocrinology 2009 7:1-37

3. PATTILLO R A, HUSSA R O, TERRAGNO N A, STORY M T, MATTINGLY R F.
Absence of prostaglandin synthesis in malignant human trophoblast in culture.
Am J Obstet Gynecol. 1973;113(1):91-94.

4. PEDERSEN A M, FULTON S K, PORTER L, FRANCIS G L.
Tumornecrosis factor- affects in vitro hormone production by JEG-3 choriocarcinoma cell cultures.
Journal Reprod Immunol. 1995;29:69-80.

5. CASEY M L, GAL D, JOHNSTON J M, MACDONALD P C.
Nicotinamide adenine dinucleotide-dependent 15 hydroxyprostaglandin dehydrogenase activity in hydatidiform mole tissue and choriocarcinoma cells.
Cancer Research. 1981;41:2581-2582.

 

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70-80%

Nausea & vomiting in pregnancy (NVP) is very common, on average it affects 70-80% of pregnant women to a greater or lesser extent.

85%

85% of pregnant women have two episodes of nausea per day.

30%

30% of pregnant women in paid employment need time off work due to NVP.

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