Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
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Enzyme
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Query: UMLS:C0476089 (
endometrial cancer
)
11,379
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Paclitaxel is one of the most effective and widely used agents in treating a variety of cancers, including
endometrial cancer
. Because of its poor solubility in water, the current intravenous pharmaceutical paclitaxel is formulated in
Cremophor EL
and dehydrated in ethanol in equal volumes.
Cremophor EL
is capable of causing complement activation, which can trigger an immediate hypersensitivity reaction. SPR064 is a pro-drug of paclitaxel which has a much higher solubility as compared to the parent drug; hence, SPR064 can be conveniently formulated in non-cremapor based medium, reducing the risk of cremaphor-related hypersensitivity reactions. The pharmacokinetics and solubility of SPR064 were evaluated in rats. The anti-tumorigenic potential of SPR064 was compared to paclitaxel in
endometrial cancer
cell lines and a genetically engineered mouse model (
Lkb
fl/fl
p53
fl/fl
) of
endometrial cancer
. Overall, SPR064 exhibited improved solubility and better exposure to drug in rats when compared to paclitaxel. SPR064 and paclitaxel inhibited cell proliferation, induced apoptosis, enhanced cellular stress and caused cell cycle G1 arrest in
endometrial cancer
cell lines, with similar potency. Both SPR064 and paclitaxel reduced tumor weight in the
Lkb
fl/fl
p53
fl/fl
mouse model under obese and lean conditions compared to their respective controls. Immunohistochemical staining demonstrated that SPR064 and paclitaxel significantly reduced the expression of Ki-67 and BCL-xL in the endometrial tumors of both obese and lean mice. In summary, SPR064 has anti-tumorigenic effects that are equivalent to paclitaxel in
endometrial cancer
cell lines and a genetically engineered mouse model of
endometrial cancer
. Thus, SPR064 may be a promising therapy for
endometrial cancer
without the significant risk of hypersensitivity reactions seen with paclitaxel.
...
PMID:SPR064, a pro-drug of paclitaxel, has anti-tumorigenic effects in endometrial cancer cell lines and mouse models. 3291 3
