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M Hawkins

Publications and source records attributed to M Hawkins.

130 records · Page 8Linked to original sources

Sequence-dependent antagonism between tamoxifen and methotrexate in human breast cancer cells.

High-dose methotrexate (MTX) cytotoxicity is decreased in MCF-7 breast cancer cells when the chemoendocrine agent tamoxifen (TAM) is given to cells 24 hours prior to MTX (early TAM). However, when breast cancer cells are exposed to TAM 24 hours after MTX (delayed TAM), MTX cytotoxicity is enhanced by TAM. The growth of cells exposed to 10 microM TAM and 10 microM MTX alone or in combination with early TAM plus MTX had the following order: TAM > TAM (early) + MTX > MTX. The percentages of control rates for TAM, MTX, and TAM (early) + MTX are 74.71 +/- 1.36%, 22.13 +/- 2.76%, and 38.17 +/- 2.75%, respectively. The inhibitory sequence from cells exposed to MTX + TAM (delayed TAM), MTX and TAM alone is MTX + TAM (delayed TAM) > MTX > TAM; and the percentages of control rates were 16.87 87% (MTX + TAM [delayed TAM]), 25.92 +/- 2.14% (MTX), and 54.08 +/- 14.79% (TAM). These studies suggest that: (a) the interactions between TAM and MTX are sequence-dependent; (b) TAM antagonizes the effect of MTX when TAM administration precedes MTX; and (c) TAM enhances the effect of MTX when TAM administration follows MTX.

Antineoplastic Combined Chemotherapy Protocols↗

Cold preservation of endothelial cells in sucrose-based solution (SbS) and University of Wisconsin (UW) solutions: comparison of normoxic or hypoxic storage.

Cold preservation of endothelial cells was studied, comparing primary endothelial cells (human umbilical vein endothelial cells - HUVECs) and a continuously growing cell line (ECV304 cells). Viability at the end of 24h cold preservation was measured by dye exclusion, whilst metabolism was assessed by Alamar blue conversion. Two preservation solutions were studied (UW solution) and sucrose-based (SbS) in both cell types. The response was similar in both cell types to preservation under normoxic conditions (with percentage dye exclusion maintained at about 80 percent in both preservation solutions) whereas under hypoxic conditions ECV304 were more sensitive to preservation in UW solution (dye exclusion reduced to 43.5+/-1.4 percent versus 73.6+/-14 percent (P<0.01). Metabolism assessed by Alamar blue conversion after cold preservation and rewarming was similar in both ECV304 and HUVECs after storage under normoxic conditions in UW solution, but in both cell types, metabolism was higher in SbS (P<0.05 and p<0.01) than in UW solution. Under hypoxic conditions, both cell types showed similar recovery of metabolism after storage in either UW or SbS. If the cells (in this case ECV304 under aerobic conditions) were stored for 24h and then allowed to rewarm in either of the respective preservation solutions (UW or SbS for 1h) before the Alamar blue test, metabolism was higher (p less than 0.01) in those exposed to SbS. UW solution and SbS provide similar protection for endothelial cells under hypoxic conditions, but SbS has some advantages under normoxic storage or if the cells experience variable temperatures in the presence of residual preservation solution at the end of cold preservation period.

Adenosine↗

Osteocalcin and bone alkaline phosphatase in the serum of women with liver disease.

To identify the types of liver disease in which osteopenia is a prominent feature and to understand the mechanisms of bone loss, bone mineral density was measured in the lumbar spine and hip, bone alkaline phosphatase, osteocalcin, and biochemical markers of calcium homeostasis were measured in 42 women, aged 33 to 52, with chronic liver disease and in 299 healthy women of similar age. In control women, bone alkaline phosphatase and osteocalcin correlated negatively with bone density at all sites (p less than 0.05). In women with liver disease, osteocalcin correlated negatively with bone density in the lumbar spine (p less than 0.007), whereas bone alkaline phosphatase did not correlate with bone density at any site. Bone alkaline phosphatase correlated positively with osteocalcin in control women (p = 0.001) and negatively with osteocalcin in women with liver disease (p = 0.03). Serum bone alkaline phosphatase in women with liver disease was increased significantly over serum bone alkaline phosphatase of control women, probably because of decreased clearance owing to defective function or decreased numbers of hepatic asialoglycoprotein receptors. Bone density was lower in the lumbar spines and hips of women with primary sclerosing cholangitis, primary biliary cirrhosis, and chronic active hepatitis or fibrosis without cirrhosis than in the lumbar spine and hips of control women. However, the differences were not significant, possibly because of the small sample size. It is concluded that, in liver disease, osteocalcin is a more reliable marker of osteoblastic function than bone alkaline phosphatase. Although our results show that bone density may decrease in women with cholestatic liver disease, larger studies are needed to determine the degree of osteopenia.

Adult↗

Emergency procedure.

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Dental Care↗