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Biomedical subjects

J W Freeman

Publications and source records attributed to J W Freeman.

136 records · Page 8Linked to original sources
PubMed1969

Cardiac abnormalities in poisoning with tricyclic antidepressants.

Of 80 consecutive admissions to a general hospital for drug overdose, 10 had taken one or other of the tricyclic antidepressants. All 10 had abnormalities of cardiac conduction as shown by prolonged Q-T(e) intervals, and eight had S-T segment and T-wave changes. Five of the 10 patients had arrhythmias and two of these died. Continuous electrocardiographic monitoring is recommended in patients with overdosage of tricyclic antidepressants.

Adult↗
PubMedDate not supplied

Efficacy of p120 antisense-mediated therapy for pancreatic cancer.

p120 antisense oligodeoxynucleotides were used to determine whether they inhibited cell growth of MIA PaCa-2, a highly tumorigenic human pancreatic carcinoma cell line. Growth inhibition assays were determined in vitro by the ability of these oligomers to inhibit DNA synthesis and cell growth. For in vivo studies, nude mice were injected with cells and palpable tumors were found in 16 of 20 animals by day 14. Sixteen animals (8 in each group) were then treated daily (25 mg/kg intraperitoneally) for up to 40 days with nonsense control oligomers or p120 antisense oligomers. p120 Antisense oligomers inhibited the in vitro proliferation of MIA PaCa-2 cells in a dose-dependent manner, and optimal growth inhibition of greater than 90% was achieved at an antisense oligomer concentration of 100 micromol/L. The tumor volume was calculated for antisense- and nonsense-treated animals. Fifteen days after the beginning of treatment, control animals had a significantly greater (P=0.0035) tumor volume (425=244 mm3 above baseline) as compared to p120 antisense-treated animals (166+/-116 mm3). Seven of the eight control animals formed tumors that had a volume greater than 1200 mm3 45 days after treatment was begun, whereas only three of eight p120 antisense-treated animals had tumors that were this large. Two of the latter three animals had relatively large, palpable tumors (>150 mm3) prior to treatment. Twenty days after treatment was stopped (day 60), all animals had tumors larger than 1200 mm3. p120 Antisense oligomers were effective for inhibiting in vitro growth of the pancreatic cancer cell line MIA PaCa-2. In preliminary studies, p120 antisense oligomers appeared to inhibit the rate of growth in nude mice; however, no cures were achieved. The most effective response was seen in animals with initial low tumor burden.

Animals↗
PubMedDate not supplied

Differential expression of transforming growth factor beta receptors in human pancreatic adenocarcinoma.

BACKGROUND: Many cancer cells show resistance to transforming growth factor beta (TGF-beta)-mediated growth inhibition. This resistance to TGF-beta is associated with an increased tumorigenic phenotype. OBJECTIVE: In this study, we determined whether a loss in expression of TGF-beta receptors or DPC4, an important down stream target of TGF-beta signaling, might account for this lack of TGF-beta sensitivity in pancreatic adenocarcinoma. MATERIALS AND METHODS: To accomplish this, six established pancreatic cancer cell lines, twenty-six surgically resected tumor specimens of pancreatic adenocarcinoma and ten non-tumor pancreas tissues were analyzed for the mRNA expression of the three TGF-beta receptors (RI, RII, and RIII) and DPC4. RESULTS: We report here that five of six pancreatic cancer cell lines were not sensitive to TGF-beta. All the ten non-tumor specimens of pancreas showed expression of RI, and DPC4; while nine of ten showed expression of RIII and eight of ten showed expression of RII. Five of six pancreatic cancer cell lines and 23 of 26 tumor specimens showed expression of RI. Two cell lines and about half (46%) of the tumor specimens did not express RII. Only two cell lines showed appreciable levels of RIII expression; while ten of 26 (38%) tumor specimens did not show expression of RIII. DPC4 expression was observed in three of the six (50%) cell lines and 19 of 24 (79%) tumor specimens. CONCLUSION: This study indicates that apart from the functional loss of DPC4 due to mutations or homozygous deletion, a lack of the TGF-beta receptors, particularly RII and RIII, may contribute to a loss of TGF-beta signaling in a population of pancreatic cancers.

Activin Receptors, Type I↗