Biomedical subjects

E K Bergsland

Publications and source records attributed to E K Bergsland.

3 recordsLinked to original sources

PubMed2005

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer.

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (> 75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P < 0.001). Using specific thresholds, patients with > or = 25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P < 0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease.

Antimetabolites, Antineoplastic↗

PubMed2001

Molecular mechanisms underlying the development of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a disease that is extremely difficult to manage and is markedly increasing in incidence. Malignant transformation generally occurs in the setting of liver dysfunction related to a number of different diseases, including viral hepatitis, alcoholic liver disease, and aflatoxin exposure. Short of surgical or ablative approaches, no standard therapy exists for HCC and the prognosis is poor. Perhaps our best hope is that further elucidation of the specific molecular features underlying the disease will translate into innovative, and potentially disease-specific strategies to manage this difficult cancer. Exposure to aflatoxin is associated with a specific mutation in the tumor-suppressor gene p53. The exact molecular events underlying hepatocarcinogenesis in the setting of viral infection have yet to be elucidated, although there is evidence to suggest that virus-encoded proteins contribute to malignant transformation. Both hepatitis B X antigen and hepatitis C core protein appear to interact with a variety of cellular proteins leading to alterations in signal transduction and transcriptional activity. These events presumably cooperate to facilitate malignant progression by promoting extended hepatocyte survival, evasion of the immune response, and acquisition of mutations through genomic instability.

Animals↗

PubMed2000

Hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a disease that is extremely difficult to manage and is increasing markedly in incidence. This presents both an opportunity and a challenge. At-risk patients can be identified and early detection of HCC is feasible. New surgical techniques and postoperative therapies, including hepatic intra-arterial radiation, may improve the outlook for some patients with resectable cancer. Unfortunately, the vast majority of patients with HCC will have unresectable cancers. Regional treatments may shrink or necrose tumors, but no clear benefit to such therapies has been demonstrated. Recent evidence suggests combination chemotherapy may help some patients, although this needs validation. Perhaps the best hope is that the further elucidation of the genetic and molecular features of HCC will lend us insight into innovative strategies to manage this difficult cancer.

Animals↗