Biomedical subjects

Timothy Kuo

Publications and source records attributed to Timothy Kuo.

6 recordsLinked to original sources

PubMed2006

Optimizing therapy for patients with brain metastases.

Brain metastases from systemic cancers are the most common malignant brain tumors encountered. Although prognosis remains poor, it is possible to stratify patients according to risk. Furthermore, an aggressive therapeutic approach for good-risk patients that includes a combination of either surgery or stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) can improve survival and decrease the risk of central nervous system progression.

Brain Neoplasms↗

PubMed2005

Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer.

PURPOSE: To determine the efficacy of concurrent 5-fluorouracil (5-FU) and intensity-modulated radiotherapy (IMRT) followed by body stereotactic radiosurgery (SRS) in patients with locally advanced pancreatic cancer. METHODS AND MATERIALS: In this prospective study, all patients (19) had pathologically confirmed adenocarcinoma and were uniformly staged. Our treatment protocol consisted of 45 Gy IMRT with concurrent 5-FU followed by a 25 Gy SRS boost to the primary tumor. RESULTS: Sixteen patients completed the planned therapy. Two patients experienced Grade 3 toxicity (none had more than Grade 3 toxicity). Fifteen of these 16 patients were free from local progression until death. Median overall survival was 33 weeks. CONCLUSIONS: Concurrent IMRT and 5-FU followed by SRS in patients with locally advanced pancreatic cancer results in excellent local control, but does not improve overall survival and is associated with more toxicity than SRS, alone.

Adenocarcinoma↗

PubMed2005

Phase II study of gefitinib, fluorouracil, leucovorin, and oxaliplatin therapy in previously treated patients with metastatic colorectal cancer.

PURPOSE: To investigate the gefitinib, fluorouracil (FU), leucovorin, and oxaliplatin regimen (IFOX) in previously treated patients with metastatic colorectal cancer. PATIENTS AND METHODS: Eligible patients had stage IV colorectal adenocarcinoma and had demonstrated progression or intolerance to a prior chemotherapy regimen not including oxaliplatin. Each cycle consisted of 14 days. Cycle 1 consisted of oxaliplatin 85 mg/m2 intravenously (IV) during 2 hours on day 1, hours 0 to 2; leucovorin 200 mg/m2 IV on days 1 and 2, hours 0 to 2; FU 400 mg/m2 IV push on days 1 and 2; and FU 600 mg/m2 IV on days 1 and 2, hours 2 to 24 (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg/d administered orally throughout the 14-day cycle. RESULTS: Twenty-seven patients were enrolled onto the study. The median number of prior chemotherapy regimens was two, and 74% of all patients received prior irinotecan. Nine of the 27 patients (33%) and six of the 20 patients (30%) who had prior FU and irinotecan had a partial response by Response Evaluation Criteria in Solid Tumors Group criteria. Median overall survival was 12.0 months. Median event-free survival was 5.4 months. Grade 3 to 4 toxicities included neutropenia (48%), diarrhea (48%), nausea (22%), and vomiting (15%). CONCLUSION: IFOX is an active regimen in patients with previously treated metastatic colorectal adenocarcinoma, demonstrating higher response rates than those reported with FOLFOX-4 alone in a similar patient population.

Adenocarcinoma↗

PubMed2005

Current status of small-molecule tyrosine kinase inhibitors targeting epidermal growth factor receptor in colorectal cancer.

The epidermal growth factor receptor (EGFR) is expressed in the majority of colorectal cancers (CRCs) and is associated with poor clinical outcome. Ample evidence suggests that inhibition of this pathway by monoclonal antibodies directed against EGFR leads to antitumor activity in CRC. Small-molecule tyrosine kinase inhibitors (TKIs) provide distinct advantages over monoclonal antibodies by virtue of lower production costs, ease of oral administration, and ability to target multiple cellular survival pathways. Despite theoretical advantages, multiple early-phase trials of EGFR TKIs fail to demonstrate single-agent activity in CRC. However, the unusually high response rates observed when gefitinib, an EGFR TKI, is combined with chemotherapy for patients with metastatic CRC suggest a possible synergistic effect. This effect is not seen in non-small-cell lung cancer (NSCLC), for which larger phase III trials have been conducted. The differences between NSCLC and CRC with respect to EGFR expression and mutation status do not completely explain this dichotomy, and further investigation into the pharmacogenomics of EGFR tyrosine kinase inhibition in CRC is under way. Significant effort is directed toward newer strategies targeted at the EGFR in CRC. A new generation of small-molecule TKIs is emerging in which multiple receptor pathways, including ErbB2 and vascular endothelial growth factor receptor, can be simultaneously targeted with EGFR. These agents are still in early-phase clinical trials, and specific data for patients with CRC are forthcoming.

Antibodies, Monoclonal↗

PubMed2004

CD1d function is regulated by microsomal triglyceride transfer protein.

CD1d is a major histocompatibility complex (MHC) class I-related molecule that functions in glycolipid antigen presentation to distinct subsets of T cells that express natural killer receptors and an invariant T-cell receptor-alpha chain (invariant NKT cells). The acquisition of glycolipid antigens by CD1d occurs, in part, in endosomes through the function of resident lipid transfer proteins, namely saposins. Here we show that microsomal triglyceride transfer protein (MTP), a protein that resides in the endoplasmic reticulum of hepatocytes and intestinal epithelial cells (IECs) and is essential for lipidation of apolipoprotein B, associates with CD1d in hepatocytes. Hepatocytes from animals in which Mttp (the gene encoding MTP) has been conditionally deleted, and IECs in which Mttp gene products have been silenced, are unable to activate invariant NKT cells. Conditional deletion of the Mttp gene in hepatocytes is associated with a redistribution of CD1d expression, and Mttp-deleted mice are resistant to immunopathologies associated with invariant NKT cell-mediated hepatitis and colitis. These studies indicate that the CD1d-regulating function of MTP in the endoplasmic reticulum is complementary to that of the saposins in endosomes in vivo.

Abetalipoproteinemia↗

PubMed2004

Hepatitis C in a Los Angeles public hepatitis clinic: demographic and biochemical differences associated with race-ethnicity.

BACKGROUND & AIMS: The goal of this study was to uncover possible racial-ethnic differences in hepatitis C presentation in an urban hepatitis clinic. METHODS: We surveyed the clinic summary cards of patients with antibodies to hepatitis C virus (HCV) seen from 1993 to 2000 for demographic and laboratory data. RESULTS: A total of 1271 HCV patients were categorized into 4 major racial-ethnic groups consisting of 95 Asian, 232 African American, 323 Caucasian, and 621 Latino patients. The latter showed significantly higher serum alanine transaminase (ALT), aspartate transaminase, and bilirubin levels (P < 0.0001) and lower serum albumin levels (P < 0.01) compared with all other racial-ethnic groups. Latinos had the lowest rate of hepatitis B coinfection (2.4%) and were significantly less likely to have normal serum ALT levels (P = 0.0002) compared with other groups. Asian patients were 10 years older than other racial-ethnic groups and were significantly more likely to be coinfected with hepatitis B virus (HBV) (P = 0.004). Asian patients also had an equal distribution of infected men and women whereas all other groups showed a male predominance. Injection drug use was a negligible cause of hepatitis C in Asian patients, but a prevalent exposure in Caucasian patients of both sexes and in African American and Latino men was seen. Transfusion was more prevalent in Asian and Latino patients. CONCLUSIONS: Hepatitis C risk factors, sex distribution, and coinfection with hepatitis B vary by race-ethnicity. Latino patients showed statistically significant biochemical differences in ALT, aspartate transaminase, bilirubin, and albumin levels compared with all other racial-ethnic groups. Further studies are required to determine the possible causes for these biochemical differences.

Adult↗