PubMed Health⌕ Search

Biomedical subjects

Derick Lau

Publications and source records attributed to Derick Lau.

10 recordsLinked to original sources
PubMed2006

Peptide ligands targeting integrin alpha3beta1 in non-small cell lung cancer.

Lung cancer is one of the most common cancers and is the leading cause of cancer death. We wish to identify peptide ligands for unique cell surface receptors of non-small lung cancer with the hope of developing these ligands as diagnostic and therapeutic agents. Using the method of 'one-bead one-peptide' combinatorial chemistry, a library of random cyclic octapeptides was synthesized on polystyrene beads. This library was used to screen for peptides that promoted attachment of lung adenocarcinoma cells employing a 'cell-growth-on-bead' assay. Consensus peptide sequences of cNGXGXXc were identified. These peptides promoted cell adhesion by targeting integrin alpha3beta1 over-expressed in non-small lung cancer cells. These peptide beads can be applied to capture cancer cells in malignant pleural fluid for purpose of diagnosis of lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Complete response of brain metastases to irinotecan-based chemotherapy.

Brain metastases occur in 15-20% of patients with cancer and are generally associated with an overall poor prognosis. Currently, radiotherapy and surgery are the mainstay of palliative therapy for patients with brain metastases, while the role of systemic chemotherapy remains uncertain. In this article, we report complete responses to irinotecan-based chemotherapy in three patients with brain metastases from parotid adenocarcinoma, esophageal adenocarcinoma and small cell lung cancer. Irinotecan-based chemotherapy may hold promise in treating patients with brain metastases. Further studies are warranted to confirm our observations.

Adenocarcinoma↗
PubMed2005

Computer-assisted image analysis of bronchioloalveolar carcinoma.

In clinical trials, response rate is an important endpoint for assessing the efficacy of an anticancer drug. The Response Evaluation Criteria for Solid Tumors (RECIST) has been widely used as a standard method to assess response. The RECIST requires only 1-dimensional measurement of tumor size. However, bronchioloalveolar carcinoma (BAC), which commonly presents as infiltrative or micronodular lesions, is not always readily assessable by RECIST. During the past 2 years, we have been developing computer-based programs to more accurately measure tumor size on chest computed tomography (CT) scans. In a first-generation computer-assisted image analysis (CAIA) system, we were able to capture and quantify lesions on CT scans by linking the software programs of eFilm, HyperSnap, and Scion. We have applied this CAIA approach to measuring BAC response to gefitinib in the Southwest Oncology Group (S0126) trial. However, this first-generation CAIA system involves multiple manual steps and is therefore labor intensive. We are now developing a fully automated CAIA program based on a versatile software platform, ImageJ, created at the National Institutes of Health. Taking theoretical and physical considerations into account, Java plug-in programs for ImageJ are created to automatically analyze CT scans in the Digital Imaging and Communications in Medicine format. We have demonstrated the feasibility of an ImageJ-based automated CAIA program for measuring BAC bidimensionally on CT scans. This automated CAIA system will be applied in a prospective clinical trial of the GVAX vaccine in patients with BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2004

Enhancement of radiotherapy with DNA topoisomerase I-targeted drugs.

Since its discovery more than a century ago, ionizing radiation has become a mainstay therapy for patients suffering from cancers. Currently, radiotherapy provides cure or palliative care for approximately one half of the cancer population. The anticancer efficacy of radiotherapy is, however, largely limited by its lack of tumor specificity and, consequently, normal tissue toxicity. There is an urgent need to develop systemic adjuncts that can enhance the efficacy and the selectivity of radiotherapy toward tumor cells. DNA topoisomerase I (TOP1)-targeted drugs such as camptothecin derivatives represent a novel class of chemotherapeutic agents that have recently been shown to be excellent radiation sensitizers. Combined modality therapy with TOP1-targeted drugs and radiotherapy represents a new promising cancer therapy. The mechanism of enhancement of radiotherapy by TOP1-targeted drugs is under intense investigation. Clinical trials using combinations of radiation and camptothecin derivatives are also currently ongoing in various solid tumors including brain, head and neck, and lung cancers. A better understanding of the radiosensitization (RS) mechanism of TOP1-targeted drugs is pivotal to their clinical application, as well as in guiding the development of better radiation sensitizers.

Animals↗
PubMed2004

Is inhibition of cancer angiogenesis and growth by paclitaxel schedule dependent?

It has been speculated that weekly paclitaxel enhances antiangiogenesis and, hence, results in a greater inhibition of cancer growth than the 3-week schedule. We compared the weekly and 3-week schedules of paclitaxel in inhibiting angiogenesis, tumor growth and bone marrow hematopoiesis in a lung cancer model. Vehicle or paclitaxel was administered i.p. to three groups of nude mice bearing a human lung cancer. The vehicle was given weekly for six doses or every 3 weeks for two doses (Group A). Paclitaxel was administered at 20 mg/kg/week for six doses (Group B) or 60 mg/kg/3 weeks for two doses (Group C). The tumor growth rate was reduced by 50% equally in both the paclitaxel-treated groups. Intratumoral microvasculature was reduced by 70% in each paclitaxel-treated group. However, white blood cell count was significantly reduced in Group C in comparison with that of Group A or B. We conclude that in this model, angiogenesis and tumor growth were inhibited to the same extent when paclitaxel was administered on a weekly or 3-week schedule. Inhibition of tumor growth by paclitaxel was associated with suppression of angiogenesis. Weekly administration of paclitaxel resulted in a lower degree of leukopenia than with the 3-week schedule, mimicking the clinical setting.

Angiogenesis Inhibitors↗
PubMed2004

Novel peptide ligands for integrin alpha 4 beta 1 overexpressed in cancer cells.

Using the "one-bead one-peptide" combinatorial technology, a library of random cyclic octapeptides and nonapeptides, consisting of natural and unnatural amino acids, was synthesized on polystyrene beads. This library was used to screen for peptides that promoted attachment and proliferation of bronchioloalveolar carcinoma cells (H1650), employing a "cell growth on bead" assay. Consensus peptide sequences of cNleDXXXXc and cXNleDXXXXc (where Nle is norleucine) were identified. With alanine scanning and site-directed deletion, a typical ligand consisted of a motif of -NleDI/V/Nle- with two flanking cysteines. These peptide ligands were specific for promoting cell attachment of the H1650 cells and the cells of lymphoid cancers (Jurkat and Raji) but not other selected human cell lines of lung cancer and fibroblast. In an antibody blocking assay, integrin alpha(4)beta(1), which was overexpressed in H1650, Jurkat, and Raji, was identified as a putative receptor for these peptide ligands. Using Chinese hamster ovary cells transfected with either wild-type or mutant integrin alpha(4), a critical binding site for these peptides was localized to the glycine residue at position 190 of integrin alpha(4).

Alanine↗
PubMed2003

Identification of lung micrometastatic tumor foci in nude mice with implanted tumor using laser capture microdissection and PCR-single-strand conformation polymorphism.

OBJECTIVE: To assess the value of the laser capture microdissection (LCM) combined with polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) technique for diagnosing micrometastatic cancer cells in the lung of nude mice with implanted tumor. METHODS: Isolation of the cells from the suspected tumor loci in the lung of nude mice with implanted tumors was performed using laser capture microdissection technique, and the genomic DNA extracted from the cells was amplified by 2 sequential PCRs. Non-radioisotopic single-strand conformation polymorphism (SSCP) was subsequently performed to analyze the point mutation of K-ras gene. RESULTS: K-ras gene (codon 12) mutation in AGT was identified in the suspected metastatic cancer cells but not in the benign nodular lesion, where wild type K-ras gene (GGT) was detected. CONCLUSION: The utilization of LCM combined with PCR-SSCP technique may serve as a crucial aid for molecular diagnosis of morphologically suspicious cancer cell populations.

Animals↗
PubMed2002

Current and future therapeutic approaches in locally advanced (stage III) non-small cell lung cancer.

In the treatment of locally advanced (stage III) non-small cell lung cancer, randomized clinical trials have shown that sequential administration of platinum-based chemotherapy followed by radiotherapy improves outcome compared with radiotherapy alone. More recently, concurrent chemoradiotherapy has been shown to be superior to sequential therapy. Incorporating full-dose chemotherapy into induction or consolidation phases is aimed at the eradication of distant micrometastases. These approaches are currently being examined in clinical trials. The role of neoadjuvant and adjuvant therapy in resectable stage IIIA patients remains controversial. Integration of newer cytotoxic agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, and irinotecan) and molecularly targeted agents into the treatment of stage-III patients may result in improved long-term outcomes and is currently under study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Premedication strategy for weekly paclitaxel.

PURPOSE: Dexamethasone and histamine antagonists have been employed commonly as premedications for prophylaxis of hypersensitivity reactions (HSRs) to paclitaxel. Frequent premedications for weekly administration of paclitaxel are associated with added side-effects and extra cost. We analyzed our experience of HSRs to paclitaxel administered every 3-4 weeks, and designed a treatment algorithm to eliminate premedications in a majority of patients receiving weekly paclitaxel. PATIENTS AND METHODS: The incidence of HSRs was analyzed retrospectively in patients who received 3-hr infusions of paclitaxel (135-225 mg/m2) every 3-4 weeks in our institution over a period of 5 years. On the basis of the results of this analysis, we designed a premedication schema for patients receiving weekly paclitaxel, 50-90 mg/m2/week, as follows: Thirty minutes prior to the first weekly dose of paclitaxel, patients received intravenously (i.v.) dexamethasone (10 mg), diphenhydramine (25 mg), and cimetidine (300 mg). If no HSRs occurred, all premedications were deleted for subsequent weekly paclitaxel doses. For patients who experienced HSRs, 20 mg of dexamethasone was given orally 12 and 6 hr prior to re-challenge with paclitaxel in addition to diphenhydramine and cimetidine. RESULTS: Over a period of 5 years, 358 patients received 1608 3-hr infusions of paclitaxel (135-225 mg/m2). Hypersensitivity reactions, which occurred exclusively during the first cycle of paclitaxel administration, were observed in 14 patients. Of these 14 patients, 11 were successfully retreated with paclitaxel without HSRs, two had recurrent HSRs upon paclitaxel re-challenge, and one refused further treatment. These observations indicate that HSRs to paclitaxel occurred in 4% of patients upon first exposure, that most of these patients can be retreated successfully with paclitaxel without recurrent HSRs, and that if no HSRs occur during the first cycle, HSRs are unlikely to occur with subsequent paclitaxel administration. The premedication schema was applied to 30 patients receiving 205 one-hr infusions of weekly paclitaxel. Using this premedication strategy, no HSRs have been observed during the initial or subsequent administration of paclitaxel. CONCLUSION: We conclude that this premedication strategy is feasible and worthy of further study for patients receiving weekly paclitaxel.

Administration, Oral↗