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Chusilp Charnsangavej

Publications and source records attributed to Chusilp Charnsangavej.

36 records · Page 2Linked to original sources
PubMed2003

Improved radiolabeling of PEGylated protein: PEGylated annexin V for noninvasive imaging of tumor apoptosis.

We have developed a one-step procedure to introduce both polyethylene glycol (PEG) and the metal chelator diethylenetriaminepentaacetic acid (DTPA) to proteins through a heterofunctional PEG precursor. The PEG precursor contains DTPA at one end and an amine-reactive isothiocyanate (SCN-) functional group at the other end. It was obtained as lyophilized powder and could be stored at 4 degrees C for several months. Protein conjugation was achieved by simply mixing the proteins and the PEG precursor SCN-PEG-DTPA in an aqueous solution. As exemplified by the PEGylation and radiolabeling of annexin V, the resulting conjugate 111In-DTPA-PEG-annexin V showed selective binding to apoptotic cells in vitro and increased blood half-life in vivo. The PEGylated, radiolabeled annexin V may be useful in the noninvasive imaging of apoptosis.

Animals↗
PubMed2002

Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin.

PURPOSE: Angiogenesis is a target for the treatment of cancer and other diseases, and its complex biology suggests that establishing the appropriate dose and schedule for antiangiogenic treatment will require extensive study. We present the initial results of a dose-finding clinical trial of recombinant human endostatin (rh-Endo) that examined potential surrogates for response to antiangiogenic therapy. PATIENTS AND METHODS: Twenty-five patients were treated with escalating doses of rh-Endo. Positron emission tomography (PET) was used to assess tumor blood flow (with [15O]H2O) and metabolism (with [18F]fluorodeoxyglucose) before the start of therapy and then every 4 weeks. To directly assess the effects of rh-Endo on endothelial cells within the tumors, biopsy specimens of tumor tissue were obtained before therapy and again at 8 weeks and evaluated for endothelial cell and tumor cell apoptosis. RESULTS: Tumor blood flow and metabolism as measured by PET scans generally decreased with increasing doses of rh-Endo; however, the effects were complex and in some analyses nonlinear. Tumor biopsy analysis revealed a significant increase in tumor cell apoptosis (P =.027) and endothelial cell apoptosis (P =.027) after 8 weeks of therapy. However, there was no statistically significant relationship between rh-Endo dose and induction of tumor cell or endothelial cell apoptosis. CONCLUSION: These initial data suggest that rh-Endo has measurable effects on tumor blood flow and metabolism and induces endothelial and tumor cell apoptosis even in the absence of demonstrable anticancer effects. Further study and validation of these biomarkers in the context of antiangiogenic therapy will be required.

Adenocarcinoma↗
PubMed2002

Phase I study of recombinant human endostatin in patients with advanced solid tumors.

PURPOSE: Endostatin, a 20-kd fragment of collagen XVIII, is a potent inhibitor of angiogenesis. We evaluated recombinant human endostatin (rh-Endo) in a phase I trial designed to assess safety, pharmacokinetics, and serum markers of angiogenesis in patients with solid tumors. PATIENTS AND METHODS: Twenty-six patients were enrolled onto a dose-finding trial of rh-Endo administered as an intravenous bolus over a 20-minute period once daily. Three patients each were treated at dose levels of 15, 30, 60, 120, 180, and 600 mg/m(2)/d, and seven patients were treated at 300 mg/m(2)/d. Treatment consisted of a minimum of two 28-day cycles. Evaluations included noninvasive imaging, pharmacokinetics, and serum biomarkers. RESULTS: Twenty-five patients were treated with rh-Endo. Treatment was well tolerated; there were no dose-limiting toxic effects. Bacteremia from frequent central line access was the most common problem. The pharmacokinetic disposition of rh-Endo was linear and best described using a two-compartmental open model. The overall mean half-life was 10.7 +/- 4.1 hours. A dose of 300 mg/m(2) achieved an area under the concentration-time curve associated with activity in preclinical models. In two patients, there was evidence of antitumor activity, but no responses were seen. Serum markers of angiogenic activity did not provide insight into rh-Endo's activity. Serum antibodies were observed against both rh-Endo and the Pichia pastoris vector, but no allergic reactions were observed. CONCLUSION: rh-Endo was safe and well tolerated. rh-Endo pharmacokinetic profiles achieved area under the concentration-time curves associated with activity in preclinical models. Evidence of minor antitumor activity was observed and further studies are indicated.

Adenocarcinoma↗
PubMed2002

Limitations of conventional doses of chemoradiation for unresectable biliary cancer.

PURPOSE: To determine, in a retrospective review, the limitations of definitive chemoradiation in the treatment of patients with unresectable extrahepatic cholangiocarcinoma and generate testable hypotheses for future prospective clinical trials. METHODS AND MATERIALS: Between 1957 and 2000, 52 patients with localized, unresectable cholangiocarcinoma were treated with radiotherapy (RT) with or without concurrent chemotherapy. Unresectable disease was defined, by evidence on imaging studies or at surgical exploration, as localized tumor abutting or involving the main portal vein, tumor involvement of secondary biliary radicals, or evidence of nodal metastases. Patients were grouped according to the RT dose: 27 patients received a total dose of 30 Gy (Group 1), 14 patients received 36-50.4 Gy (Group 2), and 11 patients received 54-85 Gy (Group 3). 192Ir intracavitary boosts (median 20 Gy) were delivered in 3 patients, and an intraoperative boost (20 Gy) was used in 1 patient. Of the 52 patients, 38 (73%) received concomitant protracted venous infusion of 5-fluorouracil (200-300 mg/m2 daily, Monday through Friday). Kaplan-Meier analysis was used to calculate the actuarial 1-year and median overall survival (OS), radiographic local progression, symptomatic progression, and distant failure. Treatment-related variables and prognostic factors were evaluated using the log-rank test. RESULTS: The first site of disease progression was local in 72% of cases. The actuarial local progression rate at 12 months for all patients was 59%. The median time to radiographic local progression was 9, 11, and 15 months in Groups 1, 2, and 3, respectively (p = 0.48). Fifteen percent of all patients developed metastatic disease (1-year OS rate 18%). The median survival rate for all patients was 10 months (1-year OS rate 44%). The RT dose, use of concurrent chemotherapy, histologic grade, initial extent of liver involvement, and extent of vascular involvement had no influence on radiographic local progression or OS. Grade 3 or greater toxicity was similar in all dose groups (22% vs. 14% vs. 27%, p = 0.718). CONCLUSION: The primary limitation of definitive chemoradiation was local progression. Although the small patient numbers limited the statistical power of this study, a suggestion of improved local control was found with the use of higher RT doses. To address this pattern of failure, future prospective investigation using high-dose conformal RT with novel cytotoxic and/or biologic agents with radiosensitizing properties is warranted.

Adult↗
PubMed2002

Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome.

PURPOSE: To evaluate the toxicity of a preoperative regimen of paclitaxel and concurrent external-beam radiation therapy, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with localized, potentially resectable pancreatic adenocarcinoma were treated with 30 Gy external-beam radiation therapy and concomitant weekly 3-hour infusions of paclitaxel (60 mg/m(2)). Radiographic restaging was performed 4 to 6 weeks after chemoradiation, and patients with localized disease underwent pancreatectomy with EB-IORT. RESULTS: Thirty-five patients completed chemoradiation; 16 (46%) experienced grade 3 toxicity. Four patients (11%) required hospitalization for dehydration due to grade 3 nausea and vomiting. Twenty (80%) of 25 patients who underwent surgery underwent pancreatectomy; EB-IORT was used in 13 patients. There were no histologic complete responses to preoperative therapy; 21% of specimens demonstrated more than 50% nonviable cells (grade 2b treatment effect). With a median follow-up period of 46 months, the 3-year overall survival rate with chemoradiation and pancreatectomy was 28%. CONCLUSION: Preoperative paclitaxel-based concurrent chemoradiation is feasible. The toxicity of this regimen seems greater than that with fluorouracil. The histologic responses and survival are similar, suggesting no advantages to paclitaxel-based preoperative treatment.

Adenocarcinoma↗
PubMed2002

CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma: results of a phase II study.

BACKGROUND: This Phase II study assessed the response rate and toxicity profile of the combination CPT-11 and cisplatin administered weekly to patients with untreated, advanced adenocarcinoma of the stomach or the gastroesophageal junction. METHODS: Patients with histologic proof of adenocarcinoma of the stomach or the gastroesophageal junction with adequate liver, kidney, and bone marrow functions were treated with 65 mg/m(2) CPT-11 plus 30 mg/m(2) cisplatin, both administered intravenously 1 day per week for 4 consecutive weeks, followed by a recovery period of 2 consecutive weeks. The response rate, time to disease progression, survival, and toxic effects were analyzed. RESULTS: Thirty-six of 38 registered patients (95%) were assessable. The median number of 6-week cycles per patient was 2.5 (range, 1-7 6-week cycles). Four patients (11%) achieved a complete response, and 17 patients (47%) had a partial response for an overall response rate of 58%. The median time to progression of carcinoma was 24 weeks, and the median survival was 9 months (range, 1-23+ months). There was one treatment-related death. Major toxic effects included diarrhea, neutropenia, and fatigue. Ninety percent of all planned doses were delivered on time; however, 53 of 79 canceled or delayed weekly doses (66%) occurred in the third or fourth week of the therapy cycle. CONCLUSIONS: The combination of CPT-11 and cisplatin is active against gastric or gastroesophageal adenocarcinoma and needs to be studied further. A modification in doses and schedules may be warranted to make the regimen more tolerable to patients. The addition of other active drugs or radiation therapy to this regimen would be of interest.

Adult↗
PubMed2002

Preoperative imaging of biliary tract cancers.

Many imaging techniques are available for the evaluation of patients with malignant obstructive jaundice. Ultrasonography, in experienced hands, is valuable for evaluating the local extent of the disease, but its usefulness for staging distant metastases is limited. When used properly, CT and MR imaging can provide valuable information about the extent of local tumor involvement and distant metastases. These noninvasive techniques provide images of the bile ducts and vascular images that are comparable in quality to those obtained with more invasive procedures, such as PTC, ERCP, and angiography, and do not have the risk for complications of these invasive techniques.

Bile Duct Neoplasms↗
PubMed2002

Angiogenesis modulation in cancer research: novel clinical approaches.

Angiogenesis--the formation of new blood vessels--is essential for tumour progression and metastasis. Consequently, the modulation of tumour angiogenesis using novel agents has become a highly active area of investigation in cancer research, from the bench to the clinic. However, the great therapeutic potential of these agents has yet to be realized, which could, in part, be because the traditional strategies that are used in clinical trials for anticancer therapies are not appropriate for assessing the efficacy of agents that modulate angiogenesis. Here, we discuss methods for monitoring the biological activity of angiogenic modulators, and innovative approaches to trial design that might facilitate the integration of these agents into anticancer therapy.

Angiogenesis Inhibitors↗
PubMed2002

Irinotecan/cisplatin in advanced, treated gastric or gastroesophageal junction carcinoma.

We conducted a phase II study to assess the response rate and toxicity profile of the irinotecan (CPT-11, Camptosar) plus cisplatin combination administered weekly to patients with at least one previous chemotherapy for advanced adenocarcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach orgastroesophageal junction with adequate liver, kidney, and bone marrow functions were treated with 50 mg/m2 of irinotecan plus 30 mg/m2 of cisplatin, both administered intravenously 1 day a week for 4 consecutive weeks, followed by a 2-week recovery period. Response rate, time to disease progression, survival, and toxic effects were analyzed. Of 32 registered patients, 29 were assessable. Nine patients (31%) achieved a partial response. Median time to disease progression was 7 weeks (range: 5-48+ weeks) and median survival time was 5 months (range: 2.5-31 months). There were no treatment-related deaths. Major toxic effects included diarrhea, neutropenia, and fatigue. Of 260 doses administered in 65 6-week courses, 46 doses were either delayed or missed. Most delayed or missed doses occurred in the third or fourth week of the cycle. We concluded that the combination of irinotecan and cisplatin is an active second-line therapy for patients with advanced gastric or gastroesophageal adenocarcinoma in whom one previous chemotherapy has failed. Modifications in doses and schedule are warranted to increase the tolerability of the regimen. Phase III trials are necessary to establish the clinical utility of irinotecan/cisplatin in these patient populations.

Adenocarcinoma↗
PubMedDate not supplied

Synthesis and characterization of poly(L-glutamic acid) gadolinium chelate: a new biodegradable MRI contrast agent.

Most currently evaluated macromolecular contrast agents for magnetic resonance imaging (MRI) are not biodegradable. The goal of this study is to synthesize and characterize poly(l-glutamic acid) (PG) gadolinium chelates as biodegradable blood-pool MRI contrast agents. Two PG chelates of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) were synthesized through the use of difunctional and monofunctional DTPA precursors. The conjugates were characterized with regard to molecular weight and molecular weight distribution, gadolinium content, relaxivity, and degradability. Distributions of the polymeric MRI contrast agents in various organs were determined by intravenous injection of (111)In-labeled polymers into mice bearing murine breast tumors. MRI scans were performed at 1.5 T in mice after bolus injection of the polymeric chelates. PG-Hex-DTPA-Gd, obtained from aminohexyl-substituted PG and DTPA-dianhydride, was partially cross-linked and was undegradable in the presence of cathepsin B. On the other hand, PG-Bz-DTPA-Gd synthesized directly from PG and monofunctional p-aminobenzyl-DTPA(acetic acid-tert-butyl ester) was a linear polymer and was degradable. The relaxivities of the polymers at 1.5 T were 3-8 times as great as that of Gd-DTPA. Both polymers had high blood concentrations and were primarily accumulated in the kidney. However, PG-Bz-DTPA-Gd was gradually cleared from the body and had significantly less retention in the blood, the spleen, and the kidney. MRI with PG-Bz-DTPA-Gd in mice showed enhanced vascular contrast at up to 2 h after the contrast agent injection. The ability of PG-Bz-DTPA-Gd to be degraded and cleared from the body makes it a favorable macromolecular MRI contrast agent.

Animals↗
PubMedDate not supplied

Hemodynamic and morphologic changes after portal vein embolization: differential effects in central and peripheral zones in the liver on multiphasic computed tomography.

OBJECTIVE: To evaluate hemodynamic and morphologic effects in the liver after portal vein embolization (PVE). METHODS: Hepatic computed tomography scans of 7 patients who had undergone preoperative PVE were retrospectively reviewed. Pre- and post-PVE computed tomography densities were evaluated for the unenhanced, late arterial, and portal venous phases in peripheral and central hepatic regions and in the 3 main hepatic veins. Relative changes in areas in these regions were assessed in 5 evaluable patients with serial post-PVE scans. RESULTS: During the late arterial phase, enhancement was significantly higher after PVE than it was before PVE in the peripheral hepatic regions, and it was higher in the peripheral regions than in the central regions. Enhancement was also significantly higher in the right main hepatic vein than in the middle and left hepatic veins during the late arterial phase. The ratio of areas of the peripheral/central regions decreased significantly after PVE. CONCLUSIONS: Zonal enhancement in the late arterial phase changed after PVE and seemed to be associated with differential parenchymal atrophy. We speculate that the hepatic arterial supply increases peripherally and that peribiliary/periportal plexuses maintain the portal supply centrally.

Absorptiometry, Photon↗
PubMedDate not supplied

Transhepatic portal vein embolization: anatomy, indications, and technical considerations.

Portal vein embolization (PVE) is increasingly being accepted as a useful procedure in the preoperative treatment of patients selected for major hepatic resection. PVE is performed via either the percutaneous transhepatic or the transileocolic route and is usually reserved for patients whose future liver remnants are too small to allow resection. It is a safe and effective method for inducing selective hepatic hypertrophy of the nondiseased portion of the liver and may thereby reduce complications and shorten hospital stays after resection. A thorough knowledge of hepatic segmentation and portal venous anatomy is essential before performing PVE. In addition, the indications and contraindications for PVE, the methods for assessing hepatic lobar hypertrophy, the means of determining optimal timing of resection, and the possible complications of PVE need to be fully understood before undertaking the procedure. Technique may vary among operators, and further research is necessary to determine the best embolic agents available and the expected rates of liver regeneration for PVE. Nevertheless, as hepatobiliary surgeons become more experienced at performing extended hepatic resections, PVE may be requested more frequently.

Contraindications↗
PubMedDate not supplied

Gastrointestinal stromal tumor: role of CT in diagnosis and in response evaluation and surveillance after treatment with imatinib.

Gastrointestinal stromal tumors (GISTs), which arise from the interstitial cells of Cajal, are the most common nonepithelial tumors of the gastrointestinal tract. It is now well known that imatinib, a new molecularly targeted tyrosine kinase receptor blocker, results in a dramatic response and markedly improved long-term survival in patients with GISTs. The increasing recognition of GISTs and the prolonged survival have made imaging increasingly important not only for diagnosis but also for monitoring the effects of treatment and detecting tumor progression. Computed tomography (CT) is the imaging modality of choice for these purposes. The imaging findings at initial presentation, during treatment, and at tumor progression were studied in 113 patients with primary and advanced GISTs before and up to 37 months after imatinib treatment. GISTs occur anywhere along the gastrointestinal tract, most commonly in the stomach and small bowel. At contrast material-enhanced CT, localized primary GISTs are typically exophytic, large, hypervascular masses. When the tumors respond to treatment, the changes in tumor size may initially vary; however, GISTs typically become homogeneous and hypoattenuating, with disappearance of enhancing tumor nodules and tumor vessels in the early posttreatment period. Development of a nodule within the treated tumor is unique to GISTs and indicates recurrence regardless of changes in tumor size.

Antineoplastic Agents↗
PubMedDate not supplied

Lymphoma.

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Adult↗