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Biomedical subjects

C Shih

Publications and source records attributed to C Shih.

At least 19 recordsLinked to original sources
PubMed2001

Trophic conversion of an obligate photoautotrophic organism through metabolic engineering.

Most microalgae are obligate photoautotrophs and their growth is strictly dependent on the generation of photosynthetically derived energy. We show that the microalga Phaeodactylum tricornutum can be genetically engineered to thrive on exogenous glucose in the absence of light through the introduction of a gene encoding a glucose transporter (glut1 or hup1). This demonstrates that a fundamental change in the metabolism of an organism can be accomplished through the introduction of a single gene. This also represents progress toward the use of fermentation technology for large-scale commercial exploitation of algae by reducing limitations associated with light-dependent growth.

Biological Transport↗
PubMed2001

Biodegradable block copolymers for delivery of proteins and water-insoluble drugs.

Release of several drugs from new ABA-type biodegradable thermal gels, ReGel, including proteins and conventional molecules, are presented. These are biodegradable, biocompatible polymers that demonstrate reverse thermal gelation properties. Organic solvents are not used in the synthesis, purification, or formulation of these polymers. The unique characteristics of ReGel hinge on the following two key properties: (1) ReGel is a water soluble, biodegradable polymer at temperatures below the gel transition temperature; (2) ReGel forms a water-insoluble gel once injected. This is consistent with a hydrophobically bonded gel state where all interactions are physical, with no covalent crosslinking. An increase in viscosity of approximately 4 orders of magnitude accompanies the sol--gel transition. The gel forms a controlled release drug depot with delivery times ranging from 1 to 6 weeks. ReGel's inherent ability to solubilize (400 to >2000-fold) and stabilize poorly soluble and sensitive drugs, including proteins is a substantial benefit. The gel provided excellent control of the release of paclitaxel for approximately 50 days. Direct intratumoral injection of ReGel/paclitaxel (OncoGel) results in a slow clearance of paclitaxel from the injection site with minimal distribution into any organ. Efficacies equivalent to maximum tolerated systemic dosing were observed at OncoGel doses that were 10-fold lower. Data on protein release (pGH, G-CSF, insulin, rHbsAg) and polymer biocompatibility are discussed.

Drug Delivery Systems↗
PubMed2001

Cryptophycin-induced hyperphosphorylation of Bcl-2, cell cycle arrest and growth inhibition in human H460 NSCLC cells.

Bcl-2 has been described as a factor that can protect from apoptosis. The protective effect of Bcl-2 may be lost if the protein is phosphorylated. Bcl-2 phosphorylation can be induced by agents that affect microtubule depolymerization or prevent microtubule assembly. In 13 human tumor cell lines there was a high degree of heterogeneity in Bcl-2 protein expression. Human H460 non-small-cell lung carcinoma (NSCLC) cells expressed high levels of Bcl-2 and were selected for study. Western blot analysis for Bcl-2 phosphorylation was carried out after 4 h and 24 h of exposure to cryptophycin 52, cryptophycin 55, paclitaxel or vinblastine. Cryptophycin 52 and cryptophycin 55 were very potent inducers of Bcl-2 phosphorylation. After 4 h of exposure, Bcl-2 phosphorylation was evident with 0.05 nM cryptophycin 52, 0.25 nM cryptophycin 55, 5 nM vinblastine and 50 nM paclitaxel. The hyperphosphorylated form of Bcl-2 was evident after 24 h exposure of H460 cells to 0.25 nM cryptophycin 52 or cryptophycin 55 and 50 nM vinblastine or paclitaxel. The effects of the compounds on the cell cycle paralleled those on Bcl-2 phosphorylation. In H460 cells 90% cell killing was obtained with 0.13 nM cryptophycin 52, 0.2 nM cryptophycin 55, 20 nM paclitaxel and > 100 nM vinblastine after 24 h of exposure as determined by colony formation. In Bcl-2-negative Calu-6 NSCLC cells, 90% cell killing was obtained with 0.03 nM cryptophycin 52, 0.1 nM cryptophycin 55, 11 nM paclitaxel and 0.5 nM vinblastine using the same experimental design. Thus, cryptophycins are potent inducers of Bcl-2 phosphorylation. The cryptophycins were more potent cytotoxic agents in Bcl-2-negative Calu-6 cells than in Bcl-2-positive H460 cells indicating that pathways triggered by Bcl-2 phosphorylation are involved in cryptophycin-induced lethality.

Antineoplastic Agents↗
PubMed2001

Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in murine lewis lung carcinoma and human Calu-6 non-small-cell lung carcinoma xenografts.

In cell culture, the compound 317615.2HCl, a potent inhibitor of VEGF-stimulated HUVEC proliferation, was not very effective against Calu-6 non-small-cell lung carcinoma cells (IC50 26 microM). Exposure to combinations of paclitaxel or carboplatin and 317615.2HCl with Calu-6 cells in culture resulted in cell survival that reflected less-than-additivity to additivity of the two agents. Administration of 317615.2HCl orally twice daily to nude mice bearing subcutaneous Calu-6 tumors resulted in a decreased number of intratumoral vessels as determined by CD31 and CD105 staining to 50% of the number in control tumors. 317615.2HCl showed antitumor activity against the Lewis lung carcinoma and increased the tumor growth delay produced by paclitaxel by 5-fold, that produced by gemcitabine by 2-fold and that produced by carboplatin by 1.7-fold. There was a decrease in the number of lung metastases in the Lewis lung carcinoma that paralleled the increased response of the primary tumor with each treatment combination. Administration of 317615.2HCl also increased the tumor growth delay produced by fractionated radiation therapy in the Lewis lung tumor. Treatment with 317615.2HCl was an effective therapy in the Calu-6 non-small-cell lung carcinoma xenograft when the compound was administered early (days 4-18) or later (days 14-30). Combination treatment regimens in which 317615.2HCl was administered along with or sequentially with paclitaxel or carboplatin were much more effective than the chemotherapeutic agents administered alone. 317615.2HCl is in early clinical testing.

Administration, Oral↗
PubMed2001

Presentation of striatal hyperintensity on T1-weighted MRI in patients with hemiballism-hemichorea caused by non-ketotic hyperglycemia: report of seven new cases and a review of literature.

Recent studies have shown unique clinicoradiologic characteristics in patients with hemiballism-hemichorea (HB-HC) caused by non-ketotic hyperglycemia; however, there is still a limited number of patients being reported. We report 7 patients (3 males and 4 females) with this type of dyskinesia, whose ages ranged from 60 to 84 years. Brain CT of these patients showed hyperdensity in the contralateral striatum, corresponding with MRI studies that showed an increased signal intensity on T1-weighted images and a decreased signal on T2-weighted images. After metabolic control had been achieved, the hyperkinetic state of these patients abruptly ceased. Follow-up neuroimaging studies in 2 patients documentied complete resolution of the striatal hyperintensity on brain CT and MRI after 3 months and 6 months, respectively. A review of patients with HB-HC caused by non-ketotic hyperglycemia reported formerly and in the present study shows that the dyskinesia tends to occur in aged diabetic patients. The age of patients with dyskinesia secondary to cerebral infarction is generelly much lower. We also found that 86% (30 out of 35 cases) patients reported with HB-HC caused by non-ketotic hyperglycemia were Asians. The prognosis of the dyskinesia was excellent, and the radiological abnormalities are completely reversible.

Aged↗
PubMed2001

Photoprotection in a zeaxanthin- and lutein-deficient double mutant of Arabidopsis.

When light absorption by a plant exceeds its capacity for light utilization, photosynthetic light harvesting is rapidly downregulated by photoprotective thermal dissipation, which is measured as nonphotochemical quenching of chlorophyll fluorescence (NPQ). To address the involvement of specific xanthophyll pigments in NPQ, we have analyzed mutants affecting xanthophyll metabolism in Arabidopsis thaliana. An npq1 lut2 double mutant was constructed, which lacks both zeaxanthin and lutein due to defects in the violaxanthin de-epoxidase and lycopene in-cyclase genes. The npq1 lut2 strain had normal Photosystem II efficiency and nearly wild-type concentrations of functional Photosystem II reaction centers, but the rapidly reversible component of NPQ was completely inhibited. Despite the defects in xanthophyll composition and NPQ, the npq1 lut2 mutant exhibited a remarkable ability to tolerate high light.

Journal Article↗
PubMed2001

Cryptophycins: a novel class of potent antimitotic antitumor depsipeptides.

The antitumor cryptophycins are synthetic derivatives of the desipeptide cryptophycins isolated from the cyanobacterium Nostoc sp. Cryptophycin 52 that is currently in clinical trial in solid tumors, is prepared by total synthesis of four key fragments that are coupled to form the final product. The mechanism of anticancer activity of the cryptophycins has been associated with their destabilization of microtubules and with their induction of bcl-2 phosphorylation leading to apoptosis. The cryptophycins maintain activity against ovarian and breast carcinoma cells that overexpress the multidrug resistance efflux pump P-glycoprotein. Cryptophycin 52 has demonstrated a broad range of antitumor activity against both murine and human tumors. In the human MX-1 breast carcinoma xenograft cryptophycin 55 produced greater-than- additive tumor response in combination with 5-fluorouracil. In human non-small cell lung carcinoma and human small cell carcinoma xenografts, administration of the cryptophycins along with gemcitabine, cisplatin or carboplatin resulted in antitumor activity greater than either agent alone. The cryptophycins appear to be additive with fractionated radiation therapy in the human H460 non-small cell lung carcinoma. In the human HCT116 colon carcinoma, the cryptophycins resulted in a greater than additive tumor response when administered sequentially with 5-fluorouracil or irinotecan. Treatment of animals bearing intraperitoneal human OVCAR-2 ovarian carcinoma with cryptophycin 52 resulted in survival times that were greater than those achieved with docetaxel or paclitaxel. Cryptophycin 52 is currently in early clinical testing.

Animals↗
PubMed2001

Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human T98G glioblastoma multiforme xenografts.

Although rare, the morbidity and mortality from brain tumors are significant. Chemotherapy has made only a small impact on these tumors. The human T98G glioblastoma multiforme cell line was used as a brain tumor model. The protein kinase Cbeta inhibitor 317615 x 2HCl was not highly cytotoxic toward T98G cells in culture and was additive in cytotoxicity with carmustine (BCNU). When nude mice bearing s.c. T98G tumors were treated with 317615 x 2HCl p.o. twice daily on days 14-30 after tumor cell implantation, the number of intratumoral vessels stained by CD31 was decreased to 37% of control, and the number of intratumoral vessels stained by CD105 was decreased to 50% of control. The compound 317615 x 2HCl was an active antitumor agent against s.c. growing T98G xenografts. A treatment regimen administering 317615 x 2HCl before, during, and after BCNU was compared with a treatment regimen administering 317615 x 2HCl sequentially after BCNU. In the tumor growth delay determination of the s.c. tumor, the sequential treatment regimen was more effective than the simultaneous treatment regimen. However, when the same treatments were administered to animals bearing intracranial T98G tumors, the survival of animals receiving the simultaneous treatment regimen increased from 41 days for those treated with BCNU alone to 102 days for animals treated with the combination, whereas animals receiving the sequential treatment regimen survived 74 days. Treatment with the protein kinase Cbeta inhibitor decreased T98G glioblastoma multiforme angiogenesis and improved treatment outcome with BCNU.

Animals↗
PubMed2000

Interaction of the antitumor compound cryptophycin-52 with tubulin.

Cryptophycin-52 (LY355703) is currently undergoing clinical evaluation for cancer chemotherapy. It is a potent suppressor of microtubule dynamics in vitro, and low picomolar concentrations appear to inhibit cancer cell proliferation at mitosis by stabilizing spindle microtubules. In the present study, using [(3)H]cryptophycin-52, we found that the compound bound to tubulin at a single high-affinity site [apparent K(a) (3.6 +/- 1) x 10(6) L/mol, 34 degrees C]. The binding of cryptophycin-52 to tubulin was rapid, not appreciably temperature-dependent, and very poorly reversible. However, we could remove [(3)H]cryptophycin-52 from [(3)H]cryptophycin-52-tubulin complex by denaturing the complex with either urea treatment or boiling. These data suggest that the binding of cryptophycin-52 to tubulin is not covalent. A van't Hoff plot of the binding data indicated that the binding of cryptophycin-52 to tubulin is primarily entropy-driven with a minimum enthalpy contribution. In addition, cryptophycin-52 perturbed the far-ultraviolet circular dichroic spectrum of tubulin and it inhibited the colchicine-induced guanosine triphosphatase activity of tubulin, indicating that its binding to tubulin induces a conformational change in the tubulin. Competition experiments with vinblastine suggest that the binding site for crytophycin-52 may overlap with the vinblastine binding site.

Animals↗
PubMed2000

A pigment-binding protein essential for regulation of photosynthetic light harvesting.

Photosynthetic light harvesting in plants is regulated in response to changes in incident light intensity. Absorption of light that exceeds a plant's capacity for fixation of CO2 results in thermal dissipation of excitation energy in the pigment antenna of photosystem II by a poorly understood mechanism. This regulatory process, termed nonphotochemical quenching, maintains the balance between dissipation and utilization of light energy to minimize generation of oxidizing molecules, thereby protecting the plant against photo-oxidative damage. To identify specific proteins that are involved in nonphotochemical quenching, we have isolated mutants of Arabidopsis thaliana that cannot dissipate excess absorbed light energy. Here we show that the gene encoding PsbS, an intrinsic chlorophyll-binding protein of photosystem II, is necessary for nonphotochemical quenching but not for efficient light harvesting and photosynthesis. These results indicate that PsbS may be the site for nonphotochemical quenching, a finding that has implications for the functional evolution of pigment-binding proteins.

Amino Acid Sequence↗
PubMed2000

A high-performance liquid chromatography method using ultraviolet and fluorescence detection for the quantitation of UCN-01, 7-hydroxystaurosporine, from human plasma and saliva.

UCN-01, 7-hydroxystaurosporine, is an antagonist of protein kinase C, as well as causing cell cycle arrest. We developed and validated an HPLC assay method for the quantitation of UCN-01. Plasma and saliva standard curves were prepared at concentrations ranging from 0.2 to 20.0 microgram/mL and 4.0 to 200.0 ng/mL, respectively. The sample preparation consisted of acetonitrile precipitation. Separation was accomplished on a phenyl column and a C-18 precolumn insert utilizing a gradient-profile consisting of ammonium acetate and acetonitrile. UV detection was set at 295 nm for UCN-01 and 323 nm for umbelliferone, the internal standard. For fluorescence detection, excitation occurred at 290 nm, while emission was at 400 nm. The retention times were around 4 min for umbelliferone and 9.1 for UCN-01. Inter- and intra-assay errors of accuracy were less than 7. 0% and 10.7%, respectively, for the plasma standard curve and less than 7.1% and 6.7%, respectively, for the saliva standard curve. The recoveries of UCN-01 and umbelliferone from saliva were 81.4 +/- 0. 9% and 106.3 +/- 10.2%, respectively. The recovery of UCN-01 from plasma was 97.9 +/- 7.1% and for umbelliferone was 103.3 +/- 2.3%. This method is suitable for quantifying UCN-01 in patient samples and further characterizing the clinical pharmacology of this compound. Published in 2000 by John Wiley & Sons, Ltd.

Alkaloids↗
PubMed2000

Antitumor activity of cryptophycins: effect of infusion time and combination studies.

INTRODUCTION/PURPOSE: Cryptophycins are a family of antitubulin antitumor agents. A synthetic cryptophycin derivative (LY355703, CRYPTO 52) is in early clinical evaluation. The effect of infusion time on the antitumor activity of four cryptophycins was assessed in rats bearing the 13762 mammary carcinoma and combination treatment regimens were assessed in nude mice bearing human tumor xenografts. METHODS: The cryptophycins were prepared in 2% PEG300/8% cremophor/90% normal saline and delivered by jugular vein catheter on days 7, 9 and 11 post tumor implant to 13762 tumor-bearing rats. The cryptophycins prepared in the same formulation were administered by intravenous bolus injection on an alternate day schedule for five doses to human tumor xenograft bearing nude mice. RESULTS: An infusion time of 2 h in the rats increased the tumor growth delay produced by CRYPTO 52 and CRYPTO 55, while increasing the infusion time to 6 h continued to increase the tumor growth delay for CRYPTO 292 and CRYPTO 296. Administering CRYPTO 292 at a higher dose two times was more effective than administering it at a lower dose three times. The tumor growth delays produced by the cryptophycins in the rat 13762 mammary carcinoma were greater than those with cisplatin, doxorubicin, 5-fluorouracil and 5 x 3 Gray and comparable with cyclophosphamide and gemcitabine. Combination studies were carried out in human tumor xenografts including the MX-1 breast carcinoma, the Calu-6 non-small cell lung carcinoma, the H82 small cell lung carcinoma and the SW-2 small cell lung carcinoma. CRYPTO 52 and CRYPTO 55 combined with doxorubicin, paclitaxel and 5-fluorouracil to form highly effective regimens against the human MX-1 breast carcinoma. CRYPTO 52 and CRYPTO 55 were also highly effective against the three lung carcinoma xenografts when combined with the antitumor platinum complexes, cisplatin, carboplatin or oxaliplatin. CONCLUSIONS: Cryptophycins represent a promising new class of antitumor agents that may be optimally administered by intravenous infusion and in combination with doxorubicin, paclitaxel and 5-fluorouracil.

Animals↗
PubMed2000

Expression of pRB, cyclin/cyclin-dependent kinases and E2F1/DP-1 in human tumor lines in cell culture and in xenograft tissues and response to cell cycle agents.

PURPOSE: Cell cycle regulatory components are interesting targets for cancer therapy. Expression of pRb, cyclin D1, cdk4, cyclin E, cdk2, E2F1 and DP-1 was determined in MCF-7 and MDA-MB-468 breast carcinoma cells, H460 and Calu-6 non-small cell lung carcinoma cells, H82 and SW2 small cell lung carcinoma cells, HCT116 and HT29 colon carcinoma cells and LNCaP and DU-145 prostate carcinoma cells. METHODS: For Western blotting, the ratio with actin expression was used to normalize the data; all lines were run on the same gels. RESULTS: In cell culture, pRb was not detected in MB-468 and H82 was low in SW2 and DU-145 and highest in HCT116; in tumors, pRb was not detected in MB-468, H82, SW2, and DU-145 and was highest in LNCaP and Calu-6. Cyclin D1 was not detected in SW2 cells in culture, was low in MB-468 and H82, and was highest in LNCaP and H460; in tumors, cyclin D1 was low in MB-468, H460, SW2 and DU 145, and was highest in LNCaP. In cell culture, cdk4 was lowest in Calu-6, HCT116, HT29 and DU-145 and highest in H82 and SW2; in tumors, cdk4 was low in MCF-7, MB-468, H460, Calu-6 and HCT116 and was very high in the SW2. Expression of cyclin E was very low in MCF-7 and HT29 and high in H460 in culture and was very low in MCF-7, H460, Calu-6, H82, HT29 and DU-145 in tumors and high in HCT116 and LNCaP. In cell culture, E2F1 was lowest in MB-468, Calu-6, HT29 and DU-145 cells and highest in LNCaP cells; in tumors, E2F1 was lowest in MCF-7, MB-468 and Calu-6 and highest in LNCaP. In cell culture, DP-1 was lowest in MB-468, HCT116 and HT29 and highest in SW2. The MCF-7 and MB-468 lines were most resistant to flavopiridol and olmoucine and the H460 and Calu-6 lines were most resistant to genistein. The SW2 tumor was most responsive to flavopiridol and olomoucine. CONCLUSIONS: There is a high degree of variability in the expression of cell cycle components in human tumor cell lines, resulting in complexity in predicting response to cell cycle directed agents.

Aged↗
PubMed2000

Suprasegmental and segmental timing models in Mandarin Chinese and American English.

This paper formalizes and tests two key assumptions of the concept of suprasegmental timing: segmental independence and suprasegmental mediation. Segmental independence holds that the duration of a suprasegmental unit such as a syllable or foot is only minimally dependent on its segments. Suprasegmental mediation states that the duration of a segment is determined by the duration of its suprasegmental unit and its identity, but not directly by the specific prosodic context responsible for suprasegmental unit duration. Both assumptions are made by various versions of the isochrony hypothesis [I. Lehiste, J. Phonetics 5, 253-263 (1977)], and by the syllable timing hypothesis [W. Campbell, Speech Commun. 9, 57-62 (1990)]. The validity of these assumptions was studied using the syllable as suprasegmental unit in American English and Mandarin Chinese. To avoid unnatural timing patterns that might be induced when reading carrier phrase material, meaningful, nonrepetitive sentences were used with a wide range of lengths. Segmental independence was tested by measuring how the average duration of a syllable in a fixed prosodic context depends on its segmental composition. A strong association was found; in many cases the increase in average syllabic duration when one segment was substituted for another (e.g., bin versus pin) was the same as the difference in average duration between the two segments (i.e., [b] versus [p]). Thus, the [i] and [n] were not compressed to make room for the longer [p], which is inconsistent with segmental independence. Syllabic mediation was tested by measuring which locations in a syllable are most strongly affected by various contextual factors, including phrasal position, within-word position, tone, and lexical stress. Systematic differences were found between these factors in terms of the intrasyllabic locus of maximal effect. These and earlier results obtained by van Son and van Santen [R. J. J. H van Son and J. P. H. van Santen, "Modeling the interaction between factors affecting consonant duration," Proceedings Eurospeech-97, 1997, pp. 319-322] showing a three-way interaction between consonantal identity (coronals vs labials), within-word position of the syllable, and stress of surrounding vowels, imply that segmental duration cannot be predicted by compressing or elongating segments to fit into a predetermined syllabic time interval. In conclusion, while there is little doubt that suprasegmental units play important predictive and explanatory roles as phonological units, the concept of suprasegmental timing is less promising.

Humans↗
PubMed2000

A frequent, naturally occurring mutation (P130T) of human hepatitis B virus core antigen is compensatory for immature secretion phenotype of another frequent variant (I97L).

A frequent mutation at codon 97 of human hepatitis B virus core antigen has been shown to cause an "immature secretion" phenotype, featuring nonselective and excessive secretions of virions containing immature viral genome. Our current study demonstrates that this abnormality can be efficiently offset by another frequent core mutation, P130T.

Cell Line↗
PubMed2000

Low-level secretion of human hepatitis B virus virions caused by two independent, naturally occurring mutations (P5T and L60V) in the capsid protein.

The functional significance of naturally occurring variants of human hepatitis B virus (HBV) remains largely unknown. Previously, we reported an immature secretion phenotype caused by a highly frequent mutation at amino acid 97 of the HBV core (capsid) protein (HBcAg). This phenotype is characterized by a nonselective and excessive secretion of virions containing an immature genome of single-stranded viral DNA. To extend our study of virion secretion to other naturally occurring variants, we have characterized mutations at HBcAg codons 5, 38, and 60 via site-directed mutagenesis. Although the phenotype of the mutation at codon 38 is nearly identical to that for the wild-type virus, our study reveals that a single mutation at codon 5 or 60 exhibits a new extracellular phenotype with significantly reduced virion secretion yet maintains normal intracellular viral DNA replication. A complementation study indicates that the mutant core protein alone is sufficient for the "low-secretion" phenotype. Furthermore, the low-secretion phenotype of the codon 5 mutant appears to be induced by the loss of a parental proline residue, rather than by the gain of a new amino acid. Our study underscores the core protein as another crucial determinant in virion secretion, in addition to the known envelope proteins. Our present results suggest that a very precise structure of both alpha-helical and nonhelical loop regions of the entire HBcAg molecule is important for virion secretion. The low-secretion variants may contribute to the phenomenon of gradually decreasing viremia in chronic carriers during the late phase of persistent infection.

Capsid↗
PubMed2000

Treatment regimens including the multitargeted antifolate LY231514 in human tumor xenografts.

The scheduling of antifolate antitumor agents, including the new multitargeted autofolate LY231514 (MTA), with 5-fluorouracil was explored in the human MX-1 breast carcinoma and human H460 and Calu-6 non-small cell lung carcinoma xenografts to assess antitumor activity and toxicity (body weight loss). Administration of the antifolate (methotrexate, MTA, or LY309887) 6 h prior to administration of 5-fluorouracil resulted in additive growth delay of the MX-1 tumor when the antifolate was methotrexate or LY309887 and greater-than-additive tumor growth delay (TGD) when the antifolate was MTA. In the H460 tumor, the most effective regimens were a 14-day course of MTA or LY309887 along with 5-fluorouracil administered on the final 5 days. In addition, the simultaneous combination of MTA administered daily for 5 days for 2 weeks with administration of gemcitabine resulted in greater-than-additive H460 TGD. MTA was additive with fractionated radiation therapy in the H460 tumor when the drug was administered prior to each radiation fraction. MTA administered along with paclitaxel produced greater-than-additive H460 TGD and additive responses along with vinorelbine and carboplatin. In the Calu-6 non-small cell lung carcinoma xenograft, MTA administered in combination with cisplatin or oxaliplatin was highly effective, whereas MTA administered in combination with cyclophosphamide, gemcitabine, or doxorubicin produced additive responses. Administration of MTA along with paclitaxel or doxorubicin resulted in additive MX-1 TGD. Thus, MTA appears to be especially effective in combination therapies including 5-fluorouracil or an antitumor platinum complex.

Animals↗