Outbreak of enteric cryptosporidiosis in cockatiels (Nymphicus hollandicus).
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
C G Lee
Publications and source records attributed to C G Lee.
The effect of temperature on swimming performance and oxygen consumption in adult sockeye (Oncorhynchus nerka) and coho (O. kisutch) salmon stocks.
Our knowledge of the swimming capabilities and metabolic rates of adult salmon, and particularly the influence of temperature on them, is extremely limited, and yet this information is critical to understanding the remarkable upstream migrations that these fish can make. To remedy this situation, we examined the effects of temperature on swimming performance and metabolic rates of 107 adult fish taken from three stocks of sockeye salmon Oncorhynchus nerka and one stock of coho salmon O. kisutch at various field and laboratory locations, using large, portable, swim tunnels. The salmon stocks were selected because of differences in their ambient water temperature (ranging from 5 degrees C to 20 degrees C) and the total distance of their in-river migrations (ranging from approximately 100 km for coastal stocks to approximately 1100 km for interior stocks). As anticipated, differences in routine metabolic rate observed among salmon stocks were largely explained by an exponential dependence on ambient water temperature. However, the relationship between water temperature and maximum oxygen consumption (MO2max), i.e. the MO2 measured at the critical swimming speed (Ucrit), revealed temperature optima for MO2max that were stock-specific. These temperature optima were very similar to the average ambient water temperatures for the natal stream of a given stock. Furthermore, at a comparable water temperature, the salmon stocks that experienced a long and energetically costly in-river migration were characterized by a higher MO2max, a higher scope for activity, a higher Ucrit and, in some cases, a higher cost of transport, relative to the coastal salmon stocks that experience a short in-river migration. We conclude that high-caliber respirometry can be performed in a field setting and that stock-specific differences in swimming performance of adult salmon may be important for understanding upstream migration energetics and abilities.
Animal Migration↗
Excess post-exercise oxygen consumption in adult sockeye (Oncorhynchus nerka) and coho (O. kisutch) salmon following critical speed swimming.
The present study measured the excess post-exercise oxygen cost (EPOC) following tests at critical swimming speed (Ucrit) in three stocks of adult, wild, Pacific salmon (Oncorhynchus sp.) and used EPOC to estimate the time required to return to their routine level of oxygen consumption (recovery time) and the total oxygen cost of swimming to Ucrit. Following exhaustion at Ucrit, recovery time was 42-78 min, depending upon the fish stock. The recovery times are several-fold shorter than previously reported for juvenile, hatchery-raised salmonids. EPOC varied fivefold among the fish stocks, being greatest for Gates Creek sockeye salmon (O. nerka), which was the salmon stock that had the longest in-river migration, experienced the warmest temperature and achieved the highest maximum oxygen consumption compared with the other salmon stocks that were studied. EPOC was related to Ucrit, which in turn was directly influenced by ambient test temperature. The non-aerobic cost of swimming to Ucrit was estimated to add an additional 21.4-50.5% to the oxygen consumption measured at Ucrit. While these non-aerobic contributions to swimming did not affect the minimum cost of transport, they were up to three times higher than the value used previously for an energetic model of salmon migration in the Fraser River, BC, Canada. As such, the underestimate of non-aerobic swimming costs may require a reevaluation of the importance of how in-river barriers like rapids and bypass facilities at dams, and year-to-year changes in river flows and temperatures, affect energy use and hence migration success.
Animal Migration↗
Airway inflammation and remodeling in asthma. Lessons from interleukin 11 and interleukin 13 transgenic mice.
Noninflammatory structural alterations, variously referred to as airway remodeling, are well documented in the asthmatic airway. However, the pathogenesis of these alterations, the importance of airway remodeling in generating the asthma phenotype, and the natural history of airway remodeling responses have not been adequately defined. Because exaggerated cytokine production is a characteristic feature of the asthmatic airway, we used constitutive and inducible overexpression transgenic systems to investigate the contributions that interleukin 11 (IL-11) and IL-13 might make to airway remodeling responses. These studies demonstrated that both cytokines produce responses in the murine airway with features similar to those in human asthmatic tissues. IL-11 caused airway fibrosis with the enhanced accumulation of interstitial collagens, myocytes, and myofibroblasts. IL-13 caused mucous metaplasia, enhanced mucin gene expression, enhanced tissue hyaluronic acid accumulation, and subepithelial fibrosis. Importantly, IL-11 was detected most readily in tissues from asthmatic subjects with severe airway remodeling that was similar to that seen in the IL-11 transgenic mice. In addition, IL-11 was shown to inhibit asthma-like inflammation while stimulating airway fibrosis. This suggests that IL-11 elaboration is, in part, an attempt at airway healing. Last, a novel triple transgenic system is described that allows transgene expression to be regulated in a true "on/off" manner. This system may be useful in defining the reversibility of transgene-induced airway remodeling responses.
Animals↗
Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA.
HIV-1 Tat is able to form a ternary complex with P/CAF and p300 and increase the affinity for CDK9/P-TEFb CTD kinase complex. Our previous study demonstrated that Tat binds to p300/CBP in the minimal HAT domain (aa 1253-1790) and that the interaction results in a change of conformation on p300/CBP. Here, we show that the Tat-p300 interaction increases the HAT activity of p300 on histone H4 that is associated with nucleosomal DNA and not with free histones. Nucleosomal histone H4 was acetylated on lysines 8, 12, and 16. Acetylation of H4 was inhibited by Lys-coenzyme A (CoA), a selective inhibitor of p300 acetyltransferase activity. Unexpectedly, we also found that Tat could autoacetylate itself, which was specific to lysine residues 41 and 71. Peptides lacking these two lysines could not enhance the HAT activity of p300. Comparison of the sequences of Tat with other HIV-1 clades and HAT containing transcription factors indicated sequence identity in the acetyl-CoA binding motif A, KGXG. Furthermore, when utilizing an in vitro transcription assay, as well as a Tat mutant virus, we found that ectopic expression of only wild-type Tat in the presence of p300, and not a lysine 41 Tat mutant, could activate HIV-1 chromatin DNA, as evidenced by the absence of HIV-1 virion antigen. Therefore, transcription of integrated viral DNA in vivo requires the HAT activity of coactivators that are modulated by Tat to derepress the HIV-1 chromatin structure and aid in activated transcription.
Acetyl-CoA C-Acetyltransferase↗
Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1).
Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-beta. To test this hypothesis we compared the regulation of TGF-beta in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-beta(1) production in transgenic animals and macrophages were the major site of TGF-beta(1) production and deposition in these tissues. IL-13 also activated TGF-beta(1) in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-beta-binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-beta(1) activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13-induced fibrosis was also significantly ameliorated by treatment with the TGF-beta antagonist soluble TGFbetaR-Fc (sTGFbetaR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-beta(1) in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9-dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-beta pathway.
Animals↗
Quantitative regulation of class switch recombination by switch region transcription.
The isotype specificity of immunoglobulin (Ig) class switching is regulated by a cytokine which induces transcription of a specific switch (S) region, giving rise to so-called germline transcripts. Although previous studies have demonstrated that germline transcription of an S region is required for class switch recombination (CSR) of that particular S region, it has not been shown whether the level of S region transcription affects the efficiency of CSR. We addressed this question by using an artificial DNA construct containing a constitutively transcribed mu switch (Smu) region and an alpha switch (Salpha) region driven by a tetracycline-responsive promoter. The construct was introduced into a switch-inducible B lymphoma line and the quantitative correlation between Salpha region transcription and class switching efficiency was evaluated. The level of Salpha transcription was linearly correlated with CSR efficiency, reaching a plateau at saturation. On the other hand, we failed to obtain the evidence to support involvement of either RNA-DNA heteroduplex or trans germline transcripts in CSR. Taken together, it is likely that S region transcription and/or transcript processing in situ may be required for CSR. We propose that because of the unusual properties of S region DNA, transcription induces the DNA to transiently be single stranded, permitting secondary structure(s) to form. Such structures may be recognition targets of a putative class switch recombinase.
Acetylation↗
The Mdm-2 amino terminus is required for Mdm2 binding and SUMO-1 conjugation by the E2 SUMO-1 conjugating enzyme Ubc9.
Covalent attachment of SUMO-1 to Mdm2 requires the activation of a heterodimeric Aos1-Uba2 enzyme (ubiquitin-activating enzyme (E1)) followed by the conjugation of Sumo-1 to Mdm2 by Ubc9, a protein with a strong sequence similarity to ubiquitin carrier proteins (E2s). Upon Sumo-1 conjugation, Mdm2 is protected from self-ubiquitination and elicits greater ubiquitin-protein isopeptide ligase (E3) activity toward p53, thereby increasing its oncogenic potential. Because of the biological implication of Mdm2 sumoylation, we mapped Ubc9 binding on Mdm2. Here we demonstrate that Ubc9 can associate with Mdm2 only if amino acids 40-59 within the N terminus of Mdm2 are present. Mdm2 from which amino acids 40-59 have been deleted can no longer be sumoylated. Furthermore, addition of a peptide that corresponds to amino acids 40-59 on Mdm2 to a sumoylation reaction efficiently inhibits Mdm2 sumoylation in vitro and in vivo. In UV-treated cells Mdm2 exhibits reduced association with Ubc9, which coincides with decreased Mdm2 sumoylation. Our findings regarding the association of Ubc9 with Mdm2, and the effect of UV-irradiation on Ubc9 binding, point to an additional level in the regulation of Mdm2 sumoylation under normal growth conditions as well as in response to stress conditions.
3T3 Cells↗
An episomally maintained MDR1 gene for gene therapy.
Potential applications of the MDR1 multidrug transporter in gene therapy include protecting sensitive bone marrow cells against cytotoxic drugs during cancer chemotherapy and serving as a dominant selectable marker when coexpressed with a corrective passenger gene. To address safety concerns associated with integrating viral systems, such as retroviruses, we tested the feasibility of maintaining a nonvirally delivered MDR1 gene (pEpiHaMA) episomally. An MDR1 vector containing the Epstein-Barr virus (EBV) origin of replication (OriP) and its nuclear retention protein (EBNA-1) was transfected into human (KB-3-1) cells. MDR1 was expressed at a higher level in cells carrying the episomal vector, pEpiHaMA, compared with the vector lacking sequences needed for episomal maintenance (pHaMA). Furthermore, more drug-resistant KB-3-1 colonies were obtained on selection after transfection with pEpiHaMA. These observations correlated with longer maintenance of episomes in cells transfected with pEpiHaMA. In addition, episomes could still be recovered for more than 1 month from tumor explants in nude mice that were injected with pEpiHaMA-liposome complexes after drug selection, suggesting that these constructs can be maintained extrachromosomally in vivo.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Intracellular domains of mouse connexin26 and -30 affect diffusional and electrical properties of gap junction channels.
To evaluate the influence of intracellular domains of connexin (Cx) on channel transfer properties, we analyzed mouse connexin (Cx) Cx26 and Cx30, which show the most similar amino acid sequence identities within the family of gap junction proteins. These connexin genes are tightly linked on mouse chromosome 14. Functional studies were performed on transfected HeLa cells stably expressing both mouse connexins. When we examined homotypic intercellular transfer of microinjected neurobiotin and Lucifer yellow, we found that gap junctions in Cx30-transfected cells, in contrast to Cx26 cells, were impermeable to Lucifer yellow. Furthermore, we observed heterotypic transfer of neurobiotin between Cx30-transfectants and HeLa cells expressing mouse Cx30.3, Cx40, Cx43 or Cx45, but not between Cx26 transfectants and HeLa cells of the latter group. The main differences in amino acid sequence between Cx26 and Cx30 are located in the presumptive cytoplasmic loop and C-terminal region of these integral membrane proteins. By exchanging one or both of these domains, using PCR-based mutagenesis, we constructed Cx26/30 chimeric cDNAs, which were also expressed in HeLa cells after transfection. Homotypic intercellular transfer of injected Lucifer yellow was observed exclusively with those chimeric constructs that coded for both cytoplasmic domains of Cx26 in the Cx30 backbone polypeptide chain. In contrast, cells transfected with a construct that coded for the Cx26 backbone with the Cx30 cytoplasmic loop and C-terminal region did not show transfer of Lucifer yellow. Thus, Lucifer yellow transfer can be conferred onto chimeric Cx30 channels by exchanging the cytoplasmic loop and the C-terminal region of these connexins. In turn, the cytoplasmic loop and C-terminal domain of Cx30 prevent Lucifer yellow transfer when swapped with the corresponding domains of Cx26. In chimeric Cx30/Cx26 channels where the cytoplasmic loop and C-terminal domains had been exchanged, the unitary channel conductance was intermediate between those of the parental channels. Moreover, the voltage sensitivity was slightly reduced. This suggests that these cytoplasmic domains interfere directly or indirectly with the diffusivity, the conductance and voltage gating of the channels.
Animals↗
Epstein-Barr virus-associated B cell lymphoproliferative disorder following mismatched related T cell-depleted bone marrow transplantation.
Epstein-Barr virus (EBV) is closely associated with the progressive and often fatal lymphoproliferative disorders (LPD) in post bone marrow transplantation (BMT) and immunocompromised hosts. The incidence increases significantly when alternative donors or manipulation of marrow graft are used. A total of 318 consecutive BMT from partially mismatched related family donors (PMRD) were performed between February 1993 and June 1998. Known risk factors for the development of EBV-LPD were analyzed which included HLA mismatches, T cell depletion, antithymocyte globulin (ATG), and graft-versus-host disease (GVHD). Eighteen patients (5.7%) developed EBV-LPD at a median of 137 days post BMT (range 48-617). The estimated probability of developing EBV-LPD was 0.13 (95% CI 0.07-0.19) at 5 years. The incidence of grade II to IV GVHD was 19.2%, which translated into an increased trend of EBV-LPD. No correlation with other risk factors was observed. Treatment consisted of supportive antiviral agents, tapering of immunosuppressive regimens, donor leukocyte infusions and radiation. Three patients are alive and disease-free at a median follow-up of 69 months (range 36-71). We observed a lower than expected incidence of EBV-LPD despite existing multiple high-risk factors. We believe prevention and early control of GVHD may contribute to this finding.
Adolescent↗
A feasibility study using three-dimensional conformal boost technique in locally advanced carcinoma of the nasopharynx.
To investigate the feasibility and efficacy of dose escalation using three-dimensional (3-D) conformal boost technique, 21 patients with stage III or IV nasopharyngeal cancer were enrolled in a prospective protocol. All patients with node metastases initially received external radiotherapy by conventional technique up to 70.2 Gy, followed by 3-D conformal radiotherapy (3-D CRT) to the boost part up to 79.2 Gy with 9 Gy increments (daily fraction of 1.8 Gy for 5 days). A modified technique with the same dose escalation of 9 Gy using 3-D CRT was applied to 7 patients without node metastases, who were treated by conventional technique up to 54 Gy, followed by 3-D CRT to boost up to a basic dose of 70.2 Gy, and then finally with dose escalation of 9 Gy. The protocol was relatively well tolerated by the majority of patients. Acute complications during the dose escalation schedule was low, with rare occurrences of grade 3 or 4 toxicity. Although late radiation-induced complications also appeared limited, 1 patient developed a temporal lobe necrosis and 2 patients suffered from sensory-neural hearing loss. There were no radiation-induced fatal complications. At a median follow-up of 48 months, only 3 patients experienced local failure and 2 patients developed distant metastases. The 5-year overall actuarial survival rate and recurrence-free survival rate for all patients were 68% and 85%, respectively. On the basis of acceptable morbidity and encouraging treatment results, we conclude that the dose escalation in 9 Gy increments using a 3-D conformal boost technique is relatively safe and efficacious, enough to be used routinely for locally advanced nasopharyngeal cancers.
Adult↗
Hemodynamic effects of lipids in humans.
Evidence suggests lipid abnormalities may contribute to elevated blood pressure, increased vascular resistance, and reduced arterial compliance among insulin-resistant subjects. In a study of 11 normal volunteers undergoing 4-h-long infusions of Intralipid and heparin to raise plasma nonesterified fatty acids (NEFAs), we observed increases of blood pressure. In contrast, blood pressure did not change in these same volunteers during a 4-h infusion of saline and heparin. To better characterize the hemodynamic responses to Intralipid and heparin, another group of 21 individuals, including both lean and obese volunteers, was studied after 3 wk on a controlled diet with 180 mmol sodium/day. Two and four hours after starting the infusions, plasma NEFAs increased by 134 and 111% in those receiving Intralipid and heparin, P < 0.01, whereas plasma NEFAs did not change in the first group of normal volunteers who received saline and heparin. The hemodynamic changes in lean and obese subjects in the second study were similar, and the results were combined. The infusion of Intralipid and heparin induced a significant increase in systolic (13.5 +/- 2.1 mmHg) and diastolic (8.0 +/- 1.5 mmHg) blood pressure as well as heart rate (9.4 +/- 1.4 beats/min). Small and large artery compliance decreased, and systemic vascular resistance rose. These data raise the possibility that lipid abnormalities associated with insulin resistance contribute to the elevated blood pressure and heart rate as well as the reduced vascular compliance observed in subjects with the cardiovascular risk factor cluster.
Adult↗
Enzyme-linked immunosorbent assay for detection of Trichinella spiralis antibodies and the surveillance of selected pig breeding farms in the Republic of Korea.
Trichinellosis is a parasitic zoonosis of public health importance. It is caused by Trichinella spiralis which has a wide host range including humans. In the present communication, the ELISA technique was employed on a total of 803 blood samples from 7 selected pig breeding farms in 1996 for diagnosis and surveillance of trichinellosis. Out of the entire 803 samples, nine were found to be suspected while one was positive by ELISA. But western blot analyses employed for further confirmation have shown that all of 10 samples did not react to larval excretory-secretory product antigens. These results indicate that pig breeding farms included in the present study are free from trichinellosis. However, it does not mean Korea is free from trichinellosis since human trichinellosis has recently been reported. The necessity of continued surveillance for trichinellosis in both pigs and wild animals was discussed.
Animals↗
Hyperfractionated re-irradiation using a 3-dimensional conformal technique for locally recurrent carcinoma of the nasopharynx; preliminary results.
To evaluate the efficacy of hyperfractionated re-irradiation using a three-dimensional conformal radiotherapy (3-D CRT) technique in patients with locally recurrent carcinoma of the nasopharynx. Four patients with locally recurrent nasopharyngeal cancer were retreated with a hyperfractionated schedule using a 3-D CRT technique. Re-irradiation was delivered in 1.1-1.2 Gy fractions twice per day (BID), with interfraction intervals of more than 6 hours. The total dose ranged from 59.4 to 69.2 Gy. A 3-D CRT technique with 5- or 6-field coplanar and/or non-coplanar beams were employed during the entire treatment procedure. All four patients achieved complete remission of locally recurrent lesions, with marked improvement of subjective symptoms, immediately after re-irradiation. All are alive and well without evidence of disease after limited follow-up periods, which range from 7 to 20 months. So far, there have been no radiation-induced neurologic complications. Four patients with locally recurrent carcinoma of the nasopharynx were successfully treated by hyperfractionated re-irradiation using a 3-D CRT technique. A relatively high re-irradiation dose of more than 60 Gy may be safely delivered with no serious acute or late radiation-induced complications in patients with local recurrences and who were initially treated with doses greater than 70 Gy.
Aged↗
Dyspnea and palpitation during pregnancy.
OBJECTIVES: Dyspnea and palpitation are common features of pregnancy. While several theories have been put forward to explain the etiology of gestational dyspnea and palpitation, there have been few systemic studies of its incidence, severity and time-course in a group of normal women. METHODS: We interviewed postpartum women, within 3 days after delivery, about dyspnea and palpitation. Separately from this interview, we performed 24-hour ECG monitoring for obstetric patients with palpitation before delivery. RESULTS: The subjects interviewed were 261 women, of whom 37.5 percent and 11.5 percent experienced dyspnea and palpitation, respectively. These symptoms had tendency to increase to term. The presence of arrhythmias could be documented in only 22% of patients having 24-hour Holter monitoring. CONCLUSION: Dyspnea and palpitation were common among normal pregnant women and had a tendency to increase to term.
Adult↗
Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones.
The HIV-1 Tat protein is required for viral replication and is a potent stimulator of viral transcription. Although Tat has been extensively studied in various reductive paradigms, to date there is little information as to how this activator mediates transcription from natural nucleosomally packaged long terminal repeats. Here we show that CREB-binding protein (CBP)/p300 interacts with the HIV-1 Tat protein and serves as a coactivator of Tat-dependent HIV-1 gene expression on an integrated HIV-1 provirus. The site of acetylation of Tat was mapped to the double-lysine motif in a highly conserved region, (49)RKKRRQ(54), of the basic RNA-binding motif of Tat. Using HLM1 cells (HIV-1(+)/Tat(-)), which contain a single copy of full-length HIV-1 provirus with a triple termination codon at the first AUG of the Tat gene, we find that only wild type, and not K50A, K51A, or K50A/K51A alone or in combination of ectopic CBP/p300, is able to produce full-length infectious virions, as measured by p24 gag ELISAs. Tat binds CBP/p300 in the minimal histone acetyltransferase domain (1253-1710) and the binding is stable up to 0.85 M salt wash conditions. Interestingly, wild-type peptide 41-54, and not other Tat peptides, changes the conformation of the CBP/p300 such that it can acquire and bind better to basal factors such as TBP and TFIIB, indicating that Tat may influence the transcription machinery by helping CBP/p300 to recruit new partners into the transcription machinery. Finally, using biotinylated wild-type or acetylated peptides, we find that acetylation decreases Tat's ability to bind the TAR RNA element, as well as to bind basal factors such as TBP, CBP, Core-Pol II, or cyclin T. However, the acetylated Tat peptide is able to bind to core histones on a nucleosome assembled HIV-1 proviral DNA.
Acetylation↗
Anti-Vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions.
Recent studies in experimental animals have shown that combining antiangiogenic therapy with radiation can enhance tumor response. Whether this enhancement is mainly attributable to angiogenesis inhibition, endothelial cell radiosensitivity, tumor cell apoptosis, or a decrease in the number of hypoxic cells (improved oxygenation) is not known. We designed this study to discern the role of tumor oxygenation. We chose an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody (mAb) which has a known target, human VEGF. We also measured interstitial fluid pressure (IFP) to test the hypothesis that the decreased vascular permeability induced by the anti-VEGF mAb can lower IFP. The effect of anti-VEGF mAb on vascular density, partial oxygen tension (pO2), and apoptosis was also measured. Athymic NCr/Sed nu/nu mice bearing 6-mm xenograft of the human glioblastoma multiforme (U87), or colon adenocarcinoma (LS174T) were treated with anti-VEGF mAb injected i.p. on alternate days for a total of six injections at a dosage of 100 microg/injection/mouse. For combined anti-VEGF and radiation, single radiation doses were given under normal blood flow (20 and 30 Gy) or clamped hypoxic conditions (30 and 40 Gy) 24 h after the sixth injection of mAb. The inhibition of the growth of U87 and LS174T tumors by the anti-VEGF mAb was associated with a significant reduction in tumor vascular density and a relatively small increase in the number of apoptotic cells. Compared with size-matched controls, IFP decreased by 74% in LS174T, and 73% in U87 in mice treated with anti-VEGF mAb. After antibody treatment PO2 increased significantly in U87, but did not change in LS174T tumors. Combined treatment induced in U87 tumors a tumor-growth delay (TGD) which was greater than additive; in LS174T except for the 40-Gy hypoxic group, the effect was only additive. In both U87 and LS174T the TGD induced by the antibody was independent of oxygen levels in the tumor at the time of radiation. The fact that the increase in TGD occurred under both normoxic and hypoxic conditions suggests that anti-VEGF mAb treatment can compensate for the resistance to radiation induced by hypoxia.
Adenocarcinoma↗