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C Clifton Ling

Publications and source records attributed to C Clifton Ling.

At least 19 recordsLinked to original sources
PubMed2007

Detecting changes in tumor hypoxia with carbonic anhydrase IX and pimonidazole.

We have used immunohistochemistry to examine the dynamics of tumor hypoxia.. Expression of CAIX is known to be influenced by tumor hypoxia, and this protein has been shown to be an endogenous hypoxia marker in several models. However, due to its long half-life, it could also be present in oxygenated tissue that had recently been hypoxic. To investigate this issue we have compared CAIX expression to the exogenous hypoxia marker, pimonidazole using HT29 (human colorectal cancer) xenografts. We manipulated tumor hypoxia with carbogen and hydralazine, treatments that respectively increased and decreased tumor oxygenation. (Carbogen was given 75 minutes and hydralazine 30 minutes before sacrifice). In tumors from the control group, CAIX and pimonidazole exhibited similar (though not identical) spatial distribution, and for both markers, the fraction of the section staining positively was similar (13.2% and 12.6% respectively). The mice treated with hydralazine showed a significant increase in pimonidazole accumulation (37.2%, p = 0.03), though the CAIX positive fraction was unchanged (14.2%). In contrast, in the carbogen group pimonidazole staining decreased to 3% (p = 0.01) though CAIX expression was again unaltered. These results suggest that comparison of CAIX and pimonidazole will allow for the detection of reoxygenation.

Animals↗
PubMed2006

From IMRT to IGRT: frontierland or neverland?

The recent enthusiasm for real-time image guidance in radiotherapy (IGRT) is in part due to the commercial availability of advanced on-line imaging technologies. Perhaps more important than its potential to improve conventional radiotherapy, IGRT may lead to a paradigm shift in facilitating hypo-fractionated or single-dose treatment. However, there are uncertainty regarding features and approaches of competing IGRT systems and as to whether a sub-set of the features of an ideal IGRT system would suffice for specific disease sites and clinical applications. Clinical studies are necessary for the quantification of benefit needed for evidence-based medicine.

Dose Fractionation, Radiation↗
PubMed2006

Hyperthermia and gene therapy: potential use of microPET imaging.

In recent years, both hyperthermia and gene-therapy have been evaluated as approaches to improve cancer radiotherapy. In addition, potential exists to combine these approaches to increase the overall therapeutic efficacy. For example, it has been reported that adenovirus-mediated heat-inducible gene expression may reduce the normal tissue toxicity associated with constitutively controlled expression of therapeutic genes. In our laboratory, we have shown that adenovirus-mediated, heat-activated antisense Ku70 expression radiosensitizes tumor cells in vitro and in vivo, suggesting a novel approach to use heat-activated gene-radiotherapy to radiosensitize human tumors.However, to optimize the application of heat-activated gene-radiotherapy in the clinic, we need to develop techniques to improve the delivery of the therapeutic adenovirus and to verify/monitor the delivery non-invasively. In an ongoing study we test the effect of mild hyperthermia in improving adenovirus-medicated vector delivery in a mouse tumor model. In addition, we evaluate the use of non-invasive microPET imaging to monitor the spread of the adenoviral vector. Our preliminary results show that (1) microPET imaging can be used to monitor non-invasively the viral vector delivery and dissemination, and (2) mild heat shock leads to significantly improved viral vector distribution, in other words, a wider spatial spread, in vivo.Here, we will present a short review on the current status of hyperthermia and heat-activated gene-radiotherapy, and the potential use of PET imaging in gene therapy.

Adenoviridae↗
PubMed2006

Measurements of partial oxygen pressure pO2 using the OxyLite system in R3327-AT tumors under isoflurane anesthesia.

The presence of oxygen-deficient tumor cells is a critical issue in cancer therapy. To identify tumor hypoxia, tissue partial oxygen pressure (pO2) can be measured directly. The OxyLite system allows determination of pO2 in tumors and permits continuous measurements of pO2 at a fixed point. In this study, this system was used to continuously measure pO2 in R3327-AT tumors in animals anesthetized with isoflurane. In addition, continuous pO2 measurement was performed in the muscle in non-tumor-bearing animals. In animals breathing isoflurane balanced by air, tumor pO2 at fixed positions decreased rapidly within 1-2 min of probe positioning but remained stable thereafter. In animals breathing isoflurane balanced by pure oxygen, tumor pO2 was higher and remained high. We also measured pO2 values at multiple positions in R3327-AT tumors of various sizes, with anesthetized animals breathing either air or pure oxygen. Our data showed that the frequency of pO2 measurements below 2.5 or 5.0 mmHg was significantly higher in animals breathing air than in animals breathing pure oxygen. Measurements in different-sized tumors showed that the mean pO2 value decreased as tumor volume increased, with the largest change occurring between tumor volumes of 100 and 200 mm3. Our data demonstrate that the OxyLite system, when used with isoflurane anesthesia, is a valuable tool in the study of tumor hypoxia.

Adenocarcinoma↗
PubMed2006

Visualization of experimental lung and bone metastases in live nude mice by X-ray micro-computed tomography.

The objective of this study was to evaluate the utility of micro-computed tomography (micro-CT) for the detection and monitoring of experimental lung and bone metastases in nude mice. Whole body micro-CT scans were performed in lung or bone metastasis-bearing nude mice under deep anesthesia. The volumes of individual lung metastases were estimated by micro-CT, and compared to direct measurements on excised tumors. The two data sets were highly correlated (p<0.0001). The smallest lung tumor detected was 0.85 mm in diameter. The progression of metastatic lung disease, including tumor growth and the development of pleural effusion, was visualized by serial micro-CT scans in live mice. In addition, multiple bony metastases, with both osteolytic and osteoblastic features, were successfully detected by micro-CT. Bone lesions identified by micro-CT were confirmed as metastases by histopathological examination. Micro-CT may be used as an accurate, noninvasive tool to detect and monitor experimental bone and lung metastases in intact live nude mice.

Adenocarcinoma↗
PubMed2005

Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study.

PURPOSE: To determine dosimetric factors for lung, lung subregions, and heart that correlate with radiation pneumonitis (Radiation Therapy Oncology Group Grade 3 or more) in the 78 evaluable patients from a Phase I dose escalation study (1991-2003) of three-dimensional conformal radiation therapy (3D-CRT) of non-small-cell lung cancer. METHODS AND MATERIALS: There were 10 > or = Grade 3 pneumonitis cases within 6 months after treatment. Dose-volume factors analyzed for univariate correlation with > or = Grade 3 pneumonitis were mean dose (MD), effective uniform dose (d(eff)), normal tissue complication probability (NTCP), parallel model f(dam) and V(D) for 5 < or = D < or = 60 Gy for whole, ipsilateral, contralateral, upper and lower halves of the lungs and heart D05, and mean and maximum doses. RESULTS: The most significant variables (0.005 < p < 0.006) were ipsilateral lung V(D) for D < 20 Gy. Also significant (p < 0.05) for ipsilateral lung were V(D) for D < 50 Gy, MD, f(dam) and d(eff); for total lung V(D) (D < 50 Gy), MD, f(dam), d(eff) and NTCP; for lower lung V(D) (D < 60 Gy), MD, f(dam) and d(eff). All variables for upper and contralateral lung were insignificant, as were heart variables. CONCLUSIONS: Previously reported correlations between severe pneumonitis and whole lung V13 and with other dose-volume factors of total lung and lower lung are confirmed. The most significant correlations were for (V05-V13) in ipsilateral lung.

Adult↗
PubMed2005

Dependence of FDG uptake on tumor microenvironment.

PURPOSE: To investigate the factors affecting the (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in tumors at a microscopic level, by correlating it with tumor hypoxia, cellular proliferation, and blood perfusion. METHODS AND MATERIALS: Nude mice bearing Dunning prostate tumors (R3327-AT) were injected with (18)F-FDG and pimonidazole, bromodeoxyuridine, and, 1 min before sacrifice, with Hoechst 33342. Selected tumor sections were imaged by phosphor plate autoradiography, while adjacent sections were used to obtain the images of the spatial distribution of Hoechst 33342, pimonidazole, and bromodeoxyuridine. The images were co-registered and analyzed on a pixel-by-pixel basis. RESULTS: Statistical analysis of the data obtained from these tumors demonstrated that (18)F-FDG uptake was positively correlated with pimonidazole staining intensity in each data set studied. Correlation of FDG uptake with bromodeoxyuridine staining intensity was always negative. In addition, FDG uptake was always negatively correlated with the staining intensity of Hoechst 33342. CONCLUSIONS: For the Dunning prostate tumors studied, FDG uptake was always positively correlated with hypoxia and negatively correlated with both cellular proliferation and blood flow. Therefore, for the tumor model studied, higher FDG uptake is indicative of tumor hypoxia, but neither blood flow nor cellular proliferation.

Animals↗
PubMed2005

Assessment of regional tumor hypoxia using 18F-fluoromisonidazole and 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) positron emission tomography: Comparative study featuring microPET imaging, Po2 probe measurement, autoradiography, and fluorescent microscopy in the R3327-AT and FaDu rat tumor models.

PURPOSE: To compare two potential positron emission tomography (PET) tracers of tumor hypoxia in an animal model. METHODS AND MATERIALS: The purported hypoxia imaging agents (18)F-fluoromisonidazole (FMISO) and (64)Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) were compared by serial microPET imaging of Fisher-Copenhagen rats bearing the R3327-AT anaplastic rat prostate tumor. Probe measurements of intratumoral Po(2) were compared with the image data. At the microscopic level, the relationship between the spatial distributions of (64)Cu (assessed by digital autoradiography) and tumor hypoxia (assessed by immunofluorescent detection of pimonidazole) was examined. (18)F-FMISO and (64)Cu-ATSM microPET images were also acquired in nude rats bearing xenografts derived from the human squamous cell carcinoma cell line, FaDu. RESULTS: In R3327-AT tumors, the intratumoral distribution of (18)F-FMISO remained relatively constant 1-4 h after injection. However, that of (64)Cu-ATSM displayed a significant temporal evolution for 0.5-20 h after injection in most tumors. In general, only when (64)Cu-ATSM was imaged at later times (16-20 h after injection) did it correspond to the distribution of (18)F-FMISO. Oxygen probe measurements were broadly consistent with (18)F-FMISO and late (64)Cu-ATSM images but not with early (64)Cu-ATSM images. At the microscopic level, a negative correlation was found between tumor hypoxia and (64)Cu distribution when assessed at early times and a positive correlation when assessed at later times. For the FaDu tumor model, the early and late (64)Cu-ATSM microPET images were similar and were in general concordance with the (18)F-FMISO scans. CONCLUSION: The difference in behavior between the R3327-AT and FaDu tumor models suggests a tumor-specific dependence of Cu-ATSM uptake and retention under hypoxic conditions.

Animals↗
PubMed2005

Cell line-dependent differences in uptake and retention of the hypoxia-selective nuclear imaging agent Cu-ATSM.

BACKGROUND: Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) [Cu-ATSM] is a potential marker for tumor hypoxia that has been under evaluation for clinical use. In this study, we examined the mechanisms underlying the uptake of (64)Cu in cells incubated with (64)Cu-ATSM. METHODS: The in vitro uptake of (64)Cu was determined as a function of oxygenation conditions and incubation time with (64)Cu-ATSM using four and two tumor cell lines of human origin and rodent origin, respectively. Additionally, the rate of (64)Cu efflux and Cu-ATSM metabolism was determined. RESULTS: (64)Cu accumulation is rapid during the first 0.5-1 h of incubation. It is highest in anoxic cells but is also significant in normoxic cells. After this initial period, the level of intracellular (64)Cu varies depending on the cell line and the oxygenation conditions and, in some circumstances, may decrease. During the first 0.5-1 h, the ratio of (64)Cu levels between anoxic and normoxic cells is approximately 2:10 and that between hypoxic (0.5% O(2)) and normoxic cells is approximately 1:2.5, depending on the cell line. These ratios generally decrease at longer times. The (64)Cu-ATSM compound was found to be metabolized during incubation in a manner dependent on oxygenation conditions. Within 2 h under anoxic conditions, (64)Cu-ATSM could no longer be detected, although 60-90% of the amount of (64)Cu added as (64)Cu-ATSM was present in the medium. Non-ATSM (64)Cu was taken up by the cells, albeit at a much slower rate. Efflux rates of (64)Cu were found to be cell line dependent and appeared to be inversely correlated with the final (64)Cu uptake levels under anoxic conditions. CONCLUSION: The uptake and retention of (64)Cu and their relation to oxygenation conditions were found to be cell line dependent. Given the complexities in the oxygen dependence and cell line-dependent kinetics of uptake and retention of Cu following exposure to Cu-ATSM, the clinical utility of this compound may be disease site specific.

Animals↗
PubMed2005

A new method of incorporating systematic uncertainties in intensity-modulated radiotherapy optimization.

Uncertainties in tumor position during intensity-modulated radiotherapy (IMRT) plan optimization are usually accounted for by adding margins to a clinical target volume (CTV), or additionally, to organs at risk (OAR). The former approach usually favors target coverage over OAR protection, whereas the latter does not account for correlation in target and OAR movement. We investigate a new approach to incorporate systematic errors in tumor and organ position. The method models a distribution of systematic errors due to setup error and organ motion with displaced replicas of volumes of interest, each representing the patient geometry for a possible systematic error, and maximizes a score function that counts the number of replicas meeting dose or biological constraints for both CTV and OAR. Dose constraints are implemented by logistic functions of Niemierko's generalized model of equivalent uniform dose (EUD). The method is applied to prostate and nasopharynx IMRT plans, in which CTV and OAR each consists of five replicas, one representing no error (the position in the planning CT) and the other four discrete systematic setup displacements in one dimension with equal probability. The resulting IMRT plans are compared with those from two other EUD-based optimizations: a standard planning target volume (PTV) approach consisting of a single replica of each OAR in the planned position and a single PTV encompassing all CTV replicas, and a PTV-PRV approach consisting of a single PTV and a single planning risk volume (PRV) for each OAR encompassing all replicas. When systematic error is present, multiple-replica optimization provides better critical organ protection while maintaining similar target coverage compared with the PTV approach, and provides better CTV-to-OAR therapeutic ratio compared with the PTV-PRV instances where there is substantial PTV-PRV overlap. The method can be used for other systematic errors due to organ motion and deformation.

Body Burden↗
PubMed2004

Improved local control with higher doses of radiation in large-volume stage III non-small-cell lung cancer.

PURPOSE: It has been suggested that larger tumor volume is associated with poor survival in patients with non-small-cell lung cancer (NSCLC). We investigated whether high-dose radiation improved local control in patients with large-volume Stage III NSCLC. METHODS AND MATERIALS: Seventy-two patients with Stage III NSCLC and gross tumor volumes (GTV) of greater than 100 cc were treated with three-dimensional conformal radiotherapy (3D-CRT). Patients were divided into two groups: those treated to less than 64 Gy (37 patients) and those treated to 64 Gy or higher (35 patients). RESULTS: The 1-year and 2-year local failure rates were 27% and 47%, respectively, for Stage III patients treated to 64 Gy or higher, and 61% and 76%, respectively, for those treated to less than 64 Gy (p = 0.024). The median survival time for patients treated to 64 Gy or higher was 20 months vs. 15 months for those treated to less than 64 Gy (p = 0.068). Multivariate analysis revealed that dose and GTV are predictors of local failure-free survival. A 10 Gy increase in dose resulted in a 36.4% decreased risk of local failure. CONCLUSIONS: Our data suggest that administration of higher doses using 3D-CRT improves local control in Stage III NSCLC patients with large GTVs.

Adult↗
PubMed2004

Measurement of lung tumor motion using respiration-correlated CT.

PURPOSE: We investigate the characteristics of lung tumor motion measured with respiration-correlated computed tomography (RCCT) and examine the method's applicability to radiotherapy planning and treatment. METHODS AND MATERIALS: Six patients treated for non-small-cell lung carcinoma received a helical single-slice computed tomography (CT) scan with a slow couch movement (1 mm/s), while simultaneously respiration is recorded with an external position-sensitive monitor. Another 6 patients receive a 4-slice CT scan in a cine mode, in which sequential images are acquired for a complete respiratory cycle at each couch position while respiration is recorded. The images are retrospectively resorted into different respiration phases as measured with the external monitor (4-slice data) or patient surface displacement observed in the images (single-slice data). The gross tumor volume (GTV) in lung is delineated at one phase and serves as a visual guide for delineation at other phases. Interfractional GTV variation is estimated by scaling diaphragm position variations measured in gated radiographs at treatment with the ratio of GTV:diaphragm displacement observed in the RCCT data. RESULTS: Seven out of 12 patients show GTV displacement with respiration of more than 1 cm, primarily in the superior-inferior (SI) direction; 2 patients show anterior-posterior displacement of more than 1 cm. In all cases, extremes in GTV position in the SI direction are consistent with externally measured extremes in respiration. Three patients show evidence of hysteresis in GTV motion, in which the tumor trajectory is displaced 0.2 to 0.5 cm anteriorly during expiration relative to inspiration. Significant (>1 cm) expansion of the GTV in the SI direction with respiration is observed in 1 patient. Estimated intrafractional GTV motion for gated treatment at end expiration is 0.6 cm or less in all cases; however; interfraction variation estimates (systematic plus random) are more than 1 cm in 3/9 patients. CONCLUSION: Respiration-correlated CT can be performed with currently available CT equipment and acquisition settings. RCCT provides not only three-dimensional information on intrafractional tumor motion and deformation, but also allows estimates of interfractional tumor variation when combined with radiographic measurements of diaphragm position variation during treatment.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

A preclinical model for noninvasive imaging of hypoxia-induced gene expression; comparison with an exogenous marker of tumor hypoxia.

PURPOSE: Hypoxia is associated with tumor aggressiveness and is an important cause of resistance to radiation therapy and chemotherapy. Assays of tumor hypoxia could provide selection tools for hypoxia-modifying treatments. The purpose of this study was to develop and characterize a rodent tumor model with a reporter gene construct that would be transactivated by the hypoxia-inducible molecular switch, i.e., the upregulation of HIF-1. METHODS: The reporter gene construct is the herpes simplex virus 1-thymidine kinase (HSV1-tk) fused with the enhanced green fluorescent protein (eGFP) under the regulation of an artificial hypoxia-responsive enhancer/promoter. In this model, tumor hypoxia would up-regulate HIF-1, and through the hypoxia-responsive promoter transactivate the HSV1-tkeGFP fusion gene. The expression of this reporter gene can be assessed with the 124I-labeled reporter substrate 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (124I-FIAU), which is phosphorylated by the HSV1-tk enzyme and trapped in the hypoxic cells. Animal positron emission tomography (microPET) and phosphor plate imaging (PPI) were used in this study to visualize the trapped 124I-FIAU, providing a distribution of the hypoxia-induced molecular events. The distribution of 124I-FIAU was also compared with that of an exogenous hypoxic cell marker, 18F-fluoromisonidazole (FMISO). RESULTS: Our results showed that 124I-FIAU microPET imaging of the hypoxia-induced reporter gene expression is feasible, and that the intratumoral distributions of 124I-FIAU and 18F-FMISO are similar. In tumor sections, detailed radioactivity distributions were obtained with PPI which also showed similarity between 124I-FIAU and 18F-FMISO. CONCLUSION: This reporter system is sufficiently sensitive to detect hypoxia-induced transcriptional activation by noninvasive imaging and might provide a valuable tool in studying tumor hypoxia and in validating existing and future exogenous markers for tumor hypoxia.

Adenocarcinoma↗
PubMed2004

Dosimetric effect of respiratory motion in external beam radiotherapy of the lung.

BACKGROUND AND PURPOSE: To study the effect of breathing motion on gross tumor volume (GTV) coverage for lung tumors using dose-volume histograms and relevant dosimetric indices. PATIENTS AND METHODS: Treatment plans were chosen for 12 patients treated at our institution for lung carcinoma. GTV volumes of these patients ranged from 1.2 to 97.3 cm(3). A margin of 1-2 cm was used to generate the planning target volume (PTV). Additional margins of 0.6-1.0 cm were added to the PTV when designing treatment portals. For the purposes of TCP calculation, the prescription dose was assumed to be 70 Gy to remove the effects of prescription differences. Setup error was incorporated into the evaluation of treatment plans with a systematic component of sigma(RL) = 0.2 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.3 cm and a random component of sigma(RL) = 0.3 cm, sigma(AP) = 0.3 cm, and sigma(SI) = 0.3 cm. Breathing motion was incorporated into these plans based on an independent analysis of fluoroscopic movies of the diaphragm for 7 patients. The systematic component of breathing motion (sigma(RL) = 0.3 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.6 cm) was incorporated into the treatment plans on a slice by slice basis. The intrafractional component of breathing motion (sigma(RL) = 0.3 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.6 cm) was incorporated by averaging the dose calculation over all displacements of the breathing cycle. Each patient was simulated 500 times to discern the range of possible outcomes. The simulations were repeated for a worst case scenario which used only breathing data with a large diaphragmatic excursion, both with and without intrafractional breathing motion. RESULTS: Dose to 95% of the GTV (D95), volume of the GTV receiving 95% of the prescription dose (V95) and TCP changed an average of -1.4+/-4.2, -1.0+/-3.3, and -1.4+/-3.8%, respectively, with the incorporation of normal breathing effects. In the worst case scenario (heavy breathers), D95 and V95 changed an average of -9.8+/-10.1 and -8.3+/-11.3%, respectively, and TCP changed by -8.1+/-9.1%. GTVs with volumes greater than 60 cm(3) showed stronger sensitivity to breathing especially if the shape was non-ellipsoidal. In the normal breathing case, the probability of a decrease in D95, V95, or TCP of a magnitude greater than 10% is less than 4%, and in the worse case scenario this probability is approximately 30-40% with intrafractional breathing motion included, and less than 10% with intrafractional breathing motion not included. CONCLUSIONS: With the PTV margins routinely used at our center, the effects of normal breathing on coverage are small on the average, with a less than 4% chance of a 10% or greater decrease in D95, V95, or TCP. However, in patients with large respiration-induced motion, the effect can be significant and efforts to identify such patients are important.

Artifacts↗
PubMed2003

Adenovirus-mediated heat-activated antisense Ku70 expression radiosensitizes tumor cells in vitro and in vivo.

Ku70 is one component of a protein complex, Ku70 and Ku80, that functions as a heterodimer to bind DNA double-strand breaks and activates DNA-dependent protein kinase. Our previous study with Ku70-/- and Ku80-/- mice, and cell lines has shown that Ku70- and Ku80-deficiency compromises the ability of cells to repair DNA double-strand breaks, increases radiosensitivity of cells, and enhances radiation-induced apoptosis. In this study, we examined the feasibility of using adenovirus-mediated, heat-activated expression of antisense Ku70 RNA as a gene therapy paradigm to sensitize cells and tumors to ionizing radiation. First, we performed experiments to test the heat inducibility of heat shock protein (hsp) 70 promoter and the efficiency of adenovirus-mediated gene transfer in rodent and human cells. Replication-defective adenovirus vectors were used to introduce a recombinant DNA construct, containing the enhanced green fluorescent protein (EGFP) under the control of an inducible hsp70 promoter, into exponentially growing cells. At 24 h after infection, cells were exposed to heat treatment, and heat-induced EGFP expression at different times was determined by flow cytometry. Our data clearly show that heat shock at 42 degrees C, 43 degrees C, or 44 degrees C appears to be equally effective in activating the hsp70 promoter-driven EGFP expression (>300-fold) in various tumor cells. Second, we have generated adenovirus vectors containing antisense Ku70 under the control of an inducible hsp70 promoter. Exponentially growing cells were infected with the adenovirus vector, heat shocked 24 h later, and the radiosensitivity determined 12 h after heat shock. Our data show that heat shock induces antisense Ku70 RNA, reduces the endogenous Ku70 level, and significantly increases the radiosensitivity of the cells. Third, we have performed studies to test whether Ku70 protein level can be down-regulated in a solid mouse tumor (FSa-II), and whether this results in enhanced radiosensitivity in vivo, as assessed by in vivo/in vitro colony formation and by the tumor growth delay. Our data demonstrate that heat-shock-induced expression of antisense Ku70 RNA attenuates Ku70 protein expression in FSa-II tumors, and significantly sensitizes the FSa-II tumors to ionizing radiation. Taken together, our results suggest that adenovirus-mediated, heat-activated antisense Ku70 expression may provide a novel approach to radiosensitize human tumors.

Adenocarcinoma↗
PubMed2003

Comparison of intensity-modulated radiotherapy with three-dimensional conformal radiation therapy planning for glioblastoma multiforme.

This study was designed to assess the feasibility and potential benefit of using intensity-modulated radiotherapy (IMRT) planning for patients newly diagnosed with glioblastoma multiforme (GBM). Five consecutive patients with confirmed histopathologically GBM were entered into the study. These patients were planned and treated with 3-dimensional conformal radiation therapy (3DCRT) using our standard plan of 3 noncoplanar wedged fields. They were then replanned with the IMRT method that included a simultaneous boost to the gross tumor volume (GTV). The dose distributions and dose-volume histograms (DHVs) for the planning treatment volume (PTV), GTV, and the relevant critical structures, as obtained with 3DCRT and IMRT, respectively, were compared. In both the 3DCRT and IMRT plans, 59.4 Gy was delivered to the GTV plus a margin of 2.5 cm, with doses to critical structures below the tolerance threshold. However, with the simultaneous boost in IMRT, a higher tumor dose of approximately 70 Gy could be delivered to the GTV, while still maintaining the uninvolved brain at dose levels of the 3DCRT technique. In addition, our experience indicated that IMRT planning is less labor intensive and time consuming than 3DCRT planning. Our study shows that IMRT planning is feasible and efficient for radiotherapy of GBM. In particular, IMRT can deliver a simultaneous boost to the GTV while better sparing the normal brain and other critical structures.

Adult↗