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C C Ling

Publications and source records attributed to C C Ling.

At least 91 records · Page 5Linked to original sources
PubMed1994

An equation for the dose response of radiation-induced apoptosis: possible incorporation with the LQ model.

Based on in vitro and in vivo data, we proposed an equation to describe the dose response of radiation-induced apoptosis. This equation can be incorporated into the LQ model to account for the contribution of apoptosis-mediated cell death in clonogenic survival curve. The modified LQ equation is a composite of the dose responses of two subpopulations, one susceptible and the other resistant to apoptotic cell death. For the apoptosis-resistant fraction, the size of which varies for different biological systems, the conventional LQ relation applies. For the susceptible subpopulation, the LQ equation is modified by e-zeta D, a functional form consistent with the observed dose-rate independence of this mode of cell death.

Algorithms↗
PubMed1994

Apoptosis induced at different dose rates: implication for the shoulder region of cell survival curves.

Apoptosis is induced by radiation, administered at different dose rates of 3-60 Gy/h, in rat embryo cells transfected with a c-myc oncogene (REC:myc(ch1)) or with a c-Ha-ras oncogene (REC:ras(ch1)). Apoptosis is evaluated in terms of altered morphology, chromatin condensation and DNA fragmentation. The apoptotic dose response of REC:myc(ch1) rises steeply at low doses (to about 40% at 5 Gy), and reaches a plateau at high doses (of about 60% at > 15 Gy). In comparison with REC:myc(ch1), the REC:ras(ch1) is much less susceptible, with a maximum apoptotic fraction of about 10%. Interestingly, radiation-induced apoptosis is nearly dose-rate independent. In parallel, we assessed radiation-induced cell-killing as assayed by colony-formation. In contrast to that observed for apoptosis, the dose response of colony-formation is strongly dependent on dose rate. Cell surviving fraction measured at 3 Gy/h decreases exponentially with dose, with REC:myc(ch1) exhibiting a steeper slope than REC:ras(ch1). Thus, the different low-dose-rate radiosensitivity of the two cell lines may in part be due to their different susceptibility to radiation-induced apoptosis. Taken together, these findings suggest that radiation-induced apoptosis contributes significantly to the initial (shoulder) region of acute dose-rate survival curves of susceptible cells, and may have implications for fractionated and low dose rate radiotherapy.

Animals↗
PubMed1994

Transfected c-myc and c-Ha-ras modulate radiation-induced apoptosis in rat embryo cells.

We studied radiation-induced apoptosis in rat embryo cells (REC) and in REC transfected with a c-myc oncogene [REC:myc(ch1)] or with a c-Ha-ras oncogene [REC:ras(ch1)], or both [REC:myc+ras(ch1)]. Apoptosis, evaluated in terms of altered morphology, dye exclusion and DNA fragmentation, was evident in all the irradiated cells. The development of apoptosis with time was initially rapid and then gradually saturated at > 36 h after irradiation. Radiation-induced apoptosis in REC:ras(ch1) was mildly reduced, but that in REC:myc(ch1) and REC:myc+ras(ch1) was significantly increased, relative to that in REC. The percentage of REC:myc(ch1) and REC:myc+ras(ch1) cells undergoing apoptosis increased rapidly at low doses to about 40% at 5 Gy irradiation and reached a plateau at high doses (of about 60% at > 15 Gy). In contrast, REC and REC:ras(ch1) were much less responsive, with a maximum of about 15 and 7%, respectively.

Animals↗
PubMed1994

Neoplastic transformation dose response of oncogene-transfected rat embryo cells by gamma rays or 6 MeV alpha particles.

We measured a dose-response relationship for induction of neoplastic transformation by 6 MeV alpha particles and 137Cs gamma rays in REC:myc and REC:ras cells, that is, rat embryo cells (REC) transfected with the c-myc or the Ha-ras oncogenes. The 6 MeV alpha particles simulated 222Rn emissions for risk assessment relative to low-LET radiations. The dose of gamma rays was approximately twice that of alpha particles for a neoplastic transformation frequency of 10(-3). The survival of the REC cells containing oncogenes was comparable to that of the commonly used C3H 10T1/2 cells for the same dose, but the former were more refractory to radiation-induced neoplastic transformation. Neoplastic transformation frequency measured in REC cells was 3 times lower than those typically measured in C3H 10T1/2 cells at a gamma-ray dose of 6 Gy, and 5-10 times lower at an alpha-particle dose of 3 Gy.

Alpha Particles↗
PubMed1994

Inflammatory fibroid polyp of the jejunum causing intussusception: a case report.

Inflammatory fibroid polyp is a rare benign lesion of the gastrointestinal tract. This report concerns a 56-year-old female who presented with intermittent abdominal pain, vomiting and diarrhea; she had had partial intestinal obstruction over a period of two months. Plain abdomen showed dilatation of the small bowels. Abdominal echo revealed intussusception of the small intestine. During exploratory laparotomy a polypoid dumb-bell shaped polyp was noted as the leading point of the jejunojejunal intussusception, segmental resection of the jejunum was performed. Histological features of the polyp met the diagnosis of inflammatory fibroid polyp.

Female↗
PubMed1993

Modeling the development of metastases from primary and locally recurrent tumors: comparison with a clinical data base for prostatic cancer.

For many types of cancer, patients who relapse locally following localized treatment such as surgery or radiation therapy are found to have a higher incidence of distant metastases than those who are locally controlled. In this study we developed a mathematical model to investigate whether the excess distant metastases arise mainly from the local recurrence or whether the primary tumors in this group of patients have an intrinsically higher metastatic potential than those of locally controlled patients of the same clinical stage. The parameters of the model were chosen to be representative of prostate cancer and the calculated results were compared with published clinical data for carcinoma of the prostate. The best agreement with the data was seen for parameters which imply somewhat more "aggressive" primary tumors for locally relapsing patients, yielding relatively high rates of micrometastatic dissemination prior to initial diagnosis. However, the model calculations indicate that more than half of the metastases in such patients originated in association with the development of a local recurrence. Therefore, achieving local control in this group of patients would be beneficial in improving long term survival.

Computer Simulation↗
PubMed1993

A CT-based evaluation method for permanent implants: application to prostate.

A computerized tomography-based 3-dimensional evaluation scheme, using semi-automatic seed localization from transverse computerized tomography-images, has been developed for permanent implants. The treatment isodose contour is generated at each scan plane and overlaid on the corresponding target contour for coverage visualization. Volume and surface dose histograms are generated for the target and neighboring normal structures. Dose inhomogeneity within the target is also estimated from the full-width at half maximum of the differential volume dose histogram. The matched peripheral dose is calculated from the ellipsoidal volume approximation for the target. The present evaluation method has been applied here to 10 actual permanent I-125 prostatic implantations. Coverages by 150 Gy and 100 Gy levels are found to range from 78-96% and 91-99% of the target volume, respectively. The average matched peripheral dose is found to be about two times the average peripheral dose (the dose encompassing 99% target) and about three times the average minimum peripheral dose (the dose encompassing 100% target). The dose inhomogeneities within the target volume, in these 10 cases, range from 220-420 Gy.

Brachytherapy↗
PubMed1993

Presence of point mutations in the N-ras gene in radiation-transformed rat embryo cells.

We study the transforming ability of X-rays in multistep carcinogenesis by irradiating primary rat cells which contain transfected c-myc oncogene. X-irradiation induces fully transformed phenotypes, including anchorage-independent growth and tumor formation in nude mice. Of seven foci examined, five exhibited an A to G conversion in codon 61 of the N-ras oncogene. Another transformed isolate has a single G to A base substitution in codon 14 in the same oncogene, while no point mutation is detected in the other focus. This is the first in vitro demonstration of the association between point mutation and X-ray-transformed cells.

3T3 Cells↗
PubMed1993

The use of a multi-leaf collimator for conformal radiotherapy of carcinomas of the prostate and nasopharynx.

We investigate the use of a multi-leaf collimator for conformal radiation therapy of carcinomas of the prostate and of the nasopharynx. Following verification of dose calculation algorithms for multi-leaf collimated fields using film dosimetry, we compute dose distributions for multi-field conformal treatment using fields shaped with either the multi-leaf collimator or conventional cerrobend blocks. We compare the two sets of treatment plans using graphical isodose displays, tissue specific dose volume histograms, tumor control probabilities, and normal tissue complication probabilities. We also incorporate setup errors into the calculated dose distributions to assess the effect of treatment uncertainties on the various criteria. Based on these comparisons, we conclude that for multi-field conformal radiotherapy for these two disease sites, the use of multi-leaf collimation is equivalent to that of conventional cerrobend blocks.

Adenocarcinoma↗
PubMed1993

Stereotactic treatment of brain tumors with radioactive implants or external photon beams: radiobiophysical aspects.

We perform calculations, based on the linear-quadratic model, to assess the biologically effective doses (BED) of tumor and normal tissue in the stereotactic irradiation of brain tumors with either radioactive implants or radiosurgery techniques. Treatment protocols for radiosurgery and radioactive implants, as obtained from the literature, are reviewed and compared. A figure of merit is defined to be the ratio of tumor to normal tissue BED, expressed in units of Gy10/Gy3. These comparisons indicate a clear radiobiological advantage for brachytherapy, unless the radiosurgery is to be delivered in a large number of fractions. The differences in dose uniformity, and in the volume of normal tissue encompassed by the high dose regions, are factors that may also influence clinical results.

Brachytherapy↗
PubMed1993

Tumor control probability for permanent implants in prostate.

The tumor control probabilities (TCPs) for 11 transperineal permanent implants of the prostate with 125I seeds have been computed, based on target-specific volume-dose histogram data. Prostate dose-response of this modality is converted from that of external beam therapy based on biologically effective dose derived from the alpha beta model. The calculated TCPs for these transperineal prostate cases are compared with the results of 679 previous retropubic implants, providing interesting insight about these two techniques. Further refinement and validation of this model await long-term followup results of sufficient number of patients.

Brachytherapy↗
PubMed1993

Perspectives of multidimensional conformal radiation treatment.

We consider the present technological advancement that underlies the implementation of computer-controlled conformal radiotherapy. We also consider the developments in modern biology that may provide input to therapy planning. The concept of multidimensional conformal radiotherapy is advanced, which integrates geometrical precision and biological conformality, to optimize the treatment planning for individual patients, with a view to improve the overall success of radiotherapy.

Humans↗
PubMed1993

Probability of radiation-induced complications in normal tissues with parallel architecture under conditions of uniform whole or partial organ irradiation.

A biologically based model is developed for normal tissue complication probability as a function of dose and irradiated volume fraction for organs such as the kidney and the lung. The organ is assumed to be composed of functional subunits (FSUs) which are arranged in a parallel architecture. The complication is produced only if a sufficiently large fraction of the FSUs are inactivated by radiation and an FSU is inactivated only when all the clonogenic cells within it are killed. The linear-quadratic model is used for the dose-response of individual cells within an FSU. The predictions of this model are compared with those of an empirical power law function for uniform whole and partial organ irradiation.

Dose-Response Relationship, Radiation↗
PubMed1993

Molecular analysis of rat embryo cell transformants induced by alpha-particles.

An immortal cell line was established by transfecting a myc oncogene into rat embryo cells (REC:myc). This cell line was diploid, contact inhibited and grew well in culture. Exposure to a single 200 cGy dose of 6 MeV alpha-particles transformed these cells with a frequency of focus formation of approximately 3.6 x 10(-4) compared with a transformation frequency of < 7.8 x 10(-6) for primary cultures of REC. Isolates of alpha-particle-induced REC:myc (REC:myc:alpha) foci displayed anchorage-independent growth in soft agar and were tumourigenic in nude mice. Molecular studies demonstrated no alteration of gene structure or expression of the transfected or of the endogenous c-myc genes. Similarly, there was no alteration of the structure of Ha-ras, Ki-ras, or N-ras. The expression of Ha-ras, Ki-ras, N-ras and raf was not altered significantly. Assay for dominant oncogenes via DNA-mediated gene transfer into NIH3T3 cells was positive for nine of 13 REC:myc:alpha transformants. All NIH3T3 isolates contained bands hybridizing to rat repetitive DNA. NIH3T3 transformants from a tertiary round of transfection were analysed by Southern blot analysis for the presence of Ki-ras, N-ras, raf, trk, abl, fms, src, mos, fos, sis, fps, erbA, erbB or neu oncogenes of REC origin, and none were detected. Tertiary NIH3T3 transformants from three REC:myc:alpha transformants contained bands corresponding to Ha-ras but no point mutations were identified at the known hotspots of exons 1 or 2 of the donor REC:myc:alpha transformants. The inactivation of the tumour suppressor genes Rb, and p53, and the anti-metastasis gene, nm23, was evaluated by Southern and Northern hybridization analysis. Southern blots demonstrated that at least one allele of Rb, p53 and nm23 was present and no large scale structural changes were detected. No expression of Rb or p53 was detected in REC:myc or the alpha-particle-induced REC:myc transformants. The expression of nm23 was not altered in the transformed cell lines. While the analysis of the role of tumour suppressor gene inactivation in radiation-induced cell transformation is only in the initial stages, the results of DNA-mediated gene transfer into NIH3T3 cells suggest that unidentified dominant oncogenes are associated with alpha-particle-induced transformation in vitro.

Alpha Particles↗
PubMed1993

Low-dose-rate irradiation of rat embryo cells containing the Ha-ras oncogene.

Rat embryo cells and derived transfectants containing the Ha-ras oncogenes were irradiated with 60Co gamma rays at dose rates of 0.72, 0.066, 0.035, and 0.018 Gy/min. The measured dose response of cell survival shows that the oncogene-containing cells exhibit higher survival levels at all doses than the parental cells at every dose rate. The response of the cells containing the ras oncogene also became dose-rate independent at a higher dose rate, perhaps indicative of a greater repair capability relative to that of the primary cells.

Animals↗