bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of DNA Transfection and Activation of Human c‐raf‐1, But Not Epidermal Growth Factor Receptor, With Certain Head and Neck Squamous Cell Carcinoma‐Derived Cell Lines
Authors: Kasid U. , Pfeifer A. , Merlino G. , Mark G. E. , Dritschilo A. 
Published: February 2007

AbstractWe have examined the mechanism of activation of c‐raf‐1 and the expression of epidermal growth factor receptor (EGF‐R) gene in the three relatively radiation resistant human squamous cell carcinoma‐derived cell lines (SCC‐35, JSQ‐3, and SQ‐20B). The human c‐raf‐1 sequences were observed in the primary G418r, human Alu+ NIH/3T3 clones transfected with these tumor cell DNAs. The human raf‐1‐related sequences were truncated, rearranged, and amplified in the primary NIH/3T3 transfectants, and a majority of the clones revealed sequences corresponding to the carboxy‐terminus of the protein product of human raf‐1 (Raf‐1). A highly tumorigenic potential of transfectant clones correlated with expression of the new (human) raf‐1‐related sequences. By contrast, the EGF‐R gene was amplified and aberrantly overexpressed in only the SQ‐20B tumor cells. The human EGF‐R‐related sequences were not detected in the human Alu+ NIH/3T3 transfectant clones, including those derived following the SQ‐20B tumor cell DNA transfection. The levels of Raf‐1‐associated serine/threonine kinase activity were comparable in SCC‐35 and SQ‐20B cells. We have previously reported that the antisense c‐raf‐1 cDNA transfection is sufficient for the down regulation of tumorigenicity and radioresistance in SQ‐20B cells. The present data suggest that the role of c‐raf‐1 in the development of the tumor phenotype may be unrelated to the amplification and activation of EGF‐R in these squamous carcinoma‐derived cells. © 1993 Wiley‐Liss, Inc.
Sequence analysis of mutational hot spots in the endogenous and transfected colony stimulating factor 1 receptor in gamma‐irradiation induced factor independent subclones of clonal hematopoietic progenitor cell lines
Authors: Romanik Elizabeth A. , Leif Jean , Sakakeeny Mary Ann , Greenberger Joel S. 
Published: February 2007

AbstractAmino acid substitutions in several proto‐oncogenes and growth factor receptors may be activating mutations. The macrophage‐colony stimulator factor (M‐CSF) receptor (c‐fms) differs from the transforming v‐fms at several sites in the extracellular domain and contains a tyrosine residue at the carboxy terminus which may be involved in the negative regulation of the receptor kinase activity. The engineering of two point mutations in human c‐fms gene (residue 301, leucine to serine; and residue 969, tyrosine to phenylalanine) induces factor independent growth and malignant transformation when expressed in murine cells. Point mutations have also been detected in c‐fms in marrow cells or peripheral blood from patients with myelodysplastic syndromes or acute myelomonocytic leukemias. We have previously shown that murine factor independent cell lines, derived from cocultivation of clonal interleukin‐3 (IL‐3) dependent hematopoietic progenitor cell lines with the gamma‐irradiated marrow stromal cell line, D2XRII, have an upregulated c‐fms expression during an intermediate stage on the way to factor independence, but that fully factor independent subclones do not have an overexpression of c‐fms. In order to determine whether the factor independent phenotype resulted from an activating mutation in c‐fms during the transient phase of overexpression, we examined both intracellular and extracellular domains of c‐fms in irradiation induced factor independent subclones of FDC‐P1 JL26 or 32D c‐fmsm cells. Polymerase chain reaction (PCR) amplification of the regions flanking residues 301 and 973 with sequence analysis by the dideoxy chain‐termination method revealed no detectable mutations at either site. These data show that the factor independence of these cell lines does not result from activating mutations at 301 or 973 of the c‐fms receptor. Thus, the induction of growth factor independence may be attributable to 1) activating mutations at other sites in c‐fms; 2) activation of sites distal to the CSF‐1 receptor in the signal transduction pathway; or 3) a mechanism independent of the c‐fms/M‐CSF pathway. © 1993 Wiley‐Liss, Inc.
Alternating and concurrent chemotherapy and radiotherapy for unresectable head and neck carcinoma
Authors: McLaughlin Patrick , Urba Susan , Thornton Allan , Forastiere Arlene , Wolf Gregory 
Published: February 2007

AbstractBetween 1987 and 1989, 12 patients with advanced unresectable head and neck carcinoma were entered on a regimen of alternating and concurrent chemotherapy and radiotherapy. During the initial phase, cisplatin (50 mg/m2/day × 3 days) was administered 1 week and alternated with 160 cGy TID radiation week 3. This alternating schedule was repeated once for a total dose of 300 mg/m2 cisplatin and a total radiation dose of 4,800 cGy. Week 9, concurrent cisplatin (20 mg/m2/day × 5 days) was administered with 200 cGy BID radiation to boost ports. In spite of the alternating schedule, acute toxicity from 160 cGy TID was severe and delays secondary to mucositis increased the average duration of therapy to 11 weeks. Unexpected chronic toxicity included 2 of 12 patients with swallowing difficulty due to a sensory neuropathy which was likely a combined modality effect. This had not been reported in previous combined modality studies. A complete response was achieved in 5 of 12 patients and a partial response in 7 of 12 patients. Overall median survival was 17 months. Although the combination of cisplatin and accelerated radiation given in the above dose schedule induced a complete or partial response in all patients, severe toxicity and lack of survival benefit discourage further use of this regimen. © 1993 Wiley‐Liss, Inc.
Functional and morphological damage after local heart irradiation and/or adriamycin in Wistar rats
Authors: Kitahara T. , Liu K. , Solanki K. , Trott K. R. 
Published: February 2007

AbstractThe hearts of Wistar rats were locally irradiated with 15–30 Gy single doses of 300 kV X‐rays or animals were intravenously injected by single doses of 1–3 mg/kg body weight of adriamycin. Animals were followed until death or for between 320 and 710 days. After irradiation, congestive heart failure occurred with a dose‐dependent latency, which was significantly longer if the atria were excluded from the irradiation field. Cardiac output started to decrease after about 3 months, well before myocardial degeneration was noted, but it did not depend on radiation dose. After adriamycin, cardiac output showed a dose‐dependent drop within 2 weeks to plateau and never recovered to the control values. Capillary density 400 days after treatment was reduced both after irradiation and after adriamycin. Irradiation with 20 Gy 6 months after adriamycin decreased capillary density even further. © 1993 Wiley‐Liss, Inc.
Proliferative assays for the assessment of radiosensitivity of tumor cell lines using 96‐well microcultures
Authors: Cross Peter , Marshall Elaine S. , Baguley Bruce C. , Finlay Graeme J. , Matthews John H. L. , Wilson William R. 
Published: February 2007

AbstractWe have compared the effectiveness of three short‐term proliferative assays [3(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction, methylene blue staining, and [3H]‐thymidine incorporation] in predicting the results of clonogenic assay of radiosensitivity in five mammalian cell lines (SCCVII, AA8, V3, FME, and MM‐96). Cells were cultured in 96‐well microculture plates and a lead wedge was employed to provide a range of radiation doses (60Co source) up to 10 Gy. Radiation dosimetry was determined by a novel modification of the Fricke/thiocyanate dosimetry technique to allow direct determination in 96‐well plates. Cells were cultured following irradiation to determine clonogenic survival curves and to calculate the survival at 2 Gy (SF2), the initial slope of the fitted linear quadratic function (α), and the mean inactivation dose (D). A broad range of radiosensitivity was obtained (SF2 = 0.14–0.92) with the clonogenic assay. All three proliferation assays provided measures of radiosensitivity which correlated with clonogenicity at low radiation dose. The thymidine incorporation assay, which provided excellent linear correlation (r = 0.98) with clonogenicity for SF2 and D, used semiautomated methods for harvesting and scintillation counting to give sample processing times comparable to the colorimetric methods. It offered the advantages of superior assay linearity and dynamic range, and reduced interference by non‐proliferating cells at high radiation dose. © 1994 Wiley‐Liss, Inc.
5‐iodo‐2‐deoxyuridine as cytotoxic chemotherapy and as a possible radiosensitizer in a mouse ovarian ascites tumor model
Authors: Epperly Michael W. , Deutsch Melvin 
Published: February 2007

AbstractThe mouse ovarian ascites tumor model was used to evaluate the intraperitoneal (IP) administration of 5‐iodo‐2‐deoxyuridine (IUDR) as a radiosensitizer and tumor cytotoxic agent. A 7 day continuous infusion of IUDR starting on the day of tumor cell implantation (1 × 106 tumor cells) was extremely effective in prolonging survival compared to no treatment or radiation alone. Infusions starting on day 7 after implantation of tumor cells were less effective. Whole abdominal irradiation (either 500 cGy × 2 or 750 cGy × 2) on days 5 and 7 from tumor cell implantation had very little beneficial effect (P = 0.15 and 0.10, respectively). The combination of radiation and IUDR as used in these experiments did not show any benefit over IUDR alone. As yet, an optimum combination of radiation and IUDR which would be superior to IUDR alone has not been demonstrated for this tumor model. However, these results suggest that the IP administration of IUDR alone or possibly with radiotherapy might be beneficial for malignancies such as ovarian cancer which tend to disseminate IP. © 1994 Wiley‐Liss, Inc.
Antiproliferative effects of ionizing radiation, all‐trans‐retinoic acid, and interferon‐α on cultured human squamous cell carcinomas
Authors: Hoffmann W. , Bamberg M. , Rodemann H. P. 
Published: February 2007

AbstractIn the present study we analyzed the antiproliferative effects of irradiation (IR), all‐trans‐retinoic acid (RA), and interferon‐α (IFN‐α) on two established human cell lines of squamous cell carcinoma of the head and neck (cell line HTB43) and of cervical cancer (cell line HTB35). The determination of the radiosensitivity of these cells using the colony formation assay revealed that the Do value, or radiation dose that reduces survival to e−1 of its previous value on the exponential portion of the survival curve, for both cell lines was identical (2 Gy). The surviving fraction at 2 Gy (SF2) could be demonstrated to be approximately 60% for both cell lines. Treatment of these carcinoma cells either with all‐trans‐RA (dose range 1–10 μM) or with IFN‐α (dose range 0.5–500 IU/ml) resulted in a significant inhibition of colony formation. When the cells were treated with a combination of RA and IFN‐α the growth potential was affected in a synergistic manner. Pretreatment of the squamous cell carcinoma cell lines with RA in combination with IFN‐α for 24 hr followed by a single IR dose of 2 Gy led to a significant potentiation of the radiosensitivity in both lines although this effect was much more pronounced in the cervical cancer cells (HTB35). Cytomorphological and cytochemical analyses revealed that the growth inhibitory activity of RA, IFN‐α, and IR may be ascribed in part to the induction of irreversible postmitotic cells with a more normalized state of differentiation. On the basis of these data, experimental strategies could be developed for future treatment concepts employing RA, IFN‐α, and IR for the therapy of squamous cell carcinomas. © Wiley‐Liss, Inc.
Expression of the human BCL‐2 transgene increases the radiation resistance of a hematopoietic progenitor cell line
Authors: Epperly M. W. , Santucci M. A. , Reed J. C. , Shields D. , Halloran A. , Greenberger J. S. 
Published: February 2007

AbstractWe investigated the effect of overexpression of a BCL‐2 transgene on the irradiation survival of the interleukin (IL)‐3‐dependent 32D cl 3 cell line in vitro. The 32D‐BCL‐2 clonal subline was selected by transfection of 32D cl 3 cells with a BCL‐2 and neor‐containing plasmid vector selecting for G418 resistance. Cell line 32D‐BCL‐2 was IL‐3‐dependent and showed detectable BCL‐2 protein expression by Western analysis of cell lysates. The cells expressing BCL‐2 showed the characteristic block of apoptosis by DNA ladder analysis of cells following deprivation of IL‐3, where a decrease in DNA fragmentation of 32D‐BCL‐2 compared to 32D cl 3 DNA was observed after 200 to 1,000 cGy irradiation. The 32D‐BCL‐2 cell line demonstrated increased radioresistance at a dose rate of 110 cGy/min with an ñ and D0 of 8.70 and 130 cGy, respectively, compared to 5.03 and 101 cGy for parent 32D cl 3 cells (P = 0.015 and 0.018, respectively). At the clinical low dose rate of 7.5 cGy/min, the ñ and D0 for 32D‐BCL‐2 were 2.51 and 178 cGy compared to 1.96 and 148 cGy for 32D cl 3 (P = 0.074 and 0.071, respectively). Thus, expression of a BCL‐2 transgene increased the gamma‐irradiation resistance of 32D cl 3 cells in vitro. These data are consistent with recently published evidence for a role of BCL‐2 in reducing intracellular free oxygen radicals. These results may explain the unexpected survival of BCL‐2‐containing tumor cells in bone marrow transplant recipients after low‐dose‐rate total body irradiation. © Wiley‐Liss, Inc.
Stereotactic radiosurgery: Relative biological effect of continuous vs. intermittent radiation exposures
Authors: Benedict S. H. , Lin P.‐S. , Zwicker R. D. , Khandelwal S. R. , Broaddus W. C. , Schmidt‐Ullrich R. K. 
Published: February 2007

AbstractLinear accelerator‐based stereotactic radiosurgery is increasingly used in place of gamma knife equipment. Conforming radiation isodoses to complex volumes requires multiple isocenters and arcs per isocenter and may result in a protracted and intermittent radiation exposure. The experiments in this study were designed to quantitate the difference between continuous and intermittent radiation schedules which are typical for gamma knife and linear accelerator‐based radiosurgery, respectively. Two radiobiologically well‐characterized cell lines, V79 Chinese hamster and U‐87MG human malignant glioma cells, were irradiated in vitro to 12 Gy delivered as a continuous 5 min exposure and an intermittent exposure lasting maximally 112 min. The effect of continuous vs. intermittent irradiation to a dose of 31.5 Gy was also measured in vivo using FSaII fibrosarcomas, implanted into C3Hf/Sed mice, in a tumor growth assay. The in vitro experiments demonstrated a significant reduction in biological radiation effect reflected in 2‐ to 3‐fold increases in cell survival with intermittent vs. continuous irradiation schemes. Similar effects were seen with the FSaII tumors. The reduced effect of the intermittent irradiation schemes is most likely due to repair processes after radiation exposure, such as Potentially Lethal Damage Repair (PLDR) and Sublethal Damage Repair (SLDR), which can occur during 5–15 min intervals between radiation increments of intermittent stereotactic radiosurgery treatments. © 1995 Wiley‐Liss, Inc.
Induction of growth factor genes in endothelial cells by ionizing radiation
Authors: Haimovitz‐Friedman A. , Witte L. , Chaudhuri A. , McLoughlin M. , Fuks Z. 
Published: February 2007

AbstractThis study reports that exposure of endothelial cells [bovine aortic endothelial cells (BAEC) and porcine aortic endothelial cells (PAEC)] to ionizing radiation leads to activation of the basic fibroblast growth factor (bFGF) and platelet‐derived growth factor (PDGF)‐B genes. Nuclear RNA run‐on experiments showed an increase in nuclear RNA of these factors within 90 min after delivery of a dose of 4 Gy. In addition, there was a dose‐and time‐dependent transient increase in bFGF and PDGF‐B mRNA transcripts, although there were differences in the kinetics of these responses between BAEC and PAEC. Radiation‐induced activation of the bFGF and PDGF‐B genes was also manifested by secretion of the corresponding proteins into the culture media of the irradiated endothelial cells. In contrast, the acidic fibroblast growth factor (aFGF), PDGF‐A, and transforming growth factor beta (TGFβ) genes were not concomitantly activated in these cells, as indicated by lack of increase in their mRNA levels. Activation of specific growth factor genes and the extracellular secretion of their products may play an important role in modulating the radidation response via autocrine or paracrine mechanisms. © 1995 Wiley‐Liss, Inc.
Prostate screening programs hosted by radiation oncologists: Feasibility and outcome
Authors: Yoskovitch Adi , Corn Benjamin W. , Bruner Deborah W. , Jacofsky David , Slivjak Anne , Hanks Gerald E. 
Published: February 2007

AbstractScreening for prostate cancer has improved early detection of the disease and may impact on mortality rates. Since all reported screening programs to date have originated in urology practices, we undertook such an effort in our department of radiation oncology where a comprehensive prostate cancer program exists.Four annual prostate cancer screening programs were conducted by our department of radiation oncology between 1990–1993. Examiners and supportive personnel included the attending staff, house staff, rotating medical students, and nurses from the department of radiation oncology. Urologists were encouraged, but not required, to assist. Eligible subjects included men ≧ 50 years old and men ≧ 40 if a family history of prostate cancer in a first degree relative was documented. The screening protocol consisted of directed history, measurement of serum prostate specific antigen (PSA), followed by digital rectal examination (DRE) performed by attending physicians. Needle biopsies were carried out on men with abnormal DRE, elevated PSA (>4 ng/mL), or both. Complete follow‐up was obtained by contacting participants and their primary physicians.During the 4‐year period, 442 men were screened (annual range: 91–202) and a total of 11 cancers were diagnosed. All patients diagnosed with cancer had negative metastatic work‐up. Among those screened, 20% (90/442) had abnormal DRE alone, 8.8% (39/442) had elevated PSA alone, while 9.2% (41/442) had both abnormal DRE and elevated PSA. Adenocarcinoma was diagnosed in 1% (1/90) of patients with abnormal DRE alone, 18% (7/39) of those with abnormal PSA alone, and in 7% (3/41) of men with both abnormalities. Among those with cancer, 63% (7/11) opted for definitive irradiation, 27% (3/11) chose prostatectomy and one patient chose observation. Among those who selected radiotherapy, 86% (6/7) were treated in our department.Prostate screening can be conducted by a radiation oncology practice and provides a valuable contribution to the community. Our screening program succeeded in diagnosing patients with organ‐confined disease. These data extend the evidence of Catalona et al. [N Engl J Med 324:1156–1161, 1991] which suggest that rectal examination can no longer be regarded as the sole or most useful means of detecting prostate cancer. Most (63%) of the patients diagnosed through this effort opted for definitive treatment by radiotherapy. The majority (86%) of patients selecting irradiation were treated at our center. Although screening for prostate cancer is feasible, controlled clinical trials comparing screened to unscreened samples are needed to determine the effect of earlier detection on morbidity and survival. © 1995 Wiley‐Liss, Inc.
Effect of a pure anti‐estrogen, ICI 182,780, on the in vitro radiosensitivity of MCF‐7 breast carcinoma cells
Authors: Noyes William R. , Timothy Mulcahy R. , Craig Bruce A. , Kinsella Timothy J. 
Published: February 2007

AbstractUse of the anti‐estrogen tamoxifen (TAM) has been demonstrated to contribute a survival advantage in postmenopausal women with early stage or advanced breast cancer. Although conflicting results exist in the literature, some reports have suggested that TAM may exert potential deleterious effects on radiation sensitivity and response of breast cancers to radiotherapy (RT). A new non‐steroidal anti‐estrogen, ICI 182,780, which, unlike TAM, is without any estrogenic properties, has been used in European clinical trials in place of TAM. This study reports the effects of ICI 182,780 on radiation sensitivity and potentially lethal damage repair (PLDR) in estrogen‐receptor positive (ER+) MCF‐7 human breast carcinoma cells irradiated in vitro. At a concentration of 10−7 M, ICI 182,780 can inhibit the growth‐stimulatory effect of 10−10M 17β‐estradiol (E2). Growth‐arrested MCF‐7 cells were divided into four treatment groups: estradiol‐deprived (−E2) and estradiol‐stimulated (+E2) cultures incubated in the presence or absence of ICI 182,780 (10−7 M). Five days later each group was exposed to γ‐irradiation and cell survival was measured by clonogenic assay in complete medium containing E2. In one series of experiments, the cells were harvested immediately after irradiation, while in a second series, the cells were held at 37°C for an additional 24 hr prior to harvesting. No statistically significant survival difference was detected between groups plated immediately after irradiation or 24 hr later, although a trend toward improved survival for the delayed plating groups was routinely observed. ICI 182,780 did not significantly alter radiation sensitivity of MCF‐7 cells regardless of their hormonal status (+/−E2), nor did it change the sensitivity of cells harvested immediately or allowed 24 hr to express PLDR. These results suggest that ICI 182,780 may be used as an adjuvant in the treatment of breast cancer without altering the radiation sensitivity of breast cancer cells to concurrent RT. © 1995 Wiley‐Liss, Inc.
Cloning and sequencing of the cDNA for the cph oncogene from neoplastic hamster fibroblasts reveal partial homology with the dbl exchange factor
Authors: Velasco Juan A. , Avila Matías A. , Cansado José , Notario Vicente 
Published: February 2007

AbstractThe combination of in vitro transformation protocols and transfection assays allowed us to isolate a new transforming gene, cph, from neoplastic Syrian hamster embryo fibroblasts chemically initiated with a single dose of 3‐methylcholanthrene. Cosmid clones encompassing cph genomic sequences were able to transform NIH/3T3 cells and showed a synergistic action with H‐ras in the transformation of the murine fibroblasts. In the present study, we describe the molecular cloning of the hamster cph oncogene cDNA. Nucleotide sequence analysis of a full‐length cDNA clone (pBl‐19), isolated from a cDNA library from neoplastic hamster cells with cph genomic probes demonstrated that the cloned cph cDNA does not show any significant global homology to sequences deposited in established databases, confirming that cph is a novel gene. The cph cDNA contained an open reading frame with coding capacity for a protein of about 26 kDa, which was synthesized from pBl‐19 by using in vitro transcription‐translation assays. The cph protein deduced from the cDNA nucleotide sequence contained a dbl‐homologous (DH) domain. The fact that the DH domain has been found primarily among GDP‐exchange factors suggests that cph may be a new member of this family of proteins. © 1995 Wiley‐Liss, Inc.