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R R Weichselbaum

Publications and source records attributed to R R Weichselbaum.

At least 91 records · Page 5Linked to original sources
PubMed1997

Radiogenetic therapy: on the interaction of viral therapy and ionizing radiation for improving local control of tumors.

Improving local tumor control is a goal of modern radiotherapy that will directly impact a majority of cancer patients. Numerous attempts to develop radiosensitizing agents have, however, met with limited clinical success. Recent advances in gene therapeutic approaches have allowed researchers to combine gene therapy with ionizing radiation to enhance tumor cell killing. In the following review, we discuss the current advances in the use of radiation-inducible promoters, the use of pro-drug converting enzymes, and cytotoxic cytokines to enhance the therapeutic efficacy of ionizing radiation.

Adenoviridae↗
PubMed1996

Angiogenesis as a predictor of long-term survival for patients with node-negative breast cancer.

BACKGROUND: Angiogenesis (the formation of new blood vessels) is necessary for tumor growth and metastasis. PURPOSE: We investigated whether angiogenesis as measured by microvessel count (MVC) predicts clinical outcome in a series of patients with axillary lymph node-negative breast cancer who received no adjuvant therapy and who were followed for a long period of time. Our long-term goal is to identify those patients who may or may not need adjuvant chemotherapy. METHODS: Pathologic archival material and clinical information were analyzed for 167 patients treated with mastectomy from 1941 through 1987; none received adjuvant treatment. The median follow-up time among living patients was 15.4 years (range, 2.6-35.8 years). Ninety-six (58%) patients had a tumor size of 2 cm or less, 52 (31%) had tumors of 2.1-3 cm, and 19 (11%) had tumors of larger than 3 cm. Paraffin-embedded tissue sections were stained for expression of CD34 antigen on microvessel-associated endothelial cells by use of a monoclonal anti-CD34 antibody. Vascularity was defined as the number of microvessels (average of the three highest counts) per high-power microscopic field (400 x magnification) in the area of highest vascular density. A high vascular count was defined as 15 or more microvessels per field. Actuarial survival curves were calculated according to the Kaplan-Meier method and comparisons were made with the logrank test. The Cox proportional hazards model was used for multivariate analysis. All P values were based on two-sided testing. RESULTS: The 20-year disease-free survival (DFS) for the 167 node-negative patients treated with mastectomy and no adjuvant therapy was 74.8% (95% confidence interval [CI] = 64.7%-82.0%). The 20-year DFS was 93.1% (95% CI = 79.9%-97.7%) if the MVC was low versus 68.9% (95% CI = 56.8%-78.0%) if the MVC was high (P = .018). This difference was maintained irrespective of tumor size: for tumor size of 2 cm or less (93.3% [95% CI = 75.3%-98.3%] versus versus 67.8% [95% CI = 50.1%-80.3%]) and for tumor size of larger than 2 cm (92.3% [95% CI = 56.6%-98.9%] versus 70.9% [95% CI = 54.6%-81.6%]). However, the likelihood of a high MVC was greater with large tumors (P = .05). The proportions of tumors with low and high MVC were 33% and 67%, respectively, if the tumor size was 2 cm or less, and 20% and 80%, respectively, if tumor size was larger than 2 cm. There was no significant difference in the 20-year DFS as a function of tumor grade (P = .2). After combining patients with tumors of nuclear grades 2 and 3 compared with those of nuclear grade 1, the 20-year DFS was 93.9% (95% CI = 77.2%-98.4%) for low MVC versus 66.9% (95% CI = 52.2%-78.0%) for high MVC (P = .02). In a multivariate analysis that included the variables tumor size, age, nuclear grade, estrogen receptor status, and MVC, only MVC appeared to be an independent prognostic indicator (P = .04). CONCLUSIONS: Angiogenesis as measured by MVC is a reliable independent prognostic marker of long-term survival in patients with node-negative breast cancer. The prognostic usefulness of this marker is maintained after more than 15 years of follow-up. A low MVC identifies a subgroup of patients with DFS of 92% or more, independent of tumor size or grade.

Adult↗
PubMed1996

Breast preservation in stage I and II carcinoma of the breast. The University of Chicago experience.

BACKGROUND: Although breast conservation has received increased acceptance, there are still unresolved issues regarding local treatment techniques, such as the extent of surgery, in relation to the final margins of excision and the use of tumor bed boost radiation. The goal of this study was to determine the local control and breast preservation with particular emphasis on the importance of the final microscopic margins in patients receiving tumor bed boost therapy. METHODS: The authors analyzed 869 cases of Stage I and II breast carcinoma in 852 women who were treated with breast-conserving surgery and radiation therapy between 1984 and 1994. The median follow-up was 43 months. Final microscopic margins were negative in 762 (88%), microscopically positive in 82 (9%), and unknown in 25 (3%) of the patients. Negative margins were defined as no tumor cells at the surgical margin. The patients were treated with external beam radiation therapy to the entire breast to a median dose of 46 Gray (Gy). A boost to the tumor bed was delivered to 863 (99%) of the patients. The median tumor bed dose was 60 Gy. A multivariate analysis of factors impacting on the local control and overall survival was performed. Variables introduced into the model included size, age, lymph node status, microscopic margins, nuclear grade, histologic grade, and estrogen and progesterone receptor status. RESULTS: The actuarial 5-year local control rate was 97%. The median time to local failure was 32 months (range, 14-69 months). In multivariate analysis, the only significant factor affecting local control was the status of margins. In patients receiving boost radiation to the excision site, the local control rate at 5 years was 98% and 89%, respectively, if the margins were negative or positive (P < 0.01). This resulted in 5-year actuarial breast preservation rates of 98% and 92% (P = 0.03). In the patients in whom the margins of excision were microscopically positive, the local control rate was 91% if the total dose to the tumor bed was > 60 Gy compared with 76% for a dose < or = 60 Gy (P = 0.05). The 5-year actuarial overall survival rate was 89%. Approximately 94% of the women considered their cosmetic outcome good to excellent. CONCLUSIONS: By obtaining microscopically negative margins and using tumor bed boost therapy, excellent local control, breast preservation, and cosmesis can be achieved. In patients with microscopically positive margins, an acceptable local control rate can be achieved if a tumor bed boost is given.

Adult↗
PubMed1996

Tumor necrosis factor alpha (TNF-alpha) gene therapy targeted by ionizing radiation selectively damages tumor vasculature.

Intratumoral injection of an adenoviral vector containing radiation-inducible DNA sequences of the Egr-1 promoter linked to a cDNA encoding tumor necrosis factor (TNF) alpha (Ad.Egr-TNF) enhances the tumoricidal action of ionizing radiation in a human epidermoid carcinoma xenograft (SQ-20B). The dominant histopathological feature in tumor-bearing animals treated with Ad.Egr-TNF and irradiation is extensive intratumoral vascular thrombosis and tumor necrosis. Thrombosis and necrosis are not observed in animals treated with either the viral construct encoding TNF-alpha or radiation and did not occur in irradiated normal tissues adjacent to tumor in animals injected with Ad.Egr-TNF. To determine if the occlusive effects of Ad.Egr-TNF and X-irradiation were specific for tumor vessels, non-tumor-bearing mice were irradiated after receiving i.m. injection of Ad.Egr-TNF at viral titers 20-100 times greater than titers injected intratumorally. No vascular thrombosis was observed in the treated normal tissues. Combined Ad.Egr-TNF and radiation produced occlusion of tumor microvessels without significant normal tissue damage. Taken together, these data suggest that the interaction between radiation inducible TNF-alpha and X-irradiation occurs selectively within the tumor vessels.

Animals↗
PubMed1996

Prolonged c-jun expression in irradiated ataxia telangiectasia fibroblasts.

PURPOSE: Ataxia telangiectasia (AT) is an autosomal recessive disorder associated with radiation sensitivity and an increased incidence of leukemia, lymphoma, and some solid tumors. After exposure to ionizing radiation, cells from patients with AT demonstrate an attenuated G1-phase checkpoint. Because c-jun is known to regulate, in part, the exit from G1 and the onset of DNA replication, we analyzed c-jun transcription in irradiated AT fibroblasts. METHODS AND MATERIALS: AT5BI fibroblasts were irradiated and RNA was extracted and assayed for c-jun expression by Northern blot analysis. Transcriptional regulation of c-jun was evaluated by use of the 5' untranslated region of the jun promoter linked to the chloramphenicol acetyl transferase (CAT) reporter gene. Deletion mutants of the RSRF, SP-1, AP-1 and CCAAT domains within the jun promoter linked to the CAT reporter were transfected into AT5BI cells. Transfectants were irradiated, and CAT expression was quantified. After x-irradiation, nuclear protein binding to CCAAT was evaluated by an electrophoretic mobility shift assay. RESULTS: X-ray-mediated c-jun expression was sustained in AT5BI cells as compared to only transient expression in irradiated normal diploid fibroblasts. Mutation of either the AP-1 or CCAAT domains within the c-jun promoter reduced transcription by 50% and combined deletion of both AP-1 and CCAAT cis-acting elements entirely eliminated radiation-mediated transcriptional activation. Electrophoretic mobility gel shift assay of the nuclear proteins isolated from irradiated AT fibroblasts demonstrated their increased binding to the CCAAT sequence at 30 min after irradiation. Competition for nuclear protein binding to the CCAAT sequence with excess cold CCAAT demonstrated that protein binding to this sequence was specific. These findings were distinct from induction by phorbol esthers in that the RSRF cis-acting element and DNA segments upstream of -132 base pairs do participate in c-jun induction by phorbol esthers but not by radiation. CONCLUSIONS: Radiation-mediated transcriptional regulation of c-jun is prolonged in AT fibroblasts and is regulated in combinatorial control by the AP-1 and CCAAT domains, and transcriptional regulation is distinct from that induced by phorbol esthers.

Ataxia Telangiectasia↗
PubMed1996

Radiation oncology.

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Androgen Antagonists↗
PubMed1996

Protein kinase C inhibition induces apoptosis and ceramide production through activation of a neutral sphingomyelinase.

We report that WEHI-231 undergo apoptosis following exposure to the protein kinase C inhibitors chelerythrine chloride and calphostin C. Following the addition of chelerythrine or calphostin C to WEHI-231 cells, ceramide production increased over baseline levels with a concurrent decrease in sphingomyelin. More detailed examinations determined that the ceramide accumulation resulted from activation of neutral, but not acidic, sphingomyelinase. These results suggest an antagonistic relationship between protein kinase C activity and ceramide in the signaling events preceding apoptosis.

Alkaloids↗
PubMed1996

Cross-talk between ceramide and PKC activity in the control of apoptosis in WEHI-231.

WEHI-231, a murine B-cell lymphoma, readily undergoes programmed cell death following surface immunoglobulin (Ig) cross-linking [1]. Ceramide has been shown to induce apoptosis in WEHI-231 following its exposure to anti-lg antibodies, dexamethasone, and irradiation [2]. Recently, Haimovitz-Friedman et al. have demonstrated in endothelial cells that PMA not only prevented ceramide mediated apoptosis, but inhibited the generation of ceramide following irradiation [3]. In this paper we use highly specific PKC inhibitors to explore the connection between PKC activity, ceramide signaling and apoptosis. Both chelerythrine chloride and calphostin C triggered rapid apoptosis in WEHI-231 and acted in synergy with exogenous ceramide to induce apoptosis. Detailed studies of chelerythrine's mechanism of action revealed that 30 minutes following addition of 10 microM chelerythrine, sphingomyelin and phosphatidylcholine (PC) mass decreased confirming our previous findings of neutral, but not acidic, sphingomyelinase activation following treatment with PKC inhibitors [4]. The novel observation that inhibition of PKC isoforms present in WEHI-231 leads to a rapid rise in cellular ceramide as a results of sphingomyelin hydrolysis further suggests an antagonistic relationship between PKC activity and ceramide in the signaling events preceding apoptosis.

Alkaloids↗
PubMed1996

DNA double-strand break rejoining rates, inherent radiation sensitivity and human tumour response to radiotherapy.

The relationship between DNA double-strand break rejoining rates, inherent radiation sensitivity and tumour response to radiation therapy was determined for a group of 25 squamous cell carcinoma (SCC) and eight sarcoma (SAR) tumours. DNA double-strand break frequencies were measured by neutral filter elution in first passage following explant tumour samples after in vitro exposure to 100 Gy of 60Co gamma-rays. There was no significant difference between SCC and SAR tumour cells in their sensitivity to break induction, but in a 1 h time period SAR tumour cells rejoined significantly fewer breaks than SCC tumour cells, consistent with the greater sensitivity of SAR and suggesting that differences in rates of break rejoining account for the different distributions of radiosensitivities seen when different tumour types are compared. The percentage of breaks rejoined in 1 h in these tumour samples correlated well with D(o) and with the beta component of the survival curve, measured in vitro by clonogenic assay in tumour cell lines established from the tumour samples, but not with SF2 or the alpha component of the survival curve. The rates of DNA double-strand break rejoining therefore appear to influence the exponential portion of survival curves and probably the interactions between breaks. The percentage of breaks rejoined in 1 h was higher in SCC tumours that subsequently failed radiotherapy and, although the differences were not significant, they suggest that rates of break rejoining are an important component of tumour response to radiation therapy.

3T3 Cells↗
PubMed1996

Re-irradiation with concomitant chemotherapy of unresectable recurrent head and neck cancer: a potentially curable disease.

PURPOSE: The purpose of this study was to review the outcome following concomitant chemoradiation therapy in previously irradiated patients with locally or regionally recurrent or persistent head and neck cancer considered unresectable for cure. METHODS AND MATERIALS: We identified 45 patients treated between 1986 and 1993 with unresectable locally or regionally recurrent disease who were treated on one of four concomitant chemoradiotherapy phase I/II studies at the University of Chicago. All patients received hydroxyurea (HU), 5-fluorouracil (5-FU) and concomitant radiation therapy on an alternate week schedule (FHX). Cisplatin was added to FHX in three of the studies. RESULTS: The overall survival, progression-free survival, and local/regional control at 5 years was 14.6%, 13.5% and 20%, respectively, in a cohort of patients whose disease is almost universally fatal. Fatal treatment related complications were observed in 5 (11%) of patients. Two of these complications were related to radiation therapy. Stepwise Cox regression analysis revealed that dose and protocol were significantly correlated with survival, progression-free survival and local/regional control. A direct correlation was observed with radiation dose and an inverse correlation was observed with the initial FHX dose escalation study. The 2-year survival was 35% in patients receiving over 58 Gy compared to 8% for those receiving less than 58 Gy. CONCLUSIONS: Our results show that aggressive re-irradiation with concomitant chemotherapy of recurrent head and neck cancer results in the cure of some patients with acceptable toxicity if tumoricidal doses are applied. These results are in contrast to historical series of chemotherapy alone which results in limited palliation of brief duration and almost no chance of cure. Thus, re-irradiation with concomitant chemotherapy should be further investigated as an alternative to chemotherapy alone in multi-center or cooperative group randomized trials.

Adult↗
PubMed1996

Natural history of node-positive breast cancer: the curability of small cancers with a limited number of positive nodes.

PURPOSE: The long-term outcome of node-positive breast cancer was analyzed to determine the risk of metastatic disease as a function of tumor size and number of positive nodes. METHODS: From 1927 to 1987, 501 women with node-positive breast cancer were treated at the University of Chicago Medical Center. Patients were treated with radical, extended radical, or modified radical mastectomy. Forty-eight patients received multiagent chemotherapy, and 118 were treated with hormonal therapy. The mean survival duration is 120 months, with a maximal follow-up time of 485 months (40 years). RESULTS: The number of nodes that contained metastatic disease and the pathologic size of the primary tumor were significant determinants of disease-free-survival (DFS) by multivariate analysis (P < .001). In patients with fewer than four positive nodes, tumor size was of prognostic importance, with small tumors more likely to be cured by local-regional therapy. The 20-year DFS rate for patients with one positive node was 69%; however, if the primary tumor was < or = 2 cm, the 20-year DFS rate was 81%, compared with 59% if the tumor was larger than 2 cm. Patients with two or three positive nodes had a 73% 20-year DFS rate if the tumor size was < or = 2 cm, compared with 53% 20-year DFS in patients with tumors larger than 2 cm. CONCLUSION: In patients with T1 lesions with less than four nodes positive, the long-term DFS rate is comparable to that for node-negative breast cancer of the same size. Four or more nodes positive is an indicator of likely systemic disease.

Adrenalectomy↗
PubMed1996

Pharmacodynamics of fluorouracil-based induction chemotherapy in advanced head and neck cancer.

PURPOSE AND METHODS: To optimize the biochemical modulation of fluorouracil (5-FU), we administered the pure I-stereoisomer of leucovorin (LV) as a 132-hour continuous intravenous infusion (CIV) with cisplatin 100 mg/m2, 5-FU 640 mg/m2/d as a 120-hour CIV, and interferon alfa-2b (IFN) at 2 MU/m2/d for 6 days for three cycles (I-PFL-IFN). Pharmacologic parameters included morning (AM) and afternoon (PM) plasma concentrations of 5-FU, LV and its active metabolite 5-methyl tetrahydrofolate (MTHF), and dihydropyrimidine dehydrogenase (DPD) activity in peripheral mononuclear cells. RESULTS: Eighty-nine patients were treated (86 stage IV). Neutropenia and mucositis were the most common toxicities. Sixty-six percent achieved a complete remission (CR). There was a trend for higher PM versus AM 5-FU concentrations (median, 1.64 v 1.51 mumoles/L; P = .08), but not for LV plus MTHF (P = .66). The mean +/- SD DPD activity was 0.21 +/- 0.14 nmol/min/mg and did not correlate with plasma concentrations of 5-FU or LV plus MTHF or clinical toxicities. Higher PM 5-FU concentrations correlated with worse leukopenia (P = .04) and severity of mucositis (P = .04). PM 5-FU concentration was higher in women than in men (P = .07), with no apparent difference in severity of toxicities. The maximum 5-FU concentration was higher in CR than non-CR patients (median, 2.01 v 1.54 mumoles/L; P = .02) and higher in women than men who achieved a CR (median, 2.77 v 1.91 mumoles/L; P = .03). No correlation of CR with dose-intensity was found. CONCLUSION: L-PFL-IFN is active in stage IV head and neck cancer. 5-FU concentration is a significant predictor of toxicity. In women, optimization of response outcome requires a higher 5-FU concentration. Individualized 5-FU dosing to obtain higher 5-FU plasma concentrations may be indicated.

Adolescent↗
PubMed1996

Attenuation of G2-phase cell cycle checkpoint control is associated with increased frequencies of unrejoined chromosome breaks in human tumor cells.

To test the hypothesis that attenuation in G2-phase checkpoint control leads to elevated frequencies of unrejoined chromosome breaks in mitosis, the relationship between G2-phase cell cycle checkpoint control and unrejoined chromosome break frequencies after radiation exposure was examined in cells of 10 human tumor cell lines: 8 squamous cell carcinoma cell lines and 2 lymphoblastoid cell lines. Most of the delay in progression through the cell cycle seen in the first cell cycle after radiation exposure in these cell lines was due to blocks in G2 phase, and there were large cell line-dependent variations in the length of the G2-phase block. There was a highly significant inverse correlation between the length of G2-phase delay after radiation exposure and the frequency of induced unrejoined chromosome breaks seen as chromosome terminal deletions in mitosis. This observation supports the hypothesis that the signal for G2-phase delay in mammalian cells is an unrejoined chromosome break and that attenuation of G2-phase checkpoint control allows cells with unrejoined breaks to progress into mitosis. Attenuation in G2-phase checkpoint control was not associated with alterations in the frequency of induced chromosome rearrangements, suggesting that most chromosome rearrangements develop prior to G2 phase, and there was no significant relationship between the length of G2-phase delay and inherent radiation sensitivity, suggesting that unrejoined chromosome breaks are not the primary toxic lesion induced by radiation in mammalian cells.

Chromosome Aberrations↗
PubMed1996

Radiation can inhibit tumor growth indirectly while depleting circulating leukocytes.

The growth of certain UV-radiation-induced tumors is suppressed by T lymphocytes, but it has been proposed that non-T lymphocytes stimulate the growth of several of these tumors. In this study, the indirect effects of X irradiation on the growth of one such tumor in T-cell-deficient nude mice was tested. Even when the site of tumor cell injection was shielded, whole-body irradiation with 6 Gy before tumor challenge inhibited subsequent tumor growth significantly. The interval during which this indirect inhibition was observed correlated with the depletion of circulating leukocytes, which did not return to normal levels until 12-21 days after irradiation. These data are consistent with earlier results using an antibody to deplete Gr-1+ leukocytes and indicate that radiation can inhibit the growth of certain tumors indirectly without direct effects on the tumor cells or the tumor bed.

Animals↗
PubMed1996

Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival.

Recent studies have shown that p53 mutations are frequently found in cancer of the head and neck, whereas others have indicated that human papilloma virus (HPV) infection may be involved. Thus far, no studies have examined both p53 and HPV in the same patient population and correlated the results with clinical characteristics and outcome. The purpose of this study was to examine any interrelationship between p53 and HPV in patients with squamous cell carcinoma (SCC) of the head and neck. We also planned to correlate the experimental findings with clinical characteristics, known risk factors, and treatment outcome to determine whether any prognostic factors could be detected. Archival material from 66 patients with SCC of the head and neck were selected for study based on the availability of tissue from the primary tumors prior to treatment. A data base was constructed containing all clinical parameters at the time of diagnosis and risk factors. Genomic DNA was isolated and amplified using PCR, followed by SSCP analysis and direct genomic sequencing of all variants to detect p53 mutations. Two independent methods were used for HPV detection: (a) PCR amplification using primers homologous to the E6 region of HPV 16, 18, and 33, followed by RFLP analysis; and (b) PCR amplification with HPV L1 consensus primers, followed by triple restriction enzyme digestion. The results were entered into the data base for statistical analysis. Twenty-four percent of patients were found to have p53 mutations, and 18% were positive for HPV infection. Only one patient was positive for both. Tonsilar cancer was strongly correlated with HPV (P = 0.0001) and inversely correlated with p53 (P = 0.03). The only clinical parameter associated with p53 mutation was a trend toward a heavier smoking history. A subset analysis of the patients with tonsilar cancer revealed inverse correlations with smoking (P = 0. 015) and alcohol use (P = 0.05). Also, white patients with SCC of the tonsil were more likely to be HPV positive (P = 0.015). No significant relationships with outcome were detected with either p53 or HPV in the entire population. A subset analysis of patients with stage IV disease revealed that HPV infection was correlated with overall survival. This is the largest study to date to examine both p53 and HPV in patients with SCC of the head and neck. Our results suggest that HPV may be involved in the development of these cancers in patients without traditional risk factors and that HPV-related cancers are more prevalent in the white race.

Adult↗
PubMed1995

C-jun and Egr-1 participate in DNA synthesis and cell survival in response to ionizing radiation exposure.

Exposure of mammalian cells to ionizing radiation results in the induction of the immediate early genes, c-jun and Egr-1, which encode transcription factors implicated in cell growth as well as the cellular response to oxidative stress. We studied the role of these immediate early genes in cell cycle kinetics and cell survival following x-irradiation of clones containing inducible dominant negatives to c-jun and Egr-1. The dominant negative constructs to c-jun (delta 9) and Egr-1 (WT/Egr) prevented x-ray induction of transcription through the AP-1 and Egr binding sites, respectively. Twenty percent of confluent, serum-deprived SQ20B human tumor cells, normal fibroblasts, and fibroblasts from patients with ataxia telangiectasia entered S phase within 5 h of irradiation. Clones containing inducible delta 9 and WT/Egr dominant negative constructs demonstrated attenuation of the percentage of cells exiting G1 phase and reduced survival following irradiation. These data indicate that the dominant negatives to the stress-inducible immediate early genes Egr-1 and c-jun prevent the onset of S phase and reduce the survival of human cells exposed to ionizing radiation.

Cell Cycle↗
PubMed1995

Genetic radiotherapy overcomes tumor resistance to cytotoxic agents.

We report that radiation enhances gene therapy of a radioresistant tumor by upregulating the induction of a chimeric gene encoding a radiosensitizing protein, tumor necrosis factor alpha (TNF-alpha). We ligated the radiation-inducible CArG elements of the radiation-inducible Egr-1 promoter/enhancer region upstream to the transcriptional start site of the human TNF cDNA (pE425-TNF). This construct was transfected using cationic liposomes into the variant murine fibrosarcoma cell line, P4L. The P4L cell line was both radioresistant (D0 = 188) and resistant to TNF. After a single intratumoral injection of 10 micrograms of pE425-TNF in cationic liposomes and two 20-Gy doses of irradiation, mean tumor volumes were significantly reduced in P4L tumors as compared to those receiving either pE425-TNF in liposomes or radiation alone (P = 0.01). TNf protein in P4L tumors was induced by radiation as high as 29 times control levels and remained detectable for 14 days. Our data indicate that combined gene therapy using liposomes, together with ionizing radiation to locally activate the induction of a radiosensitizing protein, is successful at overcoming resistance to both TNF and radiation.

Animals↗