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Biomedical subjects

J M Skibber

Publications and source records attributed to J M Skibber.

At least 19 recordsLinked to original sources
PubMed2001

Indications for immediate tissue transfer for soft tissue reconstruction in visceral pelvic surgery.

BACKGROUND: Perineal wound complications may occur after visceral pelvic surgery. We reviewed our experience to determine indications for immediate tissue transfer (TT) to prevent complications. METHODS: Hospital records and computerized data were reviewed on 175 perineal repairs in 156 patients treated at The University of Texas M.D. Anderson Cancer Center for tumors involving the alimentary tract (135 of 175), genitourinary tract (15 of 175), perineum (19 of 175), or sacrum (6 of 175). Patients had either resection of only the colorectum and anus (APR) (46 of 175) or multivisceral resection (MVR) (129 of 175), and the perineal wound was closed by using TT (108 of 175) or primary closure (PC) (67 of 175) on the basis of the surgeon's judgment. Complications were compared between PC and TT groups. RESULTS: Complications occurred in 57% (100 of 175). There was no significant difference overall in PC and TT procedures or in the APR subgroup. There were significantly fewer complications for TT patients in the MVR subgroup (P =.0001). There were significantly fewer complications for TT patients with prior irradiation in both APR (P =.01) and MVR (P =.007) subgroups. CONCLUSIONS: Immediate TT for perineal wound closure is associated with fewer healing complications than PC in a subset of patients with multivisceral resection or prior radiotherapy. Surgical planning in these cases should consider immediate soft tissue reconstruction.

Adult↗
PubMed2001

Evaluation and surgical resection of adrenal masses in patients with a history of extra-adrenal malignancy.

BACKGROUND: Adrenal abnormalities are often identified on imaging studies performed during the staging of patients presenting with a new malignancy or restaging of patients with a history of a malignancy. METHODS: We reviewed the records of patients who underwent surgical resection of an adrenal mass identified in the setting of previously or newly diagnosed extra-adrenal malignancy. RESULTS: Eighty-one patients with an adrenal mass and recently diagnosed malignancy (n = 24) or history of a malignancy (n = 57) underwent adrenalectomy. In 42 patients (52%) the adrenal mass was a metastasis. In 39 patients (48%) the adrenal mass was an additional primary adrenal tumor process: 19 pheochromocytomas, (14 syndrome-associated, 5 sporadic), 13 cortical adenomas, 3 adrenocortical carcinomas, 2 ganglioneuromas, and 2 cases of nodular hyperplasia. CONCLUSIONS: In this series nearly half of the patients with cancer and an adrenal mass had adrenal pathologic condition independent of their primary malignancy. Despite the presence of a newly diagnosed malignancy or history of malignancy, all patients with an adrenal mass should undergo a standard hormone evaluation to confirm that the mass is not a functional neoplasm. An assumption that the adrenal mass is metastatic disease will be wrong in up to 50% of such patients.

Adrenal Gland Neoplasms↗
PubMed2000

Quality of life and cost effectiveness analysis of therapy for locally recurrent rectal cancer.

PURPOSE: This study was performed to determine the quality of life and cost-effectiveness of therapeutic options for patients with locally recurrent rectal carcinoma, determined from the perspectives of patients and health care providers. METHODS: We reviewed the records of patients (N = 68) with locally recurrent rectal carcinoma evaluated from 1992 through 1995. We constructed a decision-analytic model incorporating outcomes, survival, and costs. Utilities were elicited from convenience samples of health care providers and patients using the standard gamble technique. RESULTS: The median survival for patients undergoing surgical resection (n = 40) was 42 months, compared with 16.8 months for patients undergoing diagnostic or palliative surgery (n = 16) and 18.3 months for patients treated nonoperatively (n = 12; P < 0.005). The mean cost of treatment per patient was $19,283 for the nonoperative group, $45,647 for the diagnostic or palliative surgery group, and $70,878 for the surgical resection group. The diagnostic or palliative surgical strategy was dominated by the nonoperative strategy because the former had greater costs with fewer health benefits. The incremental cost-utility ratio of surgical resection compared with nonoperative management using health care provider utilities was $109,777 per quality-adjusted life year gained; it was reduced to $56,698 using per quality-adjusted life year using mean patient utilities. CONCLUSIONS: Patients with recurrent rectal carcinoma view surgery and morbidity to be less severe than health care providers. Diagnostic or palliative surgery is expensive and affects quality-adjusted survival adversely compared with nonoperative therapy. Surgical resection may be a cost-effective use of resources, particularly when cost-effectiveness is calculated using patient preferences.

Aged↗
PubMed2000

Outcomes research in surgical oncology.

BACKGROUND: There have been significant developments and advances in the area of outcomes research in the past 25 years. Unfortunately, many surgical oncologists may not have a clear concept of outcomes research and the methodology involved. METHODS: A literature-based review article was done that included an overview of outcomes research, and study design and types, outcome measures, outcome instruments, and sources of outcome data were examined. In addition, we reviewed small area variation/volume outcome analysis as well as quality-of-life studies and their applications in surgical oncology clinical investigation. Specific examples from surgical oncology were identified. RESULTS: As the costs of health care have increased, so has the emphasis on measuring outcomes of medical and surgical care to determine the quality and appropriateness of care. Marked variations in a variety of outcomes after oncological procedures have been attributed to individual surgeon and institution characteristics. Because much of the clinical surgical oncology literature deals only with the traditional mortality and morbidity outcomes, a more comprehensive examination of patient outcomes is required to fully evaluate the impact of patient management decisions. Health-related quality of life can be measured and analyzed in several ways and decisions regarding the use of such methodology are dependent on multiple factors. CONCLUSIONS: Surgical oncologists should recognize that the true value of their interventions requires systematic and comprehensive examination of patient outcomes.

Decision Making↗
PubMed2000

Significance and management of local recurrences and limited metastatic disease in the abdomen.

The management of patients with synchronous or metachronous metastatic carcinoma, sarcoma, or melanoma in the abdomen requires a knowledge of the natural history of the disease and of the available treatment options. Patients with advanced malignant disease may be of marginal performance status yet may require large surgical procedures or combined modality therapy; the most challenging therapeutic decisions involve such patients. The authors highlight the role of surgery in selected patients with metastatic or recurrent malignancy as it is practiced at The University of Texas M. D. Anderson Cancer Center.

Abdominal Neoplasms↗
PubMed2000

NCCN Practice Guidelines for Colorectal Cancer.

The NCCN Colorectal Cancer Guidelines panel believes that a multidisciplinary approach is necessary for the management of the patient with colorectal cancer. The panel endorses the concept that treatment of patients in a clinical trial has priority over standard or accepted therapy. The recommended surgical procedure for resectable colon cancer is an en bloc resection; laparoscopic surgery should be done only in the context of a clinical trial. For patients with stage III disease, 5-FU-based adjuvant therapy is recommended. A patient who has metastatic disease in the liver or lung should be considered for surgical resection if he or she is a candidate for surgery and if surgery can extend survival. Surgery should be followed by adjuvant chemotherapy. The panel advocates a conservative post-treatment surveillance program for colon and rectal carcinoma patients. Serial CEA determinations are appropriate if the patient is a candidate for aggressive surgical resection, should recurrence be detected. Abdominal and pelvic CT scans should be utilized only when there are clinical indications of possible recurrence. Patients whose disease progresses during 5-FU-based therapy should be treated with irinotecan or encouraged to participate in a phase I or phase II clinical trial.

Colorectal Neoplasms↗
PubMed1999

Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: To evaluate the influence of response to preoperative infusional chemoradiation on outcome parameters among patients with locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy, 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2 per day), was given to 117 patients. As determined by pretreatment endorectal ultrasound (EUS), 96% of cases were Stage T3, and 51% had EUS evidence of perirectal adenopathy. Surgery was performed approximately 6 weeks after chemoradiation therapy. Postoperatively adjuvant systemic therapy, consisting of 400-425 mg/m2 of 5-fluorouracil plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for six cycles. Outcome parameters of local control (LC), freedom from distant metastases (DMC), disease-free survival (DFS) and cancer specific survival (CSS) were evaluated relative to primary tumor characteristics. RESULTS: The final post-treatment pathological tumor stages were complete response in 27%, Tis-2 N0 in 26%, T2 N1 in 5%, T3 N0 in 21%, T3 N1 in 15%, T4 N0 in 5% and T4 N1 in 1%. Down-staging occurred in 61% of cases. The pretreatment primary tumor size only influenced rates of local control (P < 0.03) and had no other influence on outcome parameters. Pretreatment evidence of perirectal lymph node involvement had no impact on outcome parameters. Pathologic evidence of nodal involvement did affect DMC (P < 0.002) and DFS (P < 0.003). Pathologic evidence of response did influence freedom from the development of distant metastases (P < 0.004). On pairwise analysis this relationship held only when responders were compared to non-responders. No difference was observed based on the level of downstaging at the primary tumor. Correspondingly, DFS was improved when non-responders were compared to downstaged patients (P < 0.01). Response to preoperative chemoradiation failed to affect rates of LC or CSS. For the group as a whole, adjuvant chemotherapy improved only CSS (P < 0.03). Adjuvant chemotherapy was given to 74 patients, 36 of whom had responded to preoperative chemoradiation. Improvements were only seen in DFS (P < 0.03) when down-staged patients were compared to the non-responders who received adjuvant chemotherapy. In addition, the DFS rates were lower in the non-responder group who received adjuvant chemotherapy even when they were compared to down-staged patients who did not receive adjuvant chemotherapy (P < 0.04). CONCLUSION: Consistent with other reports, disease free survival and subsequent development of distant metastases is reduced in the more than 60% of patients who respond to preoperative infusional chemoradiation. Evidence of response appears more significant than the degree of response. At present, no impact is seen on cancer specific survival rates. Consideration should be given for strategies that base selection of subsequent adjuvant chemotherapy on response to preoperative chemoradiation.

Adult↗
PubMed1999

Sacral chordoma: 40-year experience at a major cancer center.

OBJECTIVE: Sacral chordomas are relatively rare, locally invasive, malignant neoplasms. Despite surgical resection, adjuvant radiation therapy, and chemotherapy, recurrence is common. This study reviews our experience during the last 40 years at The University of Texas M.D. Anderson Cancer Center, to determine the effects of various treatment methods on the overall course of this disease process. METHODS: A retrospective study was performed. From 1954 to 1994, 27 patients with sacral chordomas were evaluated at our institution. RESULTS: There were 19 male and 8 female patients, with a mean age of 56 years (range, 27-80 yr). All except one of the patients presented with pain, and 17 of 27 showed evidence of autonomic dysfunction at initial presentation. Based on microscopic examination of surgical specimen margins, surgical procedures were categorized as either radical resection or subtotal excision. All patients underwent at least one surgical procedure, for a total of 67 procedures (28 radical resections and 39 subtotal excisions). Twelve patients underwent one operation, whereas nine underwent two procedures and six underwent more than two operations (range, 3-16 operations). Radiation therapy was used in conjunction with 13 of the 67 surgical procedures. The median Kaplan-Meier estimate of the overall survival time for the entire group was 7.38 years (range, 4 mo to 34 yr). Tumors recurred after 47 of the 67 procedures. The overall disease-free interval for patients undergoing radical resection was 2.27 years for each procedure, compared with 8 months for each procedure for patients treated with subtotal excision (log-rank test for the inequality between the two curves, 19.58; P<0.0001). The addition of radiation therapy prolonged the disease-free interval for patients undergoing subtotal resection (2.12 yr versus 8 mo; log-rank test for the inequality between the two curves, 5.82; P<0.02). CONCLUSION: Our results suggest frequent recurrences in the majority of patients with chordomas. Radical resection is associated with a significantly longer disease-free interval, compared with subtotal removal of the tumor. Addition of radiation after subtotal resection improves the disease-free interval, although radiation therapy can generally be used only once. Based on these findings, we think that, whenever possible, radical resection should be the treatment of choice for sacral chordomas.

Adult↗
PubMed1998

Clinical, pathologic, and economic parameters of laparoscopic colon resection for cancer.

BACKGROUND: The appropriateness of laparoscopic colon resection (LCR) as treatment for malignancy has been questioned. METHODS: From 1992 to 1997, 91 patients were entered into a prospective study of LCR for cancer. Clinical, pathologic, and economic parameters of LCR were compared in a cohort of patients matched for age, tumor stage, and type of colectomy who underwent open colon resection (OCR) during the same time period. RESULTS: With a median follow-up of 26 months, there were no significant differences in survival rate for patients in the LCR, converted colon resection, and OCR groups. There were no port-site recurrences and the number of lymph nodes harvested was similar among the procedures. Hospital stay was significantly shorter if laparoscopic resection was successful. Total hospital costs were similar for LCR and OCR; however, the costs were significantly higher for converted colon resection. CONCLUSIONS: LCR is a sound oncologic procedure that can be performed with costs similar to OCR.

Adult↗
PubMed1998

Locally advanced rectal cancer: surgical complications after infusional chemotherapy and radiation therapy.

PURPOSE: To compare the surgical complication rate after further experience with infusional chemotherapy and radiation therapy for locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative radiation therapy (45 Gy in 25 fractions over 5 weeks) and concurrent continuous infusion of 5-fluorouracil (300 mg.m-2.d-1) were given to 117 patients with rectal cancer. Approximately 6 weeks after therapy, surgery was performed. RESULTS: The histopathologic cancer stages were Tis-2N0 in 30 patients (26%), T2N1 in six (5%), T3N0 in 24 (21%), T3N1 in 18 (15%), T4N0 in six (5%), and T4N1 in one (1%); a complete response to preoperative therapy was histopathologically confirmed in 32 patients. A decrease in cancer stage allowed a sphincter-saving procedure in 68 patients (58%) and abdominoperineal resection in 49 patients (42%). Only one patient developed fistula; nine patients, perioperative wound complications; and four patients, pelvic infection. In the authors' previously reported chemotherapy and radiation therapy results (same protocol), eight (22%) of 37 patients developed fistulas and five (14%) developed pelvic abscess; in the authors' previous experience with preoperative radiation therapy only (median total dose, 45 Gy; dose range, 40.0-59.4 Gy), results were similar. CONCLUSION: Surgical complications after chemotherapy and radiation therapy are statistically significantly (P < .05) reduced with further experience.

Actuarial Analysis↗
PubMed1997

Carcinoid tumors of the rectum: effect of size, histopathology, and surgical treatment on metastasis free survival.

BACKGROUND: The purpose of this study was to determine the clinical course, effects of specific tumor histopathologic characteristics, and extent of surgical treatment on the metastatic rate in patients with rectal carcinoids. METHODS: Medical records of 44 patients who presented with rectal carcinoids were retrospectively reviewed. Primary tumors were classified by size (< 1 cm, 1-2 cm, and > 2 cm), and tumor histopathologic features (atypical or typical). Extensive surgery was defined as abdominoperineal or low anterior resection of the rectum or laparotomy with intent of curative resection. RESULTS: Median follow-up for patients who presented without metastasis was 84 months. Thirteen of the 44 patients (30%) presented with metastatic disease. The 5-year metastasis free survival rates for those patients presenting without metastatic disease were 100% for patients with tumors < 1 cm (n = 16), 73% for those with tumors 1-2 cm (n = 8), and 25% for those with tumors > 2 cm (n = 4) (P = 0.04 comparing < 1 cm with 1-2 cm and P = 0.05 comparing 1-2 cm with > 2 cm); tumor size data were not available for 3 patients. The 5-year metastasis free survival rate for patients presenting without metastatic disease with typical histology (n = 20), regardless of size, was 100%, compared with 50% for patients with tumors with atypical histology (n = 11) (P = 0.001). Nine patients underwent extensive surgery for rectal carcinoid tumors but no survival benefit was demonstrated. CONCLUSIONS: Atypical histopathologic features and a tumor size > 1 cm are associated with aggressive behavior of rectal carcinoid tumors. Extensive surgery offers no survival advantage over local excision for patients with rectal carcinoid tumors.

Adult↗
PubMed1997

Pelvic exenteration for locally advanced rectal carcinoma: factors predicting improved survival.

BACKGROUND: The purpose of this retrospective review was to determine whether a number of clinicopathologic factors (age, gender, type of exenteration, tumor extent, adjuvant therapy, tumor DNA ploidy, and S-phase fraction) that could be determined before operation were useful in predicting survival in patients undergoing pelvic exenteration for rectal cancer. METHODS: Between 1983 and 1992, 40 patients (15 male and 25 female) at our institution underwent pelvic exenteration for rectal adenocarcinoma in which tumor-free pathologic margins were obtained. Twenty-nine patients presented with primary tumors; 11 had recurrent disease. A total exenteration was performed in 20 patients, posterior exenteration in 18 patients, and an anterior exenteration in 2 patients. RESULTS: By multivariate (Cox proportional hazards regression) analysis, age, preoperative chemoradiation therapy, and an S phase of 10% or greater were found to be significant predictors of survival. Age older than 55 years was associated with a relative risk for cancer-related death (RR) of 0.13 (p = 0.02), and chemoradiation had an RR of 0.05 (p = 0.01), indicating their beneficial effect. An S-phase fraction of 10% or greater had an RR of 16.97 (p = 0.03), indicating a poor survival. The clinicopathologic factors listed above were used to derive a prognostic index (PI). A PI of less than 1.37 was associated with a 5-year survival rate of 65% (low risk), whereas patients with a PI of 1.37 or greater had a 5-year survival rate of 20% (high risk) (p = 0.005). CONCLUSIONS: These results indicate that adjuvant chemoradiation may significantly improve survival in patients who require pelvic exenteration for resection of locally advanced rectal carcinoma. An S-phase fraction of 10% or greater is also predictive of a poor outcome. Use of these factors allowed the generation of a PI that identifies high- and low-risk patients. Consideration of the ability to deliver chemoradiation and the determinates of the tumor S-phase fraction in patients requiring pelvic exenteration for rectal cancer may be helpful in predicting outcome and planning therapy.

Adenocarcinoma↗
PubMed1997

p53 immunohistochemical staining predicts residual disease after chemoradiation in patients with high-risk rectal cancer.

This study was conducted to investigate the value of p53 immunohistochemical staining of pretreatment biopsy specimens in predicting the response of rectal cancer to chemoradiation. The study group comprised 42 patients with high-risk rectal cancer treated between July 1990 and July 1995 with a preoperative chemoradiation regimen of 45 Gy of external-beam irradiation and continuous-infusion 5-fluorouracil followed by surgical resection. p53 immunohistochemical staining was performed on pretreatment biopsy specimens. p53 immunohistochemical staining pattern and standard clinical and pathological parameters were correlated with extent of residual cancer in the surgical specimen. Twenty tumors were positive for p53 on immunohistochemical staining, 19 were negative, and 3 were focally positive. Thirteen patients experienced a complete response to chemoradiation. Aberrant p53 protein accumulation, as measured by immunohistochemical staining, correlated inversely with a complete pathological response to chemoradiation (P = 0.005; correlation coefficient = -0.43) and directly with an increased likelihood of residual cancer in the lymph nodes of surgical specimens (P = 0.02; correlation coefficient = 0.39). p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer.

Adult↗
PubMed1996

Cranial irradiation after surgical excision of brain metastases in melanoma patients.

BACKGROUND: Brain metastases account for 20-54% of reported deaths from melanoma. Duration and quality of survival depend on the extent of metastatic disease and response to treatment. Treatment goals are palliation of symptoms and prolongation of life. No studies have directly compared surgery alone and surgery with adjunctive cranial irradiation in patients with solitary brain metastases. METHODS: We evaluated postoperative adjunctive cranial irradiation in 34 patients with solitary brain metastases. RESULTS: Overall survival was significantly improved in the 22 patients who received adjunctive cranial irradiation versus that in the 12 patients who had surgery alone. Twenty-eight patients subsequently relapsed. Nine of 10 patients with surgery alone had brain recurrence as a component of failure. Six of 10 patients not receiving irradiation had brain recurrences as a component of relapse at multiple sites whereas only 1 of 18 patients receiving irradiation relapsed with the brain. CONCLUSIONS: Adjunctive cranial irradiation is justified for melanoma patients who undergo surgical therapy for solitary brain metastases. Survival in patients presenting with solitary brain metastases was improved by a reduction of relapse in the brain as a component of failure by combined surgery and irradiation.

Adult↗
PubMed1996

Association of gastric adenocarcinoma with the HLA class II gene DQB10301.

BACKGROUND & AIMS: The HLA class II gene DQB1*0301 has been linked to several cancers. This study was designed to determine if HLA-DQB1*0301 is present at altered frequency in patients with gastric, colorectal, or pancreatic adenocarcinoma. METHODS: Oligotyping for HLA-DQB1*0301 was performed for 159 Caucasian patients with 160 gastrointestinal adenocarcinomas (52 gastric, 62 colorectal, and 46 pancreatic adenocarcinomas) and compared with 260 Caucasian noncancer controls. Patients with gastric adenocarcinoma underwent extended HLA class II region oligotyping. Immunoglobulin G to Helicobacter pylori was detected by enzyme-linked immunosorbent assay. RESULTS: HLA-DQB1*0301 was more common in patients with gastric adenocarcinoma than controls (54% vs. 27%; bonferroni-corrected chi 2 P = 0.003; odds ratio, 3.2). HLA-DQB1*0301 was not associated with colorectal or pancreatic adenocarcinoma. No other HLA-DQB1 allele and no HLA-DQA1 or transporter associated with antigen processing 2 (TAP2) allele were present at altered frequency in patients with gastric adenocarcinoma. Serological evidence for H. pylori infection was less frequent in HLA-DQB1*0301-positive patients with gastric adenocarcinoma compared with HLA-DQB1*0301-negative patients (52% vs. 88%; Fisher's Exact Test; P = 0.007). CONCLUSIONS: HLA-DQB1*0301 is more common in caucasian patients with gastric adenocarcinoma than noncancer controls. The mechanism linking HLA-DQB1*0301 with gastric adenocarcinoma is not likely through increased susceptibility to H. pylori infection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Preoperative infusional chemoradiation, selective intraoperative radiation, and resection for locally advanced pelvic recurrence of colorectal adenocarcinoma.

OBJECTIVE: The results of preoperative infusional chemoradiation, resection, and selective intraoperative radiation (IORT) boost in 43 previously nonirradiated patients with locally advanced pelvic recurrence of colorectal adenocarcinoma are described. SUMMARY BACKGROUND DATA: After surgery alone 10% to 30% of patients with carcinoma of the distal colon and rectum will develop isolated pelvic recurrence. In most cases, the disease is locally advanced and not amenable to curative resection. Preoperative infusional chemoradiation has been shown to increase resectability and decrease local recurrence in primary locally advanced colorectal cancer. Based on this experience, we initiated a multimodality treatment protocol to treat patients with pelvic recurrence of colorectal adenocarcinoma. METHODS: Forty-three consecutive patients with histologically proven pelvic recurrence of colorectal adenocarcinoma were enrolled on a multimodality treatment protocol. The treatment plan consisted of 5 weeks of concurrent pelvic external beam radiotherapy (45 Gy) with continuous intravenous infusion of 5-fluorouracil and/or cisplatin. This was followed by surgery that included IORT boost (10-20 Gy) for 21 patients and brachytherapy for 4 patients. RESULTS: Forty patients (93%) underwent operation and 33 (77%) underwent resection with curative intent. There were 29 (88%) margin-negative resections. Fifteen patients (48%) underwent sphincter-preserving operations. There were no treatment-related deaths. Twenty-two patients experience perioperative complications. Median follow-up for the 43 patients was 26 months. The local recurrence rate was 36%. Median survival for the patients who underwent resection was 34 months, and actuarial 5-year disease-free and overall survival were 37% and 58%, respectively. CONCLUSIONS: Tumor cytoreduction by preoperative chemoradiation can increase resectability and enable sphincter-preserving surgery in patients with locally advanced pelvic recurrence of colorectal cancer.

Adenocarcinoma↗
PubMed1996

Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation.

Wild-type p53 gene transfer into the SW620 colorectal carcinoma cell line was performed using the replication-defective adenovirus Ad5/CMV/p53 to evaluate the effect of wild-type p53 expression on radiation sensitivity. The results indicated that infection with Ad5/CMV/p53 sensitized the cells. The survival at 2 Gy was reduced from 55 to 23%. Flow cytometric analysis of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-labeled cells and in situ TUNEL staining of xenograft tumors demonstrated an increase in labeled cells with combination treatment, indicating increased apoptosis in cells treated with Ad5/CMV/p53 before irradiation. A significant enhancement of tumor growth suppression by this combination strategy was observed in a s. c. tumor animal model compared to p53 gene therapy alone. The delay in regrowth to control tumor size of 1000 mm3 was 2 days for 5 Gy, 15 days for Ad5/CMV/p53, and 37 days for Ad5/CMV/p53 + 5 Gy, indicating synergistic interactions. These data indicate that the delivery of wild-type p53 to cells with p53 mutations increases their radiation sensitivity, and this may be accomplished by adenoviral-mediated gene therapy.

Adenoviridae↗