Biomedical subjects

F C Eilber

Publications and source records attributed to F C Eilber.

8 recordsLinked to original sources

PubMed2001

Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas.

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with > or = 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with > or = 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with > or = 95% pathologic necrosis. The percentage of patients who achieved > or /= 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (> or = 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.

Adolescent↗

PubMed2000

Adenovirus-interleukin-12-mediated tumor regression in a murine hepatocellular carcinoma model is not dependent on CD1-restricted natural killer T cells.

The cytokine interleukin-12 (IL-12) has shown potent antitumor activity in several tumor models. Recently, natural killer (NK) T cells have been proposed to mediate the antitumor effects of IL-12. In this study, the antitumor response of IL-12 was investigated in a gene therapeutic model against s.c. growing mouse hepatocellular carcinomas using an adenoviral vector expressing murine IL-12 (AdVmIL-12). An adenoviral-based system was chosen because of the ability of adenoviruses to transduce dividing and nondividing cells and because of their high transduction efficiencies. Our goals were to examine the efficacy of AdVmIL-12 in a hepatocellular carcinoma model and to investigate the mechanism of the AdVmIL-12-mediated antitumor response with specific interest in the role of NK T cells. Our studies demonstrate that intratumoral AdVmIL-12-mediated regression of s.c. hepatocellular tumors is associated with rapid antitumor responses. AdVmIL-12 treatment was associated with an immune cellular infiltrate consisting of CD4 and CD8 T lymphocytes, macrophages, NK cells, and NK T cells. Antibody ablation of CD4 and CD8 T cells and use of NK cell-defective beige mice failed to abrogate the response to AdVmIL-12. Studies in T-cell- and B-cell-deficient severe combined immunodeficient and recombinase activating gene-2-deficient mice and T-cell-, B-cell-, and NK cell-defective severe combined immunodeficient/beige mice also failed to abrogate this response. AdVmIL-12 retained potent antitumor activity in mice with specific genetic defects in immune cellular cytotoxicity (perforin knockout mice) and costimulation (CD28 knockout mice). Use of mice with specific NK T cell deficiencies, Valpha14 T-cell receptor and CD1 knockout mice, also failed to abrogate the response to AdVmIL-12. Histological and immunohistochemical studies of AdVmIL-12-treated tumors showed extensive inhibition of neovascularization and a marked decrease in factor VIII-stained endothelial cells. Our studies indicate that the antitumor response of AdVmIL-12 is independent of direct cytotoxic cellular immunity (specifically, the function of NK T cells) and suggest that the initial mechanisms of AdVmIL-12-mediated tumor regression involve inhibition of angiogenesis.

Adenoviridae↗

PubMed2000

Retroperitoneal sarcomas.

The approach to the management of retroperitoneal tumors begins with a complete history and physical examination. Imaging of the abdomen and pelvis by computed tomography (CT) provides both an imaging modality and a method by which to obtain tissue for diagnosis. Because a histologic diagnosis is essential in treatment planning, adequate tissue can usually be obtained by a CT-guided core biopsy. If the diagnosis is sarcoma, additional tests necessary for staging include plain chest radiography and evaluation of the liver by either CT scan or magnetic resonance imaging (MRI). The treatment options for primary retroperitoneal sarcomas include chemotherapy, radiation therapy, surgery, or a combination of these modalities; therefore, a multidisciplinary group best manages treatment planning. Primary radiation therapy for cure is seldom effective for retroperitoneal sarcomas but can provide palliation in select cases. Systemic chemotherapy for chemosensitive lesions, such as poorly differentiated liposarcoma, malignant fibrous histiocytoma (MFH), synovial cell sarcoma, and primitive neuroectodermal tumors (PNET), can be useful when used in a neoadjuvant manner. Consequently, surgical resection continues to be the mainstay of treatment for retroperitoneal sarcomas and requires en bloc resection of the primary tumor. Frequently this includes adjacent organs such as colon, small bowel, kidney, adrenal, and pancreas. Postoperative adjuvant therapy with chemotherapy or radiation has not been proven to be of any additional benefit. Overall treatment results are predominantly influenced by tumor stage, grade, size, and margins of surgical resection. Follow-up CT scans at 6-month intervals and surgical resection of recurrences can be valuable.

Antineoplastic Agents↗

PubMed2000

Recurrent gastrointestinal stromal sarcomas.

Gastrointestinal stromal sarcomas, formerly categorized as leiomyosarcomas of gastrointestinal origin, have a common pattern of intraperitoneal dissemination. Despite surgical resection with or without adjuvant systemic chemotherapy the vast majority of these patients succumb to intraperitoneal sarcomatosis and/or hepatic metastases. In an attempt to improve upon the morbidity and mortality associated with this disease we and several other centers have begun treating these patients with intraperitoneal chemotherapy. We have found that aggressive surgical resection with postoperative intraperitoneal chemotherapy has significantly lowered the peritoneal recurrence rate in patients with recurrent gastrointestinal stromal sarcomas as compared to those who have undergone surgical resection alone. However, this treatment approach has proven to be ineffective in preventing hepatic metastases, and thus has had little effect upon overall survival. With the treatment of primary rather than recurrent disease we hope to interrupt the disease process at an earlier stage further decreasing peritoneal recurrences and potentially improving survival.

Antineoplastic Agents↗

PubMed1999

p53 selective and nonselective replication of an E1B-deleted adenovirus in hepatocellular carcinoma.

An E1B gene-attenuated adenovirus (dl1520) has been proposed to have a selective cytolytic activity in cancer cells with a mutation or deletion in the p53 tumor suppressor gene (p53-null), a defect present in almost half of human hepatocellular carcinomas (HCCs). In this study, the in vitro and in vivo antitumor activity of dl1520 was investigated focusing on two human HCC cell lines, a p53-wild type (p53-wt) cell line and a p53-null cell line. dl1520 was tested for in vitro cytopathic effects and viral replication in the human HCC cell lines Hep3B (p53-null) and HepG2 (p53-wt). The in vivo antitumor effects of dl1520 were investigated in tumors grown s.c. in a severe combined immunodeficient mouse model. In addition, the combination of dl1520 infection with systemic chemotherapy was assessed in these tumor xenografts. At low multiplicities of infection, dl1520 had an apparent p53-dependent in vitro viral growth in HCC cell lines. At higher multiplicities of infection, dl1520 viral replication was independent of the p53 status of the target cells. In vivo, dl1520 significantly retarded the growth of the p53-null Hep3B xenografts, an effect augmented by the addition of cisplatin. However, complete tumor regressions were rare, and most tumors eventually grew progressively. dl1520 had no effect on the in vivo growth of the p53-wt HepG2 cells, with or without cisplatin treatment. The E1B-deleted adenoviral vector dl1520 has an apparent p53-dependent effect in HCC cell lines. However, this effect is lost at higher viral doses and only induces partial tumor regressions without tumor cures in a human HCC xenograft model.

Adenoviridae↗

PubMed1999

Alpha-fetoprotein-specific genetic immunotherapy for hepatocellular carcinoma.

The majority of human hepatocellular carcinomas overexpress alpha-fetoprotein (AFP). Two genetic immunization strategies were used to determine whether AFP could serve as a target for T-cell immune responses. Dendritic cells engineered to express AFP produced potent T-cell responses in mice, as evidenced by the generation of AFP-specific CTLs, cytokine-producing T cells, and protective immunity. AFP plasmid-based immunization generated less potent responses. These novel observations demonstrate that this oncofetal antigen can serve as an effective tumor rejection antigen. This provides a rational, gene therapy-based strategy for this disease, which is responsible for the largest number of cancer-related deaths worldwide.

Animals↗

PubMed1999

Large, deep, high-grade extremity sarcomas: treating tumors of the flexor fossae.

Limb salvage is now possible for the majority of patients with extremity sarcomas. Although overall prognosis is primarily based on tumor size and histologic grade, complete surgical excision and local control is essential for cure. There are, however, certain anatomic locations such as the flexor fossae in which a complete surgical margin is difficult to attain, and surgery without adjuvant therapy has a high local failure and amputation rate. We have found that preoperative adjuvant therapy consisting of chemotherapy and radiation followed by surgical excision with tumor-free margins has been successful in treating flexor fossa sarcomas with high limb salvage (96%), local control (89%) and overall survival rates (70%). These results are comparable to patients with similar large, high-grade extremity tumors in other compartmental locations.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Surgical resection and intraperitoneal chemotherapy for recurrent abdominal sarcomas.

BACKGROUND: Recurrent abdominal sarcomas have an extremely high rate of recurrence and poor overall survival. A prospective study was initiated to assess the feasibility, toxicity, and benefit of surgical resection and intraperitoneal chemotherapy for improving local control of disease and overall survival. METHODS: Fifty-four patients underwent surgical excision of all gross disease and postoperative intraperitoneal chemotherapy with mitoxantrone. Thirty-five patients had peritoneal disease only (stage II), and 19 patients had peritoneal disease with hepatic metastases (stage III). RESULTS: Nine (17%) patients remain free of disease with a mean follow-up of 37 months. The remaining 45 patients (83%) have had recurrence, with a mean interval to recurrence of 11 months. Stage (P = .001) and grade (P = .005) were the only two variables found to significantly affect recurrence. There was an overall peritoneal recurrence rate of 48% and an overall hepatic failure rate of 69%. Nineteen (35%) of the patients are alive, with a mean follow-up of 46 months. The overall 5-year survival was 31%. The 5-year survival for stage II patients was 46%; for stage III patients, it was only 5%. Stage (P = .001) and grade (P = .056) were the only two variables found to significantly affect survival. There were no treatment-related deaths, and only 5 patients (9%) developed local complications. CONCLUSIONS: Aggressive surgical resection and intraperitoneal chemotherapy for recurrent abdominal sarcomas is a feasible treatment approach with minimal toxicity. Although this treatment had little effect on the hepatic spread of this disease and thus overall survival, it appears to have significantly lowered the rate of peritoneal recurrence and may provide a survival benefit for patients with disease limited to the peritoneum.

Abdominal Neoplasms↗