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J Glaspy

Publications and source records attributed to J Glaspy.

At least 37 records · Page 2Linked to original sources
PubMed1997

Transduction of murine and human tumors using recombinant adenovirus vectors.

BACKGROUND: Most cytokine-based cancer gene therapy clinical trials have used labor-intensive, retrovirus-mediated strategies resulting in unpredictable gene expression. Recombinant AdV vectors were evaluated for easier, more reproducible gene transfer into 12 human melanoma, 2 murine fibrosarcomas, and 8 other tumor cell lines. METHODS: AdV vectors contained a reporter (Escherichia coli beta-galactosidase or firefly luciferase) or cytokine gene (human interleukin-2 [IL-2] or IL-7). Transduction efficiencies and expression levels were assessed by histochemical staining, flow cytometry, polymerase chain reaction, fluorometry, and enzyme-linked immunosorbent assay. Tumorigenicity was determined by subcutaneous injection of cells into syngeneic mice. RESULTS: All cell lines studied were transduced with AdV. Most cell lines exhibited 100% transduction efficiencies (by flow cytometry) at multiplicities of infection (MOI) epsilon 10. Gene expression correlated linearly with MOI, but a cytopathic effect was observed at MOI > 100 with all vectors. Nanogram gene expression levels were routinely achieved. Irradiation (30 Gy) minimally affected expression levels. Tumorigenicity of AdV-IL-2-transduced fibrosarcoma cells in mice was inversely related to IL-2 production. A majority of mice that rejected their tumor challenge were immune to tumor rechallenge. CONCLUSIONS: E1-deleted AdV vectors may prove useful in generating tumor vaccines ex vivo with high, transient cytokine expression levels.

Adenoviridae↗
PubMed1997

Pulmonary toxicity of high-dose chemotherapy for breast cancer: a non-invasive approach to diagnosis and treatment.

Drug-induced pulmonary toxicity is one of the most frequent non-hematologic toxicities in breast cancer patients receiving high-dose chemotherapy with cyclophosphamide, cisplatin and BCNU (CY/CDDP/BCNU). A non-invasive clinical scoring system was utilized in an attempt to diagnose and treat early lung toxicity in 64 consecutive breast cancer patients undergoing CY/CDDP/BCNU supported by peripheral blood progenitor cells. Following hospital discharge, patients who developed symptoms suggestive of lung toxicity were evaluated with physical examination, DLCO, 2-min walking oximetry and a chest radiograph. Clinically weighted scores were assigned as follows: crackles on lung exam, 2; decrease in corrected DLCO by > 10% from baseline, 3; decrease in O2 saturation by > or = 4% with a 2-min walk, 3; and interstitial infiltrates on chest radiograph, 3. Patients with scores > or = 6 were treated with prednisone (60 mg p.o. twice a day followed by a 2-month taper). Treatment was instituted in 37 patients (58%) a median of 56 days after high-dose chemotherapy. Steroid therapy was associated with rapid clinical improvement in most patients. No fatal complications or chronic pulmonary fibrosis was seen. This non-invasive clinical scoring system can be utilized as a model for the early diagnosis of lung toxicity. Further investigation is warranted for the development of preventative measures against this syndrome.

Adult↗
PubMed1997

Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. Procrit Study Group.

PURPOSE: To study the impact of Procrit (epoetin alfa; Amgen Inc, Thousand Oaks, CA) on quality of life, transfusion requirements, and hemoglobin in anemic cancer patients receiving chemotherapy. PATIENTS AND METHODS: More than 500 community-based oncologists enrolled 2,342 patients with malignancies undergoing cytotoxic chemotherapy in an open-label study. Patients were treated with epoetin alfa 150 U/kg three times weekly, which could be doubled if the therapuetic response was judged inadequate. Total treatment was up to 4 months. RESULTS: Of the 2,342 patients enrolled, data were available for 2,030 patients. Of the 2,030, 1,047 patients completed all 4 months of epoetin alfa therapy. Epoetin alfa was associated with significant increases in mean self-rated scores for energy level, activity level, and overall quality of life; these improvements correlated with the magnitude of the hemoglobin increase and were independent of tumor response. In addition, epoetin alfa was associated with a significant increase in mean hemoglobin and with a significant decrease in the proportion of patients requiring transfusions (baseline to final value, P < .001). Epoetin alfa was well tolerated. CONCLUSION: Epoetin alfa is effective in improving the functional status and quality of life in anemic cancer patients receiving chemotherapy, as well as increasing hemoglobin level and decreasing transfusion requirements. Improvement in functional status can be attributed to an increase in hemoglobin level, demonstrating that quality of life in this group of patients can be improved by aggressively treating anemia. Further studies will be required to define the optimal doses and schedules for epoetin alfa.

Anemia↗
PubMed1997

Whole-body FDG-PET imaging for staging of Hodgkin's disease and lymphoma.

UNLABELLED: Accurate staging of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) is important for treatment management. In this study, the utility of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) whole-body PET was evaluated as an imaging modality for initial staging or restaging of 7 HD and 11 NHL patients. METHODS: Whole-body PET-based staging results were compared to the patient's clinical stage based on conventional staging studies, which included combinations of CT of the chest, abdomen and pelvis, MRI scans, gallium scans, lymphangiograms, staging laparatomies and bone scans. RESULTS: Accurate staging was performed in 17 of 18 patients using a whole-body PET-based staging algorithm compared to the conventional staging algorithm in 15 of 18 patients. In 5 of 18 patients, whole-body PET-based staging showed additional lesions not detected by conventional staging modalities, whereas conventional staging demonstrated additional lesions in 4 of 18 patients not detected by whole-body PET. The total cost of conventional staging was $66,292 for 16 CT chest scans, 16 CT abdominal/pelvis scans, three limited MRI scans, four bone scans, five gallium scans, two laparotomies and one lymphangiogram. In contrast, scans cost $36,250 for 18 whole-body PET studies and additional selected correlative studies: one plain film radiograph, one limited CT, one bone marrow scan, one upper GI and one endoscopy. CONCLUSION: A whole-body FDG-PET-based staging algorithm may be an accurate and cost-effective method for staging or restaging HD and NHL.

Adolescent↗
PubMed1997

The impact of epoetin alfa on quality of life during cancer chemotherapy: a fresh look at an old problem.

Untreated anemia is common in cancer patients. Previous studies have demonstrated that both the existence of cancer and treatment with chemotherapy can suppress the normal endogenous erythropoietic response to anemia, making some cancer patients transfusion cadidates. In placebo-controlled phase III studies, administration of recombinant human erythropoietin (epoetin alfa) increased hemoglobin (Hb) levels and decreased transfusion requirements in patients undergoing cancer chemotherapy. In these studies, an increase in self-perceived energy level, functional status, and overall quality of life (QOL) was noted in the subset of patients in whom hematocrit levels increased by > or = 6%. To examine more closely the relationship between epoetin alfa therapy and QOL issues in patients undergoing chemotherapy, we conducted an open-label phase IV study involving 2,030 patients treated at 570 community cancer centers in the United States. Patients initially received epoetin alfa 150 U/kg subcutaneously (s.c.) three times per week for 4 months; if response was judged inadequate, the dosage was increased after 8 weeks to 300 U/kg s.c. three times per week. Hb levels and transfusion requirements were monitored monthly. Before and after the study, each patient completed a linear analog self-assessment scale designed to measure energy level, daily activity, and overall QOL. During epoetin alfa therapy, there was a progressive and significant increase (P < .001) in Hb concentrations. Significantly fewer (P < .001) patients were transfused and fewer transfusions were administered per patient per month after the first month of epoetin alfa therapy. Fifty-eight percent of the patients who required a transfusion during the first month of epoetin alfa therapy did not require a transfusion during the subsequent 3 months of the study. The entire patient population demonstrated a significant increase in mean scores for energy level, daily activity, and overall QOL. The magnitude of the increase in these scores correlated with the magnitude of the increase in Hb concentration. Statistically significant improvement in energy scores, daily activity, and overall QOL (P < .05) were observed, regardless of tumor response. These observations require confirmation on placebo-controlled trials, but the implications for oncology practice are important. They suggest that in cancer patients undergoing chemotherapy, the tradition of leaving anemia untreated may compromise patients' ability to function and their QOL.

Administration, Cutaneous↗
PubMed1996

In vivo trafficking of adoptively transferred interleukin-2 expanded tumor-infiltrating lymphocytes and peripheral blood lymphocytes. Results of a double gene marking trial.

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and IL-2 appears to produce dramatic regressions in patients with metastatic melanoma and renal cancer. However, the in vivo mechanism of TIL function is not known. We conducted an UCLA Human Subject Protection Committee, Recombinant DNA Advisory Committee, and FDA-approved clinical trial using genetically-marked TIL to test the hypothesis that these cells have unique, tumor-specific in vivo trafficking patterns. TIL and PBL (as a control effector cell population) were isolated and expanded in parallel in vitro in IL-2-containing medium for 4-6 wk. During the expansion, TIL and PBL were separately transduced with the amphotropic retroviral vectors LNL6 and G1Na. Transduced TIL and PBL were coinfused into patients and their respective numbers measured in tumor, peripheral blood, and normal tissues; integrated provirus could be quantitated and distinguished by DNA PCR. Nine patients were treated (six melanoma, three renal) and received between 4.5 x 10(8) and 1.24 x 10(10) total cells. Both "marked" TIL and PBL could be detected circulating in the peripheral blood, in some patients for up to 99 d after infusion. Marked TIL and/or PBL could be detected in tumor biopsies in six of nine patients as early as day 6 and as late as day 99 after infusion. No convincing pattern of preferential trafficking of TIL vs. PBL to tumor was noted. Moreover, concurrent biopsies of muscle, fat, and skin demonstrated the presence of TIL/PBL in comparable or greater numbers than in tumor in five patients. The results of this double gene marking trial provide interesting insights into the life span and trafficking of adoptively transferred lymphocytes, but do not support the hypothesis that TIL specifically traffic to tumor deposits.

Adult↗
PubMed1996

Biology and clinical potential of stem-cell factor.

Stem-cell factor (SCF) is a hematopoietic growth factor that acts on both primitive and mature progenitor cells. Preclinical studies have shown that recombinant SCF can protect against lethal irradiation, elicit multilineage hematopoietic responses and increases in bone marrow cellularity, and increase the number of circulating peripheral blood progenitor cells (PBPCs) in a dose-dependent manner. Both preclinical and early clinical studies using recombinant methionyl human SCF plus recombinant methionyl human granulocyte colony-stimulating factor (Filgrastim) have demonstrated increased PBPC mobilization as compared with the use of either factor alone. These data suggest a clinical role for the combination.

Animals↗
PubMed1996

Opportunistic infections in oncologic patients.

Oncologic patients constitute a population whose susceptibility to infections is conditioned by a broad variety of factors. Advances in antineoplastic treatments have resulted in significant prevalence of severe immunosuppression among such patients. Although impairment of more than one distinct effector limb of host defenses occurs in each patient, infections can usually be attributed to a particular deficiency. Major risk factors for infections include granulocytopenia and defects of cell-mediated immunity or of humoral immunity. In the extreme situation of allogeneic bone marrow transplantation, the multitude and the timing of infections can be explained by significant dysfunction of all types of specific immune deficiencies. Treatment of bacterial infections has become more effective with the advent of broad-spectrum antibiotics; however, the dreadful emergence of polyresistant strains may be a serious problem in the near future. Prevention strategies have reduced the risk posed by important pathogens such as CMV or PCP, whereas we still lack reliable treatment against invasive mycoses. The advent of growth factors is a useful adjunct in our armamentarium; in addition to shortening the neutropenic periods after chemotherapy, they may restore qualitative defects of phagocytes. Their exact usefulness and role in managing infections remains to be defined.

Humans↗
PubMed1996

Clinical applications of stem cell factor.

Stem cell factor is an early-acting hematopoietic cytokine that probably functions constitutively to support the proliferation and survival of pluripotent progenitor cells and to increase their receptivity to lineage commitment and differentiation in response to lineage-specific cytokines. Stem cell factor also can induce proliferation and activation of mast cells. In vitro and in vivo, stem cell factor has demonstrated synergy with other hematopoietic cytokines. In clinical trials, stem cell factor has been shown to mobilize peripheral blood progenitor cells and when combined with G-CSF to increase the number of peripheral blood progenitor cells harvested. When used in lower doses and with antihistamine and beta-agonist premedication, stem cell factor therapy has been well tolerated. Phase III trials are in progress to document the efficacy of stem cell factor in peripheral blood progenitor cell harvesting protocols. Future clinical applications may include the treatment of adult and pediatric marrow failure states, the ex vivo expansion and manipulation of hematopoietic progenitor cells, and the treatment of disorders of skin pigmentation.

Adult↗
PubMed1994

Positron emission tomography diagnosis of pulmonary metastases in osteogenic sarcoma.

Positron emission tomography (PET) is an imaging technique that can produce high-quality tomographic images reflective of the metabolic characteristics of imaged tissue. Among the many positron-emitting tracers utilized in conjunction with PET is [18F]fluoride ion; it is actively taken up in bone in proportion to bone metabolic activity, analogous to standard nuclear medicine bone scanning agents such as technetium methylenediphosphonate ([99mTc]MDP). Whole-body imaging with PET and [18F]fluoride ion generates tomographic images that are useful in mapping patterns of bone metabolism, as well as identifying extraosseous site of bone formation or calcification. We report the case of a patient with polyostotic fibrous dysplasia, metastatic osteogenic sarcoma, and a breast mass, who presented with pulmonary nodules, in whom [18F] fluoride ion/PET imaging was useful in confirming the nature of the pulmonary nodules.

Adult↗
PubMed1993

An animal model for in vivo evaluation of tumor glycolytic rates with positron emission tomography.

We developed a method for evaluating tumor glycolytic rates in vivo with nude mice injected with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) and a dedicated animal positron emission tomography (PET) scanner. Animals were injected with NR-6 mouse fibroblast tumor cell lines. When tumors achieved a large enough size to be macroscopically visible, quantitative measurements of FDG uptake in vivo were obtained, using both standard nonlinear regression with the FDG tracer kinetic model to generate estimates of model parameters, including KNLR, the rate constant for net phosphorylation of FDG. Additionally, we determined the values of KPAT, the rate constant for net phosphorylation of FDG measured with a non-iterative graphical method. Estimates of K were highly correlated (r = 0.95) with both methods, and parametric images of KPAT demonstrate both the tumor location and size, but are also scaled in units of phosphorylation of FDG. The method is suitable for serial studies of tumor glucose metabolism during and after therapeutic interventions, such as chemotherapeutic trials.

Animals↗
PubMed1993

Whole-body positron emission tomography with (fluorine-18)-2-deoxyglucose can detect metastatic carcinoma of the fallopian tube.

Distant sites of metastatic fallopian tube carcinoma, including humerus, umbilicus, and groin, were clearly imaged with FDG-PET; the surgical-pathologic correlations are presented. In disorders such as ovarian or fallopian tube cancer, where a reliable means of diagnosing persistent or recurrent disease remains elusive, PET scanning offers another approach to this problem. Based on the increased rate of glucose metabolism in tumors, this modality focuses on the biochemical differences between malignant tissues and their normal counterparts in order to demonstrate positive findings on imaging. Potential uses of PET scanning in gynecologic oncology are presented.

Adenocarcinoma, Papillary↗
PubMed1993

Whole-body positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose can detect recurrent ovarian carcinoma.

The existing means of detecting recurrent ovarian carcinoma are notoriously poor. Positron emission tomography (PET) is a form of computer-assisted imaging which produces images reflective of the biochemistry of the tissues rather than their physical characteristics. PET imaging with the positron emitting glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) exploits the accelerated rate of glycolysis characteristic of malignant tissue to image tumors. To begin to study PET's ability to diagnose recurrent ovarian cancer, whole-body PET FDG scanning was performed on 13 patients prior to planned surgical exploration. Seven patients were suspected of having recurrence based upon clinical findings, and 6 patients were clinically free of disease. In all 6 of the patients with suspected recurrence who subsequently underwent surgery, PET images demonstrated increased FDG uptake in a distribution that correlated with surgical-pathologic findings. Both intraperitoneal and extraperitoneal lesions were detected by PET. All 6 patients judged clinically free of disease had negative PET scans, but in 5 of these microscopic foci of residual tumor were found at surgery. Although PET FDG cannot replace surgery in the detection of microscopic recurrence, it can accurately detect tumors greater than 1.0 cm in diameter.

Adult↗
PubMed1992

The role of positron emission tomography in oncology and other whole-body applications.

Imaging and quantifying biochemical and physiological processes with PET clearly has major potential significance for all organ systems and many disease states. Although the full utility and potential of emerging new applications of PET in organs other than the heart and brain must be demonstrated in basic and clinical research studies, the rapidly accumulating aggregate experience in oncology in particular, and in other organ systems and disease states as well, indicates that PET is now truly becoming a modality of both clinical and investigative use for the body as a whole as well as for specific organ systems. Whole-body PET FDG imaging (Fig 9) illustrates the potential of biochemical imaging to map the distribution of cancer throughout the body. With the growing list of radiopharmaceutical and quantitative techniques applicable to cancer studies with PET, this field will continue to realize significant growth.

Humans↗