PubMed Health⌕ Search

Biomedical subjects

E Galanis

Publications and source records attributed to E Galanis.

34 records · Page 2Linked to original sources
PubMed1999

Immunotherapy of advanced malignancy by direct gene transfer of an interleukin-2 DNA/DMRIE/DOPE lipid complex: phase I/II experience.

PURPOSE: We have completed a phase I study, followed by three phase I/II studies, in patients with metastatic melanoma, renal cell carcinoma (RCC), and sarcoma in order to evaluate the safety, toxicity, and antitumor activity of Leuvectin (Vical Inc, San Diego, CA), a gene transfer product containing a plasmid encoding human interleukin (IL)-2 formulated with the cationic lipid 1, 2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl-phosphatidyl-ethanolamine (DMRIE/DOPE) and administered intratumorally. PATIENTS AND METHODS: Twenty-four patients were treated in the phase I study. Leuvectin doses were 10 microg, 30 microg, or 300 microg weekly for 6 weeks. In three subsequent phase I/II studies, a total of 52 patients (18 with melanoma, 17 with RCC, and 17 with sarcoma) were treated with further escalating doses of Leuvectin: 300 microg twice a week for 3 weeks, 750 microg weekly for 6 weeks, and 1,500 microg weekly for 6 weeks. RESULTS: There were no drug-related grade 4 toxicities and only one grade 3 toxicity, but the majority of patients experienced mild constitutional symptoms after treatment. In the phase I/II studies, 45 patients were assessable for response (14 with RCC, 16 with melanoma, and 15 with sarcoma). Two patients with RCC and one with melanoma have achieved partial responses lasting from 16 to 19 months and continuing. In addition, two RCC, three melanoma, and six sarcoma patients had stable disease lasting from 3 to 18 months and continuing. The plasmid was detected by polymerase chain reaction assay in the posttreatment samples of 29 of 46 evaluated patients. Immunohistochemistry studies on serial biopsy specimens showed increased IL-2 expression and CD8(+) infiltration after treatment in the tumor samples of several patients (12 and 16, respectively). CONCLUSION: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.

Adult↗
PubMed1999

Tumor suppressor gene alterations in malignant gliomas: histopathological associations and prognostic evaluation.

We have examined a series of 135 gliomas for alterations of the p53, CDKN2A (p16) and PTEN tumor suppressor genes (TSGs) in order to evaluate the incidence of their inactivation as a function of tumor malignancy and cellular differentiation, and to examine potential associations with patient outcome. The composition of this series, classified using WHO criteria, is as follows: 27 grade 2 tumors (11 astrocytomas, 12 oligoastrocytomas, 4 oligodendrogliomas), 42 grade 3 tumors (22 astrocytomas, 16 oligoastrocytomas, 4 oligodendrogliomas), and 66 grade 4 tumors (63 astrocytomas and 3 oligoastrocytomas). Similar frequencies of p53 mutation were observed among grade 2 (37.0%), and grade 3 tumors (38.1%), as well as between astrocytomas and mixed tumors. CDKN2A and PTEN mutations were clearly associated with increasing tumor malignancy (occurring in 0% of grade 2 tumors, 14.3% and 4.8% respectively of grade 3 tumors, and 27.3% and 30.3% respectively of grade 4 tumors) and were observed at substantially higher rates among astrocytomas. For the tumor suppressor genes examined, there was no relationship between the occurrence of any two TSG inactivation events. With regard to outcome, the p53 genetic status showed no significant relationship with patient survival. The CDKN2 and PTEN alterations were negative prognostic indicators of survival when evaluated in all 135 gliomas, but failed to predict outcome when evaluated in either of the high grade (3 or 4) tumor groups.

Adolescent↗
PubMed1998

Management of recurrent meningeal hemangiopericytoma.

BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high propensity for recurrence. The purpose of this study was to analyze the efficacy of different treatment options in patients with recurrent disease. METHODS: The records of all patients with recurrent meningeal hemangiopericytoma treated at the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four consecutive patients were studied. The mainstay of treatment was brain surgery in 21 patients (62%); the median time to recurrence from surgery was 12 months. Ten patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all with lesion size < 25 mm) achieved a complete response, which persisted at a median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a median duration of 12 months, whereas 3 lesions (15%) remained stable. Two patients with inoperable CNS lesions received external beam radiation therapy and both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received radiation therapy for metastatic disease. Of these, seven patients remained stable with good symptomatic relief, and two patients experienced tumor progression. Chemotherapy with doxorubicin-containing regimens was administered in 7 patients (21%); there was only 1 PR that lasted 8 months. The median survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is important for the successful treatment of patients with recurrent meningeal hemangiopericytoma. Radiosurgery plays a definite role in the treatment of smaller recurrent CNS lesions. Radiation therapy is helpful in the management of inoperable tumors. More effective chemotherapeutic agents are needed.

Adult↗
PubMed1998

Phase II trial of nitrogen mustard, vincristine, and procarbazine in patients with recurrent glioma: North Central Cancer Treatment Group results.

PURPOSE: Previous investigators have reported responses in 52% of patients treated with mechlorethamine (nitrogen mustard), vincristine, and procarbazine (MOP) for recurrent glioma. To confirm these promising results, we conducted a phase II prospective study. PATIENTS AND METHODS: Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen. Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2, respectively, intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8, and procarbazine 100 mg/m2 orally on days 1 to 14. Cycles were repeated every 28 days. RESULTS: Of 61 patients assessable for response, eight responded (13%), with one complete response (CR). Responses were as follows: low-grade gliomas, 19%; anaplastic astrocytomas, 11%; anaplastic oligodendrogliomas or oligoastrocytomas, 25%; and glioblastomas, 4.3%. The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23% and platelet nadirs less than 25,000/microL in 13% of patients. Two patients died of infection in the setting of neutropenia. Nonhematologic toxicity included neurosensory changes in 21% of patients (severe in 3%) and severe dermatologic reactions in 8%. In multivariate analysis, Eastern Cooperative Oncology group (ECOG) performance status (PS) was the best predictor for response to chemotherapy (P=.01) and time to progression (P=.008), while PS and grade were the most important predictors of survival (P=.002 and .05, respectively). CONCLUSION: This study did not confirm the high response rate previously reported in recurrent gliomas. Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low-grade gliomas had the highest response rates (25% and 19%, respectively). In multivariate analysis, ECOG PS was the best predictor of response, while PS and tumor grade were the most important predictors of survival.

Adult↗
PubMed1998

Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results.

OBJECT: Gliosarcoma, a rare malignancy of the central nervous system, consists of gliomatous and sarcomatous elements. There are conflicting reports regarding its aggressiveness and cell line of origin compared with those of glioblastoma multiforme (GBM). The goal of this study was to compare clinicopathological features such as disease-free survival time and actual survival time in patients with gliosarcoma with a matched group of patients with GBM as well as with the entire group of patients with GBM. METHODS: The authors report on 18 cases of gliosarcoma derived from a series of 748 Grade 4 astrocytoma cases that were part of four consecutive randomized Phase III trials conducted between 1979 and 1996. In this series the gliosarcoma group represented only 2.4% of all GBMs and included 11 men and seven women with a median age of 61.5 years (range 31-81 years). The median tumor size was 5 cm (range 2-8 cm). The locations, all supratentorial, included temporal in 44%, parietal in 28%, frontal in 17%, and occipital in 11%. The 18 patients with gliosarcomas, all Grade 4 (World Health Organization classification), were compared with the entire group of 730 patients with GBM and a control group of 18 patients with GBM matched for known prognostic factors including patient age, randomization date, performance status, extent of resection, and protocol number. Patients in all treatment groups received radiation and nitrosourea-based chemotherapy. The median time to progression and the median survival times for the patients with gliosarcoma were 28.0 and 35.1 weeks as compared with 24.7 and 41.6 weeks for the entire group of patients with GBM (log rank test, p = 0.94 and 0.27, respectively) and 16.7 and 34.4 weeks in the control group (p = 0.20 and 0.84, respectively). In previous molecular cytogenetic analyses of gliosarcoma these authors have shown similar genetic changes in the gliomatous and sarcomatous components. CONCLUSIONS: The data obtained in this study support the conclusion that gliosarcoma shares significant clinical and genetic similarities with GBM and that the same principles should be applied for patient enrollment in research protocols and treatment for these two kinds of tumor.

Adult↗
PubMed1998

Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas.

The purpose of this study was to examine the incidence of gene amplification in patients with primary (de novo) and secondary high-grade gliomas (gliomas evolving from lower grade malignancies) and to assess its prognostic significance. A total of 186 prospectively collected frozen surgical specimens were analyzed. Extracted DNA was examined by Southern blot using probes corresponding to the EGFR, CDK4, MDM2, n-MYC, CYCD1, PDGFR-alpha, MET, c-MYC oncogenes. Complete clinical data regarding age, sex, tumor size, extent of surgical resection, postoperative therapy and patient survival were collected. We showed that EGFR followed by CDK4 were the most frequent oncogene amplifications. Oncogene amplification events were significantly more frequent in grade 4 than in grade 3 astrocytomas, mixed gliomas or oligodendrogliomas (P<0.001). With respect to EGFR, there was a significant difference in the frequency of amplification between primary and secondary gliomas (P=0.001); however, no difference in the amplification frequency of the other oncogenes was observed. There was no apparent correlation between the occurrence of gene amplification and patient survival, possibly because the genes amplified in human gliomas are part of larger signaling pathways.

Adolescent↗
PubMed1997

Extrapulmonary small cell carcinoma.

BACKGROUND: Extrapulmonary small cell carcinoma (EPSCCA) is often an underrecognized clinicopathologic entity, distinct from small cell lung carcinoma. The purpose of this study was to review the study institution's experience with EPSCCA with specific emphasis on the epidemiology and response to treatment of these uncommon neoplasms. METHODS: Using the tumor registry database of the study institution, the authors retrieved and reviewed the records of all patients with EPSCCA treated between 1974 and 1994. Study eligibility required that the patients had a normal chest radiograph, computed tomography scan of the chest, sputum cytology, and/or negative bronchoscopy. Patients with well differentiated neuroendocrine carcinomas and Merkel cell carcinomas of the skin were excluded. RESULTS: Primary sites of EPSCCA in the current series were: gastrointestinal system in 29 patients, ear, nose, and throat in 14, genitourinary system in 12, internal genitalia in 10, upper respiratory system in 5, unknown primary-lymph nodes in 5, unknown primary-other in 2, the thymus in 3, and the peritoneum in 1. After the initial evaluation and confirmation of histologic diagnosis, 10 of 81 patients had been lost to follow-up. Of the remaining 71 patients, 54 had limited disease. Forty of the 54 patients underwent surgical treatment of their malignancy; 10 patients (25%) remained alive and disease free at least 3 years after surgery, whereas 30 patients (75%) relapsed with a median disease free survival of 6 months. Six patients of 54 with limited disease were treated with chemotherapy and radiation. Five of these 6 (83%) relapsed at a median time of 11.5 months. Another 8 of the total of 54 patients received only radiation therapy and all had disease recurrence at a median time of 5 months. In the group of patients with extensive or recurrent disease, platinum-based chemotherapy was employed in 22 patients. There was a 72% response rate with a median duration of 8.5 months. Seven patients had doxorubicin-based chemotherapy. There was a 57% response rate with a median duration of 4.5 months. In the current study group of patients, the 3-year disease free and overall survival rates were 26% and 38%, respectively, whereas the 5-year disease free and overall survival rates were each 13%. CONCLUSIONS: EPSCCA is usually a fatal disease, with a 13% 5-year survival rate. In a small percentage of patients, surgery can be curative if the tumor is small and confined to the organ of origin. Because of the poor overall outcome, one needs to consider the possible use of adjuvant chemotherapy in appropriate circumstances if surgery is to be employed. In most patients with limited disease, the combination of chemotherapy and radiation as the primary treatment can be as effective as surgery. EPSCCA is responsive to commonly employed regimens for small cell lung carcinoma; however, the responses are short-lived. The extent of disease at diagnosis represents the most sensitive predictor of survival.

Adult↗
PubMed1997

Spontaneous pneumomediastinum in a patient with bronchiolitis obliterans after bone marrow transplantation.

After allogeneic bone marrow transplantation for chronic myelogenous leukemia, spontaneous pneumomediastinum and subcutaneous emphysema developed in a patient with bronchiolitis obliterans. Computed tomography scanning of the chest failed to reveal the cause. There was no evidence of a pulmonary process, pneumothorax, or pharyngeal or upper airway leak. Despite the alarming appearance of the patient, conservative management, including high-flow oxygen, resulted in resolution of the pneumomediastinum and subcutaneous emphysema. The cause of pneumomediastinum and subcutaneous emphysema in bone marrow transplant recipients is discussed.

Bone Marrow Transplantation↗
PubMed1997

Phase I study of immunotherapy of hepatic metastases of colorectal carcinoma by direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7.

We have completed a phase I study to test feasibility and toxicity of immunotherapy of hepatic metastases from colorectal carcinoma by direct gene transfer of HLA-B7, a MHC class I gene. Eligible patients were HLA-B7 negative, immunocompetent by PHA lymphocyte stimulation and had at least two measurable hepatic lesions on CT scan for measurement of response of the injected lesion, as well as evaluation of possible distant response. Under ultrasonographic guidance the hepatic lesions were injected with Allovectin-7, a liposomal vector containing the combination of the HLA-B7 gene with beta 2-microglobulin formulated with the lipid DMRIE-DOPE. Eligible patients were injected on two schedules. On the first schedule patients received an injection on day 1 and the injected lesion was biopsied to determine transfection every 2 weeks for 8 weeks. Doses were escalated from 10 micrograms to 50 micrograms to 250 micrograms with three patients treated at each level. The second schedule included multiple injections of 10 micrograms. Three patients received injections on days 1 and 15. Three patients received injections on days 1, 15 and 29. A total of 15 patients have completed treatment. The plasmid DNA was detected in 14 of 15 patients (93%) by PCR. In five of 15 patients (33%) mRNA was also detected. The HLA-B7 protein was detected in five of eight patients (63%) by immunohistochemistry and in seven of 14 patients (50%) tested by fluorescence activated cell sorting (FACS) analysis. There has been no serious toxicity directly attributable to allovectin-7. Our results suggest that liposomal gene transfer by direct injection is feasible and non-toxic. Further studies will be necessary in order to establish the therapeutic efficacy.

Adult↗
PubMed1997

Effective chemotherapy for advanced CNS embryonal tumors in adults.

PURPOSE: Embryonal tumors of the CNS include, among others, medulloblastoma, cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors (PNETs). Almost all data on the treatment of embryonal CNS tumors are derived from the pediatric population, since these tumors are uncommon in adulthood. The purpose of this study was to examine the rate and duration of response to chemotherapy of advanced embryonal CNS tumors in adults. PATIENTS AND METHODS: We retrospectively studied all adult (> 18 years of age) patients with advanced embryonal tumors of the CNS who received chemotherapy at our institution between 1976 and 1994. Seventeen consecutive patients were treated with regimens that contained either nitrosourea or cisplatin or both sequentially, with no patients having received the combination of nitrosourea and cisplatin concurrently. RESULTS: In patients who received cisplatin-based chemotherapy, responses were observed in 84.5% (26% complete response [CR] rate), 10.5% remained stable, and 5% progressed. The median time to progression was 18 months for patients who had a CR, 6 months for those with partial response (PR), and 10 months for stable patients. Among patients who received nitrosourea-based chemotherapy, PR was observed in 27%, 36.5% remained stable, and 36.5% progress. The median time to progression was 6 months for patients who had a PR and 6.5 months for stable patients. CONCLUSION: In adults with advanced embryonal CNS tumors, conventional-dose intravenous cisplatin-based chemotherapy regimens are able to produce responses in the majority of the patients (84.5%), even as second- or third-line regimens. Nitrosourea-based regimens less frequently produce responses (27%).

Adolescent↗
PubMedDate not supplied

Neuronal autoantibody titers in the course of small-cell lung carcinoma and platinum-associated neuropathy.

The aims of this study were to investigate, in patients with newly diagnosed small-cell lung carcinoma (SCLC), whether or not there may be a relationship between the presence, type or titer of circulating neuronal autoantibodies and (i) the extent of SCLC dissemination at presentation, (ii) the development of peripheral neuropathy during platinum chemotherapy, (iii) survival time. We studied stored serum from 58 patients with uncomplicated SCLC who had participated in two trials conducted by the North Central Cancer Treatment Group (NCCTG); 29 had extensive disease and 29 had limited disease. No patient had neuropathy or other neurological or paraneoplastic problems at the time of enrollment but each group included 14 or 15 patients respectively who developed peripheral neuropathy in the course of chemotherapy. We tested five consecutive serum specimens from each patient in blinded fashion by (i) an indirect immunofluorescence assay optimized to detect neuron-restricted nuclear and cytoplasmic antibodies (triple substrate of mouse cerebellum, gut and kidney), and (ii) immunoprecipitation assays to detect neuronal Ca2+-channel-binding antibodies (N-type and P/Q-type). Sera that were positive by immunofluorescence were analyzed further by Western blotting. Neuronal autoantibodies were significantly more frequent in patients who had limited SCLC at presentation (12/29 or 41% positive) than in those with extensive SCLC (5/29 or 17% positive, P = 0.02). Neuronal autoantibodies of nuclear or cytoplasmic specificity were found in 50% of the seropositive patients with limited SCLC (21% of the total group), but in no patient with extensive SCLC (P = 0.01). The frequency of neuronal autoantibodies did not differ significantly among patients who did and did not develop peripheral neuropathy. Titers fell progressively during chemotherapy and did not rise again when peripheral neuropathy became clinically evident. This argues against a synergism between drug toxicity and neuronal autoimmunity as the mechanism of platinum-associated peripheral neuropathy. Seropositivity for neuronal autoantibodies did not affect the survival of patients with either limited or extensive SCLC. It is conceivable that the immunosuppression attendant on combined cisplatin/etoposide therapy cancels a pre-existing protective antitumor immune response (presumably cytotoxic-T-cell-mediated) for which the nuclear and cytoplasmic paraneoplastic IgG autoantibodies serve as a surrogate marker. Testing of this hypothesis would require the survival of seropositive and seronegative patients to be compared in a larger trial, using a therapeutic modality that does not compromise immunocompetence.

Antineoplastic Agents↗
PubMedDate not supplied

An observational study of sun and heat protection during Canada Day outdoor celebration, 2003.

Attendance at summer outdoor mass gatherings may lead to heat- and sun-related illness. The purposes of this study were: (1) to estimate the proportion of people in attendance at the 2003 Canada Day celebration in the National Capital Region who used sun and heat protective items; (2) to identify factors associated with the utilization of these protective items; and (3) to provide research data to public outdoor event organizers when developing evidence-based plans for safer events. A naturalistic observational cross-sectional method was used to gather information at the 2003 Canada Day celebration in the National Capital Region on attendees' demographics, the sun and heat protective items they used and the protective resources available at the event sites. Of the 398 observed attendees, the proportion using any one of the protective items ranged from 3 percent (an open umbrella) to 51.5 percent (sunglasses). Females were more likely to use protective items more than males, and adults more likely than children. Planners of public outdoor events should consider the factors that influence the utilization of sun and heat protective behaviours and the environmental modifications that would allow participants to make safe choices.

Adolescent↗