Paclitaxel, carboplatin, and oral etoposide in advanced gastric adenocarcinoma

The prognosis of locally advanced or metastatic adenocarcinoma of the stomach is poor. In an attempt to improve therapeutic results, we undertook a phase II trial to investigate a combination of paclitaxel, carboplatin, and oral etoposide, all active drugs in this malignancy and with a synergistic effect in combination. Fourteen patients with advanced gastric adenocarcinoma were treated with paclitaxel 200 mg/m² iv, carboplatin AUC-6 iv on d 1, and oral etoposide 50 mg/d alternating with 100 mg/d on d 1–10. Cycles were repeated every 3 wk. Of the 14 patients treated, partial response was observed in 3/12 (25%) evaluable patients. Median survival for the entire group was 7 mo. The treatment was associated with severe myelotoxicity. Neutropenic fever that required hospitalization developed in 7/14 (50%) of patients, and symptomatic anemia that required red blood cell transfusion was noted in 8/14 (57%). There was one drug-related death associated with neutropenic fever, Gram negative sepsis, grade 4 thrombocytopenia, and gastrointestinal bleeding. Nonhematological toxicity was moderate. We conclude that the current regimen of paclitaxel, carboplatin, and oral etoposide is not recommended in advanced gastric carcinoma owing to unacceptable myelotoxicity.     

Entering the well-guarded fortress: alternative practitioners in hospital settings

There is a growing evidence that alternative health care practitioners and physicians are working together in collaborative patterns. The paper examines these collaborative patterns in hospital settings in Israel. On the theoretical level, the specific issues relate to theories concerning relationships between dominant institutional structures which enjoy the benefits of epistemological legitimacy as well as extensive, supportive social structures and groups of non-conformists who seek to attain many of the same goals by utilizing different methods based on other epistemologies. In the most general sense, the issues involved concern processes of accommodation and social change.Data were collected by means of semi-structured, qualitative interviews in four general hospitals in Jerusalem during 2000. Nineteen persons were interviewed including 10 alternative practitioners working in a variety of fields and nine biomedical practitioners who worked with them (six physicians and three nurses). Interviews focused on background and training, reasons for entry into the hospital, length of practice, status in the hospital system, mode of remuneration, content of work, modes of interaction with others in the hospital and problems encountered.The findings suggest a dual process of simultaneous acceptance and marginalization of alternative practitioners. While small numbers of alternative practitioners were found to be practicing in a wide variety of hospital departments and in a broad spectrum of specialties, they were in no way accepted as regular staff members and their marginality was made clear by a variety of visible structural, symbolic and geographical cues. There is a division of labour expressed by focusing on the biomedical practitioners on the diagnosis and treatment of specific disease entities, while the alternative practitioners work in the illness context, concentrating of feelings and affective states involving the alleviation of pain, suffering and efforts to improve the quality of life.     

Prolonged daily administration of oral etoposide in lymphoma following prior therapy with Adriamicin,an ifosfamide-containing salvage combination,and intravenous etoposide

Prolonged daily administration of oral etoposide has been reported to be active in refractory lymphoma. The purpose of this phase II trial was to confirm the activity of this schedule of etoposide in a selected group of heavily pretreated patients with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 26 patients (20 with NHL and 6 with HD) were entered in the trial; all had previously been treated with an Adriamycin-based chemotherapy, an ifosfamide-containing salvage combination, and i. v. etoposide. Etoposide was given in a fixed oral daily dose of 100 mg over 3 weeks; the weekly dose (500–700 mg) was selected such that the average daily dose was approximately 50 mg/m². Cycles were repeated on day 29. An objective response was seen in 16 patients (62%; 95% confidence interval, 42%–80%), with a complete response (CR) being observed in 3 cases (12%) and a partial response (PR), in 13 (50%). The median duration of PRs was 3 months. CRs lasted for 15 months in one patient and continue at 12+ and 20+ months in the remaining two patients. The overall actuarial survivial for the entire group was 40% at 2 years; the median survival time was 12 months. The main toxicity was myelosuppression; WHO grade 3 or 4 leukopenia and thrombocytopenia developed in 31% and 12% of the patients, respectively. There was no drug-related death. We conclude that oral etoposide is an effective and tolerable palliative treatment for heavily pretreated lymphoma patients.     

Differential in vitro cytotoxicity of (-)-epicatechin gallate (ECG) to cancer and normal cells from the human oral cavity.

This study evaluated the biologic activity of epicatechin gallate (ECG), a polyphenol in tea, to carcinoma HSC-2 cells and normal HGF-2 fibroblasts cells from the human oral cavity. The relative cytotoxicity of ECG, as compared to five other polyphenols in tea, was evaluated. For the HSC-2 carcinoma cells, ECG, catechin gallate (CG), and epigallocatechin gallate (EGCG) grouped as highly toxic, epigallocatechin (EGC) as moderately toxic, and catechin (C) and epicatechin (EC) as least toxic. For the HGF-2 fibroblasts, ECG and CG grouped as highly toxic, EGCG as moderately toxic, and EGC, C, and EC as least toxic. The cytotoxic effects of the polyphenols were more pronounced to the carcinoma, than to the normal, cells. The addition of ECG to cell culture medium led to the generation of hydrogen peroxide (H2O2). However, ECG, as compared to EGCG, was a poor generator of H2O2 and, hence, the cytotoxicity of ECG was unaffected by the presence of the antioxidants, N-acetyl cysteine and glutathione, and catalase. The cytotoxicity of ECG was unaffected by a metabolic activating system, i.e., a hepatic microsomal S-9 mix. DNA fragmentation, caspase-3 activity, and nuclear staining, both with acridine orange and the TUNEL procedure, were used to assess ECG-induced apoptosis. ECG induced apoptosis in the carcinoma HSC-2 cells, but not in the normal HGF-2 fibroblasts. This research supports those studies suggesting that tea green is an effective chemopreventive agent of oral carcinoma.     

The human mast cell receptor binding site maps to the third constant domain of immunoglobulin E.

The characterization of the site on the IgE molecule which accommodates the high affinity receptor for IgE (Fc epsilon RI) should allow the design of IgE analogues which can be utilized to block allergic responses. Using chimeric human IgE molecules in which different constant region domains were exchanged with their murine homologues, we demonstrate here that the C epsilon 3 in its native configuration is essential for the binding to the alpha subunit of the human Fc epsilon RI. Deletion of the human C epsilon 2 from such chimeric molecules did not impair their ability to interact with the Fc epsilon RI, indicating that C epsilon 2 is not directly involved in the human Fc epsilon RI binding site and that C epsilon 3 alone is necessary and sufficient to account for most of the human Fc epsilon RI-binding capacity.     

Effect of antiidiotypic antibodies to HLA on graft survival in renal-allograft recipients

Although the presence in the recipient of preformed antibodies to HLA antigens in the kidney of a renal-transplant donor may be associated with early graft failure, such grafts are often well tolerated. We have investigated the possibility that anti-anti-HLA (antiidiotypic) antibodies influence the outcome of renal transplantation in recipients with a history of presensitization to their donor's HLA antigens. A retrospective analysis of 20 such cases showed that in 10 patients the transplanted kidney was rejected within one month, whereas in the remaining 10 the graft was tolerated for more than a year. Nine of the 10 patients in whom the graft was tolerated had anti-anti-HLA antibodies at the time of transplantation. Nine of the 10 patients in whom the graft was rejected had antibodies that potentiated, rather than blocked, the cytotoxic activity of anti-donor-HLA antibodies. These results suggest that patients with anti-anti-HLA antibodies specific for a potential donor can safely undergo transplantation, despite a prior history of anti-HLA antibodies. At the time of transplantation, patients who have antibodies that potentiate the cytotoxic activity of a historically positive serum are at high risk of graft rejection within a short period. Taking these considerations into account may improve the reliability of cross-matching in renal transplantation.     

Plasma amino acid turnover rates and pools in rabbits: in vivo studies using stable isotopes

Gas chromatography--mass spectrometry of plasma amino acids has been used to determine the 15N enrichments of plasma glycine and alanine in rabbits in different metabolic states. Isotope-enrichment time-decay curves of plasma amino acids were linear over the course of the measurements after intravenous administration of a single dose of 15N-amino acid. Glycine and alanine pools and turnover rate constants were estimated from decay data. The effects of diurnal variation and fasting on glycine and alanine pool sizes, turnover rates, and flux in rabbits were studied to provide information on the effect of metabolic stress on amino acid kinetics in the whole body. The observations suggests that the transport of systemic glycine or alanine into the hepatocyte is under the control of a regulatory mechanism that compensates for decrease in the extracellular levels of the amino acids by enhancing the activity of the transport system. The volumes of the glycine and alanine pools were found to correspond to the extracellular space of rabbits, and the glycine and alanine pools can be identified as extracellular. We conclude that the plasma glycine and alanine 15N isotope-enrichment time-decay curves over the 1st h after a single intravenous dose of the amino acid represent mainly the hepatic uptake of glycine and alanine from the extracellular pool.     

A new packaging cell line for SV40 vectors that eliminates the generation of T-antigen-positive,replication-competent recombinants

Simian virus 40 (SV40) vectors are efficient vehicles for gene delivery to hematopoietic and hepatic cells. To ensure their replication incompetence and because of safety considerations, it is critical that the vectors do not contain T-antigen sequences. Available packaging cell lines for T-antigen replacement vectors, COS and CMT4, contain considerable sequence identity with the vectors, leading to homologous recombination and reacquisition of the T-antigen gene. We constructed a packaging cell line, COT18, with minimal sequence identity to the vector. Vector stocks produced by passaging on COT18 had high transducing activity and undetectable levels of T-antigen-positive, replication-competent contaminants. This cell line provides a means for the preparation of safe SV40 vector stocks.     

Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

PURPOSE: To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. PATIENTS AND METHODS: Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. RESULTS: One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. CONCLUSION: The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.