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Biomedical subjects

S Shu

Publications and source records attributed to S Shu.

At least 19 recordsLinked to original sources
PubMed2004

Therapeutic vaccine generated by electrofusion of dendritic cells and tumour cells.

Immunotherapy with fusion of dendritic cells (DCs) and tumour cells potentially confers the advantages of DC antigen-presenting functionality and a continuous source of unaltered tumour antigens. However, fusion using chemical or viral fusogens has been inefficient. We have recently developed a high throughput electrofusion technique with which very efficient fusion rates (15-54%) were observed in over 300 experiments, using a variety of murine and human tumour cell lines. The fused cells display a mature DC phenotype and express tumour-associated antigens. In two pre-clinical animal models (B16 melanoma transduced with the LacZ gene and the MCA 205 fibrosarcoma), a single vaccination of mice bearing tumours established in the lung, brain and skin resulted in tumour regression and prolongation of life. However, therapeutic efficacy required the administration of adjuvants such as IL-12 and OX-40R mAbs. Effective immunotherapy also required the delivery of fusion cells directly into lymphoid organs (spleen or lymph nodes). Using five defined human T cell lines derived from melanoma patients, allogeneic DCs of HLA-A2, HLA-DR4 and HLA-DR7 haplotypes fused with MART-1, gp100, tyrosinase and TRP-2 expressing 888 mel melanoma cells were analysed for their ability to stimulate specific cytokine (IFN-gamma and GM-CSF) secretion. DC-888 mel hybrids presented all tumour-associated epitopes to both CD4 and CD8 T cell lines in the context of MHC class II and I molecules, respectively. The therapeutic efficacy of a DC-tumour fusion vaccine is now being evaluated for the treatment of metastatic melanoma.

Animals↗
PubMed2002

An integrated computational pipeline and database to support whole-genome sequence annotation.

We describe here our experience in annotating the Drosophila melanogaster genome sequence, in the course of which we developed several new open-source software tools and a database schema to support large-scale genome annotation. We have developed these into an integrated and reusable software system for whole-genome annotation. The key contributions to overall annotation quality are the marshalling of high-quality sequences for alignments and the design of a system with an adaptable and expandable flexible architecture.

Animals↗
PubMed2001

Augmentation versus inhibition: effects of conjunctional OX-40 receptor monoclonal antibody and IL-2 treatment on adoptive immunotherapy of advanced tumor.

Therapeutic efficacy of adoptive immunotherapy of malignancies is proportional to the number of effector T cells transferred. Traditionally, exogenous IL-2 treatment has been used to promote the survival and function of transferred cells. Recently, we described the therapeutic effects of in vivo ligation of the costimulatory receptor, OX-40R, on activated T cells during early tumor growth. In this study, we examined the effects of IL-2 and OX-40R mAb on adoptive immunotherapy of advanced tumors. For treatment of 10-day 3-methylcholanthrene 205 pulmonary metastases, systemic transfer of 50 x 10(6) activated tumor-draining lymph node T cells resulted in >99% reduction of metastatic nodules. With either IL-2 or OX-40R mAb conjunctional treatment, only 20 x 10(6) cells were required. Advanced 10-day 3-methylcholanthrene 205 intracranial tumors could be cured by the transfer of 15 x 10(6) L-selectin(low) T cells derived from draining lymph nodes. In this situation, IL-2 administration inhibited therapeutic effects of the transferred cells. By contrast, 5 x 10(6) T cells were sufficient to cure all mice if OX-40R mAb was administrated. Studies on trafficking of systemically transferred T cells revealed that IL-2, but not OX-40R mAb, impeded tumor infiltration by T cells. Tumor regression required participation of both CD4 and CD8 T cells. Because only CD4 T cells expressed OX-40R at cell transfer, direct CD4 T cell activation is possible. Alternatively, OX-40R might be up-regulated on transferred T cells at the tumor site, rendering them reactive to the mAb. Our study suggests OX-40R mAb to be a reagent of choice to augment T cell adoptive immunotherapy in clinical trials.

Adjuvants, Immunologic↗
PubMed2001

Divergent effects of 4-1BB antibodies on antitumor immunity and on tumor-reactive T-cell generation.

4-1BB is an inducible receptor-like protein expressed rapidly by both CD4 and CD8 T-cells after activation. 4-1BB cross-linking, either by binding to 4-1BBL or by antibody ligation, delivers a costimulatory signal to enhance T-cell activation and proliferation. Previous studies have demonstrated that the administration of 4-1BB monoclonal antibodies (mAbs) induces antitumor immune responses. In the current study using several murine tumors, we examined the systemic effects of 4-1BB mAb on the growth of s.c., intracranial (i.c.), and pulmonary metastases. In addition, the effects of 4-1BB mAb on the generation of antitumor effector T cells were examined. Treatment of 3-day i.c. MCA 205 sarcoma and GL261 glioma with the antibody resulted in prolongation of survival and cure of disease in some mice, whereas only minimal therapeutic effects were observed in established s.c. and pulmonary tumors. No antitumor effects against the poorly immunogenic B16/D5 melanoma were observed. Interestingly, successful treatment of i.c. tumors induced concomitant regression of s.c. tumors. Experiments using severe combined immunodeficient mice and mice depleted of either CD4 or CD8 T cells demonstrated T-cell dependence of the antitumor effects. For generation of effector T cells in the tumor-draining lymph nodes (LNs), administration of 4-1BB mAb had adverse effects, despite the apparent hypertrophy of the LNs. During in vitro activation of tumor-draining LN T cells with anti-CD3 and interleukin 2, the 4-1BB mAb augmented proliferation, resulting in an increase in CD8 T cells. However, they were less therapeutic than not treated LN cells. In adoptive immunotherapy, the coadministration of 4-1BB mAb enhanced the therapeutic efficacy. These results thus demonstrate the limits and potential advantages of 4-1BB antibody interactions with antitumor T cells in vivo and in vitro and suggest that therapeutic interactions of the antibody may be used in a variety of immunotherapeutic approaches.

Animals↗
PubMed2001

Potent effector function of tumor-sensitized L-selectin(low) T cells against subcutaneous tumors requires LFA-1 co-stimulation.

OBJECTIVE: Animal tumor models have demonstrated that adoptive transfer of tumor-draining lymph node (TDLN) T lymphocytes can cure established tumors in many anatomic sites. However, subcutaneous tumors are relatively refractory and have required maximally tolerated doses of cells. The goals of this study were to determine whether a subset of TDLN T lymphocytes varying in expression of the cell adhesion molecule L-selectin (CD62L) had augmented therapeutic efficacy and to determine the co-stimulatory requirements for trafficking and anti-tumor effector function. STUDY DESIGN: TDLNs were recovered from mice bearing progressive MCA 205 fibrosarcomas, and the T lymphocytes were segregated into CD62L(low) and CD62L(high) subsets and activated ex vivo with anti-CD3 mAb and IL-2. Mice bearing established subcutaneous MCA 205 tumors were treated with activated T cell subsets and in some experiments with additional mAb against cell adhesion molecules. RESULTS: Adoptive transfer of as few as 5 x 10(6) activated cells cured mice bearing 3-day subcutaneous MCA 205 tumors initiated with 6 x 10(6) cells, and the tumors demonstrated a dense infiltrate of CD62L(low) cells. In marked contrast, adoptive transfer of 10 times as many T cells derived from the reciprocal CD62L(high) compartment had no effect on tumor growth. The effector function of the CD62L(low) T cells was clearly dependent on co-stimulation through the cell adhesion molecule LFA-1, because anti-LFA-1 mAb completely abrogated the anti-tumor reactivity of the transferred cells against subcutaneous tumors and inhibited tumor infiltration. In contrast, blockade of ICAM-1, VLA-4, or VCAM-1 had no inhibitory effect on the anti-tumor function. CONCLUSION: These studies demonstrate the high therapeutic activity of the CD62L(low) subset of tumor-draining LN T cells against subcutaneous tumors, a relatively refractory site, and confirm the essential role of LFA-1 for effector T cell function. SIGNIFICANCE: Identification of the phenotype and requirements for effector function of T lymphocytes sensitized to tumor antigens has implications for clinical trials of adoptive immunotherapy for head and neck carcinoma using a similar approach.

Adoptive Transfer↗
PubMed2001

Cognitive-behavioural therapy for the management of sickle cell disease pain: identification and assessment of costs.

OBJECTIVE: The aim of the present study was to investigate the economic validity of using a psychological intervention in the management of sickle cell disease (SCD). Thomas et al. (Br J Health Psychol 1999; 4: 209-29) concluded that cognitive-behaviour therapy (CBT) appears to be immediately effective for the management of SCD pain in terms of reducing psychological distress pain as well as improving coping. METHOD: The costs of management of SCD were evaluated using a societal viewpoint. This approach includes health and social services as well as costs privately borne by informal carers, but it did not include the economic loss due to patients' foregone earnings. Cost profiles were constructed for each patient taking account of cost generating events 12 months before and 12 months after CBT. RESULTS: The hypothesis of the present study, stating that CBT is economically efficient, was confirmed. However, analysis of longitudinal data suggests that CBT is most cost-effective during the first 6 months after the intervention. CONCLUSION: The present findings suggest the need for CBT to be integrated into the normal package of care available for all patients with SCD. The clinical implication is that CBT should be routinely offered to patients on a 6-monthly basis.

Adolescent↗
PubMed2001

Proposal of the genera Anaerococcus gen. nov., Peptoniphilus gen. nov. and Gallicola gen. nov. for members of the genus Peptostreptococcus.

Members of genus Peptostreptococcus have previously been found to be distantly related to the type species, Peptostreptococcus anaerobius, on the basis of 16S rDNA sequence similarities. They were divided into three major phylogenetic groups, and their peptidoglycan structure and biochemical traits differed between groups. The reclassification of the species of these three groups into three new genera, Peptoniphilus gen. nov., Anaerococcus gen. nov. and Gallicola gen. nov., is proposed. The genus Peptoniphilus gen. nov. includes the following butyrate-producing, non-saccharolytic species that use peptone and amino acids as major energy sources: Peptoniphilus asaccharolyticus comb. nov. (type species), Peptoniphilus lacrimaris comb. nov., Peptoniphilus harei comb. nov., Peptoniphilus indolicus comb. nov. and Peptoniphilus ivorii comb. nov. The genus Anaerococcus gen. nov. contains the saccharolytic, butyrate-producing species Anaerococcus prevotii comb. nov. (type species), Anaerococcus tetradius comb. nov., Anaerococcus lactolyticus comb. nov., Anaerococcus hydrogenalis comb. nov., Anaerococcus vaginalis comb. nov. and Anaerococcus octavius sp. nov. The genus Gallicola gen. nov. contains a single species, Gallicola barnesae comb. nov.

Animals↗
PubMed2001

T-cell adoptive therapy of tumors: mechanisms of improved therapeutic performance.

The T cells of many cancer patients are naturally sensitized to tumor-associated antigens (Ag), or they can readily be sensitized with vaccine maneuvers. In melanoma patients, the adoptive transfer of such T cells can often be causally linked to the objective regression of established tumors. So far, few patients have shown sustained clinical benefit from such therapy, but preclinical mouse studies have now clearly delineated the hurdles that must be overcome to render T-cell-based antitumor therapy effective. Contrary to earlier expectations, it is now established that remarkably potent CD4+ and CD8+ pre-effector T cells are naturally sensitized even in mice bearing progressive, weakly immunogenic tumors. However, such T cells often display signal transduction impairments as a consequence of the tumor environment, which limit their acquisition of optimal effector function. Extracorporealization and culture of these tumor-sensitized T cells with appropriate activation stimuli not only restores normal signal transduction, but also confers resolute effector activity that can often sustain tumor rejection upon reinfusion. In mouse studies, the L-selectin(low) fraction of T cells in tumor-draining lymph nodes (TDLN) constitutes the potent pre-effector population and comprises both CD4+ and helper-independent CD8+ T cells. Appropriate in vitro activation confers an apparently unrestricted trafficking capacity to this fraction, and even the ability to proliferate within the tumor bed, leading to unprecedented tumor rejection at anatomic sites (e.g., subcutaneous and intracranial) that were historically refractory to such treatment. Such results underscore the surprising capacity of appropriately activated effector T cells to withstand the immunosuppressive, tolerogenic, and apoptotic influences of the typical tumor environment. Given the increasingly appreciated and critical communications between T cells and host Ag-presenting cells (APC), which cross-present tumor Ag, it is likely that dendritic cell-based vaccine maneuvers that promote sensitization of T1-committed L-selectin(low) antitumor T cells will play an increasingly important role in adoptive therapy strategies.

Animals↗
PubMed2001

Adoptive immunotherapy of CNS malignancies.

Although many patients with malignant brain tumors can be rendered free of bulk disease by current surgery and radiotherapy techniques, complete tumor eradication is extremely difficult to achieve, raising interest for T-cell adoptive immunotherapy. Conclusive experimental data generated by many investigators coupled with clinical experience have debunked many of the theoretical 'obstacles' to immunotherapy in the CNS. First, there does not appear to be a significant vascular barrier in brain tumors to prevent trafficking of systemically administered activated T cells. Moreover, T cells stimulated in the periphery by DC vaccination are able to mediate regression of established intracranial tumors. Second, brain tumor patients are able to mount an immune response against autologous tumor. Not surprisingly, patient factors such as tumor burden, corticosteroid use, advanced age, or recent chemotherapy can inhibit the immune response to tumor. Directing this type of therapy to patients without these factors may improve the likelihood of response. Third, therapeutic immune responses occurring within the CNS against tumors derived from CNS tissue have not been associated with clinical signs of autoimmune reactions against normal brain tissue. The general toxicity associated with the systemic adoptive transfer of ex vivo activated LN cells is very low. Toxicity of activated T cells delivered locally into the tumor resection cavity likewise is low and transient. Current phase II clinical trials of AI are in progress to determine the response rate for patients with newly diagnosed malignant gliomas. Future developments to characterize shared brain tumor antigens and develop more effective strategies for vaccination may lead to a more effective and broadly applicable therapy for CNS malignancies.

Brain Neoplasms↗
PubMed2000

T cell-mediated tumor rejection displays diverse dependence upon perforin and IFN-gamma mechanisms that cannot be predicted from in vitro T cell characteristics.

Experimental pulmonary metastases have been successfully treated by adoptive transfer of tumor-sensitized T cells from perforin knockout (KO) or Fas/APO-1 ligand(KO) mice, suggesting a prominent role for secretion of cytokines such as IFN-gamma. In the present study we confirmed that rejection of established methylcholanthrene-205 (MCA-205) pulmonary metastases displayed a requirement for T cell IFN-gamma expression. However, this requirement could be obviated by transferring larger numbers of tumor-sensitized IFN-gamma (KO) T cells or by immunosensitizing sublethal irradiation (500 rad) of the host before adoptive therapy. Extrapulmonary tumors (MCA-205 s.c. and intracranial) that required adjunct sublethal irradiation for treatment efficacy also displayed no requirement for host or T cell expression of IFN-gamma. Nonetheless, rejection of MCA-205 s.c. tumors and i.p. EL-4 tumors, but not MCA-205 pulmonary or intracranial tumors, displayed a significant requirement for T cell perforin expression (i.e., CTL participation). The capacity of T cells to lyse tumor targets and secrete IFN-gamma in vitro before adoptive transfer was nonpredictive of the roles of these activities in subsequent tumor rejection. Adoptive therapy studies employing KO mice are therefore indispensable for revealing a diversity of tumor rejection mechanisms that may lack in vitro correlation due to delays in their induction. Seemingly contradictory KO data from different studies are reconciled by the capacity of anti-tumor T cells to rely on alternative mechanisms when treated in larger numbers, the variable participation of CTL at different anatomic locations of tumor, and the apparent capacity of sublethal irradiation to provide a therapeutic alternative to host or T cell IFN-gamma production.

Animals↗
PubMed2000

Helper-independent, L-selectinlow CD8+ T cells with broad anti-tumor efficacy are naturally sensitized during tumor progression.

We recently reported that the CD4(+) T cell subset with low L-selectin expression (CD62L(low)) in tumor-draining lymph nodes (TDLN) can be culture activated and adoptively transferred to eradicate established pulmonary and intracranial tumors in syngeneic mice, even without coadministration of IL-2. We have extended these studies to characterize the small subset of L-selectin(low) CD8(+) T cells naturally present in TDLN of mice bearing weakly immunogenic tumors. Isolated L-selectin(low) CD8(+) T cells displayed the functional phenotype of helper-independent T cells, and when adoptively transferred could consistently eradicate, like L-selectin(low) CD4(+) T cells, both established pulmonary and intracranial tumors without coadministration of exogenous IL-2. Whereas adoptively transferred L-selectin(low) CD4(+) T cells were more potent on a cell number basis for eradicating 3-day intracranial and s.c. tumors, L-selectin(low) CD8(+) T cells were more potent against advanced (10-day) pulmonary metastases. Although the presence of CD4(+) T cells enhanced generation of L-selectin(low) CD8(+) effector T cells, the latter could also be obtained from CD4 knockout mice or normal mice in vivo depleted of CD4(+) T cells before tumor sensitization. Culture-activated L-selectin(low) CD8(+) T cells did not lyse relevant tumor targets in vitro, but secreted IFN-gamma and GM-CSF when specifically stimulated with relevant tumor preparations. These data indicate that even without specific vaccine maneuvers, progressive tumor growth leads to independent sensitization of both CD4(+) and CD8(+) anti-tumor T cells in TDLN, phenotypically L-selectin(low) at the time of harvest, each of which requires only culture activation to unmask highly potent stand-alone effector function.

Adenocarcinoma↗
PubMed2000

Chimeras of Dictyostelium myosin II head and neck domains with Acanthamoeba or chicken smooth muscle myosin II tail domain have greatly increased and unregulated actin-dependent MgATPase activity.

Phosphorylation of the regulatory light chain of Dictyostelium myosin II increases V(max) of its actin-dependent MgATPase activity about 5-fold under normal assay conditions. Under these assay conditions, unphosphorylated chimeric myosins in which the tail domain of the Dictyostelium myosin II heavy chain is replaced by either the tail domain of chicken gizzard smooth muscle or Acanthamoeba myosin II are 20 times more active because of a 10- to 15-fold increase in V(max) and a 2- to 7-fold decrease in apparent K(ATPase) and are only slightly activated by regulatory light chain phosphorylation. Actin-dependent MgATPase activity of the Dictyostelium/Acanthamoeba chimera is not affected by phosphorylation of serine residues in the tail whose phosphorylation completely inactivates wild-type Acanthamoeba myosin II. These results indicate that the actin-dependent MgATPase activity of these myosins involves specific, tightly coupled, interactions between head and tail domains.

Acanthamoeba↗
PubMed2000

Cross-presentation of tumor antigens to effector T cells is sufficient to mediate effective immunotherapy of established intracranial tumors.

The systemic adoptive transfer of tumor-sensitized T cells, activated ex vivo, can eliminate established intracranial tumors. Regression of MHC class II negative MCA 205 fibrosarcomas occurs optimally following adoptive transfer of both CD4 and CD8 tumor-sensitized T cells, indicating an important function for tumor-infiltrating APC. Here, we demonstrate that during an effector response, indirect presentation of tumor Ags to transferred T cells is sufficient to mediate intracranial tumor regression. BALB/c --> CB6F1 (H-2bxd) bone marrow chimeras were challenged with the MCA 205 fibrosarcoma (H-2b). The tumor grew progressively in the H-2b-tolerant chimeras and stimulated an immune response in tumor-draining lymph nodes. Tumor-sensitized lymph node T cells were activated ex vivo with anti-CD3 and IL-2, then adoptively transferred to sublethally irradiated BALB/c or C57BL/6 recipients bearing established intracranial MCA 205 tumors. The transferred T cells eradicated MCA 205 tumors in BALB/c recipients and demonstrated tumor specificity, but had no therapeutic efficacy in the C57BL/6 recipients. These data establish that tumor-associated host cell constituents provide sufficient Ag presentation to drive effector T cell function in the complete absence of direct tumor recognition. This effector mechanism has an evident capacity to remain operative in circumstances of immune escape, where the tumor does not express the relevant MHC molecules, and may have importance even at times when direct CTL recognition also remains operative.

Adoptive Transfer↗
PubMed2000

Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth.

The OX-40 receptor (OX-40R) is a cell surface glycoprotein of the tumor necrosis factor receptor family that is expressed primarily on activated CD4 T cells. Engagement of OX-40R by the OX-40 ligand (OX-40L) is known to costimulate the production of cytokines by activated T lymphocytes and to rescue effector T cells from activation-induced cell death. It was previously reported that in vivo ligation of OX-40R by administration of OX-40L:immunoglobulin fusion protein or OX-40R monoclonal antibody (mAb) resulted in a significant prolongation of survival of tumor-bearing mice in four histologically distinct solid tumors. In this study, we demonstrate that the therapeutic efficacy of OX-40R mAb was influenced by the tumor burden, the intrinsic immunogenicity of the tumor as well as by the histological site of tumor growth. Whereas subdermal and intracranial growth of weakly immunogenic MCA 203 and MCA 205 sarcomas and GL261 glioma were susceptible to the mAb treatment, established pulmonary MCA 205 metastases were refractory to the same regimen of treatment. Furthermore, the mAb administration had no impact on the growth of the poorly immunogenic B16/D5 mela noma. Tumor regression mediated by OX-40R mAb was dependent on the participation of both CD4 and CD8 T cells and as a result of tumor rejection, a long-term tumor-specific immunity was established. Analysis of tumor-infiltrating T cells revealed the presence of a far greater number of OX-40R+ T cells of both CD4 and CD8 phenotypes in the intracranial immunogenic GL261 glioma than that in the poorly immunogenic B16/D5 melanoma. These results suggest that ligation of OX-40R on activated T cells in situ in the tumor may provide a necessary costimulatory signal to augment immune responses leading to tumor regression and immunological memory.

Animals↗
PubMed2000

I-CeuI fragment analysis of the Shigella species: evidence for large-scale chromosome rearrangement in S. dysenteriae and S. flexneri.

I-CeuI fragments of four Shigella species were analyzed to investigate their taxonomic distance from Escherichia coli and to collect substantiated evidence of their genetic relatedness because their ribosomal RNA sequences and similarity values of their chromosomal DNA/DNA hybridization had proved their taxonomic identity. I-CeuI digestion of genomic DNAs yielded seven fragments in every species, indicating that all the Shigella species contained seven sets of ribosome RNA operons. To determine the fragment identities, seven genes were selected from each I-CeuI fragment of E. coli strain K-12 and used as hybridization probes. Among the four Shigella species, S. boydii and S. sonnei showed hybridization patterns similar to those observed for E. coli strains; each gene probe hybridized to the I-CeuI fragments with sizes similar to that of the corresponding E. coli fragment. In contrast, S. dysenteriae and S. flexneri showed distinct patterns; rcsF and rbsR genes that located on different I-CeuI fragments in E. coli, fragments D and E, were found to co-locate on a fragment. Further analysis using an additional three genes that located on fragment D in K-12 revealed that some chromosome rearrangements involving the fragments corresponding to fragments D and E of K-12 took place in S. dysenteriae and S. flexneri.

Blotting, Southern↗
PubMed2000

Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study.

OBJECTIVE: To evaluate the feasibility and toxic effects of systemic adoptive T-cell immunotherapy in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN). DESIGN: Nonrandomized phase 1 clinical trial. SETTING: Academic tertiary care hospital. PATIENTS: Between April 1, 1996, and September 30, 1998, 17 patients with confirmed recurrent and metastatic SCC of the upper aerodigestive tract were enrolled. Two patients did not receive T cells because of poor vaccine response. Fifteen patients were successfully treated with T-cell immunotherapy. INTERVENTION: Patients were vaccinated on the thigh with irradiated autologous tumor cells admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by 3 additional daily injections of GM-CSF at the vaccination site. Eight to 10 days later, tumor cell vaccine-draining inguinal lymph nodes were resected, and lymph node lymphocytes were activated with staphylococcal enterotoxin A and expanded in interleukin 2 in vitro. Resulting cultured cells were infused into patients peripherally on an outpatient basis. RESULTS: Toxic effects of infusion were limited to grade 2 reactions in 3 of 16 treatments. One patient required overnight hospitalization for fever and emesis. Median cell expansion was 37 times (range, 4-416 times), and median cell dose was 7.5 x 10(9) (range, 1.3 x 10(8) to 4.2 x 10(10)). Infused cells were predominantly CD3+ (>97%), being a mixture of CD4+ and CD8+ cells. Three patients demonstrated stabilization of previously progressive disease. Two patients experienced favorable clinical courses after adoptive T-cell transfer, including 1 patient with no evidence of disease 4 years after surgical resection of a vertebral body metastasis. CONCLUSIONS: Adoptive immunotherapy is a technically feasible and safe treatment with low toxicity and may demonstrate therapeutic activity in patients with unresectable SCCHN.

Adult↗
PubMed2000

Proton MR spectroscopy in children with acute brain injury: comparison of short and long echo time acquisitions.

The aim of this study was to evaluate comparatively the information given by proton magnetic resonance spectroscopy (MRS) with short echo time (TE 20 msec) stimulated echo acquisition mode and long TE (270 msec) point-resolved spectroscopy in predicting long-term outcome in children suffering from acute brain injury. At 1.5 T, we performed single-voxel proton MRS with both methods in occipital gray matter of 70 children. A linear discriminant analysis used to predict outcomes based on MRS variables was compared with actual neurologic outcome assigned at least 6 months after injury by a pediatric neurologist. Using peak area metabolite ratios and lactate presence, the short and long TE methods were equally predictive in children over 1 month of age. In neonates less than 1 month of age, the long TE method produced a higher percentage of correct outcome predictions (91%) than the short TE method (79%). The long TE method detected lactate more often in all age groups.

Acute Disease↗