Effects of the glucolipid synthase inhibitor, P4, on functional and phenotypic parameters of murine myeloma cells

This study describes the effects of the glucolipid synthase inhibitor P4, (DL-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol), on various functional and phenotypic parameters of 5T33 murine myeloma cells. Cell recovery was reduced by >85% following incubation of the cells for 3 days in the presence of 4 μM P4 (the IC50 concentration). Both cytostatic and cytotoxic inhibition was observed with tumour cell metabolic activity and clonogenic potential reduced to 42% and 14% of controls, respectively, and viability reduced to 52%. A dose-dependent increase in cells undergoing apoptosis (from 7% to 26%) was also found. P4 induced a decrease in the number of cells expressing H-2 Class I and CD44, and a large increase in cells expressing H-2 Class II and the IgG2b paraprotein. It did not affect surface expression of CD45 or CD54 (ICAM-1). Based on these alterations in tumour cell growth, adhesion molecule expression and potential immunogenicity, it is anticipated that P4 will provide a novel therapeutic approach for the treatment of multiple myeloma. In addition, given that essentially all tumours rely heavily on overexpressed or abnormal glucosphingolipids for growth, development and metastasis, glucolipid synthase inhibitors may prove to be universally effective anti-cancer agents. © 1999 Cancer Research Campaig

Improving the Efficiency of Physical Examination Services

The objective of our project was to improve the efficiency of the physical examination screening service of a large hospital system. We began with a detailed simulation model to explore the relationships between four performance measures and three decision factors. We then attempted to identify the optimal physician inquiry starting time by solving a goal-programming problem, where the objective function includes multiple goals. One of our simulation results shows that the proposed optimal physician inquiry starting time decreased patient wait times by 50% without increasing overall physician utilization

CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies

CAR T cells targeting CD19 provide promising options for treatment of B cell malignancies. However, tumor relapse from antigen loss can limit efficacy. We developed humanized, second-generation CAR T cells against another B cell–specific marker, B cell activating factor receptor (BAFF-R), which demonstrated cytotoxicity against human lymphoma and acute lymphoblastic leukemia (ALL) lines. Adoptively transferred BAFF-R-CAR T cells eradicated 10-day preestablished tumor xenografts after a single treatment and retained efficacy against xenografts deficient in CD19 expression, including CD19-negative variants within a background of CD19-positive lymphoma cells. Four relapsed, primary ALLs with CD19 antigen loss obtained after CD19-directed therapy retained BAFF-R expression and activated BAFF-R-CAR, but not CD19-CAR, T cells. BAFF-R-CAR, but not CD19-CAR, T cells also demonstrated antitumor effects against an additional CD19 antigen loss primary patient–derived xenograft (PDX) in vivo. BAFF-R is amenable to CAR T cell therapy, and its targeting may prevent emergence of CD19 antigen loss variants

Expression of testicular genes in haematological malignancies

The gene expression of a new group of tumour antigens known as cancer/testis (CT) antigens is now well-recognized in some solid tumours. However, their expression in haematological malignancies remained unclear. In this study, we have used reverse transcription polymerase chain reaction and Southern blot analysis to examine the presence of transcripts for the three CT antigens, NY-ESO-1, SSX2 and SCP1 in haematological malignant cells. We found that transcripts for SCP1 could be detected in 10% of myeloma, 5.7% of acute myeloid leukaemia and 23% of chronic myeloid leukaemia. In contrast, NY-ESO-1 and SSX2 were not detected in any of the 107 tumour samples. © 1999 Cancer Research Campaig

Economic costs of chemotherapy-induced febrile neutropenia among patients with non-Hodgkin's lymphoma in European and Australian clinical practice

Background: Economic implications of chemotherapy-induced febrile neutropenia (FN) in European and Australian clinical practice are largely unknown. Methods: Data were obtained from a European (97%) and Australian (3%) observational study of patients with non-Hodgkin’s lymphoma (NHL) receiving CHOP (±rituximab) chemotherapy. For each patient, each cycle of chemotherapy within the course, and each occurrence of FN within cycles, was identified. Patients developing FN in a given cycle (“FN patients”), starting with the first, were matched to those who did not develop FN in that cycle (“comparison patients”), irrespective of subsequent FN events. FN-related healthcare costs (£2010) were tallied for the initial FN event as well as follow-on care and FN events in subsequent cycles. Results: Mean total cost was £5776 (95%CI £4928-£6713) higher for FN patients (n = 295) versus comparison patients, comprising £4051 (£3633-£4485) for the initial event and a difference of £1725 (£978-£2498) in subsequent cycles. Among FN patients requiring inpatient care (76% of all FN patients), mean total cost was higher by £7259 (£6327-£8205), comprising £5281 (£4810-£5774) for the initial hospitalization and a difference of £1978 (£1262-£2801) in subsequent cycles. Conclusions: Cost of chemotherapy-induced FN among NHL patients in European and Australian clinical practice is substantial; a sizable percentage is attributable to follow-on care and subsequent FN events

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Impact of relative dose intensity (RDI) in CHOP combined with rituximab (R-CHOP) on survival in diffuse large B-cell lymphoma

<p>Abstract</p> <p>Background</p> <p>Recently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma.</p> <p>Methods</p> <p>We retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients.</p> <p>Results</p> <p>A multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6–1.0; <it>P </it>= 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI.</p> <p>Conclusion</p> <p>Our data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.</p