Robert J. Hayashi

Bio: Robert J. Hayashi is an academic researcher from Washington University in St. Louis. The author has contributed to research in topics: Transplantation & Population. The author has an hindex of 40, co-authored 125 publications receiving 6543 citations. Previous affiliations of Robert J. Hayashi include St. Louis Children's Hospital & Stanford University.

The Central Role of CD4+ T Cells in the Antitumor Immune Response

Abstract: The induction of optimal systemic antitumor immunity involves the priming of both CD4+ and CD8+ T cells specific for tumor-associated antigens. The role of CD4+ T helper cells (Th) in this response has been largely attributed to providing regulatory signals required for the priming of major histocompatibility complex class I restricted CD8+ cytolytic T lymphocytes, which are thought to serve as the dominant effector cell mediating tumor killing. However, analysis of the effector phase of tumor rejection induced by vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor indicates a far broader role for CD4+ T cells in orchestrating the host response to tumor. This form of immunization leads to the simultaneous induction of Th1 and Th2 responses, both of which are required for maximal systemic antitumor immunity. Cytokines produced by these CD4+ T cells activate eosinophils as well as macrophages that produce both superoxide and nitric oxide. Both of these cell types then collaborate within the site of tumor challenge to cause its destruction.

Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging.

Abstract: OBJECTIVE. MR imaging of central nervous system (CNS) malignancies falls short of a definitive evaluation. Tissue diagnosis remains the gold standard. Diffusion-tensor MR imaging measures the apparent diffusion coefficient and diffusion anisotropy of water in tissue. The purpose of this study was to test the hypothesis that the apparent diffusion coefficient may improve the MR imaging evaluation of newly diagnosed CNS neoplasms. We examined the relationship between the apparent diffusion coefficient, anisotropy, and tumor cellularity in 12 pediatric patients.MATERIALS AND METHODS. On the basis of histopathologic evaluation, tumors in this case series were segregated into three types: low-grade gliomas, embryonal tumors, and nonembryonal high-grade tumors. Mean apparent diffusion coefficient and anisotropy values obtained from the solid components of each tumor were compared with cellularity, total cellular area, and total nuclear area derived from biopsy material.RESULTS. The apparent diffusion coefficien...

Childhood Cancer Survivors' Knowledge About Their Past Diagnosis and Treatment: Childhood Cancer Survivor Study

Abstract: ContextAdult survivors of childhood cancer are at risk for adverse effects later in life but may have limited access to information about their diagnosis and treatment. This knowledge is necessary to motivate them to seek medical follow-up and to report essential history to health care professionals.ObjectiveTo assess knowledge of adult survivors of childhood cancer about their primary cancer diagnosis and associated therapies.Design, Setting, and ParticipantsCross-sectional survey of 635 consecutive survivors (approximately 5%) drawn from 12 156 participants 18 years or older participating in the Childhood Cancer Survivor Study (a multiinstitutional cohort of individuals diagnosed between January 1, 1970, and December 31,1986, at an age <21 years, who had survived 5 years from diagnosis).The survey assessed knowledge of their cancer diagnosis and associated therapies in a 3- to 5-minute telephone questionnaire.Main Outcome MeasuresResponses were compared with medical record data for accuracy, sensitivity, specificity, and positive and negative predictive value.ResultsOverall, 72% accurately reported their diagnosis with precision and 19% were accurate but not precise. Individuals with central nervous system (CNS) cancer (odds ratio, 5.1; 95% confidence interval, 2.6-9.9) and neuroblastoma (OR, 4.2; 95% CI, 1.8-9.6) were more likely not to know their cancer diagnosis. Participants' accuracy rates for reporting their treatment history was 94% for chemotherapy, 89% for radiation, and 93% for splenectomy. Among those who received anthracyclines, only 30% recalled receiving daunorubicin therapy and 52% recalled receiving doxorubicin therapy, even after prompting with the drugs' names. Among those who received radiotherapy, 70% recalled the site of radiotherapy. History of receiving a written medical summary, attending a long-term follow-up clinic, and anxiety about late effects were not associated with greater knowledge.ConclusionsImportant knowledge deficits exist among adult survivors of childhood cancer regarding basic aspects of their diagnosis and treatment. Such deficits could impair survivors' ability to seek and receive appropriate long-term follow-up care.

Childhood Cancer Survivors' Knowledge About Their Past Diagnosis and Treatment

Abstract: summary of all of the elements oftheircancerhistory.Noonecouldpro-vide an accurate detailed summary,ie, the detailed name of the cancer,whether doxorubicin or daunorubicinwas administered, and the site of anyradiation therapy. Participants in oursample are participants in the CCSSand, thus, likely represent a motivatedand knowledgeable group. Accord-ingly, rates of diagnosis knowledgeamong childhood cancer survivors, ingeneral, may well be lower.Contrary to our a priori hypotheses,our analyses suggest that no consistentfactors identify individuals with inad-equate knowledge of their cancer diag-nosis and therapy. Of note, no interac-tionwasfoundbetweenageatdiagnosisand era of diagnosis. Also, individualswho attended a long-term follow-upclinic or received a medical summary,interventionsreceivingattentionintheliterature, 10,11 didnotdisplaygreaterun-derstandingoftheirdiagnosisandtreat-ment. In fact many of the participantsdidnotknowwhethertheyeverhadre-ceived these interventions.We observed particularly disturb-ing knowledge deficits in anthracy-cline exposure and site of radiationtherapy,withlackofawarenessamongmore than half of those who had re-ceived such treatments. These thera-piesarepotentiallyassociatedwithcon-siderabletoxiceffectsthatwarrantclosemonitoring, as reported in a consen-sus statement from the CardiologyCommittee of the Children’s CancerStudy Group.

Enhancement of antitumor immunity by CTLA-4 blockade.

Abstract: One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. It has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells.

Nitric oxide and the immune response

Abstract: During the past two decades, nitric oxide (NO) has been recognized as one of the most versatile players in the immune system. It is involved in the pathogenesis and control of infectious diseases, tumors, autoimmune processes and chronic degenerative diseases. Because of its variety of reaction partners (DNA, proteins, low–molecular weight thiols, prosthetic groups, reactive oxygen intermediates), its widespread production (by three different NO synthases (NOS) and the fact that its activity is strongly influenced by its concentration, NO continues to surprise and perplex immunologists. Today, there is no simple, uniform picture of the function of NO in the immune system. Protective and toxic effects of NO are frequently seen in parallel. Its striking inter- and intracellular signaling capacity makes it extremely difficult to predict the effect of NOS inhibitors and NO donors, which still hampers therapeutic applications.