Search

PDF file - 1810K, Detection of NY-ESO-1-specific CD4+ T cells by intracellular cytokine staining. CD4+ T cells were stimulated once with T-cell depleted PBMC pulsed with NY-ESO-1 assay OLP and after 22-23 day culture, NY-ESO-1-specific IFN-γ and IL-5 production was evaluated by intracellular cytokine staining. Peptide-pulsed or unpulsed autologous EBV-B cells pulsed or unpulsed with 20-mer NY-ESO-1 peptides covering areas indicated were used as target cells. Responses shown at week 16 after vaccination in two patients (M09 and M19) representative of Cohort 2 and 3, respectively.

PDF file - 68K

PDF file - 2015K, Injection site reaction in patient M21

PDF file - 70K, Incidence of treatment-related adverse events by maximum grade

Purpose: Long peptides are efficiently presented to both CD4+ and CD8+ T cells after intracellular processing by antigen-presenting cells. To investigate the safety and in vivo immunogenicity of synthetic overlapping long peptides (OLP) from a human tumor self-antigen, we conducted a phase I clinical trial with OLP from cancer-testis antigen NY-ESO-1 in various adjuvant combinations.Experimental Design: Twenty-eight patients with advanced ovarian cancer in second or third remission were enrolled sequentially in three cohorts and received at least one vaccination. Patients in Cohort 1 (n = 4) received 1.0 mg OLP, Cohort 2 (n = 13) received OLP in Montanide-ISA-51, and Cohort 3 (n = 11) received OLP + 1.4 mg Poly-ICLC in Montanide-ISA-51 on weeks 1, 4, 7, 10, and 13. Humoral and cellular responses were evaluated by standardized immunomonitoring techniques (ELISA, ELISPOT assay, intracellular cytokine staining, and tetramer staining).Results: The vaccine was generally well tolerated with injection site reactions and fatigue that resolved. NY-ESO-1–specific antibody and CD8+ T cells were undetectable after vaccination with OLP alone, but were found in 6 of 13 (46%) and 8 of 13 (62%) patients, respectively, after vaccination with OLP+Montanide, and in 10 of 11 (91%) and 10 of 11 (91%) patients, respectively, after vaccination with OLP+Montanide+Poly-ICLC. NY-ESO-1–specific CD4+ T cells were detected in all patients with greater frequency and polyclonality when Montanide-ISA-51 was used for vaccination. Inclusion of Poly-ICLC as an adjuvant further accelerated the induction of NY-ESO-1–specific immune responses.Conclusions: The current study shows that NY-ESO-1 OLP vaccine is safe and rapidly induces consistent integrated immune responses (antibody, CD8+ and CD4+) in nearly all vaccinated patients when given with appropriate adjuvants. Clin Cancer Res; 18(23); 6497–508. ©2012 AACR.

PDF file - 196K, Humoral immune responses to NY-ESO-1 protein and peptides in individual patients throughout vaccination with NY-ESO-1 OLP. A) Reciprocal titers of plasma IgG antibodies were measured throughout vaccination by ELISA against NY-ESO-1 recombinant protein. Each patient was tested for all available time points, from prestudy (pre) up to week (w) 16. B) IgG plasma antibody responses were analyzed using 20-mer OLP in ELISA from samples at the time points where maximal titers had been achieved against NY-ESO-1 protein following vaccination. Peaks represent titers against 20-mer individual peptides centered around amino-acids from NY-ESO-1 shown along the X-axis. Reciprocal titers were considered significant if > 100. Assays representative of at least 2 repeats.

PDF file - 65K, Immunohistochemical analysis of NY-ESO-1 expression (mAb E978) in tumor tissue and vaccine regimen

We investigated the feasibility, safety, and survival outcomes of intrathoracic cytoreduction during primary debulking surgery (PDS) for advanced ovarian cancer.We conducted a database review of patients with stage IIIB-IV ovarian (including fallopian tube and primary peritoneal) carcinoma who underwent PDS at our institution from 01/01/2006-9/30/2021. Patients who underwent intrathoracic cytoreduction as part of primary treatment were included. Patients who received neoadjuvant chemotherapy or surgery for reasons other than cytoreduction were excluded.Among 178 patients identified for inclusion, complete gross resection (CGR) in the abdomen and thorax was achieved in 131 (74%); 45 (25%) had optimal cytoreduction, and 2 (1%) had suboptimal cytoreduction. Thirty-one patients (17%) had at least one grade ≥ 3 complication; 8 were possibly related to intrathoracic cytoreduction. There were no deaths within 30 days following surgery. Median length of follow-up among survivors was 53.4 months. Among all patients, the median PFS was 33.6 months (95% CI: 24.7-61.9) and the 3-year PFS rate was 48.9% (95% CI: 41.2%-56.2%). Median OS was 81.3 months (95% CI: 68.9-103). When stratified by residual disease status, median PFS was 51.8 months when CGR was achieved versus 16.7 months with residual disease (HR: 2.17; P.001) and median OS was 97.6 months when CGR was achieved versus 65.9 months with residual disease (HR: 2.05; P = .003).Intrathoracic cytoreduction during PDS for advanced ovarian cancer is both safe and feasible. CGR can be achieved in patients with intrathoracic disease if properly selected, and could significantly improve both PFS and OS.

Frailty has been suggested as a construct for oncologists to consider in treating older cancer patients. Therefore, the authors assessed the potential of creating a deficit-accumulation frailty index (DAFI) from a largely self-administered comprehensive geriatric assessment (CGA).Five hundred patients aged ≥65 years underwent a CGA before receiving chemotherapy. A DAFI was constructed, resulting in a 51-item scale, and cutoff values were examined for patients in the robust/nonfrail (cutoff value, 0.0 0.2), prefrail (cutoff value, 0.2 0.35), and frail (cutoff value, ≥ 0.35) groups.Two hundred and fifty patients (50%) were nonfrail, 197 (39%) were prefrail, and 52 (11%) were frail. Older patients (aged ≥ 80 years) and those who had lower education, were living alone, and had higher stage disease were associated with prefrail/frail status. Prefrail/frail patients were more likely to have grade ≥3 toxicity but not to have a dose delay or reduction, and they were more likely to discontinue drug and be hospitalized. The association with grade ≥3 toxicity was attenuated by controlling for a toxicity risk calculator, but the other outcomes were not.A deficit-accumulation frailty index can be constructed from a CGA in older patients with cancer and can indicate the frailty status of the population. The frailty status so determined is associated both with outcomes likely because of chemotherapy toxicity and with those likely because of age-related physiologic and functional deficits and thus can be useful in the overall assessment of the patient. Cancer 2016;122:3865-3872. © 2016 American Cancer Society.

Brain structural deviation is known to be present in chronic patients with schizophrenia when compared with normal age-matched individuals. While the assumption is that these differences are based on a neurodevelopmental disturbance, whether they are static or continue to change throughout the disease process remains unknown. The following report describes a prospective follow-up study of first episode cases of schizophrenic illness. Analyses of MRI evaluations on an approximate annual basis for a minimum of four years are presented on 50 patients and 20 controls. Computer-assisted image analysis measuring the volume of several brain regions, using the program ANALYZE (Mayo Clinic), was performed on all scans. Patients were compared with controls for the rate of change over time in size of structures. No differences were found for the volumes of the caudate nucleus, temporal lobes, or hippocampus; and no changes in the degree of cerebral laterality were detected. However, there was a significant difference in the rate of change in the overall volumes of left and right hemispheres (P < 0.0004 and 0.001, respectively), right cerebellum (P < 0.02) and area of the isthmus of the corpus callosum (P < 0.05). The left cerebral ventricle had significantly greater enlargement over time when measured on coronal slice sequences (P < 0.02), but was not detected by axial views. These findings suggest that a subtle active brain process may be continuing through the first few years of a schizophrenic illness causing greater than the normal adult cortical deterioration. Further studies using other methods of image analysis and over a longer period of time are needed to determine the course and nature of this biologic process.

To integrate the principles of geriatric assessment into the care of older patients with cancer in order to identify vulnerable older adults and develop interventions to optimize cancer treatment.A brief, comprehensive, self-administered questionnaire and intervention algorithm were developed consisting of measures of geriatric assessment that are brief, reliable, validated, and predictive of mortality and morbidity in older patients.Academic tertiary care cancer center and community-based satellite practice.Patients aged 65 and older with cancer.The questionnaire solicits information about the patient's functional status, comorbidity, psychological status, nutritional status, and social support. A scoring algorithm for referral to a multidisciplinary team was developed.Two hundred forty-five of 250 patients completed the questionnaire (mean age 76, range 65-95). The majority of patients were women (71%), white (95%), married (52%), and retired (90%), with a variety of tumor types and stages. Most patients (78%) completed the questionnaire on their own and reported acceptance of questionnaire length (91%), no difficult questions (94%), no upsetting questions (96%), and no missing questions (89%). The mean time to completion was 15 minutes, with a median of 12.5 (standard deviation 10, range 2-60). Information from this questionnaire helped identify physical and psychological impairments, poor nutrition, lack of social support, and untreated comorbidities. Appropriate referrals to a multidisciplinary team were made.This brief, comprehensive, self-administered questionnaire is feasible for use in the outpatient oncology setting and helped identify the needs of geriatric oncology patients. Prospective trials are needed to determine the effectiveness of the interventions offered.

Objective : A cortical gray matter deficit has been found in cross-sectional studies of patients with chronic schizophrenia. The purpose of this study was to examine whether this deficit is present early in the course of illness. Method : The authors measured cortical gray matter volume on magnetic resonance images acquired within 6 months of onset of illness from 22 patients with first-episode schizophrenia and 51 age-matched comparison subjects from the Stony Brook First Episode Study. Results : A significant cortical gray matter deficit and lateral ventricular enlargement were found in schizophrenic patients relative to the comparison group. Conclusions : The presence of the cortical gray matter deficit close to onset of illness supports the role of preexisting structural brain deficits in the genesis of schizophrenia.

Brain morphological abnormalities have been reported in several independent investigations of chronic schizophrenic patients. The present study is a prospective 4-year follow-up of first-episode schizophrenic patients to determine whether some of these abnormalities may be a consequence of regional brain structural change over time after the onset of a first psychotic episode. Whole hemisphere, temporal lobes, superior temporal gyrus, hippocampus, caudate, corpus callosum, and lateral ventricles were measured in a series of MRI scans taken over a 4-year period in 20 patients and five controls. Total volume reduction was noted in both hemispheres to a greater degree in patients than controls. When adjusted for total brain size, left ventricular enlargement occurred in patients, but not controls, over time. These preliminary data suggest that subtle cortical atrophy may be occurring over time after the onset of illness.

I have pleasure in again welcoming the Society to the historical old town of Pontefract. You met here on Thursday, the 4th November, 1869, under the presidency of Lord Houghton, and thirteen years have not dimmed the recollections of that visit, to those who were then present, or relegated to oblivion the discussions which took place with regard to the geological wealth surrounding this ancient Borough, and the division of Osgoldcross, of which it considers itself the chief centre of importance. We, as residents in the town and district, hope that the speculations then hinted at have been developing cautiously, but surely, towards commercial success and realization; and we trust that the members of this Society may find that during this interval of time, industry, energy and capital have been brought to bear in the development of our underground wealth; and that they may appreciate the progress which has been accomplished by this practical application of geological science since they last honoured Pontefract with a visit. First allow me to thank the Honorary Secretary of this Society and yourselves, for the compliment you have conferred upon me, in requesting me to act as your Local President on this occasion. I ask your considerate forbearance and co-operation in undertaking the duties of this Chair. At the same time, I desire to assure you of my earnest wishes to promote the interests of this valuable Institution, with which it has been my privilege to be associated for upwards of twenty years. After ...

This paper summarizes in broad strokes the properties of mitochondrial Ca 2+ influx and efflux systems in the possible role of mitochondria in maintaining cytosolic Ca 2+ homeostasis. Recent reviews (1-3) may be consulted for some details.