tbuckley/cabot-search huggingface dataset:
Fluorescence navigation with indocyanine green for sentinel lymph node biopsy in breast cancer
Authors: Hajime Abe, Tomoharu Shimizu, Kouichi Demura, Hiroshi Tsuchihashi, Hirotomi Cho, Satoshi Murata, Yoshimasa Kurumi, Tohru Tani
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5532 

Background : Sentinel lymph node (SLN) biopsy is a useful method to assess axillary lymph node status in early breast cancer. Currently, a vital dye, radioactive tracer, or a combination of both is used to detect SLN. The dye-guide method is convenient and safe compared with the radioactive tracer-guided method, but training is required. In the study, we present a novel method that allows the detection of SLN with high sensitivity using indocyanine green (ICG) fluorescence imaging. Methods : After the induction of general anesthesia and the combination dye of ICG and indigocarmine was injected subdermally in the areolar. Fluorescence imaging (Photodynamic Eye: Hamamatsu Photonics Co.) was obtained using a charge at 760 nm as the light source. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. The SLN was then dissected by fluorescence navigation. Results : This study enrolled 18 patients with clinically node-negative breast cancer. Their average age was 54.2 years. There were 12 cases with T1 lesions and 6 cases with T2 lesions. Subcutaneous lymphatic channels and SLN were successfully visualized in all patients. SLN was observed before skin incision in two patients. The number of fluorescence SLN ranged from 1 to 6 (mean: 2.4) and blue dyed SLN ranged from 0 to 3 (mean: 1.1). In the latter, SLN was not identified in four patients. Three patients had lymph node metastases pathologically. All of them were recognized by fluorescence imagings, but, in one patient, lymph node with metastasis was not identified by a vital dye. There were no intra- or postoperative complications associated with SLN identification. Conclusions : This ICG fluorescence imaging technique is feasible and safe to detect SLN with less invasive, real-time observation and no requirement of training. We hope that this method will provide with detection rate and negative predictive value in SLN navigation surgery.
A randomized, 5‐arm dose finding study with a mite allergoid <scp>SCIT</scp> in allergic rhinoconjunctivitis patients
Authors: O. Pfaar, M. J. Nell, J. D. Boot, S. A. Versteeg, R. van Ree, A. Roger, H. Riechelmann, A. Sperl, J. N. G. Oude Elberink, Z. Diamant, C. Bachert
Journal: Allergy (2016)

Abstract Background The safety and tolerability of a mite allergoid subcutaneous allergen immunotherapy ( SCIT ) product was previously established. The aim of this study (EudraCT number: 2011–000393–61) was to find the optimally safe and effective allergoid dose by evaluating several dosages in patients with house dust mite ( HDM )‐induced allergic rhinoconjunctivitis ( ARC ) using a titrated nasal provocation test ( TNPT ). Methods In total, 290 adult ARC patients (148 females; 142 males) with established HDM allergy and with a positive TNPT were randomized to receive placebo or mite allergoid SCIT 6667, 20 000, 50 000 or 100 000 AU eq/ml for 12 months. Patients were updosed weekly, followed by monthly maintenance dosing. The primary study endpoint comprised the clinical response to TNPT after 12 months of treatment. Secondary endpoints included response to TNPT after 6 months, PNIF measurements, symptom and medication scores during the last 8 weeks of treatment, serum immunoglobulins and safety assessments. Results After 12 months, a dose–response was observed showing statistically significant improvements in the TNPT with SCIT concentrations of ≥20 000 AU eq/ml, while no significantly different outcomes were reached after 6 months. Specific serum IgG and IgG 4 levels were dose dependently increased. In the highest dose group, more treatment‐emergent adverse events were observed compared with the lower dose groups. Conclusion In this mite allergoid SCIT dose finding study in HDM ‐induced ARC , concentrations of ≥20 000 AU eq/ml showed both immunological effects and clinical efficacy in the TNPT compared with placebo. The risk–benefit ratio favours 20 000 AU eq/ml and 50 000 AU eq/ml strengths for further clinical development.
In vitro preclinical study results for a phase I adoptive immunotherapy trial using cetuximab with allogeneic NK cells in KRAS oncogene-mutated metastatic colorectal cancer patients.
Authors: F. Re, E. Todisco, D. Genovese, I. Turin, L. Rimassa, A. Ibatici, L. Castagna, A. Santoro, D. Montagna
Journal: Journal of Clinical Oncology (2010)

e14057 Background: Prognosis for metastatic colorectal-cancer (mCRC) patients is unfavorable. Futhermore mCRC patients with tumors harboring a mutation in the KRAS gene do not derive benefit from the administration of cetuximab. We hypothesized that KRAS mutated CRC cells may be susceptible to cetuximab-induced ADCC mediated by healthy donor NK cells. Methods: Purified allogeneic NK cells or preincubated with IL-2 or IL-15 were used as effectors. Seven different CRC cell lines (DLD1, HCT-116, HT-29, LOVO, SW620, SW48, SW480) labeled with 51Cr were used as target cells alone or preincubated with cetuximab for ADCC assay. Results: All but one (SW620) cell lines express EGFR and MHC molecules; 4/7 harbor KRAS mutation (DLD 1, HCT-116, SW620, SW480). All cell lines were susceptible to unstimulated NK cells lysis (mean 20% ± 4.57, at ratio 25:1; mean 15% ± 3.65, at ratio 12:1) and lytic activity is strongly enhanced by IL-2 or IL-15 (mean 48% ± 5.8, at ratio 25:1; mean 38% ± 4.3, at ratio 12:1) (p < 0.05). No difference in lytic activity was observed between IL-2 vs. IL-15 and thawed vs. fresh NK cells. The SW48, a KRAS wilde-type cell line was killed by NK cells from 38% of lysis without cetuximab to 50% with cetuximab (E/T ratio of 50:1, p < 0.05). Similarly the HCT-116, a KRAS mutated cell line was killed by NK cells from 20% without cetuximab to 36% with cetuximab (E/T ratio of 50:1, p < 0.05). When IL-2 or IL-15 activated NK cells were used as effectors, both targets lysis increased from 50% without cetuximab to 71% with cetuximab (E/T ratio of 100:1, p < 0.05). When SW620 (EGFR expression 0%) was used as target cell line, pre-coating with cetuximab did not enhanced unstimulated or pre-activated NK lysis capacity. Conclusions: allogeneic NK cells are cytotoxic versus all tested cell lines. Moreover lytic activity of thawed and fresh NK cells is similar. In ADCC assay NK cell lytic activity is significantly enhanced by cetuximab; surprisingly cetuximab mediated ADCC activity is independent from CRC cell lines KRAS oncogene mutational status and require EGFR membrane expression. Moreover lytic activity of IL-2 and IL-15 activated NK cells is increased by cetuximab. No significant financial relationships to disclose.
Clinical benefit of catumaxomab in malignant ascites in patient subpopulations in a pivotal phase II/III trial
Authors: S. Parsons, M. Hennig, R. Linke, A. Klein, A. Lahr, H. Lindhofer, M. Heiss
Journal: Journal of Clinical Oncology (2009)

e14000 Background: Parsons et al. (ASCO 2008) reported the results of a pivotal phase II/III trial in patients with malignant ascites due to epithelial cancer. Treatment with the trifunctional antibody catumaxomab resulted in a clinically relevant prolongation of puncture-free survival, defined as the time to the next therapeutic puncture or the time to death, whichever occurred first. Malignant ascites is a typical late-stage manifestation of cancer associated with a poor prognosis and survival. Effective treatment options are limited. It is thus of special interest if all patient subgroups derive objective benefit from treatment. Methods: A post-hoc analysis was performed on the 258 patients with epithelial tumors treated with catumaxomab + paracentesis or paracentesis alone (control) in the pivotal trial to investigate any association between the primary endpoint (puncture-free survival) and the primary tumor, metastases, or other prognostic parameters. Results: Puncture-free survival was lower in patients with non-ovarian vs ovarian tumors and those with a poor prognosis (metastases vs no metastases, elderly vs younger, or low vs serum protein level). However, there was always a statistically significant treatment effect for catumaxomab compared with the respective control group (p≤0.0001, log rank test, for all comparisons) (see table). Conclusion: Catumaxomab demonstrated a significant clinical benefit in patients with malignant ascites independent of the primary tumor or other prognostic factors. Therefore, catumaxomab could be considered as a treatment option for patients with a poor prognosis. [Table: see text] [Table: see text]
Prospective evaluation of treatment-related pain in patients (pts) with localized breast cancer (lbc). Preliminary report
Authors: M. C. Queinnec, E. Pichard, B. George, M. Di Palma, N. Hurtaud, F. Ben Merabet, F. Acker, P. D’Agostino, B. Falissard, J. L. Misset
Journal: Journal of Clinical Oncology (2005)

8021 Background: Treatment-related (surgery with sentinel +/- axillary dissection, radiotherapy, chemotherapy) pain in pts with LBC is insufficiently evaluated. Because no extensive pain syndrome classification is available and its influence on the quality of life is not defined, no specific management has been established. Methods: From 2001 to 2002, 1023 pts were included with a minimum follow-up of 1 yr. The existence and extent of pain, as well as quality of life score (0–10) was evaluated by the pts themselves, who completed 3 mail questionnaires (MQ) at 6 weeks, 6 months, and 1 year after initial surgery. Pts who reported pain were seen at a specialized consultation and the type of pain (nociceptive vs neuropathic), its intensity (visual analogical scale 0–100) and definition of risk factors were evaluated. A pain classification system was elaborated based on this data. Results: MQ data was collected from 1023 pts at 6 weeks, 1019 pts at 6 months and 1001 pts at 1 year. Pain was reported in 479 (46.8%), 383 (37.6%), and 311 (31%) patients, respectively. Mean score of alteration of quality of life was evaluated as being 3.2 (+/- 1.97), 3 (+/- 2.09), and 2.8 (+/- 2.79). Of the 479 pts who reported pain, 367 were seen at 6 weeks, 315 at 6 months and 248 at 1 year. Nociceptive or neuropathic pain was noted as follows: 125 (34%) and 230 (62.7%) at 6 weeks, 149 (47.3%) and 150 (47.6%) at 6 months, and 131 (54.8%) and 107 (43.1%) at 1 year. The treatment that generated the most pain was surgery with axillary dissection and reconstructive surgery (data not shown). Conclusion: This study allowed us to elaborate a classification of 12 pain syndromes related to treatment. Its apparition necessitates routine clinical evaluation at the minimal time of 6 weeks. Further statistical and qualitative analyses are required. No significant financial relationships to disclose.
제10차 춘계 학술대회 초록집 : 구연 13 ; 만성 B형 간염환자에서 발생한 간세포암에서 종양 부위와 비종양 부위의 유전자 발현 양상의 비교
Authors: 연종은, 장윤정, 이지연, 서연석, 변관수, 이창홍
Journal: Clinical and Molecular Hepatology (2004)
Prognostic factors for chemotherapy response and survival using combination chemotherapy as initial treatment of advanced head and neck squamous cell cancer.
Authors: F Cognetti, P Pinnarö, E M Ruggeri, P Carlini, A Perrino, F A Impiombato, F Calabresi, M G Chilelli, D Giannarelli
Journal: Journal of Clinical Oncology (1989)

Between May 1981 and December 1987, 152 consecutive patients with locally advanced and previously untreated head and neck squamous cell cancer (HNSCC) received two or three courses of neoadjuvant chemotherapy (NAC) prior to surgery and/or radiotherapy. Eighteen percent of patients achieved a complete response and 45% a partial response (PR), for an overall response rate of 63%. A variety of pretreatment patient and tumor characteristics were analyzed for both the tumor response to NAC and survival rate. Significantly higher CR rates were found in patients with a World Health Organization (WHO) performance status (PS) of 0 to 1 than in those patients with a PS of 2 (P = .03). Patients with stage III disease were significantly more likely to respond than those with stage IV (P = .006). Evaluation of all parameters through multivariate analysis identifies the tumor classification (P = .001) and the primary site (P = .006) as the most significant in predicting CR. The overall 5-year survival rate of the entire group of patients was 18% (median survival, 14.3 months). Analysis by PS (P = .001), stage (P = .002), and tumor (P = .001), and node (P = .01) classes showed significant differences. Patients achieving a CR after NAC had a significantly improved survival rate as compared with those with residual disease at assessment (P = .0003). With the multistep regression analysis, the tumor (P = .005) and node (P = .007) classifications, and the sex (P = .03) were significant factors, but CR (P = .0004) remained the most important and independent predictive factor. Randomized prospective trials are requested to clearly establish the role of NAC on survival rates.
Measuring health-related quality of life (HRQL) in adults with controlled or partially controlled asthma
Authors: Marcelino Vieira, Emilio Pizzichini, Cristiane Rocha, Marcia Pizzichini
Journal: European Respiratory Journal (2013)

Background: Current GINA guidelines state that the objective of asthma treatment is to achieve and maintain asthma control. When asthma is partly controlled (PCA) the guidelines indicate to consider stepping up treatment to gain control. However, there is no evidence to suggest which patient might benefit of this approach.  Objective: To investigate whether the quality of life is impaired in patients with PCA on treatment with an association of inhaled corticosteroid + long acting β2 agonist.  Methods: In this cross sectional study, HRQL was evaluated in 57 consecutive stable asthmatics with controlled asthma [CA (n=24)] or PCA (n=33) according to GINA criteria by using the Asthma Quality of Life Questionnaire (AQLQ)1. Results are expressed as mean and 95% CI. Differences between groups were examined by unpaired t test.  Results: The global AQLQ score and the scores of each domain were significantly lower in patients with PCA (Table1).  Conclusion: Patients with PCA have significant impairment of HRQL. Measuring quality of life may help clinicians to decide stepping up asthma treatment to gain control.
Association of physical and psychological symptom burden with time to death among palliative cancer outpatients
Authors: C. Zimmermann, N. Barmala, S. Zarinehbaf, L. W. Le, W. Y. Cheung
Journal: Journal of Clinical Oncology (2007)

19523 Background: Patients with terminal cancer have a high symptom burden, which tends to increase as death approaches. Previous studies have assessed the association of symptom burden with time to death (TTD) among inpatients or using baseline data for patients enrolled in a trial. Our purpose was to determine the association of symptom burden with TTD in patients who were followed by an outpatient palliative oncology clinic (OPOC). Methods: Cancer patients seen in the OPOC between January 2005 to June 2006 and who subsequently died were identified from the palliative care database. The last outpatient Edmonton Symptom Assessment Scale (ESAS) score completed in clinic was compared among patients in the last 4 months of life. Multiple linear regression was used to determine the association of ESAS total symptom distress score (SDS), physical subscore (PHS), psychological subscore (PSS) and individual symptom scores with demographic parameters, disease characteristics and TTD. Results: In total, 198 patients were identified. All patients had stage IV cancer, the mean age was 63.8 years (SD 12.9) and 55% were male. Median survival time from initial assessment was 6.6 weeks (range 0.3 to 16.7) and mean SDS was 46.0 (SD 18.0). Sites of cancer included gastrointestinal (36%), lung (12%), genitourinary (10%), hematological (8%), gynecological (8%), breast (7%) and others (19%). There was no significant association between symptom burden and gender, age or cancer site. TTD was significantly associated with SDS (p&lt;0.001) and PHS (p&lt;0.001), but not with PSS (p=0.19). Individual symptoms most strongly associated with TTD were fatigue (p=0.001), appetite (p=0.001), drowsiness (p=0.0005) and shortness of breath (p=0.0008). There was no significant association between TTD and depression (p=0.24) or anxiety (p=0.20). Conclusions: In this outpatient palliative cancer population, the association between TTD and symptoms held true only for physical symptoms, particularly constitutional symptoms and shortness of breath which are amenable to therapy. Symptoms in palliative patients should be rigorously assessed and treated, regardless of prognosis and especially at end-of-life. No significant financial relationships to disclose.
Hazards of running a marathon
Authors: I. A Laing, S. Hood
Journal: BMJ (1997)

Superficial analysis ignores evidence on efficacy of treatmentEditor-The conclusions of John Wright and colleagues have the potential to jeopardise public health as well as patients' care; their systematic review lacks the necessary depth and understanding of the issues. 1he authors note that sleep apnoea is currently viewed as a public health concern because it is prevalent and thought to be associated with morbidity and mortality.The collective evidence from the studies included in the review supports this view; the authors' conclusions that evidence for the health effects of sleep apnoea is "weak or contradictory" and that "the relevance of sleep apnoea to public health has been exaggerated" are disturbing.The authors seem to have misinterpreted the findings of some studies.In their assessment of nine studies of hypertension judged to be methodologically adequate, the authors dismiss seven studies that show an independent association between sleep apnoea and hypertension.
Prostate cancer immunohistochemical (IHC) stains and survival in stage D3 patients (pts)
Authors: S. K. Gounder, V. T. Chang, D. Hoover, M. L. Gonzalez, S. Ahmed, C. Finch-Cruz, L. Duque, F. Zhong, K. Toomey, B. S. Kasimis
Journal: Journal of Clinical Oncology (2008)

22187 Background: We investigated expression of pathways in archival prostate cancer biopsies by IHC staining. Methods: In an IRB approved protocol, primary prostate cancer specimens were obtained from archival formalin-fixed, paraffin-embedded tissue collected between 1992 and 2006 at VA New Jersey Health Care System. The most representative tumor tissue block was chosen from each of the 42 cases evaluated. ICH stains to detect tumor expression of S6 (ribosomal), p70s6, pTEN, AKT-1, BCL-1 (Cyclin D1), VEGF, c-KIT (CD117), PDGFR-alpha (C-20), and PDGFR-beta (P20) were done by US LABS (Irvine, CA). All immunostains were evaluated by two pathologists. Immunoreactivity was scored using a semiquantitative system for intensity of staining and percentage of positive cells. Staining intensity was scored as 0 (no detectable stain), 1 (weak staining detected at intermediate to high power), 2 (moderate detected at low to intermediate power) to 3 (strong detected at low power). Percentage of positive cells was scored as 0 (0%), 1 (1–33% positive cells), 2 (34–66%), or 3 (67–100%). The total score was obtained by adding the scores of intensity and percent of positive cells. Medical records were reviewed for dates of diagnosis, and demographic and laboratory information. A Cox survival model for each stain was developed with known survival variables, Gleason score, Hemoglobin (Hgb), Alkaline Phosphatase (Alk Phos), Prostate Specific Antigen (PSA), Lactate Dehydrogenase (LDH) levels at the time of D3 stage, and the ICH grade. Results: Data from 39 patients were available. The median, age was 75 yrs (range 56–94), Gleason score was 8(6–10), LDH was 186(134–899), Hgb was 12.3(6.3–15.5), PSA was 66(0.4–2675), Alk Phos was 121(45–1119).The median survival was 204 days (18–2085). None of the stains was predictive of survival on a univariate or multivariate analysis. Conclusions: The over expression of S6, p70s6, pTEN, AKT-1, BCL-1, VEGF, c-KIT, PDGFR-alpha and PDGFR-beta by ICH on archival tissue was not predictive of survival. No significant financial relationships to disclose.
The T cell repertoire for recognition of a phylogenetically distant protein antigen. Peptide specificity and MHC restriction of staphylococcal nuclease-specific T cell clones.
Authors: A Finnegan, M A Smith, J A Smith, J Berzofsky, D H Sachs, R J Hodes
Journal: The Journal of Experimental Medicine (1986)

Previous studies (1) have indicated that the repertoire of murine T cells specific for a potentially complex protein antigen is in fact specific for a limited number of antigenic epitopes on that antigen in association with a given Ia molecule. Since those studies generally analyzed responses to antigens that differ in only a few amino acids from homologous murine molecules, it was possible that tolerance to self proteins was responsible for the limited T cell repertoire seen in responses to closely related proteins. It was therefore of interest to determine whether T cell recognition of a structurally and phylogenetically more distant protein molecule would also show specificity for a limited number of immunodominant peptides on that molecule. A series of experiments was designed to study the antigen fine specificity and MHC restriction of T cell clones specific for the bacterially derived antigen staphylococcal nuclease (Nase). T cell clones generated in (H-2b X H-2a)F1 (B6AF1) T cells were shown to be specific for Nase and to be restricted by either Ab alpha Ab beta or Ek alpha Ek beta. The fine specificity of these clones was then analyzed using cyanogen bromide and tryptic fragments and a series of overlapping 20-amino-acid synthetic peptides corresponding to and spanning the entire sequence of the Nase molecule. Two Ab alpha Ab beta-restricted clones were highly responsive to peptide 91-110, and not to other synthetic Nase peptides. In contrast, seven Ek alpha Ek beta-restricted clones were consistently responsive to peptide 81-100 and not to 91-110 or to other Nase peptides. Certain of these Ek alpha Ek beta-restricted T cells expressed an interesting crossreactivity, in that they responded to peptide 51-70 as well as to 81-100, although the response to 51-70 was characterized by a markedly shifted dose-response curve, indicating a reduced efficiency of activation by this peptide. Analysis of the amino acid sequences of these regions indicates that this unexpected crossreaction may have a structural basis. A single Nase-specific T cell line generated from BALB/c T cells was, in contrast to any of the B6AF1 clones studied, responsive only to peptide 61-80 and not to other peptides, including 81-100 or 91-110. Collectively, these findings show that Nase-specific T cells are responsive to discrete Nase peptides. Moreover, the present findings suggest that in T cell recognition of a complex and highly foreign protein antigen, a limited number of peptide epitopes are preferentially recognized by T cells in association with a given Ia molecule.