tbuckley/cabot-search huggingface dataset:
Excision cross-complementing group 1 (ERCC1) single nucleotide polymorphisms (SNPs) and survival in cisplatin (cis)/docetaxel (doc)-treated stage IV non-small cell lung cancer (NSCLC) patients (p): A Spanish Lung Cancer Group study
Authors: M. Taron, V. Alberola, G. Lopez Vivanco, C. Camps, R. De Las Peñas, G. Alonso, M. Provencio, A. Salvatierra, J. Sanchez, R. Rosell
Journal: Journal of Clinical Oncology (2006)

7053 Background: SNPs are the result of historical errors in DNA replication or repair that have been inherited through generations and are now shared among individuals. ERCC1 belongs to the nucleotide excision repair pathway. We examined whether ERCC1 SNPs 118 C/T and C8092A affect the repair of cis DNA lesions and thereby influence survival in cis-treated NSCLC p. Methods: SNP genotyping of ERCC1 118C/T and C8092A was performed by the TaqMan assay, and results were correlated with median survival (MS) in 706 cis/doc-treated stage IV NSCLC p. Results: Characteristics: 590 male, 116 female; performance status (PS) 0: 216 p (30.6%), PS 1: 480 p (68%), PS 2: 10 p (1.4%); adenocarcinoma, 371 p (53%). Overall response rate: 30%. After a median follow-up of 7.8 months (m) (range, 1–47 m), overall MS was 8.9 m. SNP frequencies: 118 T/T, 40.2%; C/T, 45.4%; C/C, 14.4%; C8092A C/C, 57.6%; C/A, 36%; A/A, 6.4%. MS according to 118 C/T SNP: T/T, 8.9 m; C/T, 9.5 m; C/C, 10 m (P = 0.51). MS according to C8092A SNP: C/C, 9.3 m; C/A, 10.2 m; A/A, 7.2 m (P = 0.05). When stratified by PS, the association between C8092A and MS is stronger for p with PS 0: C/C, 15.9 m; C/A, 13.8 m; A/A, 8.7 m (P = 0.04). Conclusions: This is the largest study to date reporting the effect of ERCC1 C8092A SNP on MS in stage IV NSCLC p treated with a single regimen. The uncommon A/A genotype predicts poor survival in p treated with dis/doc. No significant financial relationships to disclose.
4-1BBL/4-1BB costimulation alleviates airway inflammation by restoring Treg/Th17 balance in allergic asthma
Authors: Xiangyan Ai, Guochao Shi, Xiaoxia Hou
Journal: European Respiratory Journal (2012)

Objective : Recent studies have demonstrated Th17/Treg imbalance in patients with asthma and the effect of 4-1BBL/4-1BB on Th17/Treg balance. This study aimed to investigate whether 4-1BBL/4-1BB costimulation alleviated airway inflammation by restoring Treg/Th17 balance in OVA-induced asthmatic mice.

Methods : BALB/c mice were randomly assigned to three groups (asthma group, 4-1BB group and control group). Mice in the asthma group were sensitized and challenged with OVA. Agonistic 4-1BB mAb was administered in the 4-1BB group. Mice in control group were treated with PBS.

Results : (1) The serum IgE concentration [23.350 (65.945–42.635) ng/L vs. 99.292 (192.185-92.893) ng/L, P <0.01], total number of cells [(17.35±3.23)×106 vs. (6.44±1.90)×106, P <0.05] and eosinophils [(9.79±3.84)×104 vs. (0.91±0.37)×104, P <0.05] in bronchoalveolar lavage fluid (BALF) and airway inflammation in the 4-1BB group were significantly reduced compared with the asthma group. (2) Agonistic 4-1BB mAb treatment decreased IL-17 [(225.747±15.000) ng/L vs. (265.730±23.121) ng/L, P <0.05] but increased TGF-β levels [(24.468±8.229) ng/L vs. (16.047±2.789) ng/L, P <0.05] in BALF in asthmatic mice. Agonistic 4-1BB mAb inhibited the expression of Th17 cells [(3.18±0.39)% vs.(6.25±2.62)%, P <0.01] and RORγt mRNA[(10.766±3.285)×10-3 vs. (30.853 ±5.686)×10-3, P <0.01] in lung.

Conclusions : Agonistic 4-1BB mAb treatment partially alleviated airway inflammation by restoring the function of Treg cells and inhibiting the proliferation and function of Th17 cells.
Abstract 363: Recovery of Exercise Intolerance and Ventricular Dysfunction of Infarcted Spontaneously Hypertensive Rats After Oral Treatment With an Agonist of Adenosine Receptor
Authors: Jaqueline S da Silva, Roberto T Sudo, Roberto Debom, Eliezer J Barreiro, Carlos A Fraga, Gisele Zapata-Sudo
Journal: Circulation Research (2015)

Severe ventricular dysfunction is observed in spontaneously hypertensive rats (SHR) submitted to myocardial infarction (MI). The present work evaluates the cardioprotective effects of oral administration of a novel agonist of adenosine A2A receptor, LASSBio-294, in infarcted SHR. Methods: Male SHR (12-14 wks old) were randomly divided into groups: sham and infarcted (MI) which were either treated orally with vehicle or LASSBio-294 (10 mg/kg) for 28 days. Before and after the animals were treated with LASSBio-294, cardiac function and exercise capacity were evaluated through the echocardiography and treadmill test. Mean blood pressure (MBP), left ventricular end diastolic pressure (LVEDP) and negative dP/dt were also determined. Fibrosis in heart sections were detected using H&amp;E staining. Immunohistochemical staining for TNF-alpha and SERCA2a in LV tissues were observed. Results: MI in SHR reduced the running distance from 257.9 ± 13.2 to 39.0 ± 4.4 m which normalized to 296.0 ± 26.4 m after treatment with LASSBio-294. Reduced anterior wall thickness was observed after MI (0.51 ± 0.14 mm) which was prevented with treatment (1.65 ± 0.21 mm). Ratio of early and late transmitral filling velocity was reduced from 1.48 ± 0.09 to 0.99 ± 0.04 and recovered to 1.35 ± 0.07 after treatment. MBP was reduced from 169.0 ± 5.6 to 120.4 ± 7.4 mmHg in SHR-IM treated with LASSBio-294. Increased LVEDP of 25.6 ± 3.2 observed in SHR-IM was reduced to 7.3 ± 1.0 mmHg after treatment. The -dP/dt was reduced in SHR-MI to -5698 ± 408.1 mmHg/s and returned to -7894 ± 631.6 mmHg/s after LASSBio-294 treatment. There was an increase in collagen deposition after MI (from 14.5 ± 3.5 to 59.8 ± 5.4 %) which was prevented with LASSBio-294 treatment (29.5 ± 2.2 %). Increase of positive staining for TNF-α was observed in SHR-MI (from 9.5 ± 1.0 to 32.3 ± 2.1%) which recovered in SHR-MI treated group (14.4 ± 1.3%). Also, the expression of SERCA2a was reduced in ventricular muscle from SHR-IM (from 68.7 ± 5.1 to 21.4 ± 2.3 %) which partially recovered to 40.6 ± 1.19% with LASSBio-294 treatment. Conclusion: LASSBio-294 reduced exercise intolerance, prevented cardiac remodeling and diastolic dysfunction in infarcted SHR.
Feasibility of concomitant chemotherapy (QT) and radiotherapy (RXT) protocol for laringeal preservation in a public hospital in Brazil.
Authors: A. L. Chaves, L. V. Muniz, R. C. Lima, L. S. Aguiar, L. C. Neto, J. A. Soares
Journal: Journal of Clinical Oncology (2010)

e16032 Background: Standard treatment for advanced laryngeal cancer (ALC) is total laryngectomy with or without RXT or concomitant chemoradiation. Brazilian head and neck cancer patients (pts) in general suffer with desnutrition, advanced tumor, and poor oral care. Objective: Evaluate the feasibility and results of concomitant QT and RXT protocol for laryngeal preservation in a public hospital in Brazil. Methods: We analyzed retrospectively pts with ALC who was submmited to concomitant QT and RXT (RTOG91-11). The inclusion criteria was espinocellular carcinoma, whose the option of the surgical treatment were total laryngectomy. We evaluate demographic informations, toxicity, treatment interruption, weight loss, oral care, survival, and larynx preservation. Results: 22 pts were submitted to laryngeal preservation protocol between Feb 2006 and Jul 09. All pts were evaluated by a multidisciplinary team. 55% (12) of the pts completed the proposed protocol without interruption or dose reduction. No significant association was found between the clinical variables (sex, age, tumor site, stage, body mass index [BMI], oral status) and treatment interruption. All pts lost weight during the treatment. 33% needed enteral nutrition. The lost weight mean and BMI variation between the treatment beginning and end were 5.8 kg, 2.9, and 2.8 kg and 1.1 for the pt who did not interrupt and interrupted the treatment respectively (p<0.05). Overall 2 yrs survival was 73%, 3 pts died of systemic and 1 pt died of locoregional recurrence. 4 pts were submitted to salvage laryngectomy. The rate of larynx preservation was 77%. Conclusions: Laryngeal preservation protocol was feasible in a Brazilian public hospital with a precise indication and multidisciplinary support. N=22 Sex M/F 16/6 ECOG 0,1 95% Age median 56ü (34-79) Glote 8 Supraglote 14 T2 5 T3 17 N0,1 15 N2,3 7 BMI mean 23.83 (16-31) Toxicity % Emesys grade 2/3 55 Neutropenia grade 2/3 9 Mucositis grade 2/3 90 Dysgeusia 95 Xerostomia 78 No significant financial relationships to disclose.
Effect of complete response pre- and post- autologous stem cell transplantation in multiple myeloma
Authors: F. Sayani, D. Stewart, L. Kmet, P. Faris, M. L. Savoie, A. Chaudhry, C. Brown, J. Russell, N. Bahlis
Journal: Journal of Clinical Oncology (2006)

7604 Background: The value of achieving a complete response (CR) pre or post high dose therapy and autologous stem cell transplant (HDT-ASCT) in multiple myeloma is still uncertain. Knowing the impact of achieving a CR prior to HDT-ASCT on survival, may lead to the incorporation of novel therapeutic agents into the front line treatment of this disease. The aim of our study was to determine whether achieving a CR before or after HDT-ASCT affects overall survival (OS) in multiple myeloma patients. Methods: We performed a retrospective analysis of 88 consecutive myeloma patients receiving HDT-ASCT at our center from 1993 to 2004. The OS of patients achieving at least 90% reduction in their M-protein, i.e. complete response and very good partial response (CR/VGPR), pre or post HDT-ASCT, was compared to that of patients achieving a partial response or less (&lt;90% reduction in M-protein). OS, defined as the number of months from HDT-ASCT to death or last follow up, was estimated by the Kaplan-Meier method. Response status was evaluated pre and at 100 days post HDT-ASCT. Results: Prior to HDT-ASCT, twenty-two (25%) patients achieved a CR/VGPR. Median follow-up time was 39 months for patients in CR/VGPR and 18 months for non-CR/VGPR group. OS at 5 years was 58% (95% CI: 21%-82%) for patients in CR/VGPR, compared to 69% (95% CI: 51%-81%) for all patients in PR or less prior to stem cell collection. Post HDT-ASCT, 48 (55%) patients achieved a CR/VGPR. Their OS estimate at 5 years was 67% (95% CI: 44%-82%) compared to 71% (95% CI: 27%-92%) for all other patients. Overall, 30% more patients achieved CR/VGPR post HDT-ASCT. However, the survival curves did not differ by response status pre or post HDT-ASCT (log-rank test p=0.58 and 0.57 respectively). Conclusions: Our results suggest that achieving a clinical CR/VGPR pre or post HDT-ASCT does not appear to impact OS. These results might have been influenced by the small sample size and the possible need for a longer follow-up time. A more robust definition of CR at the molecular level, plus the use of novel therapeutic agents in front-line treatment, may better define the impact of achieving CR in multiple myeloma. No significant financial relationships to disclose.
Gene expression profiling of neuroblastoma: Analysis of nonmetastatic versus metastatic tumors
Authors: J. Mora, M. Alaminos, N.-K. Cheung, J. Rios, W. Gerald
Journal: Journal of Clinical Oncology (2004)

8538 Background: Previously we reported a significant distinction in gene expression profile between neuroblastoma (NB) tumors and cell lines, and stroma-rich and stroma-poor NB tumors. Tumors clustered into 2 groups correlating with clinically defined prognostic groups of favorable and unfavorable tumors. In this study we analyzed tumors with and without clinically proved metastatic potential. Methods: we present the analysis of 25 locoregional and 27 stage 4 tumors all stroma poor and >1 year of age. Microarray analysis was carried out using Affymetrix Genechip Human Genome U95 SetTM with features for 63,175 gene/EST. To calculate the ability of individual genes to distinguish between sample groups we used 1. Calculation of maximal variability and >3 standard deviation between groups and 2. Step-down permutation and false discovery rate methods. For multivariate analysis, unsupervised methods like SOMS, PCA, K-nearest neighboring, and hierarchical clustering were applied. Results: By contrast analysis, 61out of 12,000 known annotated genes from chip A were differentially expressed in LR cases compared to stage 4. By permutation analysis only 3 out of the 12000 annotated genes showed statistical significance. Multivariate analysis showed a poor distinction between LR and stage 4 tumors with a third of samples classifying in the wrong groups. Classification models build to distinguish groups using support vector machines, k-nearest neighboring and log regression showed a cross validation accuracy that ranged from 76 to 89%. Conclusions: the gene expression profiles of tumors presenting as LR or disseminated disease suggest the existence of more than 2 groups of tumors. A “metastatic” gene expression profile could not be detected. No significant financial relationships to disclose.
대한간학회지 제6차 춘계학술대회 초록집 : 구연 ; 간성뇌병증에 의한 과암모니아혈증의 치료에 있어서 Rifaximin과 Lactulose의 효능 및 안전성 비교
Authors: 박인서 ( Park In Seo ), 김명환 ( Kim Myeong Hwan ), 한광협 ( Han Gwang Hyeob ), 백용한 ( Baeg Yong Han ), 문병수 ( Mun Byeong Su ), 윤석화 ( Yun Seog Hwa ), 이관식 ( Lee Gwan Sig ), 전재윤 ( Jeon Jae Yun ), 문영명 ( Mun Yeong Myeong )
Journal: Clinical and Molecular Hepatology (2000)
Unrelated donor hematopoietic cell transplantation (HCT) as treatment for acute myeloid leukemia (AML) in first remission
Authors: J. M. Pagel, T. Gooley, B. M. Sandmaier, L. Drouet, E. W. Petersdorf, M. L. Sorror, J. A. Hansen, H. J. Deeg, P. J. Martin, R. Storb, F. R. Appelbaum
Journal: Journal of Clinical Oncology (2007)

7000 Background: Unrelated donor HCT has been used with increasing frequency for the treatment of AML patients in first remission. Methods: Between 1990 and 2005, 105 adult patients with AML [66 (62%) primary and 39 (38%) secondary] received T- cell-replete HCT from unrelated donors in Seattle. Results: Median age was 44 (range, 18–74) years. Seventy-nine patients received ablative conditioning for HCT (57% conditioned with cyclophosphamide plus total body irradiation (TBI), 43% with chemotherapy alone). Non- myeloablative doses of fludarabine (FLU; 25 mg/m 2 daily for 3 days) and TBI (200 cGy) were delivered to 26 patients. Ninety-six percent of patients who underwent reduced-intensity conditioning received unrelated peripheral blood stem cells (PBSC) while 59% of myeloablative HCT patients received PBSC as their source of stem cells. For all patients, the leukemia-free survival (LFS) and non-relapse mortality estimated at 2 years were 53%, and 26%, respectively, as 27 patients died of transplant-related causes (pulmonary-6, cardiac-1, graft versus host disease (GVHD)-6, infection-5, and unknown-9). Twenty-two patients (21%) relapsed 2 to 83 months (median 5) post-transplant, and 56 patients are surviving disease-free 1 to 168 months (median 27) post-transplant. For 90 patients (86%) with intermediate-risk cytogenetics, 51 (57%) are surviving disease-free, with 16 (18%) relapsing. Fourteen patients (13%) were considered high risk based on unfavorable cytogenetics; 4 of these 14 (29%) are surviving disease-free and 6 (43%) have relapsed. The probability of grade 3/4 acute GVHD was 19% while the probability of clinical extensive chronic GVHD was 54% one year after transplant. Unfavorable cytogenetics (HR=2.16, p=.08), secondary leukemia (HR=1.71, p=.10), higher co-morbidity score (p&lt;.0001), and HLA mismatching (HR=2.35, p=.02) were associated with an increased hazard of mortality. After controlling for these factors, non-ablative conditioning was not statistically worse than ablative conditioning (HR=1.21, p=.61). Conclusions: These data suggest that HCT using unrelated allografts has the potential to provide significant LFS for patients undergoing HCT for AML in first remission when an HLA family match is not available. No significant financial relationships to disclose.
Allogeneic stem cell transplantation for X-linked agammaglobulinemia using reduced intensity conditioning as a model of the reconstitution of humoral immunity
Authors: Kazuhiro Ikegame, Kohsuke Imai, Motoi Yamashita, Akihiro Hoshino, Hirokazu Kanegane, Tomohiro Morio, Katsuji Kaida, Takayuki Inoue, Toshihiro Soma, Hiroya Tamaki, Masaya Okada, Hiroyasu Ogawa
Journal: Journal of Hematology & Oncology (2016)

We herein report the first case of X-linked agammaglobulinemia (XLA) that underwent allogeneic stem cell transplantation using reduced intensity conditioning (RIC). We chronologically observed the reconstitution of humoral immunity in this case. The patient was a 28-year-old Japanese male with XLA who previously had life-threatening infectious episodes and was referred for the possible indication of allogeneic stem cell transplantation. After a thorough discussion within specialists from different backgrounds, we decided to perform allogeneic peripheral stem cell transplantation from his HLA-identical elder brother. Due to the non-malignant nature of XLA, we selected RIC consisting of fludarabine, cyclophosphamide, anti-thymocyte globulin, and 3 Gy of total body irradiation. Neutrophil engraftment was achieved on day 11 with complete donor chimerism. No major complications, except for stage 1 skin graft-versus-host disease, were observed. The patient was discharged on day 75 and has been followed as an outpatient without any infectious episodes for more than 500 days. Regarding immune reconstitution, CD19+ cells, IgA, and IgM, which were undetectable before allogeneic stem cell transplantation (allo-SCT), started to increase in number 10 days after allo-SCT and continued to increase for more than 1 year. Anti-B antibodies appeared as early as day 10. Total IgG levels decreased after the discontinuation of IgG replacement and spontaneously recovered after day 350. However, most anti-viral IgG titers, except EB virus-virus capsid antigen IgG, disappeared after the discontinuation of IgG replacement. A seasonal vaccination to influenza was performed on day 148, with neither anti-influenza type A nor type B being positive after the vaccination. The transient transfer of allergic immunity to orchard grass was observed. Similar Bruton's tyrosine kinase (BTK) expression levels in monocytes and B-cells were observed between the patient and healthy control. B-cells in the peripheral blood (PB) of the patient on day 279 showed sufficient proliferation after a CD40L and IL-21 or CD40L and CpG stimulation. Effective immunoglobulin production and class switching were also observed after a CD40L and IL-21 or CpG stimulation. Signal joint kappa-deleting recombination excision circles (sjKRECs) became positive 16 days post-SCT, increased to 6300 copies/μg DNA at 42 days, and were maintained at a high level thereafter. The recovery of T-cell receptor excision circles (TRECs) was slow, but became detectable 1 year post-hematopoietic stem cell transplantation (HSCT).
Change of serum CEA or CA19–9 is predictive for chemotherapeutic efficacy in recurrence or metastasis gastric cancer
Authors: L. Shen, Q. Y. Lu, M. Lu
Journal: Journal of Clinical Oncology (2008)

15654 Background: To date, the clinical value of serum markers on gastric cancer remains unclear. To evaluate whether tumor markers can be used to assess response to systemic chemotherapy, we retrospective evaluated the usefulness of change of CEA and CA19–9 levels as markers in patients with recurrence or metastasis gastric cancer (mGC) treated with systematic chemotherapy. Methods: From Jul 1996 to Dec 2006, among 256 patients (median 58 years, range 26–76) with histologically proven gastric adenocarcinoma, those who had elevated CEA or CA19–9 levels at baseline and had measurements after at least 3 cycles chemotherapy were evaluable, total 100 cases by CEA and 99 cases by CA19–9 were enrolled. A responder was defined as a ≥30% reduction of CEA or a ≥50% reduction of CA19–9 for at least 4 weeks, respectively. Non responders were defined as a ≥30% rise of CEA or a ≥50% rise of CA19–9 for at least 4 weeks. The correlation between the response rate for chemotherapy assessed by CEA or CA19–9 and by WHO criteria (including median time to progression (TTP) and overall survival (OS) were analysed. Results: A CEA responder predicted true responders (CR+PR) with a sensitivity of 71.4% and specificity of 88.5%. Patients with a CEA non responder had a sensibility of progression disease of 68.5% and a specificity of 90.7%. For patients with a CA19–9 responder, a sensitivity of 47% and a specificity of 96.6% on true responders could be calculated, but it drops to 43.3% of sensibility and 91.3% of specificity on prediction progression disease in CA19–9 non responders. Our data in Table shows that both TTP and OS were significant different between responders and non responders by CEA or CA19–9 in mGC. Conclusions: The current findings suggest that the change of CEA or CA19–9 can sever as a feasible prognostic parameter and predictive indicator for response of chemotherapy in mGC. TTP and OS using Kaplan-Meier method for responders and non responders assessed by change in CEA or CA19-9 levels CEA responder n=45 CEA nonresponder n=30 P CA19–9 responder n=30 CA19–9 nonresponder n=19 P TTP(m) 6.13 2.56 0.000 6.76 2.26 0.000 OS(m) 13.46 9.30 0.074 15.13 9.46 0.024 No significant financial relationships to disclose.
Phase II study of bevacizumab (A) plus capecitabine (X) in patients (pts) with advanced/metastatic hepatocellular carcinoma (HCC): Final report
Authors: C. Hsu, T. Yang, C. Hsu, H. Toh, R. Epstein, L. Hsiao, Z. Lin, A. Cheng
Journal: Journal of Clinical Oncology (2008)

4603 Background: Asian pts (∼60–80% HBV etiology) with advanced or metastatic HCC have a dismal prognosis, with a median survival (OS) ∼2–4 months with best supportive care (BSC). A, an anti-VEGF antibody targeting tumor angiogenesis, induced objective tumor response in pts with unresectable HCC [Schwartz et al. ASCO 2006;abs 4144]. The oral fluoropyrimidine X was safe and moderately active for pts with advanced HCC in a retrospective study [Patt et al. Cancer 2004;101:578]. We evaluated the efficacy and toxicity of A+X in pts with advanced/metastatic HCC. Methods: Pts with histologically-proven or clinically diagnosed HCC who could not be treated by surgery or other loco-regional therapies received A 7.5 mg/kg iv d1 and X 825 mg/m2 bid orally d1–14, q3w. Tumor assessment was performed q6w. Primary endpoint was overall response rate (ORR) by RECIST. Results: Between May05 and Aug06, 45 Asian pts were enrolled. Baseline characteristics: male/female 40/5; median age 54 (range 23–75); Child Pugh A; TNM stage IVA/IVB 16/29; CLIP score ≤3/4 34/11; 76% of pts had no prior treatment. All pts had either extrahepatic metastasis (n=31) and/or major hepatic vessel invasion (n=25). Virology of underlying chronic liver disease were HBV/HCV/nonBnonC 30/8/10 pts. Pts received a median of 3 (range 1–31) cycles of A+X, which was generally well-tolerated. There was no grade 3/4 hematologic toxicity. Treatment-related grade 3/4 toxicities were diarrhea (n=2), nausea/vomiting (n=1), GI bleeding (n=4, 3 EV bleeding), HFS (n=4), lower respiratory tract infection (n=1), fulminant hepatitis (n=1), and proteinuria (n=1). ORR was 9%, with 4 PR and 19 SD, to give a disease control rate of 52%. PFS and OS are summarized in the table below. Conclusions: A+X is a safe outpatient regimen and has moderate antitumor activity for Asian pts with advanced HCC. The optimal dose and schedule of A+X warrants further investigation in this setting. CLIP Score Number of patients Median PFS (months) Median OS (months) ≤ 3 34 (16 CLIP score 3) 3.6 (95% CI: 1.5 - 6.0) 8.2 (95% CI: 5.0 - 11.3) = 4 11 1.4 (95% CI: 1.2 - 3.3) 3.3 (95% CI: 2.5 - 5.2) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Hoffmann-La Roche Hoffmann-La Roche