tbuckley/cabot-search huggingface dataset:
Pre-clinical studies and phase I clinical trial of the anti-CD22 immunotoxin CAT-3888 (BL22) for pediatric acute lymphoblastic leukemia (ALL)
Authors: A. Wayne, H. W. Findley, G. Lew, Y. Ahuja, L. Gu, M. Stetler-Stevenson, R. J. Kreitman, I. Pastan
Journal: Journal of Clinical Oncology (2007)

9560 Background: ALL is the most common childhood malignancy. Although highly curable, therapy is associated with multiple toxicities and ALL remains the most frequent cause of pediatric cancer mortality. Most ALL is CD22+ and we evaluated the anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22 or CAT-3888) in the treatment of pediatric ALL. Methods: In vitro cytotoxicity was assessed on blasts from 42 children with CD22+ ALL. In vivo studies were performed using a xenograft model (SCID mouse - EU1 human ALL cell line). A pediatric phase I trial of CAT-3888 was initiated. Results: CAT-3888 induced in vitro cytotoxicity against most ALL samples (median IC 50 9.8 ng/ml). A dose response was observed in murine xenografts with significant prolongation of leukemia free survival (p&lt;0.05). 18 subjects (15 ALL, 3 lymphoma; 3 - 22 years of age) were treated on a Phase I trial at doses of 10 - 40 mcg/kg QOD for 3 - 6 doses with cycles repeated every 21 - 28 days. Treatment was well tolerated and no dose limiting toxicity was seen. Pharmacokinetics were influenced by disease burden and T 1/2 showed an inverse relationship to marrow blasts (r 2 =0.5) consistent with rapid drug binding by CD22+ cells. All subjects were heavily pre-treated and had progressive high burden disease at the time of treatment. Transient clinical activity was observed in 16 of 18 subjects as evidenced by decreased peripheral blast count (8), decreased marrow infiltration (3), decreased extramedullary disease (2), increased platelet count (2), increased neutrophil count (1), increased reticulocyte count (1), improved PET scan (1), decreased tumor-associated pain (2), and/or peripheral blast count stabilization (3). A dose response was apparent with 4 of 9 (44%) achieving stable disease at or above doses of 30 mcg/kg. Conclusions: The majority of pediatric ALL blasts are highly sensitive in vitro to CAT-3888 at concentrations far below clinically achievable levels. CAT-3888 is well tolerated in pediatric patients and activity has been seen in most subjects treated on the phase I trial. CD22 represents a relevant target for pediatric ALL. A new higher affinity anti-CD22 immunotoxin (HA22 or CAT-8015) is in development. No significant financial relationships to disclose.
Clinical and technical considerations in the analysis of gingival crevicular fluid
Authors: Rebecca R. Wassall, Philip M. Preshaw
Journal: Periodontology 2000 (2015)

Abstract Despite the technical challenges involved when collecting, processing and analyzing gingival crevicular fluid samples, research using gingival crevicular fluid has, and will continue to play, a fundamental role in expanding our understanding of periodontal pathogenesis and healing outcomes following treatment. A review of the literature, however, clearly demonstrates that there is considerable variation in the methods used for collection, processing and analysis of gingival crevicular fluid samples by different research groups around the world. Inconsistent or inadequate reporting impairs interpretation of results, prevents accurate comparison of data between studies and potentially limits the conclusions that can be made from a larger body of evidence. The precise methods used for collection and analysis of gingival crevicular fluid (including calibration studies required before definitive clinical studies) should be reported in detail, either in the methods section of published papers or as an online supplementary file, so that other researchers may reproduce the methodology. Only with clear and transparent reporting will the full impact of future gingival crevicular fluid research be realized. This paper discusses the complexities of gingival crevicular fluid collection and analysis and provides guidance to researchers working in this field.
Phase I/II trial of vorinostat combined with temozolomide (TMZ) and radiation therapy (RT) for newly diagnosed glioblastoma (GBM) (N0874-ABTC0902, Alliance): Final results of the phase I trial.
Authors: Evanthia Galanis, Jann Nagina Sarkaria, S. Keith Anderson, Wenting Wu, Kurt A. Jaeckle, Caterina Giannini, Jan C. Buckner, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2013)

2046 Background: Vorinostat (VOR) is a histone deacetylase inhibitor that represents a rational targeted agent in GBM treatment. Given its single-agent activity in recurrent disease (Galanis,et al, 2009) and radiosensitizing properties, this phase I/II trial was designed to test the addition of VOR to standard chemoradiation in newly diagnosed GBM patients (pts): the phase I portion of the trial is the focus of this report. Methods: A standard cohorts of three design was used to assess the safety of VOR in combination with RT and concomitant TMZ and establish the phase II dose of the combination. VOR was given orally days 1 - 5 every wk beginning with the first dose of RT (total dose 60 Gy) and (75mg/m²/day). Following a 4 - 6 week rest, pts received up to 12 cycles of standard adjuvant TMZ in combination with VOR on days 1-7 and 15 – 21 of each cycle; dose was based on NABTT trial 04-03 (Lee, et al, 2012). Results: The phase I component is complete with 15 pts, 12 pts at dose level 0 (VOR 300 mg/day days 1 - 5, weekly x 6 wks), and 3 pts at dose level 1 (VOR 400 mg/day, days 1 – 5 weekly x 6 wks) in combination with RT/TMZ. Dose limiting toxicity (DLT) in dose level 1 included grade 3 fatigue in 2 pts, grade 3 wound dehiscence in 1 pt, and grade 4 neutropenia and thrombocytopenia in 1 pt. In dose level 0, 1/6 pts had DLT (gr 3 dyspnea). An MTD expansion cohort of 6 additional patients was added to dose level 0; one patient experienced grade 4 thrombocytopenia and grade 3 fatigue, and 1 patient experienced grade 3 febrile neutropenia. In the 12 pts treated in the phase II dose, most common toxicities were hematologic, including lymphopenia (gr 3/4 in 66.7%), thrombocytopenia (gr 3 in 16.7%, gr 4 in 16.7%) and neutropenia (gr 3 in 16.7%, gr 4 in 8.3%). Grade 3 fatigue was observed in 8.3% of the pts. Conclusions: MTD for VOR in combination with TMZ/RT in newly diagnosed GBM patients is 300 mg/d, days 1 - 5 weekly during RT. Toxicity was primarily hematologic. This dose was used in the recently completed phase II trial of the combination (110 pts). RNA expression profiling in patient samples is in process to assess vorinostat responsive signatures observed in preclinical models. Clinical trial information: NCT00731731.
Potpourri Dissected
Authors: William Silen
Journal: New England Journal of Medicine (1974)

Most textbooks define "stress ulcers" as acute esophagogastroduodenal lesions that arise in close temporal proximity to a whole host of somewhat disparate circumstances, which include shock, sepsis, burns (Curling's ulcers), intracranial lesions (Cushing's ulcers) and the administration of steroids. The common thread that has tenuously bound these conditions is barely discernible. Recently, however, real progress has been made in the understanding of the pathogenesis of these various lesions, and evidence has been adduced to support separation of this potpourri into distinctive components.The predominantly fundic gastric erosions observed by Lucas et al. in all of 40 septic and traumatized patients . . .
Tailored low-dose gemcitabine-cisplatin combination is a feasible and effective treatment in heavily pretreated advanced breast cancer patients
Authors: J. E. Alés-Martínez, S. Hernández, R. Sánchez-Escribano, P. Aramburo
Journal: Journal of Clinical Oncology (2005)

837 Background: Combining gemcitabine (G) plus cisplatin (C) at low doses is effective in advanced breast cancer. We sought to determine if this was clinically meaningful in women relapsing after a minimum of 2 prior lines of chemotherapy (CT) for advanced disease (range 2–6). The goal was to adjust frequency and dosage according to patient tolerability with no treatment discontinuation. Methods: Twenty patients with relapsed advanced BC and a minimum of two prior CT lines were offered treatment with G (initial dose: 750 mg/m2) plus G (initial dose: 30 mg/m2), days 1 and 8 on a 21-day cycle. Treatment was postponed to day 15 if it could not be given on day 8, without dose reduction. If treatment could not be given on day 15, a 20% dose reduction was allowed and treatment given on the next week. Further dose reductions were allowed. Treatment continued until disease progression or intolerable toxicity. Median age was 54.5 years (35–75). Median Karnofsky was 90 (range 80–90). Median number of prior CT lines was 3 (2–6). 90% of patients had received adjuvant CT. All had prior anthracyclines and taxanes. Other agents used included 5-FU/eniluracil, MTA, navelbine, RPR 109881A, trastuzumab, cisplatin, VP16, vinorelbine, capecitabine and irinotecan. 75% had received radiotherapy and 65% hormonal therapy (median 2 lines, range 1–4). Results: Partial responses were seen in 10% of patients and stable disease in 30%. Clinical Benefit Rate was 40%. Median time to progression was 3 months (95% CI, 2.33–5.13). Median survival was 9.43 months (95% CI, 3.27–19.4). Patients received a median of 8.5 CT administrations (range, 2–45). 43% doses were delayed. Cisplatin and gemcitabine doses were reduced in 75% and 62% of all cases, respectively. Reasons for discontinuation were progression (16 patients), death (3 patients) or other reasons (1 patient). Toxicities grade ≥ 3 were neutropenia 35% and thrombocytopenia 15%. All other toxicities were grade 2 o less. Conclusions: Flexible downwards tailoring of G and C can be used safely with acceptable disease control in heavily pretreated BC patients with good PS. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Oncology Lilly Oncology Lilly Oncology
Iron Status in Hypogammaglobulinemia
Authors: Hasan I Atrah
Journal: Journal of the Royal Society of Medicine (1985)

Iron, transferrin and ferritin were measured in serum samples from 16 patients with primary hypogammaglobulinemia. Transferrin saturation was low in 12 patients (75%) and serum ferritin was low in 9 patients (56.25%). Both parameters were low, confirming the state of iron deficiency, in 6 patients (37.5%). These figures are highly significant ( P &lt; 0.01) when compared with the prevalence of iron deficiency in the general population. Eight patients were maintained on intravenous immunoglobulin infusions and the rest on intramuscular immunoglobulin injections, their mean serum IgG being 4.4 g/l and 2.6 g/l respectively. There was no difference in the prevalence of iron deficiency between the two groups.
A population-based study on the quality of life for cancer patients as reported in a tumor registry follow-up
Authors: P. J. Novotny, J. A. Sloan, M. Frost, M. Harris, J. Huntington, C. Chute, K. Clement-Brown
Journal: Journal of Clinical Oncology (2006)

8594 Background: Between 1/96 and 3/00, 94,516 SF-36 or SF-12 Quality of Life (QOL) forms were sent to every patient on the Mayo Clinic tumor registry not seen at the clinic in the last year. This study is a descriptive summary of each patient’s first reported QOL score. Method: QOL scores were combined with tumor registry information about age, gender, tumor site, tumor stage, residence, and date of diagnosis. Responder versus non-responder characteristics were compared via Fisher’s exact tests and two-sample t-tests. Means and standard deviations were used to summarize the data. Patient reported scores and SF norms from a healthy population were compared using one sample t-tests. Results: Data were available on 28,166 patients (48,463 forms). Men were more likely to respond. More patients were male (56%) with a mean age of 66 and filled out their first SF form an average of 9 years after their initial diagnosis. Overall, mean physical and mental subscale scores were not clinically different from the age- and sex-adjusted SF normative data (Table). Within tumor sites, mental subscale scores were similar to the general population. Physical subscale scores were also approximately normal within each of the tumor sites. The exceptions were that patients with lung or musculoskeletal cancers tended to report lower physical scores than a healthy population. Conclusions: Patients responding to a tumor registry follow-up program reported QOL scores that were not clinically different from that of a healthy population. QOL deficits observed in patients with lung cancer and musculoskeletal cancers may indicate a need for targeted interventions specific for these cancer patient populations. [Table: see text] No significant financial relationships to disclose.
LP06 : Sustained virologic response after ACH-3102 and sofosbuvir treatment for 8 or 6 weeks: A phase 2 “proxy” study
Authors: E. Gane, C. Schwabe, M. Mader, V. Suri, M. Donohue, M. Huang, J. Hui, J. Yang, H. Robison, D. Apelian, H. Kocinsky
Journal: Journal of Hepatology (2015)
Prognostic value of right ventricular function in patients with severe pulmonary hypertension associated with respiratory disease
Authors: Andrew Swift, Smitha Rajaram, Dave Capener, Catherine Hill, Christine Davies, Judith Hurdman, Robin Condliffe, Charlie Elliot, Jim Wild, David Kiely
Journal: European Respiratory Journal (2013)

Introduction   The presence of pulmonary hypertension in patients with respiratory disease is an indicator of poor clinical outcome. The aim of this study was to assess the association between right ventricular (RV) function and survival in patients with severe pulmonary hypertension ‘out of proportion’ to respiratory disease (PH-RESP).   Methods   In 94 patients with pulmonary hypertension associated with respiratory disease, pulmonary function tests, high resolution computed tomography, cardiac magnetic resonance (CMR) imaging and right heart catheter were performed. RV measurements were analysed as predictors of mortality in patients with severe PH-RESP (mean pulmonary artery pressure ≥ 40 mmHg)   Results   48 of 94 patients were diagnosed with severe PH-RESP. During the follow-up period of 2.5 years (+/-8months), of the 48 patients with severe PH-RESP, 31 patients died.  WHO functional class (p=0.002), TLCO (%) (p=0.029) RVEF (p=0.024), PVRI (p=0.015) were univariate predictors of adverse outcome at Cox proportional hazards regression analysis in severe PH-RESP. At multivariate analysis, WHO functional class (p=0.036), TLCO (p=0.019), RVEF (p=0.033) remained significant predictors of outcome.   Conclusion   Patients with severe pulmonary hypertension associated with respiratory disease have a dire clinical outcome. RVEF is an independent predictor of adverse outcome in these patients and may be a powerful biomarker for use in clinical trials of targeted therapy in this population.
Thymidylate synthase polymorphisms and its mRNA expression levels as independent chemo-predictive markers in esophageal adenocarcinoma patients receiving 5-fluorouracil chemotherapy
Authors: H. Kuramochi, K. Tanaka, B. J. Lehman, C. M. Dunst, D. S. Oh, S. R. Demeester, J. A. Hagen, K. D. Danenberg, T. R. Demeester, P. V. Danenberg
Journal: Journal of Clinical Oncology (2006)

4063 Background: Thymidylate synthase (TS) has either a two or three 28bp tandemly repeated sequence in the 5’ untranslated (UTR) region. The triple repeat allele (3R) is classified into 2 subgroups (3RG, 3RC) according to a G/C polymorphism in the 3R sequences. Another polymorphism is a 6bp deletion in the 3’-UTR region. The genotype with either 3RG allele or 6bp insertion allele has been reported to be associated with high TS expression and chemoresistance to 5-FU. Methods: 83 patients with esophageal adenocarcinoma were assessed. Thirty-four had received 5-FU containing chemotherapy (16 adjuvant therapy, 12 upon recurrence, 3 both adjuvant and recurrence, 3 neoadjuvant) and 49 were treated with surgery alone. Surgically resected tumor tissues were analyzed for TS genotype and TS mRNA expression using a quantitative real-time RT-PCR method after microdissection. Results: No survival difference was seen between the patients with 3RG allele (3RG group) and non-3RG group among surgery-alone patients. However, among patients with a history of 5-FU-based chemotherapy, the non-3RG group showed significantly better overall survival compared to the 3RG group (p = 0.02). Moreover, whereas chemotherapy produced a significant increase in survival for the non-3RG group patients, those in the 3RG group obtained no survival benefit from chemotherapy. Patients with low TS mRNA levels had significantly better survival than the patients with high TS mRNA levels (p = 0.03) among chemotherapy-treated patients, despite the fact that there was no difference of median TS mRNA levels between 3RG and non-3RG group. Those who had both the non-3RG genotype and low TS mRNA levels obtained a significantly better survival benefit from chemotherapy than others (p = 0.02). The 3’-UTR polymorphism did not appeared to be associated with overall survival. Conclusions: The status of the TS 5’-UTR polymorphism and TS mRNA expression are independent predictive markers for survival benefit from 5-FU-based therapy in patients with esophageal adenocarcinoma. [Table: see text]
A phase III trial of cisplatin plus topotecan followed by paclitaxel plus carboplatin versus standard carboplatin plus paclitaxel as first-line chemotherapy in women with newly diagnosed advanced epithelial ovarian cancer (EOC) (OV.16). A Gynecologic Cancer Intergroup Study of the NCIC CTG, EORTC GCG, and GEICO
Authors: P. J. Hoskins, I. Vergote, G. Stuart, A. Cervantes, D. Tu, M. Carey, D. Provencher, D. Katsaros, P. Ghatage, E. Eisenhauer
Journal: Journal of Clinical Oncology (2008)

LBA5505 Background: Topotecan was evaluated in a novel combination regimen in comparison to standard therapy in front-line EOC. Methods: Women with newly diagnosed EOC stages IIB-IV, ECOG PS 0–1, age ≤ 75, and were randomized to one of two q 21 day regimens. Arm 1 cycles 1 to 4: cisplatin 50 mg/m2 d1 plus topotecan 0.75 mg/m2 d1–5 IV; cycles 5 to 8: paclitaxel 175 mg/m2 over 3 hrs d1 followed by carboplatin AUC5 day 1. Arm 2 paclitaxel plus carboplatin as in Arm 1 for 8 cycles. Patients (pts) were stratified for type of primary surgery/residual disease, centre, and age (< 65 vs. > 65 yrs). The primary endpoint was progression free survival (PFS). Progression was defined as the earlier of objective or CA125 progression (GCIG definition) or death. Secondary endpoints were response (in pts with measurable disease), CA125 normalization at 3 mo, overall survival, toxicity and Quality of Life. The sample size required 800 pts and 631 progression events to demonstrate an increase in PFS from 16 to 20 months with a power of 80% and alpha (2-sided) <0.05. Results: 819 pts (409 Arm 1, 410 Arm 2) were entered from Aug 2001 to June 2005. All randomized patients were included in the analysis. 650 pts have had a progression event and 406 have died. Pt characteristics were well balanced. Median age was 57 yrs (range: 28–78); 80% had debulking surgery: of these 55% had < 1 cm residual disease; 8.5% pts were stage II, 66% stage III, 25.5% stage IV. Arm 1 vs Arm 2 pts had more hematological toxicity (gr 3/4 febrile neutropenia 9.9% vs. 2.7%) and hospitalizations (11.3% cycles vs. 7.1% cycles). Conclusions: Topotecan/cisplatin followed by carboplatin/paclitaxel was more toxic and did not show any evidence of improved efficacy compared to standard therapy. Carboplatin plus paclitaxel remains the standard of care for advanced EOC. * stratified log rank; ** stratified Cochran-Mantel-Haenszel No. Pts Arm 1 Arm 2 Hazard Ratio Odds Ratio p value PFS median (mo) 819 14.6 16.2 1.10 (0.94-1.28) 0.25* CR + PR (%) 389 67.9 77.2 0.63 0.04** CA125 normal < 3 mo (%) 819 57.5 66.3 0.63 0.006** Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline
원저 : 수술로 절제된 간의 국소 결절성 증식의 임상적 특징
Authors: 황남철, 최문석, 이준혁, 고광철, Paik， Seung Woon, Yoo Byung Chul, 이종철, 이광웅, 조재원, 박철근
Journal: Clinical and Molecular Hepatology (2004)

목적: 간의 국소 결정성 과형성은 일반적으로 특별한 치료가 필요 없는 양성 종양이다. 그러나 드물지만 합병증이 발생한 경우와 진단이 불확실한 경우에는 수술을 시행하게 된다. 이에 저자들은 간절제술을 시행한 국소 결절성 과형성의 임상적, 영상학적 특징들을 알아보고자 하였다. 대상과 방법: 1995년부터 2003년까지 수술을 시행하여 조직을 확인한 국소 결절성 과형성 환자 10명을 대상으로 연령, 성별, 실험실 검사 및 영상 소견과 조직 소견을 분석하였다. 결과: 연령의 중앙값은 37.5세, 남녀 비는 1.5:1이었다. 5예에서는 간세포선종이나 간세포암종을 감별할 수 없어서 수술을 시행하였으며, 수술 후 우연히 진단된 예는 4예이었다. 간세포암종의 위험 인자를 가지고 있었던 예는 4예(B형 간염 바이러스 보유자 3예, 간경변 2예)이었다. CT검사가 시행되었던 6예 중 5예는 동맥기에서 조영 증강을 보였고 문맥기 및 지연기로 감에 따라 주변과 동일(4예)한 또는 감소(2예)되는 양상을 보여 간세포암종과의 감별이 어려웠다. 크기는 3.2±2.2㎝이었으며 위치는 간우엽의 후하구역(S6)에 가장 많았다(30.0%). 4예에서 수술 전 침생검을 시행하였으나 고분화 간세포암종이나 간세포선종과의 감별이 어려웠다. 결론: 임상상, 영상검사 및 간침생검으로도 간세포암종이나 간세포선종과의 감별이 어려운 경우 수술을 시행하였으며 수술 전에는 발견하지 못하였지만 다른 질환으로 인한 수술시 우연히 발견된 경우도 있어 국소 결절성 과형성의 수술 전 진단이 어려운 경우가 적지 않음을 알 수 있었다.
The molecular evolution of prostate cancer cell line exosomes with passage number.
Authors: D. Spetzler, T. L. Pawlowski, T. Tinder, J. Kimbrough, T. Deng, J. Kim, B. Moran, A. Conrad, P. Esmay, C. Kuslich
Journal: Journal of Clinical Oncology (2010)

e21071 Background: Exosomes are endosome-derived vesicles secreted by multiple cell types, including tumor cells. The vesicles are formed intracellularly by invagination followed by fusion with the multivesicular body (MVB). The MVB merges with the plasma membrane, resulting in the exocytosis of exosomes which have membrane protein composition similar to their cell of origin. These circulating vesicles have been shown to participate in cellular communication by transporting mRNAs, microRNAs (miRs) and proteins to target cells, eliciting biological responses. This study examined the dynamics of exosome biosignatures from prostate cancer (PCa) cell lines. Methods: Exosome-associated RNA and surface membrane protein profiles from the prostate cancer cell line VCaP were analyzed by flow sorting (FACS) and a multiplexed immunoassay. The surface membrane protein composition and RNA content of VCaP exosomes were measured through twenty cell line passages. Results: The surface membrane protein composition of VCaP exosomes changes over time as the cell line is passaged. Exosomes from early passages had high levels of exosomal tetraspanins (CD9, CD81, CD63), but low levels of prostate (PCSA, PSMA) and cancer specific (B7H3, Epcam) proteins. As the number of passages increased the levels of all the proteins increased, particularly the prostate and cancer associated markers. Exosomal messenger and miR content was also evaluated over passage number, and a four-fold increase in the amount of total RNA in an equivalent amount of exosomes was found to occur over time. Expression levels of the VCaP associated fusion transcript TMPRSS/ERG increased along with the protein signature and passage number. Conclusions: Our findings show that PCa cell line derived exosomes evolve over time. If comparable changes are occurring in tumor progression in vivo, exosome biosignature analysis might offer a useful tool to monitor tumor dynamics and response(s) to therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Caris MPI