tbuckley/cabot-search huggingface dataset:
Abstract 139: Ultrasound Stimulation Restores Impaired Neovascularization-Related Capacities of Human Circulating Angiogenic Cells
Authors: Yasuyuki Toyama, Ken-ichiro Sasaki, Katsuro Tachibana, Takafumi Ueno, Hidemi Kajimoto, Shinji Yokoyama, Msanori Ohtsuka, Hiroshi Koiwaya, Takaharu Nakayoshi, Yoshiaki Mitsutake, Hidetoshi Chibana, Naoki Itaya, Tsutomu Imaizumi
Journal: Circulation Research (2012)

Aims: Unsatisfactory effects of therapeutic angiogenesis in critical limb ischemia may be ascribed to use of circulating angiogenic cells (CACs) with impaired neovascularization-related capacities of atherosclerotic patients. We tested whether ultrasound cell stimulation can restore the impaired capacities. Methods and Results: During four-day-culture of human peripheral blood-derived mononuclear cells to achieve CACs, we stimulated the culture cells daily with low-intensity pulsed ultrasound stimulation (LIPUS). LIPUS to healthy volunteer-derived culture cells augmented generation and migration capacities of CACs, increased concentrations of angiopoietin 2 and nitrogen oxides in the culture medium, and increased expressions of phosphorylated-Akt and endothelial nitric oxide synthetase in CACs on western blotting. LIPUS to atherosclerotic patient-derived culture cells also augmented the generation and migration capacities of CACs. Although neovascularization in the ischemic hindlimb of athymic nude mice was impaired after intramuscular injection of atherosclerotic patient-derived CACs compared with that of healthy volunteer-derived CACs, LIPUS to atherosclerotic patient-derived culture cells restored the impaired neovascularization. Conclusion: Therapeutic angiogenesis with LIPUS-pretreated CACs may be a new strategy to rescue critical limb ischemia in atherosclerotic patients.
Thrombus Aspiration during Myocardial Infarction
Authors: Roberto Diletti, Patrick W Serruys
Journal: New England Journal of Medicine (2014)

To the Editor: In the Thrombus Aspiration in ST-Segment Elevation Myocardial Infarction (STEMI) in Scandinavia (TASTE) trial, Frobert et al. (Oct. 24 issue)1 report that routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI), as compared with PCI alone, did not reduce 30-day mortality in the study patients. Aspiration thrombectomy during primary PCI is recommended to reduce the coronary thrombus burden in clinical practice.2 Accordingly, we call into question the TASTE trial design. First, given the open inclusion criteria, many patients who had no or minimal evidence of thrombus on initial angiography of the target (or culprit) vessel would have been included in the study. In such circumstances, aspiration thrombectomy may have no value and may cause harm (e.g., vessel dissection). Second, balloon angioplasty may cause clot embolization and microvascular obstruction and thus limit the benefit of concomitant aspiration thrombectomy. In the TASTE trial,3 the use of balloon angioplasty before or after thrombectomy or the use of direct stenting was not described. Third, the sample size was based on the rates of cardiac death at 30 days in the Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS).4 However, the primary outcome in the TASTE study was all-cause mortality at 30 days, which raises the question of whether the study was underpowered for its primary outcome. Given these reservations, we are very concerned that the negative results of this study may militate against the appropriate use of thrombectomy in high-risk patients with STEMI.
Abstract 77: Predictive Power of Early Lactate Clearance Regarding 30-Day Neurological Outcome After Cardiac Arrest with Cardiopulmonary Bypass
Authors: Kei Hayashida, Masaru Suzuki, Akiko Shiroshita-Takeshita, Shingo Hori
Journal: Circulation (2011)

Objective: Early lactate clearance has been reported to be associated with improved mortality in patients with post cardiac arrest syndrome (PCAS). Recently, cardiopulmonary bypass (CPB) has significantly improved prognosis of those patients, however, it has been still unknown whether early lactate clearance could predict for neurological outcome in PCAS with CPB. We aimed to investigate the usefulness of the early lactate clearance in a cardiac arrest of patients resuscitated and treated with CPB. Methods: Retrospective observational study. Between January 2000 and March 2011, 46 cardiac arrest patients with cardiac causes underwent CPB in a university hospital in Tokyo. Of those, serial arterial lactate concentrations (at ICU admission and 6 hours after ICU admission) were obtained from 21 patients (19 Males, median 61 y/o). Lactate clearance was defined as the percent change after 6 hours from baseline. The patients were divided into two groups (high lactate clearance group or low lactate clearance) by median lactate clearance. Results: The lactate clearance in the high lactate clearance group was 50.3±13.1% (mean±SD) and the low lactate clearance group -14.7±23.9%. There were no significant differences between the groups for demographics, laboratories (except platelets, baseline PaO 2 ), baseline lactate (the high lactate clearance group: 11.3±3.5mg/dl, the low lactate clearance group:10.8±4.2mg/dl), baseline arterial pressure (99.9±41.1mmHg, 96.1±26.7mmHg), use of catecholamine. In the high clearance group, there was significantly higher for favorable CPC (&lt;=2) rate (44% vs 0%, OR 2.8, 95%CI [1.48-5.40]) and Kaplan-Meier survival analysis showed a survival benefit over 30 days (log-rank; p=0.02). Cut-off points with 95% specificity in predicting favorable outcome was 67.4% for early lactate clearance (sensitivity 75%). CONCLUSIONS: Early lactate clearance is specific but only moderately sensitive markers of 30-day neurological outcome. These findings suggest that post arrest tissue hypoperfusion during CPB contributes lactate clearance, regardless CPB.
Efficacy and clinical outcomes of radiotherapy with or without chemotherapy in inoperable or post-operative high-risk cholangiocarcinoma.
Authors: Nikhil Dhirendra Kalyani, Reena Engineer, Suresh Chaudhari, Tejas Dharia, Nitin Shetty, Supriya Chopra, Shyam K Shrivastava
Journal: Journal of Clinical Oncology (2013)

273 Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after radiotherapy (endobilliary and/or external RT) with or without chemotherapy in patients with unresectable or post operative high risk extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours). Methods: From Aug 2005 to July 2012, 67 patients with non-metastatic EHBDC and hilar cholangiocarcinoma were treated with radiotherapy (endobilliary and / or EBRT) with or without chemotherapy at our institution. Sixty one patients had unresectable disease while remaining six patients were post operative patients. Twenty two patients received only endobilliary RT, 20 patients received only EBRT, while 25 patients received both. Concurrent Gemcitabine during EBRT was given in 10 patients. Histopathological diagnosis was available in 50 patients (75%). Median dose for EBRT and endobilliary RT was 45 Gy (range: 25 Gy to 57 Gy) and 14 Gy (range: 12 Gy to 20 Gy) respectively. Results: Median age was 54 years (range 23-76 years) and there were 37 men and 30 women. Median follow up for whole group was 6 months (range 1-28 months). Seven patients had complete response, 22 patients had partial response, 4 patients had stable disease, while 6 patients had progressive disease after EBRT. Twenty five patients were alive at last follow up. The median overall survival was 7 months and one year survival was 30% for whole group. Patients receiving EBRT (with or without endobilliary) had better survival as compared to patients receiving only endobilliary RT (median survival 13 months Vs 5 months, p=0.001). The main sites of distant disease progression were liver and peritoneum. Eighteen patients had developed cholangitis while 3 patients developed hematemesis due to duodenitis. Conclusions: Radiation in unresectable cholangiocarcinoma is feasible with acceptable clinical outcome and toxicity. Patients receiving EBRT has better outcome as compared to those receiving only endobilliary RT.
Role of Natural Killer Cells in Tumor Growth and Metastasis: C57BL/6 Normal and Beige Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: James E. Talmadge
 5, Kenneth M. Meyers, David J. Prieur, Jean R. Starkey
Journal: JNCI Journal of the National Cancer Institute (1980)

The role of natural killer (NK) cells in tumor growth and metastasis was studied in syngeneic normal and beige inbred C57BL/6 mice. Mice with the beige point mutation have been shown to be deficient in nonstimulated NK activity. Tumor-passaged B16 malignant melanoma cells were refractory to NK activity as determined by in vitro assay, but after in vitro culture they became sensitive to NK activity. The NK-insensitive B16 tumor grew and metastasized similarly in normal and beige mice. However, the NK-sensitive B16 tumors grew more slowly and produced fewer metastases in normal mice than in NK-deficient beige mice. Activation of NK cells by lymphocytic choriomeningitis virus infection decreased the rate of growth and number of metastases of both NK-sensitive and NK-insensitive tumors in both normal and beige mice. These results suggest the importance of NK cells as a determinant of tumor growth and metastasis.
Hepatic arterial infusion (HAI) compared to systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma: A systematic review and meta-analysis of randomized controlled trials
Authors: S. Mocellin, P. Pilati, M. Lise, D. Nitti
Journal: Journal of Clinical Oncology (2007)

14519 Background: The treatment of unresectable liver confined metastatic disease from colorectal cancer is a challenging issue. Although locoregional treatments such as HAI claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, the evidence for benefit in terms of overall survival (OS) is conflicting. We aimed to quantitatively summarize the results so far described in randomized trials comparing HAI to systemic chemotherapy. Methods: To date, ten randomized controlled trials (RCT) have been published, for a total of 1,277 patients enrolled. Seven RCT (n=1,098) enrolling at least 50 patients per arm (the minimum sample size required to achieve a type II error lower than 20%) were considered for OS meta-analysis, which was based on the inverse of variance method. For tumor response rates, hazard ratios (HR) and their 95% confidence intervals (CI) were obtained from raw data; for OS, HR and CI were obtained from reported Cox model survival analyses or were calculated from Kaplan-Meier survival curves according to the Parmar method. Results: HAI regimens were based on floxuridine (FUDR) in nine out of ten RCT, while in one case 5-fluorouracil (5FU) + leucovorin (LV) were used. Systemic chemotherapy consisted of FUDR, 5FU, 5FU + LV, or a miscellany of 5FU and best supportive care in three, one, four and two studies, respectively. Tumor response and median OS were better in the HAI arm in eight and three RCT, respectively. At meta-analysis, median tumor response rate was 38.84% and 17.30% for HAI and systemic chemotherapy, respectively (HR: 2.24, CI: 1.80- 2.81; P &lt; 0.0001); on average, median OS was 16.04 and 12.64 months, respectively (HR: 0.83, CI: 0.58–1.19; P value 0.30). Conclusions: Although HAI regimens are followed by significantly higher tumor response rates, no OS advantage can be demonstrated for this locoregional treatment as compared to systemic chemotherapy. Since HAI has been so far compared to systemic chemotherapy regimens not containing modern and more effective antineoplastic agents (e.g. oxaliplatin, irinotecan), these findings do not support the clinical or investigational use of FUDR-based HAI. No significant financial relationships to disclose.
Paget's disease of the ulna: a rare location.
Authors: JOSE INFANTE, FRANCISCO GONZALEZ, JOSE GONZALEZ, CARMEN PACHECO, JUAN VALLEJO, MIGUEL TORRES, JOSE LATRE
Journal: Clinical Nuclear Medicine (2001)

INFANTE, JOSE R. Ph.D.; GONZÁLEZ, FRANCISCO M. M.D.; GONZALEZ, JOSE Ph.D.; PACHECO, CARMEN M.D.; VALLEJO, JUAN A. Ph.D.; TORRES, MIGUEL Ph.D.; LATRE, JOSE M. Ph.D. Author Information
Phase I safety and pharmacokinetic (PK) study of sunitinib (S) in combination with ifosfamide (I) in patients (pts) with advanced solid tumors (STs)
Authors: P. Hamberg, N. Steeghs, W. J. Loos, D. J. van der Biessen, M. A. den Hollander, M. Tascilar, J. Verweij, H. Gelderblom, S. Sleijfer
Journal: Journal of Clinical Oncology (2009)

e13520 Background: S is a tyrosine kinase inhibitor (TKI) of PDGFR, VEGFR and KIT. As combinations of VEGFR-TKI with cytotoxic therapy are promising, this phase I study aimed to determine the recommended phase II dose (RP2D) of S in combination with 2 different I schedules. Methods: Pts with progressive STs, good PS, organ function, and no standard therapy available, were eligible. I (3 g/m 2 /day, 72h CIV (I*3), every 3 wks) was combined with continuous S. S was started at 12.5 mg/day and to be escalated in serial cohorts of 3–6 pts. RP2D was exceeded if ≥ 1/3 pts experienced dose-limiting toxicity (DLT) within the 1 st cycle. After establishing the RP2D of S with I*3, feasibility of this S dose with I at 1.2 g/m 2 /day for 5 days CIV (I*5) every 3 wks was assessed without further scheduled dose-escalation. At RP2D, additional patients were enrolled to assess PK. Circulating endothelial cells (CECs) were measured prior to the 1 st , 3 rd and 6 th cycle. Results: 26 pts (36–68 yrs) were accrued. 12.5 mg S was not feasible with I*3 due to neutropenia &gt; 7 days in 2/6 pts. After protocol amendment, pegfilgrastim 6 mg (P) was given to all subsequent patients after each I-cycle. Using P, the RP2D was I*3 plus 12.5 mg S (in 1/9 pts DLT: febrile neutropenia), while I*3 plus 25 mg S was not feasible due to febrile neutropenia in 2/5 pts and hypertension &amp; cardiac chest pain in 1/5 pts. 12.5 mg S was also feasible using I*5 as 1/6 pts had a DLT: encephalopathy. Most frequent drug related adverse events (all grades/grade 3–4) were: neutropenia (77%/62%), thrombocytopenia (73%/31%), elevated transaminases (65%/0%), renal (42%/4%), nausea (77%/0%), vomiting (58%/0%) and alopecia (62%/0%). 4/22 pts evaluable for response had PR: 1 CUP, 1 small cell carcinoma (SCC) and 2 sarcoma pts. 7 pts had SD for ≥ 3 months: 1 CUP, 1 uveal melanoma, 1 SCC, and 4 sarcoma pts. The AUC ratio of I and its metabolites in cycles I*3 without versus with S ranged from 0.72 to 1.36. No consistent change in the number of CECs during treatment was observed. Conclusions: S at 12.5 mg/day with I*3 or I*5 every 3 weeks supported by P is tolerable in pts with advanced STs. S does not affect I-PK. Antitumor activity was observed in pts with diverse tumor entities including sarcoma. No significant financial relationships to disclose.
Effect of percutaneous biliary drainage (PBD) for malignant biliary obstruction (MBO) on quality of life (QoL)
Authors: P. M. Robson, N. Heffernan, R. Holmes, M. Gonen, J. Schubert, G. I. Getrajdman, L. A. Brody, K. T. Brown, A. M. Covey, L. H. Blumgart
Journal: Journal of Clinical Oncology (2007)

9029 Background: PBD is routinely performed to relieve MBO. The clinical effects of drainage have been well documented, but little has been reported about how PBD effects a patient's QoL. Methods: Between October, 2004 and December, 2006, eligible patients (&gt;18 years old, English speaking, clinical diagnosis of MBO) scheduled to undergo PBD at a comprehensive cancer center were invited to participate in a prospective study evaluating QoL using the Functional Assessment of Cancer Therapy Hepatobiliary (FACT-Hep) instrument, comprised of 5 subscales (physical, emotional, functional and social well being, and disease-specific concerns). FACT is the total score of the first four items; FACT-Hep is the total score of all 5 subscales. Patients completed the instrument at baseline, one week and four weeks following PBD. Instruments were scored following FACT guidelines; changes in QoL between these time points were analyzed using a mixed effect model with time as a categorical variable. Results: One hundred twenty five patients consented to participate in this study. Sixteen were not evaluable and were withdrawn from the study. One hundred nine (60 male / 49 female) patients completed the baseline instrument (100%), 57% at one week and 39% at four weeks. Thirty four patients (31%) completed all time points. The most common diagnoses included cholangiocarcinoma (30%), pancreatic cancer (29%), and metastatic colorectal cancer (17%). Mortality was 10% (N=11) at 4 weeks and 28% (N=30) 8 weeks following PBD, with one patient dying from a procedure related complication. The mean FACT scores are indicated in the table below. A declining score is associated with a decline in QoL. Conclusions: PBD for MBO does not improve overall QoL following PBD. Patients have significant disease related mortality within eight weeks of the procedure. [Table: see text] No significant financial relationships to disclose.
Clinical presentation and sensitivity to platinum-based chemotherapy (CT) of mucinous advanced epithelial ovarian carcinoma (M-AEOC): The GINECO-Group experience
Authors: J. Alexandre, I. Ray-Coquard, F. Selle, A. Floquet, P. Cottu, B. Weber, C. Falandry, D. Lebrun, E. Pujade-Lauraine
Journal: Journal of Clinical Oncology (2009)

5572 Background: M-AEOC have been consistently associated with worse prognosis than the most common serous (S) histologic subtype; however it is unclear if this observation is related to more aggressive clinical presentation and/or chemoresistance behaviour. Methods: Data from four randomized phase III and one phase II AEOC first-line clinical trials were collected and retrospectively analyzed. Study selection criteria included: completed study, platinum-based chemotherapy and stage IIB to IV AEOC patients (pts). Results: Data on 1118 pts with advanced AEOC were analysed, of whom 94% were treated with paclitaxel-carboplatin-based CT. 786 pts had S-AEOC and 54 pts M-AEOC (5%). Peritoneal metastasis (mets) appeared more limited in M- than in S-AEOC pts since stages IIB-IIIB were more frequent (31% versus 19%, p = 0.001) and complete resection more frequently obtained (45% of stage II-III pts versus 29%, p = 0.06) in M-AEOC. Extra-peritoneal mets (stage IV) were more frequent in M- than in S-AEOC pts (30% versus 15%, p = 0.004), specially liver mets (44% of stage IV pts versus 23%, p = 0.06). Progressive disease during CT was observed in 40% of pts with stage IV M-AEOC. Progression free survival (PFS) was worse in M- than in S-AEOC pts both in stage IV (1y PFS: 15% versus 51%, p = 0.02) and in stage III with optimal resection (2y PFS: 42% versus 66%, p = 0.05). Conclusions: Compared to S-AEOC, M-AEOC is characterized by more limited peritoneal carcinomatosis but more frequent liver mets. M-AEOC appears to be a highly chemoresistant disease and complete resection of peritoneal mets is unable to reverse its adverse prognosis. New therapeutics options are needed. No significant financial relationships to disclose.
A phase II trial of lithium, bevacizumab, temozolomide, and radiation for newly diagnosed glioblastomas (GBM).
Authors: Ashwatha Narayana, Moses M Tam, Deborah Beth Gruber, John Golfinos, Erik Parker, David Zagzag, Michael L. Gruber
Journal: Journal of Clinical Oncology (2013)

e13033 Background: Invasion is a dominant escape mechanism following angiogenic blockade in glioblastomas (GBM). Lithium has shown anti-invasive activity in glioma cells by inhibiting Glycogen Synthetase Kinase -3. This phase II study evaluated the safety and efficacy of using lithium and bevacizumab (BEV) in newly diagnosed GBM. Methods: From 2010 through 2012, 20 GBM patients with residual disease after surgery were treated with involved-field radiation therapy to 5940 cGy and concomitant temozolomide (TMZ) (75 mg/m2 daily for 42 days) along with BEV (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by six 28-day cycles of TMZ (150 mg/m 2 on days 1-7, BEV (10 mg/kg) on days 8 and 22, and lithium 300 mg BID. Lithium was increased every 7 days up to 600 mg BID with a serum lithium goal level of 0.8 to 1.2 mEq/L. Results: The median follow-up was 9.9 months (range 1.9-24.5). Fourteen patients (70.0%) received at least one dose of lithium and three patients completed the entire course of therapy. The median number of BEV infusion was 9 (range 2-19). Five patients discontinued trial due to skin sensitivity (n = 2), pulmonary embolism (n = 1), infection (n = 1), and hematological toxicity (n=1). Two patients experienced dose limiting lithium toxicity which included drowsiness (n = 1) and tremor (n = 1). No patients experienced grade 3/4 intra-cranial hemorrhage. The median progression free survival (PFS) was 9.3 months. The 12-month PFS and OS were 31.9% and 59.3% respectively. For the 14 patients who received lithium, the 12-month PFS and OS were 42.9% and 69.2% respectively. Conclusions: The strategy of targeting angiogenesis and invasion simultaneously in newly diagnosed GBM is effective and feasible. Clinical trial information: NCT01105702.
Low-Dose Histone Deacetylase Inhibitor Treatment Leads to Tumor Growth Arrest and Multi-Lineage Differentiation of Malignant Rhabdoid Tumors
Authors: Andrea Muscat, Dean Popovski, W. Samantha N. Jayasekara, Fernando J. Rossello, Melissa Ferguson, Kieren D. Marini, Muhammad Alamgeer, Elizabeth M. Algar, Peter Downie, D. Neil Watkins, Jason E. Cain, David M. Ashley
Journal: Clinical Cancer Research (2016)

Malignant rhabdoid tumor (MRT) and atypical teratoid rhabdoid tumors (ATRT) are rare aggressive undifferentiated tumors primarily affecting the kidney and CNS of infants and young children. MRT are almost exclusively characterized by homozygous deletion or inactivation of the chromatin remodeling gene SMARCB1 SMARCB1 protein loss leads to direct impairment of chromatin remodeling and we have previously reported a role for this protein in histone acetylation. This provided the rationale for investigating the therapeutic potential of histone deactylase inhibitors (HDACi) in MRT.Whereas previously HDACis have been used at doses and schedules that induce cytotoxicity, in the current studies we have tested the hypothesis, both in vitro and in vivo, that sustained treatment of human MRT with low-dose HDACi can lead to sustained cell growth arrest and differentiation.Sustained low-dose panobinostat (LBH589) treatment led to changes in cellular morphology associated with a marked increase in the induction of neural, renal, and osteoblast differentiation pathways. Genome-wide transcriptional profiling highlighted differential gene expression supporting multilineage differentiation. Using mouse xenograft models, sustained low-dose LBH589 treatment caused tumor growth arrest associated with tumor calcification detectable by X-ray imaging. Histological analysis of LBH589-treated tumors revealed significant regions of ossification, confirmed by Alizarin Red staining. Immunohistochemical analysis showed increased TUJ1 and PAX2 staining suggestive of neuronal and renal differentiation, respectively.Low-dose HDACi treatment can terminally differentiate MRT tumor cells and reduce their ability to self-renew. The use of low-dose HDACi as a novel therapeutic approach warrants further investigation. Clin Cancer Res; 22(14); 3560-70. ©2016 AACR.