tbuckley/cabot-search huggingface dataset:
Treatment of pancreatic ductal adenocarcinoma (PDAC) by argyrin F (AF) + gemcitabine (G).
Authors: Ruben R Plentz, Xi Chen, Samarpita Barat, Przemyslaw Bozko, Cuong Bui, Bence Sipos, Markus Kalesse, Nisar P Malek
Journal: Journal of Clinical Oncology (2016)

310 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of &lt; 5%. Early diagnosis is rare and treatment options are often limited. Recent studies have reported that the proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. The aim of the present study is to explore the anti-tumor activity of this analogue Argyrin F (AF) + Gemcitabine (G) in PDAC carcinogenesis. Methods: We analyzed the effect of AF on proliferation and epithelial plasticity of different human pancreatic cancer cell lines by using MTT-, wound healing-, invasion-, colony formation-, apoptosis- and senescence assay, as well as cell cycle analysis and Western Blot. In vivo, we assessed the effects of AF and combinational (AF + G) therapy in a genetically engineered mouse model (Pdx1- Cre; LSL-KrasG12D; p53 lox/+ ) of PDAC. Results: AF inhibited pancreatic cancer cell proliferation, migration, invasion and colony formation compared to their respective untreated controls (DMSO). We also found that AF impairs epithelial-mesenchymal-transition (EMT) and induces considerable apoptosis and senescence in a dose-and time-dependent manner. AF application resulted in cell cycle G1/S phase transition. Most importantly, double treatment by AF + G showed prolonged survival and caused significant tumor reduction. Expression of Ki67 (anti-proliferative marker) and CD34 (tumor angiogenesis marker) was reduced both after AF and AF + G treatment of PDAC tumors in mice. Conclusions: Our work demonstrates that treatment with AF can successfully inhibit the growth of PDAC cells and combinational treatment with AF + G might be also a new and promising combinational therapy for human PDAC treatment.
Solitary Thumb Acrometastasis Identified on Bone Scintigraphy
Authors: Peng Xie, Jianmin Huang
Journal: Clinical Nuclear Medicine (2017)

A 45-year-old man with a history of adenocarcinoma in the right lung 3 years ago underwent a 99mTc-MDP bone scan to evaluate possible osseous metastasis. The images demonstrated intense activity in the region of left thumb, while the tracer uptakes in other bones were not typical of metastases. A CT of the hand showed diffuse sclerotic changes with destructed trabecular structure in the proximal phalanx of the left thumb. The left thumb was subsequently resected, and the pathological examination of the resected left first metacarpal bone confirmed the diagnosis of metastasis of lung adenocarcinoma.
Professionals should act on instincts if they suspect child abuse, NICE says
Authors: Nigel Hawkes
Journal: BMJ (2017)

Professionals who work with children should be curious about “soft signs” that could signal abuse or neglect, a draft guideline from the National Institute for Health and Care Excellence (NICE) says.1

These include excessive clinginess, frequent rages at minor provocation, low self esteem, and recurrent nightmares, says the guideline, which is aimed at teachers, police officers, and others who work with children outside health settings. Separate guidance already exists for healthcare professionals.

“This guidance is intended to help at the very early stages, when instinct tells you there’s something not quite right,” said Debbie Eaton, a social worker and member …
Treatment failure due to intracerebral stem cell-like behavior of glioblastoma (GBM) cells: A reason for targeted maintenance therapy with imatinib (I) and hydroxyurea (H)? An analysis of study DE21 and DE40 (Ambrosia)
Authors: G. Dresemann, C. Hosius, J. Lilienthal, E. Schleyer, U. Bogdan, M. Weller, W. Paulus
Journal: Journal of Clinical Oncology (2008)

2048 Background: As the role of normal glia cells is not totally understood the behavior of glioblastoma cells can be described as stem cell like, able to migrate along intra cerebral cords and eluding established treatment including surgery, irradiation and chemotherapy. As PDGF-R signaling seems to play a role in GBM proliferation, PDGF-R signal transduction inhibition with I was analyzed. While monotherapy of I was not effective in GBM, the combination of I plus H (I/H) showed efficacy in a small number of progressive patients (pts), with stable disease (SD) being the main result. The role of H in this concept and the optimal treatment setting for I plus H is not clear so far. Methods: We conducted two trials: study DE21, a single-center, Phase II study to analyze the effect of I/H as maintenance treatment (MT) in patients with SD; and the multi-center, randomized, phase III, open-label, cross-over design study DE40 to analyze the efficacy of I/H versus H as induction treatment in pts with progressive disease (PD). In DE21, 30 SD GBM pts post-radiotherpy (RT) and at least one chemotherapy regimen received I 600 mg/day with H 1,000 mg/day. In DE40, 240 recurrent pts, post-temozolomide failure, received either I 600 mg/day plus H 1,000 mg/day, or H 1,500 mg/day. Results: Characteristcs of both patient populations were typical. Performance status was 0, 1 or 2. Toxicity was moderate without grade IV toxicity in both studies. In DE21 22/30 pts were in stage of SD after at least one progression. In DE21 mean progression-free survival (PFS) was 7.5 months, 36 months PFS was 17%, 4 of these 5 pts with at least one prior relapse. In DE40 mean PFS was 7 weeks, 12 months PFS less than 5%. Conclusions: The results show that MT with I/H in SD pts is superior to the treatment of PD pts. As at least in part GBM cells show a stem cell-like behavior in the brain, treatment strategies can be divided into a remission inducing strategy followed by a MT for detectable or undetectable residual disease, thus preventing these GBM cells from proliferating. For some GBM pts I/H seems to be a durable MT while the role of I/H in remission induction is inferior. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Pharma Novartis Pharma Novartis Pharma Novartis Pharma
Gallium, rituximab, and dexamethasone for relapsed NHL
Authors: S. E. Smith, K. Wren, P. J. Stiff, A. Toor, T. Rodriguez, D. van Gestel
Journal: Journal of Clinical Oncology (2007)

8079 Background: Almost 50% of patients with intermediate grade non-Hodgkin's lymphomas (NHL) treated with standard CHOP- like therapy will have less than a complete response (CR) after treatment or will relapse after obtaining a CR. Salvage chemotherapy followed in responders by an autologous stem cell transplant (ASCT) can be curative. For many patients, this is not an option due to age, comorbidities, or lack of response. A non-cross resistant agent with activity in NHL which could salvage more patients is gallium nitrate Methods: We conducted a phase II clinical trial investigating the combination 3 non-myelosuppressive agents, gallium nitrate, rituximab and dexamethasone (GaRD) for relapsed or refractory DLBCL, MCL or transformed follicular lymphomas. Gallium is given at 200mg/m 2 CIV days 1–7, rituximab 375mg/m 2 IVPB day 1 and dexamethasone 40 mg po days 1–4. Eligible patients had relapsed or refractory disease and had a SWOG PS ≤3. Patients may have failed prior ASCT or allogeneic SCT. This was a 2 stage, phase II study with initial evaluation after 22 patients of whom at least 10 responders were needed for completion of the study, as determined prior to start of trial Results: We enrolled 22 patients on study. 15 had large cell, 6 had transformed follicular and 1 had mantle cell NHL. Most of these patients were refractory to one or several prior salvage regimens [13/22 (59%)]; all had prior rituximab 22/22 (100%) and 18/22 (82%) had it with there most recent treatment. No patients developed grade 3 or 4 toxicities, except grade 4 lymphopenia in 7/22 (32%). The overall response rate was 10/22 (45%); CR/CRu 8/22 (36%); PR 2/22 (9%); SD 4/22 (18%); and PD 8/22 (36%). Five patients went on to receive stem cell transplant (including 3 allogeneic and 2 ASCT). Two of the responders were patients who had failed a prior stem cell transplant: 1 ASCT failure who remains in CR &gt;18 months and an allograft failure in CR &gt;14 months after relapse. Of the 22, 10 (46%) are alive at a median f/u of 17.2 months, of whom 7 are currently NED Conclusions: This regimen appears to be effective and relatively non-toxic for patients with relapsed and refractory NHL, including stem cell transplant failure. As CR at ASCT may be associated with an improved outcome, a trial of GaRD combined with RICE is planned to improve cytoreduction prior to ASCT in patients with relapsed NHL. No significant financial relationships to disclose.
Nab-paclitaxel as second-line treatment in advanced biliary cancer.
Authors: Gerald W. Prager, Gabriela Kornek, Werner Scheithauer, Guenther G. Steger, Christoph Zielinski, Matthias Unseld
Journal: Journal of Clinical Oncology (2015)

463 Background: Addition of nab-paclitaxel to gemcitabine has recently been demonstrated in the clinical phase III trial MPACT to be beneficial for progression free survival, overall response rate, and overall survival in advanced pancreatic cancer patients. Any potential biologic activity of nab-paclitaxel in biliary cancer is hitherto unknown. Methods: A retrospective analysis of patients with advanced biliary cancer was undertaken to determine the disease control rate (CR+PR+SD), progression-free survival and overall survival in patients who had received nab-paclitaxel-based chemotherapy after failure of a platinum-containing first-line combination chemotherapy. Results: Eleven patients were identified. 4 of 11 patients received nab-paclitaxel as second line, 7 of 11 patients as a third-line treatment. 7 of 11 patients received nab-paclitaxel in combination with gemcitabine, while in 4 of 11 patients nab-paclitaxel was combined with fluoropyrimidine. The disease control rate seen with nab-paclitaxel was 81% (nine of eleven patients). Disease was progressive in one patient, and in one patient the response status is unknown yet. One patient received partial remission and 8 patients had stable disease. As of September 13 th , 2014, three patients are still undergoing nab-paclitaxel combination therapy, but were censored by this date for analysis. The median time to progression was 4.9 months (2.3 – 18.9 months) for all patients (11/11 pts.), and 9.5 months for patients completed nab-paclitaxel treatment (8/11 pts.). Median overall survival for all eleven patients after initiation of nab-paclitaxel treatment was 7.3 month (2.6 – 21.8 month). The mean time of survival after diagnosis of advanced disease was 21.3 month, whereby 5 patients were alive at date of censoring. Conclusions: Nab-paclitaxel based chemotherapy can be an effective second-line regimen after platinum-failure in patients with advanced biliary cancer. In this small series, nab-paclitaxel appears to have a biological activity by controlling the disease and positively affecting survival. Randomized trials in this group of patients are urged.
The value of a quality metric.
Authors: J. Russell Hoverman, Jim R. Schwartz
Journal: Journal of Clinical Oncology (2012)

239 Background: The value of a quality metric is tied to improving outcomes or reducing costs while maintaining outcomes. In the last year ASCO/ONS Chemotherapy Safety metric 1F has changed from requiring current BLS (Basic Life Support) certification for all clinical personnel to requiring only one currently certified professional be present during chemotherapy administration (CA). For this study we evaluated the need for BLS training in outpatient chemotherapy delivery. Methods: Texas Oncology maintains a voluntary drug occurrence system, web-based and accessible at all sites. Occurrences with severity Grade 6 (transfer to a more intensive facility or temporary harm to patient) or higher (7 or 8) were collected for 2008-2 nd q 2011. Use of BLS and AED and outcomes were tracked through chart review. Results: There were 188 instances of Grade 6 or higher events of which 5 involved BLS. There were no events where an AED was triggered. All 5 patients were transferred alive to a hospital. All events were drug reactions. During the same period there were 779, 805 CAs, 371,693 unique patients with 15,394,601 patient visits. Facility reports were also queried for 2010 with no additional events identified. Conclusions: 1) The need for BLS recertification is unproven in this setting. 2) AED triggering did not occur in this time frame, 3) Protocols for addressing severe drug reactions are of prime importance. 4) Quality metrics may or may not add value to a quality program and require validation. 5) The original BLS requirement was burdensome. 6) The incidence of true cardiac arrest in this setting is remarkably low.
Tumor burden reduction in an orthotopic non-muscle-invasive bladder cancer model using IL-15 analogue (ALT-803) targeting T regulatory cells.
Authors: Evan Gomes, Makito Miyake, Ge Zhang, Steve Goodison, Jack Egan, Peter Rhode, Hing C. Wong, Charles Joel Rosser
Journal: Journal of Clinical Oncology (2013)

298 Background: A recent NCI review listed IL-15 as the most promising product candidate among twelve immunotherapy drugs that could potentially cure cancer. Preclinical studies using ALT-803 (mutated IL-15 analogue combined with IL-15Rα-Fc fusion) have shown promising results for obtaining prolonged drug half-life and stimulating CD8+ T cells and NK cells. Based on these results, we hypothesized that the administration of ALT-803 will generate an immunologic response which will reduce tumor burden in a rodent carcinogen induced orthotopic non muscle invasive bladder cancer model (NMIBC). Methods: We tested intravesical ALT-803 alone and ALT-803 in combination with Bacillus Calmette-Guérin (BCG) in a rodent carcinogen induced orthotopic NMIBC model. Rats were anesthetized then a 22-gauge Teflon transurethral catheter was placed in the bladder and urine completely drained from the bladder. Next, the saline (negative control), ALT-803 (experimental agent) or BCG (positive control) therapy was delivered by transurethral instillation and allowed to dwell in the bladder for 1 hr by occlusion of the urethra with a purse string suture. The intravesical therapy was administered weekly for a total of six weeks to mimic intravesical BCG therapy in humans. Results: Herein we demonstrate that ALT-803 was safe and well tolerated alone or in combination with BCG. Furthermore, ALT-803 alone reduced tumor burden by 23% whereas BCG alone reduced tumor burden by 11% compared to control. The combination of ALT-803 and BCG reduced tumor burden by 30% compared to control. Tumoral responses of the combinational treatment were associated with 76% and 80% reduction in angiogenesis and proliferation, respectively, whereas combinational therapy was associated with a 7.7-fold increase in apoptotic index compared to control. Immune monitoring suggested that the antitumor response was linked to the activation of CD8+ cells and NK cells. Conclusions: The enhanced therapeutic index provided by ALT-803 plus BCG therefore provides a powerful justification for the development of this agent for future clinical trials in subjects with non-muscle invasive bladder cancer.
Tissue-type plasminogen activator exerts EGF-like chemokinetic effects on oligodendrocytes in white matter (re)myelination
Authors: Camille Leonetti, Richard Macrez, Mathilde Pruvost, Yannick Hommet, Jérémie Bronsard, Antoine Fournier, Maxime Perrigault, Isabel Machin, Denis Vivien, Diego Clemente, Fernando De Castro, Eric Maubert, Fabian Docagne
Journal: Molecular Neurodegeneration (2017)

The ability of oligodendrocyte progenitor cells (OPCs) to give raise to myelin forming cells during developmental myelination, normal adult physiology and post-lesion remyelination in white matter depends on factors which govern their proliferation, migration and differentiation. Tissue plasminogen activator (tPA) is a serine protease expressed in the central nervous system (CNS), where it regulates cell fate. In particular, tPA has been reported to protect oligodendrocytes from apoptosis and to facilitate the migration of neurons. Here, we investigated whether tPA can also participate in the migration of OPCs during CNS development and during remyelination after focal white matter lesion. OPC migration was estimated by immunohistological analysis in spinal cord and corpus callosum during development in mice embryos (E13 to P0) and after white matter lesion induced by the stereotactic injection of lysolecithin in adult mice (1 to 21 days post injection). Migration was compared in these conditions between wild type and tPA knock-out animals. The action of tPA was further investigated in an in vitro chemokinesis assay. OPC migration along vessels is delayed in tPA knock-out mice during development and during remyelination. tPA enhances OPC migration via an effect dependent on the activation of epidermal growth factor receptor. Endogenous tPA facilitates the migration of OPCs during development and during remyelination after white matter lesion by the virtue of its epidermal growth factor-like domain.
Circulating tumor cells as a surrogate marker for determining response to chemotherapy in Japanese patients with metastatic colorectal cancer.
Authors: Satoshi Matsusaka, Mitsukuni Suenaga, Yuji Mishima, Yasuhito Terui, Eiji Shinozaki, Nobuyuki Mizunuma, Kiyohiko Hatake
Journal: Journal of Clinical Oncology (2012)

486 Background: The purpose of this study was to investigate the potential of circulating tumor cells (CTCs) as a surrogate marker of clinical outcome in metastatic colorectal cancer (mCRC) patients in order to identify Japanese patients responsive to oxaliplatin-based chemotherapy. Methods: The treatment regimen was oxaliplatin-based chemotherapy. Collection of CTCs from whole blood was performed at baseline and at 2 and 8-12 weeks after initiation of chemotherapy. Isolation and enumeration of CTCs was performed using immunomagnetics. Results: Between January 2007 and April 2008, 64 patients with mCRC were enrolled in this prospective study.Patients with ≥3 CTCs at baseline and at 2 and 8-12 weeks had a shorter median progression-free survival (8.5, 7.3, and 1.9 months, respectively) than those with &lt;3 CTCs (9.7, 10.4 and 9.1 months, respectively) (log-rank test: p=0.047, p&lt;0.001, and p&lt;0.001, respectively). Patients with ≥3 CTCs at 2 and 8-12 weeks had a shorter median overall survival (10.2 and 4.1 months, respectively) than those with &lt;3 CTCs (29.1 and 29.1 months, respectively) (p&lt;0.001 and p=0.001, respectively). A spurious early rise in CEA level was observed in 11 patients showing a partial response. On the other hand, no rise in early CTC level was observed among responders. Conclusions: The clinical utility of CTC enumeration in improving our ability to accurately assess treatment benefit and in expediting the identification of effective treatment regimens for individual Japanese patients.
Evaluation of end of life (EOL) care at a comprehensive community cancer institute.
Authors: D. E. Cowall, B. W. Yu, S. L. Heineken, E. N. Lewis, V. Chaudhry, J. M. Daugherty
Journal: Journal of Clinical Oncology (2011)

e19702 Background: The evidence-based use of resources for cancer care at EOL has the potential to relieve suffering, reduce health care costs, and extend life. Methods: A random sample of 390 patients was obtained from the 942 cancer deaths in Wicomico County, Maryland, for calendar years 2004-2008. General demographic and clinical event data were obtained from that sample using Peninsula Regional Medical Center's cancer registry and Coastal Hospice databases as well as manual chart reviews. In addition, the intensity of EOL cancer care was assessed using the indicator benchmarks proposed by Earle et al (Int J Qual Health Care 2005;17:505). The significance of potential relationships between variables was explored using chi squared analyses. Results: Mean age at death was 70 years; 52% male; 33% lung cancer; 18% noncolorectal GI; 13% colorectal; 36% other. Median survival from diagnosis to death was 8.4 months with hospice admission and 5.8 months without. Four intensity of care indicators (ICU admission, >1 hospitalization last month of life, hospital death and hospice referral <3 days before death) were higher than the above-referenced benchmarks by 1.5-2.4 fold. Associations (p<0.001) were noted between hospice admissions and decreased ICU admissions and hospital deaths (Table). Conclusions: These data suggest opportunities to improve EOL community cancer care. Hospice (211) No hospice (179) ICU 6 (2%) 24 (13%) Hospital death 5 (2%) 96 (54%)
The Novel Inhibitor PLX3397 Effectively Inhibits FLT3-Mutant AML,
Authors: Elizabeth Burton, Bernice Wong, Jiazhong Zhang, Brian West, Gideon Bollag, Gaston Habets, Allison Galanis, Hoa Nguyen, Omotayo Arowojolu, Trivikram Rajhowa, Mark J. Levis
Journal: Blood (2011)
Randomized double-blind controlled trial (RCT) of pegfilgrastim as prophylactic therapy in pediatric patients with solid tumors during myelosuppressive chemotherapy.
Authors: S. E. Anaya Aguirre, V. Wanzke Del Angel, H. Rivera Marquez, M. Villasis Keever, E. Lopez Aguilar, F. Cerecedo Diaz
Journal: Journal of Clinical Oncology (2011)

9565 Background: The objective of this study was to evaluate the effectiveness and safety of pegfilgrastim in pediatric patients with solid tumor as prophylactic therapy during dose-intensive combination chemotherapy, in comparison to filgrastim. Methods: Thirty-two cancer patients older than 2 years-old previously untreated with chemotherapy, and with Lansky scale > 50 were randomly assigned to receive a single pegfilgrastim dose of 100 mcgr/kg (n=16) or daily (during five days) filgrastim doses of 10 mcgr/kg (n=16) after chemotherapy. Outcome measures included: duration and incidence of neutropenia (<1,000 cel./mm3) and febrile neutropenia, time to neutrophil recovery, and adverse events (AE). Statistical analysis: Chi-square and Mann-Whitney U test were used. Results: One-hundred thirty-two cycles were evaluated; 66 from pegfilgrastim group (PG) and 66 from filgrastim group (FG). Their age varied from 2- to 16 years-old. Between groups, there were no differences in age, sex and type of neoplasm. Central nervous system tumors and osteosarcoma were the most frequent tumors (n=6 and n=5 in each group, respectively). Ifosfamide-carboplatin-etoposide (ICE) and cisplatin-epirubicin (CDDP/EPI) were the most common chemotherapy used (n=7 and n=4 vs. n=6 and n=5, respectively). There were 10 episodes (15.1%) of neutropenia in FG vs. 9 (13.6%) in PG; prolonged neutropenia was seen in 2 (3%) and 1 (1.5%), respectively (p>0.05). Incidence of febrile neutropenia was more frequent in FG (6 cycles, 9% vs. 1, 1.5% p=0.057). One chemotherapy cycle in each group was deferred. Regarding of AE, pain at the application site was more frequent in FG (20 cycles, 30.3% vs. 1, 1.5%; p<0.001), but bone pain was only observed in PG (10 cycles, 15.1%, p<0.01). Frequency of hyperleukocytosis (>11,000 cel./mm3) was lower in FG (5 cycles, 7.5% vs. 20 cycles, 30.3%, p=0.001). Conclusions: In children with solid tumors the effectiveness and safety of pegfilgrastim as prophylactic therapy during chemotherapy is similar to filgrastim. These results warrant a pharmacoeconomic evaluation.