tbuckley/cabot-search huggingface dataset:
Abstract 18167: MCP-1/CCR2 Desensitizes the SDF-1/CXCR4 Signaling in Bone Marrow Stem/Progenitor Cells
Authors: Shiyue Xu, Hosung Jung, Jun Tao, Richard Miller, Gangjian Qin
Journal: Circulation (2013)

Background: SDF-1/CXCR4 axis plays a pivotal role in the regulation of bone marrow (BM) stem/progenitor cell trafficking, thereby contributing to the ischemic tissue repair. CCR2 receptor is also widely expressed in the BM mononuclear cells, and the MCP-1/CCR2 axis has been shown to regulate the migration of these cells during inflammation. More recent evidence suggests that CCR2 and CXCR4 can form hetero-dimmers; however, the biological significance of the crosstalk between these two chemotactic pathways is not clear. Here, we hypothesize that MCP-1/CCR2 suppresses BM stem/progenitor cell trafficking through desensitization of SDF-1/CXCR4 signaling. Methods and Results: By using MCP1-RFP/CXCR4-eGFP double transgenic mice, we examined the endocytosis of MCP-1 in BM cells after systemic injection of lipopolysaccharide (LPS) and found that MCP-1 endocytosis occurred predominantly in CXCR4-positive stem/progenitor cells. Then we measured the MCP-1- and/or SDF-1-induced intracellular calcium transient by Fura2-based calcium imaging in the isolated BM cells. Our results showed that more than 80% of MCP-1-responsive cells also responded to SDF-1 treatment. However, in the cells pretreated with escalating doses of MCP-1 (10, 20, and 40 nM), a dose-dependent desensitization of SDF-1 activity was observed ( p &lt;0.05, 20 nM vs. 10 nM; p &lt;0.001, 40 nM vs. 10 nM or 20 nM). Moreover, systemic administration of AMD3100 in mice significantly increased CCR2-positive stem/progenitor cells in the peripheral blood (n=4 each; p &lt;0.01). Conclusions: Activation of MCP-1/CCR2 desensitizes SDF-1/CXCR4 signaling in BM stem/progenitor cells; targeting MCP-1/CCR2 axis may enhance the effectiveness of CXCR4-mediated stem/progenitor cell homing and tissue repair in ischemic heart disease.
NAT2 Gene Polymorphism in Bladder Cancer: A Study from North India
Authors: Sandeep Bhattacharya, Rajnikant Shukla, Surya Kant, Balraj Mittal
Journal: European Respiratory Journal (2012)

Purpose: This study was conducted to examine: 1) whether the NAT2 genotypes are risk factors for Lung cancer, 2) to study possible association of tobacco smoking with NAT2 genotype of these patients.

Materials and Methods: This case control study was undertaken over a period of 19 months and included 100 Lung cancer patients and 145 controls. The NAT2 genotypes were identified by PCR-RFLP method in peripheral blood DNA samples. Genotypes frequencies and the association of the genotypes among patients and controls group were assessed by χ2 test and Binary Logistic regression.

Results: The NAT2 fast acetylator genotype frequency of slow or fast acetylator genotypes was not significant in lung cancer patients alone (OR = 1.18, 95% CI: 0.69 - 2.03, p value = 0.583).in non-smoker (OR = 1.06, 95% CI: 0.43 - 2.64, p value = 0.899) and smoker (OR = 1.32, 95% CI: 0.59 - 2.93, p value = 0.494) when compared with controls.

Conclusion: These data demonstrate that the NAT2 fast or slow acetylators genotype did not associated with the risk of developing lung cancer in North Indian population when compared with controls.
Meta-analysis of stomatitis in clinical studies of everolimus: incidence and relationship with efficacy
Authors: H.S. Rugo, G.N. Hortobagyi, J. Yao, M. Pavel, A. Ravaud, D. Franz, F. Ringeisen, J. Gallo, N. Rouyrre, O. Anak, R. Motzer
Journal: Annals of Oncology (2016)

Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, is used to treat solid tumors and tuberous sclerosis complex (TSC). Stomatitis, an inflammation of the mucous membranes of the mouth, is a common adverse event associated with mTOR inhibitors, including everolimus. We conducted a meta-analysis of data from seven randomized, double-blind phase 3 clinical trials of everolimus to determine the clinical impact of stomatitis on efficacy and safety.Data were pooled from the safety sets of solid tumor [breast cancer (BOLERO-2 and BOLERO-3), renal cell carcinoma (RECORD-1), carcinoid tumors (RADIANT-2), and pancreatic neuroendocrine tumors (RADIANT-3)] and TSC studies (EXIST-1 and EXIST-2). Data from solid tumor trials and TSC trials were analyzed separately.The rate of stomatitis was 67% in the solid tumor trials (973/1455 patients) and 70% in the TSC trials (110/157 patients). Most stomatitis events were grade 1/2, with grade 3/4 events reported in only 9% (solid tumor trials) and 8% (TSC trials) of patients. Low TSC patient numbers prevented an in-depth evaluation of stomatitis and response. In the solid tumor trials, most first stomatitis episodes (89%; n = 870) were observed within 8 weeks of starting everolimus. Patients with stomatitis occurring within 8 weeks of everolimus initiation had longer progression-free survival (PFS) than everolimus-treated patients without stomatitis in BOLERO-2 {8.5 versus 6.9 months, respectively; hazard ratio (HR), 0.78 [95% confidence interval (CI), 0.62-1.00]} and RADIANT-3 [13.9 versus 8.3 months, respectively; HR, 0.70 (95% CI, 0.48-1.04)]. A similar trend was observed in RECORD-1 [HR, 0.90 (95% CI, 0.66-1.22)] and RADIANT-2 [HR, 0.87 (95% CI, 0.61-1.22)] but not in BOLERO-3 [HR, 1.01 (95% CI, 0.75-1.36)].Stomatitis did not adversely affect PFS, supporting the administration of everolimus in accordance with standard management guidelines.
Randomized phase II trial of capecitabine versus capecitabine, low molecular weight heparin, and prednisone in refractory colorectal carcinoma
Authors: E. Mak, C. Townsley, R. Buckman, E. Chen, L. Lopez, L. Wang, M. Moore, A. M. Oza
Journal: Journal of Clinical Oncology (2009)

e15126 Background: Capecitabine is widely used in the treatment of advanced colorectal cancer. Continuous low dose chemotherapy has been postulated to have anti-angiogenic effects discrete from its anti-proliferative effects on tumors (metronomic therapy). Dalteparin and prednisone have also been implicated in inhibiting tumour angiogenesis and hypothesized to have additive benefit to chemotherapy. This randomized phase II study examined the additive effect of dalteparin and prednisone with capecitabine in metastatic colorectal cancer. Methods: Patients with metastatic colorectal cancer were randomized to either capecitabine (C) 2,500 mg/m 2 in divided doses from days 1–14 in a 3-week cycle or capecitabine with dalteparin and prednisone (CDP). There was no restriction on previous treatment, other than no prior capecitabine. Dalteparin was given at 5,000 units once daily subcutaneously, and prednisone orally 10 mg daily, both on a continuous basis. Thirty patients were planned for accrual in each arm with interim analysis when accrual reached fifteen in each arm. The primary end-point was disease control defined as treatment response or stable disease &gt;4 months. Radiological evaluation was performed every 6 weeks. Treatment was discontinued if patients had progressive disease or intolerable toxicity. Results: Thirty patients were recruited. Fourteen patients had received ≥3 previous regimens (median 3 (C), 2 (CDP)). Median performance statuses were ECOG 1 (C) and 0 (CDP). Nine patients achieved stable disease greater than 6 months (5 (C)/4 (CDP)). There was no statistical difference in the median survival time and time-to- progression for the two groups (11.1 mth (C)/15.8 mth (CDP); 3.2 mth (C)/2.8 mth (CDP)). The commonest toxicities overall were myelosuppression and hand-foot syndrome (HFS). The most common Grade 3+ adverse events were HFS (6 patients) and diarrhea (4 patients). Conclusions: The combination of dalteparin, prednisone and capecitabine did not improve disease control over that seen with capecitabine in refractory metastatic colorectal cancer. No significant financial relationships to disclose.
P-273 Concordance of RAS mutation status in CRC patients by comparison of results from circulating tumour DNA and tissue-based testing
Authors: R. Scott, S. Dooley, W. Lewis, C. Meldrum, P. Pockney, B. Draganic, S. Smith, F. Jones, C. Hewitt, H. Phillimore, A. Lucas, E. Shi, K. Namdarian, T. Chan, D. Acosta, S.-P. Chan, S. Fox
Journal: Annals of Oncology (2015)
ROS-Mediated Iron Overload Injures The Hematopoiesis Of Bone Marrow By Damaging Hematopoietic Stem/Progenitor Cells In Mice
Authors: Xiao Chai, Deguan Li, Mingfeng Zhao, Wenyi Lu, Juan Mu, Xia Xiao, Yuchen Zhang, Qing Li, Juanxia Meng, Tao Sui, Aimin Meng
Journal: Blood (2013)
Current status of chemotherapy for advanced pancreatic and gastric cancer.
Authors: M J O'Connell
Journal: Journal of Clinical Oncology (1985)

There is currently no effective systemic therapy for advanced pancreatic cancer. No definitive controlled data exist that demonstrate a survival benefit for any particular regimen yet developed. A statistically significant short-term survival benefit has been seen in three consecutive GITSG trials using the FAMe regimen in patients with advanced gastric cancer. Occasional long-term responders have been seen with a variety of regimens, but there is no evidence of improved long-term (more than two years) disease-free survival with any regimen reported to date. Continuing research with emphasis on new drug development, innovative alterations in chemotherapy combinations and administration schedules, or entirely new treatment strategies, are clearly required to allow the clinical investigator and the clinical practitioner to achieve their common goal--improved long-term survival for patients with advanced pancreatic and gastric cancer.
Abstract 161: Stem Cell Transplantation Reverses Ischemic Mitral Regurgitation
Authors: Arnon Blum
Journal: Circulation (2012)

Background:  Ischemic Mitral Regurgitation (IMR) worsens prognosis in ischemic heart failure. As treatment options are limited, we tested the hypothesis that transcatheter intramyocardial injections of autologous bone marrow (BM) progenitor cells will prevent the natural history of deterioration and will improve IMR.   Methods:  Eight ischemic cardiomyopathy patients (all males, 56.5±13 years old) underwent bone marrow aspiration followed by transcatheter injection of autologous bone marrow progenitor cells (4 patients got mononuclear cells, 4 patients got mesenchymal stem cells). Cardiac MRI and echocardiogram were conducted at baseline, 3, 6, and 12 months after cell transplantation.   Results:  Five patients (57.8±15.8 years old) improved Ischemic MR and improved their left ventricular ejection fraction (LVEF) from 39±9% to 48±7.5% (p=0.02), left ventricular end systolic diameter (LVESD) from 4.7±0.7 cm to 3.7±0.6 cm (p=0.02), and left atrial (LA) diameter from 4.1±1.1 cm to 3.1±0.5 cm (p=0.05). A significant difference was observed in ΔLVESD% (p=0.03). No cell type preference was documented.   Conclusion:  1 year follow up post transcatheter intramyocardial injections of autologous BM cells in chronic ischemic cardiomyopathy patients demonstrated a significant improvement in Ischemic MR in 5 patients without worsening of MR in the other 3. These findings suggest that stem cell transplantation could have a major impact on ischemic MR and reverse ischemic MR.  Moderate IMR No IMR
Efficacy of viscous budesonide slurry for prevention of esophageal stricture formation after complete endoscopic mucosal resection of short-segment Barrett’s neoplasia
Authors: Farzan Bahin, Mahesh Jayanna, Stephen Williams, Eric Lee, Michael Bourke
Journal: Endoscopy (2015)

<b>Background and aims:</b> Complete endoscopic resection (CER) of short-segment Barrett’s esophagus with high grade dysplasia (HGD) and early esophageal adenocarcinoma (EEA) is a precise staging tool and achieves durable disease control. The major drawback is development of post-endoscopic resection esophageal stricture (PERES). No effective therapy to prevent PERES has been described. Viscous budesonide slurry (VBS) may have a role in the prevention of PERES by suppressing the post-CER inflammatory process. The study aim was to evaluate the efficacy of VBS for the prevention of PERES. <b>Methods:</b> Prospective data were collected on patients referred for CER of HGD or EEA. After January 2012, patients routinely received VBS (two 0.5-mg/2-mL budesonide respules mixed with sucralose) twice daily for 6 weeks following each stage of the CER schedule. All patients received high dose proton pump inhibitor therapy for the duration of CER and the following 3 months. Patients had no other intervention to prevent PERES. A validated dysphagia score was used (0 – 4, no dysphagia to aphagia). Endoscopic dilation was performed for dysphagia. Patients receiving VBS were compared with historical controls. The primary endpoint was the need for dilation. <b>Results:</b> Between January 2008 and January 2015, 104 of 116 eligible patients completed CER. The VBS group (n = 29) and non-VBS group (n = 75) had similar patient, disease, and procedural characteristics. Dilations were needed in 13.8 % vs. 37.3 % (<i>P</i> = 0.03), with a median of one vs. two procedures (<i>P</i> = 0.01), and median dysphagia score during CER of 0 vs. 1 (<i>P</i> = 0.02) in the VBS and non-VBS groups, respectively. No VBS-related adverse events were noted. <b>Conclusion:</b> In this pilot study VBS significantly reduced PERES and shortened the dilation program after CER.
Soundings: Nursing matters
Authors: Colin Douglas
Journal: BMJ (2000)

It is greatly to be hoped that the discord and indeed rancour that have characterised recent meetings of the medical staff committee of the newly reorganised Auchendriech United Acute Trust are simply a reflection of transition, as old interhospital rivalries are transformed by forward looking management into vibrant new complementarity and synergy. And it is perhaps a sign of progress that our meeting last Tuesday was one of the least contentious for months.

The only new item on our agenda so far this year had been raised by a senior surgeon who had heard rumours that management was about to bring in changes in nursing that would subvert consultant authority, erode the role of clinical judgment, and deprive junior medical staff of vital experience in practical procedures.

A broader discussion ensued. Nurse bed managers had yet again failed to cope with the winter crisis. Nursing jargon and previous nursing reorganisations had combined to replace ward sisters by “clinical managers with 24 hour responsibility for the ward level patient care area,” so that the fine old tradition of coffee in sister's room after the ward round was now but a distant, golden memory.

Trends in nursing education were also briefly reviewed. The daughter of a consultant physician, in training in Edinburgh, had so far spent more time in the classroom on the sociology of nursing than she had in the wards nursing, and under tutors who were by all accounts refugees not only from the wards but from the real world too.

But nothing united our consultant body more firmly than a recent proposal to establish a new grade of “consultant nurse.” Though for practical reasons our committee minutes are usually brief, a urologist insisted that his views on this concept—which he regarded as an insult, a betrayal, and a gross misuse of language—were for the record. And would these people insist on attending meetings such as this? He was sure that they would.

At 6 pm we were joined, as is usual every third meeting, by our chief executive. He was accompanied by the new director of nursing, a pleasant Glaswegian lady who outlined some over due and practical measures, developed by a joint medical and nursing working group, to extend the role of the nurse in several agreed areas. There were a few questions, followed by a brief and civil discussion. The meeting closed at 6 10 pm.
Preliminary safety data of a randomized phase III trial comparing a preoperative regimen of FEC-75 alone followed by paclitaxel plus trastuzumab with a regimen of paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab in patients with HER2-positive operable breast cancer (ACOSOG Z1041).
Authors: A. Buzdar, V. Suman, F. Meric-Bernstam, J. C. Boughey, A. M. Leitch, G. W. Unzeitig, M. J. Ellis, M. Ewer, K. Hunt
Journal: Journal of Clinical Oncology (2010)

594 Background: ACOSOG Z1041 is a phase III randomized trial for women with HER2+ operable breast cancer. The aim of the study is to compare the pathological complete response rate and safety data between the two preoperative chemotherapy regimens that differ in timing of initiation of trastuzumab. Methods: In arm A, patients receive 4 cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-75) alone followed by weekly paclitaxel combined with weekly trastuzumab for 12 weeks. In arm B, patients receive weekly paclitaxel for 12 weeks combined with weekly trastuzumab, followed by 4 cycles of FEC-75 with concomitant trastuzmab. Patients undergo cardiac evaluation with MUGA scans. All patients proceed to surgical resection after conclusion of chemotherapy. This ongoing study is designed to accrue 270 patients. 125 patients have been accrued as of January 5, 2010. Initial safety data of 50 patients who have completed all therapy as of June 2009 (arm A=25; B=25 pts) are shown in the Table. Initial safety data submission was approved by the Data Safety Monitoring Committee for this protocol to provide information about the tolerability of this study the treatment regimens. Results: See Table. No instances of unanticipated grade 3 or 4 toxicities have been seen in either study arm. There has been no clinical cardiac dysfunction. Conclusions: These preliminary safety data illustrate that both treatment arms were well tolerated without significant cardiac toxicity or side effects. This study is ongoing and updated safety data will be presented. Grade 1 2 3 4 Toxicities Arm N % N % N % N % Neutropenia 1 3 12.0 3 12.0 3 12.0 2 8.0 2 1 4.0 1 4.0 9 36.0 3 12.0 Fever/infections 1 2 8.0 6 24.0 0 0 0 0 2 4 16.0 7 28.0 0 0 0 0 Neurosensory 1 13 52.0 4 16.0 1 4.0 0 0 2 10 40.0 3 12.0 0 0 0 0 L. ventricular dysfunction 1 0 0 3 12.0 0 0 0 0 2 1 4.0 0 0 0 0 0 0 Fatigue 1 14 56.0 8 32.0 1 4.0 0 0 2 7 28.0 14 56.0 2 8.0 1 4.0 Diarrhea 1 6 24.0 7 28.0 0 0 0 0 2 12 48.0 7 28.0 0 0 0 0 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Novartis Genentech
Abstract 18711: The Adaptor Protein Skap2 is Required for Integrin-Mediated Signaling in Macrophages
Authors: Francis J Alenghat, Lily I Pao, Clifford A Lowell, Benjamin G Neel, David E Golan, Kenneth D Swanson
Journal: Circulation (2010)

Background: Integrins mediate macrophage migration and phagocytosis, processes that are central to atherogenesis. The adaptor protein Skap2 is phosphorylated in response to integrin engagement in m...
Oblimersen can be administered by subcutaneous (SC) and brief intravenous (IV) infusion: Clinical pharmacokinetics and pharmacodynamics (PK/PD) in patients with advanced cancer
Authors: C. Lin, K. Papadopoulos, A. Patnaik, K. Sankhala, C. H. Takimoto, J. Rodon, T. Julian, B. D. Brown, A. W. Tolcher
Journal: Journal of Clinical Oncology (2007)

14083 Background: Oblimersen (OBL) is a phosphorothioate oligodeoxynucleotide that decreases Bcl-2 protein levels. OBL has been administered by continuous intravenous infusion (CIVI) in most clinical studies. However, recent preclinical data suggest that equivalent or superior antitumor efficacy can be achieved with intermittent administration. We conducted a dose-ranging PK/PD study of OBL given by bolus SC injection and brief IV infusion to evaluate the feasibility of intermittent dosing. Methods: In this within-subject dose-escalation study, OBL was administered subcutaneously (SC) at doses of 75, 150 and 225 mg. In part II of the study, OBL was administered by 2-hr IV infusion beginning at 150 mg on day 1, by single-dose SC injection on day 8, and 2-hr IV daily x 5 consecutive days. Pharmacokinetics were assessed by non-compartmental analysis. Pharmacodynamic measurements of Bcl-2 levels in peripheral blood mononuclear (PBM) cells were made using Western blot analysis. Results: OBL absorption after SC administration was rapid with a T max of ∼2 hours. Mean C max values were 0.76, 1.70 and 3.10 μg/ml for the 75, 150 and 225 mg SC doses, respectively. Mean AUC 0- inf values were 7.78, 15.36 and 25.57 hr*μg/mL. Plots of dose-normalized C max and AUC vs. dose showed slopes close to zero, indicating approximate dose proportionality. AUC 0–24 exposure with the 225 mg SC dose was similar to previously established 24-hr steady-state AUCs after 3 mg/kg CIVI. SC injection was associated with an inflammatory erythematous grade 1 rash at the injection site that resolved within 7 days. The 150 mg 2-hr IV infusion x 1 or daily x 5 has been well-tolerated. Conclusions: OBL exposure from a single SC injection is similar to a 24-hr 3 mg/kg CIVI, and the 2-hr IV infusion is currently being evaluated. Both schedules appear to be well- tolerated, may reduce requirements for CIVI, and could be incorporated into intermittent dosing regimens. No significant financial relationships to disclose.
Synchronous and Metachronous Squamous Cell Carcinomas of the Head and Neck Mucosal Sites
Authors: Haldun Ş. Erkal, William M. Mendenhall, Robert J. Amdur, Douglas B. Villaret, Scott P. Stringer
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The present study presents the experience at the University of Florida with synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. PATIENTS AND METHODS: This study included 1,112 patients with squamous cell carcinomas of the oropharynx, hypopharynx, and supraglottic larynx treated with radiation therapy with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up. RESULTS: The overall survival rate was 45% and the disease-specific survival rate was 67% at 5 years after initial diagnosis of carcinoma of the head and neck mucosal sites. Seventy-seven patients (7%) presented with synchronous carcinomas of the head and neck mucosal sites and 103 patients (9%) developed metachronous carcinomas of the head and neck mucosal sites at 0.6 to 21.7 years (median, 3.6 years). The overall survival rate was 31%, and the disease-specific survival rate was 50% at 5 years after metachronous carcinomas of the head and neck mucosal sites. Seven patients (1%) developed metachronous carcinomas of the thoracic esophagus at 1 to 11.1 years (median, 2.8 years), 15 patients (1%) presented with synchronous carcinomas of the lung, and 83 patients (7%) developed metachronous carcinomas of the lung at 0.6 to 17.6 years (median, 3.5 years). CONCLUSION: Development of synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites are in part responsible for failure to improve overall survival rates for patients with squamous cell carcinomas of the head and neck mucosal sites, justifying rigorous follow-up and studies on chemoprevention.