tbuckley/cabot-search huggingface dataset:
Video-assisted thoracoscopic transdiaphragmatic liver resection for malignant tumors located in the posterosuperior segments.
Authors: Masao Sunahara, Nobuaki Kurauchi, Yusuke Tsunetoshi, Takeyuki Sawano, Hiroyuki Kasajima, Yutaka Hara, Shinsaku Suzuki, Shigeru Toyama, Jun Kimura
Journal: Journal of Clinical Oncology (2015)

469 Background: Laparoscopic liver resection has recently become more common. However, it is difficult to resect laparoscopically the liver tumor located in the posterosuperior segments (IVa, VII and VIII), especillay for patients with liver cirrhosis. Compared to laparoscopy, gaining access to tumors in the dome of the liver may be more easily obtained via thoracoscopy.Therefore, we describe the technique and outcome of a video-assisted thoracoscopic transdiaphragmatic liver resection in patients with a malignant tumor of the liver. Methods: Five female patients underwent video-assisted thoracoscopic transdiaphragmatic partial hepatectomy. The tumors were located at segment VIII in 4 patients and segment VII in 1. Three patients were preoparatively diagnosed with hepatocellular carcinoma, and two were metastatic tumor of the colorectal cancer. Underlying cirrhosis was staged as Child-Pugh B in 2 cases and Child-Pugh A in 1. Thoracoscopic transdiaphragmatic partial hepatic resection was chosen due to the tumor’s location and impaired liver function. The patient was placed in an oblique position with her left side on the table. The ports were placed around the tumor at three levels, the ninth (3cm mini-thoracotomy), the seventh (two ports, 5mm and 12mm), and the fifth (12mm) intercostals spaces. Using thoracoscopic ultrasonography, the portion of the diaphragm located just above the tumor was cut and opened using electric cautery. The partial liver resection was performed using coagulating shears and electric cautery. Results: No conversion to laparotomy occurred. The median blood loss was 200 g (20-500g), and median operating time was 220 min (135-347 min). There were no perioperative deaths, and no patients underwent reoperation. Conclusions: Thoracoscopic hepatic resection can be safely performed in patients with subdiaphragmatic tumors, especially with cirrhosis or previous upper abdominal surgery.
Surgical Irrigation of Open Fractures — A Change in Practice?
Authors: Douglas R. Dirschl
Journal: New England Journal of Medicine (2015)

The open fracture — in which the broken bone is exposed to the world outside the body — has long been a devastating injury. From the time of Hippocrates until after the American Civil War, the recommended treatment for an open fracture was amputation, with death from sepsis occurring in approximately 50% of patients. The adoption of antiseptic technique and formal surgical débridement in the late 19th century, and the introduction of antibiotic agents and improved surgical stabilization in the 20th century, all but eliminated death as an outcome. These advances, however, have not eliminated infection or nonunion, which remain . . .
Expression of chemokine receptor CXCR4 correlates with progression of pancreatic cancer
Authors: C. C. Schimanski, F. Wolfert, I. Gockel, T. Junginger, P. R. Galle, M. Moehler
Journal: Journal of Clinical Oncology (2006)

14018 Background: Despite many pathophysiological analyses, the process of tumor dissemination of pancreatic cancer remains vague. In diverse other tumor entities, expression of the chemokine receptor CXCR4 has been linked to tumor dissemination and poor prognosis. Therefore, we evaluated, if the expression of this chemokine receptor exerts similar effects in human pancreatic cancer. Methods: Expression of CXCR4 was evaluated in 120 patients with histologically confirmed pancreatic cancer and eight different pancreatic cancer cell lines. Expression intensities of tumor samples were correlated with both, tumor and patients characteristics. Results: Human pancreatic cancer samples and cell lines displayed variable intensities of CXCR4. CXCR4 revealed predominantly a cytoplasmatic, and in few specimens an additional weak membranous location. Strong CXCR4 expression was significantly associated with progressed disease as indicated by UICC status (P=0.031) and revealed a strong, yet not significant trend with distant tumor cell dissemination and locally progressed tumors (P=0.08; P=0.11, respectively). Conclusion: Strong expression of CXCR4 by pancreatic cancer is significantly associated with progressed tumor stages. No significant financial relationships to disclose.
Conjugated linoleic acid isomers differentially modulate neu/erbB2-induced mammary tumorigenesis
Authors: Margot M. Ip, Sibel O. McGee, Lihui Ou, Suzanne F. Shoemaker, Patricia A. Masso-Welch
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3176 

Conjugated linoleic acid (CLA), a family of isomers found in dairy products and ruminant meats, as well as produced synthetically, inhibits carcinogen-induced rat mammary carcinogenesis, angiogenesis, and lung metastasis in a transplantable mammary tumor model. The c9,t11 isomer of CLA, the predominant isomer in dairy products, and the t10,c12 CLA isomer, available as part of a CLA mixture in health food stores, are equally effective. The objective of the present studies was to determine the efficacy of these two CLA isomers in a breast cancer model that is representative of ∼25% of human breast cancers. Transgenic mice overexpressing wild type erbB2 in the mammary epithelium were fed synthetic diets without or with 0.5% c9,t11-CLA or t10,c12-CLA from weaning. Unexpectedly, t10,c12-CLA markedly enhanced tumor development. Tumor latency, defined as the time when 50% of the mice in the group developed a tumor, was decreased from 267 days for mice on the control diet to 169 days for mice fed t10,c12-CLA. Latency was not significantly changed in mice fed c9,t11-CLA. The stimulation was not a result of an altered expression of the transgene, since erbB2 expression and localization were comparable in all groups. Lung metastasis was also evaluated. Mice were sacrificed when tumor diameter in each mouse reached ∼18 mm in the longer diameter, so that incidence of metastasis was not confounded by differences in primary tumor size. Lung metastasis was significantly higher in mice fed t10,c12-CLA (28/30) compared to control (9/29), but was significantly reduced in mice fed c9,t11-CLA (4/28). Given the potential clinical significance of these observations, a second study was initiated in which mice were fed the control or CLA-containing diets starting after puberty at ∼70 days of age. With this protocol, the stimulatory effect of t10,c12-CLA on mammary carcinogenesis was again observed. Since this experiment is still ongoing, metastasis outcome is not yet available. These data suggested that the CLA isomers may differentially alter signaling through erbB2. As an initial approach to address this question, the effect of these dietary treatments on the erk1/2 MAP kinases was examined. Erk1 and 2 were activated in mammary tumors from mice fed t10,c12-CLA when compared to mice fed the control diet or a diet supplemented with c9,t11-CLA, suggesting that the enhanced tumor development in this group may result, at least in part, from an activation of erbB2 signaling through the MAP kinase pathway. Together with the data from the rat model, the current data suggest that c9,t11-CLA may be beneficial for the prevention of breast cancer; however, given the stimulatory effect of t10,c12-CLA on mammary carcinogenesis in a clinically relevant breast cancer model, it would be prudent to avoid CLA supplements that contain this isomer. Supported by Komen BCTR0201524 and by NIH CA61763.
Abstract #5380: Systemic anti-angiogenic activity of cationic poly-L-lysine dendrimer delays tumor growth
Authors: Khuloud Al-Jamal
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Systemic Anti-Angiogenic Activity of Cationic Poly-L-Lysine Dendrimer Delays Tumor Growth Khuloud T. Al-Jamal1, Wafa\#8217; T. Al-Jamal1, Simon Akerman 2, Jennifer E. Podesta1, John A. Turton3, Alberto Bianco4, Neil Vargesson5, Chryso Kanthou2, Alexander, T. Florence6, Gillian M. Tozer2 and Kostas Kostarelos1 1Nanomedicine Laboratory, Centre for Drug Delivery Research, The School of Pharmacy, University of London, London WC1N 1AX, UK 2Academic Unit of Surgical Oncology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK 3Centre for Toxicology, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK. 4 CNRS, Institut de Biologie Moleculaire et Cellulaire, UPR 9021 Immunologie et Chimie Therapeutiques, 67000 Strasbourg, France 5Section of Cell and Molecular Biology, Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ, UK 6 23 North Esk Road, Edzell, Angus DD9 7TW, UK. Dendrimers are three dimensional macromolecules which have already been shown to hold great potential as nanocontainers for the delivery of drugs, plasmid DNA and siRNA. In this study, we report the capacity of specific Poly-L-Lysine dendrimer (PLL-dendrimer) molecules to exhibit an intrinsic anti-angiogenic activity. A cationic PLL-dendrimer was synthesized to mimic heparin-binding macromolecules and shown to lead to tumor xenograft growth delay after systemic administration into mice in the absence of any therapeutic agent and at a non-toxic dose regime. The anti-angiogenic activity of the PLL-dendrimer was validated using a panel of in vitro and in vivo angiogenesis assays. The PLL-dendrimer inhibited tubule formation by SVEC4-10 murine endothelial cells. It also inhibited neovascularization in the chick embryo CAM assay and in Matrigel plugs implanted subcutaneously into C57BL/6 mice after systemic administration of 50mg/kg/day dendrimer only after two injections. The anti-angiogenic activity of the dendrimer molecules was further evidenced by intravital microscopy of dorsal skinfold window chamber. Normalization of tumor vasculature morphology and architecture, and fewer microvessles in P22 rat sarcoma tumors implanted in the dorsal window chamber of SCID mice were observed following single administration of the PLL-dendrimers. The antiangiogenic activity of the PLL-dendrimer was further shown to lead to statistically significant suppression of B16F10 tumor volume with delayed tumor growth and enhanced apoptosis/necrosis in PLL-dendrimer-treated tumors. This suggests that dendrimer can be used in cancer therapy for both their carrier capacity and intrinsic antiangiogenic activity.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5380.
Optimal use of aromatase inhibitors for adjuvant treatment of hormone-sensitive early breast cancer: Up front or sequenced after tamoxifen?
Authors: J. Cuzick, P. Sasieni, A. Howell
Journal: Journal of Clinical Oncology (2007)

541 Background: The aromatase inhibitors (AIs) are more effective than tamoxifen when used for the adjuvant treatment of early breast cancer. However, it is still unclear whether it is better to start initially with an AI or use it after a 2–3-year period of tamoxifen treatment. No clinical trial data are likely to be available until 2008, although earlier modeling data have shown that an upfront strategy may be more favorable (Cuzick et al. Br J Cancer 2006: 27; 460–464). Here we update the model with all newly reported data. Methods: A model has been constructed to compare the use of an AI upfront with AI sequencing after varying periods of initial treatment with tamoxifen. Recurrence rates and time lost to recurrence for the first 10 years of follow-up are modeled for a range of efficacy parameters. Results: Results predicted from the model are presented in the table . For a 5-year carryover period, the predicted recurrence rate at 10 years is 17.7% for upfront use of an AI compared with 22.9% for 5 years of tamoxifen, leading to one less recurrence for every 19 women treated. The average time lost to recurrence is reduced by 2.8% or 3.4 months. With updated data, the model predicts an AI upfront strategy will dominate a sequencing strategy. However, the model also demonstrates that using 10 years of tamoxifen, or a sequence of 5 years of tamoxifen followed by 5 years of an AI, is superior to using 5 years of tamoxifen. This indicates that longer duration of treatment with an AI is likely to be beneficial, especially for younger women, and deserves further investigation. Conclusion: The current modeling data suggest that using an AI as upfront adjuvant treatment is better than using an AI in sequence after 2 or more years of tamoxifen. [Table: see text] No significant financial relationships to disclose.
Abstract 17469: Prognostic Utility of the Hemoglobin/Hematocrit Equation for Estimating Plasma Volume Changes During Hospitalization for Acute Decompensated Heart Failure
Authors: Karl D Norrington, Hazel K Turner, Mohamad F Barakat, Klio Konstantinou, Mihir Kelshikir, Sinead O'Driscoll, Clare Screeche-Powell, Judith Chilcott, Saj Hayat, Michael Koa-Wing, Julia Graspa, Petros Nihoyannopoulos, Charlotte Manisty, Kevin Fox, Susan Connolly, Neil Chapman, Nilesh Sutaria, Prapa Kanagaratnam, Jamil Mayet, Darrel P Francis, Darlington O Okonko
Journal: Circulation (2012)

Background: Plasma volume (PV) expansion underlies systemic congestion in acute decompensated heart failure (ADHF) but changes in PV during hospitalisations are poorly estimated by clinical examina...
Tobacco Cessation May Improve Lung Cancer Patient Survival
Authors: Katharine A. Dobson Amato, Andrew Hyland, Robert Reed, Martin C. Mahoney, James Marshall, Gary Giovino, Maansi Bansal-Travers, Heather M. Ochs-Balcom, Michael A. Zevon, K. Michael Cummings, Chukwumere Nwogu, Anurag K. Singh, Hongbin Chen, Graham W. Warren, Mary Reid
Journal: Journal of Thoracic Oncology (2015)
Simple nontoxic treatment of advanced metastatic seminoma with carboplatin.
Authors: A Horwich, D P Dearnaley, G M Duchesne, M Williams, M Brada, M J Peckham
Journal: Journal of Clinical Oncology (1989)

Between 1982 and 1986, 34 patients with advanced metastatic seminoma were treated with four to six courses of single-agent carboplatin administered at 400 mg/m2 every 4 weeks either on an outpatient basis or during 24-hour admissions. Patients with raised serum alphafetoprotein (AFP) or with multiple (more than three) lung metastases were excluded since these features may indicate a nonseminomatous component. In this series 20 patients were previously untreated except for orchiectomy, and 14 patients had received prior radiotherapy restricted to infradiaphragmatic nodal areas. Treatment was extremely well tolerated. No patient suffered renal damage, neurotoxicity, or ototoxicity, and there were no episodes of neutropenic septicemia, thrombocytopenic hemorrhage, or bruising. The actuarial 2-year survival was 94% (95% confidence intervals, 83% to 100%) with follow-up of 12 to 46 months from completion of carboplatin (mean, 26 months). The actuarial chance of remaining alive and free from progressive disease at 2 years was 80% (95% confidence intervals, 66% to 94%). Of six patients who relapsed, five are currently in remission 9 to 18 months after completion of salvage treatment. This level of antitumor activity is equivalent to that seen with aggressive combination regimens. Single-agent carboplatin should be considered the treatment of choice for advanced stages of malignant seminoma when limitation of toxicity is considered important; however, the rarity, especially of extranodal metastases from seminoma, leads to the need for further investigation using this approach.
525 BMI BUT NOT AETIOLOGY OR STAGE OF LIVER DISEASE AFFECTS THE DIAGNOSTIC SENSITIVITY OF CARBOHYDRATE DEFICIENT TRANSFERRIN
Authors: K. Fagan, K. Irvine, B. McWhinney, L. Fletcher, L. Horsfall, L. Johnson, A. Clouston, J. Jonsson, P. O'Rourke, J. Martin, C. Pretorius, J. Ungerer, E. Powell
Journal: Journal of Hepatology (2013)
Netrin-1 is highly expressed and required in inflammatory infiltrates in wear particle-induced osteolysis
Authors: Aránzazu Mediero, Bhama Ramkhelawon, Tuere Wilder, P Edward Purdue, Steven R Goldring, M Zahidunnabi Dewan, Cynthia Loomis, Kathryn J Moore, Bruce N Cronstein
Journal: Annals of the Rheumatic Diseases (2015)

Objective Netrin-1 is a chemorepulsant and matrix protein expressed during and required for osteoclast differentiation, which also plays a role in inflammation by preventing macrophage egress. Because wear particle-induced osteolysis requires osteoclast-mediated destruction of bone, we hypothesised that blockade of Netrin-1 or Unc5b, a receptor for Netrin-1, may diminish this pathological condition. Methods C57BL/6 mice, 6-8 weeks old, had 3 mg of ultrahigh-molecular-weight polyethylene particles implanted over the calvaria and then received 10 µg of monoclonal antibodies for Netrin-1 or its receptors, Unc5b and deleted in colon cancer (DCC), injected intraperitoneally on a weekly basis. After 2 weeks, micro-computed tomography and histology analysis were performed. Netrin-1 expression was analysed in human tissue obtained following primary prosthesis implantation or after prosthesis revision for peri-implant osteolysis and aseptic implant loosening. Results Weekly injection of anti-Netrin-1 or anti-Unc5b-antibodies significantly reduced particle-induced bone pitting in calvaria exposed to wear particles (46±4% and 49±3% of control bone pitting, respectively, p&lt;0.001) but anti-DCC antibody did not affect inflammatory osteolysis (80±7% of control bone pitting, p=ns). Anti-Netrin-1 or anti-Unc5b, but not anti-DCC, antibody treatment markedly reduced the inflammatory infiltrate and the number of tartrate resistance acid phosphatase (TRAP)-positive osteoclasts (7±1, 4±1 and 14±1 cells/high power field (hpf), respectively, vs 12±1 cells/hpf for control, p&lt;0.001), with no significant changes in alkaline phosphatase-positive osteoblasts on bone-forming surfaces in any antibody-treated group. Netrin-1 immunostaining colocalised with CD68 staining for macrophages. The peri-implant tissues of patients undergoing prosthesis revision surgery showed an increase in Netrin-1 expression, whereas there was little Netrin-1 expression in soft tissues removed at the time of primary joint replacement. Conclusions These results demonstrate a unique role for Netrin-1 in osteoclast biology and inflammation and may be a novel target for prevention/treatment of inflammatory osteolysis.
Developmental origin of age-related coronary artery disease
Authors: Ke Wei, Ramon Díaz-Trelles, Qiaozhen Liu, Marta Diez-Cuñado, Maria-Cecilia Scimia, Wenqing Cai, Junko Sawada, Masanobu Komatsu, Joseph J. Boyle, Bin Zhou, Pilar Ruiz-Lozano, Mark Mercola
Journal: Cardiovascular Research (2015)

Age and injury cause structural and functional changes in coronary artery smooth muscle cells (caSMCs) that influence the pathogenesis of coronary artery disease. Although paracrine signalling is widely believed to drive phenotypic changes in caSMCs, here we show that developmental origin within the fetal epicardium can have a profound effect as well.Fluorescent dye and transgene pulse-labelling techniques in mice revealed that the majority of caSMCs are derived from Wt1(+), Gata5-Cre(+) cells that migrate before E12.5, whereas a minority of cells are derived from a later-emigrating, Wt1(+), Gata5-Cre(-) population. We functionally evaluated the influence of early emigrating cells on coronary artery development and disease by Gata5-Cre excision of Rbpj, which prevents their contribution to coronary artery smooth muscle cells. Ablation of the Gata5-Cre(+) population resulted in coronary arteries consisting solely of Gata5-Cre(-) caSMCs. These coronary arteries appeared normal into early adulthood; however, by 5-8 months of age, they became progressively fibrotic, lost the adventitial outer elastin layer, were dysfunctional and leaky, and animals showed early mortality.Taken together, these data reveal heterogeneity in the fetal epicardium that is linked to coronary artery integrity, and that distortion of the coronaries epicardial origin predisposes to adult onset disease.
Study design considerations for phase II trials of anaplastic gliomas and its impact on phase III survival studies
Authors: V. A. Levin, K. R. Hess
Journal: Journal of Clinical Oncology (2006)

1501 Background: Phase 2 trials for anaplastic gliomas (AG; WHO 3) such as anaplastic astrocytoma, oligoastrocytoma, and oligodendroglioma remain the most productive path for the development of new therapeutic strategies for the treatment of patients with these tumors. To better understand methodology for their conduct and impact of phase 2 trials on survival-based phase 3 studies, we reviewed a large patient database of patients treated by faculty from the UTMDACC. Methods: Combined data from contemporary (1999–2004) clinical trials and a UT MDACC patient database of AG patients treated on phase 2 studies were analyzed to determine progression-free survival (PFS) at 6, 9, and 12 months. Variables of age, KPS, number of prior chemotherapies, and response to treatment were also evaluated in an effort to define PFS with respect to treatment activity (durability). Results: A total of 547 patients in 17 phase 2 studies were analyzed. The major effecter of PFS outcome at 6, 9, and 12 months was the specific chemotherapy used. The covariates of age, KPS, treatment response rate, and number of prior chemotherapies did not significantly affect PFS to the same extent. Cluster analyses demonstrated the existence of four major therapeutic efficacy groups ranging from A to D. A-group PFS 6 was 13% and D-group 40%; for PFS 12 A-group was 15% and D-group 32%. Conclusions: The relative differences in PFS among the 4 groups was similar implying that using PFS 6 for AG studies is a valid endpoint and extending studies to PFS 12 is not cost- or time-effective (27 patients vs. 57 patients). In addition, given that 8 of the 17 studies achieved PFS 12 of &gt;25%, it raises the question whether phase 3 survival studies can or should be conducted at this time. Since there are many effective secondary and tertiary treatments for patients who fail chemotherapy, the objective of overall survival for phase 3 AG studies is a flawed objective. For phase 3 studies, PFS is a much more valuable and reliable number to reflect the true antitumor benefit of a form of chemotherapy. Since the median survival of AG patients can range from 4 to 6 years, focusing on PFS in phase 3 studies will also allow more rapid studies and, therefore, the potential to evaluate and discover more and better treatment options for our patients. No significant financial relationships to disclose.