tbuckley/cabot-search huggingface dataset:
Acute care utilization (ACU) among women receiving adjuvant chemotherapy for early breast cancer (EBC).
Authors: Katherine Enright, Eva Grunfeld, Lingsong Yun, Rahim Moineddin, Susan Faye Dent, Andrea Eisen, Maureen E. Trudeau, Leonard Kaizer, Craig Earle, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2012)

65 Background: Adjuvant chemotherapy is considered standard care for patients with lymph node (LN) positive and high risk LN negative EBC. While toxicities of chemotherapy are documented in clinical trials, the impact of toxicities on ACU at a population level is unknown. We undertook a population based study of ACU in patients undergoing adjuvant chemotherapy for EBC compared with controls. Methods: All EBC patients diagnosed 01/07 – 12/09 in Ontario, Canada, were identified from the Ontario Cancer Registry. Pt records were linked deterministically to provincial healthcare databases. All patients received ≥1 cycle of adjuvant chemotherapy. EBC cases (n = 4,718) were matched to non-cancer controls (n = 4,718) on age and geographic location. ACUs (emergency room or hospitalizations) within 30 days of chemotherapy were identified. If the primary reason for visit was a common toxicity of chemotherapy, the visit was considered chemotherapy associated (CA). All cause and CA visits were compared between cases and controls. Logistic regression models were used to identify covariates associated with ACU. Results: ACU was significantly higher in EBC pts compared with controls for both all cause (42.1% vs 9.1%, p&lt;.001) and CA (30.7% vs 2.4%, p&lt;.001) visits. Fever was the most common CA toxicity (22.9% vs 1.2%, p&lt;.001). Taxanes were significantly associated with increased ACU compared with anthracycline only. Conclusions: ACU is common among EBC receiving chemotherapy and significantly higher than among controls. Interventions aimed at mitigating CA toxicity, particularly with the use of taxanes may reduce ACUs. [Table: see text]
Tumor epithelial cell MMP-9 is a prognostic marker in colorectal cancer
Authors: David Zuzga, Ahmara Gibbons, Peng Li, Wilhelm Lubbe, Inna Chervoneva, Giovanni Pitari
Journal: Clinical Cancer Research (2008)

A40  Colorectal cancer is the second leading cause of cancer-related mortality in developed nations. Mortality from colon cancer largely reflects metastasis, the spread of the disease to distant sites. Early diagnosis of pre-metastatic disease and accurate stratification of patients with metastasis is pivotal to decrease mortality rates from colon cancer by effectively administering surgery alone or with chemotherapy. However, specific pathological markers of colorectal cancer metastasis have not emerged. Matrix metalloproteinase 9 (MMP-9) is a key regulator of metastasis and a therapeutic target in colon cancer. Here, MMP-9 overexpression in pure tumor epithelial, but nor stromal, cell populations from patients was associated with metastatic colorectal cancer progression as defined by RT-PCR and confirmed by immunostaining. Thus, tumors with increased MMP-9 expression compared to matched normal adjacent tissues always exhibited metastatic dissemination. In particular, MMP-9 overexpression in tumor epithelial cells, compared to normal epithelial cells, specifically predicted lymph node involvement. Importantly, patients with relative increase of MMP-9 levels in tumor epithelial cells were characterized by more advanced disease stages, with significantly higher proportion of regional lymph nodes harboring metastasis, compared to patients with a relative decrease in MMP-9 expression. Together, these observations suggest tumor epithelial cell MMP-9 is a novel prognostic marker that may be exploited for more efficient disease stage stratification and therapeutic regimen selection in patients with colorectal cancer.
Esophageal Cancer: The Mode of Lymphatic Tumor Cell Spread and Its Prognostic Significance
Authors: Stefan B. Hosch, Nikolas H. Stoecklein, U. Pichlmeier, Alexander Rehders, Peter Scheunemann, Axel Niendorf, Wolfram T. Knoefel, Jakob R. Izbicki
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Data on skip metastases and their significance are lacking for esophageal cancer. This issue is important to determine the extent of lymphadenectomy for esophageal resection. In this study we examined the lymphatic spread in esophageal cancer by routine histopathology and by immunohistochemistry. PATIENTS AND METHODS: A total of 1,584 resected lymph nodes were obtained from 86 patients with resected esophageal carcinoma and evaluated by routine histopathology. Additionally, frozen tissue sections of 540 lymph nodes classified as tumor-free by routine histopathology were screened for micrometastases by immunohistochemistry with the monoclonal antibody Ber-EP4. The lymph nodes were mapped according to the mapping scheme of the American Thoracic Society modified by Casson et al. RESULTS: Forty-four patients (51%) had pN1 disease, and 61 patients (71%) harbored lymphatic micrometastases detected by immunohistochemistry. Skip metastases detected by routine histopathology were present in 34% of pN1 patients. Skipping of micrometastases detected by immunohistochemistry was found in 66%. The presence of micrometastases was associated with a significantly decreased relapse-free and overall survival (56.0 v 10.0 months and &gt; 64 v 15 months, P &lt; .0001 and P = .004, respectively). Cox regression analysis revealed the independent prognostic influence of micrometastases in lymph nodes. Lymph node skipping had no significant independent prognostic influence on survival. CONCLUSION: Histopathologically and immunohistochemically detectable skip metastases are a frequent event in esophageal cancer. Only extensive lymph node sampling, in conjunction with immunohistochemical evaluation, will lead to accurate staging. An improved staging system is essential for more individualized adjuvant therapy.
Occupational exposure to carcinogens and lung cancer: impact of a dedicated professional disease consultation in a Belgian oncologic centre
Authors: Anne Pascale Meert, Isabelle Morelle, Thierry Berghmans, Ingrid C.S. Toth, Jean Paul Sculier
Journal: European Respiratory Journal (2011)

Introduction:  In epidemiological studies, 15% of lung cancers in men and 5% in women are linked to occupational exposure to carcinogens. However, there is a clear under-reporting of occupational lung cancer in Belgium: in 2006, only 67 cases were recognized by the Professional Disease Fund whereas 500 were attended.   Aim:  To appreciate the frequency of occupational lung cancer in newly diagnosed lung cancer in a Belgian oncologic hospital.   Material and method:  Since 01/09/2009, all new patients with lung cancer were sent to a dedicated consultation where a physician trained in professional disease asked information about job history and look for known or suspected lung carcinogenic exposure.   Results:  73 job stories have been recorded, 23 patients (32%) were certainly or probably exposed to a lung carcinogenic agent (known or suspected). All the patients were men (mean age 62 years), 22 workmen, 21 were smokers. Asbestos was the most common carcinogenic agent found (25%). Ten claims for occupational disease were made; 3 recognized and 7 are pending.   Conclusion:  This study shows the utility of a physician with knowledge in occupational pathology into a clinical department to reduce the under-reporting of occupational primary lung cancer and then to ensure that the victims receive the appropriate medico-legal benefits.
Phase I pharmacokinetic study of multicycle high-dose carboplatin followed by peripheral-blood stem-cell infusion in patients with cancer.
Authors: M J Johansen, T Madden, R C Mehra, J G Wood, G Rondon, V Browne, R A Newman, R E Champlin
Journal: Journal of Clinical Oncology (1997)

PURPOSE To examine the feasibility of escalating carboplatin area under the concentration-time curve (AUC), using dose predictions based on individual estimates of drug clearance, in a phase I trial of multicycle carboplatin, paclitaxel, and cyclophosphamide chemotherapy with peripheral-blood stem-cell (PBSC) replacement. PATIENTS AND METHODS Forty-four patients (37 breast, seven ovarian) received 165 courses. Initial target carboplatin AUC was 10 mg/ml x min, with interpatient escalation in increments of 25%. Initial carboplatin dose estimates used creatinine clearance (CrCl) to estimate carboplatin clearance. Subsequent clearance and dose estimates were determined using a model incorporating Bayesian estimation and two measured carboplatin plasma ultrafiltrate concentrations. RESULTS Median clearance was 80.5 mL/min/m2 (range, 41.6 to 131.8). Carboplatin doses up to 2,440 mg/m2 per course were administered without major extramedullary toxicity. Doses varied 2.6-fold at each exposure level. Using the Bayesian model, AUC was predicted with a mean accuracy of 101.2% (83% using CrCl). Ninety-six of 117 courses were within 25% of the target AUC. This model was less biased (0.15 v -2.35 mg/mL x min) and more precise (2.76 v 3.52) in predicting AUC compared with one using CrCl. Hematologic recovery was not prolonged with increasing exposure. The carboplatin maximum-tolerated systemic exposure (MTSE) was 13.3 mg/mL x min (level five). The dose-limiting toxicity was cardiac toxicity, which occurred at dose levels six and seven. CONCLUSION Results demonstrate that (1) CrCl is a poor estimator of carboplatin clearance in this population, and (2) the use of a model incorporating limited sampling and Bayesian estimation improves the precision of carboplatin clearance estimation and is suitable for targeting carboplatin exposure in an ambulatory setting.
Obstructive Sleep Apnea Syndrome
Authors: GEORGES BETTEGA, JEAN-LOUIS PÉPIN, DAN VEALE, CHRYSTÈLE DESCHAUX, BERNARD RAPHAËL, PATRICK LÉVY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The place of surgical treatment in obstructive sleep apnea syndrome (OSAS) remains unclear. Uvulopalatopharyngoplasty (UPPP) has a response rate of 41% overall and only 5% when retrolingual narrowing is present. Thus, in cases with suspected hypopharyngeal collapse maxillofacial surgery has been proposed with improved results. The Stanford group has designed a step-by-step surgical procedure tailored to the specific anatomical abnormalities encountered in each patient. The goal is to avoid a full maxillomandibular advancement osteotomy (MMO), at least in a subgroup of patients, beginning with a limited mandibular osteotomy (with or without hyoid myotomy and hyothyroidopexy and with or without UPPP) (phase 1 surgery). In this procedure MMO is performed as the second or third step (phase 2 surgery). The present study reports on our prospective experience with 51 consecutive patients (64 surgical procedures) treated by the step-by-step maxillofacial surgery previously described by the Stanford team. Only 2 of the 53 patients initially treated were lost for follow-up. Surgery was considered a success if the postoperative apnea and hypopnea index (AHI) was less than 15/h with at least a 50% reduction. Forty-four patients had phase 1 surgery. The success rate was 22.7% (10 of 44). The mean AHI was unchanged with a trend for reduction in the apnea index. Twenty patients had maxillomandibular advancement surgery (phase 2) (13 failures of phase 1, 7 patients primarily because of facioskeletal deformities). The AHI decreased from 59 ± 29/h to 11 ± 9/h after phase 2. Of the patients 75% (15 of 20) were considered to have had a successful outcome. In conclusion, phase 1 does not seem effective in most patients with OSAS. The results of phase 2 surgery are successful in young patients with severe OSAS even if the surgical technique is more aggressive.
Major toxicity of cisplatin, fluorouracil, and leucovorin following chemoradiotherapy in patients with nasopharyngeal carcinoma.
Authors: I Celik, A Kars, E Ozyar, G Tekuzman, L Atahan, D Firat
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.3.1043 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8622011 Major toxicity of cisplatin, fluorouracil, and leucovorin following chemoradiotherapy in patients with nasopharyngeal carcinoma. I CelikxI CelikSearch for articles by this author , A KarsxA KarsSearch for articles by this author , E OzyarxE OzyarSearch for articles by this author , G TekuzmanxG TekuzmanSearch for articles by this author , L AtahanxL AtahanSearch for articles by this author , D FiratxD FiratSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.3.1043 PDF "Major toxicity of cisplatin, fluorouracil, and leucovorin following chemoradiotherapy in patients with nasopharyngeal carcinoma.." Journal of Clinical Oncology, 14(3), pp. 1043–1044© 1996 by American Society of Clinical Oncology
Efficacy of Bortezomib Plus Dexamethasone Versus Bortezomib Monotherapy In Patients with Relapsed/Refractory Multiple Myeloma: An Interim Report from an International Electronic Observational Study
Authors: Meletios A. Dimopoulos, Hadewijch M De Samblanx, Maria G Roussou, Konstantinos Zervas, Eirini Katodritou, Deniz Sargin, Cyrille Hulin, Lucia Ahlberg, Javier De La Rubia, Rita Ganguly, Joris K Diels, Helgi van de Velde, Ravinder Dhawan, Michael D Spencer, Michel Delforge
Journal: Blood (2010)
miR-663 Suppresses Oncogenic Function of <i>CXCR4</i> in Glioblastoma
Authors: Yu Shi, Cong Chen, Shi-Zhu Yu, Qing Liu, Jun Rao, Hua-Rong Zhang, Hua-Liang Xiao, Ti-Wei Fu, Hua Long, Zhi-Cheng He, Kai Zhou, Xiao-Hong Yao, You-Hong Cui, Xia Zhang, Yi-Fang Ping, Xiu-Wu Bian
Journal: Clinical Cancer Research (2015)

Abstract Purpose: To identify the miRNA regulators of C–X–C motif chemokine receptor 4 (CXCR4) and the underlying mechanism as well as the therapeutic and prognostic values in human glioblastoma (GBM). Experimental Design: miRNA profile analyses and bioinformatics predictions were used to identify the mediators of CXCR4, which were confirmed by luciferase reporter assay, Western blot assay and immunohistochemistry. The effects of miR-663 on CXCR4-mediated GBM malignancy were investigated by gain-of-function experiments. Orthotopic xenografts derived from constitutive or induced miR-663–expressing GBM cells were used to determine the antitumor effects of miR-663 and CXCR4-specific antagonist AMD3100. Bivariate correlation analyses were used to examine the correlation of miR-663 and CXCR4 levels in glioma. The prognostic values of miR-663 and CXCR4 were examined in 281 cases of astrocytic glioma from our hospital and 476 cases of GBM from The Cancer Genome Atlas database using the multivariate Cox regression analysis and Kaplan–Meier analysis. Results: miR-663 negatively regulated CXCR4 expression by targeting its coding sequence in GBM and compromised the proliferative and invasive capacities of GBM cells induced by CXCR4 overexpression. Constitutive or induced miR-663 overexpression combined with CXCR4 antagonist AMD3100 suppressed orthotopic GBM growth and prolonged tumor-bearing mice survival. Clinically, miR-663 and CXCR4 were inversely correlated in GBM and composed a valuable biomarker set in predicting the outcomes of GBM patients. Conclusions: miR-663 negatively regulated CXCR4 to inhibit its oncogenic effect. Combination of miR-663 and CXCR4 can serve as a valuable prognostic biomarker set as well as molecular targets for therapeutic intervention of GBM. Clin Cancer Res; 21(17); 4004–13. ©2015 AACR.
Abstract 2683: Inhibition of BCAT1 suppresses the expression of pro-metastatic proteins and reduces cancer metastasis
Authors: Adonia E. Papathanassiu, Hong A. Vu
Journal: Cancer Research (2014)

Abstract Recent evidence suggests that the cytosolic presence of branched chain amino acid aminotransferase (BCAT1) in adult tissues is associated with diverse pathological conditions including cancer and inflammatory diseases such as rheumatoid arthritis; in these diseases, BCAT1 appears to modulate the expression of many key proteins and to be a new druggable target. In cancer, BCAT1 physically associates with CD147 and regulates the levels and the cellular localization of the protein in a number of different cell lines in vitro and in vivo. Silencing of Bcat1 gene downregulates the total expression of CD147 in MDA-MB-435 cells, while inhibition of BCAT1 by sodium 4-methyl-5-oxo-hexanoate (ERG240) leads to suppression of the extracellular CD147 in the same cells. In turn, suppression of extracellular CD147 results in downregulation of CD147-associated proteins such as MCT4, matrix metalloproteinases (MMPs), cyclophilin A, and GAPDH. Furthermore, inhibition of BCAT1 is associated with prevention of cancer cell migration and reduction in secretion of metabolic by-products such as lactate. Surprisingly, treatment of MDA-MB-231 tumor-bearing animals with 2-deoxyglucose (2DG), a well-known inhibitor of glycolysis, leads to a decrease in the levels of c-MYC and BCAT1, an increase in the total expression of CD147, and the increased shedding of the extracellular CD147 into the circulation. This observation suggests that BCAT1-driven regulation of CD147 in cancer cells involves a complex mechanism. Inhibition of tumoral BCAT1 is expected to adversely affect the metastatic potential of various tumors not only through a reduction in cell motility but also through alterations in the tumor microenvironment, driven by inhibition of extracellular CD147. Citation Format: Adonia E. Papathanassiu, Hong A. Vu. Inhibition of BCAT1 suppresses the expression of pro-metastatic proteins and reduces cancer metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2683. doi:10.1158/1538-7445.AM2014-2683
Observations on a model of proliferative lung disease
Authors: P. R. B. Caldwell, U. Echeverri, M. M. Kilcoyne, H. W. Fritts
Journal: Journal of Clinical Investigation (1970)

Measurements of gas exchange in dogs with granulomatous lung disease resembled those which have been made in similar disorders of man. The minute volume of ventilation was large, the oxygen extracted from each liter of ventilation was low, and the arterial blood oxygen saturation tended to be subnormal despite hyperventilation. When the diseased dogs breathed 21% oxygen and had alveolar oxygen tensions above 100 mm Hg, the pulmonary blood flows calculated from the Fick principle were significantly higher than those estimated by the dye-dilution method. By way of contrast, the two values agreed when the alveolar tensions were lowered. Whether the agreement of the flows is causally related to the alveolar tension remains an open question. A possible explanation may lie in the effect of alveolar tension on the oxygen consumed by the diseased lung.
Abstract 1904: Myocardial Postconditioning Against Ischemia and Reperfusion Injury by Near Infrared Electromagnetic Radiation
Authors: Phillip F Pratt, Martin Bienengraeber, Dorothee Weihrauch, Judy R Kersten, David C Warltier
Journal: Circulation (2008)

Near-infrared electromagnetic radiation (NIR) has been reported to stimulate biochemical processes within cells and tissue, but whether NIR is capable of acutely protecting myocardium against ischemia+reperfusion injury in vivo is unknown. We tested the hypothesis that NIR (670 nm, 30 nm bandwith, 50 mW/cm 2 ) exposure immediately before and during early reperfusion protects rabbit myocardium against infarction that is dependent upon reactive oxygen species (ROS), nitric oxide synthase (NOS), mitochondrial K ATP (mito K ATP ) channels and inhibition of mitochondrial permeability transition pore (mPTP) opening. Rabbits subjected to a 30 min left anterior descending coronary artery occlusion and reperfusion received no irradiation (control) or continuous NIR (beginning 3 min before and ending 7 min after reperfusion) in the presence or absence of ROS scavengers [N-acetylcysteine (NAC; 150 mg/kg), or tempol (30 mg/kg)], nonselective NOS inhibitor L-nitro-arginine methyl ester (L-NAME; 10 mg/kg), selective mitoK ATP channel antagonist 5-hydroxydecanoate (5-HD; 10 mg/kg) or mPTP opener atractyloside (5 mg/kg). Dihydroethidium and diaminofluroscein immunofluorescence were used to detect ROS and NO production, respectively, in additional rabbits with or without NIR exposure. NIR reduced infarct size (24±4% of the area at risk; triphenyltetrazolium chloride staining) compared with control (46±3%). NAC, tempol, L-NAME, 5-HD, and atractyloside alone did not affect infarct size, but these drugs abolished the cardioprotective effect of NIR. NIR increased ROS production independent of ischemia and reperfusion, and this effect was blocked by NAC. NIR also enhanced NO generation during early reperfusion. In addition, NIR increased ATP synthesis in isolated rabbit mitochondria. Thus, NIR postconditions myocardium against infarction concomitant with ROS and NO production. MitoK ATP channels and mPTP mediate cardioprotection by NIR.
Rate of Psychiatric Illness 1 Year After Traumatic Brain Injury
Authors: Shoumitro Deb, Ita Lyons, Charis Koutzoukis, Imad Ali, Geraldine McCarthy
Journal: American Journal of Psychiatry (1999)

Neurobehavioral symptoms are not uncommon after a traumatic brain injury. However, psychiatric syndromes per se have rarely been studied in patients with such an injury. The purpose of this study was to evaluate the type and extent of psychiatric syndromes in patients with traumatic brain injury.One hundred ninety-six hospitalized adults were studied 1 year after a traumatic brain injury with the use of a two-stage psychiatric diagnostic procedure. Psychiatric diagnoses were made according to ICD-10 criteria on the basis of data from the Schedules for Clinical Assessment in Neuropsychiatry interview.Of 164 patients interviewed, 30 (18.3%) had an ICD-10 diagnosis of a psychiatric illness. Among the 120 patients who were 18-64 years old, 21.7% had a psychiatric illness, compared with 16.4% in a study of the general population. A depressive illness was present in 13.9% of the traumatic brain injury patients, compared with 2.1% of the general population, and panic disorder was present in 9.0%, compared with 0.8% of the general population.In comparison with the general population, a higher proportion of adult patients had developed psychiatric illnesses 1 year after a traumatic brain injury; the rates of depressive episode and panic disorder were significantly higher in the study group. A history of psychiatric illness, an unfavorable global outcome according to the Glasgow Outcome Scale, a lower score on the Mini-Mental State examination, and fewer years of formal education seemed to be important risk factors in the development of a psychiatric illness. Compensation claims, however, were not associated with the rate of psychiatric illness.
Fibrosing alveolitis in an infant
Authors: J Riedler, A Golser, I Huttegger
Journal: European Respiratory Journal (1992)

A three month old female infant presented with unproductive cough, diffuse bilateral fine crackles, tachypnoea and failure to thrive despite a four month therapy with beta 2-agonists and antibiotics. A chest radiograph showing bilateral periphilar infiltrates and a patchy infiltrate in the right upper lobe and lingula did not explain the physical examination with diffuse bilateral fine crackles. As the condition did not improve and arterial oxygen tension (PaO2) and oxygen saturation decreased during the following two months, an open lung biopsy was performed. The surgeon described the lungs as rubbery in consistency and histological findings showed patchy mild interstitial fibrosis and thickened alveolar septa. A therapy with prednisone daily was started and given over a period of four months, but did not show sufficient improvement. Only after addition of azathioprine was clinical improvement and normalization of blood gases noted.