tbuckley/cabot-search huggingface dataset:
Consistency of Effect of Docetaxel-Containing Adjuvant Chemotherapy in Patients with Early Stage Breast Cancer Independent of Nodal Status: Meta-Analysis of 12 Randomized Clinical Trials.
Authors: S. Laporte, S. Jones, C. Chapelle, J. Jacquin, M. Martín
Journal: Cancer Research (2009)

Abstract BackgroundUp to now taxanes have been extensively evaluated in the treatment of node-positive early-stage breast cancers (ESBC). Recently, more data have become available in patients with node-negative as well as node-positive ESBC treated with docetaxel-based regimens. We conducted a meta-analysis of randomized ESBC trials in order to evaluate the efficacy of adjuvant docetaxel-based regimens in terms of disease-free survival (DFS), overall survival (OS), and whether treatment effects are maintained across different nodal status subpopulations.MethodsStudies including at least 100 patients and presented or published before December 31, 2008 were retrieved by searching the MEDLINE, CANCERLIT, and Cochrane Library databases and the proceedings of major conferences. Outcomes recorded were DFS and OS. We extracted hazard ratios (HR) and 95% CIs for DFS and OS from each trial and obtained pooled estimates using an inverse-variance model in a random effect model. In trials including both node-positive and node-negative breast cancers, and with nodal status as a clear stratification factor at randomization, HR were extracted for each subpopulation separately. A HR less than 1 indicated that docetaxel was superior to the no-taxane regimen.ResultsTwelve randomized phase III studies were included in the meta-analysis (20 698 patients). Three subsets of trials/strata were used: node-positive (10 trials or strata, 14 787 patients), node-negative (4 trials/strata, 4 274 patients), or combination of both (2 trials, 1 637 patients). Overall, the pooled HR estimate [95% CI] for DFS was 0.81 [0.74;0.89] (P&amp;lt;0.001) in favor of docetaxel-based chemotherapy. The results are the same for node-positive (HR=0.84 [0.77;0.91]) and node-negative breast cancer (HR=0.84 [0.72;0.99]). The overall estimated HR for OS was 0.81 [0.72;0.91] (P&amp;lt;0.001). Results by nodal status subpopulations are awaited.ConclusionThis meta-analysis of 12 recent randomized phase III trials shows that adjuvant docetaxel-based chemotherapy compared to regimens without taxanes is associated with an improvement in DFS and OS independent of nodal status. Other analyses will also be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 605.
Recurrent disease following endoscopic ablation of Barrett’s high-grade dysplasia with spray cryotherapy
Authors: K. Halsey, J. Chang, A. Waldt, B. Greenwald
Journal: Endoscopy (2011)

<b>Background and aims:</b> Recurrent disease after endoscopic ablation of Barrett’s esophagus should be detected early to prevent malignant progression. We assessed the incidence and patterns of disease recurrence in patients after liquid nitrogen spray cryotherapy ablation of Barrett‘s esophagus with high grade dysplasia (HGD), including the area below the neosquamocolumnar junction (NSCJ). <b>Patients and methods:</b> This is a single-center, retrospective study of prospectively collected data on consecutive cases of endoscopic ablation with liquid nitrogen spray cryotherapy for Barrett’s HGD. Post-treatment surveillance biopsies were obtained of suspicious lesions and in 4 quadrants every 1 cm in the treated esophagus and just below the NSCJ. Primary outcome measures were location and histology of recurrent disease. <b>Results:</b> 36 patients (median age 62 years, 92% men) were enrolled, and 11 (30%) developed recurrent disease in a median of 6.5 months; three developed a second recurrence. Ten recurrences (71%) were identified below the NSCJ in 9 patients, including HGD (4), low grade dysplasia (LGD) (2), and intestinal metaplasia (4). Six recurrences were identified in the treated esophagus in five patients, including intramucosal cancer (1), HGD (1), and intestinal metaplasia (4). Two patients had recurrent disease involving both locations. Ultimately 33 patients (92%) achieved a complete response. Diagnosis in the remaining three was LGD (1) and intestinal metaplasia (2). <b>Conclusion:</b> Most patients with recurrent intestinal metaplasia with or without dysplasia after ablation achieve a complete response. Recurrent disease commonly involves the area just below the NSCJ. Surveillance endoscopies should include this area to accurately identify patients with disease recurrence.
Urinary Blockade after Bilateral Catheterization
Authors: Joseph J. Kaufman, Patrick J. Moloney, Morton H. Maxwell
Journal: New England Journal of Medicine (1966)

ANURIA or oliguria after the diagnostic use of ureteral catheters is an infrequent but serious complication in urologic practice, occurring most often with differential renal-function studies for which large catheters are inserted for relatively prolonged periods. Most investigators agree that divided kidney-function tests in patients with suspected renovascular hypertension provide qualitative and quantitative data of special importance in determining individual kidney function, in predicting results of surgery and in following the effects of treatment. Clinicians have been so distressed, however, by the morbidity attending the tests that these procedures have been abandoned or greatly curtailed in many institutions. In presenting . . .
Abstract P230: Sex Disparities in Acute Myocardial Infarction Incidence: Do Migrants Differ from the Host Population?
Authors: Aloysia A van Oeffelen, Charles Agyemang, Karien Stronks, Michiel L Bots, Ilonca Vaartjes
Journal: Circulation (2013)

Background Worldwide the incidence of acute myocardial infarction (AMI) in men exceeds that in women, particularly in the young. As the extent of sex disparities varies widely between countries, it...
Abstract 776: Functional analysis of BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) in melanoma.
Authors: Raj Kumar, Ching-Ni Njauw, Zhenyu Ji, Benchun Miao, Michael Taylor, Anpuchchelvi Rajadurai, Durga Udayakumar, Hensin Tsao
Journal: Cancer Research (2013)

Abstract In the US alone, 44,250 men and 32,000 women are expected to be diagnosed with melanoma in 2012. Metastatic melanoma is the leading cause of skin cancer-related deaths worldwide. In the metastatic cutaneous melanoma (CM), anti-BRAF and anti-MEK agents have recently been shown to attenuate progression of the disease, though durable responses are still rare (NEJM articles). For metastatic ocular melanoma (OM), there is currently no established treatment strategy. Thus, one major unmet need in the field is the identification of novel “driver” physiologies which underpin the progression of disease and which can be leveraged for therapeutic gain. One new component in the ubiquitination pathway that has been recently implicated in the biology of both CM and OM is BRCA1 associated protein-1 (BAP1). Preliminary data from our laboratory showed that germline inactivating mutations of BAP1 predispose individuals to both CM and metastatic OM along with other neoplasms. In this study we examined the effects of BAP1 knockdown and overexpression on melanoma cell lines and primary melanocytes. BAP1 gene is mutated in melanoma and reported to be tumor suppressor, however suppression of BAP1 led to paradoxical growth inhibition, suggesting that the effects of BAP1 may be context dependent. Currently we are performing global gene expression and allele specific functional studies in an effort to identify novel substrates and other pathways impacted by BAP1. These findings may provide mechanistic insight into the role of BAP1 in melanoma pathogenesis. Citation Format: Raj Kumar, Ching-Ni Njauw, Zhenyu Ji, Benchun Miao, Michael Taylor, Anpuchchelvi Rajadurai, Durga Udayakumar, Hensin Tsao. Functional analysis of BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) in melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 776. doi:10.1158/1538-7445.AM2013-776
The DCC Protein and Prognosis in Colorectal Cancer
Authors: David Shibata, Michael A. Reale, Philip Lavin, Mark Silverman, Eric R. Fearon, Glenn Steele, John M. Jessup, Massimo Loda, Ian C. Summerhayes
Journal: New England Journal of Medicine (1996)

Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma.
Abstract 94: Identifying biomarkers of estrogen response in models of serous ovarian cancer.
Authors: Courtney L. Andersen, Matthew J. Sikora, Paul Haluska, Steffi Oesterreich
Journal: Cancer Research (2013)

Abstract Ovarian cancer is the fifth leading cause of cancer death among women in the United States. Despite advances in treatment for other cancers, ovarian cancer patient prognosis has not improved significantly since the advent of platinum-based chemotherapy. It is a highly heterogeneous disease with at least four distinct histological subtypes: serous, mucinous, endometrioid, and clear cell. However, no subtype- or biomarker-specific therapies are approved for ovarian cancer. Identifying targeted therapies is crucial to improving clinical outcomes. Specific therapies will likely vary based on tumor histology and biomarkers. Expression of estrogen receptor alpha (ER) is a well established biomarker of response to endocrine therapies in breast cancer. Despite the success of anti-estrogen therapies in treating breast cancer, little attention has been given to their potential in ovarian cancer. However, epidemiologic studies show that approximately 70% of epithelial ovarian tumors express ER, particularly serous and endometrioid subtypes, and that estrogen plays a role in ovarian cancer etiology. Further, clinical data suggest that a subset of ovarian cancer patients can be successfully treated with endocrine therapy. We hypothesize that some ovarian tumors require estrogen for growth and that predictive biomarkers will identify patients who will benefit from endocrine therapy. Using cell line models, we examined the response of ovarian cancer cells to estrogen (E2) and anti-estrogens with regard to gene expression and cell proliferation. E2 induces expression of canonical ER target genes (e.g. GREB1) in these cells, suggesting that they are estrogen-responsive. We observe that 4-hydroxytamoxifen and fulvestrant inhibit growth of ovarian cancer cells including the chemo-resistant line PEO4. Gene expression microarray studies identified additional E2-regulated genes in ovarian cancer cells that may be utilized as biomarkers of ER activity. We are expanding our studies to in vivo models (human primary tumor xenografts) to evaluate the role of E2 in driving tumor progression and determine the efficacy of anti-estrogens in treating serous ovarian cancer. There is a critical need for targeted therapies in ovarian cancer. Our studies will determine if endocrine responsiveness correlates with gene expression of specific biomarkers, which may lead to the identification of predictive clinical markers of response to endocrine therapy. Citation Format: Courtney L. Andersen, Matthew J. Sikora, Paul Haluska, Steffi Oesterreich. Identifying biomarkers of estrogen response in models of serous ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 94. doi:10.1158/1538-7445.AM2013-94
P17.10 * GEMISTOCYTIC ASTROCYTOMAS: MONO-INSTITUTIONAL EXPERIENCE
Authors: A. Botturi, P. Gaviani, G. Simonetti, A. Innocenti, B. Pollo, E. Lamperti, F. Legnani, A. Silvani
Journal: Neuro-Oncology (2014)

Gemistocytic astrocytoma (GA) is variant of diffuse astrocytoma, characterized by the presence of at least 20% gemistocytic neoplastic astrocytes (usually around 35%, in the past 60%). They represent 9-19% of astrocytic tumors with median age at diagnosis of 40 years. Population-based studies on low grade gliomas suggest a worse prognosis for GA compared to fibrillary or protoplasmatic variants. WHO classification does not qualify GA as a high grade astrocytoma, since there is insufficient data to define gemistocytic morphology as an independent prognostic indicator. The mOS reported is 2.5 years, with a 5-year survival rate of 30%. In the present study we retrospectively identified all consecutive patients with proven gemistocytic astrocytoma diagnosed and treated in our Institution between 1985 and 2012 with the aim to correlate the clinical and histopathological findings with survival. Primary endpoint was OS in the whole group of patients and secondary endpoint was OS correlated to age and presence of anaplasia. A total of 78 patients (28 female, and 58 male), with median age at diagnosis 46 years, underwent surgical procedure at diagnosis (42% second surgery and 8% third surgery). In 32% (25/78 patients) of patients focal signs of anaplasia were described at diagnosis. 63% (49/78) underwent postoperative radiotherapy and 70.5% (55/78) underwent chemotherapy at different time points and with different schedules and drugs (nitrosureas, PCV, fotemustine, temozolomide). Median OS (in 78 patients) was 54 months (range 3-327 months). 26 patients were alive at the end of 2012. The mOS in 53 patients without anaplasia was 86 months (p 0,7 95%CI), mOS in 25 patients with anaplasia was 51 months (p 0,7 95%CI), mOS in 51 patients < 50 years was 86 months (p 0,27 95% CI), mOS in 27 patients ≥ 50 years was 42 months (p 0,27 95%CI). Despite several limitations of the study, our data show a median OS similar to other studies, with a better prognosis in patients younger than 50 years and in patients without focal anaplasia at diagnosis (data not statistically significant). Gemistocytic astrocytoma still continues to be enigmatic both in terms of definition and prognostic implications. Whether these tumors should be considered high grade astrocytomas remains open. Future prospective studies should clarify the value of gemistocytic morphology as an independent prognostic factor, and should investigate the molecular mechanisms that promote the formation of gemistocytes.
Gastric Hypomotility in Duchenne's Muscular Dystrophy
Authors: Richard J. Barohn, Edward J. Levine, John O. Olson, Jerry R. Mendell
Journal: New England Journal of Medicine (1988)

In Duchenne's muscular dystrophy, functional impairment of smooth muscle in the gastrointestinal tract can cause acute gastric dilatation and intestinal pseudo-obstruction that may be fatal. We describe a patient with this syndrome who at autopsy had smooth-muscle degeneration of the stomach. To provide objective evidence of functional smooth-muscle impairment in Duchenne's dystrophy, we performed gastric-emptying studies in 11 patients and 11 normal controls, using technetium-99m radionuclide scintigraphy in a test meal of oatmeal. The patients with Duchenne's dystrophy had delayed gastric-emptying times (118.18±32.21 minutes [mean ±SEM]) as compared with controls (42.5±3.4 minutes, P<0.01). The cause of the pathological and functional abnormalities we describe in smooth muscle is unknown but may be a deficiency of dystrophin, the recently identified gene product of the Duchenne's muscular dystrophy locus. (N Engl J Med 1988; 319:15–8.)
AB1168 Clinical disease activity scores of knee joints in newly diagnosed JIA predicts reduction in bone pixel value detected by computed radiography
Authors: L. Pascoli, A. Mc Cann, M. Stevenson, C. Mc Allister, M. Rooney
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the relationship between Computed Radiography (CR) Pixel values and disease activity scores obtained for the knees of newly diagnosed Juvenile Idiopathic Arthritis (JIA) children. <h3>Methods</h3> Children with newly diagnosed untreated JIA were recruited. Both knees were scored for disease activity on a score of 0-3. Weight-bearing antero-posterior (AP) images of both knees were captured via CR. A hydroxyapatite phantom was fixed to an unobscured region of the phosphor cartridge during all exposures. Pixel values in the phantom region were used to determine the brightness and contrast settings of the CR system allowing conversion of the whole image to values of absolute attenuation. Scattered radiation, whose random nature interferes with measurement of tissue content, was estimated based on Monte Carlo N-particle (MCNP) simulations. Measurements of bone and soft tissue content were taken at 9 repeatable identifiable regions in AP X-rays of both knee joints. The effect of overlying soft tissue in the bone regions was compensated by extracting the residual values of bone versus soft tissue plots over the full data set. Knee joints for all patients were independently assigned clinical scores (none, mild, moderate, severe). Association of clinical score categories with soft tissue and bone residual parameters was characterized by ordinal regression with the individual subject incorporated as a blocking variable. <h3>Results</h3> Forty children were recruited and a total of 80 knees' digital images were obtained. Results showed that a higher clinical score correlates with reduced "bone density" (p=0.003) and with greater ST content (p&lt;0.0001). Moreover, the "bone loss" occurs only in the epiphyseal region compared to the diaphyseal region. Furthermore, we found good agreement between observed and predicted clinical scores on the basis of the "bone density" at the epiphyseal region (Kendall's tau 0.61). <h3>Conclusions</h3> We have demonstrated that a higher clinical score correlates with a reduced "bone density" in the periarticular epiphyseal regions, which is caused by the inflammation process. Thus, following appropriate image acquisition and analysis, CR images can be used to measure periarticular bone loss in JIA. The results obtained from standard X-rays could be of substantial value to the clinician using serial X-rays to determine joint damage over time. We are currently evaluating the CR images obtained over the 2 years of our prospective study and comparing these with disease outcome during the same time period. <h3>Disclosure of Interest</h3> None Declared
Abstract 887: Development of a robust nanoimmunoassay and immunohistochemical assay for asparagine synthetase
Authors: Philip L. Lorenzi, Lindsey E. Heathcock, Kenneth Aldape, John N. Weinstein
Journal: Cancer Research (2012)

Abstract The enzyme-drug L-asparaginase (L-ASP) has been used for four decades to treat acute lymphoblastic leukemia. However, its unique mechanism of action is still poorly understood, and its clinical efficacy has proven unpredictable. Those problems have prompted a continuing search for biomarkers that predict L-ASP response. We previously found that the expression of asparagine synthetase (ASNS) is strongly negatively correlated with L-ASP anticancer activity in ovarian cancer cell lines, suggesting that L-ASP might be effective against a low-ASNS subset of ovarian cancers if salient characteristics of the cell lines reflect clinical ovarian tumors. However, quantitatively robust, single-antibody assays for ASNS expression have been absent from the literature. We therefore used a capillary-based isoelectric focusing (IEF) platform (the NanoPro 1000) to screen twelve ASNS antibodies for their specificity and sensitivity. Only two antibodies exhibited completely on-target activity (as shown by signal ablation by ASNS siRNA) and sufficient sensitivity. The on-target activity corresponded to a single band on Western Blot and a single peak on the NanoPro 1000, suggesting the existence of just one ASNS protein isoform. Optimized, final NanoPro assay conditions yielded less than 8% CV, a 160-fold dynamic range, and Zα-factor of 0.82, indicating a robust assay that is amenable to high-throughput screening. We next used the best ASNS antibody to develop an immunohistochemistry (IHC) assay for ASNS. As with the NanoPro assay, optimized IHC conditions yielded a large dynamic range of staining intensity, and staining was completely ablated by ASNS siRNA. To test the hypothesis that subsets of various cancers express very low levels of ASNS, we have initiated ASNS IHC of more than 20 tissue arrays representing a wide variety of cancers. Using a 3-point scoring system (0 = negative, 1 = low, 2 = high), preliminary results indicate that 90/136 (66%) of bladder cancers, 29/60 (48%) of bone cancers, 16/76 (21%) of breast cancers, 29/115 (25%) of brain cancers, 51/168 (30%) of colon cancers, and 7/64 (11%) of head and neck cancers are ASNS-negative (score = 0), suggesting that a subset of each cancer type might be sensitive to the drug L-asparaginase. Efforts are underway to apply the NanoPro assay to the NCI-60 cell line panel and to continue performing ASNS IHC to survey tissue arrays for ASNS expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 887. doi:1538-7445.AM2012-887
P1085 DETERMINANTS AND IMPACT OF POOR ADHERENCE TO HBV SECOND GENERATION ANALOGS IN REAL LIFE IN FRANCE: THE MULTICENTRIC ADHEPB STUDY
Authors: M.N. Hilleret, T. Fontanges, B. Froissart, J. Dumortier, C. Colin, F. Bourrhis, J. Pofelski, J.P. Zarski, F. Bailly, V. Leroy
Journal: Journal of Hepatology (2014)
PARADOXICAL LOW-FLOW SEVERE AORTIC STENOSIS IN THE SETTING OF APICAL VARIANT HYPERTROPHIC CARDIOMYOPATHY
Authors: Karthiek R. Narala, Sandeep Banga, Mark Hsu, Marco Barzallo, Suneetha Venkatapuram, Sudhir Mungee
Journal: Journal of the American College of Cardiology (2015)
<i>Proteus mirabilis</i>Infections in a Hospital Nursery Traced to a Human Carrier
Authors: John P. Burke, David Ingall, Jerome O. Klein, Horace M. Gezon, Maxwell Finland
Journal: New England Journal of Medicine (1971)

Serious infections due to Proteus mirabilis occurred in 11 full-term newborn infants in a hospital nursery over a four-year period. Bacteremia was demonstrated in 10, meningitis in six, and osteomyelitis in two. Four of the babies died of the infection. The usual factors predisposing to neonatal infection were absent. Epidemiologic investigations pointed to one nurse as the source. The organisms were most probably transmitted to the infants by manipulation of the umbilical cord during the admitting procedures. P. mirabilis was cultured from the hands, vagina and rectum of the nurse and from the umbilicus of seven of 12 consecutive newborn infants whom she admitted, including one who became ill with bacteremia. Among the several markers of P. mirabilis studied, susceptibility to tetracycline best delineated the epidemic strains from others cultured during a study of colonization among patients in the nursery affected, and in another where there had been no infections.