tbuckley/cabot-search huggingface dataset:
Needle-knife incisional treatment of refractory esophagic caustic stenosis
Authors: M Canhoto, B Arroja, F Silva, C Gonçalves, I Cotrim, H Vasconcelos
Journal: Endoscopy (2011)

A 44-year-old man accidentally ingested sodium hydroxide solution in December 2007. Endoscopic evaluation in the emergency room revealed grade III esophagitis and extensive gastric ulcerations. After 2 weeks, the patient had considerable dysphagia in relation to solid foods. The regenerating esophageal mucosa had two 8-mm diameter strictures, at 20 and 25 cm from the central incisor, and there was antral scarring with a pyloric stricture. After multiple attempts at stenosis dilation (Savary-Gilliard and through-the-scope techniques) and betamethasone dipropionate injections (4 mg), there was resolution of the pyloric and proximal esophageal strictures but monthly interventions continued to be required for the refractory esophageal stricture at 25 cm from the incisors. In January 2010, a Polyflex esophageal stent (Boston Scientific, Natick, Massachusetts, USA; inner diameter 16 – 20 mm, length 90 mm) was placed but it was removed 3 months later. Prosthesis removal was difficult because of the presence of granulation tissue at both ends. After prosthesis removal, 9- and 11-mm diameter strictures were observed at 20 and 25 cm from the incisors and the patient attended two additional sessions of dilation and betamethasone dipropionate injections, with resolution of the distal stricture. The fibrotic proximal stricture ([Fig. 1]) was then submitted to needle-knife incisional treatment: several small cuts (Endocut mode, ICC200, ERBE Elektromedizin GmbH, Tubingen, Germany) parallel to the longitudinal axis of the esophagus were made, resulting in widening of the lumen and easy passage of the scope ([Fig. 2]). There were no complications either during or after the procedure. Endoscopic reassessment 1 and 6 months later ([Fig. 3]) showed minor fibrotic retraction. At the 1-year follow-up, no further therapeutic interventions were required as the patient remained free of dysphagia.
Abstract 3481: Development of personalized paclitaxel therapy (IG-001) for ovarian cancer.
Authors: Larn Hwang, Chao Hsiao, Kouros Motamed, Vuong Trieu
Journal: Cancer Research (2013)

Abstract Introduction: IG-001, like nab-paclitaxel, is a polymer bound nanoparticle paclitaxel. It is being developed for difficult to perfuse hypoxic tumors such as pancreatic cancer and ovarian cancer. IG-001 has shown promising activity against ovarian cancer in phase II clinical trials. In the planned phase III trial of IG-001, serum biomarkers as well as blood paclitaxel will be monitored to as prognostic indicators of response. The goal of this study is to developed point-of-care testing devices for PD biomarkers including CA125, B-type natriuretic peptide (BNP), Follicle Stimulating Hormone (FSH) and blood paclitaxel. Methods: Serum samples collected at time of diagnosis of ovarian cancer were tested using rapid and quantitative point-of-care (POC) devices for blood biomarkers (CA125, FSH, BNP, and paclitaxel) and the data were evaluated using JMP9 statistical analysis software. Results: 41 ovarian cancer patients were analyzed for CA125 prior to surgery of which 3 (7%), 11 (27%), and 27 (66%) were clear cell carcinoma, cystadenocarcinoma and adenocarcinoma, respectively. CA125 was not diagnostic of ovarian cancer. However, incidence of elevated (BNP &amp;gt; 25 pg/ml) was higher for patients (14 of 19, 74%) vs. normal controls (3 of 10, 30%, p = 0.02, Chi-square). FSH level was higher (median=151.6 mU/ml) vs. normal controls (median of 13.4 mU/ml, p = 0.01, Wilcoxon). Paclitaxel POC device was developed to monitored paclitaxel level down to 20ng/mL for paclitaxel. Conclusions: Rapid and quantitative point-of-care tests for PD biomarker testing and paclitaxel PK therapeutic drug monitoring have been developed for use in conjunction with IG-001 development against ovarian cancer. IG-001 is ideal for paclitaxel therapeutic drug monitoring (TDM) due to its dose proportional PK. Paclitaxel TDM should allow for more effective dosing of the patients and thereby improving effectiveness of IG-001. These POCTs are also patient-centric, inviting better compliance and patient participation in personalizing his/her treatment. Plasma or serum samples obtained via repetitive venipuncture represent the accepted gold standard for monitoring the pharmacodynamics (PD) and pharmacokinetics (PK) of anticancer agents. Unfortunately for research subjects, the burden of frequent venipuncture is high; and, for researchers, venipuncture samples require immediate processing and storage facilities with freezers. The work presented here resolved the operational difficulty associated with personalized therapy in general and IG-001 in specific. Citation Format: Larn Hwang, Chao Hsiao, Kouros Motamed, Vuong Trieu. Development of personalized paclitaxel therapy (IG-001) for 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 3481. doi:10.1158/1538-7445.AM2013-3481
Significance of the Positive Crossmatch Test in Kidney Transplantation
Authors: Ramon Patel, Paul I. Terasaki
Journal: New England Journal of Medicine (1969)

Crossmatch tests of the prospective kidney-transplant donor's lymphocytes with the serum of the prospective recipient in 225 transplants showed that eight of 195 with negative crossmatch failed to function immediately, in contrast to 24 of 30 with positive crossmatch (p less than 0.001). Immediate failure occurred in significantly higher numbers among patients with a higher risk of having antibodies, such as multiparous females and patients receiving secondary transplants. The effect was not a nonspecific one, for more immediate failures occurred among transplants from unrelated than among those from related donors. The corresponding frequency of positive crossmatch was also lower among related donors. The presence of preformed cytotoxic antibodies against the donor appears to be a strong contraindication for transplantation.
Language and tool making are similar cognitive processes
Authors: Ralph L. Holloway
Journal: Behavioral and Brain Sciences (2012)

Design features for language and stone toolmaking (not tool use) involve similar if not homologous cognitive processes. Both are arbitrary transformations of internal "intrinsic" symbolization, whereas non-human tool using is mostly an iconic transformation. The major discontinuity between humans and non-humans (chimpanzees) is language. The presence of stone tools made to standardized patterns suggests communicative and social control skills that involved language.
Abstract 4936: Ableson kinases negatively regulate invadopodia function and invasion in head and neck squamous cell carcinoma by inhibiting an HB-EGF autocrine loop.
Authors: Karen E. Hayes, Elyse L. Walk, Amanda G. Ammer, Laura C. Kelley, Karen H. Martin, Scott A. Weed
Journal: Cancer Research (2013)

Abstract Head and neck squamous cell carcinoma (HNSCC) has a proclivity for locoregional invasion. HNSCC mediates invasion in part through invadopodia-based proteolysis of the extracellular matrix (ECM). Activation of Src, Erk1/2, Abl and Arg downstream of epidermal growth factor receptor (EGFR) modulates invadopodia activity through phosphorylation of the actin regulatory protein cortactin. In MDA-MB-231 breast cancer cells, Abl and Arg function downstream of Src to phosphorylate cortactin, promoting invadopodia ECM degradation activity and thus assigning a pro-invasive role for Ableson kinases. We report that Abl kinases have an opposite, negative regulatory role in HNSCC where they suppress invadopodia and tumor invasion. Impairment of Abl expression or Abl kinase activity with imatinib mesylate enhanced HNSCC matrix degradation and 3D collagen invasion, functions that were impaired in MDA-MB-231. HNSCC lines with elevated EGFR and Src activation did not contain increased Abl or Arg kinase activity, suggesting Src could bypass Abl/Arg to phosphorylate cortactin and promote invadopodia ECM degradation. Src transformed Abl-/-/Arg-/- fibroblasts produced ECM degrading invadopodia containing pY421 cortactin, indicating that Abl/Arg are dispensable for invadopodia function in this system. Imatinib treated HNSCC cells had increased EGFR, Erk1/2 and Src activation, enhancing cortactin pY421 and pS405/418 required for invadopodia function. Imatinib stimulated shedding of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) from HNSCC cells, where soluble HB-EGF enhanced invadopodia ECM degradation in HNSCC but not in MDA-MB-231. HNSCC cells treated with therapeutic inhibitors of the EGFR invadopodia pathway indicated that EGFR and Src are required for invadopodia function. Collectively our results indicate that Abl kinases negatively regulate HNSCC invasive processes through suppression of an HB-EGF autocrine loop responsible for activating an EGFR-Src-cortactin cascade, in contrast to the invasion promoting functions of Abl kinases in breast and other cancer types. Our results provide mechanistic support for recent failed HNSCC clinical trials utilizing imatinib. Citation Format: Karen E. Hayes, Elyse L. Walk, Amanda G. Ammer, Laura C. Kelley, Karen H. Martin, Scott A. Weed. Ableson kinases negatively regulate invadopodia function and invasion in head and neck squamous cell carcinoma by inhibiting an HB-EGF autocrine loop. [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 4936. doi:10.1158/1538-7445.AM2013-4936
Drug Monitoring in Cancer Therapy
Authors: Kenneth R. Hande
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Drug Monitoring in Cancer Therapy Get access Kenneth R. Hande Kenneth R. Hande Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 21, 6 November 1991, Pages 1523–1525, https://doi.org/10.1093/jnci/83.21.1523 Published: 06 November 1991 Article history Received: 10 February 1991 Accepted: 10 March 1991 Published: 06 November 1991
Press: Do we need another anthrax test?
Authors: G. Yamey
Journal: BMJ (2001)

Researchers at the Mayo Clinic have unveiled a new test for anthrax “that can spot the microbe's DNA signature within 35 minutes,” the San Francisco Chronicle reported on 6 November. The “unveiling” excited the rest of the US media, and why shouldn't it, for a new and rapid way of diagnosing this deadly disease must surely be a triumph?

The lead researcher, Franklin Cockerill, did his best to persuade journalists at a press conference last week that the discovery was indeed a breakthrough. The rapid test, he said, will allow for speedier treatment of people exposed to anthrax. It will …
FRI0224 Predictive factors of response to tocilizumab in patients with active rheumatoid arthritis
Authors: D. Reina, J. Narvaez, S. García-Díaz, C. Díaz Torné, B. Magallares, M. V. Hernandez, R. Sanmartí, A. Rodriguez de la Serna, J. Llobet, H. Corominas, J. Nolla
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluatethe efficacy and identify predictors of response to tocilizumab (TCZ) in patients with rheumatoid arthritis. <h3>Methods</h3> A multi-center ambispective observational study in 126 patients with active rheumatoid arthritis treated with TCZ. The variables associated to achieve the therapeutic goal (remission of the disease defined as a DAS28 &lt;2.6) at 3 and 6 months, were identified by a logistic regression model by using the backward approach. SAS 9.3 was used for the management and statistical analysis. <h3>Results</h3> Patients’ demographic and clinical characteristics are shown in table 1, as well as response rates at 3 and 6 months of treatment. Of the 126 patients included, TCZ was administered as first biologic in 33 cases (26%), while in the remaining 93 patients was used after inadequate response (inefficacy or intolerance) to one or more biological therapies (the average of previous biological drugs tested per patient was 2.18 ±1.1, range 1-6). Only 43 (35%) patients received TCZ as monotherapy. Of all the variables analyzed by the multivariate analysis, the predictive factors that increase the likelihood of response DAS28-ESR 2.6 to 3 months were ESR&gt; 30 mm / h (OR=19.07, 95% CI: 2.7, 133.7) and the presence of extra-articular manifestations of the disease (OR = 15.5, 95% CI 2.3, 102.3). Factors that decreased it were hemoglobin (OR = 0.53, 95% CI: 0.32, 0.91), the baseline DAS28-ESR (OR = 0.30, 95% CI: 0.15, 0.64) and the number of previous DMARDs used (OR = 0.42, 95% CI: 0.22, 0.78). The only significant factor that reduced the possibility of DAS28-ESR response &lt;2.6 at 6 months was the baseline DAS28-ESR (OR = 0.55, 95% CI: 0.35, 0.88). No relationship was found in the number of previous biological therapies, nor in the decrease of the neutrophils count nor in the positivity RF/anti-PCC. <h3>Conclusions</h3> Some clinical and laboratory variables can help in the selection of the best candidates for treatment with tocilizumab. <b>Disclosure of Interest</b>: None Declared
Adult Height and Fertility in Men with Congenital Virilizing Adrenal Hyperplasia
Authors: Maria D. Urban, Peter A. Lee, Claude J. Migeon
Journal: New England Journal of Medicine (1978)

The effects of congenital adrenal hyperplasia on adult height and fertility were studied in 30 afflicted men. The patients' heights ranged from 150.0 to 178.6 cm (mean +/- 1 S.D. of 164.0 +/- 7.6), which is significantly lower than both the mean adult height for American men and that of the patients' parents (P less than 0.005). There was no correlation between adult height and the age at which therapy was begun, possibly because the patients treated before one year of age had the salt-losing form of the syndrome. Therapeutic compliance may also have been involved. Apparently normal fertility, indicated by paternity and normal sperm counts, was found in 18 out of 20 patients evaluated. This group included five untreated patients who were found to be fertile and to have normal plasma testosterone and gonadotropin but elevated androstenedione levels.
A memorable patient: Communication problems
Authors: S. Sutherland
Journal: BMJ (2002)

“Oh dear, there's no smoke” was my first thought as I approached the house. This was in the days of regular unannounced visits to elderly patients, and I was dropping in on Jean “while I was passing.”

A lifetime of service in the local mansion had been rewarded with a retirement cottage in the grounds, one of the features of which was a permanent plume of smoke from the chimney. But on that mid-January day there was none, and I was a little apprehensive as I pushed open the front door. However, there she was, lively as ever but huddled in her overcoat and mitts in front of an empty hearth.

Over the years Jean had developed a number of eccentricities. One of the most troublesome was her manner of speech. With increasing deafness, she had adopted the habit of repeating everything said to her. Presumably this started as her way of confirming the question, but by the time I knew her it was a firmly ingrained reflex. As a result, conversations took on a surreal format.

Me: “How are you today?”

Jean: “How are you today?”

Me: “No, how are you today?”

Jean: “No, how are you today?” and so on, all conducted at high volume. (Jean had a fine collection of NHS hearing aids, but she kept them in a drawer rather than her ears.)

“Have you no coal?” I shouted.

“Have you no coal?” she replied.

After much in a similar vein she eventually seemed to get the message that I was worried about her fuel supplies. She led me out to her shed. The first door opened to reveal a pathetic pile of sticks in the corner. Problem solved, I thought, but my tour was not yet finished. The next door opened on to a pile of coal the like of which I have only seen in pictures of the Titanic's boiler room.

At this moment Jean's neighbour arrived with her shopping, and I started to inquire whether he had noticed other signs of her mental health deteriorating. Gravely we discussed the possibility of dementia and whether Jean might need help from social services or even have to give up living alone.

Meanwhile, Jean had been rummaging in her shopping bag. Suddenly she let out a small cry of success, and, holding aloft a packet of firelighters, headed inside to get on with the business of the day.

There may be no smoke without fire, but there can be no fire without firelighters.
Pitfalls of Radiation Survey After Brachytherapy Implant Removal Preceding Tl-201 Study
Authors: ROBERT C. GASTON, CHARLES D. ARNOLD, BHAGWAT D. AHLUWALIA, JAGADEESH R. SONNAD, GEORGE W. MACDURMON, MICHAEL A. GOLD, CINDY K. PARRY, JOSEPH F. MONTEBELLO, NINA A. MAYR
Journal: Clinical Nuclear Medicine (2002)

An unexpected elevated postimplant radiation survey is described in an elderly patient with an interstitial low-dose-rate iridium-192 (Ir-192) needle implant for endometrial cancer. The elevated activity was related to prolonged clearance of Tl-201 from a cardiac study that had been performed 7 days earlier. The Tl-201 accumulated in the soft tissue, particularly the colon, resulting in increased survey readings over the abdomen and raising concern that an Ir-192 source remained within the patient. This case shows that delayed excretion of a diagnostic radionuclide agent can cause elevated activity high enough to confound postradiotherapy implant survey readings. The estimated surface exposure from a single iridium source left in the pelvis was determined using a phantom study. Possible factors causing decreased excretion of Tl-201 in a patient with heart disease, arteriosclerotic vascular disease, previous pelvic radiation therapy, and a brachytherapy procedure are discussed. A preloading radiation survey is recommended in patients who have had previous nuclear medicine studies involving radionuclides with long half-lives.
P2-14-08: Hormone Receptor Status and Breast Cancer Survival among Hispanic and Non-Hispanic White Women over 10 Years of Follow-Up.
Authors: SR Denkhoff, KB Baumgartner, D Yang, CM Pinkston, RN Baumgartner
Journal: Cancer Research (2011)

Abstract Introduction: The joint presence or absence of expression of estrogen receptor (ER+/−), progesterone receptor (PR+/−), and Her2neu (Her2+/−) is now widely used to define the hormone receptor (HR) phenotype of breast tumors. HR phenotype influences breast cancer etiology, response to treatment and survival, which may vary by ethnic group. The triple negative phenotype (TNT: ER-/PR-/Her2-) is associated with the poorest survival and is more common in African American than white women. Few studies have assessed how HR status differs by Hispanic (H) versus non-Hispanic white (NHW) ethnicity in relation to survival. Methods: We analyzed data from the New Mexico site of the ‘Health, Eating, Activity and Lifestyle’ (HEAL) study for breast cancer mortality over 10 years of follow-up by HR phenotype and ethnicity for 126 H and 408 NHW women with invasive (I-IIIA), first primary breast cancer. Kaplan Meier curves were used to describe differences in survival by ethnicity and HR phenotype (ER+/PR+/Her2+, referent; ER+/PR+/Her2-; ER-/PR-/Her2+; and ER-/PR-/Her2-). Hazard ratios were estimated using Cox regression models stratified by phenotype and ethnicity, adjusting for age at diagnosis, stage, and diagnosis of another cancer (yes/no). Results: Kaplan Meier (KM) analysis indicated that the TNT phenotype was associated with poorer survival, particularly during the first 5 years, although the difference was not statistically significant after 10 years of follow-up (p=0.36). The prevalence of TNT was higher in H (10.3%) than NHW (6.6%) women, and H also tended to poorer survival than NHW women (p=0.17). In multivariate-adjusted models, women with a TNT phenotype had a 26% increased risk of death (HR=1.26 95% CI 0.62−2.6). In NHW women, the risk was 12% (HR=1.12 95% CI 0.43−2.9). Among H women, those with a TNT phenotype had a 17% increased risk of death (HR=1.17 95% CI 0.35−3.8) while those with ER-/PR-/Her2+ had a 46% increase (HR= 1.46 95% CI 0.40−5.3). Discussion: Although this analysis is limited by small numbers, the results suggest that H women may have worse 10-year survival rates than NHW women and that women with TNT have a higher risk of death regardless of ethnicity. These differences in survival could be due to a higher rate of recurrence or issues related to treatment. This study suggests that there is an ethnic disparity in survival by HR subtypes that should be examined in a larger population based study. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-08.
Abstract 240: Therapeutic targeting of EMP2 reduces breast cancer stem cells.
Authors: Madhuri Wadehra, Meagan Kiyohara, Negin Ashki
Journal: Cancer Research (2013)

Abstract There is increasing evidence that tumor-initiating cancer stem cells (CSCs) contribute to tumor metastasis and therapeutic resistance. In breast cancer, metastatic CSCs are defined as CD44+/CD24- and ALDH+, and in this study, we define another marker epithelial membrane protein-2 (EMP2) as a novel target for this population of cells. EMP2 is an oncogene whose expression has been shown to correlate with tumor progression and survival in a number of human cancers including triple negative breast, ovarian, and endometrial tumors. In breast cancer, EMP2 is expressed on the majority of invasive tumors examined, and in particular 70% of triple negative breast tumors showed surface expression of this marker. Clinical data also revealed higher levels of EMP2 in metastatic lesions compared to primary tumors. In this study, we show new evidence that EMP2 is highly expressed in CSCs. New data suggests that EMP2 upregulates the expression of HIF-1α, CD44, and ALDH and directly contributes to the metastatic potential of the tumor cell. High levels of EMP2 promote mammosphere formation and increased tumor forming potential. In tumors created from these cells, high levels of ALDH+ expression were also observed. In contrast, reduction in EMP2 decreased CD44 expression and ALDH activity both in vitro and in vivo, with the net consequence of poorly vascularized and slow growing tumors. We have recently developed a novel IgG1 monoclonal antibody to EMP2 and have started testing its therapeutic efficacy. In vitro treatment with EMP2 IgG1 reduced HIF-1α, CD44, and ALDH levels, ultimately leading to caspase mediated apoptosis. Treatment of breast cancer cells with EMP2 IgG1 reduced tumor load in both subcutaneous and metastatic models of breast cancer with a significant improvement in survival. Histological examination of the tumors revealed significant necrosis and elimination of ALDH+ CSCs. These results suggest that targeting EMP2 may reduce CSCs and represent an attractive target for further therapeutic development. Citation Format: Madhuri Wadehra, Meagan Kiyohara, Negin Ashki. Therapeutic targeting of EMP2 reduces breast cancer stem cells. [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 240. doi:10.1158/1538-7445.AM2013-240