tbuckley/cabot-search huggingface dataset:
Rat Umbilical Cord Stem Cells Completely Abolish Rat Mammary Carcinomas with No Evidence of Metastasis or Recurrence 100 Days Post–Tumor Cell Inoculation
Authors: Chanran Ganta, Doi Chiyo, Rie Ayuzawa, Rajashekar Rachakatla, Marla Pyle, Gordon Andrews, Mark Weiss, Masaaki Tamura, Deryl Troyer
Journal: Cancer Research (2009)

Abstract Genetically engineered stem cells efficiently deliver therapeutic proteins to cancer and other sites of inflammation. However, a major advantage would be realized if tumor-trafficking stem cells that have not been genetically modified exhibit an inherent antitumor effect, thus circumventing the necessity of the expression of exogenous genes by the cells. We transplanted Fisher 344 rat–derived mammary adenocarcinoma cells (Mat B III) orthotopically into syngeneic F344 rats with an intact immune system. Rat umbilical cord matrix stem (rUCMS) cells derived from Wharton's jelly were then administered intratumoral (i.t) or i.v. 4 days later. The tumor attenuation effect was significantly evident starting from day 14 in i.v. and i.t. rUCMS cell–transplanted rats compared with sham-transplanted rats. In addition, unmodified rUCMS cell–transplanted rats showed complete regression of tumors to undetectable levels by 34 to 38 days with no evidence of metastasis or recurrence 100 days post–tumor cell inoculation. Dye-loaded rUCMS cells were identified within tumors only 4 days after their i.v. transplantation. In vitro colony assays with rUCMS cells as feeder layers markedly reduced Mat B III colony size and number. Growth attenuation of Mat B III cells exposed to either rUCMS cells directly or to the conditioned medium derived from rUCMS cells was associated with apoptosis indicators, including increased activated caspase-3. In addition, rUCMS cells cocultured with Mat B III cells had a dose-dependent antiproliferative effect on Mat B III cells. These findings suggest that unmodified human UCMS cells could be used for targeted cytotherapy for breast cancer. [Cancer Res 2009;69(5):1815–20]
<i>ATR</i> Mutation in Endometrioid Endometrial Cancer Is Associated With Poor Clinical Outcomes
Authors: Israel Zighelboim, Amy P. Schmidt, Feng Gao, Premal H. Thaker, Matthew A. Powell, Janet S. Rader, Randall K. Gibb, David G. Mutch, Paul J. Goodfellow
Journal: Journal of Clinical Oncology (2009)

PURPOSE Mutations in the DNA damage response gene ATR (exon 10 A10 mononucleotide repeat) have been previously described in endometrial and other cancers with defective DNA mismatch repair. In vitro studies showed that endometrial cancer cell lines with A10 repeat tract truncating mutations have a failure in the ATR-dependent DNA damage response. Cell lines carrying A10 mutations fail to trigger Chk1 activation in response to ionizing radiation and topoisomerase inhibitors. We sought to determine the frequency and clinicopathologic significance of ATR mutations in patients with endometrioid endometrial cancer. PATIENTS AND METHODS The ATR exon 10 A10 repeat was analyzed by direct sequencing in 141 tumors with microsatellite instability (MSI-positive) and 107 microsatellite stable (MSI-negative) tumors. The relationships between mutations and clinicopathologic variables, including overall and disease-free survival, were assessed using contingency table tests and Cox proportional hazard models. Results ATR mutations were identified in 12 cases (4.8%; three cases with insertions and nine cases with deletions). Mutations occurred exclusively in MSI-positive tumors (P = .02), with an overall mutation rate of 8.5%. Mutation was not associated with age, race, surgical stage, International Federation of Gynecology and Obstetrics grade, or adjuvant treatment. Multivariate analyses revealed a significant association with reduced overall survival (hazard ratio [HR] = 3.88; 95% CI, 1.64 to 9.18; P = .002) and disease-free survival (HR = 4.29; 95% CI, 1.48 to 12.45; P = .007). CONCLUSION Truncating ATR mutations in endometrial cancers are associated with biologic aggressiveness as evidenced by reduced disease-free and overall survival. Knowledge of ATR mutation status may hold promise for individualized treatment and targeted therapies in patients with endometrial cancer.
Surface-Immobilized Aptamers for Cancer Cell Isolation and Microscopic Cytology
Authors: Yuan Wan, Young-tae Kim, Na Li, Steve K. Cho, Robert Bachoo, Andrew D. Ellington, Samir M. Iqbal
Journal: Cancer Research (2010)

Abstract Exposing rare but highly malignant tumor cells that migrate from the primary tumor mass into adjacent tissue(s) or circulate in the bloodstream is critical for early detection and effective intervention(s). Here, we report on an aptamer-based strategy directed against epidermal growth factor receptor (EGFR), the most common oncogene in glioblastoma (GBM), to detect these deadly tumor cells. GBMs are characterized by diffuse infiltration into normal brain regions, and the inability to detect GBM cells renders the disease surgically incurable with a median survival of just 14.2 months. To test the sensitivity and specificity of our platform, anti-EGFR RNA aptamers were immobilized on chemically modified glass surfaces. Cells tested included primary human GBM cells expressing high levels of the wild-type EGFR, as well as genetically engineered murine glioma cells overexpressing the most common EGFR mutant (EGFRvIII lacking exons 2–7) in Ink4a/Arf-deficient astrocytes. We found that surfaces functionalized with anti-EGFR aptamers could capture both the human and murine GBM cells with high sensitivity and specificity. Our findings show how novel aptamer substrates could be used to determine whether surgical resection margins are free of tumor cells, or more widely for detecting tumor cells circulating in peripheral blood to improve early detection and/or monitoring residual disease after treatment. Cancer Res; 70(22); 9371–80. ©2010 AACR.
Peer support for patients with type 2 diabetes: cluster randomised controlled trial
Authors: S. M. Smith, G. Paul, A. Kelly, D. L. Whitford, E. O'Shea, T. O'Dowd
Journal: BMJ (2011)

<b>Objective</b> To test the effectiveness of peer support for patients with type 2 diabetes. <b>Design</b> Cluster randomised controlled. <b>Setting</b> 20 general practices in the east of the Republic of Ireland. <b>Participants</b> 395 patients (192 in intervention group, 203 in control group) and 29 peer supporters with type 2 diabetes. <b>Intervention</b> All practices introduced a standardised diabetes care system. The peer support intervention ran over a two year period and contained four elements: the recruitment and training of peer supporters, nine group meetings led by peer supporters in participant's own general practice, and a retention plan for the peer supporters. <b>Main outcome measures</b> HbA<sub>1c</sub>; cholesterol concentration; systolic blood pressure; and wellbeing score. <b>Results</b> There was no difference between intervention and control patients at baseline. All practices and 85% (337) of patients were followed up. At two year follow-up, there were no significant differences in HbA<sub>1c</sub> (mean difference −0.08%, 95% confidence interval −0.35% to 0.18%), systolic blood pressure (−3.9 mm Hg, −8.9 to 1.1 mm Hg), total cholesterol concentration (−0.03 mmol/L, −0.28 to 0.22 mmol/L), or wellbeing scores (−0.7, −2.3 to 0.8). While there was a trend towards decreases in the proportion of patients with poorly controlled risk factors at follow-up, particularly for systolic blood pressure (52% (87/166) &gt;130 mm Hg in intervention <i>v</i> 61% (103/169) &gt;130 mm Hg in control), these changes were not significant. The process evaluation indicated that the intervention was generally delivered as intended, though 18% (35) of patients in the intervention group never attended any group meetings. <b>Conclusions</b> A group based peer support intervention is feasible in general practice settings, but the intervention was not effective when targeted at all patients with type 2 diabetes. While there was a trend towards improvements of clinical outcomes, the results do not support the widespread adoption of peer support. <b>Trial registration</b> Current Controlled Trials ISRCTN42541690.
Intestinal Injury and Endotoxemia in Children Undergoing Surgery for Congenital Heart Disease
Authors: Nazima Pathan, Margarita Burmester, Tanja Adamovic, Maurice Berk, Keng Wooi Ng, Helen Betts, Duncan Macrae, Simon Waddell, Mark Paul-Clark, Rosamund Nuamah, Charles Mein, Michael Levin, Giovanni Montana, Jane A. Mitchell
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively.To investigate the role of intestinal injury and endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital heart disease.We analyzed blood levels of intestinal fatty acid binding protein and endotoxin (endotoxin activity assay) alongside global transcriptomic profiling and assays of monocyte endotoxin receptor expression in children undergoing surgery for congenital heart disease.Levels of intestinal fatty acid binding protein and endotoxin were greater in children with duct-dependent cardiac lesions. Endotoxemia was associated with severity of vital organ dysfunction and intensive care stay. We identified activation of pathogen-sensing, antigen-processing, and immune-suppressing pathways at the genomic level postoperatively and down-regulation of pathogen-sensing receptors on circulating immune cells.Children undergoing surgery for congenital heart disease are at increased risk of intestinal mucosal injury and endotoxemia. Endotoxin activity correlates with a number of outcome variables in this population, and may be used to guide the use of gut-protective strategies.
Amino acid sequence analysis of human interleukin 1 (IL-1). Evidence for biochemically distinct forms of IL-1.
Authors: P Cameron, G Limjuco, J Rodkey, C Bennett, J A Schmidt
Journal: The Journal of Experimental Medicine (1985)

The pI-6.8 species of normal human interleukin 1 (IL-1) has been isolated by ion-exchange and reverse-phase high-performance liquid chromatography. The isolated material had a molecular weight of 18,000, and had a specific bioactivity of 1.7 X 10(7) half-maximal U/mg in the murine thymocyte proliferation assay, values similar to those obtained for murine P388D1-derived IL-1 (12), and human IL-1 isolated by a previously published purification protocol (15). Amino-terminal sequence analysis revealed a single N-terminal, and resulted in the identification of 30 of the first 35 amino acid residues. Sequence of three CNBr cleavage fragments of purified IL-1 resulted in the identification of an additional 38 residues. All of the sequences agree exactly with those deduced from complementary DNA (cDNA) by Auron, et al. (18), demonstrating that this cloned cDNA, though considerably different from the cDNA reported for murine IL-1 (12), nevertheless codes for the pI-6.8 species of human IL-1. The evidence also shows that the precursor protein for human IL-1 is largely processed at the N-terminal end. Little or no processing occurs at the carboxy-terminal end. Sequence homology with interferon-inducing factor (26) suggests that the pI-6.8 species of human IL-1 is a member of a gene family. Although equally potent in the murine thymocyte proliferation assay, murine IL-1 and the pI-6.8 species of human IL-1 are structurally distinct. Further study will answer the interesting question as to the relationship of the other charged species of human IL-1 to these distinct IL-1 classes.
Cardiovascular Health: The Importance of Measuring Patient-Reported Health Status
Authors: John S. Rumsfeld, Karen P. Alexander, David C. Goff, Michelle M. Graham, P. Michael Ho, Frederick A. Masoudi, Debra K. Moser, Véronique L. Roger, Mark S. Slaughter, Kim G. Smolderen, John A. Spertus, Mark D. Sullivan, Diane Treat-Jacobson, Julie J. Zerwic
Journal: Circulation (2013)
Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): an FNCLCC/French Sarcoma Group phase II trial with a long-term follow-up
Authors: N. Penel, A. Le Cesne, B.N. Bui, D. Perol, E.G. Brain, I. Ray-Coquard, C. Guillemet, C. Chevreau, D. Cupissol, S. Chabaud, M. Jimenez, F. Duffaud, S. Piperno-Neumann, L. Mignot, J.-Y. Blay
Journal: Annals of Oncology (2010)
Transplantation in reproductive medicine: previous experience, present knowledge and future prospects
Authors: D Nugent
Journal: Human Reproduction Update (1997)

The use of transplantation in reproductive medicine has been considered by physicians and scientists alike for many years. Despite being side-tracked into futile pursuits of rejuvenation in the early days, the possibility of usefulness remains, particularly for preserving fertility in patients undergoing ablative chemo- or radiotherapy. These aims have been enhanced by advances in tissue cryopreservation. When isolated primordial follicles are transferred in the mouse, or ovarian tissue slices are grafted into sheep, it is possible to obtain follicular survival with subsequent maturation and oestrogen secretion and even restore fertility to sterilized hosts. For preservation of fertility, autografts avoid both the immunological problems of allografts and the ethical dilemmas when using donor tissue. In the male, the concept of spermatogonial cell transfer after isolation and frozen storage of cells recovered from a testicular biopsy is most attractive, since it may provide another option for rescuing fertility in cancer patients, and provide a much needed one in children. Recent results demonstrate that gonocytes from immature mice injected into the tubules of sterilized hosts restore spermatogenesis and produce fertile spermatozoa. Furthermore, the gonocytes can be stored frozen prior to transfer and still produce fertile tubules. This review presents a broad history of transplantation in the male and female genital tracts as well as attempts to anticipate possible future developments.
Overall Survival and Cause-Specific Mortality of Patients With Stage T1a,bN0M0 Breast Carcinoma
Authors: Emer O. Hanrahan, Ana M. Gonzalez-Angulo, Sharon H. Giordano, Roman Rouzier, Kristine R. Broglio, Gabriel N. Hortobagyi, Vicente Valero
Journal: Journal of Clinical Oncology (2007)

With mammographic screening, the frequency of diagnosis of stage T1a,bN0M0 breast cancer has increased. Prognosis after locoregional therapy and benefit from adjuvant systemic therapy are poorly defined. We reviewed T1a,bN0M0 breast cancer cases registered in the Surveillance, Epidemiology, and End Results (SEER) Program to investigate the impact of prognostic factors on breast cancer-specific (BCSM) and non-breast cancer-related mortality.We identified T1a,bN0M0 breast cancer cases registered in the SEER Program from 1988 to 2001, and used the Kaplan-Meier product limit method to describe overall survival (OS). We estimated the probabilities of death resulting from breast cancer and from other causes, and analyzed associations of patient and tumor characteristics with OS, BCSM, and non-breast cancer-related mortality using the log-rank test, Cox proportional hazards models, and a competing-risk model. We constructed nomograms to assist physicians in adjuvant therapy decision making.We identified 51,246 T1a,bN0M0 cases. Median follow-up was 64 months (range, 1 to 167 months). Median age at diagnosis was 65 years (range, 20 to 101 years). Ten-year probabilities of all-cause mortality and BCSM were 24% and 4%, respectively. Characteristics associated with increased probability of BCSM included age younger than 50 years at diagnosis, high tumor grade, estrogen receptor-negative status, progesterone receptor-negative status, and fewer than six nodes removed at axillary dissection. The constructed nomograms allow a comparison of predicted breast cancer-specific survival and non-breast cancer-specific survival in individual patients.Overall, the prognosis of patients with T1a,bN0M0 breast cancer is excellent. However, subgroups of patients who are at higher risk of BCSM and who should be considered for adjuvant systemic therapy can be identified.
Dentures in a small-bowel stricture
Authors: D. R Leff, A. Willis, D. Menzies
Journal: Journal of the Royal Society of Medicine (2004)

Mr Hashmi and his colleagues review the hazards of swallowed or inhaled partial dentures (February 2004 JRSM1). Here we report such an episode with possibly beneficial consequences.

The patient was seen after two weeks of abdominal pain, distension, nausea and vomiting, and constipation. He had lost 4 kg over the past two months. There was a history of coeliac disease. Barium follow-through showed gross dilatation of the stomach, duodenum and proximal jejunum, and a C-shaped foreign body was noted in a site consistent with the mid-jejunum (Figure 1). At mini-laparotomy the stricture was excised with end-to-end anastomosis. When opened, it proved to contain part of a denture. Nevertheless, the specimen was sent for histopathological examination. To our surprise, the findings included not only a broad area of severe dysplasia but also, at the stricture, a poorly differentiated adenocarcinoma of the small bowel. How long would this complication of coeliac disease have gone undetected without the intervention of the dentures?



Figure 1

Barium follow-through
The Cysteine-Rich Regions of the Regulatory Domains of Raf and Protein Kinase C as Retinoid Receptors
Authors: Beatrice Hoyos, Asiya Imam, Ramon Chua, Christina Swenson, Guo-Xia Tong, Ester Levi, Noa Noy, Ulrich Hämmerling
Journal: The Journal of Experimental Medicine (2000)

Vitamin A and its biologically active derivatives, the retinoids, are recognized as key regulators of vertebrate development, cell growth, and differentiation. Although nuclear receptors have held the attention since their discovery a decade ago, we report here on serine/threonine kinases as a new class of retinoid receptors. The conserved cysteine-rich domain of the NH(2)-terminal regulatory domains of cRaf-1, as well as several select domains of the mammalian protein kinase C (PKC) isoforms alpha, delta, zeta, and mu, the Drosophila and yeast PKCs, were found to bind retinol with nanomolar affinity. The biological significance was revealed in the alternate redox activation pathway of these kinases. Retinol served as a cofactor to augment the activation of both cRaf and PKC alpha by reactive oxygen, whereas the classical receptor-mediated pathway was unaffected by the presence or absence of retinol. We propose that bound retinol, owing to its electron transfer capacity, functions as a tag to enable the efficient and directed redox activation of the cRaf and PKC families of kinases.
Erratum: Corrigendum: Dysregulation of bacterial proteolytic machinery by a new class of antibiotics
Authors: H Brötz-Oesterhelt, D Beyer, H-P Kroll, R Endermann, C Ladel, W Schroeder, B Hinzen, S Raddatz, H Paulsen, K Henninger, J E Bandow, H-G Sahl, H Labischinski
Journal: Nature Medicine (2005)
Changes in enzyme activity in normal and histologically inflamed oesophageal epithelium.
Authors: D Hopwood, P E Ross, K R Logan, G Nicholson, I A Bouchier
Journal: Gut (1979)

Oesophageal biopsies were obtained from 74 patinets undergoing upper gastrointestinal fibreoptic endoscopy. Thirteen patients with histological evidence of inflammation had a raised alkaline phosphatase activity (2.7 +/- 1.6 nmol/mg protein/min) compared with 49 normal controls (1.2 +/- 0.68 nmol/mg protein/min: P less than 0.001). The acid phosphatase level was lower (8.4+/- 4.0 vs. 5.8 +/- 2.2 nmol/mg protein/min: P less than 0.05) and the glucuronidase activity raised (0.44 +/- 0.17 vs 0.81 +/- 0.32 nmol/mg protein/min: P less than 0.001) and their ratio declined (24.0 +/- 1.9 nmol/mg protein/min: P less than 0.001) in patients with oesophagitis. This may be due to differential secretion of membrane coating granules, a form of lysosome found isophagitis--was assessed by point counting. The volume density rose from 10.9 +/- 4.25% in normal biopsies to 46.4+/-12.5% (P less than 0.001) in oesophagitis. These results show a consistent pattern that possibly indicates an intermediate stage between the clinically, histologically, and biochemically normal oesophagus and one that is inflamed on endoscopy.
<i>ARDSNet</i> Lower Tidal Volume Ventilatory Strategy May Generate Intrinsic Positive End-Expiratory Pressure in Patients with Acute Respiratory Distress Syndrome
Authors: Gabriella de Durante, Monica del Turco, Laura Rustichini, Patrizia Cosimini, Francesco Giunta, Leonard D. Hudson, Arthur S. Slutsky, V. Marco Ranieri
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The ARDSNet trial revealed that the use of a smaller tidal volume (VT) reduced mortality by 22%. However, three earlier studies that lowered VT did not find a decrease in mortality. We tested the hypothesis that the increased respiratory rate used in the ARDSNet lower VT strategy might have led to intrinsic positive end-expiratory pressure (PEEPi), raising total PEEP (PEEPtotal). Ten patients with acute respiratory distress syndrome (ARDS) were ventilated using the ARDSNet lower VT protocol. Respiratory rate was then reduced (10–15 breaths/minute) to obtain a VT of 12 ml/kg (ARDSNet traditional VT). PEEP on the ventilator (PEEPnominal: 10.1 ± 0.7 cm H2O), FiO2 (0.7 ± 0.1), and minute ventilation (VE: 12.4 ± 1.7 L/minute) were set using the ARDSNet protocol and maintained constant during the two ventilatory strategies. Values of airway pressure at end-expiration of a regular breath (PEEPexternal) and 3–5 seconds after the onset of an end-expiratory occlusion (PEEPtotal) were measured. PEEPi was calculated by subtracting PEEPexternal from PEEPtotal. PEEPtotal and PEEPi were, respectively, 16.3 ± 2.9 and 5.8 ± 3.0 cm H2O during the lower VT strategy and 11.7 ± 0.9 and 1.4 ± 1.0 cm H2O during the traditional VT strategy (p < 0.01). The reduced mortality observed with the ARDSNet strategy may have been due to the protective effect of a higher PEEPtotal.
Intensive Glycemic Control Is Not Associated With Fractures or Falls in the ACCORD Randomized Trial
Authors: Ann V. Schwartz, Karen L. Margolis, Deborah E. Sellmeyer, Eric Vittinghoff, Walter T. Ambrosius, Denise E. Bonds, Robert G. Josse, Adrian M. Schnall, Debra L. Simmons, Trisha F. Hue, Lisa Palermo, Bruce P. Hamilton, Jennifer B. Green, Hal H. Atkinson, Patrick J. O’Connor, Rex W. Force, Douglas C. Bauer
Journal: Diabetes Care (2012)

OBJECTIVE Older adults with type 2 diabetes are at high risk of fractures and falls, but the effect of glycemic control on these outcomes is unknown. To determine the effect of intensive versus standard glycemic control, we assessed fractures and falls as outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial. RESEARCH DESIGN AND METHODS ACCORD participants were randomized to intensive or standard glycemia strategies, with an achieved median A1C of 6.4 and 7.5%, respectively. In the ACCORD BONE ancillary study, fractures were assessed at 54 of the 77 ACCORD clinical sites that included 7,287 of the 10,251 ACCORD participants. At annual visits, 6,782 participants were asked about falls in the previous year. RESULTS During an average follow-up of 3.8 (SD 1.3) years, 198 of 3,655 participants in the intensive glycemia and 189 of 3,632 participants in the standard glycemia group experienced at least one nonspine fracture. The average rate of first nonspine fracture was 13.9 and 13.3 per 1,000 person-years in the intensive and standard groups, respectively (hazard ratio 1.04 [95% CI 0.86–1.27]). During an average follow-up of 2.0 years, 1,122 of 3,364 intensive- and 1,133 of 3,418 standard-therapy participants reported at least one fall. The average rate of falls was 60.8 and 55.3 per 100 person-years in the intensive and standard glycemia groups, respectively (1.10 [0.84–1.43]). CONCLUSIONS Compared with standard glycemia, intensive glycemia did not increase or decrease fracture or fall risk in ACCORD.