tbuckley/cabot-search huggingface dataset:
Multicentre chest computed tomography standardisation in children and adolescents with cystic fibrosis: the way forward
Authors: Wieying Kuo, Mariette P.C. Kemner-van de Corput, Adria Perez-Rovira, Marleen de Bruijne, Isabelle Fajac, Harm A.W.M. Tiddens, Marcel van Straten
Journal: European Respiratory Journal (2016)

Progressive cystic fibrosis (CF) lung disease is the main cause of mortality in CF patients. CF lung disease starts in early childhood. With current standards of care, respiratory function remains largely normal in children and more sensitive outcome measures are needed to monitor early CF lung disease. Chest CT is currently the most sensitive imaging modality to monitor pulmonary structural changes in children and adolescents with CF. To quantify structural lung disease reliably among multiple centres, standardisation of chest CT protocols is needed. SCIFI CF (Standardised Chest Imaging Framework for Interventions and Personalised Medicine in CF) was founded to characterise chest CT image quality and radiation doses among 16 participating European CF centres in 10 different countries. We aimed to optimise CT protocols in children and adolescents among several CF centres. A large variety was found in CT protocols, image quality and radiation dose usage among the centres. However, the performance of all CT scanners was found to be very similar, when taking spatial resolution and radiation dose into account. We conclude that multicentre standardisation of chest CT in children and adolescents with CF can be achieved for future clinical trials.
Cytoplasmic Leucine Naphthylamidase Activity Expressed in Signet-Ring Cell Carcinoma of the Stomach
Authors: Kiyoshi Kubota, Seiji Yamada, Masao Ito, Wataru Nakamura, Takeo Nagayo
Journal: JNCI Journal of the National Cancer Institute (1977)

Histochemical studies were performed on signet-ring cells in surgically resected gastric carcinomas from 64 patients. On the basis of periodic acid-Schiff reactivity of the intracellular mucin, the signet-ring cells were classified as type A (immature), type B (intermediate), or type C (mature). Different staining reactions to Alcian blue at pH 2.5 enabled type C cells to be subclassified as C-1 or C-2. In 63 cases (98.4%), intense leucine naphthylamidase (LNAase) activity was found histochemically in the cytoplasm of nearly all cancer cells except type C-2. Localization of LNAase activity in the cytoplasm was confirmed by conventional biochemical assay. From the present results, histochemical characteristics of signet-ring cell carcinoma are discussed.
Case 33-1974
Authors: Richard C. Cabot, Robert E. Scully, Betty U. McNeely, Norman S. Lichtenstein, Robert E. Scully
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 63-year-old woman was admitted to the hospital because of a rash.She had had known hypertension for 18 years and in recent years had been treated with hydrochlorothiazide, spironolactone and alpha-methyldopa. Fourteen years before admission she had discontinued smoking three packages of cigarettes daily. Five years later acute myocardial infarction occurred and was followed by angina pectoris.One year before admission intermittent claudication developed in both calves, and she noticed painful, purplish mottling of the feet, especially in cold weather. Warfarin and isoxsuprine hydrochloride were given, without improvement. Five months before entry digoxin was begun because . . .
Long-Term Anticoagulant Prophylaxis after Myocardial Infarction
Authors: Arthur J. Seaman, Herbert E. Griswold, Ralph B. Reaume, Leonard Ritzmann
Journal: New England Journal of Medicine (1969)

In a double-blind, randomized test, long-term prophylactic anticoagulant therapy after acute myocardial infarction did not reduce mortality rate or complications. More treated patients required hospitalization than patients not receiving anticoagulant drugs. Patients continuously entered the study between 1956 and 1967. The average period at risk was about six years. All patients received six weeks of anticoagulant therapy for initial episodes of infarction, and, time and circumstances permitting, for recurrent myocardial infarctions.
Cultivation of a Filterable Agent Associated With Marek's Disease
Authors: M K Cook
Journal: JNCI Journal of the National Cancer Institute (1969)

A viral agent producing a syncytial-type cytopathic effect in chick embryo fibroblasts was isolated repeatedly from the CAL-1 strain of Marek's disease. The agent is approximately 100 mμ in diameter, is inactivated by ether and chloroform, is resistant to 5-iododeoxyuridine, and is negative in the complement fixation for avian leukosis test. It is serologically distinct from known chicken viruses and syncytium-producing agents of man. Filtrates of the tissue-culture grown virus induced a disease resembling Marek's disease when inoculated into chicks.
Comparative Study of Alterations Induced by 7,12-Dimethylbenz[&lt;italic&gt;α&lt;/italic&gt;]anthracene and Polymer Films in the Subcutaneous Connective Tissue of Rats&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: J M VASILIEV, L V OLSHEVSKAJA, N T RAIKHLIN, O J IVANOVA
Journal: JNCI Journal of the National Cancer Institute (1962)

Alterations occurring before tumor forminced cellophane films only were immation in rat tissue around subcuta-planted in control animals. A number neously implanted pellets containing of morphological and histochemical 7,12-dimethylbenz[α]anthracene and methods were used, including reactions cellophane films were compared. Pelfor: various oxidative enzymes, protein lets consisting of paraffin wax and groups, polysaccharides, lipides, nucleic acids, etc. Characteristic alterations induced by both carcinogenic agents, polycyclic hydrocarbon and polymer film, included: 1) various manifestations of injury to fibroblasts, 2) extensive, long-lasting, and distorted processes of fibrogenesis, and 3) accumulation of cells with morphological and histochemical characteristics of immature fibroblasts. Possible mechanisms of sarcoma development in the subcutaneous connective tissue of rats are discussed, and the role of distorted fibrogenesis combined with proliferation of fibroblasts is stressed.
The von Hippel-Lindau gene mutation is associated with the good-prognosis profiling subtype of clear cell renal cell carcinoma
Authors: M. Tan, B. Teh
Journal: Journal of Clinical Oncology (2006)

4532 Background: The prevalence of von Hippel-Lindau (VHL) mutations in clear cell renal cell carcinoma (ccRCC) is about 30–50%. The association between VHL mutation and patient prognosis remains controversial, despite extensive in vitro research on its role in hypoxia response. We have previously reported a robust prognostic classification of ccRCC using gene expression profiling. In view of reports of activity of anti-angiogenesis agents, we studied the association of VHL mutation with tumor profiling subtypes, survival and other clinical parameters. Methods: All exons of the VHL gene in 88 ccRCC samples were sequenced. Expression profiling using oligonucleotide arrays (54,675 probe sets) was also performed, and the samples classified using hierarchical clustering. For identification of VHL mutation specific signatures, nearest shrunken centroids with internal validation was used with a 10% misclassification cutoff. Results: 35% of the samples had VHL mutations. Mutation status was not significantly associated with survival on univariate analysis (p = 0.54). Hierarchical clustering yielded two ccRCC subtypes with divergent clinical outcomes (HR = 4.13, p &lt; 0.001). VHL mutations were significantly associated with the good-prognosis profiling subtype of ccRCC tumors (OR 3.3, p = 0.04), but no effect modification between VHL mutation and the prognostic subtypes was found (p=0.31). No standard clinical parameter was associated with VHL mutation. No significant association between VHL mutation and downstream hypoxia response gene expression, including VEGF (p = 0.14), PDGF (p = 0.5), TGF-A (p = 0.24) and GLUT1 (p = 0.45) was found. Conclusion: While VHL mutation is associated with a biologically distinct good-prognosis profiling tumor subtype, its lack of prognostic value on univariate analysis suggests an expanded study to evaluate effect modification. The absence of a specific gene classifier for VHL mutation and the lack of association between VHL gene mutation and known hypoxia response genes suggest that VHL mutations result in heterogenous tissue phenotypes. These results support molecular subtyping of ccRCC in laboratory and clinical studies; in particular, this may be critical for trials involving anti-angiogenesis agents. No significant financial relationships to disclose.
Case 33-1964
Authors: J. Malcolm McNeill, Walter G. J. Putschar
Journal: New England Journal of Medicine (1964)

Presentation of CaseA fourteen-year-old girl entered the hospital because of pain in the left hip.She had been well until sixteen months previously, when pain in the left lower extremity developed, and she began to walk with a limp. Three months later x-ray films of the left hip (Fig. 1) demonstrated a radiolucent lesion in the proximal femur. An operation on the left hip at another hospital disclosed a "cyst," which was packed with bone chips; microscopical examination of a biopsy specimen from the lesion revealed a benign chondroblastoma.During the following year the patient continued to experience pain . . .
Squamous Change in Basal-Cell Carcinoma with Drug Resistance
Authors: Katherine J Ransohoff, Jean Y Tang, Kavita Y Sarin
Journal: New England Journal of Medicine (2015)

In a 62-year-old woman with advanced basal-cell carcinoma who was treated with vismodegib, a recurrent mass was identified as a squamous-cell carcinoma that shared genetic features with the primary basal-cell tumor.
Trends in stage distribution and survival among elderly colorectal cancer patients in the U.S.
Authors: L. M. Lines, K. Lang, D. W. Lee, J. R. Korn, D. J. Vanness, C. C. Earle, J. Menzin
Journal: Journal of Clinical Oncology (2008)

4043 Background: Advances in colorectal cancer (CRC) screening and treatment have occurred over the past decade. This study used nationally representative data to examine trends in stage distribution and survival. Methods: Using SEER data from the National Cancer Institute, we identified patients newly diagnosed with adenocarcinoma of the colon (CC) or rectum (RC) from 1988–2003 and analyzed trends in stage distribution. Observed Kaplan-Meier survival was evaluated by cancer site, stage, and diagnosis year. Results: We identified 174,038 patients with de novo CRC diagnosed in 1988–2003 (75% with colon cancer). In 1988, 2% of CC patients were diagnosed at Stage 0, 19% at Stage 1, 33% at Stage 2, 21% at Stage 3, and 17% at Stage 4 (the remainder were unstaged). The corresponding distribution in 2003 was 2%, 23%, 30%, 23%, and 16% at Stages 0–4, respectively, showing no difference in the share of patients diagnosed at Stage 0, more patients now diagnosed in Stages 1 and 3 and fewer in Stages 2 and 4. In 1988, 2% of RC patients were diagnosed at Stage 0, 31% at Stage 1, 24% at Stage 2, 18% at Stage 3, and 15% at Stage 4. RC incidence was only slightly different in 2003, with 2%, 31%, 22%, 21%, and 15% diagnosed in Stages 0–4, respectively. Overall 5-yr survival rates among CC patients significantly (P<.001) improved from 43% to 47% between 1988–1999 (the last year for which 5-yr survival rates are available; see Table). Overall 5-yr survival among RC patients improved from 41% to 47% (P<.001) between 1988–1999. Nearly all of the gain in CC survival has been among Stage 3 patients, whereas the gain in RC survival has been more substantial and more evenly spread across stages. Conclusions: Rectal cancer is more likely to be diagnosed at Stage 0 or 1 than colon cancer. The changing distribution of cancer stage to include more patients diagnosed at the earliest stages, particularly in colon cancer, indicates possible progress in CRC screening. 5-Year Survival by Diagnosis Year, Site, and Stage Cancer Site Year of Diagnosis Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 All stages Colon 1988 .72 .69 .57 .37 .03 .43 1999 .70 .70 .58 .43 .05 .47 Rectal 1988 .59 .62 .49 .35 .02 .41 1999 .74 .67 .53 .45 .04 .47 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GE Healthcare GE Healthcare
Urinary Hydroxyproline Excretion in Metastatic Cancer of Bone
Authors: Warren D. Platt, Lawrence H. Doolittle, James W. S. Hartshorn
Journal: New England Journal of Medicine (1964)

HYDROXYPROLINE, a nonessential amino acid, comprises 13 per cent of the amino acid content of collagen and is almost absent in the composition of other tissue proteins.1 It is excreted in free and bound forms in human urine.2 , 3 The free form normally makes up only 4 per cent of the total. The remaining hydroxyproline can be released from its bound form (polypeptide) by acid hydrolysis.It has been found to be excreted in the urine in greater than normal quantities in the presence of increased osteoblastic activity as found in normal bone growth, acromegaly and Paget's disease or after the . . .
The outcome of surgical treatment for oldest-old patients with gastric cancer.
Authors: Makoto Hikage, Rie Makuuchi, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Yusuke Kinugasa, Teiichi Sugiura, Katsuhiko Uesaka, Masanori Terashima
Journal: Journal of Clinical Oncology (2016)

40 Background: The number of the oldest-old patients with gastric cancer has been increasing in Japan. Selecting optimal operation for these patients is difficult because coping with both radicality and tolerability of surgery is mandatory. The aim of this study is to clarify the feasibility and effectiveness of gastrectomy for these patients. Methods: A total of 721 old patients (aged 75 years old and older) with gastric cancer who underwent curative gastrectomy at Shizuoka Cancer Center between from Oct. 2002 to Aug. 2015 were included in this study. The patients were classified into oldest-old group (OOP; aged 85 years and older) and old group (OP; aged 75 to 84 years old). Characteristics of the patients and short and long-term outcomes were compared between the groups. Results: OOP group included 57 patients, and OP group 664 patients. Though median serum albumin level in OOP group (3.8 g/dl) was significantly lower than in OP group (4.1 g/dl) (p = 0.002), the other clinicopathological characteristics including gender, BMI, co-morbidity, ASA-PS, ECOG-PS and preoperative stage were not significantly different between the groups. In terms of operative results, gastrectomy with reduced extent of lymph node dissection was frequently performed in OOP group (33.3%) than in OP group (6.0%) with significant difference (p &lt; 0.001). Median operation time was significantly shorter in OOP group (195 minutes) than in OP group (222 minutes) (p = 0.001), and median blood loss was significantly less in OOP group (154 ml) than in OP group (227 ml) (p = 0.041). There was no significant difference of the incidence of postoperative complications between the groups. There was no significant difference of overall survival (p = 0.973) and disease-specific-survival (p = 0.549) between the groups. In multivariate analysis, preoperative BMI &lt; 20, serum albumin &lt; 3.8 g/dl and 15 days or more postoperative hospital stay were revealed as significant independent prognostic factors. Conclusions: Gastrectomy is safe with acceptable oncologic outcomes for OOP with optimally reducing the extent of surgery in each patient. In order to improve the outcome in OOP, preoperative nutritional management and support for home health care system should be considered.
Abstract 16: Enhancing Myocardial Repair With CardioChimeras
Authors: Pearl Quijada, Hazel T Salunga, Nirmala Hariharan, Jonathan Cubillo, Farid El-Sayed, Maryam Moshref, Kristin M Bala, Jaqueline M Emathinger, Andrea De La Torre, Lucia Ormachea, Roberto Alvarez, Natalie A Gude, Mark A Sussman
Journal: Circulation Research (2015)

Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction enhances myocardial repair and performance in large animal models relative to delivery of either cell population individually. However, a single stem cell to support both direct and indirect mechanisms of myocardial repair has yet to be identified. CardioChimeras (CCs), a progenitor cell formed by fusion between CPCs and MSCs were analysed for reparative potential after myocardial infarction (MI) relative to individual parents cell or combined parent cell delivery. Two representative CCs, CardioChimera 1 (CC1) and CardioChimera 2 (CC2) were used for this study. CC1 and CC2 improved left ventricular anterior wall thickness (AWT) at 4 weeks, but only CC1 treatment preserved AWT at 18 weeks relative to no cell treatment (PBS). Ejection fraction was enhanced at 6 weeks post injury in CC1 and CC2 groups, which was maintained in CC1, CC2 and CPC + MSC combined groups up to 18 weeks. Infarct size was decreased by 5% in CC1 and CC2 hearts, whereas CPC + MSC and CPC parent groups remained unchanged when comparing 4 to 12 week change in scar size. MSC and PBS groups displayed marked increases in infarct size (10-15%). CC1 and CC2 showed enhanced engraftment potential by 3-fold relative to CPC + MSC and CPC hearts. In contrast, MSCs were detected at low levels (0.04%). CC1 and CC2 discovered within the myocardium expressed early commitment marker cardiac troponin T relative to controls. CC1 and CC2 treatment increased capillary density within the infarct, indicating that cell persistence facilitates paracrine mediated vasculature stabilization and/or formation. CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs represent a tractable cellular system that improves upon combinatorial cell therapy approaches and supports myocardial regeneration.
77P Glycolytic marker monocarboxylate transporter 4 (MCT4) and outcome to bevacizumab (bev): An exploratory analysis in advanced non-small cell lung cancer (A-NSCLC)
Authors: L. Bonanno, F. Calabrese, A. De Paoli, G. Pasello, A. Santo, A. Favaretto, M. Chilosi, A. Del Conte, P.F. Conte, S. Indraccolo
Journal: Journal of Thoracic Oncology (2016)
Abstract 2322: The Hippo signaling pathway mediates BMP inhibition of cancer stem cells
Authors: Cecile Chartier, Shirley Ma, Dragana Antic, Elsa Quintana, Janak Raval, Min Wang, Cristina Dee-Hoskins, Ann Kapoun, Tim Hoey, John Lewicki, Austin Gurney
Journal: Cancer Research (2015)

Abstract Multiple developmental signaling pathways cooperatively regulate cancer stem cell (CSC) function. Among them, the BMP pathway has been implicated in brain CSC tumorigenicity. To examine whether BMP is a general regulator of CSCs across diverse organ systems we utilized lentivirus-mediated BMP4 expression in patient-derived xenograft models in NOD/SCID mice. The prevention of tumor growth was observed in breast, colon, ovarian, and melanoma models. Similarly, adenovirus-mediated systemic delivery of BMP4 inhibited tumor growth, dramatically affected CSC-specific cell surface markers and decreased CSC frequency. Microarray analysis of BMP4-treated tumors showed that a set of genes encoding for components of the actin cytoskeleton was significantly enriched amongst regulated genes and identified Hippo pathway genes as potential mediators of the BMP4 anti-tumor response with up-regulation of SAV1 and LATS2 and down-regulation of BIRC5. Hippo signaling regulates organ size, stem cell biology and cancer through a protein kinase complex including MST1/2, SAV1, and LATS1/2, which phosphorylates the downstream nuclear effector YAP/TAZ. Phosphorylated YAP/TAZ is unable to induce the expression of cell proliferation and anti-apoptotic genes through interaction with transcriptional co-activators such as TEAD. The Hippo pathway, known to cross-talk with BMP signaling at multiple levels, recently emerged as a cellular sensor of the physical environment through the actin cytoskeleton. We thus asked whether modulating Hippo signaling affected tumor growth. YAP1 overexpression resulted in tumor growth decrease. A deletion variant of YAP, YAP1-291, possessing a deletion of the transactivation domain has been shown to act as a dominant-negative through binding to TEAD. Intriguingly YAP1-291 was also sufficient to strongly attenuate growth of diverse BMP4-sensitive and BMP4-insensitive tumor models suggesting that transactivation through TEAD is not the only route by which YAP modulates tumor growth. YAP anti-proliferative properties were reported before. In order to reconcile the dual function of YAP in cancer, we propose that the transcriptional co-activator's TEAD-mediated oncogenic function may be counter-balanced by its potentiation of SMAD signaling in response to BMP. Citation Format: Cecile Chartier, Shirley Ma, Dragana Antic, Elsa Quintana, Janak Raval, Min Wang, Cristina Dee-Hoskins, Ann Kapoun, Tim Hoey, John Lewicki, Austin Gurney. The Hippo signaling pathway mediates BMP inhibition of cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2322. doi:10.1158/1538-7445.AM2015-2322
Clinicopathologic differences between lung cancer with EGFR gene major (exon 19 deletions and exon 21 L858R) and other minor mutations.
Authors: Y. Yamane, K. Goto, H. Kenmotsu, Y. Ohe, H. Ohmatsu, S. Niho, K. Yoh, G. Ishii, K. Nagai, Y. Nishiwaki
Journal: Journal of Clinical Oncology (2010)

7544 Background: The frequency of EGFR gene minor mutations, which are mutation other than exon 19 deletions or exon 21 L858R, have been reported about 5-10% of lung cancer with EGFR gene mutations. Little is known about clinicopathologic differences between lung cancer with EGFR gene major and other minor mutations. Methods: In National Cancer Center Hospital East, EGFR gene mutations were examined in 593 lung cancer patients between November 2005 and July 2009, and 31 patients with minor mutations (16% of all patients with EGFR gene mutations) were identified. EGFR gene mutations were analyzed by direct sequence or PCR-Invader method. Results: Thirty patients had point mutations in exon 18-21 and one had deletion in exon 18. Eleven patients had both minor and major mutations (7 with exon 19 deletions and 4 with exon 21 L858R). There were 19 males and 12 females, 22 smokers and 9 non-smokers, and 24 with adenocarcinomas and 7 with non-adenocarcinomas. The proportion of males (61%), smokers (71%), non-adenocarcinomas (23%) was significantly higher than that with major mutations. Gefitinib was administered to 9 patients with these minor mutations and only 3 patients, all had both minor and major mutations, showed clinical responses. Other 6 patients were not responded to gefitinib. Conclusions: The lung cancer patients with EGFR gene minor mutations had apparently different clinicopathologic characteristics from those with major mutations and it is possible that the minor mutation is associated with resistance to EGFR-TKI. No significant financial relationships to disclose.
Thrombolytic and pharmacokinetic properties of an immunoconjugate of single-chain urokinase-type plasminogen activator (u-PA) and a bispecific monoclonal antibody against fibrin and against u-PA in baboons
Authors: Y Imura, JM Stassen, T Kurokawa, S Iwasa, HR Lijnen, D Collen
Journal: Blood (1992)
158P: PET/CT based imaging biomarkers for response prediction of stage IV NSCLC treated with paclitaxel–carboplatin–bevacizumab with or without nitroglycerin
Authors: E.E.C. de Jong, W. Van Elmpt, R.T.H. Leijenaar, H. Groen, E. Smit, R. Boellaard, V. Van der Noort, E.G.C. Troost, P. Lambin, A.-M. Dingemans
Journal: Journal of Thoracic Oncology (2016)