tbuckley/cabot-search huggingface dataset:
Ductal Carcinoma in Situ of the Breast
Journal: New England Journal of Medicine (1988)

客观：调查胸的 ductal carcinomain situ (DCIS ) 的临床的特征，治疗和预后。方法：Clinicopathological 和后续数据与 DCIS 在 52 个病人被收集。结果：诊所数据证明 50 个病人有胸块或 / 并且乳头分泌物的症状， 2 个病人介绍反常早期胸部肿瘤Ⅹ射线测定法；2 个病人把淋巴节点深奥；并且 14 个病人伴有 intraductal papillomatosis。所有病人被接待外科的治疗。后续数据证明 1 个病人局部地在 lumpectomy 以后复发了，并且是再经历了乳房切除术，然后治好。没有病人死于 DCIS。结论：乳房切除术应该是一个标准外科的模式，并且 DCIS 的预后是有利的，但是为无征状的女人屏蔽的早期胸部肿瘤Ⅹ射线测定法应该被加强发现 DCIS。
Abstract 11314: Atrial Fibrillation in Hypertrophic Cardiomyopathy: Epidemiology and Risk of Death
Authors: Konstantinos C Siontis, Jeffrey B Geske, Kevin Ong, Steve R Ommen, Bernard J Gersh
Journal: Circulation (2013)

Background: Atrial fibrillation (AF) is a common sequela of hypertrophic cardiomyopathy (HCM). Herein we sought to evaluate the prevalence of atrial fibrillation in a large referral HCM population,...
Impact of polymorphisms in the <i>CYP2B6</i> gene on the pharmacokinetics of cyclophosphamide and thiotepa
Authors: C. Ekhart, A. Huitema, S. Rodenhuis, J. H. Beijnen
Journal: Journal of Clinical Oncology (2006)

13062 Background: Cyclophosphamide and thiotepa are frequently used simultaneously as part of high dose chemotherapy regimens for solid tumours. Although generally well tolerated, severe toxicity may occur. Relationships between pharmacokinetics and toxicity have been identified. Cyclophosphamide and thiotepa are both metabolised by cytochrome P450 (CYP)enzymes, resulting in the active metabolites 4-hydroxycyclophosphamide and tepa respectively. CYP2B6 and CYP3A4 are the major metabolising isozymes for both compounds. In this study we investigated the relationship between polymorphisms of the CYP2B6 gene and the hepatic clearance of cyclophosphamide and thiotepa in order to identify a priori patients at risk for severe toxicity. Methods: CYP2B6*2 (C64T) and variants A785G, C1459T and G516T were identified by PCR and sequencing samples from 82 patients receiving a high dose regimen consisting of cyclophosphamide (4–6 g/m2), thiotepa (320–480 mg/m2) and carboplatin (AUC 13–20 mg*min/ml). Plasma concentrations of thiotepa, cyclophosphamide and metabolites were determined using a validated LC-MS/MS method. Individual pharmacokinetic parameters were obtained using nonlinear mixed effects modelling. Results: A total of 82 patients was included. Not all data of the various variants were available. All investigated variants had an allele frequency of &gt; 3% in the population. While 94% of the patients had the wildtype genotype for CYP2B6*2, 6% were heterozygous. Heterozygous patients for *2 had a lower hepatic clearance of thiotepa compared to wildtype patients (11.7 l*h −1 vs 14.4 l*h −1 ) (P=0.03). All other allelic variants investigated showed no effect on either hepatic clearance of thiotepa or cyclophosphamide. Conclusions: This study demonstrates that the hepatic clearance of thiotepa is reduced in patients with a heterozygous CYP2B6*2 genotype. Patients with this genotype may have an increased exposure to thiotepa and may, therefore, be at increased risk for organ toxicity. No significant financial relationships to disclose.
NITRIC OXIDE AND THE KIDNEY
Authors: Leopoldo Raij
Journal: Circulation (1993)

Nitrix oxide (NO) is an endogenous vasidilator and antithrombogenic agent. NO appears to play an important role in renal physiology and pthophysiology. Under physiological conditions, NO participates in regulation of the glomerular microcirculation by modulating afferent arteriolar tone and relaxation of the mesangium. NO also may contribute to the regulation of renal sodium excretion and renin release. Endothelial dysfunction induced by a variety of injurious mechanisms can lead to decreased synthesis and release of renal NO
Safety and Exploratory Efficacy Of Ex Vivo Expanded Umbilical Cord Blood (UCB) Hematopoietic Stem and Progenitor Cells (HSPC) Using Cytokines and Stem-Regenin 1 (SR1): Interim Results Of a Phase 1/2 Dose Escalation Clinical Study
Authors: John E. Wagner, Claudio G Brunstein, David McKenna, Darin Sumstad, Suzanne Maahs, Anthony E. Boitano, Michael P. Cooke, Conrad C. Bleul
Journal: Blood (2013)
Maternal Anti-Platelet β3 Integrin Antibodies Impair Angiogenesis and Cause Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia
Authors: Yougbare Issaka, Sean Lang, Hong Yang, Pingguo Chen, Xu Zhao, Wei-She Tai, Darko Zdravic, Brian Vadasz, Conglei Li, Siavash Piran, Alexandra H. Marshall, Guangheng Zhu, Heidi Tiller, Mette Kjaer Killie, Shelley Boyd, Howard Leong-Poi, Bjorn Skogen, S. Lee Adamson, John Freedman, Heyu Ni
Journal: Blood (2014)
Transmissible Lymphoma and Simian Acquired Immunodeficiency Syndrome in Rhesus Monkeys&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: G B Baskin, L N Martin, S R Rangan, B J Gormus, M Murphey-Corb, R H Wolf, K F Soike
Journal: JNCI Journal of the National Cancer Institute (1986)

Four rhesus monkeys (Macaca mulatta) were inoculated with a homogenate of a cutaneous lepromatous leprosy lesion from a mangabey monkey (Cercocebus atys). One died of B-cell lymphoma, and another died of an immunodeficiency syndrome. Cell suspensions prepared from the tumor and spleen of the monkey with lymphoma induced lymphoma or an immunodeficiency syndrome when inoculated into additional young rhesus monkeys. The immunodeficiency syndrome was similar to simian acquired immunodeficiency syndrome and consisted of opportunistic infections, lymphoid hyperplasia or atrophy, wasting, and syncytial cell formation. Mitogen responses and percentages of T4- and T8-positive lymphocytes were normal until the animals were moribund. Lymphoblastoid cell lines became established in vitro from tumor cell suspensions. These cells were infected with a herpesvirus related to Epstein-Barr virus. In addition, a retrovirus morphologically similar to human T-cell lymphotrophic virus type III (HTLV-III) and simian T-lymphotrophic virus type III (STLV-III) was isolated from one of the lymphoblastoid cell lines (LCL). Type D retroviruses could not be demonstrated in the monkeys in the transmission study; however, a retrovirus similar to that in the LCL was isolated from 4 animals by coculture of peripheral blood lymphocytes with the human cell line H9. These results suggest that this retrovirus, STLV-III/Delta, may be associated with the immunodeficiency syndrome in these macaques and may be of mangabey origin.
Austerity cuts are eroding benefits of Sure Start children’s centres
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Epithelial cell proliferation in the rectal stump after ileorectal anastomosis for ulcerative colitis was studied in 19 patients. This was achieved through in vitro incorporation of tritiated thymidine in mucosal biopsies and radioautographic analysis of the number and position of labelled nuclei in the crypts. Rectal biopsies from nine unoperated patients with ulcerative colitis and from 10 controls, were processed simultaneously. Except for one, all patients were clinically in remission. The crypt length and number of labelled cells per crypt column were found to be similar in the rectal mucosa from the three groups of subjects. The mean labelling index, although low 8.9%, was higher (p less than 0.05) in operated patients compared with controls; but the dispersion of individual values was similar in both groups. There was an extension of the proliferative compartment towards the surface in 88% of unoperated patients and in 60% of operated patients. In addition, there was a shift of the major zone of proliferation from the lower to the middle third of the crypt in 17% of operated patients and from the lower to the upper third of the crypt in 14% of unoperated patients. No correlation was found between the labelling index and either the age of patient, the duration of disease or the period elapsed after ileorectal anastomosis. Interestingly, among operated patients with a colitis for over 10 years, 42% had a quite normal proliferative pattern with a corresponding mean postoperative period of 7.5 years.
Biological Activity of &lt;italic&gt;Pityrosporum&lt;/italic&gt;. II. Antitumor and Immune Stimulating Effect of &lt;italic&gt;Pityrosporum&lt;/italic&gt; in Mice
Authors: M Takahashi, T Ushijima, Y Ozaki
Journal: JNCI Journal of the National Cancer Institute (1986)

The antitumor activity of Pityrosporum (P. orbiculare, P. ovale, P. pachydermatis, and Pityrosporum sp.) on Ehrlich ascites carcinomas (EACs) implanted into outbred ICR mice was studied. Pityrosporum significantly prolonged the survival of mice, regardless of the administration mode. In the case of P. orbiculare, the maximum survival time was 32.3 days on the mean and was obtained by injection ip of 1 mg (dry weight) P. orbiculare for 7 consecutive days following inoculation of the tumor cells. In contrast, the mean survival time of the nontreated mice was 14.9 days. For the investigation of the mechanisms of this antitumor activity, an examination was done on the ability of intracellular killing of Salmonella typhimurium and oxygen intermediate release by Pityrosporum, as elicited by mouse peritoneal exudate cells (PEC) or mouse peritoneal macrophages (PM). With about 40-minute incubation, 60-80% of S. typhimurium phagocytized by Pityrosporum elicited PEC or PM or were killed. The amounts of superoxide released from Pityrosporum-elicited cells were 1.5 times higher than those of P. acnes-elicited ones. Furthermore, three serum proteins (LA, LB, and LC), which closely related to the anti-tumor activity of immunomodulators, increased in the mice given Pityrosporum. These results indicated that the better survival rate seen in the case of Pityrosporum administration to mice with an implanted EAC may relate to the potent activation of phagocytes and to the increase in serum proteins LA, LB, and LC.
The chemopreventive polyphenol curcumin down-regulates the expression of inflammatory cytokines CXCL1 and -2 in MDA-MB-231 breast cancer cells
Authors: Beatrice Bachmeier, Michele Di Candia, Isabelle Mohrenz, Valentina Mirisola, Marianne Jochum, Adriana Albini, Ulrich Pfeffer
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4215 

The dietary plant derived anti-oxidant, Curcumin, has been proposed for cancer chemoprevention. Curcumin acts through the inhibition of phosphorylation of the inhibitor of kappa B (IκB) which in turn reduces the nuclear translocation of nuclear factor kappa B (NFκB), a inflammation

and cell survival related transcription factor. Here we addressed early effects of Curcumin in MDA-MB-231 breast cancer cells using microarray gene expression analyses. After 6 hours of treatment, Curcumin significantly down-regulates transcription of the inflammatory cytokines CXCL1 and -2 (GROα and -β) that translates into a reduction of the related proteins. This effect is

NFκB dependent since silencing of the NFκB subunit p65 leads to a reduction in CXCL1 and -2 mRNA levels. MDA-MB-231 cells do not express the CXCL1 and -2 receptor (interleukin 8 receptor B). CXCL1 and -2 repression is therefore expected to affect tumor growth, invasion and metastasis indirectly through reduced tumor inflammation and angiogenesis. Consistent with this, we observed that the number but not growth, vitality or

histology of lung metastases formed after intracardiac injection of MDA-MB-231 cells in immunodeficient mice was significantly reduced by Curcumin. These data show that Curcumin not only exerts anti-proliferative and pro-apoptotic activities but reduces metastatic dissemination most probably through down-regulation of NFκB dependent transcription. Curcumin therefore appears suitable as an adjuvant for breast cancer chemoprevention.
PRL2 Maintains Hematopoietic Stem and Progenitor Cells Through Regulating SCF/KIT Signaling
Authors: Michihiro Kobayashi, Yuanshu Dong, Hao Yu, Yunpeng Bai, Sisi Chen, Rui Gao, Mervin C. Yoder, Reuben Kapur, Zhong-Yin Zhang, Yan Liu
Journal: Blood (2013)
A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders
Authors: Robert Keers, Jonathan R.I. Coleman, Kathryn J. Lester, Susanna Roberts, Gerome Breen, Mikael Thastum, Susan Bögels, Silvia Schneider, Einar Heiervang, Richard Meiser-Stedman, Maaike Nauta, Cathy Creswell, Kerstin Thirlwall, Ronald M. Rapee, Jennifer L. Hudson, Cathryn Lewis, Robert Plomin, Thalia C. Eley
Journal: Psychotherapy and Psychosomatics (2016)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment.
Familial Breast Cancer: Risk to the Contralateral Breast 2
Authors: Randall E. Harris, Henry T. Lynch, Hoda A. Guirgis
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Familial Breast Cancer: Risk to the Contralateral Breast Get access Randall E. Harris, Ph.D., Randall E. Harris, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry T. Lynch, M.D., Henry T. Lynch, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hoda A. Guirgis, M.D. Hoda A. Guirgis, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 5, May 1978, Pages 955–960, https://doi.org/10.1093/jnci/60.5.955 Published: 01 May 1978 Article history Received: 11 July 1977 Accepted: 25 November 1977 Published: 01 May 1978
Role of ITPR1/HIF-2α axis in protecting renal cancer cells against natural killer cells.
Authors: Yosra Messai, Zaeem Noman, Meriem Hasmim, Bassam Janji, Laurence Albiges, Bernard Escudier, Salem Chouaib
Journal: Journal of Clinical Oncology (2015)

417 Background: Clear cell renal cell carcinomas frequently display inactivation of VHL gene leading to increased level of hypoxia inducible factors (HIFs). The specific role of VHL mutations and selective activation of HIF-2 alpha in modulating RCC susceptibility to cytotoxic immune response remains largely unknown. Methods: In this study, we used 786-0 RCC VHL-mutated cell line selectively induces HIF-2 alpha stabilization.Chromium release cytotoxicity assay was regularly used to evaluate tumor target cells sensitivity to NK-mediated lysis. Confocal microscopy was aso used to analyse immunologic synapse formation and for autophagy studies. Immunochemistry staining using RCC tissue microarrays was performed to evaluate HIF-2 alpha and ITPR1 expression in RCC patients. Results: We demonstrated that the RCC cell line 786-0 with mutated VHL was resistant to NK-mediated lysis as compared to the VHL-corrected cell line (WT7). This resistance was found to require HIF-2α stabilization. Based on global gene expression profiling and ChIP assay, we found ITPR1 (inositol 1,4,5-trisphosphate receptor, type 1) as a direct novel target of HIF-2α and targeting ITPR1 significantly increased susceptibility of 786-0 cells to NK-mediated lysis. Interestingly, using a large group (235) of RCC patients,we demonstrated the existence of a significant correlation between HIF-2α and ITPR1 expression Mechanistically, HIF-2α in 786-0 cells lead to overexpression of ITPR1, which subsequently regulated the NK mediated killing through the activation of autophagy in target cells by NK derived signal. Both ITPR1 and Beclin-1 silencing in 786-0 cells inhibited NK-induced autophagy and subsequently increased Granzyme B activity in target cells. Finally, in vivo ITPR1 targeting significantly enhanced the NK-mediated tumor regression. Conclusions: Our data provide insights into the link between HIF-2α, the ITPR1-related pathway and natural immunity and strongly suggest a role for the HIF-2α /ITPR1 axis in regulating RCC cell survival. Futur NK cell-based immunotherapy should integrate HIF-2/ITPR1 axis as intrinsic feature of resistance tumor cells to improve NK cell response in RCC patients.
Abound.Sqm: a Phase 3 Randomized Study of Maintenance Nab-Paclitaxel (Nab-P) After Induction Therapy with Nab-P Plus Carboplatin (C) in Patients (Pts) with Squamous Cell (Scc) Non-Small Cell Lung Cancer (Nsclc)
Authors: D.R. Spigel, A. Ko, T.J. Ong, H. West, E. Kim, C. Reynolds
Journal: Annals of Oncology (2014)
Use of health administrative databases in the analysis of waiting times and costs for the diagnosis of non-small cell lung cancer (NSCLC)
Authors: W. Y. Cheung, J. Butler, E. Kliewer, A. Demers, G. Musto, S. Navaratnam
Journal: Journal of Clinical Oncology (2006)

6042 Background: Knowledge of waiting times and costs involved in diagnosis will help to define more effective diagnostic services. The use of administrative databases for such health services research provides a large, population-based cohort and permits an accurate calculation of costs. Methods: Patients diagnosed with NSCLC in Manitoba, Canada from 1996 to 2000 were identified by the cancer registry. Information on diagnostic and staging tests, timeline of investigations, physician visits, hospital admissions, and outcomes were obtained from detailed chart review for 472 patients and from the Manitoba Health Administrative Databases for 2,862 patients. Tariff codes for physician services were used to calculate costs. Results: An excellent correlation was observed (range 83.3 to 99.2%) between the chart review and the administrative databases with regards to timelines of imaging studies, physician services, and procedures. However, charts considerably underreported certain services. For instance, only 58% of chest x-rays performed were captured by chart review. Therefore, costs were analyzed using the administrative databases. Waiting times from chest x-ray to chest CT scan and from CT scan to definitive histologic diagnosis were a median of 8 (range 1–25) and 18 (range 3–42) days respectively by administrative databases, and 10 (range 1–31) and 18 (range 6–36) days respectively by chart review. At least 25% of 2862 patients waited more than 55 days from initial suspicion on chest x-ray to arrive at a final diagnosis. The mean cost to reach a lung cancer diagnosis was $7,578 but analysis indicates that there were large variations in costs among patients. The majority of expenses was accounted by hospital admissions and repeated primary care physician visits, while shorter waiting times to diagnosis corresponded with relatively less costs. Conclusions: Since there is an excellent correlation between chart review and administrative databases, the latter can be used in the future for large cohort studies instead of expensive, laborious chart reviews. Despite clinical suspicion, 25% of patients wait more than 8 weeks for a final diagnosis. A centralized diagnostic service may reduce waiting times and costs for diagnosis. No significant financial relationships to disclose.
Prognostic role of serum beta 2-microglobulin in Hodgkin's disease.
Authors: M A Dimopoulos, F Cabanillas, J J Lee, F Swan, L Fuller, P K Allen, F B Hagemeister
Journal: Journal of Clinical Oncology (1993)

To evaluate the role of serum beta 2-microglobulin (beta 2M) in the prognosis of patients with Hodgkin's disease.One hundred sixty previously untreated patients with Hodgkin's disease had serum beta 2M levels determined before initiation of treatment. Serum beta 2M was tested for its correlation with known prognostic factors for patients with Hodgkin's disease. These variables, including beta 2M, were correlated with complete remission (CR) rate and time to treatment failure (TTF). Univariate and multivariate analyses were performed.Serum beta 2M levels greater than 2.5 mg/L were found in 29% of patients. Such elevation was more common in patients with more advanced-stage disease. Elevated serum beta 2M was an independent and powerful factor in the prediction of lower response rate and shorter TTF. Its impact appeared to be more significant in patients with advanced disease.Serum beta 2M appears to correlate with tumor stage in patients with Hodgkin's disease and elevated serum levels of this polypeptide predict a less favorable prognosis.
Randomised Study of Axitinib (Axi) Plus Best Supportive Care (Bsc) Versus Placebo (Pbo) Plus Bsc in Patients with Advanced Hepatocellular Carcinoma (Hcc) Following Prior Antiangiogenic Therapy
Authors: Y-K. Kang, T. Yau, J-W. Park, E. Boucher, H.Y. Lim, R.T.P. Poon, T-Y. Lee, S. Obi, S.L. Chan, S.K. Qin, R.D. Kim, J. Tang, O. Valota, D. Chakrabarti, M. Kudo
Journal: Annals of Oncology (2014)
Lung cancer risk and polymorphisms in UGT1A6.
Authors: L. Kua, R. A. Soo, A. Khoo, S. Lee, T. Chin, P. Chong, D. Nur, R. C. Soong, B. C. Goh, W. Yong
Journal: Journal of Clinical Oncology (2010)

1555 Background: Uridine diphosphoglucuronosyltransferases (UGTs) 1A6, is the only UGT1A isoform expressed in lung tissue. It is responsible for the detoxifying lung carcinogens such as benezo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) from cigarette smoking. Methods: The allelic distributions of common UGT1A6 polymorphisms were determined in Chinese, Malay and Indian populations. Polymorphisms with frequencies > 1% were evaluated in a testing set of 72 Chinese cases and 62 Chinese controls, and a validating set of 95 Chinese cases and 100 Chinese controls using pyrosequencing. Results: Significant variations in allelic distribution were observed amongst 3 ethnic groups. SNPs 19T > G, 541A > G and 552A > C were significantly associated with increased lung cancer risk and SNPs 105C > T and IVS1+130G > T were associated with reduced lung cancer risk, in both testing and validating sets. Haplotype analysis suggested strong linkage between 541A>G and 552A > C. The risk of lung cancer highest in subjects with both 19T > G and 552A > C (OR = 16.6, 95% CI 5.9-46.6), and lowest in subjects with both 105C > T and IVS1+130G > T (OR = 0.03, 95% CI 0.002-0.54). Conclusions: Our data suggested that UGT1A6 polymorphisms modulate lung cancer risk and may be used to identify at risk individual for lung cancer screening. No significant financial relationships to disclose.
Isolation, Expansion and Characterization of BM-Mesenchimal Cells (MSCs) in Patients Affected By Chronic Myeloproliferative neoplasm (MPN)
Authors: Patrizia Chiusolo, Francesca Annunziata, Elena Rossi, Silvia Betti, Silvia Bellesi, Valerio De Stefano, Giuseppe Leone
Journal: Blood (2014)