tbuckley/cabot-search huggingface dataset:
Abstract 4663: Markers of anaerobic glycolysis as predictive factor in neoadjuvant chemoradiotherapy of rectal cancer
Authors: ByoungYong Shim, Ji Han Jung, Kang-Moon Lee, Hyung Jin Kim, Sook Hee Hong, Sung Whan Kim, Der Sheng Sun, Hoon-Kyo Kim, Hyun Min Cho
Journal: Cancer Research (2010)

Abstract Background: Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to resistance of radiotherapy and chemotherapy. We investigate the relationship between biomarkers related to anaerobic glycolytic metabolism (glucose transpoter-1(GLUT-1), lactate dehydrogenase (LDH)-5 and pyruvate dehydrogenase kinase (PDK)-1) and prognosis. Methods: GLUT-1, LDH-5, PDK-1 expression determined by immunohistochemistry were assessed in 109 patients with rectal cancer treated with 5 flurouracil and leucovorin neoadjuvant chemoradiotherapy. Results: This study included 74 male and 35 female patients with a median age of 63 (range 53-70 years). Stage I, II and III accounted for 7.3%, 43.1% and 49.5%. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (425 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33 and surgery was done on 7 to 10 weeks after completion of all therapies. The down staging rate of this neoadjuvant therapy was 53% and pathologic complete response rate is 18.3%. High expression of GLUT-1, LDH-5, PDK-1 was observed in 34 (31.2%), 62 (56.9%) and 45 (41.3%) patients, respectively. A negative GLUT-1 was associated with a significantly higher rate of pathologic complete response compared to positive GLUT-1 (25.3% vs. 0.02%, p=0.006). LDH-5, PDK-1 was not correlated with down staging and complete response of chemoradiotherapy. Conclusions: The GLUT-1 expression is the predictive factor of pathologic complete response in rectal cancer patients treated with 5 flurouracil and leucovorin neoadjuvant chemoradiotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4663.
A. N. Richards Supplement
Authors: W. B. BEAN
Journal: Annals of Internal Medicine (1970)

Letters and Comments1 April 1970A. N. Richards SupplementW. B. BEAN, M.D.W. B. BEAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-4-598 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I have been reading over with real pleasure the tributes to Alfred Newton Richards "Scientist and Man" in the supplement to the November issue of the ANNALS. I came to know him quite late. I was on the committee that made the presentation of the Abraham Flexner Award to Dr. Richards. During the long and windy proceedings that came before my presentation of the award and his acceptance comments, we had a great conversation about wine. He sent me shortly thereafter a book by J. M. Scott, entitledThe Man Who Made Wine, a charming story, published... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Internal Medicine University Hospitals The University of Iowa Iowa City, Iowa 52240 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1970Volume 72, Issue 4Page: 598-598KeywordsScientistsWine Issue Published: 1 April 1970 PDF DownloadLoading ...
Tumor Cell Invasion Inhibited by TIMP-2
Authors: A. Albini, A. Melchiori, L. Santi, L. A. Liotta, P. D. Brown, W. G. Stetler-Stevenson
Journal: JNCI Journal of the National Cancer Institute (1991)

The 72-kd type IV collagenase is a member of the collagenase enzyme family that has been closely linked with the invasive phenotype of cancer cells. Previous studies have shown that both normal cells and highly invasive tumor cells produce the 72-kd type IV procollagenase enzyme in a complexed form consisting of the proenzyme and a novel tissue inhibitor of metalloproteinases, TIMP-2. The balance between activated enzyme and available inhibitor is thought to be a critical determinant of the matrix proteolysis associated with a variety of pathologic processes, including tumor cell invasion. In the present study, we demonstrate that alteration of the metalloproteinase-metalloproteinase-inhibitor balance in favor of excess inhibitor blocks human fibrosarcoma HT-1080 tumor cell invasion of a reconstituted basement membrane. The HT-1080 cell line produces both the 72-kd and the 92-kd type IV collagenases. Alteration of the type IV collagenase-inhibitor balance was achieved by addition of free TIMP-2 or antibodies to 72-kd type IV collagenase. Native, purified TIMP-2 was inhibitory in the range of 1-25 micrograms/mL. Addition of specific antiserum against the 72-kd type IV collagenase, which did not cross-react with the 92-kd type IV collagenase, inhibited HT-1080 cell invasion to the same extent. These results suggest that metalloproteinases, in particular the 72-kd type IV collagenase, are critical for tumor cell invasion of the reconstituted basement membrane. Our findings demonstrate that addition of the endogenous inhibitor TIMP-2 is able to block invasion. Thus, we recommend initiation of in vivo studies of the therapeutic potential of TIMP-2 to block tumor cell invasion and intravasation into the circulation.
Pathways to the Complement System
Authors: Irwin H. Lepow, Fred S. Rosen
Journal: New England Journal of Medicine (1972)

IT has been well appreciated for many years that the serum complement system, through the concerted action of all its components, is a prime mediator of cytotoxic injury to antibody-sensitized cells. In the last several years, other functions that contribute to the inflammatory process have been attributed to reaction products of the activation of the terminal portion of the system (C3, C5 ... C9). For example, peptides derived from C3 and C5 are potent mediators of histamine release, smooth-muscle contraction, and enhancement of vascular permeability. Other examples of the phlogistic consequences of complement activation reside in the enhanced susceptibility to . . .
GW25-e2199 A Novel Drug-eluting PLLA/ACP Bioabsorbable Scaffold for Coronary Application: Preliminary Experience in Porcine Coronary Arteries
Authors: Feng Gaoke, Wang Yujue, Xiao Jianmin, Zheng Xiao-Xin, Lyu Yong-Nan, Li Hu, He Suyuan, Gu Weiwang, Tim Wu, Li Jun, Lu Zhao, Jiang Xuejun
Journal: Journal of the American College of Cardiology (2014)
Depression of peak force without altering calcium sensitivity by the superoxide anion in chemically skinned cardiac muscle of rat.
Authors: N G MacFarlane, D J Miller
Journal: Circulation Research (1992)

Among the mechanisms postulated to contribute to myocardial "stunning" is a depression of contractility by oxygen-derived free radicals. It has been suggested that these radicals might depress the calcium sensitivity of the contractile proteins. We have exposed the myofilaments (in chemically "skinned" rat cardiac muscle) to the superoxide anion and measured isometric force at controlled degrees of activation. Superoxide was generated by the xanthine/xanthine oxidase system: the effects to be described were shown to be specifically attributable to superoxide. Maximum calcium-activated force is reduced, or even completely abolished, in a dose-dependent fashion and without any alteration in calcium sensitivity. The myofilaments are highly sensitive to superoxide: significant force reduction has been shown to be caused by enzyme concentrations as low as 2 microunits/ml xanthine oxidase and with exposures of less than 1 minute to the generating system (at higher enzyme concentrations). Once force has been depressed, it cannot be recovered within the duration of the experiments described. When xanthine oxidase is applied during the calcium-induced contracture, tension falls steadily. However, a similar concentration is without immediate effect on the rigor contracture (evoked by applying ATP-free solutions). To account for the depression of maximum calcium-activated force, we conclude that some aspect of crossbridge behavior is particularly vulnerable to superoxide rather than that the radical has a nonspecific "proteolytic" effect. This action on the fundamental units of force production could contribute to myocardial stunning since the effects we report are consistent with many aspects of this phenomenon.
On the Physical Alterations of the Blood and Animal Fluids in Disease: Alterations of the blood in fever and inflammation
Authors: M. Andral
Journal: BMJ (1841)

419Wltdh, and reduces the patient to a state of great dbity, wuhich I believe wbuld destroy her, unless proper means are resorted to, to arrest the disease.The first case of the kind which fell under my care, was that of a lady who had been confined'
Early Detection of Recurrent Hepatocellular Carcinoma by Endosonographically Guided Fine-Needle Aspiration Biopsy
Authors: J. Bogstad, P. Vilmann, F. Burcharth
Journal: Endoscopy (1997)

Fine-needle aspiration guided by endoscopic ultrasonography (EUS) has shown promising results in establishing the cytological diagnosis of lesions identified during endoscopic ultrasound examinations. We report here on a case of recurrent hepatocellular carcinoma diagnosed by EUS-guided biopsy in which curative resection was possible as a result of early diagnosis.
A Comparison of Sarcoidosis in New York and London.
Authors: D. Geraint James
Journal: Annals of Internal Medicine (1968)

s1 May 1968A Comparison of Sarcoidosis in New York and London.D. Geraint James, M.D., F.R.C.P., L. E. Siltzbach, M.D.D. Geraint James, M.D., F.R.C.P.Search for more papers by this author, L. E. Siltzbach, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1191_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe patterns of the multisystem disorder, sarcoidosis, in 537 patients in London have been compared with 311 in New York. The clinical diagnosis was always confirmed histologically; in four fifths of each series, sarcoid tissue was obtained by biopsy of lymph node, skin, or liver, which, together with the Kveim test, proved the most fruitful techniques.The comparison includes clinical, radiological, and biochemical manifestations, modes of presentation, epidemiology, the immunological deficit, and treatment. Despite racial, cultural, and geographical differences, the pattern of disease was similar in both countries.This scheme will provide a basis for computer analysis on a universal... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1191-1191KeywordsBiopsyClinical epidemiologyComputersLiverLymph nodesSarcoidosis Issue Published: 1 May 1968 PDF DownloadLoading ...
Different Ways to Describe the Benefits of Risk-Reducing Treatments
Authors: Peder A. Halvorsen, Randi Selmer, Ivar Sønbø Kristiansen
Journal: Annals of Internal Medicine (2007)

Background: How physicians communicate the risks and benefits of medical care may influence patients' choices. Ways to communicate the benefits of risk-reducing drug therapies include the number needed to treat (NNT) to prevent adverse events, such as heart attacks or hip fractures, and gains in disease-free life expectancy or postponement of adverse events. Previous studies suggest that the magnitude of the NNT does not affect a layperson's decision about risk-reducing interventions, but postponement of an adverse event does affect such decisions. Objective: To examine laypersons' responses to scenarios that describe benefits as postponing an adverse event or the equivalent NNT. Design: Cross-sectional survey with random allocation to different scenarios. Setting: General community. Participants: Respondents to a population-based health study. Intervention: The survey presented scenarios regarding a hypothetical drug therapy to reduce the risk for heart attacks (1754 respondents) or hip fractures (1000 respondents). The data sources for both scenarios were clinical trials. Respondents were randomly assigned to a scenario with 1 of 3 outcomes after 5 years of treatment. For the drug to prevent heart attacks, the outcomes were postponement by 2 months for all patients, postponement by 8 months for 1 of 4 patients, or an NNT of 13 patients to prevent 1 heart attack. For the drug to prevent hip fractures, the outcomes were postponement by 16 days for all patients, postponement by 16 months for 3 of 100 patients, or an NNT of 57 patients to prevent 1 fracture. Measurements: Consent to receive the intervention and perceived ease of understanding the treatment effect. Results: The overall rate of response to the survey was 81%. In the heart attack scenarios, 93% of respondents who were presented with the NNT outcome consented to drug therapy, 82% who were presented with the outcome of large postponement for some patients consented to therapy, and 69% who were presented with the outcome of short postponement for all patients consented to therapy (chi-square, 89.6; P < 0.001). Corresponding consent rates for the hip fracture scenarios were 74%, 56%, and 34%, respectively (chi-square, 91.5, P < 0.001). Respondents who said that they understood the treatment effect were more likely to consent to therapy. Limitation: Decisions were based on hypothetical scenarios, not real clinical encounters. Conclusions: Treatment effects expressed in terms of NNT yielded higher consent rates than did those expressed as equivalent postponements. This result suggests that the description of the anticipated outcome may influence the patient's willingness to accept a recommended intervention.
Abstract 7: Knockdown of <i>EGFR</i> to investigate its therapeutic potential for treatment of non-small cell lung cancers
Authors: Junichi Soh, Kazuhiko Shien, Tsuyoshi Ueno, Kazunori Tsukuda, Kenichi Suda, Takafumi Kubo, Masashi Furukawa, Takayuki Muraoka, Yuho Maki, Norimitsu Tanaka, Hiromasa Yamamoto, Katsuyuki Kiura, Tetsuya Mitsudomi, Shinichi Toyooka, Shinichiro Miyoshi
Journal: Cancer Research (2012)

Abstract Background: Epidermal growth factor receptor (EGFR) is a transmembrane protein consisting of an extracellular ligand-binding domain, and its activation leads to a multitude of effects including cell proliferation, cell differentiation, angiogenesis, metastasis, and antiapoptosis. EGFR can be a partner of heterodimer of other EGFR family such as HER2 and HER3. EGFR is often overexpressed in non-small cell lung cancer (NSCLC). Anti-EGFR agents including EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have considered to be effective for NSCLC when drug sensitive EGFR mutation is present. However, inherent and acquired resistances are major problems of EGFR targeting therapies. In this study, we knock-downed EGFR using small interfering RNAs (siRNAs) in NSCLC cell lines to examine the significance of targeting EGFR for NSCLC therapy. Materials and methods: We treated 14 NSCLC cell lines including nine EGFR mutant and five EGFR wild-type cell lines by geftinib or siRNAs for EGFR knock-down (siR-EGFR). Three cell line, PC-9-GR-N1, RPC-9, and HCC827-Met, were experimentally established as acquired resistant cells to gefitinib. The anti-tumor effect was determined by MTS or colony formation assay. The protein expression was evaluated using Western blotting. Results: All cell lines showed the expression of EGFR protein and siR-EGFR treatment down-regulated EGFR protein in all 14 cell lines. siR-EGFR suppressed cell viability in 7 of 9 EGFR mutant cells ranged from 8.0% to 73%. PC-9-GR-N1 and RPC-9 also showed inhibition. NCI-H1670 and HCC827-Met harboured EGFR mutation but were not inhibited. Of note, PTEN was deleted in NCI-H1670 and c-MET was amplified in HCC827-Met. Cell viability of all EGFR wild-type cells was not inhibited except NCI-H411. Conclusion: Our results indicated that EGFR can be the therapeutic target of NSCLC with EGFR activation. By contrast, targeting EGFR is not appropriate strategy for tumor of which EGFR is not activated even though EGFR is expressed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 7. doi:1538-7445.AM2012-7
Man and Machine Calculating the Mind
Authors: Donald N. Bersoff
Journal: JAMA (1965)

To the Editor:—  In as rational and objective language as I can muster, I would like to make a critical rejoinder to the Swenson et al article entitled A Totally Automated Psychological Test ( JAMA  191 :925-927 [March 15] 1965). Such a program as outlined by the authors will add immeasurably to our knowledge and provide massive data for research. But, I must take violent exception to its use as an instrument for diagnostic testing or personality evaluation.  Psychological testing ought to be the last area in which dehumanization takes place. Psychological evaluation depends, to a great extent, on the analysis of the interpersonal relationship between the tester and the test taker. We are not interested in the patient's test responses; we are interested in the patient's ability to organize, relate to, and function in his environment. People are not judged on how they relate to blots, questionnaires, or computers; they
Experts call for more resources to tackle Africa's health challenges in infectious and chronic diseases
Authors: J. Zarocostas
Journal: BMJ (2011)

Poor African countries need to inject more funds and human resources to deal with pressing health challenges in the continent, say experts.

Former United Nations secretary general, Kofi Annan, speaking at the international Gateway to Africa conference held in Geneva on 4-6 April, said there had been substantial investments in recent years into health in Africa, to try and advance the UN’s Millennium Development Goals created in 2000, which included halving extreme poverty and halting the spread of HIV/AIDS.

Much, however, remains to be done to address major problems such as a lack of adequate clean …
Abstract 3422: RNAi screening identifies FGFR4 as a modulator of growth and survival in Ewing sarcoma
Authors: David O. Azorsa, Irma M. Gonzales, Shilpi Arora, R. Tanner Hagelstrom, Tanya H. Little, Robert J. Arceci, Spyro Mousses
Journal: Cancer Research (2014)

Abstract Ewing sarcoma is the second most common cancer of bone and soft tissue arising in children and young adults. Standard treatment of Ewing sarcoma includes surgery, radiation, and chemotherapy largely consisting of combinations of non-targeted cytotoxic agents. Although the survival rate has improved for patients treated for localized disease, the survival rate of patients with metastatic tumor remains lower than 30%. In order to improve therapeutic options for Ewing Sarcoma, we employed a functional genomics approach based on RNA interference (RNAi) screening to identify genes whose silencing affected the proliferation and survival of Ewing sarcoma cells. Four Ewing sarcoma cell lines, TC-32, TC-71, SK-ES-1 and RD-ES, were transfected with a library of siRNA targeting 287 cancer-associated genes. The siRNA screening data were normalized and statistical cut-offs were determined for each cell line. From the list of siRNA ‘hits,’ we identified siRNAs targeting Fibroblast growth factor 4, FGFR4, to be among the most effective in inducing cytotoxicity in Ewing sarcoma cells. Further validation was conducted showing that siRNAs to FGFR4, but not FGFR1, FGFR2, or FGFR3, were able to significantly reduce Ewing Sarcoma cell viability. Furthermore, siRNA targeting FGFR4 were able to induce Caspase 3 activity. FGFR4 protein was shown to be expressed in Ewing sarcoma by western blot analysis, with expression levels lower than FGFR4 expression on rhabdomyosarcoma cells. Targeting FGFR4 activity in Ewing sarcoma cells using a pan-FGFR inhibitor, PD-173074, demonstrated that Ewing sarcoma cells were sensitive to FGFR inhibition. Since FGFR4 in a potential therapeutic target in rhadomyosarcoma, we compared the response of the Ewing sarcoma cells to PD-173074 to that of the rhabdomyosarcoma cell lines, RH-30 and RD. The IC50s of the four Ewing sarcoma cells ranged from 3.8-4.7 µM and were slightly lower than the IC50 for the rhabdomyosarcoma cell lines RH-30 (5.6 µM) and RD (7.9 µM). These results indicate that FGFR4 is a potential therapeutic target in Ewing sarcoma and that FGFR4 targeted therapy should be tested in preclinical xenograft models of Ewing sarcoma. Citation Format: David O. Azorsa, Irma M. Gonzales, Shilpi Arora, R. Tanner Hagelstrom, Tanya H. Little, Robert J. Arceci, Spyro Mousses. RNAi screening identifies FGFR4 as a modulator of growth and survival in Ewing sarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3422. doi:10.1158/1538-7445.AM2014-3422
A simulation study of confounding in generalized linear models for air pollution epidemiology.
Authors: C Chen, D P Chock, S L Winkler
Journal: Environmental Health Perspectives (1999)

Confounding between the model covariates and causal variables (which may or may not be included as model covariates) is a well-known problem in regression models used in air pollution epidemiology. This problem is usually acknowledged but hardly ever investigated, especially in the context of generalized linear models. Using synthetic data sets, the present study shows how model overfit, underfit, and misfit in the presence of correlated causal variables in a Poisson regression model affect the estimated coefficients of the covariates and their confidence levels. The study also shows how this effect changes with the ranges of the covariates and the sample size. There is qualitative agreement between these study results and the corresponding expressions in the large-sample limit for the ordinary linear models. Confounding of covariates in an overfitted model (with covariates encompassing more than just the causal variables) does not bias the estimated coefficients but reduces their significance. The effect of model underfit (with some causal variables excluded as covariates) or misfit (with covariates encompassing only noncausal variables), on the other hand, leads to not only erroneous estimated coefficients, but a misguided confidence, represented by large t-values, that the estimated coefficients are significant. The results of this study indicate that models which use only one or two air quality variables, such as particulate matter [less than and equal to] 10 microm and sulfur dioxide, are probably unreliable, and that models containing several correlated and toxic or potentially toxic air quality variables should also be investigated in order to minimize the situation of model underfit or misfit.
The Endotoxins of Gram-Negative Bacteria and Host Resistance
Authors: Fred S. Rosen
Journal: New England Journal of Medicine (1961)

There is only one genuinely scientific treatment for all diseases, and that is to stimulate the phagocytes. Stimulate the phagocytes. Drugs are a delusion. — George Bernard Shaw, The Doctor's Dilemma (Act 1), 1906.TN 1893 Pfeiffer observed that the intraperitoneal injection of the cholera vibrio into mice resulted in the lysis of the injected bacteria by the host defense mechanisms. After this lysis the mice sickened and died. Pfeiffer conceived of a toxin that was released by the lysis from within the bacteria and thus devised the term endotoxin. It was subsequently shown that Pfeiffer was in error, that . . .