tbuckley/cabot-search huggingface dataset:
An analysis of prognostic factors of comprehensive geriatric assessment (CGA) and development of a clinical scoring system in elderly Asian cancer patients.
Authors: R. Kanesvaran, H. Li, K. Koo, D. Poon
Journal: Journal of Clinical Oncology (2010)

9165 Background: Certain components of the comprehensive geriatric assessment (CGA) correlate with survival in elderly cancer patients. The purpose of this study was to determine the impact of each CGA domain on overall survival and to develop a prognostic scoring system to stratify elderly cancer patients into risk groups. Methods: A retrospective analysis of CGA data collected from 318 consecutive cancer patients who attended the outpatient geriatric oncology clinic at the National Cancer Center Singapore, aged 70 years and above was performed. Univariate and multivariate analyses were done using Cox proportional hazard method to identify significant prognostic factors within the CGA. A simple scoring algorithm to predict overall survival was developed using the regression coefficients from the multivariate model with total clinical scores ranging from 0 to 6. Results: Median age of the 318 patients was 77 years old (range: 70-94 years). ECOG performance status, functional status (ADL/IADL) and presence of geriatric syndromes were shown to be highly co-dependent variables. In our model, poor ECOG performance status (≥ 2 vs. < 2: HR=2.28, 95% CI= 1.44 - 3.61), high malnutrition risk (high risk vs. low risk: HR=2.59, 95% CI= 1.64 -4.10) and advance stage of disease (late vs. early: HR=2.14, 95% CI= 1.25–3.67) were independent predictors of survival. The patients with high risk clinical score 5-6 (HR=4.92, 95%CI = 2.72–8.87) and moderate risk score 3-4 (HR=2.09, 95%CI = 1.09–4.02) had significantly higher mortality rates compared to those classified as low risk score 0-2. The 2-year survival rate for low, moderate and high risk groups were 74.9% (95%CI 58.9-85.4), 50.9% (95% CI 37.0–63.3) and 23.2% (95% CI 16.8–30.1) respectively. Longer term follow-up and a larger sample size may identify factors that will significantly distinguish the low and moderate risk groups. Conclusions: The results confirm the importance of the CGA in the assessment of the elderly cancer patient. The development of the risk scoring system incorporating few key prognostic factors helps stratify patients into risk groups for further intervention. No significant financial relationships to disclose.
Immunotherapy-Associated Hemolytic Anemia with Pure Red-Cell Aplasia
Authors: Ranjit Nair, Shereen Gheith, Suresh G Nair
Journal: New England Journal of Medicine (2016)

The authors report a case of immunotherapy-associated autoimmune hemolytic anemia with pure red-cell aplasia in a patient receiving the anti–PD-1 antibody pembrolizumab for therapy of mucosal malig...
Steroid receptors and hormone action: physiological and synthetic androgens and progestins can mediate inappropriate biological effects.
Authors: O A Jänne, C W Bardin
Journal: Pharmacological Reviews (1984)

Evidence is reviewed indicating that superphysiological doses of progestins and androgens have a variety of effects which cannot be attributed alone to their action by way of the progestin and androgen receptors respectively.  The analysis is restricted to a detailed examination of progestins that have effects via the androgen receptor and androgens that act via the progestin receptor.  The principles illustrated apply to the actions of other steroids that have effects by the wrong receptor when administered at high doses.  Progestins can mimic inhibit or potentiate the action of androgens.  These responses have been termed the androgenic antiandrogenic and synandrogenic actions of progestins  respectively.  The androgenic and antiandrogenic actions of this class of steroids are manifest on many tissues and on many endpoints within a given organ.  It is believed that these effects involve an early step(s) of androgen action which is common to all sensitive tissues.  The results accumulated to date suggest that this early step involves the androgen receptor.  By contrast the synandrogenic action of progestins is limited in that it is not observed on all tissues nor even on all endpoints within a single organ.  The androgenic action of progestins is believed to be similar to that of other androgens.  Androgenic progestins such as medroxyprogesterone acetate (MPA) bind to the androgen receptors and translocate them to nuclei.  This is followed by a dose-dependent increase of the concentration of specific proteins similar to what is observed after testosterone administration.  The regulatory genes which modulate androgen action have the same effect on the androgenic effect of progestins.  The fact that the potency of progestins such as MPA is less than that of testosterones is believed to relate in part to their lower affinity for the androgen receptors.  At this time it is not possible to postulate a single mechanism that will explain the synergistic action of progestins on all tissues.  This is partially because of the fact that this action is limited to a few biological endpoints and also because the synergistic action of progestins is highly dose-/ and time-dependent.  The progestins that produce this effect also may be androgenic antiandrogenic or both.  Progestational androgens bind to the progestin receptor and facilitate binding of the steroid receptor complex to nuclei followed by an increase in mRNA synthesis which in turn direct specific protein synthesis.  The potency of a given androgen for inducing progestational effects on the uterus is believed to be related to its affinity to the progestin receptor.
Disentangling common characteristics is not so easy
Authors: C. Shepherd
Journal: BMJ (1995)

EDITOR,--Over the past few years I have seen a growing number of patients with the chronic fatigue syndrome who have been told by psychiatrists and psychologists that abnormal illness behaviour and psychosocial factors are the main factors perpetuating their disability. Few patients have accepted or believed this explanation; neither have I. The ME Association now has evidence that the fashionable theory …
Once-Daily Tiotropium Respimat® Add-on to at Least Ics Maintenance Therapy in Patients with Symptomatic Asthma: Methodology of Modeling Analyses By Serum IgE and Blood Eosinophil Levels
Authors: Hendrik Schmidt, Petra Moroni-Zentgraf, Michael Engel, Ronald Dahl, Huib A.M. Kerstjens
Journal: Journal of Allergy and Clinical Immunology (2016)
Gene expression in colorectal cancer and <b><i>in vitro</i></b> chemosensitivity to 5-fluorouracil: A study of 88 surgical specimens
Authors: T. Kubota, K. Yoshinare, M. Watanabe, H. Hasegawa, H. Nishibori, M. Kitajima
Journal: Journal of Clinical Oncology (2004)

3659 Background: To predict the sensitivity of colorectal cancer to 5-fluorouracil (5-FU), we compared the gene expression of surgically obtained colorectal cancer specimens with chemosensitivity to 5-FU as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Methods: Eighty-eight patients with advanced and/or metastatic colorectal cancer provided written informed consent and entered the trial from September 2000 to October 2001. Fresh surgical specimens were used for the MTT assay, and sensitivity to 5-FU was evaluated at a cutoff concentration of 50 μg/ml and 48-h incubation time. Frozen samples were stored at -80°C until mRNA analysis of thymidylate synthetase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), es-nucleoside transporter (NT), and E2F1 by real time RT-PCR. The correlation between each variable was analyzed, and the predictive value of these mRNAs was assessed statistically using a receiver operating characteristic (ROC) curve. Results: NT and DPD, TP and DPD, and TP and NT mRNA expression correlated significantly, while TS and E2F1 did not. High NT expression was associated with low sensitivity to 5-FU (P<0.013), as was high DPD and E2F1 expression (P<0.022 for both). High TP mRNA expression correlated with low sensitivity to 5-FU (P<0.034), although TS mRNA expression did not. ROC curves indicated that DPD and NT mRNAs were possible predictors of sensitivity to 5-FU, with cutoff values of 0.6 and 0.4, respectively. Conclusions: The sensitivity of colorectal cancer to 5-FU may be regulated by a catabolic rate-limiting enzyme, DPD, and NT, an important membranous transporter of nucleosides. No significant financial relationships to disclose.
Receptor-Associated Protein Is Important for Normal Processing of Megalin in Kidney Proximal Tubules
Authors: HENRIK BIRN, HENRIK VORUM, PIERRE J. VERROUST, SØREN K. MOESTRUP, ERIK ILSØ CHRISTENSEN
Journal: Journal of the American Society of Nephrology (2000)

The receptor-associated protein (RAP) has been identified as a chaperone regulating the expression and processing of the LDL receptor-related protein. RAP also binds to the related 600-kD multiligand endocytic receptor megalin expressed in many absorptive epithelia including renal proximal tubule. The present study examines the effect of RAP gene disruption on megalin expression and subcellular distribution in the proximal tubule as well as the effect on tubular protein reabsorption. It is shown that RAP is important for the normal expression and function of megalin. Megalin expression was reduced to approximately 23% estimated by immunoblotting and supported by immunocytochemistry and by the amount of megalin recovered by RAP affinity chromatography. Light-and electron microscope immunocytochemistry as well as analyses on separated membrane fractions showed significant changes in the subcellular distribution of megalin. A significant reduction in the normal brush border labeling was observed in association with increased labeling of rough endoplasmic reticulum and the smooth paramembranous endoplasmic reticulum along the basolateral membranes. RAP deficiency was associated with changes in urinary protein composition, enabling the identification of α-amylase as a new ligand for megalin. In addition, an increased excretion of vitamin D-binding protein, a recently identified ligand to megalin, was observed supporting changes in tubular protein reabsorption. The present data show that RAP is of crucial importance for normal processing and function of megalin, suggesting a chaperone-like function of this protein in the kidney proximal tubule.
Cancer in Alaskan Indians, Eskimos, and Aleuts&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: Anne P. Lanier, M.D., M.P.H., William J. Blot, Ph.D., Thomas R. Bender, M.D., M.P.H., Joseph F. Fraumeni, Jr., M.D.
Journal: JNCI Journal of the National Cancer Institute (1980)

Standard incidence ratios for cancers that occurred during 1969–73 among Alaskan Natives (Indians and Eskimo-Aleuts) were reported. Although data suggested that the overall rate of cancer in this population was close to that of U.S. whites, differences existed for certain cancer sites. Thus increased risks in Alaskan Natives were observed for nasopharyngeal, salivary gland, kidney, and gallbladder and liver cancers. Conversely, decreased risks were found for cancers of the lung, larynx, bladder, prostate gland, breast, and corpus uterus and for melanoma and lymphoma.
Chromosome Studies in Marek's Disease
Authors: J. J. T. Owen, M. A. S. Moore, P. M. Biggs
Journal: JNCI Journal of the National Cancer Institute (1966)

Chromosome studies on the virus-induced diseases of the avian leukosis complex have been severely limited by the difficulties involved in the preparation of clear metaphase figures from avian tissues. Recently a technique has been used in this laboratory for the preparation of excellent avian metaphase figures and in the present investigation a detailed study of the chromosomal constitution of the tumor cells present in Marek's disease has been undertaken by means of this method. A total of 1,127 metaphases from ovarian and testicular tumors and 420 metaphases from normal spleens were analyzed. While most of the dividing tumor cells contained a normal diploid number of chromosomes, chromatid and isochromatid breaks were found in the largest chromosome pairs, whereas none were seen in chromosomes prepared from normal spleen cells. Chromosome breakage has not been demonstrated in avian tumor cells previously. It has also been shown that, although the disease can be most easily passaged by cell inocula, the sex chromosome complement of the tumor cells in the recipient males was ZZ, which shows that these, at least, were primary tumors and not produced by the proliferation of transplanted ovarian tumor cells. These results are discussed in relation to the probable viral etiology of Marek's disease.
The Amino Terminal Lectin-Like Domain of Thrombomodulin Is Required for Constitutive Endocytosis
Authors: Edward M. Conway, Saskia Pollefeyt, Desiré Collen, Marta Steiner-Mosonyi
Journal: Blood (1997)

Abstract Thrombomodulin (TM) is a multidomain protein that serves as a cofactor in a major natural anticoagulant system. To further characterize the structure-function of TM, we have transfected COS cells with different truncated forms of TM. In the first form, COS cells expressing TM that lacks the putative signal peptide (17 residues); the lectin-like, hydrophobic N-terminal domain (226 residues); and 12 residues of the first epidermal growth factor (EGF )-like repeat (COSdel.238 cells) were found to function normally with respect to TM transport to the cell surface and thrombin-dependent protein C activation. However, in contrast to wild-type TM, as visually studied by immunofluorescence and immunogold electron microscopy, the COSdel.238 cells did not constitutively internalize anti-TM–TM or thrombin-TM complexes. To identify the region responsible for mediating the endocytic process, deletant forms of TM lacking either the lectin-like region (residues 2-155) or the hydrophobic region of the N-terminal domain (residues 161-202) were expressed in COS cells (COSdel.2-155 and COSdel.161-202, respectively). Protein C cofactor activity was maintained in both cells. Although the COSdel.161-202 cells behaved similarly to wild-type TM-transfected cells, visual studies showed a lack of constitutive internalization of thrombin-TM or anti-TM–TM complexes in the COSdel.2-155 cells. We conclude that the lectin-like domain of human TM serves to regulate cell surface expression of TM via the endocytic route and therefore may also play a major physiologic role in controlling intracellular and extracellular accumulation of thrombin in a variety of biologic systems.
The new International Neuroblastoma Staging System: some critical notes.
Authors: N L Carlsen
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.5.935 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2185343 The new International Neuroblastoma Staging System: some critical notes. N L CarlsenxN L CarlsenSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.5.935 PDF "The new International Neuroblastoma Staging System: some critical notes.." Journal of Clinical Oncology, 8(5), pp. 935–936© 1990 by American Society of Clinical Oncology
A first-in-human dose escalation study of PEGylated recombinant human IL-10 (AM0010) in advanced solid tumors.
Authors: Jeffrey R. Infante, Aung Naing, Kyriakos P. Papadopoulos, Karen A. Autio, Patrick Alexander Ott, Deborah Jean Lee Wong, Gerald Steven Falchook, Manish R. Patel, Shubham Pant, Melinda Whiteside, Johanna C. Bendell, Todd Michael Bauer, Filip Janku, Milind M. Javle, David S. Hong, Martin Oft
Journal: Journal of Clinical Oncology (2015)

3017 Background: PEGylated IL-10 induces the expansion of tumor reactive CD8 T cells both in the periphery and within the tumor. In mice, PEG-IL-10 but not non-PEG-IL-10 induces the rejection of tumors and establishes immunological memory. Primary objectives of this FIH study were to establish the safety, tolerability and the MTD of AM0010. Secondary objectives were to assess anti-tumor-activity, pharmacokinetics, immunogenicity and induced immune activation. Methods: Patients with advanced melanoma (4), non-small cell lung cancer (1), renal cell cancer (6), colorectal cancer (16), prostate cancer (1), ovarian cancer (1) and pancreatic cancer (4) were enrolled in escalating cohorts of 3-6 patients each followed by expansion cohorts. AM0010 was self-administrated daily subcutaneously at doses of 1 to 40 μg/kg. PK, anti-drug antibodies and immune responses were monitored. Results: Since November 2013, 33 patients were enrolled in cohorts of 1, 2.5, 5, 10, 20, and 40 μg/kg. An MTD was not defined through the planned maximally administered dose. Common treatment related adverse events included injection site reaction, rash, fatigue, thrombocytopenia and anemia. Most adverse events were low grade. Eight G3 adverse events were observed including anemia (3), thrombocytopenia (1), rash (1), increased lipase (1), dyslipidemia (1), transaminitis (1). The half-life of AM0010 half-life is ~20 hrs and exposures increased linearly with increasing doses. IL-18 was dose dependently increased in the serum of all patients, IFNg, IL-4, GM-CSF and IL-7 were elevated at doses > 20 μg/kg. Activation of CD8 T cells was observed. Ongoing immune related partial responses (irPR) were observed in one RCC patient (20 μg/kg; -71% at 22 weeks) and one ocular melanoma patient (40 μg/kg; -57% at 14 weeks). Additional 9 patients had stable disease at 8 weeks (1 melanoma (duration 24+ weeks); 2 RCC (21/13); 1 CRC (40+); 3 CRC, 1 pancreatic, 1 ovarian (13)). Conclusions: AM0010 has a manageable safety profile and leads to sustained and systemic Th1 immune stimulation. The pharmacodynamics and clinical activity observed support the ongoing monotherapy expansions and future combination development in a variety of advanced malignancies. Clinical trial information: NCT02009449.
PTH-332 Pre-operative inflammatory cell ratios (NLR and PLR) predict post-operative complications and poor outcomes following surgery for rectal cancer
Authors: RJ Egan, HG Jones, R Radwan, M Davies, M Evans, J Beynon, DA Harris
Journal: Gut (2015)

<h3>Introduction</h3> Elevated post-operative inflammatory ratios have been associated with complications following colorectal surgery, and a reduction in cancer specific survival.<sup>1,2</sup>No studies have previously evaluated the value of pre-operative inflammatory ratios in predicting post-operative complications <h3>Method</h3> Consecutive rectal cancer resections in a tertiary referral centre were evaluated using prospectively maintained clinical databases, and review of clinical notes if required. Patients with post-operative septic complications (n = 54; 17=anastomotic leak; 13=flap/perineal wound complication; 21=pelvic collection; 3=wound complication/other) were compared to those with no such complications (controls; n = 161). Neutrophil-(NLR) and platelet-(PLR) lymphocyte ratios, C-reactive protein (CRP), haemoglobin and albumin were recorded pre- and post-operatively in each case, along with demographic and disease-specific data. Normally distributed data were compared with t-tests and expressed as mean [standard error of mean]. Non-parametric data were analysed using Mann-Whitney U tests (median [inter-quartile range]), and proportions compared with Fisher’s exact test. Correlations were assessed using Pearson’s correlation coefficient <h3>Results</h3> Mean age at surgery was similar between groups (66 vs. 68 [controls] years; p=NS). Mean pre-operative PLR was significantly higher in the complication group (269.2 [22.8] vs. 186.3 [6.8]; p &lt; 0.0001), as was the NLR (4.7 [0.5] vs. 3.2 [0.13]; p = 0.0002). The difference in post-op PLR (377.5 [33.2] vs. 297.6 [13.6]; p = 0.009) was significant, whilst a non-significant trend towards greater post-op NRL was seen in the complication group (15.6 [1.13] vs. 12.9 [0.72]; p = 0.065). Median post-op CRP was significantly higher in the complication group (127 [84–189] vs. 97 [56–139]; p = 0.012). There were no differences in pre- or post-operative albumin or haemoglobin between groups. Pre-op and post-op PLR have a better correlation (R=0.54) then NLR (R=0.36) in the complication groups. There were significantly more deaths (all causes) (7/54 [13%] vs. 7/161 [4.3%]; p = 0.049), disease-specific deaths (5/54 [9.3%] vs. 4/161 [2.5%]; p = 0.046) and disease-specific recurrence (11/54 [20.4%] vs. 14/161 [8.7%]; p = 0.028) in the complications group <h3>Conclusion</h3> Pre-operative elevation of inflammatory cell ratios (NLR and PLR) are novel predictors of post-operative complications following surgery for rectal cancer, and may also predict poor cancer-specific outcomes. This data suggests that tumour biology holds an important influence over complications rather than technical factors alone <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Cook EJ, Walsh SR, <i>et al</i>. Int J Surg. 2007;5(1):27–30 Proctor MJ, Morrison DS, <i>et al</i>. Eur J Cancer 2011;47(17):2633–41
Abstract 17489: Large Variability of Patient Reported Angina Frequency within Provider Assigned Canadian Cardiovascular Society Angina Class
Authors: Edward McNulty, Paul Chan, Philip Jones, Megan Coylewright, John A Spertus
Journal: Circulation (2012)

Background: Whereas the Canadian Cardiovascular Society (CCS) classification grades angina severity from providers’ perspectives, the Seattle Angina Questionnaire (SAQ) Angina Frequency scale does ...
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer
Authors: Nadine Tung, Nancy U. Lin, John Kidd, Brian A. Allen, Nanda Singh, Richard J. Wenstrup, Anne-Renee Hartman, Eric P. Winer, Judy E. Garber
Journal: Journal of Clinical Oncology (2016)

Testing for germline mutations in BRCA1/2 is standard for select patients with breast cancer to guide clinical management. Next-generation sequencing (NGS) allows testing for mutations in additional breast cancer predisposition genes. The frequency of germline mutations detected by using NGS has been reported in patients with breast cancer who were referred for BRCA1/2 testing or with triple-negative breast cancer. We assessed the frequency and predictors of mutations in 25 cancer predisposition genes, including BRCA1/2, in a sequential series of patients with breast cancer at an academic institution to examine the utility of genetic testing in this population.Patients with stages I to III breast cancer who were seen at a single cancer center between 2010 and 2012, and who agreed to participate in research DNA banking, were included (N = 488). Personal and family cancer histories were collected and germline DNA was sequenced with NGS to identify mutations.Deleterious mutations were identified in 10.7% of women, including 6.1% in BRCA1/2 (5.1% in non-Ashkenazi Jewish patients) and 4.6% in other breast/ovarian cancer predisposition genes including CHEK2 (n = 10), ATM (n = 4), BRIP1 (n = 4), and one each in PALB2, PTEN, NBN, RAD51C, RAD51D, MSH6, and PMS2. Whereas young age (P < .01), Ashkenazi Jewish ancestry (P < .01), triple-negative breast cancer (P = .01), and family history of breast/ovarian cancer (P = .01) predicted for BRCA1/2 mutations, no factors predicted for mutations in other breast cancer predisposition genes.Among sequential patients with breast cancer, 10.7% were found to have a germline mutation in a gene that predisposes women to breast or ovarian cancer, using a panel of 25 predisposition genes. Factors that predict for BRCA1/2 mutations do not predict for mutations in other breast/ovarian cancer susceptibility genes when these genes are analyzed as a single group. Additional cohorts will be helpful to define individuals at higher risk of carrying mutations in genes other than BRCA1/2.