tbuckley/cabot-search huggingface dataset:
Diet, Physical Activity, and Colorectal Cancer Among Chinese in North America and China
Authors: A. S. Whittemore, A. H. Wu-Williams, M. Lee, Z. Shu, R. P. Gallagher, J. Deng-ao, Z. Lun, W. Xianghui, C. Kun, D. Jung, C.-Z. Teh, L. Chengde, X. J. Yao, R. S. Paffenbarger, B. E. Henderson
Journal: JNCI Journal of the National Cancer Institute (1990)

In a population-based case-control study of colorectal cancer among Chinese men and women in western North America and the People's Republic of China, a common protocol was used to assess past life-style characteristics of 905 cases diagnosed during 1981–1986 and 2,488 controls. Risks for cancers of both the colon and rectum increased with increased food energy from fat, protein, carbohydrate, and all energy sources combined, for both sexes and on both continents. Yet, in multivariate analysis, colorectal cancer risk was significantly associated only with saturated fat; no relationships were seen with other dietary sources of energy. Colon cancer risk was elevated among men employed in sedentary occupations. On both continents and in both sexes, risks for cancers of both the colon and rectum increased with increasing time spent sitting. Further, the association between colorectal cancer risk and saturated fat was stronger among the sedentary than among the active. Risk among sedentary Chinese Americans of either sex increased more than fourfold from the lowest to the highest category of saturated fat intake. Among migrants to North America, risk increased with increasing years lived in North America. These observations suggest (a) that colorectal cancer risk increases with duration of exposure to a sedentary life-style and a diet rich in saturated fat; ( b ) that higher incidence among Chinese–American men relative to women is due to longer duration of these habits among men, who have lived longer in North America; and ( c ) that higher risk among Chinese Americans of both sexes relative to risk among the general population in China is due to differences in such habits. Attributable risk calculations suggest that, if these associations are causal, saturated fat intakes exceeding 10 g/day, particularly in combination with physical inactivity, could account for 60% of colorectal cancer incidence among Chinese–American men and 40% among Chinese–American women. [J Natl Cancer Inst 82:915–926, 1990]
Alkylation of Rat Liver DNA by Dimethylnitrosamine: Effect of Dosage on O 6 -Methylguanine Levels 2
Authors: Anthony E. Pegg
Journal: JNCI Journal of the National Cancer Institute (1977)

Alkylation of liver DNA was studied following administration to Sprague-Dawley rats of doses of dimethylnitrosamine (DMN) varying from 0.25 to 20 mg/kg body weight. Measurements were made of the amounts of O6-methylguanine and 7-methylguanine present in liver DNA at 4 and 24 hours after treatment with the carcinogen. There was a linear relationship between 7-methylguanine levels and dose of the nitrosamine at both of these times. In contrast, the corresponding levels of O6-methylguanine were not directly proportional to dosage but were less than expected, particularly at low doses below 2.5 mg/kg. This discrepancy was significant at 4 hours, but was even more marked at 24 hours. Only doses above 4 mg/kg at the 4-hour time point gave rise to a 0.11 ratio of alkylation of guanine at the O6-position to that at the 7-position. This ratio was that expected for the initial interaction of the alkylating species derived from DMN with DNA. Evidence was obtained to support the hypothesis that these results were due to an enzymatic removal of O6-methylguanine from liver DNA, which occurred much more efficiently at lower initial levels of alkylation. Repeated daily injections of DMN up to 11 days alos gave rise to O6-methylguanine levels that were not proportional to dosage but were relatively greater at higher dose levels. The significance of these findings in the induction of liver cancer by feeding or repeated injection of DMN was explored.
Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens
Authors: Katja Karjalainen, Diana E. Jaalouk, Carlos Bueso-Ramos, Laura Bover, Yan Sun, Akihiko Kuniyasu, Wouter H.P. Driessen, Marina Cardó-Vila, Cecilia Rietz, Amado J. Zurita, Susan O'Brien, Hagop M. Kantarjian, Jorge E. Cortes, George A. Calin, Erkki Koivunen, Wadih Arap, Renata Pasqualini
Journal: Clinical Cancer Research (2015)

The IL11 receptor (IL11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors, such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here, we evaluated the IL11R as a candidate therapeutic target in human leukemia and lymphoma.First, we show that the IL11R protein is expressed in a variety of human leukemia- and lymphoma-derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, whereas expression is absent from nonmalignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11), specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analogue with an apparent improved antileukemia cell profile.These results indicate (i) that the IL11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases.
Epidermal Growth Factor Receptor Protein Detection in Head and Neck Cancer Patients: A Many-Faceted Picture
Authors: Juliette Thariat, Marie-Christine Etienne-Grimaldi, Dominique Grall, René-Jean Bensadoun, Anne Cayre, Frédérique Penault-Llorca, Laurence Veracini, Mireille Francoual, Jean-Louis Formento, Olivier Dassonville, Dominique De Raucourt, Lionel Geoffrois, Philippe Giraud, Séverine Racadot, Sylvain Morinière, Gérard Milano, Ellen Van Obberghen-Schilling
Journal: Clinical Cancer Research (2012)

Epidermal growth factor receptor (EGFR) overexpression is associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). Despite intensive biomarker studies, a consensual method for assessing EGFR protein expression is still lacking. Here we set out to compare three EGFR detection methods in tumor specimens from HNSCC patients.Tumors were prospectively excised from a series of 79 high-risk HNSCC patients enrolled in a GORTEC-sponsored clinical trial. EGFR expression was determined using a ligand-binding assay on membranes, Western blotting (WB) on membranes and total homogenates, and immunohistochemistry (IHC) on tissue microarrays. In addition, phosphorylated EGFR (pEGFR) was measured by WB on membranes.Distributions and ranges of tumor EGFR expression were method dependent. Moderate positive correlations (Spearman coefficient r ≈ 0.50) were observed between EGFR expression measured by the binding assay and WB or IHC. pEGFR levels positively and significantly correlated with total EGFR expression measured by WB or ligand binding, but not by IHC. The highest correlation (r = 0.85) was observed between EGFR and pEGFR levels, both measured by WB on membranes. Interestingly, the fraction of phosphorylated receptor (pEGFR/EGFR both measured by WB on membranes) significantly declined with increasing tumor EGFR expression, by all assessment methods used.This study shows significant correlations between EGFR detection methods. The observed relationships between EGFR and pEGFR indicate that high-throughput pEGFR/EGFR analyses merit further investigations and consideration for routine use in patient samples.
PTU-017 Systematic Review of Endoscopic full Thickness Resection (Eftr) Techniques for Colonic Lesions: Abstract PTU-017 Table 1
Authors: A Brigic, N R A Symons, O Faiz, C Fraser, S K Clark, R H Kennedy
Journal: Gut (2013)

<h3>Introduction</h3> Introduction of the English Bowel Cancer Screening Program has resulted in increase in the number of patients diagnosed with endoscopically irresectable colonic polyps. A significant proportion of these patients undergo hemicolectomy associated with a significant risk of death, anastomotic leakage and general complications. The need for an alternative, less invasive treatment option for this patient cohort is becoming increasingly clear. <h3>Methods</h3> Systematic literature searches identified articles describing EFTR in the colon of adult pigs, published 1990–2012. Complication rates, anastomotic bursting pressures, procedure duration, specimen size and quality, and post-mortem findings were analysed. <h3>Results</h3> Four EFTR techniques using endoscopic stapling devices, T-tags, compression closure or laparoscopic assistance for defect closure before or after specimen resection were reported. 113 procedures were performed in 99 porcine models <i>(Table 1)</i>, with an overall success rate of 89% and a 4% mortality. The intraoperative complication rate was 22% (0% &gt; 67%).Post-resection closure methods (as opposed to simultaneous resection and closure) more commonly resulted in failure to close the defect (5% &gt; 55%) and a high incidence of abnormal findings at post-mortem examination (84%). Significant heterogeneity was observed in procedure duration (average 3 min to 233 min) and size of the excised specimen (average 1.7 cm to 3.6 cm). Anastomotic bursting pressures and specimen quality were poorly documented. <h3>Conclusion</h3> The technique of EFTR is in development, with experience currently limited to preclinical studies. The inability to close the resection defect reliably is the primary obstacle to further progress. This review highlights the challenges that need to be addressed in future preclinical studies. <h3>Disclosure of Interest</h3> None Declared
THE SELECTIVE LOCALIZATION OF MURINE PLEUROPNEUMONIA-LIKE ORGANISMS IN THE FEMALE GENITAL TRACT ON INTRAPERITONEAL INJECTION IN MICE
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1954)

Acute oophoritis and salpingitis were commonly observed in weanling mice injected intraperitoneally with murine pleuropneumonia-like organisms of the catarrhal type (4 strains). Organisms of the injected strain were regularly recovered in cultures from the ovary or uterus during the 3rd to the 5th week but not after the 12th week. They were also obtained from the vagina through the 5th week and with varying results, depending on the strain, from the heart's blood through the 1st week. PPLO injected into the vagina survived for some weeks but did not migrate inwardly nor were they transmitted outwardly to exposed mice. In male mice peritoneal abscesses were sometimes present but the genital organs were normal and free from PPLO. Otitis media, with positive exudate cultures, occurred more often in females and varied in rate with the strain of PPLO. PPLO of the conjunctival type failed to survive in the abdominal cavity of mice and produced no reaction in either the genital or the respiratory tract.
Chelators at the Cancer Coalface: Desferrioxamine to Triapine and Beyond
Authors: Yu Yu, Jacky Wong, David B. Lovejoy, Danuta S. Kalinowski, Des R. Richardson
Journal: Clinical Cancer Research (2006)

Abstract The importance of iron and copper in cancer biology has been well established. Iron plays a fundamental role in cellular proliferation and copper has been shown to be a significant cofactor for angiogenesis. Early observations with the chelator used for the treatment of iron overload, desferrioxamine, showed that it had promise as an anticancer agent. These results sparked great interest in the possibility of developing more effective iron chelators for cancer therapy. The recent entry into clinical trials of the iron-binding drug, Triapine, provides evidence of the potential of this antitumor strategy. Likewise, chelators originally designed to treat disorders of copper overload, such as penicillamine, trientine, and tetrathiomolybdate, have also emerged as potential anticancer drugs, as they are able to target the key angiogenic cofactor, copper. In this review, we will discuss the development of these and other chelators that show potential as anticancer agents.
Activity of the Na+/H+ exchanger is critical to reperfusion damage and preconditioning in the isolated rat heart
Authors: X Xiao
Journal: Cardiovascular Research (2000)

Objective: Removal of protons from the heart during ischemia and/or reperfusion by the cardiac Na+/H+ exchanger (NHE1) leads to Na+ entry; this causes Ca2+ influx and is thought to contribute to ischemic and/or reperfusion damage. The extent to which Na+ enters during ischemia as opposed to reperfusion is disputed and has important implications for the therapeutic use of NHE1 inhibitors as protection against ischemic damage. Preconditioning has recently been proposed to inhibit NHE1 during reperfusion. The objective of the present study was to determine the activity of NHE1 during ischemia, reperfusion and following preconditioning. Methods: The experiments were on isolated perfused rat hearts in which left ventricular developed pressure (LVDP) and intracellular sodium and pH were measured. Results: LVDP following 30 min of ischemia recovered to 14±3% of pre-ischemic level. Application of the NHE1 inhibitor HOE 642 during ischemia and reperfusion improved recovery of LVDP to 77±9%. When HOE was applied at the moment of reperfusion the recovery of LVDP was reduced to 54±6%. To overcome possible delays in the delivery of HOE, the drug was applied at 28 min of ischemia; under these conditions recovery of LVDP (71±7%) was not significantly different to HOE throughout ischemia and reperfusion. HOE had no effect on the recovery of preconditioned hearts. NHE1 activity was assessed by the [Na+]i and pHi changes in response to brief exposure to Na+ lactate (NaL). In control hearts, activity of NHE1 caused a pHi recovery of 0.034±0.007 pH units and was associated with a [Na+]i rise of 7.5±0.5 mmol/l. After 5-min reperfusion following ischemia, NaL application caused a pHi recovery (0.046±0.007) and a larger [Na+]i rise (15.8±0.6 mmol/l). After 5-min reperfusion of preconditioned hearts, NaL application caused a smaller recovery pH recovery (0.013±0.002) and a smaller [Na+]i rise (4.2±0.5 mmol/l). Conclusions: These findings suggest that NHE1 is activated in early reperfusion after ischemia but inhibited during early reperfusion in preconditioned hearts. Overall our results point to a critical period of activity of NHE1 in early reperfusion which is inhibited by preconditioning.
Does Radiotherapy Plus Androgen-Deprivation Therapy Represent the Best Treatment Approach in Elderly Patients With Locally Advanced Prostate Cancer?
Authors: Giorgio Gandaglia, Nicola Fossati, Francesco Montorsi, Alberto Briganti
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: Bekelman et al have evaluated the role of androgen-deprivation therapy (ADT) plus radiotherapy (RT) as compared with ADT alone in patients with locally advanced prostate cancer. Using the Surveillance, Epidemiology, and End Results Medicare-linked cohort, the authors demonstrated that ADT plus RT was associated with reduced risk of cancer-specific and overall mortality even in patients older than 75 years at diagnosis. The novelty of this investigation resides in the fact that this population is underrepresented in the currently available randomized clinical trials assessing the effectiveness of ADT plus RT on cancer control. Although the study by Bekelman et al is, without doubt, an important assessment, some points warrant discussion. First, ADT and RT are associated with a substantial risk of treatment-related adverse effects. This is particularly true in older and sicker patients. Therefore, a one-size-fits-all approach might not be indicated. Rather, an accurate patient selection on the basis of comorbidity status should be performed to identify patients who might benefit the most from active treatment. Unfortunately, Bekelman et al were unable to assess the beneficial impact of active treatment according to individual comorbidity profile. Second, and more important, the authors did not test the role of surgery in the treatment of elderly patients affected by locally advanced disease. Previous studies have demonstrated that radical prostatectomy is associated with a substantial reduction in the risk of cancerspecific mortality even in patients older than 65 years. Moreover, surgery allows for accurate disease staging and grading. This is key to appropriately selecting those men who might benefit from additional treatments, such as ADT and adjuvant RT. Moreover, a nonnegligible proportion of patients might eventually be treated with surgery alone. This would ultimately allow sparing of the detrimental long-term adverse effects of ADT. In conclusion, Bekelman et al are to be commended for their efforts in demonstrating a possible role of curative-intent treatments even in elderly patients with locally advanced disease. However, further investigations are needed to assess the role of surgery in this setting. In addition, validated tools conforming to individual comorbidities are required to identify which patients might benefit the most from curative-intent treatments regardless of age at surgery.
AN ANALYSIS OF THE GENETIC REQUIREMENTS FOR DELAYED CUTANEOUS HYPERSENSITIVITY REACTIONS TO TRANSPLANTATION ANTIGENS IN MICE
Authors: J. Wayne Streilein, R. E. Billingham
Journal: The Journal of Experimental Medicine (1970)

The experiments reported herein provide ample evidence that mice, like most other mammalian species, are capable of displaying readily observable and reproducible delayed cutaneous hypersensitivity reactions indicative of transplantation immunity. By employing a variety of genetically defined strains, it has been shown that a genetic requirement for the development of a positive normal lymphocyte transfer reaction in mice is a difference between host and cell donor at the H-2 locus. By contrast, the immune lymphocyte transfer reaction consistently reflected the full range of histoincompatibility, both inclusive and exclusive of the H-2. It was incidentally discovered that erythema regularly accompanied delayed cutaneous reactions in the skins of female mice, whereas no local redness accompanied their counterparts in male skins. The influence of cutaneous erythema on the scoring of delayed skin reactions is discussed.
Pharmacokinetics and safety of subcutaneous rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study
Authors: Andrew Davies, Francesco Merli, Biljana Mihaljevic, Noppadol Siritanaratkul, Phillippe Solal-Céligny, Martin Barrett, Claude Berge, Beate Bittner, Axel Boehnke, Christine McIntyre, David MacDonald
Journal: The Lancet Oncology (2014)
Validation of the 2005 St. Gallen risk categories for operated breast cancers using a database from a regional cancer center in Hong Kong
Authors: T. YAU, I. Soong, K. Chan, A. Chang, H. Sze, R. Yeung, R. Tung, S. Lau, A. Lee
Journal: Journal of Clinical Oncology (2007)

11019 Background: Breast cancer risk categories were revised by the St Gallen international expert consensus meeting in 2005. This study was to validate their application in Hong Kong. Methods: The clinical outcomes of female breast cancer patients presented from 1994 to 2002 were retrospectively analyzed. Patients with non-invasive cancers, unknown HER-2 status, unclear primary (T) or nodal (N) stage, distant metastases at presentation, induction chemotherapy or no definitive surgery were excluded. Results: 902 breast cancers were eligible for further analysis. Adjuvant radiotherapy, hormonal therapy and chemotherapy were given in 74%, 68% and 56% of patients respectively. The median follow-up was 5.4 years (range 0.3- 12.5 years). The risk categories were highly predictive of all survival outcome parameters (p&lt;0.00005; Table). In the intermediate risk category, node-negative patients with endocrine responsive/ responsiveness uncertain tumors had better 5-year distant failure-free survival (DFFS) than the rest with either 1–3 positive nodes or endocrine non-responsive tumors (95% vs 89%, p=0.005). Patients with 1–3 positive nodes and HER-2 overexpressed tumors were classified as high risk but their 5-year DFFS was similar to that in the worse subgroup of intermediate risk and significantly better than those with ≥4 positive nodes (89% vs 65%, p=0.0001). Further analysis showed that HER-2 overexpression had adverse impact on DFFS of patients with ≥4 positive nodes (hazard ratios (HR) 1.78; 95% CI, 1.12 - 2.84; p=0.015) but not on those with ≤ 3 positive nodes (HR 1.15; 95% CI, 0.67 - 1.97; p= 0.61). Conclusions: The 2005 St Gallen risk category is a useful clinical tool but we cannot confirm the adverse impact of HER-2 overexpression in our patients with ≤ 3 positive nodes. [Table: see text] No significant financial relationships to disclose.
Functional analyses of the skin surface of the areola mammae: comparison between healthy adult male and female subjects and between healthy individuals and patients with atopic dermatitis
Authors: K. Kikuchi, H. Tagami, R. Akaraphanth, S. Aiba
Journal: British Journal of Dermatology (2010)

Although the nipple and areola of the breast constitute a unique and prominent area on the chest, so far no study has been done on the functional properties of their skin surfaces.To study the stratum corneum (SC) covering the areola using noninvasive methods.Eighteen adult healthy subjects comprising nine men and nine women and 18 age- and sex-matched patients with atopic dermatitis (AD), none of whom had visible skin lesions, participated in the study. Transepidermal water loss (TEWL), skin surface hydration and skin surface lipid levels were measured on the areola and adjacent breast skin. The size of the skin surface corneocytes of these skin regions was assessed.All the healthy subjects showed significantly higher TEWL accompanied by smaller sized corneocytes on the areola than on the adjacent breast skin. Only female subjects revealed a significantly higher skin surface hydration state together with significantly increased skin surface lipid levels on the areola than on the adjacent breast skin. These sex differences were observed even in patients with AD. Comparison between healthy individuals and the patients with AD demonstrated higher TEWL, decreased skin surface hydration state and lower skin surface lipid levels associated with smaller sized corneocytes in the areola in the patients with AD, especially in male patients.In adults, the SC barrier function and SC water-binding capacity of the areola were functionally poorer than in the adjacent skin, being covered by smaller sized corneocytes and lower amounts of skin surface lipids, especially in men and in patients with AD.
Investigating an incidental finding of lymphopenia
Authors: D. Brass, P. Mckay, F. Scott
Journal: BMJ (2014)

#### Learning points

A 55 year old man had a full blood count undertaken when he presented with fatigue. There was no significant medical history of note. He was a non-smoker who took no medications. He was noted to have a lymphopenia of 0.8×109/L (reference interval 1.5-4.0×109/L). Otherwise his results were normal, with haemoglobin of 135 g/L (130-180 g/L), white cell count 4.2×109/L (4-12×109/L), and platelet count 150×109/L (140-400×109/L). He did not return for follow-up but presented to a local hospital emergency department six months later with a short history of increasing breathlessness. He was diagnosed with a severe bacterial pneumonia, from which he recovered after prolonged therapy with intravenous antibiotics. His lymphocyte count during admission ranged between 0.5 and 1.0×109/L.

### Lymphopenia and its causes

T lymphocytes make up most (60-80%) of the total peripheral …