tbuckley/cabot-search huggingface dataset:
Characterization of the Intragenomic Spread of the Human Endogenous Retrovirus Family HERV-W
Authors: Javier Costas
Journal: Molecular Biology and Evolution (2002)

This study examines the intragenomic spread of the human endogenous retrovirus family HERV-W from insertions present within the draft sequence of the human genome. Identification of shared diagnostic differences and phylogenetic analyses revealed the existence of three main subfamilies. The average divergence between sequences for each of the subfamilies suggests that most of the HERV-W elements were inserted within the genome during a short period of evolutionary time. Each one of the subfamilies consists of two types of insertions, the expected proviral sequences and other sequences resembling the structure of processed retrogenes. These HERV-W retrosequences extend from the R region of the 5′ long-terminal repeat (LTR) to the R region of the 3′ LTR (as viral genomic RNAs), end in poly(A) 3′ tails, and are flanked by direct repeats longer than the proviral integrations. Furthermore, several of the HERV-W retrosequences are 5′-truncated at different sites. I suggest the involvement of the L1 machinery in these integrations and discuss the characteristic features of the evolutionary history of HERV-W, with emphasis on the putative impact of HERV-W retrosequence integrations on the mammalian genome.
Disruption of the Y-Box Binding Protein-1 Results in Suppression of the Epidermal Growth Factor Receptor and HER-2
Authors: Joyce Wu, Cathy Lee, Daniel Yokom, Helen Jiang, Maggie C.U. Cheang, Erika Yorida, Dmitry Turbin, Isabelle M. Berquin, Peter R. Mertens, Thomas Iftner, C. Blake Gilks, Sandra E. Dunn
Journal: Cancer Research (2006)

The overexpression of the epidermal growth factor receptor (EGFR) and HER-2 underpin the growth of aggressive breast cancer; still, it is unclear what governs the regulation of these receptors. Our laboratories recently determined that the Y-box binding protein-1 (YB-1), an oncogenic transcription/translation factor, induced breast tumor cell growth in monolayer and in soft agar. Importantly, mutating YB-1 at Ser(102), which resides in the DNA-binding domain, prevented growth induction. We reasoned that the underlying cause for growth attenuation by YB-1(Ser(102)) is through the regulation of EGFR and/or HER-2. The initial link between YB-1 and these receptors was sought by screening primary tumor tissue microarrays. We determined that YB-1 (n = 389 cases) was positively associated with EGFR (P < 0.001, r = 0.213), HER-2 (P = 0.008, r = 0.157), and Ki67 (P < 0.0002, r = 0.219). It was inversely linked to the estrogen receptor (P < 0.001, r = -0.291). Overexpression of YB-1 in a breast cancer cell line increased HER-2 and EGFR. Alternatively, mutation of YB-1 at Ser(102) > Ala(102) prevented the induction of these receptors and rendered the cells less responsive to EGF. The mutant YB-1 protein was also unable to optimally bind to the EGFR and HER-2 promoters based on chromatin immunoprecipitation. Furthermore, knocking down YB-1 with small interfering RNA suppressed the expression of EGFR and HER-2. This was coupled with a decrease in tumor cell growth. In conclusion, YB-1(Ser(102)) is a point of molecular vulnerability for maintaining the expression of EGFR and HER-2. Targeting YB-1 or more specifically YB-1(Ser(102)) are novel approaches to inhibiting the expression of these receptors to ultimately suppress tumor cell growth.
FAP: another indication to treat H pylori
Authors: B Leggett
Journal: Gut (2002)

Does infection of familial adenomatous polyposis (FAP) patients with Helicobacter pylori lead to chronic atrophic gastritis and an increased risk of gastric adenoma?

The report in this issue of Gut on the impact of Helicobacter pylori infection and mucosal atrophy on gastric lesions in patients with familial adenomatous polyposis (FAP)1 highlights the complex interplay between genetic and environmental factors in the genesis of malignancy and has therapeutic implications for the management of these patients [see page485]. A similar interplay has been observed in hereditary non-polyposis colorectal cancer where gastric cancer was quite common in earlier generations but has become less common recently, a change paralleling that seen in the general Western population.2

In Western patients with FAP the incidence of gastric adenoma is of the order of 2–6%. The incidence of gastric cancer is little if at all elevated above the general population3 and the major concern with these patients is the high risk of duodenal and periampullary cancer. However, in Japan the risk of gastric cancer in these patients is significantly elevated and a high incidence of gastric adenomas has been recognised for some time.4 The incidence of 39% reported in the present study is slightly less than the 50% reported by Iida and colleagues.4

The spectrum of APC gene …
Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma
Authors: David H. Henry, Luis Costa, Francois Goldwasser, Vera Hirsh, Vania Hungria, Jana Prausova, Giorgio Vittorio Scagliotti, Harm Sleeboom, Andrew Spencer, Saroj Vadhan-Raj, Roger von Moos, Wolfgang Willenbacher, Penella J. Woll, Jianming Wang, Qi Jiang, Susie Jun, Roger Dansey, Howard Yeh
Journal: Journal of Clinical Oncology (2011)

This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma.Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression).Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading.Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.
Age at First Pregnancy and Risk of Colorectal Cancer: A Case-Control Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G R Howe, K J Craib, A B Miller
Journal: JNCI Journal of the National Cancer Institute (1985)

Results from a case-control study of colorectal cancer conducted in Toronto and Calgary, Canada, are reported with respect to pregnancy-related variables. A total of 158 female "ever-married" colon cancer cases, 71 rectum cancer cases, 242 neighborhood controls, and 257 hospital controls were interviewed to obtain a complete pregnancy history. The results indicate a strong protective effect of early age at first pregnancy for both colon and rectum cancers, with little or no effect noted for the total number of pregnancies. There is a suggestion that age at first pregnancy may have a greater effect on right colon cancer than on left colon cancer. In addition, there also is a suggestion that non-live-birth outcomes may be a risk factor for both colon and rectum cancer. The similarity of these results to those of other studies on large bowel cancer and on breast cancer support the hypothesis that carcinogenesis in the large bowel may be at least partly mediated by female sex hormones.
1419 A RANDOMIZED TRIAL COMPARING RIBAVIRIN DOSE REDUCTION VERSUS ERYTHROPOIETIN FOR ANEMIA MANAGEMENT IN PREVIOUSLY UNTREATED PATIENTS WITH CHRONIC HEPATITIS C RECEIVING BOCEPREVIR PLUS PEGINTERFERON/RIBAVIRIN
Authors: F.F. Poordad, E.J. Lawitz, K.R. Reddy, N.H. Afdhal, C. Hezode, S. Zeuzem, S.S. Lee, J.L. Calleja, R.S. Brown, A. Craxi, H. Wedemeyer, W. Deng, K. Koury, N. Boparai, L.D. Pedicone, M. Burroughs, J. Wahl, C.A. Brass, J.K. Albrecht, M.S. Sulkowski
Journal: Journal of Hepatology (2012)
Age-related patterns of care: evidence against ageism in the treatment of early-stage breast cancer.
Authors: E Guadagnoli, C Shapiro, J H Gurwitz, R A Silliman, J C Weeks, C Borbas, S B Soumerai
Journal: Journal of Clinical Oncology (1997)

PURPOSE To assess whether the use of adjuvant systemic therapy in postmenopausal women with early-stage breast cancer is influenced by patient age. METHODS A retrospective cohort study based on data collected from medical records and from patients and their surgeons was performed among 746 postmenopausal patients diagnosed with early-stage breast cancer at 30 hospitals located throughout Minnesota. The adjusted odds of receiving hormonal therapy, chemotherapy, and both hormonal therapy and chemotherapy as a function of age was determined. RESULTS Among women with negative lymph nodes, 62% received some form of adjuvant drug therapy. For these women, the likelihood of receiving hormonal therapy or both hormonal therapy and chemotherapy did not vary with patient age and the likelihood of receiving chemotherapy declined with age. Among women with positive lymph nodes, 92% received some form of adjuvant therapy. For these women, the likelihood of receiving hormonal therapy increased with age and the likelihood of receiving chemotherapy declined with age, as did the likelihood of receiving both hormonal therapy and chemotherapy. CONCLUSION The observed associations between age and the use of adjuvant systemic therapy appear to reflect, in general, available information about treatment efficacy and do not suggest underuse among elderly women with early-stage breast cancer. The use of adjuvant therapy depends on clinical factors that predict the increased risk of metastases or the increased likelihood of response to treatment, rather than other sociodemographic factors. Our results also suggest that younger postmenopausal women with positive lymph nodes compared with older women may be undertreated with respect to tamoxifen because of the substitution of chemotherapy for hormonal therapy.
Judges grill Big Tobacco's challenge to Australia's law on plain tobacco packaging
Authors: B. Burton
Journal: BMJ (2012)

Australian tobacco control groups are hopeful that a landmark legal challenge by five tobacco companies in the High Court of Australia will fail to overturn federal legislation mandating plain packaging of tobacco products. 

After the three day hearing the chief executive of Action on Smoking and Health, Anne Jones, said that the case seemed to have “gone very well.”

She added, “The turning point seemed to be that the industry can’t get over the hurdle that this is a product that kills people.” 

Five tobacco companies—British American Tobacco, Philip Morris, Van Nelle Tabak Nederland, Imperial Tobacco Australia, and Japan Tobacco International (JTI)—have challenged the validity of the Tobacco …
JAK V617F missense mutation is absent in pancreatic cancer
Authors: H M Kocher, L Mears, N C Lea, K Raj, G J Mufti
Journal: Gut (2007)

Aberrant constitutive activation of STAT3 (signal transducer and activator of transcription) leads to cellular transformation and aids tumorigenesis in pancreatic cancer and its inhibition can lead to growth arrest.1–4 The exact mechanism of this constitutive activation has not been elucidated, although downstream mediators may include ERK and p21 signalling.1–4 Blocking JAK2 (Janus Kinase), a known upstream activator of STAT3, by AG490, a tryphostin inhibitor, reduced phosphorylation of STAT3 and produced comparable in vitro effects, suggesting a role for JAK2 in pancreatic carcinogenesis.3

JAK2 V617F missense mutation has recently been shown by several independent groups to play an important role in myeloproliferative disorders5 as well as prothrombotic states such as Budd-Chiari syndrome …
Head and neck injury risks in heavy metal: head bangers stuck between rock and a hard bass
Authors: D. Patton, A. McIntosh
Journal: BMJ (2008)

To investigate the risks of mild traumatic brain injury and neck injury associated with head banging, a popular dance form accompanying heavy metal music.Observational studies, focus group, and biomechanical analysis.Head bangers.Head Injury Criterion and Neck Injury Criterion were derived for head banging styles and both popular heavy metal songs and easy listening music controls.An average head banging song has a tempo of about 146 beats per minute, which is predicted to cause mild head injury when the range of motion is greater than 75 degrees . At higher tempos and greater ranges of motion there is a risk of neck injury.To minimise the risk of head and neck injury, head bangers should decrease their range of head and neck motion, head bang to slower tempo songs by replacing heavy metal with adult oriented rock, only head bang to every second beat, or use personal protective equipment.
Sympathetic influences on electrical and mechanical alternans in the canine heart
Authors: D. E. Euler, H. Guo, B. Olshansky
Journal: Cardiovascular Research (1996)

The aim was to investigate the influence of the sympathetic nervous system on the induction of mechanical and electrical alternans in the intact canine heart.Experiments were performed on 8 open-chest dogs anesthetized with sodium pentobarbital. A micromanometer-tipped catheter was used to measure left ventricular pressure, dp/dt and the time constant of isovolumic relaxation. Rapid atrial pacing was used to induce alternans and the left stellate ganglion was stimulated electrically to alter sympathetic tone. The longest pacing cycle length that showed a significant alternation in peak systolic pressure was defined as the alternans threshold. Electrical alternans was detected by comparing the ST-T area in the surface ECG (lead II) on alternate beats.The alternans threshold was 305(s.e.m. 10.4) ms under control conditions and decreased to 271(12.1), 225(33.4), and 177(6.2)ms, as the frequency of left stellate stimulation was increased to 1, 2, and 5 Hz, respectively (P < 0.001). Tau and peak -dp/dt began to alternate at the same pacing cycle length as peak +dp/dt and peak systolic pressure. Electrical alternans was only observed during mechanical alternans and the ST-T area of the strong beat was 243(143)% greater than the ST-T area of the weak beat (P < 0.001). Timolol (1 mg.kg-1) blocked the effect of left stellate stimulation (1 and 2 Hz) on mechanical and electrical alternans.Left sympathetic activation causes a frequency-dependent reduction in the threshold cycle length for global mechanical and electrical alternans. Alternation in relaxation occurs at the same pacing cycle length as does alternation in contraction. Repolarization alternans in the surface ECG appears to reflect underlying mechanical events.
Thyroid Supplements and Breast Cancer
Authors: Broda O. Barnes
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Drs Kapdi and Wolfe are competent radiologists, but they missed one of the fundamentals of scientific research.<i>They failed to use suitable controls</i>. In their opening paragraph, they state that "a definite relationship between breast cancer and hypothyroidism has been established." This is certainly true, and the most convincing evidence for it are some personal, unpublished observations on the routine autopsies performed in Graz, Austria. Graz is a goiter area; the entire population suffers from a relative thyroid deficiency. Thyroid replacement is rarely employed there. Yet the incidence of breast cancer is as high as ten times that seen in the United States. If thyroid deficiency can predispose to breast cancer, the influence of thyroid therapy in the etiology of the cancer could only be measured by comparing the incidence in a group of untreated hypothyroid patients with that in a group receiving thyroid replacement. Comparing the
Methodology for Comparative Effectiveness Research: Potential and Limitations
Authors: Edward L. Korn, Boris Freidlin
Journal: Journal of Clinical Oncology (2012)

There is an increasing need for reliable information on the relative value of medical interventions to assist decision making on both the individual and public health levels; addressing this need is the goal of comparative effectiveness research (CER). In reading the four articles describing CER methodology in this special series about CER, one may note that the methods described (and the arguments for and against certain ones) have been used for decades by statisticians, epidemiologists, and clinicians.
Flagellin administration protects gut mucosal tissue from irradiation-induced apoptosis via MKP-7 activity
Authors: R. M. Jones, V. M. Sloane, H. Wu, L. Luo, A. Kumar, M. V. Kumar, A. T. Gewirtz, A. S. Neish
Journal: Gut (2011)

<h3>Background and aims</h3> Radiotherapy for neoplastic disease is associated with significant adverse enteric effects associated with excessive cell death. Ionising radiation induces cell death by a mechanism that is dependent on JNK (c-jun N-terminal kinase) pathway signalling. Additionally, it is known that cells exposed to extracellular bacterial products such as flagellin, pleiotropically activate a number of innate immune pathways, including that of JNK. The JNK pathway controls its own activity by inducing the transcription of mitogen-activated protein kinase phosphatase-7 (MKP-7) which directly targets phosphorylated JNK, thus functioning as a negative feedback loop. Previously, it has been shown that flagellin limits ionising radiation-induced mortality in mice, but the cellular mechanism of protection remained unknown. <h3>Methods</h3> Wild-type C57BL/6 or <i>tlr5</i><sup>−/−</sup> C57BL/6 were injected with flagellin 2 h before exposure to irradiation, and their intestines were examined for apoptosis. Candidate proteins mediating cytoprotection from irradiation were identified by expression profiling. One of these candidates, MKP-7, was cloned and packaged into adenovirus particles, used to infect cultured cells, and examined for the extent to which its activity reduced cellular apoptosis by flow cytometry or immunoblot analysis. <h3>Results</h3> Flagellin pretreatment protected mice from radiation-induced intestinal mucosal injury and apoptosis via a Toll-like receptor 5 (TLR5)-dependent mechanism. Expression profiling of flagellin-treated mice showed upregulation of MKP-7, an inducible repressor of the JNK pathway. MKP-7 expression reached a maximum at 2 h after flagellin treatment, coinciding with suppression of phosphorylated JNK and JNK pathway inhibition. Furthermore, constitutive MKP-7 expression protected cultured cells from radiation-induced apoptosis. <h3>Conclusions</h3> Flagellin is a promising adjuvant for suppressing ionising radiation-induced injury. MKP-7 activity exhibits cytoprotective effects, and is thus a candidate cellular molecule for limiting the damaging effect of radiotherapy on the gastreointestinal system.
CXCR4–SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion
Authors: Jolanta Libura, Justyna Drukala, Marcin Majka, Oana Tomescu, Jean Marc Navenot, Magda Kucia, Leah Marquez, Stephen C. Peiper, Frederic G. Barr, Anna Janowska-Wieczorek, Mariusz Z. Ratajczak
Journal: Blood (2002)
Tumour thickness in malignant melanoma: does rapid referral help?
Authors: G.M. Fairris
Journal: British Journal of Dermatology (1985)

The prognosis of patients with melanoma can be improved by early diagnosis and excision. In 1981 a ‘Pigmented Lesion Clinic’ was started in Southampton to ensure that all patients who went to their general practitioner with a possible melanoma were seen in the dermatology department within 1 week. Before the clinic started an evening lecture was given to local general practitioners and all were sent a booklet containing colour photographs of the common pigmented skin lesions. During the following 4 years 92 of the 1530 patients seen in this clinic had a malignant melanoma. Sixty‐three per cent of the patients with malignant melanoma had skin type 1 or II and 62% blue or green eyes. Nineteen per cent had lived in Asia, Africa or Australia for more than I year. There was no correlation between the length of history as given by the patient and tumour thickness. Nor were bleeding or itching, present in 47% and 35% of patients respectively, factors which speeded up the patients presentation to their general practitioners. The mean thickness of the melanomas from patients attending the ‘Pigmented Lesion Clinic’ was not significantly different to that of the 42 patients with malignant melanomas referred to other specialists in Southampton not offering a rapid referral service—2.7 mm (± 2.3 mm S.D.) and 2.3 mm (± 2.9 mm S.D.) respectively. The results suggest that education of general practitioners without education of the general public did not improve the prognosis of patients with malignant melanoma in spite of easy access to hospital.
Concurrent granulomatous Pneumocystis carinii and Mycobacterium xenopi pneumonia: an unusual manifestation of HIV immune reconstitution disease
Authors: F Chen
Journal: Thorax (2004)

This report of concurrent granulomatous <i>Pneumocystis carinii</i> pneumonia (GPCP) and <i>Mycobacterium xenopi</i> pneumonia (MXIP) in a patient with advanced HIV disease 3–5 weeks after commencing antiretroviral therapy (ART) fits the syndrome of HIV immune reconstitution/restoration disease (IRD). It may also be a unique window into the immunology of granulomatous inflammation.