tbuckley/cabot-search huggingface dataset:
Gene expression profiling on pre- and post-erlotinib tumors from HNSCC patients
Authors: J. Delord, F. Thomas, C. Allal, P. Delmar, P. McLoughlin, P. Rochaix
Journal: Journal of Clinical Oncology (2008)

17008 Background: Head and neck squamous cell carcinoma (HNSCC) accounts for 95% of the tumors appearing in the upper aerodigestive tract. HNSCC represents about 10% of cancer in men and is the fourth most common cancer after prostate cancer, lung cancer and colorectal cancer. EGFR (epidermal growth factor receptor) is overexpresssed in 85 % of HNSCC and the inhibition of its kinase activity constitutes an important therapeutic strategy. Our work aims to study the action of an EGFR inhibitor (erlotinib) in patients with HNSCC; and to identify predictive markers of response in order to select patients that can benefit of the treatment. Methods: A pilot study has been conducted in HNSCC patients pending surgery were treated with neoadjuvant erlotinib. Tumor tissues biopsies were collected before and after treatment. Despite the short time of treatment (i.e. median time 20 days), twelve patients out of the 42 included in the study, experienced a clinical response (measured by 25% tumor shrinkage) while 28 were stable and 2 underwent disease progression. Thirty nine tumors, before and after treatment with erlotinib, were valuable for gene expression assessment. We analyzed genomic expression of the tumors by using microarrays (Affymetrix HG U133A GeneChip®) to identify genes differentially expressed in responders versus non responders and to characterize erlotinib effect on gene expression. Results: Despite the high percentage of FDR (false discovery rate), by combining statistical criteria, we found 53 genes of high interest as they were overexpressed in non responders patients. Forty-three genes were overexpressed in responding patients. The effect of erlotinib on gene expression was also assessed. With the same criteria, fifty nine genes were downregulated and sixty-six genes were upregulated after treatment. Conclusions: Gene expression profiles will be presented and the multiple perspectives they offer will be discussed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Hoffmann-La Roche
Microscopic disease after neoadjuvant therapy in inflammatory breast cancer.
Authors: A. Lodhi, K. Mosalpuria, S. Krishnamurthy, S. Jackson, C. Hall, E. Andreopoulou, B. Singh, V. Valero, A. Lucci
Journal: Journal of Clinical Oncology (2010)

664 Background: Metachronous distant metastases are common in inflammatory breast cancer (IBC). We evaluated presence of microscopic disease (circulating tumor cells in peripheral blood > CTCs, and disseminated tumor cells in bone marrow > DTCs) after neoadjuvant therapy (NAC) as a possible cause of recurrence, and correlated it with response to therapy. Methods: All patients had blood and bone marrow taken after completing NAC. CTCs (per 7.5 ml blood) were detected using the Cell SearchTM system (Veridex) and were defined as nucleated cells lacking CD45 but expressing cytokeratins (CK) 8, 18, or 19. DTCs were assessed using anti-CK antibody cocktail following cytospin. The presence of ≥ 1 CK positive cells and ≥ 1 epithelial cells meeting morphologic criteria for malignancy was considered a positive result for CTCs and DTCs, respectively. Pathologic complete response (pCR) was defined as lack of residual invasive disease in primary tumor and regional lymph nodes after NAC. Statistical analyses used Chi square and Fisher's exact tests. Results: We prospectively evaluated 29 IBC patients undergoing surgery for stage I-III breast cancer. Median follow-up was 36 months and mean age was 51 years. Following NAC 33% (8/24) had DTCs and 22% (6/28) had CTCs. Nine of 29 patients (31%) had pCR. DTCs were found in 50% (4/8) and CTCs in 38% (3/8) of patients who had pCR following NAC compared to 25% (4/16) and 15% (3/20) in patients without pCR (P=NS). Distant metastasis occurred in 3/8 patients with pCR, and 1/3 had both CTCs and DTCs. Factors predicting pCR after NAC were absence of lymphovascular invasion (LVI) (67% vs. 6%; p < 0.01) and HER2-positive status in primary tumor (p > 0.01). No associations were found between lymph node status or primary tumor characteristics and CTCs and/or DTCs. Conclusions: A significant number of IBC patients achieved pCR after NAC, but DTCs and/or CTCs were found in up to 50% of these patients. Further study is needed to determine if CTCs and /or DTCs after NAC predict relapse. No significant financial relationships to disclose.
Anterior Mediastinal Mass
Authors: Daniel J. Gross, Gainosuke Sugiyama, Antonio Alfonso
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Free Needles for Intravenous Drug Users at Risk for AIDS: Current Developments in New York City
Authors: D C Des Jarlais, W Hopkins
Journal: New England Journal of Medicine (1985)

Human T-lymphotropic virus type III (HTLV-III) is spread among intravenous drug abusers primarily through the practice of needle sharing.  Public health authorities in New York are currently considering the lifting of some legal restrictions on the availability of sterile needles as a strategy for preventing acquired immunodeficiency syndrome (AIDS).  The Street Research Unit of the New York State Division of Substance Abuse Services which monitors street drug activity has reported 2 recent examples of free sterile needles in New York City.  The 1st involves a modified 2-for-1 sale in which needle sellers include an extra needle with the sale of a complete syringe and needle.  The latter combination typically sells for US$2 but the complete syringe with an extra needle costs only US$2.50.  The extra needle can be used if the 1st needle becomes clogged when the drug user is preparing to inject.  Because it is just before injection that a drug user is most likely to experience withdrawal or craving symptoms and to use any needle available the availability of a 2nd needle at this point may be an important way to keep the drug user from using someone elses needle.  The 2nd source of free needles is drug dealers who often include a free needle and syringe with US$25 or $50 bags of heroin.  Both these marketing tactics indicate an increased demand for clean needles by intravenous drug users in New York City.  They strengthen the argument that a meaningful reduction in the risks of AIDS is possible in this population.
Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications
Authors: Silvia Juliana Serrano-Gomez, Mazvita Maziveyi, Suresh K. Alahari
Journal: Molecular Cancer (2016)

The epithelial to mesenchymal transition (EMT) is a biological process in which a non-motile epithelial cell changes to a mesenchymal phenotype with invasive capacities. This phenomenon has been well documented in multiple biological processes including embryogenesis, fibrosis, tumor progression and metastasis. The hallmark of EMT is the loss of epithelial surface markers, most notably E-cadherin, and the acquisition of mesenchymal markers including vimentin and N-cadherin. The downregulation of E-cadherin during EMT can be mediated by its transcriptional repression through the binding of EMT transcription factors (EMT-TFs) such as SNAIL, SLUG and TWIST to E-boxes present in the E-cadherin promoter. Additionally, EMT-TFs can also cooperate with several enzymes to repress the expression of E-cadherin and regulate EMT at the epigenetic and post- translational level. In this review, we will focus on epigenetic and post- translational modifications that are important in EMT. In addition, we will provide an overview of the various therapeutic approaches currently being investigated to undermine EMT and hence, the metastatic progression of cancer as well.
The associations between spirituality (S), religiosity (R), and spiritual pain (SP) in advanced cancer patients (AdCa).
Authors: M. O. Delgado-Guay, D. Hui, H. A. Parsons, M. De la Cruz, K. B. Govan, L. Arciniega, S. Thorney, J. L. Palmer, E. Bruera
Journal: Journal of Clinical Oncology (2010)

9071 Background: S, R and SP may affect AdCa patients' symptom expression, coping strategies and quality of life. Limited research is available to define these concepts. In this prospective cross sectional study, we examined this association and various factors, including symptom expression and coping. Methods: We interviewed 100 AdCa patients in our palliative care outpatient clinic. Self-rated S, R and SP were assessed using numeric rating scales (0=lowest, 10=highest). Patients also completed various validated questionnaires assessing symptoms (ESAS), psychosocial distress (HADS), coping (Brief COPE, Brief R-COPE), and S (FACIT-Sp-Ex, SBI-15R). Results: The median age was 53 (range 21-85), 61% were female, 74% were Caucasian, 88% were Christians, and 4% were atheists. Almost all patients considered themselves spiritual (98%) and religious (98%), with a median score of 9 (interquartile range 7-10) and 9 (5-10), respectively. Patients reported S/R help them cope with their illness (99%), as a source of strength (100%), and have a positive impact on their physical (69%) and emotional (84%) symptoms. SP was reported in 40/91 (44%) patients, with a median score of 3 (1-6) among those with SP. Patients with SP expressed less S (median 8 v. 10, p=0.02), less R (7 v. 10, p=0.002), and were more likely to report that SP make their physical (6 v. 0, p<0.001) and emotional symptoms (6 v. 0, p<0.001) worse. SP was associated with worse ESAS depression (2 v. 1, p=0.014), anxiety (2 v. 1, p=0.03), drowsiness (3 v. 1, p=0.004) and anorexia (4.5 v. 3, p=0.04), worse HADS anxiety (8 v. 6, p=0.04), worse COPE religious coping (6 v. 7.5, p=0.03), worse Brief R-COPE positive religious coping (20 v. 24, p=0.046), and lower SBI-15R religious beliefs/practices (25 v. 28, p=0.019). SP was significantly associated with FACIT-Sp- Ex (p<0.005). After Bonferroni correction, only decreased religiosity was associated with SP. Conclusions: A vast majority of AdCa patients seen by palliative care considered themselves spiritual and religious. Patients reported that S, R and SP affect their symptoms and ability to cope. These findings support regular spiritual assessment in AdCa patients. No significant financial relationships to disclose.
Evolutionary Dynamics of Floral Homeotic Transcription Factor Protein–Protein Interactions
Authors: Madelaine Bartlett, Beth Thompson, Holly Brabazon, Robert Del Gizzi, Thompson Zhang, Clinton Whipple
Journal: Molecular Biology and Evolution (2016)

Protein–protein interactions (PPIs) have widely acknowledged roles in the regulation of development, but few studies have addressed the timing and mechanism of shifting PPIs over evolutionary history. The B-class MADS-box transcription factors, PISTILLATA (PI) and APETALA3 (AP3) are key regulators of floral development. PI-like (PIL) and AP3-like (AP3L) proteins from a number of plants, including Arabidopsis thaliana (Arabidopsis) and the grass Zea mays (maize), bind DNA as obligate heterodimers. However, a PIL protein from the grass relative Joinvillea can bind DNA as a homodimer. To ascertain whether Joinvillea PIL homodimerization is an anomaly or indicative of broader trends, we characterized PIL dimerization across the Poales and uncovered unexpected evolutionary lability. Both obligate B-class heterodimerization and PIL homodimerization have evolved multiple times in the order, by distinct molecular mechanisms. For example, obligate B-class heterodimerization in maize evolved very recently from PIL homodimerization. A single amino acid change, fixed during domestication, is sufficient to toggle one maize PIL protein between homodimerization and obligate heterodimerization. We detected a signature of positive selection acting on residues preferentially clustered in predicted sites of contact between MADS-box monomers and dimers, and in motifs that mediate MADS PPI specificity in Arabidopsis. Changing one positively selected residue can alter PIL dimerization activity. Furthermore, ectopic expression of a Joinvillea PIL homodimer in Arabidopsis can homeotically transform sepals into petals. Our results provide a window into the evolutionary remodeling of PPIs, and show that novel interactions have the potential to alter plant form in a context-dependent manner.
Combination of weekly chest radiotherapy and oral vinorelbine for the palliation of advanced non small cell lung cancer: A phase I/II study
Authors: P. O. Schwarzenberger, A. Fariss, L. Linaris, A. Millet, E. Zakris, R. Murillo, C. G. Theodossiou, L. Nedzi
Journal: Journal of Clinical Oncology (2005)

7284 Background: In an effort to design easier and more convenient strategies for palliating advanced NSCLC locally as well as systemically, we conducted a dose escalation trial combining oral vinorelbine (Navelbine) concurrently with a hypofractionated chest irradiation schedule. Methods: Patients with advanced NSCLC (stages IIIB and IV) were treated using a once weekly hypofractionated chest irradiation schedule (5 Gy in two fractions 6 hours apart once per week x 12 weeks). Patients took oral Navelbine on the morning of radiation. The starting dose was 20mg/m2/week and escalated in 10mg/m2 increments. Results: 35 patients were enrolled in intent to treat. 32 patients are available for toxicity and 23 for response analysis. Of these 32 patients, 11 were Stage IIIB and 21 Stage IV, 7 of which had stable brain disease. 21 patients had prior platinum based combination therapy. Mean age: 57 years (38 - 75) 13 females, 19 males, 15 Caucasians and 17 Black. Nine patients terminated protocol early. 70 mg/m2 was determined to be the MTD. Six patients were treated in the phase I portion, 29 in the phase II at 70 mg/m2. A total of 298 treatment cycles were administered (average of 9.3 cycles per patient). Toxicity was mainly hematological (1 grade IV, 6 grade III). One patient died of sepsis. Six patients required white cell factor and 12 red cell factors support. No other toxicities grade III or higher occurred, although grade II constipation and diarrhea were common. Five patients had to be dose reduced by one level and six patients by 2 levels. Response: One complete 13 partial and 9 stable diseases within the radiation field. Current mean survival is at 6.5 months (0.5 - 14 mo). Conclusion: Concurrent administration of oral Navelbine at therapeutic doses with systemic activity once weekly with hypofractionated chest radiation is safe and well tolerated. Side effects are mainly hematological. The recommended dose is 60 mg/m2. Compared to historic data, the response and survival data suggest this treatment schedule to have efficacy. It is a simpler, more convenient and more cost effective therapy for advanced NSCLC requiring local palliation and can provide systemic palliation at the same time. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Sexually dimorphic associations between prenatal triclosan exposure and anthropometric measures including head circumference and anogenital distance
Authors: Tina Harmer Lassen, Hanne Frederiksen, Shanna H Swan, H.B. Kyhl, Katharina Maria Main, Anna-Maria Andersson, D.V. Lind, S. Husby, Christine Wohlfahrt-Veje, Niels Erik Skakkebæk, Tina Kold Jensen
Journal: Environmental Health Perspectives (2016)
PTU-326 A positive faecal calprotectin does not predict bile acid diarrhoea
Authors: RN Appleby, TAB Dinh, JJR F. Walters
Journal: Gut (2015)

<h3>Introduction</h3> Bile acid diarrhoea (BAD) is a common disorder which in the primary, idiopathic form may affect up to 1% of the population. <sup>75</sup>Selenium Homocholic Acid Taurate (SeHCAT) 7 day retention is used in diagnosis, predicting faecal bile acid loss but is not available to primary care practitioners. The condition is chronic, causes significant morbidity and is easily treatable with bile acid sequestrants. Calprotectin is released into the intestinal lumen during neutrophil activation and apoptosis. A Faecal Calprotectin (FC) of &gt;50 µg/g in the primary care setting has been reported to have a sensitivity and specificity of 82% and 77% respectively for organic GI disease.<sup>1</sup>In 2013 NICE recommended its use in primary care as a decision aid.<sup>2</sup>Since primary BAD does not have an inflammatory pathogenesis, we hypothesised that the faecal calprotectin test was not sensitive for bile acid diarrhoea. <h3>Method</h3> Faecal calprotectin was measured in patients attending for SeHCAT testing at Imperial Healthcare NHS trust between March 2014 and July 2014. Patients with known bile acid diarrhoea, or inflammatory bowel disease were also recruited from the gastroenterology clinic during the same period. All patients had undergone lower GI endoscopy previously. Faecal samples were analysed in the Imperial Healthcare Biochemistry Laboratory using a commercially available ELISA kit (EliA, Phadia AB, Uppsala, Sweden). <h3>Results</h3> 55 patients were recruited. Of these 32 (58%) were female, the mean age was 53 (range 23–88) and 41 (75%) had a SeHCAT scan, of which 25 (61%) were positive (&lt;15% 7d retention). Overall 23 (42%) had a positive FC (&gt;50 µg/g); 21 (38%) were known, or subsequently found to have traditional organic GI disease (14 Crohn’s, 3 ulcerative colitis, 1 radiation colitis, 3 hepatobiliary). 9 (22%) patients with a positive SeHCAT had a positive FC, all patients (n = 5, 12%) with IBD and a positive SeHCAT had a positive FC. If primary bile acid diarrhoea was excluded in the definition of organic disease, FC had a negative predictive value of 88% (95% CI: 71–96%) and a sensitivity and specificity of 83% (95% CI: 61–95%) and 88% (95% CI: 71–96%) respectively. However, if primary bile acid diarrhoea was included in the definition of organic disease, then FC has a negative predictive value of 43% (95% CI: 26–62%) and a sensitivity and specificity of 54% (35% CI: 37–70%) and 88% (95% CI: 62–98%) respectively. <h3>Conclusion</h3> By including primary bile acid diarrhoea in the definition of organic disease the sensitivity of FC falls to 54%, which is unacceptable for a screening test. Patients with undiagnosed BAD are likely to be denied referral to secondary care for diagnosis and subsequent treatment due to the current guidance. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Polychronis P, <i>et al</i>. Scand J Gastroenterol. 2013;48:1048–1054 NICE diagnostics guidance 11, Issued Oct 2013
Surprises From Genetic Analyses of Lipid Risk Factors for Atherosclerosis
Authors: Kiran Musunuru, Sekar Kathiresan
Journal: Circulation Research (2016)

Observational epidemiological studies have associated plasma lipid concentrations with risk for coronary heart disease (CHD), but these studies cannot distinguish cause from mere correlation. Human genetic studies, when considered with the results of randomized controlled trials of medications, can potentially shed light on whether lipid biomarkers are causal for diseases. Genetic analyses and randomized trials suggest that low-density lipoprotein is causal for CHD, whereas high-density lipoprotein is not. Surprisingly, human genetic evidence suggests that lipoprotein(a) and triglyceride-rich lipoproteins causally contribute to CHD. Gene variants leading to higher levels of plasma apolipoprotein B-containing lipoproteins [low-density lipoprotein, triglyceride-rich lipoproteins, or lipoprotein(a)] consistently increase risk for CHD. For triglyceride-rich lipoproteins, the most compelling evidence revolves around lipoprotein lipase and its endogenous facilitator (APOA5 [apolipoprotein A-V]) and inhibitory proteins (APOC3 [apolipoprotein C-III], ANGPTL4 [angiopoietin like 4]). Combined, these genetic results anticipate that, beyond low-density lipoprotein, pharmacological lowering of triglyceride-rich lipoproteins or lipoprotein(a) will reduce risk for CHD, but this remains to be proven through randomized controlled trials.
Effects of activin and cyclin overexpression on Smad 3 function in breast cancer cells
Authors: S. Ghosh, K. S. Bryce, J. S. Jeruss
Journal: Journal of Clinical Oncology (2008)

22072 Background: Activin, a growth factor in the TGFβ superfamily, triggers the activation of Smad 3, a transcription factor that contributes to G1 cell cycle arrest in breast cancer cells. Overexpression of cyclin E, another key cell cycle regulatory protein, and its low molecular weight (LMW) forms, have been associated with poor prognosis in breast cancer. Cyclin E has been shown to mediate phosphorylation of the Smad 3 linker region by cyclin dependent kinases (cdk), resulting in inhibition of Smad 3 activity. We hypothesize that overexpression of cyclin E may exert tumorigenic effects through the functional inhibition of Smad 3 in breast cancer cells. Methods: Western blotting was used to evaluate the basal protein expression of Smad 3 and phosphorylated Smad 3 (phospho-Smad 3), in vector control and a LMW cyclin E overexpressing MCF-7 breast cancer cell line. To determine the impact of cyclin E overexpression on Smad 3 function, wild-type (WT) or linker region mutated Smad 3 constructs were co-transfected with a Smad 3 reporter into the vector control and the LMW cyclin E overexpressing MCF-7 cells. The MCF-7 cells were also treated with activin or not. Smad 3 function was then evaluated by luciferase reporter assay. Results: MCF-7 cells overexpressing the LMW cyclin E expressed a higher level of phospho-Smad 3 as compared to the vector control cells, while total Smad 3 levels remained unchanged. Expression of the linker region mutated Smad 3 in control cells resulted in greater than three-fold induction in Smad 3 reporter activity compared to the WT Smad 3. This induction was further pronounced in MCF-7 cells transfected with the linker region mutated Smad 3 and treated with activin. Interestingly, expression of the linker region mutated Smad 3 in MCF- 7 cells overexpressing the LMW cyclin E resulted in an eight-fold induction of the Smad 3 reporter, as compared to the WT Smad 3. Conclusions: This study indicates that overexpression of a LMW form of cyclin E may circumvent the growth inhibitory effects of activin/Smad 3 signal transduction through the blockade of Smad 3 function. The overexpression of phospho-Smad 3, found in the LMW cyclin E cells, may be a compensatory mechanism by activin/Smad 3 signaling to surmount the tumorigenic effects of LMW cyclin E in these cells. No significant financial relationships to disclose.