tbuckley/cabot-search huggingface dataset:
Linking altered cell motility and proteolytic activity to tumor invasion—An active role of CD97 in tumor progression
Authors: G. Aust, M. Loeffler, I. Hanisch, M. Wobus, E. Wandel, J. Galle
Journal: Journal of Clinical Oncology (2006)

10103 Background: Tumor cells at the invasion front of several carcinomas differ in their molecule pattern from cells in central tumor regions. As recently shown by us, this includes the cell surface receptor CD97 (Am J Pathol 2002,161:1657–67). Here, we link related differences in cell biological and biomechanical properties to the characteristics of tumor invasion. We combine in vitro and in vivo experiments with computer simulations of tumor progression and analyze the particular role of CD97 in this process. Methods: We compared the cDNA pattern of clones with adjustable expression of normal or C- terminal truncated CD97 using microarrays and confirmed the results at the protein level. Clonal cell motility was analyzed by time-lapse video microscopy. The scid mouse model was used to monitor tumor growth in vivo. Additionally, we introduce a novel class of individual cell-based computer models of tumor invasion into stroma. The approach enables us to analyze the impact of different cellular alterations on the organization and dynamics of the tumor invasion front and we can study several assumptions about the origin of these alterations. Results: CD97 overexpression stimulates single cell motility and increases proteolytic activity and IL-8 secretion in vitro and promotes growth of tumors in scid mice. In contrast, tumor cells overexpressing truncated CD97 show lower proteolytic activity, impaired in vitro motility and in vivo tumor growth. By computer simulation studies we demonstrate that the observed effects induced by CD97 can strongly increase the invasion capacity of tumors. Furthermore, they can cause a specific morphology of the invasion front which is known to correlate with poor prognosis. Thus, as a consequence of our computer simulations and findings in vitro and in vivo, we suggest that CD97 plays an active role in the propagation of de-differentiated carcinomas. Conclusions: Our combined experimental and theoretical computer analysis provides a novel insight in how variations of individual cell properties can be linked to different patterns of tumor cell invasion. Our results suggest that proteolytic activity at the tumor front in conjunction with elevated and directed cell motility are key steps to aggressive tumor invasion. No significant financial relationships to disclose.
The Role of Anti–U1 RNP Positivity in Predicting Survival in Patients With Connective Tissue Disease–Associated Pulmonary Arterial Hypertension: Angel or Demon? Comment on the Article by Sobanski et al
Authors: Junyan Qian, Mengtao Li, Jiuliang Zhao, Qian Wang, Zhuang Tian, Xiaofeng Zeng
Journal: Arthritis & Rheumatology (2016)
Mastering mindfulness for survival in medicine
Authors: Lisa C Kirby
Journal: Journal of the Royal Society of Medicine (2016)

We all lead busy, frantic lives. We often get so caught up in our own thoughts that we don’t see what is happening around us. This tunnel vision is self-perpetuating, and we easily become disconnected from our surroundings and enter autopilot mode. This can be useful for getting things done efficiently. However, if your mind is constantly like a busy motorway that never slows down, the more likely you are to become exhausted, suffer the effects of stress and burn out. Mindfulness can be helpful for finding a place of calm among the chaos, especially in high-stress careers like medicine.
Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis
Authors: Yael Gernez, Jeffrey Waters, Bojana Mirković, Gillian M. Lavelle, Colleen E. Dunn, Zoe A. Davies, Cassie Everson, Rabindra Tirouvanziam, Elana Silver, Sylvan Wallenstein, Sanjay H. Chotirmall, Noel G. McElvaney, Leonore A. Herzenberg, Richard B. Moss
Journal: European Respiratory Journal (2015)

The diagnosis of cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA) is clinically challenging, due to the absence of an objective biological test. Since blood basophils play a major role in allergic responses, we hypothesised that changes in their surface activation pattern discriminate between CF patients with and without ABPA.We conducted a prospective longitudinal study (Stanford cohort) comparing basophil activation test CD203c levels by flow cytometry before and after activation with Aspergillus fumigatus allergen extract or recombinant Asp f1 in 20 CF patients with ABPA (CF-ABPA) and in two comparison groups: CF patients with A. fumigatus colonisation (AC) but without ABPA (CF-AC; n=13) and CF patients without either AC or ABPA (CF; n=12). Patients were tested every 6 months and when ill with pulmonary exacerbation. We also conducted cross-sectional validation in a separate patient set (Dublin cohort).Basophil CD203c surface expression reliably discriminated CF-ABPA from CF-AC and CF over time. Ex vivo stimulation with A. fumigatus extract or recombinant Asp f1 produced similar results within the Stanford (p<0.0001) and the Dublin cohorts. CF-ABPA patients were likelier to have elevated specific IgE to A. fumigatus and were less frequently co-infected with Staphylococcus aureus.Basophil CD203c upregulation is a suitable diagnostic and stable monitoring biomarker of ABPA in CF.
Collagen-Production Inhibitors Evaluated as Antitumor Agents&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W D Klohs, R W Steinkampf, M S Wicha, A E Mertus, J B Tunac, W R Leopold
Journal: JNCI Journal of the National Cancer Institute (1985)

Proline analogues such as cis-4-hydroxy-L-proline (CHP) and L-azetidine-2-carboxylic acid (A2C) were tested for their antitumor activity in tissue culture and in vivo. In culture, CHP specifically inhibited those tumor cells that synthesized basement-membrane collagen. CHP appeared to selectively inhibit collagen biosynthesis with only a slight effect on protein synthesis. Culturing cells on type IV collagen matrix did not alter the antiproliferative effect of CHP. The inhibition of 450.1 mouse mammary tumor cells was fully reversible when cultures were incubated for 6 or 12 hours with 25 micrograms CHP/ml but was irreversible after 24 hours of exposure. Of the proline analogues tested against 450.1 tumor cells, A2C and CHP were the most potent inhibitors of cell growth. These two compounds were therefore tested in vivo using 3 transplantable tumors, all of which synthesized basement-membrane collagen. CHP and A2C were given twice daily to mice for 7 to 10 days at doses ranging from 50 mg/kg (body wt) to 600 mg/kg (body wt) per injection. Both CHP and A2C were completely inactive against the 450.1 mammary tumor and the EHS sarcoma. Both compounds also caused considerable liver toxicity. Against CD8F1 mammary tumors, treatment with maximum tolerated doses of CHP and A2C resulted in a slight but insignificant inhibition of tumor growth. While our studies confirmed previous findings that CHP specifically inhibited those tumor cells that synthesized basement-membrane collagen, CHP and A2C did not appear to be efficacious antitumor agents.
The impact of DNA methylation on the identification of recurrent prostate cancer
Authors: J. J. Alumkal, Z. Zhang, E. B. Humphreys, C. Bennett, L. A. Mangold, M. A. Carducci, A. W. Partin, E. Garrett-Mayer, A. M. DeMarzo, J. G. Herman
Journal: Journal of Clinical Oncology (2007)

21086 Purpose: Biochemical (PSA) recurrence of prostate cancer following radical prostatectomy remains a major problem. Better biomarkers are needed to identify high and low-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the impact of changes in DNA methylation on biochemical recurrence in men with prostate cancer. Methods: We examined the methylation status of fifteen genes using MSP (Methylation Specific PCR) on tissue samples from 151 patients with clinically localized prostate cancer for whom at least five years of follow-up after prostatectomy was available. Results: In a multivariable logistic regression analysis, extra capsular penetration, high Gleason score, and involvement of the lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of recurrence. In addition, samples with methylation of 2 specific genes involved in cell-cell adhesion and apoptosis were associated with biochemical recurrence with an odds ratio of 5.64 (95% CI=1.47–21.7, p=0.012) compared to samples without methylation of both of these genes. The methylation status of these 2 genes had a higher sensitivity (72.3%; 95% CI=57–84.4%) for detecting recurrences than all the clinico-pathological variables (p&lt;0.02) except extra-capsular penetration (p=0.346). The methylation status of these 2 genes had a similar negative predictive value (79.0%; 95% CI=66.8–88.3%) as the individual clinico-pathological variables examined. Conclusion: DNA Methylation of specific genes is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even one considers the prognostic clinico-pathologic variables used in the clinic today. Our findings should be validated on another larger group of patients with prostate cancer who have undergone radical prosatetectomies. No significant financial relationships to disclose.
Clinical significance of hypoxia-inducible factor-1 alpha gene polymorphisms in patients with colorectal cancer.
Authors: Y. Kim, B. Kang, J. Kim, Y. Chae, S. Sohn, S. Kim, S. Lee, J. Jeong, J. Baek
Journal: Journal of Clinical Oncology (2010)

e14045 Background: Hypoxia-inducible factor-1 (HIF-1) is the key regulator of cellular response to hypoxia and presumably plays a central role in the control of tumor growth. Recently, polymorphisms or mutations increasing its activity and stability in vitro under normoxia have been identified. Accordingly, the present study analyzed polymorphisms of HIF-1 alpha gene and their impact on the prognosis for patients with colorectal cancer. Methods: Four hundred and forty-five consecutive patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 2 polymorphisms of HIF-1 alpha gene (HIF-1 alpha C1772T and HIF-1 alpha G1790A) determined using a real-time PCR genotyping assay. Results: The median age of the patients was 64 years (range, 21–85), and 252 (56.6%) patients had colon cancer and 193 (43.4%) patients rectal cancer. Pathologic stages after surgery were as follows: stage 0/I (n = 85, 19.1%), stage II (n = 149, 33.5%), stage III (n = 148, 33.3%), and stage IV (n = 63, 14.2%). The 2 HIF-1 alpha gene polymorphisms were successfully amplified in all cases, and the frequencies of each genotype are as follows (C1772T: CC [92.1%], CT [7.9%]; G1790A: GG [93.0%], GA [7.0%]). Univariate and multivariate survival analysis including stage, age, site of disease, and CEA level showed that these polymorphisms were not associated with progression-free or overall survival. For the clinicopathologic parameters, the age, CEA level, and TNM stage were all significant prognostic factors in a Cox model for survival. Conclusions: HIF-1 alpha gene polymorphisms investigated in this study were not found to be an independent prognostic marker for Korean patients with surgically resected colorectal cancer. However, further studies are warranted to clarify the role of HIF-1 alpha gene polymorphisms as a prognostic biomarker for colorectal cancer patients. No significant financial relationships to disclose.
Gemcitabine for previously treated AIDS-related Kaposi’s sarcoma: The Western Kenya experience
Authors: K. M. Gregory, R. M. Strother, S. Pastakia, P. Were, C. Tenge, N. Busakhala, B. Jakait, E. M. Schellhase, A. G. Rosmarin, P. J. Loehrer
Journal: Journal of Clinical Oncology (2008)

10566 Background: The Academic Model for the Prevention and Treatment of HIV (AMPATH) Oncology Program in collaboration with Moi Teaching and Referral Hospital provides treatment for patients (pts) with AIDS-related Kaposi’s sarcoma (AR-KS) and other AIDS- related malignancies in Western Kenya. The objectives of this study are to evaluate the activity of gemcitabine (GEM) in previously treated pts with AR-KS and assess the feasibility of chemotherapy administration in a developing country. Methods: A retrospective chart review was conducted for 23 consecutive pts receiving GEM from Aug 2006 to Oct 2007. All pts were on HAART and failed prior doxorubicin, bleomycin, and vincristine-based therapy. Responses were evaluated 4 wks after the last dose of GEM and at the last follow-up visit. Pts free of all lesions were considered to have a complete response (CR). A partial response (PR) was defined as a >50% reduction in lesions. Clinical benefit response (CBR) was defined as ≥50% reduction in pain intensity, ≥ 50% reduction in analgesic consumption, ≥20 point increase in KPS, and/or a weight gain of ≥7%. Results: The population consisted of 19 males (82.6%) and 4 females (17.4%); the mean age was 38 yrs (range: 20–57). Average BSA was 1.73 m2 (range: 1.5–2.1). Pts were on HAART for an average of 13.4 mos (range: 4 - 41) before starting GEM. According to the AIDS Clinical Trials Group Oncology Committee classification of AR- KS, all pts were poor-risk based on tumor extent, CD4 cell count < 200 cells/mm3, systemic illness or KPS <70%. GEM dosing was: 1 g (n=19), 1 g/m2 (n=3), or both (n=1). Pts received a mean of 7.4 doses (range: 3–15). Average time between doses was 18.6 days. Objective response was seen in 11 pts (CR-3, PR-8; CR+PR= 48%); 11 were classified with stable disease (SD) and 1 with progressive disease (PD). CBR occurred in 15 pts (65%). Mean progression-free survival was 3.8 mos. With a median follow-up of 5.1 mos, 2 pts were still receiving chemotherapy, 3 were lost to follow-up, and 18 completed chemotherapy; 5 pts progressed and one died from hepatoma. Conclusions: Despite modest dosages, GEM may have activity in previously treated AR-KS. While barriers to treatment exist in Kenya, it is feasible to successfully administer GEM on a modified schedule. Further studies are warranted to confirm activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly
Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study
Authors: Armand Abergel, Tarik Asselah, Sophie Metivier, Kathryn Kersey, Deyuan Jiang, Hongmei Mo, Phillip S Pang, Didier Samuel, Véronique Loustaud-Ratti
Journal: The Lancet Infectious Diseases (2016)
Phylogenetic analysis using insertion sequence fingerprinting in Escherichia coli.
Authors: J G Lawrence, D E Dykhuizen, R F DuBose, D L Hartl
Journal: Molecular Biology and Evolution (1989)

Chromosomal DNA from 23 closely related, pathogenic strains of Escherichia coli was digested and probed for the insertion sequences IS1, IS2, IS4, IS5, and IS30. Under the assumption that elements residing in DNA restriction fragments of the same apparent length are identical by descent, parsimony analysis of these characters yielded a unique phylogenetic tree. This analysis not only distinguished among bacterial strains that were otherwise identical in their biochemical characteristics and enzyme electrophoretic mobilities, but certain aspects of the topology of the tree were consistent across several unrelated insertion elements. The distribution of IS elements was then reexamined in light of the inferred phylogenetic relationships to investigate the biological properties of the elements, such as rates of insertion and deletion, and to discover apparent recombinational events. The analysis shows that the pattern of distribution of insertion elements in the bacterial genome is sufficiently stable for epidemiological studies. Although the rate of recombination by conjugation has been postulated to be low, at least two such events appear to have taken place.
Brief Communication: Intracolonlc Injection of BeG in the Rhesus Monkey
Authors: R. C. Bast, W. G. Doos, B. Zbar, R. P. Harmel, D. W. Dalgard, A. M. Steward
Journal: JNCI Journal of the National Cancer Institute (1974)

Intramucosal injection of living BCGInto the colon and rectum was well tolerated by rhesus monkeys (Macaca mulatta). Ulceration developed at Injection sites within 3 weeks after initial injection and healed spontaneously without sigulficant hemorrhage, perforation, or functional obstruction. All animals developed systemic tuberculin hypersensitivity. A second Intrarectal Injection of BCG produced indurated mucosal lesions within 24–48 hours and local ulceration within 1 week. Inadvertent extracolonic Injection of BCG produced localized abscesses and a single Instance of focal granulomatous peritonitis. No extracolonlc lesions were observed In properly inoculated animals and there was no evidence of systemic BCG infection at necropsy.
Battle of the sex steroids in the male skeleton: and the winner is…
Authors: Thomas J. Weber
Journal: Journal of Clinical Investigation (2016)

Male osteoporosis is a multifactorial disease, although it is often in part related to hypogonadism. While testosterone replacement therapy has been shown to improve bone mineral density, studies have also linked bone loss and higher fracture risk in men to low estrogen levels. In this issue of the JCI, Finkelstein and colleagues report the results of a clinical study in a cohort of healthy adult men aimed at further discerning the specific roles of androgen and estrogen deficiency in bone loss. The results of their study support previous findings that estrogen deficiency has a dramatic effect on bone homeostasis in men. Future studies to corroborate and expand on these findings have potential to influence the clinical management of male osteoporosis.
Panel Testing for Familial Breast Cancer: Calibrating the Tension Between Research and Clinical Care
Authors: Ella R. Thompson, Simone M. Rowley, Na Li, Simone McInerny, Lisa Devereux, Michelle W. Wong-Brown, Alison H. Trainer, Gillian Mitchell, Rodney J. Scott, Paul A. James, Ian G. Campbell
Journal: Journal of Clinical Oncology (2016)

Gene panel sequencing is revolutionizing germline risk assessment for hereditary breast cancer. Despite scant evidence supporting the role of many of these genes in breast cancer predisposition, results are often reported to families as the definitive explanation for their family history. We assessed the frequency of mutations in 18 genes included in hereditary breast cancer panels among index cases from families with breast cancer and matched population controls.Cases (n = 2,000) were predominantly breast cancer-affected women referred to specialized Familial Cancer Centers on the basis of a strong family history of breast cancer and BRCA1 and BRCA2 wild type. Controls (n = 1,997) were cancer-free women from the LifePool study. Sequencing data were filtered for known pathogenic or novel loss-of-function mutations.Excluding 19 mutations identified in BRCA1 and BRCA2 among the cases and controls, a total of 78 cases (3.9%) and 33 controls (1.6%) were found to carry potentially actionable mutations. A significant excess of mutations was only observed for PALB2 (26 cases, four controls) and TP53 (five cases, zero controls), whereas no mutations were identified in STK11. Among the remaining genes, loss-of-function mutations were rare, with similar frequency between cases and controls.The frequency of mutations in most breast cancer panel genes among individuals selected for possible hereditary breast cancer is low and, in many cases, similar or even lower than that observed among cancer-free population controls. Although multigene panels can significantly aid in cancer risk management and expedite clinical translation of new genes, they equally have the potential to provide clinical misinformation and harm at the individual level if the data are not interpreted cautiously.
Association of Human Papillomavirus (Hpv) and P16 Status with Efficacy and Safety Data in the Phase III Radiotherapy (Rt)/Cetuximab (Cet) Registration Trial for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck (Lascchn)
Authors: J.A. Bonner, P.M. Harari, J. Giralt, D. Bell, D. Raben, J. Liu, J. Schulten, K.K. Ang, D.I. Rosenthal
Journal: Annals of Oncology (2014)
The utility of the MDASI-BT in assessing symptoms in patients with brain metastases
Authors: T. S. Armstrong, T. Mendoza, I. Gning, M. L. Smith, M. R. Gilbert, J. Weinberg, C. Cleeland
Journal: Journal of Clinical Oncology (2007)

2052 Background: Symptom occurrence has been shown to predict treatment course and survival in patients with solid tumors. The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) was recently validated in patients with primary brain. This study evaluated the reliability and validity of the MDASI-BT as well as symptom severity and prevalence in patients with brain metastases. Methods: Patients diagnosed with systemic cancer with brain metastases participated in this cross-sectional study. Data collection included demographic and clinical factors, and the MDASI-BT (0–10 scale). The average for the 22 symptoms and 6 interference items scores the MDASI-BT was computed. Construct validity was assessed using confirmatory factor analysis, and known-group validity was evaluated by detecting group differences due to disease severity and performance status. For reliability, Cronbach’s alpha values were computed for each subscale. Results: A sample of 124 patients participated, of which 53.2% females. Participants were primarily white (79.8%) and married (78.2%), with a variety of solid tumor malignancies represented. Factor analysis revealed six underlying constructs including affective, cognitive, focal neurologic deficit, constitutional, gastrointestinal, and interference with life. This solution explained 68.4% of the variance, and satisfied Harman’s criteria for model fit. Known-group validity was established for the MDASI-BT using the Karnofsky performance status (KPS). Mean symptom scores were 1.2 and 2.6, and mean interference were 1.8 and 4.3, for patients with good (90–100) and poor KPS (80 and below) respectively (p&lt;0.001). These subscales were also sensitive to opioid analgesic use with group differences of 1.5 and 2.2 (p&lt;0.001). Cronbach’s alpha was 0.9 for each of the two subscales. Fatigue, sleep disturbance, drowsiness, distress, and dry mouth were the most severe symptoms. Conclusions: The MDASI-BT demonstrated validity and reliability in patients with brain metastases and can be used to identify symptom occurrence related to the tumor and therapies. No significant financial relationships to disclose.
CD Antigens 1996
Authors: T. Kishimoto, S. Goyert, H. Kikutani, D. Mason, M. Miyasaka, L. Moretta, T. Ohno, K. Okumura, S. Shaw, T.A. Springer, K. Sugamura, H. Sugawara, A.E.G.Kr. von dem Borne, H. Zola
Journal: Blood (1997)