tbuckley/cabot-search huggingface dataset:
<i>CCR</i> 20th Anniversary Commentary: Prospects and Challenges of Therapeutic Nanoparticles in Cancer
Authors: Mohammad Aminur Rahman, Dong M. Shin
Journal: Clinical Cancer Research (2015)

Abstract In their review article published in the March 1, 2008, issue of Clinical Cancer Research, Cho and colleagues presented the strong potential of nanotechnology in cancer. This commentary discusses the latest advances in nanotechnology, which provide novel approaches for cancer diagnosis, imaging, drug delivery, and personalized therapy; highlights the perspectives for therapeutic nanoparticles; and describes the advantages and challenges of their multifunctionalities. Clin Cancer Res; 21(20); 4499–501. ©2015 AACR. See related article by Cho et al., Clin Cancer Res 2008;14(5) March 1, 2008;1310–6
Acetylcholine and the Regulation of REM Sleep: Basic Mechanisms and Clinical Implications for Affective Illness and Narcolepsy
Authors: P J Shiromani, J C Gillin, S J Henriksen
Journal: The Annual Review of Pharmacology and Toxicology (1987)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Vascular Smooth Muscle Cell Senescence Promotes Atherosclerosis and Features of Plaque Vulnerability
Authors: Julie Wang, Anna K. Uryga, Johannes Reinhold, Nichola Figg, Lauren Baker, Alison Finigan, Kelly Gray, Sheetal Kumar, Murray Clarke, Martin Bennett
Journal: Circulation (2015)

Although vascular smooth muscle cell (VSMC) proliferation is implicated in atherogenesis, VSMCs in advanced plaques and cultured from plaques show evidence of VSMC senescence and DNA damage. In particular, plaque VSMCs show shortening of telomeres, which can directly induce senescence. Senescence can have multiple effects on plaque development and morphology; however, the consequences of VSMC senescence or the mechanisms underlying VSMC senescence in atherosclerosis are mostly unknown.We examined the expression of proteins that protect telomeres in VSMCs derived from human plaques and normal vessels. Plaque VSMCs showed reduced expression and telomere binding of telomeric repeat-binding factor-2 (TRF2), associated with increased DNA damage. TRF2 expression was regulated by p53-dependent degradation of the TRF2 protein. To examine the functional consequences of loss of TRF2, we expressed TRF2 or a TRF2 functional mutant (T188A) as either gain- or loss-of-function studies in vitro and in apolipoprotein E(-/-) mice. TRF2 overexpression bypassed senescence, reduced DNA damage, and accelerated DNA repair, whereas TRF2(188A) showed opposite effects. Transgenic mice expressing VSMC-specific TRF2(T188A) showed increased atherosclerosis and necrotic core formation in vivo, whereas VSMC-specific TRF2 increased the relative fibrous cap and decreased necrotic core areas. TRF2 protected against atherosclerosis independent of secretion of senescence-associated cytokines.We conclude that plaque VSMC senescence in atherosclerosis is associated with loss of TRF2. VSMC senes cence promotes both atherosclerosis and features of plaque vulnerability, identifying prevention of senescence as a potential target for intervention.
Oncogenes and Male Breast Carcinoma: c-erbB-2 and p53 Coexpression Predicts a Poor Survival
Authors: Achille Pich, Elena Margaria, Luigi Chiusa
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To investigate the prognostic value of biomarkers in male breast carcinoma (MBC). PATIENTS AND METHODS: Fifty patients (mean age, 62.2 years) with invasive ductal carcinoma were retrospectively studied. All patients received surgery; 35 had adjuvant postoperative therapy. The median follow-up was 59 months (range, 1 to 230 months). c-myc, c-erbB-2, p53, and bcl-2 proteins were immunohistochemically detected on sections from formalin-fixed, paraffin-embedded tissues using 9E11, CB11, DO7, and bcl-2 124 monoclonal antibodies (mAbs). Estrogen, progesterone, and androgen receptors were detected using specific mAbs. Cell proliferation was assessed by MIB-1 mAb. RESULTS: In univariate analysis, c-myc, c-erbB-2, and p53 protein overexpression was significantly correlated with prognosis. The median survival was 107 months for c-myc–negative and 52 months for c-myc–positive patients (P = .01), 96 months for c-erbB-2–negative and 39 months for c-erbB-2–positive patients (P = .02), and 100 months for p53-negative and 33 months for p53-positive patients (P = .0008). Tumor histologic grade (P = .01), tumor size (P = .02), patient age at diagnosis (P = .03), and MIB-1 scores (P = .0004) also had prognostic value. In multivariate analysis, only c-erbB-2 and p53 immunoreactivity retained independent prognostic significance. All nine patients who did not express c-erbB-2 and p53 proteins were alive after 58 months, whereas none of the 14 patients expressing both proteins survived at 61 months follow-up (P = .0002). CONCLUSION: Overexpression of c-myc, c-erbB-2, and p53 proteins may be regarded as an additional prognostic factor in MBC. The combination of c-erbB-2 and p53 immunoreactivity can stratify patients into different risk groups.
Ambient Melamine Exposure and Urinary Biomarkers of Early Renal Injury
Authors: Chia-Fang Wu, Chiung-Yu Peng, Chia-Chu Liu, Wen-Yi Lin, Chih-Hong Pan, Ching-Mei Cheng, Hui-Min Hsieh, Tusty-Jiuan Hsieh, Bai-Hsiun Chen, Ming-Tsang Wu
Journal: Journal of the American Society of Nephrology (2015)

Information about environmental exposure to melamine and renal injury in adults is lacking. We investigated this relationship in 44 workers at two melamine tableware manufacturing factories in Taiwan (16 manufacturers, eight grinders, ten packers, and ten administrators) and 105 nonexposed workers (controls) at one shipbuilding company who were enrolled in August-December of 2012. For melamine workers, personal and area air samples were obtained at the worksite over 1 workweek (Monday-Friday). In the same week, pre- and post-shift one-spot urine samples were collected each workday and one first-spot urine sample was collected on each weekend morning and the following Monday morning. For each control, a one-spot urine sample was collected on Friday morning. A blood sample was also obtained from each participant at this time. Melamine levels were measured in air, urine, and serum, and early renal injury biomarkers were measured in urine. Urinary melamine concentrations in manufacturers increased sharply between pre- and post-shift measurements on Monday, remained significantly elevated throughout the workweek, and decreased over the weekend; changes in urinary melamine concentrations were substantially lower for other melamine workers. Manufacturers were exposed to the highest concentrations of ambient melamine and had significantly higher urinary and serum melamine concentrations than did the controls (P<0.001). Urinary melamine levels were positively associated with urinary N-acetyl β-d-glucosaminidase (NAG) levels but not microalbumin levels, and the detectable β2-microglobulin rate increased in the manufacturers group. In conclusion, ambient melamine exposure may increase the levels of urinary biomarkers of renal tubular injury in this occupational setting.
The Metabolism of Xenobiotics by Certain Extrahepatic Organs and its Relation to Toxicity*
Authors: T E Gram, L K Okine, R A Gram
Journal: The Annual Review of Pharmacology and Toxicology (1986)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody, alone reduces the growth rate of gastric cancer cell line, MKN45, in nude mice
Authors: Angela My Hui, Lydia Kw Lung, Christine Yp Wong, Wai-Keung Leung, Enders Kw Ng, Joseph Jy Sung
Journal: Cancer Research (2006)

242  Gastric cancer is the second commonest cancer worldwide. Angiogenesis, the process of new blood vessel development, is a key-step in tumor metastasis. We aim to investigate the growth inhibitory effect of bevacizumab, a humanized anti-VEGF monoclonal antibody, on gastric cancer cell line, MKN45. This anti-angiogenic drug targets and binds to VEGF, a mediator in vessel development, and has been used in combination with chemotherapy as a first-line treatment in colon cancer. In this study, fifteen 4 to 6 weeks old female nude mice were randomized into 3 groups. MKN45 cells were injected subcutaneously. Until tumor developed, the control group was injected with 0.9 % normal saline. The low dose arm was administered at a dose of 5 mg/kg and the high dose arm was 10 mg/kg of bevacizumab once weekly. The change in tumor volume and body weight of the nude mice were inspected and recorded daily. We showed that bevacizumab significantly reduced the growth rate of MKN45 on nude mice. The average tumor net weight of the control, low dose and high dose group were 1.56 g, 0.54 g and 1.02 g respectively. The tumor weight of the low dose and high dose group were only 34.6 % and 65 % respectively of the control. The increase in tumor volume of the control, low dose and high dose group was 649 %, 179 % and 49.7 % respectively. Therefore, the use of anti-vascular drug, bevacizumab, has demonstrated the growth inhibitory effect on MKN45 growth in nude mice. Therefore, the use of bevacizumab alone in blocking VEGF ligand may become a potential therapeutic against gastric cancer.
Kawasaki Syndrome (The Mucocutaneous Lymph Node Syndrome)
Authors: M E Melish
Journal: Annual Review of Medicine (1982)

Kawasaki syndrome is a newly-recognized clinical entity characterized by multisystem involvement. It has an acute onset and triphasic clinical course. Although essentially a self-limiting disease, permanent vascular damage, especially involving the coronary arteries, may result. Pathologically, the disease is characterized by widespread vasculitis. There is a monomodal age distribution, with peak occurrence during the first two years of life and few affected over the age of 8 years. Males outnumber females 1.5:1; persons of Japanese extraction are overrepresented compared with other races, caucasians underrepresented. Community-wide epidemics have been reported from diverse locations but there is no evidence for direct person-to-person transmission. Etiology remains unknown. Therapy is supportive and should be directed at careful clinical evaluation for cardiovascular abnormalities and antiplatelet aggregation therapy.
The influence of tumor-infiltrating lymphocytes (TILs) and their prognostic value in cholangiocarcinoma.
Authors: Yaman Suleiman, Domenico Coppola, TzuHua Juan, Jae K Lee, Hatem Hussein Soliman, Mokenge Peter Malafa, Richard D. Kim
Journal: Journal of Clinical Oncology (2015)

4087 Background: Cholangiocarcinoma is a malignancy arising from the epithelial cells of the biliary tract with poor prognosis. Tumor-infiltrating lymphocytes (TILs) have a prognostic impact in various solid tumors. We aimed to investigate TIL expression and programmed cell death ligand PD-L1 and their clinical relevance in cholangiocarcinoma. Methods: Formalin-fixed paraffin-embedded tumor samples from 47 pts with resected and histologically verified cholangiocarcinoma between 1990 and 2011 were immunohistochemically (IHC) stained with anti CD8, anti CD45RO and the anti-PDL1 mouseIgG1 (clone 5H1; Thompson) antibodies on a Leica automated IHC platform. The stains were semiquantitatively analyzed using the AllRed score system (range 1 to 8). IHC score > 3 considered positive. The association between PDL1, CD45R0, OS and PFS was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses. Results: Median age was 65 (41-85) with 51% male. 24%, 45%, 24% and 7 % were stage I, II, III, and IV respectively, CD8 was positive in 11/47 (23%), PD-L1 was positive in 42/47 (89 %), CD45R0 (lymph node like structure) was positive in 18/47 (38%), 17/18 (95%) of CD45R0+ tumors were PD-L1 positive. Pts with tumors exhibiting lymph node (LN) like structures (CD45R0+) has better median OS (63 months vs 18 months, P = 0.003) and median PFS (29 months vs 14.7 months, P = 0.06) than patients lacking LN like structures (CD45R0-). 5 yrs. OS in CD45R0+ was 61% vs 26% in CD45R0- (P 0.005) whereas 5 yrs. PFS in CD45R0+ was 44% vs. 18% in in CD45R0- pts (P value 0.02). Correlating PDL1 with OS and PFS was not feasible due to high expression of PD-L1 (89 %). Conclusions: Presence of LN like structures (CD45R0+) was associated with significant better outcome reflecting the immune-mediated killing of tumor cells. This LN like structures need to be further characterized to understand how they escaped the inhibitory effect of PD-L1. The high expression of PD-L1 on cholangiocarcinoma cells represents a potential therapeutic target which may enhance the immunologic response and improve the prognosis of this dismal cancer. Future trials involving PD-L1 inhibitors are warranted.
Longitudinal assessment of airway responsiveness from 1 month to 18 years in the PIAF birth cohort
Authors: Desmond W. Cox, Dave Mullane, Guicheng C. Zhang, Steve W. Turner, Catherine M. Hayden, Jack Goldblatt, Lou I. Landau, Peter N. Le Souëf
Journal: European Respiratory Journal (2015)

The Perth Infant Asthma Follow-up (PIAF) study involves a birth cohort of unselected subjects who have undergone longitudinal assessments of airway responsiveness at 1, 6 and 12 months and 6, 11 and 18 years of age. The aim of this study was to determine the relationship between increased airway responsiveness throughout childhood and asthma in early adult life. Airway responsiveness to histamine, assessed as a dose–response slope (DRS), and a respiratory questionnaire were completed at 1, 6 and 12 months and 6, 11 and 18 years of age. 253 children were initially recruited and studied. Airway responsiveness was assessed in 203, 174, 147, 103, 176 and 137 children at the above-mentioned time points, respectively (39 participants being assessed on all test occasions). Asthma at 18 years was associated with increased airway responsiveness at 6, 12 and 18 years, but not during infancy (slope 0.24, 95% CI 0.06–0.42; p=0.01; slope 0.25, 95% CI 0.08–0.49; p=0.006; and slope 0.56, 95% CI 0.29–0.83; p&lt;0.001, respectively). Increased airway responsiveness and its association with asthma at age 18 years is established between infancy and 6 years. We propose that airway responsiveness in early life reflects the initial airway geometry and airway responsiveness later in childhood increasingly reflects immunological responses to environmental influences.
Late psychosocial sequelae in Hodgkin's disease survivors: a French population-based case-control study.
Authors: F Joly, M Henry-Amar, P Arveux, O Reman, A Tanguy, A M Peny, P Lebailly, J Macé-Lesec'h, B Vié, J Y Génot, A Busson, X Troussard, M Leporrier
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate late psychosocial sequelae in long-term survivors of Hodgkin's disease (HD) in the population of Calvados, France. PATIENTS AND METHODS Ninety-three patients issued from the Calvados General Tumor Registry, treated from 1978 to 1990, free of relapse and second malignancy since January 1991, were enrolled onto cross-sectional case-control study. One hundred eighty-six healthy controls, matched for sex, age, and residency, were selected at random from electoral rolls. Two self-administered questionnaires were mailed in the spring of 1995. RESULTS Compared with controls, HD patients reported (1) more physical (P &lt; .001), role (P &lt; .001), and cognitive (P = .015) functioning impairments, as well as dyspnea (P &lt; .001) and chronic fatigue (P = .025), while no statistical difference was found in global health status; (2) to be more often childless (P = .04), fewer divorces or separations (P = .013), fewer changes in relationships with friends (P = .012), similar proportions at work but less ambitious professional plans (P &lt; .001), and greater difficulties in borrowing from banks (P &lt; .001); (3) a slight increase in the number of visits to a general practitioner (P = .05) and greater consumption of medical resources (mainly thyroid extracts, P = .05). CONCLUSION The study demonstrated that French long-term HD survivors have good global health status and good psychologic, familial, and professional status, although difficulties in borrowing from banks remain a major limitation in daily life. Although physical, role, and cognitive functioning impairments persist that might limit their activities, HD survivors seem to have learned to cope with problems related to their disease and its treatment.
A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.
Authors: D H Johnson, L H Einhorn, R Birch, R Vollmer, C Perez, S Krauss, G Omura, F A Greco
Journal: Journal of Clinical Oncology (1987)

To assess the effect of dose escalation in the treatment of small-cell lung cancer (SCLC), 298 patients with extensive-stage disease were treated with either conventional-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1 mg/m2), (CDCAV); or high-dose cyclophosphamide (1,200 mg/m2), doxorubicin (70 mg/m2), and vincristine (1 mg/m2) (HDCAV). No dose attenuation was allowed during the initial three cycles of therapy in either treatment arm. All patients received CDCAV in cycles 4 through 6, during which time dosages were adjusted according to granulocyte and platelet nadirs. No additional chemotherapy was administered until disease progression or relapse was documented. Complete responses were more frequent with HDCAV (22% v 12%; P = .045). However, overall response rate (63% v 53%) and median survival (29.3 v 34.7 weeks) were not significantly different (P greater than .05). HDCAV was substantially more toxic than CDCAV, causing more episodes of life-threatening leukopenia (ie, granulocytes less than 500/microL; 79% v 40%; P less than .05) and infections (15% v 4%; P less than .05). Dose intensification of cyclophosphamide and doxorubicin during induction chemotherapy did not produce any survival benefit compared with conventional dosages of these agents in SCLC patients with extensive-stage disease.
Cisplatin, fluorouracil with leucovorin calcium enhancement, and synchronous accelerated radiotherapy in the management of locally advanced head and neck cancer: a phase II study.
Authors: T G Wendt, R C Hartenstein, T P Wustrow, J Lissner
Journal: Journal of Clinical Oncology (1989)

In a phase II study, patients with locally advanced squamous cell carcinoma of the head and neck were treated with simultaneous chemoradiotherapy. Treatment was divided into three courses. Chemotherapy consisted of cis-diamminedichloroplatinum (II) (cisplatin [cis-DDP]) 60 mg/m2 intravenously (IV), fluorouracil (5-FUra) 350 mg/m2 IV, and folinic acid (leucovorin calcium [FA]) 50 mg/m2 IV on day 2 as bolus, and 5-FUra 350 mg/m2 over 24 hours and FA 100 mg/m2 over 24 hours on days 2 through 5. Radiotherapy consisted of 23.4 Gy over nine days divided into 13 fractions of 1.8 Gy each delivered twice a day from day 3 through day 11. This regimen was repeated on days 22 and 44. Total radiation dose amounted to 70.2 Gy over 51 days. Between August 1984 and October 1986, 62 (modified AJCC stage III, four; IV A, eight; IV B, 50) consecutive patients were entered in the study. Three patients died during treatment due to tumor hemorrhage. Of 59 patients, 48 (81%) achieved a clinically complete response (cCR); 11 (19%) achieved a partial response (cPR). Mean follow-up of the surviving patients was 29+ (24 to 44) months. Actuarial 2-year survival probability is 52%, including three early deaths from tumor bleeding. Tumor and neck nodes control rates at 2 years were 92% for stage III and IV A patients and 65% for stage IV B patients. Patients with cCR had a significantly better 2-year tumor and neck nodes control probability compared with patients who achieved cPR after therapy (P less than .001). Six patients developed distant metastases. Overall toxicity was tolerable, mucositis particularly was not a limiting factor.
A "Follow-up" Chest X-ray Survey in the Rhondda Fach
Authors: A. L. Cochrane, J. G. Cox, T. F. Jarman
Journal: BMJ (1955)

DITJOUNAL371faeces can often be felt on abdominal palpation.The con- dition is really a very severe dyschezia due to bad bowel habits, sometimes originating from defaecation fears due to pain of an anal abrasion or fissure.Absence of enuresis should exclude any psychological factor.
Acute hepatitis C in the Netherlands: characteristics of the epidemic in 2014
Authors: S.J. Hullegie, G.E.L. van den Berk, E.M.S. Leyten, J.E. Arends, F.N. Lauw, J.T.M. van der Meer, D. Posthouwer, A. van Eeden, P.P. Koopmans, C. Richter, M.E.E. van Kasteren, F.P. Kroon, W.F.W. Bierman, P.H.P. Groeneveld, K.D. Lettinga, R. Soetekouw, E.J.G. Peters, D.W.M. Verhagen, A.I. van Sighem, M.A.A. Claassen, B.J.A. Rijnders
Journal: Clinical Microbiology and Infection (2015)
A balance retraining exercise program reduced injurious falls in at-risk older community-dwelling women
Authors: Calvin Hirsch
Journal: Annals of Internal Medicine (2015)

Source Citation El-Khoury F, Cassou B, Latouche A, et al. Effectiveness of two year balance training programme on prevention of fall induced injuries in at risk women aged 75-85 living in community: Ossébo randomised controlled trial. BMJ. 2015;351:h3830. 26201510
Natural Suppressor (NS) Cells, Neonatal Tolerance, and Total Lymphoid Irradiation: Exploring Obscure Relationships
Authors: Samuel Strober
Journal: Annual Review of Immunology (1984)

Although several laboratories have shown that the appearance of naturally occurring suppressor cells in the spleens of neonatal or irradiated mice is temporarily related to the ease of induction of tolerance, the characteristics of these cells and their regulatory functions have been poorly understood until recently. The experimental data reviewed herein suggests that these cells are related to NK cells with regard to surface phenotype but differ with regard to function. The natural suppressor (NS) cells appear only briefly during the early maturation of the lymphoid tissues but can be induced in adults by manipulation of the lymphoid tissues with certain treatment regimens such as total lymphoid irradiation (TLI). In addition, the NS cells can be propagated and cloned in long-term tissue culture, thereby allowing a more detailed investigation of their properties. The cells have the unique feature of inhibiting the antigen-specific cytolytic arm of alloreactive immune responses but leaving intact the antigen-specific suppressive arm. In this way, alloreactions in the regulatory milieu of NS cells generate large numbers of antigen-specific suppressor cells that can maintain tolerance in vivo. Thus the NS cells may play an important role in the development of host-vs-graft and graft-vs-host tolerance in allogeneic bone marrow chimeras during the "window" of tolerance in which neonate and TLI-treated mice accept the infused allogeneic cells.
Liver inflammation and cancer: The role of tissue microenvironment in generating the tumor‐promoting niche (TPN) in the development of hepatocellular carcinoma
Authors: Eithan Galun
Journal: Hepatology (2015)

1Goldyne Savad Institute of Gene TherapyHadassah Hebrew University HospitalJerusalemIsrael *Address reprint requests to: Eithan Galun, M.D., Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Ein Kerem, P.O. Box 12000, Jerusalem 91120, Israel. Email: [email protected]; fax: +972‐2‐6430982.