tbuckley/cabot-search huggingface dataset:
PTH-280 Follow up after colorectal cancer: time to revise the guidance?
Authors: K Pearson, S Pugh, G Branagan, J Primrose
Journal: Gut (2015)

<h3>Introduction</h3> Follow-up practice after apparently curative resection for colorectal cancer has until recently been based on limited evidence. ACPGBI guidelines (2007) recommend a single CT during the first two years following resection whereas NICE (2014) advise a more intensive regime with a minimum of two CTs and carcinoembryonic antigen (CEA) measurement at least every six months in first three years. The recent FACS trial now provides us with evidence that that regular follow-up with CEA or CT imaging detects more treatable recurrences than minimal follow-up but that there was no advantage to combining both methods. The DISCLOSE study aimed to assess follow-up practice in seven NHS hospitals. <h3>Method</h3> Multi-centre regional audit of patients completing treatment for Dukes’ A-C colorectal cancer in 2008. <h3>Results</h3> 629 patients were included. Baseline characteristics were comparable to the FACS cohort: 347 (55%) were male, median age 73, 136 (22%) had a Dukes’ A primary, 278 (44%) Dukes’ B and 215 (34%) Dukes’ C. 558 (89%) patients met ACP follow-up guidelines for colorectal cancer. Of the remaining 71 patients, 27 died within two years post original resection and a further five patients declined follow-up. Therefore 590 (94%) patients had appropriate follow up as per ACP recommendations. Exact follow-up regimes did vary between centres and the proportion of patients meeting ACP guidance ranged from 84–99%. Fewer patients, 318 (51%), met current NICE guidelines. Both the overall incidence of recurrence (15.3%) and incidence of surgically treatable recurrence (4.3%) were similar to FACS. <h3>Conclusion</h3> The follow-up practices undertaken in this population were successful in achieving comparable incidences of surgically treatable recurrence to the FACS trial. This likely reflects the fact that the majority of patients were followed-up far more intensively than ACP guidance recommends. Whilst only half are compliant with the current recommendations by NICE, the FACS trial suggests that this guidance is too intensive. Neither ACP nor NICE guidance is based on the most up to date evidence and should be revised. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Guidelines for the Management of Colorectal Cancer. 3rd edition (2007). ACPGBI Colorectal cancer (2014) NICE guideline CG131 Primrose JN. Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: the FACS randomized clinical trial. JAMA. 2014 January 15;311(3):263–70
Cellular Immunity in Rats With Primary Brain Tumors: Inhibition of Macrophage Migration by Soluble Extracts of Avian Sarcoma Virus-Induced Tumors2
Authors: Dolph O. Adams, Robert W. Gilbert, Darell D. Bigner
Journal: JNCI Journal of the National Cancer Institute (1976)

Rats bearing primary tumors of the brain induced by avian sarcoma virus (ASV) were studied with the migration-inhibition factor (MIF) assay for the presence of cell-mediated immunity to tumor-associated antigens. Astrocytomas and sarcomas of the brain were induced in 34 neonatal F344 rats by the intracerebral inoculation of Bratislava-77 ASV. At weekly intervals from 4 to 9 weeks after the inoculation with virus, peritoneal exudate cells (PEC) from rats bearing brain tumors were tested an an MIF assay against soluble and KCl-treated extracts of a syngeneic, ASV-induced sarcoma. Incubation of the PEC with a soluble extract of syngeneic liver or with a KCl extract of a syngeneic, chemically induced tumor served as controls. Of 14 rats tested against the soluble tumor extract, 6 (43%) had statistically significant inhibition of migration (P less than or equal to 0.05). Of 23 animals tested against the KCl extract, 16 (70%) had significant inhibition. Immunity to the KCl extract was significant in most rats at each period. Ten rats were tested against a KCl extract of a hamster ASV-induced tumor; 7 gad significant inhibition of migration. None of 3 tested against a soluble extract of a syngeneic, chemically induced tumor had significant inhibition. Rats bearing ASV-induced brain tumors displayed cell-mediated immunity to tumor-associated antigen or antigens of ASV-induced tumors, which could be solubilized.
HPV in upper aerodigestive tract tumors in southern Brazil.
Authors: Luis Carlos Moreira Antunes, Antonio de Barros Lopes, Leandro Bizarro Muller, Renato Borges Fagundes
Journal: Journal of Clinical Oncology (2013)

e15083 Background: The highest rates of esophageal cancer in Brazil occur in Rio Grande do Sul (18/100,000/year for men), where squamous cell carcinoma is the most common. Furthermore, the incidence of head and neck squamous cell carcinoma (HNSCC) is significant in this region (11/100,000/year for cancer of the oral cavity and 10/100,000/year for laryngeal cancer in men). Tobacco smoking and alcohol consumption are the major risk factors for esophageal squamous cell carcinoma (ESCC) and HNSCC. The role of HPV in the development of ESCC remains controversial. Otherwise, there is some evidence that HPV-related HNSCC is a distinct entity compared with HNSCC associated with smoking and alcohol consumption. Methods: Polymerase chain reaction (PCR) was used to evaluate the presence of HPV from 218 samples from three groups of patients. Group 1 comprised 51 patients with ESCC who underwent esophagectomy, in which two samples from each patient were analyzed: one tumor sample and another from normal esophageal mucosa. Group 2 comprised 37 patients with HNSCC who underwent Lugol chromoendoscopy. In this group, we took biopsies from the primary tumor and from esophageal mucosa (unstained areas and middle esophagus when the esophageal mucosa was evenly stained). Thirty-seven dyspeptic patients, non-smokers and without alcohol consumption who underwent endoscopy, comprised Group 3, in which we took one biopsy from middle esophagus. All samples were fixed in formalin and stored in paraffin blocks. Nested-PCR with MY09/11 and GP5/6 primers was used to detect HPV L1 in those samples. Results: Of a total of 224 samples fixed in formalin and stored in paraffin, only 6 samples had insufficient material for PCR analysis: one sample from normal distal epithelium in Group 1, one sample from a stained area and 2 samples from unstained areas in Group 2 and 2 samples from normal esophageal mucosa in Group 3. PCR was positive for one of conserved genes GAPDH, G3PDH or B-globin in 218 samples, showing that DNA was adequate for analysis. The PCR results were negative for HPV DNA in all esophageal samples, as well as in all biopsies from the primary tumor of HNSCC. Conclusions: There is no evidence that HPV is involved in carcinogenesis of the upper aerodigestive tract in southern Brazil.
ON THE TREATMENT OF DIPHTHERIA.
Authors: J. W. BROWN
Journal: JAMA (1885)

Read in the Section on Diseases of Children of American Medical Association May, 1884. Omitting the historical review of the nature and origin of this malady, together with its pathological, histological and disputed theories of formation, and practically ignoring symptoms, diagnosis and prognosis as beyond the scope of the present paper and time at my disposal, and assuming that we are all familiar with this affection and that our results have been disappointing when faced by an epidemic, by the unfavorable mortality averaging, as Oertel claims, 40 to 50 per cent. the question naturally is suggested, Can we lower this fearful percentage? I present, gentlemen, a few facts gained from a study and experience of over one hundred and twenty (120) recorded cases occurring in my individual practice during a period of about fourteen (14) months. Its plan is not new, being advocated by Tropean, and endorsed by Dr. Whittaker,
An Immune-Inflammation Gene Expression Signature in Prostate Tumors of Smokers
Authors: Robyn L. Prueitt, Tiffany A. Wallace, Sharon A. Glynn, Ming Yi, Wei Tang, Jun Luo, Tiffany H. Dorsey, Katherine E. Stagliano, John W. Gillespie, Robert S. Hudson, Atsushi Terunuma, Jennifer L. Shoe, Diana C. Haines, Harris G. Yfantis, Misop Han, Damali N. Martin, Symone V. Jordan, James F. Borin, Michael J. Naslund, Richard B. Alexander, Robert M. Stephens, Christopher A. Loffredo, Dong H. Lee, Nagireddy Putluri, Arun Sreekumar, Arthur A. Hurwitz, Stefan Ambs
Journal: Cancer Research (2016)

Abstract Smokers develop metastatic prostate cancer more frequently than nonsmokers, suggesting that a tobacco-derived factor is driving metastatic progression. To identify smoking-induced alterations in human prostate cancer, we analyzed gene and protein expression patterns in tumors collected from current, past, and never smokers. By this route, we elucidated a distinct pattern of molecular alterations characterized by an immune and inflammation signature in tumors from current smokers that were either attenuated or absent in past and never smokers. Specifically, this signature included elevated immunoglobulin expression by tumor-infiltrating B cells, NF-κB activation, and increased chemokine expression. In an alternate approach to characterize smoking-induced oncogenic alterations, we also explored the effects of nicotine in human prostate cancer cells and prostate cancer–prone TRAMP mice. These investigations showed that nicotine increased glutamine consumption and invasiveness of cancer cells in vitro and accelerated metastatic progression in tumor-bearing TRAMP mice. Overall, our findings suggest that nicotine is sufficient to induce a phenotype resembling the epidemiology of smoking-associated prostate cancer progression, illuminating a novel candidate driver underlying metastatic prostate cancer in current smokers. Cancer Res; 76(5); 1055–65. ©2015 AACR.
Antibodies against carbamylated proteins are present in primary Sjögren's syndrome and are associated with disease severity
Authors: Brith Bergum, Catalin Koro, Nicolas Delaleu, Magne Solheim, Annelie Hellvard, Veronika Binder, Roland Jonsson, Valeria Valim, Daniel S Hammenfors, Malin V Jonsson, Piotr Mydel
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Herein, we investigate the presence and prognostic value of autoantibodies against carbamylated proteins (anti-CarP) in the serum of patients with primary Sjögren9s syndrome (pSS). <h3>Patients and methods</h3> Serum levels of anti-CarP antibodies were measured in Norwegian patients with pSS (n=78) and corresponding controls (n=74) using ELISA and analysed in relation with exocrine gland function, degree of salivary gland inflammation, signs of ectopic germinal centre (GC) formation and immunological markers. For univariate comparisons, the Mann–Whitney U test and χ<sup>2</sup> or Fisher9s exact tests were used. Correlations were assessed with Spearman9s rank testing. Multivariate regression analyses were used to assess the effect of anti-CarP positivity on clinical manifestations. <h3>Results</h3> Of the patients with pSS, 27% were positive for anti-CarP IgG antibodies. Levels of anti-CarP correlated positively with total IgG, IgM, rheumatoid factor and β2-microglobulin. Importantly, after adjusting for confounding factors, patients positive for anti-CarP had significantly higher focus score. Furthermore, positive anti-CarP status coincided with 9.2-fold higher odds of having developed GC-like structures in the minor salivary glands. As a patient group considered having worse disease outcome, individuals with ectopic GC-like structures also presented with significantly higher levels of anti-CarP antibodies. <h3>Conclusions</h3> Presence of anti-CarP in patients with pSS is strongly associated with increased focal lymphocytic infiltration, formation of ectopic GC-like structures in minor salivary glands, and diminished salivary gland function. Even taking into consideration our relatively small cohort we believe that anti-CarP antibodies offer new possibilities for identifying patients with more active disease and at risk of developing additional comorbidity.
Final results of a dose-finding phase II trial with a triple combination therapy in metastatic renal cell cancer (mRCC): Bevacizumab (B) plus immunotherapy (IT) plus chemotherapy (C) (BIC), antitumor effects, and variations of circulating T-regulatory cells (TREG).
Authors: R. Passalacqua, S. Buti, M. Brighenti, L. Rivoltini, C. Castelli, C. Camisaschi, C. Simonelli, G. Lo Re, R. Mattioli, S. Lazzarelli
Journal: Journal of Clinical Oncology (2010)

4615 Background: Efficacy and tolerability of chemo-immunotherapy plus anti-VEGF therapy is unknown. Aim of this study is to explore the combination of B+IT+C and to correlate its efficacy with the variations in circulating TREG. Methods: Patients (pts) with clear cell mRCC, previous nephrectomy, PS 0-1, no untreated CNS metastases and 0-2 previous systemic regimens, were treated with B (10 mg/kg days 1 and 15) plus C (gemcitabine: 1,000 mg/m2 i.v. in 1 hour followed by 5-fluorouracil 600 mg/m2 iv bolus days 1 and 8 every 28) plus IT (IL-2: 1 MUI/m2 bid sc days 8, 9, 15, 16 and 1 MUI/m2/die sc from day 10 to 12 and from 17 to 19; and IFN-α: 3 MUI sc on days 10, 12, 17, 19). The study was conducted according to two stages Minimax Simon design. CT was repeated for a maximum of 6 cycles followed by maintenance with B and IT until progressive disease (PD). In 30 pts, blood samples for TREG were collected and evaluated by FACS analysis. TREG were identified as CD4+/CD25high/FoxP3+ in PBMCs, on days: 1, 8, 15, 22, 29 of cycle 1 and at the disease progression (PD). Recist criteria and ITT analysis were applied. Results: 51 pts were included: male 66%; median age 58 ys; pre-treated 49%; MSKCC risk: low 29%, intermediate 53%, high 18%. We observed 29% partial response (PR) and 37% stable disease (SD) for an overall disease control rate (DCR) of 66%. In 26 not pre-treated pts 38% RP and 42% SD for a DCR of 80%. Median TTP was 8.8 mo and median OS 22,7 mo. In MSKCC high risk group we observed 11% PR and a DCR of 55%. Treatment was well tolerated, grade 3-4 toxicity included neutropenia non-febrile 36%, febrile 2%, thrombocytopenia 27%, flu-like syndrome 19%, hypertension 7%. We observed an increased percentage of TREG cells after treatment with IL2 + IFN and a decrease after treatment with B. The decrease was more evident in pts with PR or SD, suggesting a predictive role of TREG in the response to B. Conclusions: BIC combination is effective in all subgroups of mRCC and well tolerated. Variation in circulating TREG during first cycle seems to correlate with the response to treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Docetaxel and cisplatin as first-line chemotherapy in advanced NSCLC
Authors: D. Behera, A. N. Aggarwal, D. Gupta, S. K. Jindal, S. C. Sharma
Journal: Journal of Clinical Oncology (2005)

7343 Background: Untreated cases of advanced lung cancer in India have a median survival of few weeks only (less than 2 months). However, use of various chemotherapeutic agents increases the survival (Behera- Ind J Paed Oncol, 1995). Docetaxel in combination with cisplatin for first-line treatment is a good choice for locally advanced or metastatic NSCLC (Med Clin, Barc 2004). We describe our experience with Docetaxel and Cisplatin in a group of Indian patients with advanced NSCLC. Method: 130 patients of stage IIIB/IV histologically proved Non-small Cell Lung Cancer were included in the study. There were 116 males with their age ranging from 40 to 81 years and 14 females (age range 40–67). The performance status ranged from 60 to 100 (Kornofsky scale). Docetaxel 100mg/m2 and Cisplatin 60 mg/m2 was administered on day 1. The course was repeated every 28 days and the target was to give 5 such courses of chemotherapy. Fourty three patients received additional local radiotherapy of 20 to 50Gy. 84 patients completed 5 cycles of therapy. Result: Complete radiological response was observed in 22 (18.5%) and partial response in 28 (33%). The lesions remained stable ranging from 10 weeks to 41 weeks before they showed progression. At the time of data analysis the median survival has been 44.5+ weeks for those who completed five cycles. 118 patients (91%) are surviving beyond 6 months and 42 patients (32.3%) are alive beyond one year and 14 patients (10.7%) are still alive after 2 years. Thirty two patients gained weight during therapy with the mean increase of 4.1kg and 24 lost weight with a mean of 2.8 kg. Performance status improved in 24 and deteriorated in 9; in the remaining patients it was static. Side effects were minimal (alopecia, nausea, vomiting, diarrhea, skin changes and neuropathy) and not serious. Diarrhoea was observed in 32 (24.6%)of the patients that could be managed with usual antidiarrhoeals. Conclusion: Docetaxel and cisplatin combination as first line chemotherapy in advanced non small cell lung cancer is effective and comparable to other commonly used regimens. Although the regimen is costlier in Indian standards, it is effective with minimal side effects and should be tried in those who could afford it. No significant financial relationships to disclose.
Development of blastic phase on CML patients while on imatinib mesylate therapy: A five-year retrospective study
Authors: A. Zamecnikova, S. Al-Bahar, R. Pandita
Journal: Journal of Clinical Oncology (2008)

18030 Background: The introduction of tyrosine kinase inhibitors such as imatinib mesylate represents a major therapeutic advance in the management of chronic myelogenous leukemia. While imatinib is well tolerated an produces dramatic improvement in the treatment, little is known about its log term efficiancy and the event leading to disease transformation remains an enigma. We present and discuss 23 cases of patients with Ph-positive CML treated with imatinib who developed blastic crisis during the course of the disease. Methods: Cytogenetis, FISH and molecular-genetic studies were performed at diagnosis and during the course of the disease. Results: Out of the 87 patients receiving imatinib-based therapy, 23 patients developed blastic crisis. Among them 3 patients had variant form of the Ph translocation and in 8 patients additional chromosome anomalies were detected at diagnosis. Out of 23 patients 17 patients were non-responders or achieved only minor response to imatinib therapy. Conclusions: The aim of this retrospective study is to identify cytogenetic and molecular events associated with blast crisis in our study population. No significant financial relationships to disclose.
WITHDRAWN: S-nitrosated human serum albumin dimer as novel nano EPR enhancer applied to nano-anticancer drugs
Authors: Ryo Kinoshita, Yu Ishima, Mayumi Ikeda, Jun Fang, Hiroshi Maeda, Masaki Otagiri, Toru Maruyama
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes
Authors: G. Brent Dawe, Maria Musgaard, Mark R.P. Aurousseau, Naushaba Nayeem, Tim Green, Philip C. Biggin, Derek Bowie
Journal: Neuron (2016)

Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits.
Teniposide (VM-26), an overlooked highly active agent in small-cell lung cancer. Results of a phase II trial in untreated patients.
Authors: E Bork, M Hansen, P Dombernowsky, S W Hansen, A G Pedersen, H H Hansen
Journal: Journal of Clinical Oncology (1986)

Teniposide, VM-26 (Vumon), was administered in a dose of 60 mg/m2 on days 1 to 5 every third week to 36 patients with histologically confirmed small-cell lung cancer. None had previously received chemotherapy or radiotherapy. The median age was 73 years (range, 52 to 79). Thirty-three patients were evaluable; 21 of these had local disease. Five patients had bone marrow metastases, four had liver involvement, and one CNS metastases. All patients had a performance status less than or equal to 2 before the start of treatment. Thirty patients obtained a response (90%), ten of whom had a complete remission (30%). The median duration of remission was 8+ months (range, 1.1 to 17+ months), whereas the median survival was 8.7 months (range, 1.9 to 20 months). Toxicity was primarily hematologic, with leukopenia the only dose-limiting effect. Besides alopecia, all other side effects were minimal including nausea and vomiting. We find these results provocative in regard to the response rate and the duration of response obtained as well as in reference to the dismal results that prior investigations in previously treated patients have shown. These data may indicate the need for reconsideration of the usual strategy for performing phase II trials.
Now we tell--but how well?
Authors: J C Holland
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.5.557 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2709086 Now we tell--but how well? J C HollandxJ C HollandSearch for articles by this author https://doi.org/10.1200/JCO.1989.7.5.557 First Page PDF © 1989 by American Society of Clinical Oncology