tbuckley/cabot-search huggingface dataset:
Systemic inflammation in osteoarthritis
Authors: P. Z. Hrycaj, T. Stürmer, Hermann Brenner, W. Koenig, K. P. Günther
Journal: Annals of the Rheumatic Diseases (2004)

Several studies have shown that the acute phase response may take place in osteoarthritis (OA), suggesting that low grade systemic inflammation may be present in patients with OA.1,2 I read with interest the paper by Sturmer et al on high sensitivity C reactive protein (CRP) in relation to the severity and extent of OA.3 As assessed by high sensitivity nephelometry, serum high sensitivity CRP was higher in 770 patients with advanced OA than in 567 age and sex matched healthy controls (geometric mean 2.5 mg/l v 1.7 mg/l, respectively). Moreover, severity of pain as measured by a visual analogue scale was associated with mean high sensitivity CRP. Interestingly, neither the bilateral nor the generalised extent of OA, nor any of the dimensions of the Western Ontario and McMaster Universities OA index (WOMAC) were associated with mean high sensitivity CRP concentrations. The authors concluded that the subjective severity of pain is associated with low level systemic inflammation in OA, and measurement of high sensitivity CRP may have some potential for monitoring and/or predicting the clinical course of OA.

In contrast with CRP, some acute phase proteins like α1-acid glycoprotein (AGP) or α1-antichymotrypsin (ACT) are glycoproteins and possess glycosylation sites attached by N-glycosidically bound, complex-type oligosaccharide side chains.4 Heteroglycans of acute phase proteins share the common core structure but differ in their outer chain sequences. According to the number of these oligosaccharide chains bi-, tri- and tetra-antennary heteroglycans can be distinguished. This structural diversity (termed “microheterogeneity”) results in different reactivity with the lectin concanavalin A (con A). It has …
Expression of a mutant p53 in lung specific transgenic mice cause age-related demographic shift in lung tumor incidence
Authors: Wenrui Duan, Li Gao, Xin Wu, Gregory Otterson, Miguel Villalona-Calero.
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3857 

To investigate the role of mutant p 5 3 in lung tumorigenesis, a p53(273H) transgenic mouse model was developed. The transgene was placed under control of the human surfactant protein C (SPC) promoter to selectively express the mutant protein in lung tissue. In the previous report we summarized the lung tumor incidence of the transgenic mice up to age cohort of 13-15 months. The p53 (273H) transgenic mice were found to have a higher lung tumor rate compared to the non-transgenic controls at median age of 14 months.

We continued our study and collected the lung cancer incidence data up to 24 months. A total of 236 transgenic mice and 189 non-transgenic control mice were evaluated by necropsy at age of 4-6, 7-9, 10-12, 13-15, 16-18, 19-21, and 22-24 months. Among the 236 transgenic mice, 58 lung tumor bearing mice were identified. Among the 189 non-transgenic mice, 22 lung tumor bearing mice were identified. All tumors were identified histopathologically as adenocarcinomas. By comparison, no difference was found in lung tumor rate between the transgenic mice and non-transgenic controls at age of 4-12 and 22-24 months. However, the transgenic mice have a statistically (two tailed t-test) significant higher lung tumor rate than their non-transgenic counterparts during the age of 13-21 months.

These results indicate that expression of mutant p53 in mice lungs cause early onset of lung tumor in the transgenic mice. The long latency period for tumors to develop would suggest that in the event that the mutant p53(273H) contributes to the development of lung tumors in these mice, other genetic alterations or age related physiological changes occurring after age of 13 moth are required for malignant transformation. At the age of 22-24 months, many other genetic alterations have occurred so that mutant p53 is no longer a major event in lung tumorigenesis.
Characterization of Lymphoma-Derived Cell Lines: Comparison of Cell Lines Positive and Negative for Epstein-Barr Virus Nuclear Antigen. I. Physical, Cytogenetic, and Growth Characteristics
Authors: Magrath, Ian T., Pizzo, Philip A., Whang-Peng, Jacqueline, Douglass, Edwin C., Alabaster, Oliver, Gerber, Paul, Freeman, Charles B., Novikovs, Ligita
Journal: JNCI Journal of the National Cancer Institute (1980)

Sixteen lymphoid cell lines were derived from patients with undifferentiated lymphoma of Burkitt's or non-Burkitt's type. They were obtained directly from tumor biopsies, from serous effusions, or from bone marrow. In 10 of the cell lines, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) was undetectable; the remaining 6 lines were EBNA-positive (EB-pos). Of the 16 lines, 15 were aneuploid, with detectable chromosome "14q+ markers (11 had +8;14 translocations). These 15 lines, which included the EBNA-negative (EB-neg) lines, were believed to be of tumor cell origin. The remaining line consisted predominantly of diploid cells derived from normal lymphocytes, but some cells of tumor origin were present. Four EB-pos cell lines derived from EB-neg tumors had an aneuploid karyotype consistent with an origin from tumor cells (including no.8;14 translocation in two), which suggested that either tumor cells were infected with EBV in vitro or a tiny fraction of EB-pos tumor cells (or potential tumor cells) present in vivo gave rise to the predominant cell of the line. EB-neg B-cell lines and EB-pos cell lines established from undifferentiated lymphomas differed greatly. EB-neg lines had consistently smaller electronic mean cell volumes and narrow-angle light scatter than did EB-pos lines. This finding correlated with a lower nuclear:cytoplasmic ratio in EB-pos lines. EB-neg lines also had higher saturation cell densities than did EB-pos lines under standard culture conditions. The data indicate either that EBV influences the morphologic and physiologic characteristics of lymphoid cell lines or that EB-neg B-cell lines and EB-pos cell lines are derived ultimately from different lymphocyte subpopulations or that both may apply.
Novel progression-associated genes in pancreatic endocrine neoplasms
Authors: A. Nasir, S. McCarthy, D. Agrawal, G. Bloom, E. Zeringer, D. Chen, N. A. Nasir, S. Enkemann, D. Coppola, L. Kvols
Journal: Journal of Clinical Oncology (2008)

15516 Background: Pancreatic endocrine tumors/carcinomas (PETs/PECAs) are clinically challenging. With the development of metastases there is significant drop in patient survival. Therefore, detection of progression-associated genes in tumor tissue can have profound prognostic and therapeutic implications. Methods: Five clinically-localized primary (CLP)-PETS from 5 patients (mean age 66; 3M/2F) and 6 metastatic primary (MP)-PECAs and matched liver metastases (MLMs) (N=12) from 6 other patients (mean age 59, 3M/3F) were selected. All tumors were flash frozen within 15 minutes of surgery and macrodissected to achieve 80–98% tumor enrichment. The tumor RNA samples were run on Affymetrix U133 2.0 gene chip. Data were RMA normalized. t-test was used to identify differentially expressed genes in MP-PECAs vs. CLP-PETs and MLMs Vs. MP-PECAs. Based on statistical and pathway analyses, gene function and extensive literature review ‘candidate progression genes’ were selected for validation by immunohistochemistry and real time PCR (q-PCR) using microfluidics cards (AB, Inc.,USA). To normalize q-PCR data, we used microfluidic cards to determine our original endogenous control genes specific for frozen and archival PETs/PECAs. Results: 217 transcripts were differentially expressed between MP- PECAs and CLP-PETs, using p-value <0.05 and fold-change values >1.5/>2/>4/>8 (217/94/19/1 gene respectively). Similarly, 330 transcripts were differentially expressed between MLMs and their matched MP-PECAs, using p-value <0.05 and fold-change values >1.5/>2/>4/>8 (330/56/18/9 genes respectively). Among these the ‘candidate progression genes’ of interest include CD24, SERPIN A1, palladin, protocadherin 9, insulin-receptor, SMURF1, RERG, RUNX1T1, ST14, PDGFRL, osteonectin, APRIN, SSTR1, CHGA, NRCAM, ST18 and SMAD1. Validation of our most promising progression-associated genes on the original frozen tumor samples and larger and independent test sets of archival PETs/PECAs will be presented. Conclusions: We have discovered a novel set of potential progression genes in pancreatic endocrine carcinomas and their synchronous liver metastases. We are currently evaluating the clinical utility of these candidate genes as potential biomarkers of progression in pancreatic endocrine neoplasms. No significant financial relationships to disclose.
A phase II study of combination CPT-11 and docetaxel in patients with ovarian carcinoma refractory or resistant to combination paclitaxel and carboplatin
Authors: T. Enomoto, K. Yoshino, M. Yamasaki, Y. Nishio, A. Wakimoto, T. Miyake, K. Fujiwara, M. Takemura, K. Ito
Journal: Journal of Clinical Oncology (2006)

15036 Background: To investigate the efficacy and toxicity of combination irinotecan and docetaxel in patients with ovarian carcinoma refractory (not responded) or resistant (relapsed within 6 months after the last chemotherapy) to the first line chemotherapy with combination paclitaxel (175mg/m 2 ) and carboplatin (AUC=5). Methods: 30 refractory patients and 28 resistant patients with measurable disease were treated with combination irinotecan (60 mg/m 2 ) and docetaxel (30 mg/m 2 ) at days 1 and 8 every 3 weeks for more than 2 courses. Results: The average number of courses administered was 2.6 for refractory cases and 3.4 for resistant cases. The average number of courses administered was 2.6 for refractory cases and 3.4 for resistant cases. Using RECIST criteria, 2/28 (7%) resistant cases responded completely, 6/30 (20%) of refractory cases and 6/28 (21%) resistant cases were responded partially. 16/30 refractory cases and 14/28 cases progressed. Grade 3–4 toxicities were leukopenia (31%) neutropenia (36%) thrombocytopenia (8%) and diarrhea (6%). Conclusions: Combination chemotherapy of CPT-11 and Docetaxel at days 1 and 8 every 3 weeks is a regimen with moderate toxicity and good compliance, and shows some response to those patients who are refractory or resistant to the first-line chemotherapy with paclitaxel and carboplatin with a response rate of 20% and 29%, respectively. No significant financial relationships to disclose.
Screening programme not cost effective
Authors: D J Watmough, K Kumar
Journal: BMJ (1994)

EDITOR, - Examination of the data from the United Kingdom's breast screening programme from March 1991 to April 19921 reported by J Chamberlain and colleagues allows some tentative conclusions to be drawn about the costs and potential benefits. Altogether 1 028 984 women accepted an invitation for mammographic screening. With a recall rate of 6.2% there would have been an extra 63 797 tests, making a total of 1 092 781 tests. It is reported that 6605 cancers were detected. Of these, 1465 (22%) were impalpable. It follows that 78% of cancers …
Epigenetic silencing of Dab-2 in head and neck cancer.
Authors: C. Lo Nigro, L. Lattanzio, D. Vivenza, M. C. Merlano, T. Crook, G. Inman, M. Gasco
Journal: Journal of Clinical Oncology (2010)

10561 Background: Transcriptional silencing resulting from changes in epigenetic regulation of gene expression is a major mechanism by which genes controlling multiple cancer phenotypes, such as metastasis and drug sensitivity/resistance, are inactivated in human cancer. Methylation profiling can identify distinct subtypes of common human cancers and may have utility in predicting clinical phenotypes in individual patients. Dab-2, the human homologue of the Drosophila Disabled 2 gene, is an integrator of multiple signaling pathways, including Wnt and TGF-beta. Methods: We performed a retrospective analysis of gene methylatyion in 100 archival samples from patients with locally advanced, stage III-IV, inoperable squamous cell carcinomas of the head and neck (HNSCC). All patients were treated with cisplatin-based chemo-radiotherapy regimens. Dab-2 methylation was assessed on paraffin-embedded tissue sections at diagnosis using pyrosequencing, methylation specific PCR and qPCR. Results: Loss of expression of Dab2 via epigenetic silencing was detected in 58/100 cases. Dab2 hyper-methylation was significantly correlated with: 1) presence of loco-regional nodal metastases (p=0.0001); 2) poor response to radical chemo-radiotion (p=0.0002); 3) worse progression-free survival (p<0.0001); 4) worse overall survival (p<0.0001). The significant predictive ability of Dab-2 on progression-free and overall survival was found to be independent of sex, age, performance status, EGFR status, T, N and stage of disease (p<0.0001). Conclusions: Our data suggest that Dab-2 epigenetic silencing via hyper-methylation is associated with poor clinical outcome in advanced HNSCC and that Dab-2 could represent a valuable prognostic/ predictive biomarker in this disease. No significant financial relationships to disclose.
The General Practitioner'S Use and Expectations of An Accident and Emergency Department
Authors: W G Morrison, A G Pennycook, R M Makower, I J Swann
Journal: Journal of the Royal Society of Medicine (1990)

In an attempt to establish what the general practitioner expects from an accident and emergency department, and how closely the service provided correlates with that view, a 12-point questionnaire was sent to the general practitioners in the Glasgow Royal Infirmary catchment area. Out of the 61.2% of general practitioners who replied, the majority wish to have responsibility for their own patients for conditions which are neither accidents nor emergencies. There is less agreement as to how much should be done within an accident and emergency department and on the appropriate modes of referral and communication between the general practitioner and the hospital service. Further consultation and cooperation are necessary to interpret and resolve these differences.
Abstract #5517: Down-regulation of nuclear receptor co-repressor 2 enhances the resistance against bortezomib in U266 cells
Authors: Chansu Lee, Kwang-Sung Ahn, Juwon Park, Eun-Kyung Bae, Byung-Su Kim, Seonyang Park, Byoung Kook Kim, Sung-Soo Yoon
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Introduction: Bortezomib has excellent clinical activity in patients with multiple myeloma (MM) and it is currently being evaluated in combination with conventional chemotherapeutic agents. However, its clinical efficacy has been hampered by the emergence of drug-resistance phenomena, the molecular basis of which remains elusive. Verification of molecular mechanism by which resistance emerges is crucial for improved treatment outcome in MM. Materials and Methods: U266 cells transfected with a pool of siRNA library were incubated in soft agar plate containing 20 nM bortezomib and resistant clones against bortezomib were then isolated. After resuspending in RPMI-1640 culture media, we tested resistance against bortezomib, dexamethasone, and thalidomide using MTT assay. To identify a set of novel genes associated with bortezomib resistance, PCR cloning analysis was performed and oligonucleotide microarray was performed to examine differentially expressed genes. Function analysis of candidate genes was also performed using transfection analysis using cDNA and siRNA and their biologic behaviors were examined. Results: Five different clones (U266/ PsiRNA1 , U266/ PsiRNA2 , U266/ PsiRNA3 , U266/ PsiRNA4 ) were detected in soft agar having 105 U266 cells transfected with pool of siRNA. Even though there was little difference in IC50 values among five different clones, IC50 values of them were four folds more than IC50 values of parental cells in MTT assay. U266/ PsiRNA2 was also resistant to dexamethasone and thalidomide but others were not. Release of IL-6 and sIL-6R in U266/PsiRNA2 was higher than other clones. In PCR cloning analysis, sequencing data indicated nuclear receptor co-repressor 2 siRNA. RT-PCR analysis indicated that this gene expression was knocked-down in U266/PsiRNA. Microarray results revealed that a set of genes leading to NF-kB activation was 10 folds more than those in parental cells and a set of STAT-3 downstream genes was 12 folds less than those in parental cells. Conclusion: Our data indicated that a set of genes associated with NF-kB activation and STAT3 activation by IL-6 plays critical roles in bortezomib resistance. Especially, genes controlling the IL-6 mediated cell signaling should be involved in that response.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5517.
Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group study.
Authors: C G Leichman, T R Fleming, F M Muggia, C M Tangen, B Ardalan, J H Doroshow, F J Meyers, R F Holcombe, G R Weiss, A Mangalik
Journal: Journal of Clinical Oncology (1995)

PURPOSE A variety of fluorinated pyrimidine-based regimens for the treatment of disseminated colorectal cancer have been presented in the medical literature. The Southwest Oncology Group designed a screening trial of seven regimens of fluorouracil (5-FU) to assess efficacy and toxicity afforded by biochemical modulation or schedule variations. PATIENTS AND METHODS Six hundred twenty patients were entered into this trial between August 1989 and January 1993. Eligible patients were classified as having recurrent or disseminated disease that was measurable or nonmeasurable. All eligible patients were evaluated for toxicity and survival; patients with measurable disease were evaluated for response according to standard criteria. RESULTS No regimen achieved a higher response rate than single-agent bolus 5-FU. Eighty-four percent of patients have been monitored until death. The median survival time for the entire cohort is 14 months. Survival hazards ratios showed a positive trend in favor of the unmodulated infusion regimens, while high-grade toxicities occurred more frequently in the 5-FU bolus arms. The major high-grade toxicities were granulocytopenia and diarrhea. CONCLUSION In this trial, no regimen provided substantial improvement relative to 5-FU bolus or single-agent therapy for either response or survival in the treatment of disseminated colorectal cancer. The single-agent infusion regimens demonstrated the most encouraging results with a favorable toxicity profile and a 2-month longer survival duration than 5-FU bolus therapy.
Novel chemotherapeutic agents in the treatment of non-small-cell lung cancer.
Authors: R C Lilenbaum, M R Green
Journal: Journal of Clinical Oncology (1993)

This study attempted to identify novel chemotherapeutic agents with greater than 15% activity in non-small-cell lung cancer (NSCLC).An English language literature search, which included abstracts and original articles, and a review of bibliographies of identified articles, were used.Nine new agents, analogs, or old agents used in new doses or schedules were identified: CPT-11, topotecan, taxol, taxotere, Navelbine (Burroughs Wellcome, Research Triangle Park, NC), chronic oral etoposide, edatrexate, gemcitabine, and high-dose epirubicin. Results of phase I and II trials that involved these agents alone or as part of combination regimens are presented.Several new chemotherapeutic agents with activity against NSCLC are now available. Response rates compare favorably with those of available standard drugs. These new drugs are being integrated into multiagent combinations. Large-scale phase III trials that compare these new combinations with current standard approaches will be necessary to determine whether or not these new drugs will have a positive impact on survival in patients with NSCLC.
Mitochondrial electron transport chain identified as a novel molecular target of SPIO nanoparticles mediated cancer-specific cytotoxicity
Authors: Chengyong He, Shengwei Jiang, Haijing Jin, Shuzhen Chen, Gan Lin, Huan Yao, Xiaoyong Wang, Peng Mi, Zhiliang Ji, Yuchun Lin, Zhongning Lin, Gang Liu
Journal: Biomaterials (2016)
The safety and efficacy of laparoscopic surgical staging and debulking of apparent advanced-stage ovarian, fallopian tube, and primary peritoneal cancers.
Authors: F. Nezhat, S. M. DeNoble, C. S. Liu, J. E. Cho, D. N. Brown, L. T. Chuang, H. Gretz, P. Saharia
Journal: Journal of Clinical Oncology (2010)

e15527 Background: Advances in laparoscopic surgery have allowed a minimally invasive surgical approach to managing ovarian cancer. In advanced stage ovarian cancer, the role of laparoscopy has been described as a tool to triage for resectability and second-look evaluations, with limited studies on its role in cytoreductive procedures. The objective of this study is to describe our preliminary experience with laparoscopic total primary or interval cytoreduction in patients with advanced ovarian, fallopian, and primary peritoneal cancers. Methods: This is a retrospective analysis of a prospective case series. Women with presumed advanced (FIGO stage IIC or greater) ovarian, fallopian tube, or primary peritoneal cancers who were deemed appropriate candidates for laparoscopic debulking by the primary surgeon(s) were recruited. Results: A total of 32 patients were recruited that underwent laparoscopic evaluation. Seventeen patients underwent total laparoscopic primary or interval cytoreduction, with 88.2% optimal cytoreduction. Eleven patients underwent diagnostic laparoscopy and conversion to laparotomy for cytoreduction, with 72.7% optimal cytoreduction. Four patients had biopsies and/or limited cytoreduction. In the laparoscopy group, 9 patients have no evidence of disease (NED), 6 are alive with disease (AWD), and 2 have died of disease (DOD), with mean follow-up time of 19.7 months. In the laparotomy group, 3 patients are NED, 5 are AWD, and 3 have DOD, with mean follow-up of 25.8 months. Estimated blood loss and length of hospital stay were less for the laparoscopy group (p = 0.008 and p = 0.03), while operating time and complication rates were not different. Median time to recurrence was 31.7 months for the laparoscopy group and 21.5 months for the laparotomy group (p = 0.3). Conclusions: Laparoscopy can be used for diagnosis, triage and debulking of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer and is technically feasible in a well-selected population. No significant financial relationships to disclose.