tbuckley/cabot-search huggingface dataset:
Four-protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma
Authors: Sharifah NurAin Syed Zanaruddin, Amyza Saleh, Yang Yi-Hsin, Sharifah Hamid, Wan Mahadzir Wan Mustafa, Khairul Bariah AAN, Soo-Hwang Teo, Rosnah Binti Zain, Shin Hin Lau, Sok Ching Cheong
Journal: Clinical Cancer Research (2010)

Abstract The presence of lymph node metastasis significantly affects the survival of oral squamous cell carcinoma patients and successful detection and removal of positive lymph nodes is crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the lymph nodes, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis—positive LNs in the neck. We aimed to develop a molecular signature in the primary tumor that could predict lymph node (LN) metastasis in oral squamous cell carcinoma. The expression levels of 11 proteins was evaluated using immunohistochemical analysis in a tissue microarray (TMA) consisting of 110 specimens from 32 individuals. We used receiver operating characteristic (ROC) curve to identify proteins that could significantly differentiate patients with LN metastasis from those that did not. Unsupervised hierarchical clustering analysis was used to verify the ability of chosen biomarkers in segregating LN positive patients from those with no LN involvement. Kaplan-Meier survival curve and log rank test was utilized to determine the association between LN metastasis and biomarker expression with disease-specific survival. Of the 11 biomarkers, EGFR, HER-2/neu, LAMC2 and RHOC were found to be significantly associated with LN metastasis. Unsupervised hierarchical clustering demonstrated that expression patterns of these 4 proteins could be used to differentiate the positive LN metastasis specimens from specimens that are negative. Collectively, EGFR, HER-2/neu, LAMC2 and RHOC have a specificity of 87.5% and sensitivity of 70% with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated the LN signature could independently predict disease-specific survival (p = 0.023). In summary, we developed a 4-protein LN signature that could reliably distinguish patients with lymph node metastasis from those who were metastasis free. In addition, this LN signature is also associated with disease-specific survival indicating that would be a useful prognostic tool for the management of oral cancer patients.
Model of a Boat
Authors: M. Therese Southgate
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THE OCCURRENCE OF BIOLOGIC CRYSTALS IN TUMOR AND NONTUMOR CULTURES OF C3H-HEJ MICE.
Authors: Arnis Richters, Russell P. Sherwin
Journal: Cancer Research (1965)

Summary  Crystalline structures of various types have been found in primary tissue cultures of neoplastic and non-neoplastic tissues from C3H/HeJ mice. All of the cultures of mammary carcinoma tissue contained the crystals. The crystals were found in varying incidence in the cultures of several other tissues with the exception of those from the kidney. A ‘dialysis compartment’ was not essential for the formation of the crystals. The development of the crystals was accelerated by a modification of the culture medium.
Funding boost for prostate cancer research
Authors: Akil Fazal
Journal: BMJ (2000)

Funding for prostate cancer in England will increase fourfold under a new prostate cancer programme launched by the Department of Health last week. By 2003-4, the department will be directly funding £4.2m ($6.3m) of research a year.

At the launch of the programme Alan Milburn, the health secretary, said: “This starts the implementation of improvements in cancer services. For too long not enough has been done to detect prostate cancer or to improve treatment.”

Prostate cancer is diagnosed in about …
Abstract 892: Potential of urinary MMP-9/NGAL complex as a novel biomarker for the early detection of gastric cancer
Authors: Takaya Shimjura, Adelle Dagher, Masahide Ebi, Tamaki Yamada, Tomonori Yamada, Takashi Joh, Marsha A. Moses
Journal: Cancer Research (2014)

Abstract The early diagnosis of gastric cancer (GC) provides the opportunity for curative endoscopic resection. However, although endoscopy is a standard diagnostic method for this disease, comprehensive screening endoscopy would be invasive, expensive and could result in significant complications. To date, there is a significant lack of useful GC biomarkers. In fact, serum tumor markers such as CEA and CA19-9 have not been recommended as GC diagnostics due to their low sensitivity and specificity. With the goal of discovering non-invasive biomarkers for the early diagnosis of GC, we have conducted a pilot case-control study utilizing urine samples from individuals with gastric cancer vs. healthy control samples. A cohort of 70 patients composed of 35 patients with gastric cancer and 35 age- and sex-matched healthy controls was analyzed. Baseline clinical characteristics were tightly controlled and no significant differences were noted. Since changes in the microvasculature have been described in the very early stages of GC, we conducted an angiogenesis protein array analysis to identify potential candidate biomarkers. Three proteins, IL-8, PECAM-1, MMP-9, were found to be elevated in the urine of GC patients compared to controls by this method. In confirming the elevated levels of urinary MMP-9 by gelatin zymography, we determined that MMP-9/NGAL complex was also significantly elevated in the GC urines compared to control samples. We therefore tested all samples for the presence of IL-8, PECAM-1, MMP-9 and MMP-9/NGAL complex using monospecific ELISAs. We were able to confirm that urinary levels of MMP-9/NGAL complex were significantly higher in the GC group compared to the healthy control group (Median, 85 pg/ml (IQR, 43-224) vs. 0 pg/ml (IQR, 0-213), respectively, P=0.020). Urinary MMP-9/NGAL complex could distinguish between healthy control samples and GC samples with an area under the curve of 0.657(95%CI, 0.527-0.789) in a receiver operating characteristics analysis. A cut-off value of urinary MMP-9/NGAL complex was established and the statistical performance characteristics of this urinary biomarker were also determined. In summary, urinary MMP-9/NGAL complex emerged as a significant non-invasive biomarker for gastric cancer including early stage disease. Ongoing studies are focused on the large scale validation of these findings. Citation Format: Takaya Shimjura, Adelle Dagher, Masahide Ebi, Tamaki Yamada, Tomonori Yamada, Takashi Joh, Marsha A. Moses. Potential of urinary MMP-9/NGAL complex as a novel biomarker for the early detection of gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 892. doi:10.1158/1538-7445.AM2014-892
Trends in Cardiovascular Complications of Diabetes
Authors: Cynthia L. Leibson, K. M. Venkat Narayan
Journal: JAMA (2005)

To the Editor: The study by Dr Fox and colleagues compared cardiovascular disease (CVD) outcomes for a Framingham cohort examined in 1950-1966 with one examined in 1970-1995 and found that CVD incidence/mortality declined 49% for adults with diabetes and 35% for adults without diabetes. In contrast, studies using National Health and Nutrition Examination Survey (NHANES) data and Rochester Epidemiology Project (REP) resources found that declines in CVD mortality rates between 1970 and 1995 were significantly less for adults with diabetes compared with adults without diabetes. Fox et al attributed this difference to shorter follow-up in NHANES and REP studies and to limitations in the determination of CVD and diabetes in these studies. However, the criticismregardingCVDdeterminationdoesnotaddress those studies’ findings of significant temporal increases in the diabetesassociated risk of all-cause-mortality. While the NHANES and REP studies are more vulnerable to diabetes detection bias than is the Framingham study, earlier detection of milder diabetes in recent periods should contribute to artifactual improvement in relative survival for persons with diabetes, while both NHANES and REP studies found the opposite. Because diabetes duration is a strong predictor of CVD, the risk of CVD associated with diabetes would be artifactually reduced by any bias toward shorter duration. In the Framingham analysis, some individuals belonged to both cohorts; thus, diabetes duration at baseline was likely shorter in the later than earlier cohort. Temporal changes in the Framingham definition of diabetes also favor shorter duration in the later cohort. While follow-up in the NHANES and REP studies was intentionally truncated at 10 years, this was not the case in the Framingham study, so that relatively shorter allowable follow-up for the later Framingham cohort could also contribute to the observed reductions in the diabetes-associated risk of CVD for that cohort. The Framingham study followed up patients to 2000 and is thus more informative than the REP and NHANES studies regarding recent improvements in diabetes treatment and care. However, the latest entry in the earlier Framingham cohort (1966) preceded the earliest entry date for the NHANES and REP studies (1970). Relative survival associated with diabetes improved between 1945-1958 and 19551969. The extent to which the Framingham trends were driven by these earlier years is unknown.
Novel cell lines from pediatric brain tumors showed striking multi-drug resistance
Authors: Jingying Xu, C. Patrick Reynolds
Journal: Cancer Research (2006)

4348   The paucity of cell culture models for childhood brain tumors has stimulated us to establish such cell lines for use in biological and preclinical developmental therapeutic studies. Primitive neuroectodermal tumors (PNETs), gliomas, and astrocytomas were obtained at surgery or post-mortem, minced and cultured in lscoves DMEM + 20% fetal bovine serum and insulin, selenium, transferrin. Gentamicn was only used for the initial few weeks of culture. The initial 3 cell lines established were CHLA-200 (anaplasic astrocytoma at post mortem), CHLA-259 (posterior fossa PNET at diagnosis) and CHLA-266 (PNET with supratentorial metastasis at diagnosis). All new cell lines had unique DNA “fingerprints” using the ABI Profiler. We compared biological features of these lines and response to commonly used drugs to the DAOY posterior fossa PNET cell line. The drug cytotoxicity assay employed fluorescein diacetate and digital image microcopy (DIMSCAN); mRNA expression was quantitative RT-PCR (Taqman). All cell lines grew attached to flasks but differed in morphology and doubling time (DAOY 29hrs, CHLA-259 88hrs, CHLA-266 40hrs, CHLA-200 55hrs). In contrast to fibroblasts, all 4 cell lines expressed telomerase reverse transcriptase (hTERT) and telomerase RNA template (hTR). CHLA-256, 259+200 (but not DAOY) all showed strong expression of PGP9.5 but no expression of tyrosine hydroxylase. DAOY, CHLA-259+256 (but not CHLA-200) expressed MYCN, while CHLA-266+200 expressed c-myc. CHLA-266 and/or CHLA-200 showed striking multi-drug resistance when compared to DAOY for etoposide (ETOP), topotecan (TPT), melphalan ( L-PAM), vincristin (VINC), cyclophosphamide (4-HC), and cisplatin (CDDP) (Table 1). Unlike the commonly available line DAOY, drug resistance was seen in these new cell lines for most drugs tested. Thus, these new cell lines may provide useful models for preclinical testing of novel drugs for possible activity against multi-drug resistant pediatric brain tumors. Supported by the Devin Hock Memorial Fund of the Michael Hoefflin Foundation.
Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma
Authors: Chunping Wang, Huaming Wang, Wuwei Yang, Kaiwen Hu, Hui Xie, Ke‐Qin Hu, Wenlin Bai, Zheng Dong, Yinying Lu, Zhen Zeng, Min Lou, Hong Wang, Xudong Gao, Xiujuan Chang, Linjing An, Jianhui Qu, Jin Li, Yongping Yang
Journal: Hepatology (2014)

Radiofrequency ablation (RFA) is considered a curative treatment option for hepatocellular carcinoma (HCC). Growing data have demonstrated that cryoablation represents a safe and effective alternative therapy for HCC, but no randomized controlled trial (RCT) has been reported to compare cryoablation with RFA in HCC treatment. The present study was a multicenter RCT aimed to compare the outcomes of percutaneous cryoablation with RFA for the treatment of HCC. In all, 360 patients with Child‐Pugh class A or B cirrhosis and one or two HCC lesions ≤ 4 cm, treatment‐naïve, without metastasis were randomly assigned to cryoablation (n = 180) or RFA (n = 180). The primary endpoints were local tumor progression at 3 years after treatment and safety. Local tumor progression rates at 1, 2, and 3 years were 3%, 7%, and 7% for cryoablation and 9%, 11%, and 11% for RFA, respectively ( P = 0.043). For lesions &gt;3 cm in diameter, the local tumor progression rate was significantly lower in the cryoablation group versus the RFA group (7.7% versus 18.2%, P = 0.041). The 1‐, 3‐, and 5‐year overall survival rates were 97%, 67%, and 40% for cryoablation and 97%, 66%, and 38% for RFA, respectively ( P = 0.747). The 1‐, 3‐, and 5‐year tumor‐free survival rates were 89%, 54%, and 35% in the cryoablation group and 84%, 50%, and 34% in the RFA group, respectively ( P = 0.628). Multivariate analyses demonstrated that Child‐Pugh class B and distant intrahepatic recurrence were significant negative predictors for overall survival. Major complications occurred in seven patients (3.9%) following cryoablation and in six patients (3.3%) following RFA ( P = 0.776). Conclusion : Cryoablation resulted in a significantly lower local tumor progression than RFA, although both cryoablation and RFA were equally safe and effective, with similar 5‐year survival rates. (H epatology 2015;61:1579–1590)
Abstract 3751: The potential role of CXCR4 in cisplatin associated resistance in esophageal carcinoma
Authors: Yue Zhao, Yan Wang, Christiane Bruns
Journal: Cancer Research (2014)

Abstract Introduction CXC chemokine receptor 4 was found dys-regulated in many different types of human cancers and correlated with poor prognosis of tumor metastasis and resistance to chemotherapy. Limited data show the effect of CXCR4 on the esophageal carcinoma cells, especially with influence of chemotheraputuc reagent-cisplatin. Methods CXCR4 was detected by FACs analysis in esophageal cell lines OE19, OE21, OE33, PT1590 and LN1590. Corronsponding cisplatin resistant cells were established after selection of cisplatin treatment and further confirmed by IC50 and ERCC1. SDF-1α and AMD3100 were used as CXCR4 stimulattion or inhibition. Subcutanous model of OE19 injection in Balb/c nude mice was established and followed by treatment with cisplatin twice a week via i.p injection. Tumors were collected for the further evaluation. Results Esophageal cell line OE19, PT1590 and LN1590 have detetable amount of CXCR4+ subpopulation cells as high as 2.8%±0.9, 0.7%± 0.9 and 1.0%±0.6, respectively. OE19, PT1590 and LN1590 cisplatin resistant subline displayed increased IC50 value of 48h cisplatin treatment from 6.0±1.3 to 12.2±1.0, 1.4±0.7 to 9.1±0.7 and 1.4±0.6 to 7.2±0.6 ug/ml along with a significant overexpression of ERCC1. Interestingly only OE19 and LN1590 cisplatin resistant cell lines showed a significant enreichment of CXCR4+ cells ( 12.1%± 2.5 Vs 2.8%±0.9; 4.2%± 1.1 Vs1.0%±0.6, p&amp;lt;0.05) as compared to parental cells. Meanwhile, side population cells were also increased in those cisplatin resistant variants. There is no difference on tumor weight in control group and cisplatin treatment group in vivo. The relative expression of CXCR4 will be further evaluated by realtime PCR on mRNA level and IHC on protein level. Conclusion Overexpression of CXCR4 is significantly associated with cisplatin-based chemotherapy resistance and might be a prognostic factor in esophageal cancer. Inhibition of CXCR4 might be a strategy to address the chemoresistance of EAC cell lines. Citation Format: Yue Zhao, Yan Wang, Christiane Bruns. The potential role of CXCR4 in cisplatin associated resistance in esophageal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3751. doi:10.1158/1538-7445.AM2014-3751
Fortnightly Review: Diagnosis and management of migraine
Authors: P. J Goadsby, J. Olesen
Journal: BMJ (1996)

<h3>Summary points</h3> Before a primary headache such as migraine is diagnosed, secondary headaches should be considered and eliminated on clinical grounds or by appropriate investigations Migraine is primarily diagnosed by eliciting a history of episodic headache with characteristic associated features. The use of diagnostic headache diaries and simple calendars is strongly encouraged Optimum treatment of migraine requires explaining the problem to the patient and identifying and avoiding precipitating factors Treatment may be non-pharmacological or pharmacological. Drugs may be for treating acute attacks, which is required by nearly all patients, or prophylaxis, which is used by patients with frequent severe attacks Treatment for an acute attack should result in mild or no headache by two hours after drug ingestion, while prophylactic treatment should result in a 50% reduction in the frequency of attacks Characterisation of the 5-hydroxytryptamine receptor of the 5-HT1 class has provided better treatments for acute attack and impetus for studying mechanism of migraine
Molecular biomarker analyses using circulating tumor cells
Authors: Siminder K. Atwal, Daniel Chen, Mark Lackner, Elizabeth Punnoose
Journal: Clinical Cancer Research (2010)

Abstract Background: Evaluation of cancer biomarkers from blood and other accessible tissues could significantly enable biomarker assessment by providing a relatively noninvasive source of representative tumor material. Circulating tumor cells (CTCs) isolated from blood of metastatic cancer patients hold significant promise in this regard. Methodology/Principal Findings: Using a tumor-cell spike-in model system we evaluated CTC capture on different CTC technology platforms, including CellSearch® and two biochip platforms, and used the isolated CTCs to develop and optimize assays for molecular characterization of CTCs. We report similar performance for the various platforms tested in capturing CTCs, and find that capture efficiency is dependent on the level of EpCAM expression. We demonstrate that captured CTCs are amenable to biomarker analyses such as HER2 status, qRT-PCR for breast cancer subtype markers, KRAS mutation detection, and EGFR staining by immunofluorescence (IF). We demonstrate that cell surface expression of EGFR can be quantitated in CTCs from metastatic lung cancer patient samples. In addition, we determined HER2 status by IF and FISH in CTCs from metastatic breast cancer patients and in the majority of patients (89%) found concordance with HER2 status from patient tumor tissue, while in a subset of patients (11%), HER2 status had changed from the primary tumor at diagnosis. Surprisingly, we found CTC counts to be higher in ER+ patients in comparison to HER2+ and triple negative patients despite their more aggressive phenotype. This may be explained by our findings that the basal-like molecular subtype of breast cancer has low EpCAM expression and a more mesenchymal phenotype and CTCs will likely not be efficiently captured using EpCAM alone in tumors that arise from this subtype. Conclusions/Significance: Our data suggests that molecular characterization from captured CTCs is possible and can inform us of the patients’ current biomarker status. In this regard, CTCs hold significant promise as a source of tumor material to facilitate clinical biomarker evaluation. However, limitations exist from a purely EpCAM-based capture system and addition of antibodies to mesenchymal markers in addition to EpCAM could further improve CTC capture efficiency to enable routine biomarker analysis from CTCs.
Stable expression of human cytochrome P450 1A1, human NADPH-cytochrome p450 reductase and single copy of human N-acetyltransferase-2 in DNA nucleotide excision repair-deficient Chinese hamster ovary cells
Authors: Shuang Zhao, Christopher States, David W. Hein
Journal: Cancer Research (2004)

1536  N-acetyltransferase-2 (NAT2) plays an important role in the metabolic activation of many promutagens, procarcinogens, and drugs. Genetic polymorphism has been identified for human NAT2. To investigate the role of human NAT2 polymorphism on genotoxicity from aromatic and heterocyclic amine carcinogens, DNA nucleotide excision repair-deficient Chinese hamster ovary cells (UV5) were constructed for stable expression of human cytochrome P4501A1 (CYP1A1), human NADPH-cytochrome P450 reductase, and a single copy of human NAT2*4 (rapid acetylator) or human NAT2*5B (slow acetylator) allele. This study describes the construction of these cell lines. Briefly, full length cDNAs, encoding human CYP1A1 and human NADPH-cytochrome P450 reductase, were cloned into the bicistronic mammalian expression vector pIRES (Clontech). After sequence confirmation, the plasmid was transfected into nucleotide excision repair-deficient UV5 cells. Individual geneticin resistant colonies were selected and measured for the CYP1A1-dependent ethoxyresorufin dealkylation activity. The Flp-In expression system (Invitrogen) was used to express the single copy of human NAT2 into newly established UV5 cells expressing human CYP1A1 (UV5CYP1A1). This Flp-In expression system allows expression of a single copy of target gene at a specific genomic location, thus eliminating the potential expression variations due to the chromosomal position effect and unknown copy number of the cDNA. Briefly, pcDNA5/FRT plasmid containing human NAT2*4 or NAT2*5B coding region was transfected into UV5CYP1A1 cells, and cells were selected for hygromycin B. Experiments were performed to confirm that only a single copy of NAT2 gene was integrated and expressed at same chromosomal position in the cells. NAT2 mRNA levels and catalytic activities were determined for the cells expressing human NAT2*4 or NAT2*5B. The results showed that cells containing a single copy of NAT2 exhibited measurable sulfamethazine NAT2 activity whereas untransfected cells did not. The expression levels of NAT2 mRNA were equivalent among the cells containing a single copy of NAT2*4 or NAT2*5B. In contrast, sulfamethazine NAT2 activity in the cells containing a single copy of NAT2*4 was ∼10-fold higher than in the cells containing a single copy of NAT2*5B. These cell lines should be useful tools to study human NAT2 polymorphism and its effects on aromatic and heterocyclic amine genotoxicity. Partially supported by USPHS grant CA-34627 from the National Cancer Institute and a grant from Philip Morris, Inc.