tbuckley/cabot-search huggingface dataset:
Expression of CD133, a possible marker for cancer stem cells (CSCs), in small cell lung cancer (SCLC) cell lines and non- small cell lung cancer (NSCLC) cell lines
Authors: T. Hayashi, H. Tao, M. Jida, T. Kubo, H. Yamamoto, H. Otani, Y. Sano, S. Toyooka
Journal: Journal of Clinical Oncology (2009)

e22100 Background: Cancer stem cell (CSCs) are believed to play important roles in tumor development, recurrence or metastasis. Identification of CSCs may have a therapeutic significance. CD133 expression has been shown on a minority of various human cancer cells with high capability of self-renewal and proliferation. Therefore, CD133 is thought to be one of possible markers for CSCs. Regarding human lung cancers, the existence, prevalence or roles of CD133 positive cells has not been fully understood. Methods: We examined CD133 mRNA by quantitative real-time PCR and sorted CD133-positive cells by fluorescence-activated cell sorting (FACS) using human small cell lung cancer(SCLC) and non-small cell lung cancer (NSCLC) cell lines. We evaluated differences of cell proliferation between CD133-positive and -negative cells by MTS assay in vitro and by subcutaneous injection for non- obese diabetic/severe combined immunodeficiency (NOD/SCID) mice in vivo. Results: CD133 expression was almost restricted in SCLC cell lines. CD133 mRNA expression or CD133-positive cell population was scarcely observed in NSCLC cell lines. In two SCLC cell lines examined (NCI-H82 and NCI-H69), CD133 positive cells had higher tumorgenicity both in vivo and in vitro than NSCLC cell lines. Conclusions: The expression status of CD133 is totally different between NSCLCs and SCLCs, probably reflecting the difference of these progenitor cells. Our results indicate that CD133-positive cells in SCLC cell are responsible for tumor growth. However, in view of their wide prevalence, CD133-positive cells do not seem to be a candidate for CSCs, at least in cell lines. To investigate the molecular and functional characteristics of CD133-positive cells may lead to a new therapeutic strategy for human lung cancers, especially for SCLCs. No significant financial relationships to disclose.
Relationship of treatment-emergent symptoms and recurrence-free survival in the NCIC CTG MA.27 adjuvant aromatase inhibitor trial.
Authors: V. Stearns, J. W. Chapman, C. X. Ma, M. J. Ellis, J. N. Ingle, K. I. Pritchard, G. T. Budd, M. Rabaglio, G. W. Sledge, A. Le Maitre, J. Kundapur, L. E. Shepherd, P. E. Goss
Journal: Journal of Clinical Oncology (2011)

525 Background: New vasomotor or joint symptoms within 3 months of initiating either tamoxifen or anastrozole in the ATAC trial predicted superior recurrence-free survival (RFS). We hypothesized that women treated with anastrozole (A) or exemestane (E) in NCIC CTG Trial MA.27 who developed new or worsening vasomotor or joint symptoms would have improved RFS. There was no evidence of this correlation at the second interim analysis. We now report results by treatment arm from the final analysis. Methods: 7,576 ER+ postmenopausal women with early breast cancer were accrued to MA.27. Final analysis revealed no significant differences between A and E in the primary endpoints, event free or overall survival. We examined the effect of emergent vasomotor and joint symptoms 3 and 12 months following treatment initiation with A and E on subsequent RFS events excluding non-breast cancer deaths. We examined associations of symptoms with patient characteristics using chi-square tests, and associations of early symptoms and disease outcomes using stratified log-rank and stratified univariate and multivariate Cox modeling. Results: Of 4,812 women who were asymptomatic at baseline, 53% experienced new symptoms at 12 months; the RFS stratified univariate Cox hazard ratio (HR) for new symptoms was 0.84 (95% CI, 0.652-1.093). With all 7,246 evaluable women included, 53% of women developed new or worsening symptoms at 12 months and RFS was not statistically significant between women with or without new or worsening symptoms (HR 0.928, 95% CI, 0.755-1.142). Higher T stage (p<0.001) and more fractures prior to allocation (p=0.01) were associated with worse RFS. Only 5% of women reported new or worsening symptoms at 3 months, which were not associated with outcome. Drug assignment did not influence new or worsening symptoms. Conclusions: In contrast to findings in the ATAC trial, we did not observe an association between emergence of symptoms at either 3 or 12 months with improved RFS. Until prospective data are available, clinicians should not use treatment-emergent symptoms to counsel their patient whether to continue, or change, their prescribed adjuvant AI. PG is supported in part by the Avon Foundation NY.
Epidermal Papillomas in the Flathead Sole, &lt;italic&gt;Hippoglossoides Elassodon&lt;/italic&gt;, With Notes on the Occurrence of Similar Neoplasms in Other Pleuronectids&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S. R. Wellings, R. G. Chuinard, R. T. Gourley, R. A. Cooper
Journal: JNCI Journal of the National Cancer Institute (1964)

Numerous fish of many species were collected in the waters of the San Juan Islands, Washington, from July, 1963, to July, 1964. Surface tumors were observed only in the Pleuronectidae. In the flathead sole, Hippoglossoides elassodon, there were 281 tumor-bearing fish in a total collection of 4,364 fish (6.4% tumor incidence). Isolated instances of similar neoplasms in 3 other pleuronectids were reported. In the flathead sole, the tumors originated in the 1st year of life as small, 1 to 2 mm, angiomatous proliferations of dermal connective tissue capped by a layer of hyperplastic epidermis. These lesions were given a descriptive name: angioepithelial nodules. Some angioepithelial nodules developed into typical epidermal papillomas near the end of the 1st year of life. Simultaneously, the dermal angiomatous component usually regressed. The epidermal papillomas spread to cover extensive portions of the fish, including body, fins, eyes, and gills. The number of tumors (both angioepithelial nodules and epidermal papillomas) per fish was highest in the 1st year of life (1–23), less in the 2d year (1–5), and least in the 3d year (1–2). No tumors were observed in flathead sole older than 4 years. Angioepithelial nodules were never seen on older fish with large epidermal papillomas. No new tumors of either kind ever appeared de novo on numerous normal and tumor-bearing fish of all age groups kept alive in the laboratory for 1 to 8 months. Although tumors occurred on any portion of the outer surface, there was a significant tendency for them to be located on the pigmented (right) side. The high frequency of natural occurrence of epidermal papillomas in the flathead sole is a striking feature of the data.
Selective killing of hypoxic tumor cells by water soluble analogs of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119)
Authors: Michael F. Belcourt, Xu Kevin Lin, Li-Mou Zheng, Jing Du, Qin Wang, Louis Bai Song, Lanzhen Liu, Ala Nassar, Caroline Clairmont, Ivan King
Journal: Cancer Research (2005)

5888   Eradication of solid tumors requires strategies that address the viable populations of malignant cells within hypoxic regions of such tumors. An insufficient and poorly organized vasculature, a major characteristic of rapidly growing tumor masses, results in poor oxygenation, high interstitial pressure, and a population of cells that are hypoxic, quiescent or slowly cycling, and distal to the blood supply, thus being difficult to reach with cytotoxic levels of drugs. After treatment with oxygen-dependent cytotoxins such as x-irradiation and conventional chemotherapeutics that target the well oxygenated, rapidly growing portion of the tumor mass, the resistant hypoxic cell fraction can repopulate the tumor. Oxygen concentrations in human tumors vary considerably, with many regions measured at an oxygen partial pressure of less than 5 mmHg (less than 0.7% oxygen). Prodrugs that act as hypoxia-selective cytotoxins generally must be substrates for one electron reductases such as NADPH:cytochrome (P450) reductase. KS119 readily undergoes enzymatic one electron nitro reduction, yielding a nitro radical anion that, in the presence of oxygen, is rapidly oxidized to regenerate the parental molecule. However, under hypoxic conditions, the reaction cascade liberates the DNA alkylating species 90CE (1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine). The selective toxicity of KS119 and its water soluble analog KS119W to hypoxic cells was evaluated with EMT6 murine mammary carcinoma cells exposed to graded concentrations of drug at 0.1% oxygen for two hours or graded concentration of oxygen at fixed concentrations of drug. The results indicate that KS119 and KS119W selectively kill hypoxic cells, producing 4-5 logs of cell kill at 0.1% oxygen and pharmacologically relevant concentrations (10-25 μM) of drug. Moreover, both drugs are active at a broad range of sub-physiological oxygen concentrations that are relevant to hypoxic regions of human solid tumors with virtually no cell kill at normal, physiological levels of oxygen. Both drugs are more cytotoxic to hypoxic Chinese Hamster ovary cell lines overexpressing human NADPH:cytochrome (P450) reductase, suggesting that this enzyme contributes to the bioreductive activation of these agents.
Bronchoscopic trans-parenchymal nodule access (BTPNA) – A new real-time image-guided approach to accessing solitary pulmonary nodules (SPNs) - First in human data
Authors: Felix J.F. Herth, Daniela Gompelmann, Hans Hoffmann, Dan Sterman, Gerard Silvestri, Pallav Shah, Ralf Eberhardt
Journal: European Respiratory Journal (2014)

Background: There is a need for improving the bronchoscopic yield in accessing small SPNs, especially in the age of screening.  PURPOSE: BTPNA is a new imaging guided technique. After calculating a straight line path from an airway wall entry point (POE) to the lesion, an access sheath is fluoroscopically guided through the lung tissue to the lesion. The safety and yield in the first human trial will be presented.  METHODS: In patients highly suspicious for NSCLC, BTPNA was performed before surgery. Based on HR-CT scan, modified LungPoint software calculated and displayed a POE and prescribed a straight-line path through parenchymal tissue to the lesion. With the scope appropriately positioned, a needle pierces the POE. A balloon catheter enlarges the opening and a sheath is advanced through it. The sheath and a 15 gauge stylet are advanced to the target lesion under fused CT/fluoroscopic guidance. Once the lesion is reached biopsies are taken.  RESULTS: In 12 humans, 10 total tunnels have been created, ranging from 10 to 90 mm in length (mean 4.7 mm). The mean lesion size was 2.6 cm (R 1.7-4.0 cm). The yield was 83% (10 out of 12). The two undiagnosed lesions were both in the apices and not reachable due to an angulation limitation by the scope. There were no pneumothoraces or clinically significant bleeding in the humans. The mean procedure time was 22 min. (R 12-40 min). All surgical procedures were performed without any limitations.  CONCLUSIONS: In the first in human trial, it was shown that BTPNA could be performed without any complications and a high success rate. These results must be repeated in larger trials.
99mTc-GHA Brain SPECT in the evaluation of brain tumors
Authors: B. R. Mittal, A. Bhattacharya, B. Singh
Journal: Journal of Clinical Oncology (2005)

1549 Background: Brain tumors are of diverse histological types, the most common being from glial tissue. The clinical management and prognosis of brain tumor patients is dependent on accurate neuro-pathologic diagnosis and grading. CT scan though provides accurate information about location of the tumor. MRI may be helpful in classifying the grade of tumor. Radionuclide imaging techniques using of Tl-201 SPECT and 18F-FDG PET studies have been widely reported to evaluate malignant lesions. 99mTc-GHA (Glucoheptonate), more or less analogous to 18F-FDG, may show increased glucose metabolism and help in grading tumors. Methods: We studied 29 patients (17 M, 12 F) aged 13–60 years (35.7 ± 12.4) of brain tumors by Tc99m-GHA Brain SPECT, performed 40 min and 3 hours after radiotracer administration. Reconstruction of the SPECT data was done using standard software. Abnormal concentration of tracer at the tumor site was compared to normal uptake on the contralateral side, and ratios obtained for early (40 min) and delayed (3 hours) uptake of tracer. Retention ratio (RR), was then calculated, and compared with the final histological diagnosis. Results: Of the 29 patients studied, 13 were histologically low-grade [WHO grade] tumors while 16 were high-grade tumors. On scintigraphy, no tracer uptake was noticed in 5, very low uptake in 8, moderate uptake in 6 and very high uptake in 10. RR of all the tumors ranged from 0.72 - 1.39. Low-grade gliomas (grade II) showed a lower RR (0.72 - 0.97) (mean 0.85 ± 0.10), while high-grade gliomas (grade III/IV) had a higher RR (1.03 - 1.29) (mean 1.11 ± 0.07). On histopathological correlation, it was found that the RR at a threshold of 1.0 yielded the maximum accuracy for discriminating between low (grade I/II) and high-grade (III/IV) gliomas. This corresponded to a sensitivity of 90%, a specificity of 55.5% and an overall predictivity of 82.6% of 99mTc-GHA SPECT imaging for grading of cerebral gliomas. Conclusions: This study suggests that Tc99m-GHA SPECT with early and delayed imaging is a good indicator of brain tumor activity and may prove to be an economical and efficient technique for grading of glial tumors of the brain. It may further be hypothesized that Tc99m-GHA demonstrates the actual metabolic activity of these tumors. No significant financial relationships to disclose.
Preferences for and expectations about experimental therapy among participants in randomized trials
Authors: S. Joffe, M. Stumacher, J. W. Clark, J. C. Weeks
Journal: Journal of Clinical Oncology (2006)

6013 Background: Equipoise is often viewed as the ethical precondition for randomized controlled trials (RCTs). Equipoise is usually defined as a state of uncertainty or disagreement among expert clinicians, but some ethicists argue instead that individual participants should be indifferent between the study arms. The degree to which cancer RCT participants have preferences for either arm is not known. Methods: Adults who had enrolled in a 2-arm RCT at a Dana-Farber/Harvard Cancer Center institution within 21 days were eligible. A mailed questionnaire asked about treatment assignment, treatment preference, and expectations about the relative efficacy and toxicity of the 2 arms. The primary analysis was a goodness-of-fit chi-square test of the null hypothesis that equal proportions of respondents would prefer the standard vs. investigational arm. Results: 82 of 126 RCT participants (65%) responded. 31 (38%) were assigned to the standard arm, 26 (32%) were assigned to the experimental arm, and 25 (30%) were enrolled in blinded trials. Respondents tended to prefer assignment to the experimental rather than the standard arm (p = 0.006), and expected the investigational arm to be more effective than the standard arm (p = 0.0004). Respondents did not consistently expect that either arm would be more toxic ( Table ). Conclusions: Cancer RCT participants tend to prefer the experimental arm. Thus either the design of cancer RCTs must be altered to accommodate participant preference, or individual-participant equipoise must be abandoned. [Table: see text] No significant financial relationships to disclose.
Ultrasound (US) and ultrasound guided fine needle aspiration cytology (FNAC) reduces surgical procedures, sentinel node (SN) dissection in melanoma patients and reliably predicts lymph node involvement in cutaneous lymphoma patients
Authors: C. A. Voit, T. Mayer, G. Schäfer, S. Gellrich, M. Kron, W. Sterry, M. Schwürzer, A. Schoengen
Journal: Journal of Clinical Oncology (2005)

7537 US is a screening tool for detection and estimation of lesions occurred after spread of tumor cells. Based on the sonographer’s decision FNAC is used for confirmation of suspicious lesions. The combination was tested as diagnostic standard for verification of tumor spread in melanoma pts., melanoma sentinel nodes (SN) and cutaneous lymphoma patients. Between 1984 and 2004 835 American Joint Committee on Cancer staged melanoma patients underwent a FNAC to verify lesions detected by US. In 635 pts. data are confirmed by long time follow-up. In these 1419 FNACs diagnosis could be established with a sensitivity (Se) of 97.9% (95%CI: [96.8%;98.7%]), a specificity (Sp) of 99.8% (95%CI: [98.8%;99,9%]), a positive predictive value (ppV) of 99.9% (95%CI: [99.4%;100%]) and a negative predictive value (npV) of 95.7% (95%CI: [93.5;97.4%]). FNAC was performed within one day of sampling in an outpatient setting without side effects. Diagnosis of lesions < 6mm diagnosis could be verified with a sensitivity of 96.6% (95%CI: [90.3;99.3%]) and a specificity of 100% (95%CI: [89.4;100%]). In a second study testing the clinical applicability for predicting SN involvement following melanoma diagnosis, covering 121 patients, FNAC was performed in patients with suspect findings in ultrasound. US took place prior to SLND without knowing patients’ tumor data. 15/21 histologically/immunohistologically proven involved SNs have been detected by the combination of US/FNAC. 6/121 examinations have been false negative, with 3 of the 6 escaped SNs showing few and only immunohistologically positive cells. Thus a 12,4% (15/121) reduction of SLND procedures was obtained omitting the SLND and proceeding directly to a lymph node dissection. Maximum asymmetrical cortex thickness combined with irregular hypervascularization turned out to be the most important feature to predict SN involvement. Data will be provided concerning a 5 years’ prospective study testing the value of US in predicting LN involvement of 260 patients with cutaneous lymphoma. No significant financial relationships to disclose.
Gangliosides of Liver Tumors Induced by N -2-Fluorenylacetamide. I. Ganglioside Alterations in Liver Tumorigenesis and Normal Development 2
Authors: William D. Merritt, Carol L. Richardson, Thomas W. Keenan, D. James Morré
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Gangliosides of Liver Tumors Induced by N-2-Fluorenylacetamide. I. Ganglioside Alterations in Liver Tumorigenesis and Normal Development Get access William D. Merritt, William D. Merritt Search for other works by this author on: Oxford Academic PubMed Google Scholar Carol L. Richardson, Carol L. Richardson Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas W. Keenan, Thomas W. Keenan Search for other works by this author on: Oxford Academic PubMed Google Scholar D. James Morré D. James Morré 10 10Address reprint requests to Dr. Morré, Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, Ind. 47907. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 6, June 1978, Pages 1313–1327, https://doi.org/10.1093/jnci/60.6.1313 Published: 01 June 1978 Article history Received: 09 March 1977 Revision received: 29 November 1977 Accepted: 12 December 1977 Published: 01 June 1978
Role of EGFR but not HER2 or HER3 gene copy number in predicting sensitivity of head and neck squamous cell carcinoma (SCCHN) cell lines to EGFR tyrosine kinase inhibitors
Authors: M. Varella-Garcia, K. Acheson, G. B. Marshall, R. M. McCormack, A. Ryan, F. R. Hirsch, P. A. Bunn, D. M. Hickinson, G. Speake
Journal: Journal of Clinical Oncology (2007)

6063 Background: EGFR gene copy number has previously been reported to predict for improved overall survival in NSCLC patients treated with gefitinib (IRESSA) or erlotinib compared with placebo [JCO 2006;24:5034–42 &amp; N Engl J Med 2005;353:133–44]. The utility of EGFR gene copy number as a predictive biomarker in other tumour types such as squamous cell carcinoma of the head and neck (SCCHN) is currently under clinical investigation. The present study examined a panel of 20 SCCHN cell lines to identify potential biomarkers predicting in vitro sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Methods: A panel of 20 SCCHN cell lines was screened for sensitivity to gefitinib, vandetanib or erlotinib using a viable cell number endpoint, with G150 values determined for each cell line (inhibitor concentration required to give 50% growth inhibition). Cell lines were blinded and assessed for EGFR, HER2 and HER3 protein expression by ELISA, mutation status by dye-terminator sequencing, and gene copy number by fluorescence in situ hybridisation (FISH). Results: A broad range in sensitivity was observed for all compounds across the panel of 20 SCCHN cell lines (G150 ranging from 0.001uM to =10uM). 12 cell lines were positive for EGFR genomic gain. Sensitivity (GI50 &lt;1uM) to all EGFR TKIs was seen in 11 lines and resistance (GI50 &gt;8uM) in 5 lines. Of the sensitive cell lines, 9 were positive for EGFR genomic gain compared with only 1 of the resistant lines. Furthermore, EGFR protein expression also had a direct association with EGFR TKI sensitivity. In contrast, only 4 cell lines were positive for HER2 or HER3 genomic gain and there was no correlation with sensitivity. The most sensitive cell line was positive for EGFR genomic gain and was the only line to have an EGFR TK mutation (S768I in exon 20). Conclusions: EGFR gene copy number and protein expression appeared to have predictive value in identifying SCCHN cell lines sensitive to EGFR TKIs. No significant financial relationships to disclose.
Aerobic training decrease bronchial hyperresponsiveness and systemic inflammation in patients with moderate or severe asthma: A randomized controlled trial
Authors: Celso R.F. Carvalho, Andrezza França-Pinto, Felipe A.R. Mendes, Rafael Stelmach, Alberto Cukier, Rosana C. Agondi, Milton A. Martins, Beatriz M. Saraiva-Romanholo, Jorge Kalil, Pedro Giavina-Bianchi
Journal: European Respiratory Journal (2014)

Background:  Aerobic training (AT) improves physical capacity and clinical control in asthmatics; however, its benefits on the main features such as bronchial hyperresponsiveness (BHR) and inflammation remain unknown. We investigated the effects of AT on BHR (primary outcome) and systemic inflammation.   Methods:  Fifty-eight adults with asthma were recruited in a University hospital (34 female, 42±10 years, FEV 1 =76.8±21.4 %predicted) and were randomized into either Control (CG) or Trained groups (TG). Patients in the CG (educational program + breathing exercises, n=28) and TG (same CG + AT, n=30) were examined 2/wk during a three months period with no change in corticosteroid dosage. Serum cytokines, BHR (PC 20  doubling dose, dd), induced sputum, exhaled nitric oxide (eNO), clinical control, and cardiopulmonary exercise testing were evaluated before and after the intervention. The sample size of 34 patients was calculated based on difference of 1dd of PC 20  with a 1 standard deviation.   Results : The TG increased 1dd (0.3-1.7dd, 95%IC)  vs.  0.06dd (-0.6-0.7dd, 95%IC) in CG (p=0.04) and also decreased IL-6 (305± 278  vs  68± 122 fg.mL -1 ), IL-8 (1.5± 0.3  vs  1.2± 0.3 pg.mL -1 ) and MCP-1 (21.0± 9.5  vs  16.9± 7.8 pg.mL -1 ) (p=0.01). Sputum eosinophil and FeNO decreased in patients from TG with higher levels of inflammation (eosinophil>3% or FeNO>26ppb) (p=0.01). Exercise training also reduced asthma symptoms and exacerbation (p=0.02).   Conclusion : Our results suggest that aerobic training decreases BHR and serum pro-inflammatory cytokines and improves clinical control in adults with moderate or severe asthma.