bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A21: Lung cancer surveillance with CT scan and autofluorescence bronchoscopy
Authors: Jayaprakash Vijayvel , Loewen Gregory , Mahoney Martin , Moysich Kirsten , Yendamuri Saikrishna , Hutson Alan , Hogarth Kyle , Menezes Ravi , Mary Reid 
Published: May 2012

Abstract
Background: More than 75% of lung cancer patients are diagnosed at an advanced stage, when the survival rate is less than 15%. Sputum cytology, x-ray and CT scan have been evaluated as screening tools for early lung cancers, without much success. Auto-fluorescence bronchoscopy (AFB) has been recently shown to be effective in diagnosing central bronchial cancers. Combined surveillance with both spiral CT scan and AFB might help to increase the detection rate of the both central and peripheral lung cancers.
Methods: The study included 205 patients who were enrolled in the High Risk Lung Cancer Surveillance Cohort at Roswell Park Cancer Institute (RPCI) with at least 2 of the following risk factors: (1) radiographically documented pulmonary asbestosis or; (2) a history of previously treated aero-digestive cancer or; (3) &gt; 20 pack years smoking history or; (4) COPD with an FEV1 &lt; 70% of predicted. Patients underwent spirometry testing, chest X-ray, sputum cytology, non-enhanced low dose spiral CT scan of the chest, and conventional white light/AF bronchoscopy with biopsy.
Results: A total of 20 invasive cancers/CIS were diagnosed in the 205 patients. Seven were diagnosed at baseline, 4 within 1 year of enrollment and 9 on follow up of more than 1 year. Between them, AFB and CT scan diagnosed all baseline cancers. Only 3/7 cancers were detected on x-ray screening and only 1/7 patients demonstrated atypia on sputum cytology. Overall, 17 invasive cancers and 3 CIS were diagnosed during the surveillance study. All the 3 CIS were identified only on AFB. Of the 17 invasive cancers, CT scan detected 15 cancers (88%) and AFB detected 5 of these cancers (30%). CT scan showed a 67% relative increase in sensitivity for detecting prevalent cancers and 3 times greater sensitivity for incident and prevalent cancers compared to x-ray screening. CT scan and AFB detected 19 of the 20 CIS/cancers (95%), whereas x-ray and sputum cytology together detected only 5/20 CIS/cancers (25%). The sensitivity of CT scan and AFB in diagnosing pre-malignant lesions and cancers improved by almost two and half times relative to x-ray and sputum.
Conclusion: The addition of AFB exam to yearly spiral CT scan of the chest could be a more efficient surveillance tool to identify early stage lung cancers, both in the central and peripheral lung. A greater efficiency and cost effectiveness can be achieved by limiting the use of the combination of AFB and CT scan in very high risk patients, selected based on their exposures and risk factors.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A21.
Abstract A22: Spirometric surveillance for premalignant and malignant bronchial lesions
Authors: Jayaprakash Vijayvel , Loewen Gregory , Dhillon Samjot , Mahoney Martin , Delgado Machare , Menezes Ravi , Bogner Paul , Yendamuri Saikrishna , Hogarth Kyle , Mary Reid 
Published: May 2012

Abstract
Background: Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are diseases that share common risk factors. It has been reported that more than half of the patients diagnosed with LC also suffer from COPD. Although COPD is a well known risk factor for LC, the relationship between impaired lung function (LF) and the incidence and progression of pre-malignant lesions (PMLs) in the central airways is still unclear.
Methods: The study included 217 high-risk patients from a hospital-based lung cancer surveillance cohort who underwent bronchoscopy with endobronchial biopsy of suspicious lesions, at the Roswell Park Cancer Institute, Buffalo, New York. All patients had lung function measurement within 6 months preceding their baseline biopsy. Baseline histopathology diagnoses included 91squamous metaplasia (SM), 25 squamous dysplasia (SD), 1 in-situ carcinoma and 5 invasive bronchial carcinoma. Follow-up bronchoscopy and biopsy were performed on 69 patients. Sixteen patients had a progression of the baseline lesion to a higher grade. The relationship between the baseline LF measures and the incidence and progression of PMLs were examined using regression models.
Results: Patients with forced expiratory volume in 1 second percent predicted (FEV1%) of &lt;50% had 4.5 times greater risk of being diagnosed with PML/cancer, when compared to patients with FEV1% ≥80. Increased risk was noted for all grades of PMLs and cancers, with the risk being almost 8 times for squamous dysplasia [Odds ratio = 7.95; 95%confidence interval (CI) =1.77–35.6]. Similarly, FEV-1/FVC ratio of &lt;50% was associated with 3 times greater risk of detecting a PML/cancer. When COPD was classified based on GOLD criteria, the patients with severe COPD had 2.7 times and 4.8 times greater risk of being detected with SM and SD, respectively. The risk persisted for SD even when an age standardized classification was used to define COPD. COPD patients also had a non-statistically significant 2.5 times greater risk of their baseline lesion progressing to a higher grade [Hazard Ratio 2.48 (95% CI 0.65 – 9.41), p-value - 0.18)]. The mean time to progression from a lower grade lesion to a higher grade was 27 months for patients with COPD and 50 months for patients without COPD.
Conclusion: Impaired LF can be a good predictor of occurrence and progression of PMLs in central airways of high risk patients. Spirometric measurement of lung function can be used as an additional tool for identifying target populations in need of more aggressive LC surveillance.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A22.
Abstract A23: PSA testing and prostate cancer mortality in an Asian population: Linking prevalence of elevated PSA and mortality rate
Authors: Chiang Po-Huang , Wen Chi-Pang 
Published: May 2012

Abstract
Background: In Asian populations, prostate cancer mortality (PCM) has been increasing with the increasing use of PSA testing.
Objectives: 1) To establish prevalence of elevated PSA at different cutpoints in Taiwan and to assess the predictive relationship of PSA with PCM. 2) To compare PCM between those with PSA tested and not tested from a cohort study.
Methods: Among the cohort, 231,937, who received standard medical screening examination between 1994 and 2006 at a private screening clinic, 46,951 subjects, aged at least 50 years old, had PSA test results. Age and education were adjusted to those of Taiwan to arrive at national PSA prevalence. PCM was compared between the PSA untested (38,596) and PSA tested group (24,176), with the latter including those with a self-reported history of prostate cancer (1,675).
Results: National prevalence of PSA was 8.8% (threshold at 4) and 1.9% (threshold at 10). With national mortality rate at 30.1/100,000, the chance of dying in ten years was 3.4%, 15.8% or 27.9% among those above threshold at 4, 10, or 15, respectively, yielding false positives rates, with mortality as the outcome, 96.4%, 84.2% or 72.1%, and false negative rates, 12%, 33% or 50%, respectively. Having PSA tested, when compared with not tested, was not associated with decreased mortality from prostate cancer, even though PSA tested group, a higher educational class, had significantly decreased mortality from all cause. Increasing PSA levels were associated with increasing HRs.
Conclusion: PSA value above standard threshold of 4 is common in this Asian population (one out of 11 for age 50 and older), but only one in 29 tested positive was expected to die from prostate cancer within the next 10 years. This 10-year probability increased when threshold was 10 (1/6) but was still low. The high false positive rate of PSA (97%) and the harm associated with intervention among Asians should be communicated to the elderly patients, in view of the particularly low mortality rate of this cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A23.
Abstract A28: Improving detection through SELF (selective excitation light fluorescence) imaging
Authors: MacAulay Calum , Khojasteh Mehrnoush 
Published: May 2012

Abstract
The use of fluorescence imaging and spectroscopy for the detection of early neoplastic epithelial lesions has been well established, with clinically adopted devices in for use in the lung (Onco-LIFE, SAFE-1000, etc), the oral cavity (VELScope and Identaf 3000) and others in development for the cervix and dermatology. Primarily these imaging technologies make use of fluorescence excitation illumination of a single wavelength (predominately in the near UV to blue wavelength ranges) and differentiate between normal and not normal tissue based upon intensity changes and spectral shifts in the emitted tissue autofluorescence (not normal -darker with less green or blue relative the red fluorescence).
SELF imaging makes use of a multitude of illumination wavelengths to specifically couple to the action spectra of the fluorophores within the tissue to enhance the differentiation between tissue states, fluorophores and their immediate environment. This methodology makes use of the different absorption spectra (action spectra) of different fluorophores or similar flourophores in different environments. Conventionally this can be done through the sequential illumination with many different excitation wavelengths and sequential image capture, to collect a hyperspectral excitation image data cube followed by some form of spectra unmixing to resolve the individual targets (components) contributing to the image. Each target is identified by a unique weighted sum of pixel intensities across the excitation wavelengths in the data cube.
Through the use of a programmable light source such as the OneLight (OneLight Corp.) in which not only the wavelengths of the illumination light, but their individual intensities (alone or in combination) can be selected under computer control it is possible to not only rapidly illuminate with separate excitation wavelengths but to illuminate with a collection of weighted (each wavelength has a different selected intensity) spectra to specifically couple to selected fluorescence targets (specific fluorophores or fluorophores in specific local environments). Thus instead of needing to illuminate with a series of 10 separate excitation wavelengths and collect separate 10 images on can illuminate with a few (2–3) weighted profiles of excitation wavelengths and collect a few (2–3) images, the number of spectra used (images collected) determines the number of targets differentiated. In this fashion it is possible to detect in an image many more specific flourophore types than with conventional fluorescence imaging. SELF imaging in microscopy, wide field macroscopic imaging and ex vivo and in vivo imaging has been demonstrated and will be presented.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A28.
Abstract A29: Rectal mucosal polyamine and PGE2 levels and risk of colorectal adenomas in a phase IIb/III trial of combination difluoromethylornithine (DFMO) plus sulindac
Authors: Thompson Patricia A. , Wertheim Betsy C. , Zell Jason A. , LeFleur Bonnie , Chen Wen-Pin , McLaren Christine E. , Meyskens Frank L. , Gerner Eugene W. 
Published: May 2012

Abstract
Background: The pharmacologic targeting of polyamines and prostaglandin E2 (PGE2) has proven efficacy for colorectal adenoma prevention. However, the contribution of these analytes as biomarkers of drug response has not been investigated.
Methods: We analyzed the relationships between rectal mucosal levels of polyamines (spermidine, spermine, and putrescine) and PGE2, treatment, and risk of adenoma within the context of a phase IIb/III trial of combination difluoromethylornithine (DFMO) plus sulindac for the prevention of colorectal adenoma.
Results: We detected no differences in the change in PGE2 levels between the two groups for any time points, but we show a statistically significant decrease in spermidine:spermine levels and in putrescine levels in the DFMO/sulindac group at 12 and 36 months compared to the placebo arm. When we asked whether or not change in polyamine or putrescine levels was associated with adenoma recurrence in the treatment arm only, we found no difference in the rate of metachronous events by change in polyamine or PGE2 levels in the treatment arm. We also found no evidence that polyamine or PGE2 levels were associated with risk of adenoma when we restricted the analysis to the placebo arm only. Of interest, we found that participants with low baseline spermidine:spermine levels who received DFMO/sulindac achieved a significantly greater benefit from treatment (RR = 0.15, 95% CI = 0.06 to 0.40) than those with high baseline spermidine:spermine receiving drug (RR = 0.50, 95% CI = 0.27 to 0.92).
Conclusions: DFMO/sulindac significantly suppressed the production of rectal mucosal polyamines, but the magnitude of change was not predictive of response to intervention. This was likely due to the large effect of DFMO/sulindac on adenoma recurrence. We found no evidence in the placebo arm that baseline polyamine or PGE2 were associated with the risk of developing adenoma. The modulating effect of baseline spermidine:spermine levels on metachronous adenoma, in those individuals receiving the drug combination, provides evidence of differential agent-effectiveness by steady-state polyamine levels that should be investigated in future studies.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A29.
Abstract A3: MicroRNA-related polymorphisms are associated with clinical outcomes in early stage non-small cell lung cancer patients
Authors: Pu Xia , Lu Charles , Stewart David J. , Gu Jian , Hildebrandt Michelle A.T. , Lin Jie , Lippman Scott M. , Wu Xifeng 
Published: May 2012

Abstract
MicroRNAs (miRNA) can function as oncogenes or tumor suppressors. In this study, to test the hypothesis that genetic variation within miRNA processing genes or miRNA binding sites on cancer-related genes may alter clinical outcomes in non-small cell cancer (NSCLC) patients, we genotyped 77 single nucleotide polymorphisms (SNPs) from eight miRNA processing genes and 163 SNPs from 133 predicted miRNA binding sites in 598 patients with early stage (stage I, IIA and IIB) NSCLC to determine the effect of these variations on progression risk and overall survival. We further conducted a subset analysis to exclude potential bias due to different treatment regimens. We identified 37 SNPs associated with overall survival. In the surgery-only patients, 22 SNPs modulated overall survival, including FZD4:rs713065 that remained significant for decreased risk after multiple comparisons (HR: 0.53, 95% CI: 0.36–0.77). For progression risk, 21 and 25 SNPs were found to be significant in the entire and surgery-only patient populations, respectively. Following multiple comparison, ICAM1:rs281437 (HR: 1.80, 95% CI: 1.29–2.52) and MDM4:rs10900596 (HR: 2.01, 95% CI: 1.26–3.19) remained significant increase in progression risk, while FAS:rs2234978 (HR: 0.58, 95% CI: 0.41–0.80) displayed a significantly protective effect. CDC7:rs12125947 (HR: 2.19, 95% CI: 1.37–3.51) remained significant risk effect in the surgery-only patients. A strong cumulative, dose-effect of these variant genotypes to increase risk and dramatically decrease median event-free time was consistently observed. We also identified potential higher-order gene-gene interactions among these SNPs. With validation, our result can be used in the prognosis of clinical outcomes for early stage NSCLC patients.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A3.
Abstract A30: Cost-effectiveness analysis of HER2 testing methods in adjuvant treatment of HER2 breast cancer
Authors: Ashok Mahima , Griffin Paul , Halpern Michael 
Published: May 2012

Abstract
Background: Trastuzumab is a targeted therapy indicated for the treatment of HER2-postive breast cancers, an aggressive form of this disease. HER2 status can be assessed using two tests: florescence in situ hybridization (FISH), which tests for HER2 gene amplification; or immunohistochemistry (IHC), which tests for HER2 protein overexpression. There is considerable debate regarding which of these tests should be used for HER2 detection due to differences in cost, accuracy, and health outcomes.
Objective: To compare the outcomes and cost effectiveness of FISH and IHC for HER2 testing in breast cancer.
Design: Based on data from outpatient electronic medical records, decision models were designed for FISH, IHC and No Test scenarios (in which all patients received trastuzumab without being tested). Each model considered costs and health outcomes. Treatment possibilities included chemotherapy (with or without trastuzumab), radiation therapy, and surgery. Cost for trastuzumab adverse events were also included. Point estimate analysis and Monte Carlo simulations (varying false positive rates of tests) were used to determine results.
Data: A hypothetical cohort of 100,000 female breast cancer patients. Interventions: Testing with FISH or IHC followed by subsequent trastuzumab treatment when indicated (i.e., when the test result is positive for HER2), which included false positive and false negative results.
Outcome Measures: Medical costs, Quality Adjusted Life Years (QALYs) and percentage of patients correctly tested (true positives who test as positive and true negatives who test as negative).
Results: The expected per-patient costs of the No-test model, IHC model and FISH model were $166,360, $72,405, and $64,626 respectively. The expected values of total QALYs experienced by IHC and FISH groups were essentially identical. Using Monte Carlo analysis to vary test accuracy rates also indicated decreased costs and improved outcomes for FISH. In addition, FISH had increased levels of correct HER2 status detection when compared with IHC: if tested with FISH rather than IHC, there was a 3.58% increase in probability that a patient who is HER2 positive will be diagnosed as positive and a 15.66% increase in probability that a patient who is HER2 negative will be diagnosed as negative.
Conclusions: FISH should replace IHC as the preferred method of choice for HER2 testing. This would result in increased cost-effectiveness of testing and treatment for HER2 breast cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A30.
Abstract A31: The role of microRNA 125a-3P in the pathogenesis of lung cancer
Authors: Hazra Saswati , Gardner Brian K. , Krysan Kostyantyn , Walser Tonya C. , Brothers John , Larsen Jill E. , Pertsemlidis Alexander , Shay Jerry W. , Minna John D. , Spira Avrum , Dubinett Steven M. 
Published: May 2012

Abstract
Tobacco exposure results in specific oncogene and tumor suppressor gene alterations in lung epithelial cells that often lead to lung cancer development. Activating point mutation of the K-ras proto-oncogene is one of the most frequently occurring genetic changes found in lung cancer both in active and former smokers. Understanding how K-ras mutations mediate the malignant phenotype may yield more effective prevention and diagnosis strategies to be applied to individuals at elevated risk for lung cancer. Micro RNAs are a class of short (19–24 nucleotides) noncoding RNAs that play a critical role in posttranscriptional gene regulation. A rapidly developing literature supports an important role for micro RNAs in the regulation of lung carcinogenesis and tumor progression. In order to better understand the role of micro RNAs in the K-ras-mutated bronchial epithelium, we utilized hTERT- and Cdk4-immortalized human bronchial epithelial cells (HBEC) expressing mutant KrasV12. We next generated the micro RNA profile (TaqMan miRNA array v.2, Applied Biosystems, Foster City, CA), gene expression profile (Affymetrix U133 plus 2 array), and protein expression profile (50-plex inflammatory marker panel) of the K-ras mutated and vector control HBECs. We found that the micro RNA miR-125a-3p was significantly suppressed in K-ras-mutated HBECs compared to the vector control cells. We then evaluated basal expression of miR-125a-3p in both HBECs and NSCLC cell lines containing mutated K-ras by real time RT-PCR. Both K-ras-mutated HBECs and NSCLC cell lines expressed low levels of miR125a-3P. In order to further evaluate the role of miR-125a-3p, we stably expressed this micro RNA in K-ras-mutated HBECs. Our results indicate that miR-125a-3p expression down-regulates several tumor-promoting factors, including Gro-α, HGF, VEGF, GM-CSF, and G-CSF. Further studies revealed that suppression of Gro-α and HGF, but not VEGF, is regulated at the level of mRNA expression. Overexpression of miR-125a-3p suppressed proliferation of the K-ras-mutated HBECs but did not alter the proliferation of the vector control HBECs. Based on these findings, we anticipate that loss of miR-125a-3p may have a broad impact in the bronchial epithelium that harbors K-ras mutations, potentially regulating cellular proliferation, angiogenesis and inflammation. Further exploration is required to evaluate the role of this micro RNA and its downstream effects as potential screening tools and targets of prevention and therapy in the setting of K-ras-mutated lung cancers.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A31.
Abstract A37: Differential response of LH and hCG on ovarian granulosa cells
Authors: Gupta Chanchal , Chhabra Yash , Chapekar Trimbak , Sinha Subrata , Luthra Kalpana 
Published: May 2012

Abstract
LH hyperstimulation has been linked to conditions like PCOD and granulosa cell tumor. Chapekar had established a model of ovarian tumorigenesis by bilateral ovariectomy and splenic transplantation of ovaries, resulting in sustained LH levels because of absence of feedback inhibition. An in vitro model of the same phenomenon has resulted in goat ovarian granulosa cell line after exposure of primary granulosa cells to LH.
In this study, we have exposed primary ovarian granulosa cells to either hCG or LH in a sustained manner (4 weeks). We observed a marked difference in the morphology and growth pattern between the LH treated, hCG treated and untreated cells. LH treated cells were transparent, spindle shaped with elongated cell extensions. hCG treated cells were distinctly polygonal with shorter cell extensions, while untreated cells were smaller with fewer extensions and lesser in number as compared to the hormone treated cells. Functional characterization of the granulosa cells was done by estimation of progesterone in supernatant by ELISA. Levels of progesterone were similar in all three subsets in primary culture. The untreated and hCG exposed cells showed markedly reduced cell proliferation after the fourth week of exposure while LH treated cells were proliferating rapidly even after 4 weeks. There were marked differences in downstream signaling molecule cAMP after short term (5 days) and long term stimulation (two weeks) with LH and hCG. Intacellular cAMP was assessed by ELISA. On prolonged exposure to LH and hCG, level of cAMP was significantly higher in hCG treated cultures as compared to LH treated cultures. Elevated cAMP levels on hCG stimulation is known to promote apoptosis in cells.
This in vitro model system is suitable to study the effect of sustained hormonal stimulation on granulosa cells and can help in understanding the role of LH and hCG in etiology and pathogenesis of granulosa cell tumor which constitutes 1–2% of ovarian tumors.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A37.