bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B64: Pleomorphic lobular carcinoma in situ shows a consistent ER-positive, CK5/6- and CK14-negative phenotype: Biologic, diagnostic, and therapeutic implications
Authors: Ho Bernard C. , Lee Andrew H.S. , Ellis Ian O. 
Published: May 2012

Abstract
Introduction: Pleomorphic lobular carcinoma in situ (PLCIS), a rare variant of LCIS depicting a more aggressive morphology, has been recognized, for which controversy exists as to its biology, classification and management. In this study, we aimed to compare the immunophenotypic features of PLCIS with classical LCIS (CLCIS) and determine if PLCIS exhibits characteristics more closely associated with some forms of high grade ductal carcinoma in situ (DCIS) e.g. basal and HER2+ types.
Methods: A total of 46 lesions of in situ lobular neoplasia {23 PLCIS and 23 classical lobular neoplasia (CLN)} from 42 women (4 had both CLCIS and PLCIS) diagnosed in consultation from January 2005 to September 2009 were studied. A diagnosis of PLCIS required acinar distension by dyscohesive tumor cells with nuclear pleomorphism score 3 using the Nottingham grading system for invasive breast cancer. Immunohistochemistry for estrogen receptor (ER) (n=33), CK5/6 (n=34), CK14 (n=30), GCDFP-15 (n=2), E-cadherin (EC) (n=44), keratin 34BE12 (n=4) and HER2 (n=2) was performed with the biotin-avidin method, and results were assessed with the H-scoring system.
Results: PLCIS lesions were largely (16/17, 94%) and intensely ER positive {H-score distribution:0–9 (n=1),10–49 (n=3), 50–99 (n=0), 100–199 (n=2), 200–300 (n=11)}. One PLCIS lesion was both ER (H-score 225) and HER2 (H-score 300) positive. The single ER negative case (H-score=0) was GCDFP-15 positive (H-score 270) with overt apocrine histology. PLCIS lesions were uniformly negative (H-scores=0) for CK5/6 (n=17) and CK14 (n=15). 18/23 (78%) PLCIS lesions were EC negative, while five disclosed patchy, attenuated EC reactivity (1+ intensity, H-scores 10–50). In comparison, all lesions of CLN were ER positive (16/16) {H-score distribution: 0–49 (n=0), 50–99 (n=1), 100–199 (n=3), 200–300 (n=12)}. They were similarly negative for CK5/6 (n=17) and CK14 (n=15) (H-scores=0). 19/21(90%) CLN lesions were non-reactive for EC, while two were weakly EC reactive (1+ intensity, H-scores 10–50). CLN lesions were HER2 negative (n=1, H score 0), GCDFP-15 negative (n=1) and keratin 34BE12 positive (n=4, H-scores 200–300).
Conclusions: PLCIS exhibits a similar immunoprofile to CLN, a finding in keeping with recent molecular data, implying that it is more closely related to the LN family, rather than a variant of E-cadherin negative high grade DCIS. Furthermore, PLCIS, despite expression of keratin 34BE12, exhibits consistent ER positivity with CK5/6 and CK14 negativity and therefore appears an unlikely precursor of basal-like breast cancer. Like CLN, PLCIS may be amenable to therapeutic hormonal intervention.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B64.
Abstract B72: Citrus secondary metabolites: Potential natural compounds inhibiting human cancer cells
Authors: Patil Bhimanagouda S. , Jayaprakasha G. K. , Chidambara Murthy Kotamballi N. 
Published: May 2012

Abstract
Citrus provide protection against certain types of cancer due to the presence of specific bioactive compounds such as flavonoids, carotenoids and tri-terpenoids (mainly limonoids). Limonoids are known to inhibit number of human cancer cells through altering various biochemical pathways. Limonoids have shown induction of Phase II enzymes (both GST and QR) in mice suggesting their potential role in cancer prevention detoxification. Research form our laboratory has shown limonoids can induce apoptosis in colon, breast carcinoma and neuroblastom cells. Certain limonoids and flavonoids have shown induction of caspase mediated apoptosis and our recent in vivo study has shown inhibition of inflammatory proteins expression in Azoxymethane induced rats. Limonin and its glucoside have shown induction of intrinsic apoptosis, though involvement of Ca++ in SW-480 cells. These limonoids were non-toxic against 112CoN and NIH3T3 cells. Nomilin, one of the abundant limonoids found in citrus, has shown to arrest cell cycle of colon cancer cells when treated at 200µM. On the other hand, flavonoids of citrus demonstrated structure-related inhibition of colon cancer cells. Among the eight major flavonoids of citrus (which includes flavone, flavonols and flavanones), molecules with double bond at carbon 2nd and 3rd position have shown potential inhibition. Furthermore, the flavonoids, with higher number of hydroxyl groups, have shown significant induction of apoptosis. Apigenin and Quercetagetin have shown significant induction of apoptosis in colon cancer cells. The results of these findings will be discussed in detail. These results are based on the work supported by the USDA-CSREES # 2009-34402-19831 “Designing Foods for Health” through the Vegetable and Fruit Improvement Center.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B72.
Abstract B73: Chemopreventive effect of Streblus asper, a bonsai plant, on osteosarcoma cells: A preliminary study
Authors: Seeni Azman , Wahab Ridhwan Abdul , Zulkepli Nur Ayunie , Sulaiman Wan Nur Hidayati Wan , Yahya Muhammad Zuhaili Nor , Hamdan Mohammad Razak 
Published: May 2012

Abstract
Epidemiological studies have demonstrated a positive correlation between consumption of vegetables, fruits and beverages with reduced risk of cancer. It is estimated there are around 8,100 plant species in the Malaysian rain forests, with 10% of them reported to have some medicinal value. However, to date in Malaysia, not much investigation has been done on chemopreventive activities on cancer although Malaysian plants are an exclusive source of effective chemopreventive agents and therefore, this background leads to the premise that our local plants such as Streblus asper could have greater potential for the chemoprevention activities. Streblus asper is well known as an expensive bonsai plant which is indigenous to tropical countries such as Malaysia, Thailand, Sri Lanka and India. It is used traditionally in leprosy, piles, diarrhea, dysentery, elephantiasis and cancer. It finds place in Ayurvedic Pharmacopoeia of India and also been described in some monographs, but none have reported its activity as chemopreventive agents and the underlying mechanisms remain unclear. In the present study, we try to identify its biological properties and the cytotoxicity effect on normal liver and kidney cells. Using the osteosarcoma cells as our in vitro model, the IC50 of Streblus asper root extract was determined and observed its effect on the osteosarcoma cells morphology that changes within time, the anti-proliferative pattern and live-death analysis under confocal microscope analysis. The results showed that the root extracts did not contained any heavy metals compound such as mercury and cadmium and with less arsenic (0.02 ppm) and plumbum (0.07 ppm) and showing non-cytotoxic effect on vero cells (normal kidney cells) and WRL-68 cells (normal liver cells). Our HPLC profiling analysis also revealed antioxidants compounds exist in the Streblus asper root extracts such as caffeic acid which has been shown to act as a carcinogenic inhibitor. Although the low-level of anti-oxidants been found from the extracts but it still can inhibit the growth of the osteosarcoma cells which also exert apoptosis features like cell shrinkage (atrophy) and vocalization in time and dose-dependent manner. The plant extracts IC50 doses was at 0.05% of root extracts and it also demonstrated the anti-proliferative effect by suppressed the cells growth as early as 12 hours of treatment and marked cell death till day 6. On live-death analysis under confocal microscope using Calcein and Ethidium staining confirmed that Streblus asper root extract exert cell death to osteosarsoma cells. This study is just a preliminary study as to identify its pharmacological properties on carcinogenesis and further investigation is still on-going to develop it as the chemopreventive agent especially to determine the signaling pathway involved.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B73.
Abstract CN02-03: Hopes and challenges for early detection of ovarian cancer
Authors: Helzlsouer Kathy J. 
Published: May 2012

Abstract
Ovarian cancer has a low survival rate with the disease most often detected in advanced stages. Women at high risk may choose risk-reducing salpingo-oophorectomy with its associated clinical costs, because of the lack of known effective screening. The optimum screening test to improve the early detection of ovarian cancer and hopefully reduce mortality is an area of active research. Screening for the early detection of ovarian cancer presents challenges. The validity of the test is critical and requires high sensitivity and specificity to be effective, especially when applying the testing the general population. The low prevalence in the general population results in low positive predictive values even for tests with high sensitivity and specificity. Applying to high risk populations improves the predictive value, but reduces the overall sensitivity of any overall screening program. The recent developments in biomarkers for ovarian cancer will be reviewed and their potential applications in screening programs.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN02-03.
Abstract CN05-03: Energy balance in cancer patients: Are we ready to intervene?
Authors: Goodwin Pamela J. 
Published: May 2012

Abstract
There is growing evidence that aspects of energy balance, including overweight/obesity and physical inactivity are associated with poor outcomes in some cancers, notably breast and colorectal. In breast cancer, evidence is strongest for overweight/obesity; recent evidence suggests physical activity may have important independent associations with outcomes. In colorectal cancer, evidence is strongest for physical activity. Clinical mechanisms that have been postulated for these associations include presentation of cancer at a more advanced stage or receipt of less than optimal therapy in overweight or obese individuals. Potential biologic mechanisms have included sex hormones, insulin and related IGFs, adipocytokines and inflammatory markers. In breast cancer there is growing evidence that insulin (and associated insulin resistance) may play a key role in mediating these prognostic associations - high insulin levels have been associated with increased risk of breast cancer recurrence or death. Breast cancer cells commonly overexpress insulin receptors (frequently a fetal form of the receptor that may hybridize with the IGF-1 receptor) that are not downregulated by circulating insulin; as a result, cancer cell growth may be stimulated by high circulating insulin levels. Observational clinical studies linking energy balance to prognosis of breast and colorectal cancer will be reviewed, along with early intervention work demonstrating the feasibility, short-term benefits (e.g. on QOL) and biologic (mechanistic) changes associated with lifestyle interventions in breast and colon cancer survivors. The impact of the available evidence on clinical practice and the role of large scale clinical trials of energy balance modification with recurrence or survival endpoints (completed, ongoing and planned) will be reviewed, with an emphasis on issues relating to feasibility, cost and the need for embedded correlative research to investigate biologic mechanisms for any survival effects that are identified. Related metformin trials (which target insulin and AMPK/mTOR signaling), notably NCIC MA.32, an adjuvant trial in early breast cancer that will be activated early in 2010, will also be reviewed.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN05-03.
Abstract CN06-04: Optical coherence tomography imaging of preneoplastic lung lesion
Authors: Lam Stephen , Lee Anthony , Lane Pierre , MacAulay Calum , Yang Victor 
Published: May 2012

Abstract
Although autofluorescence bronchoscopy improves the detection rate of high grade dysplasia and carcinoma in-situ compares to white-light examination, the natural history of preneoplastic bronchial lesions is still poorly understood because the biopsy procedure for histological confirmation can mechanically remove these small lesions. The lack of accurate information regarding the spontaneous progression and regression rates of preneoplastic lesions make if difficult to assess the effect of chemoprevention agents. It is therefore important to develop non-biopsy methods that can characterize preneoplastic lesions in the bronchial epithelium.
Optical coherence tomography (OCT) is an optical imaging method that can visualize cellular and extra-cellular structures at and below tissue surface. In principle, it is similar to B-type ultrasound. Instead of using sound waves, a low coherence near infra-red light such as from a broadband 1300 nm superluminescent diode source is passed into the tissue. By detecting the reflected light as it interacts with tissue structures as a function of depth, a cross sectional image is created through optical interferometry. Its contrast is the backscattered light from interfaces at different depths in the tissue, due to the heterogeneity of optical refractive indices from different tissue compositions and densities. Changes in the extracellular matrix can be readily seen due to the strong back-scattering properties of collagen and elastin. OCT provides cross-sectional tomographic images about anatomic layered structures of tissues with a large field-of-view, a spatial resolution of 3 to 16 microns and a depth penetration of 2 – 3 mm to provide near-histological images. The imaging procedure is performed using fiber optic probes that can be miniaturized to enable imaging of airways down to the terminal bronchiole. Unlike ultrasound, light waves do not require liquid based coupling medium and thus are more compatible with airway imaging. There are no associated risks from the weak near infrared light. OCT has distinct advantages over CT and MRI for imaging small airways in-vivo in that it has superior resolution approaching near-microscopic resolution and requires no ionizing radiation. It has advantages over confocal microscopy in that it can penetrate tissue three times deeper, does not require contact with the tissue surface and is less susceptible to motion artifacts due to real-time image acquisition. In addition to morphometric information, functional OCT, such as Doppler OCT, can also provide quantitative information on blood flow of blood vessels and micro-vasculature. OCT imaging has been applied to study bronchial and lung tissues and has been shown to be promising in the detection and characterization of preneoplastic lesions tumor in central and peripheral airways.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN06-04.
Abstract ED05-03: Global tobacco control: Preventing 10 million cancer deaths by 2030
Authors: Cummings K. Michael 
Published: May 2012

Abstract
Tobacco use is responsible for one in three cancer-related deaths. Thanks to 50 years of aggressive public education efforts, tobacco use is declining in most industrialized countries. However, worldwide, tobacco consumption is actually increasing, driven in part by population growth and economic development in China, India, Indonesia, and parts of Africa and the Middle East. There are now approximately 1.3 billion smokers in the world, and 84% of them reside in the developing world. Tobacco use is the world's leading cause of preventable death, directly causing 30% of the 11.5 million annual cancer predicted by 2030 deaths. In recognition of this enormous threat, the member countries of the WHO adopted the Framework Convention on Tobacco Control [FCTC], the first international treaty devoted to health. The FCTC has been ratified by over 160 countries, but some large countries such as the United States and Russia have yet to ratify the treaty. Ratification obligates countries to implement a comprehensive set of common sense policies intended to reduce the demand for tobacco use. These policies include measures to: keep the price of tobacco high; protect nonsmokers from exposure to tobacco smoke; regulate products; control packaging and labeling of tobacco products; ban tobacco product marketing; educate the public; promote and assist tobacco cessation and prevention; prevent sales to minors; and promote alternative uses for tobacco croplands. Estimates indicate that aggressive implementation of FCTC policies could prevent 10 million excess cancer deaths anticipated over the next 20 years. The policies included in the FCTC were selected on the basis of scientific evidence. However, as the FCTC continues with its critical implementation phase in the next 5 years, and as nations that have ratified the treaty decide what specific policies will be implemented to meet their treaty obligations, it will become increasingly important that scientific evidence continue to guide the adoption of policies that will work effectively. There is already evidence that the tobacco industry is working to undermine the FCTC by encouraging countries to adopt policies that, although compliant with the FCTC, are suboptimal. As in clinical medicine, good public health practice demands that rigorously evaluated evidence guide the adoption of new tobacco control interventions. Thus, in the next few years, amassing a strong body of evidence from a methodologically sound evaluation of FCTC policies will be critical. This can then be used to guide governmental policymakers in the future.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):ED05-03.
Abstract PL02-05: Aberrant crypt foci as surrogate markers for chemoprevention
Authors: Rosenberg Daniel W. 
Published: May 2012

Abstract
Aberrant crypt foci (ACF) are putative preneoplastic lesions that occur in the colons of rodent tumor models and are abundant in the colorectum of humans. Although their presence within the colonic mucosa is incontrovertible, their clinical significance remains a source of controversy. In the following presentation, we will review the history of ACF from their first identification in rodent carcinogen models to their identification and characterization in human colons. In order to better define ACF, one must consider their histopathology, and, here, the difference between rodent and human is striking. Whereas in the rodent a single crypt can acquire dysplastic features, such is not the case in human where ACF as large as 50–100 crypts across are rarely dysplastic. In over 1500 lesions we have examined from approximately 500 patients, we observe that if endoscopic criteria are strictly adhered to, ACF are almost always hyperplastic lesions, with either a “distended” or “serrated” appearance when studied en face. We and others have clearly identified a number of colon cancer risk factors that also associate with at least the density of ACF in the distal 20 cm of colorectum. These risk factors include central obesity, increased bioavailability of IGF-1, prior or synchronous colon neoplasia, family history of colonic neoplasia and cigarette smoking. In fact, a history of 20 pack-years or more of smoking is associated with an increased likelihood (adjusted OR=3.45; 95% CI 1.93–6.18) of having more than the median number of ACF (≥ 15) compared to non-smokers (Anderson et al., under review). Considering their prevalence in the colons of cancer patients, their corresponding association with a panel of key colon cancer risk factors and their cancer-related molecular aberrations, we argue that these lesions may provide an important signal of one or more risk factors, and are likely part of the ‘field effect’ within the colonic mucosa. If a clearer association can be established with high-grade adenomas, we believe ACF will ultimately be of great utility as surrogate markers for cancer prevention studies.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL02-05.
Abstract PL03-04: Challenges in using genetic information and family history in primary care
Authors: Ramsey Scott D. 
Published: May 2012

Abstract
Several expert groups now advocate family history screening (FHS) as an approach to identify persons at increased risk for disease, but the clinical and economic implications of programs to improve FHS have not been established. The economic implications of implementing population-wide family history assessment programs are likely to be substantial. Although the costs of assessing family history will be small at the individual level, the societal costs of assessing millions of individuals could potentially be very large. Moreover, the initial family history screen could result in a number of downstream interventions, with potentially high costs. Because the impact of FHS and FHS-based care on outcomes are at present uncertain, understanding the economic costs involved with FHS is an important endeavor. In this presentation, I will outline the conceptual issues involved in economic evaluation of FHS, and some challenges to measuring the economic impact of family history screening.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL03-04.
Abstract PL04-05: Vitamin D: Panacea or a Pandora's box for prevention?
Authors: Helzlsouer Kathy J. ,   Steering Committee Vitamin D Pooling Project of Rarer Cancers
Published: May 2012

Abstract
Widespread interest in the possible preventive role of vitamin D against cancer emerged from ecological studies of the association between latitude and cancer mortality, in-vitro studies of the effects of vitamin D on proliferation and apoptosis, and presence of vitamin D receptors in many tissues. Observational studies of colorectal cancer provide the most promising data supporting a potential preventive benefit for vitamin D but this effect, so far, is not supported by results from randomized trials. Observational studies for other common cancers such as prostate and breast provide little support for a significant preventive effect of vitamin D. The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) is a consortial effort including 10 prospective cohorts from the United States, Finland and China to examine the association between concentrations of 25-hydroxyvitamin D (25(OH)D) and risk of seven types of rarer cancers: endometrial, esophageal, gastric, kidney, non-Hodgkin's lymphoma, pancreatic and ovarian. No associated benefit, and potential harms, were observed including confirmation of prior reports of an increased risk of pancreatic cancer with higher concentrations of 25(OH)D. The association between mortality and 25(OH)D concentrations was examined in the Third National Health and Nutrition Examination Survey (NHANES III). The mortality rate ratio was statistically significantly higher for those with vitamin D concentrations in the deficient range, defined as &lt;45nmol/L. Among women, an increased rate of mortality was observed both for deficient concentrations and very high concentrations (&gt;124nmol/L). Results suggest that caution should be exercised in using very high dose vitamin D supplementation in prevention trials that may result in high concentrations of vitamin D (&gt;100nmol/L).
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL04-05.