bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A63: Superoxide-dependent MKP-1 degradation and JNK activation contribute to luteolin-induced cytotoxicity in lung cancer cells
Authors: Bai Lang , Xu Shanling , Wang Xia , Ju Wei , Chen Wenjie , Lin Yong 
Published: May 2012

Abstract
Epidemiological studies have suggested luteolin (3′,4′,5,7-tetrahydroxyflavone) as a potential cancer preventive agent. Recently we found that luteolin selectively kills lung cancer but not immortalized human normal bronchial epithelial cells (HBECs). To elucidate the mechanism of luteolin's cancer cell killing activity, we used an in vitro cell culture system to investigate the cytotoxic cellular signaling pathway in lung cancer cells. The results show that luteolin potently induced both apoptosis and necrosis, which was associated with mitochondrion-dependent superoxide accumulation in lung cancer cells. The c-Jun N-terminal kinase (JNK) was substantially activated in luteolin treated cancer cells and luteolin-induced cytotoxicity was effectively blocked when JNK was inhibited. The reactive oxygen species scavengers BHA and NAC, which effectively block luteolin-induced superoxide accumulation, potently suppressed luteolin-induced JNK activation and cytotoxicity, suggesting that luteolin's lung cancer cell killing requires superoxide-mediated JNK activation. Furthermore, JNK activation was tightly associated with a superoxide-dependent rapid reduction of the JNK inactivating phosphatase MKP-1, which was mainly due to destabilizing MKP-1 protein. These results suggest that inhibiting MKP-1 is the main mechanism for luteolin-induced JNK activation. Thus, luteolin activates a novel cytotoxic pathway consisting of superoxide, MKP-1 and JNK in lung cancer cells. Interestingly, although luteolin-induced superoxide accumulation was comparable to that in lung cancer cells, it failed in inducing JNK activation and cell death in the HBECs. Therefore, luteolin-induced cellular signaling in normal and lung cancer cells diverges at the step of JNK activation. Taken together, our results suggest that activation of the speroxide/MKP1/JNK pathway underlies the main mechanism of luteolin's selective ctyotoxicity in lung cancer cells and manipulation of this pathway could be a useful approach for applying luteolin for lung cancer prevention and therapy.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A63.
Abstract A67: Dietary xanthones for prostate cancer chemoprevention: From fruit extract to structure activity relationship studies
Authors: Johnson Jeremy J. , Syed Deeba N. , Adhami Vaqar M. , Siddiqui Imtiaz A. , Rasmussen John T. , Handa Harleen , Mukhtar Hasan 
Published: May 2012

Abstract
The purple mangosteen fruit (Garcinia mangostana) is native to southeast Asia and has been reported to contain a variety of health promoting properties that include antioxidant, anti-inflammatory, anit-microbial and anti-diabetic properties. The principle constituents isolated from the mangosteen fruit are the xanthones with well over 50 unique entities isolated to date. Here we report on the properties of dietary xanthones for cancer chemoprevention using prostate cancer (PCa) as a model disease. Using a mangosteen fruit extract (MFE) standardized to alpha-mangostin (40%) and three other xanthones a significant decrease in cell viability was observed against four different prostate cancer cell lines (LNCaP, CWR22, PC3, DU145). Next, using an athymic nude mouse model implanted with CWR22Rv1 cells we randomized mice to receive intraperitoneally the standardized mangosteen fruit extract (MFE) or placebo two times weekly with tumors measured twice weekly once tumors reached a volume of 200 mm3. At the conclusion of the study the treatment group had a significantly smaller tumor with an average tumor volume of (143 mm3) compared to the placebo group (1135 mm3) representing an 87.5% smaller tumor in the treatment group. To gain an understanding of the pharmacology we selected alpha-mangostin as the lead compound and evaluated alpha-mangostin against fifty different protein kinases deregulated in cancer with 11 unique kinase targets identified. The three kinases displaying the most inhibition by alpha-mangostin included cyclinD1/CDK4, cyclinA1/CDK2, and Mek1. Using two different cells lines (LNCaP and DU145) we have evidence suggesting alpha-mangostin promoted G1 cell cycle arrest by flow cytometry and western blot analysis of cyclins and CDKs with observed effects in the range of 5–10 µM. A preliminary pharmacokinetic analysis of mice administered 1 mg of alpha-mangostin intraperitoneally resulted in a plasma concentration of 7.3 µM - within the concentration of in vitro mechanistic studies. Next, using an athymic nude mouse model implanted with CWR22Rv1 cells we randomized mice to receive intraperitoneally the alpha-mangostin (&gt;95%) or placebo two times weekly with tumors measured twice weekly. At the conclusion of the study the treatment group had a significantly smaller tumor with an average tumor volume of (400 mm3) compared to the placebo group (1225 mm3) representing a 69% smaller tumor in the treatment group. Based on these promising results we used purified xanthones from the mangosteen fruit and selected 9 xanthones for structure activity relationship studies against cyclinD1/CDK4 and CyclinA1/CDK2 using cell free biochemical assays and molecular modeling. Collectively these data indicate that alpha-mangostin could be a promising agent for PCa prevention.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A67.
Abstract A69: High-throughput library screening identifies phytochemical inducers of phase II metabolism enzymes GSTP1 and NQO1 in human lung cells
Authors: Tan Xiang-Lin , Shi Miao , Massimi Aldo B. , Han Weiguo , Spivack Simon D. 
Published: May 2012

Abstract
Many phytochemicals possess cancer-preventive properties, some putatively through phase II metabolism-mediated mutagen/oxidant quenching. However, in studies to date, most candidate agents are not active in human lung cells. In vitro and in vivo screening studies for discovery are clearly needed for new, more potent chemopreventive agents for lung cancer. Here we applied a gene expression-based high-throughput screening approach to identify phytochemical inducers of phase II metabolism enzymes GSTP1 and NQO1 in primary normal human bronchial epithelial (NHBE) cells and immortalized human bronchial epithelial cells (HBEC). We have screened 800 compounds in the MicroSource Natural Products Library for inducers of GSTP1 and NQO1 expression, and identified 2, 3-dihydroxy-4-methoxy-4′-ethoxybenzophenone, triacetylresveratrol, ivermectin, sanguinarine sulfate, and daunorubicin as new inducers for GSTP1 and NQO1 mRNA expression. Consistent with this effect, the induction of NQO1 protein expression by immunoblot was found for all these agents in both HBEC and NHBE cells at the same concentration (1.0 µM, final concentration) that induced NQO1 mRNA expression. However, GSTP1 protein expression did not significantly change with any selected agents. Proliferation/viability assays showed that HBEC and NHBE were significantly inhibited by ivermectin, sanguinarine sulfate, and daunorubicin. These data demonstrate the feasibility of high-throughput screening for inducers of NQO1. Moreover, the data identify 2, 3-dihydroxy-4-methoxy-4′-ethoxybenzophenone and triacetylresveratrol as most potent and low toxicity inducers [12-fold, and 10-fold, respectively, at the protein level], implying they are potential new agents for further in vitro and preclinical in vivo testing for prevention of tobacco-related lung cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A69.
Abstract A71: Isolation of aglycons and glycosides from Scutellaria baicalensis and exploration of responsible constituents on human breast cancer chemoprevention
Authors: Wang Chong-Zhi , Yuan Chun-Su 
Published: May 2012

Abstract
Numerous effective anticancer drugs have been developed from botanical sources. Although the anticancer properties of Scutellaria baicalensis extract (SbE) have been reported, in some of our studies, SbE did not inhibit the growth of breast cancer cells significantly. In certain concentrations, it increased cancer cell growth. To identify the active anticancer constituents in SbE, we isolated a baicalin-knockout fraction (SbF1) and a baicalin-fraction (SbF3). We evaluated the anti-breast cancer activities of the fractions and their constituents on human breast cancer MCF-7 cells. Using a Waters 2960 high performance liquid chromatography (HPLC) instrument and a Phenomenex Prodigy ODS(2) column, we determined the contents in the extract and fractions: scutellarin, baicalin, baicalein and wogonin. The antiproliferative effects were assayed using the modified trichrome stain (MTS) method. The active properties of the fraction/constituents on the cancer cell cycle and on apoptosis were evaluated using a BD FACScan flow cytometer. A one-way ANOVA was used to measure statistical significance. HPLC data showed that the content of scutellarin, baicalin, baicalein and wogonin in SbE were 0.03, 15.67, 5.19 and 1.42%, respectively. The major constituents of SbF1 are the aglycons, baicalein (40.54%) and wogonin (12.35%). SbF3 contains only the glycoside baicalin (16.68%). SbF1 showed a significant antiproliferative effect. Treatment with 100 g/ml of SbF1 for 72 h inhibited MCF-7 cell growth by 81.6% (P&lt;0.01); at the same treatment concentration, SbF3 increased cell growth by 22.6% (P&lt;0.01). Therefore, SbF1 is the active fraction of SbE. Compared to control (48% of G1-phase, 33% of M-phase, and 10% of G2/M-phase), after treatment with 50 g/mL of SbF1 for 72 h, 27% of cells were in G-phase, 41% of cells were in M-phase, and 23% of cells were in G2/M-phase. SbF1 increased the S- and G2/M-phases in MCF-7 cells. After treatment for 48 h, the percentage of early apoptotic cells induced by 50 g/mL of SbF1 was 12.4%; by 100 g/mL, the percentage was 24.2%. SbF1 significantly increased induction of cell apoptosis compared to control, 6.7%. Studying the effects of four flavonoids in SbE, two glycosides (scutellarin and baicalin) and two aglycons (baicalein and wogonin), on MCF-7 cell proliferation showed that baicalein and wogonin significantly inhibited MCF-7 cell growth at 10–100 µM. In contrast, at certain concentrations (5–50 µM), the glycosides scutellarin and baicalin increased cancer cell growth. These phytochemical and biological data suggest that the active anticancer constituents in SbE are flavonoid aglycons. Since the two glycosides promoted MCF-7 cells at certain concentrations, these compounds should be removed from the S. baicalensis extract to ensure chemopreventive activities.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A71.
Abstract A78: A randomized phase II presurgical trial of weekly tamoxifen versus raloxifene versus placebo in premenopausal women with breast cancer
Authors: Serrano Davide , Lazzeroni Matteo , Gandini Sara , Pagani Gianmatteo , Johansson Harriet , Pelosi Giuseppe , Mora Serena , Gonzaga Aliana Guerrieri , De Censi Andrea , Bonanni Bernardo 
Published: May 2012

Abstract
Background: The presurgical model is a useful tool to test drug activity on surrogate biomarkers of breast cancer, including proliferation measured by Ki-67. We previously demonstrated that 1 or 5 mg/per day of tamoxifen (T) given for 4 weeks before surgery reduced Ki-67 to the same extent than the standard 20 mg/d. Given the long half-life of T and its metabolites, a weekly dose (10 mg/w) may be worth testing. Raloxifene (R), another SERM, has been shown to reduce Ki-67 in a preoperative setting and to be an effective breast cancer (BC) preventive agent in postmenopausal women.
Methods: 125 premenopausal estrogen receptor positive BC patients were randomly assigned to either T 10mg/w or R 60 mg/d or placebo (P) for 6 weeks before surgery in a 2:2:1 ratio. The primary endpoint was tissue change of Ki67. Secondary endpoints were other tissue and circulating biomarkers.
Results: The median age was 44, 46, 44 and the median BMI was 23, 22, 22 in the P, R and T group, respectively. Tissue biomarkers (Ki-67, ER, PgR) were not significantly modulated by treatment. Only PgR was modestly down regulated by T and more by R but with not statistically significance. More evident were the effects on the circulating biomarkers. Both SERMs significantly reduced IGF-I/BP-3 ratio (mean change P:0; T:-0.01; R:-0.02; p=0.007) and cholesterol (mean change P: 13.73; T: -10.82; R: -8.96; p&lt;.0001) with no difference between the two drugs. Both T and R modulated significantly fibrinogen level (mean change P: 9.3; T: -14.24; R: -35.88 p=0.002) and in particular R was more effective than T (p=0.034). Antithrombin III showed a significant reduction by treatment vs. placebo (mean change P: -2.28; T: -6.19; R: -6.85; P=0.04). SHBG levels were positively influenced by both T and R (mean change P: -10.21; T: 5.95; R: 6.2; p=0.002). Overall compliance measured with pill count was above 80%. No severe adverse events occurred.
Conclusions: Our findings show a lack of effect of both SERMs on breast cancer cells proliferation, possibly due to insufficient doses in premenopausal women with elevated estrogen levels. In contrast, both T at very low dose and R at the standard dose were effective on circulating biomarkers. Interestingly, R was more active than T in reducing fibrinogen level, in line with its safer vascular profile.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A78.
Abstract A82: Role of curcumin as an adjuvant in cervical cancer therapeutics
Authors: Banerjee Ayan , Das Prasenjit , Palanichamy Jayanth Kumar , Jain Sunesh Kumar , Rath Goura Kishore , Julka Pramod Kumar , Singh Neeta 
Published: May 2012

Abstract
Introduction: Human papilloma virus (HPV) is a causative factor in the genesis of cervical cancer. Curcumin can act as an adjuvant in cancer therapy with essentially no side effects. In this study, we elucidated the role of curcumin as an adjuvant to chemo and radiotherapy in patients suffering from cervical cancer.
Experimental Design: This was a pilot study of a Phase III, randomized control, double blind clinical trial. Forty five histopathologically confirmed patients of cervical cancer (stage IIb to IIIb) were enrolled. The patients were randomized into Group A/Group B and given curcumin (4gm/day for 3 months)/placebo along with chemo and radiotherapy. Cervical scrapes / pap smears were collected at baseline, 1 month (1st follow up) and 6 months (2nd follow up) post treatment. HPV status, viral load, PCNA and P16INK4A protein expression were investigated. CT scan was done at 6 months to see the final outcome of treatment.
Results: A significant drop in the viral load post treatment was seen in both groups but not between the groups. A non significant decrease in PCNA was seen at 1st follow up which increased at 2nd follow up in both the groups. Increased P16INK4A expression was seen at 1st follow up that decreased at 2nd follow up, similarly in both groups, but was not significant. No significant difference in outcome between both the groups was observed at 6 months post treatment.
Conclusion: Group A patients received curcumin and Group B received placebo. This is the first clinical trial with curcumin in advanced cases of cervical cancer. Curcumin was well tolerated. No significant difference was found between the two groups which could be due to the small sample size or short duration of follow up. No correlation was found between HPV viral load, PCNA and P16INK4A protein expression.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A82.
Abstract A85: Moving to centralized follow-up from a site-based model in a large cancer prevention study
Authors: Goodman Phyllis J. , Hartline Jo Ann , Lippman Scott M. , Klein Eric A. 
Published: May 2012

Abstract
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a randomized, double blind, placebo-controlled prostate cancer prevention study of 35,533 men from 427 study sites in the United States, Canada and Puerto Rico. Men were randomly assigned to one of 4 treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo) between August 2001 and June 2004. Men were seen at their study site every 6 months for evaluation of medical events, ascertainment of endpoints and dispensing of study supplements.
On September 15, 2008, the Independent Data and Safety Monitoring Committee recommended the discontinuation of study supplements because the alternative hypothesis of no evidence of benefit from either study agent was convincingly demonstrated (p &lt;.0001) and there was no possibility of a benefit to the planned degree with additional supplementation.
In order to refine the estimate of prostate cancer incidence in the 4 arms and to assess the long term effects of the supplements, participants on the trial will continue to be followed. This allows us to complete the previously approved ancillary studies and maintain the cohort for future research. Follow-up will transition from in-person study site visits to an annual questionnaire sent by the SELECT Coordinating (previously Statistical) Center. With participant consent, the Coordinating Center will obtain detailed participant contact information for mailing the questionnaire as well as the SELECT newsletters. Medical releases will be obtained to collect additional data on specific endpoints. With approved funding, additional questions may be added to the annual form.
The decision to centralize the follow-up was due to efficiency of scale and because participants no longer need to be seen to assess acute toxicities or dispense study supplements.
With the change in the follow-up procedures, many tasks needed to be accomplished in a short amount of time. These included revising the study protocol; development and Coordinating Center IRB approval of a new Informed Consent; defining activities for the final participant visit and training of the local staff for implementation; development of new forms and procedures with a direct participant focus; development of computer applications that move data collection from a web-based model to a paper-based model with scannable forms augmented with a web-based option.
One of the major challenges has been the approval of local IRBs of the protocol amendment and revised Informed Consent allowing the Coordinating Center to directly contact participants. Additional challenges are the loss of experienced trained study site staff with longstanding relationships with participants, training Coordinating Center staff for direct participant contact for answering questions and collecting data via telephone for non-responders to the questionnaire.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A85.
Abstract A87: Correlation between microsatellite instability and clinical characteristics and outcome of colorectal cancer in an Iranian population
Authors: Khatami Fatemeh , Fatemi Seyed Reza , Malek Fatemeh Nemat , Molaee Mahsa , Shivarani Sepideh , Zali Mohammad R. 
Published: May 2012

Abstract
Widespread microsatellite instability (MSI) occurs in nearly 15% of sporadic colorectal cancers. Large bowel carcinomas with high-frequency MSI (MSI-H) (instability at &gt; or = 30% of microsatellite loci) are believed to display distinctive pathologic features and to behave less aggressively than microsatellite-stable (MSS) tumors and carcinomas with low-frequency MSI (MSI-L) (instability at &lt; 30% of microsatellite loci). In this study we would like to show the impression of MSI on clinical condition and outcome of patients with colorectal adenocarcinoma.
Methods: MSI status was evaluated in 600 large bowel adenocarcinomas using polymerase chain reaction (PCR) and sequencing. Tumors that showed instability with at least two microsatellite markers were classified as MSI-H, whereas the other tumors were classified as MSI-L (instability at one locus) or MSS (no instability).
Results: MSI-H was detected in 51.6% of CRC patients. The prevalence of proximal lesions in the MSI-H group (38.7%) was higher than in the MSS group (27.4%). The percentage of moderately differentiated tumors was slightly lower in the MSI-H group (16.3%) when compared to the MSS group. Eight mutations were detected in five patients with 32 MSI-H.
Conclusion: Assessment of MSI status is an essential step in discovering genetic characterizations of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A87.
Abstract A88: Cancer awareness through close circle experience of the disease: An increasing trend
Authors: Eisinger Francois , Pivot Xavier , Coscas Yvan , Viguier Jerôme , Calazel-Benque Anne , Blay Jean-Yves , Roussel Claire , Morère Jean-François 
Published: May 2012

Abstract
In a Cartesian perspective, knowing a threat is the first mandatory step for risk management. Cancer awareness is a strong momentum for risk mitigation. We have used the EDIFICE program, an iterative nationwide survey collecting data on people use of cancer screening procedures and its explicative factors, to analyze the trend for cancer awareness and its impact on cancer screening.
Materials and Methods: Two nationwide observational studies were carried out in France: EDIFICE 1 was conducted from 18 January 2005 to 2 February 2005 among a representative sample of 1504 subjects aged between 40 and 75 years. EDIFICE 2 was conducted from 12 December 2007 to 7 January 2008 among a representative sample of 1802 subjects aged between 40 and 75 years. Two questions focused on awareness/experiential perspectives. Do you know someone affected with a cancer in your close circle of friends and family? Which location?
Results: In 2005, 67% (993/1482) of people interviewed declared having someone in their close circle affected with a cancer. In 2008, the figure was 80% (1158/1454). Interestingly the increasing awareness is much more important for the close circle of friends and colleagues rising from 24% to 42% rather than for relatives (from 56% to 61%). The OR for close circle of friends is 2.3 (IC95% 2.0–2.7) and for relatives 1.2 (IC95% 1.1–1.4)
With regard to location, three types of cancer exhibit a significant increase: breast from 25% in 2005 to 36% in 2008, prostate from 6% to 13% and colorectal from 7% to 12%, while for other locations (as a whole) no change occurred: 31% in 2005 and 30% in 2008.
In our survey, having someone in its close circle affected with a cancer does not increase the rate of screening for breast cancer (already high at above 80%). Nevertheless, it does increase the rate of screening for colorectal cancer OR=2.3 (IC95% 1.6–3.3) and prostate cancer OR=2.2 (IC95% 1.4–3.5). The increase is more important for specific location (prostate cancer in its close circle increases prostate cancer screening), but it is also significant without taking into account the anatomical location of affected people in their close circle.
For breast cancer, the mean age for the 1st mammogram carried out is 45.6 years (sd:9.6) for women with no one affected in their close circle of friends and family compared to 43.4 years (sd=9.2) for women with at least one known case p&lt;0.05
Comment and Conclusion: We observed a significant increase in awareness through experience of cancer in close circle, probably related to less social stigma on cancer. This increased awareness through experience impacts on cancer screening behaviors with a higher rate of declared attendance.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A88.