This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. Thes... more Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. These tumors are characterized by increased rates of proliferation and invasive migration as well as angiogenesis. To date few therapeutic options exist for the treatment and management of GBMs, therefore we decided to investigate the anti-oncogenic properties of extracts from the rosehip plant. Rosehip extracts have been used for centuries as alternative therapies. Currently, rosehip extracts are being used as over the counter supplements and recent studies demonstrate that it has an anti-tumor effect. Therefore, we tested the anti-migratory and antiproliferative capacity of extracts from the rosehip (Rosa canina) plant in GBM cell lines. Three human GBM cell lines, U-251 MG, U-1242MG and A-172, were treated with rosehip extracts (1 mg/mL - 25ng/mL) and demonstrated a decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to the decrease of cell proliferation observed when U0126 (10µM), a know inhibitor of GBM cell proliferation was utilized. Utilizing a fluorescent-based labeling strategy (Live-Dead Assay), we examined whether rosehip extracts prevented cell proliferation by initiating apoptosis. Pretreatment of the GBM cells with rosehip extracts (1 mg/mL - 25ng/mL) induced the inhibition of cell proliferation without promoting apoptosis; whereas, cells treated with staurosporine (1 µM), a known inducer of apoptosis, showed an increase in cell apoptosis. Additional studies demonstrated that rosehip extracts prevent GBM cell proliferation by decreasing the active state of MAPK and AKT. Furthermore, rosehip extract-treated GBM cells also prevent cell migration by regulating actin remodeling. Taken together, these data suggest that rosehip extracts inhibit cell proliferation via a cytostatic mechanism that does not by induce apoptosis while also serving as a migration inhibiting agent. These data suggest that, rosehip extracts may serve as an alternative, or supplement, to current therapeutic regimens for GBMs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1986. doi:1538-7445.AM2012-1986
The United States is increasingly racially and ethnically diverse. In fact, California is now a m... more The United States is increasingly racially and ethnically diverse. In fact, California is now a majority-minority region, with a greater percentage of its population comprised of racial minorities than whites. Yet, minorities are continually under-represented in clinical research trials, which provide crucial information on which the future of cancer treatments is built. Without representative inclusion of participants of color in clinical research, we cannot develop effective preventative and treatment approaches for everyone. This current study investigates the factors, including characteristics of study consenters, that may influence women—particularly women of color (WOC)—to accept or decline participation in breast cancer-related trials. We assess these factors through a brief survey, administered to patients immediately after they were invited to participate in a breast cancer-related clinical study. From the beginning of study accrual to the present, twenty-three patients have taken the survey. We anticipate accruing 200 participants at a rate of 25 per month. For the preliminary analyses, we split participants in two groups: white women (WW) (n = 14) and women of color (WOC) (n = 9). We conducted independent sample t-tests to compare the responses of WW and WOC. More WOC (M = 1.44, SD = 0.73) reported that it is important that their consenter is of the same ethnicity or race than WW (M = 1.00, SD = .00), t (21) = -2.32, p < .05. Similarly, WOC (M = 1.44, SD = .73) also reported that it is important that the person inviting them to participate in research look like people in their community, compared to the importance placed on this factor by WW (M = 1.00, SD = .00), t (21) = -2.32, p < .05). More WOC (M = 2.33, SD = 1.23) also cited “feeling overwhelmed” with their medical condition as influential in their decision to participate in clinical research than WW (M = 1.31, SD = .48), t (20) = -2.75, p < .05. Although both groups positively rated their interaction with the consenter, we observed marginal differences between WOC and WW. WOC (M = 7.00, SD = .00) gave higher ratings to the variable of “consenter created an atmosphere of trust and support” compared to ratings given by WW (M = 6.29, SD = 1.07), t (21) = -1.99, p = .06. Though participants are generally satisfied with their consenter interaction, different factors influence WW and WOC as they decide whether to participate in clinical research. When identified, these factors can be used to inform more inclusive consenting processes. Citation Format: Noe R. Chavez, Alan Nunez, Angela K. Wong, Tanya A. Chavez, Ellen Rippberger, Christine Thai, Angelica Sanchez, Ombeni M. Idassi, Krista M. Round, Kendall Kennedy, Margarita Robles, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Chidimma M.K. Kalu, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Courtney Vito, Karen Harold, Terry Hyslop, Carola M. Zalles, Daniel B. Schmolze, Christopher Sistrunk, Victoria L. Seewaldt. Influencing women's attitudes toward participation in breast cancer clinical research: Improving inclusion of women of color [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A082.
Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress... more Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress of preventative measures and treatments for all races and ethnicities. However, Northern European whites (NE/W) continue to be disproportionally enrolled (e.g., 93.5% were non-Hispanic white in the STAR trial), while minorities such as Asians, blacks, Latinas, and Native Americans (NA) lag in participation. Current studies suggest that minorities are not approached as frequently as NE/W; however, they are just as willing to participate. Here we present a successful recruitment strategy to improving minority accrual in CTs at a Comprehensive Cancer Center located in Duarte, CA. Method: Results from community focus groups suggested the need to mentor local youth who strive to pursue a career in the medical field. Consequently, from February 2016 to July 2018, four bilingual, bicultural clinical research assistants (CRAs) were recruited from the catchment area of City of Hope (CoH). The CRAs, in collaboration with seven surgeons, two radiologists, and one medical oncologist, led the recruitment for three nontherapeutic BC prevention CTs at CoH. Results: All four CRAs were 1) first-generation American, 2) fluent in Spanish or Vietnamese, 3) born and raised in Southern California, and 4) pre-health. Of the 3,148 patients who were screened, 398 were eligible for enrollment, 369 consented, and 58 declined. Primary languages and races/ethnicities of those who declined include the following: 7% Armenian, 9% Chinese, 78% English, 2% Thai, and 5% Spanish; 28% Asian, 3% black, 28% Latina, 2% NA, and 67% white (22% NE, 17% Middle Eastern/North African). Demographics of the consenting population include the following: primary language - >1% Armenian, 4% Chinese, 89% English, >1% Korean, and 7% Spanish; race/ethnicity - 14% Asian, 6% black, 30% Latina, 5% NA, and 75% white (40% NE). Of the white population (n = 277), 11% were Middle Eastern/North African, 53% NE, and 36% Latina. Accrual surpassed both the CoH catchment area (11.3% Asian, 8% black, 24% Hispanic, 1% NA, and 32% NE/W) and the CoH interventional/nontherapeutic CT population (10% Asian/Pacific Islander, 4% black, 21% Hispanic, >1% NA, and 55% NE/W). Conclusion: Contrary to current accrual of CTs, here we show that minorities can have a large representation in CT accrual, as long as they are provided the opportunity. Accrual of Asians, Latinas, and NAs exceeded the catchment area and accrual of other CoH CTs. Interestingly, Chinese-speaking women comprised the highest declination group of the non-English speakers, and Asians and Latinas declined the most outside of non-whites. Cultural competency and bilingualism appear to be characteristics of a CRA that may help in accruing minority women into CTs. Our findings suggest that they are just as willing to participate, and the first step is to simply ask. Citation Format: Tanya A. Chavez, Christine Thai, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney A. Vito, Noé R. Chávez, Alan Nuñez, Ellen J. Rippberger, Angela K. Wong, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni Idassi, Kendall J. Kennedy, Terry Hyslop, Carola M. Zalles, Christopher Sistrunk, Victoria L. Seewaldt. Diversifying breast cancer clinical trial accrual: An approach to recruitment at a Comprehensive Cancer Center [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A083.
The United States (US) is racially and culturally diverse. Still, white women disproportionately ... more The United States (US) is racially and culturally diverse. Still, white women disproportionately comprise clinical trial participants, stemming largely from the fact that minorities often decline participation. Clinical trial findings, therefore, have not been representative of the diverse patient population, and have stymied progress in precision medicine and cancer prevention. According to the CDC, among Asian/Pacific Islander females, the leading cause of death is cancer. Moreover, they have more total cancer-related deaths than any other racial group. Per the 2017 US Census, Asians are the third largest minority group of the population (6.6%). Despite the grave health disparities faced by a sizable proportion of the population, the literature is sparse with regards to their research engagement. For example, several studies have focused on Black and Hispanic consenting rates, including one study that demonstrated no significant differences between the two groups (Wendler, Kington, Madans, Wye, Christ-Schmidt, Pratt et al., 2005) and another that indicated relatively lower enrollment rates among Hispanics and Blacks (Murthy, Krumholz, Gross, 2004). This gap in research is largely due to the marked heterogeneity with respect to language, nationality, and acculturation status. We examined Asian participation in three therapeutic, noninterventional trials that aim to develop early detection methods and accurate prognosis in women at high risk for breast cancer. Primarily, we collect leftover tissue and/or cells from fine needle aspirations (FNA) to better understand the cellular microenvironment that correlates with breast cancer development. We analyzed demographic data across these studies to investigate refusal rates among Asian women. Across the three trials, 3,119 participants were screened. Of the total number screened, 426 participants were eligible, 368 consented, and 58 declined. Of those who declined, 23.5% were Asians, 13.9% Hispanic, 8.3% Blacks, 5.6% Native Americans, and 11.4% White/non-Hispanic. Notably, Asians had the highest refusal rate. Fisher's exact test (two-tailed) was conducted to examine refusal rates for Asians compared to Whites, Blacks, and Hispanics. Results suggest that Asians had significantly higher rates of compared to Whites (p = .02, observed odds ratio = .42, 95% CI [.20, .86]), but were not significantly different than Blacks or Hispanics. The under-representation of Asians in research may exacerbate health disparities. Thus, further studies should examine ways, such as increasing racial and cultural competency, for increasing Asian representation in clinical research studies. Ultimately, we believe that illuminating under-representation of the “forgotten” Asian population in clinical research can inform future interventions that promote chemoprevention and treatment of this high-risk population. Citation Format: Stacey N. Doan, Christine Thai, Angela K. Wong, Tanya A. Chavez, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney Vito, Alan Nunez, Ellen J. Rippberger, Noe R. Chavez, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni M. Idassi, Kendall J. Kennedy, Christopher Sistrunk, Victoria L. Seewaldt. The forgotten race: Under-representation of Asians in clinical research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A084.
Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who d... more Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who do not have a BRCA 1, BRCA 2 or other highly penetrant cancer susceptibility mutation. Background: Breast cancer is the most common cancer in women and the second most prevalent cause of cancer death of women in the United States; the lifetime risk for breast cancer in women is approximately 12%. Women may be at increased risk for breast cancer for many reasons including family history, genetic alterations, age, reproductive status and menstrual history. Most women who are at increased risk of developing breast cancer do not have a BRCA 1, BRCA 2 or other mutation. The majority of breast cancer diagnoses are due to acquired somatic mutations; only 5 to 10% of breast cancer diagnoses are attributable to highly penetrant Mendelian cancer susceptibility genes. White women with Ashkenazi Jewish ancestry tend to have a higher incidence of BRCA 1 and 2 mutations; traditionally, most research efforts about highly penetrant genes have been focused on this group rather than other racial and ethnic groups. However, there is a great need to study breast cancer risk-reduction strategies in racial and ethnic minorities in the United States, particularly because most breast cancers are not caused by BRCA 1 and 2 mutations. City of Hope is located approximately 21 miles northeast of Los Angeles and operates 13 clinical practice locations including Los Angeles, Orange, Riverside, San Bernardino and Ventura counties. These five counties are home to the majority of California's multicultural and ethnic residents where San Bernardino County has the highest percentage of Hispanics (49.9%) and blacks (8.3%), Ventura County has the highest percentage of whites (48.1%), and Orange County has the highest concentration of Asians (18.2%). It has been established in the literature that the greatest benefit from breast cancer prevention strategies comes from treating women who are at high risk of the disease. While it is important to build a high-risk breast cancer clinic for women with genetic mutations, it is equally important to build a high-risk breast clinic for women who are at increased risk of breast cancer but do not have a mutation, particularly because most breast cancer is diagnosed in this population. In addition, it is crucial to educate high-risk patients that although they may have tested negative for a genetic mutation if they have a family history of breast cancer, they warrant close clinical surveillance. Methods: We are proposing a retrospective, descriptive study of data that will be collected as part of a high-risk breast cancer program implemented by City of Hope. Results/Conclusions: We expect to discuss the findings related to serving women of all races and ethnicities who do not have a mutation in a highly penetrant gene mutation. Citation Format: Karen Herold, Lisa D. Yee, Chidimma M. Kalu, Laura L. Kruper, Veronica C. Jones, Amy C. Polverini, Sharon Clancy, Tanya A. Chavez, Jackelyn A. Alva-Ornelas, Noe R Chavez, Ellen J. Rippberger, Jerneja Tomsic, Christopher Sistrunk, Ombeni Idassi, Daniel B. Schmolze, Courtney Vito, Alan Nunez, Angela K. Wong, Krista M. Round, Christine Thai, Angelica Sanchez, Margarita Robles, Kendall Kennedy, Terry Hyslop, Victoria L. Seewaldt. Architecture of increased breast cancer risk [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B109.
Despite cancer being the leading cause of death across most racial/ethnic groups, Hispanic women ... more Despite cancer being the leading cause of death across most racial/ethnic groups, Hispanic women have the second highest mortality rate attributed to diabetes (4.7%) according to the Centers for Disease Control and Prevention (CDC). While cancer and diabetes are two distinct diseases, previous studies have demonstrated that diabetic women have a poor chance of breast cancer survival when compared to nondiabetic women. Well-known key drivers of hyperinsulinemia and insulin resistance, such as insulin and AMPK, are also those involved in breast cancer. This link could possibly contribute to the increased mitogenic effects and risk for aggressive breast cancers in Hispanic women. Based on these findings, metformin, a drug standardly used to treat and prevent hyperglycemia, may be a possible alternative (other than tamoxifen) for breast cancer prevention. Eat, Move, Live (EML), a 5-week community-based program, focuses on targeting possible treatments of chronic diseases and risk reduct...
The goal of curing children and adults with sickle cell disease (SCD) is to maximize benefits and... more The goal of curing children and adults with sickle cell disease (SCD) is to maximize benefits and minimize intermediate and long-term adverse outcomes so that individuals can live an average life span with a high quality of life. While greater than 2000 individuals with SCD have been treated with curative therapy, systematic studies have not been performed to evaluate the long-term health effects of hematopoietic stem cell transplant (HSCT) in this population. Individuals with SCD suffer progressive heart, lung, and kidney disease prior to curative therapy. In adults, these sequalae are associated with earlier death. In comparison, individuals who undergo HSCT for cancer are heavily pretreated with chemotherapy, resulting in potential acute and chronic heart, lung, and kidney disease. The long-term health effects on the heart, lung, and kidney for children and adults undergoing HSCT for cancer have been extensively investigated. These studies provide the best available data to extra...
Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation t... more Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. KCNK9 encodes for TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. However, KCNK9 gene amplification accounts for increased expression in <10% of these breast cancers. Here, we showed that KCNK9 is imprinted in breast tissue and identified a differentially methylated region (DMR) controlling its imprint status. Hypomethylation at the DMR, coupled with biallelic expression of KCNK9, occurred in 63% of triple-negative breast cancers (TNBC). The association between hypomethylation and TNBC status was highly significant in African-Americans (p = 0.006), but not in Caucasians (p = 0.70). KCNK9 hypomethylation was also found in non-cancerous tissue from 77% of women at high-risk of developing breast cancer. Functional studies demonstrated that the KCNK9 gene produc...
Cancer Epidemiology, Biomarkers & Prevention, 2020
Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who d... more Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who do not have a BRCA 1, BRCA 2 or other highly penetrant cancer susceptibility mutation. Background: Breast cancer is the most common cancer in women and the second most prevalent cause of cancer death of women in the United States; the lifetime risk for breast cancer in women is approximately 12%. Women may be at increased risk for breast cancer for many reasons including family history, genetic alterations, age, reproductive status and menstrual history. Most women who are at increased risk of developing breast cancer do not have a BRCA 1, BRCA 2 or other mutation. The majority of breast cancer diagnoses are due to acquired somatic mutations; only 5 to 10% of breast cancer diagnoses are attributable to highly penetrant Mendelian cancer susceptibility genes. White women with Ashkenazi Jewish ancestry tend to have a higher incidence of BRCA 1 and 2 mutations; traditionally, most research ef...
Cancer Epidemiology, Biomarkers & Prevention, 2020
The United States (US) is racially and culturally diverse. Still, white women disproportionately ... more The United States (US) is racially and culturally diverse. Still, white women disproportionately comprise clinical trial participants, stemming largely from the fact that minorities often decline participation. Clinical trial findings, therefore, have not been representative of the diverse patient population, and have stymied progress in precision medicine and cancer prevention. According to the CDC, among Asian/Pacific Islander females, the leading cause of death is cancer. Moreover, they have more total cancer-related deaths than any other racial group. Per the 2017 US Census, Asians are the third largest minority group of the population (6.6%). Despite the grave health disparities faced by a sizable proportion of the population, the literature is sparse with regards to their research engagement. For example, several studies have focused on Black and Hispanic consenting rates, including one study that demonstrated no significant differences between the two groups (Wendler, Kington...
Cancer Epidemiology, Biomarkers & Prevention, 2020
Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress... more Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress of preventative measures and treatments for all races and ethnicities. However, Northern European whites (NE/W) continue to be disproportionally enrolled (e.g., 93.5% were non-Hispanic white in the STAR trial), while minorities such as Asians, blacks, Latinas, and Native Americans (NA) lag in participation. Current studies suggest that minorities are not approached as frequently as NE/W; however, they are just as willing to participate. Here we present a successful recruitment strategy to improving minority accrual in CTs at a Comprehensive Cancer Center located in Duarte, CA. Method: Results from community focus groups suggested the need to mentor local youth who strive to pursue a career in the medical field. Consequently, from February 2016 to July 2018, four bilingual, bicultural clinical research assistants (CRAs) were recruited from the catchment area of City of Hope (CoH). The CR...
Cancer Epidemiology, Biomarkers & Prevention, 2020
The United States is increasingly racially and ethnically diverse. In fact, California is now a m... more The United States is increasingly racially and ethnically diverse. In fact, California is now a majority-minority region, with a greater percentage of its population comprised of racial minorities than whites. Yet, minorities are continually under-represented in clinical research trials, which provide crucial information on which the future of cancer treatments is built. Without representative inclusion of participants of color in clinical research, we cannot develop effective preventative and treatment approaches for everyone. This current study investigates the factors, including characteristics of study consenters, that may influence women—particularly women of color (WOC)—to accept or decline participation in breast cancer-related trials. We assess these factors through a brief survey, administered to patients immediately after they were invited to participate in a breast cancer-related clinical study. From the beginning of study accrual to the present, twenty-three patients hav...
Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy.... more Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy. Previous reports have shown that extracts made from rosehip plants are able to reduce cell proliferation of cancer cells. In this study, we investigated the efficacy of rosehip extracts in preventing cell proliferation of three human glioblastoma cell lines A-172, U-251 MG and U-1242 MG cell lines. Each of the glioblastoma cell lines treated with rosehip extracts (1 mg/mL-25 ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when inhibitors of the MAPK (U0126, 10 µM) or AKT (LY294002, 20 µM) signaling pathways were utilized. Additionally, pretreatment of the these cell lines with Rosehip extracts (1 mg/mL-25 ng/mL) selectively decreased AKT, MAPK, and p70S6K phosphorylation suggesting these extracts prevent glioblastoma multiforme cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from colorimetric cell death assays, cell cycle analysis by flow cytometry, as well as western blot studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Moreover, rosehip extracts were able to increase the efficacy of Temozolomide, a chemotherapeutic agent used to treat patients with glioblastomas. Surprisingly, rosehip extracts demonstrated a greater inhibition of cell proliferation than in combination with Temozolomide (100 µM) or Temozolomide as a single agent. Taken together these data suggest that rosehip extracts are capable of decreasing glioblastoma cell proliferation without promoting apoptosis and demonstrate a greater cell proliferation inhibitory effect than Temozolomide. More importantly, rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for glioblastomas.
Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. Thes... more Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. These tumors are characterized by increased rates of proliferation and invasive migration as well as angiogenesis. To date few therapeutic options exist for the treatment and management of GBMs, therefore we decided to investigate the anti-oncogenic properties of extracts from the rosehip plant. Rosehip extracts have been used for centuries as alternative therapies. Currently, rosehip extracts are being used as over the counter supplements and recent studies demonstrate that it has an anti-tumor effect. Therefore, we tested the anti-migratory and antiproliferative capacity of extracts from the rosehip (Rosa canina) plant in GBM cell lines. Three human GBM cell lines, U-251 MG, U-1242MG and A-172, were treated with rosehip extracts (1 mg/mL - 25ng/mL) and demonstrated a decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to the decrease of cell proliferation observed when U0126 (10µM), a know inhibitor of GBM cell proliferation was utilized. Utilizing a fluorescent-based labeling strategy (Live-Dead Assay), we examined whether rosehip extracts prevented cell proliferation by initiating apoptosis. Pretreatment of the GBM cells with rosehip extracts (1 mg/mL - 25ng/mL) induced the inhibition of cell proliferation without promoting apoptosis; whereas, cells treated with staurosporine (1 µM), a known inducer of apoptosis, showed an increase in cell apoptosis. Additional studies demonstrated that rosehip extracts prevent GBM cell proliferation by decreasing the active state of MAPK and AKT. Furthermore, rosehip extract-treated GBM cells also prevent cell migration by regulating actin remodeling. Taken together, these data suggest that rosehip extracts inhibit cell proliferation via a cytostatic mechanism that does not by induce apoptosis while also serving as a migration inhibiting agent. These data suggest that, rosehip extracts may serve as an alternative, or supplement, to current therapeutic regimens for GBMs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1986. doi:1538-7445.AM2012-1986
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. Thes... more Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. These tumors are characterized by increased rates of proliferation and invasive migration as well as angiogenesis. To date few therapeutic options exist for the treatment and management of GBMs, therefore we decided to investigate the anti-oncogenic properties of extracts from the rosehip plant. Rosehip extracts have been used for centuries as alternative therapies. Currently, rosehip extracts are being used as over the counter supplements and recent studies demonstrate that it has an anti-tumor effect. Therefore, we tested the anti-migratory and antiproliferative capacity of extracts from the rosehip (Rosa canina) plant in GBM cell lines. Three human GBM cell lines, U-251 MG, U-1242MG and A-172, were treated with rosehip extracts (1 mg/mL - 25ng/mL) and demonstrated a decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to the decrease of cell proliferation observed when U0126 (10µM), a know inhibitor of GBM cell proliferation was utilized. Utilizing a fluorescent-based labeling strategy (Live-Dead Assay), we examined whether rosehip extracts prevented cell proliferation by initiating apoptosis. Pretreatment of the GBM cells with rosehip extracts (1 mg/mL - 25ng/mL) induced the inhibition of cell proliferation without promoting apoptosis; whereas, cells treated with staurosporine (1 µM), a known inducer of apoptosis, showed an increase in cell apoptosis. Additional studies demonstrated that rosehip extracts prevent GBM cell proliferation by decreasing the active state of MAPK and AKT. Furthermore, rosehip extract-treated GBM cells also prevent cell migration by regulating actin remodeling. Taken together, these data suggest that rosehip extracts inhibit cell proliferation via a cytostatic mechanism that does not by induce apoptosis while also serving as a migration inhibiting agent. These data suggest that, rosehip extracts may serve as an alternative, or supplement, to current therapeutic regimens for GBMs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1986. doi:1538-7445.AM2012-1986
The United States is increasingly racially and ethnically diverse. In fact, California is now a m... more The United States is increasingly racially and ethnically diverse. In fact, California is now a majority-minority region, with a greater percentage of its population comprised of racial minorities than whites. Yet, minorities are continually under-represented in clinical research trials, which provide crucial information on which the future of cancer treatments is built. Without representative inclusion of participants of color in clinical research, we cannot develop effective preventative and treatment approaches for everyone. This current study investigates the factors, including characteristics of study consenters, that may influence women—particularly women of color (WOC)—to accept or decline participation in breast cancer-related trials. We assess these factors through a brief survey, administered to patients immediately after they were invited to participate in a breast cancer-related clinical study. From the beginning of study accrual to the present, twenty-three patients have taken the survey. We anticipate accruing 200 participants at a rate of 25 per month. For the preliminary analyses, we split participants in two groups: white women (WW) (n = 14) and women of color (WOC) (n = 9). We conducted independent sample t-tests to compare the responses of WW and WOC. More WOC (M = 1.44, SD = 0.73) reported that it is important that their consenter is of the same ethnicity or race than WW (M = 1.00, SD = .00), t (21) = -2.32, p &lt; .05. Similarly, WOC (M = 1.44, SD = .73) also reported that it is important that the person inviting them to participate in research look like people in their community, compared to the importance placed on this factor by WW (M = 1.00, SD = .00), t (21) = -2.32, p &lt; .05). More WOC (M = 2.33, SD = 1.23) also cited “feeling overwhelmed” with their medical condition as influential in their decision to participate in clinical research than WW (M = 1.31, SD = .48), t (20) = -2.75, p &lt; .05. Although both groups positively rated their interaction with the consenter, we observed marginal differences between WOC and WW. WOC (M = 7.00, SD = .00) gave higher ratings to the variable of “consenter created an atmosphere of trust and support” compared to ratings given by WW (M = 6.29, SD = 1.07), t (21) = -1.99, p = .06. Though participants are generally satisfied with their consenter interaction, different factors influence WW and WOC as they decide whether to participate in clinical research. When identified, these factors can be used to inform more inclusive consenting processes. Citation Format: Noe R. Chavez, Alan Nunez, Angela K. Wong, Tanya A. Chavez, Ellen Rippberger, Christine Thai, Angelica Sanchez, Ombeni M. Idassi, Krista M. Round, Kendall Kennedy, Margarita Robles, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Chidimma M.K. Kalu, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Courtney Vito, Karen Harold, Terry Hyslop, Carola M. Zalles, Daniel B. Schmolze, Christopher Sistrunk, Victoria L. Seewaldt. Influencing women's attitudes toward participation in breast cancer clinical research: Improving inclusion of women of color [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A082.
Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress... more Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress of preventative measures and treatments for all races and ethnicities. However, Northern European whites (NE/W) continue to be disproportionally enrolled (e.g., 93.5% were non-Hispanic white in the STAR trial), while minorities such as Asians, blacks, Latinas, and Native Americans (NA) lag in participation. Current studies suggest that minorities are not approached as frequently as NE/W; however, they are just as willing to participate. Here we present a successful recruitment strategy to improving minority accrual in CTs at a Comprehensive Cancer Center located in Duarte, CA. Method: Results from community focus groups suggested the need to mentor local youth who strive to pursue a career in the medical field. Consequently, from February 2016 to July 2018, four bilingual, bicultural clinical research assistants (CRAs) were recruited from the catchment area of City of Hope (CoH). The CRAs, in collaboration with seven surgeons, two radiologists, and one medical oncologist, led the recruitment for three nontherapeutic BC prevention CTs at CoH. Results: All four CRAs were 1) first-generation American, 2) fluent in Spanish or Vietnamese, 3) born and raised in Southern California, and 4) pre-health. Of the 3,148 patients who were screened, 398 were eligible for enrollment, 369 consented, and 58 declined. Primary languages and races/ethnicities of those who declined include the following: 7% Armenian, 9% Chinese, 78% English, 2% Thai, and 5% Spanish; 28% Asian, 3% black, 28% Latina, 2% NA, and 67% white (22% NE, 17% Middle Eastern/North African). Demographics of the consenting population include the following: primary language - &gt;1% Armenian, 4% Chinese, 89% English, &gt;1% Korean, and 7% Spanish; race/ethnicity - 14% Asian, 6% black, 30% Latina, 5% NA, and 75% white (40% NE). Of the white population (n = 277), 11% were Middle Eastern/North African, 53% NE, and 36% Latina. Accrual surpassed both the CoH catchment area (11.3% Asian, 8% black, 24% Hispanic, 1% NA, and 32% NE/W) and the CoH interventional/nontherapeutic CT population (10% Asian/Pacific Islander, 4% black, 21% Hispanic, &gt;1% NA, and 55% NE/W). Conclusion: Contrary to current accrual of CTs, here we show that minorities can have a large representation in CT accrual, as long as they are provided the opportunity. Accrual of Asians, Latinas, and NAs exceeded the catchment area and accrual of other CoH CTs. Interestingly, Chinese-speaking women comprised the highest declination group of the non-English speakers, and Asians and Latinas declined the most outside of non-whites. Cultural competency and bilingualism appear to be characteristics of a CRA that may help in accruing minority women into CTs. Our findings suggest that they are just as willing to participate, and the first step is to simply ask. Citation Format: Tanya A. Chavez, Christine Thai, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney A. Vito, Noé R. Chávez, Alan Nuñez, Ellen J. Rippberger, Angela K. Wong, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni Idassi, Kendall J. Kennedy, Terry Hyslop, Carola M. Zalles, Christopher Sistrunk, Victoria L. Seewaldt. Diversifying breast cancer clinical trial accrual: An approach to recruitment at a Comprehensive Cancer Center [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A083.
The United States (US) is racially and culturally diverse. Still, white women disproportionately ... more The United States (US) is racially and culturally diverse. Still, white women disproportionately comprise clinical trial participants, stemming largely from the fact that minorities often decline participation. Clinical trial findings, therefore, have not been representative of the diverse patient population, and have stymied progress in precision medicine and cancer prevention. According to the CDC, among Asian/Pacific Islander females, the leading cause of death is cancer. Moreover, they have more total cancer-related deaths than any other racial group. Per the 2017 US Census, Asians are the third largest minority group of the population (6.6%). Despite the grave health disparities faced by a sizable proportion of the population, the literature is sparse with regards to their research engagement. For example, several studies have focused on Black and Hispanic consenting rates, including one study that demonstrated no significant differences between the two groups (Wendler, Kington, Madans, Wye, Christ-Schmidt, Pratt et al., 2005) and another that indicated relatively lower enrollment rates among Hispanics and Blacks (Murthy, Krumholz, Gross, 2004). This gap in research is largely due to the marked heterogeneity with respect to language, nationality, and acculturation status. We examined Asian participation in three therapeutic, noninterventional trials that aim to develop early detection methods and accurate prognosis in women at high risk for breast cancer. Primarily, we collect leftover tissue and/or cells from fine needle aspirations (FNA) to better understand the cellular microenvironment that correlates with breast cancer development. We analyzed demographic data across these studies to investigate refusal rates among Asian women. Across the three trials, 3,119 participants were screened. Of the total number screened, 426 participants were eligible, 368 consented, and 58 declined. Of those who declined, 23.5% were Asians, 13.9% Hispanic, 8.3% Blacks, 5.6% Native Americans, and 11.4% White/non-Hispanic. Notably, Asians had the highest refusal rate. Fisher's exact test (two-tailed) was conducted to examine refusal rates for Asians compared to Whites, Blacks, and Hispanics. Results suggest that Asians had significantly higher rates of compared to Whites (p = .02, observed odds ratio = .42, 95% CI [.20, .86]), but were not significantly different than Blacks or Hispanics. The under-representation of Asians in research may exacerbate health disparities. Thus, further studies should examine ways, such as increasing racial and cultural competency, for increasing Asian representation in clinical research studies. Ultimately, we believe that illuminating under-representation of the “forgotten” Asian population in clinical research can inform future interventions that promote chemoprevention and treatment of this high-risk population. Citation Format: Stacey N. Doan, Christine Thai, Angela K. Wong, Tanya A. Chavez, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney Vito, Alan Nunez, Ellen J. Rippberger, Noe R. Chavez, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni M. Idassi, Kendall J. Kennedy, Christopher Sistrunk, Victoria L. Seewaldt. The forgotten race: Under-representation of Asians in clinical research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A084.
Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who d... more Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who do not have a BRCA 1, BRCA 2 or other highly penetrant cancer susceptibility mutation. Background: Breast cancer is the most common cancer in women and the second most prevalent cause of cancer death of women in the United States; the lifetime risk for breast cancer in women is approximately 12%. Women may be at increased risk for breast cancer for many reasons including family history, genetic alterations, age, reproductive status and menstrual history. Most women who are at increased risk of developing breast cancer do not have a BRCA 1, BRCA 2 or other mutation. The majority of breast cancer diagnoses are due to acquired somatic mutations; only 5 to 10% of breast cancer diagnoses are attributable to highly penetrant Mendelian cancer susceptibility genes. White women with Ashkenazi Jewish ancestry tend to have a higher incidence of BRCA 1 and 2 mutations; traditionally, most research efforts about highly penetrant genes have been focused on this group rather than other racial and ethnic groups. However, there is a great need to study breast cancer risk-reduction strategies in racial and ethnic minorities in the United States, particularly because most breast cancers are not caused by BRCA 1 and 2 mutations. City of Hope is located approximately 21 miles northeast of Los Angeles and operates 13 clinical practice locations including Los Angeles, Orange, Riverside, San Bernardino and Ventura counties. These five counties are home to the majority of California's multicultural and ethnic residents where San Bernardino County has the highest percentage of Hispanics (49.9%) and blacks (8.3%), Ventura County has the highest percentage of whites (48.1%), and Orange County has the highest concentration of Asians (18.2%). It has been established in the literature that the greatest benefit from breast cancer prevention strategies comes from treating women who are at high risk of the disease. While it is important to build a high-risk breast cancer clinic for women with genetic mutations, it is equally important to build a high-risk breast clinic for women who are at increased risk of breast cancer but do not have a mutation, particularly because most breast cancer is diagnosed in this population. In addition, it is crucial to educate high-risk patients that although they may have tested negative for a genetic mutation if they have a family history of breast cancer, they warrant close clinical surveillance. Methods: We are proposing a retrospective, descriptive study of data that will be collected as part of a high-risk breast cancer program implemented by City of Hope. Results/Conclusions: We expect to discuss the findings related to serving women of all races and ethnicities who do not have a mutation in a highly penetrant gene mutation. Citation Format: Karen Herold, Lisa D. Yee, Chidimma M. Kalu, Laura L. Kruper, Veronica C. Jones, Amy C. Polverini, Sharon Clancy, Tanya A. Chavez, Jackelyn A. Alva-Ornelas, Noe R Chavez, Ellen J. Rippberger, Jerneja Tomsic, Christopher Sistrunk, Ombeni Idassi, Daniel B. Schmolze, Courtney Vito, Alan Nunez, Angela K. Wong, Krista M. Round, Christine Thai, Angelica Sanchez, Margarita Robles, Kendall Kennedy, Terry Hyslop, Victoria L. Seewaldt. Architecture of increased breast cancer risk [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B109.
Despite cancer being the leading cause of death across most racial/ethnic groups, Hispanic women ... more Despite cancer being the leading cause of death across most racial/ethnic groups, Hispanic women have the second highest mortality rate attributed to diabetes (4.7%) according to the Centers for Disease Control and Prevention (CDC). While cancer and diabetes are two distinct diseases, previous studies have demonstrated that diabetic women have a poor chance of breast cancer survival when compared to nondiabetic women. Well-known key drivers of hyperinsulinemia and insulin resistance, such as insulin and AMPK, are also those involved in breast cancer. This link could possibly contribute to the increased mitogenic effects and risk for aggressive breast cancers in Hispanic women. Based on these findings, metformin, a drug standardly used to treat and prevent hyperglycemia, may be a possible alternative (other than tamoxifen) for breast cancer prevention. Eat, Move, Live (EML), a 5-week community-based program, focuses on targeting possible treatments of chronic diseases and risk reduct...
The goal of curing children and adults with sickle cell disease (SCD) is to maximize benefits and... more The goal of curing children and adults with sickle cell disease (SCD) is to maximize benefits and minimize intermediate and long-term adverse outcomes so that individuals can live an average life span with a high quality of life. While greater than 2000 individuals with SCD have been treated with curative therapy, systematic studies have not been performed to evaluate the long-term health effects of hematopoietic stem cell transplant (HSCT) in this population. Individuals with SCD suffer progressive heart, lung, and kidney disease prior to curative therapy. In adults, these sequalae are associated with earlier death. In comparison, individuals who undergo HSCT for cancer are heavily pretreated with chemotherapy, resulting in potential acute and chronic heart, lung, and kidney disease. The long-term health effects on the heart, lung, and kidney for children and adults undergoing HSCT for cancer have been extensively investigated. These studies provide the best available data to extra...
Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation t... more Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. KCNK9 encodes for TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. However, KCNK9 gene amplification accounts for increased expression in <10% of these breast cancers. Here, we showed that KCNK9 is imprinted in breast tissue and identified a differentially methylated region (DMR) controlling its imprint status. Hypomethylation at the DMR, coupled with biallelic expression of KCNK9, occurred in 63% of triple-negative breast cancers (TNBC). The association between hypomethylation and TNBC status was highly significant in African-Americans (p = 0.006), but not in Caucasians (p = 0.70). KCNK9 hypomethylation was also found in non-cancerous tissue from 77% of women at high-risk of developing breast cancer. Functional studies demonstrated that the KCNK9 gene produc...
Cancer Epidemiology, Biomarkers & Prevention, 2020
Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who d... more Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who do not have a BRCA 1, BRCA 2 or other highly penetrant cancer susceptibility mutation. Background: Breast cancer is the most common cancer in women and the second most prevalent cause of cancer death of women in the United States; the lifetime risk for breast cancer in women is approximately 12%. Women may be at increased risk for breast cancer for many reasons including family history, genetic alterations, age, reproductive status and menstrual history. Most women who are at increased risk of developing breast cancer do not have a BRCA 1, BRCA 2 or other mutation. The majority of breast cancer diagnoses are due to acquired somatic mutations; only 5 to 10% of breast cancer diagnoses are attributable to highly penetrant Mendelian cancer susceptibility genes. White women with Ashkenazi Jewish ancestry tend to have a higher incidence of BRCA 1 and 2 mutations; traditionally, most research ef...
Cancer Epidemiology, Biomarkers & Prevention, 2020
The United States (US) is racially and culturally diverse. Still, white women disproportionately ... more The United States (US) is racially and culturally diverse. Still, white women disproportionately comprise clinical trial participants, stemming largely from the fact that minorities often decline participation. Clinical trial findings, therefore, have not been representative of the diverse patient population, and have stymied progress in precision medicine and cancer prevention. According to the CDC, among Asian/Pacific Islander females, the leading cause of death is cancer. Moreover, they have more total cancer-related deaths than any other racial group. Per the 2017 US Census, Asians are the third largest minority group of the population (6.6%). Despite the grave health disparities faced by a sizable proportion of the population, the literature is sparse with regards to their research engagement. For example, several studies have focused on Black and Hispanic consenting rates, including one study that demonstrated no significant differences between the two groups (Wendler, Kington...
Cancer Epidemiology, Biomarkers & Prevention, 2020
Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress... more Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress of preventative measures and treatments for all races and ethnicities. However, Northern European whites (NE/W) continue to be disproportionally enrolled (e.g., 93.5% were non-Hispanic white in the STAR trial), while minorities such as Asians, blacks, Latinas, and Native Americans (NA) lag in participation. Current studies suggest that minorities are not approached as frequently as NE/W; however, they are just as willing to participate. Here we present a successful recruitment strategy to improving minority accrual in CTs at a Comprehensive Cancer Center located in Duarte, CA. Method: Results from community focus groups suggested the need to mentor local youth who strive to pursue a career in the medical field. Consequently, from February 2016 to July 2018, four bilingual, bicultural clinical research assistants (CRAs) were recruited from the catchment area of City of Hope (CoH). The CR...
Cancer Epidemiology, Biomarkers & Prevention, 2020
The United States is increasingly racially and ethnically diverse. In fact, California is now a m... more The United States is increasingly racially and ethnically diverse. In fact, California is now a majority-minority region, with a greater percentage of its population comprised of racial minorities than whites. Yet, minorities are continually under-represented in clinical research trials, which provide crucial information on which the future of cancer treatments is built. Without representative inclusion of participants of color in clinical research, we cannot develop effective preventative and treatment approaches for everyone. This current study investigates the factors, including characteristics of study consenters, that may influence women—particularly women of color (WOC)—to accept or decline participation in breast cancer-related trials. We assess these factors through a brief survey, administered to patients immediately after they were invited to participate in a breast cancer-related clinical study. From the beginning of study accrual to the present, twenty-three patients hav...
Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy.... more Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy. Previous reports have shown that extracts made from rosehip plants are able to reduce cell proliferation of cancer cells. In this study, we investigated the efficacy of rosehip extracts in preventing cell proliferation of three human glioblastoma cell lines A-172, U-251 MG and U-1242 MG cell lines. Each of the glioblastoma cell lines treated with rosehip extracts (1 mg/mL-25 ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when inhibitors of the MAPK (U0126, 10 µM) or AKT (LY294002, 20 µM) signaling pathways were utilized. Additionally, pretreatment of the these cell lines with Rosehip extracts (1 mg/mL-25 ng/mL) selectively decreased AKT, MAPK, and p70S6K phosphorylation suggesting these extracts prevent glioblastoma multiforme cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from colorimetric cell death assays, cell cycle analysis by flow cytometry, as well as western blot studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Moreover, rosehip extracts were able to increase the efficacy of Temozolomide, a chemotherapeutic agent used to treat patients with glioblastomas. Surprisingly, rosehip extracts demonstrated a greater inhibition of cell proliferation than in combination with Temozolomide (100 µM) or Temozolomide as a single agent. Taken together these data suggest that rosehip extracts are capable of decreasing glioblastoma cell proliferation without promoting apoptosis and demonstrate a greater cell proliferation inhibitory effect than Temozolomide. More importantly, rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for glioblastomas.
Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. Thes... more Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. These tumors are characterized by increased rates of proliferation and invasive migration as well as angiogenesis. To date few therapeutic options exist for the treatment and management of GBMs, therefore we decided to investigate the anti-oncogenic properties of extracts from the rosehip plant. Rosehip extracts have been used for centuries as alternative therapies. Currently, rosehip extracts are being used as over the counter supplements and recent studies demonstrate that it has an anti-tumor effect. Therefore, we tested the anti-migratory and antiproliferative capacity of extracts from the rosehip (Rosa canina) plant in GBM cell lines. Three human GBM cell lines, U-251 MG, U-1242MG and A-172, were treated with rosehip extracts (1 mg/mL - 25ng/mL) and demonstrated a decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to the decrease of cell proliferation observed when U0126 (10µM), a know inhibitor of GBM cell proliferation was utilized. Utilizing a fluorescent-based labeling strategy (Live-Dead Assay), we examined whether rosehip extracts prevented cell proliferation by initiating apoptosis. Pretreatment of the GBM cells with rosehip extracts (1 mg/mL - 25ng/mL) induced the inhibition of cell proliferation without promoting apoptosis; whereas, cells treated with staurosporine (1 µM), a known inducer of apoptosis, showed an increase in cell apoptosis. Additional studies demonstrated that rosehip extracts prevent GBM cell proliferation by decreasing the active state of MAPK and AKT. Furthermore, rosehip extract-treated GBM cells also prevent cell migration by regulating actin remodeling. Taken together, these data suggest that rosehip extracts inhibit cell proliferation via a cytostatic mechanism that does not by induce apoptosis while also serving as a migration inhibiting agent. These data suggest that, rosehip extracts may serve as an alternative, or supplement, to current therapeutic regimens for GBMs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1986. doi:1538-7445.AM2012-1986
Uploads
Papers by Ombeni Idassi