Friday
A protein corona-enabled blood test for early cancer detection
Experimental Drug Delivers One-Two Punch to Prostate Cancer Cells
An experimental drug that targets abnormally high levels of a protein linked to cancer growth appears to significantly reduce the proliferation of prostate cancer cells in laboratory cell cultures and animals, while also making these cells considerably more vulnerable to radiation, according to results of a study led by Johns Hopkins scientists.
The findings, published Sept. 12 in Cancer Research, could advance the search for novel combination treatments that make more effective and safer use of radiation against prostate cancer, the most common nonskin cancer in men and the second leading cause of cancer-related deaths in men in the United States.
Of the nearly 200,000 men diagnosed with prostate cancer each year in the United States, radiation is a first-line therapy considered for all but the most advanced disease. However, some of these cancers become resistant to the effects of radiation over time, according to Venu Raman, Ph.D., an associate professor of radiology and radiological science and of oncology at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Kimmel Cancer Center.
In a search for ways of extending the value of radiation and limiting the collateral damage to healthy tissue that necessarily high doses of radiation may inflict, Raman worked with Phuoc Tran, M.D., Ph.D., an associate professor of radiation oncology and molecular radiation sciences, oncology, and urology, and also a member of the Kimmel Cancer Center.
They and colleagues from Johns Hopkins and University Medical Centre Utrecht had earlier discovered that a protein called DDX3 appears to be "dysregulated" in many cancers, including breast, lung, colorectal, sarcoma and prostate. The researchers found that the more aggressive the cancer, the higher the expression of this protein, which helps maintain cellular stability.
The researchers then developed a molecule referred to as RK-33 that was designed to disrupt DDX3's function by locking on to a portion of the protein. They showed in previous studies with cell cultures that when adding RK-33 to malignant lung and other cancerous cells that highly express DDX3, proliferation slowed or halted, and the cells' ability to form colonies was impaired. Additionally, RK-33 appeared to be a radiosensitizer, making the destructive effects of radiation more pronounced.
In the new study, the researchers began by examining prostate cancer tissue samples from University Medical Centre Utrecht. Of the 23 samples with a Gleason score greater than seven, eight had high DDX3 expression. As with results of their earlier studies, the investigators found that the higher the expression of this protein, the more aggressive the cancer, which is determined by how the cells invade other tissue types and their ability to form tumors in laboratory models of cancers. When the researchers used gene engineering techniques to knock out DDX3 expression in laboratory-grown cell cultures that highly expressed this protein, cell proliferation was half that of cell cultures with high DDX3 expression.
Incubating cultured cells with RK-33 had a similar effect, knocking down DDX3 expression in cells that highly express this protein and hampering their ability to multiply. When researchers combined the drug with radiation, the effects were synergistic, they report, killing from two to four times more cells than radiation alone. Next, the researchers tested the effects of RK-33 and radiation in mice that had been injected with human prostate cancer cells that highly express DDX3. The animals formed tumors within a few weeks. Together, Raman says, this dual-mode treatment produced cell-killing results that paralleled their experiments in cell cultures.
Raman adds that the experimental drug appeared to have no toxicity in the mice, suggesting that it could be a promising drug to test in humans. Compounds based on RK-33, he says, might have value in treating a broad array of cancers that highly express DDX33 or as a supplement to radiation, making conventional doses more effective or improving the killing ability of lower doses. "A lot of work still needs to be done to develop this into a chemotherapy drug," Raman cautions. "But based on our findings, we think it could fill an unmet need in making the most common treatment for prostate cancer more effective."
Of the nearly 200,000 men diagnosed with prostate cancer each year in the United States, radiation is a first-line therapy considered for all but the most advanced disease. However, some of these cancers become resistant to the effects of radiation over time, according to Venu Raman, Ph.D., an associate professor of radiology and radiological science and of oncology at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Kimmel Cancer Center.
In a search for ways of extending the value of radiation and limiting the collateral damage to healthy tissue that necessarily high doses of radiation may inflict, Raman worked with Phuoc Tran, M.D., Ph.D., an associate professor of radiation oncology and molecular radiation sciences, oncology, and urology, and also a member of the Kimmel Cancer Center.
They and colleagues from Johns Hopkins and University Medical Centre Utrecht had earlier discovered that a protein called DDX3 appears to be "dysregulated" in many cancers, including breast, lung, colorectal, sarcoma and prostate. The researchers found that the more aggressive the cancer, the higher the expression of this protein, which helps maintain cellular stability.
The researchers then developed a molecule referred to as RK-33 that was designed to disrupt DDX3's function by locking on to a portion of the protein. They showed in previous studies with cell cultures that when adding RK-33 to malignant lung and other cancerous cells that highly express DDX3, proliferation slowed or halted, and the cells' ability to form colonies was impaired. Additionally, RK-33 appeared to be a radiosensitizer, making the destructive effects of radiation more pronounced.
In the new study, the researchers began by examining prostate cancer tissue samples from University Medical Centre Utrecht. Of the 23 samples with a Gleason score greater than seven, eight had high DDX3 expression. As with results of their earlier studies, the investigators found that the higher the expression of this protein, the more aggressive the cancer, which is determined by how the cells invade other tissue types and their ability to form tumors in laboratory models of cancers. When the researchers used gene engineering techniques to knock out DDX3 expression in laboratory-grown cell cultures that highly expressed this protein, cell proliferation was half that of cell cultures with high DDX3 expression.
Incubating cultured cells with RK-33 had a similar effect, knocking down DDX3 expression in cells that highly express this protein and hampering their ability to multiply. When researchers combined the drug with radiation, the effects were synergistic, they report, killing from two to four times more cells than radiation alone. Next, the researchers tested the effects of RK-33 and radiation in mice that had been injected with human prostate cancer cells that highly express DDX3. The animals formed tumors within a few weeks. Together, Raman says, this dual-mode treatment produced cell-killing results that paralleled their experiments in cell cultures.
Raman adds that the experimental drug appeared to have no toxicity in the mice, suggesting that it could be a promising drug to test in humans. Compounds based on RK-33, he says, might have value in treating a broad array of cancers that highly express DDX33 or as a supplement to radiation, making conventional doses more effective or improving the killing ability of lower doses. "A lot of work still needs to be done to develop this into a chemotherapy drug," Raman cautions. "But based on our findings, we think it could fill an unmet need in making the most common treatment for prostate cancer more effective."
Story Source:
Materials provided by Johns Hopkins Medicine. Note: Content may be edited for style and length.
Materials provided by Johns Hopkins Medicine. Note: Content may be edited for style and length.
Journal Reference:
- M. Xie, F. Vesuna, S. Tantravedi, G. M. Bol, M. R. Heerma van Voss, K. Nugent, R. Malek, K. Gabrielson, P. J. van Diest, P. T. Tran, V. Raman. RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3. Cancer Research, 2016; 76 (21): 6340 DOI: 10.1158/0008-5472.CAN-16-0440
Thursday
Novel Prostate Cancer Drug Target Identified
A protein critical to the development and growth of prostate cancer has been discovered by LSU Health Sciences Center researchers. The findings are published online in the Early Edition of Proceedings of the National Academy of Sciences, available the week of February 6, 2012
Dr. Liu and his team discovered a protein called ARD1 which is involved with the male hormone, androgen, and its receptor. Prostate cancer is a hormone-regulated disease and the main hormone is androgen. Androgen activates its receptor - androgen receptor (AR) to play a critical role in the development and progression of prostate cancer. Therefore, androgen deprivation therapy has been a standard treatment for advanced prostate cancer.
"However, a majority of tumors invariably relapse and become an androgen-independent prostate cancer from which most patients eventually die," notes Dr. Liu, who is also a member of the LSUHSC Stanley S. Scott Cancer Center.
To find an alternative strategy to treat prostate cancer, Dr. Liu's group is studying androgen receptor activators and increasing levels of these activators leading to prostate cancer. Following the discovery of this new protein, they determined that ARD1 is overproduced in the majority of prostate cancer samples, that it activates the androgen receptor, and that it is an essential component of prostate cancer cell growth.
"In addition, we demonstrated that inactivation of ARD1 inhibits the function of androgen receptors resulting in complete suppression of prostate cancer cell growth in tissue culture and prostate tumor growth in mice," reports Dr. Liu. "Furthermore, we revealed that the role of ARD1 in the development of prostate cancer is to modify the androgen receptor to enhance its activity."
According to the National Cancer Institute, about 242,000 American men will be diagnosed with prostate cancer this year. It is the second most diagnosed cancer among men, only behind skin cancer. An estimated 28,170 men will die from prostate cancer in 2012.
"Our study provides a novel avenue for controlling AR-mediated prostate tumor development by directly inhibiting the function of ARD1 or AR-ARD1 interaction," says Dr. Liu. "Developing an ARD1-specific inhibitor or an AR-ARD1 interaction-disrupting compound may be of therapeutic benefit in the treatment of prostate cancer."
Source-Eurekalert
Dr. Liu and his team discovered a protein called ARD1 which is involved with the male hormone, androgen, and its receptor. Prostate cancer is a hormone-regulated disease and the main hormone is androgen. Androgen activates its receptor - androgen receptor (AR) to play a critical role in the development and progression of prostate cancer. Therefore, androgen deprivation therapy has been a standard treatment for advanced prostate cancer.
"However, a majority of tumors invariably relapse and become an androgen-independent prostate cancer from which most patients eventually die," notes Dr. Liu, who is also a member of the LSUHSC Stanley S. Scott Cancer Center.
To find an alternative strategy to treat prostate cancer, Dr. Liu's group is studying androgen receptor activators and increasing levels of these activators leading to prostate cancer. Following the discovery of this new protein, they determined that ARD1 is overproduced in the majority of prostate cancer samples, that it activates the androgen receptor, and that it is an essential component of prostate cancer cell growth.
"In addition, we demonstrated that inactivation of ARD1 inhibits the function of androgen receptors resulting in complete suppression of prostate cancer cell growth in tissue culture and prostate tumor growth in mice," reports Dr. Liu. "Furthermore, we revealed that the role of ARD1 in the development of prostate cancer is to modify the androgen receptor to enhance its activity."
According to the National Cancer Institute, about 242,000 American men will be diagnosed with prostate cancer this year. It is the second most diagnosed cancer among men, only behind skin cancer. An estimated 28,170 men will die from prostate cancer in 2012.
"Our study provides a novel avenue for controlling AR-mediated prostate tumor development by directly inhibiting the function of ARD1 or AR-ARD1 interaction," says Dr. Liu. "Developing an ARD1-specific inhibitor or an AR-ARD1 interaction-disrupting compound may be of therapeutic benefit in the treatment of prostate cancer."
Source-Eurekalert
Monday
Alcohol consumption and risk of renal cell cancer: the NIH-AARP diet and health study
Background:
The effect of moderate to heavy drinking (>15 g per day) on renal cell cancer (RCC) risk is unclear.
Method:
The relationship between alcohol consumption and RCC was examined in the NIH-AARP Diet and Health Study (n=49 2187, 1814 cases).
Results:
Compared with >0 to <5 g per day of alcohol consumption, the multivariate relative risk (95% confidence intervals) for 15 to <30 and 30 g per day was, 0.75 (0.63–0.90) and 0.71 (0.59–0.85), respectively, in men and 0.67 (0.42–1.07) and 0.43 (0.22–0.84), respectively, in women.
Conclusion:
Alcohol consumption was inversely associated with RCC in a dose–response manner. The inverse association may be extended to 30 g per day of alcohol intake.
British Journal of Cancer 104, 537-541 (1 February 2011)
The effect of moderate to heavy drinking (>15 g per day) on renal cell cancer (RCC) risk is unclear.
Method:
The relationship between alcohol consumption and RCC was examined in the NIH-AARP Diet and Health Study (n=49 2187, 1814 cases).
Results:
Compared with >0 to <5 g per day of alcohol consumption, the multivariate relative risk (95% confidence intervals) for 15 to <30 and 30 g per day was, 0.75 (0.63–0.90) and 0.71 (0.59–0.85), respectively, in men and 0.67 (0.42–1.07) and 0.43 (0.22–0.84), respectively, in women.
Conclusion:
Alcohol consumption was inversely associated with RCC in a dose–response manner. The inverse association may be extended to 30 g per day of alcohol intake.
British Journal of Cancer 104, 537-541 (1 February 2011)
Tuesday
Women's Cancer Program
Overview:
The Women's Cancers Program Area addresses research, clinical and educational activities for malignancies in women. The program fosters interactive and collaborative activities between and among members in order to develop multidisciplinary research in the areas of breast and women's reproductive cancers. It takes a comprehensive approach to clinical cancer research with a focus on translational research.
Goals:
Establish genetic-based risk assessment and counseling by understanding high-risk/genetic predisposition
Evaluate and implement prevention and screening strategies by understanding high-risk/genetic predisposition
Investigate the molecular/genetic and environmental conditions that give rise to cancers in women for possible early intervention by understanding early cellular transformation events
Develop targeted therapeutics for women’s cancers by understanding the mechanisms of solid tumor progression/angiogenesis/invasion
Identify targets and develop new, rational, highly effective and minimally toxic therapeutic approaches by understanding established tumors/motility/metastasis
Meetings and Events:
Multiple weekly clinical meetings within each of the clinics
Monthly Ovarian Cancer Research Group meetings
Monthly joint Cedars Sinai-UCLA gynecologic oncology journal club for fellows and residents
Bi-annual meeting of Women’s Cancers Program Area members, with oral and poster presentations and an invited visiting research expert
Leadership:
Dr. John Glaspy serves as director of the Women's Cancers Program Area and is the inaugural recipient of the Estelle, Abe and Marjorie Sanders Endowed Chair in Cancer Research at UCLA in recognition of his distinguished contributions in the area of cancer research and his eminence as a faculty member in the David Geffen School of Medicine. A professor of medicine, Glaspy earned a medical degree at UCLA concurrently with a master's degree in public health from the UCLA School of Public Health. He has gained a national reputation in clinical medicine as an acute diagnostician and outstanding clinician. His research includes understanding the role of gene therapy in cancer and developing new and more efficient molecularly targeted therapies for melanoma and breast cancer. Glaspy played a major role in developing a community-based oncology research network designed to bring UCLA expertise and clinical research programs to regional oncology offices in California and several surrounding states.
Associate Director Dr. Robin Farias-Eisner, a professor of obstetrics and gynecology, serves as Chief of Gynecologic Oncology at UCLA. His research interests include developing better treatments for cervical and uterine cancer and better detection and treatment for ovarian cancer. Farias-Eisner and his colleagues are working on developing a test for the early detection of ovarian cancer that could join the mammogram, colonoscopy, and pap smear in the screening arsenal and save thousands of lives now lost every year to the cancer known as the "silent killer." The simple blood test can detect ovarian cancer when there are no physical signs of disease - when ovaries appear normal and CA 125, a biomarker for ovarian cancer, is normal. In a small study, Farias-Eisner and his team were able to diagnose early stage ovarian cancer with 100 percent accuracy using a panel of four biomarkers that create a specific protein signature. The work currently is being confirmed in a larger study.
The Women's Cancers Program Area addresses research, clinical and educational activities for malignancies in women. The program fosters interactive and collaborative activities between and among members in order to develop multidisciplinary research in the areas of breast and women's reproductive cancers. It takes a comprehensive approach to clinical cancer research with a focus on translational research.
Goals:
Establish genetic-based risk assessment and counseling by understanding high-risk/genetic predisposition
Evaluate and implement prevention and screening strategies by understanding high-risk/genetic predisposition
Investigate the molecular/genetic and environmental conditions that give rise to cancers in women for possible early intervention by understanding early cellular transformation events
Develop targeted therapeutics for women’s cancers by understanding the mechanisms of solid tumor progression/angiogenesis/invasion
Identify targets and develop new, rational, highly effective and minimally toxic therapeutic approaches by understanding established tumors/motility/metastasis
Meetings and Events:
Multiple weekly clinical meetings within each of the clinics
Monthly Ovarian Cancer Research Group meetings
Monthly joint Cedars Sinai-UCLA gynecologic oncology journal club for fellows and residents
Bi-annual meeting of Women’s Cancers Program Area members, with oral and poster presentations and an invited visiting research expert
Leadership:
Dr. John Glaspy serves as director of the Women's Cancers Program Area and is the inaugural recipient of the Estelle, Abe and Marjorie Sanders Endowed Chair in Cancer Research at UCLA in recognition of his distinguished contributions in the area of cancer research and his eminence as a faculty member in the David Geffen School of Medicine. A professor of medicine, Glaspy earned a medical degree at UCLA concurrently with a master's degree in public health from the UCLA School of Public Health. He has gained a national reputation in clinical medicine as an acute diagnostician and outstanding clinician. His research includes understanding the role of gene therapy in cancer and developing new and more efficient molecularly targeted therapies for melanoma and breast cancer. Glaspy played a major role in developing a community-based oncology research network designed to bring UCLA expertise and clinical research programs to regional oncology offices in California and several surrounding states.
Associate Director Dr. Robin Farias-Eisner, a professor of obstetrics and gynecology, serves as Chief of Gynecologic Oncology at UCLA. His research interests include developing better treatments for cervical and uterine cancer and better detection and treatment for ovarian cancer. Farias-Eisner and his colleagues are working on developing a test for the early detection of ovarian cancer that could join the mammogram, colonoscopy, and pap smear in the screening arsenal and save thousands of lives now lost every year to the cancer known as the "silent killer." The simple blood test can detect ovarian cancer when there are no physical signs of disease - when ovaries appear normal and CA 125, a biomarker for ovarian cancer, is normal. In a small study, Farias-Eisner and his team were able to diagnose early stage ovarian cancer with 100 percent accuracy using a panel of four biomarkers that create a specific protein signature. The work currently is being confirmed in a larger study.
National Institute of Health Cancer Statistics
http://seer.cancer.gov Welcome to the Surveillance, Epidemiology and End Results (SEER) Program, a premier source for cancer statistics in the United States. We collect information on incidence, prevalence and survival from specific geographic areas representing 28 percent of the US population and compile reports on all of these plus cancer mortality for the entire country. Our site is intended for anyone interested in US cancer statistics or cancer surveillance methods.
Overview of the SEER ProgramThe Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) is an authoritative source of information on cancer incidence and survival in the United States. SEER currently collects and publishes cancer incidence and survival data from population-based cancer registries covering approximately 28 percent of the US population. For more information on this, please view the SEER Research Data. SEER coverage includes 26 percent of African Americans, 41 percent of Hispanics, 43 percent of American Indians and Alaska Natives, 54 percent of Asians, and 71 percent of Hawaiian/Pacific Islanders. (Details are provided in the table: Number of Persons by Race and Hispanic Ethnicity for SEER Participants.)
The SEER Program registries routinely collect data on patient demographics, primary tumor site, tumor morphology and stage at diagnosis, first course of treatment, and follow-up for vital status. The SEER Program is the only comprehensive source of population-based information in the United States that includes stage of cancer at the time of diagnosis and patient survival data. The mortality data reported by SEER are provided by the National Center for Health Statistics. The population data used in calculating cancer rates is obtained periodically from the Census Bureau. Updated annually and provided as a public service in print and electronic formats, SEER data are used by thousands of researchers, clinicians, public health officials, legislators, policymakers, community groups, and the public.
NCI staff work with the North American Association of Central Cancer Registries (NAACCR) to guide all state registries to achieve data content and compatibility acceptable for pooling data and improving national estimates. The SEER team is developing computer applications to unify cancer registration systems and to analyze and disseminate population-based data. Use of surveillance data for research is being improved through Web-based access to the data and analytic tools, and linking with other national data sources. For example, a Web-based tool for public health officials and policy makers, State Cancer Profiles, provides a user-friendly interface for finding cancer statistics for specific states and counties. This Web site is a joint project between NCI and CDC and is part of the Cancer Control PLANET Web site which provides links to comprehensive cancer control resources for public health professionals. SEER staff also work with a number of collaborating organizations that are involved in cancer surveillance and related disciplines.
Read Goals of the SEER Program for more information about SEER's activites
Overview of the SEER ProgramThe Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) is an authoritative source of information on cancer incidence and survival in the United States. SEER currently collects and publishes cancer incidence and survival data from population-based cancer registries covering approximately 28 percent of the US population. For more information on this, please view the SEER Research Data. SEER coverage includes 26 percent of African Americans, 41 percent of Hispanics, 43 percent of American Indians and Alaska Natives, 54 percent of Asians, and 71 percent of Hawaiian/Pacific Islanders. (Details are provided in the table: Number of Persons by Race and Hispanic Ethnicity for SEER Participants.)
The SEER Program registries routinely collect data on patient demographics, primary tumor site, tumor morphology and stage at diagnosis, first course of treatment, and follow-up for vital status. The SEER Program is the only comprehensive source of population-based information in the United States that includes stage of cancer at the time of diagnosis and patient survival data. The mortality data reported by SEER are provided by the National Center for Health Statistics. The population data used in calculating cancer rates is obtained periodically from the Census Bureau. Updated annually and provided as a public service in print and electronic formats, SEER data are used by thousands of researchers, clinicians, public health officials, legislators, policymakers, community groups, and the public.
NCI staff work with the North American Association of Central Cancer Registries (NAACCR) to guide all state registries to achieve data content and compatibility acceptable for pooling data and improving national estimates. The SEER team is developing computer applications to unify cancer registration systems and to analyze and disseminate population-based data. Use of surveillance data for research is being improved through Web-based access to the data and analytic tools, and linking with other national data sources. For example, a Web-based tool for public health officials and policy makers, State Cancer Profiles, provides a user-friendly interface for finding cancer statistics for specific states and counties. This Web site is a joint project between NCI and CDC and is part of the Cancer Control PLANET Web site which provides links to comprehensive cancer control resources for public health professionals. SEER staff also work with a number of collaborating organizations that are involved in cancer surveillance and related disciplines.
Read Goals of the SEER Program for more information about SEER's activites
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