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News Article | May 10, 2017
Site: www.eurekalert.org

Study shows that slow-moving meditation practice works just as well as talk therapy, and better than medication If you've ever had insomnia, you know worrying about sleep makes it even harder to fall asleep. For the 30 percent of breast cancer survivors who have insomnia, sleepless nights can lead to depression, fatigue and a heightened risk of disease. Now, new UCLA research shows that tai chi, a form of slow-moving meditation, is just as effective as cognitive behavioral therapy, which has been considered the "gold standard" treatment, with both showing enduring benefits over one year. The results, published today in the Journal of Clinical Oncology, show that tai chi promotes robust improvements in sleep health in breast cancer survivors with insomnia, with additional benefits of improving depressive symptoms and fatigue. Furthermore, both tai chi and cognitive behavioral therapy, which is a form of talk therapy, showed similar rates of clinically significant improvements in symptoms or remission of insomnia. The American Academy of Sleep Medicine considers cognitive behavioral therapy the treatment of choice for insomnia. This approach involves identifying and changing negative thoughts and behaviors that are affecting the ability to fall asleep and stay asleep. While cognitive behavioral therapy treats insomnia, it's too expensive for some people and there is a shortage of trained professionals in the field, said Dr. Michael Irwin, the study's lead author and a UCLA professor of psychiatry and director of the Cousins Center for Psychoneuroimmunology at the Semel Institute for Neuroscience and Human Behavior. "Because of those limitations, we need community-based interventions like tai chi," Irwin said. Free or low-cost tai chi classes are often offered at libraries, community centers or outdoors in parks. Do-it-yourselfers can find instructional videos on YouTube and smartphone apps. In previous research, Irwin and colleagues found that tai chi, which relaxes the body and slows breathing, reduced inflammation in breast cancer survivors with the potential to lower risk for disease including cancer recurrence. To test tai chi's effect on insomnia, researchers recruited 90 breast cancer survivors, who had trouble sleeping three or more times per week and who also reported feeling depressed and fatigue during the daytime. The participants ranged in age from 42 to 83 and were randomly assigned to weekly cognitive behavioral therapy sessions or weekly tai chi instruction for three months. The tai chi group learned a Westernized form of the practice called tai chi chih. The researchers evaluated the participants at intervals for the next 12 months to determine if they were having insomnia symptoms, as well as symptoms of fatigue and depression, and determined whether they showed improvement. At 15 months, nearly half of the participants in both groups (46.7 percent in the tai chi group; 43.7 percent in the behavioral therapy group) continued to show robust, clinically significant improvement in their insomnia symptoms. "Breast cancer survivors often don't just come to physicians with insomnia. They have insomnia, fatigue and depression," said Irwin, who is also a member of the UCLA Jonsson Comprehensive Cancer Center. "And this intervention, tai chi, impacted all those outcomes in a similar way, with benefits that were as robust as the gold standard treatment for insomnia." Many of the tai chi participants continued to practice on their own after the study concluded, reflecting the motivation he's observed among breast cancer survivor, Irwin said. "They often are seeking health-promoting activities because they recognize that the mindfulness approach, or health-based lifestyle interventions, may actually protect them," he said. The study's other authors include Carmen Carrillo, Perry Nicassio, Richard Olmstead and Nina Sadeghi, all of the Cousins Center for Psychoneuroimmunology; Dr. Patricia Ganz of the UCLA Fielding School of Public Health and JCCC; and Julienne Bower professor of psychology and a member of the JCCC. The study was supported by grants from the National Cancer Institute (R01 CA 119159), the National Institutes of Health (R01-AG034588, R01-AG026364, R01 CA160245-01, CA195637-01) and the Cousins Center for Psychoneuroimmunology at UCLA's Semel Institute.


News Article | May 10, 2017
Site: www.biosciencetechnology.com

A new study by scientists at the UCLA Jonsson Comprehensive Cancer Center could be a significant step toward understanding how certain cases of advanced melanoma shield themselves from pembrolizumab, the FDA-approved treatment that harnesses the immune system to attack the disease. The researchers, led by UCLA’s Dr. Antoni Ribas, studied how melanoma cancer cells react to the interferon gamma pathway, which guides cell signaling and can affect the way cancer cells react to pembrolizumab. The team then discovered and mapped out the molecules involved in the signaling pathway. The findings lay the groundwork for developing new and improved combination therapies for patients who are resistant to stand-alone immunotherapy treatments. Pembrolizumab (marketed as Keytruda) works by signaling the patient’s immune system to recognize and attack cancer cells, with minimal side effects. It was approved in 2014 by the U.S. Food and Drug Administration to treat advanced melanoma, and approved recently to treat people with advanced non-small cell lung cancer. The medication is currently being tested as a treatment for other types of cancer. In February, a study published by Ribas and colleagues in Cancer Discovery showed that people with cancers containing genetic mutations JAK1 or JAK2 (which are known to prevent tumors from recognizing or receiving signals from T cells to stop growing), will receive little or no benefit from pembrolizumab. This discovery enabled the scientists to determine why some people with advanced melanoma or colon cancer will not respond to the drug. That built on 2016 research by Ribas and colleagues, published in the New England Journal of Medicine, in which they analyzed pairs of tumors both before a patient had undergone immunotherapy treatment and after relapse. The results showed that one of the tumors lost a gene called B2M, which resulted in a change in how the cancer is recognized by the immune system. The disruption caused JAK1 and JAK2 to function improperly and prevented the immune system from attacking the cancer. The new study was conducted over a two-year period; the scientists analyzed dozens of melanoma cell lines and several tumor samples from patients. In the laboratory, researchers also used an advanced technology called a lentivirus shRNA screen to locate which molecules were involved in the interferon receptor pathway signaling process. The research allows further investigations into how the immune systems of patients with advanced cancers can resist anti–PD-1 immunotherapy treatments, the class of treatments that includes pembrolizumab. The study is published in Cell Reports.


News Article | May 10, 2017
Site: www.prnewswire.com

"Finally, we look forward to presenting the more detailed and updated global Phase 3 STS results to the medical community at the upcoming 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.  This Phase 3 trial, along with the combination trial of aldoxorubicin with ifosfamide/mesna, continue to build upon the body of clinical data supporting aldoxorubicin's potential as a new and better treatment for patients with STS," Mr. Kriegsman commented. Strengthened the Balance Sheet with $15 Million in Financing and $2 Million in Warrant Proceeds.  In early May 2017, CytRx completed the sale of approximately 30 million shares of common stock in a public offering at a price of $0.50 per share, resulting in net proceeds to the Company of approximately $13.9 million after deducting placement agent's fees and other estimated offering expenses.  Additionally, the Company received approximately $1.9 million from the exercise of warrants resulting in a total raise of $15.8 million subsequent to March 31, 2017. Concluded Phase 3 Trial Evaluating Aldoxorubicin in Relapsed or Refractory STS.  Based on its goal to submit a rolling NDA, subject to approval from the FDA, the Company has concluded its Phase 3 study evaluating aldoxorubicin compared to investigator's choice in patients with relapsed or refractory STS. Aldoxorubicin Clinical Trial Data in Patients with STS Selected for Oral Presentation at the 2017 American Society of Clinical Oncology Annual Meeting (ASCO).  In April 2017, CytRx announced that an abstract describing results from its global Phase 3 clinical trial evaluating aldoxorubicin versus investigators' choice in patients with relapsed and refractory STS was selected for an oral presentation at ASCO 2017, taking place June 2-6, 2017 in Chicago.  The oral presentation (abstract #11000) will be given by Principal Investigator, Sant Chawla, M.D., F.R.A.C.P., Director of the Sarcoma Oncology Center in Santa Monica, on Friday, June 2, 2017 between 3:00-6:00 pm CT.  In addition to the STS presentation, a poster (abstract #11051) highlighting updated data from CytRx's ongoing Phase 1/2 clinical trial combining aldoxorubicin with ifosfamide/mesna in patients with first-line soft tissue sarcomas will also be presented by Frederick C. Eilber, M.D., Director of the UCLA Sarcoma Translational Research Program within the Jonsson Comprehensive Cancer Center, on Sunday, June 4, 2017 between 8:00-11:00 am CT. Announced FDA Agreement on Regulatory Pathway to Approval for Aldoxorubicin in STS.  In April 2017, CytRx announced that it had reached an agreement with the FDA on the pathway for a NDA submission for aldoxorubicin as a treatment for STS.  The Company's goal is to submit a rolling NDA under section 505(b)(2) to the FDA in the fourth quarter of 2017.  The commercial launch of aldoxorubicin is projected for 2018 in the U.S.  Aldoxorubicin has received Orphan Drug Designation from the FDA for the treatment of STS, which provides for several benefits including seven years of market exclusivity after approval, certain R&D related tax credits and protocol assistance from the FDA.  CytRx also plans to discuss with the European Medicines Agency a path to filing a Marketing Authorization Application.  European regulators granted aldoxorubicin Orphan Medicinal Product Designation for STS which confers ten years of market exclusivity among other benefits. On May 2, 2017, CytRx completed a public offering of 30 million shares of its common stock at a price of $0.50 per share.  The net proceeds to CytRx from the offering, after deducting placement agent's fees and other estimated offering expenses, were approximately $13.9 million.  In addition, CytRx received $1.9 million in proceeds from the exercise of warrants in April and May 2017. Net loss for the quarter ended March 31, 2017, was $11.0 million, or $(0.10) per share, compared with a net loss of $12.6 million, or $(0.19) per share, for the quarter ended March 31, 2016.  During the first quarter of 2017, the Company recognized a non-cash loss of $0.03 million on the fair value adjustment of warrant derivative liability related to warrants issued in 2016, compared to a non-cash loss of $0.2 million during the first quarter of 2016 related to now expired warrants. Research and development (R&D) expenses were $6.8 million for the first quarter of 2017, and included development expenses of $4.0 million for aldoxorubicin, approximately $0.6 million for pre-clinical development of new albumin-binding, ultra-high potency cancer drugs (German lab), and approximately $2.2 million for general operation of our clinical programs.  R&D expenses were $8.2 million for the first quarter of 2016. General and administrative (G&A) expenses were $3.0 million for the first quarter of 2017, compared with $4.0 million for the first quarter of 2016. CytRx Corporation is a biopharmaceutical research and development company specializing in oncology. CytRx currently is focused on the clinical development of aldoxorubicin, its improved version of the widely used chemotherapeutic agent doxorubicin.  CytRx is also expanding its pipeline of oncology candidates at its laboratory facilities in Freiburg, Germany, through its LADR™ (Linker Activated Drug Release) technology platform, a discovery engine designed to leverage CytRx's expertise in albumin biology and linker technology for the development of a new class of anti-cancer therapies. This press release contains forward-looking statements. Such statements are not promises or guarantees, and involve numerous risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements.  These risks include: the timing and final results of CytRx's clinical testing of aldoxorubicin; timing of CytRx's preparation and submission of an NDA for aldoxorubicin for the treatment of STS and FDA acceptance and review of any NDA; the risk that CytRx may be unsuccessful in obtaining FDA approval or, if approval is obtained, in commercializing aldoxorubicin in the United States or elsewhere; risks related to CytRx's need for and ability to raise additional capital or enter into strategic partnerships to fund its ongoing working capital needs and development efforts; risks related to CytRx's ability to manufacture its drug candidates in a timely fashion, cost-effectively or in commercial quantities in compliance with stringent regulatory requirements; risks relating to preclinical testing of CytRx's LADR™ linker technology platform; risks related to pending lawsuits against CytRx and its officers and directors; and the other risks and uncertainties described in CytRx's Annual Report on Form 10-K for the year ended December 31, 2016 filed with the Securities and Exchange Commission. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/cytrx-reports-first-quarter-2017-financial-results-300455045.html


News Article | May 23, 2017
Site: www.prweb.com

Vortex Biosciences, provider of circulating tumor cell (CTC) capture systems, today announced the publication of “Label-free isolation of prostate circulating tumor cells using Vortex microfluidic technology” in Nature Precision Oncology on May 8th. The peer reviewed publication is the result of a collaboration with Dr. Dino Di Carlo and Dr. Matthew Rettig at the University of California, Los Angeles. The publication describes the use of Vortex technology for the isolation and characterization of CTCs from 22 patients with advanced prostate cancer. CTCs can provide both genetic and phenotypic information about tumor evolution, potentially from both primary and metastatic sites. In this paper, the utility of the Vortex technology to support the capture and characterization of CTCs from prostate cancer patients was demonstrated. The Vortex technology isolates and collects CTCs directly from whole blood based on the greater deformability and larger size of the cells. CTCs are collected unbiased by their molecular characteristics and available for a wide range of analysis, providing a window into a patient’s cancer biology. The paper describes the capturing of CTCs from prostate cancer patients with high purity (from 1.74 to 37.59%) and efficiency (from 1.88 to 93.75 CTCs/7.5mL). Interestingly, atypical large circulating cells were identified in 5 age-matched healthy donors (46-77 years old; 1.25-2.5 CTCs/7.5 mL) but not in 5 healthy donors <30 years-old (21-27 years old; 0.00 CTC/7.5 mL). Using a threshold calculated from the 5 age-matched healthy donors (3.37 CTCs/mL), CTCs were identified at levels above the healthy threshold in 80% of the prostate cancer patients. A fraction of the cells collected (11.5%) did not express epithelial prostate markers (CK and/or PSA) and some instead expressed markers of epithelial-mesenchymal transition (EMT), i.e. vimentin and N-cadherin. "We are excited to see how effective the Vortex technology is for isolating CTCs independent of their epithelial properties, making them available for both genomic and phenotypic analysis,“ said Dr. Dino Di Carlo, Director of the Microfluidic Biotechnology Laboratory at UCLA and Director of the Cancer Nanotechnology Program of the Jonsson Comprehensive Cancer Center. "The work demonstrated in this paper shows what a powerful window into patient cancer biology CTCs can be with the right collection system." The fully automated VTX-1 Liquid Biopsy System from Vortex represents the next step in CTC isolation. The Vortex system utilizes a proprietary microfluidic chip to stably trap and capture CTCs in micro-scale vortices based on their larger size and greater deformability than the white and red blood cells. With excellent CTC recovery, best in class CTC purity, and collected CTCs being viable, and ready for downstream analysis, the VTX-1 offers the best CTC samples available today. About Vortex Biosciences Vortex Biosciences is a cancer research and diagnostics company that integrates cancer biology, microfluidic engineering and informatics to develop tools for isolating and characterizing circulating tumor cells. The Vortex VTX-1 instrument harvests intact circulating tumor cells from whole blood samples for use in downstream research and clinical applications such as patient stratification in clinical trials, monitoring disease progression and drug treatment effectiveness. With a mission to enable noninvasive diagnosis of cancer and real-time monitoring throughout a patient’s treatment, Vortex is at the forefront of accelerating cancer research and improving patient outcomes. Vortex is a core subsidiary of NetScientific plc, a transatlantic healthcare technology group with an investment strategy focused on sourcing, funding and commercializing technologies that significantly improve the health and well-being of people with chronic diseases. For more information, visit http://www.vortexbiosciences.com.


Daniel Levitt, M.D., Ph.D., Chief Operating Officer and Chief Medical Officer of CytRx, commented, "The data from both of these important clinical trials evaluating aldoxorubicin in sarcomas, along with our several other completed clinical and preclinical studies, will form the basis of our planned New Drug Application submission to the U.S. Food and Drug Administration, and we are pleased to share these more mature and detailed results in this peer-reviewed forum with the medical and scientific communities." Details for the presentations at ASCO 2017: Title: Phase III study of aldoxorubicin vs investigators' choice as treatment for relapsed/refractory soft tissue sarcomas Presenter: Sant Chawla, M.D., F.R.A.C.P., Director of the Sarcoma Oncology Center in Santa Monica, and Principal Investigator Abstract #: 11000 Session Title: Oral Abstract Session: Sarcoma Location: S100bc Date and Time: Friday, June 2, 2017; 3:00pm-6:00pm CT Summary:  This multicenter, randomized, open-label Phase 3 trial enrolled 433 patients at 79 sites.  The data summarized here are as of August 2016.  In patients with leiomyosarcoma and liposarcoma (n=246), aldoxorubicin demonstrated median progression-free survival (PFS) of 5.32 months, compared to a median PFS of 2.96 months for investigator's choice therapy, a statistically significant improvement of 2.36 months (p=0.007; hazard ratio (HR)=0.62, 95% CI 0.44-0.88), representing a 38% reduction in the risk of tumor progression.  In patients treated in North America plus Australia (n=312), aldoxorubicin demonstrated a median PFS of 4.21 months, compared to a median PFS of 2.96 months for investigator's choice therapy, a statistically significant improvement of 1.25 months (p=0.023, HR=0.71, 95% CI 0.53-0.96).  In the overall intent to treat (ITT) trial population (n=433), aldoxorubicin performed better than investigator's choice demonstrating a median PFS of 4.11 months, compared to a median PFS of 2.96 months for investigator's choice therapy, narrowly missing statistical significance (p=0.087; HR=0.81, 95% CI 0.64-1.03).  All responses in this study were determined by an independent, blinded central lab assessment of scans. Key safety findings included that aldoxorubicin caused no clinically significant cardiac, renal, or hepatic toxicities.  Aldoxorubicin administered at 350mg/m2 per cycle showed no cardiotoxicity up to 40 cycles.  Importantly, left ventricular ejection fraction (LVEF) below 50% of expected values were reported in 4.2% of patients treated with aldoxorubicin, compared to 19.1% for patients receiving investigator's choice.  Additionally, ≥20% decreases in LVEF from baseline were reported in 3.8% of patients treated with aldoxorubicin, compared to 8.5% for patients receiving investigator's choice.  For the global trial population, the most commonly reported (≥10%) Grade ≥3 adverse events were neutropenia, anemia, febrile neutropenia, stomatitis and decreased white blood cell count, and were manageable with standard supportive care.  The non-cardiac Grade ≥3 adverse events associated with aldoxorubicin were similar to doxorubicin despite exposure up to 3-4 times the standard doxorubicin dose. Updated data relating to the trials other secondary endpoints, including objective response rate (ORR), disease control rate (DCR), overall survival, and other safety parameters were in line with what has previously been reported by CytRx and will be included in the oral presentation being given at ASCO 2017. Following conclusion of Dr. Chawla's presentation, a PDF copy of the oral presentation slides will be available at http://cytrx.com/investors/presentations. Title: Administration of aldoxorubicin and 14 days continuous infusion of ifosfamide/Mesna in metastatic or locally advanced sarcomas Presenter: Frederick C. Eilber, M.D., Director of the UCLA Sarcoma Translational Research Program within the Jonsson Comprehensive Cancer Center Abstract #: 11051 Session Title: Poster Session: Sarcoma Location: Hall A Poster board#: 374 Date and Time:  Sunday, June 4, 2017; 8:00am-11:30am CT Summary:  This ongoing open-label Phase 1/2 clinical trial is designed to assess the preliminary safety and activity of aldoxorubicin plus I-M as a first- or second-line treatment in patients with STS.  Patients were administered 1 of 2 dose levels of aldoxorubicin (170mg/m2 or 250mg/m2 [125mg/m2 or 185mg/m2 doxorubicin equivalent]) on Day 1, then I-M (1g/m2 of each per day) was administered for up to 14 days as a continuous infusion.  Chemotherapy cycles were repeated at 28 day intervals, but I-M was limited to a maximum of 6 cycles to avoid cumulative bone marrow toxicity.  Aldoxorubicin was continued per investigator decision in either responding or stable disease (SD) patients.  Patients were followed for tumor response by CT scans and echocardiogram for cardiac toxicity every 8 weeks along with standard labs. Of the 44 evaluable patients as of May 10, 2017, 16 patients (36%) achieved a partial response (PR), 25 patients (57%) achieved SD, with 20 patients (45%) achieving SD for ≥4 months, for an overall disease control rate (DCR) of 82% (PR+SD≥4).  Twenty-two of 44 (50%) patients received at least 6 cycles of aldoxorubicin (>1,300 mg/m2 cumulative doxorubicin equivalent).  As of the data cutoff date, the median PFS had not been reached.  The most commonly reported Grade ≥3 adverse event (AEs; >20%) were neutropenia and anemia.  Reported serious adverse events (SAEs) included febrile neutropenia (14%, n=6), anemia (5%, n=2), thrombocytopenia (2%, n=1), stomatitis (2%, n=1) and pyrexia (2%, n=1).  No clinically significant cardiotoxicity has been observed and no patients had a clinically significant decrease in LVEF or QTc prolongation, despite administration of median cumulative doses of doxorubicin equivalents of 1364-1965mg/m2.  No treatment related deaths occurred.  These results support the thesis that aldoxorubicin can be administered safely and for prolonged periods with continuous infusion I-M and achieves high response rates and SD, with substantial tumor necrosis.  Based on these results, the decision was made to stop further aldoxorubicin dose escalation and continue to enroll only in the 250mg/m2 cohort. Following conclusion of the poster presentation, a PDF copy of the poster will be available at http://cytrx.com/investors/presentations. Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue.  It can arise anywhere in the body at any age.  STS remains a high unmet medical need because of the difficulty in treating the more than 50 types of this aggressive cancer.  According to the American Cancer Society, in 2016 more than 12,300 new cases were diagnosed in the U.S. and approximately 5,000 Americans died from this disease.  In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market. Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream.  Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites.  In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 6,500 mg/m2 of doxorubicin equivalents. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS. CytRx Corporation is a biopharmaceutical research and development company specializing in oncology. CytRx currently is focused on the clinical development of aldoxorubicin, its improved version of the widely used chemotherapeutic agent doxorubicin.  CytRx is also expanding its pipeline of oncology candidates at its laboratory facilities in Freiburg, Germany, through its LADR™ (Linker Activated Drug Release) technology platform, a discovery engine designed to leverage CytRx's expertise in albumin biology and linker technology for the development of a new class of anti-cancer therapies. This press release contains forward-looking statements. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks and uncertainties relating to the preparation and submission of an NDA for aldoxorubicin for the treatment of STS and FDA acceptance and review of any NDA, the risk that CytRx may be unsuccessful in obtaining FDA approval or, if approval is obtained, in commercializing aldoxorubicin in the United States or elsewhere, and other risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx's most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/cytrx-to-present-global-phase-3-aldoxorubicin-clinical-data-in-patients-with-soft-tissue-sarcomas-at-the-2017-american-society-of-clinical-oncology-annual-meeting-300459626.html


News Article | May 1, 2017
Site: www.eurekalert.org

IMAGE:  Ovarian cancer tumors with higher percentages of cIAP-expressing cells, shown in red at left, were more sensitive to a potential combination therapy than tumor cells without cIAP-expressing cells. view more Researchers have been trying to understand why up to 85 percent of women experience recurrence of high-grade serous ovarian cancer -- the most common subtype of ovarian cancer -- after standard treatment with the chemotherapy drug carboplatin. Preclinical research from Dr. Sanaz Memarzadeh, who is a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, has potentially solved this mystery and pinpointed a combination therapy that may be effective for up to 50 percent of women with ovarian cancer. Memarzadeh's research, published in the journal Precision Oncology, shows a new combination therapy of carboplatin and an experimental drug called birinapant can improve survival in mice with ovarian cancer tumors. Additional findings reveal that testing for a specific protein could identify ovarian tumors for which the treatment could be effective. Importantly, the treatment could also target cancers that affect other parts of the body, including the bladder, cervix, colon and lung cancer. In 2015, Memarzadeh and her team uncovered and isolated carboplatin-resistant ovarian cancer stem cells. These cells have high levels of proteins called cIAPs, which prevent cell death after chemotherapy. Since the cancer stem cells survive carboplatin treatment, they regenerate the tumor; with each recurrence of ovarian cancer, treatment options become more limited. Memarzadeh showed that birinapant, which degrades cIAPs, can make carboplatin more effective against some ovarian cancer tumors. "I've been treating women with ovarian cancer for about two decades and have seen firsthand that ovarian cancer treatment options are not always as effective as they should be," said Memarzadeh, director of the G.O. Discovery Lab and member of the UCLA Jonsson Comprehensive Cancer Center. "Our previous research was promising, but we still had questions about what percentage of tumors could be targeted with the birinapant and carboplatin combination therapy, and whether this combination could improve overall survival by eradicating chemotherapy-resistant ovarian cancer tumors." In this new study, the research team first tested whether the combination therapy could improve survival in mice. Half of the mice tested had carboplatin-resistant human ovarian cancer tumors and the other half had carboplatin-sensitive tumors. The team administered birinapant or carboplatin as well as the two drugs combined and then monitored the mice over time. While birinapant or carboplatin alone had minimal effect, the combination therapy doubled overall survival in half of the mice regardless of whether they had carboplatin-resistant or carboplatin-sensitive tumors. "Our results suggest that the treatment is applicable in some, but not all, tumors," said Rachel Fujikawa, a fourth year undergraduate student in Memarzadeh's lab and co-first author of the study. To assess the combination therapy's rate of effectiveness in tumors, the team went on to test 23 high-grade serous ovarian cancer tumors from independent patients. Some were from patients who had never been treated with carboplatin and some were from patients who had carboplatin-resistant cancer. With these samples, the researchers generated ovarian cancer tumors utilizing a method called disease-in-a-dish modeling and tested the same treatments previously tested in mice. Once again, carboplatin or birinapant alone had some effect, while the combination of birinapant and carboplatin successfully eliminated the ovarian cancer tumors in approximately 50 percent of samples. Importantly, the combination therapy worked for both carboplatin-resistant and carboplatin-sensitive tumors. The researchers also measured cIAPs (the target for the drug birinapant) in the tumors. They found a strong correlation between cancer stem cells with high levels of cIAP and a positive response to the combination therapy. Since elevated levels of cIAPs have been linked to chemotherapy resistance in other cancers, the researchers wondered if the combination therapy could effectively target those cancers as well. The team created disease-in-a-dish models using human bladder, cervix, colon and lung cancer cells and tested the combination therapy. Similar to the ovarian cancer findings, 50 percent of the tumors were effectively targeted and high cIAP levels correlated with a positive response to the combination therapy. "I believe that our research potentially points to a new treatment option. In the near future, I hope to initiate a phase 1/2 clinical trial for women with ovarian cancer tumors predicted to benefit from this combination therapy," said Memarzadeh, gynecologic oncology surgeon and professor at the David Geffen School of Medicine at UCLA. The research was supported by an American Cancer Society Research Scholar Grant (RSG-14-217-407 01-TBG), the Phase One Foundation, the Ovarian Cancer Circle Inspired by Robin Babbini, a STOP Cancer Margot Lansing Memorial Seed award, the National Institutes of Health (R01CA183877 and #U54 MD007598) and the UCLA Broad Stem Cell Research Center.


News Article | February 15, 2017
Site: www.eurekalert.org

Scalp cooling can lessen some chemotherapy-induced hair loss - one of the most devastating hallmarks of cancer - in certain breast cancer patients, according to a new multicenter study from UC San Francisco, Weill Cornell Medicine and three other medical centers. A majority of the study's patients, all women with stage 1 or 2 breast cancer who underwent scalp cooling, retained more than half of their hair after completing chemotherapy, the investigators learned. The study, which tracks patients over five years, used standardized photographs to grade hair loss. The study will be published Feb. 14 in JAMA, the Journal of the American Medical Association. "Hair loss is almost universal among breast cancer patients receiving adjuvant chemotherapy and is one of the most distressing of adverse side effects," said first author Hope S. Rugo, MD, the corresponding author who led the study. Rugo is a UCSF professor of medicine specializing in breast cancer research and treatment, and director of the breast oncology and clinical trials education program at the UCSF Helen Diller Family Comprehensive Cancer Center. "We found that scalp cooling during commonly used chemotherapy regimens was well tolerated and was associated with significantly less hair loss, as well as improvement in several quality-of-life indicators," Rugo said. "While further research is needed, the data suggest that when scalp cooling is successful at decreasing hair loss, it could improve the treatment experience for women undergoing adjuvant chemotherapy for early-stage breast cancer." Breast cancer is the most common cancer in women around the world, both in developed countries and less developed ones, according to the World Health Organization. Scalp cooling has been used in more than 30 countries as a way to potentially prevent hair loss in patients receiving chemotherapy; in Europe it's been used for several decades. Two types of cooling caps are typically used: frozen caps that need to be replaced every half hour, or cooling systems that continually circulate coolants into a cap during the entire chemotherapy session. Scalp cooling is thought to reduce hair loss due to reduced delivery of chemotherapy to the scalp and hair follicle, Rugo said. The cold temperatures also are thought to slow the hair follicle cell division, making the cell less susceptible to the damaging effects of chemotherapy. In the United States, scalp cooling has been limited because of factors including insufficient scientific data and concern about the theoretic risk of scalp metastases. For the JAMA study, researchers investigated the effectiveness of one device: the DigniCap scalp cooling system manufactured by the Swedish public company Dignitana AB, which partly funded the research. In December 2015, based on preliminary results from the study, the U.S. Food and Drug Administration cleared the DigniCap for use in the U.S., the first and only cooling cap to date to receive such clearance. In the JAMA paper, 122 women with stage 1or stage 2 breast cancer were studied - all received non-anthracycline adjuvant chemotherapy, which generally causes severe hair loss. Of those women, 101 were enrolled in scalp cooling; 16 others, also undergoing chemotherapy but not scalp cooling, were in the control arm. Scalp cooling began 30 minutes prior to each chemotherapy cycle and involved a close fitting of the silicone cap on the patient's head, followed by an insulating neoprene cap. The silicone cap was then gradually cooled. The DigniCap is set to cool at 3 degrees Celsius (37 degrees Fahrenheit) with a temperature variance of plus or minus 2 degrees. Of 101 patients who underwent scalp cooling, 67 of them (66.3 percent) retained half or more of their hair, the authors wrote. In the parallel control group, all the patients lost their hair. Additionally, three of five quality-of-life measures were significantly better for the women who underwent scalp-cooling, including feeling more physically attractive. "Enabling a woman to preserve her hair during chemotherapy is empowering," said senior author Tessa Cigler, MD, MPH, an assistant professor of clinical medicine in the Weill Cornell Breast Center at Weill Cornell Medicine. "Scalp cooling allows patients to protect their privacy and maintain their self-esteem and sense of well-being. This study provides long-awaited evidence for an effective and practical scalp cooling method." The mean age of the cold cap patients was 53 years. Some 77 percent of the patients were white, 9 percent were black and nearly 11 percent were Asian. The study was conducted between August 2013 and October 2014. The average duration of chemotherapy was 2.3 months. Many of the patients reported mild headaches or scalp pain associated with the scalp cooling. Two patients discontinued scalp cooling due to feeling cold. There has been no evidence of scalp metastases in any patient after approximately 30 months of follow up. All patient follow up will continue for a total of five years. The study was funded partially by the Lazlo Tauber Family Foundation (awarded to UCSF); the Anne Moore Breast Cancer Research Fund (awarded to Weill Cornell Medicine); and the Friedman Family Foundation (awarded to Mount Sinai Beth Israel). Dignitana AB supported the design and conduct of the study, including collection, management, analysis and interpretation of the data. Study co-authors also included researchers from the Icahn School of Medicine at Mount Sinai, New York; Wake Forest Baptist Health Medical Center; and the Jonsson Comprehensive Cancer Center at UCLA. From UCSF, co-authors are Michelle E. Melisko, MD, and Laura Esserman, MD, MBA; from Weill Cornell Medicine, Anne Moore, MD, was also a co-author. A complete list of authors can be found in the paper. About UCSF: UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises three top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospitals in San Francisco and Oakland, and other partner and affiliated hospitals and healthcare providers throughout the Bay Area. Please visit http://www. . About Weill Cornell Medicine: Weill Cornell Medicine is committed to excellence in patient care, scientific discovery and the education of future physicians in New York City and around the world. The doctors and scientists of Weill Cornell Medicine - faculty from Weill Cornell Medical College, Weill Cornell Graduate School of Medical Sciences, and Weill Cornell Physician Organization - are engaged in world-class clinical care and cutting-edge research that connect patients to the latest treatment innovations and prevention strategies. Located in the heart of the Upper East Side's scientific corridor, Weill Cornell Medicine's powerful network of collaborators extends to its parent university Cornell University; to Qatar, where an international campus offers a U.S. medical degree; and to programs in Tanzania, Haiti, Brazil, Austria and Turkey. Weill Cornell Medicine faculty provide comprehensive patient care at New York-Presbyterian/Weill Cornell Medical Center, New York-Presbyterian/Lower Manhattan Hospital and New York-Presbyterian/Queens. Weill Cornell Medicine is also affiliated with Houston Methodist. For more information, visit Weill.Cornell.edu.


News Article | February 15, 2017
Site: www.eurekalert.org

Sandra Horning, MD, Chief Medical Officer and executive vice president of global development for Roche and Genentech, a member of the Roche Group, has been named the 2017 recipient of the Duane Roth Memorial Award, which will be presented February 16 at the annual Industry/Academia Translational Oncology Symposium at UC San Diego Moores Cancer Center. The award celebrates Duane Roth, who was Chief Executive Officer of Connect, a San Diego-based organization that promotes technology innovation and entrepreneurship. Roth died in 2013 from injuries suffered in a bicycling accident. Horning has had a long and distinguished career in cancer treatment and research, first as a practicing oncologist, investigator and professor at Stanford University for 25 years, then at the San Francisco-based biotech company Genentech, which merged with the Swiss firm Roche in 2009. Horning, a cancer survivor, has focused much of her work on developing new treatments for lymphoma, a cancer that affects the immune system, including leading clinical trials that eventually resulted in new, approved drug treatments. She was president of the American Society of Clinical Oncology in 2005-2006. "Throughout her impressive career, Sandra Horning has been an unwavering champion of personalized therapies and shifting the focus from treatment of cancer to a more holistic approach of treating the patient as an individual, mindful of his or her family and anticipating survivorship issues, such as fertility, secondary malignancies, cardiopulmonary and endocrine side-effects and more," said Ida Deichaite, PhD, director of UC San Diego Moores Cancer Center's Office of Industry Relations and an organizer of the symposium. "Her scientific achievements in oncology have been amazing and continue to give life, but it's her passion and commitment to promoting empathetic treatment plans that exemplify how establishing collaborations across disciplines can truly improve cancer treatment." The Roth award is bestowed upon leaders in health care whose work has overcome numerous scientific, financial, institutional, political and cultural obstacles to create new paradigms in research and treatment, said Deichaite. Past recipients include: Dennis Slamon, MD, PhD, UCLA Jonsson Comprehensive Cancer Center; Brian Druker, MD, Knight Institute at Oregon Health and Science University; and Laura Esserman, MD, UCSF Helen Diller Family Comprehensive Cancer Center. The symposium, now in its 13th year, is a day-long event at Moores Cancer Center, bringing together scientists, physicians and biopharma representatives to discuss innovations and new collaborations in cancer research and treatment.


O'Connell R.M.,University of Utah | Rao D.S.,Laboratory Medicine | Rao D.S.,Jonsson Comprehensive Cancer Center | Rao D.S.,University of California at Los Angeles | And 2 more authors.
Annual Review of Immunology | Year: 2012

The mammalian inflammatory response is a rapid and complex physiological reaction to noxious stimuli including microbial pathogens. Although inflammation plays a valuable role in combating infection, its dysregulation often occurs in people and can cause a variety of pathologies, ranging from chronic inflammation, to autoimmunity, to cancer. In recent years, our understanding of both the cellular and molecular networks that regulate inflammation has improved dramatically. Although much of the focus has been on the study of protein regulators of inflammation, recent evidence also points to a critical role for a specific class of noncoding RNAs, called microRNAs (miRNAs), in managing certain features of the inflammatory process. In this review, we discuss recent advances in our understanding of miRNAs and their connection to inflammatory responses. Additionally, we consider the link between perturbations in miRNA levels and the onset of human inflammatory diseases. © 2012 by Annual Reviews. All rights reserved.


Cole S.W.,University of California at Los Angeles | Cole S.W.,Jonsson Comprehensive Cancer Center | Cole S.W.,Norman Cousins Center | Sood A.K.,University of Houston
Clinical Cancer Research | Year: 2012

Beta-adrenergic signaling has been found to regulate multiple cellular processes that contribute to the initiation and progression of cancer, including inflammation, angiogenesis, apoptosis/anoikis, cell motility and trafficking, activation of tumor-associated viruses, DNA damage repair, cellular immune response, and epithelial-mesenchymal transition. In several experimental cancer models, activation of the sympathetic nervous system promotes the metastasis of solid epithelial tumors and the dissemination of hematopoietic malignancies via β-adrenoreceptor-mediated activation of protein kinase A and exchange protein activated by adenylyl cyclase signaling pathways. Within the tumor microenvironment, β-adrenergic receptors on tumor and stromal cells are activated by catecholamines from local sympathetic nerve fibers (norepinephrine) and circulating blood (epinephrine). Tumor-associated macrophages are emerging as key targets of β-adrenergic regulation in several cancer contexts. Sympathetic nervous system regulation of cancer cell biology and the tumor microenvironment has clarified the molecular basis for long-suspected relationships between stress and cancer progression, and now suggests a highly leveraged target for therapeutic intervention. Epidemiologic studies have linked the use of β-blockers to reduced rates of progression for several solid tumors, and preclinical pharmacologic and biomarker studies are now laying the groundwork for translation of β-blockade as a novel adjuvant to existing therapeutic strategies in clinical oncology. ©2011 AACR.

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