Intelligent gel attacks cancer

This new injectable ‘biogel’ developed by researchers at the University of Montreal Hospital Research Centre (CRCHUM) is effective in delivering anti-cancer agents directly into cancerous tumours and killing them. The compound is made from chitosane, a biodegradable material extracted from the shells of crustaceans, to which gelling agents are added. The results of that study have been published recently in Biomaterials. CREDIT: CRCHUM


A new injectable ‘biogel’ is effective in delivering anti-cancer agents directly into cancerous tumours and killing them. This technology, developed by researchers at the University of Montreal Hospital Research Centre (CRCHUM), has already been successfully tested in the laboratory. If it works in patients, the therapy could one day revolutionize treatment for many forms of cancer.

Unlike ‘jello,’ the biogel is liquid at room temperature and gels at 37 degrees Celsius, human body temperature. “The strength of this biogel is that it is compatible with anti-cancer immune cells. It is used to encapsulate these cells and eventually administer them using a syringe or catheter into the tumour or directly beside it. Instead of injecting these cells or anti-cancer drugs throughout the entire body via the bloodstream, we can treat the cancer locally. We hope that this targeted approach will improve current immunotherapies,” said Réjean Lapointe, co-author of a study on the technology that was recently published in Biomaterials.

One form of immunotherapy involves treating cancer patients with anti-cancer immune cells. This is called adoptive cell therapy. These cells (T lymphocytes or T cells) are produced naturally by the body and have the ability to destroy cancer cells, but they are generally too weak and too few to eradicate the cancer alone. T cells are therefore cultivated in the laboratory, often the patient’s own cells, and then reinjected into the patient’s blood. While this form of immunotherapy has shown promising results in cases of advanced cancer, it is not always possible to generate enough T cells. Moreover, high doses of interleukin-2, a hormone added to maximize the therapy have a toxic effect.

With our technique, we only need to administer a few dozen million T cells, instead of the billions currently required. We can also administer compounds that ‘awaken’ the immune system to fight against cancer,” explained Lapointe, who is a researcher at the CRCHUM and professor at the University of Montreal.The recipe for this promising biogel was developed by Sophie Lerouge, a researcher at the CRCHUM and professor in the Department of Mechanical Engineering at the École de technologie supérieure. “The compound is made from chitosane, a biodegradable material extracted from the shells of crustaceans, to which gelling agents are added. The formulation is liquid at room temperature, which facilitates its injection, but quickly takes on a cohesive and resistant structure at 37 degrees. We also needed a hydrogel that was non-toxic for the body and provided excellent survival and growth of the encapsulated cells,” said the engineer. A real challenge for Lerouge’s team, who tested several formulations before arriving at this “intelligent” biogel.

The biogel was successfully tested in several in vitro models, including melanoma and kidney cancer. “The T lymphocytes in the gel are functional and can grow for two to three weeks, be released from the gel, and kill the cancerous cells,” explained Lapointe. The next step is to demonstrate the effectiveness of the biogel in animals and humans. If the trials are successful, this new approach could be added to current cancer therapies in a few years.

Monette et al. Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies. Biomaterials. 2016; 75: 237–249 [Abstract]

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Risk of undetected cancer in gynecologic surgery higher than previously thought

Minimally invasive gynecologic surgeries have advantages for patients, including shorter hospital stays, quicker recoveries, and less pain. However, power morcellation, a technique which cuts the uterus or fibroid into small pieces in order to extract them from the abdomen through a small incision, may worsen a woman’s prognosis if a cancer is morcellated unintentionally.

Using a national insurance database of 55 million women, Boston Medical Center (BMC) researchers looked at cases from 19,500 women who underwent laparoscopic hysterectomies or myomectomies, procedures which typically incorporate power morcellation, to determine how frequently women are diagnosed with cancer after undergoing a gynecologic surgery for a problem that is believed to be benign. The study revealed that 1 in 352 women had an unsuspected cancer at the time of gynecologic surgery for disease that was thought to be benign. The study is published online in advance of print in the journal Women’s Health Issues.

Our findings show that the risk for morcellating cancer is much higher than previously understood,” said Michael Paasche-Orlow, MD, MPH, general internal medicine physician at BMC and associate professor of medicine at Boston University School of Medicine (BUSM) who is the study’s senior author. “It makes sense to avoid morcellation for women with cancerous or pre-cancerous lesions. As it is difficult to ascertain in advance, safer alternatives are needed.”

The study also determined that more than half of the patients who were diagnosed with uterine cancer or endometrial hyperplasia, a pre-cancerous condition of the lining of the uterus, did not undergo endometrial testing prior to surgery. Thus, researchers suggest improving how physicians evaluate patients undergoing hysterectomies or myomectomies before they reach the operating room.

We are continually seeking opportunities to move gynecologic surgery forward,” said Rebecca Perkins, MD, a practicing gynecologist at BMC and associate professor of obstetrics and gynecology at BUSM who is the study’s lead author. “Because minimally invasive surgery has many advantages, future research should seek to improve techniques to create safer procedures for women.”

Perkins et al. Risk of Undetected Cancer at the Time of Laparoscopic Supracervical Hysterectomy and Laparoscopic Myomectomy: Implications for the Use of Power Morcellation. Women’s Health Issues. 2015; DOI: 10.1016/j.whi.2015.09.008 [pdf]

Two studies examine long-term outcomes in childhood and young adult cancer survivors

JAMA Oncology published two studies and a related editorial focused on long-term outcomes in survivors of childhood or young adult cancer.

In the first study, Kathrine Rugbjerg, PhD, and Jørgen Olsen, MD, DMSc, of the Danish Cancer Society Research Center, Copenhagen, examined the risk for hospitalization up to 34 years after a diagnosis of adolescent and young adult cancer survivors. The study included 33,555 five-year cancer survivors diagnosed from 1943 through to 2004 with a comparison group from the general population. The authors identified 53,032 hospitalizations in cancer survivors for one or more of 97 disease categories.

Cancer survivors had an overall increased risk of hospitalization compared with those in the general population. Cancer survivors at highest risk for hospitalizations were leukemia, brain cancer and Hodgkin lymphoma survivors.

Survivors of adolescent and young adult cancers face persistent risks for a broad range of somatic diseases requiring hospitalization. The morbidity pattern, which is highly dependent on the type of cancer being treated, underscores the need for further implementation of strict evidence-based sex-, age- and cancer-specific follow-up plans for survivors, thereby increasing the likelihood for early detection and ultimately prevention of treatment-induced morbidities.

In the second study, Kevin Krull, PhD, of St. Jude Children’s Research Hospital, Memphis, and coauthors examined neurocognitive and patient-reported outcomes in adult survivors of childhood osteosarcoma, a type of bone cancer. The study included 80 survivors of osteosarcoma who were an average age of nearly 39 years and almost 25 years past diagnosis. The cancer survivors were compared with 39 community members unrelated to the cancer survivors. Long-term survivors had lower average scores in reading skills, attention, memory and processing speed. However, plasma concentration of methotrexate following high-dose intravenous administration during chemotherapy was not associated with neurocognitive outcomes at nearly 25 years after diagnosis.

Long-term survivors of osteosarcoma are at risk for neurocognitive impairment, which is related to current chronic health conditions and not to original treatment with high-dose methotrexate. … Our results demonstrate the need for increased attention in this diagnosis, with prospective studies to delineate the evolution of impairment over the course of therapy and long-term survival,” the authors conclude.

In a related editorial, Karen E. Effinger, MD, MS, and Michael P. Link, MD, of the Stanford University School of Medicine, California, write: “Advances in cancer therapy have led to increased survival; there are more than 9 million 5-year survivors of cancer in the United States. As this number continues to grow, focus on improved health and quality of life becomes a priority. … Going forward, we must apply our knowledge of late effects to improve monitoring and interventions for patients. While the progress made in the management of cancer in children and young adults has been gratifying, we must remember the words of Giulio D’Angio, who reminds us that ‘cure is not enough.'”Rugbjerg et al. Long-term Risk of Hospitalization for Somatic Diseases in Survivors of Adolescent or Young Adult Cancer. JAMA Oncol. Published online November 19, 2015. doi:10.1001/jamaoncol.2015.4393 [Article]Krull et al. Neurocognitive and Patient-Reported Outcomes in Adult Survivors of Childhood Osteosarcoma. JAMA Oncol. Published online November 19, 2015. doi:10.1001/jamaoncol.2015.4398 [Abstract]

Malignant network makes brain cancer resistant

Incurable astrocytomas, including the particularly malignant glioblastomas, diffusively grow like mycelium into healthy brain tissue. Therefore, these tumors cannot be completely removed by surgery and invariably start growing again at some point despite intensive treatment. They appear to have effective resistance mechanisms.

In their latest publication, scientists co-working with Frank Winkler from the Clinical Cooperation Unit (CCU) “Neurooncology” of the DKFZ and Heidelberg University Hospital, describe a striking feature of astrocytoma cells: They form extremely thin and long extensions of their cellular membrane, which they use to constantly scan the healthy brain, thus invading and colonizing it. As the tumor grows, the cancer cells use these extensions to interconnect to a large network where they communicate intensively and via long distances, making astrocytomas appear like highly complex, organ-like entities. “Our first thought was: this looks like the formation of a new brain within the existing one,” Winkler said. “The tumor cells were interconnected in a network that resembles the ones we know of neurons and other cell types in the brain.”

For up to one year, the researchers observed the growth of human glioblastoma cells that they had transferred to mice. They used a special microscopy technique that facilitates insights into the brain’s deep zones. In this way, they discovered that the cancer cells exchanged molecules via their membrane microtubes which they also used as communication channels.The investigators also found this network of tumor microtubes in tissue samples from brain cancer patients. The more the cancer cells were interconnected, the more malignant and resistant the tumor subtype was.

The scientists therefore hypothesized that the tumor microtube networks must be linked to therapy resistance. They observed that the tumors in fact recognize damage to the network and repair it immediately. Radiation therapy – the standard treatment in glioblastoma – fails to kill mainly the tumor cells that are part of the network, whereas cancer cells outside the network die.

How do the tumor cells form these extraordinary membrane extensions? An analysis of the gene activities in tumor tissue from 250 brain cancer patients provided a clue. For building their network, the cancer cells make use of specific molecular signaling pathways that are normally active during early development of the nervous system. Experiments in which the scientists blocked these pathways in mice showed that the animals subsequently developed smaller tumors with fewer interconnections that responded very sensitively to radiotherapy.

The resistance of astrocytomas, particularly glioblastomas, against all types of therapy is an enormous problem,” says Wolfgang Wick, who heads the CCU as well as the Neurology Department of Heidelberg University Hospital. “For the first time, our results show a long sought-after new approach toward breaking this resistance and thus enabling us eventually to enhance the treatment efficacies of these tumors. The results also explain why a specific subtype of brain cancer responds much better to therapy. Their capability of building networks seems to be limited.” Matthias Osswald, the article’s first author, adds: “Even though this discovery does not immediately enable us to offer a new treatment to our brain tumor patients, it does show the direction that therapy development should take: we have to destroy the malignant network.”

Osswald et al. Brain tumour cells interconnect to a functional and resistant network. Nature. 2015; DOI: http://dx.doi.org//10.1038/nature16071 [Abstract]

Cancer survivors less likely to receive callbacks from potential employers

Job applicants who are cancer survivors are less likely to receive callbacks from potential retail employers than those who did not disclose their health history, according to a recent study by Rice University and Penn State University researchers.

The study, published recently in the Journal of Applied Psychology by the American Psychological Association, focused on retail employers and compared two groups of job applicants: applicants who ostensibly never had cancer and applicants who indicated on their resumes they were cancer survivors and wore a hat that read “cancer survivor” when applying for a job. Applicants disclosing a cancer history received fewer callbacks from managers than the applicants who did not disclose a history of cancer. For the cancer survivor group, 21 percent received callbacks. For the control group, nearly 37 percent received callbacks, a statistically significant difference, according to the researchers.

This is especially problematic as people with chronic and past illnesses are protected from discrimination by the Americans with Disabilities Act, and our findings indicate that cancer survivors do tend to disclose their cancer histories with interviewers at relatively high rates,” said lead researcher Larry Martinez, assistant professor of hospitality management at Penn State.Martinez, who earned his undergraduate degree, master’s degree and Ph.D. at Rice University under the guidance of co-author Mikki Hebl, professor of psychology and management, began the research for this study as part of his graduate work.

This study is based on this idea that Mikki has been working on for a while now,” Martinez said. “Basically, people are more likely to discriminate in very subtle interpersonal ways. There’s less eye contact. There are shorter interaction times when speaking with managers. There are more negative interpersonal behaviors from managers, like frowning, brow furrowing and less smiling – fewer cues that communicate to applicants that they are interested in hiring them for the job.”

Part of the study targeted 121 retail managers at three large shopping malls in a metropolitan area in the southern part of the United States. Five undercover researchers, two men and three women between ages 21 and 29, were assigned randomly to disclose a history of cancer or provide no information about a history of cancer. Prior to data collection, researchers confirmed each establishment was hiring. Researchers excluded employers who used a strict online-only application process. Only one applicant entered each store.Participants presented managers with resumes that included their actual work experience; however, resumes were modified to fit the work history and job requirements for the retail position and to remove any experience that would make the applicant overqualified. Participants’ resumes were also standardized for length, formatting and level of experience.

While researchers make clear that no hiring laws were broken, they found evidence of discrimination. “Despite the fact that cancer survivors are protected under the Americans with Disabilities Act, we did see this difference in callbacks between them and the general public, as well as the negative interpersonal treatment they received,” Martinez said. Also as part of the study, researchers conducted an online survey with 87 participants who were employed full time, most of whom had management experience or experience as an interviewer. Participants were asked to provide their opinions regarding how people feel about cancer survivors in the workplace. The results indicated that workers with a history of cancer were rated higher in “warmth” than in competency.

Researchers concluded that while diversity efforts have generally increased over the last decade, health characteristics are often not included in diversity programs.”Managers and employees should be mindful of the fact that although societal attitudes toward cancer survivors are generally quite positive, with people often viewing them as champions who have successfully overcome a traumatic experience, we nonetheless might perceive them as being less desirable employees simply because of their history with cancer,” Martinez said.

Next steps in this area could include training managers to be mindful of subtle biases they might have toward people with past and chronic health conditions, according to Martinez and Hebl. “We could train applicants who might be prone to experiencing discrimination how to present themselves in interviews in ways to reduce possible negativity they might experience,” Martinez said.

Martinez et al. Selection BIAS: Stereotypes and discrimination related to having a history of cancer. J App Psychol. 2015; DOI: http://dx.doi.org/10.1037/apl0000036 [Abstract]