A new UCSF study sheds light on the diversity within the most common type of pediatric liver tumor and suggests a way forward for more precise chemotherapy treatment.
The study, published in Nature Communications, used single-cell transcriptomic techniques to analyze hepatoblastoma specimens from infants and children under age four. From nine samples, the researchers identified five hepatoblastoma tumor signatures that may account for the heterogeneity in this cancer, and that may predict responses to chemotherapy treatments.
"Many pediatric tumors originate from an embryonic cell and some are bland in terms of their mutational burden," said study co-author Amar Nijagal, assistant professor in the Division of Pediatric Surgery at UCSF Benioff Children's Hospital, San Francisco. "The fact that this tumor has significant heterogeneity made us question what was driving this heterogeneity, and we wanted to learn more."
Researchers from three different labs at UCSF worked on the study, combining expertise in pediatric surgery, hepatology, and genomics, which facilitated the rare opportunity to analyze tumors directly from the operating room, Nijagal said.
Researchers are exploring a potential new therapeutic approach for triple negative breast cancer treatment. Amir Abdo Alsharabasy, a CÚRAM doctoral candidate working in the laboratory of Professor Abhay Pandit, is working on the design of nitric oxide scavengers to form a new treatment approach for this aggressive form of breast cancer.
Triple-negative breast cancer is invasive breast cancer that does not respond to hormonal therapy medicines or the current medicines that target the HER2 protein. Triple-negative breast cancer is usually more aggressive, harder to treat, and more likely to recur than cancers that are hormone receptor-positive or HER2-positive.
"Nitric oxide is one of the prominent free radicals produced by the tumor tissue", explains Amir, "It, at certain concentrations, plays a significant role in breast cancer progression by inducing the cancer cells to spread to other parts of the body Our goal is to develop injectable hydrogel formulations, which can reduce the levels of, or 'scavenge' the nitric oxide, while enhancing the generation of carbon monoxide, so that we can potentially design a new treatment approach for triple negative breast cancer."
Nitric oxide interacts with different components of the large network of proteins and other molecules that surround, support, and give structure to tumor cells and tissues in the body. Hyaluronic acid is one of the main components of this network and is the material of choice for fabricating these hydrogels.
The immune system has evolved to safeguard the body from a wildly diverse range of potential threats. Among these are bacterial diseases, including plague, cholera, diphtheria and Lyme disease, and viral contagions such as influenza, Ebola virus and SARS CoV-2.
Despite the impressive power of the immune system's complex defense network, one type of threat is especially challenging to combat. This arises when the body's own native cells turn rogue, leading to the phenomenon of cancer. Although the immune system often engages to try to rid the body of malignant cells, its efforts are frequently thwarted as the disease progresses unchecked.The illustration shows a cancer cell (center) surrounded by immune T-cells augmented with an oncolytic (cancer-fighting) virus. A new study describes how a combination of immunotherapy and virotherapy, using myxoma virus, provides new hope for patients with treatment resistant cancers.
In new research appearing in the journal Cancer Cell, corresponding authors Grant McFadden, Masmudur Rahman and their colleagues propose a new line of attack that shows promise for treatment-resistant cancers.
A joint research team led by Prof. Wang Hui, Prof. Zhang Xin and Prof. Qian Junchao from the Hefei Institutes of Physical Science (HFIPS) of the Chinese Academy of Sciences (CAS) has proposed a new kind of near-infrared-triggered nanozyme based on iron oxide nanocrystals embedded in N-doped carbon nanosheets (IONCNs), which is promising for synergistic cascade tumor therapy.
The study was published in ACS Applied Materials & Interfaces.
Chemodynamic therapy is an efficient cancer treatment method determined by the striking difference between the tumor microenvironments and normal tissues. By triggering the Fenton or Fenton-like reaction, it can generate highly toxic hydroxyl radical (·OH) to kill tumor cells.
Unfortunately, the overexpression of glutathione in tumor microenvironments limits the therapeutic efficacy by counteracting ·OH generation. Moreover, the normal cells or inflammatory cells are easily affected simultaneously owing to their similar characteristics to the tumor microenvironments. Therefore, it is necessary to develop an exogenous triggered nanozyme to realize tumor-specific catalytic therapy.
EPFL scientists have discovered a rare gene in the tumors of some colorectal cancer patients. This finding could lead to more accurate diagnoses and, eventually, personalized treatments that target the protein expressed by the gene.
Colorectal cancer is one of the most common forms of cancer in the Western world, especially in people over 50. Some 4,500 patients are diagnosed with it every year in Switzerland alone. Major therapeutic advancements in recent decades have drastically reduced the mortality rate, but scientists are still struggling to understand the molecular abnormalities that lead to tumor formation. And diagnosing colorectal cancer can be difficult, since symptoms generally don't appear until the disease has progressed to an advanced stage—at which point effective treatment options are lacking.
Colorectal cancer occurs when alterations in the DNA of cells in the colon or rectum lining cause the cells to proliferate and become tumorous. To better understand the underlying mechanisms, a team of scientists at EPFL's Laboratory of Virology and Genetics (Trono Lab) combed through data from a study in Denmark that analyzed the tumors of over 300 colorectal cancer patients. They found that some tumors contain a gene that promotes the growth and metastatic potential of cancer cells. Their findings were published in Nature Communications on 20 August 2022.
In animal studies led by researchers at Duke Cancer Institute, a drug approved to treat leukemia successfully disrupted the ability of HER2-positive breast cancer tumors from colonizing the brain.
The finding, appearing online Aug. 30 in the journal Cell Reports, provides evidence for human trials and suggests a potential new approach to derail one of the main ways that breast cancer turns deadly.
"We have made huge strides in treating HER2-positive breast cancers, but when tumors escape the therapies, they often metastasize to the brain," said senior author Ann Marie Pendergast, Ph.D., professor and vice chair of the Department of Pharmacology and Cancer Biology at Duke University School of Medicine.
"When brain metastasis occurs, treatments are unsuccessful either because the tumors have developed resistance, or the therapies cannot penetrate the blood-brain barrier," Pendergast said. "This remains a devastating diagnosis for patients."
Pendergast and colleagues looked at how HER2 promotes breast cancer growth, particularly after becoming resistant to targeted treatments that have been highly successful in prolonging lives. The HER2 protein is a driving force in 30% of breast cancers, with approximately 45% of these leading to brain metastases.
A groundbreaking study at Tel Aviv University effectively eradicated glioblastoma, a highly lethal type of brain cancer. The researchers achieved the outcome using a method they developed based on their discovery of two critical mechanisms in the brain that support tumor growth and survival: one protects cancer cells from the immune system, while the other supplies the energy required for rapid tumor growth. The work found that both mechanisms are controlled by brain cells called astrocytes, and in their absence, the tumor cells die and are eliminated.
The study was led by Ph.D. student Rita Perelroizen, under the supervision of Dr. Lior Mayo of the Shmunis School of Biomedicine and Cancer Research and the Sagol School of Neuroscience, in collaboration with Prof. Eytan Ruppin of the National Institutes of Health (NIH) in the U.S.. The paper was published in the journal Brain and was highlighted with special commentary.
Researchers at Sanford Burnham Prebys, led by Ze'ev Ronai, Ph.D., have shown for the first time that inhibiting a key metabolic enzyme selectively kills melanoma cells and stops tumor growth. Published in Nature Cell Biology, these findings could lead to a new class of drugs to selectively treat melanoma, the most severe form of skin cancer.
"We found that melanoma is addicted to an enzyme called GCDH," says Ronai, professor and director of the NCI-designated Cancer Center at Sanford Burnham Prebys. "If we inhibit the enzyme, it leads to changes in a key protein, called NRF2, which acquires its ability to suppress cancer. Now, our goal is to find a drug, or drugs, that limit GCDH activity, potentially new therapeutics for melanoma."
Because tumors grow rapidly and require lots of nutrition, researchers have been investigating ways to starve cancer cells. As promising as this approach may be, the results have been less than stellar. Denied one food source, cancers invariably find others.
GCDH, which stands for Glutaryl-CoA Dehydrogenase, plays a significant role in metabolizing lysine and tryptophan, amino acids that are essential for human health. When the Ronai lab began interrogating how melanoma cells generate energy from lysine, they found GCDH was mission-critical.
In the summer and fall of 2019, some cancer patients experienced interruptions in their treatment. The reason was a shortage of the drugs vinblastine and vincristine, essential chemotherapeutic medicines for several types of cancer.
There are no alternatives to these drugs that are isolated from the leaves of the Madagascar periwinkle plant, Catharanthus roseus. Two active ingredients from the plant-vindoline and catharanthine—together form vinblastine, which inhibits the division of cancer cells.
Although the plant is common, upwards of 2000 kg of dried leaves are needed to produce 1 g of vinblastine. The 2019 shortage that lasted until 2021 was mainly caused by delays in the supply of these ingredients.
A cross-disciplinary international team of scientists led by DTU researchers has genetically engineered yeast to produce vindoline and catharanthine. They have also managed to purify and couple the two precursors to form vinblastine. Thus, a new, synthetic approach to making these drugs has been discovered. Their results are published today in the journal Nature.
A study led by researchers at the University of Arizona Health Sciences discovered new information about the inner workings of the immune system that could have a profound impact on T cell therapies for cancer and other diseases.
T cells are a type of white blood cell essential to the immune system and defending the body against infection. The CD4 molecule is found on the surface of many T cells and has historically been thought to only play a supporting role in the cell's functions. The paper, "Enhancing and inhibitory motifs regulate CD4 activity," published in eLife, shows CD4 plays a more active role in regulating T cell receptor signaling.
The study took a unique evolutionary approach to the immune system by examining the ways T cells have changed or remained the same over time. Michael Kuhns, Ph.D., associate professor in the UArizona College of Medicine—Tucson's Department of Immunobiology, and Koenraad Van Doorslaer, Ph.D., assistant professor in the UArizona College of Agriculture and Life Sciences' School of Animal and Comparative Biomedical Sciences, assembled a team that focused on the evolution and function of CD4.
"This study is giving us a better appreciation for how CD4 works in concert with the T cell receptor to naturally direct T cells," said Dr. Kuhns, who serves on the Center for Advanced Molecular and Immunological Therapies advisory committee. "CD4 is very much a co-equal player in antigen recognition and T cell activation."
