Day: December 21, 2021

Categories : CancerTags :

Why Cancer Cells Linger to Create Metastatic Cancer

On By ModernMedia
Colon cancer cells. Source: National Cancer Institute on Unsplash

A major mystery in cancer research has been solved: How cancer cells remain dormant for years after leaving a tumour before awakening to create metastatic cancer.

According to findings by Mount Sinai researchers which were reported in Nature Cancer, the cells remain quiet by secreting a type of collagen, called type III collagen, in the environment around themselves, and only turn malignant once the level of collagen tapers off. The researchers found that by enriching the environment around the cells with this collagen, they could force the cells to remain in a dormant state and prevent tumour recurrence.

“Our findings have potential clinical implications and may lead to a novel biomarker to predict tumour recurrences, as well as a therapeutic intervention to reduce local and distant relapses,” said senior author Jose Javier Bravo-Cordero, PhD, Associate Professor of Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at Mount Sinai. “This intervention aimed at preventing the awakening of dormant cells has been suggested as a therapeutic strategy to prevent metastatic outgrowth. As the biology of tumour dormancy gets uncovered and new specific drugs are developed, a combination of dormancy-inducing treatments with therapies that specifically target dormant cells will ultimately prevent local recurrence and metastasis and pave the way to cancer remission.”

Most cancer deaths result from metastases, which can occur several years after removal of a tumour. Previous work looked at how dispersed tumour cells awaken from dormancy; this new work showed how the cells remain dormant.

The study used high-resolution imaging techniques, including intravital two-photon microscopy, a technology that allows the visualisation of dormant cells in their environment in real time in a living animal. This technology allowed the researchers to track dormant tumour cells in mouse models using cancer cell lines. By using this technology, the researchers were able to visualise the changes in the architecture of the extracellular matrix as tumour cells became dormant and how it changed when these cells awoke.

The researchers demonstrated that an abundance of the collagen could potentially be used as a predictor of tumour recurrence and metastasis. In the mouse models, when type III collagen was increased around cancer cells that had left a tumour, cancer progression was interrupted and the disseminated cells were forced into a dormant state. Similar to wound treatment, in which collagen scaffolds have been proposed to treat complex skin wounds, this study suggests that by enriching the tumour microenvironment in type III collagen, metastasis may be prevented by sending tumour cells into a dormant state.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Categories : COVIDTags :

Convalescent Plasma was Effective in Early Pandemic

On By ModernMedia

Convalescent plasma from COVID patients was likely of benefit to patients early on in the pandemic, before the introduction of remdesivir and corticosteroids as treatments, according to results of a landmark study published in JAMA Internal Medicine.

The randomised clinical trial, CONTAIN COVID-19, was established to evaluate the safety and efficacy of convalescent plasma in hospitalised coronavirus patients. Overall, the trial showed that convalescent plasma was safe and well tolerated. It worked best in the early days of the pandemic, when plasma had higher antibody levels, when it was given early in the disease, and particularly for immunosuppressed people.

“This landmark study shows once and for all that convalescent plasma is an important countermeasure early in a pandemic when no other therapies are available. It was an important finding that lays the foundation for the rapid response to future pandemics,” said Luis Ostrosky, MD, professor and director of the Division of Infectious Diseases at McGovern Medical School at UTHealth Houston. “This trial, the largest of its kind, also showed that with proper funding and structure, researchers across the country were able to come together quickly in the middle of a global crisis to explore this therapeutic intervention.”

Trial results also showed a drop in efficacy after the introduction of remdesivir and corticosteroids, and by the end of the 11-month trial, there was no difference in outcome between plasma and placebo in patients at 14 and 28 days. However, patients on corticosteroids, but not remdesivir, appeared to benefit from convalescent plasma at day 14.

Since the patient characteristics, available treatments, and the virus, all changed over time, subgroup analyses were done, which showed a possible benefit for patients in the first quarter of the trial, a period from April to June 2020.

Participants in that first quarter were older, less severely ill, had a longer duration of symptoms, and received high-titer plasma. Shorter symptom duration can indicate a more severe case of the viral infection.

“Convalescent plasma could be an important early treatment tool in places that don’t have access to monoclonal antibodies, corticosteroids, remdesivir, or other therapies,” said the study’s co-investigator, Professor Bela Patel, MD. “It should also be considered for patients who are immunosuppressed and those whose B cell function is compromised.”

The researchers also suggested that, in addition to the introduction of corticosteroids and remdesivir, the decrease in efficacy over time may have been due to using convalescent plasma that originated from New York City before the emergence of other SARS-Co-V-2 variants .

Source: University of Texas Health Science Center at Houston