Zika virus could help combat brain cancer — ScienceDaily

Zika virus, feared for causing microcephaly in babies whose mothers were infected during pregnancy by attacking the cells that will give rise to the fetus’s cerebral cortex, could be an alternative for treatment of glioblastoma, the most common and aggressive kind of malignant brain tumor in adults.

This discovery was made by researchers at the University of Campinas’s School of Pharmaceutical Sciences (FCF-UNICAMP) in São Paulo State, Brazil.

“Zika virus, which has become a threat to health in the Americas, could be genetically modified to destroy glioblastoma cells,” said Rodrigo Ramos Catharino, a professor at FCF-UNICAMP and head of the institution’s Innovare Biomarker Laboratory.

Through the mass spectrometry analysis of Zika virus-infected glioblastoma cells, scientists also identified the presence of digoxin, a molecule which induced the death of tumoral cells of skin and breast cancer in previous experiments.

Resulting from a Thematic Project supported by the Sao Paulo Research Foundation — FAPESP , the study is described in an article posted to bioRxiv, a preprint repository for the biological sciences, and accepted for publication by Journal of Mass Spectrometry.

Previous research conducted recently in Brazil and elsewhere points to increased mortality rates for human neural progenitor cells (hNPCs) infected by Zika virus, as well as growth inhibition and morphological abnormalities.

Alterations in these cells, which are precursors of brain cells and become cortical neurons in embryos and fetuses, may be a cause of microcephaly in babies whose mothers have been infected by Zika. Other studies have shown that the virus is capable of moving into brain cells, modifying the regulation of the cell cycle, and inducing their death.

In light of these findings, the researchers at FCF-UNICAMP set out to investigate the effects of Zika virus when it infects glioblastoma cells. To do this, they infected human malignant glioblastoma cells with Zika and recorded microscope images of them 24 hours and 48 hours after infection in order to observe any metabolic alterations (cytopathic effects) caused by inoculation of the virus.

The results of the analysis showed that the glioblastoma cells displayed moderate cytopathic effects 24 hours after infection, such as rounded, swollen cell bodies and formation of syncytia, masses of cytoplasm in which the membrane contains several nuclei.

The most severe cytopathic effects were observed 48 hours after infection, with a larger number of rounded, swollen cells, more syncytium formation and pronounced loss of cell integrity, all of which denote cell death.

“The cytopathic effects of Zika infection on glioblastoma cells were observed most clearly after 48 hours. Cell morphology was almost totally altered during this period,” Catharino said.

Key molecule

To identify the main compounds (metabolites) produced by glioblastoma cells during infection by Zika, the researchers analyzed the cells using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI).

The technique consists of breaking down the atoms or molecules in a sample so that they become charged with more or fewer electrons than the original (ionization) and then separating them by mass/charge ratio in order to identify and quantify them.

The mass spectrometry data were submitted to statistical analysis, which showed that 24 hours after infection, the cells began to produce cardiac glycosides, especially digoxin.

Previous in vitro studies conducted by researchers in other countries showed that this molecule was able to reduce the multiplication and increase the mortality of cells from melanoma, the most aggressive type of skin cancer, as well as breast cancer and neuroblastoma, a tumor that typically affects patients aged 15 or younger.

Because digoxin and other cardiac glycosides have been shown to induce cancer cell death, the researchers concluded that infection by Zika triggered synthesis of the molecule in glioblastoma cells and that this phenomenon is probably one of the factors that lead to neuronal cell death. “Digoxin could be the key molecule that activates glioblastoma cell death during Zika infection,” Catharino said.

Based on these findings, the researchers suggest that a genetically engineered Zika virus could eliminate the effects of infection and leave only the viral particles that synthesize digoxin. Thus, the virus could be an alternative for the treatment of glioblastoma, which is highly resistant to chemotherapy drugs.

“The use of oncolytic viruses [viruses genetically engineered to destroy tumor cells] is at an advanced stage, especially to treat skin cancer and myeloma [bone marrow cancer],” Catharino said. “Zika could be a candidate for the treatment of glioblastoma.”

Durvalumab Approved by FDA for Reducing NSCLC Progression

The FDA recently approved durvalumab (Imfinzi) for the treatment of patients with stage 3 non-small cell lung cancer (NSCLC) whose tumors are unresectable and whose disease has not progressed following treatment with chemoradiation, according to a press release. This application was previously granted priority review and breakthrough therapy designations.

“This is the first treatment approved for stage 3 unresectable non-small cell lung cancer to reduce the risk of the cancer progressing, when the cancer has not worsened after chemoradiation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research.

Lung cancer is a leading cause of death in the United States and a majority of diagnoses are the NSCLC subtype. Stage 3 NSCLC is characterized by metastases in the lymph nodes or other nearby parts of the body. Durvalumab is a checkpoint inhibitor that works by blocking the PD-1/PD-L1 pathways, which is thought to bolster the body’s defense against cancer, according to the FDA.

The new approval was based on positive findings from a clinical trial including 713 patients with NSCLC whose disease had not progressed following chemoradiation. The study evaluated progression-free survival (PFS) for durvalumab versus placebo. The researchers found that the median PFS for patients taking durvalumab was 16.8 months compared with only 5.6 months for those taking placebo, according to the release.

Common adverse events associated with durvalumab in patients with NSCLC include cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash. The FDA warns that durvalumab comes with serious risks. These risks include immune-mediated adverse events, in which the immune system attacks cells or organs, such as the lungs, liver, colon, hormone-producing glands, and kidneys. Other serious risks include infection and infusion-related reactions, according to the release. In 2017, durvalumab was granted accelerated approval by the FDA for the treatment of patients with advanced or metastatic bladder cancer.

“For patients with stage 3 lung cancer that cannot be removed surgically, the current approach to prevent progression is chemoradiation. Although a small number of patients may be cured with the chemoradiation, the cancer may eventually progress,” Dr Pazdur said. “Patients now have an approved therapy that has been shown to keep the cancer from progressing for a longer time after chemoradiation.”

This article originally appeared on Specialty Pharmacy Times.

News digest – ‘Ultra-processed’ foods, clinical trials boost, ovarian cancer risk and… tiny DNA robots?

  • Ultra-processed’ foods were linked with cancer this week following a large study. Researchers defined ready meals, packaged cakes, sugary drinks, and more as ‘ultra-processed’. As we told the BBC, it’s difficult to untangle whether the increased cancer risk is caused by the foods themselves or their effects on bodyweight. Sky News and the Guardian also have more on this one.

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  • Clinical trials are crucial for bringing new treatments to cancer patients. That’s why we’re investing £45 million into our network of clinical trials’ units across the UK. Check out our press release and Express coverage for details on how the cash will be spent.
  • Pancreatic cancer survival remains stubbornly low. In a bid to develop better treatments for the disease, we announced £1.5m in funding to scientists at the University of Liverpool. They’ll be studying how pancreatic cancer spreads in the hope of identifying new ways to tackle the disease. The BBC has the details.
  • New research suggests that newly discovered gene faults that may raise the risk of ovarian cancer could be passed down from a father to his daughters. The research could lead to a better understanding of ovarian cancer risk in people with a family history of the disease. The BBC, Telegraph and others picked up this story.
  • Scientists have created an anti-cancer vaccine in mice using stem cells. Human cancers are complex though, so it’s too soon to say whether it could prevent the disease in healthy people as some reports suggested.
  • Chemicals used in an array of products, including non-stick cooking utensils and food packaging, have been linked with weight gain by new research. While the chemicals have been studied for other health conditions before, it’s too soon to say that they can affect bodyweight, reports the Guardian.
  • More on obesity: could eating slowly help tackle bodyweight? New research has suggested so, at least in people with type 2 diabetes. The Guardian and Daily Mail report that scientists have discovered a link between slower eating speeds and both a lower BMI and slimmer waist. But there are other factors playing a role too, so it’s not clear how big an impact the pace people eat might have on bodyweight.
  • Two important cancer drugs have been given the green light for use in the NHS in Scotland, one for advanced bladder cancer and another for a type of skin cancer. Read our news report for why the decision has been hailed as ‘fantastic news‘.

And finally

  • Much more than folding paper cranes, scientists have used ‘DNA origami‘ to create tiny ‘robots‘ that deliver a drug directly to tumours. They’ve shown that a blood-clotting molecule can cut off a tumour’s blood supply in mice when delivered by the DNA nanorobot, causing the tumour to shrink and helping mice live longer. Drugs already exist that are designed to starve tumours of blood, but they’ve shown mixed results in cancer patients. This approach might have great potential if explored with different treatments in the future.

Justine

FDA OKs Durvalumab (Imfinzi) for Reducing Risk for NSCLC Progression

The US Food and Drug Administration (FDA) today approved durvalumab (Imfinzi, AstraZeneca) for the treatment of patients with stage III non-small cell lung cancer (NSCLC) whose tumors are unresectable and whose cancer has not progressed after chemoradiation.

The immunotherapy becomes the first treatment approved to reduce the risk of the cancer progressing in this setting.

“For patients with stage III lung cancer that cannot be removed surgically, the current approach to prevent progression is chemoradiation. Although a small number of patients may be cured with the chemoradiation, the cancer may eventually progress. Patients now have an approved therapy that has been shown to keep the cancer from progressing for a longer time after chemoradiation,” Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research commented in a news release.

Durvalumab is an anti-programmed death ligand 1 (PD-L1) inhibitor and has one previous FDA approval, for certain patients with locally advanced or metastatic bladder cancer.

The new approval is based on results from the 173-patient PACIFIC trial, in which all of the patients had nonprogressive cancer after chemoradiation. In the randomized study, durvalumab significantly improved progression-free survival (PFS) compared with placebo; the median PFS was 16.8 months with durvalumab vs 5.6 months with placebo (hazard ratio, 0.52; P < .0001).

The objective response rate was significantly higher with durvalumab than with placebo, at 28.4% vs 16.0% (P < .001).

The findings were presented last year at the European Society for Medical Oncology annual meeting and were simultaneously published online in the New England Journal of Medicine.

Various lung cancer experts have commented that these results change the treatment paradigm because they show — for the first time — that an immunotherapy is beneficial at an earlier stage of lung cancer (ie, locally advanced unresectable stage III NSCLC). All the previous trials with immunotherapy in lung cancer have been in later-stage disease: advanced and metastatic NSCLC.

In the pivotal trial, grade 3/4 adverse events were slightly more common with durvalumab than with placebo, seen in 29.9% vs 26.1% of patients, with adverse events leading to discontinuation experienced by 15.4% of durvalumab patients and 9.8% of placebo patients.

Grade 3/4 immune-related adverse events were recorded in 3.4% of durvalumab patients vs 2.6% of patients given placebo. In contrast, any grade immune-related events were seen in 24.2% and 8.1% of the respective patient groups.

“This is an important advance,” commented Michael Boyer, MD, clinical professor of medicine at the University of Sydney, Australia, last year at the World Conference on Lung Cancer, as reported by Medscape Medical News, where he acted as a meeting discussant of trial quality-of-life data. Numerous previous trials have attempted to improve outcomes in this patient population, and all have failed, he observed.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc

How Many Kinds of Cancer Cells Are There?

Learning more about cancer is an effective method for prevention on its own. The more you know the more likely you are to get frequent screenings and notice the symptoms early, if you fall ill. It is worth finding out more about the different kinds of cancer cells first.

Before you read any further it is worth looking at the definition of cancer. This disease is defined as the rapid and uncontrolled growth of abnormal cells in an organ, gland or another type of body tissue. As these cells grow, they go on to form a larger formation called a tumor. It should be pointed out that cancer usually refers to malignant tumors and not to benign ones.

There are over 100 kinds of cancer cells that can affect each different part of the body, including organs, tissues and glands. It is worth pointing out that not all tumor cells that grow in a certain organ or gland are the same. For instance, there are a number of lung, liver and pancreatic cancers because the tumor cells can affect different parts of these organs. In these different parts the cells differ. Additionally, the change that goes on in the cell so that it becomes malignant can be different as well. If you take into account these changes to differentiate between the different kinds of cancer, their number can grow to over 200.

Each type of cancer bears the name of the organ or tissue it affects. For this reason, it is worth looking at the different types by looking at the different body systems and organs of the body that this dangerous disease can affect.

Starting from the head, the first kind of cancer in the list is brain cancer. Adults can get a condition called adult brain tumor that refers to a malignant growth in the brain. There are six other types of malignant tumors that affect primarily children. These include brain stem glioma and cerebellar astrocytoma.

Many people do not know this, but eye cancer also exists. Just like the skin tissue, the upper layer of eye tissue can be harmfully affected by the UV rays of the sun. In turn, intraocular melanoma can be developed. The other type of cancer that can affect the eyes is called retinoblastoma.

The cancers that can affect the mouth, throat and sinuses are commonly referred to as oral cancer. This type includes malignant tumors in the tongue and the lips. Other kinds of the disease that can affect the head and neck area include metastatic squamous neck cancer and salivary gland cancer.

Thyroid cancer is defined as a malignant tumor growing in this gland, which is located in the lower part of the front neck. This condition is the most common kind of endocrine system cancer. Other less common conditions include adrenocortical carcinoma and pituitary tumor.

Breast cancer is one of the most common types of cancer. It affects over 200,000 women each year in the US alone. There are two main types ductal carcinoma in situ and lobular carcinoma in situ.

Lung cancer is the most common disease of this type. Its main cause is smoking. There are two major types – small cell and non-small cell.

Different types of cancer cells can affect all parts of the gastrointestinal system. The most common types include cancer of the esophagus, gallbladder, pancreas, liver, stomach, colon, rectum and anus.

There are also different kinds of malignant tumors that can affect different parts of the urinary tract. The most common diseases are kidney cancer and bladder cancer.

Diseases that can affect the male reproductive system include prostate cancer, an extremely common type, penile cancer and testicular cancer.

Almost all parts of the female reproductive system can be affected by this disease. The most common types of gynecological cancers include ovarian cancer, endometrial cancer and cervical cancer.

There are two main types of cancer that affect the blood. These are leukemia and lymphoma. The former can affect both adults and children while the litter typically occurs in adults.

Even though bone cancer is very rare, skin cancer is an extremely common condition. Melanoma is the most serious and dangerous kind of skin cancer.

There are many kinds of cancer. Some of them are less common while others affect hundreds of thousands of people a year. The optimistic news is that research is massive and continues to produce more and more promising results.