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Researchers at Osaka University have developed a technique of attacking cancer cells with lethal alpha rays from within by using a nutrient transporter to deliver radionuclides into malignant tumors.

A cancer-specific L-type amino acid transporter 1 (LAT1) is highly expressed in cancer tissues. Inhibiting the function of LAT1 has been known to have anti-tumor effects, but there has been limited progress in the development of radionuclide therapy agents targeting LAT1. Now, a multidisciplinary research team at Osaka University has established a targeted alpha-therapy with a novel drug targeting LAT1.

Alpha ray missile therapy tumor cells attacked from intracellular region

Image credit: ColiNOOB via Pixabay (Free Pixabay license)

The researchers first produced the alpha-ray emitter 211Astatine, no easy task given that Astatine (At) is the rarest naturally occurring element on Earth. Targeted alpha-therapy selectively delivers α-emitters to tumors; the advantage over conventional β-therapy is that alpha decay is highly targeted and the high linear energy transfer causes double-strand breaks to DNA, effectively causing cell death. The short half-life and limited tissue penetration of alpha radiation ensures high therapeutic effects with few side-effects to surrounding normal cells.

Next, to carry the radioisotope into cancer cells, the researchers attached it to α-Methyl-L-tyrosine, which has high affinity for LAT1. This subterfuge exploits the elevated nutrient requirements of rapidly multiplying cancer cells.

1610414780 490 Alpha ray missile therapy tumor cells attacked from intracellular region

The efficacy of 211At-AAMT using the PANC-1 xenograft model. Tumor growth inhibition by 211At-AAMT (left). Coronal images of 211At-AAMT in tumor-bearing model (right). Image credit: Osaka University

“We found that 211At-labeled α-methyl-L-tyrosine (211At-AAMT) had high affinity for LAT1, inhibited tumor cells, and caused DNA double-strand breaks in vitro,” reports Associate Professor Kazuko Kaneda-Nakashima, lead author. “Extending our research, we assessed the accumulation of 211At-AAMT and the role of LAT1 in an experimental mouse model. Further investigations on a human pancreatic cancer cell line showed that 211At-AAMT selectively accumulated in tumors and suppressed growth. At a higher dose, it even inhibited metastasis in the lung of a metastatic melanoma mouse model.”

Professor Atsushi Shinohara, senior author, explains, “We could establish the efficacy of 211Astatine in the treatment of cancer including advanced and metastatic malignancies, as well as the utility of the amino acid transporter LAT1 as a vehicle for radionuclide therapy. As the drug is delivered cancer-specifically it can attack from inside the cell after being taken in as a nutrient.”

Adding to efficacy is dosing convenience. As an injectable short-range radiopharmaceutical, 211At-AAMT may be administered in outpatient clinics, a huge advantage over conventional radiation protocols, and may even be an alternative to surgery in specific cancers. This approach has immense potential to revolutionize radionuclide therapy of not only pancreatic cancer but other malignancies that lack effective treatment including advanced or metastatic disease.

The article, “α-Emitting cancer therapy using 211At-AAMT targeting LAT1,” was published in Cancer Science at DOI: https://doi.org/10.1111/cas.14761

Source: EurekAlert!




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How to check if someone else accessed your Google account

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Review your recent Gmail access, browser sign-in history, and Google account activity to make sure no one other than you has used your account.

Illustration: Andy Wolber/TechRepublic

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Whenever a computer is out of your direct view and control, there’s always a chance that someone other than you can gain access. A person who returns from a trip might wonder if their computer and accounts have been accessed during their absence. A person might notice odd activity in Gmail, not aware that their password has been made public (or “pwned“). Or, in some cases, a person might be surveilled by a partner, a family member, a colleague, or even an unknown party.

To secure an account, you might first change your password, enable two-factor authentication, or even enroll in Google’s Advanced Protection Program. Those steps will help you secure your account. However, in cases where people are unsafe because of domestic abuse, these steps will likely not be encouraged by an abuser–help is available.

The following steps can help you figure out if someone, other than you, is accessing your Gmail or Google account.

SEE: Google Sheets: Tips and tricks (TechRepublic download) 

Did someone access my Gmail account?

In a desktop web browser, Gmail allows you to review recent email access activity. Select Details in the lower-right area below displayed emails, below Last Account Activity (Figure A). 

Figure A

GIF showing selection of DETAILS (in lower right, below displayed emails), which then reveals recent Gmail account access activity (type of activity, IP address, and date/time)

If your Gmail account has been accessed in other locations or on other devices, you may display recent activity while signed in to Gmail from a desktop-class web browser.

The system will show you information about the most recent 10 times your Gmail account has been accessed, along with the access type (browser, POP, mobile, etc.), location (IP address), and the date and time of access. This can help you identify if any of this access is from an unexpected device, place, or time. 

Note: If you use a virtual private network or a hosted desktop, the location data may reflect information related to your service provider, instead of your physical address.

In a few cases, I’ve had clients concerned about access in an expected location, but at an unexpected time. Sometimes, this was simply because they’d left a computer on, with their browser or mail client open: The system could be configured to auto-check mail periodically. In one case, access occurred after a power outage. They’d configure the system to automatically power on after an outage, so it signed in and downloaded new mail shortly after power was restored.

Did someone access my browser?

In the Chrome browser–and on any Chromebook or Chrome OS device–press Ctrl+H to display browser history. Alternatively, type chrome://history in the omnibox, or select the three-vertical dot menu in the upper-right, then choose History | History. On macOS, press Command+Y. You may scroll through all available sites visited. Review these to see if any sites displayed are unexpected.

Additionally, you may enter search terms in the box displayed above the historical URLs listed. For example, search for “sign in,” or copy and paste this link into your browser omnibox: chrome://history/?q=sign%20in to display most site login pages (Figure B). Again, review the results for any sites you don’t expect. You might search for “gmail.com” as well.

Figure B

Screenshot of Chrome history, with search active to show only items with

Use Ctrl+H (or on macOS, Command+Y) to display your browser history. You also may search history for terms, such as “login” or “sign in,” as shown.

Did someone access my Google account?

Go to https://myactivity.google.com/ to access your Google account history across all devices and Google services, such as YouTube, Google Maps, Google Play, and more (Figure C). Depending on your security settings, you may need to re-authenticate when you attempt to access this information. Again, review any recorded data to make sure it corresponds with your usage.

Figure C

Screenshot of

The My Google Activity page displays any recorded access of web sites, apps, location, and YouTube.

Similarly, go to https://myaccount.google.com/device-activity to review a list of devices to which you’ve signed in with your Google account (Figure D). You may select the three-vertical dots in the upper-right of any displayed devices, then choose Sign Out to prevent any future access without re-authentication on a device. 

Figure D

Screenshot shows

You also may review the devices Where You’re Signed In to your Google account. Select the three-dot menu in the upper-right corner of the box for each device to Sign Out of any device.

Go through Google’s Security Checkup (https://myaccount.google.com/security-checkup) for a step-by-step review of every item Google’s system identifies as a potential security issue (Figure E).

Figure E

Screenshot of Security Checkup screen, with all items indicated as checked and green to indicated completion.

Google’s Security Checkup helps you review the security of your account, step-by-step.

Use Google Workspace (formerly G Suite)? Ask an administrator for help.

If you use Gmail and Google Workspace as part of an organization (e.g., work or school), an administrator may be able to do additional review of your account access data. To do this, the administrator will need to sign in to the admin console at https://admin.google.com. From the Admin console, they might go to https://admin.google.com/ac/, select your account, then review security settings as well as connected apps and devices. Next, they might review all login information by going to the login report at https://admin.google.com/ac/reporting/audit/login, then filtering for your account (Figure F). Since this information is centrally logged by the system, access records will remain, even if the person accessing your account attempts to cover their tracks (e.g., by locally deleting browser history).

Figure F

GIF that alternates between two images: one a list of account sign ins for the author's Google Workspace email account address, the other that indicates the security and connected apps linked to the author's account.

For organizational accounts, a Google Workspace administrator may review account settings (e.g., security, apps, and devices) and audit logs (e.g., account sign ins), as displayed in these two alternating screenshots.

What’s your experience?

If you’ve wondered whether someone else has accessed your Google account, what steps have you taken? What did you learn when you completed the above access review of your Google account? Let me know any additional steps you suggest, either in the comments below or on Twitter (@awolber).   

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New computational method detects disrupted pathways in cancer

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Cancer is a notoriously complex disease, in part because it may be caused by mutations among hundreds or even thousands of genes. In addition, most cancers exhibit an extraordinary amount of variation among genetic mutations, even between patients with the same types of cancers.

Consequently, cancer researchers have chosen to study interactions among groups of genes in certain biological pathways that are disrupted.

When genes in certain pathways are frequently mutated or disrupted, that pathway may play a critical role in the initiation or development of cancer. But unravelling the molecular mechanisms underlying those disruptions is extremely complex.

Nw, University at Buffalo researchers have developed a new, statistically more powerful method called FDRnet that can more effectively detect key functional pathways in cancer using genomics data generated by next-generation sequencing technology.

Published in Nature Computational Science, the new method has the potential to give biologists more precise data with which to zero in on therapeutic targets.

“Using the new method, we can find biological pathways in which genes are significantly mutated or disrupted,” explained Yijun Sun, PhD, associate professor of bioinformatics in the Department of Microbiology and Immunology in the Jacobs School of Medicine and Biomedical Sciences at UB and the corresponding author. “It addresses some key challenges in molecular pathway analysis in cancer studies. Once the tumor biologists obtain this information, they can use it to verify our findings, and from there develop new cancer treatments,” he said.

“By overcoming the limitations of existing approaches, FDRnet can facilitate the detection of key functional pathways in cancer and other genetic diseases,” said Sun.

When Sun and his co-authors tested FDRnet on simulation data and on breast cancer and B-cell lymphoma data, they found that FDRnet was able to detect which subnetworks or pathways are significantly perturbed in these cancers, potentially leading tumour biologists to identify new therapeutic targets.

Source: State University of New York at Buffalo




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Tom & Jerry Release Date in India Set for February 19, a Week Before the US

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Tom & Jerry will now release February 19 in cinemas in India, a full week earlier than originally announced. Warner Bros. India revealed the new release date on Thursday via its social media channels. That puts the Indian release date a week prior to the US, where Tom & Jerry releases February 26 on (US-exclusive streaming service) HBO Max and in cinemas. In India, the hybrid live-action/ animated Tom and Jerry movie will be available in English (the original language), in addition to three local-language dubs: Hindi, Tamil, and Telugu.

The 42 Most Anticipated Movies of 2021, Including Tom & Jerry

However, India won’t be the first market to catch the big-screen return of the iconic cat and mouse duo. Tom & Jerry premieres February 10 in Netherlands, followed by Brazil and Singapore on February 11. India is among the next wave of markets on February 19, alongside Iceland and Lithuania. Russia and Slovakia will follow on February 25, before Tom & Jerry arrives in the US on February 26. Argentina, Czechia, Croatia, and Portugal follow on March 4, with Spain and France release set for March 5. In the UK, Ireland, and Japan, Tom & Jerry is due March 19.

Of course, whether any of this goes according to plan depends on how the COVID-19 situation fares locally. For instance, around 65 percent of theatres remain closed in the US (including the major metropolitan hubs of New York and Los Angeles). Theatres are indefinitely shut across the UK where a third stringent nationwide lockdown is in effect. That is also the case in France, at least until the end of January. In Spain, cinemas are operating at 30–50 percent capacity. But while Americans have the option to watch Tom & Jerry at home (on HBO Max), others do not.

Tom & Jerry Hindi trailer

Tom & Jerry Tamil trailer

Tom & Jerry Telugu trailer

Chloë Grace Moretz (Kick-Ass) is the human lead as event planner Kayla opposite Tom and Jerry in the new movie, alongside the likes of Michael Peña (Ant-Man and the Wasp) the hotel’s deputy general manager Terrance, Rob Delaney (Catastrophe) as the hotel manager Mr. DuBros, Ken Jeong (Community) as the hotel chef Jackie, Colin Jost (Saturday Night Live) as wedding groom Ben, and Pallavi Sharda (Besharam) as the bride Preeta.

William Hanna, Mel Blanc, and June Foray provide vocal effects for Tom and Jerry through archival audio recordings. Hanna is the co-creator of Tom and Jerry along with Joseph Barbera. Tim Story (Ride Along) is directing Tom & Jerry off a script by Kevin Costello (Brigsby Bear). Tom & Jerry is a production of Warner Animation Group, Turner Entertainment Company, and The Story Company.

Watch the First Trailer for the Tom & Jerry Movie

Here’s the official synopsis of Tom & Jerry, from Warner Bros.:

One of the most beloved rivalries in history is reignited when Jerry moves into New York City’s finest hotel on the eve of “the wedding of the century,” forcing the event’s desperate planner to hire Tom to get rid of him, in director Tim Story’s “Tom & Jerry.” The ensuing cat and mouse battle threatens to destroy her career, the wedding and possibly the hotel itself. But soon, an even bigger problem arises: a diabolically ambitious staffer conspiring against all three of them. An eye-popping blend of classic animation and live action, Tom and Jerry’s new big-screen adventure stakes new ground for the iconic characters and forces them to do the unthinkable… work together to save the day.

Tom & Jerry is out February 19 in India in English, Hindi, Tamil, and Telugu.

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