Memorex began as a computer tape producer and expanded to become a major IBM plug compatible peripheral supplier. It is now a consumer electronics brand of Imation specializing in disk recordable media for CD and DVD drives, flash memory, computer accessories and other electronics. Wikipedia.
News Article | August 27, 2016
Tech executive John Bosworth is ready to take my questions. As I fire up a note-taking app on my iPad, he leans back behind a desk at his San Francisco-based startup, Mutiny, surrounded by computers and other tools of his trade. For a business reporter, this would be just another typical day on the beat. Except that we're not really in a San Francisco office but a painstaking replica of one constructed on a soundstage in Atlanta. And the computers it contains aren’t sleek iMacs or ThinkPads: They’re chunky, beige, floppy drive-equipped Commodore 64s. Oh, and if you want to get technical, the guy I'm interviewing is not Bosworth but the actor who plays him, Toby Huss, who has opted to sink into the set's cushy office chair rather than perch on the folding studio chair that a PR handler has fetched. Bosworth—I mean Huss—and I are chatting on the set of Halt and Catch Fire, AMC’s drama about tech startups in the 1980s. For the show’s third season, now airing on Tuesdays—the first two episodes are available for free streaming—the characters uproot themselves from Dallas and relocate to the San Francisco Bay Area en masse. He’s explaining to me that on some level, it doesn’t matter that the show takes place in San Francisco and Silicon Valley in 1986. "It could be set anywhere," he argues. "It just happens to be in technology. But you’re watching these people start something." He’s right. And yet Halt and Catch Fire takes its setting as seriously as any TV series I’ve ever seen. Much of the time, Hollywood is so disinterested in portraying technology accurately that it can’t even be bothered to show a computer display that looks like a computer display. The creators of this show, by contrast, are obsessive about getting the details right. It's not just that the scripts are crunchy with allusions, from PETSCII (a variant of ASCII code used by Commodore computers) to "Sandy" (Lerner, cofounder of Cisco), that are integrated so seamlessly that they enrich the experience if you get them and don't detract if they sail past your head. Like Mad Men, another prestige period piece that this one would bring to mind even if they weren’t both AMC shows, Halt and Catch Fire is in part about how we got from the past to the present. During season three, the show's underdog entrepreneurs figure out how to accept online payments of the sort we'd eventually take for granted; establish themselves as an intermediary for peer-to-peer commerce, presaging what eBay did a decade later; blithely violate their customers' privacy in ways reminiscent of what a modern-day unicorn or two has been known to do; and devise the business model we now call "freemium." The details are made up, but the arc of history is real. "Our characters don’t know what happens after," says Scoot McNairy, who plays nerdy engineer Gordon Clark, as we commandeer the plush living room of Diane Gould, a venture capitalist played by Annabeth Gish in the new season, for an interview. But we 2016 TV watchers know how Halt and Catch Fire not only captures 1986 but hints at what was to come in 1996, 2006, and 2016. And the fact that the show is so deeply informed about its topic makes it one of the best pieces of filmed entertainment ever done about technology. "The best compliment we can get," says Christopher Cantwell, who created the show with Christopher C. Rogers, "is when somebody says, 'I lived through it, and that's exactly what it felt like.'" When the show debuted in 2014, it was set in 1983 in Dallas, at a time when Texas’s "Silicon Prairie" rivaled Silicon Valley in importance to the burgeoning PC industry. Its main characters were Joe MacMillan (Lee Pace) and McNairy’s Gordon Clark and its plot involved the race to build clones of the IBM PC by reverse-engineering its BIOS code—an effort that was very much inspired by reality, but so obscure and nerdy that I did a double-take when I heard that someone was building a TV show around it. By the second season, the storyline had shifted to focus on Mutiny, an online gaming company founded by Gordon’s wife, Donna (Kerry Bishé), and engineer Cameron Howe (Mackenzie Davis). In that season’s last episode, the Clarks, Howe, and Bosworth decide to move Mutiny to San Francisco while MacMillan simultaneously relocates there to start MacMillan Utility, a PC software company. Why the move? It felt inevitable, Cantwell says: "Our characters were becoming too big for that Silicon Prairie pond. They were ambitious enough and we wanted to see what happened when they made the move to the big leagues." "There’s an immediate impact on the story," says his co-creator Rogers. "We wanted to feel a dramatic increase in scope, entering a larger arena and competing not with upstarts but established companies with a lot of sway. Venture capitalists enter in a major way. Major empires will be built over the course of a number of months." "Many people don’t know much about the history of personal technology beyond "first came Steve Jobs and Bill Gates and then after that the World Wide Web and then Pokémon Go," Rogers adds. "We wanted to explore the lesser-known histories of the companies that had huge roles and were ahead of their time." Both of the show’s startups are engaged in businesses that were bleeding-edge in 1986 and eventually became huge. The new season centers on Mutiny’s expansion beyond gaming into communications and commerce, reminiscent of the early development of proprietary online services such as America Online, which was known as Quantum Link at the time. Meanwhile, MacMillan is founding MacMillan Utility just as PC security starts to matter. In the real world, the first widespread IBM PC virus hit in 1986 and John McAfee released the first version of his VirusScan software the next year. At Halt and Catch Fire’s replica of 1980s San Francisco on its Atlanta soundstage, the Mutiny office is a set so sprawling that you could squeeze a decent-sized actual 2016 early-stage startup into it. As I take a self-guided tour of the brick-walled quarters, I see rows of desks equipped with Commodore 64 PCs; 5 1/4" floppy disks of multiple makes, including Memorex, 3M, and BASF FlexyDisk; a manual for Frogger for the Atari 2600; a copy of a spreadsheet program known as MicroPro CalcStar; technical books such as Structured Systems Programming; and countless other little pieces of history. The whole space is so dense with evocative artifacts that I wish I could channel Scrooge McDuck and burrow through them like a gopher. Downstairs from Mutiny’s office—which is really on an adjoining set, not another floor—is the second-hand mainframe computer that powers Mutiny’s online service, an IBM 3033 in a rust-orange metal case equipped with add-ons such as IBM 3480 tape units. Also nearby is the headquarters of MacMillan Utility, a comparatively tidy, corporate space outfitted with gear such as a Mac Plus and a Radio Shack Tandy 1000 PC. Even the house where the Clarks and Cameron live is appropriately decked out with tech. Anyone who watches attentively may notice that the TV set in the living room is not just any 1980s TV set, but a J.C. Penney one. Which seems like the perfect choice. As much as the Halt and Catch Fire's creators and writers, it's production designer Craig Stearns, property master Jason Davis, and all the other people responsible for how the show looks who are responsible for bringing its world to life. "For most of the time we were sitting in Studio City in this conference room talking to a bunch of writers and dreaming up ten episodes," says Mark Lafferty, the author of "Yerba Buena," the third season’s fifth episode, which was in production the day I visited the set. "It all feels very abstract even if you’ve done it before. To walk onto the Mutiny set … It’s so vast and capacious and lovely to look at. And I can sit at a desk and look at a 5 1/4" floppy or a Byte magazine or Atari instruction manual I recognize from my youth. It’s a head trip and really wonderful." Starting with season two, the show worked with the historians at Seattle's Living Computer Museum, started by Microsoft cofounder Paul Allen, to outfit the Mutiny office and other sets with computers and related paraphernalia. Even if you're aware that Commodore 64s remain readily available from eBay and other sources, it's dazzling to see so many in one place—all in good condition and all outfitted with the correct floppy-disk drives, monitors, and dial-up modems. Vintage IBM mainframes are a bit harder to come by than Commodores, not to mention more difficult to transport. So unlike most of the tech depicted on the show, the single most important computer on Halt and Catch Fire, the IBM mainframe, is a replica, not a relic. It's a full-scale model built for the set, based on the original plans from IBM's archives and reconstructed in consultation with the Living Computer Museum. It's so ambitious a piece of fakery that when I saw it in person, I wasn't sure if it was the real deal or not, and had to ask. I'm on the Halt and Catch Fire set eavesdropping on a conversation between producer/writer Lafferty and costar Bishé, who's filming a scene with a mention of a Bay Area bedroom community: Lafferty: Kerry, one pronunciation thing—take it or leave it. Lafferty: You’re not mispronouncing it. You’re saying it correctly, Los Gatos. I’m from Los Gatos. If you’re a local, you say "Las Gaddis" Lafferty and Bishé go on to ruminate that Bishé's character, Donna Clark, went to school in Berkeley and might know that the people who live in Los Gatos don’t know how to say "Los Gatos." For the record: In the show as broadcast, she pronounces it as if she were saying "the cats" in Spanish, as someone who’d recently relocated from Texas might well do. But the fact that this debate happened at all is a sign of the care that goes into making Halt and Catch Fire feel authentic. For most of Halt and Catch Fire’s principal actors, the program’s setting is less nostalgic than novel. After all, at the beginning of 1986, McNairy, Pace, Bishé, were eight years old, six, and one, respectively, and Davis had not yet been born. "I love the world that we’re exploring and I learn too much every day, because it’s a world that I’m really not personally familiar with, outside of the show," Davis says. Only Huss, at 19, was more or less an adult during the show’s era. But even he doesn’t claim to be an expert on its era’s technology. When he first saw the basement set’s IBM mainframe-which occupies multiple giant cabinets—he wasn’t sure what it was. "I asked Mackenzie and Kerry, ‘What are these called?,’" he says, recreating the conversation. "And Mackenzie went ‘Oh, these are the big computers.’ And I went, ‘Those aren’t computers.’ She said, ‘No, they’re filled with computers.’ I went, ‘What do you mean, they’re filled with computers?’ She said, ‘I don’t know what they are!’ And Kerry went, ‘I think they’re the mainframes.’ They may not be tech historians, but the cast members like knowing that plot points and the tech detritus on the set are period-accurate. That allows them to focus on the people they portray rather than the setting. And it’s the Silicon Valley ethos that they find interesting, more than the accoutrements. "My job is to understand the people who understand the computer stuff." "That’s what’s intriguing about the characters. All they want to do is create and build and change the world," says McNairy. "They don’t care about anything other than that. I love that they just throw money around, or give it away. They don’t care about the money, they care about the work." "The writers do their homework so well, and I do a different kind of homework," says Bishé. "I tried to understand the computer stuff, until I realized that my job isn’t to try to understand the computer stuff. My job is to understand the people who understand the computer stuff." The writers do indeed do their homework, pretty much literally. When writing began on season three, with an all-new staff, creators Cantwell and Rogers kicked things off by providing a detailed overview of what was going on in the technology business, pop culture, and the world at large in 1986. Then the writers dived into works of history that provided useful context, such as Walter Isaacson’s Steve Jobs, Po Bronson’s The Nudist on the Late Shift, and David A. Kaplan’s The Silicon Boys. Of course, the writers weren’t telling the stories of any of the companies mentioned in these books. For a work of fiction like For Halt and Catch Fire, accuracy is less about sticking to the precise facts than it is about retaining a basic level of plausibility. "Mutiny is not just PlayNet or Q-Link or the Source or CompuServe or anything," says Rogers. "But the tech they’re chasing should feel viable and like what people were doing in 1986." (The show both references real companies and borrows bits of them for its imaginary startups: For instance, Mutiny's avatar-based chat certainly seems to derive aesthetic inspiration from Lucasfilm's Habitat, which was offered on Quantum Link, later to be known as America Online, in real-world 1986.) As the authors of Halt and Catch Fire episodes crammed their work with tech references, they called on writers' assistant Katie Edgerton for research help. "She's supernatural," Lafferty says. Since the show’s beginning, its creators and writers have also been aided in their quest for accuracy by technical consultant Carl Ledbetter. Currently a venture capitalist, he has a decades-long résumé including experience at tech companies from AT&T to Sun Microsystems to Prime Computer. Ledbetter was introduced to Cantwell and Rogers as they were creating the show, and helped them ground their fictional tale of the PC industry in reality. During the period depicted in the first season, he was an executive at IBM, albeit not in its PC division: "I was just far enough removed to have a neutral view, but close enough to have seen it," he says. After briefing the the show’s creators on the early days of the PC business, he found glimmers of actual history showing up in their storyline. It’s not a coincidence, he says, that the names Gordon Clark and Donna Clark sound vaguely like those of Gary Kildall and Dorothy Kildall, the husband and wife who started Digital Research, once Microsoft’s archrival among PC software companies—even though the Clarks are not otherwise modeled on the Kildalls in any specific fashion. Over three seasons, the questions Ledbetter has fielded as technical consultant include "What did an IBM mainframe cost?," "What were venture-backed valuations in 1982?," and "How did you actually recover data of a disk?" Some of the answers are permanently lodged in his brain; others are in reference materials he has on hand; and in some cases they involve far-flung research. He even writes code from scratch so that if an engineer is shown at work, the lines of programming shown on the PC monitor are real and appropriate. If you bother to fact-check the show's dialog, as I did while watching the third season's first five episodes, you get a sense of how much care has gone into the little details that make 1986 feel like 1986. Even Mad Men got in trouble for minor violations of reality such as showing IBM Selectric typewriters a year before they were available. But when Gordon mentioned having been obsessed with CompuServe's CB Simulator chat service a few years earlier, I was confident that he could have been. (Turns out the service launched in 1980.) Almost everything checks out so well that on the rare occasion that I spot anything that's even arguably off, it feels like a little victory—like when Joe makes a reference to Coleco being in the video game business, an industry it abandoned in late 1985. But you know what? I'll bet that even in the real world, people still thought of Coleco as a video game company in 1986. "Nobody wants to see a show where someone's arguing for the Betamax." Sometimes Ledbetter's contributions go beyond mere verification of facts and help shape the story. Case in point: During one scene I witnessed being filmed, Donna and Cameron have an intense debate about whether their service should accept credit cards or not. As I watched, I realized I couldn’t remember offhand what the state of online credit-card acceptance was in 1986. Ledbetter told me he was similarly foggy on the details when the script was in the works: "I had the exact same issue, even though I lived through that era." As Ledbetter helped make sure that plot point was accurate, the discussion stretched to dozens of emails; in the end, he advised that "it was just barely doable in the era of 1986, when that occurred." But he also pointed out that at the time, Mutiny could have used SWIFT numbers to accept payment via electronic bank withdrawals, a period-appropriate touch that made it into the final episode. As I watched Bishé and Davis perform take after take of Donna and Cameron's heated argument over whether the online world should be sullied with credit-card transactions, it felt real even though the long-term upshot was obvious. That's a tightrope walk the show frequently has to walk: "Nobody wants to see a show where it’s a foregone conclusion and someone's arguing for the Betamax when everyone knows it loses,' Rogers says. At the end of season two's final episode, "Heaven is a Place," Halt and Catch Fire teed up the current episodes by showing the Mutiny staff on a plane to California. "We write every season like it can be a satisfying, fully fledged story with a beginning, a middle, and an end," says Cantwell. "But we do like to leave some things hanging." For a while, it looked like they might leave things hanging forever. Though generally well-reviewed by critics and beloved by its fans, the show has been far from a smash ratingswise. AMC didn't announce that it was renewing the series until October 2015, a couple of months after TV watchers learned the characters were on their way to San Francisco. Its fate after the first season had been similarly suspenseful: When TV critic James Poniewozik praised it in August 2014, he wrote about it in the past tense. "After the first season I went ‘Well, that was fun. I don’t know if they’re going to pick this up again,’" recalls Huss. "And they did, and we got season two. We all thought, ‘That was fun, that was a great time. I’m going to miss those guys.’ And they picked it up. It's always a surprise. A nice one." "I’m sure the network would prefer for it to be another way, but there’s this thing about the show that I love so much," says Davis. "It’s like acting camp for us in the spring, and then it comes out. And the people who know about it really care about it. It feels cool. It feels like this thing that you have to choose to find." Whatever happens to Halt and Catch Fire after this season, it's nowhere near running out of history to mine. Some of the richest material of all would come in the next few years after 1986, as the migration began from proprietary online networks like Mutiny's service to the open, commercialized internet. (Season three's final episode, airing in October, is titled "NeXT"—a tantalizing reference to Steve Jobs's second startup, which bridged the gap between his first and second eras at Apple.) In a way, Halt and Catch Fire is a startup about startups. AMC produces the show as well as airing it; if the company can create a sustainable business model, the series can continue on as long as its creators have tales left to tell. The network, says Cantwell, "has been a wonderful partner. They believe in the show, they believe in us, and they believe in the story. They too want to know what's next."
News Article | June 9, 2015
Right before he introduced the new, revamped Apple Music, Tim Cook rolled another classic inspirational Apple film. It was meant to illustrate how their new service fits into the history of humans and our relationship to music — from the good old days when we all gathered ‘round the victrola to listen to the latest ragtime joint, to modern times when we all gather round the DJ booth to hop up and down to the latest bleep bloops. And that's where Apple Music comes in! Apple Music wants to be your one-stop-shop for every level of your musical consumption — whether that's discovering music via trusted curators (BeatsOne radio), getting it directly from artists you already like (Connect), or through algorithms that figure out what you want to listen to so you don't have to. Gone are the days when you have to toggle awkwardly between a Spotify playlist and your personal collection of music files. Now, ostensibly, they will all be a part of the same app, and not just any app — an app connected to the most dominant, effortless music store on the planet. The barrier between streaming and purchasing will be lower than ever. If you have an iPhone and are already a paid Spotify user, I can't think of a single reason why you would stick with the service after June 30th. iTunes was the first digital Case Logic binder Jimmy Iovine, Eddy Cue, or Drake didn't say anything today about buying albums, and the notion that streaming services serve any kind of sizeable "try before you buy" function has long since been debunked. We can assume that the iTunes Store isn't going anywhere, but the innovation of Apple Music — and any of the competitors it's now jumping into the ring with — is not to have to choose which albums you own and don't own. If nothing else, it's evidence of Apple's adaptability, because the original iTunes application started out as a kind of digital intermediary between the era of lovingly organizing your record collection along the wall, and downloading literally every album you could think of off Napster. You could scroll through your friend's iTunes library and the experience was an obvious analog (perhaps that's not the best word) to flipping through their giant 208-disc Case Logic binder. If you grew up with that idea of personal collection and curation, you knew how pivotal it could be for building your personal identity. Everyone had a music collection — whether in files or on vinyl — and the size and nature of it said something important about you. I remember staring with dissatisfaction at my modest CD collection (music was expensive back then! Much more than $9.99 a month) at various stages throughout my adolescence, thinking it was alternately "too pop," "too rock," "too novelty," or the unbearable "too mainstream." Later into college it frequently risked being "too pirated" — I preferred having that original album art to slide into each sleeve, rather than an ugly Memorex CD-R with some Sharpie writing on it, but sometimes convenience won out. This isn't another piece about how it feels so good to put a needle on a record and hold an album in your hands and feel Jack White or whoever's beating heart through the warmth of the vinyl. When I got my first iPod (which had my entire music library on its 60 GB, and which definitely was "too pirated") I still took pride in spinning through that impossibly huge artist list and feeling a sense of pride at my vast yet still somehow specific musical taste. This is about the idea of owning the things you like and taking care of them and investing some part of your identity in them. Buying records was a very brief obsession in the history of humans and music Because if you grew up with that idea of collection and curation, you were actually a part of a very brief era in how humans do music. As much as we like to think of them as some vital part of our heritage, record stores really only enjoyed a heyday of about a half a century. Prior to that, music was less a market of things to acquire and more a substance that flowed out of every car speaker and jukebox. And before that, it was something you played with friends after dinner, in the parlor or around the campfire. Our oldest musical traditions, like sacred and folk music, were important because they were an experience people could share, not a way to differentiate one's self. When all we had was hymns, you weren't going to turn up your nose at a song because everyone else was singing it; you were just stoked because everyone else knew the same song you knew and you weren't alone in the universe. Individual taste has been around as long as we've had our five senses, but it didn't manifest itself as choice-based consumer activity until about halfway through the 20th century. Which brings me back to the Inspirational Apple Promo: in a way, the shot of the millennials raging at the EDM show has more in common with dust bowlers gathering 'round for some radio time than it does with the guys blasting the latest track out of their souped-up subwoofers. People who pay hundreds of dollars to attend one of an ever-growing number of big electronic music festivals aren't going so much for a predetermined song or artist or moment so much as to be submerged in a kind of music, a kind of activity, for an extended period of time, and with people who are all having the same experience at the same time. Fans like this are as likely to build a playlist of their favorite dance anthems as to just search YouTube for one of many thousands of three-hour "Trance megamixes." Music as a substance: open the spigot and get your fill. And hopefully, feel less alone. So perhaps Apple Music's egoless combo is more timeless than it seems on the surface, give or take some modern conveniences: We'll have access to everything, but it will be curated and filtered by third parties and algorithms and our own personal playlists so as not to overwhelm our poor little info-saturated brains. (I've said it before and I'll say it again: radio will never die, and Apple making such an investment in BeatsOne seems like further evidence of that — some deep down part of us LOVES the simplicity of being told what to listen to!) The question of what you own will be taken out of the equation; all we really have to do is some arranging and prioritizing to optimize the flow of content. We won't define ourselves by our music, because everyone will be varying flavors of musical omnivore. The only place where I really pause then, is the notion of all of it — every level of our music experience — being chaperoned by a single company. With Connect essentially asking musicians to move all their social media and marketing content to the same platform they sell music on, the legwork of being a fan — of a specific artist or a genre — has been reduced to zero. And all the while, our patterns of consumption are all being fed back to Apple HQ. Apple's asking us to consolidate everything about how we do music to a kind of self-contained Truman Show, where we have everything we could ever want and the freedom to integrate it into our lives in a way that feels specific and personal. But if we ever so much as think about trying to operate past the confines of its dome, it will immediately be apparent how reliant we are on them for everything. It might be really good for us in the long run to revert to a more global, holistic approach to how we do music, as nostalgic as I am for my old CD towers. But then the collection fetish has just moved upstairs — from the customers, to the corporate bodies that gather them up like so many stacks of used discs. Maybe the nostalgia we feel won't be so much for the records and files themselves, but for the diversity of experiences that brought them to us.
Roomi M.W.,Memorex |
Kalinovsky T.,Memorex |
Rath M.,Memorex |
Oncology Reports | Year: 2012
Cancers of the breast, cervix, uterus and ovary are the most prevalent cancers in women worldwide. Proteases play a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. Strong clinical and experimental evidence demonstrates association of elevated levels of urokinase plasminogen activators (u-PA) and matrix metalloproteinases (MMPs) with cancer progression, metastasis and shortened patient survival. MMP activities are regulated by specific tissue inhibitors of metalloproteinases (TIMPs). Our main objective was to study the effect of a nutrient mixture (NM) on the activity of u-PA, MMPs and TIMPs in human breast, cervix, uterine and ovarian cancer cell lines. Human breast (MDA-MB-231 and MCF-7), cervical (HeLa), uterine (SK-UT-1) and ovarian (SKOV3) cancer cell lines were cultured in their respective media and treated at confluence with NM at 0, 50, 100, 250, 500 and 1000 μg/ml. Analysis of u-PA activity was carried out by fibrin zymography, MMPs by gelatinase zymography and TIMPs by reverse zymography. Both breast and uterine cancer cell lines expressed u-PA, which was inhibited by NM in a dose-dependent manner. However, no bands corresponding to u-PA were detected for HeLa and SK-OV-3 cell lines. On gelatinase zymography, MDA-MB-231 and MCF-7 showed one band corresponding to MMP-9, HeLa showed two bands, an intense band corresponding to MMP-2 and a faint band corresponding to MMP-9, SK-UT-1 showed PMA-induced MMP-9, and SK-OV-3 showed a band corresponding to MMP-2. NM inhibited their expression in all cell lines. The activity of TIMPs was upregulated in all cancer cell lines in a dose-dependent manner. Analysis revealed a positive correlation between u-PA and MMPs and a negative correlation between u-PA/MMPs and TIMPs. These findings suggest the therapeutic potential of NM in the treatment of female cancers.
Niedzwiecki A.,Memorex |
Roomi M.W.,Memorex |
Kalinovsky T.,Memorex |
Cancer and Metastasis Reviews | Year: 2010
Consumption of a plant-based diet has been associated with prevention of the development and progression of cancer. We have developed strategies to inhibit cancer development and its spread by targeting common mechanisms used by all types of cancer cells that decrease stability and integrity of connective tissue. Strengthening of collagen and connective tissue can be achieved naturally through the synergistic effects of selected nutrients, such as lysine, proline, ascorbic acid and green tea extract (NM). This micronutrient mixture has exhibited a potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines. Its anti-cancer effects include inhibition of metastasis, tumor growth, matrix metalloproteinase (MMP) secretion, invasion, angiogenesis, and cell growth as well as induction of apoptosis. Many cancers are often diagnosed at later stages, when metastasis has occurred, which standard treatment has been unable to control. Our studies on NM effects on hepatic and pulmonary metastasis demonstrated profound, significant suppression of metastasis in a murine model. Evaluation of effects of NM on xenografts in murine models demonstrated significant reduction in tumor size and tumor burden in all human cancer cell lines tested. In vitro studies demonstrated that NM was very effective in inhibition of cell proliferation (by MTT assay), MMP secretion (by gelatinase zymography), cell invasion (through Matrigel), cell migration (by scratch test), induction of apoptosis (by live green caspase) and induction of pro-apoptotic genes in many diverse cancer cell lines. Furthermore, in vivo and in vitro studies of effects of individual micronutrients compared to their specific combination demonstrated synergistic effects resulting in improved anticancer potency. © 2010 Springer Science+Business Media, LLC.
Roomi M.W.,Memorex |
Kalinovsky T.,Memorex |
Niedzwiecki A.,Memorex |
International Journal of Oncology | Year: 2014
Brain tumors are highly aggressive tumors that are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the extracellular matrix (ECM) and basement membrane, allowing cancer cells to spread to distal organs. Proteases play a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. Strong clinical and experimental evidence demonstrates association of elevated levels of urokinase plasminogen activators (uPA) and MMPs with cancer progression, metastasis and shortened patient survival. MMP activities are regulated by specific tissue inhibitors of metalloproteinases (TIMPs). Our main objective was to study the effect of a nutrient mixture (NM) on the activity of uPA, MMPs and TIMPs in various human gliomas. Human glioblastoma (LN-18, T-98G and A-172) cell lines (ATCC) were cultured in their respective media and treated at confluence with NM at 0, 50, 100, 250, 500 and 1000 μg/ml. Analysis of uPA activity was carried out by fibrin zymography, MMPs by gelatinase zymography and TIMPs by reverse zymography. Glioblastoma cell lines LN-18 and T-98G expressed uPA, which was inhibited by NM in a dose-dependent manner. However, no bands corresponding to uPA were detected for the A-172 cell line. On gelatinase zymography, all three cell lines showed bands corresponding to MMP-2 and LN-18 and T-98G showed PMA (100 ng/ml)-induced MMP-9. NM inhibited their expression in a dose-dependent manner. Activity of TIMP-2 was upregulated by NM in all glioma cell lines in a dose-dependent manner. Analysis revealed a positive correlation between uPA and MMP-2 and a negative correlation between uPA/MMPs and TIMP-2. These findings suggest the therapeutic potential of NM in the treatment of gliomas.