Glejak wielopostaciowy, GBM - diagnoza, leczenie, nowości

[moto_kate]

"Mało znany antybiotyk o nazwie siomycyna A działa przeciwnowotworowo, hamując ekspresję genu niezbędnego dla rozwoju raka."

Cały artykuł tu: http://zdrowie.onet.pl/1363307,2056,,,, ... ostki.html

[Crono5]

Dzis w wiadomosciach o 15:00 bylo o antybiotyku wplywajacemu na apotoze komurek nowotworowych.
link do wczorajszych wiadomosci o 15:00 (7 minuta i 56 sekunda) wiadomosci:

http://www.itvp.pl/informacje/video.html?channel_id=499&site_id=835&genre_id=-1&form_id=-1&video=26248

przedruk z: http://abclocal.go.com/kgo/story?sectio ... id=5525939

Na stronie jest takze reportaz video.


Stanford researchers have found a way to make cancer cell in mice self destruct. This discovery could lead to new treatment in cancer patients. The study was released today and published in the proceedings of the National Academy of Sciences.

Every cell in our body divides, producing new cells. When they get old, they die. But cancer cells have found a way to turn the mortality switch off, becoming immortal.

Natalie Wu, Stanford Researcher: "These cells just keep proliferating without shutting itself off."



Flip of genetic switch causes cancers in mice to self-destruct, Stanford researchers find


przedruk z:
http://med.stanford.edu/news_releases/2007/july/senescence.html

By Louis Bergeron




STANFORD, Calif. — Killing cancerous tumors isn’t easy, as anyone who has suffered through chemotherapy can attest. But a new study in mice shows that switching off a single malfunctioning gene can halt the limitless division of tumor cells and turn them back to the path of their own planned obsolescence.

The surprising possibility that a cell’s own natural mechanism for ensuring its mortality could be used to vanquish tumors opens the door to a new approach to developing drugs to treat cancer patients, according to Dean Felsher, MD, PhD, associate professor of oncology and of pathology at the Stanford University School of Medicine. Felsher is the senior author of the study published July 30 in the advance online version of the Proceedings of the National Academy of Sciences.

“Our research implies that by shutting off a critical cancer gene, tumor cells can realize that they are broken and restore this physiologic fail-safe program,” said Felsher.

Cancer can be notoriously resistant to medical treatment. Not only do cancer cells proliferate uncontrollably, they somehow circumvent the mechanism that causes normal cells to die when they get old or malfunction. That makes cancer cells effectively immortal unless doctors manage to squelch them.

The gene Felsher’s team studied produces a protein called Myc (pronounced “mick”), which promotes cell division. A mutation of the gene causes cells to overproduce the protein, prompting perpetual cell division and tumor growth. By turning off the mutated gene, the researchers found that not only did uncontrolled cell division cease, but the cells also reactivated a normal physiological mechanism, called senescence, which makes it possible for a cell to eventually die.

“What was unexpected was just the fact that cancer cells had retained the ability to undergo senescence at all,” said Felsher. Cancer researchers had long thought the senescence process had to be irreversibly disrupted for a tumor to develop.

The researchers worked with a series of mice engineered to have Myc-triggered cancers of either the liver, blood or bones, along with a specially constructed version of the Myc gene that they could switch off by feeding the mice antibiotics. When the mice dined on doses of the drugs, invariably, the tumors ceased growing and then diminished, with some disappearing over the course of just a few days.

Although Felsher’s lab had previously shown that mouse tumors diminished and disappeared when Myc was switched off, they hadn’t been sure how the process actually worked. Historically, most research involving genetic methods of battling cancer cells has focused on reactivating genes called tumor-suppressor genes, which are generally overcome by a proliferating cancer. No one had explored the idea that senescence might play a key role in diminishing tumors.

Felsher described senescence as acting like a fail-safe mechanism to stop cancer. When a cell detects a deleterious mutation, it launches the senescence process, resulting in the permanent loss of the cell’s ability to proliferate, thus halting any cancer.

“In order to become tumor cells, those cells have to overcome senescence,” said Chi-Hwa Wu, PhD, postdoctoral researcher in Felsher’s lab and first author of the study. Wu had the inspiration to explore whether the sudden diminishment they had observed in the tumors might be due to the reactivation of some latent remnant of the trigger for senescence.

Through a series of experiments looking at enzymes associated with the senescence process, as well as some molecular markers, Wu confirmed her suspicion. And not only was senescence occurring in cells that had been thought to be incapable of it, the process was reactivated in all the different tumors they studied.

Consider it a cell version of the Jekyll-and-Hyde transformation. “It’s sort of like Mr. Hyde realizing that there’s something wrong with him and then being able to put himself back into his normal state as Dr. Jekyll,” Felsher said.

In addition to the deepened understanding of how the process of senescence works, Felsher and Wu see a lot of potential for new approaches to treating cancer, beyond the traditional tactic of trying to kill cancer cells directly. “This work implies that maybe part of the strategy should involve figuring out how to get the cancer cells to just be allowed to do what they originally wanted to do anyway, which is to not be proliferating endlessly and growing uncontrolled,” said Felsher.

The next step for the team is to see how well the approach works in human cancer cells. “And we’re also trying to figure out what the mechanism is,” Felsher said. “What are the molecular mechanisms of this, so that we can figure out how to better treat cancer?”

Other authors on the research paper are Jan van Riggelen, PhD, postdoctoral researcher; Alper Yetil, graduate student in cancer biology; Alice Fan, MD, instructor in oncology, and medical student Pavan Bachireddy.



STANFORD, Calif. — Killing cancerous tumors isn’t easy, as anyone who has suffered through chemotherapy can attest. But a new study in mice shows that switching off a single malfunctioning gene can halt the limitless division of tumor cells and turn them back to the path of their own planned obsolescence.





Natalie Wu is a Stanford researcher. She and other scientists have isolated a gene which produces a protein called myc (pronounced mick). Myc acts like a regulator, promoting cell division.

These researchers asked themselves what would happen if they could switch off this gene in mice.

Jan Van Rigglen, Stanford Researcher: "We switch off the oncogene and the cells in the end die."

A mouse they studied went from having cancer cells to none at all in just four days. The myc gene can be turned off by injecting the mouse with antibiotics.

Natalie Wu: "Antibiotics cannot cure the cancer, but this way the cancer gene is regulated by adding or removing the antibiotics."

The next step for this research team is to see how well this process works in human cancer cells.

Copyright 2007, ABC7


Switching Off Gene Halts Cancer, Stanford Team Says

przedruk z:
http://www.nysun.com/article/59523

LONDON — Switching off a single faulty gene can halt the limitless division of cancer cells, according to a study published today that opens up a promising way to combat the disease.

The possibility that natural mechanisms for wiping out cancerous cells could be used to kill off liver, blood, or bone tumors comes from a team at Stanford University School of Medicine.

Cancer cells proliferate uncontrollably because of DNA damage and mutations, and they circumvent the mechanisms that cause normal cells to die when they get old or malfunction. By using drugs to turn off a single gene that can play a central role, this process can be halted.

The gene studied is responsible for making a protein called Myc (pronounced "mick"), which enables cells to divide.

A mutation causes cells to overproduce the protein, prompting perpetual cell division — the hallmark of cancer. Faulty versions of Myc are present in 70% of cancers. By turning off the mutated gene, researchers found that not only did uncontrolled cell division cease, but the cells also reactivated a normal physiological mechanism, called senescence. This allowed the cancer cells to die.
"By shutting off a critical cancer gene, tumor cells can realize that they are broken and restore this physiological fail-safe program," said Dr. Dean Felsher of Stanford, senior author of the study published in the Proceedings of the National Academy of Sciences. "What was unexpected was just the fact that cancer cells had retained the ability to undergo senescence at all."

The researchers made their discovery using mice that were genetically engineered to have Myc-triggered cancers of either the liver, blood, or bones. The mice's Myc gene was designed so it could be switched off with antibiotics.

When the mice ate the drugs, the tumors stopped growing and then diminished. Some disappeared in a few days.

The work was described as exciting yesterday by Alan Clarke of Cardiff University. However, he cautioned that although faulty Myc is common in cancer, far fewer tumors are totally dependent — "addicted to Myc" — which could limit the effects of a treatment based on this find.

He added that the study was highly idealized, with scientists engineering mice to make abnormal amounts of Myc protein to develop tumors, then turning off excess Myc to treat the cancer.

The authors had shown that the tumor regression depended on the presence of other genes and these other genes were frequently mutated.

Therefore, "in these contexts, tumor regression by reducing Myc would not necessarily work," Mr. Clarke said.

dodatkowe info.
W artykule z 2004 roku pojawia sie nazwa antybiotyku odzdzialywujacego na proteine MYC:

Cancer cells can revert to harmless cells by switching off a single gene, shows a study of liver cancer in mice.

The gene, which produces a protein called MYC - pronounced “mick” - usually controls cell division. It is implicated in several human cancers, where overexpression of the protein causes rapid cell division, forming tumours.

In the new study, researchers used transgenic mice in which the MYC gene was constantly switched ‘on’ so that too much MYC protein was produced, inducing liver cancer in the mice.

Giving the mice the common antibiotic doxycycline turned the gene ‘off’, and the cells reverted to normal liver cells, but were not destroyed.

“We were definitely surprised that we could make liver cancer cells look like normal liver cells,” says Dean Felsher at Stanford University, California, US, who led the study. “Cells differentiate into more than one cell type and stay that way for months.”
Lying dormant

Withdrawing the antibiotic turned the gene back on so more MYC protein was produced and the cancer, which had been lying dormant, returned. A green dye was used to tag the cells so they could be monitored as they turned from liver cells to cancer cells and back again. The researchers could therefore be certain that the tumours forming were from the same group of cells and not from elsewhere.

“The model is ingenious in that they have constructed an artificial way of turning this gene on or off in the liver of mice,” says Hakon Leffler from Lund University, Sweden. “Humans and normal animals do not have this switch in any of their cells, healthy or cancerous,” he adds, so the technique could not be directly transferred to humans. However, Leffler says the study does suggest a new way of fighting cancer by targeting abnormally high levels of MYC.

“You’d have to target the protein or switch the gene expression off in some way,” agrees John Lunec from Cancer Research UK.
Organ regeneration

The researchers believe stem cell activity is involved. “Liver is really unusual,” says Felsher, as “you can’t usually regenerate an organ but you can with liver tissue”.

If the liver cells retained some stem cell characteristics, he says, it would explain why they were able to revert to normal liver cells with the antibiotic. It would also explain why the tumours were able to reappear once the antibiotic was withdrawn and MYC became overexpressed for the second time.

There is still much to understand. “The next step is to target the MYC protein,” Felsher told New Scientist, “and to validate that it also works on humans.” If it does, it will be a big step forward as the results may apply to several types of cancer.

“The MYC gene is known to be overactive in many types of cancer,” says Elaine Vickers from Cancer Research UK. “Estimates suggest that the gene may contribute to as many as one in seven cancer deaths.”


dodatkowe info [ENG]:
http://news-service.stanford.edu/news/2004/october13/med-felsher-1013.html
http://www.sciencenews.org/articles/20041016/fob8.asp

[Crono5]

przedruk z: http://www.pierwszapomoc.com/1458/

Mało znany antybiotyk o nazwie siomycyna A działa przeciwnowotworowo, hamując ekspresję genu niezbędnego dla rozwoju raka. Wyniki badań naukowców z University of Illinois at Chicago College of Medicine opublikowano w najnowszym numerze pisma “Cancer Research”.

Budowa siomycyny A:



Główny autor badania, Andrei Gartel, mikrobiolog i immunolog, tłumaczy, że badany gen FoxM1 jest bardzo aktywny w komórkach większości nowotworów. Jest odpowiedzialny za włączanie ekspresji genów niezbędnych do podziałów komórki (proliferacji) i wyłączania tych genów, które je hamują. Jak wiadomo niekontrolowana proliferacja jest główną cechą charakterystyczną komórek nowotworowych.


PhD Andrei Gartel

Na potrzeby badania naukowcy opracowali nowy system do identyfikacji małych cząsteczek, które hamują działanie białek włączających i wyłączających geny. Przy użyciu tego systemu odkryli, że antybiotyk o nazwie siomycyna A działa specyficznie na FoxM1 nie wpływając na żadne inne białka komórki.

W następnych doświadczeniach wykonanych na hodowlach komórek, badacze wykazali, że siomycyna A indukowała samobójstwo (apoptozę) komórek nowotworowych, ale nie normalnych prawidłowych komórek w hodowli.

Gartel mówi, że nowa technika oferuje naukowcom szybki sposób identyfikacji substancji, które wpływają na onkogeny - geny, których aktywacja powoduje rozwój nowotworu. Pierwszym związkiem odkrytym w ten sposób jest siomycyna A, substancja bardzo obiecująca ponieważ nie jest toksyczna.

Teraz lek musi przejść dalsze badania laboratoryjne z użyciem innych rodzajów komórek i wstępne testy na zwierzętach zanim będzie można rozpocząć badania kliniczne.

nieco nowszy artykul opisuje potepy w badaniach:

A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment.

The forkhead box m1 (Foxm1) transcription factor is essential for initiation of carcinogen-induced liver tumors; however, whether FoxM1 constitutes a therapeutic target for liver cancer treatment remains unknown. In this study, we used diethylnitrosamine/phenobarbital treatment to induce hepatocellular carcinomas (HCCs) in either WT mice or Arf(-/-)Rosa26-FoxM1b Tg mice, in which forkhead box M1b (FoxM1b) is overexpressed and alternative reading frame (ARF) inhibition of FoxM1 transcriptional activity is eliminated. To pharmacologically reduce FoxM1 activity in HCCs, we subjected these HCC-bearing mice to daily injections of a cell-penetrating ARF(26-44) peptide inhibitor of FoxM1 function. After 4 weeks of this treatment, HCC regions displayed reduced tumor cell proliferation and angiogenesis and a significant increase in apoptosis within the HCC region but not in the adjacent normal liver tissue. ARF peptide treatment also induced apoptosis of several distinct human hepatoma cell lines, which correlated with reduced protein levels of the mitotic regulatory genes encoding polo-like kinase 1, aurora B kinase, and survivin, all of which are transcriptional targets of FoxM1 that are highly expressed in cancer cells and function to prevent apoptosis. These studies indicate that ARF peptide treatment is an effective therapeutic approach to limit proliferation and induce apoptosis of liver cancer cells in vivo.

dodatkowe info:


http://www.biolog.pl/article3449.html
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7287582&dopt=AbstractPlus

dodatkowe info [eng]
http://cancerres.aacrjournals.org/cgi/content/abstract/66/19/9731 - [demo view]
http://www.level1diet.com/research/id/471033
http://www.ncbi.nlm.nih.gov/sites/entrez?term=17018632&cmd=search&db=pubmed
http://www.rxpgnews.com/antibiotics/Antibiotic_inhibits_cancer_gene_activity_5025_5025.shtml
http://www.drugresearcher.com/news/ng.asp?id=70978-cancer-siomycin-a-side-effects
http://www.emaxhealth.com/51/7692.html

http://www.osel.cz/index.php?clanek=2184 [CZ]

Dokument m.in na temat siomcyny:
http://diss.kib.ki.se/2005/91-7140-202-0/thesis.pdf

Informacje o genie FoxM1:
http://www.uic.edu/com/bcmg/costa.html
http://genomics.senescence.info/genes/entry.php?hugo=FOXM1

pokrewne info o blokowaniu rozrostu guza, przy uzyciu blokowania tylko jednego enzymu:
http://www.eurekalert.org/pub_releases/2006-10/uotm-ssc092606.php

[Crono5]

Prawdopodobnie uda mi sie dostac tazke doxycycline, znajomy, ktory jest teraz w USA, mowil ze byc moze uda mu sie go zalatwic.


15-08-2007:

Aj, tak cos mi sie wydalo ze nie doczytalem. Nie bedzie tak hop siup. Skubancy sobie sami zmodyfikowali MyC do testow. tak w nim nakombinowali zeby zadzialal na oddzialywanie tego antybiotyku, zeby mogli sprawdzic czy faktycznie wylaczenie go zadziala . Trzeba szukac dalej