Znalezionych wyników: 343

Jeszcze raz:

http://gisttrials.fmgatew...ternational.pdf

Najblizej masz Niemcy i Austrie...

Francja
http://clinicaltrials.gov...how_locs=Y#locn

Cytat:

ASCO: Missing Mutations Hold Clue to Imatinib (Gleevec) GIST Resistance

By Michael Smith, North American Correspondent, MedPage Today
Published: May 16, 2008
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

PHILADELPHIA, May 16 -- Some imatinib (Gleevec)-resistant patients with gastrointestinal stromal tumors (GIST) don't respond because they are missing the mutations in two genes that are usually integral to the disease.

Niektorzy pacjenci chorujacy na GIST nie reaguja na leczenie imatinibem (Gleevec) poniewaz nie posiadaja mutacji w dwoch genach bedacych zazwyczaj integralnym elementem choroby.

Instead of mutations in c-KIT or PDGFRα, found researchers here, the GIST patients have extra copies of a gene for insulin-like growth factor 1 receptor (IGF-1R) and markedly higher expression of the protein created by the gene.

Zamiast mutacji w c-KIT lub PDGFRa pacjenci z GIST maja dodatkowe kopie genu receptora IGF-1R i wyraznie wieksza ekspresje bialka kodowanego przez ten gen.

The same also appears to be true in many cases of pediatric GIST, which are also resistant to imatinib, reported Andrew Godwin, Ph.D., of the Fox Chase Cancer Center and colleagues.

In laboratory studies, Dr. Godwin said, blocking the gene's expression led to the death of tumor cells, suggesting that such an approach might have therapeutic value.

"Our real excitement," Dr. Godwin said, "is that we think this might be the oncogenic driving force" behind wild-type GIST.

Some compounds aimed at blocking the gene are already in early clinical studies in other types of cancer and Dr. Godwin and colleagues are hoping to leap on that bandwagon.

"We're talking to companies right now about possible clinical trials," Dr. Godwin said.

The research results are to be presented orally at the American Society of Clinical Oncology meeting from May 30 through June 3 in Chicago. A full paper is slated to appear in the June 1 issue of the Proceedings of the National Academy of Sciences.

Most patients with GIST have mutations in either c-KIT or PDGFRα that cause the genes to be more active, mutations that are blocked by imatinib. But between 10% and 15% of patients don't have such mutations and their tumors are resistant to the drug, Dr. Godwin said.
Wiekszosc pacjentow z GIST posiada mutacje w C-KIT lub PDGFRa. Gleevec blokuje te mutacje. 10 do 15 % pacjentow mutacji tych nie posiada i ich guzy sa odporne na dzialanie Gleevec'u.

Instead, they have from three to five extra copies of the IGF-1R gene, compared with standard GISTs that have c-KIT or PDGFRα mutations. The difference was statistically significant at P=0.0163, the researchers found.
Zamiast tego pacjenci Ci maja 3 do 5 dodatkowych kopii genu IGF-1R.

On the other hand, expression of the IGF-1R protein is about 50 times higher in wild-type than in mutated GIST, a difference that was significant at P=0.000002.

The extra gene copies are not enough to cause the additional protein expression[/b], Dr. Godwin said, and he and colleagues are now trying to figure out else is going on.
Niemniej jednak te ekstra kopie genu nie sa wystarczajace by spowodowac dodatkowa ekspresje bialka.

The researchers tested an inhibitor of the gene -- a compound dubbed NVP-AEW541 and made by Novartis, as is imatinib -- and found that, both alone and in combination with imatinib, it induced a "strong cytotoxic response."
Badacze przetestowali inhibitor genu nazwany NVP-AEW541 (wyprodukowany, podobnie jak Gleveec, przez firme Novartis) i stwierdzili, ze zarowno dzialanie samego inhibitora jak i w polaczeniu z imatinibem powodowalo silna reakcje cytotoksyczna.

The findings might usher in an age of "personalized medicine" for GIST, which is now treated with imatinib in a one-size-fits-all fashion. Other inhibitors of c-KIT and PDGFRα are also available, but are usually reserved for second-line therapy.

But Dr. Godwin said his institution, which already tests GISTs for c-KIT and PDGFRα mutations, will soon be able to test for the copy number changes in IGF-1R, although no therapy is approved for those patients.

Robert Benjamin, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston, who was not involved with the New York research, called the report exciting. "It opens the distinct possibility that inhibiting the IGF pathway may be a new approach to therapy for these patients," he commented.

The study was supported by the NIH and the GIST Cancer Research Fund. The researchers reported financial links with Novartis, Pfizer, MedImmune, Human Genome Sciences, Johnson & Johnson, Transgenomic Inc., and MolecularMD.

Primary source: Journal of Clinical Oncology
Source reference:
Godwin AK, et al "Insulin-like growth factor 1 receptor (IGF-1R): A potential therapeutic target for gastrointestinal stromal tumors (GIST)" J Clin Oncol 26: 2008 (May 20 suppl; abstr 10507).

http://www.medpagetoday.c...erage/ASCO/9492

Tutaj jest lista aktywnych badan klinicznych dot odpornego na Gleevec /Sutent GIST
(stan na 8/05/2010). Niestety zaden polski osrodek na niej nie figuruje :-(

Clinical Trials for Gleevec/Sutent-resistant GIST
http://www.liferaftgroup.org/treat_trials.html

Inna lista - jw
http://gisttrials.fmgatew...ternational.pdf

Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors
Chi Tarn*,†, Lori Rink*,†, Erin Merkel*, Douglas Flieder‡, Harsh Pathak*,Daphne Koumbi§, Joseph R. Testa§, Burton Eisenberg,Margaret von Mehren*, and Andrew K. Godwin*,‖

In conclusion, we have shown that IGF1R is amplified and overexpressed in the majority of GISTs that lack c-KIT or PDGFRα mutations. More importantly, we have shown that imatinib-sensitive and -resistant GIST cells respond equally well to a small molecular inhibitor of IGF1R, suggesting an alternative and/or complementary therapeutic regimen in the clinical management of GIST, especially in tumors that respond less favorably to imatinib-based therapy, including pediatric cases. These findings are particularly exciting given the number of agents targeting IGF1R that are currently being tested in clinical trials. It is feasible in the near future to initiate clinical trials by using IGF1R-targeted therapies for imatinib-refractory GIST patients, initially focusing on adult and pediatric GIST patients lacking c-KIT or PDGFRα mutations and expanding possibly to all GIST patients.
http://www.pnas.org/content/105/24/8387.full

Wergra,
Nie desperuj!
Czy Mama jest leczona w Cetrum Onkologii?
Jezeli nie wiedza to dlaczego u diabla nie skonsultuja sie ze specjalistami ze znanych osrodkow zagranicznych?!
Usciski,
Zosia

DSS,
1.W mojej wypowiedzi zabraklo partykuly wy -(leczenia)= CR (Complete Response).
Mea culpa!

Cytat:

Powyższe dane to mediana (w uproszczeniu: najczęściej odnotowywana wartość)

Nie, mediana to nie jest najciesciej odnotowywana wartosc.
Mediana = 28 miesiace oznacza, ze polowa pacjentow bedzie miala czas OS dluzszy od 28 miesiecy a polowa krotszy.

Cytat:

RCC: update
At ASCO 2008, Dr Robert Figlin presented updated data from the final study analysis, including overall survival. The primary endpoint of median PFS remained superior with sunitinib: 11 months versus 5 months for IFNα, P<.000001. Objective response rate also remained superior: 39-47% for sunitinib versus 8-12% with IFNα, P<.000001.[9][10]
Sunitinib was associated with somewhat longer overall survival, although this was not statistically significant.
Median OS was 26 months with sunitinib vs 22 months for IFNα regardless of stratification (P-value ranges from .051 to .0132, depending on statistical analysis).
The first analysis includes 25 patients initially randomized to IFNα who crossed over to sunitinib therapy, which may have confounded the results; in an exploratory analysis that excluded these patients, the difference is becomes more robust: 26 vs 20 months, P=.0081.
Patients in the study were allowed to receive other therapies once they had progressed on their study treatment. For a “pure” analysis of the difference between the two agents, an analysis was done using only patients who did not receive any post-study treatment. This analysis demonstrated the greatest advantage for sunitinib: 28 months vs 14 months for IFNα, P=.0033. The number of patients in this analysis was small and this does not reflect actual clinical practice and is therefore not meaningful.
Also worth noting in this presentation was the fact that the updated percentage of patients that had to discontinue sunitinib due to adverse events was 19%.This is a clinically meaningful number.
This was the largest comparative trial in RCC to date, and sunitinib is the first agent to demonstrate an overall survival longer than 2 years in these patients. Dr. Figlin concluded his presentation by reinforcing that “Sunitinib is the reference standard for the first-line treatment of mRCC.” [9]

(9) Figlin RA et al.. "Overall survival with sunitinib versus interferon alfa (IFN-α) as first-line treatment of metastatic renal cell carcinoma (mRCC). Abstract no. 5024.". Presented at ASCO 2008. Available at: http://www.asco.org/ASCO/...stractID=32895.

(10) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma.
Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G,Thompson JA, Kim ST, Chen I, Huang X, Figlin RA.
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. [email protected]
Comment in:
Nat Rev Clin Oncol. 2010 Jan;7(1):7-8.
J Clin Oncol. 2009 Aug 1;27(22):3573-4.
http://www.ncbi.nlm.nih.gov/pubmed/19487381

OS sie zgadza (28 miesiecy vs 14) natomiast jest znaczna rozbieznosc miedzy Twoimi danymi dot. niepozadanych rekacji prowadzacych do przerwania stosowania Sutentu (19% vs 8%) oraz pozytywnej odpowiedzi na leczenie (39-47% vs 80%).
80% PR dotyczy Nexavaru, to pewne.
Czy masz jakies zrodlo na poparcie tezy, ze Sutentu rowniez?
Idem dla danych dot. skutkow niepozadanych.
Dzieki,
Zosia

Wynik badania: Carcinoma planoepitheliale akeratodes G2 praecipue praeinvasium cum focis invasiones parvis CM 8071 31.

Rak plaskonablonkowy NIErogowaciejacy G2 - to jest ten element , o ktory dopytywal sie Richelieu. G2 czyli srednio zlosliwy (w skali 3 stopniowej). Nieinwazyjny z malymi ogniskami inwazyjnymi (naciekania). Duzy (3x5, o ile dobrze pamietam?)

Ale w dalszym ciagu brakuje klasyfikacji w skali TNM...
http://pl.wikipedia.org/wiki/Rak_szyjki_macicy

TIb2N0M0?

Cytat:

Jak Wam się widzi? Czy to możliwe, aby już zakończyła się "przygoda" z rakiem...?

W onkologii przyjmuje sie, ze o wyleczeniu mozna mowic dopiero po uplywie 5 lat od zakonczenia leczenia...

Pozdrawiam serdecznie,
Zosia

Cytat:

Nottingham Prognostic index = 0,2x17mm +3+2=8,4.

No, tutaj sie pan pato nie popisal...

NPI liczony wg formuly nizej powinien wyniesc 5,34 (a nie 8.4 jak w zapisie)!
czyli prognoza umiarkowana - przezycie 5-letnie bez nawrotu choroby =70% .
Czyli zdecydowanie lepszy news niz ten sugerowany przez opis pataloga (nasuwa mi sie inne slowo na pe

Zlosliwosc guza G (Grade) = 2
Zaatakowane wezly chlonne L (Lymph node involvment) = (niestety) 3
Rozmiar guza W CENTYMETRACH!!! S (Size) 1.7 cm x 0.2 = 0.34

razem daje to : 2 +3 + 0.34 = 5.34

Cytat:

The Nottingham Prognostic Index was developed in 1982 as an aid to the management of breast cancer.[1][2][3]
By using multivariate analysis, 3 factors were found to be significant: tumour grade, number of lymph nodes involved and size of the tumour.
Tumour grade (G) gives a score 1-3 based on the modified Bloom-Richardson grading

Cytat:

Lymph node involvement (L

) gives a score 1-3
- No nodes
- 1-3 nodes
- >3 nodes

With tumour size in cm(S) factored in the NPI can be worked out by:

G + L + ( S x 0.2)

This has been shown to give the following prognoses:
NPI and survival

NPI score Prognosis 5-year survival
2.0-2.4 Excellent 93%
2.4-3.4 Good 85%
3.4-5.4 Moderate 70%
>5.4 Poor 50%

http://www.ganfyd.org/ind...rognostic_index

A co z Estrogenem, Progesteronem i HER2-neu?

Pozdrawiam serdecznie,
Zosia

Cytat:

O samym rodzaju raka piszesz, że wykazano zależność od faktu zakażenia wirusem Epsteina−Barr. Gdzie można zarazić się takim wirusem?

Artykul na temat EBV
http://www.poradnikmedycz...eń_wirusem.html

Cytat:

Czy to, że przeżycie jest 5 letnie oznacza do 5 lat, czy też jest 5 lat i potem człowiek jest zdrowy

Dla potrzeb statystyk onkologicznych przyjmuje sie, ze pacjent jet wyleczony jezeli przezyl 5 lat bez nawrotu choroby (od chwili zakonczenia leczenia).

Pozdrawiam serdecznie,
Zosia

Ilustracyjnie - video producenta urzadzenia (po prawej stronie ekranu wiecej filmow ilustrujacych dzialanie/uzycie Gamma Knife):

Leksell Gamma Knife-Perfexion with Extend program

http://www.youtube.com/watch?v=GkGFwxDsGF8&NR=1

Mietek,

G2 oznacza posredni stopien zlosliwosci (skala jest trzystopniowa).
Prawdopodobnie IIb (guz o srednicy wiekszej niz 2 cm ale mniejszej niz 5cm i zajety/te wezel/wezly chlonny/e.).

Brakuje wynikow immunochemii : ER, PR oraz HER-2/neu.

Chirurgia - mastektomia najprawdopodobniej.
Usuniecie wezlow chlonnych.
Chemia.
Byc moze naswietlania.

Nie martw sie na zapas! Przed wtorkiem jest weekend - wykorzystajcie go na max.
Moze wez wolny poniedzialek i wyjedzcie gdzies razem na 3 dni :?:

Pozdrawiam serdecznie
zosia

En effet, c'est une TRES bonne nouvelle :-D

Plein de bisous,

Zosia

Cytat:

Zosiu, 50 PLN za paczkę papierosów dla Australijczyka miesięcznie zarabiającego średnio ok. 14.350 PLN brutto to niemal to samo co 10 PLN dla Polaka, który zarabia w tym czasie średnio ok. 3.200 PLN Tak więc cena paczki papierosów nie wydaje się być w Australii jakoś nadzwyczajnie wygórowana.

Tak, ale palaczmi sa przede wszystkim ludzie o niskich dochodach lub na zasilkach ( low socio-economic class, to oryginalne okreslenie, ktore cie tak oburzylo ). Ci sami, ktorzy sa konsumentami junk food oraz duzych ilosci alkoholu.
To, jak sadze, calkowicie zmienia rownanie.

Zapewniam Cie DSS, ze czytuje rowniez prase polska. Ciesze sie, ze cos sie rusza mimo pamietnego wystepu polskiej pani minister zdrowia. Niemniej jednak dluga droga przed wami :-(

zanim zejdziecie z 30% do 16%. Komunizm nie ma tu nic do rzeczy!

Cytat:

cellulae carcinomatosae

i nic więcej. Co to jest za typ nowotworu?

Po polsku = komorki rakowe -opis raczej dosc lakoniczny w tresci :-(

Nicos,

Czy to byla biopsja cienkoiglowa czy gruboiglowa?
Skad wiadomo, ze wezly chlonne sa czyste?

pzdr
zosia