Glejak wielopostaciowy, GBM - diagnoza, leczenie, nowości

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Witamina D oraz Izotretinoina inhibituje wzrost GBM >50%

Effects of vitamin D and retinoic acid on human glioblastoma cell lines
przedruk z:
http://www.springerlink.com/content/q316j49523x4x673/


L. Magrassi1, 2, G. Butti1 Contact Information, S. Pezzotta1, L. Infuso1 and G. Milanesi2
(1) Department of Surgery, Section of Neurosurgery, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy
(2) IGBE CNR, Pavia, Italy

Summary
The biological significance of vitamin D receptors expressed by glioblastoma and other glial tumours is still unclear. In an effort to clarify this issue we studied the effects of increasing concentrations of 25-dihydroxyvitamin D3 and its metabolite 1 agr, 25-dihydroxyvitamin D3 on two human glioblastoma cell lines. Both substances were capable of inducing a significant (> 50%) reduction in growth of the two glioblastoma cell lines at dosages over 5 mgrM. When the HU 70 cell line was treated by increasing dilutions of 25-dihydroxyvitamin D3 combined with 1 mgrM all trans-retinoic acid, significant inhibition was apparent even after addition of 25-dihydroxyvitamin D3 in the nanomolar range. Reduction of growth index was mainly due to induced cell death.
Our results providein vitro evidence that vitamin D metabolites alone or in combination with retinoids may be potentially useful agents in the differentiation therapy of human malignant gliomas.

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Witamina D oraz Izotretinoina inhibituje wzrost GBM >50%

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Na temat witaminy D było tutaj:

Witamina D - nie tylko dla kości

oraz w ramach protokołu stosowanego przez Oracle:
Protokół Oracle - dla żony z nowotworem płuc

Izotretonina jest tez stosowana przeciwko nowotworowi płuc:

http://f.kafeteria.pl/temat.php?id_p=3396234&start=330 (post [12.10.2008] 09:10 - autor:wm)
http://www.czytelniamedyczna.pl/nm_de38.php
http://www.cancernetwork.com/cancer-man ... 65/1170066 (13-cis-retinoic acid)

Stosują ja także niektórzy forumowicze:
viewtopic.php?p=14205#p14205

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Wpływ witaminy D oraz kwasu retinowego na linie komórkowe ludzkiego glejaka

tłumaczenie z
http://www.springerlink.com/content/q316j49523x4x673/


L. Magrassi1, 2, G. Butti1 Contact Information, S. Pezzotta1, L. Infuso1 and G. Milanesi2
(1) Department of Surgery, Section of Neurosurgery, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy
(2) IGBE CNR, Pavia, Italy
Streszczenie

Biologiczne znaczenie receptorów witaminy D, ekspresjonowanych przez glioblastoma oraz inne guzy nadal jest niejasne. W celu wyjaśnienia tej kwestii badaliśmy wpływ zwiększającego się stężenia 1,25-di-hydroksywitaminy oraz jego metabolitu 1 agr, 1,25-di-hydroksywitaminy na dwóch liniach komórkowych ludzkiego glioblastoma. Obie substancje były zdolne do indukcji znacznej (>50%) redukcji wzrostu dwóch linii komórkowych glioblastoma przy dawkach powyżej 5 mgrM. Kiedy linia komórkowa HU 70 była leczona 1,25-di-hydroksywitaminą D w zwiększanym rozcieńczeniu w połączeniu z 1 mgrM Izotretoniny znacząca inhibicja była widoczna nawet po dodaniu 25-D3 dihydroksycholekalcyferolu w bardzo niskim stężeniu (nanomolar range). Redukcja wskaźnika wzrostu wynikała głównie z indukowania śmierci komórkowej.
Nasze wyniki dostarczają dowodów in vitro, na to że same metabolity witaminy D lub w połączeniu z retinoidami mogą być potencjalnie użytecznymi środkami w zróżnicowanej terapii ludzkich złośliwych glejaków.

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Concurrent radiotherapy with temozolomide followed by adjuvant temozolomide and cis-retinoic acid in children with diffuse intrinsic pontine glioma

przedruk z:
http://jco.ascopubs.org/cgi/content/abstract/21/12/2305

Kurt A. Jaeckle, Kenneth R. Hess, W.K. Alfred Yung, Harry Greenberg, Howard Fine, David Schiff, Ian F. Pollack, John Kuhn, Karen Fink, Minesh Mehta, Timothy Cloughesy, M. Kelly Nicholas, Susan Chang, Michael Prados

From the University of Texas M.D. Anderson Cancer Center, Houston; University of Texas Health Science Center, San Antonio; and University of Texas Southwestern Medical Center, Dallas, TX; University of Michigan, Ann Arbor, MI; Dana-Farber Cancer Institute, Boston, MA; University of Pittsburgh and Children’s Hospital of Pittsburgh, Pittsburgh, PA; University of Wisconsin, Madison, WI; University of California at Los Angeles, Los Angeles; University of California at San Francisco, San Francisco, CA; University of Chicago, Chicago, IL.





Purpose: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG.

Patients and Methods: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12.

Results: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%).

Conclusion: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).

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13-cis-Retinoic acid in the treatment of recurrent glioblastoma multiforme

przedruk z:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871997/

Siew-Ju See, Victor A. Levin, W.-K. Alfred Yung, Kenneth R. Hess, and Morris D. Groves1

Departments of Neuro-Oncology (S.-J.S., V.A.L., W.-K.A.Y., M.D.G.) and Biostatistics (K.R.H.), University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
1 Address correspondence to Morris D. Groves, Department of Neuro-Oncology, Box 431, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA ( Email: mgroves@mdanderson.org)
Received October 29, 2003; Accepted March 16, 2004.

Abstract:
Basic science and clinical investigations have demonstrated that 13-cis-retinoic acid (cRA) has activity against malignant gliomas. To assess its effectiveness in the setting of recurrent glioblastoma multiforme (GBM), we performed a retrospective analysis of the medical records and neuroimaging results of patients with recurrent GBM who were treated with cRA. The toxicity profile of cRA, response, and effect on progression-free survival from initiation of treatment were end points of our analysis. Eighty-two of 85 patients with a median age of 51 years received at least 1 full cycle of cRA. At the initiation of cRA treatment, the median Karnofsky performance score was 80. All patients had failed conventional radiotherapy. Seven patients were chemonaïve, whereas 75 patients had received some form of chemotherapy. Radiographic partial responses, minor responses, and stable disease were seen in 4%, 8%, and 34% of patients, respectively. Two patients were not assessable. Progression-free survival and overall survival after initiation of cRA were 10.0 and 24.6 weeks, respectively. Six-month progression-free survival was 19% for the entire group. Grade 3 or 4 toxicity developed in 14 patients (16%), one of whom developed pancreatitis and died. The results of this study demonstrate only modest efficacy for cRA therapy in this cohort of heavily pretreated patients with recurrent GBM. This data supports the use of cRA in such patients, but its further evaluation in larger, prospective, controlled studies with or without other noncytotoxic and cytotoxic agents may be warranted.

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Concurrent radiotherapy with temozolomide followed by adjuvant temozolomide and cis-retinoic acid in children with diffuse intrinsic pontine glioma

przedruk z:
http://neuro-oncology.dukejournals.org/ ... t/10/4/577

Nongnuch Sirachainan, Samart Pakakasama, Anannit Visudithbhan, Surang Chiamchanya, Lojana Tuntiyatorn, Mantana Dhanachai, Jiraporn Laothamatas and Suradej Hongeng

Departments of Pediatrics (N.S., S.P., A.V., S.C., S.H.) and Radiology (L.T., M.D., J.L.), Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Address all correspondence to Suradej Hongeng, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Rd., Bangkok 10400, Thailand (rashe@mahidol.ac.th).

The prognosis of children with diffuse intrinsic pontine glioma (DIPG) is very poor. Radiotherapy remains the standard treatment for these patients, but the median survival time is only 9 months. Currently, the use of concurrent radiotherapy with temozolomide (TMZ) has become the standard care for adult patients with malignant gliomas. We therefore investigated this approach in 12 children diagnosed with DIPG. The treatment protocol consisted of concurrent radiotherapy at a dose of 55.8-59.4 Gy at the tumor site with TMZ (75 mg/m2/day) for 6 weeks followed by TMZ (200 mg/m2/day) for 5 days with cis-retinoic acid (100 mg/m2/day) for 21 days with a 28-day cycle after concurrent radiotherapy. Ten of the 12 patients had a clinical response after the completion of concurrent radiotherapy. Seven patients had a partial response, four had stable disease, and one had progressive disease. At the time of the report, 9 of the 12 patients had died of tumor progression, one patient was alive with tumor progression, and two patients were alive with continuous partial response and clinical improvement. The median time to progression was 10.2 ± 3.0 months (95% confidence interval [CI], 4.2-16.1 months). One-year progression-free survival was 41.7% ± 14.2%. The median survival time was 13.5 ± 3.6 months (95% CI, 6.4-20.5 months). One-year overall survival was 58% ± 14.2%. The patients who had a partial response after completion of concurrent radiotherapy had a longer survival time (p = 0.036) than did the other patients (those with stable or progressive disease). We conclude that the regimen of concurrent radiotherapy and TMZ should be considered for further investigation in a larger series of patients.