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Wednesday, August 6, 2008

Fwd: Is there a qualitative interaction between adjuvant trastuzumab and size of the primary tumor in breast cancer?



---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: Is there a qualitative interaction between adjuvant trastuzumab and size of the primary tumor in breast cancer?
To: mesothelioma77@gmail.com


[1]Neoplasma. 2008; 55(5): 375-80
P V, B M

Benefit of adjuvant trastuzumab in breast cancer has been reported in four randomized trials of phase III, and these results are consistent in showing improvement in disease-free survival (DFS). Current evidence for homogeneity of this DFS benefit in subgroups of patients with the different size of the primary HER2-positive tumor treated according to the HERA trial is reviewed. It is evident that current published evidence is insufficient to rule out that there is a cohort of patients with HER2-positive disease who do not achieve a reduction in the risk of recurrence by adjuvant treatment with trastuzumab after completion of previous adjuvant chemo- and radiotherapy. An alternative interpretation of results of the HERA trial currently available in two primary reports (1-year, and 2-year median follow- up, respectively) is discussed. The risk factors of central nervous system (CNS) metastases in breast cancer and problem of CNS metastases in HER2-positive tumors are briefly reviewed. A hypothesis on the relations between brain metastases, their risk factors, the size of the primary tumor, and their impact on the DFS in patients with HER2-positive tumors treated with adjuvant trastuzumab is proposed based on the results of the HERA trial. Altogether, some direct evidence is presented here based on the published results of the HERA trial, and still more indirect evidence based on the information on related topics in literature, to show that current clinical practice of adjuvant trastuzumab in mono-therapy, which is based on assumption that there is a homogeneous benefit as for disease-free survival for all sizes of primary HER2-positive tumors above 1 cm, may not be based on such firm evidence as is commonly presented. Key words: breast cancer; trastuzumab; adjuvant; brain metastases.



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Source: http://www.hubmed.org/display.cgi?uids=18665746
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Fwd: Cytosine deaminase expressing human mesenchymal stem cells mediated tumour regression in melanoma bearing mice.



---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Aug 3, 2008 at 8:08 AM
Subject: Cytosine deaminase expressing human mesenchymal stem cells mediated tumour regression in melanoma bearing mice.
To: mesothelioma77@gmail.com


[1]J Gene Med. 2008 Aug 1;
Kucerova L, Matuskova M, Pastorakova A, Tyciakova S, Jakubikova J, Bohovic R, Altanerova V, Altaner C

BACKGROUND: Previously, we validated capability of human adipose tissue-derived mesenchymal stem cells (AT-MSC) to serve as cellular vehicles for gene-directed enzyme prodrug molecular chemotherapy. Yeast fusion cytosine deaminase : uracil phosphoribosyltransferase expressing AT-MSC (CD(y)-AT-MSC) combined with systemic 5-fluorocytosine (5FC) significantly inhibited growth of human colon cancer xenografts. We aimed to determine the cytotoxic efficiency to other tumour cells both in vitro and in vivo. METHODS: CD(y)-AT-MSC/5FC-mediated proliferation inhibition against a panel of human tumour cells lines was evaluated in direct and indirect cocultures in vitro. Antitumour effect was tested on immunodeficient mouse model in vivo. RESULTS: Although culture expansion of CD(y)-AT-MSC sensitized these cells to 5FC mediated suicide effect, expanded CD(y)-AT-MSC/5FC still exhibited strong bystander cytotoxic effect towards human melanoma, glioblastoma, colon, breast and bladder carcinoma in vitro. Most efficient inhibition (91%) was observed in melanoma A375 cell line when directly cocultured with 2% of therapeutic cells CDy-AT-MSC/5FC. The therapeutic paradigm of the CDy-AT-MSC/5FC system was further evaluated on melanoma A375 xenografts on nude mice in vivo. Complete regression in 89% of tumours was achieved when 20% CD(y)-AT-MSC/5FC were co-injected along with tumour cells. More importantly, systemic CD(y)-AT-MSC administration resulted in therapeutic cell homing into subcutaneous melanoma and mediated tumour growth inhibition. CONCLUSIONS: CD(y)-AT-MSC capability of targeting subcutaneous melanoma offers a possibility to selectively produce cytotoxic agent in situ. Our data further demonstrate beneficial biological properties of AT-MSC as a cellular vehicle for enzyme/prodrug therapy approach to molecular chemotherapy. Copyright (c) 2008 John Wiley & Sons, Ltd.



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Source: http://www.hubmed.org/display.cgi?uids=18671316
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