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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?



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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.



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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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Fwd: Localization of laminin alpha3B chain in vascular and epithelial basement membranes of normal human tissues and its down-regulation in skin cancers.



---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Aug 3, 2008 at 8:08 AM
Subject: Localization of laminin alpha3B chain in vascular and epithelial basement membranes of normal human tissues and its down-regulation in skin cancers.
To: mesothelioma77@gmail.com


[1]J Mol Histol. 2008 Aug 1;
Kariya Y, Mori T, Yasuda C, Watanabe N, Kaneko Y, Nakashima Y, Ogawa T, Miyazaki K

The basement membrane (BM) proteins laminins, which consist of alpha, beta and gamma chains, play critical roles in the maintenance of tissue structures. One of laminin alpha chains, alpha3 has two isoforms, the truncated form alpha3A and the full-sized form alpha3B. In contrast to alpha3A laminins, little is known about alpha3B laminins. To show the histological distribution of the laminin alpha3B chain, we prepared alpha3B-specific monoclonal antibodies. Immunohistochemical analysis showed that the alpha3B chain was colocalized with the alpha3A, beta3 and gamma2 chains in the epithelial BMs of the skin, esophagus, breast and lung, suggesting the presence of laminin-3B32 (laminin-5B) and laminin-3A32 (laminin-5A). In the lung alveoli, laminin-3B32 was dominant over laminin-3A32, but vice versa in other epithelial BMs. In contrast, the BMs of blood vessels including capillaries were strongly positive for alpha3B, but almost or completely negative for alpha3A, beta3 and gamma2. alpha3B was colocalized with beta1 and gamma1 in these BMs. The alpha3B chain was scarcely detected in the vessels of malignant skin cancers, though the gamma2 and beta3 chains were highly expressed in the cancer cells. These results strongly suggest that the laminin alpha3B chain is widely expressed in vascular BMs of normal tissues, probably as laminin-3B11/3B21 (laminin-6B/7B).



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Source: http://www.hubmed.org/display.cgi?uids=18670895
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Fwd: Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study.



---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Aug 3, 2008 at 8:08 AM
Subject: Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study.
To: mesothelioma77@gmail.com


[1]Breast Cancer Res Treat. 2008 Aug 1;
Buijs C, Mom CH, Willemse PH, Marike Boezen H, Maurer JM, Wymenga AN, de Jong RS, Nieboer P, de Vries EG, Mourits MJ

Purpose Breast cancer patients with treatment-induced menopause experience frequent and severe hot flashes (HF). We compared venlafaxine and clonidine for the treatment of HF with regard to side effects, efficacy, quality of life and sexual functioning. Methods In a double-blind, cross-over study, 60 breast cancer patients experiencing HF were randomized to 8 weeks venlafaxine followed by 2 weeks wash-out, and 8 weeks clonidine or vice versa. HF frequency and severity, side effects, quality of life and sexuality were assessed. Results Thirty patients started with venlafaxine and 30 with clonidine. Premature discontinuation for toxicity occurred in 14/59 during venlafaxine and 5/53 during clonidine (P = .038). Venlafaxine induced more side effects. Median reduction in HF score was 49% for venlafaxine and 55% for clonidine (ns). Conclusion Venlafaxine and clonidine are equally, but moderately effective in HF reduction. Side effects are the main reason for drug discontinuation, occurring more often with venlafaxine.



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Source: http://www.hubmed.org/display.cgi?uids=18670875
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