We studied the expression of antioxidant enzymes (AOEs) and related proteins manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR), and the catalytic (GLCL‐c) and regulatory (GLCL‐r) subunits of glutamate cysteine ligase (γ‐glutamylcysteinesynthetase) in 433 astrocytomas. Expression of MnSOD was found in 91%, Trx in 46%, TrxR in 66%, GLCL‐c 73% and GLCL‐r in 89% of the cases. Diffuse astro‐cytomas showed more intense staining for Trx (p= 0.002), TrxR (p=0.004), GLCL‐c (p=0.001), GLCL‐r (p=0.04) and MnSOD (p=0.01) than pilocytic astrocytomas. Within diffuse astrocytomas only Trx (p= 0.0001) and TrxR (p=0.04) significantly associated with increased malignancy grade. Necrotic tumors were more often immunopositive for Trx (p=0.001) and TrxR (p=0.02) and AOE expression was generally higher in mitotically active tumors. Expression of Trx and lack of MnSOD expression was associated with a worse prognosis in diffuse astrocytomas. None of the AOEs had any prognostic value in pilocytic grade I astrocytomas. Familial astrocytomas, which included 23 of the cases studied, did not differ in their expression of MnSOD from sporadic ones. The results show that MnSOD and Trx may influence the biological behaviour of astrocytomas, possibly by modulating cell proliferation and necrosis in these tumors.

Twenty-four Finnish families with 2 or more glioma patients were identified through questionnaires sent to 369 consecutive glioma patients receiving surgery at Tampere University Hospital during 1983-94. To explore whether unusual cancer susceptibility is involved, the cancer risk of 2,664 family members was estimated using population-based data from the Finnish Cancer Registry. Among the total cohort of relatives, 88 cancers were observed during 1953-97. The overall cancer risk among 12 families with juvenile onset gliomas was significantly decreased (standardized incidence ratio [SIR] 0.6, 95% confidence interval [CI]: 0.4 -0.9). Among 12 families with adult onset gliomas, the overall cancer risk was equal to that of the reference population (SIR 1.1, 95% CI: 0.8 -1.4) whereas the risk of skin melanoma (SIR 4.0, 95% CI: 1.5-8.8) and meningioma (SIR 5.5, 95% CI: 1.1-16) were significantly increased. Several other tumors, including those associated with neurofibromatosis 1 and 2, tuberous sclerosis and Li-Fraumeni and Turcot syndromes were surveyed, but no elevated risks were observed. In conclusion, the presence of meningiomas and skin melanomas in glioma families may indicate a novel association as a cancer susceptibility trait.

Abstract. Aim Metastatic breast cancer remains an incurable disease (1, 2). In Finland, nearly 5,000 patients are diagnosed with invasive breast cancer every year, and the incidence has increased steadily over the past decades. The Finnish cancer registry data from 2014 shows that 815 women died of metastatic breast cancer, which was the most common cause of cancer death in women (3). In the CONCORD-2 study, a central analysis of population-based registry data worldwide for cancer survival was conducted, and the results were published in The Lancet in November 2014. The study reported that the treatment results of breast cancer in Finland are among the best in the world. The 5-year-survival rate of patients with breast cancer in Finland was 86.8% [95% confidence interval (CI)=85.9-87.7%) from [2005][2006][2007][2008][2009], and was the highest in Northern Europe (4). However, new treatment options for advanced human epidermal growth factor receptor 2 (HER2)-negative disease are rare, and the overall survival benefit observed in these patients is modest (5, 6). For this reason, advanced HER2-negative breast cancer is a treatment challenge worldwide.Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial cell proliferation by blocking the binding of vascular endothelial growth factor A (VEGFA) to its receptor, therefore inhibiting tumor angiogenesis (7). Bevacizumab improves the outcomes of cytotoxic treatment in many metastatic malignancies, including colorectal, kidney, lung and ovarian cancer (8-11). There has been much debate about the status of bevacizumab treatment in metastatic breast cancer. Currently, the European Medicines Agency has only approved bevacizumab when combined with paclitaxel or capecitabine in a first or second-line setting (http://www.e ma.europa.eu/ema/). In 2011, the US Food and Drug Administration revoked its accelerated approval of a breast cancer indication for bevacizumab due to the lack of a benefit in breast cancer overall survival and, in addition, due to the potentially life-threatening side-effects (http://www.fda.gov/). 6431Τhis article is freely accessible online. In locally advanced and metastatic breast cancer, taxanebased treatment (docetaxel or paclitaxel), either in combination with another agent or as single-agent, therapy is considered one of the most effective choices for first-line treatment (5, 12), when cytotoxic treatment is needed. Combining bevacizumab with chemotherapy has been studied in certain phase III studies (13)(14)(15)(16)(17)(18). Most of these studies investigated the benefit of bevacizumab combined with a taxane. Furthermore, other chemotherapy regimens have been explored, including capecitabine, anthracycline, vinorelbine and gemcitabine. Adding bevacizumab has led to higher response rates and longer progression-free survival (PFS) throughout the trials, but no significant differences in overall survival (OS) have yet been observed.In addition to chemotherapy options, bevacizumab can also be combined with endocri...

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Familial occurrence of gliomas, in the absence of well‐defined hereditary multisystem disorders, is reported occasionally. We describe 17 families that have been afflicted with two or more gliomas but do not raise suspicion of other inheritable syndromes. The families were identified among 369 consecutive glioma patients operated at the Tampere University Hospital during 1983–1994. We applied comparative genomic hybridization (CGH) analysis on 21 gliomas occurring in these 17 families. The most frequent genetic alterations, detected in over 20% of the tumors, were losses of 6q, 10, 4q, 9p and gains of 7, 19, 20q, 1p. We compared the chromosomal alterations detected in the familial gliomas to those reported previously on 209 sporadic gliomas in nine different CGH studies. In this comparison, the familial gliomas more often showed losses of chromosome arms 4q and 6q and gains of 1p and 22q. The most frequent losses (9/21 tumors) in the familial gliomas resided on chromosome arm 6q (P = 0.005, Fisher's exact test; with Bonferroni correction, P = 0.04). The loss of 6q was also the most common intrafamilial aberration, present in four separate gliomas belonging to two families. The minimal common area of loss on this chromosome resided at 6q14–16. In conclusion, we have found several characteristic aberrations by CGH in the familial gliomas and we present new chromosomal regions possibly involved in the familial predisposition to gliomas. © 2000 Wiley‐Liss, Inc.