Late Quaternary Sea Level Changes on Brock and Prince Patrick Islands, Western Canadian Arctic Archipelago

Emerged shorelines are few and poorly defined on Prince Patrick and Brock islands. The sparse radiocarbon dates show emergence of only 10 m through the Holocene on the Arctic Ocean coast, increasing to 20 m 100 km to the east. Hence, from Brock Island, representative of westernmost coasts, the sea level curve since the latest Pleistocene has a very low gradient, whereas on eastern Prince Patrick Island the curve takes the more typical exponential form. A decline in isobases towards the west is thus registered. Drowned estuaries, breached lakes, and coastal barriers, particularly in southwest Prince Patrick Island, suggest that the sea is now transgressing at a rate that decreases towards the north end of the island, hence there is also a component of tilt to the south. Delevelling is assumed to result from undefined ice loads, but may have a tectonic component. The sole prominent raised marine deposit is a ridge probably built in a period of more mobile sea ice, possibly at a time of stable or slightly rising sea level in the middle or early Holocene. It winds discontinuously along several hundred of kilometres of the shores of the Arctic Ocean and connecting channels, declining to the south.Les rivages émergés sont peu nombreux et mal définis dans les îles Brock et du Prince-Patrick. Les rares datations au radiocarbone n'indiquent qu'une émergence de 10 m des côtes de l'océan Arctique, au cours de l'Holocène, s'accroissant à 20 m, à 100 km vers l'est. Ainsi, à partir des côtes de l'île Brock, représentatives de la partie la plus occidentale, le niveau marin depuis le Pléistocène supérieur a un très faible gradient; par contre, dans la partie est de l'île du Prince-Patrick, la courbe du niveau marin a un caractère nettement exponentiel. On enregistre donc un abaissement des isobases vers l'ouest. Les estuaires submergés, les lacs ébréchés et les barrières littorales, surtout dans le sud-ouest de l'île du Prince-Patrick, semblent indiquer qu'il y a actuellement transgression marine à un taux qui décroît vers le nord de l'île; il y a donc aussi inclinaison vers le sud. On présume que le dénivelé découle de charges glaciaires indéterminées, mais peut aussi avoir une composante tectonique. Le seul dépôt marin soulevé d'importance est une crête probablement édifiée alors que la glace de mer était plus mobile, pendant que le niveau marin était stable ou légèrement en hausse, au début ou au milieu de l'Holocène. La crête serpente de façon irrégulière sur plusieurs centaines de kilomètres de côtes de l'océan Arctique et de chenaux adjacents, tout en s'abaissant vers le sud.Auf-getauchte Uferlinien sind rar und kaum festgelegt auf den Insein Prince Patrick und Brock. Die spàrlichen Radiokarbondaten zeigen im Holozàn ein Auftauchen an der arktischen Ozeankùste von nur 10 m, das 100 km ostlich auf > 20 m ansteigt. So hat die Meeresniveaukurve von der lnsel Brock ausgehend, welche fur die am westlichsten gelegenen Kùsten reprâsentativ ist, seit dem spàtesten Pleistozàn ein sehr niedriges Gefàlle, wohingegen die Kurve im ôstlichen Teil der Insel Prince Patrick die mehr typische exponentielle Form hat. Man registriert also eine Senkung der Isobasen nach Westen hin. Ùberflutete Gezeitenmûndungen, geschartete Seen und Kùstendamme, besonders im Westen der Prince Patrick-lnsel, lassen vermuten, dassjetztdie horizontale Verlagerungsrate des Meeres zum Nordende der Insel hin abnimmt, folglich gibt es auch eine Neigung nach Sùden hin. Man fùhrt die Verstellung auf unbes-timmte Eisfrachten zurùck, doch kônnte sie eine tektonische Komponente haben. Die einzige herausragende marine Auftauchablagerung ist eine Schwelle, die wohl in einer Période mobileren Meereises gebaut wurde, môglicherweise in einer Zeit mit sta-bilem oder gering ansteigendem Meeresniveau im mittleren oderfrùhen Holozàn. Sie windet sich diskontinuierlich ùber mehrere hundert Kilometer an den Kùsten des arktischen Ozeans und der angrenzenden Kanàle entlang und senkt sich nach Sùden

Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting

Hypoxia-specific targets in cancer therapy: role of splice variants

Tumour hypoxia is a well known adverse prognostic factor in the treatment of solid tumours. Hypoxia-inducible factor 1α (HIF-1α), a transcription factor subunit regulating a large number of hypoxia-responsive genes, is considered an attractive target for novel treatment approaches, due to a frequently reported association between HIF-1α overexpression and poor outcome in clinical series. This month in BMC Medicine, Dales et al. report on splice variants of HIF-1α in fresh frozen tissue samples of early human breast cancer, finding an association of mRNA levels of the variant HIF-1αTAG with adverse clinical factors (lymph node status, hormone receptor status) and poor metastasis-free survival. This preliminary study addresses the possibility that specific targeting of individual isoforms resulting from alternative splicing may play a role in HIF-1-directed treatment approaches

Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT) in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

<p>Abstract</p> <p>Background</p> <p>The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally.</p> <p>Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR) as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT) has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose.</p> <p>Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment.</p> <p>Methods/design</p> <p>The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy.</p> <p>A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border), heart, vertebral bodies and pelvic bones.</p> <p>Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival.</p> <p>Discussion</p> <p>Intensity-modulated WAR provides a new promising option in the consolidation treatment of ovarian carcinoma in patients with a complete pathologic remission after adjuvant chemotherapy. Further consequent studies will be needed to enable firm conclusions regarding the value of consolidation radiotherapy within the multimodal treatment of advanced ovarian cancer.</p> <p>Trial registration</p> <p>Clinicaltrials.gov: <a href="http://clinicaltrials.gov/ct2/show/NCT01180504">NCT01180504</a></p

Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer

The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen + tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage >50% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (P<0.01 and <0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l(-1) onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, P<0.05) and 13.0 g/dl(-1) (81.0 vs 57.6%, P<0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels </=13 g dl(-1) showed a lower treatment-induced reduction in Ki67 expression (P<0.04) and a higher Ki67 expression at postoperative evaluation (P<0.02) than their counterparts. In conclusion, low Hb levels may negatively influence the response rate of chemotherapy in breast cancer patients. Inhibition of antiproliferative activity could be a possible mechanism

Patterns of recurrence in the randomised PORTEC-3 trial of chemoradiotherapy for endometrial cancer

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