Quantifying the effects of climate change and water abstraction on a population of barramundi (Lates calcarifer), a diadromous estuarine finfish

Many aquatic species are linked to environmental drivers such as temperature and salinity through processes such as spawning, recruitment and growth. Information is needed on how fished species may respond to altered environmental drivers under climate change so that adaptive management strategies can be developed. Barramundi (Lates calcarifer) is a highly prized species of the Indo-West Pacific, whose recruitment and growth is driven by river discharge. We developed a monthly age- and length-structured population model for barramundi. Monte Carlo Markov Chain simulations were used to explore the population's response to altered river discharges under modelled total licenced water abstraction and projected climate change, derived and downscaled from Global Climate Model A1FI. Mean values of exploitable biomass, annual catch, maximum sustainable yield and spawning stock size were significantly reduced under scenarios where river discharge was reduced; despite including uncertainty. These results suggest that the upstream use of water resources and climate change have potential to significantly reduce downstream barramundi stock sizes and harvests and may undermine the inherent resilience of estuarine-dependent fisheries. © 2012 CSIRO

Detection of mammaglobin mRNA in peripheral blood is associated with high grade breast cancer: Interim results of a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>We sought to examine the detection rate of cancer cells in peripheral blood (PBL) and in bone marrow (BM) using an established 7-gene marker panel and evaluated whether there were any definable associations of any individual gene with traditional predictors of prognosis.</p> <p>Methods</p> <p>Patients with T1-T3 primary breast cancer were enrolled into a prospective, multi-institutional cohort study. In this interim analysis 215 PBL and 177 BM samples were analyzed by multimarker, real-time RT-PCR analysis designed to detect circulating and disseminated breast cancer cells.</p> <p>Results</p> <p>At a threshold of three standard deviations from the mean expression level of normal controls, 63% (136/215) of PBL and 11% (19/177) of BM samples were positive for at least one cancer-associated marker. Marker positivity in PBL demonstrated a statistically significant association with grade II-III (vs. grade I; p = 0.0083). Overexpression of the mammaglobin (<it>mam</it>) gene alone had a statistically significant association with high tumor grade (p = 0.0315), and showed a trend towards ER-negative tumors and a high risk category. There was no association between marker positivity in PBL and the pathologic (H&E) and/or molecular (RT-PCR) status of the axillary lymph nodes (ALN).</p> <p>Conclusion</p> <p>This study suggests that molecular detection of circulating cancer cells in PBL detected by RT-PCR is associated with high tumor grade and specifically that overexpression of the <it>mam </it>gene in PBL may be a poor prognostic indicator. There was no statistically significant association between overexpression of cancer-associated genes in PBL and ALN status, supporting the concept of two potentially separate metastatic pathways.</p

Multimarker RT–PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients

The presence of metastases in lymph nodes is the most powerful prognostic factor in breast cancer patients. Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. The aim of the present study was to develop a multimarker reverse transcriptase–polymerase chain reaction (RT—PCR) assay for the detection of minimal residual disease in sentinel nodes of breast cancer patients. RNA was extracted from 30 sentinel lymph nodes (SLN) obtained from 28 patients, three primary breast cancers (positive controls), three lymph nodes from patients with benign diseases, and peripheral blood lymphocytes of 10 healthy volunteers (negative controls). RT–PCR was performed using the following markers; cytokeratin (CK)-19, NY-BR-1 and mammaglobin B. RT–PCR results were compared to enhanced histopathologic examination and immunohistochemistry (IHC). All three positive controls showed strong PCR amplification for all three markers. None of the 13 negative controls was amplified by any of the three markers. Among the 30 SLN analysed, breast cancer metastases were detected in six SLNs by routine histology, in eight by IHC and in 15 by RT–PCR. We conclude that a multimarker RT–PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination. This method may prove to be of value in breast cancer staging and prognosis evaluation

Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients

Prediction of peritoneal relapse is extremely important for gastric cancer patients after curative surgery. The present study prospectively validates the prognostic ability of quantifying carcinoembryonic antigen (CEA) mRNA in peritoneal washes by real-time reverse transcriptase–polymerase chain reaction. Based on a retrospective study of 197 curatively resected gastric cancer patients (training set), we determined a cutoff value of CEA mRNA using receiver-operating characteristic curve. We used this cutoff value to validate the risk of peritoneal recurrence in a new cohort of 86 gastric cancer patients (validation set) between July 2000 and December 2002 in a prospective study. During the median 30 months of postoperative surveillance, 20 of the 86 patients died, and 13 of the 20 developed peritoneal metastases. Peritoneal recurrence-free survival as well as overall survival was significantly worse in patients with positive CEA mRNA (P<0.0001). Multivariate analysis with the Cox proportional hazards model showed that positive CEA mRNA was a significant independent risk factor with both survival (P=0.0130) and peritoneal recurrence-free survival (P=0.0006) as end points. These results indicate that quantitation of CEA mRNA in peritoneal washes is a reliable prognostic indicator of peritoneal recurrence in the clinical setting

Potential effects of climate change on Australian estuaries and fish utilising estuaries: a review

Estuaries are especially vulnerable to the impacts of climate change because changes in climatic and hydrologic variables that influence freshwater and marine systems will also affect estuaries. We review potential impacts of climate change on Australian estuaries and their fish. Geographic differences are likely because southern Australian climates are predicted to become warmer and drier, whereas northern regions may see increased precipitation. Environmental factors, including salinity gradients, suspended sediment, dissolved oxygen and nutrient concentrations, will be influenced by changing freshwater input and other climate variables. Potential impacts will vary depending on the geomorphology of the estuary and the level of build-up of sand bars across estuarine entrances. Changes to estuarine fish assemblages will depend on associated changes to salinity and estuarine-mouth morphology. Marine migrants may be severely affected by closure of estuarine mouths, depending on whether species 'must' use estuarine habitat and the level of migratory v. resident individuals. Depending on how fish in coastal waters locate estuaries, there may be reduced cues associated with estuarine mouths, particularly in southern Australia, potentially influencing abundance. In summary, climate change is expected to have major consequences for Australian estuaries and associated fish, although the nature of impacts will show significant regional variation

Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells

Mammaglobin-A (Mam-A) is a 10 kD secretory protein that is overexpressed in 80% of primary and metastatic human breast cancers. Previous studies from our laboratory demonstrated that Mam-A cDNA vaccine can induce Mam-A specific CD8 T-cell responses and mediate regression of human breast cancer xenografts in NOD/SCID mice. In this report, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells. Specimens from seven patients with stage IV metastatic cancer were available for these analyses. Patients were vaccinated with a Mam-A cDNA vaccine on days 0, 28 and 56, and immune responses were assessed at serial time points following vaccination. At six months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4(+)ICOS(hi) T cells from 5 ± 2% pre-vaccination to 23 ± 4% (p<0.001), with a concomitant decrease in the frequency of CD4(+)Foxp3(+) T cells (Treg) from 19 ± 6% to 10 ± 5% (p<0.05). ELISpot analysis of CD4(+)ICOS(hi) sorted T-cells demonstrated that following vaccination the cytokines produced by Mam-A-specific T cells switched from IL-10 (78 ± 21 spm pre-vaccination to 32 ± 14 spm 5 months post-vaccine p<0.001) to IFN-γ (12 ± 6 spm pre-vaccination to 124 ± 31 spm 5 months post-vaccine p<0.001). The ratio of CD4(+)ICOS(hi) T cells to CD4(+)Foxp3(+) T cells increased from 0.37 ± 0.12 prior to vaccination to 2.3 ± 0.72 (p=0.021) following vaccination. Further, these activated CD4(+) ICOS(hi) T-cells induced preferential lysis of human breast cancer cells expressing Mam-A protein. We conclude that mammaglobin-A cDNA vaccination is associated with specific expansion and activation of CD4(+)ICOS(hi) T cells, with a concomitant decrease in Treg frequency. These encouraging results strongly suggest that Mam-A cDNA vaccination can induce antitumor immunity in breast cancer patients