Temporal and spatial drivers of the structure of macroinvertebrate assemblages associated with <em>Laminaria </em><em>hyperborea </em>detritus in the northeast Atlantic

\ua9 2024Kelp forests occur on more than a quarter of the world\u27s coastlines, serving as foundation species supporting high levels of biodiversity. They are also a major source of organic matter in coastal ecosystems, with the majority of primary production released and exported as detritus. Kelp detritus also provides food and shelter for macroinvertebrates, which comprise important components of inshore food-webs. Hitherto, research on kelp detritus-associated macroinvertebrate assemblages remains relatively limited. We quantified spatiotemporal variability in the structure of detritus-associated macroinvertebrate assemblages within Laminaria hyperborea forests and evaluated the influence of putative drivers of the observed variability in assemblages across eight study sites within four regions of the United Kingdom in May and September 2015. We documented 5167 individuals from 106 taxa with Malacostraca, Gastropoda, Isopoda and Bivalvia the most abundant groups sampled. Assemblage structure varied across months, sites, and regions, with highest richness in September compared to May. Many taxa were unique to individual regions, with few documented in all regions. Finally, key drivers of assemblage structure included detritus tissue nitrogen content, depth, sea surface temperature, light intensity, as well as L. hyperborea canopy density and canopy biomass. Despite their dynamic composition and transient existence, accumulations of L. hyperborea detritus represent valuable repositories of biodiversity and represent an additional kelp forest component which influences secondary productivity, and potentially kelp forest food-web dynamics

A quantitative synthesis of approaches, biases, successes, and failures in marine forest restoration, with considerations for future work

1. Marine forests is a term commonly used for coastal marine habitats formed by dense stands of brown macroalgae, typically consisting of kelp and fucoids. These habitats are highly productive, offer habitat to numerous marine organisms, and support a range of invaluable ecosystem services. Despite their importance, marine forests are declining in many regions around the world as a result of interacting global, regional, and local-scale stressors. Consequently, interest in restoration as a tool to mitigate these declines and reinstate marine forests is growing. 2. Recent reviews have provided insights into marine forest restoration; however, for the most part, a synthesis of restoration success is lacking. A meta-analysis and quantitative review of published marine forest restoration efforts was conducted to examine: (i) how restoration affects the abundance and morphology of marine forest species; and (ii) trends in marine forest restoration success. 3. The meta-analysis of 25 studies revealed that restoration positively influences the abundance and morphology of marine forest species. The quantitative review of 63 studies demonstrated that taxa and restoration technique were important factors influencing restoration success, and revealed a bias towards the monitoring and reporting of abundance and morphological response variables. The review also highlighted a lack of monitoring and/or reporting of environmental variables at restoration sites, and limited comparative research across environmental contexts and restored species. 4. It is shown that successful marine forest restoration is possible at experimental scales, but that better monitoring and reporting of restoration efforts, alongside increased project durations, could improve our understanding of restoration success at the ecosystem level. Considerations for future marine forest restoration efforts are also provided. It is hoped that the review will advance marine forest restoration efforts, allowing the preservation of these valuable ecosystems and their associated services

HER2 expression in cervical cancer as a potential therapeutic target

BACKGROUND: Trastuzumab, a humanized monoclonal antibody against the HER2 receptor is currently being used in breast and other tumor types. Early studies have shown that a variable proportion of cervical carcinoma tumors overexpress the HER2 receptor as evaluated by diverse techniques and antibodies. Currently it is known that a tumor response to trastuzumab strongly correlates with the level of HER2 expression evaluated by the Hercep Test, thus, it seems desirable to evaluate the status of expression of this receptor using the FDA-approved Hercep Test and grading system to gain insight in the feasibility of using trastuzumab in cervical cancer patients. METHODS: We analyzed a series of cervical cancer cell lines, the primary tumors of 35 cases of cervical cancer patients and four recurrent cases, with the Hercep Test in order to establish whether this tumor type overexpress HER2 at level of 2+/3+ as trastuzumab is currently approved for breast cancer having such level of expression. RESULTS: The results indicate that only 1 out of 35 primary tumors cases overexpress the receptor at this level, however, two out of four recurrent tumors that tested negative at diagnosis shifted to Hercep Test 2+ and 3+ respectively. CONCLUSIONS: The low frequency of expression in primary cases suggests that trastuzumab could have a limited value for the primary management of cervical cancer patients, however, the finding of "conversion" to Hercep Test 2+ and 3+ of recurrent tumors indicates the need to further evaluate the expression of HER2 in the metastatic and recurrent cases

Biologic markers of risk in nipple aspirate fluid are associated with residual cancer and tumour size

We previously demonstrated that nipple aspirate fluid (NAF) can be obtained from virtually all non-Asian women between the ages of 30 and 72. The focus of this report is to (1) determine the association of candidate markers of breast cancer risk in NAF obtained from fresh mastectomy specimens with residual breast carcinoma, and (2) evaluate the association of the markers with breast tumour progression. Nipple aspiration was performed on 97 specimens. Cytology, DNA index (including % hypertetraploid cells), cell cycle parameters (S phase fraction, % cells in G2/M), prostate-specific antigen (PSA), epidermal growth factor (EGF), testosterone, carcinoembryonic antigen (CEA) and prostaglandin D synthase (PGDS) were evaluated in NAF for their association with (1) residual ductal carcinoma in situ (DCIS) or invasive cancer, and (2) pathologic tumour size. NAF was obtained from 99% (96/97) of specimens. Atypical and malignant NAF cytology were significantly associated with residual DCIS or invasive cancer (P = 0.001) and with larger tumours (P = 0.004). One hundred per cent and 88% of subjects with malignant and atypical NAF cytology, respectively, had residual carcinoma. The percentage of cells in G2/M and DNA index were associated both with risk of residual carcinoma (P = 0.01 for each) and larger tumour size (DNA index, P = 0.03; G2/M, P = 0.05), although neither biomarker improved the ability of NAF cytology, to predict residual breast cancer. Higher DNA index was associated with atypical cytology (P = 0.0001). In summary, atypical and malignant NAF cytology are associated with larger tumour size, and are highly predictive of residual carcinoma after needle or excisional biopsy of the breast. © 1999 Cancer Research Campaig

Assessment of interactions between 205 breast cancer susceptibility loci and 13 established risk factors in relation to breast cancer risk, in the Breast Cancer Association Consortium.

BACKGROUND: Previous gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions. METHODS: Analyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions. RESULTS: Noteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth. CONCLUSIONS: Overall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors

Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6

A new human breast cancer cell line, KPL-4, was recently isolated from the malignant pleural effusion of a breast cancer patient with an inflammatory skin metastasis. This cell line can be cultured under serum-free conditions and is tumorigenic in female athymic nude mice. Flow cytometric analysis revealed the expression of Erb B-1, -2 and -3. Dot blot hybridization showed a 15-fold amplification of the erbB-2. Reverse transcription-polymerase chain reaction analysis showed a detectable level of mRNA expression of all the Erb B family receptors. In addition, all the receptors were autophosphorylated under a serum-supplemented condition. Unexpectedly, transplanted KPL-4 tumours induced cachexia of recipient mice. A high concentration of interleukin-6 (IL-6) was detected in both the culture medium and the serum of mice. The weight of tumours significantly correlated with the serum IL-6 level. The antiproliferative effect of a humanized anti-Erb B-2 monoclonal antibody, rhuMAbHER2, was investigated. This antibody significantly inhibited the growth of KPL-4 cells in vitro but modestly in vivo. Loss of mouse body weight was partly reversed by rhuMAbHER2. These findings suggest that KPL-4 cells may be useful in the development of new strategies against breast cancer overexpressing the Erb B family receptors and against IL-6-induced cachexia. © 1999 Cancer Research Campaig

Adaptive Reprogramming of the Breast Cancer Kinome

Our understanding of cancer has grown considerably with recent advances in high-throughput genome and transcriptome sequencing, but techniques to comprehensively analyze protein activity are still in development. Methods to quantitatively measure the activation of signaling pathways within tumors at baseline and following therapeutic intervention will prove critical to the design of proper treatment regimens. Focusing on breast cancer, we present such a method to understand kinase signaling using multiplexed kinase inhibitor beads coupled with mass spectrometry (MIB/MS)

Molecular Evidence for Differences in Endometrium in Severe Versus Mild Endometriosis

Women with stage III/IV versus stage I/II endometriosis have lower implantation and pregnancy rates in natural and assisted reproduction cycles. To elucidate potential molecular mechanisms underlying these clinical observations, herein we investigated the transcriptome of eutopic endometrium across the menstrual cycle in the setting of severe versus mild endometriosis. Proliferative (PE), early secretory (ESE), and mid-secretory (MSE) endometrial tissues were obtained from 63 participants with endometriosis (19 mild and 44 severe). Purified RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway Analysis and subsequently validated. Comparison of differentially regulated genes, analyzed by cycle phase, revealed dysregulation of progesterone and/or cyclic adenosine monophosphate (cAMP)-regulated genes and genes related to thyroid hormone action and metabolism. Also, members of the epidermal growth factor receptor (EGFR) signaling pathway were observed, with the greatest upregulation of EGFR in severe versus mild disease during the early secretory phase. The extracellular matrix proteoglycan versican (VCAN), which regulates cell proliferation and apoptosis, was the most highly expressed gene in severe versus mild disease. Upregulation of microRNA 21 (MIR21) and DICER1 transcripts suggests roles for microRNAs (miRNAs) in the pathogenesis of severe versus mild endometriosis, potentially through regulation of gene silencing and epigenetic mechanisms. These observed differences in transcriptomic signatures and signaling pathways may result in poorly programmed endometrium during the cycle, contributing to lower implantation and pregnancy rates in women with severe versus mild endometriosis