121 research outputs found
Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index
Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P<0.05), and allowed the distinction between benign and malignant lesions (P<0.05). Even if without statistical significance, the amount of cfDNA was also affected by tumor necrosis and correlated with tumor size and apoptotic markers expression. A significant (P<0.01) increase of Bcl-2 in malignant tumors was observed, and in metastatic CMTs the evasion of apoptosis was also suggested. This study, therefore, provides evidence that cfDNA could be a diagnostic marker in dogs carrying mammary nodules suggesting that its potential application in early diagnostic procedures should be further investigated
The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients
Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer,
but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma
telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome.
Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after
CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels
and total cell-free RNA were determined using real-time PCR.
Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT
levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction
model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with
detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI
1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels.
Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal
cancer patients who undergo neoadjuvant therapy
Clinical relevance and biology of circulating tumor cells
Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer
ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors
Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases
Sampling circulating tumor cells for clinical benefits: how frequent?
Circulating tumor cells (CTCs) are cells shed from tumors or metastatic sites and are a potential biomarker for cancer diagnosis, management, and prognostication. The majority of current studies use single or infrequent CTC sampling points. This strategy assumes that changes in CTC number, as well as phenotypic and molecular characteristics, are gradual with time. In reality, little is known today about the actual kinetics of CTC dissemination and phenotypic and molecular changes in the blood of cancer patients. Herein, we show, using clinical case studies and hypothetical simulation models, how sub-optimal CTC sampling may result in misleading observations with clinical consequences, by missing out on significant CTC spikes that occur in between sampling times. Initial studies using highly frequent CTC sampling are necessary to understand the dynamics of CTC dissemination and phenotypic and molecular changes in the blood of cancer patients. Such an improved understanding will enable an optimal, study-specific sampling frequency to be assigned to individual research studies and clinical trials and better inform practical clinical decisions on cancer management strategies for patient benefits
Response of Quercus ilex seedlings to Phytophthora spp. root infection in a soil infestation test
[EN] Phytophthora species are the main agents associated with oak (Quercus spp.) decline, together with the changing environmental conditions and the intensive land use. The aim of this study was to evaluate the susceptibility of Quercus ilex to the inoculation with eight Phytophthora species. Seven to eight month old Q. ilex seedlings grown from acorns,
obtained from two Spanish origins, were inoculated with P. cinnamomi, P. cryptogea, P. gonapodyides, P. megasperma, P. nicotianae, P. plurivora, P. psychrophila and P. quercina. All Phytophthora inoculated seedlings showed decline and symptoms including small dark necrotic root lesions, root cankers, and loss of fine roots and tap root. The most aggressive species were P. cinnamomi, P. cryptogea, P. gonapodyides, P. plurivora and P. psychrophila followed by P. megasperma., while Phytophthora quercina and P. nicotianae were the less aggressive species. Results obtained confirm that these Phytophthora species could constituted a threat to Q. ilex ecosystems and the implications are further discussed.The authors are grateful to A. Solla and his team from the Centro Universitario de Plasencia-Universidad de Extremadura (Spain) for helping in the acorns collection and to the CIEF (Centro para la Investigación y Experimentación Forestal, Generalitat Valenciana, Valencia, Spain) for providing the acorns. This research was supported by funding from the project AGL2011- 30438-C02-01 (Ministerio de Economía y Competitividad, Spain).Mora-Sala, B.; Abad Campos, P.; Berbegal Martinez, M. (2018). Response of Quercus ilex seedlings to Phytophthora spp. root infection in a soil infestation test. European Journal of Plant Pathology. https://doi.org/10.1007/s10658-018-01650-6SÁlvarez, L. A., Pérez-Sierra, A., Armengol, J., & García-Jiménez, J. (2007). Characterization of Phytophthora nicotianae isolates causing collar and root rot of lavender and rosemary in Spain. Journal of Plant Pathology, 89, 261–264.Balci, Y., & Halmschlager, E. (2003a). 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Transcriptome of Aphanomyces euteiches: New Oomycete Putative Pathogenicity Factors and Metabolic Pathways
Aphanomyces euteiches is an oomycete pathogen that causes seedling blight and root rot of legumes, such as alfalfa and pea. The genus Aphanomyces is phylogenically distinct from well-studied oomycetes such as Phytophthora sp., and contains species pathogenic on plants and aquatic animals. To provide the first foray into gene diversity of A. euteiches, two cDNA libraries were constructed using mRNA extracted from mycelium grown in an artificial liquid medium or in contact to plant roots. A unigene set of 7,977 sequences was obtained from 18,864 high-quality expressed sequenced tags (ESTs) and characterized for potential functions. Comparisons with oomycete proteomes revealed major differences between the gene content of A. euteiches and those of Phytophthora species, leading to the identification of biosynthetic pathways absent in Phytophthora, of new putative pathogenicity genes and of expansion of gene families encoding extracellular proteins, notably different classes of proteases. Among the genes specific of A. euteiches are members of a new family of extracellular proteins putatively involved in adhesion, containing up to four protein domains similar to fungal cellulose binding domains. Comparison of A. euteiches sequences with proteomes of fully sequenced eukaryotic pathogens, including fungi, apicomplexa and trypanosomatids, allowed the identification of A. euteiches genes with close orthologs in these microorganisms but absent in other oomycetes sequenced so far, notably transporters and non-ribosomal peptide synthetases, and suggests the presence of a defense mechanism against oxidative stress which was initially characterized in the pathogenic trypanosomatids
Identifying key questions in the ecology and evolution of cancer
The application of evolutionary and ecological principles to cancer prevention and treatment, as well as recognizing cancer as a selection force in nature, has gained impetus over the last 50 years. Following the initial theoretical approaches that combined knowledge from interdisciplinary fields, it became clear that using the eco‐evolutionary framework is of key importance to understand cancer. We are now at a pivotal point where accumulating evidence starts to steer the future directions of the discipline and allows us to underpin the key challenges that remain to be addressed. Here, we aim to assess current advancements in the field and to suggest future directions for research. First, we summarize cancer research areas that, so far, have assimilated ecological and evolutionary principles into their approaches and illustrate their key importance. Then, we assembled 33 experts and identified 84 key questions, organized around nine major themes, to pave the foundations for research to come. We highlight the urgent need for broadening the portfolio of research directions to stimulate novel approaches at the interface of oncology and ecological and evolutionary sciences. We conclude that progressive and efficient cross‐disciplinary collaborations that draw on the expertise of the fields of ecology, evolution and cancer are essential in order to efficiently address current and future questions about cancer
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