• We found that locally activated neutrophils were key drivers of the tumor-supportive preconditioning of the lung microenvironment, governed by enhanced regenerative Notch signaling. (nature.com)
  • Therefore, damaging the MECs layer resulted in the release of various factors (such as SDF1/CXCL12, CXCL14, MMP, and tenascin) [ 11 , 12 ] with a potential to modify the tumour microenvironment and facilitate the paracrine communication between the tumour epithelial cells and the enclosed stroma enhancing the tumour aggressiveness [ 11 , 13 ]. (biomedcentral.com)
  • His laboratory has followed two primary interests: 1) the transcription factor networks that regulate fate determination in various cells that make blood, and 2) the cell surface proteins expressed by hematopoietic stem cells that and allow them to communicate with their microenvironment. (ubc.ca)
  • γδ T cells recruited into the tumor microenvironment can act as effector cells to mediate cancer immune surveillance. (explorationpub.com)
  • Therefore, an in-depth understanding of γδ T cells that play conflicting roles in the tumor microenvironment is necessary. (explorationpub.com)
  • Upon ADT treatments, we postulate that lots of PCa cells would be undergoing cell death through the therapeutically inhibited AR function, and dying PCa cells may possibly prompt the recruitment of macrophages, which may offer a supportive microenvironment for the possible interaction between the macrophages and surviving PCa cells. (cathepsin-s.com)
  • Our prior study on molecular pathways linking AR function in macrophages and wound healing associated inflammation displaying that the deficit of AR in mice tends to make an immunosuppressive microenvironment that favours wound healing (Lai et al, 2009). (cathepsin-s.com)
  • Interestingly, a single report showed that tumourassociated macrophages (TAMs) have already been the significant players to promote the development of hormonal resistance of PCa cells (Zhu et al, 2006), supporting a protumour function for TAMs in the prostate tumour microenvironment. (cathepsin-s.com)
  • Invasive micropapillary carcinoma of the breast (IMPC) is a rare subtype of breast cancer that has a high frequency of lymph node (LN) involvement and metastasis to distant organs. (jcancer.org)
  • We reported here that plakoglobin, as a key component in cell adhesion, can promote collective metastasis through facilitating IMPC clusters formation. (jcancer.org)
  • In comparing the clinicopathological features of 451 IMPC patients and 282 IDC-NST patients, our results showed that tumor emboli were significantly higher in IMPC patients and were associated with a high frequency of metastasis. (jcancer.org)
  • Patient developed infiltrating ductal carcinoma of underlying breast tissue with axillary lymph metastasis. (medscape.com)
  • We exposed healthy mouse lung tissue to radiation before the induction of metastasis and observed a strong enhancement of cancer cell growth. (nature.com)
  • No significant tumor regression was detected at the end of cerulenin treatment, but IHC staining showed higher expression of EMT/metastasis markers in H157CisR cell-derived tumors than H157P cell-derived tumors, and showed dramatic reduction of these markers in tumor tissues of cerulenin-treated mice, confirming the in vitro results. (oncotarget.com)
  • Subsequent radiotherapy in case of incompletely resected tumors can be an important option to avoid recurrence or metastasis even though this occurs rarely. (hindawi.com)
  • Cysteine-rich protein 61 (CCN1/Cyr61) has been implicated as an important mediator in the proliferation and metastasis of breast cancer. (molcells.org)
  • Extra importantly, Loberg et al employed a xenograft model of PC3 cells to demonstrate that CCL2 may possibly enhance prostate tumour growth/metastasis in vivo by growing the recruitment of TAMs and angiogenesis (Loberg et al, 2007). (cathepsin-s.com)
  • These results recommend a significant role for inflammatory cells in promoting castration resistance and metastasis of PCa cells. (cathepsin-s.com)
  • This predict the likelihood of a later recurrence, i.e., an indicator that unique longitudinal sample material was collected from each pa- allows risk assessment for breast cancer metastasis, would be tient between 0 and 36 mo after the primary operation. (lu.se)
  • Herein in this review, we aimed to address the roles delivered by MECs in breast cancer progression and decipher the molecular mechanisms regulating proper MECs' physiology, integrity, and terminal differentiation. (biomedcentral.com)
  • Hitherto the involvement of the MECs in mammary gland orchestration and morphogenesis [ 4 ] and in affording fortification against tumour progression and invasion [ 5 , 6 ] has re-established the attention in studying and characterizing the MECs. (biomedcentral.com)
  • Next, we re-evaluate the important role of MECs in breast cancer evolution and progression. (biomedcentral.com)
  • He has delineated the function of these molecules in diverse set of biological processes including: 1) gut and kidney formation, 2) vascular permeability, 3) mucosal inflammatory disease, 4) stem cell homing and migration, and 5) epithelial tumor progression. (ubc.ca)
  • These studies located a potential part for AR in mediating inflammatory responses throughout PCa progression since gene signatures of wound healing responses are very similar to genes identified in studies of progressive breast cancer with high metastatic possible (Chang et al, 2005). (cathepsin-s.com)
  • In this study, we tested our hypothesis that suppressing AR function by means of siRNA in PCa could possibly simultaneously trigger undesirable inflammatory signals that would prompt macrophage infiltration and thereafter could supply tumour supporting signals to stimulate progression of PCa. (cathepsin-s.com)
  • Metastatic spread is responsible for the majority of cancer-associated deaths and is affected by a variety of factors, including the deregulation of gene expression, signal transduction, and epigenetic modification, as well as epithelial-to-mesenchymal transition (EMT) and the transformation of tumor cells into stem/progenitor cells. (jcancer.org)
  • Interestingly, a cell population was identified that displayed an epithelial-to-mesenchymal transition (EMT) and which had a stem cell phenotype. (biomedcentral.com)
  • These cisplatin-resistant cells showed slight growth retardation, but exhibited higher epithelial-mesenchymal transition (EMT) and increased metastatic potential compared to parental cells. (oncotarget.com)
  • Epithelial-mesenchymal transition (EMT) is a critical step in the acquisition of the migratory and invasive capabilities associated with metastatic competence. (molcells.org)
  • The epithelial-mesenchymal transition (EMT) is an essential process in multiple biochemical changes, including embryonic development, tissue remodeling and wound healing. (molcells.org)
  • We identified CCL2 as a crucial player in mediating STAT3 activation and epithelial esenchymal transition (EMT) of PCa cells and addressed the essential difficulty of why targeting AR with siRNA could le. (cathepsin-s.com)
  • High-grade serous ovarian cancer (HGSOC) comprises the major malignant histotype (70%) of epithelial ovarian cancers and bears a molecular signature in the overexpression of MUC16/cancer antigen 125 (CA125), a serum biomarker for ovarian cancer ( 3 ). (snmjournals.org)
  • By thorough histologic examination, Muir documented intraepidermal extension of malignant ductal epithelial cells through the lactiferous ducts and ductules into the epidermis (epidermotropism). (medscape.com)
  • Malignant epithelial (Paget) cells infiltrate and proliferate in the epidermis, causing thickening of the nipple and the areolar skin. (medscape.com)
  • Malignant Paget cells are derived from luminal lactiferous ductal epithelium (A) of breast tissue with retrograde extension of cancerous Paget cells into epidermis of overlying nipple (B). Enlarged circle shows details that reveal thickening both of lining epithelium of breast duct and of nipple skin. (medscape.com)
  • Mammary Paget cells are malignant epithelial cells derived from underlying ductal adenocarcinoma of the breast that invade into the skin of nipple and areolar areas. (medscape.com)
  • The cause of TIO are usually small, slowly growing tumors of mesenchymal origin (phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) [ 5 , 7 - 10 ]. (hindawi.com)
  • Vimentin is a developmentally regulated intermediate filament protein (IFP) found in cells of mesenchymal origin. (thermofisher.com)
  • Over the past decades, luminal epithelial cell lineage has gained considerable attraction as the functionally milk-secreting units and as the most fruitful acreage for breast cancer launching. (biomedcentral.com)
  • The ductal system is coated by a chain of luminal epithelial cells (LECs) situated on a layer of myoepithelial cells (MECs) and encompassed by a distinguished basement membrane. (biomedcentral.com)
  • Additionally, MECs contributed effectively to maintaining the right luminal cells' polarization and further separating them from the adjacent stroma by making an integrated fence. (biomedcentral.com)
  • Two major cell types cooperate to build up the ductal units: inner polarized luminal epithelial cells (LECs) embraced by a layer of myoepithelial cells (MECs), both cell types are rimmed by a cohesive basement membrane (BM) [ 2 ]. (biomedcentral.com)
  • These tumorous epithelial cells are derived from luminal lactiferous ductal epithelium of the breast tissue (see the image below). (medscape.com)
  • Both in vitro and in vivo data showed overexpression of plakoglobin in both the cell membrane and the cytoplasm of IMPC clusters. (jcancer.org)
  • Using mouse models, we validated the metastatic potential of tumor clusters was higher than single cells in vivo . (jcancer.org)
  • Fig. 8: Inhibition of Notch signaling attenuates the radiation-driven enhancement of metastatic growth in vivo. (nature.com)
  • Ex vivo analysis of tumors and lymph nodes was performed via autoradiography, histopathology, and immunohistochemistry. (snmjournals.org)
  • Subsequent in vitro and in vivo studies have demonstrated the initial steps of cancer cell invasion and dissemination by disrupting the integrity of the myoepithelial belt that encircles the LECs [ 7 , 8 , 9 , 10 , 11 ]. (biomedcentral.com)
  • No recurrence or metastatic disease was noted at 6-year follow-up. (medscape.com)
  • Vicini, F. A., Kestin, L., Huang, R. & Martinez, A. Does local recurrence affect the rate of distant metastases and survival in patients with early-stage breast carcinoma treated with breast-conserving therapy? (nature.com)
  • PET imaging of CA125 expression by ovarian cancer cells may enhance the evaluation of the extent of disease and provide a roadmap to surgery as well as detect recurrence and metastases. (snmjournals.org)
  • The risk of distant recurrence in breast cancer patients is difficult to prognostic indices, such as the Nottingham Prognostic Index (6, 7), assess with current clinical and histopathological parameters, and have proven valuable in identifying patients with poor prognosis. (lu.se)
  • In a series of 175 human adult tumors, gene expression was highest in ovarian serous carcinomas. (nature.com)
  • Histopathologic analysis of the immuno-PET-positive lymph nodes revealed the presence of grossly metastasized ovarian cancer cells within the lymphoid tissues. (snmjournals.org)
  • Indeed, among epithelial ovarian cancers, the frequency of CA125 positivity is higher in serous histotypes than in mucinous or clear cell disease ( 4 ). (snmjournals.org)
  • Invasive micropapillary carcinoma of the breast (IMPC) accounts for 5 % of all breast cancers, and displays relatively uncommon and distinct histomorphological features [ 1 ]. (jcancer.org)
  • Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancers, with the current standard regimen of care for NSCLC including chemotherapy with pemetrexed as a single agent or in combination with platinum-based agents, e.g. cisplatin. (biomedcentral.com)
  • Breast cancer is the most frequently diagnosed cancer in females worldwide and according to data from the World Health Organization comprises 16% of all female cancers. (molcells.org)
  • After resection of the tumor, hypophosphatemia and the increased levels of FGF-23 normalized within a few days. (hindawi.com)
  • Tumor resection of PMTMCTs is the therapy of choice. (hindawi.com)
  • before resection of the primary tumor and then postoperatively every 6-12 mo, resulting in three to five samples per patient. (lu.se)
  • A major challenge currently facing the scientific community is that a large number of breast cancer patients present with metastatic cancer or relapse and metastasize after initial response to standard cancer therapy. (molcells.org)
  • The results from this prevali- the field of cancer biomarkers (11-13), and that approach was dation study showed that patients could be classified into high- adopted here to define predictive serum biomarkers associated versus low-risk groups for developing metastatic breast cancer with tumor relapse in breast cancer patients. (lu.se)
  • At 5-year follow-up, she was alive, without recurrent or metastatic tumor. (medscape.com)
  • No metastatic tumor was noted in axillary lymph node. (medscape.com)
  • Knowledge of the expression patterns of HE4 in our survey is useful for application in histopathologic diagnosis, and should be taken into consideration in future studies that examine the role of HE4 as a serological tumor biomarker or as a target for gene-based therapy. (nature.com)
  • We discuss the implications of our results in terms of the potential role for HE4 in histopathologic diagnosis, as a serum tumor biomarker, and as a therapeutic target. (nature.com)
  • FGF-23 levels were significantly increased, and total body magnetic resonance imaging (MRI) revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor-induced osteomalacia (TIO). (hindawi.com)
  • Diagnosis of TIO is often extremely difficult since tumors can be too small for detection by conventional radiological methods. (hindawi.com)
  • In Sweden, there has been a steady prostate-specific antigen (PSA) velocity for the diagnosis of pros- decrease in age-standardized breast cancer mortality in women up tate cancer (15). (lu.se)
  • In TIO most tumors overexpress the protein fibroblast growth factor-23 (FGF-23) inhibiting renal phosphate reabsorption in the proximal tubules and acting as a phosphaturic factor [ 1 , 3 , 11 ]. (hindawi.com)
  • In this respect, in contrast to predictors based for each serum protein was determined by comparing the samples upon tumor characteristics at the time of surgery, serum is a par- collected at the primary operation and then 3-6 mo later. (lu.se)
  • Moreover, efforts have been engendered to study the relationships between the MECs and the LECs and their engagement in breast cancer tumorigenesis and plasticity. (biomedcentral.com)
  • Additionally, these cells show highly flexible and dynamic plasticity and are extremely easily polarized into regulatory phenotypes. (explorationpub.com)
  • Similar to αβ T cells, γδ T cells also develop in embryos, and their intra-thymic development shows strict regulation and flexible plasticity [ 2 ]. (explorationpub.com)
  • Similarly, it has been shown that castrationinduced B cells infiltration and B cellderived cytokines in PCa may possibly play a key role in helping PCa cells become castration resistant (Ammirante et al, 2010). (cathepsin-s.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Using tissue microarrays and full tissue sections of normal and 448 neoplastic tissues, HE4 immunoreactivity was found in normal glandular epithelium of the female genital tract and breast, the epididymis and vas deferens, respiratory epithelium, distal renal tubules, colonic mucosa, and salivary glands, consistent with HE4 gene expression. (nature.com)
  • Proper recognition of this disorder is required to initiate an appropriate workup (eg, skin biopsy) for differentiating it from other benign inflammatory dermatoses and for detecting an underlying breast carcinoma. (medscape.com)
  • [ 5 ] Like Paget cells of both mammary and extramammary sites, Toker cells contain prominent clear (vacuolated) cytoplasm, and they are considered benign counterparts of Paget cells. (medscape.com)
  • Toker cells are benign and may sometimes proliferate, resulting in a condition known as clear cell papulosis. (medscape.com)
  • [ 7 ] reported that the chromosomal alterations seen in Paget cells (eg, loss of heterozygosity and mitochondrial DNA displacement loop sequence analysis) are different from those seen in underlying breast carcinoma cells. (medscape.com)
  • The human breast is made up of an extensively branching ductal system intervening by copious lobular units. (biomedcentral.com)
  • Paget cells and underlying ductal carcinoma cells have been shown to be positive for the oncogene HER2/neu, suggesting common genetic alterations for both the epidermal and breast tumor cells. (medscape.com)
  • [ 6 ] reported on the immunohistochemical expression of apomucin MUC1, MUC2, and MUC5AC in PD and concluded that both epidermal Paget cells and underlying ductal carcinoma exhibit the same phenotypic apomucins that are also expressed by the Toker cells. (medscape.com)
  • Axillary PD can arise from underlying axillary accessory breast tissue. (medscape.com)
  • Radiotherapy is one of the most effective approaches to achieve tumor control in cancer patients, although healthy tissue injury due to off-target radiation exposure can occur. (nature.com)
  • Importantly, these tissue perturbations endowed arriving cancer cells with an augmented stemness phenotype. (nature.com)
  • Subsequent microscopic examination and immunohistochemical analysis revealed a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) showing a positive expression of somatostatin receptor 2A (SSTR2A), CD68, and Periostin. (hindawi.com)
  • However, the resected margins showed no tumor-free tissue, and therefore a subsequent postoperative radiotherapy was performed. (hindawi.com)
  • Indeed, disruption of the MECs layer was reported to facilitate the invasion of the cancer cells to the surrounding stroma. (biomedcentral.com)
  • Nonetheless, MECs were also found to exhibit cancer-promoting effects and provoke tumour invasion and dissemination by displaying distinct cancer chemokines. (biomedcentral.com)
  • In the present study, we report that baicalein significantly inhibits the expression of Cyr61 and migration and invasion of MDA-MB231 human breast cancer cells. (molcells.org)
  • Invading cancer cells can utilize different modes of migration including single cell migration and collective migration. (jcancer.org)
  • Fig. 6: Radiation exposure boosts Notch signaling and stemness in metastatic cells. (nature.com)
  • Through gene knockout studies he has shown that these molecules act as a type of molecular "Teflon" to make cells more mobile and invasive and also facilitate chemotaxis. (ubc.ca)
  • Recognition of the effective involvement of the myoepithelial cells in mammary gland development and in hampering tumorigenesis has renewed the interest in investigating the biological roles of this second main mammary lineage. (biomedcentral.com)
  • The pathogenesis of mammary PD and the origin of Paget cells were once controversial. (medscape.com)
  • Schematic diagram of female breast depicting widely accepted concept of pathogenesis of mammary Paget disease. (medscape.com)
  • NSCLC comprises 85% of lung cancer cases [ 2 ] and constitutes a heterogeneous population of squamous, adenocarcinoma, and large cell carcinomas [ 1 ]. (oncotarget.com)
  • Prolonged pemetrexed pretreatment for 48 h prior to cisplatin treatment maximally delayed long-term cell growth and significantly reduced the number of recovering clones. (biomedcentral.com)
  • There was slight growth inhibition, but significantly reduced EMT/metastatic potential in cisplatin-resistant cells upon inhibitor treatment. (oncotarget.com)
  • MECs were found to express numerous proteinase inhibitors, anti-angiogenic factors, and tumour suppressors proteins. (biomedcentral.com)
  • There he worked with Dr. Max D. Cooper (Howard Hughes Medical Institute, National Academy of Sciences) and his research focused on cell surface proteins expressed by preB cells that regulate B cell maturation and homing. (ubc.ca)
  • In addition, he identified a number of novel hematopoietic stem cell surface proteins and began analyzing their function. (ubc.ca)
  • In this regard, his lab has identified a novel family of hematopoietic cell surface proteins, called the CD34 family, and shown that these are essential for a number of developmentally important processes. (ubc.ca)
  • According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. (explorationpub.com)
  • similarly, low-activity concentrations of 89 Zr-DFO-mAb-B43.13 accumulated in CA125-negative SKOV3 tumors. (snmjournals.org)
  • We hypothesized that prolonged pretreatment with pemetrexed could be beneficial, as prior depletion of nucleotide pools could sensitize cancer cells to subsequent treatment with cisplatin. (biomedcentral.com)
  • We observed a highly up-regulated fatty acid synthase (FASN) level in A549CisR and H157CisR cells compared to parental cells and the up-regulation of FASN was also detected in A549P and H157P cells after short time treatment with cisplatin, suggesting that the high level of FASN in cisplatin-resistant cells may be from the accumulated cellular responses during cisplatin-resistance developmental process. (oncotarget.com)
  • In addition, a subpopulation of therapy resistant cells with EMT and cancer stem cell features was identified that was resistant to the standard treatment regimen but sensitive to pemetrexed pretreatment combined with cisplatin. (biomedcentral.com)
  • There his work focused on transcriptional control of hematopoietic stem cell maturation and cell fate. (ubc.ca)
  • He is a member of the Stem Cell Network Centre of Excellence (past member of the Stem Cell Policy Committee and Research Management Committee and current Sub-chair of the Training and Education Committee), and a member of the AllerGen Network Centre of Excellence (Research Management Committee and Co-Chair of the Biomarkers Program). (ubc.ca)
  • involvement of the male breast is rarely reported and may be more aggressive. (medscape.com)
  • Biodistribution studies revealed accretion of 89 Zr-DFO-mAb-B43.13 in the OVCAR3 tumors, ultimately reaching 22.3 ± 6.3 percentage injected dose per gram (%ID/g) at 72 h after injection. (snmjournals.org)
  • These cells may be a key factor ultimately mediating the deviation of the antagonistic response between tumor inhibition and tumor promotion. (explorationpub.com)
  • In this review, we provided an overview of the myoepithelial cells' histogenesis, molecular and biological markers, and physiological commitments. (biomedcentral.com)
  • This review further emphasizes the diversified cross-talk between γδ T cells and other immune cells. (explorationpub.com)
  • It is hoped that the host immune status can be accurately predicted and gradually advance γδ T cell precise individualized medicine. (explorationpub.com)
  • as many as two thirds of patients have a palpable breast tumor. (medscape.com)
  • In recent literature, Gallium Dotatate PET has emerged as a virtually ideal investigation to localize tumors causing TIO as well and performed better than F-FDG PET/CT in some studies and seems to be a promising diagnostic tool in patients in whom 111In-octreotide SPECT/CT prior failed to detect a tumor [ 15 , 16 ]. (hindawi.com)
  • However, a simple way to screened 240 sera from 64 patients with primary breast cancer. (lu.se)
  • The samples were collected from breast cancer patients rent procedures. (lu.se)
  • Lung cancer is heterogeneous and histologically divided into two types: small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). (oncotarget.com)
  • However, adenocarcinomas of the lung, and occasional breast, transitional cell and pancreatic carcinomas had moderate or high levels of HE4 expression. (nature.com)
  • For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alpha calcitriol) is a therapeutic option [ 9 ]. (hindawi.com)
  • The cells possess microscopic features of glandular cells. (medscape.com)
  • We next investigated whether the inhibition of FASN by using a specific FASN inhibitor, cerulenin, can influence growth and EMT/metastatic potential of A549CisR and H157CisR cells. (oncotarget.com)
  • Cell growth and colony formation as well as senescence induction were quantified after treatment. (biomedcentral.com)
  • NSCLC A549 and H460 cells were treated with pemetrexed for 72 h. (biomedcentral.com)
  • Cisplatin-resistant A549CisR and H157CisR cell lines were developed by treating parental A549 (A549P) and H157 (H157P) cells. (oncotarget.com)
  • Retraction of the nipple or the presence of palpable nodules indicates an underlying breast cancer. (medscape.com)
  • Nipple invagination, deformed nipple-areola complex, marked erythema, and alternating hyperpigmentation and hypopigmentation noted in adjacent skin of breast in 65-year-old woman with biopsy-proven Paget disease. (medscape.com)
  • Nipple changes were associated with intraductal carcinoma of breast. (medscape.com)
  • It has been speculated that Paget cells may derive from glandular stem cells or epidermal Toker cells (clear cells of the nipple epithelium). (medscape.com)
  • Activated γδ T cells exhibit strong cytotoxic activity and cytokine secretion functions and are effective antitumor lymphocytes with simple and direct recognition modes and rapid responses. (explorationpub.com)
  • In brief, frozen sections of profiled tumors were examined by hematoxylin-and-eosin, and areas rich in neoplastic cells were cut from the frozen blocks. (nature.com)
  • These results provide a convincing rationale for the high metastatic propensity seen in IMPC. (jcancer.org)
  • High-resolution magnetic resonance imaging (MRI) of the whole body is the currently proposed method of choice to confirm the location of the tumor. (hindawi.com)
  • The active, un-phosphorylated form of GSK3β maintains both (i) epithelial phenotypes by inhibiting the expression and stabilization of Snail and Slug and (ii) high E-cadherin expression ( Boble and Woodgett, 2007 ) in resting epithelial cells. (molcells.org)
  • Mice were injected with cerulenin or vehicle after tumors were developed. (oncotarget.com)
  • At present, the phenotypic heterogeneity and functional variation of human γδ T cells are increasing. (explorationpub.com)
  • In this review, we use the Heilig nomenclature to describe human γδ T cells [ 1 ]. (explorationpub.com)
  • MTA thereby interferes with the proliferation and survival of replicating cancer cells. (biomedcentral.com)