Papers by Harris Pratsinis
Bioorganic & medicinal chemistry letters, 2005
A series of novel xanthenone aminoderivatives and their pyrazole-fused counterparts possessing st... more A series of novel xanthenone aminoderivatives and their pyrazole-fused counterparts possessing structural analogy to the potent anticancer agent 9-methoxypyrazoloacridine (PZA) reported. These compounds exhibited an interesting cytotoxic activity against a panel of cell lines. Most noticeably, they retain activity against the multidrug resistant MES-SA/Dx5 subline, showing resistant factors close to 1.
Journal of Cancer Research and Clinical Oncology, 2010
Purpose To elucidate the role of D-type cyclins in both superWcial (Ta-T1) and muscle-invasive (T... more Purpose To elucidate the role of D-type cyclins in both superWcial (Ta-T1) and muscle-invasive (T2-T4) urothelial carcinomas (UCs), investigating their potential prognostic usefulness. Methods ParaYn-embedded tissues from 157 patients with bladder UC were immunostained for cyclins D1, D2 and D3. Results Cyclin D1 expression positively correlated with D2 and negatively with D3. Cyclin D1 expression decreased with increasing grade (P = 0.0001) and tumour T-category in the entire cohort and in muscle-invasive carcinomas (P = 0.0001 and P = 0.0033). Cyclin D2 correlated with grade (P = 0.0005) and T-category (P = 0.0078), a relationship which remained signiWcant in muscle-invasive (P = 0.0135). Cyclin D3 immunoreactivity increased with histologic grade and T-category in the entire cohort (P = 0.0001 in both relationships), in superWcial (P = 0.0034) and in muscle-invasive carcinomas (P = 0.0036, respectively). Survival analysis in superWcial tumours showed that higher cyclin D1 (P = 0.0001) and higher cyclin D3 levels (P = 0.0032) were correlated with a lesser probability of survival. In muscle-invasive tumours, lower cyclin D1 (P = 0.0234), and D2 (P = 0.0424) and higher cyclin D3 (P = 0.0322) correlated with shortened survival. In multivariate analysis in superWcial tumours only cyclin D3 expression remained signiWcant. Cyclin D3 expression also retained its adverse signiWcance in muscle-invasive tumours. Conclusions Cyclin D1 overexpression seems to be more important during early T-categories of bladder carcinogenesis, whereas cyclin D3 is implicated in the acquisition of a more aggressive phenotype. Cyclin D3 overexpression emerges as an independent adverse prognostic marker in both superWcial and muscle-invasive tumours. Cyclin D1 is an independent indicator of shortened survival only in muscle-invasive tumours.
Seminars in Cancer Biology, 2019
While research on cancer development is traditionally focusing mainly on the neoplastic cell per ... more While research on cancer development is traditionally focusing mainly on the neoplastic cell per se, nowadays the role of tumor stroma in this process is indisputable. The stroma-mainly composed of extracellular matrix (ECM)-is a source of mediators and signals originating from heterotypic cell-cell and cell-matrix interactions that steer the progression of the disease in a context-and a cancer type-dependent manner. With advancing age the stroma exhibits alterations, important being the accumulation of senescent cells. Senescence is often triggered by exogenous stresses, including genotoxic anticancer treatment modalities (such as chemotherapy or radiotherapy) and is manifested as an inhibition of cell proliferation, ascribing to cellular senescence the role of a potent antitumor barrier. On the other hand, senescent cells, through their specific senescence-associated secretory phenotype (SASP)comprising cytokines, growth factors, ECM components and ECM-degrading enzymes-can establish an immunosuppressive, inflammatory and catabolic microenvironment that may
Transforming Growth Factor-β (TGF-β) is the prototype of a growth factor family playing central r... more Transforming Growth Factor-β (TGF-β) is the prototype of a growth factor family playing central roles in a wide variety of functions both at the tissue and the organismal levels, ranging from the regulation of cell proliferation, and the enhancement of extracellular matrix accumulation to immunosuppression and a dual role in cancer development. Here, we present a brief description of TGF-β in terms of structural and functional aspects, including the major signal transduction pathways activated by it. The role of TGF-β as an inducer of cellular senescence in normal, malignant and stem cells is documented, as well as, its ability to induce or reinforce senescence when acting in an autocrine or paracrine fashion, as part of the senescence-associated secretory phenotype. The interplay of TGF-β with the two major intracellular protein degradation systems, i.e. autophagy and the ubiquitin-proteasome system, is also discussed, given their associations with senescence and age-related pathol...
Advanced Drug Delivery Reviews, 2018
An essential element of tissue homeostasis is the response to injuries, cutaneous wound healing b... more An essential element of tissue homeostasis is the response to injuries, cutaneous wound healing being the most studied example. In the adults, wound healing aims at quickly restoring the barrier function of the skin, leading however to scar, a dysfunctional fibrotic tissue. On the other hand, in fetuses a scarless tissue regeneration takes place. During ageing, the wound healing capacity declines; however, in the absence of comorbidities a higher quality in tissue repair is observed. Senescent cells have been found to accumulate in chronic unhealed wounds, but more recent reports indicate that their transient presence may be beneficial for tissue repair. In this review data on skin wound healing and scarring are presented, covering the whole spectrum from early embryonic development to adulthood, and furthermore until ageing of the organism.
Osteoarthritis and Cartilage, 2016
Antioxidants
Skin health is heavily affected by ultraviolet irradiation from the sun. In addition, senile skin... more Skin health is heavily affected by ultraviolet irradiation from the sun. In addition, senile skin is characterized by major changes in the collagen, elastin and in the hyaluronan content. Natural products (NPs) have been shown to delay cellular senescence or in vivo aging by regulating age-related signaling pathways. Moreover, NPs are a preferable source of photoprotective agents and have been proven to be useful against the undesirable skin hyperpigmentation. Greek flora harvests great plant diversity with approximately 6000 plant species, as it has a wealth of NPs. Here, we report an extensive screening among hundreds of plant species. More than 440 plant species and subspecies were selected and evaluated. The extracts were screened for their antioxidant and anti-melanogenic properties, while the most promising were further subjected to various in vitro and cell-based assays related to skin aging. In parallel, their chemical profile was analyzed with High-Performance Thin-Layer Ch...
Cancers
Down-regulation of the small leucine-rich proteoglycan decorin in the stroma is considered a poor... more Down-regulation of the small leucine-rich proteoglycan decorin in the stroma is considered a poor prognostic factor for breast cancer progression. Ionizing radiation, an established treatment for breast cancer, provokes the premature senescence of the adjacent to the tumor stromal fibroblasts. Here, we showed that senescent human breast stromal fibroblasts are characterized by the down-regulation of decorin at the mRNA and protein level, as well as by its decreased deposition in the pericellular extracellular matrix in vitro. Senescence-associated decorin down-regulation is a long-lasting process rather than an immediate response to γ-irradiation. Growth factors were demonstrated to participate in an autocrine manner in decorin down-regulation, with bFGF and VEGF being the critical mediators of the phenomenon. Autophagy inhibition by chloroquine reduced decorin mRNA levels, while autophagy activation using the mTOR inhibitor rapamycin enhanced decorin transcription. Interestingly, t...
International Journal of Molecular Sciences
Recent studies have linked the activity of ER aminopeptidase 2 (ERAP2) to increased efficacy of i... more Recent studies have linked the activity of ER aminopeptidase 2 (ERAP2) to increased efficacy of immune-checkpoint inhibitor cancer immunotherapy, suggesting that pharmacological inhibition of ERAP2 could have important therapeutic implications. To explore the effects of ERAP2 inhibition on the immunopeptidome of cancer cells, we treated MOLT-4 T lymphoblast leukemia cells with a recently developed selective ERAP2 inhibitor, isolated Major Histocompatibility class I molecules (MHCI), and sequenced bound peptides by liquid chromatography tandem mass spectrometry. Inhibitor treatment induced significant shifts on the immunopeptidome so that more than 20% of detected peptides were either novel or significantly upregulated. Most of the inhibitor-induced peptides were 9mers and had sequence motifs and predicted affinity consistent with being optimal ligands for at least one of the MHCI alleles carried by MOLT-4 cells. Such inhibitor-induced peptides could serve as triggers for novel cytot...
Biomimetics
Targeted delivery of chemotherapeutics in order to overcome side effects and enhance chemosensiti... more Targeted delivery of chemotherapeutics in order to overcome side effects and enhance chemosensitivity remains a major issue in cancer research. In this context, biocompatible oil-in-water (O/W) microemulsions were developed as matrices for the encapsulation of DPS-2 a benzothiophene analogue, exhibiting high cytotoxicity in various cancer cell lines, among them the MW 164 skin melanoma and Caco-2 human epithelial colorectal adenocarcinoma cell lines. The microemulsion delivery system was structurally characterized by dynamic light scattering (DLS) and electron paramagnetic resonance (EPR) spectroscopy. The effective release of a lipophilic encapsulated compound was evaluated via confocal microscopy. The cytotoxic effect, in the presence and absence of DPS-2, was examined through the thiazolyl blue tetrazolium bromide (MTT) cell proliferation assay. When encapsulated, DPS-2 was as cytotoxic as when dissolved in dimethyl sulfoxide (DMSO). Hence, the oil cores of O/W microemulsions wer...
Planta medica, Jan 24, 2016
The Cretan diet, as the basis of the Mediterranean diet, has provided traditional remedies for th... more The Cretan diet, as the basis of the Mediterranean diet, has provided traditional remedies for the general well being of people through the long-established consumption of cooked wild greens and vegetables. The intake of the water decoctions of Cichorium spinosum and Cichorium intybus in the context of the daily dietary regime in Greece has been long associated with "liver detoxifying" properties. In the current study, we performed an in-depth investigation of the water decoctions traditionally prepared from C. spinosum and C. intybus through qualitative UHPLC-HRMS profiling and direct quantification of cichoric and caftaric acid as major antioxidant components of the decoction. In addition, we developed a one-step countercurrent chromatography method for the isolation of the two phenolic acids, along with a sulfoconjugate sesquiterpene lactone present only in the Cretan C. spinosum. All water decoctions were found not to be cytotoxic in human fibroblasts, whereas they all...
Wound Repair and Regeneration, 2004
Wound Repair and Regeneration, 2013
Senescent cells observed in the area of chronic wounds have been proposed to affect wound healing... more Senescent cells observed in the area of chronic wounds have been proposed to affect wound healing. Therapeutic approaches against chronic wounds include, among others, the local application of living cell constructs (LCCs), containing fibroblasts and/or keratinocytes. Accordingly, the aim of the present work was to examine the effects of factors secreted by early passage neonatal fibroblasts and LCCs--in the form of a conditioned medium (CM)--on senescent adult dermal fibroblasts regarding functions related to the healing process, i.e., cell proliferation, alpha-smooth muscle actin and metalloproteinase expression, and collagen synthesis. Target cells were fibroblasts senescent either due to subsequent divisions (replicative senescence) or due to an exogenous stress (stress-induced premature senescence). No effect on the proliferation of senescent fibroblasts was observed, as expected. All CMs were found to inhibit overall collagen synthesis both in early passage and in senescent fibroblasts. The LCC-derived CM was found to be more potent than fibroblast-derived CMs and, furthermore, to inhibit alpha-smooth muscle actin expression. In conclusion, these results may indicate anti-contractile and anti-fibrotic activities of factor(s) secreted by neonatal skin fibroblasts, and more intensely by LCCs on adult donor-derived fibroblasts. These activities seem to persist during senescence of the target cells.
Steroids, 2004
We have isolated from the plant Onobrychis ebenoides three novel arylobenzofurans with binding af... more We have isolated from the plant Onobrychis ebenoides three novel arylobenzofurans with binding affinity for the estrogen receptor. In this study, we evaluated these arylobenzofurans, namely ebenfuran I, ebenfuran II and ebenfuran III for their potential selective estrogen receptor modulator (SERM)-like properties. We examined their ability, (1) to induce the insulin growth factor binding protein-3 (IGFBP-3) in MCF-7 breast cancer cells, (2) to stimulate differentiation and mineralization of osteoblastic cell culture by histochemical staining for alkaline phosphatase, Alizarin RedS staining and calcium levels in the supernatants and (3) to inhibit cell proliferation of cervical adenocarcinoma (Hela) cells by use of the MTT assay. An estrogen receptor mediated effect was investigated by carrying out chloramphenicol acetyl transferase (CAT) assay on transient MCF-7 transfectants. Estradiol and the "pure" antiestrogen ICI 182780 were included to serve as control samples of the estrogenic and antiestrogenic effect respectively. Our data reveal that ebenfuran II is a highly potent SERM, exhibiting antiestrogenic activity in breast cancer cells via the estrogen receptor, estrogenic effect on osteoblasts and no stimulatory effect on cervix adenocarcinoma cells. In conclusion, our study is the first to demonstrate that plant derived arylobenzofurans show a SERM profile and may be considered for the prevention and treatment of diseases such as breast cancer, cervical cancer and osteoporosis.
Planta Medica, 2003
Bioassay-guided fractionation of the neutral extract of the bark of Sarcomelicope megistophylla r... more Bioassay-guided fractionation of the neutral extract of the bark of Sarcomelicope megistophylla resulted in the isolation of the new nor-neolignan sarcomeginal ( 1), together with the known ailanthoidol ( 2) and (+/-)-seco-isolariciresinol ( 3). The structure of 1 was determined by spectroscopic means. Estrogenic activity of the isolated compounds was tested using estrogen receptor-positive MCF7 and estrogen receptor-negative MDA-MB-231 human mammary adenocarcinoma cell lines. Compound 3 displayed significant estrogenic activity.
Phytomedicine, 2008
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:
Laboratory Investigation, 2005
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Papers by Harris Pratsinis