Hydride-doped coinage metal superatoms and their catalytic applications.

Superatomic constructs have been identified as a critical component of future technologies. The isolation of coinage metal superatoms relies on partially reducing metallic frameworks to accommodate the mixed valent state required to generate a superatom. Controlling this reduction requires careful consideration in reducing the agent, temperature, and the ligand that directs the self-assembly process. Hydride-based reducing agents dominate the synthetic wet chemical routes to coinage metal clusters. However, within this category, a unique subset of superatoms that retain a hydride/s within the nanocluster post-reduction have emerged. These stable constructs have only recently been characterized in the solid state and have highly unique structural features and properties. The difficulty in identifying the position of hydrides in electron-rich metallic constructs requires the combination and correlation of several analytical methods, including ESI-MS, NMR, SCXRD, and DFT. This text highlights the importance of NMR in detecting hydride environments in these superatomic systems. Added to the complexity of these systems is the dual nature of the hydride, which can act as metallic hydrogen in some cases, resulting in entirely different physical properties. This review includes all hydride-doped superatomic nanoclusters emphasizing synthesis, structure, and catalytic potential.

Hydride-Containing Pt-doped Cu-rich Nanoclusters: Synthesis, Structure, and Electrocatalytic Hydrogen Evolution.

A structurally precise hydride-containing Pt-doped Cu-rich nanocluster [PtH2 Cu14 {S2 P(Oi Pr)2 }6 (CCPh)6 ] (1) has been synthesized. It consists of a bicapped icosahedral Cu14 cage that encapsulates a linear PtH2 unit. Upon the addition of two equivalents of CF3 COOH to 1, two hydrido clusters are isolated. These clusters are [PtHCu11 {S2 P(Oi Pr)2 }6 (CCPh)4 ] (2), which is a vertex-missing Cu11 cuboctahedron encaging a PtH moiety, and [PtH2 Cu11 {S2 P(Oi Pr)2 }6 (CCPh)3 ] (3), a distorted 3,3,4,4,4-pentacapped trigonal prismatic Cu11 cage enclosing a PtH2 unit. The electronic structure of 2, analyzed by Density Functional Theory, is a 2e superatom. The electrocatalytic activities of 1-3 for hydrogen evolution reaction (HER) were compared. Notably, Cluster 2 exhibited an exceptionally excellent HER activity within metal nanoclusters, with an onset potential of -0.03 V (at 10 mA cm-2 ), a Tafel slope of 39 mV dec-1 , and consistent HER activity throughout 3000 cycles in 0.5 M H2 SO4 . Our study suggests that the accessible central Pt site plays a crucial role in the remarkable HER activity and may provide valuable insights for establishing correlations between catalyst structure and HER activity.

Locating Interstitial Hydrides in MH2@Cu14 (M = Cu, Ag) Clusters by Single-Crystal X-ray Diffraction.

Two structures, [Cu15H2(S2CNnBu2)6(C≡CPh)6][CuCl2] (1) and [AgH2Cu14{S2P(OiPr)2}6(C≡CPh)6][PF6] (2), are characterized by X-ray crystallography with high-quality single crystals. The position of interstitial hydrides can be accurately located. In addition, the refinement of the hydrides with anisotropic displacement parameters (ADPs) was successful. The distances between the central atom and copper atoms, as well as the distances within the metal cages surrounding the hydrides, are analyzed and compared with similar MH2@Cu14 (M = Cu, Ag, Pd) compounds. This work provides a thoughtful and accurate assessment of the considerations and challenges associated with anisotropic refinement for H atoms, particularly in X-ray data collection.

A heteroleptic fused bi-cuboctahedral Cu21S2 cluster.

A new dicationic cluster, [Cu21S2{S2CNnBu2}9(C2Ph)6]2+, where the Cu21S2 kernel consists of two S@Cu12 cuboctahedra sharing a triangular Cu3 face is reported. Its waist part is bridged by three dithiocarbamate ligands, each in a hexaconnective, hexametallic (µ3, µ3) coordination pattern, an unprecedented feature in Cu nanocluster chemistry.

Hydride-containing 2-Electron Pd/Cu Superatoms as Catalysts for Efficient Electrochemical Hydrogen Evolution.

The first hydride-containing 2-electron palladium/copper alloys, [PdHCu11 {S2 P(Oi Pr)2 }6 (C≡CPh)4 ] (PdHCu11 ) and [PdHCu12 {S2 P(Oi Pr)2 }5 {S2 PO(Oi Pr)} (C≡CPh)4 ] (PdHCu12 ), are synthesized from the reaction of [PdH2 Cu14 {S2 P(Oi Pr)2 }6 (C≡CPh)6 ] (PdH2 Cu14 ) with trifluoroacetic acid (TFA). X-ray diffraction reveals that the PdHCu11 and PdHCu12 kernels consist of a central PdH unit encapsulated within a vertex-missing Cu11 cuboctahedron and complete Cu12 cuboctahedron, respectively. DFT calculations indicate that both PdHCu11 and PdHCu12 can be considered as axially-distorted 2-electron superatoms. PdHCu11 shows excellent HER activity, unprecedented within metal nanoclusters, with an onset potential of -0.05 V (at 10 mA cm-2 ), a Tafel slope of 40 mV dec-1 , and consistent HER activity during 1000 cycles in 0.5 M H2 SO4 . Our study suggests that the accessible central Pd site is the key to HER activity and may provide guidelines for correlating catalyst structures and HER activity.

Unusual core engineering on a copper hydride nanoball.

A neutral polyhydrido copper cluster, [Cu27H15{S2CNnBu2}12] (abbreviated as [Cu27H15]), was prepared by the reaction of dithiocarbamates (dtc), Cu(I) salts and NaBH4. The isolated cluster provides insights into core engineering, demonstrating its novel ability to reversibly add or remove one copper atom from the cluster core. Single-crystal X-ray analysis reveals that the new core-shell structure exhibits a Cu24 rhombicuboctahedral outer cage and an inner Cu3 triangular kernel. The two core-shell clusters, [Cu27H15{S2CNnBu2}12] and previously published [Cu28H15(S2CNnBu2)12]+ (abbreviated as [Cu28H15]+), are only differentiated by one copper atom in their inner core. Importantly, we demonstrate core engineering with the controllable reversible transition between an irregular Cu4 tetrahedron and a Cu3 triangle, whilst maintaining their outer Cu24 shell intact. The 15 hydride atoms in [Cu27H15], coordinated in three different modes, are co-incident with the hydride positions in [Cu28H15]+. The degradation of [Cu27H15] in solution or the addition of one eq. of Cu(I) ions leads to the conversion of [Cu27H15] into [Cu28H15]+, while the reverse transformation can be achieved by the addition of either formic acid or a reducing agent to [Cu28H15]+. A dicationic species was observed in the ESI mass spectrum, and the composition is formulated as [Cu56H30(S2CNnBu2)24]2+, a dimer of [Cu27H15(S2CNnBu2)12 + Cu+]22+. The dimeric species was further explored by DFT calculations, suggesting that the lowest energy structure consists of a [Cu28H15]+ and a [Cu27H15] cluster connected through one Cu+ atom bridge. As a result, [Cu27H15] is considered an intermediate species in the formation of the more stable [Cu28H15]+ nanoball.

Synthesis, structural studies, and photophysical properties of heteroleptic inverse-coordination clusters.

Two series of hyper-coordinated halide-centered M12 cuboctahedral clusters, [M12(µ12-X){S2P(OnPr)2}6{CCPh}4](PF6), 1a-c and 2a-c (where M = Cu, 1; Ag, 2; X = Cl, a; Br, b; I, c), were synthesized and fully characterized by ESI-MS, multi-NMR spectroscopy, IR and UV-Vis spectroscopy, photoluminescence analysis, and single-crystal X-ray crystallography. Structures 1c, 2b, and 2c show a twelve-coordinated halide encapsulated in the M12 cage, which is stabilized by six dithiophosphate and four alkynyl ligands. Compound 2b is the first Ag(I) cluster containing a twelve-coordinated bromide. The structural features of all six clusters are highly similar, providing a comparison basis of the inverse coordination for halides. Besides, the detailed structural analysis illustrates how the inverse coordination of a halide has influenced the size of the cuboctahedral M12 framework.

Reactivities of Interstitial Hydrides in a Cu11 Template: En Route to Bimetallic Clusters.

In sharp contrast to surface hydrides, reactivities of interstitial hydrides are difficult to explore. When treated with a metal ion (Cu+ , Ag+ , and Au+ ), the stable CuI dihydride template [Cu11 H2 {S2 P(Oi Pr)2 }6 (C≡CPh)3 ] (H2 Cu11 ) generates surprisingly three very different compounds, namely [CuH2 Cu11 {S2 P(Oi Pr)2 }6 (C≡CPh)3 ]+ (1), [AgH2 Cu14 {S2 P(Oi Pr)2 }6 ((C≡CPh)6 ]+ (2), and [AuCu11 {S2 P(Oi Pr)2 }6 (C≡CPh)3 Cl] (3). Compounds 1 and 2 are both MI species and maintain the same number of hydride ligands as their H2 Cu11 precursor. Neutron diffraction revealed the first time a trigonal-pyramidal hydride coordination mode in the AgCu3 environment of 2. 3 has no hydride and exhibits a mixed-valent [AuCu11 ]10+ metal core, making it a two-electron superatom.

Synthesis and Luminescence Properties of Two-Electron Bimetallic Cu-Ag and Cu-Au Nanoclusters via Copper Hydride Precursors.

The synthesis, structural characteristics, and photophysical properties of luminescent Cu-rich bimetallic superatomic clusters [Au@Cu12(S2CNnPr2)6(C≡CPh)4]+ (1a+), [Au@Cu12{S2P(OR)2}6(C≡CPh)4]+ (2+), (2a+ = iPr; 2b+ = nPr), [Au@Cu12{S2P(C2H4Ph)2}6(C≡CPh)4]+ (2c+), and [Ag@Cu12{S2P(OnPr)2}6(C≡CPh)4]+ (3+) were studied. Compositionally uniform clusters 1+-3+ were isolated from the reaction of dithiolato-stabilized, polyhydrido copper clusters with phenylacetylene in the presence of heterometal salts. By using X-ray diffraction, the structures of 1a+, 2a+, 2b+, and 3+ were able to be determined. ESI-mass spectrometry and elemental analysis confirmed their compositions and purity. The structural characteristics of these clusters are similar with respect to displaying gold (or silver)-centered Cu12 cuboctahedra surrounded by six dithiocarbamate/dithiophosph(in)ate and four alkynyl ligands. The doping of Au and Ag atoms into the polyhydrido copper nanoclusters significantly enhances their PL quantum yields from Ag@Cu12 (0.58%) to Au@Cu12 (55%) at ambient temperature in solution. In addition, the electrochemical properties of the new alloys were investigated by cyclic voltammetry.

Isolation and Structural Elucidation of 15-Nuclear Copper Dihydride Clusters: An Intermediate in the Formation of a Two-Electron Copper Superatom.

Highly reactive copper-dihydride clusters, [Cu15 (H)2 (S2 CNR2 )6 (C2 Ph)6 ](PF6 ) {R = n Bu (1H ), n Pr (2H ), i Bu (3H )}, are isolated during the reaction of [Cu28 H15 {S2 CNn Bu2 }12 ](PF6 ) with ten equivalents of phenylacetylene. They are found to be intermediates in the formation of the earlier reported two-electron superatom [Cu13 (S2 CNR2 )6 (C2 Ph)4 ]+ . Better yields are obtained by reacting dithiocarbamate sodium salts, [Cu(CH3 CN)4 ](PF6 ), BH4- and phenylacetylene. The presence of two hydrides in the isolated clusters is confirmed by the synthesis and characterization of its deuteride analogue [Cu15 (D)2 (S2 CNR2 )6 (C2 Ph)6 ]+ , and a single-crystal neutron structure of 2H . Structural characterization of 1H reveals a new bicapped icosahedral copper(I) cage encapsulating a linear copper dihydride (CuH2 )- unit. Reaction of 3H with Au(I) salts yields a highly luminescent [AuCu12 (S2 CNi Bu2 )6 (C2 Ph)4 ]+ cluster.

Evaluation of the prognostic value of fibrinolytic elements in invasive breast carcinoma patients.

Breast cancer (BrC) is one of the most serious oncological problems in the world. The aim of the study was to evaluate concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) and their ratios: t-PA/PAI-1 and PAI-1/t-PA in breast cancer patients and in healthy individuals and to estimate the ability of fibrinolytic parameters in predicting neoplasm disease and disease relapse. One hundred and five women were enrolled in the study, including 60 cases with primary BrC, (M0) and 45 healthy females. Follow-up was completed in all BrC patients with a 16.7% recurrence rate. An immunoassay of t-PA, PAI-1 in all cases was made as well as the immunohistochemistry of estrogen and progesterone receptors, human epidermal growth factor receptor 2, E-cadherin, and Ki-67 was performed in BrC subjects. A significantly higher PAI-1 concentration in breast cancer patients below the age of 55 than in controls was obtained. According to the ROC curve analysis, the PAI-1 concentration demonstrates the most accurate prognostic value with the cut-off point at 33.91 ng/ml, with 90% sensitivity and 36% specificity, which discriminates between controls and cancer patients. However, t-PA presents the highest area under the receiver-operating characteristic curves (AUCROC)=0.634 in predicting disease relapse with the cut-off value of 5.3 ng/ml. According to the Kaplan-Meier curves, a high concentration of t-PA (>5 ng/ml) and a lower PAI-1/t-PA ratio (<7.5) are associated with shorter survival. Evaluation of plasma t-PA and PAI-1 concentrations may deliver relevant prognostic information for breast cancer patients.

Copper Clusters Containing Hydrides in Trigonal Pyramidal Geometry.

Structurally precise copper hydrides [Cu11H2{S2P(OiPr)2}6(C≡CR)3], R = Ph (1), C6H4F (2), and C6H4OMe (3), were first synthesized from the polyhydrido copper cluster [Cu20H11{S2P(OiPr)2}9] with nine equivalents of terminal alkynes. Later, their isolated yields were significantly improved by direct synthesis from [Cu(CH3CN)4](PF6), [NH4][S2P(OiPr)2], NaBH4, and alkynes along with NEt3 in THF. 1, 2, and 3 were fully characterized by single-crystal X-ray diffraction, ESI-MS, and multinuclear NMR spectroscopy. All three clustershave 11 copper atoms, adopting 3,3,4,4,4-pentacapped trigonal prismatic geometry, with two hydrides inside the Cu11 cage, the position of which was ascertained by a single-crystal neutron diffraction structure of cluster 1 co-crystallized with a [Cu7(H){S2P(OiPr)2}6] (4) cluster. Six dithiophosphate and three alkynyl ligands stabilize the Cu11H2 core in which the two hydrides adopt a trigonal pyramidal coordination mode. This coordination mode is so far unprecedented for hydride. The 1H NMR resonance frequency of the two hydrides appears at 4.8 ppm, a value further confirmed by 2H NMR spectroscopy for their deuteride derivatives [Cu11(D)2{S2P(OiPr)2}6(C≡CR)3]. A DFT investigation allows understanding the bonding within this new type of copper(I) hydrides.

Heparanase link between vasculogenesis and angiogenesis as well as a predictive factor of a shorter survival rate.

Heparanase concentration is low in normal epithelia cells but its overexpression is reported in many carcinomas, including sarcomas and haematological malignancies. The purpose of this study was to investigate the association with selected angiogenic parameters as well as in the number of circulating endothelial progenitors (EPCs) in respect to low, moderate and high concentrations of heparanase. Also, we estimated the diagnostic usefulness of the heparanase concentration for disease recurrence prediction in breast cancer cases. Eighty-six patients with IA-IIB stage invasive breast carcinoma who passed a comprehensive clinicopathologic evaluation were included in the study. The median tumour diameter was 1.5 cm. Twenty cases showed lymph node metastasis (N1). Follow-up was completed in all patients a median follow-up was 33.5 months with a 11.6% recurrence rate. An immunoassay of selected angiogenic parameters, heparanase, as well as an immunohistochemistry of oestrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), Ki67 and E-cadherin was performed in all cases. Circulating EPCs were determined by flow cytometry. Higher levels of heparanase in oestrogen and progesterone receptor negative cancers than in positive ones were noted. A higher concentration of heparanase was observed in T2 cases than T1 subjects. Significant positive associations between circulating EPCs, soluble forms of VEGF receptors and increasing plasma levels of heparanase were obtained. Follow-up revealed a significantly higher incidence of disease relapse in breast cancer patients with high baseline concentrations of heparanase. Heparanase was the most accurate biomarker with an AUCROC = 0.72. The cut-off value of 213.74 pg/mL was identified in order to discriminate between disease recurrence patients and those without disease relapse. We suggest, that a high concentration of heparanase next to tumour size and oestrogen and progesterone receptor expression may serve as an indicator of a more an aggressive character of tumour cells and a shorter survival rate.

Synthesis of Bimetallic Copper-Rich Nanoclusters Encapsulating a Linear Palladium Dihydride Unit.

The structurally precise Cu-rich hydride nanoclusters [PdCu14 H2 (dtc/dtp)6 (C≡CPh)6 ] (dtc: di-butyldithiocarbamate (1); dtp: di-isopropyl dithiophosphate (2)) were synthesized from the reaction of polyhydrido copper clusters [Cu28 H15 (S2 CNn Bu2 )12 ]+ or [Cu20 H11 {S2 P(Oi Pr)2 }9 ] with phenyl acetylene in the presence of Pd(PPh3 )2 Cl2 . Their structures and compositions were determined by single-crystal X-ray diffraction and the results supported by ESI-mass spectrometry. Hydride positions in 1 were confirmed by single-crystal neutron diffraction. Each hydride is connected to one Pd0 and four CuI atoms in slightly distorted trigonalbipyramidal geometry. The anatomies of clusters 1 and 2 are very similar and DFT calculations allow rationalizing the interactions between the encapsulated [PdH2 ]2- unit and its Cu14 bicapped icosahedral cage. As a result, Pd has the highest coordination number (14) so far recorded.

Synthesis and structural characterization of inverse-coordination clusters from a two-electron superatomic copper nanocluster.

We have synthesized and structurally characterized a series of centred cuboctahedral copper clusters, namely [Cu13{S2CNR2}6{C[triple bond, length as m-dash]CR'}4](PF6), 1a-d (where a: R = n Bu, R' = CO2Me; b: R = n Bu, R' = CO2Et; c: R = iPr, R' = CO2Et; d: R = n Pr, R' = 3,5-(CF3)2C6H3); [Cu12(µ12-S){S2CNR2}6{C[triple bond, length as m-dash]CR'}4], 2a-c; [Cu12(µ12-Cl){S2CNR2}6{C[triple bond, length as m-dash]CR'}4](PF6), 3a-e (where e: R = n Bu, R' = Ph); [Cu12(µ12-Br){S2CN n Bu2}6{C[triple bond, length as m-dash]CPh}4](PF6), 4e; and [Cu12(µ12-Cl)(µ3-Cl){S2CN n Bu2}6{C[triple bond, length as m-dash]CCO2Me}3]+ 5a. Cluster 1a is the first structurally characterized copper cluster having a Cu13 centered cuboctahedral arrangement, a miniature of the bulk copper fcc structure. Furthermore, the partial Cu(0) character in the 2-electron superatoms 1 was confirmed by XANES. Inverse coordination clusters 2-5 are the first examples of copper clusters containing main group elements (Cl, Br, S) with a hyper-coordination number, twelve. A combined theoretical and experimental study was performed, which shows that the central copper (formally Cu1-) in nanoclusters 1 can be replaced by chalcogen/halogen atoms, resulting in the formation of clusters 2-5 which show enhanced luminescence properties and increase in the ionic component of the host-guest interaction as Br ≈ Cl > S > Cu, which is consistent with the Cu-X Wiberg indices. The new compounds have been characterized by ESI-MS, 1H, 13C NMR, IR, UV-visible, emission spectroscopy, and the structures 2a-b, 3d-e, 4e and 5a were established by X-ray diffraction analysis.

Synthesis of Two-Electron Bimetallic Cu-Ag and Cu-Au Clusters by using [Cu13 (S2 CNn Bu2 )6 (C≡CPh)4 ]+ as a Template.

Atomically precise Cu-rich bimetallic superatom clusters have been synthesized by adopting a galvanic exchange strategy. [Cu@Cu12 (S2 CNn Bu2 )6 (C≡CPh)4 ][CuCl2 ] (1) was used as a template to generate compositionally uniform clusters [M@Cu12 (S2 CNn Bu2 )6 (C≡CPh)4 ][CuCl2 ], where M=Ag (2), Au (3). Structures of 1, 2 and 3 were determined by single crystal X-ray diffraction and the results were supported by ESI-MS. The anatomies of clusters 1-3 are very similar, with a centred cuboctahedral cationic core that is surrounded by six di-butyldithiocarbamate (dtc) and four phenylacetylide ligands. The doped Ag and Au atoms were found to preferentially occupy the centre of the 13-atom cuboctahedral core. Experimental and theoretical analyses of the synthesized clusters revealed that both Ag and Au doping result in significant changes in cluster stability, optical characteristics and enhancement in luminescence properties.

Elevated plasma levels of tissue factor as a valuable diagnostic biomarker with relevant efficacy for prediction of breast cancer morbidity.

The aim of this study was to evaluate the concentrations of tissue factor (TF) and its inhibitor (TFPI), vascular endothelial growth factor A (VEGF-A), soluble forms of VEGF receptors type 1 and 2 (sVEGFR1 and aVEGFR2) in patients diagnosed with luminal A breast cancer (BrC) and in healthy individuals and to find associations of analyzed factors with demographic, clinical and pathological characteristics in a homogeneous breast cancer group. Study group consisted of 60 women aged 40 - 69 years, diagnosed with luminal-A subtype of BrC, without distant metastases (M0). Control group comprised 40 healthy women aged 45 - 63 years. Blood samples were collected from each patient in order to determine plasma levels of TF, TFPI, VEGF-A and sVEGFR1 and sVEGFR2. The examined parameters were measured by enzyme-linked immunosorbent assay (ELISA). The capacity of angiogenic and hemostatic parameters in predicting neoplasm disease was analyzed using receiver operating characteristic (ROC) curve analysis. According to ROC curve analysis, the optimum cut-off point for TF was 304.58 pg/ml, with 100% sensitivity and 100% specificity, which was calculated to discriminate between controls and malignancy patients. In luminal A BrC patients there were significantly higher concentrations of VEGF-A and TF than in controls. On the contrast the levels of sVEGF receptors type 1 and 2 as well as TFPI in luminal-A BrC cases were significantly lower in respect to healthy volunteers. Levels of examined factors in the study group varied depending on age, menopausal status, lymph node involvement and histological type. We concluded that altered levels of examined factors in patients diagnosed with luminal-A breast cancer indicate increased activation of angiogenesis and hemostasis. The results obtained may be indicative of a mutual connection between angiogenesis and hemostasis processes in tumor development and progression. Clinical and pathological parameters may possibly affect levels of angiogenic and coagulation factors.

Increased number of endothelial progenitors in peripheral blood as a possible early marker of tumour growth in post-menopausal breast cancer patients.

The aim of the study was to evaluate the number of circulating endothelial progenitor cells (circulating EPCs) in the blood of patients diagnosed with breast cancer and to make an attempt at finding associations with the number of circulating EPCs and selected clinic-pathological factors; TNM and histological grading, molecular subtype of breast cancer, hormonal status, the expression of Ki-67 and the size of tumour. The study involved 96 Caucasian ethnicity post-menopausal women. Sixty-six women aged 48 - 63 (mean age 55) with breast cancer diagnosis without distant metastases (M0). The median value of the tumour diameter was 1.51 cm. The control group consisted of 30 healthy, non-smoking, post-menopausal women, mean age 49, range 44 - 54 years of age. The exclusion criteria for all the participants were hypertension, hyperlipidaemia, and hyperglycaemia, acute and chronic infection. With regard to the fresh blood samples the number of circulating endothelial progenitors was determined using flow cytometry. The fluorescence of 100,000 cells was measured during the analysis. Circulating EPCs were identified with the immune-phenotype CD45-, CD34+, CD133+, CD31+. A significantly higher number of circulating EPCs in the study group, as compared to the controls (P = 0.0001) and a significantly higher number of circulating EPCs in women over 60 with breast cancer than in the younger women (P = 0.0029) were reported. A positive correlation was noted between circulating EPCs and age as well as between circulating EPCs and HER-2 (P = 0.0231, P = 0.0414, respectively), and a negative correlation between circulating EPCs and histological grading of breast cancer (P = 0.0272). The study has shown a higher number of circulating EPCs in breast cancer patients, which indicates stimulation of neovascularization. Additionally, since bone morrow-derived circulating EPCs are more intensively mobilised in older and overweight breast cancer patients, we can speculate that more aggressive neo-angiogenesis can occur in those patients.