Background
The protease uPA and its inhibitor PAI-1 play major roles in hemostasis and are also involved in cancer progression. This is mainly caused by their ability to degrade extracellular ...matrix-facilitating tumor cell migration. This study aimed to investigate the impact of uPA/PAI-1 and disseminated cytokeratin-positive cells (dCK+) on the outcome and the existence of synergistic effects.
Methods
We retrospectively analyzed a cohort of 480 breast cancer cases with known uPA/PAI-1 and dCK+ status. uPA/PAI-1 was tested on fresh tumor samples using a commercial ELISA test. Bone marrow aspirates were investigated immunocytochemically for CK18.
Results
DCK+ cells were identified in 23% of cases. uPA positivity was significantly associated with the occurrence of dCK+ cells (P = 0.028). uPA and PAI-1 were significantly associated with outcome in the subgroup of early-stage cases without chemotherapy. DCK+ cells alone were not prognostic. However, we found synergistic effects. In the subgroup of node-negative cases with and without chemotherapy, the prognostic impact of uPA and PAI-1 was enhanced in cases with additional dCK-positivity (triple +). In cases without chemotherapy, triple-positive status was independently prognostic (HR: 9.3 CI: 1.1–75) next to T stage.
Conclusions
uPA and PAI-1 seem to influence the metastatic potential of dCK+ cells, which underlines its important role in tumor progression.
The 5th International Consensus Conference for Advanced
Breast Cancer (ABC5) took place on November 14–16, 2019,
in Lisbon, Portugal. Its aim is to standardize the treatment of
advanced breast cancer ...based on the available evidence and
to ensure that all breast cancer patients worldwide receive
adequate treatment and access to new therapies. This year,
the conference focused on developments and study results
in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the
world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a
working group of German breast cancer experts comments
on the results of the on-site ABC5 consensus votes by ABC
panelists regarding their applicability for routine treatment
in Germany. These comments take the recommendations of
the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie;
AGO) into account. The report and assessment presented
here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in
Annals of Oncology and The Breast.
In the coming decades, East Asian economies must face the challenges of an increasingly globalized marketplace. This book explores the changing parameters of competition in East Asia, and argues that ...success ultimately will depend on the ability of the region’s firms to harness the potential of global production networks and to build their own innovative capability. Presenting the latest findings on global production networks and the evolution of technological capabilities, it provides researchers, students, and policymakers with in-depth information and analysis on key issues related to growth and development in East Asia. East Asian firms must not only achieve greater efficiency but also become more innovative, offering differentiated products in order to vie with other first-tier suppliers of multinational corporations. These firms will also need to develop a technological edge if they are to compete with corporations from the leading OECD countries and form their own global production networks. Global Production Networking and Technological Change in East Asia argues that a development strategy linked to technological advance will be necessary to foster the growth of innovative national firms that can remain competitive in global markets.
The coordinatively unsaturated dinickel(II) complex (L2)Ni2(BPh4)2 (2), where (L2)2− represents the dianionic form of the 'N4S2' ligand ...N,N′‐bis(2‐thio‐3‐aminomethyl‐5‐tert‐butylbenzyl)propane‐1,3‐diamine), has been investigated with respect to its ability to function as a building block for the preparation of polynuclear nickel complexes with a high‐spin ground state. Treatment of 2 with pyridazine (pydz) followed by addition of two equivalents of NH4SCN afforded the dinuclear μ‐pyridazine complex (L2)Ni2(μ‐pydz)(NCS)2 (4). The reaction of 2 with pyridazine and NaN3 in a 1:1:1 molar ratio gave the tetranuclear nickel(II) complex {(L2)Ni2(μ‐pydz)(N3)}2(BPh4)2 (5). Both complexes have been characterized by X‐ray crystallography and variable‐temperature magnetic susceptibility studies. In complex 4 two fac‐(SCN)N2NiII units are linked by two thiophenolate sulfur atoms and a μ‐pydz ligand to give a (SCN)N2Ni(μ‐S)2(μ‐pydz)NiN2(NCS) core structure with a pseudoconfacial bioctahedral geometry. The two NCS− groups occupy opposite coordination sites, each is in a cis position to the pydz bridge. Analyses of the susceptibility data indicate the presence of an intramolecular ferromagnetic exchange interaction between the two NiII (S=1) ions. Complex 5 is composed of two binuclear (L2)Ni2(μ‐pydz)2+ subunits which are linked by two azide ions to give a rectangular array of four six‐coordinate NiII ions. The binuclear (L2)Ni2(μ‐pydz)2+ fragments in 4 and 5 are isostructural. Analyses of the susceptibility data of 5 reveal ferromagnetic exchange interactions between the NiII ions of the binuclear subunit as well as for the μ1,3‐N3‐bridged NiII ions. Thus, compound 4 has an S=2 ground state, whereas in 5 it is S=4.
A coordinatively unsaturated NiII2 complex 1 with an S=2 pair state is used as a building block for the preparation of the novel tetranuclear nickel(II) complex 2 with an S=4 ground state.
A series of dinickel(II) complexes with the 24‐membered macrocyclic hexaazadithiophenol ligand H2LMe was prepared and examined. The doubly deprotonated form (LMe)2− forms complexes of the type ...(LMe)Ni${{{\rm II}\hfill \atop 2\hfill}}$(μ‐L′)n+ with a bioctahedral N3NiII(μ‐SR)2(μ‐L′)NiIIN3 core and an overall calixarene‐like structure. The bridging coordination site L′ is accessible for a wide range of exogenous coligands. In this study L′=NO3−, NO2−, N3−, N2H4, pyrazolate (pz), pyridazine (pydz), phthalazine (phtz), and benzoate (OBz). Crystallographic studies reveal that each substrate binds in a distinct fashion to the (LMe)Ni22+ portion: NO2−, N2H4, pz, pydz, and phtz form μ1,2‐bridges, whereas NO3−, N3−, and OBz− are μ1,3‐bridging. These distinctive binding motifs and the fact that some of the coligands adopt unusual conformations is discussed in terms of complementary host–guest interactions and the size and form of the binding pocket of the (LMe)Ni22+ fragment. UV/Vis and electrochemical studies reveal that the solid‐state structures are retained in the solution state. The relative stabilities of the complexes indicate that the (LMe)Ni22+ fragment binds anionic coligands preferentially over neutral ones and strong‐field ligands over weak‐field ligands. Secondary van der Waals interactions also contribute to the stability of the complexes. Intramolecular ferromagnetic exchange interactions are present in the nitrito‐, pyridazine‐, and the benzoato‐bridged complexes where J=+6.7, +3.5, and +5.8 cm−1 (H=−2 JS1S2, S1=S2=1) as indicated by magnetic susceptibility data taken from 300 to 2 K. In contrast, the azido bridge in (LMe)Ni2(μ1,3‐N3)+ results in an antiferromagnetic exchange interaction J=−46.7 cm−1. An explanation for this difference is qualitatively discussed in terms of bonding differences.
Accommodating capsules! The capability of the dinuclear complex fragment (LMe)Ni22+ to accommodate a range of small molecules L′ in its bowl‐shaped cavity is demonstrated herein (see picture). Owing to the confined environment in the binding pocket only one of possible coordination modes of L′ is realized. The coligands influence many properties of the dinuclear complex fragment, such as complex stability, redox potential, and spin ground state.
Abstract
A series of dinickel(
II
) complexes with the 24‐membered macrocyclic hexaazadithiophenol ligand H
2
L
Me
was prepared and examined. The doubly deprotonated form (L
Me
)
2−
forms complexes ...of the type (L
Me
)Ni
${{{\rm II}\hfill \atop 2\hfill}}$
(μ‐L′)
n
+
with a bioctahedral N
3
Ni
II
(μ‐SR)
2
(μ‐L′)Ni
II
N
3
core and an overall calixarene‐like structure. The bridging coordination site L′ is accessible for a wide range of exogenous coligands. In this study L′=NO
3
−
, NO
2
−
, N
3
−
, N
2
H
4
, pyrazolate (pz), pyridazine (pydz), phthalazine (phtz), and benzoate (OBz). Crystallographic studies reveal that each substrate binds in a distinct fashion to the (L
Me
)Ni
2
2+
portion: NO
2
−
, N
2
H
4
, pz, pydz, and phtz form μ
1,2
‐bridges, whereas NO
3
−
, N
3
−
, and OBz
−
are μ
1,3
‐bridging. These distinctive binding motifs and the fact that some of the coligands adopt unusual conformations is discussed in terms of complementary host–guest interactions and the size and form of the binding pocket of the (L
Me
)Ni
2
2+
fragment. UV/Vis and electrochemical studies reveal that the solid‐state structures are retained in the solution state. The relative stabilities of the complexes indicate that the (L
Me
)Ni
2
2+
fragment binds anionic coligands preferentially over neutral ones and strong‐field ligands over weak‐field ligands. Secondary van der Waals interactions also contribute to the stability of the complexes. Intramolecular ferromagnetic exchange interactions are present in the nitrito‐, pyridazine‐, and the benzoato‐bridged complexes where
J
=+6.7, +3.5, and +5.8 cm
−1
(
H
=−2
J
S
1
S
2
, S
1
=S
2
=1) as indicated by magnetic susceptibility data taken from 300 to 2 K. In contrast, the azido bridge in (L
Me
)Ni
2
(μ
1,3
‐N
3
)
+
results in an antiferromagnetic exchange interaction
J
=−46.7 cm
−1
. An explanation for this difference is qualitatively discussed in terms of bonding differences.
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