Sites of Failure in Breast Cancer Patients with Extracapsular Invasion of Axillary Lymph Node Metastases: No Need for Axillary Irradiation?!

Background and Purpose:: Extracapsular spread (ECS) is frequent, but the specific sites of relapse are seldom given in the literature. In this study it was evaluated, if ECS might be an indicator for axillary irradiation. Patients and Methods:: After a retrospective review of pathology reports, the information about ECS was available in 254 lymph node-positive patients: ECS was absent in 34% (ECS-negative; n = 87) and present in 66% (ECS-positive; n = 167). All patients were irradiated locally, 78 patients got periclavicular and 74 axillary irradiation (median total dose: 50.4 Gy). 240/254 patients (94.5%) received systemic treatment/s. Mean follow-up was 46 months. Results:: The regional relapse rate was 4.6% without ECS versus 9.6% with ECS. The 5-year axillary relapse-free survival was 100% in ECS-negative and 90% in ECS-positive patients (p = 0.01), whereas corresponding values for periclavicular relapse-free survival (with ECS: 91% ± 4%; without ECS: 94% ± 3%; p = 0.77) and local relapse-free survival (with ECS: 86% ± 4%; without ECS: 91% ± 3%; p = 0.69) were not significantly different. χ2-tests revealed a high correlation of ECS with T-stage, number of positive lymph nodes and progesterone receptor status, comparisons with estrogen receptor, grade, or age were not significant. In multivariate analysis number of positive lymph nodes was solely significant for regional failure. Dividing the patients into those with one to three and those with four or more positive lymph nodes, ECS lost its significance for axillary failure. Conclusion:: ECS was accompanied by an enhanced axillary failure rate in univariate analysis, which was no longer true after adjusting for the number of positive lymph node

Accurate gas-phase structure of para -dioxane by fs Raman rotational coherence spectroscopy and ab initio calculations

p-Dioxane is non-polar, hence its rotational constants cannot be determined by microwave rotationalcoherence spectroscopy (RCS). We perform high-resolution gas-phase rotational spectroscopy ofpara-dioxane-h8and -d8using femtosecond time-resolved Raman RCS in a gas cell atT= 293 Kand in a pulsed supersonic jet atT∼130 K. The inertial tensor ofp-dioxane-h8is strongly asym-metric, leading to a large number of asymmetry transients in its RCS spectrum. In contrast, thed8-isotopomer is a near-oblate symmetric top that exhibits a much more regular RCS spectrum withfew asymmetry transients. Fitting the fs Raman RCS transients ofp-dioxane-h8to an asymmetric-top model yields the ground-state rotational constantsA0= 5084.4(5) MHz,B0= 4684(1) MHz,C0= 2744.7(8) MHz, and (A0+ B0)/2 = 4884.5(7) MHz (±1σ). The analogous values forp-dioxane-d8areA0= 4083(2) MHz,B0= 3925(4) MHz,C0= 2347.1(6) MHz, and (A0+ B0)/2 = 4002.4(6) MHz.We determine the molecular structure with a semi-experimental approach involving the highly corre-lated coupled-cluster singles, doubles and iterated triples method and the cc-pCVXZ basis set seriesfrom double- to quadruple-zeta (X = D, T, Q). Combining the calculated vibrationally averaged rotational constants Acalc0(X),Bcalc0(X),Ccalc0(X) for increasing basis-set sizeXwith non-linear extrap-olation to the experimental constantsAexp0,Bexp0,Cexp0allows to determine the equilibrium groundstate structure ofp-dioxane. For instance, the equilibrium C–C and C–O bond lengths arere(CC)= 1.5135(3) Å andre(CO) = 1.4168(4) Å, and the four axial C–H bond lengths are 0.008 Å longerthan the four equatorial ones. The latter is ascribed to thetrans-effect (anomeric effect), i.e., the partialdelocalization of the electron lone-pairs on the O atoms that are orientedtrans, relative to the axialCH bonds

Spin cascade and doming in ferric hemes: Femtosecond X-ray absorption and X-ray emission studies

The structure-function relationship is at the heart of biology, and major protein deformations are correlated to specific functions. For ferrous heme proteins, doming is associated with the respiratory function in hemoglobin and myoglobins. Cytochrome c (Cyt c) has evolved to become an important electron-transfer protein in humans. In its ferrous form, it undergoes ligand release and doming upon photoexcitation, but its ferric form does not release the distal ligand, while the return to the ground state has been attributed to thermal relaxation. Here, by combining femtosecond Fe K-alpha and K-beta X-ray emission spectroscopy (XES) with Fe K-edge X-ray absorption near-edge structure (XANES), we demonstrate that the photocycle of ferric Cyt c is entirely due to a cascade among excited spin states of the iron ion, causing the ferric heme to undergo doming, which we identify. We also argue that this pattern is common to a wide diversity of ferric heme proteins, raising the question of the biological relevance of doming in such proteins

An excitonic coupling to the haem governs the ultrafast tryptophan fluorescence decay of tryptophan in Cytochrome c

Processed XAS and XES data from the manuscript "An excitonic coupling to the harm governs the ultrafast tryptophan fluorescence decay in Cytochrome c" and corresponding scripts used to analyse the data and produce the figures. Raw data generated at SwissFEL (PSI) and European XFE

Ultrafast Energy Transfer from Photoexcited Tryptophan to the Haem in Cytochrome c

We report femtosecond Fe K-edge absorption (XAS) and nonresonant X-ray emission (XES) spectra of ferric cytochrome C (Cyt c) upon excitation of the haem (>300 nm) or mixed excitation of the haem and tryptophan (<300 nm). The XAS and XES transients obtained in both excitation energy ranges show no evidence for electron transfer processes between photoexcited tryptophan (Trp) and the haem, but rather an ultrafast energy transfer, in agreement with previous ultrafast optical fluorescence and transient absorption studies. The reported (J. Phys. Chem. B 2011, 115 (46), 13723-13730) decay times of Trp fluorescence in ferrous (∼350 fs) and ferric (∼700 fs) Cyt c are among the shortest ever reported for Trp in a protein. The observed time scales cannot be rationalized in terms of Förster or Dexter energy transfer mechanisms and call for a more thorough theoretical investigation