A Pilot Evaluation of Alternating Preoperative Chemotherapy in the Management of Patiens with Locoregionally Advanced Breast Carcinoma

BACKGROUND: This prospective trial was conducted to evaluate the outcome of patients treated with preoperative and post operative chemotherapy, mastectomy, and irradiation for locoregionally advanced breast carcinoma. METHODS: Between June 1986 and September 1990, 71 patients received 2 cycles of doxorubicin that alternated with 2 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil prior to mastectomy; irradiation was administered when the tumor was not amenable to surgical resection. Additional chemotherapy and tamoxifen, in hormone receptor-positive tumors, was used after mastectomy. Post-operative irradiation was given on a selective basis for patients at high risk for locoregional disease recurrence. RESULTS: Although 5 patients (7%) had disease progression, clinical partial or complete tumor response to preoperative chemotherapy was noted in 46 patients (65%). Sixty-eight patients (96%) underwent mastectomy. With a median follow-up of 52 months, the relapse-free and overall survival rates at 5 years were 42% and 57% respectively. Locoregional tumor recurrence occurred in 14 patients (20%), and 28 patients (39%) developed metastatic disease. Menopausal status, clinical presentation (noninflammatory vs. inflammatory), and American Joint Committee on Cancer clinical stage were independent covariates associated with patient outcome. CONCLUSIONS: Preoperative alternating chemotherapy, with the selective use of irradiation, resulted in significant locoregional disease regression and the successful integration of mastectomy into the therapeutic strategy. Locoregional tumor control and relapse-free and overall survival estimates for the approach described herein compared favorably with other comtemporary reports for this condition

Sites of strong Rec12/Spo11 binding in the fission yeast genome are associated with meiotic recombination and with centromeres

Meiotic recombination arises from Rec12/Spo11-dependent formation of DNA double-strand breaks (DSBs) and their subsequent repair. We identified Rec12-binding peaks across the S. pombe genome using chromatin immunoprecipitation after reversible formaldehyde cross-linking combined with whole-genome DNA microarrays. Strong Rec12-binding coincided with previously identified DSBs at the recombination hotspots ura4A, mbs1, and mbs2, and correlated with DSB formation at a new site. In addition, Rec12-binding corresponded to eight novel conversion hotspots and correlated with crossover density in segments of chromosome I. Notably, Rec12-binding inversely correlated with GC content, contrary to findings in S. cerevisiae. Although both replication origins and Rec12-binding sites preferred AT-rich gene-free regions, they seemed to exclude each other. We also uncovered a connection between binding sites of Rec12 and meiotic cohesin Rec8. Rec12-binding peaks lay often within 2.5 kb of a Rec8-binding peak. Rec12-binding showed preference for large intergenic regions and was found to bind preferentially near to genes expressed strongly in meiosis. Surprisingly, Rec12-binding was also detected in centromeric core regions, which raises the intriguing possibility that Rec12 plays additional roles in meiotic chromosome dynamics

Erosion, screening, and migration of tungsten in the JET divertor

The erosion of tungsten (W), induced by the bombardment of plasma and impurity particles, determines the lifetime of plasma-facing components as well as impacting on plasma performance by the influx of W into the confined region. The screening of W by the divertor and the transport of W in the plasma determines largely the W content in the plasma core, but the W source strength itself has a vital impact on this process. The JET tokamak experiment provides access to a large set of W erosion-determining parameters and permits a detailed description of the W source in the divertor closest to the ITER one: (i) effective sputtering yields and fluxes as function of impact energy of intrinsic (Be, C) and extrinsic (Ne, N) impurities as well as hydrogenic isotopes (H, D) are determined and predictions for the tritium (T) isotope are made. This includes the quantification of intra- and inter-edge localised mode (ELM) contributions to the total W source in H-mode plasmas which vary owing to the complex flux compositions and energy distributions in the corresponding phases. The sputtering threshold behaviour and the spectroscopic composition analysis provides an insight in the dominating species and plasma phases causing W erosion. (ii) The interplay between the net and gross W erosion source is discussed considering (prompt) re-deposition, thus, the immediate return of W ions back to the surface due to their large Larmor radius, and surface roughness, thus, the difference between smooth bulk-W and rough W-coating components used in the JET divertor. Both effects impact on the balance equation of local W erosion and deposition. (iii) Post-mortem analysis reveals the net erosion/deposition pattern and the W migration paths over long periods of plasma operation identifying the net W transport to remote areas. This W transport is related to the divertor plasma regime, e.g. attached operation with high impact energies of impinging particles or detached operation, as well as to the applied magnetic configuration in the divertor, e.g. close divertor with good geometrical screening of W or open divertor configuration with poor screening.JET equipped with the ITER-like wall (ILW) provided unique access to the net W erosion rate within a series of 151 subsequent H-mode discharges (magnetic field: B-t = 2.0 T, plasma current: I-p = 2.0 MA, auxiliary power P-aux = 12 MW) in one magnetic configuration accumulating 900 s of plasma with particle fluences in the range of 5-6 x 10(26) D+ m(-2) in the semi-detached inner and attached outer divertor leg. The comparison of W spectroscopy in the intra-ELM and inter-ELM phases with post-mortem analysis of W marker tiles provides a set of gross and net W erosion values at the outer target plate. ERO code simulations are applied to both divertor leg conditions and reproduce the erosion/deposition pattern as well as confirm the high experimentally observed prompt W re-deposition factors of more than 95% in the intra- and inter-ELM phase of the unseeded deuterium H-mode plasma. Conclusions to the expected divertor conditions in ITER as well as to the JET operation in the DT plasma mixture are drawn on basis of this unique benchmark experiment

Long-lived coupled peeling ballooning modes preceding ELMs on JET

In some JET discharges, type-I edge localised modes (ELMs) are preceded by a class of low-frequency oscillations (Perez et al 2004 Nucl. Fusion 44 609). While in many cases the ELM is triggered during the growth phase of this oscillation, it is also observed that this type of oscillation can saturate and last for several tens of ms until an ELM occurs. In order to identify the nature of these modes, a wide pre-ELM oscillation database, including detailed pedestal profile information, has been assembled and analysed in terms of MHD stability parameters. The existence domain of these pre-ELM oscillations and the statistical distribution of toroidal mode numbers (n) up to n = 16 have been mapped in ballooning alpha (alpha(ball)) and either edge current density (J(edge)) or pedestal collisionality (nu(ee,ped)*) coordinates and compared to linear MHD stability predictions. The pre-ELM oscillations are reliably observed when the J/alpha ratio is high enough for the pedestal to access the coupled peeling-ballooning (PB) domain (aka stability nose). Conversely, when the pedestal is found to be in or near the high-n ballooning domain (which is at low J/alpha ratio), ELMs are usually triggered promptly, i.e. with no detectable pre-ELM oscillations, or with pre-ELM oscillations only observable on ECE whose n appears to be too high to be resolved by the magnetics. Individual discharges can sometimes exhibit a fairly wide range of pre-ELM mode numbers, but for a wider database, the statistical n-number domains are found to be well ordered along the J - alpha stability boundary and behave as expected from PB theory: the higher the J/alpha ratio, the lower the mode's measured n tends to be. Within the measurement uncertainties, the measured n is usually found to be compatible with the most unstable n predicted by the linear stability code MISHKA1. These results confirm the earlier hypothesis that these modes are coupled peeling-ballooning modes, and extend and generalise to higher-mode numbers the work by Huysmans et al (1998 Nucl. Fusion 38 179), who identified the lowest n modes as pure external kink modes. Since the destabilisation of PB modes is widely accepted to give rise to ELMs, the mode saturation and delayed ELM triggering that is sometimes observed is rather unexpected. Possibilities to reconcile the extended lifetime of these modes with current ELM models are briefly discussed, but will require further investigation