Pregnancy-associated breast cancer - Special features in diagnosis and treatment

For obvious psychological reasons it is difficult to associate pregnancy - a life-giving period of our existence with life-threatening malignancies. Symptoms pointing to malignancy are often ignored by both patients and physicians, and this, together with the greater difficulty of diagnostic imaging, probably results in the proven delay in the detection of breast cancers during pregnancy. The diagnosis and treatment of breast cancer are becoming more and more important, as the fulfillment of the desire to have children is increasingly postponed until a later age associated with a higher risk of carcinoma, and improved cure rates of solid tumors no longer exclude subsequent pregnancies. The following article summarizes the special features of the diagnosis and primary therapy of pregnancy-associated breast cancer with particular consideration of cytostatic therapy

In vitro synchrotron-based radiography of micro-gap formation at the implant–abutment interface of two-piece dental implants

Micro-radiography using hard X-ray synchrotron radiation is the first potential tool to allow an evaluation of the mechanical behavior of the dental implant–abutment complex during force application, thus enabling the enhancement of the design of dental implants which has been based on theoretical analysis to date

Primary radiation damage in bone evolves via collagen destruction by photoelectrons and secondary emission self-absorption

X-rays are invaluable for imaging and sterilization of bones, yet the resulting ionization and primary radiation damage mechanisms are poorly understood. Here we monitor in-situ collagen backbone degradation in dry bones using second-harmonic-generation and X-ray diffraction. Collagen breaks down by cascades of photon-electron excitations, enhanced by the presence of mineral nanoparticles. We observe protein disintegration with increasing exposure, detected as residual strain relaxation in pre-stressed apatite nanocrystals. Damage rapidly grows from the onset of irradiation, suggesting that there is no minimal ‘safe’ dose that bone collagen can sustain. Ionization of calcium and phosphorous in the nanocrystals yields fluorescence and high energy electrons giving rise to structural damage that spreads beyond regions directly illuminated by the incident radiation. Our findings highlight photoelectrons as major agents of damage to bone collagen with implications to all situations where bones are irradiated by hard X-rays and in particular for small-beam mineralized collagen fiber investigations

The rupture of a single liquid aluminium alloy film

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The present study is based on the idea of understanding the rupture of films in metal foams by studying free standing metallic films as a model system. Liquid dynamics, the velocity of the rupturing material as well as the behaviour of ceramic particles inside the melt were analysed optically ex situ and by synchrotron X-ray radiography in situ. It was found that the resistance of films to rupture is mainly based on the interaction between solid particles and an immobile oxide skin, the formation of which depends on the oxygen content of the surrounding atmosphere and the presence of magnesium

Bicyclic imidazolium inhibitors of Gli transcription factor activity

Gli transcription factors within the Hedgehog (Hh) signaling pathway direct key events in mammalian development and promote a number of human cancers. Current therapies for Gli‐driven tumors target Smoothened (SMO), a G protein‐coupled receptor‐like protein that functions upstream in the Hh pathway. Although these drugs can have remarkable clinical efficacy, mutations in SMO and downstream Hh pathway components frequently lead to chemoresistance. In principle, therapies that act at the level of Gli proteins, through direct or indirect mechanisms, would be more efficacious. We therefore conducted a screen of 325,120 compounds for their ability to block the constitutive Gli activity induced by loss of Suppressor of Fused (SUFU), a scaffolding protein that directly inhibits Gli function. Our studies reveal a family of bicyclic imidazolium derivatives that can inhibit Gli‐dependent transcription without affecting the ciliary trafficking or proteolytic processing of these transcription factors. We anticipate that these chemical antagonists will be valuable tools for investigating the mechanisms of Gli regulation and developing new strategies for targeting Gli‐driven cancers

Fabrication, Dynamics, and Electrical Properties of Insulated SPM Probes for Electrical and Electromechanical Imaging in Liquids

Insulated cantilever probes with a high aspect ratio conducting apex have been fabricated and their dynamic and electrical properties analyzed. The cantilevers were coated with silicon dioxide and a via was fabricated through the oxide at the tip apex and backfilled with tungsten to create an insulated probe with a conducting tip. The stiffness and Q-factor of the cantilevers increased after the modifications and their resonances shifted to higher frequencies. The coupling strength between the cantilever and the coating are determined. The applications to conductive and electromechanical imaging of ferroelectric domains are illustrated, and a probe apex repair process is demonstrated.Comment: 3 fig

Prognostic relevance of disseminated tumor cells in the bone marrow and biological factors of 265 primary breast carcinomas

Introduction The prognostic significance of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients has been demonstrated in many studies. Yet, it is not clear which of the primary tumors' biological factors predict hematogenous dissemination. We therefore examined `tissue micro arrays' (TMAs) of 265 primary breast carcinomas from patients with known bone marrow ( BM) status for HER2, Topoisomerase IIa ( Top IIa), Ki 67, and p53. Methods BM analysis was performed by cytospin preparation and immunocytochemical staining for cytokeratin (CK). TMAs were examined by immunohistochemistry (IHC) for HER2, Top IIa, Ki 67 and p53, and fluorescence in situ hybridization ( FISH) for HER2. Results HER2 ( 2+/ 3+) was positive in 35/167 (21%) cases ( FISH 24.3%), Top IIa (> 10%) in 87/187 (46%), Ki 67 in 52/ 184 (28%) and p53 (> 5%) in 61/174 cases (34%). Of 265 patients, 68 (25.7%) showed DTC-BM with a median of 2/2 x 106 cells ( 1 to 1,500). None of the examined factors significantly predicted BM positivity. Significant correlation was seen between HER2 IHC and Top IIa ( p = 0.06), Ki 67 ( p = 0.031), and p53 ( p <.001). Top IIa correlated with Ki 67 and p53, and Ki 67 also with p53 ( p = 0.004). After a median follow-up of 60.5 months ( 7 to 255), the presence of DTC-BM showed prognostic relevance for overall survival ( p = 0.03), whereas HER2 ( IHC, p = 0.04; FISH, p = 0.03) and Ki 67 ( p = 0.04) correlated with disease free survival, and HER2 with distant disease free survival ( IHC, p = 0.06; FISH, p = 0.05). Discussion The congruence of the examined factors' expression rates indicates a causal line of suppressor, proliferation, and mitosis markers, and growth factor receptors. Hematogenous tumor cell spread seems to be an independent process. The examination of these factors on DTC-BM is the aim of ongoing research

Toxicity Analysis in the ADEBAR Trial: Sequential Anthracycline-Taxane Therapy Compared with FEC120 for the Adjuvant Treatment of High-Risk Breast Cancer

Background: Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer. Patients and Methods: The ADEBAR trial was a multicenter phase Ill trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4x epirubicin (90 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 3 weeks (q3w), followed by 4x docetaxel (100 mg/m(2)) q3w (EC-Doc arm), or 6x epirubicin (60 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1 and 8 and cyclophosphamide (75 mg/m(2)) on days 1-14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility. Results: Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009). Conclusion: The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy

Luminescence Properties of Thin Film Ta2 Zn3 O8 and Mn Doped Ta2 Zn3 O8

Blue luminescence from TaZZn30g and green luminescence from Mn doped TaZZn30g has been observed under low voltage cathodoluminescent excitation, In this article , the luminescence mechanisms of TaZZn30g and Mn doped TaZZn30 g are discussed in detail. The results suggest that the intrinsic blue luminescence of TaZZn30g results from a metal-to-ligand transition, whereas the green luminescence of Mn doped TaZZn30g results from the Mn 4T 1-6A I transition. The suppression of the blue intrinsic luminescence in Mn doped TaZZn30g suggests that efficient energy transfer from the host material to the Mn occurs. This energy transfer phenomenon is also discussed by comparing the photoluminescence excitation spectra of both thin film materials. Finally, the relative efficiency versus voltage and current density is demonstrated and discussed pertaining to field emission device operation