Current medical treatment of estrogen receptor-positive breast cancer

Approximately 80% of breast cancers (BC) are estrogen receptor (ER)-positive and thus endocrine therapy (ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of (i) ovarian function suppression (OFS), usually obtained using gonadotropin-releasing hormone agonists (GnRHa), (ii) selective estrogen receptor modulators or down-regulators (SERMs or SERDs), (iii) aromatase inhibitors (AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs (i.e. tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs (i.e. fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type I are permanent steroidal inhibitors of aromatase, while type II are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs (i.e. anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors (palbociclib) and mammalian target of rapamycin (mTOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness

Longitudinal spin Seebeck coefficient: heat flux vs. temperature difference method

The determination of the longitudinal spin Seebeck effect (LSSE) coefficient is currently plagued by a large uncertainty due to the poor reproducibility of the experimental conditions used in its measurement. In this work we present a detailed analysis of two different methods used for the determination of the LSSE coefficient. We have performed LSSE experiments in different laboratories, by using different setups and employing both the temperature difference method and the heat flux method. We found that the lack of reproducibility can be mainly attributed to the thermal contact resistance between the sample and the thermal baths which generate the temperature gradient. Due to the variation of the thermal resistance, we found that the scaling of the LSSE voltage to the heat flux through the sample rather than to the temperature difference across the sample greatly reduces the uncertainty. The characteristics of a single YIG/Pt LSSE device obtained with two different setups was $(1.143\pm0.007)\cdot 10^{-7}$ Vm/W and $(1.101\pm0.015)\cdot 10^{-7}$ Vm/W with the heat flux method and $(2.313\pm0.017)\cdot 10^{-7}$ V/K and $(4.956\pm0.005)\cdot 10^{-7}$ V/K with the temperature difference method. This shows that systematic errors can be considerably reduced with the heat flux method.Comment: PDFLaTeX, 10 pages, 6 figure

Active shape correction of a thin glass/plastic X-ray mirror

Optics for future X-ray telescopes will be characterized by very large aperture and focal length, and will be made of lightweight materials like glass or plastic in order to keep the total mass within acceptable limits. Optics based on thin slumped glass foils are currently in use in the NuSTAR telescope and are being developed at various institutes like INAF/OAB, aiming at improving the angular resolution to a few arcsec HEW. Another possibility would be the use of thin plastic foils, being developed at SAO and the Palermo University. Even if relevant progresses in the achieved angular resolution were recently made, a viable possibility to further improve the mirror figure would be the application of piezoelectric actuators onto the non-optical side of the mirrors. In fact, thin mirrors are prone to deform, so they require a careful integration to avoid deformations and even correct forming errors. This however offers the possibility to actively correct the residual deformation. Even if other groups are already at work on this idea, we are pursuing the concept of active integration of thin glass or plastic foils with piezoelectric patches, fed by voltages driven by the feedback provided by X-rays, in intra-focal setup at the XACT facility at INAF/OAPA. In this work, we show the preliminary simulations and the first steps taken in this project

TBA-like equations and Casimir effect in (non-)perturbative AdS/CFT

We consider high spin, $s$, long twist, $L$, planar operators (asymptotic Bethe Ansatz) of strong ${\cal N}=4$ SYM. Precisely, we compute the minimal anomalous dimensions for large 't Hooft coupling $\lambda$ to the lowest order of the (string) scaling variable $\ell \sim L/ (\ln \mathcal{S} \sqrt{\lambda})$ with GKP string size $\sim\ln \mathcal{S}\equiv 2 \ln (s/\sqrt{\lambda})$. At the leading order $(\ln \mathcal{S}) \cdot \ell ^2$, we can confirm the O(6) non-linear sigma model description for this bulk term, without boundary term $(\ln \mathcal{S})^0$. Going further, we derive, extending the O(6) regime, the exact effect of the size finiteness. In particular, we compute, at all loops, the first Casimir correction $\ell ^0/\ln \mathcal{S}$ (in terms of the infinite size O(6) NLSM), which reveals only one massless mode (out of five), as predictable once the O(6) description has been extended. Consequently, upon comparing with string theory expansion, at one loop our findings agree for large twist, while reveal for negligible twist, already at this order, the appearance of wrapping. At two loops, as well as for next loops and orders, we can produce predictions, which may guide future string computations.Comment: Version 2 with: new exact expression for the Casimir energy derived (beyond the first two loops of the previous version); UV theory formulated and analysed extensively in the Appendix C; origin of the O(6) NLSM scattering clarified; typos correct and references adde

Clinical evaluation of seven tumour markers in lung cancer diagnosis: can any combination improve the results?

In this study we compared the diagnostic utility of: (1) neuron-specific enolase (NSE); (2) squamous cell carcinoma antigen (SCC); (3) carcinoembryonic antigen (CEA); and (4) cytokeratin markers (CYFRA 21-1, TPA, TPM, TPS) in patients with small-cell lung cancer (SCLC) (21 cases) and non-small-cell lung cancer (94 cases). For comparison we also studied 66 patients with benign lung diseases and nine with pleural mesothelioma. NSE levels in SCLC patients were significantly higher than those in all the other groups studied. No significant variations were found among the SCC levels in all groups. CEA levels in patients with adenocarcinoma were significantly higher than those in all other groups studied. CYFRA 21-1 serum levels significantly increased in patients with squamous cell carcinoma and mesothelioma, while TPA, TPS and TPM increased in patients with lung cancer irrespective of the histological type. In patients with SCLC, high levels of all markers except SCC were found when the disease was extensive. In patients with non-SCLC, the highest levels of all tumour markers were usually found in those with advanced disease, although CYFRA 21-1 gave a sensitivity of 44% when a specificity of 95% was fixed in stage I non-SCLC patients. An analysis of receiver operating characteristic curves revealed that the highest diagnostic accuracies in distinguishing benign from malignant lung diseases were achieved with TPM (81%), CYFRA 21-1 (72%), CEA (78%) or TPA (78%) when using cut-off values of 46 Ul-1, 3.0 micrograms l-1, 2.0 micrograms l-1 and 75 Ul-1 respectively. When all patients were considered, the combined evaluation of more than one marker did not significantly improve the results obtained with TPM alone. However, taking into consideration the fact that CYFRA 21-1 is the most sensitive index of early lung tumours and that its combined determination with TPM did not worsen the overall sensitivity and specificity of the latter, the combined use of these two markers may be suggested as a useful took for the diagnosis of lung tumours

Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications.

Background: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. Methods: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. Results: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. Conclusions: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic facto

Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?

BACKGROUND: Our aim was to identify the pancreatic cancer diabetogenic peptide. METHODS: Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. RESULTS: A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. CONCLUSIONS: The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus

Noise Measurement of Interacting Ferromagnetic Particles with High Resolution Hall Microprobes

We present our first experimental determination of the magnetic noise of a superspinglass made of < 1 pico-liter frozen ferrofluid. The measurements were performed with a local magnetic field sensor based on Hall microprobes operated with the spinning current technique. The results obtained, though preliminary, qualitatively agree with the theoretical predictions of Fluctuation-Dissipation theorem (FDT) violation [1].Comment: 4pages, 2 figure