Solid phase microextraction, mass spectrometry and metabolomic approaches for detection of potential urinary cancer biomarkers: a powerful strategy for breast cancer diagnosis

A sensitive assay to identify volatile organic metabolites (VOMs) as biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. Therefore the aim of this study was to establish the urinary metabolomic profile of breast cancer patients and healthy individuals (control group) and to explore the VOMs as potential biomarkers in breast cancer diagnosis at early stage. Solid-phase microextraction (SPME) using CAR/PDMS sorbent combined with gas chromatography–mass spectrometry was applied to obtain metabolomic information patterns of 26 breast cancer patients and 21 healthy individuals (controls). A total of seventy-nine VOMs, belonging to distinct chemical classes, were detected and identified in control and breast cancer groups. Ketones and sulfur compounds were the chemical classes with highest contribution for both groups. Results showed that excretion values of 6 VOMs among the total of 79 detected were found to be statistically different (p < 0.05). A significant increase in the peak area of (−)-4-carene, 3-heptanone, 1,2,4-trimethylbenzene, 2-methoxythiophene and phenol, in VOMs of cancer patients relatively to controls was observed. Statiscally significant lower abundances of dimethyl disulfide were found in cancer patients. Bioanalytical data were submitted to multivariate statistics [principal component analysis (PCA)], in order to visualize clusters of cases and to detect the VOMs that are able to differentiate cancer patients from healthy individuals. Very good discrimination within breast cancer and control groups was achieved. Nevertheless, a deep study using a larger number of patients must be carried out to confirm the results.

The possibility of primordial black hole direct detection

This thesis explores the possibility of directly detecting blackbody emission from Primordial Black Holes (PBHs). A PBH might form when a cosmological density uctuation with wavenumber k, that was once stretched to scales much larger than the Hubble radius during ination, reenters inside the Hubble radius at some later epoch. By modeling these uctuations with a running{tilt power{law spectrum (n(k) = n0 + a1(k)n1 + a2(k)n2 + a3(k)n3; n0 = 0:951; n1 = ????0:055; n2 and n3 unknown) each pair (n2,n3) gives a di erent n(k) curve with a maximum value (n+) located at some instant (t+). The (n+,t+) parameter space [(1:20,10????23 s) to (2:00,109 s)] has t+ = 10????23 s{109 s and n+ = 1:20{2:00 in order to encompass the formation of PBHs in the mass range 1015 g{1010M (from the ones exploding at present to the most massive known). It was evenly sampled: n+ every 0.02; t+ every order of magnitude. We thus have 41 33 = 1353 di erent cases. However, 820 of these ( 61%) are excluded (because they would provide a PBH population large enough to close the Universe) and we are left with 533 cases for further study. Although only sub{stellar PBHs ( 1M ) are hot enough to be detected at large distances we studied PBHs with 1015 g{1010M and determined how many might have formed and still exist in the Universe. Thus, for each of the 533 (n+,t+) pairs we determined the fraction of the Universe going into PBHs at each epoch ( ), the PBH density parameter (PBH), the PBH number density (nPBH), the total number of PBHs in the Universe (N), and the distance to the nearest one (d). As a rst result, 14% of these (72 cases) give, at least, one PBH within the observable Universe, one{third being sub{stellar and the remaining evenly spliting into stellar, intermediate mass and supermassive. Secondly, we found that the nearest stellar mass PBH might be at 32 pc, while the nearest intermediate mass and supermassive PBHs might be 100 and 1000 times farther, respectively. Finally, for 6% of the cases (four in 72) we might have substellar mass PBHs within 1 pc. One of these cases implies a population of 105 PBHs, with a mass of 1018 g(similar to Halley's comet), within the Oort cloud, which means that the nearest PBH might be as close as 103 AU. Such a PBH could be directly detected with a probability of 10????21 (cf. 10????32 for low{energy neutrinos). We speculate in this possibility.