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Caves serve as time capsules, preserving significant markers of tectonic activity and offering insights into geological history. Fault geometries and past activations found in caves can be correlated with known deformational events in the broader area, temporally delimiting the speleogenesis. More specifically, cave passage formation is suggested to be affected by the regional stress-field. The Asprorema Cave in Northern Greece is a typical example of a fracture guided cave, with passage geometry influenced by relative sidewall movements, revealing these discontinuities as faults. This study constructs the timeframe and conceptual model of speleogenesis in relation to tectonic events, geomorphological evolution and hydrological zones, and verifies its relation to the stress-field. Active tectonics, mineralogy and cave geomorphology are investigated. Results suggest syntectonic speleogenesis under phreatic and epiphreatic conditions. The absence of corrosion on fault slip surfaces implies recent activations post cave's shift to the vadose zone. Structural analysis identifies three main neotectonic phases: NNW-SSE striking faults (oldest group of structures), NE-SW striking faults with dextral strike-slip movement (post-middle Miocene), and NE-SW striking normal faults indicating extensional stress-regime (Quartenary). The last two phases affect cave passage shape causing wall displacement, highlighting passage formation along discontinuities perpendicular to the horizontal minimum stress axis. [ABSTRACT FROM AUTHOR]

Characterized by an aggressive clinical course and relatively poor prognosis, triple-negative breast cancer (TNBC) refers to a diverse group of tumors with distinct molecular characteristics rather than to a single entity. The recognition of distinct gene expression subtypes within the group of TNBC and the description of an ever-expanding set of genetic events has led to improved understanding of the underlying biology. However, the improvement of clinical results has been incremental despite undergoing efforts to evaluate the role of molecularly targeted agents in the treatment of TNBC. The relative rarity of each one of these genetic events increases the difficulty of conducting large clinical trials, further hindering our ability to identify meaningful, personalized treatment approaches. Herein, we summarize current knowledge on TNBC, focusing on molecular pathology and emerging treatment approaches.

Iron oxide deposits in the form of crusts are examined in the field and in the laboratory with scanning electron microscopy. Samples came from two caves developed in different geological settings but assumed by previous studies to be of hydrothermal-hypogene origin. The relation of iron oxide crusts to cave wall and ceiling morphology created by the cave's primary dissolution (speleogenesis), as well as to the formation of other speleothems, is investigated. Scanning electron microscope (SEM) elemental analysis showed a high iron content (20-78 % by weight) consistent with iron oxide minerals such as goethite, hematite, magnetite, etc. Three distinct types of iron oxide crusts were identified from the four samples that were analyzed: (1) high iron content crusts with some porosity formed on the host rock surface and discontinuities, (2) high iron content (but lower than type 1) crusts, including limestone clasts and pores originating from dissolved clasts, and (3) high iron content, significantly-porous crusts that are formed by a network of filaments that indicate microbial activity. The formation of these deposits in relation to other speleothems and to dissolution events is discussed. [ABSTRACT FROM AUTHOR]

Firn from an ice cave in the highest mountain of Greece, Mount Olympus, was sampled and analyzed to determine the tritium content in order to estimate rates of accumulation and to date the ice plug. The presence of a sharp raise of tritium content indicating the nuclear testing era was expected to be preserved into ice beds. Tritium concentrations were found to vary from 0.9 to 11 TU. This peak did not appear in the analyzed samples, providing an upper age limit of less than 50 years for the oldest sampled layer. It is suggested that the rate of melting is responsible for the absence of older firn layers. [ABSTRACT FROM AUTHOR]

Two of the most well-known caves of northern Greece, Petralona and Maaras, were morphometrically analyzed. They were strategically chosen for this morphometric study because they represent caves formed by different speleogenetic factors, resulting in patterns that clearly discriminate them from each other. Caves can display substantial variation in their patterns, depending on the local geology, hydrogeology, tectonics, and other factors. These qualitative parameters of speleogenesis, such as geological and hydrogeological controls, can be reflected in a cave's pattern. The different speleogenetic factors that create the patterns of the caves can be expressed in the mathematical indices, designating them as morphometrical tools for properly discriminating the two cave patterns. Petralona Cave falls into the category of a ramiform cave pattern. The cave's hypogenic origin is also supported by meso-scale cave morphology, and the hydrothermal activity of the surrounding area. On the other hand, Maaras Cave has a typical underground river pattern. The horizontal patterns of the two caves were morphometrically scrutinized using Euclidean and fractal geometry. [ABSTRACT FROM AUTHOR]

From the Early Villafranchian site of Milia (Grevena) in northern Greece a mandible fragment of a porcupine with part of the incisor has been recorded. Despite its fragmentary nature, morphologically the fossil has been referred unambiguously to the genus Hystrix; according to various size parameters it belongs to the species H. refossa. A compilation of all known porcupine fossils attributed to this species indicates that the find from Milia is the oldest record of H. refossa so far, the age of which is correlated with the early part of the informal Mammal Sub-Zone MN 16a. Age and location of the record suggest that--in parallel to the preceding species H. primigenia and H. depereti -- the porcupine species H. refossa spread from south-east Europe (Balkans) eventually over Europe. The Milia porcupine presumably inhabited vegetated river banks within a mosaic of open and forested terrain under warm and humid conditions. [ABSTRACT FROM AUTHOR]

Orpiment, tamarugite and pickeringite occur in close association above the surface of thermal water cave pools in the active sulfuric acid caves of Aghia Paraskevi on the Kassandra peninsula, northern Greece. Gypsum also occurs as small interstitial crystals or encrustations. Orpiment is of high significance since it has not previously been reported as a cave mineral. In addition, tamarugite and pickeringite rarely occur in karst caves. Water from a borehole and a spring is of Na-Cl type and contains traces of CO2 and H2S. The B/Cl ratios indicate seawater participation with a possible mixing with geothermal water of meteoric origin. Oxidation of fumarolic H2S and incorporation of seawater is a possible cause for the deposition of tamarugite. Orpiment accumulated from vapors under sub-aerial conditions at low temperatures in acidic conditions through an evaporation-condensation process. Fluid cooling and/or acidification of the solution resulting from H2S oxidation were responsible for orpiment precipitation. Oxidation of H2S to sulfuric acid dissolved the limestone bedrock and deposited gypsum. [ABSTRACT FROM AUTHOR]

Background/aim: PTEN-loss and PIK3CA mutations have been addressed as markers of PI3K activation in breast cancer. We evaluated these markers in early high-risk breast cancer (EBC) focusing on PTEN immunohistochemistry (IHC) issues, particularly in HER2-positive disease., Materials and Methods: We examined PTEN-loss and PIK3CA mutations in 1265 EBC patients treated with adjuvant chemotherapy within two clinical trials. Two different methods for the evaluation of PTEN IHC were used, one upfront binary (loss; no-loss) and the other initially multi-scale allowing for the classification of "grey zone" tumors with low and very low PTEN protein expression., Results: PTEN-loss (33.4% and 22.1%, depending on the IHC method) and PIK3CA mutations (29.6%) were associated with ER/PgR/HER2-negative and ER/PgR-positive disease, respectively. Concordance of the two IHC methods was moderate (Cohen's kappa 0.624). PTEN-loss discrepancy and intra-tumor heterogeneity concerned "grey zone" tumors that were prevalent among HER2-positive cancers. PTEN-loss independently conferred higher risk for relapse and death. Compared to single PIK3CA mutations,single PTEN-loss was independently associated with increased risk for relapse and death. Depending on the evaluation method, in HER2-positive cancer, PTEN-loss was without- or of marginal unfavorable prognostic significance., Conclusion: In EBC, PTEN-loss is an independent predictor of poor outcome. When occurring singly, PTEN-loss and PIK3CA mutations have opposite prognostic impact. In HER2-positive disease, assessment of PTEN-loss by IHC appears unreliable and the marker is without clear prognostic significance., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Biliary tract cancer (BTC) represents a heterogeneous disease with dismal outcome. Herein, we examined genotype and angiogenesis features in BTC. We applied genotyping (Sanger, qPCR, 101-gene panel NGS), mRNA relative quantification methods, and β-catenin immunohistochemistry in 84 FFPE BTC (55 gallbladder [GBC], 14 intrahepatic [ICC], 15 extrahepatic [ECC] carcinomas). We identified 541 mutations in 68 (81%) tumors. Top mutated genes were CTNNB1 (36%); PTEN (33%); TP53 (31%); PIK3R1 (29%); PIK3CA (13%); BRCA2 and KRAS (12%); BRCA1 (11%). Six GBCs were hypermutated [hm] displaying a distinct mutational pattern. Mutations in TP53 and PI3K, Wnt and RAS components were prevalent among non-hypermutated tumors. All hmGBCs carried mutations in BRCA2 and other homologous recombination repair (HRR) genes, in PD1, but not in CTNNB1 and KRAS. None of the pathogenic BRCA2 p.D2723G and BRCA1 p.Q563* and c.5266dupC was present at frequencies expected for germline mutations. We observed copy gains (>6 copies) in EGFR (9% of informative tumors), PRKAR1A (7%), PIK3CA (6%), ERBB2 (5%) and MET (4%). TP53 mutations were prevalent in GBC (P<0.001) and PRKAR1A copy gains in ICC (P=0.007). PTEN was frequently co-mutated with CTNNB1 (P<0.001). Unrelated to CTNNB1 mutations, nuclear β-catenin was detected in 45% of tumors, among them in 5/6 hmGBC. We observed strong mRNA expression correlation of the two neuropilins (NRP1 and NRP2) with each other (Spearman's rho 0.59) and with the endothelin receptor (NRP2 rho 0.66; NRP2 rho 0.51), and between VEGFA and its receptors (FLT1 rho 0.49; KDR rho 0.45). All PIK3CA mutated tumors expressed endothelin 1 mRNA (P=0.010). Most tumors expressing nuclear β-catenin were negative for VEGFC (P=0.009) and FLT4 (P=0.002) mRNA expression. In conclusion, we confirmed the presence of known genomic aberrations in BTC and different genotypes between BTC subsets. Novel findings are the coexistence of PI3K and WNT pathway gene alterations in BTC, their association with angiogenesis, and the hypermutated GBCs with HRR gene mutations, all of which may be considered for new treatment options in this difficult to treat disease., Competing Interests: None.

Background: The retinoblastoma (RB) gene is a tumor-suppressor gene that plays a central role in regulating the cell cycle. Inactivation of this gene is involved in breast cancer., Patients and Methods: A total of 827 patients with breast cancer treated with taxane-based adjuvant chemotherapy were included in the study. Protein expression of RB, phosphorylated RB (pRB), p16, cyclin D1 and p53 was evaluated by immunohistochemistry., Results: Neither of the retinoblastoma markers (RB and pRB) reached statistical significance in terms of their association with disease-free or overall survival. Nevertheless, when clustering analysis was performed, patients with tumors featuring low levels of p16, cyclin D1 and p53 with concomitantly high levels of pRB had reduced risk for relapse (Wald's p=0.015)., Conclusion: The p53-mediated sensitivity of breast cancer cells to chemotherapeutic agents appears to be driven mostly by pRB. Using agents that enhance RB phosphorylation might possibly increase the chemosensitivity of breast cancer cells., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)