21. Real-world outcomes, treatment patterns and T790M testing rates in non-small cell lung cancer patients treated with first-line first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors from the Slovenian cohort of the REFLECT studyNina Turnšek, Rok Devjak, Natalija Edelbaher, Ilonka Osrajnik, Mojca Unk, Dušanka Vidovič, Tina Jerič, Urška Janžič, 2022, original scientific article Abstract: Background. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC). However, routine clinical practice is different between countries/institutions. Patients and methods. The REFLECT study (NCT04031898) is a retrospective medical chart review that explored real-life treatment and outcomes of EGFRm NSCLC patients receiving first-line (1L) first-/second-generation (1G/2G) EGFR TKIs in 8 countries. This study included adult patients with documented advanced/metastatic EGFRm NSCLC with 1L 1G/2G EGFR TKIs initiated between Jan 2015 – Jun 2018. We reviewed data on clinical characteristics, treatments, EGFR/T790M testing patterns, and survival outcomes. Here, we report data from 120 medical charts in 3 study sites from Slovenia. Results. The Slovenian cohort (median age 70 years, 74% females) received 37% erlotinib, 32% afatinib, 31% gefitinib. At the time of data collection, 94 (78%) discontinuations of 1L TKI, and 89 (74%) progression events on 1L treatment were reported. Among patients progressing on 1L, 73 (82%) were tested for T790M mutation yielding 50 (68%) positive results, and 62 (85%) received 2L treatment. 82% of patients received osimertinib. Attrition rate between 1L and 2L was 10%. The median (95% CI) real-world progression free survival on 1L EGFR TKIs was 15.6 (12.6, 19.2) months; median overall survival (95% CI) was 28.9 (25.0, 34.3) months. Conclusions. This real-world study provides valuable information about 1G/2G EGFR TKIs treatment outcomes and attrition rates in Slovenian EGFRm NSCLC patients. The reduced attrition rate and improved survival outcomes empha-size the importance of 1L treatment decision.
Keywords: real-world study, non-small cell lung cancer, epidermal growth factor receptor, lung cancer
Published in DiRROS: 25.07.2024; Views: 173; Downloads: 78
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23. Fungi between extremotolerance and opportunistic pathogenicity on humansCene Gostinčar, Janja Zajc, Metka Lenassi, Ana Plemenitaš, Sybren de Hoog, Abdullah M. S. Al-Hatmi, Nina Gunde-Cimerman, 2018, original scientific article Abstract: Numerous agents of infections in humans and other mammals are found among fungi that are able to survive extreme environmental conditions and to quickly adapt to novel habitats. Nevertheless, the relationship between opportunistic potential and polyextremotolerance was not yet studied systematically in fungi. Here, the link between polyextremotol- erance and opportunistic pathogenicity is shown in a kingdom-wide phylogenetic analysis as a statistically significant co- occurrence of extremotolerance (e.g. osmotolerance and psychrotolerance) and opportunism at the level of fungal orders. In addition to extremotolerance, fungal opportunists share another characteristic%an apparent lack of specialised virulence traits. This is illustrated by a comparative genomic analysis of 20 dothideomycetous and eurotiomycetous black fungi. While the genomes of specialised fungal plant pathogens were significantly enriched in known virulence-associated genes that encode secreted proteases, carbohydrate active enzyme families, polyketide synthases, and non-ribosomal peptide synthetases, no such signatures were observed in human opportunists. Together the presented results have several implications. If infection of human hosts is a side effect of fungal stress tolerance and adaptability, the human body is most likely neither the preferred habitat of such species, nor important for their evolutionary success. This defines opportunism as opposed to pathogenicity, where infection is advantageous for the species% fitness. Since opportunists are generally incapable of the host-to-host transmission, any host-specific adaptations are likely to be lost with the resolution of the infection, explaining the observed lack of specialised virulence traits. In this scenario opportunistic infections should be seen as an evolutionary dead end and unlikely to lead to true pathogenicity.
Keywords: fungi, pathogenicity, infections in humans
Published in DiRROS: 24.07.2024; Views: 192; Downloads: 3459
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24. Fifty Aureobasidium pullulans genomes reveal a recombining polyextremotolerant generalistCene Gostinčar, Martina Turk, Janja Zajc, Nina Gunde-Cimerman, 2019, original scientific article Abstract: The black yeast Aureobasidium pullulans is a textbook example of a generalistic and ubiquitous fungus thriving in a wide variety of environments. To investigate whether A. pullulans is a true generalist, or alternatively, whether part of its versatility can be attributed to intraspecific specialization masked by cryptic diversification undetectable by traditional phylogenetic analyses, we sequenced and analysed the genomes of 50 strains of A. pullulans from different habitats and geographic locations. No population structure was observed in the sequenced strains. Decay of linkage disequilibrium over shorter physical distances (<100 bp) than in many sexually reproducing fungi indicates a high level of recombination in the species. A homothallic mating locus was found in all of the sequenced genomes. Aureobasidium pullulans appears to have a homogeneous population genetics structure, which is best explained by good dispersal and high levels of recombination. This means that A. pullulans is a true generalist that can inhabit different habitats without substantial specialization to any of these habitats at the genomic level. Furthermore, in the future, the high level of A. pullulans recombination can be exploited for the identification of genomic loci that are involved in the many biotechnologically useful traits of this black yeast.
Keywords: black yeast, genome
Published in DiRROS: 24.07.2024; Views: 140; Downloads: 111
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25. Genomic evidence of recombination in the basidiomycete Wallemia mellicolaSun Xiaohuan, Cene Gostinčar, Fang Chao, Janja Zajc, Hou Yong, Song Zewei, Nina Gunde-Cimerman, 2019, original scientific article Abstract: One of the most commonly encountered species in the small basidiomycetous sub-phylum Wallemiomycotina is Wallemia mellicola, a xerotolerant fungus with a widespread distribution. To investigate the population characteristics of the species, whole genomes of twenty-five strains were sequenced. Apart from identification of four strains of clonal origin, the distances between the genomes failed to reflect either the isolation habitat of the strains or their geographical origin. Strains from different parts of the world appeared to represent a relatively homogenous and widespread population. The lack of concordance between individual gene phylogenies and the decay of linkage disequilibrium indicated that W. mellicola is at least occasionally recombining. Two versions of a putative mating-type locus have been found in all sequenced genomes, each present in approximately half of the strains. W. mellicola thus appears to be capable of (sexual) recombination and shows no signs of allopatric speciation or specialization to specific habitats.
Keywords: population genomics, halotolerance, xerotolerance, basidiomycete, allergenic fungus, recombination
Published in DiRROS: 23.07.2024; Views: 214; Downloads: 144
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26. Stress-tolerant yeasts : opportunistic pathogenicity versus biocontrol potentialJanja Zajc, Cene Gostinčar, Anja Černoša, Nina Gunde-Cimerman, 2019, original scientific article Abstract: Stress-tolerant fungi that can thrive under various environmental extremes are highly desirable for their application to biological control, as an alternative to chemicals for pest management. However, in fungi, the mechanisms of stress tolerance might also have roles in mammal opportunism. We tested five species with high biocontrol potential in agriculture (Aureobasidium pullulans, Debayomyces hansenii, Meyerozyma guilliermondii, Metschnikowia fructicola, Rhodotorula mucilaginosa) and two species recognized as emerging opportunistic human pathogens (Exophiala dermatitidis, Aureobasidium melanogenum) for growth under oligotrophic conditions and at 37 °C, and for tolerance to oxidative stress, formation of biofilms, production of hydrolytic enzymes and siderophores, and use of hydrocarbons as sole carbon source. The results show large overlap between traits desirable for biocontrol and traits linked to opportunism (growth under oligotrophic conditions, production of siderophores, high oxidative stress tolerance, and specific enzyme activities). Based on existing knowledge and these data, we suggest that oligotrophism and thermotolerance together with siderophore production at 37 °C, urease activity, melanization, and biofilm production are the main traits that increase the potential for fungi to cause opportunistic infections in mammals. These traits should be carefully considered when assessing safety of potential biocontrol agents.
Keywords: opportunistic pathogen, biocontrol agent, virulence, stress tolerance, secretome, CAZy, protease, thermotolerance, oligotrophism, melanin, siderophore, biofilm
Published in DiRROS: 23.07.2024; Views: 213; Downloads: 186
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27. Bridging biotremology and chemical ecology : a new terminologyValerio Mazzoni, Gianfranco Anfora, Reginald Bifield Cocroft, Fatouros Nina E., Meta Virant-Doberlet, 2024, review article Abstract: Living organisms use both chemical and mechanical stimuli to survive in their environment. Substrate-borne vibrations play a significant role in mediating behaviors in animals and inducing physiological responses in plants, leading to the emergence of the discipline of biotremology. Biotremology is experiencing rapid growth both in fundamental research and in applications like pest control, drawing attention from diverse audiences. As parallels with concepts and approaches in chemical ecology emerge, there is a pressing need for a shared standardized vocabulary in the area of overlap for mutual understanding. In this article, we propose an updated set of terms in biotremology rooted in chemical ecology, using the suffix ‘-done’ derived from the classic Greek word ‘δονέω’ (pronounced ‘doneo’), meaning ‘to shake’.
Keywords: vibrational communication, chemical ecology, biotremology, semiophysicals, pherodones, allelodones, zoology
Published in DiRROS: 23.07.2024; Views: 213; Downloads: 140
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28. Preoperative serum CA-125 level as a predictor for the extent of cytoreduction in patients with advanced stage epithelial ovarian cancerSebastjan Merlo, Nikola Bešić, Eva Drmota, Nina Kovačević, 2021, original scientific article Abstract: Background. Ovarian cancer is the seventh most common cancer in women worldwide and the eighth most common cause of cancer death. Due to the lack of effective early detection strategies and the unspecific onset of symptoms, it is diagnosed at an advanced stage in 75% of cases. The cancer antigen (CA) 125 is used as a prognostic marker and its level is elevated in more than 85% of women with advanced stages of epithelial ovarian cancer (EOC). The standard treatment is primary debulking surgery (PDS) followed by adjuvant chemotherapy (ACT), but the later approach is neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Several studies have been conducted to find out whether preoperative CA-125 serum levels influence treatment choice, surgical resection and survival outcome. The aim of our study was to analyse experience of single institution as Cancer comprehensive center with preoperative usefulness of CA-125. Patients and methods. At the Institute of Oncology Ljubljana a retrospective analysis of 253 women with stage FIGO IIIC and IV ovarian cancer was conducted. Women were divided into two groups based on their primary treatment. The first group was the NACT group (215 women) and the second the PDS group (38 women). The differences in patient characteristics were compared using the Chi-square test and ANOVA and the Kaplan-Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). Results. The median serum CA-125 level was higher in the NACT group than in the PDS group, 972 IU/ml and 499 IU/ ml, respectively. The PFS in the NACT group was 8 months (95% CI 6.4%9.5) and 18 months (95% CI 12.5%23.4) in the PDS group. The median OS was lower in the NACT group than in the PDS group, 25 months (95% CI 20.6%29.5) and 46 months (95% CI 32.9%62.1), respectively. Conclusions. Preoperative CA-125 cut off value of 500 IU/ml is a promising threshold to predict a successful PDS.
Keywords: ovarian cancer, tumour marker, neoadjuvant chemotherapy, CA-125
Published in DiRROS: 22.07.2024; Views: 179; Downloads: 55
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29. Surgical treatment and fertility perservation in endometrial cancerNina Kovačević, 2021, review article Abstract: Endometrial cancer (EC) represents a high health burden in Slovenia and worldwide. The incidence is increasing due to lifestyle and behavioural risk factors such as obesity, smoking, oestrogen exposure and aging of the population. In many cases, endometrial cancer is diagnosed at an early stage due to obvious signs and symptoms. The standard treatment is surgery with or without adjuvant therapy, depending on the stage of the disease and the risk of recurrence. However, treatment modalities have changed in the last decades, considerably in the extent of lymphadenectomy. Conclusions. The gold standard of treatment for is surgery, which may be the only treatment modality in the early stages of low-grade tumours. In recent years, a minimally invasive approach with sentinel node biopsy (SNB) has been proposed. A conservative approach with hormonal treatment is used if fertility preservation is desired. If EC is in advance stage, high-risk histology, or high grade, radiotherapy, chemotherapy, or a combination of both is recommended.
Keywords: endometrial cancer, uterus, treatment, minimally invasive surgery
Published in DiRROS: 22.07.2024; Views: 203; Downloads: 53
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30. Natural analogues in pH variability and predictability across the coastal pacific estuaries : extrapolation of the increased oyster dissolution under increased ph amplitude and low predictability related to ocean acidificationNina Bednaršek, Marcus W. Beck, Greg Pelletier, Scott Lee Applebaum, Richard Alan Feely, Robert Butler, Maria Byrne, Betsy Peabody, Jonathan Davis, Jasna Štrus, 2022, original scientific article Abstract: Coastal-estuarine habitats are rapidly changing due to global climate change, with impacts influenced by the variability of carbonate chemistry conditions. However, our understanding of the responses of ecologically and economically important calcifiers to pH variability and temporal variation is limited, particularly with respect to shell-building processes. We investigated the mechanisms driving biomineralogical and physiological responses in juveniles of introduced (Pacific; Crassostrea gigas) and native (Olympia; Ostrea lurida) oysters under flow-through experimental conditions over a six-week period that simulate current and future conditions: static control and low pH (8.0 and 7.7); low pH with fluctuating (24-h) amplitude (7.7 ± 0.2 and 7.7 ± 0.5); and high-frequency (12-h) fluctuating (8.0 ± 0.2) treatment. The oysters showed physiological tolerance in vital processes, including calcification, respiration, clearance, and survival. However, shell dissolution significantly increased with larger amplitudes of pH variability compared to static pH conditions, attributable to the longer cumulative exposure to lower pH conditions, with the dissolution threshold of pH 7.7 with 0.2 amplitude. Moreover, the high-frequency treatment triggered significantly greater dissolution, likely because of the oyster’s inability to respond to the unpredictable frequency of variations. The experimental findings were extrapolated to provide context for conditions existing in several Pacific coastal estuaries, with time series analyses demonstrating unique signatures of pH predictability and variability in these habitats, indicating potentially benefiting effects on fitness in these habitats. These implications are crucial for evaluating the suitability of coastal habitats for aquaculture, adaptation, and carbon dioxide removal strategies.
Keywords: ocean acidification, diel pH variability, amplitude, shell dissolution, predictability
Published in DiRROS: 17.07.2024; Views: 200; Downloads: 251
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