RESUMEN

AIMS: Compared to primary breast sarcoma (BSs), radiotherapy-induced sarcoma (RIS) is a less frequent type of secondary breast sarcoma. Undifferentiated pleomorphic sarcoma (UPS) is an even rarer occurrence within the RIS category. This study aimed to present the clinicopathologic and molecular features of breast radiotherapy-induced UPS. METHODS: A retrospective study was conducted at the Third Affiliated Hospital of Soochow University to analyze three patients with radiation-induced undifferentiated pleomorphic sarcoma (UPS) following breast cancer, spanning from 2006 to 2023. The clinical and pathological variables were extracted from the medical records, while immunohistochemistry was employed to analyze the immunophenotypes of these tumors. Genomic characteristics were assessed through DNA and RNA sequencing techniques. Another 15 cases from the literature were also reviewed to better characterize the tumor. RESULTS: The affected areas encompass the chest wall and breasts, with an incubation period ranging from 6 to 17 years. The tumor cells exhibit pleomorphism and demonstrate a high degree of pathological mitosis. Notably, two cases displayed an accelerated disease progression, characterized by recurrent tumors and metastases occurring within short intervals of 48 and 7 months respectively subsequent to the initial diagnosis. The two prevailing identified genes were TP53 (2/3, 66.7%) and RB1 (1/3, 33.3%). Through analysis of somatic copy number variation (CNV), it was discovered that two oncogenes, MCL1 (1/3, 33.3%) and MYC (1/3, 33.3%), had experienced gains in CNV. The Tumor Mutational Burden (TMB) values for case 1, case 2, and case 3 were 5.9 mut/Mb, 1.0 mut/Mb, and 3.0 mut/Mb, respectively. Moreover, the analysis of RNA-NGS (next-generation sequencing) revealed the presence of a novel gene fusion, named COL3A1-GULP1, in case 2. CONCLUSIONS: Based on our thorough analysis of research findings and previous reports, it is evident that radiotherapy-induced UPS exhibits a highly diverse and frequently severe clinical and biological behavior. Identifying tumor formation using genome sequencing can help understand its biological behavior and determine personalized treatments.

Asunto(s)

Neoplasias de la Mama , Neoplasias Inducidas por Radiación , Sarcoma , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Sarcoma/genética , Sarcoma/patología , Neoplasias Inducidas por Radiación/genética , Neoplasias Inducidas por Radiación/patología , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Biomarcadores de Tumor/genética , Anciano , Proteínas de Unión a Retinoblastoma/genética , Ubiquitina-Proteína Ligasas

RESUMEN

Breast adenoid cystic carcinoma (AdCC) with a solid-basaloid component is rare. The solid-basaloid component is usually characterized by solid nests composed of basal-like cells with marked nuclear atypia, high mitotic activity, and necrosis. Given the rarity of such tumors, information on their clinicopathological and genomic characteristics is limited. Herein, we report a case of advanced breast cancer with a poor prognosis with histological and immunohistochemical characteristics of AdCC with a solid-basaloid component. For the solid-basaloid component, fluorescence in situ hybridization (FISH) analysis revealed rearrangement of the EWSR1 and MYB genes, and immunohistochemical staining indicated MYB positivity. Next-generation sequencing-based technology revealed a novel EWSR1-MYB fusion. To our knowledge, this is the first report of an EWSR1-MYB fusion in AdCC with a solid-basaloid component and a poor prognosis. Our findings may extend the genetic understanding of AdCC and aid in the clinical diagnosis of AdCC.

Asunto(s)

Neoplasias de la Mama , Carcinoma Adenoide Quístico , Femenino , Humanos , Mama/patología , Neoplasias de la Mama/patología , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Hibridación Fluorescente in Situ , Proteína EWS de Unión a ARN/genética

RESUMEN

Candida albicans and Candida glabrata are two commonly seen opportunistic fungi in clinical settings and usually co-isolated from the population inflicted with denture stomatitis and oropharyngeal candidiasis. Although C. albicans and C. glabrata mixed biofilm is deemed to possess enhanced virulence compared with their individual counterparts (especially C. albicans single biofilm), the relevant descriptions and experimental evidence on the relationship of Candida virulence with their individual cell number in mixed biofilms are contradictory and insufficient. In this study, two standard C. glabrata isolate and eight C. albicans ones were used to test the cell quantities in their 24- and 48-h single and mixed biofilms. A series of virulence factors including antifungal resistance to caspofungin, secreted aspartic proteinase (SAP) and phospholipase (PL) levels, efflux pump function and ß-glucan exposure were evaluated. Through this study, the declines of individual cell counting were observed in the 24- and 48-h Candida mixed biofilms compared with their single counterparts. However, the antifungal resistance to caspofungin, the SAP and phospholipase levels, the rhodamine 6G efflux and the efflux-related gene expressions were increased significantly or kept unchanged accompanying with reduced ß-glucan exposure in the mixed biofilms by comparison with the single counterparts. These results reveal that there is a competitive interaction between C. albicans and C. glabrata strains in their co-culture without at the expense of the mixed biofilm virulence. This study presents a deep insight into the interaction between C. albicans and C. glabrata and provides new clues to combat against fungal infections caused by Candida mixed biofilms.

RESUMEN

Fungal infections caused by Candida albicans poses a great threat to human health. The ability of biofilm formation is believed to be associated with resistance-related Candida infections. Currently, knowledge on extracellular matrix (EM) of C. albicans biofilm is limited. In this study, we introduced ion exchange resin, i.e., cation exchange resin (CER) and anion exchange resin (AER), in EM extraction of C. albicans biofilm as well as several non-albicans Candida (NAC) biofilms under static and dynamic states in combination with vortexing and ultrasonication (VU). The metabolites extracted from the dynamic C. albicans biofilm matrix using the CER-VU and VU were identified with ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) via untargeted filtration. Compared with other physical and chemical extraction methods, CER-VU was demonstrated to be an ideal approach with high-yield acquisitions of EM constituents including proteins, triglycerides and carbohydrates and low-level damages on fungal cell viability and integrity. The untargeted MS analysis further showed the high efficacy of CER-VU, as a large quantity of metabolites (217 versus 198) was matched comprising a great number of lipids, carbohydrates, amino acids, nucleic acids and their derivatives together with a high involvement of signaling pathways compared with the VU alone. However, combining the results from both the CER-VU and VU methods could generate more metabolites. In summary, the EM analysis of the dynamic C. albicans biofilm expands our understanding upon a comprehensive depiction of matrix components and provides another effective approach for EM extraction.

RESUMEN

Candida albicans is a commonly isolated opportunistic yeast and can endanger immune-compromised human health. As increasingly isolated strains present resistance to currently used antifungals, it is necessary to develop novel antimycotics. In a previous study, sodium houttuyfonate (SH) alone or in combination with fluconazole revealed relatively strong antifungal potential against C. albicans, and the underlying mechanism might be likely to be associated with ß-glucan synthesis and transportation (Shao et al., 2017). In the present experiment, we used a standard C. albicans isolate and a phr1 mutant (phr1-/-) to investigate the interaction of SH with ß-glucan, one of the critical components in cell wall and biofilm matrix. We showed that lyticase was the most effective enzyme that could significantly increase the antifungal inhibition of SH at 64 µg/mL in C. albicans SC5314 but became futile in phr1-/-. Although the minimum inhibitory concentrations (MICs) of SH were comparable in the two Candida strains used, phr1-/- appeared to be more susceptible to SH compared with C. albicans SC5314 in biofilms (64 versus 512 µg/mL). The peak areas of SH decreased markedly by 71.6, 38.2, and 62.6% in C. albicans SC5314 and by 70% and 53.2% in phr1-/- by ultra-performance liquid chromatography (UPLC) analysis after co-incubation of SH with laminarin, extracellular matrix (EM) and cell wall. The chitin appeared to not interact with SH. We further demonstrated that sub-MIC SH (8 µg/mL) was able to induce cell wall remodeling by unmasking ß-1,3-glucan and chitin in both C. albicans SC5314 and phr1-/-. Based on these findings, we propose that ß-1,3-glucan can block the entrance of SH through non-specific absorption, and then the fungus senses the interaction of SH with ß-1,3-glucan and exposes more ß-1,3-glucan that contributes to SH blocking in turn.

RESUMEN

Fungal infections caused by Candida albicans and non-albicans Candida [NAC] species are becoming a growing threat in immunodeficient population, people with long-term antibiotic treatment and patients enduring kinds of catheter intervention. The resistance to one or more than one conventional antifungal agents contributes greatly to the widespread propagation of Candida infections. The severity of fungal infection requires the discovery of novel antimycotics and the extensive application of combination strategy. In this study, a group of Candida standard and clinical strains including C. albicans as well as several NAC species were employed to evaluate the antifungal potentials of palmatine (PAL) alone and in combination with fluconazole (FLC)/itraconazole (ITR) by microdilution method, checkerboard assay, gram staining, spot assay, and rhodamine 6G efflux test. Subsequently, the expressions of transporter-related genes, namely CDR1, CDR2, MDR1, and FLU1 for C. albicans, CDR1 and MDR1 for Candida tropicalis and Candida parapsilosis, ABC1 and ABC2 for Candida krusei, CDR1, CDR2, and SNQ2 for Candida glabrata were analyzed by qRT-PCR. The susceptibility test showed that PAL presented strong synergism with FLC and ITR with fractional inhibitory concentration index (FICI) in a range of 0.0049-0.75 for PAL+FLC and 0.0059-0.3125 for PAL+ITR in planktonic cells, 0.125-0.375 for PAL+FLC and 0.0938-0.3125 for PAL+ITR in biofilms. The susceptibility results were also confirmed by gram staining and spot assay. After combinations, a vast quantity of rhodamine 6G could not be pumped out as considerably intracellular red fluorescence was accumulated. Meanwhile, the expressions of efflux-associated genes were evaluated and presented varying degrees of inhibition. These results indicated that PAL was a decent antifungal synergist to promote the antifungal efficacy of azoles (such as FLC and ITR), and the underlying antifungal mechanism might be linked with the inhibition of efflux pumps and the elevation of intracellular drug content.