LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development. We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial–mesenchymal transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2 inhibitors and discuss their potential in HCC precision treatment.

The precise differentiation of renal cell tumors (RCTs) is sometimes hard to achieve using standard imaging and histopathological methods, especially for those with eosinophilic features. It has been suggested that the vast overabundance of mitochondria, as a well-known hallmark of eosinophilic cytoplasm, and could be a characteristic of distinct tumor types with opposing clinical outcomes. Thus, we intended to explore the associations between mitochondrial distribution patterns in different RCTs, including 43 cell renal cell carcinomas (ccRCCs), 15 papillary renal cell carcinomas (pRCCs), 20 chromophobe renal cell carcinomas (chRCCs), and 18 renal oncocytomas (ROs). Tumor samples were stained with two anti-mitochondrial antibodies (mitochondrial antibody Ab-2, clone MTC02; prohibitin, II-14-10, MA5-12858), applying immunohistochemistry and immunofluorescence to define mitochondrial distribution patterns (coarse scanty, moderate granular, and diffuse granular). Our results revealed significantly different expression patterns among the investigated RCTs (p < 0.001). The majority of ccRCCs exhibited coarse scanty mitochondrial staining, while all chRCCs had moderate granular expression. Nevertheless, all ROs, all pRCCs, and two cases of ccRCC presenting with higher nuclear grade and eosinophilic cytoplasm had diffuse granular mitochondrial expression. Moreover, with increased distribution of mitochondria, the intensity of staining was higher (p < 0.001). Here we present a strategy that utilizes fast and easy mitochondrial detection to differentiate RO from chRCC, as well as other eosinophilic variants of RCC with high accuracy.

LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with aggressive phenotype and represents a poor prognostic factor. Here, we focus on mechanisms by which LOXL2 orchestrates multiple oncogenic functions in HCC development. We are reviewing current knowledge about the roles of LOXL2 in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial-mesenchymal transition. Also, we are highlighting the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize current LOXL2 inhibitors and discuss their potential in HCC precision treatment.

The precise differentiation of renal cell tumours (RCTs) is sometimes hard to achieve using standard imaging and histopathological methods. This study investigated 43 cell renal cell car-cinomas (ccRCC), 15 papillary renal cell carcinomas (pRCC), 20 chromophobe renal cell carcino-mas (chRCC), and 18 renal oncocytomas (RO), stained with anti-mitochondria antibody (Thermo Scientific) by immunohistochemistry and immunofluorescence, and assessed by electron micros-copy, in order to define mitochondria distribution pattern (coarse scanty, moderate granular and diffuse granular). Thus, the majority of males had coarse granular staining in the tumours, while females were almost equally distributed among groups (p=0.005). An average patient age, tumour side and dimension, and tumour stage were similar in all staining pattern groups. However, pathohistological tumour types had significantly different expression patterns, with the lower amount of staining detected in majority of ccRCC, moderate expression in all chRCC, and diffuse expression in all RO, pRCC and two cases of ccRCC (p<0.001) presented with higher nuclear grade (p=0.005). Moreover, with increased distribution of mitochondria, the intensity of staining was higher (p<0.001). Here we present a strategy that utilizes mitochondria detection to differentiate RO from chRCC, as well as to distinguish other frequent RCTs, such as ccRCC and pRCC.

Multiphoton microscopy (MPM) is a cutting-edge nonlinear microscopy technique known for its exceptional capabilities in imaging dense tissues, making it an ideal tool for exploring human kidney tissue. This study delves into the application of MPM in evaluating renal cell tumors and characterizing tumor capsules. MPM encompasses two core methods: two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG). It leverages femtosecond lasers to provide deep tissue imaging while minimizing phototoxicity, making it well-suited for live tissue analysis. The study analyzed 100 formalin-fixed paraffin-embedded (FFPE) kidney tissue samples, ensuring compliance with ethical standards. Using a Ti:Sapphire laser for femtosecond pulses and a variety of optical components and filters, the researchers captured TPEF and SHG signals, facilitating image analysis. Normal kidney tissue exhibited distinctive structures like glomeruli and tubules under MPM. Renal cell carcinoma (ccRCC) displayed unique TPEF patterns with eccentrically located nuclei and indistinct cytoplasmic membranes. Papillary RCC (pRCC) exhibited a papillary pattern with dark nuclei, while chromophobe RCC (chRCC) showcased distinct features like thick cell membranes, strong TPEF signal in nuclei, and granular cytoplasm. Renal oncocytoma (RO) presented strong TPEF signals in cuboidal cells with microcyst-like arrangements. Overall, MPM proved invaluable in assessing human kidney tissue, offering distinct TPEF patterns for different renal cell tumor types. This non-invasive technique has the potential to enhance pathological examinations and advance our understanding of complex biological processes, ultimately contributing to improved diagnostics and treatment strategies for renal diseases.