Malignant Features Research Articles

A Retrospective Study on the Clinical Characteristics and Computed Tomography, Biochemical, and Blood Parameters of Duodenal Papillary Diseases.

This study was conducted to investigate the imaging information, laboratory data, and clinical characteristics of duodenal papillary malignancies, aiming to contribute to the early diagnosis of these diseases. The clinical characteristics, laboratory data, and computed tomography (CT) findings of 17 patients with adenoma of the major duodenal papilla (the adenoma group) and 58 patients with cancer of the major duodenal papilla (the cancer group) were retrospectively analyzed. The measurement data were analyzed using t test and expressed as mean ± standard deviation. The counting data were analyzed using the χ2 test and expressed in n (%). Pearson correlation analysis was also conducted, and a scatter plot was drawn. There were significant differences in the diameter, shape, margin, and target sign of the major duodenal papilla, pancreatic duct diameter, common bile duct diameter, enhancement uniformity, fever, direct bilirubin, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9, and jaundice between the adenoma group and the cancer group (P < .01). The enhancement magnitude of the duodenal papilla was correlated with the lesion size, and the venous phase CT value of the enhanced scan was correlated with the duodenal papilla diameter (P < .05). Additionally, 12 patients in the cancer group suffered from malignant transformation of adenomas. Firstly, CT is of high value in the diagnosis of duodenal papilla diseases. Secondly, the enhancement magnitude of the duodenal papilla is correlated with the lesion size. Thirdly, patients with duodenal papilla adenomas have a risk of progression into adenocarcinoma, thereby requiring close follow-up.

A Retrospective Cross-sectional Analysis of Renal Complications in Association with Cancer: Insights from 120 Autopsies

Introduction: Kidney diseases frequently complicate cancer and its treatment, contributing to both morbidity and mortality. Malignancies can give rise to various kidney issues, such as glomerulonephritis and Chronic Kidney Disease (CKD). This association operates bidirectionally, with patients experiencing the development of renal diseases due to cancer, and CKD predisposing to cancer. Furthermore, nephrotoxicity induced by chemotherapy can result in Acute Tubular Injury (ATI) and necrosis, imposing limitations on its application. Aim: To evaluate the spectrum of renal pathology in autopsies of malignancies. Materials and Methods: This was a retrospective crosssectional study of complete autopsies of all cases of malignancies performed in the Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. The study was carried out over a 5-year period from January 2015 to December 2019. Analysis of cases with respect to demographics, type of primary malignancy, gross and microscopic features, and the final cause of death was conducted. These findings were meticulously tabulated, with frequencies and percentages calculated for each category. Results: A total of 4392 autopsies were conducted throughout the study period, with 120 of them revealing the presence of malignancies. A total of 38 (31.6%) malignancies were diagnosed for the first time at autopsy. The commonest renal findings on gross were scars (superficial and deep) seen in 40 (33.33%), followed by cortical cysts in 25 (20.83%), granular contracted kidney in 15 (12.50%), mass lesions in 7 (5.83%), abscesses in 7 (5.83%), and swollen, oedematous kidneys in 6 (5%) autopsies. The most frequent renal pathology on microscopy were infective lesions seen in 43 (35.83%), Acute Tubular Necrosis (ATN) in 32 (26.66%), ATI in 30 (25%), followed by malignancies- primary and secondary in 11 (9.16%), tubular casts in 6 (5%), etc. Rare findings included membranous glomerulonephritis and Tumour Lysis Syndrome (TLS) (Acute urate nephropathy) in 1 (0.83%) each. The TLS case had classic histomorphological features of TLS, apart from laboratory parameters. Extensive deposits of uric acid crystals were seen obstructing the tubules as well as some of the glomeruli on microscopy. Conclusion: In one-third of the cases, the malignancy was exclusively discovered during the autopsy. The study revealed a diverse array of lesions, encompassing pyelonephritis, ATN, primary and metastatic renal tumours, cast nephropathy, membranous glomerulonephritis, and TLS. One-fifth of the cases had end-stage renal disease (advanced renal disease). A significant number of the cases exhibited tumour masses within the kidneys. One-fifth of the cases had renal pathology contributing to the final cause of death, further highlighting the association between malignancies and renal pathology

Development and epigenetic regulation of Atypical teratoid/rhabdoid tumors in the context of cell-of-origin and halted cell differentiation.

Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors primarily observed in infants. The only characteristic, recurrent genetic aberration of AT/RTs is biallelic inactivation of SMARCB1 (or SMARCA4). These genes are members of the mSWI/SNF chromatin-remodeling complex, which regulates various developmental processes, including neural differentiation. This review explores AT/RT subgroups regarding their distinct SMARCB1 loss-of-function mechanisms, molecular features, and patient characteristics. Additionally, it addresses the ongoing debate about the oncogenic relevance of cell-of-origin, examining the influence of developmental stage and lineage commitment of the seeding cell on tumor malignancy and other characteristics. Epigenetic dysregulation, particularly through the regulation of histone modifications and DNA hypermethylation, has been shown to play an integral role in AT/RTs' malignancy and differentiation blockage, maintaining cells in a poorly differentiated state via the insufficient activation of differentiation-related genes. Here, the differentiation blockage and its contribution to malignancy are also explored in a cellular context. Understanding these mechanisms and AT/RT heterogeneity is crucial for therapeutic improvements against AT/RTs.

Real-time monitoring of abnormal mitochondrial viscosity in glioblastoma with a novel mitochondria-targeting fluorescent probe.

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

Importance of targeting various cell signaling pathways in solid cancers.

Most adult human cancers are solid tumors prevailing in vital organs and lead to mortality all over the globe. Genetic and epigenetic alterations in cancer genes or genes of associated signaling pathways impart the most common characteristic of malignancy, that is, uncontrolled proliferation. Unless the mechanism of action of these cells signaling pathways (involved in cell proliferation, apoptosis, metastasis, and the maintenance of the stemness of cancer stem cells and cancer microenvironment) and their physiologic alteration are extensively studied, it is challenging to understand tumorigenesis as well as develop new treatments and precision medicines. Targeted therapy is one of the most promising strategies for treating various cancers. However, cancer is an evolving disease, and most patients develop resistance to these drugs by acquired mutations or mediation of microenvironmental factors or due to tumor heterogeneity. Researchers are striving to develop novel therapeutic options like combinatorial approaches targeting multiple responsible pathways effectively. Thus, in-depth knowledge of cell signaling and its components remains a critical topic of cancer research. This chapter summarized various extensively studied pathways in solid cancer and how they are targeted for therapeutic strategies.

Oncofetal TRIM71 drives liver cancer carcinogenesis through remodeling CEBPA-mediated serine/glycine metabolism.

Rationale: Tumor cells remodel transcriptome to construct an ecosystem with stemness features, which maintains tumor growth and highly malignant characteristics. However, the core regulatory factors involved in this process still need to be further discovered. Methods: Single cell RNA-sequncing (scRNA-seq) and bulk RNA-sequencing profiles derived from fetal liver, normal liver, liver tumors, and their adjacent samples were collected to analyze the ecosystem of liver cancer. Mouse models were established to identify molecular functions of oncofetal-related oncogenes using hydrodynamic tail vein injection. Results: We found that liver cancer rebuilt oncofetal ecosystem to maintain malignant features. Interestingly, we identified a group of RNA-binding proteins (RBPs) that were highly overexpressed with oncofetal features. Among them, TRIM71 was specifically expressed in liver cancers and was associated with poor outcomes. TRIM71 drove the carcinogenesis of hepatocellular carcinoma (HCC), and knockdown of TRIM71 significantly abolished liver cancer cell proliferation. Mechanistically, TRIM71 formed a protein complex with IGF2BP1, bound to and stabilized the mRNA of CEBPA in an m6A-dependent manner, enhance the serine/glycine metabolic pathway, and ultimately promoted liver cancer progression. Furthermore, we identified that all-trans-retinoic acid (ATRA) combined with e1A binding protein p300 (EP300) inhibitor A-485 repressed TRIM71, attenuated glycine/serine metabolism, and inhibited liver cancer cell proliferation with high TRIM71 levels. Conclusions: We demonstrated the oncofetal status in liver cancer and highlighted the crucial role of TRIM71 and provided potential therapeutic strategies and liver cancer-specific biomarker for liver cancer patients.

CircSP3 encodes SP3-461aa to promote ccRCC progression via stabilizing MYH9 and activating the PI3K-Akt signaling pathway.

Clear cell renal cell carcinoma (ccRCC) is a primary kidney cancer with high aggressive phenotype and extremely poor prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) play pivotal roles in the occurrence and development of various human cancers. However, the expression, clinical significance and regulatory role of circRNAs in ccRCC remain largely unclear. Here we report that circSP3 to be increased in tissues from ccRCC patients and ccRCC cells, and to positively correlate with ccRCC malignant features. Knockdown of circSP3 inhibits proliferation, triggers apoptosis, and reduces migration and invasion in different ccRCC cells in vitro. Correspondingly, circSP3 overexpression Promote ccRCC tumorigenicity in a mouse xenograft model. Mechanistically, circSP3 could bind with the ribosome to initiate the translation process to encodes a novel 461-amino acid peptide referred to as SP3-461aa, which protects the MYH9 protein from proteasomal degradation. SP3-461aa played a pivotal role in mediating the oncogenic effects of circSP3 by interacting with the MYH9 protein and activating the PI3K-Akt signaling pathway. These findings suggested that circSP3 plays an important role in ccRCC development and could be a potential biomarker for the treatment and prognosis of ccRCC.

MiR-497-5p Expression and Biological Activity in Gastric Cancer.

Background: This research aims to investigate the expression and biological roles of miR-497-5p in gastric cancer (GC), and its possible mechanisms. Methods: Real Time Quantitative PCR (RT-qPCR) was performed to detect miR-497-5p in GC and normal tissues, as well as GC cell lines versus normal gastric mucosal cells (GES-1). The effects of miR-497-5p overexpression on proliferation were measured by the cell counting kit-8 (CCK8) assay and ethidium bromide (EdU) assay. Flow cytometry was used to assess the cell cycle. The migration and invasion were evaluated by scratch assay and Transwell assay, respectively. Gene targets of miR-497-5p were predicted using "multiMiR" R package combined with mirTarPathway database. And then luciferase reporter experiment was used to evaluate the activity of ERBB2 by miR-497-5p mimics in GC cell line. Besides, functional experiments were performed to verify the impact of miR-497-5p /ERBB2 on phenotypes of GC cells. Results: Compared with the normal tissues and mucosal cells, miR-497-5p was reduced in GC tissues and GC cell lines. miR-497-5p significantly decreased proliferation, migration, and invasion capacity, with an elevated apoptosis ratio of gastric cancer cells. Bioinformatics indicated that ERBB2 might be the potential target of miR-497-5p Dual-luciferase reporter experiments showed it adversely regulated ERBB2 3'UTR luciferase activity. The expression of ERBB2 in GC tissues and cells is significantly higher compared to normal tissues and cells. Over-expression of ERBB2 in gastric cancer cells significantly reduced miR-497-5p's inhibitory effect on the malignant behavior of GC cells. Conclusion: miR-497-5p was significantly down-regulated in GC tissues and cells, which inhibited the malignant features of GC cells by targeting ERBB2.

Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer.

Purpose: Platinum-based chemotherapy is effective but limited by resistance in high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing (scRNA-seq) can reveal tumour cell heterogeneity and subclonal differentiation. We aimed to analyze resistance mechanisms and potential targets in HGSOC using scRNA-seq. Methods: We performed 10× genomics scRNA-seq sequencing on tumour tissues from 3 platinum-sensitive and 3 platinum-resistant HGSOC patients. We analyzed cell subcluster communication networks and spatial distribution using cellchat. We performed RNA-seq analysis on TACSTD2, a representative resistance gene in the E0 subcluster, to explore its molecular mechanism. Results: Epithelial cells, characterized by distinct chemotherapy resistance traits and highest gene copy number variations, revealed a specific cisplatin-resistant cluster (E0) associated with poor prognosis. E0 exhibited malignant features related to resistance, fostering growth through communication with fibroblasts and endothelial cells. Spatially, E0 promoted fibroblasts to protect tumour cells and impede immune cells infiltration. Furthermore, TACSTD2 was identified as a representative gene of the E0 subcluster, elucidating its role in platinum resistance through the Rap1/PI3K/AKT pathway. Conclusions: Our study reveals a platinum-resistant epithelial cell subcluster E0 and its association with TACSTD2 in HGSOC, uncovers new insights and evidence for the platinum resistance mechanism, and provides new ideas and targets for the development of therapeutic strategies against TACSTD2+ epithelial cancer cells.

Pure squamous cell carcinoma of primary pancreatic origin

Introduction. Primary, ?pure? squamous cell carcinoma (SCC) is an exceptionally rare pancreatic malignancy that has been described in sporadic case reports. The appearance of this rare entity created a diagnostic dilemma for us, therefore, in this case report, we are focused on the radiological detection and characterization, pathogenesis, and therapeutic options of pure pancreatic SCC. Case outline. In an 80-year-old female patient, a partially necrotic mass in the tail of the pancreas was detected by computed tomography, which is the rarest localization of this tumor. On the performed imaging, the tumor showed predominantly malignant features with a surprising definitive histopathological diagnosis in the direction of pure SCC. Distal pancreatectomy with splenectomy was performed because of the infiltration of lienal vascular structures. Conclusion. Due to the very aggressive form of this tumor and poor prognosis, early detection, risk factors control, genetic burden, and optimization of surgical and therapeutic management can improve the quality of life and prolong the overall survival period.

Early real-world experience monitoring circulating tumor DNA in resected early-stage non–small cell lung cancer

ObjectiveThe study objective was to evaluate the impact of monitoring circulating tumor DNA on the detection and management of recurrence in patients with resected early-stage non–small cell lung cancer. MethodsBetween October 2021 and March 2023, postoperative circulating tumor DNA was monitored in patients with non–small cell lung cancer (N = 108). Longitudinal blood samples (n = 378 samples) were collected for prospective circulating tumor DNA analysis at 3-month intervals after curative-intent resection. A tumor-informed assay was used for the detection and quantification of circulating tumor DNA. The primary outcome measure was a circulating tumor DNA–positive result. The secondary outcome measure was changes in practice after a circulating tumor DNA–positive result. ResultsThe mean age of the patients in this cohort was 68.1 years. Of the 108 patients, 12 (11.1%) were circulating tumor DNA positive at least at 1 timepoint postsurgery, of whom 8 (66.7%) had a clinically evident recurrence and the remaining 4 had limited clinical follow-up. Of the 10 patients with recurrent disease, 8 demonstrated circulating tumor DNA positivity and the remaining 2 patients had brain-only metastases. Postoperative clinical care was altered in 100% (12/12) of circulating tumor DNA–positive patients, with 58.3% (7/12) receiving an early computed tomography scan and 100% (12/12) receiving an early positron emission tomography computed tomography scan as part of their surveillance strategy. Among the patients who received an early positron emission tomography scan, 66.6% (8/12) were positive for malignant features. ConclusionsRoutine monitoring of tumor-informed circulating tumor DNA after curative intent therapy improved patient risk stratification and prognostication.

Exosomal microRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer.

Oral cancer, a malignancy that is prevalent worldwide, is often diagnosed at an advanced stage. MicroRNAs (miRNAs) in circulating exosomes have emerged as promising cancer biomarkers. The role of miRNA let-7c-5p in oral cancer remains underexplored, and its potential involvement in tumorigenesis warrants comprehensive investigation. Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content. Isolation of the exosomes was confirmed through transmission electron microscopy. Quantitative PCR was used to assess the miRNA profiles. The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability, migration, and invasion were analyzed via CCK-8 and Transwell assays. Moreover, we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes. let-7c-5p was upregulated in serum-derived exosomes of patients with oral cancer. Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative, migratory, and invasive capacities, and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness. Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes. We further identified TAGLN as a direct target of let-7c-5p, which has been implicated in modulating the oncogenic potential of oral cancer cells. Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells. Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression, highlighting its potential as a diagnostic and therapeutic strategy.

Analysis of the role of dihydromyricetin derived from vine tea (Ampelopsis grossedentata) on multiple myeloma by activating STAT1/RIG-I axis.

Multiple myeloma (MM) is a plasma cell malignancy and remains incurable as it lacks effective curative approaches; thus, novel therapeutic strategies are desperately needed. The study aimed to explore the therapeutic role of dihydromyricetin (DHM) in MM and explore its mechanisms. Human MM and normal plasma samples, human MM cell lines, and normal plasma cells were used for in vitro experiments. Cell counting kit-8 (CCK-8), flow cytometry, and trans-well assays were performed for the assessment of cell viability, apoptosis, migration, and invasion, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA expression of signal transducer and activator of transcription 1 (STAT1) and retinoic acid-inducible gene I (RIG-I). Western blotting was employed to assess E-cadherin, N-cadherin, signal transducer, STAT1, p-STAT1, and RIG-I protein expression. A tumor xenograft model was used for in vivo experiments. Here, dihydromyricetin (DHM) dose-dependently restrained viability, apoptosis, migration, and invasion, and facilitated apoptosis of U266 cells. After DHM treatment, the E-cadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells, suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition (EMT) in MM. Besides, the levels of p-STAT1/STAT1 and RIG-I were down-regulated in MM. However, the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 cells. Also, DHM inhibited MM tumor growth and EMT, and activated STAT1/RIG-I pathway in vivo. Collectively, this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling, which provides a novel drug for the treatment of MM.

IRE1 endoribonuclease signaling promotes myeloid cell infiltration in glioblastoma.

Intrinsic or environmental stresses trigger the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), leading to ER stress. To cope with this, cells have evolved an adaptive mechanism named the unfolded protein response (UPR) which is hijacked by tumor cells to develop malignant features. Glioblastoma (GB), the most aggressive and lethal primary brain tumor, relies on UPR to sustain growth. We recently showed that IRE1 alpha (referred to IRE1 hereafter), 1 of the UPR transducers, promotes GB invasion, angiogenesis, and infiltration by macrophage. Hence, high tumor IRE1 activity in tumor cells predicts a worse outcome. Herein, we characterized the IRE1-dependent signaling that shapes the immune microenvironment toward monocytes/macrophages and neutrophils. We used human and mouse cellular models in which IRE1 was genetically or pharmacologically invalidated and which were tested in vivo. Publicly available datasets from GB patients were also analyzed to confirm our findings. We showed that IRE1 signaling, through both the transcription factor XBP1s and the regulated IRE1-dependent decay controls the expression of the ubiquitin-conjugating E2 enzyme UBE2D3. In turn, UBE2D3 activates the NFκB pathway, resulting in chemokine production and myeloid infiltration in tumors. Our work identifies a novel IRE1/UBE2D3 proinflammatory axis that plays an instrumental role in GB immune regulation.

CAM-QUS guided self-tuning modular CNNs with multi-loss functions for fully automated breast lesion classification in ultrasound images

Objective. Breast cancer is the major cause of cancer death among women worldwide. Deep learning-based computer-aided diagnosis (CAD) systems for classifying lesions in breast ultrasound images can help materialise the early detection of breast cancer and enhance survival chances. Approach. This paper presents a completely automated BUS diagnosis system with modular convolutional neural networks tuned with novel loss functions. The proposed network comprises a dynamic channel input enhancement network, an attention-guided InceptionV3-based feature extraction network, a classification network, and a parallel feature transformation network to map deep features into quantitative ultrasound (QUS) feature space. These networks function together to improve classification accuracy by increasing the separation of benign and malignant class-specific features and enriching them simultaneously. Unlike the categorical crossentropy (CCE) loss-based traditional approaches, our method uses two additional novel losses: class activation mapping (CAM)-based and QUS feature-based losses, to capacitate the overall network learn the extraction of clinically valued lesion shape and texture-related properties focusing primarily the lesion area for explainable AI (XAI). Main results. Experiments on four public, one private, and a combined breast ultrasound dataset are used to validate our strategy. The suggested technique obtains an accuracy of 97.28%, sensitivity of 93.87%, F1-score of 95.42% on dataset 1 (BUSI), and an accuracy of 91.50%, sensitivity of 89.38%, and F1-score of 89.31% on the combined dataset, consisting of 1494 images collected from hospitals in five demographic locations using four ultrasound systems of different manufacturers. These results outperform techniques reported in the literature by a considerable margin. Significance. The proposed CAD system provides diagnosis from the auto-focused lesion area of B-mode BUS images, avoiding the explicit requirement of any segmentation or region of interest extraction, and thus can be a handy tool for making accurate and reliable diagnoses even in unspecialized healthcare centers.

The Impact of BRAF V600E Mutation Allele Frequency on the Histopathological Characteristics of Thyroid Cancer.

A BRAF V600E mutation in papillary thyroid cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all BRAF V600E PTCs behave aggressively. Allele frequency (AF) is the number of mutated molecules divided by the total number of wild-type molecules at a specific location in the genome. The relationship between BRAF V600E AF and the histopathological features of thyroid malignancies is not well understood. We hypothesized that the BRAF V600E AF will correlate directly with aggressive histopathological behavior. The aim of this study was to examine this relationship. A retrospective chart review was performed for patients treated for BRAF V600E thyroid malignancies from 2019 to 2022 at McGill University tertiary care hospitals (n = 317). Patients with BRAF V600E-positive malignancies that included information on AF were included (n = 44). The correlation between AF and tumor histopathological features was analyzed. Out of the 44 nodules with a BRAF V600E mutation, those with aggressive features of PTC had a mean AF of 25.8%, which was significantly higher than the non-aggressive group with a mean AF of 10.25% (p = 0.020). Additionally, there was a statistically significant difference in mean AF between patients with a positive sentinel LN (29%) and those with a negative sentinel LN (17.8%) (p = 0.021). Classical PTC was present in 29.5% (13/44) of nodules, with a mean AF of 15.6%. The tall cell subtype was found in 64% (28/44) of nodules, with a mean AF of 23%. Solid and hobnail subtypes were less common in this study, and there was no statistically significant relationship between AF and histopathological subtypes (p = 0.107). Nodules smaller than 1cm had a mean AF of 13.3%, while nodules ranging from 1 2cm had a mean AF of 20.6%, and those larger than 2cm had a mean AF of 27.7%. However, no statistical difference was observed between AF and nodule size (p = 0.160). In this study, BRAF V600E mutations in conjunction with AF help to determine whether thyroid malignancies will display aggressive behavior. This pre-operative finding can help thyroid specialists to determine the extent of thyroidectomy and whether lymph node dissection is required.

Ultrasound findings of hepatic epithelioid hemangioendothelioma: comparison with other malignant hepatic tumors.

To investigate and compare the ultrasonic features of hepatic epithelioid hemangioendothelioma (HEHE) and other common hepatic malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepatic metastatic tumor (HMT). A total of 37 patients with pathologically proven HEHE, 37 HCC cases, 37 ICC cases, and 37 HMT cases were enrolled from single hospital. The clinical characteristics and ultrasonic features of all cases were summarized and statistically analyzed. There were significant differences in sex and age between the HEHE group and other three groups (P < 0.001). The probability of HEHE infection with hepatitis B virus was lower than that of HCC and ICC groups (P < 0.05). The probability of elevated serum tumor markers in HEHE was significantly lower than that in the other three groups (P < 0.05). On conventional ultrasound (CUS), the probability of multiple lesions in HEHE was significantly higher than that in the other three groups (P < 0.05). On contrast-enhanced ultrasound (CEUS), the time to wash out in HEHE was significantly shorter than that of the other three groups (P < 0.001). The proportion of synchronous or slow enhancement in HEHE was significantly higher than that of the other three groups (P < 0.001). The proportion of HEHE with iso- or hypo-enhancement was significantly higher than in HCC and HMT groups (P < 0.05). HEHE mainly performed multiple hypoechoic lesions on CUS and displayed greater odds of synchronous enhancement in arterial phase, iso- or hypo-enhancement in peak time and wash out more quickly on CEUS, which allowed for differentiation from other common malignant tumors.

A synergistic regulation works in matrix stiffness-driven invadopodia formation in HCC

Growing evidence has suggested that increased matrix stiffness can significantly strengthen the malignant characteristics of hepatocellular carcinoma (HCC) cells. However, whether and how increased matrix stiffness regulates the formation of invadopodia in HCC cells remain largely unknown. In the study, we developed different experimental systems in vitro and in vivo to explore the effects of matrix stiffness on the formation of invadopodia and its relevant molecular mechanism. Our results demonstrated that increased matrix stiffness remarkably augmented the migration and invasion abilities of HCC cells, upregulated the expressions of invadopodia-associated genes and enhanced the number of invadopodia. Two regulatory pathways contribute to matrix stiffness-driven invadopodia formation together in HCC cells, including direct triggering invadopodia formation through activating integrin β1 or Piezo1/ FAK/Src/Arg/cortactin pathway, and indirect stimulating invadopodia formation through improving EGF production to activate EGFR/Src/Arg/cortactin pathway. Src was identified as the common hub molecule of two synergistic regulatory pathways. Simultaneously, activation of integrin β1/RhoA/ROCK1/MLC2 and Piezo1/Ca2+/MLCK/MLC2 pathways mediate matrix stiffness-reinforced cell migration. This study uncovers a new mechanism by which mechanosensory pathway and biochemical signal pathway synergistically regulate the formation of invadopodia in HCC cells.

Frequency and features of malignant tumors clinically mimicking cutaneous cysts: A retrospective chart review.

Many cutaneous lesions are clinically suspected as "cyst"; however, following histopathological examination, are found to be more significant lesions. Here, we examine the frequency and features of malignancies with cutaneous cysts in the clinical differential. A retrospective study of surgical pathology specimens at the James A. Haley Veterans' Hospital from January 2018 to December 2022 was conducted. Cutaneous specimens containing the clinical diagnosis of "cyst" were included. The clinicopathological features were summarized. Premalignant or malignant neoplasms accounted for 4.5% of all specimens submitted with cysts in the clinical differential. Most cyst-mimicking cancers were basal cell carcinoma (BCC) or squamous cell carcinoma (SCC); however, cancers with poorer prognoses, such as Merkel cell carcinoma and melanoma, also clinically masqueraded as cysts. The BCCs were predominately nodular, and the SCCs were largely well-differentiated and invasive. Many exhibited clinical signs and symptoms compatible with benign cysts, such as central punctum, pain, and rapid growth. Identified risk factors included history of prior non-melanoma skin cancer diagnosis, previous excision, and immunosuppression. Many lesions clinically concerning cutaneous cysts were found to be malignancies following histopathological review. Accordingly, following biopsy all cyst-like lesions should be examined microscopically, especially in certain clinical contexts in which the incidence of skin cancer is increased.

FABP5 can substitute for androgen receptor in malignant progression of prostate cancer cells.

Fatty acid‑binding protein 5 (FABP5) and androgen receptor (AR) are critical promoters of prostate cancer. In the present study, the effects of knocking out the FABP5 or AR genes on malignant characteristics of prostate cancer cells were investigated, and changes in the expression of certain key proteins in the FABP5 (or AR)‑peroxisome proliferator activated receptor‑γ (PPARγ)‑vascular endothelial growth factor (VEGF) signaling pathway were monitored. The results obtained showed that FABP5‑ or AR‑knockout (KO) led to a marked suppression of the malignant characteristics of the cells, in part, through disrupting this signaling pathway. Moreover, FABP5 and AR are able to interact with each other to regulate this pathway, with FABP5 controlling the dominant AR splicing variant 7 (ARV7), and AR, in return, regulates the expression of FABP5. Comparisons of the RNA profiles revealed the existence of numerous differentially expressed genes (DEGs) comparing between the parental and the FABP5‑ or AR‑KO cells. The six most abundant changes in DEGs were found to be attributable to the transition from androgen‑responsive to androgen‑unresponsive, castration‑resistant prostate cancer (CRPC) cells. These findings have provided novel insights into the complex molecular pathogenesis of CRPC cells, and have demonstrated that interactions between FABP5 and AR contribute to the transition of prostate cancer cells to an androgen‑independent state. Moreover, gene enrichment analysis revealed that the most highly enriched biological processes associated with the DEGs included those responsive to fatty acids, cholesterol and sterol biosynthesis, as well as to lipid and fatty acid transportation. Since these pathways regulated by FABP5 or AR may be crucial in terms of transducing signals for cancer cell progression, targeting FABP5, AR and their associated pathways, rather than AR alone, may provide a new avenue for the development of therapeutic strategies geared towards suppressing the malignant progression to CRPC cells.