High aggressiveness of papillary thyroid cancer: from clinical evidence to regulatory cellular networks.

The global incidence of thyroid cancer has increased over recent decades. Papillary thyroid cancer (PTC) is the most common type of thyroid cancer and accounts for nearly 90% of all cases. Typically, PTC has a good prognosis.

Homogentisic acid metabolism inhibits papillary thyroid carcinoma proliferation through ROS and p21-induced cell cycle arrest.

Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed therein. Although PTC has been studied extensively, our understanding of the altered metabolism and metabolic profile of PTC tumors is limited. We identified that the content of metabolite homogentisic acid (HGA) in PTC tissues was lower than that in adjacent non-cancerous tissues.

DNMT3A Cooperates with YAP/TAZ to Drive Gallbladder Cancer Metastasis.

Gallbladder cancer (GBC) is an extremely lethal malignancy with aggressive behaviors, including liver or distant metastasis; however, the underlying mechanisms driving the metastasis of GBC remain poorly understood. In this study, it is found that DNA methyltransferase DNMT3A is highly expressed in GBC tumor tissues compared to matched adjacent normal tissues. Clinicopathological analysis shows that DNMT3A is positively correlated with liver metastasis and poor overall survival outcomes in patients with GBC.

Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT for the Early and Late Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Prospective Study.

Ga-labeled fibroblast activation protein inhibitor (Ga-FAPI) PET/CT has demonstrated promising clinical results, with a higher SUV and tumor-to-background ratio (TBR) in breast cancer (BC) patients than F-FDG PET/CT. Here, we aimed to evaluate the suitability of Ga-FAPI PET/CT for the early and late prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in BC. Twenty-two consecutive patients with newly diagnosed BC and an indication for NAC were prospectively included.

Targeting c-Jun inhibits fatty acid oxidation to overcome tamoxifen resistance in estrogen receptor-positive breast cancer.

Tamoxifen-based endocrine therapy remains a major adjuvant therapy for estrogen receptor (ER)-positive breast cancer (BC). However, many patients develop tamoxifen resistance, which results in recurrence and poor prognosis. Herein, we show that fatty acid oxidation (FAO) was activated in tamoxifen-resistant (TamR) ER-positive BC cells by performing bioinformatic and functional studies.

Construction of a risk model based on N -methyladenosinerelated lncRNAs for predicting the prognosis of breast cancer.

N-methyladenosine modification and lncRNAs are closely related to the prognosis and immunotherapy response of breast cancer patients. LncRNAs related to m A-associated genes were predicted based on coexpression analysis of the TCGA database. We established a novel 7-m A-associated lncRNA signature for predicting patient prognosis and validated it.

SENP3 promotes tumor progression and is a novel prognostic biomarker in triple-negative breast cancer.

Background: The clinical outcome of triple-negative breast cancer (TNBC) is poor. Finding more targets for the treatment of TNBC is an urgent need. SENPs are SUMO-specific proteins that play an important role in SUMO modification.

Combining polyp diameter and polyp-to-bile ratio by dynamic contrast-enhanced CT scanning can improve the diagnostic specificity of gallbladder neoplastic polyps.

Objective: This study aimed to distinguish between cholesterol and neoplastic gallbladder polyps using dynamic contrast-enhanced CT.

Methods: The dataset retrospectively comprised 222 cases, including 106 cases of cholesterol polyps and 116 cases of neoplastic polyps (59 adenoma and 57 adenocarcinoma). The perception and Hounsfield units of the polyps and gallbladder bile were assessed by contrast-enhanced CT, and the polyp-to-bile ratio (PBR) was calculated.

Histone deacetylase inhibitor panobinostat in combination with rapamycin confers enhanced efficacy against triple-negative breast cancer.

Triple-negative breast cancer (TNBC) accounts for about 15% of diagnosed breast cancer patients, which has a poor survival outcome owing to a lack of effective therapies. This study aimed to explore the in vitro and in vivo efficiency of histone deacetylase (HDAC) inhibitor panobinostat (PANO) in combination with mTOR inhibitor rapamycin (RAPA) against TNBC. TNBC cells were treated with PANO, RAPA alone or the combination of drugs, then cell growth and apoptosis were evaluated by CCK-8, colony formation and flow cytometry.

MiR-4733-5p promotes gallbladder carcinoma progression via directly targeting kruppel like factor 7.

Gallbladder carcinoma (GBC) is highly aggressive with poor prognosis. Accumulating reports show that miRNAs play critical roles in tumor progression. Previous studies have identified several miRNAs that promoted or inhibited GBC cell proliferation and/or metastasis.

NR4A1 promotes LEF1 expression in the pathogenesis of papillary thyroid cancer.

The morbidity of papillary thyroid cancer (PTC) is on the rise, but its pathogenesis is still poorly understood. NR4A1 is a transcription factor primarily involving a wide range of pathophysiological responses, but its relationship with PTC malignancy remains unclear. This study demonstrates that high NR4A1 expression is strongly associated with poor survival outcomes in PTC patients.

Epigenetic activation of the elongator complex sensitizes gallbladder cancer to gemcitabine therapy.

Background: Gallbladder cancer (GBC) is known for its high malignancy and multidrug resistance. Previously, we uncovered that impaired integrity and stability of the elongator complex leads to GBC chemotherapy resistance, but whether its restoration can be an efficient therapeutic strategy for GBC remains unknown.

Methods: RT-qPCR, MS-qPCR and ChIP-qPCR were used to evaluate the direct association between ELP5 transcription and DNA methylation in tumour and non-tumour tissues of GBC.

Loss of ID3 drives papillary thyroid cancer metastasis by targeting E47-mediated epithelial to mesenchymal transition.

Papillary thyroid cancer (PTC) is the main histological type of thyroid cancer and accounts for almost all increased cases worldwide. Patients with PTC exhibit a favorable prognosis, but the fact that PTC is often accompanied by a high prevalence of lymph node metastasis (LNM) means that the overall recurrence-free survival rate in PTC patients is relatively low. Herein, we identified that ID3 expression is subdued in PTC tissues and closely associated with LNM and a poor disease-free survival outcome in PTC patients.

Modulation of mTOR and epigenetic pathways as therapeutics in gallbladder cancer.

Gallbladder cancer (GBC) is the most common malignancy of the biliary tract, with extremely dismal prognosis. Limited therapeutic options are available for GBC patients. We used whole-exome sequencing of human GBC to identify the ErbB and epigenetic pathways as two vulnerabilities in GBC.

Deoxycholic acid modulates the progression of gallbladder cancer through N-methyladenosine-dependent microRNA maturation.

Bile acids (BAs), well-defined signaling molecules with diverse metabolic functions, play important roles in cellular processes associated with many cancers. As one of the most common BAs, deoxycholic acid (DCA) is originally synthesized in the liver, stored in the gallbladder, and processed in the gut. DCA plays crucial roles in various tumors; however, functions and molecular mechanisms of DCA in gallbladder cancer (GBC) still remain poorly characterized.

Genome-wide CRISPR screen identifies ELP5 as a determinant of gemcitabine sensitivity in gallbladder cancer.

Gemcitabine is the first-line treatment for locally advanced and metastatic gallbladder cancer (GBC), but poor gemcitabine response is universal. Here, we utilize a genome-wide CRISPR screen to identify that loss of ELP5 reduces the gemcitabine-induced apoptosis in GBC cells in a P53-dependent manner through the Elongator complex and other uridine 34 (U) tRNA-modifying enzymes. Mechanistically, loss of ELP5 impairs the integrity and stability of the Elongator complex to abrogate wobble U tRNA modification, and directly impedes the wobble U modification-dependent translation of hnRNPQ mRNA, a validated P53 internal ribosomal entry site (IRES) trans-acting factor.

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer.

Gallbladder cancer (GBC) is the leading malignancy of biliary system showing refractory chemoresistance to current first-line drugs. Growing epidemiological evidences have established that the incidence of GBC exhibits significant gender predominance with females two-threefold higher than males, suggesting oestrogen/oestrogen receptors (ERs) signalling might be a critical driver of tumorigenesis in gallbladder. This study aims to evaluate the antitumour activity of tamoxifen (TAM), a major agent of hormonal therapy for breast cancer, in preclinical GBC model.

Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription.

Background: CircRNAs are found to affect initiation and progression of several cancer types. However, whether circRNAs are implicated in gallbladder cancer (GBC) progression remains obscure.

Methods: We perform RNA sequencing in 10 pairs of GBC and para-cancer tissues.

Variants in oxidative stress-related genes affect the chemosensitivity through Nrf2-mediated signaling pathway in biliary tract cancer.

Background: Oxidative stress and their effectors play critical roles in carcinogenesis and chemoresistance. However, the role of oxidative stress-related genes variants in biliary tract cancer (BTC) chemoresistance remains unknown. In this work, we aim to investigate oxidative stress-dependent molecular mechanisms underlying chemoresistance, and find potential biomarkers to predict chemotherapy response for BTC.

PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway.

Background: Gallbladder cancer (GBC) is an extremely malignant tumor with a high mortality rate. Little is known about its invasion and metastasis mechanism so far.

Methods: To identify the driver genes in GBC metastasis, we performed a mRNA microarray of metastatic GBC and paired non-tumor samples, and found PLEK2 was markedly upregulated in GBC tissues.

Guided chemotherapy based on patient-derived mini-xenograft models improves survival of gallbladder carcinoma patients.

Background: Gallbladder carcinoma is highly aggressive and resistant to chemotherapy, with no consistent strategy to guide first line chemotherapy. However, patient-derived xenograft (PDX) model has been increasingly used as an effective model for in preclinical study of chemosensitivity.

Methods: Mini-PDX model was established using freshly resected primary lesions from 12 patients with gallbladder to examine the sensitivity with five of the most commonly used chemotherapeutic agents, namely gemcitabine, oxaliplatin, 5-fluorouracil, nanoparticle albumin-bound (nab)-paclitaxel, and irinotecan.

PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating IFIT2.

Gallbladder cancer (GBC) is a malignant cancer with very poor prognosis. Although promyelocytic leukemia zinc-finger protein (PLZF) was reported to be deregulated in numerous cancers and also relevant to clinical prognosis, its role in GBC progression has been little known. In this study, we found PLZF expression was decreased in GBC, correlating to advanced TNM stage, distant metastasis, and shorter overall survival.

Epithelial-to-mesenchymal transition in gallbladder cancer: from clinical evidence to cellular regulatory networks.

Gallbladder cancer (GBC), with late diagnosis, rapid disease progression and early metastasis, is a highly aggressive malignant tumor found worldwide. Patients with GBC have poor survival, low curative resection rates and early recurrence. For such a lethal tumor, uncovering the mechanisms and exploring new strategies to prevent tumor progression and metastasis are critically important.