In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species.
View Article and Find Full Text PDFThe clinical use of potent androgen receptor (AR) inhibitors has promoted the emergence of novel subtypes of metastatic castration-resistant prostate cancer (mCRPC), including neuroendocrine prostate cancer (CRPC-NE), which is highly aggressive and lethal . These mCRPC subtypes display increased lineage plasticity and often lack AR expression . Here we show that neuroendocrine differentiation and castration-resistance in CRPC-NE are maintained by the activity of Nuclear Receptor Binding SET Domain Protein 2 (NSD2) , which catalyzes histone H3 lysine 36 dimethylation (H3K36me2).
View Article and Find Full Text PDFDespite major advancements in lung cancer treatment, long-term survival is still rare, and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune evasion mechanisms. Here we performed in-depth mass spectrometry (MS)-based proteogenomic analysis of 141 tumors representing all major histologies of non-small cell lung cancer (NSCLC). We identified six distinct proteome subtypes with striking differences in immune cell composition and subtype-specific expression of immune checkpoints.
View Article and Find Full Text PDFBackground: Fibroblast growth factor 21 (FGF21) is expressed in several metabolically active tissues, including liver, fat, and acinar pancreas, and has pleiotropic effects on metabolic homeostasis. The dominant source of FGF21 in the circulation is the liver.
Objective And Methods: To analyze the physiological functions of hepatic FGF21, we generated a hepatocyte-specific knockout model (LKO) by mating albumin-Cre mice with FGF21 flox/flox (fl/fl) mice and challenged it with different nutritional models.
In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete.
View Article and Find Full Text PDFBackground: The aim of the present study was to evaluate the prognostic significance of perineural invasion (PNI) in locally advanced gastric cancer patients who underwent D2 gastrectomy and adjuvant chemotherapy.
Methods: The records of a series of 103 patients undergoing D2 gastrectomy with curative intent combined with adjuvant chemotherapy from January 2004 to December 2014 were retrospectively reviewed.
Results: PNI was positive in 47 (45.
In this work, the authors will discuss about a new protocol and rapid alternative to isolate the mesenchymal stromal cells from the stromal vascular fraction, without the use of collagenase, to regenerate the bone tissue in the maxillo-facial region. This method employs a device that allows the isolation and concentration of stromal vascular fraction by means of lipoaspirates, which separate the lipid component and fragments of the extracellular matrix. The innovative element consists in using a filtration device instead of a centrifuging device to separate the different components.
View Article and Find Full Text PDFWith the widespread availability of biological antitumor drugs, the current scene of chemotherapies is changing. New chemotherapy agents, such as crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK) and ROS1, usually used in pretreated advanced ALK-positive non-small-cell lung carcinoma, are more often used, and a description of the onset of side effects with suggestions for their management could be of interest for physicians. We describe a case of diffuse and aggressive renal polycystosis induced by crizotinib, which regressed after therapy, which could be of interest considering its wide extension and disappearance after the end of treatment.
View Article and Find Full Text PDFJ Cardiovasc Med (Hagerstown)
December 2016
: We report a rare case of a patient with AL amyloidosis and pseudoxanthoma elasticum skin lesions. An association between these two diseases has been previously described as amyloid elastosis in only six cases, but cardiac findings were not fully elucidated. The peculiarity of our case is that a severe cardiac involvement influenced the prognosis negatively.
View Article and Find Full Text PDFPure adenocarcinomas of the urothelium are very rare and their location in the pelvis is uncommon. Although their pathogenesis is not well defined, adenocarcinomas are likely to originate from neoplastic transformation of the glandular cells of the urothelial intestinal metaplasia usually arising in response to chronic irritating stimuli, such as long-duration inflammation, urolithiasis, and hydronephrosis. We report a case of an 81-year-old woman who underwent right nephrectomy for relapsing renal abscess due to a staghorn calculus.
View Article and Find Full Text PDFPleomorphic adenoma is a common benign salivary gland tumor, which represents about 66 % of benign neoplasms of the salivary glands. Although it can occur in any salivary gland, it is most frequently found in the parotid. Pleomorphic adenomas are renowned for their cytomorphological and architectural heterogeneity that are characterized by intermixed epithelial and mesenchymal-like components.
View Article and Find Full Text PDFMetastases of non-thyroid malignancies to the thyroid gland have been reported in 1.4% to 3% of patients undergoing thyroid surgery for thyroid malignancy. We report a case of thyroid metastases from renal cell carcinoma in a 57-year-old man, who underwent a left nephrectomy 11 years earlier for a renal cell carcinoma.
View Article and Find Full Text PDFBackground: We have previously demonstrated that expression of COX-2 is upregulated by hepatocyte growth factor in thyroid papillary carcinoma (TPC) cells and is associated with increased invasiveness of tumor cells. COX-2 upregulation was associated with downregulation of KAI-1/CD82, a metastasis suppressor molecule that has been associated with the metastatic potential of several solid tumors. In the present study, we have investigated the possibility that downregulation of KAI-1/CD82 may contribute to the invasiveness of papillary carcinoma cells.
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