Lung cancers are broadly divided into two categories: non-small-cell lung carcinoma (NSCLC), which accounts for 80–85% of all cancer cases, and small-cell lung carcinoma (SCLC), which covers the remaining 10–15%. Recent advances in cancer biology and genomics research have allowed an in-depth characterization of lung cancers that have revealed new therapy targets (EGFR, ALK, ROS, and KRAS mutations) and have the potential of revealing even more biomarkers for diagnostic, prognostic, and targeted therapies. A new source of biomarkers is represented by non-coding RNAs, especially microRNAs (miRNAs). MiRNAs are short non-coding RNA sequences that have essential regulatory roles in multiple cancers. Therefore, we aim to investigate the tumor microenvironment (TME) and miRNA tumor profile in a subset of 51 early-stage lung cancer samples (T1 and T2) to better understand early tumor and TME organization and molecular dysregulation. We analyzed the immunohistochemistry expression of CD4 and CD8 as markers of the main TME immune populations, E-cadherin to evaluate early-stage epithelial-to-mesenchymal transition (EMT), and p53, the main altered tumor suppressor gene in lung cancer. Starting from these 4 markers, we identified and validated 4 miRNAs that target TP53 and regulate EMT that can be further investigated as potential early-stage lung cancer biomarkers.

The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays a crucial role in driving tumor progression, shaping treatment responses, and influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) tumor stroma, highlighting its key constituents and their dynamic contributions. We examine how significant changes within the cSCC ECM—specifically, alterations in fibronectin, hyaluronic acid, laminins, proteoglycans, and collagens—promote cancer progression, metastasis, and drug resistance. The cellular composition of the cSCC TME is also explored, detailing the intricate interplay of cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, and various immune cell populations. These diverse players modulate tumor development, angiogenesis, and immune responses. Finally, we emphasize the TME’s potential as a therapeutic target. Emerging strategies discussed in this review include harnessing the immune system (adoptive cell transfer, checkpoint blockade), hindering tumor angiogenesis, disrupting CAF activity, and manipulating ECM components. These approaches underscore the vital role that deciphering TME interactions plays in advancing cSCC therapy. Further research illuminating these complex relationships will uncover new avenues for developing more effective treatments for cSCC.

Inflammation and hyperlipidemia play an essential role in the pathophysiology of endothelial dysfunction as well as atherosclerotic plaque formation, progression and rupture. Colchicine has direct anti-inflammatory effects by inhibiting multiple inflammatory signaling pathways. The purpose of our study was to evaluate colchicine activity in an animal model of hyperlipidemia induced by diet. A total of 24 male rats (wild type, WT) were divided into three groups: group one fed with a basic diet (BD) (WT + BD, n = 8), group two fed with a high-fat diet (HFD) (WT + HFD, n = 8)), and group three which received HFD plus drug treatment (colchicine, 0.5 mg/kg, i.p., daily administration). Total cholesterol, LDL-, HDL-cholesterol and triglycerides were determined. In addition, plasma transaminases, inflammation of oxidative stress markers, were measured. Tissue samples were evaluated using hematoxylin-eosin and red oil stain. At the end of the study, rats presented increased serum lipid levels, high oxidative stress and pro-inflammatory markers. The aortic histopathological section revealed that HFD induced signs of endothelial dysfunction. Colchicine treatment significantly resolved and normalized these alterations. Moreover, colchicine did not influence NAFLD activity score but significantly increased ALT and AST levels, suggesting that colchicine amplified the hepatocellular injury produced by the diet. Colchicine reduces plasma lipid levels, oxidative stress and inflammation markers and leads to more favorable histopathologic vascular and cardiac results. However, the adverse effects of colchicine could represent an obstacle to its safe use.

Background: Hyperlipidemia and inflammation are critical components in the pathophysiology of endothelial disorder, which can lead to vascular complications. Our study aimed to evaluate the effects of immunomodulatory therapy (methotrexate and infliximab) in a diet-induced hyperlipidemia rat model. Methods: Sprague-Dawley (wild type (WT), male, n = 32) rats were divided into four groups: one group fed with standard diet (SD), one group fed with high lipid diet (HLD), and two groups that received HLD and drug treatment (methotrexate (Mtx) or infliximab (Ifx)). In order to evaluate if modifications to the endothelial cells may influence the risk of vascular complications following hyperlipidemia or treatment reactivity, each group was doubled by a rats group that overexpressed beta-3 receptors on the endothelial cells (transgenic (TG-beta 3), male, n = 32). Serum lipid profile, liver enzymes, oxidative stress, and inflammation markers were determined. Histopathologic analysis of the liver and aorta was performed. Results: After 9 weeks of HLD, rats exhibited significant pathologic serum lipid profiles, elevated oxidative stress, and pro-inflammatory markers. Additionally, the aortic histopathological analysis revealed aorta media-intima thickening (p < 0.05) in the transgenic group. Methotrexate and infliximab significantly decreased inflammation and oxidative stress parameters, but presented opposing effects on lipid profiles (methotrexate decreased, whereas infliximab increased the atherosclerosis index). Drug treatment decreased the aorta media-intima thickness (p < 0.05) only in transgenic rats. Conclusions: HLD was associated with hyperlipidemia, inflammation and oxidative stress. The overexpression of beta-3 receptors on endothelial cells increased aortic thickening in response to the HLD. Methotrexate and infliximab reduced oxidative stress and inflammation in all groups, but led to favorable histopathologic vascular results only in the transgenic groups.

Neuroendocrine tumors (NEN) are a type of heterogenous, slow-growing tumors, that only in about half of the cases can be found in the gastrointestinal tract. Half of these is in the small intestine. The ampullary NENs are rare, accounting for less than 1% of gastroenteropancreatic NENs. Gastrointestinal stromal tumors (GIST) are a more common type of tumors of the gastrointestinal tract that consist of pacemaker cells. The occurrence of both tumors simultaneously is rare, but in patients with neurofibromatosis type 1, the co-existence of NEN and GIST is more often. Here we report a case of simultaneous occurrence of a well-differentiated NEN and a GIST in a patient without neurofibromatosis. Also, we provide a short review of the current knowledge and treatment strategies regarding these tumors.

The global incidence of cutaneous squamous cell carcinoma (cSCC), a prevalent and aggressive skin cancer, has risen significantly, posing a substantial public health challenge. This study investigates the tumor microenvironment (TME) of cSCC by focusing on the spatial distribution patterns of immune and vascular markers (CD31, CD20, CD4, and CD8) using fractal dimension (FD) analysis. Our analysis encompassed 141 cases, including 100 invasive cSCCs and 41 specimens with pre-invasive lesions exclusively, and the rest were peripheral pre-invasive lesions from the invasive cSCC class. The FD values for each marker were computed and compared between pre-invasive and invasive lesion classes. The results revealed significant differences in FD values between the two classes for CD20 and CD31 markers, suggesting distinct alterations in B cell distribution and angiogenic activity during cSCC progression. However, CD4 and CD8 markers did not exhibit significant changes individually. Still, the CD4/CD8 ratio showed a significant difference, suggesting a potential shift in the balance between T helper and cytotoxic T cell responses, impacting the immune landscape as lesions progressed from pre-invasive to invasive stages. These findings underscore the complexity and heterogeneity of the TME in cSCC and highlight the potential of FD analysis as a quantitative tool for characterizing tumor progression. Further research is needed to elucidate the implications of these differences in the clinical management of cSCC.