Malignant Research Articles

Pancancer analysis of NDUFA4L2 with focused role in tumor progression and metastasis of colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with a high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although NDUFA4L2 has high expressions in various tumors and affects tumor progression, its role in COAD remains unclear. The role of NDUFA4L2 in COAD was analyzed utilizing datasets available from public databases including The Cancer Genome Atlas, The Genotype-Tissue Expression (GTEx), Gene Expression Omnibus, Alabama Cancer Database (UALCAN), and The Human Protein Atlas databases. The prognostic value of NDUFA4L2 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NDUFA4L2 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NDUFA4L2 expression and immune cell infiltration levels was examined through single-sample gene set enrichment analysis (ssGSEA). The NDUFA4L2 expression levels in COAD patients and cell lines were validated through immunohistochemistry, immunofluorescence, qRT-PCR, and Western blot. Wound healing assay was also performed to evaluate the effect of NDUFA4L2 on COAD metastasis. Furthermore, the NDUFA4L2 mediated competing endogenous RNA (ceRNA) regulatory network was predicted and constructed through a variety of databases. The comprehensive pan-cancer analysis showed that NDUFA4L2 possesses diagnostic and prognostic value in many cancers, especially in COAD. GO-KEGG and GSEA analyses indicated that NDUFA4L2 was associated with multiple biological functions including epithelial-mesenchymal transition and adaptation to hypoxia. The ssGSEA analysis showed that NDUFA4L2 expression was associated with immune infiltration. In vitro experiments confirmed upregulation of NDUFA4L2 in COAD tissues and cell lines, and NDUFA4L2 overexpression significantly promoted migration of COAD cells. In addition, the C9orf139 /miR-194-3p axis was speculated as the possible upstream regulators of NDUFA4L2 in COAD. This study demonstrated that NDUFA4L2 upregulation was correlated with tumor progression, relapsed prognosis and aggressive migration of COAD, suggesting that NDUFA4L2 can act as an effective prognostic biomarker and a promising therapeutic target for COAD treatment.

Copper Nanoparticles Green-Formulated byCurcuma longa Extract Induce Apoptosis via P53 and STAT3 Signaling Pathways in Bladder Carcinoma Cell.

The study outlines the production of new copper nanoparticles infused with Curcuma longa extract to trigger apoptosis through P53 and signal transducer and activator of transcription 3 (STAT3) signaling pathways in bladder carcinoma cells. The structural characteristics of the nanoparticles that were synthesized were analyzed through various sophisticated methods such as transmission electron microscopy (TEM), field emission-scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy (FT-IR). During the antioxidant evaluation, the IC50 values for copper nanoparticles and butylated hydroxytoluene (BHT) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals were found to be 116µg/mL and 31µg/mL, respectively. The cells treated with copper nanoparticles underwent evaluation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for 48h to determine their anticancer properties on TCCSUP bladder carcinoma cell. The TCCSUP cell line exhibited an IC50 of 290µg/mL when exposed to copper nanoparticles. The viability of malignant cells decreased upon treatment with copper nanoparticles. Furthermore, the copper nanoparticles presence led to a 65-75% increase in cell apoptosis, along with an increase in Bax and cleaved caspase-8 and a decrease in the Bcl-2. Furthermore, the copper nanoparticles presence resulted in the suppression of colony formation. Notably, the molecular pathway analysis in cells treated with copper NPs demonstrated an increase in p53 expression, along with a decrease in the expression of both total and phosphorylated STAT3. This offers that p53 and STAT3 play a crucial role in the biological efficacies induced by the nanoparticles in human carcinoma cells. The data of our research suggest that copper NPs could have significant potential as an anticancer treatment for human bladder carcinoma cells.

Potential Player of Platelet in the Pathogenesis of Cardiotoxicity: Molecular Insight and Future Perspective.

Cancer patients may encounter the onset of cardiovascular disease due to tumor advancement or chemotherapy, commonly known as "cardiotoxicity." In this respect, the conventional chemotherapy treatment protocol involves a mixture of different medications. These medications can be detrimental to cardiac tissue, consequently exposing the patient to the possibility of irreversible cardiac injury. The enhancement of oxidative stress and inflammation is an important mechanism of chemotherapeutic agents for developing cardiotoxicity. Regarding their dual pro- and anti-inflammatory functions, platelets can significantly influence the progression or suppression of cardiotoxicity. Therefore, the expression of platelet activatory markers can serve as valuable prognostic indicators for cardiotoxicity. The primary objective of this study is to examine the significance of platelets in cardiotoxicity and explore potential strategies that could effectively target malignant cells while minimizing their cytotoxic impact, such as cardiotoxicity and thrombosis.

Identification of Phospholipids Relevant to Cancer Tissue Using Differential Ion Mobility Spectrometry

Phospholipids are the main building components of cell membranes and are also used for cell signaling and as energy storages. Cancer cells alter their lipid metabolism, which ultimately leads to an increase in phospholipids in cancer tissue. Surgical energy instruments use electrical or vibrational energy to heat tissues, which causes intra- and extracellular water to expand rapidly and degrade cell structures, bursting the cells, which causes the formation of a tissue aerosol or smoke depending on the amount of energy used. This gas phase analyte can then be analyzed via gas analysis methods. Differential mobility spectrometry (DMS) is a method that can be used to differentiate malignant tissue from benign tissues in real time via the analysis of surgical smoke produced by energy instruments. Previously, the DMS identification of cancer tissue was based on a ‘black box method’ by differentiating the 2D dispersion plots of samples. This study sets out to find datapoints from the DMS dispersion plots that represent relevant target molecules. We studied the ability of DMS to differentiate three subclasses of phospholipids (phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine) from a control sample using a bovine skeletal muscle matrix with a 5 mg addition of each phospholipid subclass to the sample matrix. We trained binary classifiers using linear discriminant analysis (LDA) and support vector machines (SVM) for sample classification. We were able to identify phosphatidylcholine, -inositol, and -ethanolamine with SVM binary classification accuracies of 91%, 73%, and 66% and with LDA binary classification accuracies of 82%, 74%, and 72%, respectively. Phosphatidylcholine was detected with a reliable classification accuracy, but ion separation setups should be adjusted in future studies to reliably detect other relevant phospholipids such as phosphatidylinositol and phosphatidylethanolamine and improve DMS as a microanalysis method and identify other phospholipids relevant to cancer tissue.

Emerging Role of CAR-T Therapy in Acute Myeloid Leukemia

Acute myeloid leukemia (AML), a malignant clonal disease originating from hematopoietic stem cells. In the past few decades, AML treatment has been dominated by a "3+7" regimen (anthracyclines + cytarabine), and the survival curve has stagnated. However, these procedures are associated with serious adverse effects. The development of chimeric antigen receptor (CAR)-T cell treatment provides a viable alternative, with decreased non-relapse death rates. Despite its potential, CAR-T cell therapy for AML confronts significant obstacles due to the disease's heterogeneity and accompanying toxicity. Genetic alteration strategies are being investigated to improve its safety and efficacy. Engineering CAR-T cells to express inhibitory receptors or suicide genes can help regulate T cell activity and prevent excessive immune activation. In summary, while CAR-T cell treatment has promise for AML, overcoming its hurdles through genetic modification and target refining is crucial. This review focuses on the existing landscape and future directions of CAR-T cell treatment for AML.

Research Progress on Photothermal Therapy of Malignant Tumor Cells

Malignant tumors, also known as cancer, are among the diseases with the highest incidence and mortality rates in the world. Photothermal therapy (PTT) involves injecting materials with high photothermal conversion efficiency (PTA) into the human body and using the principle of photothermal conversion to kill malignant tumor cells at the lesion site with high temperatures. This paper reviews various methods of photothermal therapy for malignant tumors, summarizes the basic therapeutic logic of photothermal therapy, and forecasts the future development prospects of this treatment method.

Predictors of Failed Outcomes in Ureteral Reconstruction: A Real-World Retrospective Study

Background and Objectives: Ureteral reconstruction is aimed at maintaining ureteral patency without the need for long-term catheters like ureteral stents or percutaneous nephrostomies. Different surgical strategies are adopted based on the etiology, the location of the injury, and the severity of the injury. We aimed to analyze the parameters that can predict which patients might not be free from further catheterization after reconstruction. Materials and Methods: This study included patients who underwent ureteral reconstruction from January 2007 to December 2021. The success of ureteral reconstruction was defined as being free from further catheterization after the operation. Results: A total of 184 patients underwent ureteral reconstruction. Malignant disease with ureteral invasion and iatrogenic injuries accounted for 79.9% of the cases. The majority (79.3%) did not have to undergo subsequent interventions. Predictors for a failed result of ureteral reconstruction included a history of radiotherapy (OR = 2.75, p = 0.01), chronic kidney disease (CKD) (OR = 3.42, p < 0.001), and an upper ureteric location of the injury (OR = 5.68, p = 0.042). Conclusions: A history of radiation therapy, an upper third ureteric location of the injury, and CKD were identified as predictors of a failed ureteral reconstruction. Malignant diseases, surgical methods, and repair techniques did not significantly affect the outcome of the operation.

Pharmaceutical Agents for Targeting Autophagy and Their Applications in Clinics

Autophagy is the process by which damaged regions of the cytoplasm and intracellular pathogens are degraded. This mechanism often serves an adaptive role in cells, enhancing their survival. It plays a direct or indirect role in the development of various pathological conditions within the body. This phenomenon is common in various malignant diseases, where autophagy is associated with the resistance of transformed cells to chemotherapy. Conversely, abnormal activation of autophagy can trigger cell death, a process often seen in neurodegenerative conditions. Given that dysregulation of autophagy is associated with the progression of numerous pathological conditions, this is of significant interest to the developers of drugs that can effectively modulate autophagy for both basic research and clinical applications. Here, we provide a brief description of the mechanism of macroautophagy, the most prevalent form of autophagy identified in humans. We also discuss the clinical potential of drugs that can modulate autophagy, highlighting their use in combating diseases associated with direct or indirect dysregulation of this essential process.

Estimates of natural frequencies for nuclear vibration, and an assessment of the feasibility of selective ultrasound ablation of cancer cells

Selective ablation of cancer cells by ultrasound would be transformative for cancer therapy, but has not yet been possible. A key challenge is that cancerous and non-cancerous cells typically have similar acoustic impedance and are thus indistinguishable as materials in their responses to ultrasound. However, in certain cancers, cytoskeletal and nuclear lamin structures differ between healthy and malignant cells, opening the possibility of exploiting structural differences that manifest as different vibrational responses. To assess the possibility that the nuclei of certain cancerous cells might vibrate at different frequencies, we measured sizes and effective indentation moduli of a range of cancerous and non-cancerous cells from several cell lines and regions of the brain, and estimated the natural frequencies for nuclear vibration. Results suggest a potential difference in natural frequency for nuclear vibration between certain cancerous and non-cancerous cells, on the order of tens of kHz. This gap is potentially sufficient for selective ablation and motivates future experimentation on these specific cell types.

Multi-omic analysis identifies the molecular mechanism of hepatocellular carcinoma with cirrhosis

Hepatocellular carcinoma with cirrhosis promotes the advancement of malignancy and the development of fibrosis in normal liver tissues. Understanding the pathological mechanisms underlying the development of HCC with cirrhosis is important for developing effective therapeutic strategies. Herein, the RNA-sequencing (RNA-seq) data and corresponding clinical features of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) database using the University of California Santa Cruz (UCSC) Xena platform. The enrichment degree of hallmarkers for each TCGA-LIHC cohort was quantified by ssGSEA algorithm. Weighted gene co-expression network analysis (WGCNA) revealed two gene module eigengenes (MEs) associated with cirrhosis, namely, MEbrown and MEgreen. Analysis of these modules using AUCell showed that MEbrown had higher enrichment scores in all immune cells, whereas MEgreen had higher enrichment scores in malignant cells. The CellChat package revealed that both immune and malignant cells contributed to the fibrotic activity of myofibroblasts through diverse signaling pathways. Additionally, spatial transcriptomic data showed that hepatocytes, proliferating hepatocytes, macrophages, and myofibroblasts were located in closer proximity in HCC tissues. These cells may potentially participate in the process of stimulating myofibroblast fibrotic activity, which may be related to the development of liver fibrosis. In summary, we made full use of multi-omics data to explore gene networks and cell types that may be involved in the development and progression of cirrhosis in HCC.

Single-Cell Transcriptomics Reveals Cellular Heterogeneity and Drivers in Serrated Pathway-Driven Colorectal Cancer Progression

Serrated lesions are common precancerous pathways in colorectal cancer (CRC), but the process by which they progress to malignancy remains unclear. We aimed to elucidate this progression through a single-cell RNA landscape. We conducted single-cell RNA sequencing on three normal colonic tissues and fifteen SLs (including HPs, SSLs, SSLD, and TSAs) and integrated these data with datasets containing tumor samples. We identified three invasive malignant epithelial cell subtypes related to CRC progression: SLC1, SLC2, and tumor cell. SLC1, specific to SSLs, is involved in cell proliferation and shows a continuum of malignancy in gene expression. TSA-specific SLC2 exhibited FOXQ1 upregulation and active EMT, indicating invasiveness. The trajectory analysis showed that HPs do not progress to cancer, and different SL types are linked to the MSI status of advanced CRCs. We validated molecular drivers in premalignant lesions and later carcinogenesis. In the tumor microenvironment, CAF and pre-CAF fibroblast subtypes associated with progression were identified. During the premalignant stage, SLC1 triggered CD8+ T cell responses, while at the advanced stage, CAFs promoted tumor invasion and metastasis via FN1-CD44, influencing tumor progression and the treatment response. Our findings highlight transcriptional changes across serrated pathway stages, aiding in early CRC diagnosis and treatment.

Comparison of 35 trace elements content in malignant breast tumors with their content in the normal female mammary gland: Original data and a mini-review

Objective: In many countries, including Russia, breast cancer ranks first in the incidence of cancers in women. The etiology of this disease remains largely unclear, but there is evidence indicating that disturbances in the somatic homeostasis of trace elements may be involved in the process of oncogenesis. Therefore, this study was aimed at identifying changes in the content of trace elements during malignant transformation of breast tissue.Methods: For this purpose, an effective method of small sample analysis by means of inductively coupled plasma mass spectrometry was developed. The method makes it possible to determine the content of 35 trace elements in microsamples (with mass ≥ 10 mg) of breast tissue obtained by puncture biopsy. With the help of this technique, the samples of cancerous (n = 43) and normal (n = 38) breast tissue were studied.Results: In malignant breast tissue, the content of Al, As, B, Cd, Co, Cs, Cu, Mg, Mn, Mo, Ni, Rb, Se, Sr, Ti, Tl, U, V, Zn, and Zr was higher, while the content of Ge, Pb, Sb and Th was lower than in healthy gland tissue. All the identified differences were statistically significant.Conclusions: The significant disruption of somatic homeostasis of trace elements resulting from malignant transformation of breast tissue has been described, but its cause has not been determined, so additional research is required. Further the method we employ, which we have developed and described here, requires tissue samples weighing only a few milligrams, so it is possible to use it with tissue obtained from puncture tissue biopsies.

EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT

B-ALL is the most common subtype of childhood Acute Lymphoblastic Leukemia (ALL), affecting approximately 85% of children worldwide. Minimal Residual Disease (MRD) monitoring during treatment of ALL is important for the prognosis of the disease. MRD monitoring, which enables early detection of relapse, determination of risk percentage and understanding the effectiveness of treatment, can be performed with multiple methods such as flow cytometry, qRT-PCR and NGS. Asparaginase is an enzyme that has been used in the treatment of ALL since the 1960s, converting asparagine to ammonia and aspartic acid, lowering serum asparagine levels and causing the death of malignant cells. In this study, we investigated the effect of asparaginase added to the ALL IC BFM 2009 treatment protocol in 62 B-ALL patients aged 0-18 years with MRD monitoring by flow cytometry. In our study, Escherichia Coli (E.Coli.) asparaginase was used primarily and PEG-asparaginase was used after allergy development. The effect of asparaginase on treatment was evaluated by evaluating asparagine concentration and asparaginase activity measured at TP1 (4th week after induction treatment) together with MRD levels. As a result of the study, it was observed that the added asparaginase positively affected the treatment and increased the negativity in MRD levels.

Anticancer Activity of Vitamin D, Lumisterol and Selected Derivatives against Human Malignant Melanoma Cell Lines.

Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D3 and lumisterol (L3) exert photoprotective and antiproliferative effects on the skin, while UV radiation is a major environmental risk factor for melanoma. Thus, many natural metabolites and synthetic analogs of steroidal and secosteroidal molecules have been tested on various cancer cells and in animal models. In this study, we tested the anti-melanoma properties of several natural derivatives of vitamin D3 and L3 in comparison to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). A significant decrease in melanoma cell proliferation and cell mobility was observed for selected derivatives, with (25R)-27-hydroxyL3 showing the highest potency (lowest IC50) in A375 cells but lower potency in SK-MEL-28 cells, whereas the parent L3 failed to inhibit proliferation. The efficacy (% inhibition) by 1,24,25(OH)3D3 and 1,25(OH)2D3 were similar in both cell types. 1,25(OH)2D3 showed higher potency than 1,24,25(OH)3D3 in SK-MEL-28 cells, but lower potency in A375 cells for the inhibition of proliferation. As for 1,25(OH)2D3, but not the other derivatives tested, treatment of melanoma cells with 1,24,25(OH)3D3 markedly increased the expression of CYP24A1, enhanced translocation of the vitamin D receptor (VDR) from the cytoplasm to the nucleus and also decreased the expression of the proliferation marker Ki67. The effects of the other compounds tested were weaker and occurred only under certain conditions. Our data indicate that 1,24,25(OH)3D3, which has undergone the first step in 1,25(OH)2D3 inactivation by being hydroxylated at C24, still shows anti-melanoma properties, displaying higher potency than 1,25(OH)2D3 in SK-MEL-28 cells. Furthermore, hydroxylation increases the potency of some of the lumisterol hydroxy-derivatives, as in contrast to L3, (25R)-27(OH)L3 effectively inhibits proliferation and migration of the human malignant melanoma cell line A375.

Integrating Metabolic RNA Labeling-Based Time-Resolved Single-Cell RNA Sequencing with Spatial Transcriptomics for Spatiotemporal Transcriptomic Analysis.

Metabolic RNA labeling-based time-resolved single-cell RNA sequencing (scRNA-seq) has provided unprecedented tools to dissect the temporal dynamics and the complex gene regulatory networks of gene expression. However, this technology fails to reveal the spatial organization of cells in tissues, which also regulates the gene expression by intercellular communication. Herein, it is demonstrated that integrating time-resolved scRNA-seq with spatial transcriptomics is a new paradigm for spatiotemporal analysis. Metabolic RNA labeling-based time-resolved Well-TEMP-seq is first applied to profile the transcriptional dynamics of glioblastoma (GBM) cells and discover two potential pathways of EZH2-mediated mesenchymal transition in GBM. With spatial transcriptomics, it is further revealed that the crosstalk between CCL2+ malignant cells and IL10+ tumor-associated macrophages in the tumor microenvironment through an EZH2-FOSL2-CCL2 axis contributes to the mesenchymal transition in GBM. These discoveries show the power of integrative spatiotemporal scRNA-seq to elucidate the complex gene regulatory mechanism and advance the understanding of cellular processes in disease.

Anticancer Drug Discovery from Natural Compounds Targeting PI3K/AKT/mTOR Signaling Pathway.

The term cancer is used to describe a complex pathology characterized by the uncontrollable proliferation of cells, which displays a fast metastatic spread, being a disease with difficult treatment. In this context, Phosphatidylinositol 3-kinase (PI3K) represents a promising pathway to be inhibited, aiming to develop anticancer agents, since it performs a pivotal role in regulating essential cellular processes, including cell proliferation, growth, autophagy, and apoptosis. In parallel, natural compounds can effectively represent a therapeutic strategy to fight against malignant cells. Then, compounds derived from various plant sources, such as flavonoids, terpenoids, alkaloids, coumarins, and lignans, have exhibited remarkable in vitro and in vivo anticancer properties. This review focused in the exploration of natural products targeting the PI3K/AKT/m-TOR signaling pathway, demonstrating that these compounds could even further investigated to reveal novel and effective anticancer drugs in the future.

FUT2 promotes colorectal cancer metastasis by reprogramming fatty acid metabolism via YAP/TAZ signaling and SREBP-1

Colorectal cancer (CRC) ranks as the second most lethal cancer worldwide because of its high rate of metastasis, and approximately 20% of CRC patients have metastases at initial diagnosis. Metabolic reprogramming, a hallmark of cancer cells, has been implicated in the process of metastasis. We previously demonstrated that fucosyltransferase 2 (FUT2) promotes the malignancy of CRC cells, however, the underlying mechanisms remain unclear. Here, bioinformatic analysis revealed that FUT2 is associated with the malignant phenotype and fatty acid metabolism in CRC. FUT2 knockdown decreased glucose uptake and de novo fatty acid synthesis, which in turn inhibited the proliferation and metastasis of CRC cells. Mechanistically, FUT2 promotes YAP1 nuclear translocation and stabilizes mSREBP-1 by fucosylation, thus promoting de novo fatty acid synthesis in CRC cells. In summary, this study demonstrates that FUT2 promotes the proliferation and metastasis of CRC cells by reprogramming fatty acid metabolism via YAP/TAZ signaling and SREBP-1, indicating that FUT2 might be a potential target for developing therapeutic strategies against CRC.

Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions.

Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high risk for colon cancer were enrolled in a clinical trial to evaluate the feasibility of using a MUC1 peptide vaccine to prevent colon cancer. Anti-MUC1 antibodies elicited by this vaccine were cloned using peripheral blood B cells and sera collected two weeks after a one-year booster. Twelve of these fully human monoclonal antibodies (mAb) were tested for binding to MUC1+ target cells, and three with the highest binding were further evaluated for various effector functions important for tumor rejection. Immune cells were incubated together with target cells expressing variations in the number, distance, and membrane anchoring properties of the MUC1 epitope in the presence of each mAb. All three mAbs mediated antibody-dependent cytokine release (ADCR), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Two also mediated antibody-dependent trogocytosis/trogoptosis (ADCT). None were capable of complement-dependent cytotoxicity (CDC). ADCP and ADCT functions were more efficient when antibodies bound epitopes proximal to and anchored to the membrane, providing insight for future therapeutic antibody validation strategies.

Urea and Thiourea Derivatives of Salinomycin as Agents Targeting Malignant Colon Cancer Cells.

Since it was discovered that a natural polyether ionophore called salinomycin (SAL) selectively inhibits human cancer cells, the scientific world has been paying special attention to this compound. It has been studied for nearly 15 years. Thus, a very interesting research direction is the chemical modification of SAL structure, which could give more biologically active agents. We evaluated the anticancer activity of (thio)urea analogues class of C20-epi-aminosalinomycin (compound 3b). The studies covered the generation of reactive oxygen species (ROS), proapoptotic activity, cytotoxic activity, and lipid peroxidation in vitro. Thioureas 5a‒5d showed antiproliferative activity against selected human colon cancer cell lines greater than that of chemically unmodified SAL, with a 2~10-fold higher potency towards a metastatic variant of colon cancer cells (SW620). Mechanistically, SAL derivatives showed pro-apoptotic activity in primary colon cancer cells and induced the production of reactive oxygen species (ROS) in these cells. In SW620 cells, SAL derivatives increased lipid peroxidation with a weak effect on apoptosis and low ROS formation with cytotoxic effects followed by cytostatic ones, suggesting different modes of action of the compounds against primary and metastatic colon cancer cells. The results of this study suggested that urea and thiourea derivatives of SAL provide promising leads for the rational development of new anticancer active agents.

Sarcomatoid mesothelioma presenting as a mediastinal mass: A case report

Sarcomatoid mesothelioma (SM) is a subtype of mesothelioma, a deadly cancer strongly related to asbestos exposure. Herein, we present the case of a 50-year-old female who presented with back pain and non-specific symptoms for approximately 9 months. The diagnostic investigation revealed a large, centrally necrotic mass in the thorax that appeared to arise from the mediastinum and surrounded vital structures, including the superior vena cava. A biopsy of the thoracic mass revealed SM. The patient developed hematemesis, and emergent endoscopy revealed a gastric ulcer composed of malignant SM cells, a rare finding in pleural mesothelioma. Her disease was too advanced for surgical resection and conventional therapy. She tragically died weeks after diagnosis. The findings of this report highlight the varied presentation of SM to underscore the importance of early diagnosis and treatment of patients in improving overall survival.