Search Results (1,127)

Epilobium parviflorum Schreb. is used in folk and modern medicine for the treatment of prostate diseases. It is also known to alleviate gastrointestinal ailments. The aim of the present study is to define the chemical composition of diverse extracts from the herb, to test their inhibitory properties toward post-proline-specific peptidases and to elucidate the mechanisms of their antitumor activity on colorectal carcinoma cells in vitro. The extractions were performed using mono- or biphasic systems of solvents. Their chemical compositions were defined by LC-HRMS. Inhibitory properties towards prolyloligopeptidase (POP) and fibroblast activation protein (FAP) were studied by kinetic assays on human recombinant enzymes. Antioxidant activity was measured by three methods. Genotoxicity to HT-29 colorectal carcinoma cells was analyzed with the comet assay. FACS analyses and flow cytometry were used to evaluate the extracts effect on the cell cycle and their pro-apoptotic properties on HT-29 cells. The extract derived using 80% ethanol was chosen for the next studies due to its efficient and selective inhibition of POP. It contains mainly oenotein B and myricetin-3-O-rhamnoside. Its antioxidant and moderate genotoxic activities can contribute to the antitumor effect on HT-29 cells. The extract has a small effect on the cell cycle but a pronounced pro-apoptotic action on those cells. In conclusion, the 80% ethanol extract of E. parviflorum concentrates the ellagitannin oenotein B, which is a selective inhibitor of POP. Antitumor activity of the extract towards HT-29 cells may be due to the inhibition of POP, the antioxidant, genotoxic and pro-apoptotic activities. Full article

Introduction: The objective of this study was to analyze and compare the outcomes of two surgical techniques in the emergency management of obstructed colorectal carcinoma. Methods: This is a retrospective analysis of patients’ data from a tertiary referral university hospital. The medical records of patients who underwent emergency surgery for obstructed colorectal cancer between May 2014 and August 2019 were evaluated. The cases were divided primarily into two groups: Primary Resection and Anastomosis (PRA) and Hartmann’s Procedure (HP). The clinical characteristics, peri-operative outcomes and oncological results including early postoperative complications, morbidity and mortality (30-day, 1-year and 5-year survival) were compared between groups. Results: In this retrospective study, 110 patients with obstructing colorectal cancer undergoing emergency surgery were analyzed. Patients were divided into two groups: 65 cases of Primary Resection and Anastomosis (PRA) and 45 cases of Hartmann’s Procedure (HP). PRA patients had significantly shorter hospital stays (8.7 ± 4.1 vs. 11.2 ± 5.2 days, p = 0.02), lower complication rates (33% vs. 66%, p = 0.003), and superior survival outcomes, with a 5-year survival rate of 33.8% compared to 22.2% in the HP group (p = 0.003). Subgroup analysis revealed significant differences, including higher complication rates and repeat surgery requirements in patients with a diverting ostomy or undergoing resection without anastomosis. Conclusion: PRA demonstrated favorable perioperative and long-term outcomes compared to HP in the emergency management of obstructing colorectal cancer. These findings highlight the potential benefits of avoiding permanent stoma formation when appropriate patient selection criteria are met. Full article

Sessile serrated lesions (SSLs) are well-known precursors of colorectal cancer in the general population, but their role in inflammatory bowel disease (IBD) is less clear. This narrative review summarizes what is known about the prevalence, molecular features, endoscopic detection, malignant potential, and management of SSLs in patients with IBD, highlighting where evidence supports action nowadays and where prospective studies are urgently needed. IBD-associated colorectal cancer has long been considered a consequence of the inflammation–dysplasia–carcinoma sequence, distinct from the conventional adenoma–carcinoma pathway. Increasing evidence, however, suggests that the serrated pathway, typically characterized by SSLs and traditional serrated adenomas (TSAs), may also contribute to IBD-related oncogenesis. This review synthesizes histopathological, molecular, endoscopic, and clinical data on SSLs in patients with IBD, with contextual reference to TSAs, sessile serrated lesions with dysplasia, and serrated epithelial change only when relevant to their interpretation or risk stratification. SSLs are now more frequently identified in IBD surveillance, especially in ulcerative colitis and the proximal colon, although prevalence estimates remain heterogeneous due to evolving definitions and significant interobserver variability. Molecular studies indicate that IBD-associated serrated lesions often harbor BRAF mutations but display a lower CpG island methylator phenotype than their sporadic counterparts, suggesting an inflammation-modified biology. While most hyperplastic polyps and non-dysplastic SSLs appear to pose limited neoplastic risk, dysplastic serrated lesions carry a markedly higher likelihood of synchronous or metachronous advanced neoplasia. Advances in high-definition endoscopy and chromoendoscopy improve the detection of these subtle, mucus-capped, flat lesions, while endoscopic resection is nowadays feasible in expert hands. Future priorities should include prospective multicenter cohorts integrating molecular profiling to refine surveillance strategies. Full article

The traditional management of resectable colorectal liver metastases (CLMs) includes systemic therapy and curative (R0) surgery. Hepatocellular carcinoma (HCC) treatment options include R0 surgery, liver transplantation (LT), chemoembolisation, and targeted chemotherapy. Ablative techniques (radiofrequency ablation and microwave ablation) targeting liver lesions were until recently considered suitable only for patients deemed unfit for surgical resection. However, over time, data suggesting the non-inferior results of radical (A0) ablation compared with radical surgery have started to emerge. Given the lower complication rate of ablative therapies compared with surgery, the question arises as to whether ablation has the potential to replace the role of surgery in the treatment of HCC and colorectal cancer metastases to the liver. In this review, we address the current evidence on the topic and its possible impact on future clinical practice. Full article

Optineurin (OPTN) is a multifunctional adaptor protein that regulates diverse cellular processes, including inflammatory signaling, autophagy, vesicular trafficking, and immune responses. This multifaceted role of OPTN is made possible by the presence of a complex structure comprising multiple domains that interact with different proteins to exert various functions important for modulating key signaling processes. Mutations in OPTN are linked with several human pathologies including glaucoma, Paget’s disease of bone, Crohn’s disease, and neurodegenerative diseases such as amyotrophic lateral sclerosis, and dementia. Emerging evidence suggests that OPTN has a complex and context-dependent role in cancer biology as well. It is upregulated in pancreatic ductal adenocarcinoma and hepatocellular carcinoma but downregulated in lung and colorectal cancers, indicating its dual role as a potential oncogene or tumor suppressor depending on the cellular environment. Additionally, OPTN plays a critical role in preventing immune evasion in colorectal cancer by maintaining interferon-gamma receptor 1 (IFNGR1) expression and supporting dendritic cell-mediated T-cell priming, thereby enhancing antitumor immune responses. Despite its significance in oncogenic pathways and immune regulation, the therapeutic potential of targeting OPTN in cancer remains largely unexplored. This review aims to provide a comprehensive understanding of OPTN’s pleiotropic functions, highlighting its role in autophagy, inflammation, immune surveillance, and cancer progression. By elucidating its diverse regulatory mechanisms, we seek to encourage further research into the therapeutic implications of OPTN in cancer treatment and immunotherapy. Full article

RNA triple helices are relatively understudied, including their interactions with small molecules. In this study, we evaluated eight previously reported triplex-binding molecules (TBMs) for their functional effects on the premature and mature MALAT1 triple helix. Based on UV thermal denaturation experiments, the TBMs berberine, coralyne, sanguinarine, berenil, and neomycin selectively stabilize the Hoogsteen interface of the MALAT1 triple helix. Moreover, fisetin, luteolin, and quercetin were more sensitive to nucleotide composition, whereas berberine, coralyne, sanguinarine, and berenil were more sensitive to changes in the length of the major-groove triple helix. Most TBMs could not outcompete MALAT1 triple helix-binding proteins, except for neomycin. Surface plasmon resonance experiments demonstrated that berberine and sanguinarine display relatively quick association and dissociation binding profiles. Treating human colorectal carcinoma cells with each of the TBMs reduced MALAT1 levels by ~20–60%. This study demonstrates that TBMs broadly recognize the premature and mature MALAT1 triple helix but exhibit subtle sensitivities, suggesting that TBMs can be designed to selectively bind triple helices based on nucleotide composition, length, and structural context. Full article

Background/Objectives: To elucidate the differential transcriptional and intercellular signaling features of tumor components across various cancers, we conducted a comparative analysis using single-cell RNA sequencing (scRNA-seq). This technology enables detailed characterization of tumor ecosystems and may explain variations in tumor behavior among distinct cancer types. Methods: We analyzed publicly available scRNA-seq datasets (GEO) from seven cancer types—pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), thyroid cancer (TC), gastric cancer (GC), and colorectal cancer (CRC)—to define their unique molecular characteristics and intercellular interactions. Results: PDAC displayed a distinct tumor microenvironment (TME) dominated by myeloid cells (~42%), including abundant CXCR1/CXCR2-expressing tumor-associated neutrophils (TANs) that preferentially interacted with immune rather than cancer cells. The competitive receptor ACKR1 was minimally expressed on endothelial cells, consistent with PDAC hypo-vascularity. In HCC, tumor cells lacked EPCAM and expressed complement and stem cell markers; cancer-associated fibroblasts (CAFs) were scarce, and stellate cells expressed the pericyte marker RGS5. CAFs were abundant in ESCC and BC, with IGF1/2 expression, while in GC, these markers were uniquely found in plasma cells. Since BC and GC subtypes exhibit distinct TME patterns, it is necessary to perform subtype-specific analyses for these cancers. TC showed high expression of tumor-suppressor genes, including HOPX, in tumor cells. Differential interactions and the presence of “dominant signaling cell populations “ with dominant outgoing signals may underlie the heterogeneity in tumor aggressiveness across these cancers. Conclusions: Comparative scRNA-seq analysis of multiple cancers reveals distinct tumor phenotypes and cell–cell communication patterns, offering insights into the molecular architecture of human solid tumors. Full article

Collagens comprise a large, diverse family of proteins that are abundantly expressed throughout most tissues. As a main component of the extracellular matrix (ECM), it is becoming increasingly appreciated how vital collagens are to tumor development, progression, and metastasis. COL6A3, which encodes the alpha 3 chain of type VI collagen, is a unique member of the collagen family that encodes a C-terminal peptide with powerful signaling capabilities, named endotrophin (ETP). Expression of COL6A3 is required for the survival, migration, and invasion of many cancer cell lines, including breast, bladder, liver, and colorectal cancers. ETP, which was originally discovered to be enriched in the adipocytes of mammary tumors, is a powerful oncopeptide that can alter signaling of tumor and stromal cells. ETP has greater signaling potential than the parental COL6A3 as it can induce EMT and promote chemoresistance, metastasis, and stemness in an TGF-β-like manner. ETP can also function independently of TGF-β to recruit endothelial cells and macrophages. In this review, we examine the molecular implications of COL6A3 and ETP expression and their effects on tumor growth, metastasis, and therapeutic response. Finally, we speculate on the potential of serum ETP as a prognostic biomarker in both carcinomas and sarcomas. In summary, COL6A3 and ETP are powerful drivers of tumor growth that have potential as noninvasive diagnostic and prognostic tools for the clinical management of cancer. Full article

In the last decade, knowledge of gut microbiota has expanded. Several studies have demonstrated a correlation between certain diseases and alterations in gut microbiota. A comprehensive understanding of this complex ecosystem is still lacking; however, this review highlights the importance of microorganisms in oncology. Recently, several studies have demonstrated that the gut microbiota influences therapeutic efficacy and tumor formation, also known as tumorigenesis. We must remember that these microorganisms also play a crucial role in tumor prognosis. Since the discovery of Fusobacterium nucleatum in colorectal carcinoma (CRC), it has been established that tumor tissues are not sterile and contain microorganisms that can lead to either beneficial or harmful pathways, affecting tumor size and response to chemotherapeutic agents. Additionally, it should be noted that data on the pediatric population are limited, as this area has not been widely researched due to the low number of cases and the complexity of therapeutic approaches. In children, the only available data are mainly based on hematological malignancies, such as acute lymphoblastic leukemia (ALL). For a better understanding, larger cohorts are required. Full article

Background/Objectives: Since its emergence, COVID-19—caused by the novel coronavirus SARS-CoV-2—has affected millions globally and led to over 1.2 million deaths in the United States alone. This global impact, coupled with the emergence of five new human coronaviruses over the past two decades, underscores the urgency of understanding its pathogenic mechanisms at the molecular level—not only for managing the current pandemic but also preparing for future outbreaks. Small non-coding RNAs (sncRNAs) critically regulate host and viral gene expression, including antiviral responses. Among the molecular regulators implicated in antiviral defense, the microRNA-processing enzyme Drosha has emerged as a particularly intriguing factor. In addition to its canonical role, Drosha also exerts a non-canonical, interferon-independent antiviral function against several RNA viruses. Methods: To investigate this, we employed q/RT-PCR, Western blot, and immunocytochemistry/immunofluorescence in an immortalized normal human lung/bronchial epithelial cell line (NuLi-1), as well as a human colorectal carcinoma Drosha CRISPR knockout cell line. Results: In this study, we observed a striking shift in Drosha isoform expression following infection with multiple SARS-CoV-2 variants. This shift was absent following treatment with the viral mimetic poly (I:C) or infection with other RNA viruses, including the non-severe coronaviruses HCoV-OC43 and HCoV-229E. We also identified a distinct alteration in Drosha’s cellular localization post SARS-CoV-2 infection. Moreover, Drosha ablation led to reduced expression of SARS-CoV-2 genomic and sub-genomic targets. Conclusions: Together, these observations not only elucidate a novel aspect of Drosha’s antiviral role but also advance our understanding of SARS-CoV-2 host–pathogen interactions, highlighting potential therapeutic avenues for future human coronavirus infections. Full article

Background and Objectives: Non-urothelial bladder tumors and secondary bladder involvement from extravesical primaries are uncommon but clinically challenging. We compared clinicopathologic patterns between primary non-urothelial tumors and secondaries, and explored correlates of adverse pathologic features to inform diagnostic triage and surgical planning. Methods: We performed a single-center retrospective cohort (2014–2024) of consecutive bladder lesions meeting WHO 2022 criteria and AJCC 8th staging. Eligible cases were primary non-urothelial malignancies (squamous cell carcinoma (SCC), adenocarcinoma (ADK), small-cell/neuroendocrine (NEC), sarcomatoid) or secondary bladder involvement (colorectal, prostate, cervix, ovary, uterus, breast). Outcomes included advanced pT (≥pT3), lympho–vascular invasion (LVI), perineural invasion (PNI), nodal metastasis, margin status, and composite adverse events. Results: Of 235 analyzable cases, 59 were primary and 176 were secondary. Age and sex distributions were similar. Secondaries had a higher adverse burden: advanced pT 56.8% vs. 23.7%, LVI 47.2% vs. 27.1%, PNI 40.3% vs. 22.0%, node-positive 11.9% vs. 0%, and any adverse 65.3% vs. 33.9% (all significant). Histology composition differed (p < 10⁻⁶): secondaries were ADK-dominant (59.1%), whereas primaries were enriched for SCC (38.5%), sarcomatoid (28.8%), and NEC (21.2%). Among secondaries, prostate origin showed the most ominous profile (advanced pT 97.5%, PNI 77.5%, positive margins 64.7%); colorectal cases combined high advanced pT (70.2%) with lower margin positivity (27.6%). Adverse-feature count correlated with pT (ρ = 0.586). Conclusions: Secondary bladder involvement carries substantially higher adverse-pathology rates than primary non-urothelial tumors, with origin-specific risk gradients (prostate > colorectal ≳ cervix). Rigorous origin adjudication and a margin-focused, anatomy-adapted surgical strategy may improve outcomes; prospective outcome-linked validation is warranted. Full article

We report for the first time a method for forming polyacrylate nanoparticles using N-acryloylciprofloxacin as a sole monomer for emulsion polymerization. The procedure involves a free radical-induced emulsion polymerization of N-acryloylciprofloxacin monomer to produce a stable aqueous emulsion comprising uniformly sized polyacrylate nanoparticles. Dynamic light scattering analysis of the emulsions showed a single population of nanoparticles having an average diameter of 970 nm and average surface charge of −63 mV, indicative of the high stability of the emulsion and significantly enhance lipophilicity of the polymeric matrix of the nanoparticle. Antibacterial testing of the emulsions against the Gram-positive microbe Staphylococcus aureus and the Gram-negative Escherichia coli found in vitro activities identical to those of the reference clinical agent, ciprofloxacin. Assays against human colorectal carcinoma cells and human embryonic kidney cells showed essentially no cytotoxicity. This is the first study on the synthesis of aqueous nanoparticle emulsions assembled solely from a single monomer derived from the antibiotic agent. Full article

Periodontal disease (PD), a chronic inflammatory condition driven by oral microbial dysbiosis, is increasingly implicated in systemic diseases, including colorectal cancer (CRC). The “red complex” bacteria—Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola—play a central role in PD progression and exhibit virulence factors that promote inflammation, immune evasion, and epithelial colonization. A literature search in PubMed, Google Scholar, and ScienceDirect (English and Slovenian, up to September 2025) identified 12 eligible studies. Only original clinical, in vivo, or in vitro research directly addressing red complex pathogens and colorectal cancer was included. The search results showed that most of the literature focuses on the association between Porphyromonas gingivalis and CRC, particularly its role in tumor immune evasion, alteration of the gut microbiota, creation of a pro-inflammatory microenvironment, and promotion of carcinoma cell proliferation. Infection with Porphyromonas gingivalis has also been linked to poorer cancer prognosis. The other red complex bacteria are primarily mentioned in the context of generating a pro-inflammatory microenvironment and contributing to chronic inflammation, which supports tumor growth and survival. Full article

Background/Objectives: T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, yet its anticancer potential remains unexplored. The aim of this study was to investigate TP5’s antitumor efficacy and underlying immunological mechanisms. Methods: We evaluated TP5’s therapeutic effects in multiple murine tumor models, including B16-F10 melanoma, MC38 colorectal carcinoma, Hepa 1-6, and LM3 hepatocellular carcinoma. Immune cell populations and functional states were characterized using flow cytometry, ELISAs, and immunofluorescence analyses. The potential of TP5 as an adjuvant for T cell-based therapies was also systematically assessed. Results: The TP5 treatment markedly suppressed tumor growth across caner models through strictly T cell-dependent mechanisms. Critically, TP5 promoted thymic rejuvenation under immunocompromised conditions, restoring the thymus–tumor immunological balance and revitalizing peripheral T cell immunity. TP5 functionally reprogrammed T cell states, preserving effector function while ameliorating exhaustion. Furthermore, TP5 demonstrated synergistic efficacy when combined with adoptive T cell therapies, enhancing both proliferation and effector functions. Conclusions: TP5 represents a promising immunomodulator that addresses fundamental limitations of current T cell therapies by simultaneously enhancing T cell function and reversing thymic involution under immunocompromised conditions. Our findings provide compelling evidence for TP5’s clinical translation in cancer treatment. Full article

Background/Objectives: Colorectal neuroendocrine carcinomas (NECs) are rare, aggressive tumors with poorly defined clinicopathologic and molecular features. Their biological behavior and optimal treatment strategies remain unclear. Additionally, a subset of anorectal NECs may be associated with high-risk human papillomavirus (HPV) infection, suggesting potential heterogeneity in pathogenesis. Methods: We retrospectively reviewed 12 cases of colorectal NECs. Clinical outcomes, histologic morphology, immunohistochemistry, molecular profiling, including common oncogenic mutations, and HPV status were analyzed. Results: Seven cases demonstrated small cell NECs, and five showed large cell NECs. The majority of NECs (n = 9) arose in the rectum. TP53 mutations were the most common (75%), followed by KRAS, RB1, FBXW7, and BRAF mutations. One case demonstrated mismatch repair (MMR) deficiency. High-risk HPV was detected in one rectal NEC, which lacked common oncogenic mutations and was the only long-term survivor (54 months). p16 expression did not correlate consistently with HPV in situ hybridization (ISH) status. Among small cell NECs with follow-up, platinum-based chemotherapy resulted in significantly longer survival than FOLFOX (13.5 vs. 4 months, p = 0.0209). Conclusions: Colorectal NECs display histologic and molecular heterogeneity. The tumors of small cell NECs potentially benefit more from platinum-based chemotherapy. HPV-associated NECs may represent a distinct subset with better prognosis, but p16 is not a reliable surrogate marker. Routine subclassification into small vs. large cell types and comprehensive molecular profiling, including HPV testing, may aid clinical decision-making and prognostication. Full article