OBJECTIVES: The incidence of oral and oropharyngeal cancer is continually rising and affects increasingly younger patients. Consequently, many studies focus on early diagnosis using appropriate biomarkers. Neopterin and interleukin-6 (IL-6) are promising predictive and prognostic markers of immune response activation, both systemic and local, due to the anatomical proximity of malignancies to the salivary glands. MATERIAL AND METHODS: We collected oral fluid samples from 50 patients before and after the surgical resection of squamous cell carcinoma of the oral cavity and oropharynx. Additionally, blood samples were withdrawn from 20 of these patients and levels of neopterin and IL-6 were estimated using ELISA commercial kits. All gathered data were subsequently statistically analyzed for evaluation and compared to values from a control group of healthy individuals. RESULTS: In patients with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC), there was a significant decrease in neopterin and IL-6 levels in saliva following the surgical removal of the malignancy. These postoperative levels approached those of the control group. There was no significant decrease in neopterin and IL-6 levels in plasma. CONCLUSION: Detection of neopterin and IL-6 in saliva is a reliable diagnostic method for early detection of OSCC and its recurrence, as well as for monitoring therapeutic success, compared to plasma. Neopterin and IL-6 appear to be promising prognostic and predictive markers of the disease.

• Keywords
• interleukin‐6, neopterin, squamous cell carcinoma of head and neck,
• MeSH
• Adult MeSH
• Interleukin-6 * blood   analysis   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor * blood   analysis   metabolism   MeSH
• Oropharyngeal Neoplasms * blood   metabolism   surgery   diagnosis   MeSH
• Mouth Neoplasms * blood   metabolism   surgery   diagnosis   MeSH
• Neopterin * blood   analysis   metabolism   MeSH
• Prospective Studies MeSH
• Aged MeSH
• Saliva * chemistry   metabolism   MeSH
• Carcinoma, Squamous Cell * blood   surgery   metabolism   diagnosis   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• IL6 protein, human MeSH Browser
• Interleukin-6 * MeSH
• Biomarkers, Tumor * MeSH
• Neopterin * MeSH

Cancer-associated fibroblasts (CAFs) represent an important component of the cancer ecosystem, influencing the broad scale of biological properties of tumour cells, including the capacity for metastasis formation. An important CAF subpopulation, known as myCAFs, typically expresses α-smooth muscle actin. Transcriptomic analysis demonstrated that activated fibroblasts isolated from various pathological tissues also express the ACTG2 gene encoding γ-smooth muscle actin. This was further validated by immunocytochemistry. Using the scratch test in vitro, it was possible to demonstrate that γ-smooth muscle actin may be associated with the epithelial-mesenchymal transition, which was also shown by transcriptomic analysis. The presence of γ-smooth muscle actin-positive fibroblasts in histopathological sections of human tumours verified the expression of this protein as a new potential marker of CAFs.

• Keywords
• CLEC12A, TPD52L1, Cancer-associated fibroblast, Epithelial-mesenchymal transition, γ-smooth muscle actin,
• MeSH
• Actins * metabolism   genetics   analysis   MeSH
• Cancer-Associated Fibroblasts * metabolism   pathology   MeSH
• Humans MeSH
• Biomarkers, Tumor * metabolism   genetics   analysis   MeSH
• Neoplasms * pathology   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• ACTA2 protein, human MeSH Browser
• Actins * MeSH
• Biomarkers, Tumor * MeSH

Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.

• Keywords
• IL-6, cancer-associated fibroblasts, granulation tissue, myofibroblasts, wound healing,
• MeSH
• Autoimmunity * MeSH
• Wound Healing * immunology   MeSH
• Interleukin-6 * metabolism   immunology   MeSH
• Humans MeSH
• Tumor Microenvironment * immunology   MeSH
• Neoplasms * immunology   metabolism   pathology   MeSH
• Aging * immunology   MeSH
• Inflammation * immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Interleukin-6 * MeSH

Head and neck cancers (HNC) are aggressive, difficult-to-treat tumors that can be caused by genetic factors but mainly by lifestyle or infection caused by the human papillomavirus. As the sixth most common malignancy, it presents a formidable therapeutic challenge with limited therapeutic modalities. Curcumin, a natural polyphenol, is appearing as a promising multitarget anticancer and antimetastatic agent. Numerous studies have shown that curcumin and its derivatives have the potential to affect signaling pathways (NF-κB, JAK/STAT, and EGFR) and molecular mechanisms that are crucial for the growth and migration of head and neck tumors. Furthermore, its ability to interact with the tumor microenvironment and trigger the immune system may significantly influence the organism's immune response to the tumor. Combining curcumin with conventional therapies such as chemotherapy or radiotherapy may improve the efficacy of treatment and reduce the side effects of treatment, thereby increasing its therapeutic potential. This review is a comprehensive overview that discusses both the benefits and limitations of curcumin and its therapeutic effects in the context of tumor biology, with an emphasis on molecular mechanisms in the context of HNC. This review also includes possibilities to improve the limiting properties of curcumin both in terms of the development of new derivatives, formulations, or combinations with conventional therapies that have potential as a new type of therapy for the treatment of HNC and subsequent use in clinical practice.

• Publication type
• Journal Article MeSH
• Review MeSH

MicroRNAs (miRNAs) are involved in post-transcriptional gene expression regulation and in mechanisms of cancer growth and metastases. In this light, miRNAs could be promising therapeutic targets and biomarkers in clinical practice. Therefore, we investigated if specific miRNAs and their target genes contribute to laryngeal squamous cell carcinoma (LSCC) development. We found a significant decrease of miR-449a in LSCC patients with nodal metastases (63.3%) compared with patients without nodal involvement (44%). The AmpliSeq Transcriptome of HNO-210 miR-449a-transfected cell lines allowed the identification of IL6-R as a potential target. Moreover, the downregulation of IL6-R and the phosphorylation reduction of the downstream signaling effectors, suggested the inhibition of the IL-6 trans-signaling pathway. These biochemical effects were paralleled by a significant inhibition of invasion and migration in vitro and in vivo, supporting an involvement of epithelial-mesenchymal transition. These findings indicate that miR-449a contributes to suppress the metastasization of LSCC by the IL-6 trans-signaling block and affects sensitivity to external stimuli that mimic pro-inflammatory conditions.

• Keywords
• IL-6 trans-signaling, LSCC, MT: non-coding RNAs, gene expression, metastases miR-449a, microRNAs,
• Publication type
• Journal Article MeSH

Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studies revealed strong binding energy values for quinestrol, quercetin, and bazedoxifene, indicating their potential to inhibit PD-1 and CTLA-4. Quercetin and bazedoxifene, known to modulate EGFR and IL-6R alongside estrogen receptors, can influence the immune checkpoint functionality. We discuss the impact of SERMs on PD-1 and CTLA-4, suggesting that these SERMs could have therapeutic effects through immune checkpoint inhibition. This study highlights the potential of SERMs as inhibitory ligands for immune checkpoint proteins, emphasizing the importance of considering PD-1 and CTLA-4 inhibition when evaluating SERMs as therapeutic agents. Our findings open new avenues for cancer immunotherapy by exploring the interaction between various SERMs and immune checkpoint pathways.

• MeSH
• CTLA-4 Antigen MeSH
• B7-H1 Antigen MeSH
• Programmed Cell Death 1 Receptor MeSH
• Immunotherapy MeSH
• Humans MeSH
• Estrogen Receptor Modulators MeSH
• Neoplasms * therapy   MeSH
• Immune Checkpoint Proteins * MeSH
• Quercetin MeSH
• Selective Estrogen Receptor Modulators pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• CTLA-4 Antigen MeSH
• B7-H1 Antigen MeSH
• Programmed Cell Death 1 Receptor MeSH
• Estrogen Receptor Modulators MeSH
• Immune Checkpoint Proteins * MeSH
• Quercetin MeSH
• Selective Estrogen Receptor Modulators MeSH

BACKGROUND: The aim of this prospective study was to evaluate the role of serum IL-6 as a potential predictive biomarker of postoperative complications (POC) in elective colorectal surgery. METHOD: A total of 115 patients underwent colorectal surgery for malignancy. IL-6 was measured on the first and third postoperative days (POD1, POD3), and C-reactive protein (CRP) was measured on the POD3. POC was analysed in subgroups according to Clavien‒Dindo (CD), antibiotic (ATB) treatment, intensive care unit (ICU) and hospital length of stay. The predictive power of variables for evaluated endpoints was analysed using receiver-operating characteristic (ROC) analysis and described by area under the curve (AUC). ROC analysis was adopted for the identification of optimal cut-offs. Histological analysis was performed to verify IL-6 production by the tumour. RESULTS: Out of 115 patients who were analysed, 42% had POC. Patients with POC had significantly higher serum levels of IL-6 on POD1 (p < 0.001) and POD3 (p < 0.001). IL-6 early on POD1 as a predictor of antibiotic treatment, ICU stay and hospital stay (AUC 0.818; 0.811; 0.771) did not significantly differ from the AUC of CRP late on POD3 (0.879; 0.838, 0.752). A cut-off IL-6 value of 113 pg/ml on POD1 and 180.5 pg/ml on POD3 in severe complications (CD > 3a) resulted in 75% and 72% sensitivity, 78.6% and 99% specificity, negative predictive value 96.4% and 97% and positive predictive value 29% and 88.9%. CONCLUSION: The serum level of interleukin-6 can predict severe (CD > 3a) POC early on POD1. On POD3, IL-6 is superior to CRP in terms of high positive predictive power of severe POC. Interestingly, the advantage of IL-6 on POD1 is early prediction of the need for antibiotic treatment, ICU stay and hospital stay, which is comparable to the CRP serum level late on the third POD.

• Keywords
• Colorectal surgery, Infection, Interleukin-6, Postoperative complications,
• MeSH
• Anti-Bacterial Agents MeSH
• Biomarkers MeSH
• C-Reactive Protein analysis   MeSH
• Interleukin-6 * MeSH
• Colorectal Surgery * MeSH
• Humans MeSH
• Postoperative Complications etiology   MeSH
• Prospective Studies MeSH
• ROC Curve MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Biomarkers MeSH
• C-Reactive Protein MeSH
• IL6 protein, human MeSH Browser
• Interleukin-6 * MeSH