Mucosal Cancer Research Articles

Clinico-pathological specificities of gingival carcinoma among 32 patients with oral cancer: a cross sectional retrospective and observational study

BackgroundThe study aimed to examine the prevalence of gingival cancers compared to other oral mucosal sites, analyze patient profiles, and identify risk factors.Materials and MethodsA retrospective monocentric study was conducted at the Department of Oral Medicine of Bretonneau Hospital in Paris, France. 32 patients diagnosed with oral mucosal cancer were included. Data extracted from electronic medical records encompassed patient demographics, cancer type, lesion location, and tobacco/alcohol use.Results46.9% were diagnosed with gingival cancer. Patients with gingival cancer had a mean age of 74.2 years old, higher than the mean age of 63.9 years old for those with non-gingival cancer. Men accounted for 60% of cases in the gingival cancer group. Squamous cell carcinoma was the predominant cancer type observed in both gingival and non-gingival cancers. Notably, 26.7% of gingival cancer patients used both alcohol and tobacco, all of them male. Among non-gingival cancer patients, 23.5% used both substances, with both sexes represented.ConclusionThis study provides insights into the higher prevalence of oral squamous cell carcinoma among men with risk factors and highlights characteristics of gingival squamous cell carcinoma. Effective management strategies should include comprehensive clinical assessments to ensure early detection and intervention for improved outcomes.

Differentially Expressed Somatostatin (SST) and Its Receptors (SST1-5) in Sporadic Colorectal Cancer and Normal Colorectal Mucosa.

Colorectal cancer (CRC) is one of the most common human malignancies worldwide. The somatotropin-releasing inhibitory factor/somatostatin (SRIF/SST) acts through activation of five membrane receptors (SSTRs, SST1-5). The diagnostic and prognostic role of these peptides in sporadic CRC remains unclear. This study aimed to determine the role of tissue expression of SST and all SSTRs in the pathogenesis, diagnosis, and prognosis of sporadic CRC. The expression of SST and all SSTRs was assessed in the tissues of CRC patients, control colorectal mucosa and lymph node metastasis from the same patients using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Decreased SST (mRNA and peptide) and higher SST2 and SST5 (mRNA and peptide) expression in CRC vs. control was noted. A negative correlation between SST mRNA expression and patient's age in CRC and control groups were observed. IHC study confirmed the coexpression of SSTRs in all tissue groups and significant dependence on the cellular localization. Immunoexpression of SST2 and SST3 showed the most correlations with clinicopathological data in CRC patients. Interestingly, only control tissue showed differences in SST1-5 expression depending on the colon segment. Reduced SST expression in CRC indicates a weakening in its antitumor effect in this cancer in vivo. Overexpression of SST2 and SST5 in CRC suggests that these receptors play an important role in the pathogenesis of this cancer. Analysis of SST1-5 tissue expression allows for differentiation between the mucinous and nonmucinous CRC subtypes. The coexpression of all SST1-5 and overexpression of not only SST2 and SST5 in CRC may have applications for future therapy based on the SRIF system in sporadic CRC.

French Dentists’ knowledge, attitudes and practices toward oral cancer detection: A national survey

BackgroundFrance is ranked 6th in Europe in terms of oral cancer incidence. Dental surgeons are on the front line in examining the oral mucosa, but little is known about the knowledge, attitudes and practices of French dental surgeons with respect to lesions suspected of malignancy. MethodsAn online survey including 18 self-administered questions was widely shared on social media using major networks of French dentists. Items included socio-demographic characteristics of the respondents, their self-assessed knowledge, screening practices and training on oral cancer detection and care. ResultsA total of 676 dental surgeons participated in this survey. The vast majority, 92.8 %, were general dental surgeons, 83.9 % had a private practice and 49.1 % had less than 5 years of dental experience. Almost 55 % declared that they did not conduct systematic examinations of the oral mucosa and 45 % reported that they did conduct such examinations. In-hospital practice, lower patient age, dental surgeon experience, and specialty were all positively associated with systematic examination of the oral mucosa. Conversely, absence of a patient complaint, absence of an obvious lesion, lack of time, and lack of training/skills were all negatively associated. DiscussionThis is the first survey to analyze the practices of French dental surgeons in oral cancer screening. Only half of the respondents, the best trained, performed systematic oral mucosa examinations which objectively help to early detect mucosal cancer lesions. To improve oral cancer early detection, we recommend mandatory screening training programs for all dental students and dental surgeons.

Immunomodulatory effects of live and UV-killed Bacillus subtilis natto on inflammatory response in human colorectal adenocarcinoma cell line in vitro.

Colorectal cancer (CRC) is a heterogeneous disease of the colon or rectum arising from adenoma precursors and serrated polyps. Recently, probiotics have been proposed as an effective and potential therapeutic approach for CRC prevention and treatment. Probiotics have been shown to alleviate inflammation by restoring the integrity of the mucosal barrier and impeding cancer progression. In this study, we aimed to investigate the immunomodulatory effects of live and UV-killed Bacillus subtilis natto on the inflammatory response in CRC. Caco-2 cells were exposed to various concentrations of live and UV- killed B. subtilis natto, and cell viability was assessed using MTT assay. Gene expression analysis of IL-10, TGF-β, TLR2 and TLR4 was performed using RT-qPCR. Our findings showed that both live and UV-killed B. subtilis natto caused significant reduction in inflammatory response by decreasing the gene expression of TLR2 and TLR4, and enhancing the gene expression of IL-10 and TGF-β in Caco-2 cells as compared to control group. The results of this study suggest that live and UV-killed B. subtilis natto may hold potential as a therapeutic supplement for modulating inflammation in CRC.

Mucosal Cancers Arising in Potentially Malignant Lesions of the Oral Mucosa Are Marjolin Ulcers: New Insights Into Old Concepts.

Several disparate mucocutaneous diseases present oral mucosal lesions that have been classically labeled as "pre-cancerous", "pre-malignant", or "potentially malignant". These include oral lichen planus, dyskeratosis congenita, tertiary syphilitic glossitis chronic graft-versus-host-disease, and oral discoid lupus erythematosus. There is much confusion in literature regarding the real malignant potential of these oral lesions in relation to the incidence of squamous cell carcinoma. We tried to unify the occurrence of squamous cell carcinoma in some oral mucosal diseases into the classic concept of "Marjolin ulcer". We analyzed the most relevant published evidence of the occurrence of squamous cell carcinoma arising in oral lichen planus, dyskeratosis congenita, tertiary syphilitic glossitis chronic graft-versus-host-disease, and oral discoid lupus erythematosus, and tried to establish a logical link between them. Reported cases of squamous cell carcinoma occurring in oral lesions of these diseases seem to appear in old standing, scarring lesions. Oral lichen planus, dyskeratosis congenita, tertiary syphilitic glossitis, chronic graft-versushost-disease, and oral discoid lupus erythematosus are not "pre-malignant diseases", their long-lasting mucosal scars are prone to the development of squamous cell carcinomas. In this sense, this tumor can be considered a mucosal type of Marjolin ulcer.

Increased infiltration of M2-polarized tumour-associated macrophages is highly associated with advanced disease stage and high expression of PD-L1 in buccal mucosa carcinoma

ObjectiveTo assess the infiltration characteristics of tumour-associated macrophages (TAMs) in buccal mucosa carcinoma (BMC) and the correlation of these features with clinicopathological factors.Materials and methodsImmunohistochemistry was used to detect the expression of TAM-related markers (CD68, CD163, CD206), CD8+ T cell markers, PD-L1, and epidermal growth factor receptor (EGFR) in 46 patients with mucosal cancer after radical surgery. In addition, the correlation between TAM infiltration and clinical characteristics, PD-L1 expression, and EGFR expression was analysed.ResultsA high infiltration level of M2-polarized (CD206+) TAMs and M2-polarized (CD163+) TAMs was more common in stage T3–T4, N+, III–IV patients than in other patient groups (P < 0.05). The infiltration degree of M2-polarized (CD68+) TAMs was positively correlated with the PD-L1 TPS (P = 0.0331). The infiltration level of M2-polarized (CD206+) TAMs was higher in the EGFR high expression group than in the EGFR low expression group (P = 0.040).ConclusionHigh infiltration of M2-polarized TAMs is highly associated with advanced disease stage and higher expression of PD-L1 and EGFR in BMCs, suggesting that M2-polarized TAMs infiltration can serve as a potential therapeutic target.

BIOLOGICAL AND PROGNOSTIC IMPORTANCE OF CYTOKINES IN ORAL CANCER

Epidemiological data indicate high rates of morbidity and mortality of oral mucosal cancer worldwide. At the same time, even visual accessibility does not allow detecting oral cancer in the early stages. The purpose of the study. Assessment of the involvement of cytokines in the development and progression of oral cancer. Materials and methods. The search for publications was carried out in the databases of the RSCI, PubMed, Scopus 2019-2023 years for the following queries: cancer of the oral mucosa; potentially malignant diseases of the oral cavity; precancerous diseases of the oral cavity, inflammation and cancer, cytokines, saliva cytokines, serum cytokines. Results. It is now recognized that under the influence of inflammation, neoplastic and stromal cells interact and control tumor evolution by producing cytokines. Modern studies demonstrate the important role of cytokines such as TNF-α, IL-8, IL-6, IL-1β in the development and progression of oral cancer. A review of the conducted studies indicates that cytokines released by tumor cells of oral cancer, as well as the tumor microenvironment, contribute to cell proliferation, survival, and migration of tumor cells of this localization, although they activate immune cells, contributing to the modulation of the antitumor immune response. Hyperproduction of cytokines, registered at the local and systemic levels, appears to be a consequence of dysregulation of proliferative processes and at the same time one of the causes of tumor spread. Conclusion. Modern research demonstrates the important role of various cytokines in the development and progression of cancer of the oral mucosa. In this regard, therapeutic approaches that limit their growthstimulating activity should be considered.

Longer-term surveillance imaging and endoscopy critical for majority of patients in detection of sinonasal malignancy recurrence.

Sinonasal malignancy surveillance paradigms are often based on Head and Neck National Comprehensive Cancer Network guidelines, which do not recommend standard surveillance imaging beyond 6 months without concerning symptomatology or physical examination findings. This was a retrospective analysis of all patients who underwent resection of sinonasal malignancy at a tertiary care center over a 20-year period from 2000 to 2020, with an ensuing surveillance period demonstrating recurrence. Fifty-two patients with sinonasal malignancy recurrence were included, with an average time to recurrence of 30.9 months and a follow-up period of over 60 months. Recurrence was diagnosed by routine imaging or endoscopy in asymptomatic patients in a majority (60%) of cases, while the remaining minority of diagnoses followed new symptomatology. Asymptomatic recurrence was associated with perineural spread of tumor at initial resection (p=0.025), but not with age (p=0.85) or stage at diagnosis (p=0.68). Expectedly, positron emission tomography/computed tomography (CT) more often detected regional or distant recurrence, while structural imaging (CT/magnetic resonance imaging) demonstrated more frequent detection of recurrence in those with perineural spread of tumor (p=0.01). Our findings support high rates of asymptomatic recurrence in sinonasal malignancy, with the majority of recurrences diagnosed by routine endoscopy or imaging. Tailored and extended surveillance guidelines are necessary relative to those utilized for other head and neck mucosal cancers, and are especially appropriate when features such as perineural spread are present.

Identification of maximal tumor size associated with negligible lymph node metastasis for endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

When treating undifferentiated-type early gastric cancer (UD-EGC) that is limited to the mucosa (clinically T1a), endoscopic submucosal dissection (ESD) can be considered if the tumor is 2cm or less and is not ulcerated. However, there is insufficient evidence to determine the relationships between tumor size and oncological safety of ESD in UD-EGC. The pathology reports of Korean patients who were diagnosed with UD-EGC (n=5286) were retrospectively reviewed. The cumulative incidence of lymph node metastasis (LNM) according to tumor size was evaluated in subgroups. The tumor-size cut-off was identified as the upper limit of the 95% confidence interval (CI) of cumulative LNM incidence that did not exceed 1.0%. We identified 1516 patients with non-ulcerated T1a tumors ≤2cm in size. Among patients without lymphatic invasion, 1.5% (95% CI 0.91-2.16%) had LNM. In patients with poorly differentiated tubular adenocarcinoma (PD), LNM increased from 0 to 0.74% based on a tumor size of 1.0cm. Regardless of tumor size, smaller percentages of undifferentiated-type (UD) and poorly cohesive carcinoma (PCC) patients experienced LNM than did those with PD. In non-ulcerated mucosal cancer without lymphatic invasion and tumor size ≤0.9cm, no LNM was observed in patients with UD (95% CI 0-0.53%), PCC (95% CI 0-0.59%), or PD (95% CI 0-0.86%) histologic type. In patients diagnosed with non-ulcerated T1a UD-EGC, ESD can be performed if the tumor size is 0.9cm or less, regardless of histologic type.

Accuracy of Narrow-Band Imaging-Guided Histopathology and Ki-67 Index in Head and Neck Carcinoma.

All patients were first examined under white light and then under NBI endoscopy, and a biopsy was obtained from suspected lesions and sent for histopathological examination (HPE) and Ki-67 index. Eighty patients were examined out of which, 68 patients having lesions in the oral cavity, oropharynx, larynx, and hypopharynx were examined. The rate of detecting cancerous lesion by white light and NBI were respectively 92% and 100% for oral cavity lesions, 69% and 100% for oropharyngeal lesions, 38% and 100% for hypopharyngeal lesions, and 37% and 100% for laryngeal carcinoma. However, we have found no significant difference in detecting T2-T4 tumors. Hence, we concluded that NBI mode can be a significantly better diagnostic tool than white light mode in detecting early mucosal cancer in head and neck cancer. We have concluded that NBI combined with Ki-67 estimation is a very promising tool that helps in the early diagnosis of mucosal lesions in head and and neck cancer.

Comparative analysis of resection boundaries depending on the defect elimination method in oral mucosal cancer

Introduction. Surgical intervention remains the main method for treatment of the oral mucosa cancer. The generally accepted standard of the resection boundary that provides optimal local control is 5 mm. Adequate boundaries of indentation and choice of the reconstruction method are important issues facing specialists in head and neck tumors. Aim. To evaluate parameters of the resection edge in the surgical treatment of malignant neoplasms of the oral mucosa depending on the method of eliminating of the post-resection defect and its effect on the frequency of local relapse. Materials and methods. A retrospective analysis included 168 primary patients (50 % men and 50 % women) who received surgical treatment in the head and neck tumor department of the Republican Clinical Oncology Dispensary of the ministry of Health of the Republic of Bashkortostan (ufa) from 2019 to 2023. The median age of patients was 63 years (interquartile range (IQR) 55–69 years). most often, the primary tumor was located in the tongue – in 59.5 % (100/168) of cases. According to the method of post-resection defect removal, the patients were divided into 3 groups. In group 1, reconstruction was performed with local tissues (n = 71), in group 2 – with pedicle flaps (n = 41), and in group 3 – with revascularized flaps (n = 56). The median follow-up period was 18 months (IQR 8–28 months). Results. Resection boundaries in group 1 were 7.0 mm (IQR 5.0–12.5 mm), in group 2 – 6.5 mm (IQR 5–13 mm), and in group 3 – 12.5 mm (IQR 7.5–15.0 mm). The overall frequency of near/positive resection boundaries was 14.8 % (25/168). In group 1, it was 15.5 % (11/71), in group 2 – 19.5 % (8/41), in group 3 – 10.7 % (6/56). According to the analysis, relapse of the disease after radical treatment was noted in 32 % (55/168) of patients, of which 14.8 % (25/168) had a local relapse, 12.5 % (21/168) had a regional relapse, and 5.4 % (9/168) developed distant metastases. The frequency of local relapse in group 1 was 18.3 % (13/71), in group 2 – 23.8 % (10/41), in group 3 – 5.5 % (3/56). According to the analysis data, statistically significant differences in the boundary of indentation in the groups were revealed depending on the reconstruction method (p = 0.005). Conclusion. Based on the results of the present retrospective analysis, the choice of reconstruction method affects the resection boundary in real clinical practice. Limitations in the surgical indentation that surgeon faces when choosing a method for eliminating a post-resection defect are demonstrated.

Microfluidic device featuring micro-constrained channels for multi-parametric assessment of cellular biomechanics and high-precision mechanical phenotyping of gastric cells

BackgroundCellular biomechanics plays a significant role in the regulation of cellular physiological and pathological processes. In recent years, multiple methods have been developed to evaluate cellular biomechanics, such as atomic force microscopy (AFM), micropipette aspiration, and magnetic tweezers. However, most of these methods only focus on a single parameter and cannot automate the process at a high-efficiency level. A novel microfluidic method is necessary to achieve the simultaneous multi-parametric measurement of cellular biomechanics and high-precision cellular mechanical phenotyping at high throughput. ResultsTo tackle the issue concerning the low-throughput and cellular single-parameter evaluation, we designed and fabricated a microfluidic chip featuring multiple micro-constrained channels structure, providing a simultaneous multi-parametric assessment of cellular biomechanics, including elastic modulus, recovery capability, and deformability. We compared the biomechanical properties of normal human gastric mucosal epithelial cells (GES-1) and human gastric cancer cells (AGS and MKN-45) by the chip. Results demonstrated that the elastic modulus of GES-1, AGS, and MKN-45 cells decreased sequentially, which was the opposite of their invasiveness and metastasis potential, suggesting the inverse correlation between cellular elastic modulus and malignancy. Meanwhile, the recovery capability and deformability of GES-1, AGS, and MKN-45 cells increased sequentially, demonstrating the positive correlation between cellular deformability and malignancy. Furthermore, multiple parameters were used to distinguish gastric cancer cells from normal gastric cells via machine learning. An accuracy of over 94.8% for identifying gastric cancer cells was achieved. SignificanceThis study provides a deep insight into the biophysical mechanism of gastric cancer metastasis at the single-cell level and possesses great potential to function as a valuable tool for single-cell analysis, thereby facilitating high-precision and high-throughput discrimination of cellular phenotypes that are not easily discernible through single-marker analysis.

RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation

BackgroundMolecular analysis of advanced tumors can increase tumor heterogeneity and selection bias. We developed a robust prognostic signature for gastric cancer by comparing RNA expression between very rare early gastric cancers invading only mucosal layer (mEGCs) with lymph node metastasis (Npos) and those without metastasis (Nneg).MethodsOut of 1003 mEGCs, all Npos were matched to Nneg using propensity scores. Machine learning approach comparing Npos and Nneg was used to develop prognostic signature. The function and robustness of prognostic signature was validated using cell lines and external datasets.ResultsExtensive machine learning with cross-validation identified the prognostic classifier consisting of four overexpressed genes (HDAC5, NPM1, DTX3, and PPP3R1) and two downregulated genes (MED12 and TP53), and enabled us to develop the risk score predicting poor prognosis. Cell lines engineered to high-risk score showed increased invasion, migration, and resistance to 5-FU and Oxaliplatin but maintained sensitivity to an HDAC inhibitor. Mouse models after tail vein injection of cell lines with high-risk score revealed increased metastasis. In three external cohorts, our risk score was identified as the independent prognostic factor for overall and recurrence-free survival.ConclusionThe risk score from the 6-gene classifier can successfully predict the prognosis of gastric cancer.

Endoscopic submucosal dissection for early esophageal adenocarcinoma: low rates of metastases in mucosal cancers with poor differentiation

Background and aimsEndoscopic resection (ER) is accepted as standard treatment for intramucosal esophageal adenocarcinoma (EAC) with well or moderate differentiation. Poor differentiation (PD) is judged as a risk factor for lymph node metastasis (LNM) and surgery is recommended. However, the evidence for this recommendation is weak. Study aim was to analyze the clinical course of patients after ER of EAC with PD. Patients and methodsPatients undergoing endoscopic submucosal dissection for EAC were included from 16 German centers. Inclusion criteria were PD in the resection specimen, R0 resection and endoscopic follow-up. Primary outcome was the metastasis rate during follow-up. Analysis was performed retrospectively in a prospectively collected database. Results25 patients with PD as single risk factor (group A) and 15 patients with PD and additional risk factors (submucosal invasion and/or lymphovascular invasion) were included. The metastasis rate was was 1/25 (4.0%; 95%CI 0.4-17.2) in group A and 3/15 (20.0%; 95%CI 6.0-44.4%) in group B, respectively (p=0.293). The rate of EAC-associated deaths was 1/25 (4%; 95%CI 0.4-17.2%) versus 3/15 (20%; 95%CI 6.0-44.4%) in group B (p=0.293) while the overall death rate was 7/25 (28.0%; 95%CI 13.5-47.3%) versus 3/15 (20%; 95%CI 6.0-44.4%) (p=0.715). Median follow-up was 30 months (IQR 15-53). ConclusionsDuring long-term follow-up the risk of metastasis is low after ER of mucosal EAC with PD as single risk factor. A conservative approach seems justified in this small patient group. However, the treatment strategy has to be determined on an individualized basis until further prospective data are available.

Profile of matrix‐entrapped extracellular vesicles of microenvironmental and infiltrating cell origin in decellularized colorectal cancer and adjacent mucosa

AbstractCellular elements that infiltrate and surround tumours and pre‐metastatic tissues have a prominent role in tumour invasion and growth. The extracellular vesicles specifically entrapped and stored within the extracellular matrix (ECM‐EVs) may reflect the different populations of the tumour microenvironment and their change during tumour progression. However, their profile is at present unknown. To elucidate this aspect, we isolated and characterized EVs from decellularized surgical specimens of colorectal cancer and adjacent colon mucosa and analyzed their surface marker profile. ECM‐EVs in tumours and surrounding mucosa mainly expressed markers of lymphocytes, natural killer cells, antigen‐presenting cells, and platelets, as well as epithelial cells, representing a multicellular microenvironment. No difference in surface marker expression was observed between tumour and mucosa ECM‐EVs in stage II‐III tumours. At variance, in the colon mucosa adjacent to stage IV carcinomas, ECM‐EV profile showed a significantly increased level of immune, epithelial and platelet markers in comparison to the matrix of the corresponding tumour. The increase of EVs from immune cells and platelets was not observed in the mucosa adjacent to low‐stage tumours. In addition, CD25, a T‐lymphocyte marker, resulted specifically overexpressed by ECM‐EVs from stage IV carcinomas, possibly correlated with the pro‐tolerogenic environment found in the corresponding tumour tissue. These results outline the tissue microenvironmental profile of EVs in colorectal carcinoma‐derived ECM and unveil a profound change in the healthy mucosa adjacent to high‐stage tumours.

L-Menthol for Color Difference Change Between Early Gastric Cancer and Surrounding Mucosa: A Prospective Study.

L-Menthol sprayed on early gastric cancer (EGC) has been reported to improve the visibility of the lesion. However, its impact when used in combination with novel image-enhanced endoscopy has not been investigated. This study aimed to evaluate the visual effect of spraying L-menthol on EGC under linked color imaging (LCI). This open-label, single-arm, prospective study investigated the color difference between EGC and the surrounding mucosa (ΔEG) before and after spraying L-menthol. The primary endpoint was the percentage of lesions with ΔEG ≥ 5 on LCI. The percentage of lesions with ΔEG ≥ 5 on white light imaging (WLI) and blue laser imaging (BLI), ΔEG before and after spraying L-menthol, and percentage of lesions with increased ΔEG after spraying L-menthol constituted the secondary endpoints. Sixty patients were included in the final analysis. 100% lesions had ΔEG ≥ 5, both before and after spraying L-menthol on LCI, with similar results observed in WLI as well as BLI. The median ΔEG on LCI, WLI, and BLI increased after spraying L-menthol (LCI: 16.9 vs. 21.5, p < 0.01; WLI: 10.4 vs. 13.4, p < 0.01; BLI; 12.1 vs. 15.7, before and after, respectively, p < 0.01); and LCI demonstrated the highest percentage of lesions with increased ΔEG (LCI, WLI, and BLI: 98.3%, 81.7%, and 76.7%, respectively, p < 0.01). Although spraying L-menthol did not improve the visibility of EGC under LCI observation, a significant increase in ΔEG was observed in LCI (jRCTs 021200027).

Role of chemokine receptors in gastrointestinal mucosa.

Chemokine receptors are essential for the immune response in the oral and gut mucosa. The gastrointestinal mucosa is characterized by the presence of immune populations because it is susceptible to inflammatory and infectious diseases, necessitating immune surveillance. Chemokine receptors are expressed on immune cells and play a role in gastrointestinal tissue-homing, although other non-immune cells also express them for various biological functions. CCR9, CXCR3 and CXCR6 play an important role in the T cell response in inflammatory and neoplastic conditions of the gastrointestinal mucosa. However, CXCR6 could also be found in gastric cancer cells, highlighting the different roles of chemokine receptors in different pathologies. On the other hand, CCR4 and CCR8 are critical for Treg migration in gastrointestinal tissues, correlating with poor prognosis in mucosal cancers. Other chemokine receptors are also important in promoting myeloid infiltration with context-dependent roles. Further, CXCR4 and CXCR7 are also present in gastrointestinal tumor cells and are known to stimulate proliferation, migration, and invasion into other tissues, among other pro-tumorigenic functions. Determining the processes underlying mucosal immunity and creating tailored therapeutic approaches for gastrointestinal diseases requires an understanding of the complex interactions that occur between chemokine receptors and their ligands in these mucosal tissues.

A microfluidic co-culture model for investigating colonocytes-microbiota interactions in colorectal cancer.

Changes in the abundance of certain bacterial species within the colorectal microbiota correlate with colorectal cancer (CRC) development. While carcinogenic mechanisms of single pathogenic bacteria have been characterized in vitro, limited tools are available to investigate interactions between pathogenic bacteria and both commensal microbiota and colonocytes in a physiologically relevant tumor microenvironment. To address this, we developed a microfluidic device that can be used to co-culture colonocyte spheroids and colorectal microbiota. The device was used to explore the effect of Fusobacterium nucleatum, an opportunistic pathogen associated with colorectal cancer development in humans, on colonocyte gene expression and microbiota composition. F. nucleatum altered the transcription of genes involved in cytokine production, epithelial-to-mesenchymal transition, and proliferation in colonocytes in a contact-independent manner; however, most of these effects were significantly diminished by the presence of commensal microbiota. Interestingly, F. nucleatum significantly altered the abundance of multiple bacterial clades associated with mucosal immune responses and cancer development in the colon. Our results highlight the importance of evaluating the potential carcinogenic activity of pathogens in the context of a commensal microbiota, and the potential to discover novel inter-species microbial interactions in the CRC microenvironment.

Layer-by-layer nanoparticle encapsulating all-trans retinoic acid and CpG as a mucosal adjuvant targeting colorectal cancer.

Colorectal cancer (CRC) ranks among the most prevalent cancers globally, demanding innovative therapeutic strategies. Immunotherapy, a promising avenue, employs cancer vaccines to activate the immune system against tumors. However, conventional approaches fall short of eliciting robust responses within the gastrointestinal (GI) tract, where CRC originates. Harnessing the potential of all-trans retinoic acid (ATRA) and cytosine-phosphorothioate-guanine (CpG), we developed layered nanoparticles using a layer-by-layer assembly method to co-deliver these agents. ATRA, crucial for gut immunity, was efficiently encapsulated alongside CpG within these nanoparticles. Administering these ATRA@CpG-NPs, combined with ovalbumin peptide (OVA), effectively inhibited orthotopic CRC growth in mice. Our approach leveraged the inherent benefits of ATRA and CpG, demonstrating superior efficacy in activating dendritic cells, imprinting T cells with gut-homing receptors, and inhibiting tumor growth. This mucosal adjuvant presents a promising strategy for CRC immunotherapy, showcasing the potential for targeting gut-associated immune responses in combating colorectal malignancies.

Salivary cortisol levels in patients with potentially malignant oral disorders and oral mucosal cancer: a case-control study.

The relationship between salivary cortisol secretion and the presence of cancer in the oral cavity has not been completely clarified. Due to this, we proposed carrying out a study to determine salivary cortisol levels in patients with potentially malignant disorders (PMD), oral squamous cell carcinoma (OSCC) and healthy individuals. Cross-sectional case-control study, among 80 patients seen at the Faculty of Dentistry of the National University of Rosario, Argentina, between January 2018 and April 2020. 40 cases represented by Leukoplakia, Lichen, Erythroplakia and SCC and 40 controls were included. Smoking habit and alcohol consumption were included. The presence of stress was determined. Morning salivary cortisol levels were measured with the Roche electrochemiluminescence method (Traceability: St by ID-MS). Patients with SCC presented elevated salivary cortisol values. Individuals with stage III tumors showed levels higher than 8.74 ng/ml in all cases. A significant association between cortisol levels and stress was detected in patients in the control group (p<0.005) and in individuals with PMD (p=0.009). This association was not significant in patients with SCC (p=0.999). After applying the logistic regression method, when adjusting odds ratios according to tobacco and alcohol consumption and the presence of stress, the association between cortisol levels and presence of stress was highly significant (p<0.001). The possibility of presenting undetectable cortisol results was 94% lower in patients with stress. The increase in salivary cortisol levels in patients with PMD and SCC, is related to stress conditions, being able to generate alterations tending to immunosuppression of the cellular microenvironment.