Comparative analyses of short- and long-term outcomes between endoscopic submucosal dissection and endoscopic laryngo-pharyngeal surgery for superficial pharyngeal carcinomas.

Objectives: Endoscopic treatment of superficial pharyngeal carcinomas includes endoscopic submucosal dissection (ESD; usually performed by endoscopists), and endoscopic laryngo-pharyngeal surgery (ELPS; primarily performed by otolaryngologists). Few studies have compared the efficacy of the two techniques in treating superficial pharyngeal carcinomas. In this study, we compared the outcomes of these two techniques to determine the advantages. Methods: We retrospectively examined the short- and long-term outcomes of 93 consecutive patients with superficial pharyngeal carcinoma who either underwent an ESD or ELPS between August 2008 and December 2021. Results: There were 35 lesions among 29 patients and 93 lesions among 71 patients in the ESD and ELPS groups, respectively. The ELPS group had a significantly shorter procedure time (121.2 ± 97.4 min vs. 54.7 ± 40.2 min, p<0.01), greater procedure speed (0.10 ± 0.06 min/min vs. 0.30 ± 0.23 min/min, p<0.01), and less laryngeal edema than that of the ESD group. There were no significant differences in the 3-year overall, relapse-free, or disease-specific survival rates between the two groups. Intervention with ESD during ELPS was most commonly required when it was difficult to secure the visual field. Conclusions: There were no differences in batch resection rates or long-term prognoses between the two groups; nevertheless, the ELPS group had a shorter treatment time and less laryngeal edema than the ESD group. However, the treatment of narrow areas, such as the esophageal inlet patch, is a technical limitation of ELPS; thus, ELPS should be combined with ESD techniques.

Visibility of esophageal squamous cell carcinoma under iodine staining on texture and color enhancement imaging.

Objective: Iodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining. Methods: Twenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow-band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging. Result: The median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow-band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01). Conclusions: The visibility of ESCC after iodine staining was greater on TXI than on WLI.

Anterior lamellar corneoscleral keratoplasty for the management of corneal thinning following treatment with mitomycin-C and interferon to treat highly suspected ocular surface squamous neoplasia: a case report

ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

Chewing betel quid induced a critical metastatic squamous cell carcinoma of the lower lip: A case report.

Betel quid chewing is a common practice in many cultures and has been associated with various health risks, including an increased likelihood of developing squamous cell carcinoma (SCC). This case study presents a critical instance of metastatic SCC of the lower lip induced by betel quid chewing. A 45-year-old male with a history of betel quid chewing presented with a persistent and enlarging sore on his lower lip. A biopsy revealed SCC, and subsequent imaging confirmed metastasis to the lungs. This case highlights the potential for betel quid chewing to induce metastatic SCC and emphasizes the need for awareness and cessation of this habit to prevent such severe health outcomes. The aggressive nature of metastatic SCC warrants immediate and effective treatment strategies.

[Dermatologic surgery during pregnancy and lactation]. / Dermatochirurgie in Schwangerschaft und Stillzeit.

It may be necessary for patients to undergo (dermato-)surgical procedures during pregnancy or lactation. Often, there are no drug approvals or guidelines in this context. The following article describes the most common dermatologic surgical conditions during pregnancy and lactation, as well as the special therapeutic considerations and risks to be aware of during treatment. Dermatosurgical procedures are subject to strict indications. Most of these procedures can be performed during pregnancy, but the risks to the mother and fetus must be carefully weighed against the disadvantages of nonsurgical therapy. Although surgery can be performed safely in any trimester, the second trimester and immediate postpartum period are optimal. Surgery should not be delayed for melanoma or high-risk skin cancer. Perioperative positioning and choice of analgesics, antiseptics, anesthetics and antibiotics must be considered carefully to avoid risks to the patient, fetus and infant.

Decoding the Rarity: A Unique Case of Clear-Cell Variant of Oral Squamous Cell Carcinoma.

The clear-cell variant of oral squamous cell carcinoma is an extremely rare histological variant and an incompletely understood entity. Clear cell appearance in squamous cell carcinoma may be attributed to hydropic degeneration of neoplastic cells. We report a case of a 32-year-old male patient who presented with an ulceroproliferative growth in the left maxillary posterior region on the hard palate and gingiva, obliterating the buccal vestibule. Histopathologic examination revealed thick anastomosing strands of round to ovoid neoplastic cells with predominantly clear cytoplasm and marked cellular and nuclear pleomorphism infiltrating into the fibro-cellular connective tissue stroma. Special staining and immunohistochemistry (IHC) were performed to rule out the differentials of clear-cell variants of different sites such as salivary gland, odontogenic origin, and metastatic tumors. The clear cells were negative for periodic acid Schiff (PAS) and mucicarmine. The malignant clear cells showed positive reactions with IHC markers pan-cytokeratin and P63 and yielded negative results for S100 and CD10, confirming the diagnosis as a clear-cell variant of oral squamous cell carcinoma. We emphasize the importance of prompt and comprehensive diagnostic work-up to identify this rare, aggressive, and possibly fatal neoplasm.

Prevalence and Pattern of Oral and Maxillofacial Pathology in Al-Qassim Region, Saudi Arabia.

Objective: The purpose of this study is to determine the prevalence and features of oral and maxillofacial lesions found in the residents of Al-Qassim region, Saudi Arabia. Methods: A retrospective study was conducted at King Fahad Specialist Hospital, Buraidah, Qassim, KSA. The data for all biopsied oral and maxillofacial lesions were retrieved from January 2014 until August 2022. All patients' data including age, gender, location of the lesion, and histopathologic diagnosis were reviewed and analyzed using IBM SPSS version 23 and Microsoft Excel. Results: A total of 381 oral pathology biopsies for individuals aged 18 and above were included in a descriptive analysis. One hundred ninety five (51.18%) of patients were male, and 186 (48.82%) were female. The site most commonly biopsied was the oral mucosa (26%). The diagnosis was categorized according to the histopathological diagnosis into 13 categories including all pathological lesions in the oral and maxillofacial area. The frequently biopsied category was soft tissue pathological lesion category (26%), second to that is the odontogenic cyst category (22%), and third is the immunological-mediated lesion category (13%). The sub-diagnosis that was mostly observed was radicular cyst, lichen planus, and focal fibrous hyperplasia with the percentages of 13.6%, 10.8%, and 9.4%, respectively. Conclusion: The findings provide important information about the oral and maxillofacial pathology in Al-Qassim region, Saudi Arabia. This study found that biopsied oral lesions were more prevalent in males and in patients in the fourth decade of life. The oral mucosa was the most biopsied site, and the majority of the biopsies were soft tissue pathological lesions and radicular cyst was the most frequent diagnosis. Knowledge of such demographic and clinical features of oral and maxillofacial pathology cases helps in prediction of disease incidence and subsequent proper patient care in the region.

Non­obstructive mesenteric ischaemia during drug therapy for maxillary cancer: A case report.

Non-occlusive mesenteric ischaemia (NOMI) refers to irreversible intestinal ischaemia and necrosis in the absence of organic obstruction to the mesenteric blood vessels. In cases of delayed diagnosis, the prognosis is poor and the mortality rate is 58-70%, being the highest among patients with acute mesenteric ischaemia. The risk factors for this disease include heart disease, sepsis, and administration of catecholamines and digitalis; however, there are few reports of its onset during drug therapy for malignant tumours. The present study reported the case of an 85-year-old man who developed NOMI during drug therapy for maxillary cancer. The patient was diagnosed with right maxillary carcinoma, for which paclitaxel, carboplatin and cetuximab (PCE) therapy was administered. Four days after starting the second course of PCE therapy, the patient visited the emergency department of our hospital with chief complaints of melena and abdominal pain. Contrast-enhanced computed tomography revealed ischaemia from the transverse to the descending colon, leading to a diagnosis of NOMI. Colectomy and colostomy were performed during the emergency surgery on the same day. Although the patient's general condition improved, he was transferred to a recuperation facility for palliative care.

Loss of MACROD2 drives radioresistance but not cisplatin resistance in HPV-positive head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. In recent years, there has been an increase in the rate of HNSCC cases attributed to the infection of the oropharynx by the human papillomavirus (HPV). Given the significant treatment-related toxicities of the current standard of care for HPV-positive HNSCC, there is an urgent need for the development of precision patient stratification and treatment strategies to improve patients' quality of life while maintaining excellent survival rates. We have previously carried out whole genome sequencing of HPV+ HNSCC tumors that failed concurrent cisplatin and radiation treatment and discovered that MACROD2 deletion is enriched among these tumors. In the current study, we sought to investigate the mechanistic role of MACROD2 in HPV+ HNSCC treatment resistance. Our results indicate that MACROD2 depletion in HNSCC cell lines leads to increased cell viability and colony formation capacity. Interestingly, MACROD2 depletion did not alter cisplatin sensitivity but led to an increase in radiation resistance of HPV+ HNSCC cell lines. RNA sequencing and immunofluorescence microscopy demonstrated that MACROD2-depleted HPV+ HNSCC cells displayed elevated levels of hypoxia and an altered DNA damage response. Taken together, this study establishes and characterizes the role of MACROD2 in HPV+ HNSCC radioresistance. Further work is needed to validate MACROD2 as a biomarker of treatment failure and to understand how to overcome the identified molecular mechanisms of resistance.

A case report of primary intrahepatic adeno squamous cell cholangiocarcinoma.

INTRODUCTION: Hepatocellular carcinoma is the most common form of primary liver cancer. Intrahepatic cholangiocarcinoma and fibrolamellar carcinoma make up most other cases. The vast majority of intrahepatic cholangiocarcinoma's are adenocarcinoma in nature. Few reports have indicated pure squamous cell or mixed squamous glandular histopathology. PRESENTATION OF CASE: We present the case of a 35-year-old female whose preoperative diagnosis indicated primary keratinizing squamous cell carcinoma (SCC) of the liver. However, histological analysis of surgical resections later confirmed intrahepatic cholangiocarcinoma composed of 95 % squamous and 5 % glandular features. DISCUSSION: The change in diagnosis post-operatively is indicative of the pre-operative diagnostic difficulties associated with these newly classified variants. While adenomatous differentiation is the most common form of intrahepatic cholangiocarcinoma, a squamous and mixed histology can be observed. CONCLUSION: Surgeons must be aware of new histological variants of cholangiocarcinoma, potential differentials, and direct further research to improve their poor prognosis.

Enhanced computed tomography radiomics predicts solute carrier family 7, member 11 in head and neck squamous cell carcinoma.

Introduction: Traditional prognostic indicators for head and neck squamous cell carcinoma (HNSCC), such as clinicopathological features, human papillomavirus status, and imaging examinations, often lack precision in guiding medical therapy. Therefore, discovering novel tumor biomarkers that can accurately assess prognosis and aid in personalized medical treatment for HNSCC is critical. Solute carrier family 7, member 11 (SLC7A11), is implicated in ferroptosis, and various malignant tumor therapies regulate its expression. However, the mechanisms regulating SLC7A11 expression, the transporter activity, and its specific role in controlling ferroptosis in cancer cells remain unknown. Thus, in this study, we aimed to develop an improved computed tomography (CT) radiomics model that could predict SLC7A11 expression in patients with HNSCC. Methods: We used patient genomic data and corresponding augmented CT images for prognostic analysis and building models. Further, we investigated the potential molecular mechanisms underlying SLC7A11 expression in the immune microenvironment. Our radiomics model successfully predicted SLC7A11 mRNA expression in HNSCC tissues and elucidated its association with relevant genes and prognostic outcomes. Results: SLC7A11 expression level was high within tumor tissues and was connected to the infiltration of eosinophil, CD8+ T-cell, and macrophages, which was associated with poor overall survival. Our models demonstrated robust predictive power. The distribution of radiomics scores (RAD scores) within the training and validation sets was markedly different between the high- and low-expression groups of SLC7A11. Conclusion: SLC7A11 is likely an important factor in the prognosis of HNSCC. SLC7A11 expression can be predicted effectively and reliably by radiomics models based on enhanced CT.

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). The use of corticosteroids as pretreatment might reduce immunotherapy efficacy. AIM: To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy (nIC) outcomes in locally advanced ESCC patients. METHODS: Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included. Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment. Antiallergic efficacy and safety were evaluated, as well as its impact on short-term efficacy [complete pathological response (pCR), major pathological response (MPR)] and long-term efficacy [overall survival (OS), progression-free survival (PFS)] of nIC. RESULTS: From September 2019 to September 2023, 142 patients were analyzed. No severe treatment-related adverse events or deaths were observed. Allergy occurrence was greater in the antihistamine group (P = 0.014). Short-term efficacy was not significantly different: The pCR rates were 29.9% and 40.0%, and the MPR rates were 57.9% and 65.7% in the dexamethasone and antihistamine groups, respectively. The long-term efficacy was not significantly different: The 2 years OS rates were 95.2% and 93.5%, and the 2 years PFS rates were 90.3% and 87.8%. Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the < 20 mg dexamethasone group, but PFS was significantly greater in the 20 mg dexamethasone group (93.9% vs 56.4%, P = 0.001). CONCLUSION: Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short- or long-term efficacy. Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

Integrated analyses reveal IDO1 as a prognostic biomarker coexpressed with PD-1 on tumor-associated macrophages in esophageal squamous cell carcinoma.

Background: Inhibition of indolamine-2,3-dioxygenase 1 (IDO1) has been proposed as a promising strategy for cancer immunotherapy; however, it has failed in clinical trials. Macrophages in the tumor microenvironment (TME) contribute to immune escape and serve as potential therapeutic targets. This study investigated the expression pattern of IDO1 in TME and its impact on prognosis and therapeutic response of patients with esophageal squamous cell carcinoma (ESCC). Methods: RNA sequencing data from 95 patients with ESCC from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic value of IDO1. Bioinformatics tools were used to estimate scores for stromal and immune cells in tumour tissues, abundance of eight immune cell types in TME, and sensitivity of chemotherapeutic drugs and immune checkpoint (IC) blockage. The results were validated using digitalized immunohistochemistry and multiplexed immunofluorescence in ESCC tissue samples obtained from our clinical center. Results: TCGA and validation data suggested that high expression of IDO1 was associated with poor patient survival, and IDO1 was an independent prognostic factor. IDO1 expression positively correlated with macrophages in TME and PDCD1 within diverse IC genes. Single-cell RNA sequencing data analysis and multiplexed immunofluorescence verified the coexpression of IDO1 and PD-1 in tumor-associated macrophages (TAMs). Patients with high IDO1 expression showed increased sensitivity to various chemotherapeutic drugs, while were more likely to resist IC blockage. Conclusion: This study identifies IDO1 as an independent prognostic indicator of OS in patients with ESCC, reveals a compelling connection of IDO1, PD-1, and TAMs, and explores the sensitivity of patients with high IDO1 expression to chemotherapeutic drugs and their resistance to IC blockade. These findings open new avenues for potential targets in ESCC immunotherapy.

High microvessel and lymphatic vessel density predict poor prognosis in patients with esophageal squamous cell carcinoma.

Background: Microangiogenesis and lymphangiogenesis are essential for tumor growth in the tumor microenvironment, contributing to tumor invasion and metastasis. Limited literature exists on these processes in esophageal squamous cell carcinoma (ESCC). Therefore, the purpose of this study is to explore the impacts of microangiogenesis and lymphangiogenesis on the occurrence, progression, and prognosis assessment of ESCC. Methods: Surgical specimens and paraffin-embedded human tissues were procured from ESCC patients, encompassing 100 ESCC tissues and 100 cancer-adjacent normal (CAN) tissues. CD34 and D2-40 were utilized as markers for microvessel endothelial cells and lymphatic vessel endothelial cells, respectively. Microvascular density (MVD) and lymphatic vessel density (LVD) were evaluated through immunohistochemical quantification. Results: We found that tumor tissues in ESCC patients had significantly higher MVD and LVD than cancer-adjacent normal (CAN) tissues. High MVD and LVD were associated with lymph node metastasis and advanced tumor clinical stages. Additionally, both high MVD and high LVD were strongly linked to poorer prognosis among cancer patients. Furthermore, a positive correlation was found between high MVD and high LVD (p < 0.05). The presence of these markers individually indicated a worse prognosis, with their combined assessment showcasing enhanced prognostic value. Conclusions: Overall, the increased MVD and LVD indicates higher invasion and metastasis of ESCC, closely correlating with unfavorablefor poor prognosis of ESCC patients.

A bioengineered tumor matrix-based scaffold for the evaluation of melatonin efficacy on head and neck squamous cancer stem cells.

Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that closely resemble tumor heterogeneity could help to better understand the effects of this molecule. This study developed a tumor scaffold based on patient fibroblast-derived decellularized extracellular matrix that mimics the HNSCC microenvironment. Our study investigates the antitumoral effects of melatonin within this context. We validated its strong antiproliferative effect on HNSCC CSCs and the reduction of tumor invasion and migration markers, even in a strongly chemoprotective environment, as it is required to increase the minimum doses necessary to impact tumor viability compared to the non-scaffolded tumorspheres culture. Moreover, melatonin exhibited no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel. This scaffold-based platform allows an in vitro study closer to HNSCC tumor reality, including CSCs, stromal component, and a biomimetic matrix, providing a new valuable research tool in precision oncology.

Surgery, chemoradiotherapy, or chemoradiation plus immunotherapy: Treatment strategies for nonmetastatic anal squamous cell carcinoma.

The current standard of care for anal squamous cell carcinoma (ASCC) is definitive concurrent chemoradiotherapy (CRT). However, about a third of patients may experience treatment failure. Recently, immunotherapy has emerged as a novel strategy for metastatic ASCC patients. We evaluated the efficacy and safety of surgery, CRT alone, and CRT with immunotherapy (CRT-I) in 100 nonmetastatic ASCC patients, treated from April 2012 through May 2023, by determining survival outcomes and acute adverse events. The median (range) follow-up was 30.7 (7.6 to 134.9) months. The study cohort 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were 80.7 %, 62.2 %, 71.1 %, and 67.6 %, respectively. The Surgery group had significantly lower rates than the CRT and CRT-I groups for 3-year PFS (33.1% vs. 65.2% vs. 92.9 %, P < 0.001), DMFS (46.7% vs. 74.6% vs. 92.9 %, P = 0.002) and LRFS (37.0% vs. 73.3% vs. 92.9 %, P < 0.001), respectively. All patients receiving CRT-I were alive at last follow-up. Of 100 patients, 26 (26.0 %) experienced severe (≥ grade 3) acute toxicity. Of 24 patients receiving CRT-I, 8 (33.3 %) had severe acute toxicity. Using immunohistochemistry, peritumoural stromal infiltration by CD8+ T cells was significantly higher after CRT-I compared to before CRT-I and to after CRT alone. The addition of immunotherapy to CRT may be an effective first-line treatment option with favourable survival outcomes and acceptable toxicity for patients with ASCC. A prospective, randomized trial assessing the efficacy of CRT combined with a PD-1 inhibitor in patients with locally advanced ASCC is in progress.

Research advances in signaling pathways related to the malignant progression of HSIL to invasive cervical cancer: A review.

The progression of high-grade squamous intraepithelial lesion (HSIL) to invasive cervical cancer (ICC) is a complex process involving persistent human papillomavirus (HPV) infection and changes in signal transduction regulation, energy and material metabolism, cell proliferation, autoimmune, and other biological process in vaginal microenvironment and immune microenviroment. Signaling pathways are a series of interacting molecules in cells that regulate various physiological functions of cells, such as growth, differentiation, metabolism, and death. In the progression of HSIL to ICC, abnormal activation or inhibition in signaling pathways plays an essensial role. This review presented some signaling pathways related to the malignant progression of HSIL to ICC, including p53, Rb, PI3K/AKT/mTOR, Wnt/ß-catenin, Notch, NF-κB, MAPK, TGF-ß, JAK-STAT, Hippo, and Hedgehog. The molecular mechanisms involved in the biological process of pathway regulation were also analyzed, in order to illustrate the molecular pathway of HSIL progression to ICC and provide references for the development of more effective prevention and treatment methods.

S100A9 induces tissue remodeling of human nasal epithelium in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Chronic inflammation triggers tissue remodeling in human nasal epithelial (HNE) cells. S100A9, a protein secreted by inflammatory cells, exhibits potent proinflammatory activity. However, its effect on HNE cell remodeling, such as squamous metaplasia, remains unclear. Therefore, this study aimed to determine the effects and underlying pathways of S100A9 on HNE cell remodeling and investigate its clinical implications in chronic rhinosinusitis (CRS). METHODS: Cultured HNE cells were treated with S100A9. Bulk RNA sequencing was performed to analyze gene ontology (GO). Ingenuity pathway analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also analyzed. Additionally, immunohistochemistry and multiplex immunofluorescence were performed on tissue samples obtained from 60 patients, whose clinical informations were also reviewed. RESULTS: GO enrichment analysis indicated that S100A9 induced tissue remodeling in HNE cells toward squamous metaplasia. IPA and KEGG commonly showed that S100A9 affected HNE cells associated with the IL-17 signaling pathway, including target molecules such as matrix metalloproteinase 1 (MMP1) and small proline-rich protein 2A (SPRR2A). Squamous metaplasia with a marked expression of S100A9 was observed in 50% of CRS with nasal polyps (CRSwNPs). In addition, in multiplex immunofluorescence, the S100A9 in sub-epithelium was co-expressed with myeloperoxidase, a neutrophil marker, and MMP1 and SPRR2A were strongly expressed in epithelial remodeling. Clinically, the expression of S100A9 correlated with sino-nasal outcome test-22 (r = 0.294, p = 0.022) and Lund-Mackay scores (r = 0.348, p = 0.006). CONCLUSION: S100A9 induces tissue remodeling in HNE cells. Its increased expression in CRSwNP, particularly squamous epithelium, correlates with disease severity. This suggests the clinical potential of S100A9 as a biomarker for CRS severity.

Inhibition of Benzo[a]pyrene-induced DNA Adduct in Buccal Cells of Smokers by Black Raspberry Lozenges.

Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage-induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in non-smokers; these results suggest the potential contribution of B[a]P in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC at late stages even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings we tested the hypothesis, in a Phase 0 clinical study, that BRB administration reduces DNA damage induced by B[a]P in buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected at four weeks after BRB cessation (washout period). B[a]P-induced DNA damage (BPDE-N2-dG) was evaluated by LC-MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (p = 0.01506) compared to baseline, 36.1% at the end of BRB administration (p = 0.00355), and 16.6% after BRB cessation (p = 0.007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC.