Common Head Research Articles

A Discourse of Deviance: Blame, Shame, Stigma and the Social Construction of Head and Neck Cancer.

Cancer of the head and neck is a confronting condition, as the disease and its treatments alter the appearance and function of body organs associated with physical appearance and identity. Many of the risk factors for head and neck cancers, including tobacco, alcohol, and human papilloma virus, can also have significant negative social and moral permutations. Language and action (discourse) plays an important role in constructing disease and illness and shape the way it is managed, both institutionally and socially. This research used a critical constructionist lens to investigate how the common discourses surrounding head and neck cancer are constructed within the healthcare context and how this influences patients and healthcare professionals' responses to the illness. Data were collected through semi-structured interviews, field noting, journaling and literature reviews. Analysis was guided by a three-dimensional approach to critical discourse analysis that investigated text, discursive practices, and social context. The overarching finding was that deviance dominates the common discourse and shapes head and neck cancer and responses to it. Deviance is channelled through metaphors, adjectives, descriptors, and collective nouns and is made overt through labelling, avoidance, blaming, shame, and categorization. Discourse is contextualized by a sociocultural understanding that when someone deviates from what is perceived as normal, they are devalued. Open dialogue and reflection on head and neck cancer discourse could enable better understanding of how people experience their condition and inform more supportive responses.

Photodynamic Therapy with an Association of Methylene Blue and Toluidine Blue Promoted a Synergic Effect against Oral Squamous Cell Carcinoma

Among the most malignant cancers, oral squamous cell carcinoma (OSCC) stands out as the most common malignant head and neck tumor. Despite advances in the field of treatment, the prognosis of patients with OSCC remains poor. Aiming to overcome the limitations of the currently existing therapies against OSCC, the present work aims to investigate the potential of photodynamic therapy (PDT) with phenothiazine derivatives used alone or in combination. The incorporation of methylene blue (MB) and toluidine blue (TB) was evaluated in OSCC cell lines (HSC-3 and SCC-9) and a nontumor cell line (Hfib). Both compounds exhibited concentration and time-dependent incorporation, with higher rates observed in tumor cells. Regarding dark-phase cytotoxic activity, SCC-9 cells were the most sensitive cell line with an IC50 value of 362.6 µM and 41.4 µM for MB and TB, respectively. Using PDT, all lineages showed greater sensitivity, presenting lower IC50 values when compared to the dark phase values. The combination index values of 0.69 (dark phase) and 0.73 (clear phase) associated with concave isobolograms, in both phases, revealed that MB and TB have synergistic effects when combined against SCC-9 cells. These findings suggest that MB or TB assisted with PDT holds promise for OSCC treatment.

Aquatic invertebrate mandibles and sclerotized remains in Quaternary lake sediments

Subfossil remains of aquatic invertebrates found in lacustrine sediments are useful paleoenvironmental indicators. Strongly scleroticized chitinous body parts from the exoskeleton or exuviae from invertebrates are often the most resistant to degradation during syn- and post-depositional processes. Invertebrate mandibles and body parts that superficially resemble mandibles, such as claw-like appendages and pygopodia, are frequently found in sieved Quaternary lacustrine, palustrine, and deltaic sediments. Guides, catalogs and atlases have been published that are well suited for the identification of subfossil remains for several invertebrate groups, such as chironomids, cladocerans, and ostracods, among others. However, aquatic invertebrate remains of several ecologically important invertebrate groups continue to be underused in paleoenvironmental studies, in part, because there are few visual keys or other documentation sources (e.g. descriptions, catalogs or atlases) that increase awareness and facilitate identification. Here we present sets of digital photomicrographs of pre-identified aquatic invertebrate specimens collected from streams, lakes and ponds that have been chemically cleared to preserve structures that are observed in subfossil remains in sieved sediment samples, commonly the > 100 μm size fractions. In addition, we present examples of these structures from Quaternary lake-sediment samples and cite the dispersed literature that demonstrate that these remains are preserved and remain identifiable in the fossil record. We document mandibles from several taxonomic groups that include Crustacea: Amphipoda, Isopoda, Ostracoda, and Notostraca; and Insecta orders: Coleoptera, Diptera, Ephemeroptera, Hemiptera, Odonata, Lepidoptera, Megaloptera, Plecoptera, and Trichoptera. The compilation of microphotographs also includes pygopodia and claw appendages of Plecoptera and Trichoptera, with additional images of other common invertebrate mouthpart and head remains. We describe several types of fossilizing structures that are, to our knowledge, not previously described in the paleoecological literature (e.g. mandibles of amphipods or plecopterans) but also show that some structures are considerably more variable than expected based on available descriptions, such as the mandibles of Ephemeroptera or Trichoptera, and that these can potentially be separated into different morphotypes useful for identification of subfossil material. We also discuss the potential of analyzing and interpreting the additional remains together with the remains of more commonly analyzed invertebrate groups (e.g. Chironomidae) to contribute to paleoenvironmental interpretations, which will allow assessments of functional groups (e.g. predators, shredders, grazers) or habitat types (e.g. littoral, profundal or lotic environments) that aquatic invertebrate remains originate from.

FDG PET/CT reveals bone marrow oligometastasis in laryngeal squamous carcinoma: a case report with favorable outcome

Laryngeal carcinoma is the most common head and neck cancer. The vast majority of laryngeal carcinomas are of squamous-cell histologic type. Metastasis of laryngeal cancer typically occurs within the cervical lymph nodes and seldom in other regions. Although a small percentage of patients experience distant metastases, bone marrow metastasis from laryngeal cancer is among the least common metastatic sites. Previous literature has suggested that bone marrow carcinomatosis is aggressive and has a poor outcome, particularly in patients with supraglottic tumors. Ante-mortem diagnosis of this metastatic pattern has been limited. To our knowledge, this case report highlights the first documented occurrence wherein the utilization of 18-fluorine fludeoxyglucose positron emission tomography/CT imaging played a pivotal role in the early detection of bone marrow metastasis in a patient diagnosed with transglottic laryngeal cancer. A solitary metastatic distant bone marrow lesion was identified early during follow-up. As a consequence, the patient exhibited a remarkable and unforeseen favorable clinical outcome.

NFE2L1 restrains ferroptosis by transcriptionally regulating HJURP and participates in the progress of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy with increasing mortality and high recurrence. In this work, we aim to explore the functional role of NFE2 like bZIP transcription factor 1 (NFE2L1) in OSCC progression. Based on databases analysis, we found that NFE2L1 was overexpressed in OSCC tumor tissues, and elevated NFE2L1 level induced poor prognosis of OSCC patients. Our results showed that NFE2L1 is upregulated in OSCC cells and overexpression of NFE2L1 promotes cell proliferation, and reduces the sensitivity of OSCC cells to erastin-induced ferroptosis. NFE2L1 upregulation decreased the levels of Fe2+, lipid reactive oxygen species and content of malondialdehyde, and increased the level of the key negative regulator of ferroptosis, GPX4 and SLC7A11. In NFE2L1 suppressed cells, these trends were reversed. Further results of dual luciferase reporter and chromatin immunoprecipitation assays confirmed that NFE2L1 could bind to the promoter of Holliday junction recognition protein (HJURP) to increase the transcriptional activity of HJURP, thus upregulating its expression. Inhibition of HJURP attenuated the proliferation and ferroptosis inhibition in NFE2L1 upregulated cells. In vivo tumorigenicity assay further proved that NFE2L1 promotes OSCC tumor growth. In summary, NFE2L1 restrains ferroptosis by transcriptionally regulating HJURP and participates in the progress of OSCC. Thus, NFE2L1 plays a key role in OSCC development and may be a promising therapeutic target for OSCC.

PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study.

laryngeal and hypopharyngeal squamous cell carcinoma (SCC) is a common head and neck cancer with significant impact on quality of life due to its crucial roles in vocalization, airway protection, and swallowing. This retrospective study aims to evaluate the efficacy and larynx organ preservation of neoadjuvant treatment with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin for locally advanced laryngeal and hypopharyngeal SCC. Medical records of consecutive patients diagnosed with histologically or cytologically confirmed locally advanced SCC of the larynx and hypopharynx, who received PD-1 inhibitor therapy at a single tertiary care center, were reviewed from January 1, 2019, to December 15, 2022. The patients were treated with a combination of PD-1 inhibitors, paclitaxel (Albumin-bound) 260mg/m2, and cisplatin 60mg/m2 (TP) as their first-line therapy. Survival outcomes, laryngectomy-free survival (LFS) rates and response rates were assessed. The study cohort comprised 156 patients, predominantly male, with a median age of 60.4 years. The estimated one-year overall survival (OS) rate was 94.1%, two-year OS rate was 82.5%, one-year progression-free survival (PFS) rate was 80.4%, and two-year PFS rate was 66.3%. The one-year LFS was 86.4%, and the two-year LFS rate was 73.0%. The overall response rate after TP + PD-1 inhibitors therapy was 88.5%. Common treatment-associated adverse events included rash, thyroid function abnormalities, myelosuppression, and colitis. Neoadjuvant therapy with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin showed promising efficacy and tolerability for larynx preservation in locally advanced laryngeal and hypopharyngeal SCC. The high response rates and favorable survival outcomes suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings and establish the role of immunotherapy in larynx preservation.

Answering head and neck cancer questions: An assessment of ChatGPT responses

PurposeTo examine and compare ChatGPT versus Google websites in answering common head and neck cancer questions. Materials and methodsCommonly asked questions about head and neck cancer were obtained and inputted into both ChatGPT-4 and Google search engine. For each question, the ChatGPT response and first website search result were compiled and examined. Content quality was assessed by independent reviewers using standardized grading criteria and the modified Ensuring Quality Information for Patients (EQIP) tool. Readability was determined using the Flesch reading ease scale. ResultsIn total, 49 questions related to head and neck cancer were included. Google sources were on average significantly higher quality than ChatGPT responses (4.2 vs 3.6, p = 0.005). According to the EQIP tool, Google and ChatGPT had on average similar response rates per criterion (24.4 vs 20.5, p = 0.09) while Google had a significantly higher average score per question than ChatGPT (13.8 vs 11.7, p < 0.001) According to the Flesch reading ease scale, ChatGPT and Google sources were both considered similarly difficult to read (33.1 vs 37.0, p = 0.180) and at a college level (14.3 vs 14.2, p = 0.820.) ConclusionChatGPT responses were as challenging to read as Google sources, but poorer quality due to decreased reliability and accuracy in answering questions. Though promising, ChatGPT in its current form should not be considered dependable. Google sources are a preferred resource for patient educational materials.

Prospective Evaluation of Locoregional Control in Oral Cavity Squamous Cell Carcinoma with Infratemporal Fossa Involvement Treated with Surgery and Adjuvant Concurrent Chemoradiotherapy

Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck cancer in India. Definitive surgery with or without post-op radiotherapy (PORT) with or without chemotherapy (CT) provides better outcomes in locally advanced OCSCC as compared to definitive chemoradiotherapy. T4b OCSCC with infra temporal fossa (ITF) involvement has varied outcome depending on the extent of ITF involvement, with low and mid ITF having relatively favorable prognosis. We aimed to prospectively evaluate outcomes in patients of OCSCC with low or mid ITF involvement treated with curative surgery followed by adjuvant concurrent chemoradiotherapy (CCRT). A total of 20 patients of T4b OCSCC (as per AJCC 8th edition) with low or mid ITF involvement were included in this single arm prospective interventional study from January 2021 to October 2022. Patients with involvement of skull base, carotid artery, prevertebral fascia and/or pterygomaxillary fissure were excluded. All patients were treated with definitive surgery with ITF clearance followed by adjuvant CCRT as indicated. Loco-regional control (LRC), Disease free survival (DFS), Overall survival (OS) were assessed using Kaplan-Meier survival analysis. Acute toxicities were assessed according to the CTCAE v5.0. Patient characteristics are summarized in table 1. Median follow-up was 11.5 months (4-21months). All patients received adjuvant CCRT with weekly cisplatin 40mg/m2 to a median number of 6 cycles (5-7 cycles). Median RT dose was 64Gy (60-64Gy). All patients tolerated treatment well. Grade 3 oral mucositis, odynophagia were seen in 8 (40%) patients each and skin toxicity, oral pain in 6 (30%) and 5 (25%) patients respectively. No grade 4 toxicities were observed LRC at three month was 73.68% with 4 local and 1 locoregional failure only. LRC at one year was 36.8% with 8 local, 1 locoregional, 2 locodistant and 1 distant failure only. Median DFS was 10.4 months. Median OS was not reached; four patients died. LRC at three months was better for patients with low ITF disease as compared to mid ITF disease (85.7% vs. 40% (p = 0.04) and at one year was 42.8% vs. 40% (p = 0.50). Selected patient of locally advanced OCSCC with low ITF involvement may benefit from trimodality therapy of surgery with ITF clearance followed by adjuvant CCRT. Acute toxicity profile was acceptable in our study.

Nasopharyngeal Cancer Incidence and Mortality in 185 Countries in 2020 and the Projected Burden in 2040: Population-Based Global Epidemiological Profiling.

Nasopharyngeal cancer (NPC) is one of the most common head and neck cancers. This study describes the global epidemiological profiles of NPC incidence and mortality in 185 countries in 2020 and the projected burden in 2040. The estimated numbers of NPC cases and deaths were retrieved from the GLOBOCAN 2020 data set. Age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were calculated using the world standard. The future number of NPC cases and deaths by 2040 were estimated based on global demographic projections. Globally, approximately 133,354 cases and 80,008 deaths from NPC were estimated in 2020 corresponding to ASIRs and ASMRs of 1.5 and 0.9 per 100,000 person-years, respectively. The largest numbers of both global cases and deaths from NPC occurred in Eastern Asia (65,866/133,354, 49.39% and 36,453/80,008, 45.56%, respectively), in which China contributed most to this burden (62,444/133,354, 46.82% and 34,810/80,008, 43.50%, respectively). The ASIRs and ASMRs in men were approximately 3-fold higher than those in women. Incidence rates varied across world regions, with the highest ASIRs for both men and women detected in South-Eastern Asia (7.7 and 2.5 per 100,000 person-years, respectively) and Eastern Asia (3.9 and 1.5 per 100,000 person-years, respectively). The highest ASMRs for both men and women were found in South-Eastern Asia (5.4 and 1.5 per 100,000 person-years, respectively). By 2040, the annual number of cases and deaths will increase to 179,476 (46,122/133,354, a 34.58% increase from the year 2020) and 113,851 (33,843/80,008, a 42.29% increase), respectively. Disparities in NPC incidence and mortality persist worldwide. Our study highlights the urgent need to develop and accelerate NPC control initiatives to tackle the NPC burden in certain regions and countries (eg, South-Eastern Asia, China).

Cycling-related cranio-spinal injuries admitted to a Major Trauma Centre in the cycling capital of the UK

Background The increased popularity of cycling is leading to an anticipated increase in cycling-related traffic accidents and a need to better understand the demographics and epidemiology of craniospinal injuries in this vulnerable road user group. This study aims to systematically investigate and characterise cycling-related head and spine injuries seen in the Major Trauma Centre for the Eastern region, which has the highest cycling rates in the UK. Methods We performed a retrospective cohort study comparing the incidence, patterns, and severity of head and spine injuries in pedal cyclists presenting to the Major Trauma Centre in Cambridge between January 2012 and December 2020. Comparisons of injury patterns, characteristics, and associations were made according to mechanism of injury, helmet use, patient age and gender. Results A total of 851 patients were admitted after being involved in cycling-related collisions over the study period, with 454 (53%) sustaining head or spine injuries. The majority of victims (80%) were male and in mid-adulthood (median age 46 years). Head injuries were more common than spine injuries, with the most common head injuries being intracranial bleeds (29%), followed by skull fractures (12%), and cerebral contusions (10%). The most common spine injuries were cervical segment fractures, particularly C6 (9%), C7 (9%), and C2 (8%). Motorised collisions had a higher prevalence of spine fractures at each segment (p < 0.001) and were associated with a higher proportion of multi-vertebral fractures (p < 0.001). These collisions were also associated with impaired consciousness at the scene and more severe systemic injuries, including a lower Glasgow coma scale (R = −0.23, p < 0.001), higher injury severity score (R = 0.24, p < 0.001), and longer length of stay (R = 0.21, p < 0.001). Helmet use data showed that lack of head protection was associated with more severe injuries and poorer outcomes. Conclusion As cycling rates continue to increase, healthcare providers may expect to see an increase in bicycle-related injuries in their practice. The insights gained from this study can inform the treatment of these injuries while highlighting the need for future initiatives aimed at increasing road safety and accident prevention.

Prediction of skull fractures in blunt force head traumas using finite element head models.

Traumatic head injuries remain a leading cause of death and disability worldwide. Although skull fractures are one of the most common head injuries, the fundamental mechanics of cranial bone and its impact tolerance are still uncertain. In the present study, a strain-rate-dependent material model for cranial bone has been proposed and implemented in subject-specific Finite Element (FE) head models in order to predict skull fractures in five real-world fall accidents. The subject-specific head models were developed following an established image-registration-based personalization pipeline. Head impact boundary conditions were derived from accident reconstructions using personalized human body models. The simulated fracture lines were compared to those visible in post-mortem CT scans of each subject. In result, the FE models did predict the actual occurrence and extent of skull fractures in all cases. In at least four out of five cases, predicted fracture patterns were comparable to ones from CT scans and autopsy reports. The tensile material model, which was tuned to represent rate-dependent tensile data of cortical skull bone from literature, was able to capture observed linear fractures in blunt indentation loading of a skullcap specimen. The FE model showed to be sensitive to modeling parameters, in particular to the constitutive parameters of the cortical tables. Nevertheless, this study provides a currently lacking strain-rate dependent material model of cranial bone that has the capacity to accurately predict linear fracture patterns. For the first time, a procedure to reconstruct occurrences of skull fractures using computational engineering techniques, capturing the all-in-all fracture initiation, propagation and final pattern, is presented.

Profile of Nasopharyngeal Carcinoma in Dr. Wahidin Sudirohusodo Hospital Makassar 2011 – 2021

Background: Nasopharyngeal carcinoma (NPC) is Indonesia’s most common head and neck malignancy. NPC presents non-specific signs and symptoms, which lead to a late or missed diagnosis. Early detection and prevention are essential based on the NPC profile. Objective: This study aimed to assess NPC’s sociodemographic and clinical characteristics in Dr. Wahidin Sudirohusodo Hospital Makassar 2011 – 2021.

Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Cancer-associated fibroblasts (CAFs) are the main stromal cells in the tumor microenvironment (TME). As CAFs promote tumor progression and hypoxia in the TME, regulating the conversion of normal fibroblasts (NFs) into CAFs is essential for improving the prognosis of patients with OSCC. We have previously reported the antitumor effects of transcutaneous carbon dioxide (CO2) application in OSCC. However, the effects of reducing hypoxia in the TME remain unclear. In this study, we investigated whether CO2 administration improves the TME by evaluating CAFs marker expression. Human OSCC cells (HSC-3) and normal human dermal fibroblasts (NHDF) were coinjected subcutaneously into the dorsal region of mice. CO2 gas was applied twice a week for 3 weeks. The tumors were harvested six times after transcutaneous CO2 application. The expression of CAFs markers (α-SMA, FAP, PDPN, and TGF-β) were evaluated by using real-time polymerase chain reaction and immunohistochemical staining. The expression of α-SMA, FAP, PDPN, and TGF-β was significantly increased over time after co-injection. In the CO2-treated group, tumor growth was significantly suppressed after treatment initiation. In addition, the mRNA expression of these markers was significantly inhibited. Furthermore, immunohistochemical staining revealed a significant decrease in the protein expression of all CAFs markers in the CO2-treated group. We confirmed that transcutaneous CO2 application suppressed CAFs marker expression and tumor growth in OSCC xenograft mouse model.

MicroRNA Profiling in Circulating Exosomes in Oral Squamous Cell Carcinoma: A Systematic Review.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with several risk factors. Exosomes are extracellular vesicles generated by the fusion of multivesicular structures with the cell membrane and play an important role as intercellular messengers. MicroRNA (miRNA) is a noncoding RNA and regulates post-transcriptional modification. The present systematic review aims to identify and correlate the possible association and role of circulating exosomes with OSCC. Using the search strategy, articles fulfilling the inclusion criteria, published between January 2012 to March 2022, were retrieved from online databases including PubMed, Scopus, Web of Science, and Cochrane Library. About 904 articles were found using an electronic database and a human search. After reviewing the titles and abstracts, 614 studies were eliminated, and duplicate articles were removed. Five studies were included in this systematic review. Circulating exosomal expression of miRNA27, miRNA 21, and miRNA 155 showed significant upregulation in OSCC patients. Circulating exosomes could be potential biomarkers to be used in the detection of patients with OSCC. More studies are warranted in this area to gain a better understanding of the pathophysiology of OSCC and the function of molecular markers from circulating exosomes. Understanding the role of molecular markers from circulating exosomes in pathogenesis will provide a better understanding of the development of the disease, necessitating more study in this area. According to this review, circulating exosomes might be a potential approach to the identification of OSCC.

NUP62CL as an Immunological and Prognostic Biomarker of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a high mortality rate and poor prognosis. The exploration and understanding of biomarkers will help to further improve the diagnosis and treatment of OSCC. Tumor tissue samples from 319 OSCC patients were retrospectively collected, along with their clinical information. In combination with bioinformatics tools and multiplex immunohistochemistry (mIHC) analyses, we evaluated NUP62CL protein expression and its relationship to tumor-infiltrating immune cells (TIICs) and immune checkpoints in the tumor microenvironment (TME), as well as its association with clinical features and prognosis of OSCC. We identified high-NUP62CL expression in OSCC tissues, and high-NUP62CL protein expression was associated with large tumor size, advanced clinical stage and poor prognosis. In addition, NUP62CL protein expression was positively associated with the abundance of CD3+CD4+ T cells (P<0.01), CD3+CD8+ T cells (P<0.01), CD56+ NK cells (P<0.05), CD68+CD86+ macrophages (P<0.01) and CD68+CD163+ macrophages (P<0.01), as well as the immune checkpoints, including PD-1 (P<0.001), PD-L1 (P<0.001), and CTLA-4 (P<0.001) protein expression. In conclusion, NUP62CL could be an effective prognostic and immunological biomarker for OSCC patients.

ZC3H13 reduced DUOX1-mediated ferroptosis in laryngeal squamous cell carcinoma cells through m6A-dependent modification

Laryngeal squamous cell carcinoma (LSCC) is the second most common head and neck cancer. To identify the link between ferroptosis and LSCC, we targeted the dual oxidase 1 (DUOX1) gene. This study aimed to reveal the intrinsic mechanism by which the DUOX1-zinc-finger CCCH domain-containing protein 13 (ZC3H13) ferroptosis axis affected the LSCC process. GEPIA was used to investigate the expression of DUOX1 in LSCC, and the expression levels of DUOX1 and ZC3H13 were manipulated by overexpression and RNA interference. MTT assay was used to detect cell proliferation. Chromatin immunoprecipitation (CHIP) detected the binding of DUOX1 and ZC3H13, and ROS assessment and intracellular Fe2+ content determination were performed to examine the ferroptosis. MeRIP was used to analyze the m6A methylation of DUOX1. Ferroptosis-related proteins were detected by qRT-PCR. DUOX1 was found to be poorly expressed in LSCC cells, low DUOX1 level promoted LSCC cell proliferation, and low ZC3H13 level decreased LSCC cell proliferation. Besides, there was an interaction between DUOX1 and ZC3H13. DUOX1 could inhibit the expression levels of ferroptosis-related genes GPX4 and F1H1 in LSCC cells DUOX1 inhibited the expression levels of ROS and ferroptosis-related genes GPX4 and F1H1 and increased intracellular iron content in LSCC cells, but ZC3H13 reversed this phenomenon by inhibiting DUOX1 gene through m6A methylation modification. ZC3H13 reduced DUOX1-mediated ferroptosis in LSCC cells through m6A-dependent modification. The regulatory pathway of DUOX1 and ferroptosis are potential targets for designing diagnostic and combination therapeutic strategies for LSCC patients.

NLG-919 combined with cisplatin to enhance inhibitory effect on cell migration and invasion via IDO1-Kyn-AhR pathway in human nasopharyngeal carcinoma cell.

As a common aggressive head and neck cancer, nasopharyngeal carcinoma (NPC) received cisplatin treatment as a first-line chemotherapy. Platinum-induced resistance is a major limitation of current treatment strategy in the advanced NPC. Increased indoleamine 2,3-dioxygenase (IDO1) activities are found in cisplatin-resistant NPC cells versus cisplatin-sensitive NPC cells. As an IDO1 immunosuppressant, NLG-919 has entered clinical phase I to treat advanced solid tumors. To reverse cisplatin resistance, we investigated the combinatory application of cisplatin and NLG-919 in NPC treatment. In vitro biological studies on cisplatin-resistant and cisplatin-sensitive NPC cells were taken to imply that the combination of NLG-919 and cisplatin got a stronger impact on the induction of cell apoptosis and the inhibition of cell migration, exploring superior effect of antitumor over single drug. We proved that the mechanism of the combined therapy could inhibit the activity of IDO1, blocking amino acid tryptophan conversion to kynurenine through the kynurenine pathway, which further inhibited the aryl hydrocarbon receptor expression. Our study underscored the combination of cisplatin and NLG-919 as a potent therapeutic way for the reversal of cisplatin resistance.

Single-cell RNA sequencing reveals tumor immune microenvironment in human hypopharygeal squamous cell carcinoma and lymphatic metastasis.

Human hypopharygeal squamous cell carcinoma (HSCC) is a common head and neck cancer with a poor prognosis in advanced stages. The occurrence and development of tumor is the result of mutual influence and co-evolution between tumor cells and tumor microenvironment (TME). Tumor immune microenvironment (TIME) refers to the immune microenvironment surrounding tumor cells. Studying TIME in HSCC could provide new targets and therapeutic strategies for HSCC. We performed single-cell RNA sequencing (scRNA-seq) and analysis of hypopharyngeal carcinoma, paracancerous, and lymphoid tissues from five HSCC patients. Subdivide of B cells, T cells, macrophages cells, and monocytes and their distribution in three kinds of tissues as well as marker genes were analyzed. Different genes of IGHG1 plasma cells and SPP1+ macrophages between HSCC tissues, adjacent normal tissues and lymphatic tissues were analyzed. Additionally, we studied proliferating lymphocytes, T cells exhaustion, and T cell receptor (TCR) repertoire in three kinds of tissues. Transcriptome profiles of 132,869 single cells were obtained and grouped into seven cell clusters, including epithelial cells, lymphocytes, mononuclear phagocytics system (MPs), fibroblasts, endothelial cells (ECs), plasmacytoid dendritic cells (pDCs), and mast cells. Tumor metastasis occurred in three lymphoid tissues. Four distinct populations were identified from lymphocytes, including B cells, plasma cells, T cells and proliferating lymphocytes. We found IGHA1 and IGHG1 specific plasma cells significantly overexpressed in HSCC tissues compared with normal hypopharygeal tissues and lymphatic tissues. Five distinct populations from MPs were identified, including macrophages, monocytes, mature dendritic cells (DCs), Type 1 conventional dendritic cells (cDC1) and Type 2 conventional dendritic cells (cDC2). SPP1+ macrophages were significantly overexpressed in HSCC tissues and lymphatic tissues compared with normal hypopharygeal tissues, which are thought to be M2-type macrophages. Exhaustion of CD8+ Teff cells occurred in HSCC tissues. At last, we verified that IgA and IgG1 protein expression levels were significantly up-regulated in HSCC tissues compared to adjacent normal tissues. Overall, this study revealed TIME in HSCC and lymphatic metastasis, and provided potential therapeutic targets for HSCC.

Neck weakness in individuals with motor neurone disease: an insight into head support

Background/Aims Neck weakness and head drop can occur in individuals with motor neurone disease, further contributing to disability and lower quality of life. The aims of this study were to explore the characteristics of neck weakness in motor neurone disease and the different types of head support used by patients. Methods A cross-sectional study was performed, where 33 participants with motor neurone disease-related neck weakness answered a 17-item questionnaire. The questions covered their neck weakness and the types of head support they used at the time. Results All participants reported that their quality of life was negatively impacted by their neck weakness. Of the participants, 51.5% reported forward head drop and 42.4% reported that their head dropped both forward and to the side. The most common head support strategy was tilting their chair backwards, followed by the soft neck collar and a rigid collar (Aspen Vista). The majority used either two or three head support strategies in a given day. A total of 26 participants used neck collars, with 11 requiring modifications to their neck collars and 13 reporting not being able to use their neck collar for as long as they wished. Conclusions This study identified the negative impact that neck weakness has on the quality of life for people living with motor neurone disease, and how varied people’s experiences are of living with and attempting to manage this symptom. This is a complex symptom for allied health professionals to manage and an individualised approach is required.

Association Between VEGF-2578 Gene Polymorphism with Clinicopathological Appearance of Year 2021 Patients with Nasopharyngeal Cancer in RSUP Prof. Dr. I.G.N.G Ngoerah Denpasar Bali

Cancer has a close association with aging. Nasopharyngeal cancer (NPC) is the most common head and neck cancer found in Indonesia. One of the factors that plays a role in the development of NPC is VEGF. VEGF is coded in VEGF gene which is very polymorphic. One of the polymorphisms in VEGF gene that influences the expression of the gene itself is VEGF-2578C/A gene polymorphism which has never been studied before in Indonesia. This research aims to study the association between VEGF-2578 gene polymorphism (clinical stadium, T stadium (tumor size), N stadium (local metastasis), M stadium (distant metastasis), and histopathological typing) of year 2021 patients with nasopharyngeal cancer in RSUP Prof. dr. I.G.N.G Ngoerah Denpasar Bali. This research uses the cross-sectional method and was done in the Biomedical Laboratory in Udayana University Faculty of Medicine from June to December 2022. 43 samples were used in the form of DNA from stored biological specimens of nasopharyngeal cancer patients that were treated in ENT-Oncology polyclinic in RSUP Prof. dr. I.G.N.G Ngoerah in 2021. Secondary data was available from the Biomedical Laboratory in Udayana University Faculty of Medicine. To detect polymorphism from the DNA samples, gene amplification was done using PCR, confirmed using electrophoresis, and sent for sequencing in Genetika Science Jakarta. From 43 samples, it was found that there were 36 (83,7%) CC genotip and 7 (16,3%) AA genotip. A significant association was found between VEGF-2578C/A gene polymorphism with T stadium (tumor size) with p value = 0,028. Late stage of T stadium (T3-T4) was found significantly more on subjects with CC genotip (75%) compared to AA genotip (28,6%). The effect of confounding variables which are age and gender have been minimalized. It was also found that there was no significant association between VEGF-2578C/A gene polymorphism with clinical stadium, N stadium, M stadium, or histopathological typing on the research subjects. In conclusion, this research found that there was a significant association between VEGF-2578C/A gene polymorphism with T stadium, but not with clinical stadium, N stadium, M stadium, or histopathological typing of year 2021 patients with nasopharyngeal cancer in RSUP Prof. dr. I.G.N.G Ngoerah Denpasar Bali. Keywords: Nasopharyngeal cancer, Polymorphism, Tumor size, VEGF-2578C/A, Clinicopathological appearance