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.

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma

Abstract Background Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. Objective This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. Methods The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. Results The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. Study limitations No animal experiments were conducted to further verify the results. Conclusion Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

METTL3-mediated HPV vaccine enhances the effect of anti PD-1 immunotherapy to alleviate the development of cutaneous squamous cell carcinoma

Abstract Background Cutaneous squamous cell carcinoma (cSCC) develops from epithelial keratinocytes by dysregulation of self-renewal and differentiation. Recent studies have found that the size and number of cSCC tumors gradually decrease or even disappear after HPV vaccination. However, the role of the HPV vaccine in the cSCC mechanism is poorly understood. Objective The aim of this study is to investigate the effect and mechanism of the HPV vaccine in cSCC. Methods Immunofluorescence was used to study the immune infiltrating cells in the tumor tissues of patients with cSCC. The effects of the HPV vaccine on cSCC cells and tissues were studied by Cell Culture, Real-time PCR, Western Blot, Cytotoxicity Assay, Enzyme-linked Immunosorbent Assay, m6A Blotting, CCK-8 Assay, m6A Ribonucleic acid Methylation Quantification and tumor transplantation. Results The HPV vaccine enhanced the toxic effect of CD8+T cells on cSCC cells and promoted the secretion of multiple cytokines by CD8+T cells. In addition, HPV vaccines can increase tumor sensitivity to anti-PD-1 therapy by downregulating METTL3 in tumor tissue, with the combination of HPV vaccine and PD-1 monoclonal antibodies producing enhanced immune cell infiltration compared to PD-1 blockade alone. Study limitations It is important to note the limitations of this study, including the small sample size, the construction of the mouse model, and the choice of HPV vaccine and PD-1 monoclonal antibody, which may limit the generalization of our findings to a wider population. Conclusions It is hoped that this research will contribute to a deeper understanding of the role of the HPV vaccine in the treatment of cSCC. HPV vaccine is expected to become an important approach to alleviate the development of cSCC.

Carcinoma de células escamosas de lábio inferior: Excisão e reconstrução com retalho nasolabial / Squamous cell carcinoma of the lower lip: Excision and reconstruction with nasolabial flap

Introdução: O carcinoma de células escamosas é o tumor maligno mais frequente dos lábios e acomete principalmente o lábio inferior. O tratamento adequado desta neoplasia deve ser precoce e radical, pois metástases podem ocorrer. Considerando que os lábios têm extrema relevância na dinâmica e motricidade da face, a reconstrução labial após grandes ressecções nesta região é um desafio para o cirurgião na busca de bons resultados estéticos e funcionais. Este estudo busca apresentar uma técnica já consagrada e confiável para a reconstrução do lábio inferior após ressecções tumorais, o retalho de Karapandizic. Método: Nesta revisão de casos são avaliados, retrospectivamente, 4 pacientes que tiveram o lábio inferior reconstruído por meio da técnica de Karapandzic no período de 2013-2022. Resultados: As complicações mais frequentemente observadas foram cicatriz hipertrófica, deiscência de sutura em vermelhão de lábio e microstomia (redução da abertura oral). A redução da fenda labial (microstomia) foi corrigida parcialmente através do uso de órteses odontológicas, não havendo necessidade de indicação de comissuroplastia em nenhum dos casos. Outra colaboração deste trabalho refere-se à utilização do ecoDoppler colorido pré-operatório, que permite o planejamento do retalho verificando a viabilidade do pedículo vascular e o real posicionamento deste pedículo, reduzindo as chances de lesão inadvertida dos vasos durante a cirurgia. Conclusão: Mesmo sendo a microstomia uma limitação deste retalho, concluímos que esta técnica atende à necessidade de reconstrução de lábio inferior em grandes ressecções, uma vez que é capaz de proporcionar resultados satisfatórios em termos oncológicos, funcionais e estéticos.

Introduction: Squamous cell carcinoma is the most common malignant tumor of the lips and mainly affects the lower lip. Adequate treatment of this neoplasm must be early and radical, as metastases can occur. Considering that the lips are extremely important in the dynamics and motricity of the face, lip reconstruction after major resections in this region is a challenge for the surgeon in the search for good aesthetic and functional results. This study seeks to present an already established and reliable technique for reconstructing the lower lip after tumor resection, the Karapandizic flap. Method: In this case review, 4 patients with lower lips reconstructed using the Karapandzic technique in 2013-2022 are retrospectively evaluated. Results: The most frequently observed complications were hypertrophic scar, lip vermilion suture dehiscence, and microstomia (reduction of oral opening). The cleft lip (microstomia) reduction was partially corrected through dental orthoses, with no need for commissuroplasty in any of the cases. Another contribution of this work is the use of preoperative color echoDoppler, which allows flap planning by checking the viability of the vascular pedicle and the actual positioning of this pedicle, reducing the chances of inadvertent injury to the vessels during surgery. Conclusion: Even though microstomy is a limitation of this flap, we conclude that this technique meets the need for lower lip reconstruction in large resections, as it can provide satisfactory results in oncological, functional, and aesthetic terms.

Survival of patients living with HIV and cancer in Cali, Colombia

Background: People living with HIV have an increased risk of cancer compared to the general population. However, with the increase in life expectancy and advances in antiretroviral therapy, the survival of patients with cancer and HIV has changed. Objective: To determine the survival of patients living with HIV and cancer in Cali, Colombia Methods: A retrospective cohort study was conducted at the Fundación Valle del Lili, Cali, Colombia. Data from the HIV database was crossed with data from the hospital and population-based cancer registries between 2011-2019. Patients <18 years, limited available clinical information on the diagnosis and treatment of HIV and cancer, and non-oncological tumor diagnosis were excluded. Results: A total of 173 patients were included. The frequencies of AIDS-defining neoplasms were: Non-Hodgkin lymphoma (42.8%), Kaposi sarcoma (27.8%), and cervical cancer (4.6%). Overall survival was 76.4% (95% CI 68.9-82.3) at five years. Poorer survival was found in patients with AIDS-defining infections (56.9% vs. 77.8%, p=0.027) and non-AIDS-defining infections (57.8% vs. 84.2%, p=0.013), while there was better survival in patients who received antiretroviral therapy (65.9% vs. 17.9%, p=0.021) and oncological treatment (66.7% vs. 35.4%, p<0.001). The presence of non-AIDS-defining infections increases the risk of dying (HR = 2.39, 95% CI 1.05-5.46, p=0.038), while oncological treatment decreases it (HR = 0.33, 95% CI 0.14-0.80, p=0.014). Conclusions: In people living with HIV, Non-Hodgkin lymphoma and Kaposi sarcoma are the most common neoplasms. Factors such as AIDS-associated and non-AIDS-associated infections have been identified as determinants of survival. Cancer treatment seems to improve survival.

Antecedentes: Las personas que viven con VIH tienen un riesgo mayor de cáncer en comparación con la población general. Sin embargo, con el aumento de la esperanza de vida y los avances en la terapia antirretroviral, la supervivencia de los pacientes con cáncer y VIH ha cambiado. Objetivo: Determinar la supervivencia de los pacientes que viven con VIH y cáncer en Cali, Colombia. Métodos: Se realizó un estudio de cohorte retrospectivo en la Fundación Valle del Lili, Cali, Colombia. Los datos de la base de datos de VIH se cruzaron con los datos de los registros de cáncer de base hospitalaria y poblacional entre 2011-2019. Se excluyeron los pacientes <18 años, con información clínica limitada disponible sobre el diagnóstico y tratamiento del VIH y el cáncer y los casos con diagnóstico de tumor no oncológico. Resultados: Se incluyeron un total de 173 pacientes. Las frecuencias de neoplasias definitorias de SIDA fueron: linfoma no Hodgkin (42.8%), sarcoma de Kaposi (27.8%) y cáncer cervical (4.6%). La supervivencia global fue del 76.4% (IC 95% 68.9-82.3) a los cinco años. Se encontró una peor supervivencia en pacientes con infecciones definitorias de SIDA (56.9% vs. 77.8%, p=0.027) e infecciones no definitorias de SIDA (57.8% vs. 84.2%, p=0.013), mientras que hubo una mejor supervivencia en pacientes que recibieron terapia antirretroviral (65.9% vs. 17.9%, p=0.021) y tratamiento oncológico (66.7% vs. 35.4%, p<0.001). La presencia de infecciones no definitorias de SIDA aumentó el riesgo de morir (HR = 2.39, IC 95% 1.05-5.46, p=0.038), mientras que el tratamiento oncológico lo disminuyó (HR = 0.33, IC 95% 0.14-0.80, p=0.014). Conclusiones: En las personas que viven con VIH, el linfoma no Hodgkin y el sarcoma de Kaposi son las neoplasias más comunes. Se han identificado factores como las infecciones asociadas al SIDA y las infecciones no asociadas al SIDA como determinantes de la supervivencia. El tratamiento del cáncer parece mejorar la supervivencia.

Cutaneous traction as a complement to the parascapular flap in major cancer loss: case report / Tração cutânea como complemento ao retalho paraescapular em grande perda oncológica: relato de caso

Introduction: Squamous cell carcinoma (SCC) is a malignant epidermal keratinocyte tumor closely related to sun exposure. When diagnosed, through biopsy, its staging, tumor resection with oncological safety margins must be performed, and lymph node dissection and treatment of metastases, if present, may be performed. Case Report: Skin traction is reported as a complement to the parascapular flap, used reconstructively after the excision of a large SCC in the left shoulder. Conclusion: The technique used proved effective for the satisfactory correction of large dehiscence in the postoperative period of the parascapular flap, promoting partial closure of the defect, reduced time to perform, and correction of the residual defect in a single step.

Introdução: O carcinoma espinocelular (CEC) é um tumor maligno dos queratinócitos epidérmicos e está intimamente relacionado à exposição solar. Quando diagnosticado, por meio de biópsia, deve ser realizado seu estadiamento, ressecção tumoral com margens de segurança oncológica, podendo ser feito esvaziamento ganglionar e tratamento de metástases, caso presentes. Relato de Caso: Reporta-se a utilização da tração cutânea como complemento ao retalho paraescapular, utilizado reconstrutivamente pós excisão de CEC de grande dimensão em ombro esquerdo. Conclusão: A técnica utilizada mostrou-se eficaz para correção satisfatória de grandes deiscências em pós-operatório de retalho paraescapular, promovendo fechamento parcial do defeito, tempo reduzido para realização e correção do defeito residual em tempo único.

Marjolin ulcer: the importance of early diagnosis and excision / Úlcera de Marjolin: a importância do diagnóstico e excisão precoces

Introduction: Marjolin's ulcer is a rare disease characterized by the malignancy of chronic wounds that present healing disorders, often due to chronic irritation and repetitive trauma in this area. The diagnosis is made mainly through clinical history and histopathological examination. The differential diagnoses of other diseases that course with ulcers must always be researched and ruled out. Method: The present work presents a bibliographic review to elucidate the subject's relevance for medical students, physicians and nurses, to assist in early diagnosis. Results: Nine observational studies were selected to compose the discussion. Conclusion: The most effective treatment for this condition is surgery, and lymph node dissection is suggested in some cases. Chemotherapy has not shown satisfactory results, while radiotherapy is used in selected cases. Given the rapid evolution, tissue damage, and worse prognosis, diagnosis, and excision should be performed early for a better clinical outcome.

Introdução: A úlcera de Marjolin é uma doença rara, caracterizada pela malignização de feridas crônicas que apresentaram distúrbios cicatriciais, muitas vezes devido à irritação crônica e a traumas repetitivos nesta área. O diagnóstico é realizado sobretudo através da história clínica e de exame histopatológico. Os diagnósticos diferenciais de outras doenças que cursam com úlceras devem sempre ser pesquisados e afastados. Método: O presente trabalho apresenta uma revisão bibliográfica, a fim de elucidar a relevância do tema para acadêmicos de medicina, médicos e enfermeiros, com o propósito de auxiliar no diagnóstico precoce. Resultados: Foram selecionados 9 estudos observacionais para compor a discussão. Conclusão: O tratamento mais eficaz desta condição é o cirúrgico, e o esvaziamento linfonodal é sugerido em alguns casos. A quimioterapia não demonstrou resultados satisfatórios, enquanto a radioterapia é utilizada em casos selecionados. O diagnóstico e a excisão devem ser feitos precocemente para melhor desfecho clínico, visto a rapidez da evolução, o prejuízo tecidual e pior prognóstico.

Non-melanoma skin cancer: an analysis of compromised margins in excisions / Câncer de pele não melanoma: uma análise do comprometimento de margens em excisões

Introduction: Non-melanoma skin cancer is the most frequent neoplasm in Brazil, with an estimated 176,930 new cases during the 2020-2022 period, with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) as the most common subtypes. Surgical treatment of the lesions is effective, with a recurrence rate varying between 3 and 23%, with compromised margins being an important prognostic factor for this recurrence, increasing the importance of complete excision of the tumor. Method: To prepare this work, 1127 lesions treated at the Hospital de Amor Amazônia were analyzed, seeking to quantify cases and analyze surgically compromised margins through a retrospective analytical descriptive study. For this, histopathological reports of the operated patients were reviewed, dividing them according to sex, age, lesion topography, date of excision, lesion diameter, lesion depth, presence of ulceration, compromised margins, and histological type. Results: Among the lesions treated, 65% were BCC and 35% SCC, both histological types presenting a low incidence of compromised margins. In cases of CPB impairment, treatment via exeresis was chosen in 100% of cases. Concerning BCC impairment, the majority opted for clinical follow-up, with reapproach in only 9% of cases. Conclusion: This study demonstrates that the cases treated at the Hospital de Amor Amazônia align with the epidemiological data in the main literature, except for finding a higher incidence of non-melanoma skin cancer in men. In addition, this work demonstrates good results in the clinical approach of compromised margins in BCC lesions.

Introdução: O câncer de pele não melanoma é a neoplasia mais frequente no Brasil, com uma estimativa de 176.930 novos casos durante o triênio 2020-2022, tendo o carcinoma basocelular (CBC) e o carcinoma espinocelular (CEC) como subtipos mais presentes. O tratamento cirúrgico das lesões é efetivo, apresentando taxa de recorrência variando entre 3 e 23%, sendo o comprometimento de margens importante fator prognóstico para essa recorrência, aumentando a importância da excisão completa do tumor. Método: Para a elaboração deste trabalho, foram analisadas 1127 lesões abordadas no Hospital de Amor Amazônia, buscando quantificar casos e analisar margens cirurgicamente comprometidas por meio de um estudo descritivo analítico retrospectivo. Para isso, foram revisados laudos histopatológicos dos pacientes operados, dividindo-os de acordo com sexo, idade, topografia da lesão, data de excisão, diâmetro da lesão, profundidade da lesão, presença de ulceração, comprometimento de margens e tipo histológico. Resultados: Dentre as lesões abordadas, 65% eram CBC e 35% CEC, ambos os tipos histológicos apresentando baixa incidência de margens comprometidas. Nos casos de comprometimento em CEC, optou-se pelo tratamento via exérese em 100% dos casos. Já em relação ao comprometimento em CBC, optou-se majoritariamente pelo acompanhamento clínico, com reabordagem em apenas 9% dos casos. Conclusão: Este estudo demonstra que os casos abordados no Hospital de Amor Amazônia vão ao encontro dos dados epidemiológicos presentes nas principais literaturas, com ressalva, apenas, ao encontrar uma maior incidência de câncer de pele não melanoma em homens. Além disso, esse trabalho demonstra bons resultados na abordagem clínica de margens comprometidas em lesões de CBC.

Effects of the interaction between Brahma-related gene 1 and activating transcription factor 2 on the proliferation, migration and invasion of cutaneous squamous cell carcinoma cells / 中华皮肤科杂志

Objective:To determine the expression of Brahma-related gene 1 (BRG1) in cutaneous squamous cell carcinoma (cSCC) tissues and cells, and to investigate molecular mechanisms underlying the regulatory effect of its interaction with activating transcription factor 2 (ATF2) on the proliferation, migration and invasion of cSCC cells.Methods:From 2015 to 2021, 66 paraffin-embedded actinic keratosis (AK) tissue samples and 80 paraffin-embedded cSCC (including squamous cell carcinoma in situ) tissue samples were collected from the Department of Dermatology, Affiliated Hospital 2 of Nantong University, and the diagnoses of all the cases were confirmed histopathologically; at the same time, 35 paraffin-embedded normal skin tissue samples obtained by cosmetic surgery served as normal control group. Immunohistochemical staining was performed to determine the BRG1 expression in cSCC, AK, and normal skin tissues, and correlations between BRG1 expression and clinicopathological parameters of cSCC patients were analyzed. Fresh tissue samples were collected from 12 cSCC patients and 12 healthy controls, and cSCC cell lines A431 and Scl-1 and a human immortalized keratinocyte cell line HaCaT were routinely cultured; real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to determine the mRNA expression of BRG1 in tissues and cells, and co-immunoprecipitation assay and cellular immunofluorescence staining were conducted to analyze the interaction between BRG1 and ATF2. The expression of BRG1 (BRG1 siRNA1 - 5 groups) and ATF2 (ATF2-shRNA group) in A431 and Scl-1 cells was knocked down by RNA interference, and cells transfected with negative control siRNA or shNC served as controls (control siRNA group and shNC group, respectively), cell counting kit-8 (CCK8) assay, colony formation assay, cell scratch assay, and Transwell assay were conducted to evaluate effects of knocking down BRG1 and ATF2 on the proliferation, migration, and invasion of cSCC cells. Comparisons of measurement data among multiple groups were conducted using one-way analysis of variance, and multiple comparisons were conducted using Dunnett- t test. Results:Immunohistochemical staining showed that the expression intensity of BRG1 protein was significantly lower in the cSCC and AK tissues than in the normal skin tissues ( χ2 = 44.40, P < 0.001). qRT-PCR showed that the mRNA expression level of BRG1 was significantly lower in the cSCC tissues (1.345 ± 0.956) than in the normal skin tissues (2.499 ± 1.501, t = 2.25, P = 0.035), and also significantly lower in A431 and Scl-1 cells (0.041 ± 0.002, 0.026 ± 0.003, respectively) than in HaCaT cells (0.135 ± 0.033, t = 4.95, 5.73, P = 0.008, 0.005, respectively). The low expression of BRG1 was associated with tumors at sun-exposed sites ( P = 0.041), low tumor differentiation ( P = 0.001), and high Broder′s grade ( P < 0.001) in the cSCC patients. In both A431 cells and Scl-1 cells, the BRG1 siRNA1 group and BRG1 siRNA2 group showed significantly increased numbers of cell colonies, migratory cells and invasive cells, as well as cell migration rates compared with the control siRNA group (all P < 0.05). Co-immunoprecipitation assay showed that BRG1 protein could bind to ATF2 protein in A431 and Scl-1 cells, and immunofluorescence staining showed that the two proteins were co-localized; compared with the control siRNA group, the BRG1 siRNA1 group (both A431 and Scl-1 cells) and BRG1 siRNA2 group (A431 cells) both showed increased phosphorylation and activation of ATF2 (all P < 0.05) ; in both A431 cells and Scl-1 cells, the shATF2 group showed significantly decreased numbers of cell colonies (both P = 0.001), cellular proliferative activity at 24 - 96 hours (all P < 0.001), and numbers of migratory cells and invasive cells compared with the shNC group (all P ≤ 0.001) . Conclusion:BRG1 was lowly expressed in the cSCC and AK tissues, and could inhibit the proliferation, migration, and invasion of cSCC cells; ATF2 could promote the proliferation, migration, and invasion of cSCC cells; BRG1 may exert an anti-tumor effect by interacting with ATF2 protein and inhibiting phosphorylation-dependent activation of ATF2.

Value of apparent diffusion coefficient of diffusion-weighted magnetic resonance imaging in evaluating the radiotherapy efficacy for advanced cervical squamous cell carcinoma / 肿瘤研究与临床

Objective:To explore the correlation of apparent diffusion coefficient (ADC) of magnetic resonance diffusion weighted imaging (DWI) examination before radiotherapy in patients with advanced cervical squamous cell carcinoma with clinicopathological characteristics and radiotherapy efficacy.Methods:The clinical data of 80 patients with advanced cervical cancer who were admitted to the Second Hospital of Nanjing from September 2019 to March 2022 were retrospectively analyzed. All patients underwent magnetic resonance imaging (MRI) DWI examination. The differences in ADC values among cervical squamous cell carcinoma patients with different clinicopathological characteristics were analyzed. The patients were divided into the effective group (complete remission+partial remission) and the ineffective group (stable disease+progressive disease) based on the radiotherapy effect, and the differences in ADC values between the two groups were compared. The logistic regression model was used to analyze the factors affecting the radiotherapy efficacy of patients with advanced cervical squamous cell carcinoma.Results:Among 80 patients with advanced cervical squamous cell carcinoma, 21 achieved complete remission, 31 achieved partial remission, 25 achieved stable disease, and 3 achieved progressive disease after radiotherapy; there were 52 cases in the effective group and 28 cases in the ineffective group. The ADC value of the effective group before radiotherapy was higher than that of the ineffective group [(0.99±0.14)×10 -3mm 2/s vs. (0.76±0.20)×10 -3mm 2/s], and the difference was statistically significant ( t = 6.01, P < 0.001); after radiotherapy, the ADC value of the effective group was also higher than that of the ineffective group [(1.43±0.25)×10 -3mm 2/s vs. (1.11±0.23)×10 -3mm 2/s), and the difference was statistically significant ( t = 5.61, P < 0.001); the ADC values of both the effective and ineffective groups increased after radiotherapy compared to before radiotherapy (both P < 0.05). The ADC values of patients with different International Federation of Obstetrics and Gynecology (FIGO) stage, degree of pathological differentiation, depth of lesion infiltration, Ki-67 expression, lymph node metastasis, and distant metastasis were statistically significant (all P < 0.05). The results of multivariate logistic regression analysis showed that ≥FIGO stage Ⅲ, low differentiation, lymph node metastasis, lymphatic vessel infiltration, distant metastasis, and low ADC value before radiotherapy were independent risk factors for efficacy of radiotherapy in patients with advanced cervical squamous cell carcinoma (all P < 0.05). Conclusions:The ADC value before radiotherapy is a factor that affects the radiotherapy effect of patients with advanced cervical squamous cell carcinoma. The lower the ADC value before radiotherapy is, the worse the radiotherapy effect of patients will be.

Application of radiotherapy combined with immunotherapy in the treatment of head and neck squamous cell carcinoma / 国际肿瘤学杂志

Immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma (HNSCC) has shown significant clinical benefit. Some studies have shown that radiotherapy combined with immunotherapy can produce synergistic effects, and several phase Ⅰ/Ⅱ clinical trials have suggested that radiotherapy combined with immunotherapy has good safety and preliminary efficacy benefits in locally advanced HNSCC. However, the timing of combination therapy, the selection of radiotherapy dose/fractionation mode and patients are still unclear. This article further discusses the synergistic mechanism, clinical research status and challenges of radiotherapy combined with immunotherapy in the treatment of HNSCC, aiming to guide the clinical practice and improve the prognosis of HNSCC patients.

Advances in immune checkpoint inhibitors in the treatment of recurrent or metastatic head and neck squamous cell carcinoma / 国际肿瘤学杂志

With the increasing understanding of the complex interaction between the tumor microenvironment and immune therapy, the role of immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma (HNSCC) has gained significant attention. Immune checkpoint inhibitors targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) , cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) , and T cell immunoglobulin domain and mucin domain-3 (TIM-3) , such as pembrolizumab, durvalumab, tremelimumab, ipilimumab, and LY3321367, have been applied in numerous clinical trials as monotherapies and combination therapies for the treatment of recurrent or metastatic HNSCC. Further research into the efficacy and safety of these immune checkpoint inhibitors in clinical trials may provide more effective strategies for the treatment of patients with recurrent or metastatic HNSCC.

Research progress in animal models of oral squamous cell carcinoma and common oral mucosal diseases / 中国基层医药

The pathogeneses of oral squamous cell carcinoma and most oral mucosal diseases are unclear. Therefore, establishing animal models with similar pathogeneses is significant for clinical prevention, diagnosis, and treatment of related diseases. At present, scholars have established animal models for different focuses. This paper aims to introduce the methods for establishing animal models of oral squamous cell carcinoma and common oral mucosal diseases, compare their advantages and disadvantages, and provide evidence for related basic research.

Efficacy of quantitative parameters of dual-layer spectral detector CT in preoperative prediction of Ki-67 expression in esophageal squamous cell carcinoma / 中华放射学杂志

Objective:To explore the efficacy of quantitative parameters of dual-layer spectral CT in preoperative prediction of Ki-67 expression in esophageal squamous cell carcinoma (ESCC).Methods:From December 2021 to December 2022, 64 patients with histopathologically diagnosed ESCC were retrospectively analyzed at Liaoning Cancer Hospital & Institute. The expression level of Ki-67 in ESCC tumor tissue was detected by the immunohistochemical method. The patients were divided into the Ki-67 high expression group (the Ki-67 expression index≥30%, 47 cases) and the Ki-67 low expression group (the Ki-67 expression index<30%, 17 cases). The quantitative parameters of spectral CT were measured, including traditional 120 kVp CT value, 40 keV CT value, iodine density (ID), normalized iodine density (NID), and Z-effective in arterial and venous phases. Independent sample t test was used to compare the differences in the parameters between the Ki-67 high and low expression groups. The receiver operating characteristic (ROC) curve was drawn to evaluate the efficacy of each parameter in predicting Ki-67 expression. DeLong test was used to compare the area under the curve (AUC). Results:The 120 kVp CT value, 40 keV CT value, ID, and Z-effective in the arterial phase and the 120 kVp CT value, 40 keV CT value, ID, NID, Z-effective in venous phase in the Ki-67 high expression group were all higher than those in the Ki-67 low expression group ( P<0.05). There was no statistically significant difference in arterial phase NID between the two groups ( t=1.85, P=0.070). NID in the venous phase had the highest AUC in predicting high expression of Ki-67 in ESCC (AUC=0.965, 95%CI 0.923-1.000). With a venous phase NID value of 0.28 as the diagnostic threshold, the sensitivity and specificity were 93.6% and 100%. There was no significant difference in AUC between venous phase NID and venous phase ID (AUC=0.926) and Z-effective (AUC=0.909) ( Z=-1.52, 1.81, P=0.128, 0.071), but there was a significant difference of AUC between venous phase NID and 120 kVp CT value (AUC=0.719) and 40 keV CT value (AUC=0.747) ( Z=3.41, 3.30, P=0.001, 0.001). There were statistical differences of AUC between venous phase NID and each parameter of arterial phase ( P<0.05). Conclusion:The three spectral CT parameters (ID, NID, and Z-effective) in the venous phase have high diagnostic efficacy in predicting ESCC Ki-67 expression.

A preliminary study of apoptosis in tongue squamous cell carcinoma cells induced by hyperthermia via downregulation of Notch1/Jagged1/Hes1 / 中华放射肿瘤学杂志

Objective:To observe the optimal time interval of multiple short-term hyperthermia in tongue squamous carcinoma Cal-27 cells, and investigate the role of Notch signaling pathway in hyperthermia-induced apoptosis of Cal-27 cells.Methods:Cal-27 cells were placed into a 42℃ incubator for 45 min, and the second hyperthermia was performed at 6 h,12 h, 24 h, 48 h and 72 h later, respectively. Cell proliferation capacity was detected by CCK-8 assay at 0 h, 12 h and 24 h after the end of hyperthermia. After determining the optimal time interval of hyperthermia, multiple cycles of hyperthermia were performed, and the effects of hyperthermia on the proliferation and apoptosis of Cal-27 cells were detected by CCK-8 assay and flow cytometry, respectively. The changes in the expression of Notch1, Jagged1 and hairy and enhancer of split homolog-1 (Hes1) mRNA and proteins were analyzed by real-time reverse transcription PCR (qRT-PCR) and Western blot. All data were expressed as mean±SD. Two-group comparison was performed by one-way ANOVA.Results:Hyperthermia at 42℃ for 45 min every 12 h consistently inhibited the proliferation of Cal-27 cells ( P<0.05). Compared with the control group, hyperthermia in the experiment group significantly inhibited the proliferation and induced the apoptosis of Cal-27 cells after 7 cycles of hyperthermia ( P<0.05), and the expression levels of Notch1, Jagged1 and Hes1 mRNA and proteins in the hyperthermia group were significantly down-regulated (all P<0.05). Conclusions:The optimal time interval of hyperthermia to inhibit the proliferation of tongue squamous cells carcinoma Cal-27 cells is 12 h. Hyperthermia might induce the apoptosis of Cal-27 cells by inhibiting the Notch signaling pathway.

Expression of NF45 in laryngeal squamous cell carcinoma and its effect on radiation sensitivity of tumor cells / 中华放射肿瘤学杂志

Objective:To investigate the expression of double-stranded RNA-binding protein nuclear factor 45 (NF45) in laryngeal squamous cell carcinoma (LSCC), and the effect of NF45 on the radiation sensitivity of LSCC cells and its mechanism.Methods:NF45 expression in LSCC and adjacent tissues was detected by real-time reverse transcription PCR (qRT-PCR) and immunohistochemical staining. The NF45-ShRNA lentivirus was transfected into Hep-2 cells, and cell transfection efficiency was determined by qRT-PCR and Western blot . Hep-2 cells were randomly divided into the control group, 2 Gy group, sh-NC+2 Gy group and sh-NF45+2 Gy group. Lentivirus infection and 2Gy X-ray irradiation treatment were carried out. Cell proliferation activity was assessed by CCK-8 assay. Apoptosis rate was determined by flow cytometry. Hep-2 cells in each group were treated with mCherry-EGFP-LC3B. The levels of autophagy were detected by immunofluorescence staining. The ratio of autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3)-Ⅱ/LC3-Ⅰ and the expression levels of Beclin-1 and p62 proteins were determined by Western blot.Results:The expression level of NF45 in LSCC tissues was significantly higher than that in adjacent tissues ( P<0.01). The relative expression levels of NF45 mRNA and protein in Hep-2 cells infected with NF45-shRNA were significantly lower than those in the control and sh-NC groups (all P<0.05). Compared with the control group, the cell proliferation activity was decreased, the apoptosis rate was increased, the intracellular autophagy-lysosome were increased, the ratio of LC3-Ⅱ/LC3-Ⅰ was increased, the relative expression levels of Beclin-1 protein were up-regulated, and the relative expression levels of p62 protein were down-regulated in the 2 Gy, sh-NC+2 Gy and sh-NF45+2 Gy groups (all P<0.05). Compared with the 2 Gy group, the cell proliferation activity was decreased, the apoptosis rate was increased, the intracellular autophagy lysosomes were increased, the LC3-Ⅱ/LC3-Ⅰ ratio was increased, the relative expression of Beclin-1 protein was up-regulated, and the relative expression of p62 protein was down-regulated in the sh-NF45+2 Gy group (all P<0.05). Conclusions:The expression of NF45 is up-regulated in LSCC tissues. Targeted down-regulation of NF45 expression can inhibit the proliferation activity of LSCC cells, promote cell apoptosis, and improve the sensitivity of tumor cells to radiation. The mechanism may be related to the regulation of autophagy levels.

Expression of glucose transporter 3 in cutaneous squamous cell carcinoma and its effect on the proliferation, invasion and migration of A431 cells / 中华皮肤科杂志

Objective:To determine the expression of glucose transporter 3 (GLUT3) in cutaneous squamous cell carcinoma (cSCC), and to evaluate its effect on the cSCC cell line A431.Methods:From June 2016 to December 2020, 22 paraffin-embedded tissue specimens were collected from patients with pathologically confirmed cSCC in the Department of Dermatology, Peking University Third Hospital, and 20 discarded normal skin tissues after dermatological surgeries served as controls. Immunohistochemical assay was performed to determine the GLUT3 expression in cSCC tissues and normal skin tissues. Cultured A431 cells were divided into two groups: GLUT3 overexpression group transfected with a lentiviral vector carrying the SLC2A3 gene, and negative control group transfected with an empty lentiviral vector. Real-time fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of GLUT3 in A431 cells in different groups, the cell proliferation assay (MTS assay) was performed to estimate the cell proliferative activity, and the live-cell analysis system Incucyte S3 was used for real-time evaluation of the migratory and invasive abilities of A431 cells in different groups. The relative glucose consumption and lactic acid production in A431 cells at 48 hours were measured by using glucose and lactic acid assay kits, retrospectively. Two independent samples t-test was used for comparisons between two groups, and one-way analysis of variance was used for comparisons among multiple groups. Results:The GLUT3 expression was significantly higher in the cSCC tissues than in the normal skin tissues (immunohistochemical assay score: 9.39 ± 2.56 points vs. 2.30 ± 2.60 points; t = 8.91, P < 0.05). Compared with the negative control group, the mRNA and protein expression of GLUT3 markedly increased in the GLUT3 overexpression group. MTS assay showed significantly increased proliferative activity of A431 cells in the GLUT3 overexpression group compared with the negative control group after 24- and 96-hour treatment ( t = 2.49, 3.54, P = 0.048, 0.012, respectively); cell fusion rates in the scratched area were significantly higher in the GLUT3 overexpression group than in the negative control group in the cell migration assay at 6, 12 18, and 24 hours and cell invasion assay at 12, 18, and 24 hours (all P < 0.05). At 48 hours, the relative glucose consumption and lactic acid production in A431 cells were significantly higher in the GLUT3 overexpression group than in the negative control group ( t = 2.98, 2.20, P = 0.011, 0.038, respectively) . Conclusion:GLUT3 was highly expressed in the cSCC tissues, and may participate in the occurrence and development of cSCC by providing energy to cSCC cells via promoting glucose uptake in cells to enhance their proliferative, migratory and invasive abilities.

Distribution features of resident CD8 + T cells in human esophageal cancer tissues and its effects on the prognosis / 中华消化杂志

Objective:To explore the distribution features of resident CD8 + T cells infiltration in human esophageal cancer tissues and its clinical significance. Methods:Data from the Cancer Genome Atlas database were retrieved, the correlation between CD103 + CD8 + T cells and infiltration degree of conventional type 1 dendritic cell (cDC1), conventional type 2 dendritic cell (cDC2), type 3 dendritic cell(DC3) was investigated. From January 2006 to December 2008, 78 esophageal cancer tissues and 75 adjacent normal tissues from 78 esophageal cancer patients were collected by Shanghai Outdo Biotechnology Co., Ltd, the clinical data of patients was followed up by telephone until July 2015. The distribution of CD8 + T cells and CD103 + CD8 + T cells in cancer tissues and adjacent normal tissues was detected by multi-color labeling techniques and multispectral tissue imaging. The differences of the number and the ratio of CD8 + T cells and CD103 + CD8 + T cells in cancer tissues and adjacent normal tissues were compared. The Kaplan-Meier survival curves of patients with tissue infiltration of CD8 + T cells and CD103 + CD8 + T cells at different levels were drawn through the R language " survminer" package, and the best cut-off value was obtained. TNM stage, pathological stage and other clinical parameters of patients with high and low infiltration of CD8 + T cells, CD103 + CD8 + T cells were compared. Wilcoxon rank sum test, chi-square test, log-rank test and Cox proportional risk regression model statistical analysis were used to evaluate the prognostic value of the above indicators. Spearman correlation analysis was used for correlation analysis. Results:In the cancer tissues of patients with esophageal cancer, the infiltration degree of CD103 + CD8 + T cells was positively correlated with the infiltration degree of cDC1 cells, cDC2 cells and DC3 cells ( r=0.67, 0.53 and 0.47, all P<0.001). The percentage of CD8 + T cells in all cells in the whole tissue core of tumor tissues (63.09% (42.14%, 76.21%)) was higher than that of adjacent normal tissues (2.56% (1.68%, 5.38%)), and the difference was statistically significant ( U=41.00, P<0.001). The proportion of CD103 + CD8 + T cells in all cells in the whole tissue core of tumor tissues (7.92% (1.60%, 20.61%)) was higher than that of adjacent normal tissues (0.04% (0.01%, 0.10%)), and the difference was statistically significant ( U=857.50, P<0.001). The percentage of high CD8 + T cells infiltration in esophageal cancer tissues of patients with pathological stage Ⅰ+ Ⅱ was lower than that of patients with stage Ⅲ+ Ⅳ (57.9%, 33/57 vs. 85.7%, 18/21); the percentage of high CD103 + CD8 + T cells in CD8 + T cells in esophageal cancer tissues of patients with TNM stage Ⅰ+ Ⅱ was lower than that of patients with stage Ⅲ+ Ⅳ (21.6%, 8/37 vs. 48.8%, 20/41), and the differences were both statistically significant ( χ2=5.25 and 6.23, P=0.022 and 0.013). The results of Kaplan-Meier survival analysis and univariate Cox proportional risk regression model showed that the overall survival (OS) of patients with high CD8 + T cell infiltration was longer than that of patients with low CD8 + T cell infiltration ( HR=0.57, 95% confidence interval (95% CI) 0.34 to 0.96, P=0.034). There was no significant difference in OS between patients with high CD103 + CD8 + T cell infiltration and patients with low CD103 + CD8 + T cell infiltration ( HR=0.66, 95% CI 0.40 to 1.08, P>0.05). Conclusion:The high infiltration of CD103 + CD8 + T cells in esophageal cancer tissues are expected to be used as a prognostic predictor for patients with esophageal cancer, which is an important component of anti-tumor immune response in tumor microenvironment of esophageal cancer.

Expressions of STMN1, BubR1, bcl-2 and Bad in patients with esophageal squamous cell carcinoma and their relationship with chemotherapy effect of paclitaxel-containing regimen / 肿瘤研究与临床

Objective:To investigate the correlation between the expression levels of STMN1, BubR1, bcl-2 and Bad and the chemotherapy effect of paclitaxel-containing regimen in patients with esophageal squamous cell carcinoma (ESCC).Methods:The clinical data of ESCC patients who received paclitaxel-containing chemotherapy at Fenyang Hospital Affiliated to Shanxi Medical University from September 2016 to June 2021 were retrospectively analyzed. Among them, 59 cases received maintenance chemotherapy and 27 cases received surgery after 3 courses of neoadjuvant chemotherapy. The expression levels of STMN1, BubR1, bcl-2 and Bad in tumor tissues before chemotherapy were detected by immunohistochemistry. The imaging efficacy after 3 courses of chemotherapy and pathological efficacy after neoadjuvant chemotherapy were evaluated. The imaging efficacy, pathological efficacy and progression-free survival (PFS) were compared between the high expression group and the low expression group of each protein.Results:The proportion of patients with stage Ⅳ (46.3%, 19/41), the proportion of patients with low differentiation (22%, 9/41) and the incidence of lymph node metastasis (95.1%, 39/41) in STMN1 high expression group were higher than those in STMN1 low expression group (17.8%, 8/45; 4.4%, 2/45; 64.4%, 29/45), and the differences were statistically significant (all P < 0.05). The proportion of patients with stage Ⅳ in Bad high expression group was lower than that in Bad low expression group, and the difference was statistically significant ( P < 0.05). In the evaluation of imaging efficacy, the chemotherapy sensitivity rates in STMN1 and BubR1 high expression groups (29.3%, 12/41; 37.9%, 22/58) were lower than those in STMN1 and BubR1 low expression groups (75.6%, 34/45; 85.7%, 24/28), and the chemotherapy sensitivity rate of patients in Bad high expression group (65.9%, 27/41) was higher than that in Bad low expression group (42.2%, 19/45), and the difference was statistically significant (all P < 0.05). There was no statistical correlation between bcl-2 expression and chemotherapy sensitivity rate ( P > 0.05). In the evaluation of pathological efficacy, the proportion of patients with tumor regression grade (TRG) score 0-1 after neoadjuvant therapy in STMN1 high expression group (27.3%, 3/11) was lower than that in STMN1 low expression group (75.0%, 12/16), and the difference was statistically significant ( P = 0.022). There were no statistical differences in the proportions of patients with TRG score 0-1 after neoadjuvant therapy between high and low expression groups of BubR1, bcl-2 and Bad (all P > 0.05). The PFS rate was 15.2% (9/59) for patients received maintenance chemotherapy, and the median PFS time was 6 months. Kaplan-Meier analysis showed that PFS in STMN1 low expression group was better than that in STMN1 low expression group ( χ2 = 12.90, P < 0.001). PFS in BubR1 low expression group was better than that in BubR1 high expression ( χ2 =12.04, P < 0.001). PFS in Bad high expression group was better than that in Bad low expression group ( χ2 =9.69, P = 0.004). There was no statistical difference in PFS between high and low bcl-2 expression groups ( χ2 =1.43, P = 0.320). Conclusions:ESCC patients with low expression of STMN1, low expression of BubR1 and high expression of Bad have better chemotherapy effect after receiving paclitaxel-containing regimen, but there is no correlation between bcl-2 expression and chemotherapy efficacy.

Expression of p21-activated kinase 2 in laryngeal squamous cell carcinoma and its correlation with clinicopathological characteristics and chemosensitivity / 肿瘤研究与临床

Objective:To investigate the expression of p21-activated kinase 2 (PAK2) in laryngeal squamous cell carcinoma and its relationship with the clinicopathological characteristics and chemosensitivity of patients.Methods:Transcriptome sequencing (RNA-seq) data for laryngeal squamous cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA) database, and 123 patients were included in the study (12 cases had cancer tissues and normal tissues data, and the remaining 111 only had cancer tissues data). Differential expression of PAK2 in cancer and para-cancer tissues was analyzed by using R software, and the potential function of PAK2 in laryngeal squamous cell carcinoma was investigated by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database signaling pathway enrichment. A total of 34 patients with primary laryngeal squamous cell carcinoma tissues and corresponding para-carcinoma 34 tissue specimens who underwent surgical resection were retrospectively selected from Chaoyang Central Hospital between April 2016 and June 2021, and 20 cases of normal laryngeal mucosa tissues were selected as the controls. Immunohistochemistry was used to detect the expression of PAK2 in various tissues, and its correlation with clinicopathological factors was analyzed. A total of 35 supraglottic primary laryngeal squamous cell carcinoma patients were retrospectively collected before induction chemotherapy during the same period, including 20 patients sensitive to chemotherapy and 15 patients resistant to chemotherapy. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of PAK2 mRNA in cancer tissues.Results:Analysis of TCGA database data showed that PAK2 expression was increased in cancer tissues compared with that in para-cancer tissues ( P = 0.012); KEGG database signaling pathways showed that the high expression of PAK2 in laryngeal squamous cell carcinoma was related to signal transduction pathways, cell cycle, and cancer. Immunohistochemistry showed that the proportion of PAK2 positive in 34 cases of laryngeal squamous cell carcinoma tissues was higher than that in adjacent tissues and normal tissues [58.82% (20/34) vs. 0.03% (1/34), 0 (0/20), all P < 0.001]. There were statistically significant differences in the proportion of PAK2 positive patients stratified with different degrees of differentiation [high differentiation vs. low or middle differentiation: 33.33% (6/18)vs. 87.50% (14/16)], lymph node metastasis [presence vs. absence: 90.91% (10/11) vs. 43.48% (10/23)], TNM staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 82.35% (14/17) vs. 35.29% (6/17)] (all P < 0.05), and PAK2 positive patients were not associated with clinical type, tumor size, smoking history, drinking history, and age (all P > 0.05). qRT-PCR showed that the relative expression level of PAK2 mRNA in the chemotherapy-resistant group was higher than that in the chemotherapy-sensitive group (3.89±0.12 vs. 0.78±0.23, P < 0.001). Conclusions:The expression level of PAK2 in laryngeal squamous cell carcinoma tissues is increased, and the high expression of PAK2 is closely related to the malignant clinical characteristics of patients with laryngeal squamous cell carcinoma. The high expression of PAK2 may indicate the insensitivity to traditional chemotherapy regimens, and PAK2 may be a potential gene that targets and regulates the chemosensitivity of laryngeal squamous cell carcinoma.