LINC01133 contributes to the malignant phenotypes of non-small cell lung cancer by targeting miR-30b-5p/FOXA1 pathway.

This study aimed to explore the mechanism of action of LINC01133 in non-small cell lung cancer. LINC01133 expression in NSCLC patient tissues and cells was detected by qRT-PCR. After transfecting siRNA-LINC01133 in NSCLC cells, the proliferation and invasive migration ability of the cells were assessed via CCK-8 and Transwell assay, respectively. The sublocalization of LINC01133 in NSCLC cells was analyzed by bioinformatics prediction and nucleoplasm separation assay and RNA-FISH assay. Analysis of the binding relationship between LINC01133, FOXA1 and miR-30b-5p was all through bioinformatics website analysis, dual-luciferase reporter and RNA Pulldown assay. Functional rescue experiments confirmed the character of miR-30b-5p and FOXA1 in LINC01133 regulating the NSCLC cells biological behavior. LINC01133 high expressions were found in NSCLC tissues and cells. siRNA-LINC01133 treatment inhibited NSCLC cells malignant behavior. Mechanistically: LINC01133 promoted FOXA1 expression through adsorption binding of miR-30b-5p. Knocking down miR-30b-5p expression or up-regulating FOXA1 expression was able to reverse siRNA-LINC01133 inhibitory effect of tumor cell malignant behavior. LINC01133 promoted FOX1 expression by competitively binding miR-30b-5p, which attenuated the targeting inhibitory effect of miR-30b-5p on FOXA1 and ultimately promoted proliferation and invasive migration of NSCLC cells.

LINC00472 suppresses non-small cell lung cancer progression via regulating miR-23a-3p/CCL22 axis.

Long non-coding RNA (lncRNA) LINC00472 has a close connection with the development of tumors. The aim was to explore the role of LINC00472 on NSCLC cell biological function in vivo and its potential mechanisms. The mRNA levels of LncRNA 00472 and microRNA-23a-3p, were determined by RT-qPCR. Cell Counting Kit-8, cell scratches and western blot assays were used to analyze the proliferation, migration and level of apoptosis-associated proteins. Luciferase reporter assay validates the binding between LINC00472/CCL22 and miR-23a-3p. LINC00472 and CCL22 were lowly expressed in NSCLC tissues and cells, while miR-23a-3p expression was upregulated. LINC00472 overexpression significantly depressed NSCLC cell cellular behavior, whereas promoting cell death. MiR-23a-3p could reverse these above-mentioned biological behavior changes caused by LINC00472 overexpression. Additionally, LINC00472 increased CCL22 expression through sponging miR-23a-3p. Knocking down CCL22 antagonized the inhibitory effect of LINC00472 on NSCLC cell survival. LINC00472 may reduce the cellular growth, and accelerate death of NSCLC through increasing CCL22 expression by targeting miR-23a-3p.

Killing capacity analysis of tumor-infiltrating cytotoxic lymphocytes and impact on lymph node metastasis in differentiated papillary carcinoma of thyroid with the BRAF V600E mutation.

BACKGROUND: Cytotoxic lymphocytes (CLs) express potent toxins, including perforin (P) and granzyme-B (G), which brings about target cell death. The purpose of this study was to evaluate the killing capacity of tumor-infiltrating CLs by means of P and G analysis, and explore the association with lymph node metastasis in papillary carcinoma of thyroid (PTC) without Hashimoto's thyroiditis (HT). METHODS: Infiltration of lymphocytes in PTC was observed in frozen sections. Both fresh tumor tissues and paracancerous tissues with lymphocyte infiltration were collected and prepared into a single cell suspension. Flow cytometry was used to detect the percentages of CD3+P+, CD3+G+, CD8+P+, and CD8+G+ T lymphocytes (TLs) and CD16-CD56+P+ and CD16-CD56+G+ natural killer (NK) cells. Finally, we investigated differential expression of P and G in NK cells and cytotoxic T lymphocytes (CTLs) in paired tumor tissues (group T, n = 44) and paracancerous tissues (group N, n = 44) from patients with PTC with the BRAF V600E mutation. Furthermore, patients were divided into two groups according to whether cervical central lymph node metastasis (CCLNM) existed: group A (with lymph node metastases, n = 27) and group B (with nonlymph node metastases, n = 17). Patients were also divided into three groups according to the total number of positive CCLNM: group B, group C (with low-level lymph node metastases, less than 5, n = 17) and group D (with high-level lymph node metastases, no less than 5, n = 10). RESULTS: The percentage of CD3+P+ CTLs was significantly higher in group N than in group T (P < 0.05). The percentage of CD8+G+ CTLs was significantly higher in group T than in group N (P < 0.05). The percentages of CD3+G+, CD16-CD56+P+and CD16-CD56+G+ NK cells showed no significant difference in either group T or group N (P > 0.05). The percentages of CD3+P+ CTLs in group A and group C were significantly higher in the paracancerous tissue than in the tumor tissue (P < 0.05). The percentages of CD8+G+ CTLs in group A and group C were significantly higher in the tumor tissues than in the paracancerous tissues (P < 0.05). The percentage of CD16-CD56+G+ NK cells in group D was significantly higher in the tumor tissues than in the paracancerous tissues (P < 0.05). CONCLUSIONS: The killing capacity of infiltrating CLs in PTC differed between tumor tissues and paracancerous tissues. In cases with CCLNM, higher expression of CD16-CD56+G+ NK cells in tumor tissues may be associated with a high risk of lymph node metastasis.

Hierarchical integration of DNA nanostructures and NanoGold onto a microchip facilitates covalent chemistry-mediated purification of circulating tumor cells in head and neck squamous cell carcinoma.

It is well-established that the combined use of nanostructured substrates and immunoaffinity agents can enhance the cell-capture performance of the substrates, thus offering a practical solution to effectively capture circulating tumor cells (CTCs) in peripheral blood. Developing along this strategy, this study first demonstrated a top-down approach for the fabrication of tetrahedral DNA nanostructure (TDN)-NanoGold substrates through the hierarchical integration of three functional constituents at various length-scales: a macroscale glass slide, sub-microscale self-organized NanoGold, and nanoscale self-assembled TDN. The TDN-NanoGold substrates were then assembled with microfluidic chaotic mixers to give TDN-NanoGold Click Chips. In conjunction with the use of copper (Cu)-catalyzed azide-alkyne cycloaddition (CuAAC)-mediated CTC capture and restriction enzyme-triggered CTC release, TDN-NanoGold Click Chips allow for effective enumeration and purification of CTCs with intact cell morphologies and preserved molecular integrity. To evaluate the clinical utility of TDN-NanoGold Click Chips, we used these devices to isolate and purify CTCs from patients with human papillomavirus (HPV)-positive (+) head and neck squamous cell carcinoma (HNSCC). The purified HPV(+) HNSCC CTCs were then subjected to RT-ddPCR testing, allowing for detection of E6/E7 oncogenes, the characteristic molecular signatures of HPV(+) HNSCC. We found that the resulting HPV(+) HNSCC CTC counts and E6/E7 transcript copy numbers are correlated with the treatment responses in the patients, suggesting the potential clinical utility of TDN-NanoGold Click Chips for non-invasive diagnostic applications of HPV(+) HNSCC.

High-grade tumor budding is a risk factor for survival in patients with laryngeal squamous cell carcinoma

Abstract Objective: With the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods: 268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. Results: Tumor budding was divided into low-grade tumor budding (0-6/0.785mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1 -6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. Conclusions: Smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of Evidence: Level 4.

High-grade tumor budding is a risk factor for survival in patients with laryngeal squamous cell carcinoma.

OBJECTIVE: With the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. METHODS: 268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. RESULTS: Tumor budding was divided into low-grade tumor budding (0-6/0.785 mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1-6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. CONCLUSIONS: Smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. LEVEL OF EVIDENCE: Level 4.

Neoadjuvant Camrelizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone for Chinese Patients With Resectable Stage IIIA or IIIB (T3N2) Non-Small Cell Lung Cancer: The TD-FOREKNOW Randomized Clinical Trial.

Importance: The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. Objective: To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. Design, Setting, and Participants: In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Interventions: Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. Main Outcomes and Measures: The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Results: Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. Conclusions and Relevance: This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04338620.

Ceruminous adenoma of the external auditory canal: 9 cases series with imaging and pathologic findings.

Objectives: Ceruminous adenoma is a rare benign tumor of the external auditory canal. This study aimed to present the clinical characteristics, imaging findings, pathological results and the management outcomes of the ceruminous adenoma. Study design: Retrospective case series review. Setting: Tertiary referral center. Patients and methods: Patients undergoing surgery for ceruminous adenoma of the external auditory canal between the years 2004 to 2018. All patients with ceruminous adenoma were analyzed for demographic, clinical, radiological features and pathologic findings. The outcomes of the management were also evaluated. Results: Nine patients with ceruminous adenoma were included in the study. Hearing loss was the most common complaint (5/9, 56%), followed by otalgia (4/9, 44%), pruritus (4/9, 44%), and otorrhea (2/9, 22%). The tumors originated mostly from the cartilaginous portion of the external auditory canal (8/9, 89%) and merely from the bony portion of the external auditory canal (1/9, 11%). Pathohistological study indicated that the ceruminous adenomas were divided into three types: the ceruminous gland adenoma (6/9, 67%), the ceruminous pleomorphic adenoma (2/9, 22%) and the ceruminous syringocystadenoma papilliferum (1/9, 11%). No recurrence was found during follow-up for two to fifteen years after surgical resection. Conclusion: Ceruminous adenomas are rare entities. They originate mainly from the cartilaginous portion of the EAC, but occasionally from the bony portion of the EAC. The surgical section with enough margin is adequate for management of these tumors.

JMJD6 functions as an oncogene and is associated with poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high prevalence and poor prognosis. It is an urgent problem to deeply understand the molecular mechanism of ESCC and develop effective diagnostic and prognostic methods. METHODS: Using tumor tissue and corresponding paracancerous samples from 141 resected ESCC patients, we assessed Jumonji domain-containing protein 6 (JMJD6) expression using Immunohistochemical (IHC) staining. Kaplan-Meier survival analysis and univariate or multivariate analysis were used to investigate the relationship between JMJD6 expression and clinicopathological features. The expression status and prognostic value of JMJD6 were analyzed by bioinformatics and enrichment analysis. RESULTS: The expression of JMJD6 in ESCC samples was higher than that in the corresponding paracancerous samples, and high expression of JMJD6 was positively associated with poor prognosis of ESCC patients. In addition, bioinformatics analysis of the expression and prognosis of JMJD6 in a variety of tumors showed that high expression of JMJD6 was significantly associated with poor overall survival (OS) in ESCC patients. Enrichment analysis indicated that the high expression of genes similar to JMJD6, such as Conserved oligomeric Golgi 1(COG1), Major facilitator superfamily domain 11 (MFSD11) and Death Effector Domain Containing 2 (DEDD2), was associated with poor prognosis of ESCC, suggesting that JMJD6 might be involved in the occurrence and prognosis of ESCC. CONCLUSION: Our study found that JMJD6 expression was significantly increased in ESCC patients and positively correlated with prognosis, indicating that targeting JMJD6 might be an attractive prognostic biomarker and provides a potential treatment strategy for ESCC. TRIAL REGISTRATION: The study was approved by Tangdu Hospital ethics committee (No. TDLL-202110-02).

Angiectatic nasal polyps with pleomorphism ‒ a diagnostic pitfall.

OBJECTIVE: To generalise the features of PANP in case of potential clinical and pathological pitfall of diagnosis. METHODS: Thirteen patients diagnosed as PANP were retrospectively analyzed in the Pathology Department of Capital Medical University from August 2014 to December 2019. Immunohistochemical staining with CD34, CK, Vim, Calponin, Ki67, Bcl-2, and STAT-6 was performed with envision-two steps method. RESULTS: PANP is a benign tumor presenting with gross variegated tan to gray soft fleshy tissue with foci of obvious hemorrhage and necrosis. The imaging shows internal heterogeneous hyperintensity with a peripheral hypointense rim while postcontrast images display a strong nodular and patchy enhancement. Vimentin (Vim) stain was consistently positive, while negative for CD34, STAT-6 and Bcl-2 (focal positive in two cases). Calponin and CK stain was positive in nine cases, respectively. CONCLUSION: PANP is a clinically rare tumor which may simulate malignancy lesion. Recognizing of characteristic features in these thirteen patients would be beneficial to avoid misdiagnosis and unnecessary aggressive treatment. LEVEL OF EVIDENCE: This work was Level 2 of evidence according to the Guide for Authors.

Development and validation of a MUC16 mutation-associated immune prognostic model for lung adenocarcinoma.

Mucin 16 (MUC16) mutation ranks third among all common mutations in lung adenocarcinoma (LUAD), and it has a certain effect on LUAD development and prognostic outcome. This research aimed to analyze the effects of MUC16 mutation on LUAD immunophenotype regulation and determine the prognostic outcome using an immune prognostic model (IPM) built with immune-related genes. The MUC16 mutation status and mRNA expression profiles were analyzed using diverse platforms and among several LUAD patients (n = 691). An IPM was then constructed using differentially expressed immune-related genes (DEIRGs) in MUC16MUT LUAD cases, and the data were compared with those of MUC16WT LUAD cases. The IPM's performance in distinguishing high-risk cases from low-risk ones among 691 LUAD cases was verified. Additionally, a nomogram was built and applied in the clinical setting. Furthermore, a comprehensive IPM-based analysis of how MUC16 mutation affected the tumor immune microenvironment (TIME) of LUAD was performed. MUC16 mutation decreased the immune response in LUAD. As revealed by functional annotation, the DEIRGs in the IPM were most significantly enriched in the humoral immune response function and the immune system disease pathway. Moreover, high-risk cases were associated with increased proportions of immature dendritic cells, neutrophils, and B-cells; enhanced type I interferon T-cell response; and increased expression of PD-1, CTLA-4, TIM-3, and LAG3 when compared with low-risk cases. MUC16 mutation shows potent association with TIME of LUAD. The as-constructed IPM displays high sensitivity to MUC16 mutation status and can be applied to discriminate high-risk LUAD cases from low-risk ones.

Orbital primary solitary fibrous tumor: a proposed recurrence risk prediction model based on 92 cases.

Orbital primary solitary fibrous tumors (OPSFTs) are rare. To further characterize the clinical and pathological features of OPSFTs, 92 cases of OPSFT were analyzed to develop a risk prediction model. OPSFTs were equally distributed between males (n = 45) and females (n = 47) with a mean patient age of 40.8 years (median 39 years; range 5-70 years) at initial diagnosis. The mean tumor size was 2.79 cm (median 2.5 cm). Microscopically, the tumor cells were irregularly arranged in spindle, ovoid, or round shapes with varying amounts of collagen and branching blood vessels. Immunohistochemical staining showed positive STAT6 nuclear expression in all cases, loss of CD34 expression in seven cases, and a mean Ki-67 label index of 5.25% (range 1%-30%). All patients were initially surgically resected and had a median follow-up of 99 months: 33 patients recurred, 6 of whom presented with multiple recurrences and 1 with distant metastases. A predictive model for the risk of recurrence based on tumor size, mitosis, Ki-67 label index, and dominant constituent cell (DCC) was developed based on our results. In conclusion, OPSFTs are rare but can be reliably diagnosed based on characteristic morphological features and STAT6 immunohistochemistry. The rate of local recurrence of orbital tumors tends to be higher than the rate of distant metastases, which can be predicted by a risk stratification model specific to orbital tumors. Long-term clinical follow-up is recommended as advanced disease is common.

Primary signet­ring cell melanoma of the anorectum: A case report.

Malignant melanoma is one of the most common malignant tumors. Although its incidence rate is generally low among the Chinese population, it has grown rapidly in recent years. The incidence of primary malignant melanoma in the digestive tract is very low. The incidence in the esophagus and rectum are more common, while reports in the colon are only reported in <10 cases. Primary signet ring cell carcinoma of the rectum is also a rare and unique tumor. This paper reports a case of rectal malignant melanoma with signet ring cell carcinoma.

The Novel Circular RNA circTRIO Silence Inhibits the Progression of Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is the most common and prevalent malignant tumor in head and neck squamous cell carcinoma. Recent studies have shown that circular RNAs (circRNAs) play a vital role in cancer development, but their specific role in the tumorigenesis and development of LSCC remains unclear. We selected five pairs of LSCC tumor tissues and paracancerous tissues for RNA sequencing. Reverse transcription-quantitative PCR (RT-qPCR), Sanger sequencing, and fluorescence in situ hybridization were utilized to study the expression, localization, and clinical significance of circTRIO in LSCC tissues, and TU212 and TU686 cell lines. Furthermore, cell counting Kit-8, colony-forming assay, Transwell, and flow cytometry assays were assessed to illustrate the crucial role played by the circTRIO in proliferation, colony-forming ability, migration, and apoptosis in LSCC cells. Finally, the molecule's role as a microRNA (miRNA) sponge was analyzed. In the results, we screened out a promising upregulated novel circRNA-circTRIO in LSCC tumor tissues compared with paracancerous tissues using RNA sequencing. Then, we used qPCR to evaluate the expression of circTRIO in 20 additional paired LSCC tissues and two cells, and the results showed that circTRIO was highly expressed in LSCC and that this high expression was closely related to the malignant progression of LSCC. Furthermore, we examined circTRIO expression in the Gene Expression Omnibus data sets GSE142083 and GSE27020, and circTRIO expression was considerably higher in tumor tissues compared with the adjacent tissues. Kaplan-Meier survival analysis showed that the expression of circTRIO was associated with worse disease-free survival. The Gene Set Enrichment Analysis biological pathway evaluation results demonstrated that circTRIO was mainly enriched in cancer pathways. Moreover, we confirmed that silencing circTRIOs can help to significantly inhibit LSCC cell proliferation and migration while triggering apoptosis. Upregulated circTRIO expression levels may play an important role in the tumorigenesis and development of LSCC.

Bispecific anti-CD3×anti-CD155 antibody mediates T-cell immunotherapy in human haematologic malignancies.

T cells are important components in the cell-mediated antitumour response. In recent years, bispecific antibodies (Bi-Abs) have become promising treatments because of their ability to recruit T cells that kill tumours. Here, we demonstrate that CD155 is expressed in a wide range of human haematologic tumours and report on the ability of the bispecific antibody anti-CD3 x anti-CD155 (CD155Bi-Ab) to activate T cells targeting malignant haematologic cells. The specific cytolytic effect of T cells armed with CD155Bi-Ab was evaluated by quantitative luciferase assay, and the results showed that the cytolytic effect of these cells was accompanied by an increase in the level of the cell-killing mediator perforin. Moreover, compared with their unarmed T-cell counterparts, CD155Bi-Ab-armed T cells induced significant cytotoxicity in CD155-positive haematologic tumour cells, as indicated by lactate dehydrogenase assays, and these results were accompanied by increased granzyme B secretion. Furthermore, CD155Bi-Ab-armed T cells produced more T-cell-derived cytokines, including TNF-α, IFN-γ, and IL-2. In conclusion, CD155Bi-Ab enhances the ability of T cells to kill haematologic tumour cells, and therefore, CD155 may serve as a novel target for immunotherapy against haematologic malignancies.

A Familial Case of Multiple Endocrine Neoplasia 2A: From Morphology to Genetic Alterations Penetration in Three Generations of a Family.

This paper illustrates a rare syndrome of multiple endocrine neoplasia type 2A (MEN2A) in a family of three generations. In our case, the father, son and one daughter developed phaeochromocytoma (PHEO) and medullary thyroid carcinoma (MTC) over a period of 35 years. Because of the metachronous onset of the disease and lack of digital medical records in the past, the syndrome was not found until a recent fine needle aspiration of an MTC-metastasized lymph node from the son. All resected tumors from the family members were then reviewed and supplemented with immunohistochemical studies, previously wrong diagnoses were then corrected. Further molecular study of targeted sequencing also revealed a RET germline mutation (C634G) in the family tree including the three members with onset of the disease and one granddaughter who had no disease at the time of testing. Despite the syndrome being well-known, it may still be misdiagnosed because of its rarity and long disease onset. A few lessons can be learned from this unique case. Successful diagnosis requires high suspicion and surveillance and a tri-level methodology including a careful review of family history, pathology and genetic counselling.

Prognostic significance of PD-1, CTLA-4, CD4, and CD8 expression in olfactory neuroblastoma.

There are limited data regarding immune surveillance mechanisms in olfactory neuroblastoma. We investigated the expression of programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD4, and CD8 in olfactory neuroblastoma to identify potential therapeutic targets. Immunohistochemistry was used to detect PD-1 and CTLA-4 and measure the numbers of CD4+ and CD8+ T cells in 56 patients with olfactory neuroblastoma. The relationships between these molecules in tumor microenvironment, clinicopathological features, and survival were analyzed. The prevalence of PD-1 in Kadish C stage was 24.14%, significantly greater than in Kadish A and B stage. CD4+ T-cell and CD8+ T-cell levels correlated with higher Hyams histological grade and Kadish stage. In addition, PD-1 was related positively with CTLA-4, CD4+ T cells, and CD8+ T cells in olfactory neuroblastoma. Univariate survival analysis showed that higher PD-1 positivity, CD8+ T cells, and Hyams grade correlated with worse clinical outcome. Multivariate analysis showed that the expression of PD-1 was an independent parameter for poor prognosis. In conclusion, olfactory neuroblastoma with PD-1 expression had more aggressive clinicopathological features and worse prognosis. PD-1 may potentially predict the outcome of olfactory neuroblastoma patients.

A Nomogram Model for Predicting the Postoperative Recurrence of Localized Laryngeal Amyloidosis.

OBJECTIVE: To analyze the factors related to postoperative recurrence in patients with localized laryngeal amyloidosis (LocLA) and to construct a nomogram prediction model (NPM). METHODS: We collected the data for LocLA patients diagnosed from March 2000 to May 2019 and clinical characteristics data were extracted. Factors related to recurrence were analyzed using multivariate logistic regression. The NPM was constructed for predicting the recurrence risk of LocLA. The receiver operating characteristic (ROC) curve evaluated the distinguishing ability using the area under curve (AUC). The calibration curve was created to evaluate the consistency of the NPM. RESULTS: A total of 226 confirmed LocLA cases were included. One hundred seventy-five cases (77.4%) had localized single nodule, and 51 cases had more than one lesions. Sixty-three (27.9%) cases had no multinucleated giant cell (MGC) around amyloid, and 163 (72.1%) cases had MGC around amyloid. Multivariate logistic regression analysis showed that more than one lesions (odds ratio [OR] = 3.206 and 95% confidence interval [CI]: 1.492-6.888; P value: .003), subglottic involvement (OR = 2.926 and 95% CI: 1.300-6.585; P = .010), and no multinucleated giant cell (MGC) around amyloid (OR = 2.503 and 95% CI: 1.173-5.342; P = .018) had a statistically significant effect on postoperative LocLA recurrence (P < .05). The AUC of the ROC curve was 0.753 (95% CI: 0.667-0.832). The bias-corrected curve approached the ideal curve, with an average absolute error of 0.037. CONCLUSIONS: More than one lesions, subglottic involvement, and no MGC around amyloid are risk factors for postoperative recurrence of LocLA. The NPM constructed has good applicability.

Angiectatic nasal polyps with pleomorphism ‒ a diagnostic pitfall

Abstract Objective To generalise the features of PANP in case of potential clinical and pathological pitfall of diagnosis. Methods Thirteen patients diagnosed as PANP were retrospectively analyzed in the Pathology Department of Capital Medical University from August 2014 to December 2019. Immunohistochemical staining with CD34, CK, Vim, Calponin, Ki67, Bcl-2, and STAT-6 was performed with envision-two steps method. Results PANP is a benign tumor presenting with gross variegated tan to gray soft fleshy tissue with foci of obvious hemorrhage and necrosis. The imaging shows internal heterogeneous hyperintensity with a peripheral hypointense rim while postcontrast images display a strong nodular and patchy enhancement. Vimentin (Vim) stain was consistently positive, while negative for CD34, STAT-6 and Bcl-2 (focal positive in two cases). Calponin and CK stain was positive in nine cases, respectively. Conclusion PANP is a clinically rare tumor which may simulate malignancy lesion. Recognizing of characteristic features in these thirteen patients would be beneficial to avoid misdiagnosis and unnecessary aggressive treatment. Level of evidence: This work was Level 2 of evidence according to the Guide for Authors.