Recent advances in patient-derived tumor organoids for reconstructing TME of head and neck cancer.

BACKGROUND: The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient-derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine. METHODS: We conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient-derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions. RESULTS: In tumor development, the interaction between cellular and non-cellular components in the tumor microenvironment (TME) has a crucial role. Co-culture, Air-liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis. CONCLUSION: An accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer.

Refractory pneumoparotid in children: a case report and literature review / 口腔疾病防治

Objective @#To discuss the treatment of pneumoparotid and to provide a reference for clinical practice. @*Methods@# A case of refractory pneumoparotid was reported, and the diagnosis and treatment of parotid emphysema were reviewed and analyzed in combination with the literature.@*Results @#This child had parotid gland enlargement without any obvious cause for more than 1 month. Conservative treatment, such as anti-inflammatory agents, psychological interventions and physical compression were ineffective. The patient had a history of cerebral palsy with epilepsy and involuntary cheek bulging behavior. Therefore, we considered it a refractory case. It was cured after parotid duct ligation and partial parotidectomy of the superficial lobe. A literature review showed that a pneumoparotid is a rare parotid enlargement. Most of the clinical cases were considered to be caused by the return of air into the parotid gland through the parotid duct due to an increase in oral pressure. The diagnosis of pneumoparotid mainly depends on intermittent parotid gland swelling and other clinical manifestations and imaging examination methods, such as ultrasound, CT, MRI and angiography. Its treatment mainly includes conservative anti-inflammatory treatment, physical therapy and psychological intervention. Surgical treatment is indicated for refractory parotid emphysema.@*Conclusion@# Pneumoparotid cases may further develop into parotid inflammation, which is generally treated conservatively. For some severe, recurrent and poor compliance cases, surgical treatment is sometimes needed.

Parotid duct anastomosis with an epidural catheter as a stent and evaluation of postoperative gland function / 口腔疾病防治

Objective @#To investigate the feasibility of epidural catheters in parotid gland duct anastomosis and the function of the affected side gland after parotid gland duct anastomosis. @* Methods@# Thirteen patients who were treated in the Department of Oral and Maxillofacial Surgery of Xuzhou Central Hospital using an epidural catheter as the scaffold for parotid gland catheter anastomosis were enrolled from Jan. 2019 to June 2021. The swelling, salivary fistula and catheter patency in the parotid gland area were evaluated two weeks after the operation. 99mTcO4- single photon emission computed tomography (SPECT) was used for quantitative detection of salivary gland secretion function@*Results@# Thirteen patients had no swelling or salivary fistula in the parotid gland area of the affected side two weeks after the operation, and the catheter secretion was unobstructed. There was no significant difference in the uptake rate between the parotid gland on the affected side and the parotid gland on the healthy side (t = -0.859, P = 0.399), and there was no significant difference in the excretion rate between the parotid gland on the affected side and the parotid gland on the healthy side (t = 0.693, P = 0.495). The parotid gland excretion function of the affected side was excellent three months after the operation.@*Conclusion @#Parotid duct anastomosis with an epidural catheter as the stent has good feasibility, and parotid gland secretion function recovers well after the operation, which is worthy of clinical application.

Effect of tension on recovery of the donor site of a modified forearm flap / 口腔疾病防治

Objective @#To investigate the effect of tension on donor site recovery of modified forearm flaps (closed forearm donor site skin flaps).@*Methods @# From October 2018 to April 2021, 12 patients with oral cancer underwent forearm flap repair at Xuzhou Central Hospital. Handgrip strength and wrist motion were recorded before surgery. During the surgical incision at the donor site of the forearm, the triangular full-thickness skin of the donor site was used to close part of the surgical incision, and the other part of the surgical incision was directly closed and sutured. Tension was measured with a tension meter during the surgical incision at the donor site. Patients were followed up after surgery to observe whether there were postoperative complications such as necrosis and poor healing of donor site wounds, as well as forearm grip strength, wrist range of motion and appearance satisfaction.@* Results@#Among the 12 patients, there was only one elderly patient with postoperative necrosis near the wrist in the donor site skin, and the average tension of the patient was 0.65 kg; the lesion healed after dressing changes. All of the other patients recovered well without postoperative complications. The mean tension of 12 patients was (0.51 ± 0.05) kg. The preoperative and postoperative grip strength of 12 patients was (23.7 ± 10.3) kg and (22.3 ± 10.7) kg, respectively, and the difference was not statistically significant (t=5.872, P<0.001). The mean range of motion of the wrist was (47.6 ± 8.3)°, (45.8 ± 5.8)°; dorsiflexion (54.6 ± 3.2)°, (53.9 ± 2.3)°; radial deviation (37.0 ± 2.3)°, (36.1 ± 2.2)°; ruler deviation (27.1 ± 1.9)°, (26.4 ± 1.3)°, respectively. The t values were 1.64, 1.636, 2.116 and 1.412, and the P values were 0.129, 0.130, 0.058 and 0.186, respectively. All 12 patients were satisfied with the appearance of the donor site of the forearm.@*Conclusion@#When the average tension during suturing is less than 0.5 kg, there is a lower risk of complications at the donor site of the forearm one month after surgery, a lower risk of impaired donor site function, and a greater possibility of patient satisfaction with the appearance of the donor site.

[Analysis of curative effect of ultrasonic hyperthermia combined with TPF chemotherapy on 19 elderly with advanced oral squamous cell carcinoma].

PURPOSE: To evaluate the efficacy and safety of ultrasound hyperthermia combined with TPF chemotherapy for advanced oral squamous cell carcinoma in the elderly. METHODS: Nineteen elderly patients who had definite pathological diagnosis were enrolled in this clinical trail from June 2017 to January 2020. Docetaxel (75 mg/m2) + cisplatin (75 mg/m2) were given on the 1st day , and 5,Fu (750 mg/m2) on the 1st to 5th day of the cycle. Five times of hyperthermia were performed in the course of chemotherapy, respectively on the l, 3, 5, 7 and 9 days after the beginning of chemotherapy. All patients received 2 cycles of thermo -chemotherapy. Statistical analysis was performed using SPSS 20.0 software package. Kaplan-Meire method was used to calculate survival rate. RESULTS: According to the efficacy evaluation standard for solid tumor (version 1.0), complete response (CR) was seen in 3 cases, partial response (PR) was seen in 10 cases, stable disease(SD) was seen in 5 cases，progressive disease(PD) was seen in 1 case. The overall responding rate was 68.4%. The median follow-up time was 36 months(8-48 months), and the 2-year overall survival rates were 63.2%. No serious adverse reactions were observed. CONCLUSIONS: Ultrasound hyperthermic therapy combined with chemotherapy has a synergistic anti-tumor effect on patients with advanced oral squamous cell carcinoma, which is safe and effective, and is worthy of becoming another choice of tumor treatment.

Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma.

Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets.

miR-448 downregulates MPPED2 to promote cancer proliferation and inhibit apoptosis in oral squamous cell carcinoma.

The incidence of oral squamous cell carcinoma (OSCC) is continuously increasing while its survival rate has not notably improved. There is a pressing need for improved understanding of the genetic regulation of OSCC tumorigenesis and progression. In this study, the function of miR-448 in the regulation of OSCC growth and its putative target were thoroughly analyzed in vitro. The expression of miR-448 was detected in human OSCC specimens and OSCC cell lines (Cal-27 and Scc-9) by reverse transcription-quantitative polymerase chain reaction. The function of miR-448 was investigated in Cal-27 cells transfected with miR-448 inhibitor, and its putative target determined using a luciferase reporter assay. MTT and wound healing assays and flow cytometry were used to evaluate the effects of miR-448 on OSCC proliferation, metastasis and apoptosis. The level of miR-448 was significantly elevated in human OSCC tissues and the Cal-27 cell line. Suppression of miR-448 expression attenuated cell proliferation and migration, and induced apoptosis of Cal-27 cells. Furthermore, miR-448 bound with the 3'-untranslated region of metallophosphoesterase domain containing 2 (MPPED2) mRNA, thereby reducing the MPPED2 protein level. Thus, it appears that miR-448 acts as a tumor inducer, causing OSCC growth by inhibiting the expression of its target MPPED2. These results demonstrate that miR-448 plays a critical role in OSCC tumorigenesis, and is a potential therapeutic target.

Differential mRNA expression profiling of oral squamous cell carcinoma by high-throughput RNA sequencing.

Differentially expressed genes are thought to regulate the development and progression of oral squamous cell carcinomas (OSCC). The purpose of this study was to screen differentially expressed mRNAs in OSCC and matched paraneoplastic normal tissues, and to explore the intrinsic mechanism of OSCC development and progression. We obtained the differentially expressed mRNA expression profiles in 10 pairs of fresh-frozen OSCC tissue specimens and matched paraneoplastic normal tissue specimens by high-throughput RNA sequencing. By using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, the functional significance of the differentially expressed genes were analyzed. We identified 1,120 significantly up-regulated mRNAs and 178 significantly down-regulated mRNAs in OSCC, compared to normal tissue. The differentially expressed mRNAs were involved in 20 biological processes and 68 signal pathways. Compared to adjacent normal tissue, the expression of MAGEA11 was up-regulated; TCHH was down-regulated. These findings were verified by real-time PCR. These differentially expressed mRNAs may function as oncogenes or tumor suppressors in the development and progression of OSCC. This study provides novel insights into OSCC. However, further work is needed to determine if these differentially expressed mRNAs have potential roles as diagnostic biomarkers and candidate therapeutic targets for OSCC.