Comparison between spleen and liver stiffness measurements by sound touch elastography for diagnosing cirrhosis at different aminotransferase levels: a prospective multicenter study.

OBJECTIVES: To compare the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by sound touch elastography (STE) for the diagnosis of cirrhosis at different alanine aminotransferase (ALT) levels, and to compare the applicability and repeatability of SSM with LSM performed by STE, a new two-dimensional shear wave elastography technology. METHODS: This prospective multicenter study included 25 centers and recruited chronic hepatitis B (CHB) patients with liver biopsy between May 2018 and November 2019. All patients underwent LSM and SSM by STE. Success and reliability rates were calculated and compared. Intra-observer agreement was assessed using intraclass correlation coefficients (ICCs). Differences between areas under the receiver operating characteristic curves (AUCs) of LSMs and SSMs at different ALT levels were compared using the Delong test. RESULTS: Among 603 CHB patients, the success and reliability rates of SSM were 94.53% (570/603) and 85.74% (517/603), respectively, which were similar to those of LSM (p > 0.05), respectively. The ICC for intra-observer agreements of SSM was 0.964 (p < 0.001). In the total cohort, ALT ≤ 2 × upper limit of normal (ULN) group, and A0-1 group, the AUCs of SSMs were significantly lower than those of LSMs for the diagnosis of cirrhosis (p < 0.001). In the ALT > 2 × ULN group and A2-3 group, the AUC of SSM improved and was not significantly different from that of LSM (p = 0.342, p = 0.510, respectively). CONCLUSIONS: SSM by STE achieved applicability and repeatability equivalent to those of LSM. SSM might be a good substitute to LSM in patients with high ALT levels. KEY POINTS: • Spleen stiffness measurement performed by sound touch elastography was proven to have similar applicability and repeatability to liver stiffness measurement in this prospective multicenter study. • Spleen stiffness measurement demonstrated a poorer diagnostic performance for cirrhosis compared with liver stiffness measurement in the total cohort and low ALT level group, yet it showed a similar diagnostic performance to liver stiffness measurement in patients with high ALT levels.

[Change of T lymphocyte subsets, interleukin-2 and tumor necrosis factor-alpha in tumor-bearing mice and patients with oral cancer receiving thermo-chemotherapy].

OBJECTIVE: To investigate the change of T lymphocyte subsets, interleukin (IL)-2 and tumor necrosis factor (TNF)-alpha in the tumor- bearing mice and patients with oral cancer receiving thermo-chemotherapy, and investigate the correlation among them. METHODS: After treatments, the expression of lymphocyte transformation index (LTI), IL-2 and TNF-alpha in the tumor-bearing mice were detected with methyl thiazolyl tetrazolium (MTT), the expression of IL-2 and TNF-alpha in the patients with oral cancer were detected with MTT, the expression of LTI, CD4+ and CD8+ were detected with 3H-TdR incorporation. RESULTS: LTI, IL-2 and TNF-alpha of thermo-chemotherapy group (HP group) had no significant difference comparing with those of normal mice group (N group) (P>0.05), but which were significantly higher than those of chemotherapy group (P group) and no treatment group (NT group) (P<0.01). In clinical trials, the expression of LTI, CD4+, CD4+/CD8+, IL-2 and TNF-alpha on oral cancer patients after thermo-chemotherapy were significantly higher than those before thermo-chemotherapy (P<0.01). CONCLUSION: After thermo-chemotherapy, the expression of LTI, IL-2 and TNF-alpha of tumor-bearing hosts are significantly improved, there is a significant correlation between IL-2 and T cell.

Thermochemotherapy of lower lip squamous cell carcinoma without metastases: an experience of 31 cases.

INTRODUCTION: The aim of this study was to evaluate the efficacy, functional and aesthetic results, and safety of a novel treatment, thermochemotherapy, for lower lip squamous cell carcinoma (LLSCC) without metastases. PATIENTS AND METHODS: A combination of local hyperthermia delivered by a 915MHz microwave heating system and the chemotherapy of pingyangmycin (bleomycin A(5) hydrochloride) (PYM) and methotrexate (MTX), was administered to 31 patients of LLSCC twice per week for a period of 4.5-7.5 weeks. Patients with complete response (CR) have been followed up for a full five-year period, whereas partial response (PR) patients were excluded for further analysis. The local control of tumour, functional and cosmetic outcomes, recurrence, regional lymph node and distant metastases, and complications were assessed by clinical and imaging examination. RESULTS: Clinical CR was observed in twenty-nine (93.55%) patients and PR in two (6.45%), the total response rate was 100%, while the adverse effects were extremely minimal and tolerable in all 31 patients including 6 elderly patients with a compromised general condition. All 29 CR, including 8 extensive lesions, achieved excellent cosmetic and functional preservation. During the follow-up period, local relapse was seen in 1 case, 1 patient died, and the remainder obtained a complete remission. CONCLUSION: This clinical study suggests that thermochemotherapy may be a feasible treatment for primary LLSCC without cervical metastases, especially for patients with extensive lesions and a compromised general condition.

Hypoxia inducible factor-alpha expression correlates with vascular endothelial growth factor-C expression and lymphangiogenesis/angiogenesis in oral squamous cell carcinoma.

BACKGROUND: The number of blood vessels correlates with metastasis in solid tumors, including oral squamous cell carcinoma (OSCC). Hypoxia inducible factor-1alpha (HIF-1alpha) could play a role in tumor lymphangiogenesis by regulating the lymphatic expression of vascular endothelial growth factor-C (VEGF-C). HIF-1alpha protein expression, VEGF-C protein expression, lymphatic vessel density (LVD) and blood vessel density (BVD) in OSCC were investigated. MATERIALS AND METHODS: HIF-1alpha and VEGF-C protein expression were investigated by means of immunohistochemistry in samples from 65 cases of OSCC. The density of the lymphatic microvessels and blood microvessels immunohistochemically stained by LYVE-1 and CD34 antibody, respectively, was calculated. The association between the HIF-1alpha expression and the clinicopathological parameters was evaluated. RESULTS: HIF-1alpha overexpression occurred in 43 out of the 65 tumor samples (66.2%), while VEGF-C overexpression was observed in 34 out of the 65 tumor samples (52.3%). Higher LVD was found in both high HIF-1alpha and high VEGF-C expression cases. HIF-1alpha overexpression was significantly correlated with VEGF-C overexpression (p = .018, Chi-square test), higher LVD (p < 0.001, Mann-Whitney U-test), and regional lymph nodal involvement (p = 0.004, Chi-square test) as well as UICC TMN classification (p = 0.043, Chi-square test), respectively. In addition, higher BVD existed in the high HIF-1alpha and VEGF-C expression groups (p < 0.001, Mann-Whitney U-test). CONCLUSION: HIF-1alpha might play a crucial role in regional lymph node metastasis as a regulator of lymphangiogenesis and angiogenesis in OSCC with a possible novel pathway involving VEGF-C. Therefore, HIF-1alpha might be a particularly promising target for controlling regional lymph node metastases by a combination of antiangiogenic and anti-lymphangiogenic effects in OSCC.

RNAi-mediated downregulation of urokinase plasminogen activator receptor inhibits proliferation, adhesion, migration and invasion in oral cancer cells.

RNA interference (RNAi) has emerged as an effective method to target specific genes for silencing. Overexpression of urokinase-type plasminogen activator receptor (uPAR) has been implicated in progression and metastasis of oral cancer. In our study, RNAi was introduced to downregulate the expression of uPAR in the highly malignant oral squamous cell carcinoma (OSCC) cells. Our data demonstrated that siRNA targeting of uPAR leads to the efficient and specific inhibition of endogenous uPAR mRNA and protein expression as determined by quantitative real-time RT-PCR and Western blotting. Furthermore, simultaneous silencing of uPAR resulted in a dramatic reduction of tumor cell proliferation activity, adhesion, migration and invasion in vitro compared to the controls. These findings provide further evidence for the involvement of uPAR in a variety of cancer key cellular events as a versatile signaling orchestrator, and suggest that RNAi-directed targeting of uPAR can be used as a potent and specific therapeutic tool for the treatment of oral cancer, especially in inhibiting and/or preventing cancer cell invasion and metastasis.

[Influence of thermochemotherapy on the activity of cytotoxic T lymphocyte in oral maxillofacial cancer patients].

OBJECTIVE: To study the influence of thermochemotherapy on the activity of cytotoxic T lymphocyte (CTL) in peripheral blood of patients with oral maxillofacial cancer. METHODS: Twenty-one subjects with oral maxillofacial cancer were treated by thermochemotherapy, and the activity of CTL in peripheral blood was analyzed. RESULTS: Thermochemotherapy can obviously enhance the activity of CTL (P<0.01). CONCLUSION: Thermochemotherapy can enhance the activity of CTL, thus enhance the patient's immune function. Therefore, it can enhance the antitumor response in whole body.

[Relationship between nuclear factor kappa B signal transduction way and the sensitivity of tongue carcinoma cell to Pingyangmycin chemotherapy].

OBJECTIVE: To examine the relationship between NF-kappaB signal transduction way and the sensitivity of Tca8113 carcinoma cell to Pingyangmycin chemotherapy. METHODS: 2 mg/L antisense p65 oligodeoxynucle-otides (5'-GAACAGTTCGTCCATGGCCG-3') was transfected into Tca8113 cells through Lepofectin vectin, then the cells were treated with 8 mg/L Pingyangmycin. After 3 h and 6 h, the expression of p65 in nucleus was studied with immunohistochemical methods and Western blot analyses. After 48 h, the inhibitory rate of cell growth was detected with MTT assay. RESULTS: The NF-kappaB/p65 signal transduction way in Tca8113 cells was activated after treated with Pingyangmycin. But the transfection of antisense p65 oligodeoxynucle-otides inhibited the activation of the signal transduction, the p65 expression in nucleus was decreased significantly (P < 0.05) at 6 h, and the inhibitory rate of cell growth was increased significantly (P < 0.05) at 48 h. CONCLUSION: The results suggested the chemotherapeutic sensitivity of Tca8113 carcinoma cell to Pingyangmycin was improved by the inhibition of NF-kappaB/p65 signal transduction.

[High expression of p65 transcription factor and its significance in tongue carcinoma].

OBJECTIVE: To examine the correlation between p65 expression and the metastasis and prognosis in tongue carcinoma. METHODS: The immunohistochemical expression of p65 was examined in 50 cases of tongue carcinoma, and the clinical and histopathologic records were retrospectively analyzed. RESULTS: Overexpression of p65 in cytoplasma and nucleus was found in 64% cases of tongue carcinoma. There was significant difference of p65 expression among different TNM stages, and the higher expression rate of p65 was found in higher stages. Overexpression of p65 was also related to lymph node metastasis. Significantly greater increase in expression levels of p65 was found in the metastatic cases (n = 22) compared to the nonmetastatic cases (n = 10). However, there was no significant difference of p65 expression among different histopathologic grading. The 5-year survival rate of p65 positive and negative group was 59.3% and 88.9% respectively, and there was significant difference in Kaplan-Meier survival curve (chi2 = 5.6, P < 0.05). CONCLUSION: The results suggest that the expression of p65 was important to predict the metastasis and prognosis in tongue carcinoma.

[Effect of hypoxia on the expression of urokinase-type plasminogen activator in human tongue squamous cell carcinoma cells (Tca8113)].

OBJECTIVE: To observe the expression of urokinase-type plasminogen activator (uPA) in human tongue squamous carcinoma cells (Tca8113) under hypoxia, in order to explore the relation between hypoxia and invasion and metastasis of oral cancer. METHODS: Under different hypoxic times(0, 3, 6, 12, 24 h), the expression of uPA protein was examined quantitatively using immunohistochemical technique (IH) and flow cytometry (FCM). RESULTS: Hypoxia promoted the expression of uPA. The longer hypoxic time was, the higher expression of uPA was. CONCLUSION: Hypoxia can promote invasion and metastasis of oral squamous carcinoma through stimulating the expression of uPA.

[Effects of thermochemotherapy on immunologic function of patients with lip cancer].

OBJECTIVE: To evaluate the effects of thermochemotherapy on the immunologic function of lip cancer patients and to provide a theoretical basis for the clinical application of thermochemotherapy. METHODS: Twenty patients were heated by microwave at (42.5 +/- 0.2) degree C for 40 minutes after venoclysis of Pingyangmycin (8 mg) and Methotrexate (20 mg). Each of the patients received the therapy twice a week for 5 weeks. Venous blood was obtained before the first thermochemotherapy and after the tenth thermochemotherapy. Lymphocyte transformation index was examined by 3H-TdR method, and CD4+ and CD8+ T cells were assayed by flow cytometry. RESULTS: The tumors of the 20 patients were completely extinctive. The lymphocyte transformation index after treatment was significantly higher than that before treatment (P < 0.01). The CD4+ T cells and CD4+/CD8+ after treatment were significantly higher than those before treatment (P < 0.05); the CD8+ T cells after treatment was lower than that before treatment, but there was no statistically significant difference (P > 0.05). CONCLUSION: Thermochemotherapy can enhance the lip cancer patient's T lymphocyte immunologic function, which possibly plays an important role in the treatment of lip cancer.

[Effect of microwave thermocoagulation on oral benign tumor].

OBJECTIVE: The purpose of this article was to observe the effect of by microwave thermocoagulation on oral benign tumor and to provide theoretical basis for clinic treatment of oral benign tumor. METHODS: 165 patients with oral benign tumor were included. There were 83 patients with oral bursa cyst, 42 patients with hemangioma, 19 patients with papilloma, 14 patients with fibrous hyperplasia and 7 patients with epulis. All the patients were treated by WB-100 microwave thermocoagulation. RESULTS: 144 patients were effective after the first treatment and 21 patients were effective after the second treatments. No side effect and reoccurrence were found after 3 years. CONCLUSION: Microwave thermocoagulation is an effective and safe method in clinic treatment of oral benign tumor.

[The expression of urokinase-type plasminogen activator in oral squamous cell carcinoma].

OBJECTIVE: The aim of this study was to reveal the relations between expression and tumor behavior such as invasion, metastasis and prognosis in oral squamous cell carcinoma (SCC) through analyzing the expression of urokinase-type plasminogen activator (UPA). METHODS: With Labelled streptavidin biotin method (LsAB), the expression of UPA was analyzed in 80 cases of oral squamous cell carcinoma, 10 cases of oral normal mucosa and 10 cases of oral leukoplakia. RESULTS: Compared to oral normal mucosa and oral leukoplakia, the expression of UPA was significantly higher in SCC. The expression of UPA in SCC cases with lymph node metastasis was significantly higher than in cases without metastasis. The expression in cases with good prognosis was significantly higher than in those with poor prognosis and the expression was significantly higher in cases with invasive growth than in those with ulcerative and papillary growth. CONCLUSION: The results obtained indicated that high expression of UPA in SCC might be closely related to lymph node metastasis, invasive growth and poor prognosis.

[The effect of heat shock on the expression of urokinase-type plasminogen activator in human tongue squamous cell carcinoma cell line (Tca8113)].

OBJECTIVE: The aim of this study was to observe the expression of urokinase-type plasminogen activator (UPA) in human tongue squamous cell carcinoma cell line (Tca8113) after heat shock with different dosage. METHODS: The expression of UPA protein of Tca8113 after different heating temperatures(37 degrees C, 40 degrees C, 43 degrees C and 45 degrees C) treatment was examined by immunohistochemical technique (IH) and flow cytometry (FCM). RESULTS: Compared with 37 degrees C group, the UPA protein expression in 40 degrees C and 43 degrees C groups decreased significantly (P < 0.05); however, the UPA protein expression in 45 degrees C group decreased but no statistical difference was found. CONCLUSION: Hyperthermia could inhibit invasion and metastasis of oral squamous cell carcinoma and could be considered as a safe method in curing the tumor.