Moyi Sun

Bleomycin A5 sclerotherapy for cervicofacial lymphatic malformations

OBJECTIVES The purpose of this study was to document the results of bleomycin A5 sclerotherapy for cervicofacial lymphatic malformations (LMs), and the clinical data of 65 patients between October 2004 and October 2007 were reviewed. METHODS Of the 65 patients in the study, 60 patients were given intralesional injection of bleomycin A5. Five patients underwent partial resection, and then an injection of bleomycin A5 for the remaining lesion. The outcomes were assessed by physical examination and Doppler ultrasonography scan. The follow-up time was from 6 months to 3 years after the last injection (mean, 16 months). RESULTS Among the 65 patients, 41 were men and 24 were women (1.7:1 male:female ratio), the age range was 3 months to 45 years (mean, 12 years). Thirty-two lesions (49%) were macrocystic, 30 (46%) were microcystic, and 3 (5%) were combined. Each patient received 1 to 10 injections (mean, 3.0 injections) for the whole course of treatment, and the total dose of bleomycin A5 was from 8 to 80 milligrams (mean, 24.0 mg). Twenty-six of 32 macrocystic lesions (81%) showed greater than 90% reduction, whereas another 6 (19%) exhibited 50% to 90% reduction. Nineteen of 30 microcystic lesions (63%) showed greater than 90% reduction; 10 (33%) had 50% to 90% reduction; and 1 (4%) had less than 50% size reduction. Of the 3 combined lesions, 2 (67%) had greater than 90% shrinkage, and 1 (3%) had less than 50% reduction. The complications included ulceration of oral mucosa, minor soft tissue atrophy, mild fever, and hematoma. There was no recurrence throughout the follow-up period. CONCLUSION These data suggest bleomycin A5 is a safe and effective intralesional agent for the treatment of macrocystic LMs, superficial oral mucosa LM, and localized deep microcystic lesions. For extensive macrocystic LMs involving contiguous anatomic areas and diffuse microcystic lesions involving deep tissues, bleomycin A5 injection combined with resection is necessary.

Inhibition of CD146 gene expression via RNA interference reduces in vitro perineural invasion on ACC-M cell

BACKGROUND Overexpression of melanoma cell adhesion molecule (MCAM or CD146), a novel member of the immunoglobulin gene superfamily, promotes invasion, metastasis, growth and survival of malignant cells. MATERIALS AND METHODS Here, we used a human U6 promoter-driven DNA template approach to induce short hairpin RNA (shRNA)-triggered RNA interference to block CD146 gene expression in the human high-metastatic adenoid cystic carcinoma (ACC) cell line ACC-M. reverse transcription-polymerase chain reaction, Western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, flow cytometry analysis and in vitro perineural invasion (PNI) assay were used to investigate the effects of CD146 on cell growth, cell cycle distribution and cell PNI activity in ACC-M cells. RESULTS We have demonstrated that different shRNAs can specifically knockdown the transcription of CD146, resulting in the inhibition of cell proliferation, and G(0)/G(1) to S phase arrest in ACC-M cells. Knockdown of CD146 by shRNA resulted in decrease of the ACC-M PNI activity in vitro. CONCLUSION These findings suggested that CD146 was an ACC-related gene and CD146 may play an important role in the carcinogenesis, progression and PNI activity of ACC.

Bleomycin A5 plus dexamethasone for control of growth in infantile parotid hemangiomas

OBJECTIVE The purpose of this study was to evaluate the efficacy of bleomycin A5 (pingyangmycin) plus dexamethasone for control of growth in infantile parotid hemangiomas. STUDY DESIGN We reviewed and analyzed the data of 31 cases undergoing therapy of intralesional injection with small-dosage and low-concentration bleomycin A5 plus dexamethasone between June 2004 and October 2007. Clinical manifestations, image characteristics, and therapeutic outcomes were reviewed. The therapeutic outcomes were evaluated by physical examination, photographs, and Doppler ultrasonography. The follow-up was from 6 months to 3 years after ending treatment. RESULTS Twenty-five patients (80.6%) had a response rate greater than 90% reduction in tumor size. Three patients (9.7%) had a response rate between 75% and 90% reduction in tumor size. Another 3 patients (9.7%) had a response rate between 50% and 75% reduction in size. No patients had less than a 50% response rate. There was no recurrence, allergic reaction, pulmonary fibrosis, fever, or other complication during or after the course of treatment. CONCLUSIONS The controlling therapy with small-dosage and low-concentration bleomycin A5 plus dexamethasone can treat the parotid hemangiomas of infants effectively, especially for lesions in the early phase and proliferative phase. Early control and long-term observation are the key aspects of treatment.

Preliminary Study of Fibrin Glue Combined With Pingyangmycin for the Treatment of Venous Malformations in the Oral and Maxillofacial Region

PURPOSE To observe the outcome of using fibrin glue (FG) combined with Pingyangmycin (Tianjin Taihe Pharmaceutical Co Ltd, Tianjin, China) in the treatment of venous malformations (VMs) in the oral and maxillofacial region. MATERIALS AND METHODS The treatment data of 7 patients with VMs from January 2005 to January 2006 were reviewed. All these patients were injected with FG combined with Pingyangmycin. The vital signs and symptoms were observed and recorded immediately after injections. Radiographic examination was used for the evaluation of pulmonary conditions. The therapeutic effect was evaluated by clinical examination and Doppler ultrasonography. The follow-up time was from 1 to 2 years. RESULTS Of the 7 patients, 4 were male and 3 were female, with ages ranging from 10 to 62 years. Four of the 7 recovered to near-normal appearance, without any abnormal bloodstream detectable within the lesions. Two lesions were slightly asymmetrical in appearance, but no abnormal bloodstream could be detected in the lesions. Two patients had a fever during treatment, and one of them stopped treatment because of continuous high fever. No allergic reactions, pulmonary embolisms, or other complications were found during or after treatment. CONCLUSION The therapeutic modality of FG combined with Pingyangmycin for VMs in the oral and maxillofacial region was effective, and the extent of morbidity was acceptable. However, the further long-term observation of severe complications such as deep venous thrombosis and pulmonary embolism should be performed in additional biological and clinical studies.

Nomograms predicting long-term overall survival and cancer-specific survival in head and neck squamous cell carcinoma patients

This study aimed to develop nomograms to predict long-term overall survival and cancer-specific survival in patients with head and neck squamous cell carcinoma (HNSCC). We conducted prognostic analyses and developed nomograms predicting survival outcome using HNSCC patient data collected from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. An external dataset of 219 patients was used to validate the nomograms. Of 36,179 HNSCC patients, 9,627 (26.6%) died from HNSCC and 4,229 (11.7%) died from other causes. Median follow-up was 28 months (1-107 months). Nomograms predicting overall survival (OS) and cancer-specific survival (CSS) were developed according to 10 clinicopathologic factors (age, race, sex, tumor site, tumor grade, surgery, radiotherapy and TNM stage), with concordance indexes (C-indexes) of 0.719 and 0.741, respectively. External validation C-indexes were 0.709 and 0.706 for OS and CSS, respectively. Our results suggest that we successfully developed nomograms predicting five- and eight-year HNSCC patient OS and CSS with high accuracy. These nomograms could help clinicians tailor surgical, adjuvant therapeutic and follow-up strategies to more effectively treat HNSCC patients.

The CCL5/CCR5 axis contributes to the perineural invasion of human salivary adenoid cystic carcinoma

Salivary adenoid cystic carcinoma (SACC) has a unique tendency for perineural invasion (PNI), which results in tumor recurrence and poor prognosis. Recent studies have shown that the chemokine CCL5 and its receptor CCR5 play important roles in tumor invasion and metastasis. However, the role of the CCL5/CCR5 axis in the PNI of SACC has not been studied to date. In the present study, we evaluated the expression of CCL5 and CCR5 in SACC cases and nerve tissues, and performed a series of in vitro assays with the SACC cell line, SACC-83, to indicate the role of the CCL5/CCR5 axis in the PNI of SACC. We found that CCL5 (35.9%; 23/64) and CCR5 (70.3%; 45/64) were positively expressed in SACC cases, and the expression of CCR5 was significantly associated with the PNI of SACC (P<0.05). We also found that SACC-83 cells expressed the functional receptor, CCR5, for the chemokine CCL5, as demonstrated by calcium mobilization and actin polymerization assays. Furthermore, we found that exogenous CCL5 significantly facilitated the migration, invasion and PNI activity of SACC-83 cells in vitro (P<0.05). Further study showed that the CCR5 inhibitor (maraviroc) effectively blocked the migration, invasion and PNI activity of SACC-83 cells with or without CCL5 stimulation (P<0.05). These results indicate that the CCL5/CCR5 axis plays a critical role in the PNI of SACC, and that antagonists against CCR5 may be an effective anti-PNI agent for SACC therapy.

Surgical treatment of a giant neurofibroma.

AbstractNeurofibromatosis type 1, an autosomal dominant inherited disease, presents pathologic symptoms of multiple systems, including neurofibromatosis, skeletal dysplasia, café-au-lait spots in skins, and so on. A 45-year-old man with neurofibromatosis type 1 was reported in this article. The patient presented a giant neurofibroma in his head and neck, dysplasia of skull, facial bones and spinal columns, and multiple café-au-lait spots in systematic skins. Satisfactory curative effects were obtained in this case after tumor resection and prosthesis implantation.

Nomograms for predicting long-term overall survival and cancer-specific survival in patients with major salivary gland cancer: a population-based study

In this study, we aimed to develop and validate nomograms for predicting long-term overall survival (OS) and cancer-specific survival (CSS) in major salivary gland cancer (MSGC) patients. These nomograms were developed using a retrospective cohort (N=4218) from the Surveillance, Epidemiology, and End Results (SEER) database, and externally validated using an independent data cohort (N=244). We used univariate, and multivariate analyses, and cumulative incidence function to select the independent prognostic factors of OS and CSS. Index of concordance (c-index) and calibration plots were used to estimate the nomograms’ predictive accuracy. The median follow-up period was 34 months (1–119 months). Of 4218 MSGC patients, 1320 (31.3%) died by the end of the follow-up; of these 1320 patients, 883 (20.9%) died of MSGC. The OS nomogram, which had a c-index of 0.817, was based on nine variables: age, sex, tumor site, tumor grade, surgery performed, radiation therapy and TNM classifications. The CSS nomogram, which had a c-index of 0.829, was based on the same nine variables plus race. External validation c-indexes were 0.829 and 0.807 for OS and CSS, respectively. Based on SEER database, we have developed nomograms predicting five- and eight-years OS and CSS for MSGC patients with perfect accuracy. These nomograms will help clinicians customize treatment and monitoring strategies in MSGC patients.

Overexpression of KAI1/CD82 suppresses in vitro cell growth, migration, invasion and xenograft growth in oral cancer

KAI1/CD82 is a metastatic suppressor gene in human prostate cancer and several other types of cancer in humans. The present study aimed to examine the role of the overexpression of KAI1 in the progression of oral cancer. Human KAI1/CD82 cDNA was transfected into OSCC-15 and 293T cell lines, and its effects on OSCC-15 cell proliferation, invasion and apoptosis were assessed by performing a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, Matrigel invasion and Annexin V-FITC staining, respectively. In addition, a xenograft model was used to assess the effect of KAI1/CD82 on the in vivo growth of tumors. The overexpression of KAI1/CD82 inhibited the proliferation and invasion of OSCC-15 cells. It also enhanced the apoptotic rate of the OSCC-15 cells. Furthermore, the overexpression of KAI1/CD82 inhibited tumor growth in the xenograft model. The results demonstrated that the overexpression of KAI1/CD82 significantly inhibited the proliferation and invasion of human oral cancer cells, and inhibited tumor growth in the xenograft model. Therefore, KAI1/CD82 may be considered as a potential therapeutic target in oral cancer.

Silencing P12CDK2AP1 with a lentivirus promotes HaCaT cell proliferation

The tumor suppressor P12CDK2AP1 negatively regulates cyclin-dependent kinase 2 (CDK2) activities and suppresses DNA replication. Notably, P12CDK2AP1 is known to be downregulated in head and neck squamous cell carcinomas (HNSCCs). Silencing of specific gene expression by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) using expression vectors and retroviruses has become a powerful tool for the genetic analysis of mammalian cells. In the present study, we utilized lentivirus‑mediated shRNA for functional gene knockdown in normal human skin keratinocytes (HaCaT) cells in order to assess the potential role of P12CDK2AP1 in HNSCCs. Lentivirus‑mediated RNA interference (RNAi) effectively reduced endogenous P12CDK2AP1 expression in HaCaT cells and significantly promoted HaCaT cell proliferation in vitro. Lentiviral vectors have the ability to infect dividing and non-dividing cells as well as to achieve long‑term multilineage gene expression. Thus, additional studies are needed to investigate the use of such vectors as a therapeutic tool for the delivery of siRNAs.