Objective To report the clinical outcome and prognostic factors for locally recurrent nasopharyngeal carcinoma(NPC)treated with intensity modulated radiotherapy(IMRT).Methods From January 2001 to August 2004,the data of 132 such NPC patients were analyzed retrospectively;104 male and 28 female with a median of 44.5 years(range 21-73 years).Ninety-eight patients(74.2%)were confirmed by biopsy as having NPC:9 with WHO TypeⅡand 89 WHO TypeⅢ.The other 34 patients were only diagnosed by MRI scan because of the extension/invasion was in the base of skull and/or cavernous sinus.Median interval time were 24 months(range 6-184 months).According to the 1992 Chinese Fuzhou Staging System:stageⅠ3.8 %,Ⅱ10.6 %,Ⅲ22.0% andⅣa 63.6%;T1 5.3%,T2 10.6%,T3 22.7% and T4 55.3%.Twenty-two patients had recurrence in the neck lymph nodes.IMRT was given with the sequential tomotherapy system(NOMOS Peacock systems)of 6 MV X-rays.Prescription dose was 60-70 Gy in GTV,with the fractional dose of 1.94-2.8 Gy.Sixty patients were also supplemented with two to six courses of cisplatin-based chemotherapy.Results The median volume of GTV was 39.5 cm~3(range 0.8-158.9 cm~3).The D95,V95,mean dose and fractionation dose of GTV was 66.9 Gy,98.3%,69.8 Gy and 2.32 Gy,respectively.The median follow-up time was 12 months(range,2-47 months).The 1-,2-and 3-year local progression-free rate was 96.4%,88.4% and 85.3%,respectively.The overall 1-,2-and 3-year survival rate was 6.5.9%,49.6% and 41.6%,respectively.Eleven patients developed distant metastases.Forty-seven patients were observed to devdop mucosa necrosis and/or massive hemorrhage in the nasopharynx.On univariate and multivariate analysis,fractional dose and vohane of GTV were significant prognostic factors for overall survival(P=0.016,0.009).Conclusions The local control and survival rate can be improved for patients with locally recurrent nasopharygeal carcinoma after treatment of intensity modulated radiotherapy.The fractional dose and volume of GTV are independent prognostic factors for the overall survival. The main death reasons are mucosa necrosis and/or massive hemorrhage in the nasopharynx.

Based on the octahedral modifiable structures and kinetic inertness, platinum (IV) complexes have become antitumor prodrug candidates to mitigate platinum (II) drug resistance and side effects. The nitrobenzoxadiazole derivative (NBDHEX) can inhibit the activity of glutathione S-transferases (GSTs) and be introduced to conjugate with platinum(II) complexes DN603 and DN604 to yield two platinum (IV) complexes DN603/DN604-NBD. In vitro assays demonstrated that DN603/DN604-NBD could significantly inhibit the proliferation of cisplatin-sensitive A549 and resistant A549/cDDP cancer cells. The uptake of DN603/DN604-NBD in A549/cDDP cells was much higher than that of cisplatin, causing a higher rate of cell apoptosis and a greater ratio of Bax/Bcl-2, the activation of caspase-3 and cleavage of DNA repair enzyme (PARP), inducing the mitochondria-dependent cell apoptosis pathway. DN603/DN604-NBD could induce higher reactive oxygen species (ROS) levels, significantly enhance phosphorylation of histone H2AX on Ser-139 (γ-H2AX) fluorescence intensity and cause a greater degree of DNA double-stranded damage. Studies have shown that GSTs kinase GSTP1 was highly expressed in cisplatin-resistant cancer cells. Moreover, DN603/DN604-NBD targeted GSTP1 to suppress its expression level. By using the ROS scavenger NAC and the c-Jun N-terminal kinase (JNK) inhibitor SP600125 in advance, it was found that DN603/DN604-NBD could significantly increase the number of living cells and decrease the phosphorylation levels of JNK and c-Jun. The results indicated that DN603/DN604-NBD could produce higher levels of ROS to activate JNK-mediated signaling pathway, induce apoptosis in tumor cells to overcome cisplatin resistance. All the animal experiments were approved by Animal Ethics Committee of Southeast University (grant No. 20210303025). In vivo assays confirmed that DN603/DN604-NBD could inhibit the growth of A549 xenograft tumors with nearly no toxicity and fewer side effects. Taken together, DN603/DN604-NBD are investigated as two potential novel platinum (IV) prodrug candidates for anticancer therapy.

OBJECTIVETo explore the surgical method and clinical curative effect of Ilizarov technique combined with limited surgical treatment for neurotrophic malnutrition equinovarus accompanied with weight-bearing area ulcer.

METHODSFrom July 2004 to December 2011, 21 cases of neurological disorders equinovarus with skin ulcer in weight-bearing area were treated including 14 males and 7 females with an average age of 21.3 years old ranging from 8 to 32 years. Among them,19 cases with talipes equinovarus were on account of spina bifid and 2 cases on account of spinal cord injury of lumbar sacral segment. Nine cases were on the left foot and 12 cases were right foot. The ulcer area in out-below side of the fifth metatarsal bone was in 6 cases, in basement of the fifth metatarsal bone in 5 cases,in lateral of calcaneocuboid joint 2 cases, and in lateral of subtalar joint in 8 cases. Surgical procedure included plantar medial release technique, tendo-chilles lengthenning, and three-joint partial osteotomy. During operation,the skin and soft tissue of ulcer were resected and the incision was sutured when the ulcer was in the lateral of subtalar joint, and ankle Ilizarov external fixation for extension was installed after correcting talipes equinovarus partially. For the legacy skin ulcer in weight-bearing area,the Shenrg-ji cream (Chinese characters) was used after operation for one time per day until the wound healed. Adjusting Ilizarov external fixation for correcting residual deformity until it is satisfaction. During this process weight-bearing walking was keeping.

RESULTSAll cases were followed up from 6 to 52 months with an average of 28 months. All ulcers were healing and no recurrence. The ulcer healing time was 14 to 36 days postoperative (26 days in average). Eighteen deformity feet were corrected satisfactorily, and recovered fully plantar foot, 3 feet appeared mild deformity after 1 year. Ankle joint activity appeared limited in 15 cases and got completely rigidity in 6 cases. The AOFAS increased from preoperative 34.0±7.2 to 86.0±8.5 postoperatively; 8 feet got excellent, 10 good,3 fair.

CONCLUSIONThe clinical effect of Ilizarov technique combined with limited operation and the Sheng-ji cream in correction of the talipes equinovarus with skin ulcer in weigh-bearing area on account of neurotrophic malnutrition is satisfactory, the surgical method is simple and the treating course in security, and serious complications can be avoided.

Adolescent ; Adult ; Child ; Clubfoot ; surgery ; External Fixators ; Female ; Foot Ulcer ; surgery ; Humans ; Ilizarov Technique ; Male

OBJECTIVETo study the effects of monocyte-macrophages (THP-1) in malignant transformation of human bronchial epithelial cells (BEAS-2B) cells induced by coal tar pitch (CTP) and the expression of TNF-α in the process of the cell malignant transformation.

METHODSBEAS-2B cells and THP-1 Cells were divided into four groups: coal tar pitch (CTP) group, benzo(a)pyrene [B(a)P] group, dimethyl sulfoxide (DMSO) group, BEAS-2B and THP-1 co-culture (co-culture group) group. Carcinogenesis model was established. The soft agar colony formation, chromosome aberrations and cell cycle tests were used to detect the cellular malignant transformation. The ELISA assay was utilized to measure the levels of TNF-α in the supernatant of CTP group and co-culture group.

RESULTSThe chromosome number abnormalities could be observed in early stage of the experiment (the 10th generation cells), which showed the increased ratio of aneuploid to polyploid, and the decreased number of diploid. The colony formation rate of co-culture group (the 20th generation cells) was 17.63‰ ± 0.97‰, which was significantly higher than that (13.94‰ ± 0.84‰) of CTP group and that (12.96‰ ± 1.62‰) of B(a)P group (P < 0.05). The proportion of S phase cells in the co-culture group was 44.49% ± 0.68%, which was significantly higher than that (38.19% ± 1.26%) of CTP group and that (36.41% ± 1.19%) of B(a)P group (P < 0.05). The TNF-α level in the co-culture group was significantly higher than that in CTP group (P = 0.001).

CONCLUSIONMonocyte-Macrophages can accelerate the malignant transformation of BEAS-2B cells induced by CTP and increase the expression level of TNF-α.

Bronchi ; cytology ; Cell Line ; Cell Transformation, Neoplastic ; chemically induced ; Coal Tar ; toxicity ; Coculture Techniques ; Epithelial Cells ; cytology ; drug effects ; pathology ; Humans ; Macrophages ; cytology ; Monocytes ; cytology ; Tumor Necrosis Factor-alpha ; metabolism

Studies have proved that microRNA-101 (miR-101) functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in osteosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptosis have not been fully elucidated. In this study, we found that the expression of miR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthesized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR-101. Overexpression of miR-101 significantly decreased the expression of mTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting cells apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells. mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy by down-regulating mTOR expression.
Apoptosis ; Bone Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; Osteosarcoma ; genetics ; metabolism ; pathology ; RNA, Neoplasm ; genetics ; metabolism ; TOR Serine-Threonine Kinases ; genetics ; metabolism

Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties. The purpose of this study is to investigate the HBV DNA replication inhibition in the mouse model with betulinic acid. Hydrodynamic injection method via the tail vein with the Paywl. 3 plasmid was used to establish the animal mode (n = 15), and the mice were randomly divided into the PBS control group (n = 5), Betulinic acid treatment group (n = 5) and lamivudine control group (n = 5). The day after successful modeling , the mice would have taken Betulinic acid (100 mg x kg(-1)), lamivudine (50 mg x kg(-1)), PBS drugs orally, once daily for 7 days, blood samples were acquired from the orbital venous blood at 3, 5, 7 days after the administering, HBsAg and HBeAg in serum concentration were measured by ELISA and the mice were sacrificed after 7 days, HBV DNA southern detections were used with part of mice livers. The results showed that betulinic acid significantly inhibited the expression of HbsAg in the mice model at the fifth day compared with the control group, and there was no significant differences between the effects of lamivudine and the PBS control group; both the betulinic acid and lamivudine groups had no significant inhibition for the HBeAg expression; the HBV DNA expressions of the liver tissue from the betulinic acid and lamivudine groups were inhibited compared with the control group. Taken together, these results reveal betulinic acid can inhibit the HBsAg expression and replication of the liver HBV DNA in the mouse model.
Acute Disease ; Animals ; Antiviral Agents ; pharmacology ; DNA Replication ; drug effects ; DNA, Viral ; biosynthesis ; Hepatitis B ; blood ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; immunology ; physiology ; Male ; Mice ; Plasmids ; genetics ; Triterpenes ; pharmacology ; Virus Replication ; drug effects

Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.
Adolescent ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; administration & dosage ; Central Nervous System Neoplasms ; therapy ; Child ; Child, Preschool ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; statistics & numerical data ; Disease-Free Survival ; Etoposide ; administration & dosage ; Female ; Humans ; Male ; Neoplasm Recurrence, Local ; Neoplasms, Germ Cell and Embryonal ; therapy ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVETo investigate the clinical characteristics and treatment of localized Castleman's disease (CD), and review the literatures to improve the diagnosis and management of this disease.

METHODSThe clinical symptoms, histopathology, CT, MRI findings and results of surgery in 20 patients with localized CD were evaluated retrospectively.

RESULTSThe average age of the patients was 37.7 years. The lesions were located in the retroperitoneal space (9 cases), mediastinum (7 cases), pelvic cavity (1 case), neck (1 case), upper arm (1 case), and axillary (1 case). All patients underwent surgical resection, including 9 cases for retroperitoneal resection (6 cases had open operation and 3 cases laparoscopic resection) and 7 cases for mediastinal resection (open operation in 5 cases and thoracoscopic resection in 2 cases). The Castleman's disease was confirmed by histopathology. There were hyaline vascular type of CD in 17 cases, plasma cell type of CD in 1 case, and mixed cellularity type of CD in 2 cases. The duration of follow-up ranged from 12 to 165 months for 16 cases. Among them 15 patients were alive without recurrence, and 1 case had recurrence in the primary site at 47 months after the operation.

CONCLUSIONSPatients with Castleman's disease have no typical clinical symptoms and have normal laboratory results. The majority of patients are of hyaline vascular type of the disease. Imaging examination is helpful to diagnosis, and the final diagnosis depends on pathologic examination. Complete surgical resection of the tumor is the best treatment for localized Castleman's disease.

Adult ; Castleman Disease ; diagnosis ; diagnostic imaging ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Mediastinum ; Middle Aged ; Recurrence ; Retroperitoneal Space ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome ; Young Adult

OBJECTIVETo study therapeutic effects of limited internal fixation combined with external fixation in the treatment of deformity of distal end of femur, as well as to explore its effect on the function of knee joint.

METHODSFrom June 2004 to June 2009, 38 patients with deformity of distal end of femur were treated with osteotomy at femoral supracondylar and internalfixation combined with hybrid external fixator. Among the patients, 19 patients were male and 19 patients were female, ranging in age from 14 to 58 years, with an average of 26 years. Six patients had genu valgum, 4 patients had varus of the distal end of femur, 2 patients had varus combined with rotation deformity,3 patients had genu recurvation and 23 patients had deformity of genuflex. The function of knee joint was evaluated according to Dimeglio clinical assessment after the treatment.

RESULTSAll the patients were followed up and the during ranged from 6 to 48 months, with a mean period of 23 months. All the deformity obtained satisfactory correction, without complications such as limitation of motion of the knee joint, under correction or over correction,displacement of the section of the osteotomy,internal fixation loosening and fracture. Nineteen patients got an excellent result, 12 good, 5 poor and 2 bad.

CONCLUSIONSupracondylar femoral osteotomy and internal fixation combined with hybrid external fixator is a safe and effective surgery for the treatment of deformity of distal end of femur. This method combines the advantages of internal fixation and external fixation.

Adolescent ; Adult ; External Fixators ; Female ; Femur ; abnormalities ; surgery ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged

BACKGROUNDTreatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy. In this study, we intended to investigate the effects of 2-propylpentanoic acid (VPA), a histone deacetylase inhibitor, on chemosensitivity and radiosensitivity in human glioma cell lines.

METHODSHuman glioma cell lines, T98-G, and SF295, were treated with temozolomide (TMZ) or irradiation (IR), with or without VPA (1.0 mmol/L). Then, cytotoxicity and clonogenic survival assay was performed. Cell cycle stage, apoptosis, and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay. One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups.

RESULTSMild cytotoxicity of VPA was revealed in both cell lines, T98-G and SF295, with the 50% inhibiting concentration (IC50) value of (3.85 ± 0.58) mmol/L and (2.15 ± 0.38) mmol/L, respectively; while the IC50 value of TMZ was (0.20 ± 0.09) mmol/L for T98-G and (0.08 ± 0.02) mmol/L for SF295. Moreover, if combined with VPA (1.0 mmol/L) for 96 hours, the sensitivity of glioma cells to TMZ was significant increased (P < 0.05). The surviving fractions at 2 Gy (SF2) of T98-G and SF295 cells exposed to IR alone were 0.52 and 0.58. However, when VPA was combined with IR, the SF2 of T98-G and SF295 dropped to 0.39 (P = 0.047) and 0.49 (P = 0.049), respectively. Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P < 0.01).

CONCLUSIONVPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy, and thus could be a potential sensitizer of glioma treatment.

Apoptosis ; drug effects ; radiation effects ; Blotting, Western ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Dacarbazine ; analogs & derivatives ; pharmacology ; Flow Cytometry ; Glioma ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Valproic Acid ; pharmacology