Comparison between normal and loose fragment chondrocytes in proliferation and redifferentiation potential

Loose fragments in osteochondritis dissecans (OCD) of the knee require internal fixation. On the other hand, loose fragments derived from spontaneous osteonecrosis of the knee (SONK) are usually removed. However, the difference in healing potential between OCD- and SONK-related loose fragments has not been elucidated. In this study, we investigated proliferative activity and redifferentiation potential of normal cartilage-derived and loose fragment-derived chondrocytes. Cells were prepared from normal articular cartilages and loose fragment cartilages derived from knee OCD and SONK. Cellular proliferation was compared. Redifferentiation ability of pellet-cultured chondrocytes was assessed by real-time PCR analyses. Mesenchymal differentiation potential was investigated by histological analyses. Positive ratio of a stem cell marker CD166 was evaluated in each cartilaginous tissue. Normal and OCD chondrocytes showed a higher proliferative activity than SONK chondrocytes. Chondrogenic pellets derived from normal and OCD chondrocytes produced a larger amount of safranin O-stained proteoglycans compared with SONK-derived pellets. Expression of chondrogenic marker genes was inferior in SONK pellets. The CD166-positive ratio was higher in normal cartilages and OCD loose fragments than in SONK loose fragments. The OCD chondrocytes maintained higher proliferative activity and redifferentiation potential compared with SONK chondrocytes. Our results suggest that chondrogenic properties of loose fragment-derived cells and the amount of CD166-positive cells may affect the repair process of osteochondral defects

Contrast-enhanced Computed Tomography Screening Is Effective for Detecting Venous Thromboembolism not Prevented by Prophylaxis after Total Knee Arthroplasty

Venous thromboembolism (VTE) is a potential complication occurring after total knee arthroplasty (TKA). We investigated the incidence of VTE after TKA using contrast-enhanced computed tomography (CT), and assessed the efficacy of VTE prophylaxis (fondaparinux and enoxaparin). At our hospital, 189 patients (225 knees) underwent TKA between April 2007 and October 2011. The 225 knees were divided into a control group with no VTE prophylaxis (31 cases), a fondaparinux group (107 cases), and an enoxaparin group (87 cases). Contrast-enhanced CT screening for VTE was performed in all cases on day 5 or 6 after TKA. D-dimer levels were measured on day 5 after TKA, and were significantly lower in the fondaparinux (9.8±3.8) and enoxaparin groups (9.4±4.9) than in the control group (15.6±9.8) (p＜0.001). However, no statistically significant difference in the incidence of VTE was observed among the groups (control, 61.3%;fondaparinux, 49.5%;enoxaparin, 50.6%). Prophylaxis was not effective for the prevention of VTE as detected by contrast-enhanced CT after TKA. CT should be performed after TKA, even when VTE prophylaxis is used

A case of small-cell esophageal cancer with chronic renal failure undergoing hemodialysis safely treated with cisplatin and etoposide

A 54-year-old male undergoing hemodialysis was admitted to our hospital because of difficulty in swallowing. Esophagography and esophageal endoscopy revealed an irregular ulcerated lesion in the cervical esophagus. It was diagnosed as a small-cell esophageal cancer from the biopsy sample. Computed tomography showed a tumor infiltrating the trachea and a few lymph node metastases in the cervix, upper mediastinum, and abdomen. The patient was started on chemotherapy with cisplatin (CDDP) and etoposide (VP-16), which had been reported to be effective for small-cell lung cancer. The patient was treated with CDDP (80 mg/m2) on day 1 and VP-16 (100 mg/m2) on days 1, 3, and 5, every 4 weeks. On the days of chemotherapy, hemodialysis was started as soon as possible after completion of administration of the agents. No severe side effects were observed. After 4 courses of therapy, the patient achieved a partial response

Effects of Carbon-ion Radiotherapy combined with a Novel Histone Deacetylase Inhibitor, Cyclic Hydroxamic-acid -containing Peptide 31 in Human Esophageal Squamous Cell Carcinoma

BACKGROUND: Carbon-ion radiotherapy has several potential advantages over X-rays. This therapy has been applied for various solid tumors including esophageal squamous cell carcinoma (SCC). However, some patients have shown resistance to this treatment. A new effective combined treatment strategy is required for improving the therapeutic effects. Histone deacetylase inhibitors (HDACIs) are new therapeutic candidates for cancer treatment. Several studies have evaluated the combination of X-rays and HDACIs, but, to date, no study has evaluated carbon-ion radiotherapy combined with HDACIs. MATERIALS AND METHODS: Radio-sensitization to carbon-ion radiotherapy when combined with a novel HDACI cyclic hydroxamic-acid-containing peptide 31(CHAP31) was assessed in human esophageal SCC both in vitro and in vivo. Changes of expression of genes related to DNA repair, by CHAP31 were assessed by quantitative real-time reverse transcriptional PCR analysis. RESULTS: CHAP31 induced sensitization to carbon-ion radiotherapy in vitro and tumor growth was significantly suppressed by the combination of carbon-ion radiotherapy with CHAP31 in comparison to either agent alone in in vivo experiments. CHAP31 inhibited the expression of genes related to DNA repair. CONCLUSION: CHAP31 sensitizes SCC cells to carbon-ion radiotherapy and this combinatory treatment may be a potentially useful therapeutic strategy for esophageal SCC

Analysis of Non-genetic Risk Factors for Adverse Skin Reactions to Radiotherapy among 284 Breast Cancer Patients

We analyzed non-genetic risk factors for adverse skin reactions to irradiation at 4 collaborating Japanese institutions, to design future investigation into genetic risk factors for adverse skin reactions to irradiation in a multicenter setting.Methods: From April 2001, 284 breast cancer patients, who underwent radiotherapy with breast-conserving surgery, were enrolled from 4 collaborating institutions in Japan. We graded skin reactions according to international scoring systems. Clinical factors were tested against adverse effects.Results: Grade 1+ skin reactions were observed in 261 (92%) of the patients in less than 3 months, 118 (42%) at 3 months, and 29 (10%) at 6 months in the late phase. Univariate analysis of treatment risk factors (such as the use of a multi-leaf colimeter, wedge-filter, or immobilization device) for skin reactions revealed a significant association (p< 0.0001). After a variable selection procedure with logistic regression, the institution, operative procedure, and magnitude of photon energy remained significantly associated with acute skin reactions. Only the institution was an explanatory variable for skin reactions at 3 and 6 months in the final logistic model.Conclusion: After stratification, substantial remaining variations in the occurrence of skin reactions of a given level suggested that individual genetic factors contribute markedly to individual radiosensitivity. Analysis of genetic factors associated with adverse effects would be possible by stratifying patients according to institution. Selection of eligible institutions, where appropriate treatment modalities could be performed, would also be possible when planning such a study

DNA repair capacity measured by high throughput alkaline comet assays in EBV-transformed cell lines and peripheral blood cells from cancer patients and healthy volunteers

We collected peripheral blood (PB) from 556 patients with various types of cancer who had undergone radiotherapy and from 81 healthy volunteers. We exposed whole PB and Epstein-Barr virus-transformed lymphoblastoid cell lines (EBLs) derived from the PB mononucleocytes to X-irradiation (5 Gy). Using the alkaline comet assay, we measured the immediate DNA damage and, at 15 min, the % residual damage. In PB, the immediate damage was similar in patients and healthy volunteers while the % residual damage (mean+/-S.D.) was significantly higher in patients with breast (54.3+/-A23.9), cervical (54.7+/-A23.9), head/neck (56.8+/-A24.4), lung (60.1+/-23.5), or esophageal cancers (59.5+/-A33.7) than in healthy donors (42.9+/-19.6) (P<0.05). We did not observe such differences in the EBV-transformed cell lines. Thus, radiation sensitivity of fresh PB cells measured by the alkaline comet assay was related to cancer status