Overnight Polygraphic Studies of Infantile Spasms — Influence of Hormone Therapy on Sleep States, Pulse, Respiration and Seizure Activities

The influence of hormone therapy on sleep states, pulse, respiration and seizure actihties of infantile spasms was examined by means of overnight sleep polygraphy. Also the correlation between the changes of these parameters and the prognosis was investigated. The results were as follows: 1) In all cases, the awake time of TIB during hormone therapy was longer than before hormone therapy. The reduction of REM sleep time of SPT and lowering of REM density were remarkable during hormone therapy in cases with delayed psychomotor development as compared with cases with a considerable degree of psychomotor development. During hormone therapy, the NREM sleep time of SPT was shortened in cases with ACTH therapy, and prolonged in case with hydrocortisone therapy. 2) During hormone therapy, the pulse rate increased significantly in cases with a considerable degree of psychomotor development, but decreased significantly in cases with delayed psychomotor development.     

A case of recurrent esophageal cancer successfully treated with weekly paclitaxel in combination with radiotherapy

A 48-year-old man underwent subtotal esophagectomy for pStage III (pT 3 pN 3) thoracic esophageal carcinoma on June 20, 2002, in combination with chemotherapy (5-FU 500 mg/day day 1-14, CDDP 10 mg/day day 1-14, VDS 3 mg on days 1 and 8) before and after the operation. Recurrence was seen 7 months after the operation in right pleura and lower mediastinum. Chemo (same regimen)-radiotherapy (50 Gy) was then performed but without effect. Thereafter, lung and upper mediastinal metastases were found, and weekly administration of paclitaxel (70 mg/m2, day 1, 8, 15, q 4w) was initiated in combination with radiotherapy (40 Gy). Two cycles of treatment resulted in PR, and CR was achieved after the 8th cycle was completed. Although treatment was terminated after the 12 th cycle due to development of peripheral neuropathy (grade 2), CR was still maintained 8 months after the completion of treatment. These results suggested the effectiveness of the treatment in cases that show resistance to conventional 5-FU-based chemotherapy.     

An evaluation of busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation

BACKGROUND: Busulfan (BU) pharmacokinetics (PK) are shown to be highly variable and thus their evaluation is critical for the success of hematopoietic stem cell transplantation (HST) in Caucasians. However, there are no data available for Japanese patients. METHODS: BU PK were evaluated in seven Japanese adult patients who underwent allogeneic HST. Four patients received 16 doses of 1 mg/kg of oral BU every 6 h for over 4 days followed by 120 mg/kg of intravenous cyclophosphamide, while three patients were given eight doses of 1 mg/kg of oral BU over 2 days in addition to 180 mg/kg of intravenous fludarabine with or without 2 Gy of total body irradiation. Blood samples were collected for PK analysis after the sixth dose of BU was administered. RESULTS: The average plasma BU concentrations at steady state (Css) ranged from 745 to 2422 ng/ml. Four of seven patients had BU Css >1000 ng/ml, the previously defined concentration associated with an increased risk of regimen-related toxicity (RRT). Indeed, one of them developed hepatic veno-occlusive disease. On the other hand, no severe toxicity greater than grade II except stomatitis was observed in the remaining patients whose Css were <1000 ng/ml. CONCLUSION: A possible increased risk of RRT associated with high plasma BU concentrations should be kept in mind after oral administration of BU. A prospective trial of adjusting BU doses depending on the BU PK is warranted for Japanese patients.     

Vasculitic condition following instillation of epirubicin hydrochloride in an outpatient chemotherapy

The appearance of vasculitis is often observed following the use of epirubicin hydrochloride in outpatients. As it is important to continue to provide a safe treatment for outpatient with little or no side effects, the aim of this study was to reveal causes underlying the outbreak of vasculitis or the vasculitic state of patients who had undergone instillation of epirubicin hydrochloride as an adjuvant therapy following a breast cancer surgery. The study was conducted based on past investigation records. We extracted relevant factors such as age, previous illness, physical condition and dosage of epirubicin hydrochloride from past records which may all be connected to the outbreak of vasculitis. We administered one dose of epirubicin hydrochloride that was diluted into 50-100 ml of normal saline solution or 5% glucose and instilled over a period of 30 minutes. As a result of this instillation of epirubicin hydrochloride, 35 out of 45 cases displayed vasculitis. We did not observe any relationship among the aged (over 60), previous illness or physical condition (BMI over 25) and the appearance of vasculitis. When a dosage amount of more than 110 mg of epirubicin hydrochloride was administered, 23 out of 29 cases displayed vasculitis. From the past records, it was observed that the cause of vasculitis was dependent on the administrative method itself. As previous studies reported that vasculitis was low when epirubicin hydrochloride was retained in blood vessels for only a short time, our study, however, concentrated on how to administer epirubicin hydrochloride. Our results suggested that an adoption of a single dosage system may suppress the outbreak of vasculitis.     

The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death

Drosophila tumor suppressor WARTS (Wts) is an evolutionally conserved serine / threonine kinase and participates in a signaling complex that regulates both proliferation and apoptosis to ensure the proper size and shape of the fly. Human counterparts of this complex have been found to be frequently downregulated or mutated in cancers. WARTS, a human homolog of Wts, is also known as tumor suppressor and mitotic regulator, but its molecular implications in tumorigenesis are still obscure. Here, we show that WARTS binds via its C-terminus to the PDZ domain of a proapoptotic serine protease Omi / HtrA2. Depletion of WARTS inhibited Omi / HtrA2-mediated cell death, whereas overexpression of WARTS promoted this process. Furthermore, WARTS can enhance the protease activity of Omi / HtrA2 both in vivo and in vitro. Activation of Omi / HtrA2-mediated cell death is thus a potential mechanism for the tumor suppressive activity of WARTS.     

Enhanced expression of the secreted form of clusterin following neoadjuvant hormonal therapy as a prognostic predictor in patients undergoing radical prostatectomy for prostate cancer

The objective of this study was to characterize changes in clusterin expression in prostate cancer before and after neoadjuvant hormonal therapy (NHT), and to assess the prognostic significance of clusterin expression following NHT in patients undergoing radical prostatectomy. Paired needle biopsy and corresponding radical prostatectomy (RP) specimens obtained from 76 patients were analyzed for expression of clusterin protein by immunohistochemical staining with an antibody recognizing all of the clusterin isoforms. RP specimens following NHT demonstrated stronger expression of clusterin than the corresponding needle biopsy specimens. Clusterin protein was present in the cytoplasm of both biopsy and RP specimens; however, there was no nuclear staining identified in any specimens. The expression level of clusterin in biopsy specimens was significantly associated with the biopsy Gleason score, but not with other parameters available before RP. Furthermore, clusterin expression in RP specimens was significantly associated with the preoperative prostate specific antigen value and pathological stage, but not with other pathological factors. Biochemical recurrence-free survival in patients with strong clusterin expression in RP specimens was significantly lower than that in those with weak clusterin expression; however, the level of clusterin expression could not be used as an independent predictor of biochemical recurrence. These findings suggest that despite the lack of independent significance, the expression level of the secreted form of clusterin in prostate cancer tissue after NHT, which may inversely reflect the therapeutic effect of NHT, could be a useful parameter predicting biochemical recurrence in patients undergoing RP.     

Clinical outcome of combined immunotherapy with low-dose interleukin-2 and interferon-α for Japanese patients with metastatic renal cell carcinoma who had undergone radical nephrectomy: a preliminary report

Background The objective of this study was to evaluate the clinical outcome of combined immunotherapy with interferon-α (IFN-α) and low-dose interleukin-2 (IL-2) for Japanese patients with metastatic renal cell carcinoma (RCC) who had undergone radical nephrectomy. Methods This study included 13 patients who were diagnosed as having metastatic RCC following radical nephrectomy. These patients received a subcutaneous injection of IFN-α (6 × 10⁶ IU per day) three times per week and an intravenous injection of IL-2 (1.4 × 10⁶ IU per day) twice per week. Tumor response was evaluated every 16 weeks, and as a rule, this weekly regimen was repeated 50 times in patients with evidence of objective response or stable disease. Results One of the 13 patients dropped out because of severe toxicity; hence, 12 patients were evaluable, with a median follow-up period of 18 months after the start of this combined therapy. Six patients (50.0%) achieved objective responses, with 1 complete response (CR), while only 2 (16.7%) demonstrated progressive disease. The median duration of response in the 6 responders was 13.5 months. Toxicity associated with this combined immunotherapy was limited to WHO grade 1 or 2 in these 12 patients. All patients were alive at last follow-up, and 2 remain disease-free after 1 additional patient showed a CR following surgical resection of the remaining metastatic disease. Conclusion Our preliminary experience suggests that long-term, repeated treatment with IFN-α and low-dose IL-2 is feasible in Japanese patients with metastatic RCC who have undergone radical nephrectomy. Although it will be necessary to accumulate data from a larger number of patients with a longer follow-up period, the combined immunotherapy tested in this study may become the preferred therapy for Japanese patients with metastatic RCC.     

A case of amyotrophic lateral sclerosis and breast cancer

We report a case of breast cancer occurring in a patient with amyotrophic lateral sclerosis (ALS). A 58-year-old Japanese woman diagnosed with ALS 6 years previously noticed a mass in the left breast. We performed a modified radical mastectomy for the mass lesion. Invasive ductal carcinoma without lymph node metastasis was diagnosed. During the operation, she had no worsening of her neurological symptoms. The patient has been cancer-free for 11 months since her operation and no improvement has been seen in her neurological condition. To the best of our knowledge, this is the first case of breast cancer occurring in a patient with ALS in Japan.