N-acetyl-L-cysteine inhibits bleomycin-induced interleukin-8 secretion by bronchial epithelial cells.

OBJECTIVE: Bleomycin (BLM) has proven effective for the treatment of cancers, but the most serious dose-limiting side-effect is the development of pulmonary toxicity. Although the precise mechanism in the pathogenesis of BLM-induced lung injury has not been determined, oxygen radicals and neutrophils are indicated to play a key role in it. Interleukin-8 (IL-8) is thought to be an important mediator of the pathogenesis of acute lung injury. METHODOLOGY: The IL-8 production from bronchial epithelial cell line, BEAS-2B cells was measured by enzyme-linked immunosorbent assays for IL-8. RESULTS: The concentrations of IL-8 were reportedly elevated in BLM-induced lung injury, suggesting the involvement of IL-8 in the pathogenesis of BLM-induced lung injury. In the present study, we showed that BLM induced the expression of IL-8 protein and mRNA in BEAS-2B cells, and N-acetyl-L-cysteine (NAC) inhibited IL-8 expression. In addition, the structurally unrelated antioxidant, pyrrolidine dithiocarbamate (PDTC) also effectively inhibited BLM-induced IL-8 production. CONCLUSION: These results suggest that anti-oxidant-sensitive mechanism might be involved in the inhibition of IL-8 secretion by BLM-stimulated bronchial epithelial cells and that NAC might be useful for the treatment of BLM-induced lung injury.

Thalamic gliomas: a clinicopathologic analysis of 20 cases with reference to patient age.

Twenty patients (M 11, F9; ranging from 1-77 years old) with histologically proven glial tumours in the thalamic region, treated from 1979 until 1994 at Kyushu University Hospital were retrospectively reviewed and analysed in order to elucidate their clinical and neuropathological characteristics. The initial common clinical manifestations were those of increased intracranial pressure or motor weakness. The histological diagnosis of the tumour was pilocytic astrocytoma in 2 patients, fibrillary astrocytoma in 7, anaplastic astrocytoma in 7, and glioblastoma multiforme in 4. The initial treatment was surgery alone in 4 patients, surgery followed by radiation therapy in 5, surgery followed by radiation therapy and chemotherapy in 9, and conventional radiation therapy alone in 2 patients. The 3-year overall actuarial survival rate for all patients was 20% but was related to both the histological type and the age of the patients: As a result, the rate was 44% for patients with low-grade astrocytoma compared to 0% for those with high-grade astrocytoma. While 5 out of 11 patients under the age of 25 years at their initial presentation have survived for from 2-16 years after the diagnosis, all patients presenting after the age of 25 years died within 3 years after treatment. Thalamic glial tumours are not a homogeneous group of tumours in terms of clinical behaviour and histopathological features, and the poor overall results, especially in adult tumours, thus emphasise the need for continued research in the treatment of these tumours.

Chemotherapy for progressive pilocytic astrocytomas in the chiasmo-hypothalamic regions.

Over the past 25 years, we have treated 17 patients with chiasmo-hypothalamic astrocytomas. Before 1988, the initial treatments consisted of surgery and/or radiotherapy, while since 1989, 4 children (1 male, 3 females, aged 3-8 years) were treated primarily with chemotherapy. None of them was associated with neurofibromatosis. After a biopsy of the tumor, the intravenous administration of ranimustine (MCNU; 30-86 mg/m2) and/or nimustine (ACNU; 30.3-64.1 mg/m2) was given without radiation therapy. Chemotherapy was usually given as an out-patient, with a total of 5-13 courses. The total doses of MCNU and ACNU administered ranged from 150 to 570 mg and from 64.8 mg to 100 mg, respectively. After chemotherapy 2 patients showed clinical improvement and tumor regression on neuro-imaging, while one patient showed clinical improvement and tumor size stabilization on neuro-imaging. The remaining one child, however, showed a clinical worsening and tumor progression on neuro-imaging studies. He was thus treated with a second chemotherapy regimen with carboplatin and etoposide, which brought about tumor regression. The acute and subacute toxicity of chemotherapy was mild. All patients are now leading almost normal lives with a median of 43 months after diagnosis. Although a longer and more careful clinical observation is required, the authors conclude that chemotherapy with MCNU and/or ACNU may benefit patients with unresectable pilocytic astrocytoma requiring treatment. The advantages of this therapy include its mild side effects and the lack of any hospitalization in most patients. It may also delay the need for radiation therapy, which can have a deleterious effect on the young developing brain.

Germ cell tumor in the hypothalamo-neurohypophysial region: clinical features and treatment.

Twenty-one patients with germ cell tumors (17 germinomas and 4 teratomas) involving the hypothalamic-neurohypophysial (HN) region were reviewed retrospectively. Eleven patients were males and 10 females, and their ages ranged from 7 to 45 years (average 18.5 years). Diabetes insipidus was the initial and the most prominent symptom in most germinomas; in teratomas the most prominent symptom was visual disturbance. Fifteen patients with germinomas were treated by radiotherapy, and 4 with teratomas were treated by surgical resection alone. Two recent germinoma patients with extensive CSF dissemination were treated with systemic chemotherapy consisting of anticancer platinum drugs and etoposide, which resulted in a complete disappearance of the tumors. Patients with germinoma treated after the introduction of CT scanning had a greatly improved mortality rate, and their actual survival rate was 87.5% over 10 years. On the basis of this review, the authors consider that diagnosis at an early stage of the disease and chemotherapy, which can be an effective therapeutic alternative to radiation therapy, may improve not only the mortality rate but also the quality of life of patients with HN germ cell tumors.