Activation of JNK and high expression level of CD133 predict a poor response to sorafenib in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. While sorafenib, a multikinase inhibitor targeting the Raf/extracellular signal-regulated protein kinase (ERK) pathway, has been shown recently to provide a survival advantage to patients with advanced HCC, a predictive biomarker has not been developed. We studied whether c-Jun N-terminal kinase (JNK), which promotes liver carcinogenesis in mice, affects therapeutic response to sorafenib in HCC patients. METHODS: We collected pathological specimens from 39 patients with advanced HCC before starting sorafenib treatment, and measured JNK activity in HCCs. RESULTS: In patients treated with sorafenib, the expression of phospho-c-Jun in HCC, as a read out of JNK activity, was significantly higher (P<0.001) in the non-responder group than in the responder group. c-Jun N-terminal kinase activation in HCC was associated with a decreased time to progression and a poor overall survival (P=0.0028 and P=0.0008, respectively). CONCLUSION: In addition, JNK activity was significantly correlated with CD133 expression level. Correspondingly, high expression level of CD133 was linked to a poor response to sorafenib. Furthermore, D-JNKi, a specific JNK inhibitor, reduced the growth of xenografted CD133(+) cells in athymic mice. In conclusion, JNK activation was positively correlated with CD133 expression level and inversely correlated with the therapeutic response to sorafenib, suggesting that JNK activity may be considered as a new predictive biomarker for response to sorafenib treatment.

[Role of ultrasonography in diagnosis of neutropenic enteritis: a study of 4 cases].

Neutropenic enteritis is a septic or inflammatory disease of the colon. It is usually encountered in patients with hematological malignancy who have undergone chemotherapy, and it presents as fever, diarrhea, and abdominal pain, although the symptoms are not always specific. The diagnostic features of neutropenic enteritis revealed by barium enema, CT and ultrasonography have been reported previously. Here we report 4 cases of neutropenic enteritis in which ultrasound was used for diagnosis, and also for monitoring the clinical course of the disease. Because neutropenic enteritis is rapidly progressive, early diagnosis and therapeutic intervention are required. We believe that ultrasonography is a useful method for examining patients with neutropenic enteritis, being noninvasive, mobile, and providing rapid results in real time, thus aiding early diagnosis and clinical follow-up.

Anti-metastatic gene therapy utilizing subcutaneous inoculation of EC-SOD gene transduced autologous fibroblast suppressed lung metastasis of Meth-A cells and 3LL cells in mice.

We have previously reported that superoxide stimulates the motility of tumor cells and the administration of Cu-Zn superoxide dismutase (SOD) significantly suppresses metastasis. However, ideally, anti-metastatic therapy should be long-lasting, systemically effective and have low toxicity. The half-life of Cu-Zn SOD in plasma is so short that it cannot provide long-lasting effects. Therefore, in this study we have developed a gene therapy in a mouse model utilizing extracellular SOD (EC-SOD), which is the most prevalent SOD isoenzyme in extracellular fluids. We retrovirally transfected fibroblasts (syngeneic) with the EC-SOD gene and established EC-SOD-secreting fibroblasts. Inoculation of EC-SOD-secreting fibroblasts suppressed both artificial and spontaneous metastatic lung nodules in mouse metastasis models. These data indicate the feasibility of anti-metastatic gene therapy utilizing the EC-SOD gene.

[Two cases of advanced breast cancer effectively treated with chemoendocrine therapy and radiotherapy].

We reported 2 cases of breast cancer with lymph node metastasis treated with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and medroxyprogesterone acetate (MPA). Case 1 was stage IV [T4b, N3 M1 (lung)] and case 2 was stage IIIa (T1, N2, M0). The two cases responded well to CAF and MPA therapy in local and systemic lesions, and then underwent radiotherapy and lymph node resection without mastectomy. After these treatments, both cases were thought to be disease-free. Major side effects were allopecia, obesity, and leukopenia. These results suggest that combination chemoendotherapy, radiotherapy, and surgery can be utilized for most patients with moderately advanced breast cancer.

Solitary pyogenic thalamic abscess--two case reports.

We report two patients with solitary thalamic abscesses, occurring among 91 consecutive patients (2.2%) with computed tomography (CT)-diagnosed and surgically-verified brain abscess experienced in our college during 1975 to 1991. A 9-year-old girl with congenital heart disease experienced frequent vomiting followed by left hemiparesis and deterioration of consciousness. CT demonstrated a right thalamic ring-enhanced lesion. Purulent material was aspirated via a burr hole. She died of heart failure on the 5th postoperative day. Autopsy disclosed diffuse brain swelling and an encapsulated abscess in the right thalamus, which had ruptured into the third ventricle. A 30-year-old female experienced headache, nausea, and vomiting, which progressed to somnolence and right hemiparesis. CT demonstrated a left thalamic ring-enhanced lesion. Purulent material was aspirated by stereotactic procedures. All symptoms had resolved by the end of the 2nd postoperative week.