Acromegaly associated with suprasellar and pulmonary hemangiopericytomas. Case report

The authors report the case of a 35-year-old acromegalic woman who developed amenorrhea and decreased left vision, and who was found to have suprasellar and pulmonary hemangiopericytomas. Total removal of the suprasellar hemangiopericytoma resulted in normalization of the plasma human growth hormone (GH) level and a marked decrease in size of the pulmonary hemangiopericytoma. Immunoperoxidase studies for GH and human hypothalamic growth hormone-releasing factor (GHRF) demonstrated immunoreactive intracellular GH only in the suprasellar hemangiopericytoma, with no immunoreactive intracellular GHRF evident in either the suprasellar or pulmonary hemangiopericytoma.     

Stimulation of osteoblastic cell differentiation by Notch.

Notch is a transmembrane protein that plays a critical role in the determination of cellular differentiation pathways. Although its importance in the development of mesenchymal tissues has been suggested, its role in skeletal tissues has not been well investigated. Northern blot experiments showed the expression of Notch1 in MC3T3-E1 osteoblastic cells at early differentiation stages. When a Notch1 cytoplasmic domain (Notch-IC [NIC]) delivered by an adenovirus vector was expressed in osteoblastic MC3T3-E1 cells, a significant increase in calcified nodule formation was observed in long-term cultures. Activation of endogenous Notch in MC3T3-E1 by coculturing them with Delta-like-1 (Dll1)-expressing myeloma cells also resulted in a stimulation of calcified nodule formation. Not only affecting nodule formation, Notch activation also had effects on osteoblastic differentiation of multipotent mesenchymal cells. Osteoblastic differentiation of C3H10T1/2 cells induced by bone morphogenetic protein 2 (BMP-2) was significantly stimulated, whereas adipogenic differentiation was suppressed strongly, resulting in a dominant differentiation of osteoblastic cells. NIC expression in primary human bone marrow mesenchymal stem cells (hMSCs) also induced both spontaneous and stimulated osteoblastic cell differentiation. These observations suggest that osteoblastic cell differentiation is regulated positively by Notch and that Notch could be a unique and interesting target molecule for the treatment of osteoporosis.     

Prolongation of G1 phase in cultured glioma cells by cis-dichlorodiammineplatinum (II) (CDDP): Analysis using bromodeoxyuridine (BrdU)-Hoechst technique

Summary The cytokinetic response of three murine (AC) and human (GB-1 and GB-2) glioma cell lines to cis-dichlorodiammineplatinum (II) (CDDP) was investigated by flow cytometry. Using the 5-bromodeoxyuridine (BrdU)-Hoechst technique, percentages of cultured glioma cells in the various phases of the cell cycle, and relative phase duration were calculated. This technique proved to be a rapid and easily performed method to characterize phase length and transition rate for the complete cell cycle. In the presence of CDDP IC₁₀ (a concentration in which 10% inhibition of cell growth be induced as compared to controls), perturbations of the cell cycle in AC and GB-1 cells included G₂ delay or block, decreased transit velocity from G₁ to S phase, and prolongation of G₁ phase. The mean cell cycle time increased 1.4 times in AC and 1.6 times in GB-1 as compared to controls. In CDDP IC₅₀-treated GB-2 cells, the mean cell cycle time was prolonged three times longer than control: however, duration of each phase could not be calculated because of significant perturbation of cell cycle. These results suggest that CDDP influences glioma cells at the G₁/S boundary and in the G₂ phase, resulting in prolongation of the G₁ phase and, to a minor degree, in block of the G₂ phase.     

Postoperative adjuvant chemotherapy with cisplatin, etoposide, and pirarubicin for endometrial carcinoma patients with lymph node metastasis: A pilot study

We evaluated the effects of a combined chemotherapy regimen on endometrial carcinoma in 14 patients with lymph node metastasis. After surgery, the patients were treated with 3 cycles of chemotherapy (PVP regimen) every 4 weeks. The PVP regimen consisted of 75 mg/m2 cisplatin on day 1, 40 mg/m2 pirarubicin (P) on day 1, and 75 mg/m2 etoposide (VP-16: V) on days 2, 3 and 4. The effect of adjuvant chemotherapy was evaluated based on progression-free survival (PFS), overall survival (OS), and adverse effects. The 5-year PFS rate was 52% [95% confidence interval (CI), 10-94%], and the 5-year OS rate was 50% (95% CI, 16-84%). The major toxicity was myelosuppression. One hundred percent of patients had neutropenia above grade 3, but all recovered from myelosuppression. PVP therapy may be an effective adjuvant therapy for endometrial carcinoma patients with lymph node metastasis used as an alternative to radiation therapy.     

Changing patterns of intraocular inflammatory disease in Japan

Purpose: We investigated the frequencies and clinical characteristics of Japanese patients with uveitis. Methods: Records of 189 patients referred from April 1999 to March 2001 were retrospectively reviewed. Results: Fifty-six patients (29.6%) had anterior uveitis, 13 (6.9%) intermediate uveitis, 59 (31.2%) posterior uveitis, 58 (30.7%) panuveitis, and three (1.6%) papillitis. The most common diagnoses were Vogt-Koyanagi-Harada (VKH) disease (10.1%), biopsy-proven or presumed sarcoidosis (9.5%), acute anterior uveitis (7.9%), tuberculosis (6.9%), and Behçet’s disease (5.8%). Seventy-three patients (38.6%) were treated with local therapy alone, and 95 patients (50.3%) required systemic therapy. Ocular complications developed in 19.6% of patients, and systemic complications in 2.1%. Conclusions: These results confirm a continued high frequency of VKH disease and sarcoidosis, but suggest a decreased frequency of Behçet’s disease and an increased frequency of tuberculosis. Roughly one-half of the patients required systemic treatment in addition to local therapy, and ocular and/or systemic complications developed in one-fifth of the patients.     

Treatment outcomes of cervical esophageal cancer patients

Background

Although systemic therapy for esophageal carcinoma has advanced dramatically over the last several decades, the consensus of treatment for cervical esophageal carcinoma (CESCC) has yet remained controversial.

Patients and methods

We analyzed 56 CESCC patients who underwent various therapies in our hospital between January 2000 and December 2013.

Results

Thirteen cases underwent surgery without neo-adjuvant therapy (NAT), while 20 cases underwent surgery after NAT. Definitive chemo-radiotherapy (dCRT) was administered to 23 cases. Five cases underwent salvage surgery after dCRT. Three-year overall survival rates (3-year-OS) were similar between the NAT and dCRT groups (53.3 vs. 51.5 %). These cases were divided into clinical T2/T3 and T4 cases, and a differential analysis was performed. The 3-year-OS achieved by NAT in T2/T3 cases (90.9 %) tended to be better than that by dCRT (62.5 %). In contrast, the 3-year-OS achieved by NAT in T4 cases (12.5 %) tended to be worse than that by dCRT (34.2 %). The prognosis of CESCC patients undergoing salvage surgery after dCRT was very good, with 3-year-OS of 100 % in T2/T3 cases and 66.6 % in T4 cases. A comparative analysis of postoperative complications was performed between CESCC patients undergoing surgery after neo-adjuvant chemotherapy and chemo-radiotherapy to evaluate the operative risk for CESCC patients after CRT. The rates of postoperative complications were similar between these groups.

Conclusion

We analyzed the treatment outcomes of CESCC patients by dividing them according to the clinical tumor invasion depth. Salvage surgery may be an effective therapy for CESCC patients and needs to be considered.

     

Detection of p53 gene mutations in human esophageal squamous cell carcinomas using a p53 yeast functional assay: possible difference in esophageal carcinogenesis between the young and the elderly group.

A p53 yeast functional assay, which cannot only detect p53 gene mutations but also can assess p53 gene function, was used to screen for p53 gene dysfunction in human esophageal squamous cell carcinomas. Surgically resected frozen tissues of esophageal squamous cell carcinomas from 57 patients were examined for p53 gene mutation. Because the mean age of the patients diagnosed with esophageal squamous cell carcinoma was 64 years, we classified those who were <65 years of age as the Young Group and classified the others as the Elderly Group. The incidence of p53 gene mutations was 43 of 57 (75%). The incidence of p53 gene mutations observed in the Young Group was significantly higher than in the Elderly Group (P = 0.0007). Alcohol and smoking status did not relate to p53 gene mutation expression. Survival rate after surgery was not significantly associated with the presence of p53 gene mutation. However, in the Young Group with p53 gene mutation, those who had null mutations had a significantly shorter survival than those without null mutations (P = 0.0455). No other clinicopathological factors were associated with p53 gene mutations. Possibly, there may be a difference in esophageal carcinogenesis between the Young and the Elderly groups, because the incidence of p53 gene mutations is different between the two groups. In the Young Group, p53 gene mutation may cause esophageal carcinogenesis, and null mutation for p53 gene is a significant prognostic factor.     

Mutations in the 11-cis retinol dehydrogenase gene in Japanese patients with Fundus albipunctatus

PURPOSE: To detect mutations in the RDH5 gene encoding 11-cis retinol dehydrogenase in patients from Japan with fundus albipunctatus. METHODS: Polymerase chain reaction and direct genomic sequencing techniques were used to detect mutations of the RDH5 coding exons (exons 2-5) in two unrelated patients with fundus albipunctatus. Selected alleles that altered the coding region or intron splice sites were evaluated further through segregation analysis in the families of the index cases. RESULTS: Two novel RDH5 mutations were identified. One of these was a missense mutation Val264Gly in exon 5, and the other was an in-frame insertion of 3 bp in exon 5. CONCLUSIONS: The data indicate that mutations in RDH5 are the primary cause of fundus albipunctatus.