Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type

Natural killer (NK) cell lymphomas/leukemias are highly aggressive lymphoid malignancies, but little is known about their genomic alterations, and thus there is an urgent need for identification and analysis of NK cell lymphomas/leukemias. Recently, we developed our own array-based comparative genomic hybridization (array CGH) with an average resolution of 1.3 Mb. We performed an array CGH analysis for 27 NK-cell lymphoma/leukemia cases that were classified into two disease groups based on the World Health Organization Classification (10 aggressive NK-cell leukemia cases and 17 extranodal NK/T-cell [NK/T] lymphomas, nasal type). We identified the differences in the genomic alteration patterns of the two groups. The recurrent regions characteristic of the aggressive NK-cell leukemia group compared with those of the extranodal NK/T lymphoma, nasal-type group, were gain of 1q and loss of 7p15.1-p22.3 and 17p13.1. In particular, gain of 1q23.1-24.2 (P = 0.041) and 1q31.3-q44 (P = 0.003-0.047), and loss of 7p15.1-p22.3 (P = 0.012-0.041) and 17p13.1 (P = 0.012) occurred significantly more frequently in the former than in the latter group. Recurrent regions characteristic of the extranodal NK/T lymphoma, nasal-type group, compared with those of the other group were gain of 2q, and loss of 6q16.1-q27, 11q22.3-q23.3, 5p14.1-p14.3, 5q34-q35.3, 1p36.23-p36.33, 2p16.1-p16.3, 4q12, and 4q31.3-q32.1. Our results can be expected to provide further insights into the genetic basis of lymphomagenesis and the clinicopathologic features of NK-cell lymphomas/leukemias.     

Effects of subconjunctival injection of mitomycin-C on iridial circulation in rabbits.

PURPOSE. To determine the effects of a subconjunctival injection of mitomycin-C (MMC) on iridial circulation in rabbits. METHODS. Dutch rabbits anesthetized with pentobarbital received a 0.2-ml subconjunctival injection of 0.4 mg/ml or 0.1 mg/ml MMC; the contralateral eye received 0.2 ml physiological saline. Intraocular pressure (IOP) and NB( iris), a quantitative index of iridial tissue blood velocity, were measured up to 24 hours after treatment. RESULTS. At a dosage of 0.4 mg/ml MMC, NB iris obtained from the iridial area adjacent to the injection site decreased significantly by 13.6% and 18.6% at 1 and 2 hours (P = 0.03, 0.01, respectively) after treatment; NB iris obtained on the contralateral side of the injection showed no significant change. In eyes treated with 0.1 mg/ml MMC, NB iris did not change significantly. The mean IOP was significantly lower by 3.1, 3.0, and 1.8 mm Hg at 6, 12, and 24 hours after the 0.4 mg/ml injection of MMC compared with the fellow eyes (P = 0.03, 0.01, and 0.03, respectively), the IOP decreased by 1.7 mm Hg at 4 hours in the eyes treated with 0.1 mg/ml MMC (P = 0. 04). CONCLUSIONS. Subconjunctival injections of 0.2 ml of 0.4 mg/ ml MMC caused not only a significant decrease of IOP but also a transient but significant effect on iridial circulation.     

Transurethral Needle Ablation of the Prostate: Report of Initial United States Clinical Trial

Purpose

We studied the efficacy and safety of transurethral needle ablation of the prostate for treatment of symptomatic benign prostatic hyperplasia (BPH).

Materials and Methods

A total of 12 patients with symptomatic BPH underwent transurethral needle ablation of the prostate. Voiding outcomes, including American Urological Association symptom scores, bother scores, quality of life scores, peak urinary flow rates, residual urine volumes and urodynamic pressure flows, were measured with time, and immediate and short-term (6 months) complications were assessed.

Results

Transurethral needle ablation of the prostate was performed with local intraurethral lidocaine anesthesia in 11 patients and general anesthesia in 1. At 6 months there was a 61.7 percent improvement in American Urological Association symptom score (25.6 to 9.8, p = 0.0001), 61.1 percent improvement in bother score (18.8 to 7.3, p = 0.0002), 70.0 percent improvement in quality of life score (13.7 to 4.1, p = 0.0001), 73.0 percent increase in peak flow rate (7.8 to 13.5 cc per second, p less than 0.0001) and 54.9 percent decrease in the post-void residual (111 to 50 cc, p = 0.0457). Prostate volumes, maximum detrusor pressures and detrusor opening pressures decreased significantly. There were no intraoperative complications. Postoperatively, all 12 patients had mild dysuria for 1 to 7 days, 5 had transient urinary retention for 1 to 4 days, 3 had hematuria for 1 to 2 days and 1 had retrograde ejaculation.

Conclusions

This initial United States trial confirms previous experience, and shows that transurethral needle ablation of the prostate appears to be a simple, safe and efficacious procedure for treatment of symptomatic BPH. In addition, it can be performed in the majority of patients using topical urethral anesthesia.     

A case of ovarian cancer with liver metastasis successfully treated by PAC therapy

Surgery was attempted in a case of stage IV ovarian cancer with a hepatic metastatic lesion measuring 119 x 96 mm. However, radical surgery was impossible and the operation ended up as no more than exploratory laparotomy. Before closing, Cisplatin 100 mg and Etoposide 200 mg were instilled into the intraperitoneal cavity. Two courses of systemic chemotherapy with PAC (Cisplatin 50 mg, Pirarubicin 40 mg, Cyclophosphamide 400 mg) were instituted. To examine shrinkage of the hepatic metastasis and the peritoneal tumors, A "Second look" operation was conducted. Abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, omentectomy and partial sigmoidectomy resulted in no residual lesions in the peritoneal cavity with the exception of the hepatic metastatic lesion (69 x 57 mm). Two additional courses of PAC therapy were administered after the "Second look" operation. The hepatic metastatic lesion shrank to 45 x 41 mm; a decrease of 83.8% compared to the pre-therapy in size. Liver function tests and tumor chemical markers (TPA, CA 125, SLX) revealed decreased values that were consistent with a tumor size reduction. Good PR was achieved with only a systemic chemotherapy; i.e., without resorting to local injections of chemotherapeutic agents into the liver.     

Targeting of nuclear factor kappaB Pathways by dehydroxymethylepoxyquinomicin, a novel inhibitor of breast carcinomas: antitumor and antiangiogenic potential in vivo.

We previously designed and synthesized the new nuclear factor kappaB (NF-kappaB) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) derived from the structure of the antibiotic epoxyquinomicin C. We looked into the effect of DHMEQ on cellular phenotypes and tumor growth in mice injected with human breast carcinoma cell line MDA-MB-231 or MCF-7. In estrogen-independent breast adenocarcinoma cell line MDA-MB-231, NF-kappaB is constitutively activated. The addition of DHMEQ (10 microg/mL) completely inhibited the activated NF-kappaB for at least 8 hours. On the other hand, NF-kappaB is not activated in estrogen-dependent MCF-7 cells. In this cell line, DHMEQ completely inhibited the tumor necrosis factor-alpha-induced activation of NF-kappaB. DHMEQ did not inhibit the degradation of IkappaB but inhibited the nuclear translocation of NF-kappaB by both p65/p50 and RelB/p52 pathways. MDA-MB-231 cells secrete interleukin (IL)-6 and IL-8 without stimulation, and DHMEQ decreased the secretion levels of both cytokines. When MDA-MB-231 or MCF-7 cells were stimulated by tumor necrosis factor-alpha, the inhibitory effects of DHMEQ were still maintained. I.p. administration of DHMEQ (thrice a week) significantly inhibited the tumor growth of MDA-MB-231 (12 mg/kg) or MCF-7 (4 mg/kg) in severe combined immunodeficiency mice. No toxicity was observed during the experiment, including the loss of body weight. An immunohistological study on resected MCF-7 tumors showed that DHMEQ inhibited angiogenesis and promoted apoptosis. Furthermore, in Adriamycin-resistant MCF-7 cells highly expressing multidrug resistance gene-1, DHMEQ also exhibited the above capability, including down-regulation of IL-8. Thus, DHMEQ might be a potent drug for the treatment of various breast carcinomas by inhibiting the NF-kappaB activity.     

Successful therapy with argatroban for superior mesenteric vein thrombosis in a patient with congenital antithrombin deficiency

A 38-year-old woman was admitted with superior mesenteric vein (SMV) thrombosis, which was refractory to anticoagulation therapy. The plasma antithrombin activity was decreased and hardly compensated by concentrated antithrombin preparation due to high consumption rate. However, successful anticoagulation was achieved by administration of direct thrombin inhibitor, argatroban. Family studies of antithrombin activity revealed that she had type I congenital antithrombin deficiency. A novel heterozygous mutation in the gene for antithrombin (single nucleotide T insertion at 7916 and 7917, Glu 272 to stop in exon 4) was identified. Argatroban administration would be effective in the treatment of congenital antithrombin deficiency with SMV thrombosis.     

Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy

This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals. A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs. The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.     

Development of Epstein-Barr virus-associated gastric cancer: Infection,inflammation, and oncogenesis

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells originate from a single-cell clone infected with EBV. However, more than 95% of patients with gastric cancer have a history of Helicobacter pylori (H. pylori) infection, and H. pylori is a major causative agent of gastric cancer. Therefore, it has long been argued that H. pylori infection may affect the development of EBVaGC, a subtype of gastric cancer. Atrophic gastrointestinal inflammation, a symptom of H. pylori infection, is observed in the gastric mucosa of EBVaGC. Therefore, it remains unclear whether H. pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H. pylori and EBV infections act independently on gastric cancer formation. It has been reported that EBV infection assists in the onco-genesis of gastric cancer caused by H. pylori infection. In contrast, several studies have reported that H. pylori infection accelerates tumorigenesis initiated by EBV infection. By reviewing both clinical epidemiological and experimental data, we reorganized the role of H. pylori and EBV infections in gastric cancer formation.