Systemic Delivery of Synthetic MicroRNA-16 Inhibits the Growth of Metastatic Prostate Tumors via Downregulation of Multiple Cell-cycle Genes

Recent reports have linked the expression of specific microRNAs (miRNAs) with tumorigenesis and metastasis. Here, we show that microRNA (miR)-16, which is expressed at lower levels in prostate cancer cells, affects the proliferation of human prostate cancer cell lines both in vitro and in vivo. Transient transfection with synthetic miR-16 significantly reduced cell proliferation of 22Rv1, Du145, PPC-1, and PC-3M-luc cells. A prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic miR-16 to tumor cells on bone tissues in mice when injected into tail veins. In the therapeutic bone metastasis model, injection of miR-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. Cell model studies indicate that miR-16 likely suppresses prostate tumor growth by regulating the expression of genes such as CDK1 and CDK2 associated with cell-cycle control and cellular proliferation. There is a trend toward lower miR-16 expression in human prostate tumors versus normal prostate tissues. Thus, this study indicates the therapeutic potential of miRNA in an animal model of cancer metastasis with systemic miRNA injection and suggest that systemic delivery of miR-16 could be used to treat patients with advanced prostate cancer.     

A Study on the Prognostic Evaluation of Carbon Ion Radiotherapy for Head and Neck Adenocarcinoma with C-11 Methionine PET

Purpose  

Carbon ion radiotherapy (CIRT) has been developed, and a phase I/II CIRT trial has been conducted in patients with adenocarcinoma in the head and neck region. We evaluated whether the l-methyl [11C]-methionine (MET) uptake could be an early predictor for local recurrence, metastasis, and the prognosis in patients with adenocarcinoma in the head and neck region.     

Estimation of intraocular pressure in rabbits with commonly used tonometers.

BACKGROUND AND OBJECTIVES: To validate accuracy and reproducibility of the Perkins tonometer, pneumatonometer, and Tono-Pen XL (Medtronic Solan, Jacksonville, FL) in estimating intraocular pressure (IOP) in rabbits. MATERIALS AND METHODS: IOP was increased from 5 to 50 mm Hg in 5-mm increments. Measurements were compared to readings of two digital manometers simultaneously measuring real IOP in the anterior chamber and vitreous cavity. Interobserver accuracy was evaluated using 4 eyes with the Perkins tonometer. RESULTS: The Perkins tonometer and Tono-Pen XL underestimated IOP and were more accurate at pressures less than 30 mm Hg. No statistically significant difference was found between real IOP and Tono-Pen XL readings. The pneumatonometer overestimated pressures in the low ranges but was accurate at pressures greater than 40 mm Hg. The Tono-Pen XL had more variability than the Perkins tonometer and pneumatonometer at high IOP. CONCLUSIONS: None of the tonometers are accurate or reproducible in estimating IOP in rabbits over the tested range. Pneumatonometry, although not very accurate, has the advantage of having acceptable variability.     

Prevention of Neonatal HBV Infection with the Combination of HBIG and HBV Vaccine and Its Long-Term Efficacy in Infants Born to HBeAg Positive HBV Carrier Mothers

Seventy-three infants born to HBeAg positive HBV carrier mothers were protected from neonatal HBV infection with our standard prevention schedule consisting of two doses of HBIC (0, 2 mo) and three doses of HBV vaccine (2, 3, 5 mo). In 62 infants who successfully responded to HBV vaccine with a titer of anti-HBs greater than 2³, anti-HBs titer was monitored for as long as 48 months (25.6 ±11.0 mo) and found to decrease as follows: 5.1 ± 1.7 at 12 mo., 4.5 ± 1.8 at 18 mo., 4.2 ± 1.8 at 24 mo., 4.0± 1.6 at 30 mo., 3.7 ± 1.7 at 36 mo., 32 ± 2.0 at 48 mo. During the follow-up period, eight HBV events (11.9%) were demonstrated: one case showed an increase of anti-HBs, three showed a reappearance of anti-HBc alone, three showed a reappearance of anti-HBc with increase of anti-HBs, and one became a chronic HBV carrier. All infants were further divided into three groups by their maximal response of anti-HBs to HBV vaccine: Group I (2⁶), Group II (2³-2⁵), and Group III (2²). Group I sustained a higher titer from 12 to 30 months of age and had less HBV events than (3-II and G-III. Our study suggests that acquisition of a high titer of anti-HBs is important in long-term prevention of HBV infection as well as in the neonatal period in infants born to HBeAg positive HBV carrier mothers.     

Leiomyosarcoma of the Pancreas: Report of a Case Diagnosed by Fine Needle Aspiration Biopsy

We present a case of pancreatic leiomyosarcoma with liver metastasisdiagnosed by liver tumor biopsy. A 66-year-old man had a pancreatictumor and hepatic tumors, which were hypoechoic and mixed echoicon ultrasonography, respectively. They were stained in enhancedcomputed tomography and angiography. A fine needle aspirationbiopsy of the liver tumor was performed, and the pathologicalexamination of the biopsied specimen suggested the tumor cellsto have originated from smooth muscle. Under a diagnosis ofpancreatic leiomyosarcoma with liver metastasis, the patientwas treated with several anticancer agents. The tumor, however,spread to multiple organs and he dies of the disease two yearsnine months after the start of treatment. The diagnosis of pancreaticleiomyosarcoma was confirmed by autopsy.     

Leisure-time physical activity and related lifestyle characteristics among middle-aged Japanese. Japan Lifestyle Monitoring Study Group

The present study describes leisure-time physical activity status and related lifestyle factors in middle-aged Japanese. Data were obtained from 1,893 (905 men, 988 women) participants aged 40-69 years who had either been selected from a public registry or who had visited a healthcare facility. Subjects responded to a self-administered questionnaire and were interviewed using an assessment method for leisure-time and on-the-job physical activity within the last 12 months by trained interviewers. According to the leisure-time physical activity score, men and urban residents tended to engage in more leisure-time physical activity than did women and rural residents, respectively. Leisure-time physical activity tended to be inversely associated with on-the-job physical activity in all cases aside from women in urban regions, and also to be associated with higher levels of education in rural regions. Subjects engaging in more leisure-time physical activity had higher odds ratios of certain lifestyle factors, indicating a healthy lifestyle that included a variety of foods in their diet and a subjective sense of wellness in both men and women, in addition to non-smoking and drinking milk in men. These results suggested that leisure-time physical activity is influenced by socio-environmental factors, and that it is accompanied by other healthy behavior.     

Urinary Fibrin and Fibrinogen Degradation Products and the Origin of Hematuria

We examined urinary fibrin and fibrinogen degradation product (U-FDP) concentrations in pediatric patients with hematuria using the rapid and highly-sensitive latex particle agglutination test (LPAT), and assessed the value of this test for the localization of the site of hematuria. Patients with hematuria were divided into two groups: 60 with glomerular hematuria and 46 with non-glomerular hematuria. If U-FDP concentrations less than 0.25 μg/ml are Accepted as an indicator of glomerular bleeding, the sensitivity and specificity of localization of glomerular hematuria in the present study were 78% (47/60) and 89% (41/46), respectively. The high U-FDP concentrations observed in patients with non-glomerular hematuria may reflect direct bleeding into the urinary tract. Since all 13 patients with glomerular hematuria and U-FDP concentrations of 0.25 μg/ml or more had coexistent erythrocyte cylindruria, the U-FDP test seems to be compensated with combined urinalysis for the relatively lower sensitivity. We conclude that a knowledge of U-FDP concentrations by LPAT can be of help in localizing the site of bleeding in hematuria.     

Clinical Response to Systemic Combined Chemotherapy with 5-Fluorouracil and Cisplatin (FP Therapy) in Patients with Advanced Pancreatic Cancer

Pancreatic cancer shows high mortality and has a poor prognosis.Although the rate of response to all chemotherapeutic regimensis low, some patients have shown improvement of their symptomsafter chemotherapy and/or radiotherapy without obvious tumorregression. We assessed the clinical benefit of systemic combinedchemotherapy with 5-fluorouracil and cisplatin (FP therapy)in 21 patients with advanced cancer of the pancreas. The clinicalresponse to FP therapy was evaluated using two parameters: pain(intensity of pain and consumption of morphine) and performancestatus. A patient was considered to be a clinical responderif one of two parameters was positive and the other was positiveor stable. Four patients (19%) responded. Two of the respondersachieved partial response according to the objective tumor response,and the remaining two showed no change. The survival periodin responders was significant longer than in the other patients.The clinical response may be one parameter for evaluating theresults of treatment for pancreatic cancer, and the longer survivalperiod of the clinical responders in this study supports thisnotion.     

Randomized comparative study of omeprazole and famotidine in reflux esophagitis

BACKGROUND: Although proton pump inhibitors (PPI) and H2-receptor antagonists (H2-RA) are routinely used in the treatment of reflux esophagitis (RE), no consensus has been reached yet as to whether the first-choice drug should be PPI or H2-RA. In this study, the effects of omeprazole (OMP) and famotidine (FAM) on RE have been examined in a randomized comparative study. METHODS: Protocols of OMP 20 mg once daily or FAM 20 mg twice daily for 8 weeks were allocated to 56 cases with RE at random, using an envelope randomization method. Their efficacy in achieving healing was examined endoscopically and a relief from subjective symptoms was compared. RESULTS: Patient's background such as sex, age, recurrence, hiatal hernia, smoking and drinking habits, and complications, and the severity of esophagitis at the time of enrolment were not significantly different between the two groups. Healing in the OMP group and the FAM group was observed in 72 and 32% (P = 0.025) of patients at week 4 and 95 and 53% (P = 0.003) of patients at week 8, respectively. Subjective symptoms were relieved more frequently in the OMP group (at week 2, 67% compared with 29%, P = 0.005; at week 4, 95% compared with 55%, P = 0.009), but this superiority was not significant at week 8 (94% compared with 65%, P = 0.085). No serious adverse events occurred. CONCLUSIONS: Omeprazole provided quicker healing and a greater relief from subjective symptoms than did FAM in the treatment of RE, and was considered more suitable as a first-choice drug.