Drug release properties of a gel bead prepared with pectin and hydrolysate.

A calcium-induced pectin gel bead (PB) containing pectin hydrolysate was prepared, and the drug release profiles and degradation properties of the PB were investigated in aqueous media. The stiff PB swelled in physiological saline and its drug release rate decreased with exposure to increasing concentrations of CaCl2 during preparation. And erosion of the PB was not observed in physiological saline. However, the PB did disintegrate in phosphate buffer (pH 6.8) and the rate of disintegration depended on the calcium chloride concentration used to prepare the PB. In addition, the drug release rate of the PB in buffer solution decreased as the rate of gel erosion declined. Consequently, it appears that the PB gel matrix is an effective medium by which to control the release of drug within the gastrointestinal tract.     

Impaired consciousness caused by a metastatic adrenal tumor of pulmonary adenocarcinoma

We report a case of pulmonary adenocarcinoma metastasizing to the adrenal glands, which caused adrenal insufficiency leading to impaired consciousness. A 62 year-old man was admitted with impaired consciousness. The patient started chemotherapy from 2004 for pulmonary adenocarcinoma. In August 2004, a metastatic adrenal tumor was detected and chemotherapy was continued thereafter. From July 2005, the patient started to have mild hyperkalemia, anorexia and general malaise, which progressed to disturbance of consciousness. At admission, physical examination showed generalized pigmentation in the skin and mucosa. Blood test revealed hypoglycemia, hyponatremia and hyperkalemia. A dexamethasone suppression test and a rapid ACTH loading test led to a diagnosis of primary hypoadrenalism (Addison's disease). Treatment with hydrocortisone improved the physical status and blood test values. However, the patient subsequently died of disseminated intravascular coagulation due to the tumor.     

Antisense oligonucleotides of hepatoma-derived growth factor (HDGF) suppress the proliferation of hepatoma cells

BACKGROUND/AIMS: Human hepatoma-derived growth factor, purified from the conditioned medium of hepatoma-derived cell line, HuH-7, stimulates the growth of Swiss 3T3 fibroblasts and HuH-7 cells. To evaluate the role of hepatoma-derived growth factor on the growth of hepatoma cells, we investigated the effects of recombinant hepatoma-derived growth factor protein and hepatoma-derived growth factor antisense oligonucleotides on the proliferation of several hepatoma cell lines. METHODOLOGY: We examined the effects of hepatoma-derived growth factor antisense oligonucleotides on the growth of hepatoma cells by cell growth assay. RESULTS: Hepatoma-derived growth factor stimulated the proliferation of some hepatoma cells (HuH-7, HLF, HepG2, AH66tc cells) about 15-70% over than the control. Hepatoma-derived growth factor antisense oligonucleotides, phosphorothioate-linked or encapsulated in liposome, can inhibit the growth of hepatoma cells. The ID50 of hepatoma-derived growth factor antisense phosphorothioate oligonucleotides for HuH-7 cells, in which hepatoma-derived growth factor expression was abundant, was 3 microM by the assay of cell proliferation and [3H]-thymidine incorporation. Their ID50 for AH66tc cells, on which the effects of exogenous hepatoma-derived growth factor were weak, was higher than 10 microM. To omit the toxic effects due to phosphorothioate modification of oligonucleotides and keep the cellular uptake more without their destruction in the culture medium, we used oligonucleotides encapsulated in cationic liposome. Hepatoma-derived growth factor antisense oligonucleotides encapsulated in liposome suppressed the growth of hepatoma cells effectively (ID50:2.0 microM). CONCLUSIONS: These findings suggest that hepatoma-derived growth factor is one of important autocrine, and/or intracrine factors for hepatoma cells, and that hepatoma-derived growth factor anti-sense oligonucleotides may be useful for human hepatocellular carcinoma as an anti-cancer agent.     

Suppression of body weight gain preserves acute insulin response to glucose in the portal vein of spontaneously type 2 diabetic rats with visceral obesity

The age-related changes in acute insulin response after glucose loading and the influence of suppression of body weight gain were investigated by using blood samples from portal and peripheral veins. We placed indwelling catheters in the portal vein of 12- and 24- wk-old Otsuka Long-Evans Tokushima fatty (OLETF) rats (n = 8, 12), and age-matched control Long-Evans Tokushima Otsuka (LETO) rats (n = 8, 6). To suppress the body weight gain, 6 out of 12 OLETF rats were fed chow containing 50 ppm voglibose (VOG) from 8 until 24 wk of age. After fasting for 17 h, rats underwent 1 g/kg oral glucose tolerance test (OGTT). Peripheral glucose levels after glucose loading were significantly higher in 12- and 24-wk-old OLETF rats than in the age-matched LETO rats. Values for delta insulin 15 min/delta glucose 15 min (delta I15 min/delta G15 min) in portal blood were 0.029 +/- 0.011 and 0.009 +/- 0.009 (12 wk of age) and 0.03 +/- 0.03 and -0.01 +/- 0.01 (24 wk of age) in the LETO rats and OLETF rats. At the age of 24 wk, the body weights in VOG-treated OLETF rats were significantly lower than those in the OLETF rats. And there was significantly greater acute insulin response to glucose in VOG-treated OLETF rats than in the OLETF rats. Acute insulin response to glucose decreased with advancing age and the suppression of body weight gain preserved the response in spontaneously type 2 diabetic rats with visceral fat obesity.     

Efficacy of modified bevacizumab-XELOX therapy in Japanese patients with stage IV recurrent or non-resectable colorectal cancer

BackgroundNeoadjuvant chemotherapy (NAC) has been conducted for patients with non-resectable colorectal cancer; however, few reports of a systematic approach to NAC exist. At our hospital, bevacizumab with capecitabine and oxaliplatin (B-mab XELOX) has been used as chemotherapy for Stage IV colorectal cancer since 2014. We aimed to evaluate the efficacy and safety of NAC with a molecular-targeting agent for Stage IV colorectal cancer.MethodsA retrospective, single-institute analysis was performed including 27 patients with advanced recurrent cancer following primary tumor resection and 43 patients with non-resectable tumors and remote metastasis. At the time of resection, 17 were receiving chemotherapy. All 70 patients received at least 3 cycles of B-mab XELOX (total: 920 cycles). We determined the 1-year progression-free survival (1Y-PFS), 1-year overall survival (1Y-OS), 3Y-PFS, 3Y-OS, and number of treatment cycles. The objective response rate, clinical benefit rate, and adverse events were assessed. The number of chemotherapy cycles, survival time, and R0 surgery rate were determined for patients who underwent RO conversion surgery.ResultsThe 1Y-PFS was 28.5% [median survival time (MST): 7.4 months], 1Y-OS was 76.6% (MST not reached), 3Y-PFS was 5.5% (MST: 7.4 months), and 3Y-OS was 26.4% (MST: 25.2 months). The mean and median number of cycles of B-mab XELOX was 13.1 and 10.5, respectively. The objective response rate was 28.6%, and the clinical benefit rate was 58.6%. Grade 1 or Grade 2 adverse events occurred in 60 patients (85.7%); however, they all resolved without intervention. A single Grade 4 event (perforation of the primary tumor) occurred in 1 patient (1.4%). RO conversion surgery was performed in 7 patients (10.0%; primary + liver in 2 patients, primary + lung in 1 patient, liver in 3 patients, and primary in 1 patient). These patients received 3 to 10 cycles preoperatively (mean: 7.3; median: 6.5). R0 surgery was achieved in 5 of the 7 patients (71.4%). Postoperative survival ranged from 1 to 26 months (MST: 8 months).ConclusionsThis modified regimen was safe and effective in Japanese patients, and a high quality of life/quality-adjusted life-year was achieved. To further evaluate PFS and OS, more patients are being investigated.     

Fractional anisotropy and tumor cell density of the tumor core show positive correlation in diffusion tensor magnetic resonance imaging of malignant brain tumors

A noninvasive technique for assessing tumor tissue characteristics is required to assist preoperative surgical planning for malignant brain tumors. Preoperative information on tumor cell density within a tumor would help better define the target for tumor biopsy, resulting in more accurate diagnosis and grading of malignant brain tumors. One possible source of this information is diffusion tensor imaging (DTI), although to date studies have focused on its ability to delineate white matter fiber tracks by fiber-tracking and to detect tumor infiltration around the tumor and normal white matter interface. However, the use of DTI for providing information on cell density has also been examined, although with the controversial results. In addition the exact relationships between cell density and the two key values that DTI provides, namely fractional anisotropy (FA) and mean diffusivity (MD), still need to be investigated. In the present study we performed a retrospective investigation of tumor cell density and FA and MD values in biopsy cases. We found that FA has a good positive correlation (R=0.75) and MD has a good negative correlation (R=0.70) with tumor cell density within the tumor core. Similar correlation was observed between the Ki-67 labeling index and FA (R=0.71) and MD (R=0.62). Thus, measurement of both FA and MD within the tumor core has a potential to provide detailed information on tumor cell density within the tumor. Although data obtained from DTI should be interpreted carefully and comprehensively with other imaging modalities such as positron emission tomography, DTI seems to be informative for planning the best biopsy target containing the highest cell density.