The overt effects of the anticancer drugs such as cisplatin and taxol appear to be DNA modification and microtubule stabilization respectively. But the mechanism by which these drugs affect tumor cell cycle perturbation and their correlation to apoptosis and cytotoxicity are not well understood, especially in combined sequential treatment of cisplatin and paclitaxel (taxol). In this study, to elucidate the action mechanisms as a function of cell cycle changes and cytotoxicities and to determine the adequate treatment sequence of cisplatin and taxol to acquire more enhanced cytotoxic effects when they are combined, we evaluated the cell cycle perturbations and its correlation to cytotoxic effects, which is measured by the extents of apoptosis and the fractions of cellular debris and live cells after combination treatment of cisplatin and taxol changing their treatment sequences in NIHOVCAR-3 ovarian cancer cell line. Our results were as follows; (1) The accumulation in S phase inhibited the entrance of tumor cells to G2M phase when the cisplatin treatment was preceded to taxol in their combination. (2) The tumor cells were not accumulated in S phase but most of them entered to and accumulated in G2M phase and they were leading to cell death when the taxol treatment was preceded to cisplatin in their combination. (3) Apoptotic peaks in taxol pretreatment group were detected earlier and persisted longer than that of cisplatin pretreatment group. (4) The cytotoxicities represented by the decreased fractions of live cells and the increased fractions of cellular debris were higher in taxol pretreatment group than those of cisplatin pretreatment group. These results suggested that the taxol pretreatment is more effective in combination of cisplatin and taxol and the relative decrease in the cytotoxicity in cisplatin pretreatment group was considered to be derived from the inhibition of entrance of tumor cells to G2M and protected them from the action by taxol. From these results, we concluded that the taxol pretreatment will enhance the cytotoxic effects to tumor cells when cisplatin and taxol will be administered and it indicates that correlations between cell cycle perturbation, apoptosis and cell death have to be considered in the future combination treatment of other drugs and in the development of new treatment regimens.
Apoptosis ; Cell Cycle* ; Cell Death* ; Cell Line* ; Cisplatin* ; DNA ; Microtubules ; Ovarian Neoplasms ; Paclitaxel* ; S Phase

The Heterotopic pancreas is defined as the presence of pancreatic tissue lacking anatomical and vascular continuity with the main body of pancreas. Heterotopic pancreas or ectopic pancreas is found in 0.55% to 13.7% of autopsy series and also found one in approximately every 500 operations in abdominal surgery. The most common sites are the antrum of stomach, duodenum, and proximal jejunum. Most masses of heterotopic pancreas in stomach were encountered in the distal one third, usually within 5 or 6 cm of pylorus. We have recently experienced a case of hetertopic pancreas that was located in fundus which is not the usual site. Gastrofiberscopy revealed a 2 2.5 cm sized protruding mass on the fundus. There was apperared an umbilical shaped dimple on the center with a relatively normal mucosa. Endoscopic ultrasonography revealed a 2.5 cm sized hypoechoic mass of fundus, originating from submucosal and muscular layer. It was considered a submucosal tumor, such as leiomyoma, and subsequently wedge resection was performed. Histologic finding showed pancreatic acni.
Autopsy ; Duodenum ; Endosonography ; Jejunum ; Leiomyoma ; Mucous Membrane ; Pancreas* ; Pylorus ; Stomach*

OBJECTIVE: The purpose of the present study was to investigate the efficacy, safety, and tolerability of aripiprazole in patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder during acute treatment phase. METHODS: Prospective, multicenter, single group, and 8-week study was conducted in patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder. A total of 300 patients were enrolled in the present study. The primary efficacy measure was the Positive and Negative Syndrome Scale (PANSS) total score, and secondary efficacy measures were the PANSS positive and negative subscales scores, and Clinical Global Impression-Severity of Illness (CGI-S) score. Treatment-emergent adverse events, extrapyramidal symptoms (EPS), weight, vital signs, and laboratory tests were assessed as measures of tolerability and safety. RESULTS: Significant improvements in all efficacy measures were achieved by aripiprazole as early as 1-week and sustained through 8-week period. First-episode patients showed greater improvements in PANSS total, positive subscale score, and CGI-S score, compared with recurrent patients. Slightly increased akathisia (+0.32 from baseline score of Barnes Akathisia Rating Scale, p=0.033) and weight gain (1.15+/-3.44 kg, p<0.001) were observed by aripiprazole during 8-week acute treatment phase. CONCLUSION: The present study demonstrated that aripiprazole was effective in acute treatment of positive and negative symptoms of schizophrenia, schizophreniform disorder, and schizoaffective disorder. In general, aripiprazole showed favorable safety and tolerability profiles, although clinicians needed to pay attention to the possibility of akathisia and weight gain by aripiprazole in first-episode patients during acute treatment phase.
Humans ; Piperazines ; Prospective Studies ; Psychomotor Agitation ; Psychotic Disorders ; Quinolones ; Schizophrenia ; Vital Signs ; Weight Gain ; Aripiprazole

OBJECTIVE: The purpose of the present study was to investigate the efficacy, safety, and tolerability of aripiprazole in patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder during acute treatment phase. METHODS: Prospective, multicenter, single group, and 8-week study was conducted in patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder. A total of 300 patients were enrolled in the present study. The primary efficacy measure was the Positive and Negative Syndrome Scale (PANSS) total score, and secondary efficacy measures were the PANSS positive and negative subscales scores, and Clinical Global Impression-Severity of Illness (CGI-S) score. Treatment-emergent adverse events, extrapyramidal symptoms (EPS), weight, vital signs, and laboratory tests were assessed as measures of tolerability and safety. RESULTS: Significant improvements in all efficacy measures were achieved by aripiprazole as early as 1-week and sustained through 8-week period. First-episode patients showed greater improvements in PANSS total, positive subscale score, and CGI-S score, compared with recurrent patients. Slightly increased akathisia (+0.32 from baseline score of Barnes Akathisia Rating Scale, p=0.033) and weight gain (1.15+/-3.44 kg, p<0.001) were observed by aripiprazole during 8-week acute treatment phase. CONCLUSION: The present study demonstrated that aripiprazole was effective in acute treatment of positive and negative symptoms of schizophrenia, schizophreniform disorder, and schizoaffective disorder. In general, aripiprazole showed favorable safety and tolerability profiles, although clinicians needed to pay attention to the possibility of akathisia and weight gain by aripiprazole in first-episode patients during acute treatment phase.
Humans ; Piperazines ; Prospective Studies ; Psychomotor Agitation ; Psychotic Disorders ; Quinolones ; Schizophrenia ; Vital Signs ; Weight Gain ; Aripiprazole