Size-based analysis of virus removal filter fouling using fractionated protein aggregates.

Fouling by protein aggregates reduces virus removal filter performance. In the present study, we investigated the effects of different-sized protein aggregates on fouling and aggregate retention in order to better understand the fouling mechanisms. Human immunoglobulin G was denatured by heating to produce aggregates of various sizes and then fractionated by size exclusion chromatography into different-sized aggregates with a narrow size distribution. The fractionated aggregates were filtered on Planova 20N, a virus removal filter known for its stable filtration capability. Analysis of flux behavior demonstrated different flux decrease patterns for different-sized aggregates. Observation of aggregate retention by staining revealed that larger aggregates were captured closer to the inner surface of the membrane while smaller aggregates penetrated farther into the membrane. These findings demonstrate that Planova 20N has a gradient structure with decreasing pore size from the inner to the outer surface of the membrane. This structure minimizes fouling and enables stable filtration by protecting the smaller pores located closer to the outer surface from clogging by large aggregates. Applying the predominant clogging models to the present filtrations revealed that clogging behavior transitioned from complete blocking to cake filtration as filtration progressed. In this combination model, after a certain number of pores are blocked by complete blocking, newly arrived aggregates begin to accumulate on previously captured aggregates, generating cake between capture layers within the membrane. Application of the approaches described here will facilitate elucidation of membrane fouling and virus removal mechanisms.

[A case of gastric cancer with peritoneal dissemination who achieved long survival from control of ascites for over 2 years by successive treatments with S-1 in combination with docetaxel as first-line followed by irinotecan in combination with cisplatin as second-line].

The patient was a 66-year-old male, admitted and diagnosed as having advanced gastric cancer with peritoneal dissemination, leading to ascites and obstructive jaundice. After reducing the degree of obstructive jaundice, combination chemotherapy of S-1 80mg/m2/day(2 weeks administration and 1 week rest)and docetaxel(TXT)40mg/m2(day 1)was administered from February, 2008. After 3 courses of this regimen, CT revealed no evidence of ascites, and this chemotherapy was successively continued on an outpatient basis until June, 2009. After the relapse of ascites from July, 2009, combination chemotherapy of irinotecan(CPT-11)60mg/m2 and cisplatin(CDDP)30mg/m2 biweekly was performed as second-line chemotherapy, and the ascites disappeared again after around 2 courses of this regimen. This chemotherapy was continued on an outpatient basis until February, 2010. No major adverse reaction to either chemotherapy was observed. This case suggests that these chemotherapies, such as the combination chemotherapy of S-1 plus TXT as a first-line treatment and CPT-11 plus CDDP as the following second-line treatment, can be administered to an outpatient, can keep good patient's QOL and can be one of the effective chemotherapy options for advanced gastric cancer with peritoneal dissemination.

[A case of advanced ampullary carcinoma successfully resected after primary chemotherapy with s-1 and gemcitabine].

The patient was a 53-year-old male who was admitted on an emergency basis with obstructive jaundice. He was diagnosed as having advanced ampullary carcinoma(T4 N0 H1, Stage IV b). To reduce the degree of obstructive jaundice, a self-expandable metallic stent was placed in the area of the biliary obstruction. Immediately after relief from obstructive jaundice, combination chemotherapy of S-1 and gemcitabine was given. Subsequently, CA19-9, the tumormarker level was reduced, the metastatic liver tumor disappeared, and the size of the primary lesion was remarkably reduced. Therefore, a curative surgical resection was done. This is a very instructive case for developing effective chemotherapy options to treat biliary tract cancers involving ampullary carcinoma.