Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions.

Galectins are ß-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and-9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,-3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. N-glycan branching on lymphocytes and oligodendroglial progenitors mediated by ß1,6-N-acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.

Cell- and stage-specific localization of galectin-3, a ß-galactoside-binding lectin, in a mouse model of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease in which pathogenic T cells play an important role, and an experimental autoimmune encephalomyelitis (EAE) is used as an animal model of MS. Galectins are ß-galactoside-binding lectins and involved in various physiological and pathological events. Among fifteen members of galectins, galectin-1, -8, and -9 play immunosuppressive roles in MS and EAE; however, the role of galectin-3 (gal-3) is complex and controversial. We examined expression of gal-3 in the spinal cord and nerve roots of EAE mice. No immunohistochemical signals were detected in naïve mice, whereas gal-3 appeared at lower lumbar levels of the spinal cord and nerve roots in EAE mice. In the spinal cord, gal-3-positive cells were activated microglia and/or infiltrating macrophages, which were round in shape and intensified for the lysosomal enzyme, cathepsin D, indicating elevated phagocytic activity. Gal-3-positive cells in the spinal cord were most abundant during the peak symptomatic period. In the recovery period, they disappeared from the spinal parenchyma but remained at moderate levels in the pia mater. Interestingly, gal-3-positive cells selectively appeared in ventral, but not dorsal, nerve roots running through the spinal canal, with expression peaking during the recovery period. In ventral nerve roots, the major cell type expressing gal-3 was a specific population of Schwann cells that surround unmyelinated axons and express the biosynthetic enzyme for l-serine, a potent neurotrophic amino acid. Gal-3 was also induced in Iba1/F4/80-positive macrophages, which engulf damaged myelin and axon debris. Thus, gal-3 is induced in distinct cell types that are engaged in removal of damaged axons and cell debris and axon regeneration and remyelination, suggesting a potential neuroprotective role of gal-3 in EAE mice.

Daikenchuto stimulates colonic motility after laparoscopic-assisted colectomy.

BACKGROUND/AIMS: Paralytic ileus after laparoscopic-assisted surgery often occurs. We investigated whether daikenchuto (DKT), a traditional Japanese herbal medicine, improves intestinal motility in patients undergoing laparoscopic-assisted colectomy for colon cancer. METHODOLOGY: Fifty-four patients who underwent colectomy at Iwate Medical University Hospital between October 2010 and March 2012 were randomized to either the DKT group (7.5 g/day, p.o.) or the control group (lactobacillus preparation, 3g/day, p.o.). Primary endpoints included time to first flatus, bowel movement, and tolerance of diet after extubation. Secondary endpoints were WBC count, C-reactive protein (CRP) level, length of hospital stay, and postoperative ileus. Colonic transit time was measured using radiopaque markers and abdominal radiographs. RESULTS: Fifty-one patients (DKT, 26 vs. control, 25) were included in the per-protocol analysis. The DKT group had significantly faster time until first flatus (67.5 +/- 13.6h vs. 77.9 +/- 11.8h, P < 0.01) and bowel movement (82.9 +/- 17.8h vs. 99.5 +/- 18.9h, P < 0.01) and colonic transit time (91.9 +/- 19.8h vs. 115.2 +/- 12.8 h, P < 0.05). There were no significant intergroup differences in secondary endpoints and adverse events. CONCLUSIONS: DKT accelerates colonic motility in patients undergoing laparoscopic-assisted colectomy for colon cancer.

Laparoscopic-assisted proctocolectomy with prolapsing technique for familial adenomatous polyposis.

PURPOSE: The role of laparoscopic total proctocolectomy (TPC) and ileal pouch-anal anastomosis (IPAA) for familial adenomatous polyposis (FAP) has been controversial, given its technical difficulty of selecting the appropriate distal transection line and achieving safe anastomosis. We herein describe our initial experience with the prolapsing technique for laparoscopic-assisted TPC and IPAA (J-pouch) in the treatment of FAP. METHODS: A consecutive series of patients with FAP undergoing laparoscopic-assisted TPC with IPAA were identified from a prospectively collected database between June 2004 and February 2012. Medical records were reviewed for patient demographics, operative outcomes, and follow-up. RESULTS: The surgery was successfully completed in all 6 patients without any conversion to open surgery. The median operating time was 279 minutes (range, 240 to 386 min) and the median blood loss was 17.5 mL (range, 5 to 161 mL). No patient required blood transfusion. The median length of diet resumption and postoperative hospital stay were 7 days (range, 6 to 10 d) and 15 days (range, 13 to 21 d), respectively. A postoperative complication, wound infection, occurred in 1 patient. No anastomotic leakages or small bowel obstructions occurred. At a median follow-up of 59 months (range, 14.2 to 107.5 mo), no carcinoma had developed at the pouch or at the anastomotic site. Sexual function and fertility were unchanged as compared with preoperatively in 2 male patients. None of the patients experienced night-time incontinence or had to use a pad. CONCLUSIONS: Our limited experience suggests that this prolapsing technique helps prevent problems with laparoscopic-assisted TPC and IPAA for FAP patients.

Is ultrasound-guided central venous port placement effective to avoid pinch-off syndrome?

PURPOSE: Ultrasound (US)-guided internal jugular vein access has been the standard practice of central venous port (CVP) placement. The subclavian vein (SCV) access has also been preferred, but has potential risk of pinch-off syndrome (POS). The purpose of this study was to examine the effect of US-guided SCV access to avoid POS in patients with CVP. METHODS: Included in this study were patients who had undergone CVP placement via the SCV. We mainly assessed the computed tomography (CT) findings from two different placement techniques of a CVP via the SCV: (i) venipuncture point described by the ratio between the distance from the venipuncture point to the sternoclavicular joint and the clavicular length; and (ii) presence of direct attachment of the catheter to the clavicle. Secondary outcome was POS rate associated with two different placement techniques of CVP via the SCV. RESULTS: A total of 237 patients were included in this study between August 2007 and January 2011. A total of 100 patients (42.2%) underwent CVP placement using the landmark technique while 137 patients (57.8%) underwent CVP placement by US guidance. CT revealed that the US-guided technique tended to be lateral SCV approach compared with the landmark technique (p<0.001). A total of four patients (1.7%) experienced POS, all of them in the landmark group. CONCLUSION: Our results showed that the US-guided technique determines a more lateral SCV approach, with a reduced POS risk than the landmark venipuncture technique.

Potential value of sonazoid-enhanced intraoperative laparoscopic ultrasonography for liver assessment during laparoscopy-assisted colectomy.

PURPOSE: Laparoscopy-assisted colectomy (LAC) has gained acceptance for the treatment of colorectal cancer. However, conventional palpation of the liver and adequate observation of the abdominal cavity are not achievable during LAC. The aim of this study was to assess the clinical value of using Sonazoid (contrast enhanced)-intraoperative laparoscopic ultrasonography (S-IOLUS) in patients with primary colorectal cancer. METHODS: From May 2005 to August 2008, 454 patients underwent 339 LACs and 115 open colectomies for colorectal cancer. One hundred forty-eight patients with clinical stage II or III colorectal cancer, as determined by preoperative imaging, who were undergoing LACs were prospectively enrolled. RESULTS: Although IOLUS did not detect any lesions, small hypoechoic lesions were detected by the S-IOLUS (n = 71) in the Kupffer-phase view of two patients (2.8%). None of the 71 patients who underwent S-IOLUS showed liver metastases within 6 months after LAC. In the conventional IOLUS group (n = 77), metastatic lesions were identified in two patients (2.6%). The new liver metastases in these two patients were detected within 6 months after LAC. CONCLUSIONS: S-IOLUS of the liver during colorectal cancer surgery is useful for staging and as a diagnostic modality. It can identify lesions that are undetectable by preoperative imaging, and may be considered for routine use during LAC.

[A case of unresectable multiple liver metastases of colorectal cancer in which ALTA(ZION), used to control internal hemorrhoidal bleeding, enabled administration of bevacizumab].

Our patient was a 58-year-old woman with internal bleeding hemorrhoids who was undergoing FOLFOX6 treatment for unresectable multiple hepatic metastases of colorectal cancer. Response evaluation after 6 courses showed stable disease (SD), but side effects necessitated a change in regimen. Hemorrhoidal bleeding had also increased, and hemorrhoid-sclerosing therapy with ALTA(ZION)injections was administered. Because no bleeding was evident after treatment and the clinical course was uneventful, chemotherapy with bevacizumab was restarted. No hemorrhoidal bleeding occurred after bevacizumab administration, and the patient is currently continuing chemotherapy. In patients with advanced cancer who have bleeding internal hemorrhoids that cannot be controlled with conservative treatment, hemorrhoid-sclerosing therapy using ALTA appears to offer an effective treatment variation that enables the use of bevacizumab in cases with limited available therapeutic regimen options.

[Efficacy and safety of pregabalin for oxaliplatin- and paclitaxel-induced peripheral neuropathy].

This study included patients who were prescribed pregabalin, vitamin B12, amitriptyline, clonazepam, or carbamazepine to improve oxaliplatin(L-OHP)- or paclitaxel(PTX)-induced peripheral neuropathy at Iwate Medical University Hospital between April 2011 and July 2012. The efficacy and safety of pregabalin was evaluated by comparing 27 patients with L-OHP-induced peripheral neuropathy and 28 with PTX-induced peripheral neuropathy prescribed pregabalin(pregabalin group) with 20 patients with L-OHP-induced peripheral neuropathy and 25 with PTX-induced peripheral neuropathy prescribed other drugs(non-pregabalin group). Response was defined as a decrease in neuropathy of at least 1 grade from baseline. The response rates were 40.7% and 10.0% for L-OHP-induced peripheral neuropathy patients and 28.6% and 12.0% for PTX-induced peripheral neuropathy patients in the pregabalin and non-pregabalin groups, respectively. The severity of peripheral neuropathy before and after the administration of pregabalin differed significantly[L-OHP, 1.33±0.48(mean±SD) vs. 1.00±0.78 and PTX, 1.46±0.69 vs. 1.21±0.88]. In 28-37% of patients, pregabalin was associated with adverse events, with drowsiness and dizziness being frequently observed. In conclusion, pregabalin was efficacious in reducing the severity of L-OHP- and PTX-induced peripheral neuropathy.

Hybrid stereoisomers of a compact molecular probe based on a jasmonic acid glucoside: syntheses and biological evaluations.

12-O-ß-D-glucopyranosyl jasmonic acid (JAG) shows unique biological activities, including leaf-closing of Samanea saman. It is expected that the mode of action for such regulation is distinct from that of other jasmonates. We developed high-performance compact molecular probes (CMPs) based on JAG that can be used for the FLAG-tagging of JAG target. We synthesized four hybrid-type JAG-CMP stereoisomers (7, ent-7, 8, and ent-8), which are composed of (-)-12-OH-JA (2)/D-galactopyranoside, (-)-2/L-galactopyranoside, (+)-ent-2/d-galactopyranoside, and (+)-ent-2/L-galactopyranoside moieties, respectively, and we examined their biological features, such as the stereospecific induction of shrinkage, rate of the cellular response, and dependence on potassium channel activity. These features of the JAG-CMPs were completely consistent with those of the original JAG. These results indicate the biological equivalence of JAG and the JAG-CMPs. During the course of such biological evaluations, it was revealed that the biological activity of the CMPs is greatly dependent on the d/l-stereochemistry of a glycon moiety. To the best of our knowledge, this is the first study suggesting that the d/l-stereochemistry of the glycon moiety significantly affects the biological activity of the associated glycoside.

Molecular marker identification for relapse prediction in 5-FU-based adjuvant chemotherapy in gastric and colorectal cancers.

To confirm the clinical significance of NF-κB and JNK protein expression from experimentally identified candidates for predicting prognosis for patients with 5-FU treatment, we evaluated the protein expression of surgically removed specimens. A total of 79 specimens were obtained from 30 gastric and 49 colorectal cancer patients who underwent R0 resection followed by postoperative 5-FU based adjuvant chemotherapy. Immunohistochemical examinations of NF-κB and JNK on tissue microarrays (TMAs) revealed that significantly shorter time-to-relapse (TTR) in both NF-κB(+) and JNK(-) subgroups in both gastric (NF-κB(+), p = 0.0002, HR11.7. 95%CI3 3.2-43.4; JNK(-), p = 0.0302, HR4.4, 95%CI 1.2-16.6) and colon (NF-κB(+), p = 0.0038, HR36.9, 95%CI 3.2-426.0; JNK(-), p = 0.0098, HR3.2, 95%CI 1.3-7.7) cancers. These protein expression patterns also show strong discriminately power in gastric cancer patients for overall survival rate, suggesting a potential utility as prognostic or chemosensitivity markers. Baseline expression of these proteins using gastric cancer cell lines demonstrated the reciprocal patterns between NF-κB and JNK, while 5-FU exposure of these cell lines only induced NF-κB, suggesting that NF-κB plays a dominant role in the response to 5-FU. Subsequent siRNA experiments confirmed that gene knockdown of NF-κB increased 5-FU-specific sensitivity, whereas that of JNK did not affect the chemosensitivity. These results suggest that the expression of these proteins may aid in the decisions involved with adjuvant chemotherapy for gastrointestinal tract cancers.

Central venous port-related infection in patients with malignant tumors: an observational study.

PURPOSE: We evaluated the characteristics of central venous port (CVP)-related infection with microbiological assessments in patients with malignant tumors. MATERIALS AND METHODS: In a prospective setting, patients with CVP for the treatment of malignant tumors were enrolled in this study. The incidence of CVP-related infection during three months was determined. Microbiological surveillance from skin swab was performed before and after CVP placement. RESULTS: Fifty-nine patients were enrolled in this study, and 60 CVPs were implanted. Thirty-six (61%) patients had head and neck malignancies. Access route was subclavian vein in 43 (71.7%) CVPs and forearm vein in 17 (28.3%). CVP-related infection was observed in three (5.1%) patients: port-pocket infection in one and probable CVP-related infection in two patients, respectively. No definitive CVP-related bloodstream infection was observed. Before the placement of CVP, colonization at the insertion site was observed in ten subclavian CVP patients, while no colonization was observed in the forearm CVP patients. At 1 and 4 weeks, detection rates of colonization were also higher in subclavian CVP patients. No definitive relationship was demonstrated between skin colonization and clinical development of CVP-related infection. CONCLUSION: The rate of CVP-related infection in this prospective evaluation in patients with malignant tumors was comparable to previous studies. Colonization of the skin was more prominent in the subclavian site than in the forearm site. Although skin colonization was not proven to be a risk factor of infection, these results may draw attention to the adequate maintenance of CVP. ( TRIAL REGISTRATION: UMIN000003664).

[A novel Cisplatin delivery system for malignant ascites-bearing mice-a basic experimentation].

The authors used 70% deacetylated chitin and cisplatin (CDDP) to devise a novel anticancer drug delivery system (DDS). We examined in vitro release of the CDDP from the system. The novel system was intraperitoneally( ip) given to malignant ascites-bearing mice, and the survival time of each animal was recorded. The related oncolytic mechanism was immunologically investigated. More than 70-90% of the CDDP was gradually delivered from the system in 24 hours. Nineteen animals among 30 treated with our system survived for longer than 4 weeks, and a recurrence of ascites was nil. A 4- week survival rate of the animals with ip injected conventional CDDP was 5/14. All non-treated animals had massive ascites and died within 4 weeks. Immunologic studies suggested that cytotoxic immunoresponse was induced in the mice treated with the novel system. Our newly devised system warrants for clinical applications in the treatment of malignant ascites.

Primary retroperitoneal spindle cell liposarcoma: pathological and immunohistochemical findings.

Spindle cell liposarcoma (SCLS) is presently regarded as a rare variant of well-differentiated liposarcoma (WDLPS), which has the potential for aggressive clinical behavior. WDLPS occurs most frequently in the limbs and retroperitoneum. The most common site of SCLS occurrence is the upper limbs or shoulder girdle. Herein we report the first case of primary retroperitoneal SCLS. A 60-year-old Japanese man presented with a right inferior abdominal mass. Complete excision of the mass displayed a yellowish spherical tumor with a well-circumscribed appearance measuring 98 x 95 mm. Pathological examination of the tumor revealed a neural-like spindle cell proliferation set in a fibrous background that was associated with an atypical lipomatous component, which usually included lipoblasts. Mitotic cells were scarce. Immunohistochemical analysis demonstrated that lipoblasts were S100 positive, spindle cells were CD34 positive, and both spindle cells and lipoblasts were MDM2 negative. The Ki-67 labeling index was <2%. At one year follow up, the patient was alive without local recurrence or metastasis. Although the proliferative activity of this tumor did not indicate strong malignancy, retroperitoneal liposarcoma generally has a poor prognosis. Accumulation of cases of SCLS is necessary to facilitate a more accurate evaluation of the pathology and clinical behavior of this tumor.

[Anticancer efficacy with cisplatin delivery systems].

The authors devised two different types of cisplatin (CDDP) delivery systems; namely, System A and System B. The anticancer efficacy with each system was examined using cancer-bearing animals. Seventy-percent deacetylated chitin (DAC-70) was used as the drug carrier in the system. Cancer-bearing animals were prepared by intra-peritoneally (ip) inoculating the MM-46 cancer cells to C3H mice. Each novel system was also ip injected to the cancer-bearing mouse, and then survival time of each animal was recorded to evaluate the anti-cancer efficacy of the system. Both Systems A and B were viscoelastic sol at 25°C and slowly changed to gel at 37°C. Four-week survival rate of each animal treated with the System was as follows: System A 6/10 (60%), System B 10/11 (90.9%), conventional CDDP alone 3/9 (33.3%) and non-treated 0/7 (0%). No signs of recurrence of ascites were encountered in the long-term survived animals treated with System A and B. Our newly devised systems provided a favorable antitumor efficacy in vivo. Now, we will carry out further studies by making a clinically applicable novel conjugated system, DAC-70 and CDDP.

[A novel formulation of cisplatin (CDDP)].

The study aimed to assess our newly devised CDDP delivery system designed to provide targeting potential and a sustained release of the anticancer agent. Seventy percent deacetylated chitin was applied as a drug carrier. We prepared two different types of systems with two different procedures: namely, system A with direct method and system B with indirect method. The targeting property of the system was evaluated ex vivo with measuring adhesive force between each system and human colonic mucosa. The release behavior of the CDDP from the system was examined in vitro. The anticancer activities of the released CDDP were also examined in vitro using human gastric cancer cell line, MKN-45. Each system was a viscose elastic solution. The adhesive forces of the novel systems were stronger at 37 degrees C than that of 25 degrees C. Each system provided a sustained release of CDDP. The released CDDP demonstrated effective growth suppression activity against the MKN-45 cancer cells. The novel systems basically showed a favorable targeting function and a sustained release of CDDP, which effectively provided a growth inhibition potential against human cancer cell line. Our newly devised CDDP delivery systems are promising as a novel approach to cancer chemotherapy.

DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer.

The L1 cell adhesion molecule (L1CAM) has been identified as a target gene of beta-catenin-TCF signaling in colorectal cancer (CRC) and associated with aggressive tumor behavior such as invasion and metastasis. We investigated the methylation status at the L1CAM gene promoter and/or L1CAM mRNA/protein expression in 4 CRC cell lines and 71 primary CRCs. Aberrant L1CAM expression was immuno histochemically observed in 31 (43.7%) of 71 cases, and correlated with advanced stage and presence of lymph node and distant metastases (P<0.05). Treatment with a demethylating agent induced L1CAM mRNA/protein expression in two cell lines lacking L1CAM expression. Bisulfite-modified genome sequencing suggested that DNA methylation status at core promoter and putative TCF-binding sites within the L1CAM promoter was correlated with L1CAM mRNA/protein expression in 4 CRC cell lines. Using the crypt isolation followed by bisulfite-modified genome sequencing and methylation-specific PCR methods, we confirmed that the DNA hypomethylation at core promoter and putative TCF-binding sites was well correlated with the aberrant L1CAM protein expression in primary CRC samples. These results suggest that DNA hypomethylation at the L1CAM CpG islands might induce L1CAM aberrant expression and contribute to the acquisition of aggressive tumor behavior in CRC.

[Chitin/cisplatin--an adhesive anticancer drug].

The authors devised an adhesive anticancer drug delivery system using 70% deacetyalated chitin (DAC-70) and cisplatin (CDDP). We prepared two different types of the drug carriers; namely, DAC-70 viscous solution and DAC-70 lyophilized granules, which easily provided viscous solution when mixed with a liquid. We then formed a novel CDDP-loaded system by mixing each vehicle with CDDP solution. Each product showed a stronger tissue-adhesive force at 37 degrees C than that of 25 degrees C. More than 90% of total CDDP was released from the system within 24 hours. A large amount of the CDDP released from the system revealed it to be free CDDP when the DAC granule was used as the carrier, while the amount of free CDDP was less than 20% in the case of the DAC viscous solution. When the DAC-CDDP solution was given into the peritoneal cavity of rats, the CDDP remained there and only a little was transferred into the peripheral blood. We could also provide loco-regional pleurodesis by injecting the novel solution into the rat pleural cavity. These data suggest that our newly devised system has a great potential in cancer chemotherapy for the patients with malignant pleural effusion and ascites.

[A novel anticancer drug delivery system -DAC-70/CDDP].

We devised a muco-adhesive anticancer drug delivery system using 70% deacetylated chitin (DAC-70) and cisplatin (CDDP) and 5-fluorouracil (5-FU). The adhesive force between the system and human colonic mucosa was measured ex vivo, and a release profile of each drug was examined in vitro. Each system demonstrated a stronger muco-adhesive force at 37 degrees C than that of 25 degrees C. The CDDP-loaded system showed a sustained release of the drug while the 5-FU-loaded system exhibited an initial bursting of the agent. We presume that the release profile of CDDP and 5-FU is closely related to both degradability of the chitin and interactions between the chitin and each drug. The DAC-70/CDDP system would be clinically promising in loco-regional cancer chemotherapy.

[A novel approach to loco-regional cancer chemotherapy with a chitosan-CDDP solution].

The authors applied 70% deacetylated chitin (DAC 70, chitosan) as a vehicle of cis-platinum (CDDP) to achieve loco-regional cancer chemotherapy, in an attempt to hold the drug in the target region with a locally sustained release. The DAC-70 powder was dissolved in a 0.1 M HCI solution into where CDDP solution and glycerol phosphate solution were added. The resulting product, DAC-70/CDDP became a muco-adhesive solution. The adhesiveness between the solution and human colonic mucosa was measured ex vivo by our own method, and a release profile of the CDDP was examined in vitro using an atomic absorption method. The adhesive force was stronger at 37 degrees C than that of at 25 degrees C. Ten percent of the CDDP was gradually delivered for 6 hours, while the release was maintained at the same levels for the following 72 hours. The release rate increased by 10-20% when lysozyme was added in the incubation systems. However, the release profile of the drug showed no remarkable changes. The DAC-70/CDDP solution provided a favorable adhesiveness with human colonic mucosa, while in situ degradability of the solution should be improved further more.