ZG16p, an Animal Homologue of Plant ß-Prism Fold Lectins: Purification Methods of Natural and Recombinant ZG16p and Inhibition Assay of Cancer Cell Growth Using ZG16p.

ZG16p is a soluble 16-kDa protein abundantly expressed in the pancreas and gut, and has a ß-prism fold structure similar to that of mannose-binding Jacalin-related lectins (mJRLs) such as BanLec, Heltuba, and Artocarpin. ZG16p binds to mannose via the well-conserved GXXXD loop among mJRLs and sulfated glycosaminoglycans (e.g., heparin and heparan sulfate) via the basic patch of molecular surface. In addition to the above binding activities, ZG16p has inhibitory activity against proliferation of colon cancer cells. This manuscript describes purification of rat pancreatic ZG16p and recombinant ZG16p expressed in Escherichia coli expression system, and cell growth inhibition assay using ZG16p as an inhibitor.

Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its carbohydrate-binding sites.

Zymogen granule protein 16 (ZG16p) is a soluble lectin that binds to both mannose and heparin/heparan sulfate. It is highly expressed in the human digestive tract and is secreted into the mucus. In this study, we investigated the effect of ZG16p on the proliferation of human colorectal cancer cells. Overexpression of ZG16p in Caco-2 cells decreased cell growth. Recombinant ZG16p markedly inhibited proliferation of Caco-2, LS174T, HCT116 and HCT15 cells. Caco-2 cell growth was not inhibited by two mutated ZG16p proteins, D151A and M5 (K36A, R37A, R53A, R55A and R79A) lacking mannose- and heparin-binding activities, respectively. Immunofluorescent cell staining revealed that ZG16p-D151A maintained its binding to the Caco-2 cell surface, whereas ZG16p-M5 failed to bind to the cells. These results suggest that ZG16p interacts with the cell surface via basic amino acids substituted in ZG16p-M5 and inhibits Caco-2 cell proliferation via Asp151. In addition, growth of patient-derived colorectal tumor organoids in a 3D intestinal stem cell system was suppressed by ZG16p but not by ZG16p-M5. Taken together, our findings indicate that ZG16p inhibits the growth of colorectal cancer cells via its carbohydrate-binding sites in vitro and ex vivo. In this study, a novel pathway in cancer cell growth regulation through cell surface carbohydrate chains is suggested.

[A retrospective study of carboplatin and weekly paclitaxel combination chemotherapy for elderly patients with advanced non-small cell lung cancer].

OBJECTIVE: To perform a retrospective analysis of carboplatin (CBDCA) and weekly paclitaxel (PTX) combination chemotherapy for elderly patients with unresectable non-small cell lung cancer (NSCLC) in order to evaluate both treatment efficacy and toxicity. SUBJECTS: 48 patients aged more than 70 years with non-resectable NSCLC who received CBDCA+weekly PTX from January 2001 to March 2008. RESULTS: The median age of the patients (32 male, 16 female) was 74 years. Patients received 1-6 courses of this chemotherapy (median 4 courses). The overall response rate, time to progression, median survival time and 1-year survival rate was 51%, 183 days, 411 days and 52%, respectively. With regard to toxicity, grade 3-4 neutropenia was observed in 38% of patients and anemia in 25% of the patients, and 29% of the patients had grade 2 and above periferal nerve disorder. CONCLUSION: This regimen showed a good response and was safe for elderly patients with advanced NSCLC, but a high incidence of neuropathy was observed.

[Retrospective analysis of amrubicin hydrochloride monotherapy in patients with previously treated small-cell lung cancer].

We retrospectively investigated amrubicin hydrochloride(AMR)monotherapy as second or thirdline chemotherapy for small-cell lung cancer(SCLC)and assessed its efficacy and safety. AMR was intravenously administered at 25-45mg/m2 for 3 consecutive days every 3-4 weeks. Fifty-three patients were enrolled. Response rates and median survival times were as follows: total cases, 32% and 7. 4 months; sensitive relapse cases, 64% and 16. 4 months; refractory relapse cases, 27% and 5. 9 months. Neutropenia was major toxicity(Grade 3 or 4 was observed in 72% of the subjects), whereas nonhematologic toxicities were mild. Treatment with AMR appeared effective in SCLC patients previously treated with chemotherapy. On the other hand, it must be used carefully because of its relatively severe hematologic toxicities.

[Clinical investigation of weekly Carboplatin and Paclitaxel with concurrent radiation therapy for locally advanced non-small cell lung cancer].

PURPOSE: The aim of this study was to evaluate retrospectively chemotherapy of weekly carboplatin and paclitaxel with concurrent radiation therapy for patients with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Between January 2000 and March 2008, 38 patients were treated by chemotherapy with carboplatin and paclitaxel once a week, repeated for 6 weeks, with thoracic radiation therapy of 1 or 2 times a day on weekdays. After concurrent chemoradiotherapy, we planned consolidation chemotherapy of carboplatin(AUC 5-6)and weekly paclitaxel(70- 80 mg/m(2)) on day 1, 8 and 15, when possible. RESULTS: The enrolled patients were 31 men and 7 women, with the median age of 59 years (39-76 years), stage III A/III B: 10/28, Ad/Sq/AdSq/Un: 17/17/2/2. The response rate of this chemoradiotherapy was 78. 9%. The median survival time and time to progression were 24. 7 months and 8. 1 months, respectively. Grade 3 or 4 hematological toxicities during concomitant chemoradiotherapy were leukocytopenia(5. 2%)and neutropenia(5. 2%). Grade 3 or 4 non-hematological toxicities were esophagitis(2. 6%)and pneumonitis (5. 2%). There was a therapy-associated death by radiation pneumonitis. CONCLUSION: Carboplatin and paclitaxel with concurrent radiation therapy for a patient with stage III NSCLC showed a good response with relatively mild side effects. We reached the conclusion that concurrent chemoradiotherapy would be a useful choice for locally advanced non-small cell lung cancer on the practical clinic.

[Two cases of lung injury due to inhalation of waterproofing spray--with special reference to pulmonary function disorder].

CASE 1: A 57-year-old man experienced severe dyspnea 24 hours after inhalation of waterproofing spray. Computed tomography (CT) revealed diffuse ground glass opacities in bilateral lungs. Pulmonary function tests showed mixed ventilatory disturbance with a low expiratory flow rate near the end of forced expiration and a normal diffusing capacity with normal functional residual capasity. The pulmonary function disorder was quickly improved by steroid therapy. CASE 2: A 59-year-old man smoked after inhaling waterproofing spray and soon developed dyspnea. The findings of CT were similar to those of case 1. His pulmonary function test revealed restrictive ventilatory disturbance and normal pulmonary diffusing capacity with low functional residual capacity. These findings improved without steroid treatment. However, it took more time for the pulmonary function to recover. There was probably specific inflammation around bronchioles, and the inflammation might have spread to the alveolar region in such cases with severe pulmonary function disorder. Steroid treatment seems to be useful to improve both the pulmonary function disorder and the clinical feature due to inhalation of waterproofing spray.

[A foreigner case of pulmonary tuberculosis with patient's and doctor's delay].

A 80-year-old man who came from Korea a few days previously, had a high fever and dyspnea. Chest radiography and computed tomography showed various shadow suggesting tumors, small nodules and reticular shadows with effusion. We made a clinical diagnosis of lung cancer with pneumonia. Finally, however, the culture of bronchial lavage fluid and transbronchial biopsy revealed tuberculosis. It was obvious that there were delaying factors such as the patient's social and economical situation as well as the diagnostic difficulty concerning the chest image findings. Whenever we find a abnormal shadow on chest images, we should consider mycobacterium infection in the differential diagnosis disease.

[Clinical study of 37 pneumonia patients in whom MRSA was identified from sputum].

When we studied the clinical aspects of 37 pneumonia patients with underlying respiratory disease in whom MRSA 1 + was identified from sputum, 43.2% of these 37 pneumonia cases were diagnosed as MRSA colonization. The whole clinical course of these pneumonia patients with MRSA colonization was average 39.5 days, on the other hand, the whole clinical course of MRSA pneumonia group was 55.3 days. We should consider that MRSA must be a cause of pneumonia, in only such cases as follows; (1) patients with unstable diabetes mellitus, or with long-term administration of steroid, (2) patients with infiltrative shadows appeared not only in the lower lobe but also the upper lobe in the chest x-ray films, (3) patients with remarkable decrease of PaO2 or patients who failed to recover within one month from MRSA isolation, (4) patients with nosocomial pneumonia or patients with poor performance status or poor prognosis, (5) patients with purulent sputum containing MRSA or other bacteria such as K. pneumoniae etc and patients who failed to respond to general antibacterial agents.

[A case of systemic amyloidosis treated by chemotherapy with autologous peripheral blood stem cell transplantation].

A 67-year-old woman was admitted to our hospital because of breathlessness. Systemic amyloidosis had been diagnosed 5 years previously. Her chest X-ray film showed multiple nodules in both lung fields. Chest computed tomography (CT) revealed some of the nodules had calcifications. Bronchoscopy demonstrated amyloid deposits in the bronchial walls. The serum titer of anti-SS-A antibody was high. Results of both the Schirmer Test and the Rose-Bengal Test were positive. The final diagnosis was systemic amyloidosis with Sjögren's syndrome. She was treated by chemotherapy using high dose melphalan with autologous peripheral blood stem cell transplantation (PBSCT). It was obvious that her chest X-ray film findings and bronchoscopic findings had improved 9 months after high dose chemotherapy with PBSCT. The disappearance of M protein and improvement of thirst, a symptom of Sjögren's syndrome, were also observed.

[A case of natural killer cell lymphoma with high adenosine deaminase level in pleural effusion].

A 61-year-old man was admitted to our hospital with cough, breathlessness, anorexia and chest pain. Chest radiograph showed right pleural effusion and also a chest CT scan showed right pleural effusion with thickening of the right visceral pleura, pericardial effusion and a liver tumor. The pleural effusion was slightly bloody and exudative. The adenosine deaminase (ADA) level in the pleural effusion was elevated. Because the cytological examintion of the pleural effusion showed no malignancy, we diagnosed pleuritis tuberculosa. The serum-soluble interleukin-2 receptor level was also elevated. His general condition worsened in spite of the chemotherapy with antibiotics and antituberculous drugs. We finally diagnosed the case as natural killer (NK) cell lymphoma from CT-guided needle biopsy just before death, and necropsy. In this case, the high level of ADA in the pleural effusion suggested lymphoma.

[Case of pulmonary carcinosarcoma and a summary of 17 cases reported in Japan].

The patient was a 69-year-old man who complained of dyspnea and severe general fatigue. Chest CT showed a large tumor (6 x 5 cm) in the left S3 together with left pleural effusion. Despite pleurodesis and chemotherapy, he died 1.5 months after admission. At autopsy, a final diagnosis of pulmonary carcinosarcoma was obtained. We have summarized 17 cases of pulmonary carcinosarcoma reported in Japan. All patients were men, and had an average age of 68 years. The majority of the patients were heavy smokers. Death was reported in 70% of cases, the median survival period being 5 months, whereas the patients reported as living had operable cases of T2 tumor without distant metastatic lesions.