Biomedical subjects

Y Nio

Publications and source records attributed to Y Nio.

157 records · Page 9Linked to original sources

PubMedDate not supplied

Binding and internalization of human immunoglobulin G conjugated with melphalan (K18) to human tumor cell lines.

The binding and internalization of melphalan-conjugated human immunoglobulin G (K18) to human tumor cell lines were studied using 14C-K18 (IgG conjugated with 14C-melphalan) and were compared with those of 14C-melphalan. K18 and melphalan dose-dependently bound to tumor cells, and the saturation binding analysis revealed a receptor-mediated binding of K18 but not of melphalan, to tumor cells. Intracellular distribution of 14C-K18 differed from that of 14C-melphalan, but a DNA unwinding experiment using a hydroxylapatite column showed that 14C-melphalan or 14C-K18 bound to DNA. These results suggest that after being bound to receptors K18 may be internalized in a macromolecular form and degraded into peptide binding melphalan. Moreover, the quantity of K18 that bound to 7 different human tumor cell lines was significantly larger than those that bound to lymphocytes of normal donors. These results suggest that K18 may be beneficial for cancer chemotherapy.

Antineoplastic Agents↗

PubMedDate not supplied

The inhibitory effect of a conjugate of human immunoglobulin G and melphalan, K18, on DNA synthesis of human tumor cells.

K18 is a conjugate of human immunoglobulin G and melphalan and has been reported to accumulate selectively in the tumor. In the present study, the in vitro antitumor effect of K18 was assessed in a total of 107 fresh human tumors by DNA synthesis (3H-thymidine incorporation) inhibition assay, and compared with that of other drugs. Human tumor cells showed a variety of sensitivities to K18: gastric, breast, pancreatic, liver or ovarian cancer cells were comparatively sensitive to K18, while esophageal or colorectal cancers were insensitive. These results suggest that the conjugation of melphalan with IgG did not reduce the antitumor activity of melphalaln and that K18 may be applied in cancer chemotherapy instead of melphalan.

DNA, Neoplasm↗

PubMedDate not supplied

Selective accumulation of a new antineoplastic agent, K-18 (human immunoglobulin conjugated melphalan), in Ehrlich carcinoma transplanted in mice.

The absorption of K-18 (human IgG conjugated melphalan) through the intestine and its selective accumulation in the tumor were studied. After oral administration of 14C-melphalan and 14C-K-18 to ICR mice with subcutaneously transplanted Ehrlich carcinoma, K-18 was detected at the tumor site by autoradiogram after 48 hrs, but melphalan was not. Immunofluorescence study showed that orally administered K-18 was absorbed from the intestine via both the portal and the lymphatic route. Moreover, immunoperoxidase staining revealed K-18 in cytoplasm of tumor cells, but not in bone marrow cells. These results demonstrate the absorption of K-18 from the intestine after oral administration and its selective affinity for tumor tissue.

Animals↗

PubMedDate not supplied

Antitumor activity of orally administered streptococcal preparation, OK-432 on murine solid tumors and its absorption from the gut.

OK-432 is an immunopotentiator which is normally administered by injection. In the present study, the antitumor activity of orally administered OK-432 on various solid tumors and the absorption of OK-432 from the gut were studied. Orally administered OK-432 inhibited the growth of Meth-A and BAMC-1 fibrosarcomas which had been subcutaneously transplanted in BALB/c mice. Autoradiograms of mice which had been administered 14C-labelled OK-432 orally demonstrated the absorption of OK-432 from the gut, and about 6% of orally administered OK-432 was absorbed 24 hrs after its administration. Moreover, an immunofluorescent study using an anti-OK-432 antibody revealed specific fluorescence in the mesenteric lymph node of mice which had been orally administered with OK-432. These results suggest that oral administration of OK-432 may be a beneficial immunotherapy.

Administration, Oral↗

PubMedDate not supplied

In vivo inhibitory effect of a conjugate of immunoglobulin G and melphalan, K18, on human tumors transplanted in nude mice.

Various human tumor lines, including gastric, colonic, esophageal, pancreatic, lung and breast cancer, were transplanted in nude mice, and the effect of K18 (IgG conjugated melphalan) on them was assessed and compared with that of melphalan. Melphalan (1 mg/kg) or K18 (100 mg/kg) were administered to mice for 28 days. The tumor growth was significantly inhibited in 5 out of 6 tumors by both agents, although only the esophageal line was insensitive to both agents. Significant loss of body weight was observed in mice after treatment. K18 had no influence on body weight. These results suggested that K18 may be useful in cancer chemotherapy.

Animals↗

PubMedDate not supplied

[Action of granulocyte-colony stimulating factor and cisplatin on two models of human digestive, esophageal and colonic, cancers].

A combined therapy using a colony-stimulating factor and a chemotherapeutic agent has been designed, in vitro and in vivo, on digestive tumor cells to assess the effects of these agents administered alone or in combination, on the cells' or the tumor's growth rate. A recombinant human granulocyte colony-stimulating factor (rh G-CSF) and Cisplatin (CDDP) has been administered at various concentrations in vitro on oesophageal (ECYO) or on colonic (COLO 205) cell lines and in vivo on oesophagal tumor transplanted in Nude mice. In vitro, the oesophagal model is sensitive to G-CSF. The administration of G-CSF induces a stimulation of the cell proliferation. The DNA synthesis is stimulated or inhibited by low or high concentrations of G-CSF without any dose-response relationship. CDDP inhibits the DNA synthesis in ECYO cells. The association of the two agents leads to an activation of the DNA synthesis but only for some concentrations. On the contrary, the colonic model treated or not by CDDP is not sensitive to G-CSF. In vivo, G-CSF does not allow any inhibition or activation of oesophagal tumor's growth rate. CDDP alone is also inefficient. When G-CSF is administered before CDDP, there is no effect on the tumors. On the contrary, when G-CSF is administered with or after the chemotherapeutic agent, there is a significant inhibition of the tumor's growth rate.

Animals↗

PubMedDate not supplied

p53 protein expression as prognostic factor in human pancreatic cancer.

Mutations in the p53 tumor suppressor gene are considered to play an important role in the carcinogenesis of pancreatic cancer. The present study was designed to assess the clinicopathological significance of the expression of p53 protein in human pancreatic cancer. A total of 64 specimens of pancreatic cancer (44 primary and 20 metastatic lesions) were obtained by surgery in our department between 1982 and 1995, and p53 protein was stained using an immunohistochemical staining method (strepto-avidin-biotin complex method) with 2 kinds of anti-p53 monoclonal antibodies (DO-1 and PAb240). DO-1-p53 was usually stained in the nucleus of cancer cells and was positively expressed in 35 out of 64 specimens (54.7%): 21 out of 44 primary lesions (47.7%), and 14 out of 20 metastatic lesions (70.0%). On the other hand, PAb240-p53 was stained in both the nucleus and cytoplasm in 45 out of 64 specimens (70.3%): 33 out of 44 primary lesions (75.0%) and 12 out of 20 metastatic lesions (60.0%). The survival rate of the patients with DO-1-p53 (+) pancreatic cancer after pancreatectomy was significantly lower than that of patients with DO-1-p53 (-) pancreatic cancer. On the other hand, there were no significant implications of PAb240-p53 protein expression on survival after pancreatectomy. With regard to the clinicopathological characteristics, the rate of DO-1-p53 protein expression was significantly higher in elderly patients (> or = 65 y.o.). As a result, DO-1-p53 protein expression may be a beneficial prognostic factor for patients with pancreatic cancer, and it is a factor independent of the stage and other clinicopathological factors.

Adenoma↗

PubMedDate not supplied

A splenic-inferior mesenteric venous anastomosis prevents gastric congestion following pylorus preserving pancreatoduodenectomy with extensive portal vein resection for cancer of the head of the pancreas.

BACKGROUND: In order to prevent gastric congestion after both of the splenic and coronary veins were taken as part of extensive portal vein resection in pylorus preserving (PP) pancreatoduodenectomy (PD), we made a splenic-inferior mesenteric venous (SpIMV) anastomosis. MATERIALS AND METHODS: Four patients underwent PP subtotal PD with such extensive portal vein resection under the diagnosis of pancreas head cancer. The portal vein was reconstructed by end-to-end anastomosis, and the coronary vein was ligated. Since the stump of the splenic vein could not be approximated to the portal or superior mesenteric vein, shunting the splenic venous flow to the inferior mesenteric vein was attempted by making a SpIMV anastomosis in 3 patients and by preserving the SpIMV confluence in a patient. Postoperative celiac angiography showed that venous outflow from the stomach, spleen and remnant pancreas collected into the splenic vein and passed through the SpIMV anastomosis or confluence, and finally drained into the portal vein by inferior mesenteric to superior mesenteric collateral. RESULTS: No remarkable congestion of the stomach was observed. CONCLUSIONS: In conclusion making a SpIMV anastomosis or preserving the SKpIMV confluence is beneficial for preventing gastric congestion following PP PD with extensive portal vein resection for cancer of the head of the pancreas.

Aged↗

PubMedDate not supplied

Clinicopathological significance of epidermal growth factor and its receptor in human pancreatic cancer.

The expression of epidermal growth factor (EGF) and its receptor (EGF-R) was examined immunohistochemically in 60 primary and 26 metastatic lesions of pancreatic carcinoma. EGF was stained mainly in the cytoplasm of tumor cells, and EGF-R was stained mainly on the surface of cells. The expression rates of EGF and EGF-R were 28% and 43% for primary lesions, and 46% and 46% for metastatic lesions, respectively. The expression of EGF and EGF-R alone did not correlate with any clinicopathological factors such as clinical stage, tumor size, nodal involvement, histology, etc. The median survival period after pancreatectomy was 21.4 months for patients with EGF(+) cancers and 25.1 months for those with EGF (-) ones. On the other hand, the median survival period was 22.7 months for patients with EGF-R (+) cancers and 25.0 months for those with EGF-R (-) cancers. There were no significant differences in survival between groups of patients differing in EGF or EGF-R expression. When the expression of EGF and EGF-R was analysed in combination, the survival curve of patients with EGF(+) and EGF-R(+) cancers was found to be lower than that of the rest of the patients (p = 0.07), and especially the survival curve of patients with EGF(+)EGF-R(+) cancers was significantly lower than that of patients with EGF(+)EGF-R(-) cancers (p = 0.02), and EGF(-)EGF-R(+) cancers (p = 0.06). These results indicate that the expression of EGF or EGF-R alone in pancreatic cancer does not reflect the prognosis of patients; however the coexpression of EGF and EGF-R may be a beneficial prognostic factor for pancreatic cancer.

Adenocarcinoma↗

PubMedDate not supplied

Neoadjuvant chemotherapy of gastric cancer with oral UFT (a mixture of uracil and fturafur) during the waiting period for surgery.

Our previous experience has demonstrated that growth of gastric cancer during the waiting period for surgery cannot be neglected, and some patients hope to receive prophylactic treatment to inhibit the growth of tumor until surgery. The present study was designed to assess the clinical benefits of preoperative chemotherapy with oral UFT for gastric cancer during the waiting period for surgery. Fifty patients with gastric cancer (24 early, 25 advanced and 1 recurrent cancers) were treated with oral UFT at 300-600 mg/day for 7-36 days before surgery and the objective responses and the postsurgical survivals were evaluated. In 42 of 50 patients objective responses of primary lesions were assessed by endoscopy or upper gastrointestinal series examination, and 2 CRs, 15 PRs and 25 NCs were seen (40% response). The histological effect was evaluated in 50 patients and the following classifications were made: grade 3 (complete disappearance or necrosis of tumor cells), 2; grade 2 (necrotic changes > 2/3 area), 4; grade 1b (> 1/3 area), 7; grade 1a (< 1/3 area), 15; and grade 0 (no histological changes), 22. A longer period of UFT administration was associated with CR or PR. All the patients underwent gastrectomy (38 curative and 12 palliative gastrectomies): all patients with Stage I-III primary gastric cancer are alive after surgery, and the 50% survival period of the patients with Stage IV cancer was 20 months. The side effects were not serious, including slight myelotoxicity, liver dysfunction and anorexia. It is concluded that preoperative chemotherapy for gastric cancer with oral UFT on outpatient basis may result in down-staging as well as the prevention of tumor growth during the waiting period for surgery without serious side effects.

Administration, Oral↗

PubMedDate not supplied

Anticancer chemosensitivity and growth rate of freshly separated human colorectal cancer cells assessed by in vitro DNA synthesis inhibition assay.

The present study was designed to assess the chemosensitivity profile of freshly separated colorectal cancer cells and to screen effective agents for the design of new combination regimens. The DNA synthesis and chemosensitivity (% inhibition of DNA synthesis by the anticancer agent) were successfully assessed in 184 samples (107 primary and 77 metastatic or recurrent lesions) from 152 patients with colorectal cancer using an 3H-thymidine incorporation assay, and the correlations between these two measures and various clinicopathological factors were analysed. DNA synthesis was highest in nodal metastasis followed by malignant effusion, primary lesion, liver metastasis, and local recurrence. DNA synthesis liver metastasis and local recurrence were significantly lower than in other lesions. The results of the chemosensitivity assay are as follows: 5-FU seems to be the most beneficial for primary colorectal cancer; carboquone (CQ), etoposide (VP-16), 5-FU, and mitomycin-C (MMC) for nodal metastasis; CQ, cisplatin (CDDP), 5-FU, adriamycin (ADR) and VP-16 for malignant effusion; and VP-16, CDDP and CQ for liver metastasis. However, the present results showing the chemosensitivity profiles in different lesions suggest that regimens including 5-FU with VP-16 and CQ in addition to MMC or ADR may be applicable for all kinds of colorectal cancer lesions. These results demonstrated the heterogeneity in the chemosensitivity of colorectal cancer, which suggests not only the necessity of patient-specific chemotherapy dependent on the sensitivity assay, but also the usefulness of the present results in the choice of agents for widely applicable combination regimens for colorectal cancer.

Antineoplastic Agents↗

PubMedDate not supplied

p53 expression affects the efficacy of adjuvant chemotherapy after resection of invasive ductal carcinoma of the pancreas.

p53 tumor suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair, suggesting its involvement in the mechanisms of drug resistance or chemosensitivity. The present study assessed the implication of p53 expression in the prognosis of patients and the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma (IDC) of the pancreas. A total of 58 patients with primary IDC of the pancreas underwent pancreatectomy between 1982 and 1996: 28 patients received surgery alone and 30 patients received postsurgical adjuvant chemotherapy. p53 protein was stained immunohistochemically with anti-p53 monoclonal antibody. p53 was positively expressed in 29 out of 58 primary lesions (50%), and the survival curve of the patients with p53 (+) pancreatic cancer is lower than that of those with p53 (-) cancer. On the other hand, the survival curve of adjuvant chemotherapy group was also higher than that of surgery alone group, and furthermore, in patients with p53 (+) cancer, the survival curve of adjuvant chemotherapy group was significantly better than that of the surgery alone group. A multivariate analysis showed that p53 expression or adjuvant chemotherapy is not a significant risk-factor for prognosis, but that adjuvant chemotherapy is a significant risk factor for the patients with p53 (+) pancreatic cancer, which suggests that p53 expression affects the efficacy of chemotherapy. p53 expression may be beneficial as an indicator for introduction of adjuvant chemotherapy in pancreatic cancer patients.

Adult↗

PubMedDate not supplied

Epidermal growth factor and its receptor as prognostic indicators in Chinese patients with pancreatic cancer.

The expression of epidermal growth factor (EGF) and its receptor (EGFR) was studied immunohistochemically in fifty-seven Chinese patients with primary invasive ductal carcinoma (IDC) of the pancreas. The frequency of expression of EGF and EGFR was 73.7% and 68.4%, respectively. The frequency of their co-expression was 61.4%. No significant relationships were seen between the expression of EGF and its receptor and the patients' age, gender, site of the tumor, stage, and grade. Positive co-expression of EGF and EGFR was significantly associated with the poor prognosis. The median survival of the EGF(-)EGFR(-) group for 17.2 months was longer than that of the EGF(+)EGFR(+) group for 9.7 months (p = 0.02), as well as that of the other groups of EGR(+)EGFR(-), EGF(-)EGFR(+), and EGF(+)EGFR(+) for 9.9 month (p = 0.03). These results suggested that EGF and EGFR were frequently expressed in Chinese patients with IDC of the pancreas. Their co-expression may be a useful prognostic indicator for pancreatic cancer.

Adult↗