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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 91 records · Page 5Linked to original sources
PubMed1997

MR changes in the calcarine area resulting from retinal degeneration.

PURPOSE: To study MR images for atrophic changes in the calcarine area resulting from retinal degeneration. METHODS: MR images from nine patients with retinal degeneration confirmed by ophthalmologic examination and from 30 healthy volunteers were reviewed. The causes of retinal degeneration were hereditary pigmentary degeneration of the retina (four patients), high myopia (two patients), and chorioretinal atrophy (three patients); all patients had visual disturbances and visual field abnormalities. To estimate the morphological changes of the calcarine area, the widths of the right and left calcarine fissures were measured on T1-weighted sagittal images and compared with images from age-matched control subjects. RESULTS: The calcarine fissures were significantly dilated in the patients with retinal degeneration. The anterior and middle points, which represent the peripheral visual field center, were more dilated than the posterior point. CONCLUSION: The MR findings suggested calcarine atrophy related to retinal degeneration. Transneuronal degenerative changes may occur in the calcarine area after retinal degeneration.

Aged↗
PubMed1997

[Salvage surgery for the T4 esophageal cancer following downstaging by neoadjuvant chemoradiotherapy].

The standard modality of the treatment for the patients with T4 esophageal cancer, whose prognosis still remains quite poor, is not established yet. Salvage surgery for the T4 esophageal cancer following downstaging by neoadjuvant chemo-radiotherapy has become to be available. During the period from 1992 to 96, 30 patients with the suspected T4 esophageal cancer underwent chemoradiotherapy, which consisted of two courses of CDDP/5-FU with-sequential or concurrent 50-60Gy radiotherapy. Among them eleven patients became to be resectable by means of thoracotomy and laparotomy and pathological CRs were obtained in either primary lesions or lymph nodes. The longest survival term following surgery is 36 months. Three patients died of cancer recurrence including the organ metastasis and one died from pyothorax without cancer due to severe immunosuppression attributable to chemoradiation. Our results warrants further studies of neoadjuvant chemoradiotherapy for the patients with T4 esophageal cancer.

Aged↗
PubMed1997

[Recent advances in antireflux surgery for gastroesophageal reflux diseases--from open surgery to laparoscopic surgery].

Gastroesophageal reflux diseases (GERD) are common in the western countries and have been well studied about diagnosis and treatment. Nissen technique (a complete wrap) and Toupet technique (a partial wrap) are usually transabdominal fundoplication. Hill technique is a transabdominal posterior gastropexy. Allison technique is a transthoracic reduction method of the herniated cardia back into the abdomen, but is not frequently employed today. Belsey Mark VI technique is a transthroacic anterior plication. Collis gastroplasty is an esophageal lenghening technique and is used with standard repairs (Nissen, Belsey, and Hill). Good result rate of above mentioned surgery are about 90%. Recently, laparoscopic Nissen/Toupet technique are a standard antireflex surgery because of minimal invasiveness and more than 90% of good results. After introducing laparoscopic surgery the indication of antireflex surgery for GERD can be changed because of quality of life of patients and medicoeconomical reasons.

Fundoplication↗
PubMed1997

Pancreatic lymph nodal and plexus micrometastases detected by enriched polymerase chain reaction and nonradioisotopic single-strand conformation polymorphism analysis: a new predictive factor for recurrent pancreatic carcinoma.

K-ras point mutations have been observed in approximately 90% of pancreatic carcinomas. We genetically analyzed cases of pancreatic regional lymph nodal and plexus micrometastases in invasive ductal carcinoma of the pancreas who were node negative or had metastases limited histopathologically to pancreaticoduodenal lymph nodes. These cases underwent curative resection in our institute. The utility of genetic analysis was compared with that of histopathological study, in terms of postoperative clinical outcome, as a predictive factor for recurrent pancreatic carcinoma. Samples for DNA extraction were obtained from formalin-fixed, paraffin-embedded specimens. A 0.5-microg quantity of DNA was subjected to enriched PCR and nonradioisotopic single-strand conformation polymorphism analysis. K-ras codon 12 mutations were detected in 83% (10 of 12) of invasive ductal carcinomas. In four cases, the genetic analysis of regional lymph nodal metastases and pancreatic plexus invasion of the pancreatic carcinoma yielded results concordant with those of histopathological analysis. In six cases, however, the metastases detected by genetic analysis were more advanced than was indicated by the histopathological examination. The survival rate of cases with metastases beyond the pancreaticoduodenal lymph nodes was significantly lower than that of cases with metastases limited to the pancreaticoduodenal lymph nodes or with no nodal involvement based on genetic analysis (P < 0.05). Intraoperative analysis of point mutations at K-ras codon 12 in the regional lymph nodes and the pancreatic plexus by enriched PCR/nonradioisotopic single-strand conformation polymorphism analysis is a highly accurate predictive factor for recurrent pancreatic carcinoma.

Adult↗
PubMed1997

Altered p16/MTS1/CDKN2 and cyclin D1/PRAD-1 gene expression is associated with the prognosis of squamous cell carcinoma of the esophagus.

The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate cyclin-dependent kinase 4-mediated phosphorylation of pRB in the cell cycle of normal cells. p16/CDKN2 gene and cyclin D1/PRAD-1 gene alterations have been detected in squamous cell carcinoma cell lines and in several primary squamous cell carcinomas of the esophagus. We immunohistochemically assessed p16 and cyclin D1 expression in 111 squamous cell carcinomas of the esophagus after evaluation of the antibodies against p16 and cyclin D1 protein using four squamous cell carcinoma cell lines. Loss of p16 expression was detected in 56 of 111 cases (50%). The mean number of metastatic lymph nodes without p16 expression was significantly higher than the number of nodes with p16 expression (P = 0.04). The postoperative survival rate for patients without p16 expression was significantly lower than that of patients with p16 expression (P = 0.04). Cyclin D1 overexpression was found in 28 of the 111 cases (25%) and correlated with distant organ metastasis after curative surgery (P = 0.05). The survival rate of patients with cyclin D1 overexpression was significantly lower than that of patients without cyclin D1 overexpression (P = 0.01). A positive correlation between the loss of p16 expression and cyclin D1 overexpression was observed (P = 0. 03). The loss of p16 expression and overexpression of cyclin D1 may be useful prognostic indicators in patients with squamous cell carcinomas of the esophagus. It may be possible to select more suitable treatment for patients with squamous cell carcinomas of the esophagus by evaluating the status of p16 and cyclin D1 expression.

Adult↗
PubMed1997

Tumor growth and metastasis of human colorectal cancer cell lines in SCID mice resemble clinical metastatic behaviors.

Ten human colorectal cancer (CRC) cell lines were implanted orthotopically into the ceca and also into the livers, muscles and peritoneal cavities of SCID mice in order to analyze the characteristics regulating metastatic behaviors of CRCs. All the CRC cell lines formed tumors in the muscle and cecum, but they could be classified into two groups: (1) six cell lines with high tumorigenicity in the liver (HTLs) forming differentiated tumors, and (2) four with no tumorigenicity in the liver (NTLs) forming poorly differentiated tumors in SCID mice. After orthotopic implantation, NTLs never metastasized to the liver, whereas HTLs did. Therefore, intrahepatic tumorigenicity and differential status were closely associated with liver metastasis whereas differentiation was not associated with lung metastasis. The 6 HTLs demonstrated an inverse correlation between liver metastases and peritoneal dissemination, and immunohistochemistry indicated expression of sLeX, CA19-9 and carcinoembryonic antigen in tumors which correlated well with the liver metastatic rate. We found a strong correlation between liver metastasis and intrahepatic tumorigenicity and could reproduce the clinical correlations between the pattern of the metastatic spread and the differentiation phenotype of CRC in vivo. We consider further examination using this model will be useful for analyzing the complex mechanisms involved in clinically metastasizing CRCs.

Adenocarcinoma↗
PubMed1996

Human colorectal carcinomas specifically accumulate Mr 42,000 ubiquitin-conjugated cytokeratin 8 fragments.

Recent studies have shown that various tumor cells accumulate ubiquitin (Ub)-conjugated proteins, the profiles of which differ from those of normal cells. To identify the Ub-conjugated proteins accumulated specifically by human carcinoma cells, a two-dimensional immunoblot analysis of 31 surgically resected human primary colorectal carcinoma tissues was performed using an anti-Ub monoclonal antibody, KM691. Two distinct Mr 42,000 and 45,000 proteins in the Triton X-insoluble fractions of carcinoma tissues reacted with this antibody, whereas only one Mr 45,000 protein reacted in normal tissues. The Mr 42,000 Ub-conjugated proteins were specific to carcinoma tissues from 25 patients (80.6%). One of the purified Mr 42,000 proteins was digested with Achromobacter protease I. This protein was identified as a cytokeratin 8 (CK 8) fragment based on both molecular mass determination and molecular mass searching of Achromobacter protease I-digested fragments of proteins registered in a protein sequence data base. Two-dimensional immunoblot analysis with an anti-CK 8 antibody confirmed that all of the Mr 42,000 proteins were CK 8 degradation products. These results demonstrate that human colorectal carcinomas specifically accumulate Mr 42,000 Ub-conjugated CK 8 fragments. This accumulation was observed frequently not only in advanced (18/22, 81.8%), but also in early stage cases (7/9, 77.8%), suggesting that it occurs even in the early stages of colorectal carcinoma progression.

Adult↗
PubMed1996

Antitumour activity of cis-diamminedichloroplatinum (II) against human tumour xenografts depends on its area under the curve in nude mice.

A pharmacodynamic analysis of cis-diamminedichloroplatinum(II) (DDP) was conducted using two human gastric cancer xenografts, SC-1-NU and MKN-45, and one human breast cancer xenograft, MX-1, grown serially in BALB/c nu/nu mice. DDP was administered intraperitoneally (i.p.) at a total dose of 5, 10, or 20 mg/kg in a schedule of q7d x 3 or (qd x 5) x 3. DDP was also administered i.p. to BALB/c +/? mice, whose plasma was used for the assay of total and free platinum by the atomic absorption method. A total dose of 20 mg/kg DDP seemed to be the maximum tolerated dose that was effective on MX-1 and SC-1-NU. When the totally administered doses were equivalent, the antitumor effects of the q7d x 3 and (qd x 5) x 3 schedules were similar to each other. The antitumor activity of DDP against MKN-45 was dependent on the total administered dose as well as the area under the curve of free and total platinum in the plasma. Side effects were significantly reduced using a schedule of (qd x 5) x 3 in terms of body and spleen weight loss when a total of 10 or 20 mg of DDP per kg was administered. These results suggest that DDP would be useful when administered using a daily schedule for obtaining the same antitumor activity as that of bolus injection but with reduced adverse effects.

Animals↗
PubMed1996

Potentiation of antitumor activity of mitomycin C by estradiol: studies of human breast carcinoma xenografts serially transplanted into nude mice.

The effect of experimental cancer chemotherapy with mitomycin C (MMC) was studied using three estrogen-receptor (ER)-positive (MCF-7, R-27, and Br-10) and one ER-negative (MX-1) human breast carcinoma xenograft serially transplanted into nude mice, and the effect of estradiol (E2) priming on the antitumor activity of MMC was investigated. Intramuscular injection of E2 at 1 mg/kg changed the ER state and increased the growth fraction detected by flow cytometry, although the growth rate of ER-positive tumors was not effective by E2 priming. MMC suppressed the growth of the four xenografts in a dose-dependent manner. When 1 mg/kg E2 was administered 1 h before MMC treatment, which was given intraperitoneally at a dose of 3 mg/kg, the antitumor activity of MMC was increased in comparison with MMC alone in ER-positive strains, although the effect of MMC on MX-1 was not changed by E2-priming. Priming with E2 at this dose increases the growth fractions of ER-positive breast carcinoma cells, which are sensitive to MMC, resulting in increased antitumor activity of MMC. This E2-primed MMC chemotherapy may be of value in the treatment of ER-positive human breast cancer.

Animals↗
PubMed1996

Pharmacokinetics of cis-diamminedichloroplatinum (II) given as low-dose and high-dose infusions.

A pharmacokinetic analysis of cis-diamminedichloroplatinum (II) (DDP) was conducted comparing low-dose daily bolus infusions, and high-dose drip infusions. Eight patients with gastric cancer were treated with low-dose daily bolus infusions of DDP to a total daily dose of 75 mg/m2 bid for 5 days. Four patients with esophageal cancer and one patient with gastric cancer were treated with high-dose drip infusions of DDP to a total daily dose of 70-80 mg/m2. Side effects were assessed in all the patients, and the platinum concentration in plasma was determined by an atomic absorption method. The peak plasma concentration (Cmax) and area under the curve (AUC) were calculated in four cases of the low-dose therapy, and three cases of the high-dose therapy. The side effects of DDP were evaluated according to the World Health Organization (WHO) grading, paying particular attention to nausea/vomiting, appetite loss, renal toxicity, and bone marrow suppression. The incidence of nausea/vomiting and appetite loss was significantly reduced with low-dose daily bolus infusions when compared to the high-dose drip infusions. Bone marrow toxicity and renal toxicity were similar with both administration methods, although hydration was required for the high-dose drip infusions to prevent renal toxicity. The peak plasma concentration (Cmax) of total and free platinum, and the area under the curve (AUC) of total platinum, were similar with both administration methods, while the AUC of free platinum was higher with the low-dose daily bolus infusions compared to the high-dose drip infusions. The time when the concentration of total platinum was > 1 microgram per ml (holding time) was significantly longer with the high-dose drip infusions than with the low-dose daily bolus infusions. The present study suggests that low-dose daily bolus infusions of DDP would be useful in reducing gastrointestinal toxicity, without reducing the area under the curve which is important for antitumor activity.

Adult↗
PubMed1996

Improvement of pharmacokinetics and antitumor activity against human hepatoma cell line by using adriamycin-entrapped stealth liposomes.

Preferential accumulation in the reticuloendothelial system is one of the major obstacles to the use of liposomes as a drug carrier for targeting therapy. To reduce their uptake, ganglioside GM1 was introduced into the components of conventional liposomes that had been used in our targeting experiments. Two types of such liposomes were prepared. Tissue distribution studies on Adriamycin entrapped in both types of liposomes clearly indicated that the uptake of Adriamycin by liver and spleen decreased to the level comparable to that of free Adriamycin administration. By contrast, the level of Adriamycin in the serum remains high, and some increase was observed in the accumulation to the tumor. Furthermore, Adriamycin in these liposomes, which were conjugated with anti-alpha-fetoprotein (AFP) antibody, inhibited the growth of AFP-positive human hepatoma Li-7 more efficiently than free Adriamycin or Adriamycin in antibody-conjugated conventional liposomes.

Animals↗
PubMed1996

Effectiveness of an adriamycin immunoconjugate that recognizes the C-erbB-2 product on breast cancer cell lines.

Adriamycin (ADM) was chemically conjugated to a murine monoclonal antibody, A0011, which recognizes the c-erbB-2 product, via a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane (2-IT). The molar ratio of ADM to the monoclonal antibody ranged from 15:1 to 25:1 and enzyme-linked immunosorbent assay (ELISA) showed that the binding activity of the conjugate was almost retained. We compared the efficacy of A0011 alone, ADM alone, the A0011-ADM conjugate, against the human breast cancer cell lines SK-BR-3, MDA-MB-361, MCF-7, and BT-20. The A0011-ADM conjugate was observed to be ten times more cytotoxic to the cell lines overexpressing the c-erbB-2 product, namely, SK-BR-3 and MDA-MB-361, than free ADM, but it showed weak cytotoxicity against the cell lines with a low level of c-erbB-2 product expression, namely, MCF-7 and BT-20. However, free A0011 and nonspecific murine IgM-ADM conjugate showed no cytotoxicity toward any of the four cell lines, while the addition of a tenfold molar excess of A0011 inhibited conjugate cytotoxicity. These data suggest that conjugate cytotoxicity is antibody-mediated. Moreover, conjugate cytotoxicity at 10(-6)M was correlated with antigen volume, and the data were fitted to the regression equation y = -11.63logX + 116.38 where the correlation coefficient = 0.950. Our results indicate that targeting therapy aiming at the c-erbB-2 product may be useful in the treatment of breast cancers overexpressing the c-erbB-2 product.

Antibiotics, Antineoplastic↗