[Adjuvant chemo-endocrine therapy for early breast cancer patients--review of the literature].
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Publications and source records attributed to M Kitajima.
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The treatment of hepatocellular carcinoma associated with liver cirrhosis necessitates local therapy in some patients because of severe hepatic dysfunction. Percutaneous ethanol injection therapy, the local therapy for such cancer of the liver, and percutaneous microwave coagulation therapy are detailed. The significant disadvantages of these procedures is their inability to evaluate precisely whether the tumor will develop complete necrosis after treatment because the cancer tissue cannot be excised with use of these procedures. Conversely, laparoscopic hepatectomy, which is minimally invasive surgery, has a disadvantage, that is, its difficulty in complex maneuvers, including hemostasis, ligation, and suture. The authors developed laparoscopic-assisted hepatectomy, which is hepatectomy by small incision during laparotomy with the use of laparoscopic observation. This report describes laparoscopic-assisted hepatectomy, which may allow the solving of problems with percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy, and laparoscopic hepatectomy.
This study aimed to examine whether an elevated activity of heme oxygenase (HO)-1 in the tissue attenuates endothelial cell-leukocyte interactions microvessels in vivo. When rats were pretreated with an intraperitoneal injection of hemin, an HO-1 inducer, mesenteric tissues, including their microvessels, displayed a marked induction of HO-1 concurrent with an increase in plasma concentrations of bilirubin-IXalpha, the product of HO-catalyzed degradation of protoheme IX. In these rats, oxidative stress such as superfusion with H(2)O(2) and ischemia-reperfusion of the tissues neither induced rolling nor exhibited adherent responses of leukocytes in venules. In contrast, the oxidative stresses evoked marked rolling and adhesion of leukocytes in the control rats without HO-1 induction. The HO-1 induction also downregulated leukocyte adhesion elicited by other pro-oxidant stimuli such as N(omega)-nitro-L-arginine methyl ester. The decreases in the oxidant-elicited leukocyte adhesive responses under HO-1-inducing conditions were restored by perfusion with zinc protoporphyrin-IX, an HO inhibitor, but not with copper protoporphyrin-IX, which did not inhibit the enzyme. Furthermore, the effects of zinc protoporphyrin-IX were repressed by superfusion with bilirubin or biliverdin at the micromolar level, but not by the same concentration of carbon monoxide, another product of HO. These results indicate that induction of the HO-1 activity serves as a potential stratagem to prevent oxidant-induced microvascular leukocyte adhesion through the action of bilirubin, a product of HO reaction.
We established in vitro heterotypic co-cultures of a human colon carcinoma cell line, HT-29, and a human hepatocyte line, tPH5CH, using transwells to investigate possible interactions between colon carcinoma cells and hepatocytes during the metastatic process. Co-culture, but not HT-29 conditioned medium, inhibited tPH5CH cell proliferation, and this inhibition was blocked by an anti-TGF-beta1 antibody. Significantly more activated TGF-beta1 was released by co-culture than by each cell line cultured alone, whereas there were no significant differences between the total TGF-beta1 released by the individual cultured cell lines and that released by co-culture. These data indicate that an interaction between human colon carcinoma cells and hepatocytes activates TGF-beta1 in vitro.
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The sialyl Lewis a antigen is a well known tumor marker, CA19-9, which is frequently elevated in the serum in gastrointestinal and pancreatic cancers. UDP-galactose:N-acetylglucosamine beta1, 3-galactosyltransferase(s) (beta3Gal-Ts) are required for the synthesis of the sialyl Lewis a epitope. In the present study, a novel beta3Gal-T, named beta3Gal-T5, was isolated from a Colo205 cDNA library using a degenerate primer strategy based on the amino acid sequences of the four human beta3Gal-T genes cloned to date. Transfection experiments demonstrated that HCT-15 cells transfected with the beta3Gal-T5 gene expressed all the type 1 Lewis antigens. In gastrointestinal and pancreatic cancer cell lines, the amounts of beta3Gal-T5 transcripts were quite well correlated with the amounts of the sialyl Lewis a antigens. The beta1,3Gal-T activity toward agalacto-lacto-N-neotetraose was also well correlated with the amounts of beta3Gal-T5 transcripts in a series of cultured cancer cells, and in Namalwa and HCT-15 cells transfected with the beta3Gal-T5 gene. Thus, the beta3Gal-T5 gene is the most probable candidate responsible for the synthesis of the type 1 Lewis antigens in gastrointestinal and pancreatic epithelia and tumor cells derived therefrom. In addition, beta3Gal-T5 is a key enzyme that determines the amounts of the type 1 Lewis antigens including the sialyl Lewis a antigen.
Classic cadherins can be grouped based on their deduced primary structures. Among them the type I cadherins have been well characterized; however, little is known about non-type I cadherins. In this study we characterized two human type II cadherins, cadherin-6 and cadherin-14, using a cDNA transfection system. They were each detected as two bands electrophoretically, were expressed on the external cell surface at cell-cell contact sites, and were associated with caten- ins. Direct sequencing of the N-terminal amino acids showed that the two bands of cadherin-14 corresponded to precursor and mature forms, whereas the two bands of cadherin-6 both had the N-terminal sequence of the mature form. Unlike type I cadherins, both cadherin-6 and -14 were not protected from trypsin degradation by Ca2+. We evaluated their adhesive functions by a long term cell aggregation method. The results suggest that both cadherin-6 and -14 have cell-cell binding strengths virtually equivalent to that of E-cadherin and that their binding specificities are distinct from that of E-cadherin. Cadherin-6 and -14 interacted with each other in an incomplete manner. They have a QAI tripeptide in the first extracellular subdomain instead of the HAV motif that is characteristic of type I cadherins and is intimately involved in the adhesive function. The QAI tripeptide, however, appeared not to be involved in the adhesive functions of cadherin-6 and -14.
BACKGROUND: Bone metastasis from breast cancer is often recognized clinically, but there are nonetheless several difficulties in diagnosis. In this study we used an animal model of bone metastasis from breast cancer and clarified the relationship between the urinary Pyd/Cr and Dpd/Cr and the progression of bone metastasis, compared with other bone related markers: serum alkaline phosphatase bone isozyme (ALP-BI), osteocalcin, and calcium. METHODS: The evaluation of bone metastasis was assessed by histological examination of the thoracic and lumbar vertebrae. According to the histological findings 4 weeks after the tumor cell injection, 11 animals were retrospectively divided into 2 subgroups: (1) tumor-bearing rats with bone destruction due to bone metastasis (TBR-BD(+), n = 5), (2) tumor-bearing rats without bone destruction (TBR-BD(-), n =6). These animals were compared to age-matched controls without tumor cell injection (n =6). An additional 5 animals were sacrificed at 2 weeks after the tumor cell injection to evaluate micrometastasis to bone. RESULTS: The values of other markers for bone metastasis in animals with micrometastatic foci in bone marrow did not differ significantly from those of the controls. Pyd/Cr and Dpd/Cr in the TBR-BD(+) group were significantly higher than those of the TBR-BD(-) and the control group (233 +/- 78.3 vs 93.8 +/- 6.5, 98.5 +/- 18.7, 123.1 +/- 35.9 vs 67.9 +/- 6.2, 60.6 +/- 9.8, p< 0.01), while there were no significant differences between TBR-BD(-) and the control. CONCLUSION: Both Pyd/Cr and Dpd/Cr are correlated significantly with the volume of bone metastasis, and are useful for the diagnosis and evaluation of progression of bone metastasis compared with other markers.
BACKGROUND AND OBJECTIVES: Development of the system to express a suicide gene selectively in tumor cells is essential for gene therapy. We constructed a plasmid containing the diphtheria toxin A (DTA) fragment linked to human alpha-fetoprotein (AFP) promoter and enhancer, and tested whether it can exert its cytocidal effect selectively on AFP-producing cells. METHODS: The chloramphenical acetyltransferase (CAT) reporter gene or DTA gene was linked to the 5' upstream region of the AFP gene. The plasmids were transfected into AFP-producing or non-producing cells by the lipopolyamine-coated DNA method. Expression of CAT activity and effects on cell growth of transfected cells were assessed. RESULTS: When the AFP-producing cells HuH-7 or HepG2 were cotransfected with CAT reporter plasmid and pAF5.1DTA plasmid, the CAT activity was greatly suppressed. In contrast, cotransfection with pAF5.1DTA-R, the inversely inserted DTA gene, did not inhibit CAT activity. Furthermore, cell growth of HuH-7 cells transfected with pAF5.1DTA plasmid was significantly inhibited compared with HuH-7 cells transfected with DTA-R plasmid. CONCLUSIONS: Our results indicate that selective killing of AFP-producing cells will be attained by introducing the DTA gene linked to the promoter and enhancer region of AFP.
BACKGROUND AND OBJECTIVES: The mechanism of the desmoplastic response in gastric carcinoma tissues is largely unknown. The objective of this study is to determine the localization of prolyl 4-hydroxylase (PH), an enzyme that plays a crucial role in collagen biosynthesis. METHODS: Freshly prepared gastric carcinoma tissues from 51 cases, including 13 of the scirrhous type (diffusely infiltrative type), were immunostained by using monoclonal antibodies to human placental PH. RESULTS: Although cytoplasmic staining for PH was observed in both fibroblasts and carcinoma cells, there was increased expression of the alpha-subunit in fibroblasts and no difference in expression between the scirrhous and non-scirrhous type gastric carcinomas. In scirrhous type samples, there was increased PH expression in fibroblasts located in the tumor periphery when compared with fibroblasts in the tumor center. These findings suggested that maintenance of a balance between production and degradation of collagen in gastric carcinoma tissues might be important for stroma formation. CONCLUSIONS: It is speculated that activated fibroblasts participate in collagen biosynthesis at the tumor periphery rather than in the tumor center and that increased collagen biosynthesis at the tumor periphery in scirrhous gastric carcinoma may assist further invasion of tumor cells.
The purpose of this study was to examine distribution and time history of oxidative stress during the hyperacute period of reperfusion in the liver grafts undergoing cold ischemia and to investigate roles of Kupffer cells as a potential oxidant source. Rat livers were harvested at 4 degrees C in University of Wisconsin solution and followed by reperfusion with Krebs-Henseleit buffer under monitoring bile excretion. To investigate oxidative changes, laser-confocal microfluorography was performed in reperfused livers preloaded with dichlorodihydrofluorescein diacetate succinimidyl ester, a fluorescence precursor sensing intracellular hydroperoxide generation. Livers undergoing the 16-hour cold storage displayed an impaired recovery of bile acid-dependent bile output concurrent with a marked increase in hydroperoxide generation in hepatocytes, which occurred as early as 5 minutes after the onset of reperfusion, whereas the status of lobular perfusion was well maintained. Pretreatment with liposome-encapsulated dichloromethylene diphosphonate, a Kupffer cell-depleting reagent, did neither alter the reperfusion-induced periportal oxidative changes nor improve the recovery of bile output in the graft. On the other hand, EPCK, a hepatotropic antioxidant composed of vitamin E phosphate ester bound to vitamin C, not only diminished the oxidative changes but also improved the reduction of bile acid-dependent bile output. Furthermore, the reagent was capable of inhibiting H(2)O(2)-induced oxidative stress in cultured hepatocytes. These results suggest that hepatocytes constitute a major site of the oxidative insult triggered through Kupffer cell-independent mechanisms and serve as an important cellular component to be protected by antioxidant therapeutics.
Although a complete remission of Crohn's disease can be induced by conservative therapy, surgical treatment is often required for patients with intestinal stenosis or fistulas, for whom minimally invasive laparoscopic surgery appears to be most appropriate. We herein report on a 26-year-old patient with Crohn's disease, who presented with an ileorectal fistula and severe stenosis of the terminal ileum and thus underwent laparoscopic surgery. The ileorectal fistula was divided intracorporeally using an autostapling device. The return to full activity after laparoscopic surgery is earlier than after open surgery, and the former approach is often beneficial for some patients with Crohn's disease. This is the first report of laparoscopic surgery for Crohn's disease associated with ileorectal fistula.
Sixty-one patients who were diagnosed with mucosal gastric cancer have been successfully treated with two laparoscopic techniques at our institute from March 1992 to March 1997. One is laparoscopic wedge resection of the stomach using a lesion-lifting method for lesions of the anterior wall, the lesser curvature, and the greater curvature of the stomach. The other is laparoscopic intragastric mucosal resection for lesions of the posterior wall of the stomach and near the cardia or the pylorus. Indications are as follows: (1) preoperatively diagnosed mucosal cancer; (2) <25 mm diameter elevated lesions; and (3) <15 mm diameter depressed lesions without ulcer formation. Patients were discharged in 4 to 8 days uneventfully. There was no major complication or mortality. The resected specimens had sufficient surgical margins horizontally (16 +/- 5 and 8 +/- 4 mm, respectively) and vertically. In one patient histologic examination revealed slight tumor infiltration into the submucosal layer with lymphatic invasion. He underwent gastrectomy with lymph node dissection 1 month after surgery. Otherwise, histologic examination revealed curative surgery. All patients in the series have survived during the 4- to 65-month follow-up period. There have been two recurrences in the series, both of which were found near the staple line 2 years after the initial surgery and were still mucosal lesions. They were successfully treated by open gastrectomy and laser irradiation. A separate early gastric cancer was found 2 years after the initial surgery in one patient, who then underwent curative open gastrectomy. In conclusion, if the patients are selected properly, these laparoscopic procedures are curative, minimally invasive treatment for early gastric cancer.
In an attempt to improve the guidelines for concurrent management of concomitant abdominal aortic aneurysm (AAA) and symptomatic malignancy, a retrospective study was undertaken. A total of 186 AAA repairs were performed electively, and 25 patients (13.4%) had concurrent symptomatic malignancy from April 1986 to March 1997. Fourteen patients underwent a one-stage operation, including five abdominoperineal rectal resections, four subtotal gastrectomies, three total gastrectomies, and two right hemicolectomies. Eleven others underwent a two-stage operation, including four with total gastrectomy and left hemicolectomy followed by AAA repair, as well as two with right hemicolectomy and one with left hemicolectomy prior to AAA repair. There were no operative deaths or severe postoperative complications. Of the 25 patients, 22 (88.0%) are still alive during follow-up ranging from 8 months to 11 years. Our surgical approach to both lesions is as follows: (1) Using the transperitoneal approach alone, subtotal gastrectomy and abdominoperineal rectal resection can be safely done simultaneously. (2) Although total gastrectomy can also be performed concurrently, the approach used for each lesion is separate. (3) Colorectal resection is generally done separately. However, a one-stage operation can be performed using the thromboexclusion procedure for AAA repair in patients with right-sided colonic cancer or a temporary transverse colostomy for left-sided colorectal cancer.
Near-infrared spectroscopy (NIRS) is a noninvasive biomeasurement system with rays in the near-infrared region that possess high permeability to biological tissues. NIRS was applied to liver allografts undergoing rejection in rats treated with deoxyspergualin (DSG) or tacrolimus (FK506). The nitrosyl hemoglobin (Hb) levels detected in the liver grafts increased 3 days and 5 days after grafting in both allogeneic and syngeneic transplantation. The levels on day 8 remained high in the allogeneic graft, but markedly decreased in the syngeneic graft. Although the serum levels of nitrite and nitrate were extremely low 8 days after grafting in allografted recipients treated with DSG or FK506, the nitrosyl-Hb level in DSG-treated graft was much higher than that in FK506-treated graft. There was no significant difference in survival time between DSG-treated and FK506-treated recipients. In conclusion, DSG and FK506 have a different effect on NO production in allografted liver with ongoing rejection, and circulating nitrite and /nitrate levels do not reflect the local levels of NO in the graft.
A gastric tube-to-airway fistula is a very rare complication after esophageal reconstruction. A patient with a gastric tube-to-tracheal fistula that developed more than 9 years after surgery for cancer of the cervical esophagus was treated with transposition of a pedicled latissimus dorsi myocutaneous flap. Careful perioperative respiratory management helped save the patient's life.
Genomic instability is sometimes due to impairment of DNA repair systems, which results in a change in the number of microsatellite repeats in tumor cells, produced by slippage during DNA replication. Such abnormal repeats are manifested as microsatellite instability (MSI). We have devised a simple assay using four-color fluorescence for the detection of MSI by an automatic sequencer. Using this method, MSI and loss of heterozygosity (LOH) at four microsatellite loci can be identified simultaneously. We have also developed an algorithm and software for automated analysis of MSI and LOH with this method. Using our method for the detection of MSI in four microsatellite loci and the algorithm and software that we developed, 18 (94.7%) of 19 patients with hereditary nonpolyposis colorectal cancer (HNPCC), meeting the Amsterdam Minimum Criteria, were found to exhibit MSI.
BACKGROUND/PURPOSE: This report describes a technique of hepatic portoenterostomy (HPE) to keep sustained bile drainage in biliary atresia patients. In conventional HPE, the medial posterior row of the anastomosis is placed behind the main portal vein. But around both lateral corners where the portal branches enter the liver parenchyma, the anastomosis is placed across and outside of the portal veins. Resultantly, the proximal part of the portal veins become included in anastomosis attaching directly to the dissected area where bile ducts are copious. In a devised procedure designated as invaginating anastomosis (IA), an anastomotic line was placed to invaginate the medial branch of the right portal vein and also placed behind the veins even at their roots. This technique puts all portal branches outside of the anastomosis, preventing cicatricial adhesion at the dissected area with the posterior wall of the veins. METHODS: The effect of IA was evaluated in terms of resolution of jaundice and long-term outcome compared with conventional anastomosis (CA). Group IA consisted of 20 patients and group CA of 18 patients. RESULTS: Patients in whom jaundice resolved included 19 (95%) in group IA and 11 (61%) in group CA (P < .05). Reoperation was needed in only one infant in group IA, and in six in CA (P < .05). In patients with reoperation in group CA, the portahepatis was found to be contracted with dense cicatricial tissues. The survival rates for patients with a native liver, calculated excluding those in whom the cause of death was not liver deterioration, was 87% for IA compared with 41% for CA (P < .05). Averaged biliary atresia prognostic index at the last follow-up evaluation was 20.2+/-24.5 for group IA and 62.6+/-29.8 for group CA (P < .001). CONCLUSION: The invaginating anastomosis in portoenterostomy promised a sustained bile drainage and improved long-term outcome by preventing cicatricial contraction of the portahepatis.