Biomedical subjects

T Takayama

Publications and source records attributed to T Takayama.

At least 163 records · Page 9Linked to original sources

PubMed2000

Pharmacologic intervention with angiotensin II and kininase inhibitor enhanced efficacy of radioimmunotherapy in human colon cancer xenografts.

UNLABELLED: Induced hypertension and kininase inhibition can enhance tumor targeting of radiolabeled monoclonal antibody (MAb) by altering tumor circulation. This study investigated the effect of this manipulation on the antitumor efficacy of radioimmunotherapy (RIT). METHODS: Mice bearing human colon cancer xenografts were administered 2.0 microg/kg/min of angiotensin II (AT-II) for 1 h and 30 microg of a kininase inhibitor, enalapril maleate, before the administration of 3.7 MBq (131)I-A7, an IgG1 against 45-kDa glycoprotein on colorectal cancer, and tumor growth was observed thereafter. The mechanism of the manipulation effect was investigated by estimation of the tissue absorbed dose and radioluminography of tumors. RESULTS: The pharmacologic manipulation with AT-II and enalapril improved the tumor quadrupling time (Tq) of 3.7 MBq RIT from 24.3 +/- 2.75 d to 33.1 +/- 2.83 d (P < 0.05). Addition of this manipulation made 3.7 MBq RIT as effective as 9.25 MBq RIT alone (Tq, 37.2 +/- 2.97 d). Dose estimation showed that the manipulation increased the tumor absorbed dose 1.55-fold without affecting the doses to normal tissues. Uniform intratumoral distribution in the manipulated tumors was shown by radioluminography. CONCLUSION: Larger and more uniform tumor radiation produced by this pharmacologic manipulation can benefit RIT with (131)I-MAb.

Angiotensin II↗

PubMed2000

[Feasibility study of SPECT quantification using CdTe semiconductor detector].

Quantification of SPECT using CdTe semiconductors as a detector head in nuclear medicine equipment was investigated. A prototype of semiconductor detectors with an effective field-of-view as small as 2.54 cm x 5.08 cm was constructed, and a cylindrical phantom containing four spherical phantoms with capacities 71, 56, 42, and 15 ml, was used. Water was placed in three of these spherical phantoms (71, 56, and 42 ml), and 8.362 MBq of 99mTc was poured into the remaining 15 ml phantom. In the outer cylindrical phantom, 925 MBq (6200 ml) of 99mTc was placed. A Toshiba LEHR (Low Energy High Resolution) collimator was attached to the semiconductor detectors, and SPECT acquisition with a rotation radius 132 mm was performed. It was found that in the data thus acquired using the semiconductor detector, the amount of scattered gamma-rays decreased by 33% as compared to data acquired using NaI(Tl) scintillators under the same condition. Moreover, when attenuation correction was applied to SPECT data from the CdTe semiconductor detector, the measurement accuracy of radioactivity improved by 16% as compared to SPECT data from NaI(Tl) scintillators with the same acquisition and post-correction conditions. Finally, the CdTe detector data with only attenuation correction was found to have almost the same grade of accuracy as NaI scintillator data with both attenuation and TEW scatter corrections.

Feasibility Studies↗

PubMed2000

Overexpression of retinoblastoma protein predicts decreased survival and correlates with loss of p16INK4 protein in gallbladder carcinomas.

This study was designed to determine whether the level of retinoblastoma protein (pRb) expression predicts tumor progression and prognosis in gallbladder carcinomas (GBCs) and the relationship between pRb and pl6INK4 protein expression. The expression of these two proteins was evaluated immunohistochemically in 37 tumors from 36 patients with GBC. pRb loss and overexpression were observed in 5 (13.5%) and 18 (48.6%) of the 37 tumors, respectively. Both pRb loss and overexpression were significantly correlated with advanced TNM stage, lymph node metastasis, and tumor perineural invasion. Moreover, pRb overexpression was significantly associated with decreased overall survival (P = 0.001; log-rank test). Further analysis indicated that the influence of pRb overexpression on survival was independent of TNM stage and lymph node metastasis. Loss of p16INK4 protein was observed in 28 of the 37 GBCs (75.7%), but was not significantly associated with any clinicopathological factors or survival. pRb overexpression was significantly associated with the loss of p161NK4 protein (P < 0.0001). These results suggest that pRb overexpression significantly predicts decreased survival in GBCs.

Aged↗

PubMed2000

Cyclin D1 overexpression is a critical event in gallbladder carcinogenesis and independently predicts decreased survival for patients with gallbladder carcinoma.

This study was designed to test the hypothesis that cyclin D1 overexpression is involved in the multistep process of gallbladder carcinogenesis and can be used to predict poor prognosis for patients with gallbladder carcinoma (GBC). Cyclin D1 expression was examined immunohistochemically in a series of specimens, including 8 normal epithelia, 8 benign adenomyoma lesions, 6 precancerous adenomas, and 37 carcinomas of the gallbladder. Four of the 6 (67%) adenomas and 15 of the 37 (41%) adenocarcinomas demonstrated cyclin D1 overexpression (>5% nuclear staining), whereas all normal epithelia and adenomyoma lesions were negative for cyclin D1. Kaplan-Meier curves showed that cyclin D1 overexpression was significantly related to decreased overall survival (P < 0.05) in patients with GBCs. The Cox proportional hazards model identified cyclin D1 overexpression as an independent prognostic marker for death (P = 0.024; risk ratio, 4.2; 95% confidence interval, 1.2-14.7). To test whether cyclin D1 overexpression is a critical event in gallbladder neoplasms, cyclin-dependent kinase inhibitor p27Kip1 was introduced to ascertain how cyclin D1 affects clinical outcomes. Subsequently, neoplasms were divided into three groups on the basis of the combination of cyclin D1 expression and p27Kip1 status, which had been determined previously. Group 1 showed no abnormality in either cyclin D1 or p27Kip1 expression. Group 2 showed aberrant expression of one of the two proteins, whereas group 3 showed concurrent abnormalities in both proteins. Results indicated that overall survival was greatest in group 1, followed by a significant decrease in group 2 and a more precipitous decrease in group 3. In conclusion, cyclin D1 overexpression is an early event in gallbladder carcinogenesis and independently predicts decreased survival for patients with GBC.

Aged↗

PubMed2000

Oxalate synthesis in mammals: properties and subcellular distribution of serine:pyruvate/alanine:glyoxylate aminotransferase in the liver.

Primary hyperoxaluria Type 1 (PH1) is caused by a functional deficiency of a liver enzyme, serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), which catalyzes transamination between L-serine or l-alanine as an amino acid substrate and glyoxylate or pyruvate as an alpha-keto acid substrate. A high affinity for glyoxylate is a notable feature of this enzyme, suggesting a role in glyoxylate metabolism in vivo. Another conspicuous feature of SPT/AGT is its species-specific and food habit-dependent subcellular distribution. Thus, the enzyme is located in peroxisomes in herbivores and man, largely in mitochondria in carnivores, and in both the organelles in rodents. The mechanism of the species-specific dual organelle localization of SPT/AGT is either transcription of the gene from two different start sites or loss of the upstream translation initiation ATG codon by mutations. It appears that the mitochondrial versus peroxisomal distribution of SPT/AGT in different animal species is indispensable in meeting the metabolic needs caused by their respective food habits. As for the peroxisomal localization, glycolate is contained in plants much more than in animal tissues, and when ingested, it is converted to glyoxylate, an immediate precursor of oxalate, in liver peroxisomes. Therefore, peroxisomal localization of SPT/AGT may be indispensable for herbivores to convert the glyoxylate formed in peroxisomes into glycine in situ rather than forming oxalate. On the other hand, our recent studies showed that SPT/AGT contributed substantially to serine metabolism in rabbit, human, and dog livers; i.e., irrespective of its mitochondrial or peroxisomal localization. Thus, the mitochondrial localization of SPT/AGT was not a prerequisite for the metabolism of L-serine. Another source of glyoxylate is the metabolism of L-hydroxyproline, and in this case, the enzyme responsible for the glyoxylate formation has been reported to be a mitochondrial matrix enzyme. Collagen accounts for about 30% of total animal proteins and contains about 13% (w/w) hydroxyproline. It is therefore possible that both mitochondrial and peroxisomal SPT/AGT contribute to the metabolism of glyoxylate and serine, but the subcellular site for glyoxylate metabolism is different in herbivores and carnivores.

Animals↗

PubMed1999

Transduction of dendritic cell progenitors with a retroviral vector encoding viral interleukin-10 and enhanced green fluorescent protein allows purification of potentially tolerogenic antigen-presenting cells.

BACKGROUND: Dendritic cells (DC) are important antigen-presenting cells that play critical roles in the initiation and modulation of immune responses. Genetic engineering of DC to express immunosuppressive molecules is a novel approach to the inhibition of allograft rejection. Retroviral delivery of viral interleukin (vIL)-10 to replicating myeloid DC progenitors (DCp) impairs their T-cell stimulatory capacity and promotes the induction of antigen-specific T-cell hyporesponsiveness. However, transduction efficiency with retroviral vectors is comparatively low. Enhanced green fluorescent protein (EGFP) is important both as a marker of gene transduction and for the selection of transduced cells. Our aims were to construct a retroviral vector encoding both vIL-10 and EGFP, to positively select transduced DC, and to assess the impact of these highly purified, vIL-10-secreting antigen-presenting cells on allogeneic T-cell responses. METHODS: DCp propagated from bone marrow of C57BL10 (H2b) mice in granulocyte-macrophage colony-stimulating factor (GM-CSF)+IL-4 were transduced with a retroviral vector encoding both vIL-10 and EGFP by centrifugal enhancement. Gene transfer efficiency was determined by flow cytometry. Transduced cells were flow sorted, and vIL-10 secretion was quantified by ELISA. DC function was assessed by the ability of the cells to induce naive allogeneic (C3H; H2k) T-cell proliferation and cytotoxic T lymphocyte generation. RESULTS: Retrovirally transduced DC expressed both vIL-10 and EGFP gene products. Approximately 20% of unsorted cells expressed EGFP, as determined by flow cytometry. vIL-10 was produced at a mean rate of 31 ng/40 hr/10(6) cells. After sorting, the incidence of EGFP+ DC was increased dramatically to at least 95%, and the production of vIL-10 was increased approximately three- to fourfold, to a mean of 107 ng/40 hr/10(6) cells. These highly purified, vIL-10-secreting DC exhibited markedly diminished capacity to induce allogeneic T-cell proliferative and cytotoxic responses. CONCLUSIONS: DCp retrovirally transduced to express both vIL-10 and EGFP can be rapidly identified and sorted to high levels of purity. The availability of highly enriched preparations of vIL-10-transduced DC facilitates studies of their immunoregulatory function and may enhance their therapeutic potential in transplantation or autoimmune disease.

Animals↗

PubMed1999

Over-expression and lack of retinoblastoma protein are associated with tumor progression and metastasis in hepatocellular carcinoma.

To determine the role of retinoblastoma (Rb) gene alteration in hepatocarcinogenesis, we examined Rb protein expression immuno-histochemically in a series of surgically resected specimens including non-cancerous liver tissues with cirrhosis or chronic hepatitis, large regenerative nodules, pre-cancerous adenomatous hyperplasias as well as primary and metastatic lesions of hepatocellular carcinoma (HCC). All of the non-cancerous liver tissues, large regenerative nodules and adenomatous hyperplasias showed normal Rb protein expression. Altered Rb protein expression was observed in 31 (lack of Rb protein in 16 and over-expression in 15) of the 81 primary HCCs (38%) and was significantly associated with tumor differentiation grade: altered Rb protein expression occurred in 1 of 23 (4%), 16 of 43 (37%) and 14 of 15 (93%) well-, moderately and poorly differentiated tumors (moderately vs. well-differentiated p < 0.01; poorly vs. moderately differentiated p < 0.001). Incidences of both Rb protein absence and over-expression were higher for moderately differentiated than for well-differentiated tumors and even higher for poorly differentiated tumors. Rb protein absence and over-expression were observed in 9 (39%) and 10 (44%) of the 23 metastatic lesions of HCC, respectively, and the incidence of altered Rb protein expression (absence or over-expression) was significantly higher than in primary lesions (83% vs. 38%, p < 0.001). Our observations suggest that elevated and absent Rb protein are closely associated with tumor progression and developing metastatic disease rather than tumor initiation in cases of HCC. Int. J. Cancer (Pred. Oncol.) 84:604-608, 1999.

Adolescent↗

PubMed1999

Portal venoplasty for recipients in living-related liver transplantation.

BACKGROUND: In living-related liver transplantation (LRLT) in small children, standard end-to-end portal vein (PV) anastomosis is usually difficult because of a inadequate total PV length, or because of a size mismatch between the graft and the recipient PV. In this report, we present our new portal venoplasty technique for the recipient PV. METHODS: After dissection of the recipient PV, the wall between the right and left branches of the PV is severed longitudinally as in the branch patch technique. The anterior and posterior edges of both branches are joined using running sutures, to form a longer and wider PV for anastomosis. RESULTS: This new portal venoplasty technique was used in 7 of 28 child cases, and gave good results without thrombosis or other complications. CONCLUSIONS: Our new portal venoplasty technique is useful in LRLT in small children when the recipient or graft PV is not long enough.

Adult↗

PubMed1999

Combination radioimmunotherapy with local hyperthermia: increased delivery of radioimmunoconjugate by vascular effect and its retention by increased antigen expression in colon cancer xenografts.

Hyperthermia (HT) may increase tumor targeting of a radiolabeled antibody by its effects on tumor vasculature and antigen expression. Expression of a 45-kDa glycoprotein antigen on LS180 colon cancer cells was 2.7-fold enhanced 2 days after heating at 43 degrees C for 1 h. Preferential tumor accumulation of 125I-A7 recognizing this antigen was doubled and the antitumor effect of 131I-A7 was significantly improved by HT. Hyperthermia also increased tumor uptake of an irrelevant antibody but its radioactivity was rapidly cleared. These results indicate that HT increased the initial delivery of an antibody to a tumor by its vascular effect, and radioactivity was retained in tumors by increased specific binding, resulting in a better radioimmunotherapy outcome.

Animals↗

PubMed1999

Clinical utility of negative contrast intravascular ultrasound to evaluate plaque morphology before and after coronary interventions.

Although intravascular ultrasound (IVUS) is used for evaluation of plaque volume and lumen size as well as detection of vessel wall structures after catheter-based interventions, differentiation between the lumen and plaque structures can be difficult. This study attempted to evaluate the efficacy of negative contrast IVUS imaging for assessment of vessel wall morphology after coronary interventions. IVUS studies were performed in 67 lesions in 66 patients before and after coronary interventions. After the baseline ultrasound imaging run, warm 5% glucose solution was injected manually through the guiding catheter into the coronary artery to washout blood from the lumen to avoid speckled reflections from red blood cells (negative contrast). Quantitative measurements were obtained and plaque morphology was assessed for the presence and extent of medial dissections and intimal flaps. There was no difference in each quantitative parameter between baseline images and negative contrast images. The vessel wall boundary was clearly delineated from the lumen, which was defined as effective negative contrast in 51 of 67 lesions (76%). The baseline images revealed plaque dissection in 9 lesions (18%) and an intimal flap in 13 lesions (25%). In addition, 4 dissections (8%) and 16 intimal flaps (31%) were visualized during the infusion of negative contrast. Additional treatment was performed in 4 lesions (8%) based on the images with negative contrast. Negative contrast IVUS was more sensitive in demonstrating a plaque fracture than were baseline images. This method is useful for enhancing the diagnostic capability of IVUS imaging and may influence the decision-making process during interventional procedures.

Anatomy, Cross-Sectional↗

PubMed1999

Distinctive structure of the human GSTM3 gene-inverted orientation relative to the mu class glutathione transferase gene cluster.

The sequence and exon-intron structure of the human class mu GSTM3 glutathione transferase gene and its orientation with respect to the remainder of the human class mu GSTM gene cluster were determined. The GSTM3 gene is 2847 bp long and is thus considerably shorter than the other class mu genes in the cluster, which range in size from 5325 to 7212 bp. Outside the protein-coding region, the GSTM3 gene does not share significant sequence similarity with other class mu glutathione transferase genes. Identification of overlapping cosmid clones that span the region between GSTM5, the next nearest glutathione transferase gene, and GSTM3 showed that the two genes are about 20,000 bp apart. PCR primers developed from sequences 3'-downstream from the GSTM5 gene were used to identify clones containing the GSTM3 gene. Amplification with these primers showed that the orientation of the GSTM3 gene is 5'-GSTM5-3'-3'-GSTM3-5'. Long-range PCR reactions confirmed this orientation both in the GSTM-YAC2 YAC clone, which contains the five class mu glutathione transferase genes on chromosome 1, and in human DNA. This tail-to-tail orientation is consistent with an evolutionary model of class mu glutathione transferase divergence from a pair of tail-to-tail "M1-like" and "M3-like" class mu glutathione transferase genes that was present at the mammalian radiation to the current organization of multiple head-to-tail M1-like genes tail-to-tail with a single M3-like gene with distinct structural properties and expression patterns.

Base Sequence↗

PubMed1999

No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach.

BACKGROUND: Low resectability rates and significant morbidity and mortality rates often make surgery for hepatocellular carcinomas (HCCs) unfeasible. HYPOTHESIS: Our policy for surgical treatment of cirrhotic and noncirrhotic patients with HCC is adequate and safe. DESIGN: Prospective validation cohort study. SETTING: University hospital. PATIENTS: One hundred seven consecutive patients with HCCs. Associated cirrhosis was present in 64 (59.8%), and only 7 (6.5%) had normal livers. INTERVENTIONS: The presence of ascites, serum bilirubin level, and indocyanine green retention rate at 15 minutes were considered when selecting patients for surgery. Preoperative recovery of liver function was achieved with portal venous branch embolization, liver volumetry, bed rest, and control of serum aminotransferase levels. The surgical techniques mainly involved bloodless dissection using intraoperative ultrasonography and intermittent warm ischemia. The main perioperative care regimen was fresh frozen plasma infusion and strict limitation of blood transfusion. MAIN OUTCOME MEASURES: The 30-day postoperative mortality and morbidity rates. RESULTS: All the patients underwent surgery (37 major resections, 45 segmentectomies, and 25 limited resections), with no 30-day postoperative mortality, overall morbidity of 26.2%, and no major complications. Multiple logistic regression analysis revealed that only the type of operation was associated with a significantly higher morbidity risk (P = .05). CONCLUSION: With high resectability, low morbidity, and no mortality, our policy represents a solution to the drawbacks of surgical resection for treatment of HCCs, especially in patients with associated liver cirrhosis.

Adolescent↗

PubMed1999

Steatosis and intrahepatic hepatitis C virus in chronic hepatitis.

Hepatic steatosis has been reported as one of the characteristics which discriminates hepatitis C from other forms of hepatitis, besides lymphoid follicles and bile duct damage. However, it is unclear whether or not the presence of hepatitis C virus (HCV) itself is associated with the development of steatosis. The possibility that the HCV itself is directly related to the development of steatosis was examined. The intrahepatic core protein levels, as a marker of the HCV load, were correlated with the presence of steatosis in 43 patients with chronic hepatitis C. Among 43 patients studied by Western blotting, the core protein was detected in the liver in 27 (62.8%). On the other hand, hepatic steatosis was observed in 21 (48.8%) of the 43 patients. Importantly, the core protein was detectable in 19 (90.4%) of the 21 patients with steatosis, while it was detected in only 8 (36.4%) of the 22 patients without steatosis (P = 0.008). However, serum HCV-RNA levels as determined by the Amplicor monitor were not significantly different between patients with and without steatosis. Multivariate analysis showed that the serum alanine aminotransferase level (P = 0. 013), body mass index (P = 0.038), and intrahepatic HCV core protein positivity (P = 0.038) were the independent parameters best predictive of steatosis. These results indicate a close relationship between intrahepatic HCV and the development of steatosis, and suggest a possible role of the HCV itself or core protein in the pathogenesis of steatosis in human chronic hepatitis C.

Aged↗

PubMed1999

Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy.

Fine-needle biopsy (FNB) is associated with problems, such as tumor seeding, which are probably underestimated. The aim of this study was to validate prospectively the accuracy of our diagnostic work-up without FNB, for defining indications for surgery in a cohort of patients with focal liver lesions (FLLs). Between January 1997 and December 1998, 160 consecutive patients carrying 225 FLLs admitted to our department were evaluated prospectively. Preoperative diagnoses were established by means of clinical histories, serum tumor marker levels, ultrasonography, and spiral computed tomography (CT). Angiography, magnetic resonance imaging (MRI), and Lipiodol-CT were performed when it was considered necessary to plan the surgical strategy. All the patients underwent surgery and results of pathological examinations were obtained for all of them. The preoperative diagnoses of 221 of the 225 lesions (98.2%) were confirmed, and the indications for liver resection in 156 of the 160 patients (97.5%) were correct. The respective accuracy, sensitivity, specificity, and positive and negative predictive values were 99.6%, 100%, 98.9%, 99.3%, and 100% for diagnosis of hepatocellular carcinoma (HCC); 99.1%, 100%, 98.8%, 96.9%, and 100% for metastases; 99.6%, 100%, 99.5%, 91%, and 100% for cholangiocellular carcinomas (CCCs); all 100% for mixed HCC-CCCs; and 98.7%, 57.1%, 100%, 100%, and 98.6% for benign tumors. In view of these results, the fact that the real risks of FNB have yet to be established and the possibility that tumor seeding has a major impact on patient prognosis, the use of FNB should be drastically limited.

Angiography↗

PubMed1999

Decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, influence recurrence and survival of patients with resectable extrahepatic bile duct carcinoma.

This study was undertaken to identify potential abnormalities of p27(Kip1) and cyclin D1 expression in extrahepatic bile duct carcinomas and to assess the prognostic significance of p27(Kip1) and cyclin D1 levels for patients with this disease. Decreased p27(Kip1) expression (<50% nuclei staining) and cyclin D1 overexpression (>5% nuclei staining) was observed immunohistochemically in 19 (56%) and 23 (68%) of the 34 tumors examined, respectively. Both decreased p27(Kip1) and cyclin D1 overexpression were associated with relapse (P =.0005 for p27(Kip1) and P =.0004 for cyclin D1). Kaplan-Meier curves showed that both decreased p27(Kip1) and cyclin D1 overexpression correlate significantly with shortened survival rates (for p27(Kip1), P =.0419 and P =.002 for overall and disease-free survival; for cyclin D1, P =.0392 and P =.0021 for overall and disease-free survival). Cox regression model analyses identified decreased p27(Kip1) and cyclin D1 overexpression as independent markers predicting death from relapse (P =.0371, risk ratio: 3.891 for p27(Kip1); P =.0429, risk ratio: 8.31 for cyclin D1). Decreased p27(Kip1) was associated with cyclin D1 overexpression (P =.0202), and coincident abnormalities of the 2 proteins occurred in 16 of the 34 (47%) tumors, indicating that extrahepatic bile duct carcinoma progression may require synchronous dysfunction of p27(Kip1) and cyclin D1 in about half of patients. Patients with tumors showing coincident abnormalities of p27(Kip1) and cyclin D1 showed even more frequent recurrence than patients with an alteration in only 1 of the 2 proteins. In conclusion, decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, predict poor prognosis in patients with resectable extrahepatic bile duct carcinoma.

Aged↗

PubMed1999

Genetic engineering of dendritic cells to express immunosuppressive molecules (viral IL-10, TGF-beta, and CTLA4Ig).

There is growing evidence that, in addition to their role as initiators of immune responses, dendritic cells (DC) can exhibit tolerogenic properties. Immature DC deficient in cell surface costimulatory/accessory molecules can prolong organ and pancreatic islet allograft survival, whereas in vitro manipulation of DC by exposure to a variety of factors (e.g., viral interleukin-10; CTLA4Ig) can confer tolerogenic properties on these cells. Genetic engineering of DC to express immunosuppressive molecules is, in theory, an attractive approach to the therapy of allograft rejection and possibly, autoimmune disorders.

Abatacept↗

PubMed1999

Anterior transhepatic approach for isolated resection of the caudate lobe of the liver.

We have devised a new technique for isolated caudate lobe resection in which we access the caudate lobe by separating the liver parenchyma along the interlobar plane. The safety and radicality of the procedure were evaluated in five patients: four with hepatocellular carcinoma (HCC) and one with metastatic rectal cancer. All of the tumors were located mainly in the paracaval portion of the caudate lobe. The patients with HCC (three of four) underwent an anatomic caudate lobe resection by identification of the right margin of the caudate lobe. Two patients required red blood cell transfusion, and one showed bile leakage after surgery. All of the patients are alive without recurrence more than 4 years after surgery, except one with rectal carcinoma who developed lung metastases. The anterior transhepatic approach is a safe and potentially curative surgical option for a tumor in the paracaval portion of the caudate lobe.

Aged↗

PubMed1999

Efficacy, toxicity and mode of interaction of combination radioimmunotherapy with 5-fluorouracil in colon cancer xenografts.

PURPOSE: The feasibility of radioimmunotherapy (RAIT) combined with 5-fluorouracil (5-FU) was examined in colon cancer xenografts. The mode of interaction of the two treatments was also investigated. METHODS: Mice bearing human colon cancer were treated with a combination of 4.63 MBq (L-RAIT) or 9.25 MBq (H-RAIT) (131)I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg(-1)day(-1) for 5 days. Myelotoxicity was monitored by blood cell counts and intestinal toxicity was assessed by the dosimetry. The results were compared with those of a single-modality therapy. RESULTS: The combination of 5-FU with H-RAIT enhanced the antitumor effect, improving the tumor quadrupling time from 25.3 +/- 9.59 days to 31.3 +/- 8.32 days (P < 0.05) and inducing tumor regression in 7 out of 10 mice, compared to 3 out of 9 mice treated with H-RAIT alone. The efficacy of L-RAIT was also improved by the combination. Analysis of the dose/response relationship showed an additive interaction of the two modalities. The combination of 5-FU with RAIT induced slightly more severe myelotoxicity than a single-modality treatment, but blood cell counts recovered similarly. Dose estimation suggested that RAIT does not increase the intestinal toxicity of 5-FU. CONCLUSION: The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.

Animals↗