Biomedical subjects

M Toyoda

Publications and source records attributed to M Toyoda.

At least 109 records · Page 6Linked to original sources

PubMed1999

Scavenging mechanisms of (-)-epigallocatechin gallate and (-)-epicatechin gallate on peroxyl radicals and formation of superoxide during the inhibitory action.

The scavenging effects of (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) on peroxyl radicals and their mechanisms were studied by investigating the products formed during the first stages by 2,2'-azobis(2-aminopropane) hydrochloride (AAPH)-induced oxidation, without any isolation, using LC/MS, spectrophotometry, chemiluminescence analyses, and semiempirical molecular orbital (MO) calculations. The results show that EGCG can be converted to an anthocyaninlike compound followed by cleavage of the gallate moiety by oxidation. On the other hand, ECG can be converted to an anthocyaninlike compound after cleavage of the gallate moiety. The calculated C-H bond dissociation enthalpies (BDEs) for EGCG and ECG at the C-2 position were quite low (62.7 and 66.8 kcal/mol, respectively) compared with O-H BDEs at the phenolic sites (ca. 70 kcal/mol), suggesting that the C-2 hydrogen can be abstracted by free radicals. The addition of superoxide dismutase (SOD) decreased the chemiluminescence in EGCG by one-half during the inhibitory action. Active oxygen including superoxide (O2-) would be produced in EGCG, but not in ECG. The authors proposed the antioxidative mechanisms of EGCG and ECG depending on the experimental results and theoretical calculations.

Amidines↗

PubMed1999

Lung allograft dysfunction correlates with gamma-interferon gene expression in bronchoalveolar lavage.

BACKGROUND: Preceding episodes of acute cellular rejection (ACR) may predispose lung allografts to the subsequent development of irreversible dysfunction or bronchiolitis obliterans syndrome (BOS). Other histologic patterns such as bronchiolitis obliterans with organizing pneumonia (BOOP), organizing pneumonia, lymphocytic bronchiolitis and diffuse alveolar damage (DAD) may also adversely affect allograft function. We have previously reported the predominant expression of Th1 cytokines (IL-2 and interferon gamma) in rejecting and Th2 (IL-10) in a tolerant model of rat lung transplantation. Here we correlate the "Th1/Th2 paradigm" in clinical lung transplantation with histologic findings and assess the effect on serial spirometric function. METHODS: We examined the mRNA expression of IL-2, interferon gamma, IL-10 and ICAM-1 in 53 bronchoalveolar lavage (BAL) specimens from 23 lung transplant (LT) recipients utilizing qualitative "nested" reverse transcriptase polymerase chain reaction (RT-PCR). We also measured IgG1 and IgG2 levels in 44 BAL specimens by ELISA. The mRNA expression for cytokines, ICAM-1 and the IgG2/IgG1 ratios were correlated with the presence or absence of ACR and alternate "histologic patterns". Serial spirometry were analyzed for the 2-3 month interval before bronchoscopic (FOB) assessment to derive "baseline" forced expiratory volume-one second (FEV1) values. The change in FEV1 coincident with (deltaFEV1 pre) and for the 2-3 month interval subsequent to (deltaFEV1 post) FOB were expressed relative to "baseline" spirometric indexes. RESULTS: Detection of mRNA for interferon gamma and ICAM-1 correlated significantly with ACR, whereas IL-2 and IL-10 expression did not correlate. IL-10 was virtually "ubiquitous" in most BAL samples irrespective of the presence or absence of ACR. The highest correlation was observed with interferon gamma for acute cellular rejection whereupon the sensitivity was 77.7%, specificity 87.7%, positive predictive value 73.6% and negative predictive value 88.2%, although for ICAM-1 these values were 75%, 65.7%, 50.0% and 85.0%, respectively. Nevertheless, 4 of 5 episodes of respiratory tract infection (bacterial, CMV, Aspergillus spp.) were similarly associated with cytokine mRNA. The ratios of IgG2 to IgG1, a reflection of Th1/Th2 influence, were not statistically different when analyzed for the presence or absence of ACR (0.91+/-0.53 vs. 1.02+/-0.70, respectively; p = NS). By analysis of FEV1 trends, expression of interferon gamma was associated with a greater and persistent decrement (deltaFEV1 pre: -0.265+/-0.78 liters, and post: -0.236+/-0.1161; mean +/- SE) than ACR in the absence of interferon gamma expression (+0.158 +/- +0.065 and +0.236+/-0.007 liters, respectively) (Student-Newman-Keuls, p<.05). CONCLUSION: Our findings suggest that interferon gamma mRNA expression and ICAM-1 may be valuable in both the diagnosis and prognosis for lung allograft ACR. IL-10, a Th2 cytokine, was locally expressed both in the presence and absence of ACR. Expression of mRNA for interferon y in BAL and, to a lesser extent ICAM-1, were associated with increased lung allograft dysfunction. Whether BAL cytokine "immunosurveillance" would complement or possibly supplant a specific "histologic pattern" and thereby direct different therapies after lung transplantation, may be potentially rewarding areas of further investigation.

Acute Disease↗

PubMed1999

Expression of gamma-IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients.

Various cytokines are upregulated in acute allograft rejection (AR). Local production of Th-1 cytokines is suggested to play a pathogenic role in AR, and Th-2 cytokines in the development of allograft tolerance. The purpose of this study was to correlate the expression of Th-1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN)], and Th-2 [interleukin-10 (IL-10)] cytokines in bronchoalveolar lavage (BAL) fluid with AR in lung transplant (LT) recipients. The role of Th-1 dominance expressed as IgG2/IgG1 ratio in BAL in AR was also examined. The mRNA expression for IL-2, gamma-IFN and IL-10 was examined in 64 BAL specimens from 23 LT recipients using reverse transcriptase-polymerase chain reaction (RT-PCR). IgG1 and IgG2 levels were measured in 55 BAL specimens by enzyme-linked immunosorbent assay (ELISA). The expression on mRNA for these cytokines, and the ratio of IgG2/IgG1 was correlated with AR (early AR occurring within 3 months of transplant and late AR occurring after 3 months). Ten patients had 17 episodes of biopsy proven AR. Twelve episodes of AR (6 patients) occurred within the first 3 months of transplantation. In 5 patients, AR was diagnosed 4, 5, 6, 9 and 24 months post-transplantation. Detection of gamma-IFN mRNA correlated significantly with early AR (p < 0.001), whereas it lacked correlation with late AR. Expression of IL-2 and IL-10 mRNA did not correlate with AR. IL-10 was present in most samples irrespective of the presence or absence of AR. The ratio of IgG2/IgG1 was similar in patients with or without AR. Our findings suggest that the detection of gamma-IFN mRNA in BAL by RT-PCR is useful for immune monitoring of early AR in LT recipients. Absence of elevated IgG2/IgG1 ratio, and presence of IL-10 in BAL during AR suggests that Th-1 cytokines may not be the sole mediator of rejection in LT recipients.

Acute Disease↗

PubMed1999

Calcitonin gene-related peptide upregulates melanogenesis and enhances melanocyte dendricity via induction of keratinocyte-derived melanotrophic factors.

It has recently been shown that cutaneous axon terminals and epidermal melanocytes make contact via chemical synapses in human skin and that calcitonin gene-related peptide (CGRP) induces melanocyte proliferation. To further clarify the effect of neuropeptides on the biology and morphology of melanocytes, especially with respect to melanogenesis and melanocyte dendricity, organ cultures of normal human skin and cultured melanocytes were exposed to various neuropeptides present in intraepidermal nerve endings. Of the neuropeptides examined, skin exposed to CGRP in organ culture showed increases in melanocyte number, epidermal melanin content, melanosome number, and degree of melanization. CGRP alone had no significant effect on melanogenesis of cultured melanocytes, whereas the addition of medium conditioned by CGRP-stimulated keratinocytes (CGRP-KCM) induced melanogenesis as indicated by biochemical assays of tyrosinase activity and melanin content. Furthermore, CGRP-KCM significantly enhanced melanocyte dendricity, a crucial factor affecting epidermal pigmentation. These findings suggest that keratinocytes produce and secrete some melanotrophic factors following stimulation with CGRP, which modulate growth, melanin synthesis, and dendricity of melanocytes. These data demonstrate intimate interactions between the cutaneous nervous system and melanocytes within the epidermal environment.

Calcitonin Gene-Related Peptide↗

PubMed1999

The induction by topical minoxidil of increased fenestration in the perifollicular capillary wall.

We report the induction by topical minoxidil of increased fenestration in the perifollicular capillary wall. Male 30-day-old Wistar rats were divided into two groups, i.e. an experimental group which received 4% minoxidil solution topically on the dorsal skin, and a control group which received only vehicle solution topically. Using transmission electron microscopy, follicular and subepidermal capillaries and dermal fibres were compared between both groups. There were no obvious differences in subepidermal capillaries or dermal fibres between the two groups. However, topically applied minoxidil increased fenestration in follicular capillary walls around anagen hair bulbs.

Administration, Topical↗

PubMed1999

Amyloid deposition in renal angiomyolipoma.

An irregular tumor shadow, seen on the left kidney in a 48-year-old woman by computed tomography, was pathologically diagnosed as 'angiomyolipoma'. HMB-45 immunoreactivity distinguished angiomyolipoma from renal cell carcinoma of sarcomatoid type. The amyloid deposition was limited to the tumor. M-protein and Bence-Jones protein were negative. For amyloid protein characterization, immunohistochemical studies were performed with antiamyloid A, anti-kappa, anti-lambda, anti-prealbumin and anti-beta-2 microglobulin, but none reacted with the amyloid. This is the first documented case of amyloid deposition in angiomyolipoma and may represent a novel precursor protein of amyloid.

Amyloid↗

PubMed1999

Isolation, identification and determination of a magenta subsidiary colour in food blue no. 1 (brilliant blue FCF).

A magenta subsidiary colour was isolated from commercial Food Blue No. 1 (B-1; Brilliant Blue FCF). The absorption maximum for this subsidiary colour at 580 nm is outside of the range of 614-628 nm found for other subsidiary colours and m,m-B-1. On the basis of MS and NMR analyses, the structure of the subsidiary colour was elucidated as the disodium salt of 2-[[4-[N-ethyl-N-(3-sulphophenylmethyl)amino]phenyl][4-oxo- 2,5-cyclohexadienylidene]methyl]benzenesulphonic acid. HPLC analyses revealed that 24 batches of commercial Food Blue No. 1 (three manufacturers) contain 0.1-0.8% (average: 0.5%) of the magenta subsidiary colour.

Benzenesulfonates↗

PubMed1999

Immunohistochemical and molecular analysis of giant cell carcinoma of the pancreas: a report of three cases.

We performed molecular biological studies as well as immunohistochemical analysis of three cases of giant cell carcinoma of the pancreas. Histologically, one case was a pleomorphic giant cell carcinoma consisting of pleomorphic giant/ small cells and spindle cells, one an osteoclast-like giant cell tumor composed of osteoclastoid giant cells and pleomorphic small cells, and one a pleomorphic giant cell carcinoma with osteoclastoid giant cells. Immunohistochemically, pleomorphic giant cells and small pleomorphic cells were positive for epithelial and mesenchymal markers throughout the cases. Osteoclastoid cells were strongly positive for PG-M1 (CD68), but negative for lysozyme and epithelial markers. Pleomorphic spindle cells showed the same immunoreactivity as pleomorphic giant/small cells. Genetically, all cases contained a mutation in the K-ras (codons 12, 13) oncogene, but neither p53 (exons 5-8) nor p16INK4 (exons 1, 2) gene mutations were found in any case. Furthermore, Loss of heterozygosity (LOH) of the p53, p161NK4. APC, and DPC4 gene loci was not found in any of the cases. Immunohistochemical study demonstrated this tumor to be of epithelial origin with mesenchymal differentiation. Genetically, initiation of the tumor is similar to that of usual ductal adenocarcinoma, but progression might be rather different. The peculiar histologic and biologic features of this tumor would be the result of changes in other functional genes.

Aged↗

PubMed1999

Detection of apoptotic cells in human colorectal cancer by two different in situ methods: antibody against single-stranded DNA and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) methods.

We comparatively investigated the extent of apoptotic cell loss in human colorectal cancers evaluated by two methods, namely the conventional terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling (TUNEL) method and immunohistochemistry for single-stranded (ss) DNA. The apoptotic index (AI) obtained with the TUNEL method was higher than that shown by the immunohistochemistry for ssDNA. However, a significant correlation in AIs evaluated by these methods was found. The AIs obtained by both methods were significantly higher in the advanced cancers than in the early cancers. Cellular proliferation activity was assessed in terms of positivity rate (PR) for expression of proliferating cell nuclear antigen (PCNA). The PR of advanced cancers was significantly higher than that of early cancers. The present results indicate that immunohistochemistry for ssDNA is useful (as is the TUNEL method) for evaluation of apoptotic tumor cells in colorectal carcinomas. In addition, it was confirmed that there is a remarkable increase of not only proliferation activity, but also tumor cell apoptosis in the process of progression of colon cancer from early to advanced stages of the disease.

Adult↗

PubMed1999

Prevalence of hepatitis G virus in liver disease.

The prevalence of hepatitis G virus (HGV) in liver disease of non-A, -B, -C viral hepatitis, hepatitis B and hepatitis C was determined. Two of 44 patients (4.5%) with liver injury without any hepatitis A, B or C marker were positive for HGV. One of five cases of hepatocellular carcinoma was positive for HGV. One of three cases with fulminant hepatitis was positive for HGV. This case was negative at the onset of fulminant hepatitis and became positive after plasmapheresis. No patient with acute (n=8) or chronic (n=5) hepatitis or liver cirrhosis (n=8) was positive for HGV in non-A, -B, -C liver disease. One of 30 patients with various HBV-positive liver diseases and nine (17.3) of 52 patients with type C liver disease were positive for HGV. In patients with hepatitis C, four (28.6%) of 14 HGV-co-infected patients were complicated with diabetes mellitus compared with four (10.5%) of 38 single hepatitis C virus (HCV)-infected patients (not significant). In 12 HGV-positive patients, eight of 10 (80%) had a history of blood transfusion. In HCV-positive patients, co-infection with HGV was not a risk factor in patients with diabetes mellitus as a complication. HGV appeared to cause non-A, -B, -C hepatitis rarely, and its main route of infection was blood transfusion.

Adolescent↗

PubMed1999

Constituents in watercress: inhibitors of histamine release from RBL-2H3 cells induced by antigen stimulation.

Histamine release inhibitors in watercress (Nasturtium officinale) were isolated using a monitoring system with antigen-stimulated RBL-2H3 cells. Of the 15 compounds isolated, flavonols and megastigmanes significantly inhibited histamine release. Two flavonols, 3-O-sophorosides of rhamnetin and rhamnazin, were new compounds. To investigate the inhibitory mechanism, the effects of rhamnetin, rhamnetin 3-O-sophoroside and an isolated megastigmane glucoside on the increase in the intracellular free calcium concentration were examined at a concentration providing 60% inhibition of histamine release. The results suggest that these compounds did not affect the calcium influx at that concentration. The structure-activity relationships of the megastigmanes on histamine release were also investigated.

Animals↗

PubMed1999

The effect of feeding carrots on immunoglobulin E production and anaphylactic response in mice.

Carrot juice was administered orally to BALB/c mice immunized intraperitoneally with dinitrophenylated (DNP)-OVA for about 1 month. The titers of DNP-specific IgE, DNP-specific IgG, and the levels of total IgE in mouse sera were determined. The DNP-specific IgE production by mice fed carrot juice was significantly inhibited. On the other hand, the DNP-specific IgG production and the level of total IgE in mice fed carrot juice were not significantly different from those in control mice. We also examined the effect of feeding carrots on immediate-type hypersensitivity. One hour after antigen stimulation, the ears of mice fed carrots swelled less than those of control mice. Furthermore, the rise in serum histamine in the mice fed carrots under active systemic anaphylaxis was lower than in controls. We then examined the pattern of cytokine production by spleen cells from mice followed by restimulation with DNP-OVA in vitro. The spleen cells from the mice fed carrots produced more interferon-gamma than those from the control group. In contrast, the spleen cells from the mice fed carrots produced less interleukin-4 than those from the control group. Furthermore, the interleukin-12 production of the spleen cells from mice fed carrots was also higher than that of the control group. These findings suggest that feeding carrots improves the helper T cell (Th)1/Th2 balance, inhibiting specific IgE production and antigen-induced anaphylactic response.

Anaphylaxis↗

PubMed1999

Genetic analysis of nothoapiol formation in Perilla frutescens.

A new essential oil chemotype of Perilla frutescens was found in that plant variety from Che-ju island in Korea. The steam-distilled oil of this plant was examined by GC-MS and 32 compounds were identified. Its principal constituents were beta-caryophyllene, dillapiol and nothoapiol. Also, crossing experiments were performed between the new chemotype and known chemotypes to clarify the genetic control of the production of nothoapiol. The gene Na, which promotes conversion from dillapiol to nothoapiol, was suggested, and was considered to be closely linked with the allele D.

Allylbenzene Derivatives↗

PubMed1999

Expression of megsin mRNA, a novel mesangium-predominant gene, in the renal tissues of various glomerular diseases.

Mesangial cells play an important role in maintaining a structure and function of the glomerulus and in the pathogenesis of glomerular diseases. Recently, we discovered a new mesangium-predominant gene termed "megsin." Megsin is a novel protein that belongs to the serine protease inhibitor (serpin) superfamily. To elucidate the pathophysiologic role of megsin in the kidney, the expression and localization of megsin mRNA in renal tissues of patients with IgA nephropathy (IgA-N), diabetic nephropathy (DN), minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN), and normal human kidney (NHK) was evaluated by in situ hybridization using digoxigenin-labeled oligonucleotide. Individual cells positive for megsin mRNA were observed only in glomeruli in all renal tissues. Their localization coincided with those of mesangial cells. The percentage of positive cells for megsin mRNA in total glomerular cells was significantly greater in IgA-N than in MCNS, MN, and NHK. It was also significantly greater in DN than in MCNS and NHK. In IgA-N, the percentage of megsin mRNA-positive cells was greater in tissues from those with mesangial cell proliferation and slightly mesangial matrix expansion (periodic acid-Schiff-positive area in the total glomerulus area, <30%; cell number in mesangial matrix area, >30; assessed in cross-sections through their vascular poles) than in tissues from those with severe mesangial matrix expansion (periodic acid-Schiff-positive area in total glomerulus area, >30%; cell number in mesangial matrix area, <30). In conclusion, megsin mRNA was predominantly expressed in glomerular mesangial cells in all renal tissues. The expression of megsin mRNA was upregulated in IgA-N and DN, both of which are diseases accompanied with mesangial cell proliferation and/or mesangial matrix expansion. These data suggest a link of megsin expression to the pathogenesis of IgA-N and DN, two major causes of end-stage renal failure.

Actins↗

PubMed1999

[Studies on simultaneous determination of 17 organochlorine and 9 pyrethroid pesticides of agricultural products].

A method for simultaneous determination of 17 organochlorine and 9 pyrethroid pesticides in agricultural products by capillary GC with ECD detection was studies. The samples were extracted with acetone under acidic conditions followed by Florisil column clean-up and then injected into a GC-ECD. The organochlorine pesticides used in this study included unstable captan and captafol in the homogenized preparations of fruits and vegetables. Captan and captafol were also found to decompose in rice and wheat samples when the samples were allowed to stand after the addition of water. Addition of phosphoric acid to the samples was effective in preventing the decomposition of captan and captafol. Recovery of the pesticides investigated in this study was not decreased by the addition of phosphoric acid. Addition of phosphoric acid was also effective in removing interfering substances from onion extract. Recovery of organochlorine and pyrethroid pesticides from samples spiked at levels of 0.05-0.25 ppm by the proposed method was 51.4-100.8% for rice and wheat and 60.1-119.0% for vegetables.

Chromatography, Gas↗

PubMed1999

[Computational study on antioxidation mechanism of catechins].

All C-H and O-H bond dissociation enthalpies (BDE's) in catechins, (-)-epigallocatechin) were calculated by semi-empirical molecular orbital calculation using the SPARTAN program. The BDE's of benzyl hydrogens (C-2 position in catechins) were found to be quite low. This suggests that abstraction of benzyl hydrogen is crucial step for antioxidative activity. This is corroborated by the reported results of LC/MS and spectrophotometric analysis of reaction intermediates from catechins treated with AAPH.

Antioxidants↗

PubMed1998

Prevention and preemptive therapy of postransplant lymphoproliferative disease in pediatric liver recipients.

BACKGROUND: We have previously reported a 10% incidence of posttransplant lymphoproliferative disease (PTLD) in pediatric patients receiving first liver grafts and primarily immunosuppressed with tacrolimus. To decrease the incidence of PTLD, we developed a protocol utilizing preemptive intravenous ganciclovir in high-risk recipients (i.e., donor (D)+, recipient (R)-), combined with serial monitoring of peripheral blood for Epstein Barr virus (EBV) by polymerase chain reaction (PCR). METHODS: Consecutive pediatric recipients of a first liver graft were immunosuppressed with oral tacrolimus (both induction and maintenance), and low-dose prednisone. EBV serologies were obtained at the time of orthotopic liver transplant in recipients and donors. Recipients were divided into groups: group 1, high-risk (D+R-), and group 2, low-risk (D+R+; D-R-; D-R+). In group 1 (high-risk), all patients received a minimum of 100 days of intravenous ganciclovir (6-10 mg/kg/day), while, in group 2 (low-risk), patients received intravenous ganciclovir during their initial hospitalization and then were converted to oral acyclovir (40 mg/kg/day) at discharge. Semiquantitative EBV-PCR determinations were made at 1-2-month intervals. In both groups, patients with an increasing viral copy number by EBV-PCR had tacrolimus levels decreased to 2-5 ng/ml. Tacrolimus was stopped, and intravenous ganciclovir reinstituted for PTLD. A positive EBV-PCR with symptoms, but negative histology, was defined as EBV disease; PTLD was defined as histologic evidence of polyclonal or monoclonal B cell proliferation. RESULTS: Forty children who had survived greater than 2 months were enrolled. There were 18 children in group 1 (high-risk; mean age of 14+/-15 months and mean follow-up time of 243+/-149 days) and 22 children in group 2 (low-risk; mean age of 64+/-65 months and follow-up time of 275+/-130 days). In group 1 (high-risk), there was no PTLD and one case of EBV disease (mononucleosis-like syndrome), which resolved. In group 2 (low-risk), there were two cases of PTLD; both resolved when tacrolimus was stopped. Both children were 8 months old at time of transplant. Neither received OKT3, and they had one and two episodes of steroid-sensitive rejection, respectively. One child had EBV disease (mild hepatitis), which resolved. CONCLUSIONS: Since instituting this protocol, the overall incidence of PTLD has fallen from 10% to 5% for children receiving primary tacrolimus therapy after OLT. No high-risk pediatric liver recipient treated preemptively with intravenous ganciclovir developed PTLD. Both children with PTLD were less than 1 year at OLT and considered low-risk. However, their positive EBV antibody titers may have been maternal in origin and not have offered long-term protection. Serial monitoring of EBV-PCR after pediatric OLT is recommended to decrease the risk of PTLD by allowing early detection of EBV infection, which is then managed by decreasing immunosuppression and continuing intravenous ganciclovir.

Antiviral Agents↗

PubMed1998

Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer.

Deregulated inhibition of apoptosis (programmed cell death) may facilitate the insurgence of neoplasia, but whether it also influences the outcome of common cancers has remained controversial. In this study, we investigated the expression of a novel inhibitor of apoptosis, survivin, in colorectal cancer and its relationship with tumor cell apoptosis and overall prognosis. By immunohistochemistry, survivin was expressed in 91 of 171 (53.2%) cases of colorectal carcinomas of histological stages 0 to IV. In contrast, normal colon epithelium did not express survivin. Although survivin expression did not correlate with p53 abnormalities (46.5% versus 58.0%; P = 0.18), survivin-positive cases were strongly associated with bcl-2 expression (72.5% versus 27.4%; P < 0.0001) and reduced apoptotic index (0.76% +/- 0.39% versus 1.17% +/- 0.62%; P < 0.0001). Expression of survivin alone in bcl-2-negative (discordant) cases also resulted in reduced apoptotic index (0.82% +/- 0.57% versus 1.16% +/- 0.66%; P = 0.0046). When analyzed for prognostic significance, patients with low apoptotic index (< 0.97%) had worse survival rates than the group with high apoptosis (P < 0.001), and a multivariate Cox proportional hazard model identified reduced apoptosis as an independent predictive factor for overall survival (P < 0.0001). These data demonstrate that apoptosis inhibition by survivin, alone or in cooperation with bcl-2, is an important predictive/prognostic parameter of poor outcome in colorectal carcinoma and identify survivin as a new diagnostic/therapeutic target in cancer.

Adult↗