Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric cancers producing alpha-fetoprotein (AFP) have a poor prognosis and a high incidence of liver metastasis. Hepatocyte growth factor (HGF) and its receptor, c-Met, are known to induce mitosis and cell movement and to promote tumor progression. In the present study, c-Met and HGF expression in AFP-producing gastric cancer was compared with those gastric cancers that do not produce AFP. Twenty-six patients with AFP-producing gastric cancers [AFP(+)] and 26 patients stage-matched gastric cancers without AFP production [AFP(-)] were evaluated for c-Met and HGF expression and proliferating cell nuclear antigen-labelling index using immunohistochemical analysis. A higher frequency of c-Met expression was observed in the AFP(+) group than in the AFP(-) group (p < 0.01). A higher expression of c-Met might be one explanation for the poorer prognosis of AFP-producing gastric cancers.
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PMID:High frequency of c-Met expression in gastric cancers producing alpha- fetoprotein. 1097 Nov 74

Mutations of p53 as a tumor suppressor gene in hepatocellular carcinoma (HCC) have been reported to occur with varying frequency in different geographic regions, which might be different etiology for HCC. Overexpressions of p53 (well known for its implications in mutations of the p53 gene), PCNA and alpha-fetoprotein (AFP) have been reported to be associated with carcinogenesis and/or tumor progression and poor prognosis in various types of cancer. To estimate the geographical difference of the p53 gene, PCNA and AFP in HCC, we examined 14 Japanese HCC cases, 8 Indonesian HCC cases, and 27 Indonesian chronic active hepatitis (CAH) or liver cirrhosis cases, using immunohistochemical approaches. Overexpression of p53 was identified in 37.5% of Japanese HCC, in 62.5% of Indonesian HCC and none in CAH. The mean PCNA Labeling Index of Japanese HCC, Indonesian HCC and CAH was detected in 48.6%, 30.4%, and 43.5%, respectively. AFP was detected in 35.7% of Japanese and 25% of Indonesian HCC. The rate of p53 overexpression in Indonesian HCC was as high as in HCC of southern part of China, which might share the similar etiology in both regions.
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PMID:Immunohistochemical study of P53, PCNA and AFP in hepatocellular carcinoma, a comparison between Indonesian and Japanese cases. 1141 97

The paper gives a historical overview of the origin and experimental analysis of alpha-fetoprotein (AFP) regulation and its reexpression in malignant tumors. It shows how a specific hepatoma-specific antigen that was later identified as the major protein component of embryonic serum was found and isolated during searches for murine hepatoma-specific antigens. Later on it was shown that AFP was synthesized by the yolk sac endoderm of the embryo and, later, by the fetal liver and its synthesis drastically diminishes in the adult animal liver. AFP synthesis restores in the moderately differentiated hepatomas and temporarily in the murine regenerating liver. The same regularity, but in other quantitative ratio, occurs in man. Analyzing the causes of AFP reexpression in the regenerating liver has indicated that suppression of AFP synthesis in the mature hepatocytes is reversible and controlled by the position of a hepatocyte in the liver plate: when the hepatocyte is included into the plate, it becomes fully differentiated with AFP suppression. Hepatocytic isolation from the plate leads to its "dedifferentiation" and AFP reexpression. AFP reexpression takes place in the perinecrotic cell layer in the liver poisoned by CCl4. Hepatocytic isolation from the liver and explantation into the cultured tissue results in strong reexpression of AFP while incorporation of the isolated hepatocytes in the three-dimensional extracellular matrix (ECM) leads to AFP suppression together with hepatocytic "maturation". Hepatocytic interaction with defective ECM does not suppress AFP synthesis. Our hypothesis suggests that disturbance of cell-ECM interactions during transformation and tumor progression is the main reason of AFT reappearance in liver tumors.
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PMID:[alpha-Fetoprotein (biology)]. 1167 63

Orthotopic liver transplantation (OLT) is potentially curative for patients with early stage hepatocellular carcinoma (HCC). However, tumor progression before OLT remains a problem. Ninety-three patients were listed for transplantation with HCC or diagnosed with HCC following listing between March, 1997 and September, 2001. Modified TNM Stage was I/II in 82 patients and III in 11 patients. Seventy-one patients (76%) were transplanted with a median waiting time of 3.4 months, and 22 (24%) patients were delisted owing to tumor progression (14), noncompliance (5), and death from liver failure (3). Using a cox model competing risks approach, higher baseline alpha-fetoprotein (AFP) >or= 100 ng/mL was the only factor independently associated with a higher hazard rate of delisting owing to tumor progression (p = 0.00003), whereas four separate factors were independently associated with a lower hazard rate of transplantation: more recent listing year (1999-2001, p = 0.010), blood type O (p = 0.013), Stage I HCC (p = 0.029), and serum bilirubin < 4 mg/dL (p = 0.032). By logistic regression, AFP >/= 100 ng/mL was the only factor that significantly influenced the probability of delisting owing to tumor progression (p = 0.001). In conclusion, the initial AFP level may be useful along with tumor stage in defining an urgency score for liver transplant candidates with HCC.
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PMID:Competing risks analysis of predictors of delisting owing to tumor progression in liver transplant candidates with hepatocellular carcinoma. 1508 74

Chromosome 4q exhibits high frequency of allelic loss in hepatocellular carcinoma (HCC). This study aimed to elucidate the interaction of the frequent aberrant mRNA expression of alpha-fetoprotein (AFP), osteopontin (OPN) and a novel short isoform of annexin A10 (ANXA10S) at 4q in the tumor progression among 294 patients who received surgical resection of unifocal primary HCC. AFP overexpression, OPN overexpression and ANXA10S down-regulation correlated with high-grade and high-stage tumors, early tumor recurrence (all P<0.0001), and lower 10-year survival (all P=0.000001). The AFP overexpression correlated with OPN overexpression (P=0.0026) and ANXA10S down-regulation (P=0.00001), while OPN overexpression correlated with ANXA10S down-regulation (P=0.00001). Pair-wise combinations revealed interactive effects between these genetic variants for tumor grade, tumor stage and early recurrence (all P<0.0001). HCCs with more genetic aberrations had more frequent high tumor grade, portal vein invasion (stage IIIB-IV) and early recurrence (all P<0.0001). The 10-year survival rate for HCCs with all three genetic alterations was the lowest (7%), followed by those with two (22%) or one event (29%), and the highest for those without these changes (43%), P=0.000001. The prognostic stratification using these molecular factors was similar to that of histopathological staging. These three genetic alterations also helped to identify different subgroups of patients of stage II HCC but with different prognosis (P=0.015). In conclusion, the aberrant expressions of AFP, OPN and ANXA10S cooperatively contribute to tumor progression and poor prognosis, and are useful for molecular staging of HCC and the subclassification of stage II HCC without vascular invasion.
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PMID:Aberrant expressions of annexin A10 short isoform, osteopontin and alpha-fetoprotein at chromosome 4q cooperatively contribute to progression and poor prognosis of hepatocellular carcinoma. 1575 2

The dropout from the waiting list for liver transplantation among patients with hepatocellular carcinoma (HCC) is reportedly as high as 12% to 40% per year, mostly due to tumor progression. Considering the scarcity of donor organs, it would be beneficial if we could retain them within the Milan criteria with a bridging therapy. We retrospectively analyzed the prognosis of 288 HCC patients with relatively preserved liver function we treated with ablation therapy between 1997 and 2001, concentrating on whether they subsequently remained in the criteria, and analyzed the risk factors of dropout with Cox proportional hazards model. During a median follow-up period of 39 months (range, 1-86 months), 33 (11%) died without tumor progression, while 85 (30%) dropped out due to tumor progression. The overall dropout rate was 9.0% and 32.8% at 1 and 3 years, respectively, and that due to tumor progression was 6.2% and 23.0%. Cox regression analysis indicated that a high serum level of alpha-fetoprotein or des-gamma-carboxy prothrombin, and a tumor size exceeding 3 cm in diameter affected the dropout due to tumor progression, while low albumin concentration was a risk factor of death independently of tumor progression. In conclusion, local ablation therapy for HCC was effective in containing the tumor progression within the Milan criteria in selected patients.
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PMID:Ablation therapy in containing extension of hepatocellular carcinoma: a simulative analysis of dropout from the waiting list for liver transplantation. 1583 78

The aim of this pilot study was to determine VEGF serum levels (S-VEGF) at diagnosis and at restaging in children diagnosed with cancer, and to investigate whether this parameter provides prognostic information for remission after induction therapy and response to treatment. S-VEGF levels of 35 consecutive pediatric patients with various types of cancer were assayed at diagnosis and at restaging. Levels of VEGF were determined using a commercially available ELISA anti-human VEGF immunoassay kit. Thirty-one children went into complete remission or had a very good partial response to first-line therapy; 4 patients developed tumor progression. At diagnosis average S-VEGF level was 495 pg/mL (range, 0.89--2220 pg/mL) and at restaging it decreased to 118.36 pg/mL (range, 7.44--487 pg/mL). (p=.0039). The 4 patients with tumor progression had increased S-VEGF levels at restaging. The comparison between the levels of S-VEGF at diagnosis and at restaging showed a significant difference for the patients who responded to treatment with decreased S-VEGF and the patients who developed tumor progression with increased S-VEGF (p=.0019). One child with metastatic Ewing sarcoma developed progressive disease after several weeks, with significantly progressively higher S-VEGF levels. One child with Hodgkin disease, who had a higher level at first restaging and developed progressive disease, responded to reinduction therapy and had a significantly lower level at the second restaging. The child with metastatic hepatoblastoma responded to first-line chemotherapy with concomitant decrease in S-VEGF and alpha-fetoprotein levels, but developed local recurrence with elevation in both parameters. Changes in S-VEGF levels correlated with response to treatment for most of the children diagnosed with cancer. This provides a rationale for exploring clinical interest in S-VEGF measurements of a larger group of children with malignancies, and using the test for clinical trials of antiangiogenic therapies.
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PMID:Serum vascular endothelial growth factor as a significant marker of treatment response in pediatric malignancies. 1616 18

The pituitary tumor transforming gene 1 (PTTG1) protein is cell-cycle regulated and is identified as a human securin that inhibits sister chromatid separation and is involved in transformation and tumorigenesis. PTTG1 has very low or undetectable expression in most normal human tissues, but it is abundantly expressed in malignant cell lines and pituitary tumors. In this study, we investigated human PTTG1 expression in 62 hepatocellular carcinoma (HCC) specimens using quantitative real-time reverse transcription polymerase chain reaction analysis. We found that, compared with corresponding noncancerous liver tissues, PTTG1 was remarkably overexpressed in HCCs (PTTG1/beta-actin; 0.443 +/- 0.073 vs. 0.068 +/- 0.007; P < .0001). Furthermore, we found a significant correlation between PTTG1 expression and serum alpha-fetoprotein level (P < .001). Univariate and multivariate analyses revealed that the PTTG1 messenger RNA (mRNA) expression was an independent prognostic factor for disease-free (odds ratio 2.70; P = .037) and overall (odds ratio 5.35; P = .007) survival. Moreover, we discovered a significant relationship between PTTG1 expression and intratumoral microvessel density. Our data supported an important role for PTTG1-mediated upregulation of fibroblast growth factor (FGF)-2, one of angiogenesis and modulation of tumor progression, in hepatocarcinogenesis. In conclusion, PTTG1 might be critically involved in the development of HCCs through the promotion of angiogenesis. PTTG1 is overexpressed in HCC and our results suggest that PTTG1 mRNA expression has prognostic significance for the survival of postoperative patients with HCC.
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PMID:Overexpression of pituitary tumor transforming gene 1 in HCC is associated with angiogenesis and poor prognosis. 1713 95

Increased serum haptoglobin concentration and changes in its glycosylation have been reported in certain cancer types. Information for hepatocellular carcinoma (HCC) has not yet been available. In this study, we aimed to carry out a systematic analysis of serum concentrations of haptoglobin (Hp) and its glycoforms in the patients with HCC and noncancer patients only with chronic liver diseases (CLD) and to examine their clinical values. This study was divided into two major parts, (1) measurement of serum Hp concentration, and investigation of its value in the diagnosis of HCC, and (2) quantitative analysis of Hp glycoforms with alpha-2,6-sialylation and/or alpha-1,6-fucosylation by using lectin affinity purification and 2D gel electrophoresis and investigation of their relationships with tumor stage. The concentrations of serum Hp in HCC patients were significantly higher than those in noncancer patients with CLD. With the use of serum concentrations of Hp and alpha-fetoprotein, a logistic regression (LR) model was developed from the training data set and used to classify the validation cases. At a specificity of 95%, the sensitivity for HCC detection was 79%. Comparing serum concentrations of alpha-2,6-sialylated Hp (S-Hp) and alpha-1,6-fucosylated Hp (F-Hp) between HCC and CLD patients suggests that purification of S-Hp and F-Hp could enrich the glycosylation variants associated with HCC. 2D gel analysis of S-Hp and F-Hp identified a total of 18 glycoforms. A unique pattern of Hp glycoforms comprising both hypersialylated fucosylated and hyposialylated fucosylated species was found in the HCC patients. Serum concentrations of these glycoproteins were significantly higher in the patients with advanced tumors, suggesting their tumor-specific nature. We have shown that serum Hp is a potential biomarker in the diagnosis of HCC. The combined use of Hp and AFP could greatly improve the diagnostic accuracy. A unique pattern of Hp glycoforms with altered sialylation and fucosylation is specific to HCC and associated tumor progression.
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PMID:Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: a glycoproteomic approach. 1702 40

The purpose of this study was to retrospectively determine the safety and effectiveness of percutaneous cryoablation, monitored with computed tomography (CT) and ultrasonographic (US) guidance, for the treatment of hepatocellular carcinoma (HCC). Four patients with small HCCs underwent one percutaneous cryoablation treatment session monitored with CT and US guidance. All patients underwent pretreatment blood chemistry testing and imaging evaluation. We treated lesions with simultaneous insertion of multiple 17-G cryoprobes (two or three) and defined technical success when the extension of a visible iceball was beyond 5 mm from the tumor margin. Intralesional enhancement or tumoral size increase was defined as local progression compared with that on images obtained immediately after ablation. We evaluated complications and follow-up (at 1, 3, and 6 months). All patients survived without short- or long-term complications. Cryoablation was technically successful in all patients at the end of the procedure. During follow-up two patients developed disease recurrence. One patient developed local tumor progression on the margin of the lesion; the other, a new HCC. In the case of local tumor progression a new elevation of alpha-fetoprotein (alphaFP) levels occurred at first follow-up control. In the other case levels of alphaFP remained stable during the first 3 months after the procedure, then demonstrated a progressive increase in alphaFP levels beginning at the fourth month, without tumor evidence during CT control at 3 months. We conclude that percutaneous cryotherapy with US guidance and CT monitoring is a feasible, safe, and effective for treatment of HCC. If local ablative procedures of hepatic lesions are to be performed, percutaneous cryoablation, not laparotomic, should be discussed as an alternative therapeutic measure. Longer follow-up should provide proof of the effectiveness of this technique.
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PMID:Percutaneous cryoablation of small hepatocellular carcinoma with US guidance and CT monitoring: initial experience. 1823 4


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