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)

A previously reported Phase I/II multimodality program for non-resectable hepatocellular cancer began with external beam-radiation and chemotherapy, followed by administration of 131I antiferritin-specific radioimmunoglobulin and led to a 48% remission (7% complete remission and 41% partial remission). Survival and response depended on alpha fetoprotein status. AFP+ patients had a median survival of 5 months; AFP- patients had a median survival of 10.5 months. No acute effects occurred relative to treatment with radiolabeled antibody. A randomized prospective study was designed to compare full dose chemotherapy consisting of 60 mg/m2, doxorubicin and 500 mg/m2 of 5-fluorouracil administered every 3 weeks, to 131I antiferritin administration every 8 weeks and allowed for crossover treatment if tumor progression occurred. Overall, radiolabeled antibody administration and full dose chemotherapy led to equivalent partial remission rates (22-30% vs 23-25%) and survival rates compared to chemotherapy (6 month median; AFP+ 5 months; AFP- 10 months). The most important new observations were the response in AFP- patients who, following chemotherapy failure, achieved remission using 131I radiolabeled antibody (7/11) and a subset of patients (7%) who were treated with radiolabeled antibody and converted from non-resectable to resectable status followed by surgical excision.
 ...
PMID:A randomized prospective trial comparing full dose chemotherapy to 131I antiferritin: an RTOG study. 185 Jul 22

Tumor antigens (CEA and AFP) were studied by radioimmunoassay and immunoglobulins A, M and G--after Mancini in blood plasma from 144 cases of colorectal cancer. In most patients, raised levels of CEA, AFP, IgA and IgG were identified. A 5-10-fold increase in CEA and AFP levels matched by a pronounced dysimmunoglobulinemia or IgG deficit (under 10 mg/ml) were prognostically unfavorable. If said shifts persist at days 25-30 after surgery, suspicion of inadequate removal of tumor, its occult dissemination and unfavorable prognosis is justified. Similarly inauspicious are concomitant low antigenic activity in tumor and IgC deficit or a marked dysimmunoglobulinemia. Therefore, a complex assay of tumor-associated antigens (CEA and AFP) and immunoglobulins A, M and G makes a contribution to evaluation of surgery, course of tumor progression and its prognosis.
 ...
PMID:[Possibilities of prognosis in cancer of the transverse colon and rectum using CEA, AFP and immunoglobulins A, M and G]. 243 47

Serum SP-1 levels were measured serially in 94 patients with non-seminomatous germ cell tumors to evaluate its clinical significance as a tumor marker. In 12 out of 80 patients (15%) with active tumors serum SP-1 was found to be elevated, whereas serum HCG and AFP in the same sample were raised in 53 and 45% respectively. Elevation of serum SP-1 levels was always associated with raised HCG levels, and with AFP in 7 patients. During chemotherapy, serum SP-1 and HCG disappeared when a complete remission was obtained. In contrast to HCG, serum SP-1 failed to detect tumor progression in two patients. Serum HCG and AFP are superior as tumor markers to serum SP-1.
 ...
PMID:Evaluation of pregnancy-specific beta 1-glycoprotein in patients with non-seminomatous testicular germ cell tumors. 618 95

Serum ferritin levels in patients with gynecological malignancy were measured by radioimmunoassay and in addition CEA, AFP and CRP were measured simultaneously. No samples had elevated values more than 200 ng/ml in none malignancy. The serum ferritin levels was elevated (greater than 200 ng/ml) in many patients with advanced cervical cancer and its recurrence, while early stage were almost within normal ferritin range. Patients with ovarian cancer showed normal ferritin levels, but its recurrence showed almost within normal levels than other groups. Serial measurements of serum ferritin showed a fall in patients who responded to radiation therapy or chemotherapy. In patients with tumor progression during therapy, ferritin values increased. The highest ferritin levels were found in patients with the time of recurrence and death. Ferritin levels showed low values in 5 cases of ovarian cancer without symptoms of recurrence on follow-up over 18 months. No correlation was found between ferritin and CEA or AFP levels in different patients except some cases. These results suggest that determination of serum ferritin may be useful to detect recurrence and to monitor the result of treatment.
 ...
PMID:[Serum ferritin levels in patient with gynecological malignancy--especially the judgement of therapeutic response and the monitor during the post-therapeutic follow-up period (author's transl)]. 731 Jan 97

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.
 ...
PMID:Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential. 1181 39

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.
 ...
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 evaluate the long-term survival results and complications of percutaneous radiofrequency ablation (RFA) in patients with early-stage hepatocellular carcinoma (HCC). Between April 1999 and May 2005, 570 patients with 674 early-stage HCCs underwent percutaneous RFA as a first-line treatment option in a single institution. We evaluated the effectiveness rates, local tumor progression rates, survival rates, and complications. We also assessed the prognostic values of survival rates by using Cox proportional hazard models. The primary technique effectiveness rate was 96.7% (652 of 674). The cumulative rates of local tumor progression at 1, 2, and 3 years were 8.1%, 10.9%, and 11.8%, respectively. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 95.2%, 82.9%, 69.5%, 60.8%, and 58.0%, respectively. Patients with Child-Pugh class A cirrhosis, of younger age (<or=58 years), or having lower AFP level (<or=100 microg/L) demonstrated better survival results (P < 0.05). A total of 11 major complications (1.9% per treatment) were found during the follow-up period. There was no procedure-related death. Percutaneous RFA can be used successfully as a first-line treatment modality for early-stage HCCs. Child-Pugh class, age, and AFP level before RFA were significant prognostic predictors of long-term survival.
 ...
PMID:Percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma as a first-line treatment: long-term results and prognostic factors in a large single-institution series. 1709 64

Most patients with hepatocellular carcinoma (HCC) also have cirrhosis, an independent cause of death. We considered an alternative definition of tumor-related death in patients with HCC and attempted to validate our definition. Two hundred thirty-seven HCC patients were diagnosed, followed, and died over a 12-year period and were evaluated every 2 months, including their last 6 months of life. We defined death by cancer if there was, in the last 6 months of life, a CT scan increase of >25% in the sum of tumor index lesions' cross-sectional areas or new onset of, or increase in, either vascular invasion or metastatic disease (Group 1). Patients with stable cancer were considered to have died from any other cause (Group 2). We found that 135 (57%) patients died from cancer progression (Group 1), whereas 102 (43%) patients did not (Group 2). There was a statistically significant difference between Group 1 and Group 2 patients in percentage with bilobar disease (P = 0.03), more than one tumor (P = 0.01), an increase in AFP (P = 0.04), vascular invasion (P = 0.001), and the presence of metastases (P = 0.01). We conclude that 57% of patients with unresectable HCC died as a direct result of cancer progression, but 43% did not. The latter died from complications of their cirrhosis, including sepsis, GI bleeds, and renal failure.
 ...
PMID:Causes of death in patients with unresectable hepatocellular carcinoma. 1743 87

Cancer cells with a high glycolytic rate have an advantage in tumor growth. Hepatocellular carcinoma (HCC) often exhibits an aberrant expression of glycolytic enzymes, particularly type II hexokinase (HKII) and aldolase B (ALDOB). This study examined the aberrant expression of HKII and ALDOB in 203 surgically resected HCCs. A dramatic down-regulation of ALDOB was found in 116 HCCs (57%), while 43% of HCCs maintained the expression. HKII mRNA was overexpressed in 70 (35%) primary HCCs. The ALDOB down-regulation and HKII overexpression correlated with high-grade (grade II-IV) HCC (all ps<0.0001), portal vein invasion (stage IIIB-IV) (ps<1x10(-6)), early tumor recurrence (ETR) (p<0.001 and p<0.01, respectively) and a lower 5-year survival (p=0.000001 and p=0.0062, respectively). Notably, in stage II HCC which had no vascular invasion, the ALDOB down-regulation was associated with ETR (p<0.05) and a lower 5-year survival (p=0.015). The down-regulation of ALDOB correlated with a high AFP (p=1x10(-8)), whereas the overexpression of HKII, which has two functional motifs for the mutant p53, correlated with the p53 mutation, p<0.01. The three factors (ALDOB down-regulation, HKII overexpression and p53 mutation) not only correlated with tumor progression, but also interacted with one another, leading to a more aggressive HCC with a portal vein invasion and various extent of intrahepatic metastasis by more than four-fold (ps<1x10(-6)) and frequent ETR by more than two-fold (ps<0.0001) compared with HCCs without the events. In conclusion, the aberrant expression of ALDOB and HKII is associated with advanced disease, ETR and poor prognosis, and ALDOB down-regulation in stage II HCC is a predictive marker of ETR and an unfavorable outcome.
 ...
PMID:Aberrant expression of the glycolytic enzymes aldolase B and type II hexokinase in hepatocellular carcinoma are predictive markers for advanced stage, early recurrence and poor prognosis. 1835 95

Hepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically validated biomarkers that can predict natural history of malignant progression are lacking. The present study explored the proteome-wide patterns of HCC to identify biomarker signature that could distinguish cancerous and nonmalignant liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and both the tumor and adjacent nontumor tissues were subjected to proteome-wide expression profiling by 2-DE method. The subjects were randomly divided into the training (n = 55) and validation (n = 25) subsets, and the data analyzed by classification-and-regression tree algorithm. Protein markers were characterized by MALDI-ToF/MS and confirmed by immunohistochemistry, Western blotting and qPCR assays. Proteomic expression signature composed of six biomarkers (haptoglobin, cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa protein 1, lysosomal proteinase cathepsin B, keratin I) was developed as a classifier model for predicting HCC. We further evaluated the model using both leave-one-out procedure and independent validation, and the overall sensitivity and specificity for HCC both are 92.5%, respectively. Clinical correlation analysis revealed that these biomarkers were significantly associated with serum AFP, total protein levels and the Ishak's score. The described model using biomarker signatures could accurately distinguish HCC from nonmalignant tissues, which may also provide hints on how normal hepatocytes are transformed to malignant state during tumor progression.
 ...
PMID:Proteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma. 1916 26


1 2 3 Next >>