Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present phase I/II study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) loaded with an allogeneic tumor cell lysate in advanced melanoma patients. DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practices. Fifteen patients with metastatic melanoma (stage III or IV) received four subcutaneous, intradermal, and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein (HBs) and/or tetanus toxoid (TT). No grade 3 or 4 adverse events related to the vaccination were observed. Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented, as well as immune responses to HBs/TT antigens. Four out of nine patients who received the full treatment survived for more than 20 months. Two patients showed signs of clinical response and received 3 additional doses of vaccine: one patient showed regression of in-transit metastases leading to complete remission. Eighteen months later, the patient was still free of disease. The second patient experienced stabilization of lung metastases for approximately 10 months. Overall, our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients. Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation.
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PMID:Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate. 1618 85

Studies reported that there is a close relationship between hepatocellular carcinoma (HCC) and testis carcinoma. Both tumors can be presented as synchronal tumors, or as testicular metastases of HCC or as hepatic metastases of testicular tumor( [7] ). HCC is one of the most common malignancies worldwide and the incidence of HCC increases with age( [8] ). The relationship between hepatitis B incidence and HCC rates is also well recognized. Alpha fetoprotein (AFP) is produced by 70% of HCC. Though a level of AFP >400 ng/mL is diagnostic for HCC, in the presence of active hepatitis B infection, the cut-off level should be considered to be at least 1 000-4 000 ng/mL. Like HCC, germ cell tumors of the testis also release AFP; but it is shown that some of Sertoli cell tumors of testis can also release AFP( [10] ). Herein we have reported about the first case of HCC in the literature which is presented concomitantly with Sertoli-Leydig tumor of testis, leading to extremely high level of AFP in a 21-year-old man.
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PMID:Very high alpha-fetoprotein in a young man due to concomitant presentation of hepatocellular carcinoma and Sertoli cell testis tumor. 1643 17

A rare autopsy case of combined hepatocellular and cholangiocarcinoma, occurring in a 54-year-old man with liver cirrhosis, is presented. Initial laboratory data included CEA 52.1 ng/mL, DUPAN-2 1600 U/mL, AFP 2 ng/mL, and negativity for hepatitis B surface antigen, hepatitis B early antigen and hepatitis B core antibody. Ultrasonography and CT scan showed a large tumor node in the liver with ringed enhancement, swelling of several para-aortic lymph nodes, and ascites. Clinically, it was not possible to determine whether the hepatic tumor was an intrahepatic cholangiocarcinoma or a metastatic carcinoma. Histologically, the primary lesion was composed solely of hepatocellular carcinoma (HCC) with a trabecular pattern, and the intrahepatic metastases consisted of a variable admixture of HCC and cholangiocarcinoma (CC) with excessive mucin production. Interestingly, the tumor cell cluster showing a trabecular growth pattern produced mucin and had immunohistochemical expression of hepatocyte, cytokeratins 7 and 8. It is concluded that these hepatic tumor cells had both HCC and CC characters.
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PMID:Combined hepatocellular carcinoma and cholangiocarcinoma with components of mucinous carcinoma arising in a cirrhotic liver. 1663 69

Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA-positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc]-negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc-positive) groups, then randomized to IFN-alpha (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09-0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment.
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PMID:Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. 1713 92

To analyze the clinical features of hepatocellular carcinoma (HCC) in patients with signs and symptoms of nervous system involvement as the initial presentation. Over a period of 11 years (January 1993 to December 2003), 15,008 HCC patients were identified at the Chang Gung Memorial Hospital in Kaohsiung, Taiwan. Amongst them, 42 cases had nervous system involvement, of which six had nervous system involvement as their initial presentation. These six cases were enrolled in this study and their clinical and laboratory data were analyzed. The clinical features of the other 36 HCC cases with nervous system involvement were also analyzed for comparison. The six cases were all males, aged 36-68 years old. The involved parts of the nervous system were the cerebellar hemisphere (one), the frontal lobe (one), the sphenoid sinus, sellar turcica, and cavernous sinus (one), the cervical spine (one), and the thoracic spine (two). Their corresponding neurologic presentations were back pain, headache, consciousness disturbance, visual disturbance, and limb weakness. Whilst three out of six patients presenting with nervous system manifestations were found to have concurrent systemic metastases in other expected sites (lung, bone), three had isolated nervous system involvement even after extensive work up. The associated medical conditions of the six cases included hepatitis B (three), hepatitis C (one), liver cirrhosis (two), portal vein thrombosis (three), and diabetes mellitus (two). All the six died within 9 months after the detection of nervous system involvement. The prevalence of nervous system involvement in HCC patients is 0.28% (42/15,088), with 0.04% (6/15,088) having this as their initial presentation. The prognosis of HCC with nervous system involvement is grave. Their clinical and laboratory data are not unique but the diagnosis could only be confirmed by hepatic and nervous system imaging studies, histopathologic examination, and serum alpha-fetoprotein detection. This consideration should be emphasized especially in areas that are hyperendemic for HCC and if the original focus of metastatic lesion is obscure.
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PMID:Hepatocellular carcinoma presenting as nervous system involvement. 1738 89

Liver transplantation with a part of the liver from a healthy living donor can be life saving for selected patients with end-stage liver failure. The experiences with the first 3 adult patients in the Netherlands were as follows. The first patient was a 56-year-old man with primary sclerosing cholangitis, who received half of the liver from his 53-year-old sister. Postoperatively, the donor developed a urinary tract infection, which was treated with antibiotics. The recipient developed fever and paralytic ileus 6 days after transplantation. Relaparotomy revealed minimal bile leakage from the cut surface of the liver, which was corrected with a suture. Three years after donation, both donor and recipient were doing well. The second patient was a 63-year-old man with hepatic cirrhosis due to hepatitis B, recurrent bleeding from varices, and hepatocellular carcinoma. The carcinoma was treated percutaneously with radiofrequency ablation. He was given a liver transplant from his 28-year-old son. The donor later developed transient ileus and mild liver function disorders. The recipient developed a bacterial infection of the ascites, which was treated with antibiotics, and later Candida-oesophagitis and a herpes simplex infection, which were also treated successfully. More than 2 years after donation and transplantation, both donor and recipient were in good condition. The third patient was a 42-year-old man with a chronic hepatitis B virus infection and 2 hepatocellular carcinomas. The donor was his 34-year-old sister-in-law. The recipient developed prolonged jaundice due to stenosis at the site of the bile duct anastomosis, for which a stent was placed. He was discharged in good condition but died 11 months later of cerebral metastases. One year after the procedure, the donor was doing well. The Rotterdam liver transplantation programme with living donors demonstrates that excellent results can be accomplished with minimal risk for the donor.
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PMID:[Liver transplantation with a living donor: the first 3 cases in Rotterdam]. 1849 25

Hepatocarcinogenesis is a multistep process, but systematic analysis using a genetic or molecular approach to accurately delineate the different stages of hepatocellular carcinoma (HCC) development is scarce. In this study, we used genome-wide allelotyping to systematically evaluate the allelic alterations in the multisteps of hepatitis B virus-associated hepatocarcinogenesis. The overall fractional allelic loss (FAL) indices of cirrhosis, dysplastic nodules (DN), and HCC were significantly different, with a clear stepwise increase (P < 0.001). Loss of heterozygosity (LOH) was uncommon in cirrhotic livers (n = 24; mean FAL index +/- SD, 0.09 +/- 0.09; median, 0.07). In contrast, LOH was common in our 74 HCC nodules, which were predominantly hepatitis B virus-associated (mean FAL index +/- SD, 0.40 +/- 0.23; median, 0.38). The 18 DNs had FAL index (mean +/- SD, 0.27 +/- 0.19; median, 0.20) in between that of cirrhosis and HCC. Importantly, high-grade DNs had FAL index significantly higher than that of low-grade DNs (P = 0.031) and close to that of HCC, indicating that high-grade DNs were genetically closer to HCC. However, there was no significant difference in FAL indices between primary HCCs and their corresponding intrahepatic metastases, but this absence of major allelic losses in this transformation to a metastatic phenotype does not exclude small-scale chromosomal losses or gene deletions. To conclude, hepatitis B virus-associated hepatocarcinogenesis is a multistep process accompanied by stepwise increase in allelic losses from cirrhosis and low- and high-grade DN to HCC. Such allelic losses contribute to promote tumor development and progression.
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PMID:Hepatitis B virus-associated multistep hepatocarcinogenesis: a stepwise increase in allelic alterations. 1863 55

Metastasis is a key aspect of tumor malignancy, and several malignant tumors show expression of various mature N-type glycans. In particular, beta1-6 branching N-acetylglucosamine (GlcNAc) is abundantly expressed as a part of high-mannose glycans in various highly metastatic cancers. Phaseolus vulgaris agglutinin-L(4) isolectin (L(4)-PHA), which adheres to beta1-6 GlcNAc specifically, has been used for in situ cancer diagnosis. Bionanocapsules (BNCs), hollow particles with a diameter of approximately 80 nm and composed of hepatitis B surface antigen (HBsAg) and a lipid bilayer, have been developed as human liver-specific nanocapsules for in vivo drug delivery system. In this study, we have generated L(4)-PHA-displaying BNCs (PHA-BNCs) and examined whether L(4)-PHA could retarget the BNCs to malignant tumors as a "biosensor" distinguishing tumor metastaticity. Fluorescence-labeled PHA-BNCs injected systemically into a mouse xenograft model were found to accumulate in beta1-6 GlcNAc-expressing malignant tumors. The PHA-BNCs were able to deliver DNA to the malignant cancer cells. These results open up the possibility of using L(4)-PHA lectin as a targeting molecule in a drug delivery system, and of using PHA-BNCs as a novel nanodevice for malignant tumor-specific bioimaging and drug delivery.
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PMID:In vivo delivery of bionanocapsules displaying Phaseolus vulgaris agglutinin-L4 isolectin to malignant tumors overexpressing N-acetylglucosaminyltransferase V. 1871 44

Brain metastases from hepatocellular carcinoma are extremely rare. The objectives of the current study were to assess the natural history, outcome, and possible prognostic factors in patients with brain metastases from hepatocellular carcinoma. Between 1995 and 2006, 6,919 patients with hepatocellular carcinoma were treated at Yonsei University Health System. Of those, 62 (0.9%) had a diagnosis of brain metastasis. We carried out a retrospective review of these 62 patients and performed a statistical analysis. The median age at the time patients were diagnosed with brain metastasis was 54 years. Forty-seven patients (76%) were male, and 53 patients had hepatitis B. Median time from diagnosis of hepatocellular carcinoma to brain metastasis was 18.2 months, and 5 patients had brain involvement as their initial presentation. Intracranial hemorrhage was frequently associated (54.8%) with brain metastasis. The most common presenting symptoms were motor weakness, mental change, and headache. Metastases were treated with whole-brain radiation therapy (WBRT) alone in 17 patients and gamma knife surgery alone in 10 patients. Six patients underwent surgical resection and 5 patients were treated with surgical resection followed by WBRT. Twenty-four patients (39%) received steroids only. Median survival after diagnosis of brain metastasis was 6.8 weeks (95% confidence interval: 3.8-9.8 weeks). Univariate analysis showed that treatment modality, number of brain lesions, alpha-fetoprotein, ECOG performance score, recursive partitioning analysis (RPA) class, and Child-Pugh classification had a statistically significant impact on survival. In multivariate analysis, treatment modality, number of brain lesions, and Child-Pugh classification were statistically significant prognostic factors for survival. The overall prognosis of patients with brain metastases from hepatocellular carcinoma is extremely poor. Nevertheless, some subsets of patients manifested the most favorable survival criteria (single brain metastasis and good liver function); thus, for at least these patients, treatment may result in an improved survival time.
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PMID:Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC. 1894 45

Hepatocellular carcinoma (HCC) is the most frequent malignant tumour of the liver. The risk of HCC in chronically hepatitis B virus (HBV) infected individuals is approximately 100-fold higher than in the uninfected population. Despite all therapeutic advances, the benefit of systemic chemotherapy in patients with HCC has limited. But, the phase III clinical trial conducted in patients with advanced HCC treated with sorafenib has showed significant improvements in both overall and progression-free survival Metastasis from liver to extrahepatic tissues is reported to be quite uncommon and has a poor prognosis. Here we present a case of HCC which metastasized to the vertebrae, lung and kidney in order of appearance and controlled with immunotherapy and antiviral therapy following resection.
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PMID:A case of recurrent metastatic hepatocellular cancer controlled with immunotherapy and antiviral therapy following resection. 1968 14


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