Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In summary, of the 460 patients of primary carcinoma of the liver admitted to the University Surgical Unit at the Queen Mary Hospital over a period of 12 years, more than 40% could not be treated, and only 91 of the patients were candidates for curative resection. The cure rate is very small; a 1- to 2-year survival was obtained in 46% of 15 resections. From 1964 to 1969, out of 22 patients with resections, 3 are still alive more than 5 year after the operation. Lin30 reported a 19.1% 5-year survival. When the hepatoma has ruptured and bleeding takes place, surgical treatment is obligatory to control the hemorrhage. Ninety-eight patients underwent a clinical trial of 5 categories: hepatic dearterialization, hepatic arterial cannulation and infusion of 5-FU, hepatic arterial ligation and portal venous infusion of 5-FU, radiotherapy and no treatment. The results show that the advantage of each form of treatment when compared with no treatment is marginal. Thus a gloomy picture of primary hepatoma is held. Since the operative mortality of hepatic resection for a solitary secondary carcinoma of the liver is negligible, it should be done in each instance because a long-term survival may be possible. This is especially true with primary carcinoma of the colon.
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PMID:Techniques and therapies for primary and metastatic liver cancer. 8 19

The authors report four new cases of primary digestive carcinoma other than hepatoma with alpha 1 feto-protein in the serum (greater than 200 ng/ml). Two were carcinoma of the colon without liver metastases. The remaining two were also colonic carcinoma but with liver metastases. In the first cases, alpha 1 feto-protein disappear after surgical procedure. In spite of the rareness of primary digestive carcinoma with presence of alpha 1 feto-protein noted until now, these cases require reconsideration of the idea that AFP is specific for hepatoma.
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PMID:[Serum alpha 1-fetoprotein and extrahepatic digestive cancers. Apropos of 4 further cases]. 8 30

The prognostic and therapeutic significance of tumor vascularity was studied in 36 patients with hepatoma or metastatic colon cancer in the liver. All patients had nonresectable tumor and were treated by hepatic artery ligation and hepatic arterial infusion chemotherapy. Chemotherapy consisted of methotrexate, actinomycin-D, 5-fluorouracil and cyclophosphamide. Hepatic tumors were categorized into Grades I to III in the order of increasing vascularity as determined by preoperative hepatic angiography. Tumor vascularity of 15 patients with hepatoma was Grade III in 11 (73%) and Grade II in 4 (27%). No patient with hepatoma had a Grade I tumor. The median survival of patients was 10 and 6 months for Grade III and II hepatomas, respectively, after hepatic artery ligation, and 18 and 8.5 months for Grade III and II, respectively, from the time of diagnosis of hepatoma. Tumor vascularity of 21 patients with metastatic colon cancer was as follows: Grade III in 3 (14%); Grade II in 10 (48%); and Grade I in 8 (38%). The median survival was 11, 10.5 and 4 months for Grades III, II and I, respectively, after hepatic artery ligation, and 17, 14.5 and 7.2 months for Grades III, II and I, respectively, from the time of diagnosis of hepatic metastases of colon cancer. The results indicate that the more vascular the hepatic tumor on angiogram, the better the prognosis following hepatic artery ligation and infusional chemotherapy.
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PMID:Tumor vascularity as a prognostic factor for hepatic tumors. 18 91

CT and US findings of 7 cases of splenic metastases are described and the prevalence of splenic metastases at autopsy in 641 cases with malignant tumors were evaluated. Metastatic foci in spleen appeared mostly as poorly-defined low density masses on CT. Iodinated contrast material was administered in 2 cases, but no contrast enhancement was observed. US showed both hypoechoic and hyperechoic patterns. These appearances were nonspecific, but were similar to those of metastatic lesions in the liver which were often visible on CT associated with splenic metastases. At autopsy splenic metastases were found in 34 of 641 cases (5.3%). Gastric, colon, lung and ovarian cancers were most common primary tumors. However, the rate of splenic metastasis per tumor was highest in ovarian cancer (50.0%), followed by malignant melanoma (33.3%), colon cancer (16.2%) and gastric cancer (8.2%). Hepatoma which had the biggest number of autopsy cases in this series showed the lowest rate of splenic metastasis (0.8%).
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PMID:[Radiological diagnosis of splenic metastasis and its prevalence at autopsy]. 165 70

Tumor targeting by monoclonal antibodies (MAbs) can be enhanced by (a) increasing the percentage of injected dose taken up by the tumor and/or (b) increasing the tumor:nontumor ratios. Several groups have demonstrated that one can increase tumor to nontumor ratios by the use of antibody fragments or the administration of second antibodies. Several other modalities are also possible: (a) the use of recombinant interferons to up-regulate the expression of specific tumor associated antigens such as carcinoembryonic antigen or TAG-72 on the surface of carcinoma cells and thus increase MAb tumor binding has proved successful in both in vitro and in vivo studies; (b) the intracavitary administration of MAbs. Recent studies have demonstrated that when radiolabeled B72.3 is administered i.p. to patients with carcinoma of the peritoneal cavity, it localizes tumor masses with greater efficiency than does concurrent i.v. administered antibody. Studies involving the comparative pharmacology of intracavitary administration of radiolabeled MAb in patients and several animal models will be discussed; (c) it has been reported that prior exposure of hepatoma to external beam radiation will increase radiolabeled MAb tumor targeting. We and others have not been able to duplicate this phenomenon with a human colon cancer xenograft model and radiolabeled MAbs to two different colon carcinoma associated antigens. The possible reasons for these differences will be discussed; (d) the cloning and expression of recombinant MAbs with human constant regions and subsequent size modification constructs will also undoubtedly alter the pharmacology of MAb tumor binding in both diagnostic and therapeutic applications.
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PMID:Innovations that influence the pharmacology of monoclonal antibody guided tumor targeting. 168 34

The pineal hormone melatonin (MLT) is able to exert an oncostatic action. Its possible use in the treatment of human tumors, however, has not yet been investigated. The present study was carried out to evaluate the effects of MLT in patients with metastatic solid tumors resistant to conventional therapies. The study included 54 patients, most of them were affected by lung cancer or colorectal carcinoma. MLT was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; this induction phase was followed by a maintenance period at a dose of 10 mg orally in responder patients or in those with an improvement in performance status (PS). The clinical response was as follows: 1 partial response (cancer of pancreas), 2 minor responses (colon cancer and hepatocarcinoma) and 21 with stable disease. The remaining 30 patients rapidly progressed within the first 2 months of therapy. An evident improvement in PS was achieved in 18 of 54 (33%) cases. These results, by showing an apparent control of the neoplastic growth and an improvement in the quality of life in a reasonable number of cancer patients for whom no other standard therapy is available, would justify further clinical trials to better define the impact of MLT therapy on the survival and quality of life of untreatable advanced cancer patients.
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PMID:Clinical results with the pineal hormone melatonin in advanced cancer resistant to standard antitumor therapies. 174 79

We have compared by SDS-PAGE Western blotting the molecules detected by two human monoclonal antibodies, C-OU1 and 16.88. The antibodies have previously been shown to detect a cytoplasmatic antigen with an Mr of 43 kD present in colon adenocarcinoma cell lines and in colon cancer tissues. We now demonstrate that these antibodies differ significantly in their fine specificity, resulting in a quite dissimilar tumor selectivity. The antibody 16.88, in addition to reactivity with the 43-kD molecule, also recognizes a 190-kD molecule present both in melanoma cells and in cells previously reported as 16.88 antigen positive. The 16.88 antibody does not detect a 43-kD molecule in extracts of melanoma cells. The 190-kD component was not detectable in hepatoma or mamma carcinoma cells, both of which showed presence of the 43-kD molecule. The C-OU1 antibody shows no reactivity with the 190-kD molecule in any of the cells tested or with other proteins in melanoma cells. Radiolabeled 16.88 antibody shows better localization to melanoma cancer than to colon cancer xenograft transplanted onto nude mice. These findings indicate the presence of a tumor-associated antigen not previously described and have obvious implications for potential clinical uses of the antibodies.
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PMID:Antigens recognized by two human monoclonal IgM anticolon cancer antibodies, 16.88 and C-OU1 (B9165). 175 84

Phosphotyrosine-containing proteins in various human cancer cell lines were studied by immunoblotting with anti-phosphotyrosine antibody. Of 29 cell lines derived from oral epidermoid cancer, esophageal cancer, gastric cancer, colon cancer, pancreatic cancer, hepatocellular carcinoma and malignant melanoma, 3 of the 6 gastric cancer cells showed aberrant elevation of tyrosine-specific phosphorylation. On the other hand, both esophageal cancer cells and colon cancer cells, which were reported to have amplified epidermal growth factor receptor and activated p60v-src kinase, respectively, showed no apparent elevation of tyrosine-specific phosphorylation, and their profiles of phosphorylation were similar to that of normal human fibroblasts. Two gastric cancer cells, NUGC-4 and MKN-45, showed similar profiles of phosphorylation but their responses to growth factors differed from each other. Tyrosine phosphorylation in NUGC-4 was strongly activated by treatment with epidermal growth factor and quickly reduced by the acid treatment which is effective in removing growth factors from cellular surface receptors. On the contrary, phosphorylation in MKN-45 did not respond to either growth factor or acid treatment. These results suggest that NUGC-4 and MKN-45 have tyrosine kinases which are activated by different mechanisms but share similar substrates.
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PMID:Aberrant elevation of tyrosine-specific phosphorylation in human gastric cancer cells. 177 66

Tumor-infiltrating lymphocytes (TIL) were isolated from 22 human primary and metastatic liver tumors, and expanded in vitro in the presence of either interleukin-2 (IL-2, 100 U/ml) plus tumor necrosis factor alpha (TNF alpha, 1000 U/ml), IL-2 (1000 U/ml) plus IL-4 (1000 U/ml) or IL-2 (1000 U/ml) alone. TIL proliferated in culture in 20/22 cases. Among different cytoline combination, TNF alpha and IL-2 were most effective in promoting the outgrowth of CD3+CD8+T lymphocytes (mean +/- SEM: 90% +/- 5) in the cultures of TIL from primary liver tumors. Cytotoxicity against autologous tumor cells was demonstrated in all early cultures of TIL from primary liver cancers in the presence of IL-2 plus TNF alpha. In contrast, cultures of TIL derived from colon cancer metastatic to liver had significantly lower levels of autotumor cytotoxicity and proportions of CD3+CD8+ cells (40% +/- 13) than those of TIL from primary liver tumors. The addition on day 0 of interferons (alpha or gamma) to TIL cultured in the presence of TNF alpha and IL-2, significantly augmented cytotoxicity against autologous tumor. In contrast, incubation of TIL in the presence of IL-4 and IL-2 did not result in increased autotumor responses in the cultures of TIL from primary liver tumors. The expansion (-fold) of TIL (day 30) cultured in the presence of IL-2 alone compared to that in the presence of TNF alpha and IL-2 was significantly greater for hepatocellular carcinoma (median, 280 vs 260) than for autologous peripheral blood lymphocytes (36 vs 27), cholangiocarcinoma (42 vs 51) or TIL from metastatic colon cancer (39 vs 30). Outgrowth of TIL in IL-2 plus TNF alpha offers an opportunity for in vitro enrichment in cells with autotumor cytotoxicity in primary liver tumors. However, this cytokine combination was unable to promote and sustain growth of autotumor effectors from TIL in metastatic liver cancer.
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PMID:Effects of cytokines on in vitro growth of tumor-infiltrating lymphocytes obtained from human primary and metastatic liver tumors. 184 44

The purpose of this study was to develop the technique of intra-operative portal angioscopy using a portal angioscope, and to demonstrate its potential use in the therapy for patients with hepatocellular carcinoma (HCC) bearing a portal thrombus. Portal angioscopes, Olympus BF3C10 and CHFP10 of a diameter of 3.5 mm and 4.8 mm, respectively, were used during operation in five dogs, two patients with hepatic metastasis from colon cancer and three patients with HCC having a portal tumour thrombus. The portal vein and hepatic artery were ligated simultaneously, and the angioscope was immediately introduced under direct vision through a small portal venotomy. Blood in the portal vein was almost fully diverted by infusion of heparinized saline through a channel of the angioscope at a rate of 3 mL/min in dogs and 5 mL/min in patients with hepatic metastasis. Rates of 6 mL/min and 10 mL/min in dogs and patients, respectively, were adequate to clear completely the portal vein of blood. In patients with HCC, portal tumour thrombectomy was performed with a Fogarty balloon catheter by suctioning thrombi through a channel of the fibrescope after visual study of the portal thrombus. Observation and treatment of portal thrombus by angioscopy may become an important part of surgical treatment of HCC with portal invasion, but further technical improvement is desirable before this technique becomes a routine procedure.
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PMID:Direct observation of the portal vein interior by intra-operative angioscopy in the dog and man. 196 81


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