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

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR (sTfR) has been identified in animal and human serum. Soluble TfR is a truncated monomer of tissue receptor, lacking its first 100 amino acids, which circulates in the form of a complex of transferrin and its receptor. The erythroblasts rather than reticulocytes are the main source of serum sTfR. Serum sTfR levels average 5.0+/-1.0 mg/l in normal subjects but the various commercial assays give disparate values because of the lack of an international standard. The most important determinant of sTfR levels appears to be marrow erythropoietic activity which can cause variations up to 8 times below and up to 20 times above average normal values. Soluble TfR levels are decreased in situations characterized by diminished erythropoietic activity, and are increased when erythropoiesis is stimulated by hemolysis or ineffective erythropoiesis. Measurements of sTfR are very helpful to investigate the pathophysiology of anemia, quantitatively evaluating the absolute rate of erythropoiesis and the adequacy of marrow proliferative capacity for any given degree of anemia, and to monitor the erythropoietic response to various forms of therapy, in particular allowing to predict response early when changes in hemoglobin are not yet apparent. Iron status also influences sTfR levels, which are considerably elevated in iron deficiency anemia but remain normal in the anemia of inflammation, and thus may be of considerable help in the differential diagnosis of microcytic anemia. This is particularly useful to identify concomitant iron deficiency in a patient with inflammation because ferritin values are then generally normal. Elevated sTfR levels are also the characteristic feature of functional iron deficiency, a situation defined by tissue iron deficiency despite adequate iron stores. The sTfR/ferritin ratio can thus describe iron availability over a wide range of iron stores. With the exception of chronic lymphocytic leukemia (CLL) and high-grade non-Hodgkin's lymphoma and possibly hepatocellular carcinoma, sTfR levels are not increased in patients with malignancies. We conclude that soluble TfR represents a valuable quantitative assay of marrow erythropoietic activity as well as a marker of tissue iron deficiency.
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PMID:Soluble transferrin receptor for the evaluation of erythropoiesis and iron status. 1258 62

Fever of unknown origin (FUO) is defined as fever of more than 38.3 degrees C, the cause of which remains elusive after 1 week of intensive investigation. Most cases of FUO are restricted to infections, malignancies, and inflammatory diseases. FUO was previously reported as the presenting symptom of a few solid tumors such as lymphoma, renal cell carcinoma, and hepatocellular carcinoma. Colon carcinoma manifesting as FUO has been rarely reported. We describe three female patients who presented with classical FUO and microcytic anemia. As a control, we retrospectively evaluated 28 matched patients with carcinoma of colon and no fever. The evaluation included review of patient files, clinical and laboratory data, and pathologic specimens. In the three patients (mean age, 58 years) who presented with FUO and had left-sided colon carcinoma and microcytic anemia, pathologic evaluation of the tumor tissues demonstrated a severe organized inflammatory process forming abscesses in the pericolic fat. The 28 control matched patients showed no such histopathologic changes. In patients presenting with FUO, especially those who present with microcytic anemia, even with no bowel disturbances or elevated carcinoembryonic antigen levels, diagnostic workup should include a search for occult colorectal carcinoma. In our three cases, it appears that microabscesses in the pericolic fat are the cause of fever.
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PMID:Carcinoma of colon presenting as fever of unknown origin. 1595 76

Anemia of inflammation develops in settings of chronic inflammatory, infectious, or neoplastic disease. In this highly prevalent form of anemia, inflammatory cytokines, including IL-6, stimulate hepatic expression of hepcidin, which negatively regulates iron bioavailability by inactivating ferroportin. Hepcidin is transcriptionally regulated by IL-6 and bone morphogenetic protein (BMP) signaling. We hypothesized that inhibiting BMP signaling can reduce hepcidin expression and ameliorate hypoferremia and anemia associated with inflammation. In human hepatoma cells, IL-6-induced hepcidin expression, an effect that was inhibited by treatment with a BMP type I receptor inhibitor, LDN-193189, or BMP ligand antagonists noggin and ALK3-Fc. In zebrafish, the induction of hepcidin expression by transgenic expression of IL-6 was also reduced by LDN-193189. In mice, treatment with IL-6 or turpentine increased hepcidin expression and reduced serum iron, effects that were inhibited by LDN-193189 or ALK3-Fc. Chronic turpentine treatment led to microcytic anemia, which was prevented by concurrent administration of LDN-193189 or attenuated when LDN-193189 was administered after anemia was established. Our studies support the concept that BMP and IL-6 act together to regulate iron homeostasis and suggest that inhibition of BMP signaling may be an effective strategy for the treatment of anemia of inflammation.
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PMID:Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. 2139 79

Delayed gastrointestinal metastasis is a rare complication of hepatocellular carcinoma (HCC). We present the case of a patient who presented with melaena and microcytic anaemia 6 years after receiving an orthotopic liver transplant for hepatitis B-induced HCC. Oesophagogastroduodenoscopy revealed a fungating gastric mass at the lesser curve and histology from biopsies confirmed metastatic recurrence of HCC in the stomach. The route of metastasis is likely due to iatrogenic seeding of tumour cells during pre-transplant endoscopic ultrasound (EUS) and fine needle aspiration (FNA) biopsy. Subsequent positron emission tomography and magnetic resonance imaging failed to reveal further metastatic disease and the patient was managed with a total gastrectomy. This is the first reported description in the literature of needle-track metastasis in the stomach due to liver EUS-FNA for HCC.
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PMID:Seeding of hepatocellular carcinoma into the stomach wall following endoscopic ultrasound and fine-needle aspiration biopsy. 3004 50