Effect of laparotomy on the fate of circulating Walker tumour cells in Wistar rats.
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A 65-year-old man with chronic hepatitis C showed a markedly elevated serum alpha-fetoprotein concentration. Computed tomography revealed a huge tumor occupying the entire right hepatic lobe. Three months later, the tumor regressed spontaneously from 12 cm to 7 cm in diameter without any medical treatment. A right hepatic lobectomy was performed 4 months after the initial diagnosis. The main tumor, located in the posterior inferior segment, was completely necrotic, and had a thick fibrous capsule. Many inflammatory cells had also infiltrated into the tumor. Only a small portion of a tumor thrombus in the portal vein and one of three intrahepatic metastases contained viable cancer cells. The tumor was found to be poorly differentiated hepatocellular carcinoma. Tumor regression may have been caused by a disturbance in hepatic circulation associated with the portal vein thrombus.
We report an unusual case of a two-year-old girl with metastatic retinoblastoma and massive bone marrow involvement who showed the overt presence of circulating retinoblastoma cells in peripheral blood smears a few days before death. This extended disease developed after an early relapse that followed abandoned primary chemotherapy. To the best of our knowledge, there are no previous reports about the presence of circulating retinoblastoma cells in peripheral blood films. We conclude that the search for bone marrow invasion in patients with disseminated retinoblastoma should be exhaustive to achieve an accurate staging assessment. Peripheral blood smears should be examined cautiously to detect occasional circulating retinoblastoma cells when the bone marrow is massively involved.
Nucleic acid based molecular techniques have been introduced into the diagnosis of malignant melanoma similarly to other cancers. They were applied for refinement of staging and to detect minimal residual disease. There are several good melanocyte-specific genetic markers such as tyrosinase, gp100, Melan-A/MART-1 and MIA. Unlike in the case of the lymph nodes, peripheral blood or bone marrow do not contain melanocytes excluding the possibility of fals positive reactions. Considering the pronounced heterogeneity of melanoma cells the most reliable molecular marker is the expression of tyrosinase. Several studies indicate that the quantity of circulating melanoma cells correlates with tumor burden and disease progression and reflects the effect of therapy. On the other hand, molecular techniques detect circulating melanoma cells much more frequently than the clinical manifestation of the disease progression (molecular recurrence), questioning the clinical significance of the detection of a small number of melanoma cells in the circulation. Based on these data molecular diagnostics is not part of the melanoma protocols yet and further studies are necessary to define its diagnostic role.
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Circulation time of isotope labeled ascites tumor cells was measured after intravenous injection into mice. Circulation time was approximately doubled by pretreatment with the platelet aggregation inhibitor compound bencyclan.
The distribution of neoplastic--JWS sarcoma and lymphatic leukemia L-1210 cells after intravenous injection into allogeneic recipients is presented. Cells were labelled with two labels: cytoplasmic (sodium chromate-51CR) and nuclear (iododeoxyuridine-125IUDR). Radioactivity of blood, lungs, liver, spleen and kidneys was measured 90 minutes and 24 hours after cell transplantation. The pattern of cell trapping, destruction and elimination from the circulation was characteristic of cell line injected. Destruction and elimination processed faster in allogeneic system than in syngeneic one.
AIM: To investigate whether the current manipulation of liver resection for hepatocellular carcinoma (HCC) causes dissemination of liver tumor cells into blood circulation. METHODS: Fifty patients with HCC, but without evidences of metastases, were enrolled for the study. Samples of peripheral blood before skin incision and after abdominal wall suture, and those of hepatic venous blood and portal venous blood after liver parenchyma dissection,were obtained. AFP-mRNA was extracted from the blood samples and detected with reverse transcription polymerase chain reaction assay. The changes of its expression during the operation were accessed by the ratio of fluorescence of AFP and beta-actin primers-amplified products. RESULTS: The rate of its expression before and after operation in peripheral blood, and during operation in portal venous and hepatic venous blood was 42.0 %, 34.0 %, 42.0 % and 56.0 % respectively, There was no difference between them. However, the ratio of fluorescence of AFP and beta-actin primers-amplified products from hepatic venous blood during operation is significantly higher than the other three types of samples (P<0.05). CONCLUSION: the current manipulation of liver resection for HCC can cause the releases of AFP mRNA-expressed cells from the liver, probably including tumor cells, into hepatic vein. These cells may spread into blood circulation and become the source of recurrence after operation.
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This article describes various adhesion molecules and reviews evidence to support a mechanistic role for adhesion molecules in the process of cancer metastasis. A variety of evidence supports the involvement of specific adhesion molecules in metastasis. 1. For example, some cancer cells metastasize to specific organs, irrespective of the first organ encountered by the circulating cancer cells. This ability to colonize a specific organ has been correlated with the preferential adhesion of the cancer cells to endothelial cells derived from the target organ. This suggests that cancer cell/endothelial cell adhesion is involved in cancer cell metastasis and that adhesion molecules are expressed on the endothelium in an organ-specific manner. 2. Further, inclusion of peptides that inhibit cell adhesion, such as the YIGSR- or RGD-containing peptides, is capable of inhibiting experimental metastasis. 3. Metastasis can be enhanced by acute or chronic inflammation of target vessels, or by treatment of animals with inflammatory cytokines, such as interleukin-1. In vitro, cancer cell/endothelial cell adhesion can be enhanced by pretreating the endothelial cell monolayer with cytokines, such as interleukin-1 or tumor necrosis factor-alpha. This suggests that, in addition to organ-specific adhesion molecules, a population of inducible endothelial adhesion molecules is involved and is relevant to metastasis. 4. Further support for this model is found in the comparison to leukocyte/endothelial adhesion during leukocyte trafficking. Convincing evidence exists, both in vivo and in vitro, to demonstrate an absolute requirement for leukocyte/endothelial adhesion before leukocyte extravasation can occur. The relevance of this comparison to metastasis is reinforced by the observation that some of the adhesion molecules involved in leukocyte/endothelial adhesion are also implicated in cancer cell/endothelial adhesion. The involvement of adhesion molecules suggests a potential therapy for metastasis based on interrupting adhesive interactions that would augment other treatments for primary tumors.
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In breast cancer patients, hematogenous tumor cell dissemination can be detected, even at the single cell level, by applying immunocytochemical and molecular assays. Various methods for the detection of circulating tumor cells in the peripheral blood have been described. Results from recently reported studies suggest that circulating tumor cell levels may serve as a prognostic marker and for the early assessment of therapeutic response in patients with metastatic breast cancer. However, in early-stage breast cancer, the impact of circulating tumor cells is less well established than the presence of disseminated tumor cells in bone marrow; several clinical studies have demonstrated that cells of the latter type are an independent prognostic factor at primary diagnosis. In this article we briefly summarize recent studies examining the presence of circulating tumor cells in the blood and discuss further clinical applications.
OBJECTIVES: To investigate the clinical value of human glandular kallikrein (hK2) reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of prostate cells in circulation and to compare the results with those obtained from prostate-specific antigen (PSA) RT-PCR. METHODS: We examined peripheral blood (PB) and bone marrow (BM) samples of 13 patients with advanced-stage prostate cancer and 63 patients with clinically localized disease for the presence of circulating prostate cells. An RT-PCR protocol with a two-step amplification cycle and hot-start conditions was used. RESULTS: The limit of detection of the PCR portion is similar for PSA and hK2 (5 to 10 copies of the plasmid containing the cDNA). The RT-PCR limit of detection is one LNCaP cell in 10(8) peripheral blood mononuclear cells (PMBC) for PSA, and one LNCaP cell in 10(7) PMBC for hK2. Of the BM samples obtained prior to radical prostatectomy, 71.4% were positive for PSA mRNA and 41.3% were positive for hK2 mRNA. In PB, the PSA positivity was 19% and hK2 positivity 12.7%. In advanced-stage patients, there were 76.9% PSA-positive samples in BM versus 38.5% hK2-positive samples; 46.2% of patients were positive in PB for PSA versus 30.8% for hK2. CONCLUSIONS: We have developed a sensitive RT-PCR protocol for detection of hK2 mRNA and evaluated the suitability of hK2 mRNA in comparison with PSA mRNA as an additional marker for detection of prostate cells in circulation. Combining results of these two tests increased the sensitivity of detection.