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PubMed1998

Dissemination of tumor cells in patients undergoing surgery for colorectal cancer.

The majority of patients with colorectal cancer present at a stage when the primary cancer can be resected with curative intent. However, despite the high resectability rate, about 30-50% of these patients subsequently develop metastatic disease. In these patients, neoplastic cells were disseminated either before or during surgery of the primary cancer. Due to the lack of appropriate detection systems, the extent of pre- and intraoperative hematogenic tumor cell dissemination has not yet been determined. Using a reverse transcription-PCR assay to amplify cytokeratin 20 transcripts, we were able to detect 10 colorectal cancer cells in 10 ml of blood. Blood samples were taken from 65 patients undergoing resection of primary colorectal cancer or liver metastasis of colorectal cancer pre-, intra-, and postoperatively. Circulating tumor cells were detected in 24 of 58 patients with colorectal resections in correlation to the tumor stage and in 6 of 7 patients who underwent hemihepatectomy for liver metastasis. In 8 of 58 patients with colorectal resection and in 5 of 7 patients with hemihepatectomy, tumor cells could only be detected during or during and after surgery. These results demonstrate that hematogenic tumor cell dissemination is a frequent and early event in colorectal cancer. Surgery enhances the release of tumor cells into the circulation. The long-term follow-up of our patient cohort will provide data on the prognostic relevance of circulating tumor cells and might lead to new therapeutic concepts for perioperative prophylaxis of tumor cell implantation or postoperative adjuvant therapy regimens.

Adult↗
PubMed2003

Detection of epidermal growth factor receptor mRNA in peripheral blood of cervical cancer patients.

OBJECTIVE: Epidermal growth factor receptor (EGFR) has been reported to be expressed by immunohistochemistry in invasive cervical cancers. We evaluated the feasibility of detecting EGFR mRNA by EGFR-based reverse transcription polymerase chain reaction (RT-PCR) in peripheral blood of patients with cervical cancer. METHODS: Expression of EGFR mRNA, cytokeratin (CK)-19 mRNA, and CK-20 mRNA was examined by RT-PCR in 12 human cervical cancer cell lines. All 12 cell lines expressed both EGFR mRNA and CK-19 mRNA, but only 4 of 12 (33.3%) cell lines expressed CK-20 mRNA. Peripheral blood samples from 20 healthy donors and 45 cervical cancer patients were also examined. RESULTS: In peripheral blood from 20 healthy donors, neither EGFR mRNA nor CK-20 mRNA was expressed, but CK-19 mRNA was expressed in 13 of 20 (65%). In contrast, EGFR mRNA was expressed in 12 of 45 (26.7%) patients with cervical cancer (P = 0.0071, 2 test, patient vs control). On the other hand, expression of EGFR was observed in 98% of tumor tissues by immunohistochemistry. CK-19 mRNA and CK-20 mRNA were found in 35 of 45 (77.8%) and 0 of 45 (0%) patients, respectively (NS, chi(2) test, patient vs control). The rate of detection of EGFR mRNA in peripheral blood correlated with FIGO stage (P = 0.049). CONCLUSION: Both CK-19 mRNA and CK-20 mRNA showed no diagnostic value as markers of circulating tumor cells in cervical cancers. However, EGFR mRNA in blood might be a useful marker of circulating tumor cells in cervical cancers.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Transcatheter oily chemoembolization for the treatment of large hepatocellular carcinoma with an accompanying tumor thrombus in the right main branch of the portal vein and arterioportal shunting: report of one patient still surviving after more than seven years.

A patient having a large hepatocellular carcinoma with an accompanying tumor thrombus in the right main branch of the portal vein and arterioportal shunting was treated with transcatheter oily chemoembolization with adriamycin emulsion in Lipiodol plus Gelfoam. The whole right hepatic lobe regressed together with the tumor, and the tumor thrombus in the portal vein disappeared. The patient is still alive more than seven years after the treatment, with normal levels of alpha-fetoprotein. The response of this patient is interesting in discussing potential indications for therapy.

Atrophy↗
PubMed2001

Relationship between tumour vascularity and circulating cancer cells in patients with colorectal carcinoma.

BACKGROUND: Colorectal cancer vascularity correlates with risk of metastasis. Greater tumour vascularity may increase haematogenous dissemination by providing a larger vessel area for tumour cell invasion into the circulation. We assessed whether the prevalence of tumour cells in the circulation of colorectal carcinoma patients (CTC) increased with tumour vascularity. METHODS: Pre-operative blood samples were assessed for circulating tumour cells using RT-PCR for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) mRNA. Vessel count and volume were morphometrically assessed from tumour biopsies after vasculature staining. RESULTS: Thirty-three colorectal cancer patients (M:F, 20:13; mean age 66 years, SD 11 years) were studied. One or more blood samples were RT-PCR positive for either CEA or CK20 mRNA or both, in 28 (85%) patients. There were no significant differences in the prevalence of RT-PCR positive patients between high and low tumour vascularity groups, or in tumour vessel counts or volume in RT-PCR positive compared with negative patients. CONCLUSIONS: These results do not support vascularity related variation in access of tumour cells to the circulation as an explanation for the correlation between tumour vasculature and metastasis. Tumour vascularity and metastatic potential may be linked phenotypes rather than cause and effect.

Aged↗
PubMed2005

Association of disease progression and poor overall survival with detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer.

The aim of this study was to define the frequency and clinical relevance of cytokeratin positive metastatic tumor cells in the peripheral circulation of patients with stage IV breast cancer. Peripheral blood was collected from 32 consecutive patients with metastatic breast cancer and 23 healthy donors. Tumor cells were enriched using positive selection with anti-HEA125-microbeads and cytospins were prepared of the positive selection eluate. Slides were incubated with a Fab2 fragment of the pancytokeratin antibody A45-B/B3 conjugated with alkaline phosphatase (AKP) and a CAM5.2-AKP monoclonal antibody and developed with an alkaline phosphatase anti-alkaline phosphate reaction (APAAP). All samples were evaluated using light microscopy and an automated image analysis system. In 8/32 (25%) patients cytokeratin positive (CK+) cells could be detected after anti-HEA125 enrichment in the peripheral blood whereas in none out of 23 healthy donors. One to 1000 (median 5) positive cells per patient sample were observed and cluster of tumor cells in one patient. Automated image analysis was as powerful in detecting micrometastases as conventional light microscopy. All patients with CK+ cells in the peripheral circulation (8/8, 100%) showed progressive disease at the time-point of blood draw whilst only 9/24 (37.5%) showed disease progression without detection of positive cells. The median overall survival of CK+ patients was 4+/-2 months compared to 13+/-7 months of CK- patients (p<0.001). CK+ cells are detectable in the peripheral circulation of 25% of patients with metastatic breast cancer after positive selection with anti-HEA125. Detection of tumor cells in the peripheral circulation might be correlated with progression of disease and shorter overall survival.

Adult↗
PubMed1992

Biomechanical interactions of cancer cells with the microvasculature during hematogenous metastasis.

Different aspects of hematogenous metastasis are discussed from the viewpoint of biomechanics. The processes considered include the role of primary tumor pressure, cell locomotor forces and degradation, in invasion of tissues and intravasation by cancer cells. Consideration of the fluid dynamics of cancer cell movement along capillaries lead to the view that in vivo, arrest is primarily due to mechanical trapping of cancer cells, and that the pathobiologic role of so-called adhesion molecules is not mainly in the arrest and adhesion of cancer cells, but rather in stimulating their proliferation by signal induction. As a consequence of deformation from spherical-to-cylindrical shape in the microvasculature, demands for increased surface membrane area leads to increases in surface membrane tension above critical levels for rupture, and the cancer cells are rapidly and lethally damaged. The possibility is briefly discussed of increasing the susceptibility of circulating cancer cells to mechanical trauma, as a form of anti-metastatic therapy.

Animals↗
PubMed2000

Two-step selective clamping of IVC for removal of hepatocellular carcinoma with intracaval extension.

Hepatocellular carcinoma (HCC) with retrohepatic intracaval extensions are difficult to treat. HCC may sometimes extend into the inferior vena cava (IVC) through two routes: via the right hepatic vein and via the inferior right hepatic vein. In such cases, in which tumor emboli are located both above and below the confluence of the hepatic vein with the IVC, we first remove the upper embolus during THVE, and then remove the lower one while the IVC is clamped obliquely in order to preserve the residual liver circulation.

Carcinoma, Hepatocellular↗
PubMed1986

The influence of prior total body irradiation on the tissue distribution of mouse lymphoma/leukemia.

The effect of a single dose of 10 Gy X rays on the distribution of subsequently injected mouse lymphoma/leukemia cells was studied. The organ distribution of an acute myeloid leukemia (A46) was not affected by prior (90 days) administration of 10 Gy X rays. A T-cell lymphoblastic lymphoma/leukemia (A55) and a B-cell lymphoblastic lymphoma/leukemia (A31) produced enhanced infiltration of the lung when 10 Gy of total body irradiation (TBI) was given 90 days before the tumor cells. The infiltration was predominantly in the peribronchiolar and perivascular spaces. Enhancement was not seen in any tissues other than lung. The possibility is raised that in those acute lymphoblastic leukemia patients whose treatment includes TBI, residual circulating cells may be encouraged to infiltrate the lung.

Animals↗
PubMedDate not supplied

Detection of rare circulating breast cancer cells by filtration cytometry and identification by DNA content: sensitivity in an experimental model.

Current methods of detecting micrometastases in breast cancer fail in a large proportion of patients. Therefore an improved method for detection of metastases in blood samples could be of great clinical interest both for prognosis and selection of patients for adjuvant systemic therapy. We have developed a new non-invasive method which associates immuno-magnetic separation and filtration cytometry. The sensitivity of our procedure was evaluated in a model system using a mixture from a human breast cancer cell line (MCF-7) and a normal human blood sample. The identification of tumoral cells was achieved by measuring DNA content in comparison with standard cells. The lowest concentration of MCF-7 detected was 1 tumoral cell in 500,000 white blood cells. In addition, filtration cytometry provides a visual control of nuclei permitting the elimination of all doubtful cases and an automatic count of tumoral cells directly per ml of blood, which may be an independent predictor of early relapse. This new method may avoid unnecessary axillary lymph node dissection in patients with negative nodes. Our procedure seems suitable for the detection of rare circulating cells in routine laboratory testing and could be used in other applications.

Breast Neoplasms↗
PubMed2003

Changes in the presence of multiple markers of circulating melanoma cells correlate with clinical outcome in patients with melanoma.

PURPOSE: Melanoma cells can be found in the circulation of patients with melanoma. The following study was conducted to examine whether changes in their presence could provide an early marker of response to therapy. EXPERIMENTAL DESIGN: We measured the presence of several markers of melanoma cells in the peripheral blood of 118 patients with resected stage IIb, III, or IV melanoma before and after immunotherapy with a polyvalent, shed antigen, melanoma vaccine using reverse transcription-PCR assays for tyrosinase, gp100, MART-1, and MAGE-3. Assays were conducted at baseline and after 3, 5, and 11 months of therapy. RESULTS: Overall, 47% of patients were positive for at least one marker during the study. Before vaccine treatment, circulating melanoma cell markers were present in 23% of patients. After 5 and 7 months of vaccine therapy, the proportion of patients with circulating markers decreased by 27% and 55%, respectively (P for trend = 0.02). The recurrence-free survival of patients whose melanoma cell markers disappeared during vaccine treatment was significantly longer than that of patients in whom they increased, i.e., the percentage of patients who were recurrence free at 1 year was 80% versus 58% (P = 0.03). CONCLUSIONS: Therapy with a polyvalent melanoma vaccine was associated with clearance of melanoma cell markers from the circulation, and the clearance was associated with an improved prognosis. These findings suggest that the sequential assay of tumor cells in the circulation by reverse transcription-PCR may provide an early indication of the effectiveness of cancer therapy.

Adolescent↗
PubMed2005

Lack of apoptosis of Sézary cells in the circulation following oral bexarotene therapy.

BACKGROUND: Apoptosis of malignant cells has been suggested as an important mechanism of the action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL). OBJECTIVES: Our purpose was to examine the in vivo and in vitro responses of patients with Sézary syndrome treated with oral bexarotene and assess them for apoptosis of the Sézary cells. METHODS: Six patients with CTCL with circulating Sézary cells, participating in a clinical trial of oral bexarotene (300 mg m(-2) daily) were included in the study. Peripheral blood from the patients was analysed for in vivo and in vitro apoptosis. RESULTS: None of the six patients demonstrated in vivo apoptosis. In vitro apoptosis of Sézary cells was demonstrated in one patient following exogenous bexarotene. CONCLUSIONS: Apoptosis is not detectable in the circulation of patients with Sézary syndrome treated with bexarotene.

Administration, Oral↗
PubMed1975

Quantitation of cell shedding into efferent blood of mammary adenocarcinoma.

The rate of tumor cell shedding into efferent tumor blood was measured in growing and regressing MTW9 rat mammary carcinomas. The hormone-dependent tumor, grown as an 'isoession was induced by reduction of mammotropin level in the host. Tumor cells were differentiated from normal leukocytes by indirect immunofluorescence. Growing tumors shed 3.2 x 10-6 and regressing tumors shed 4.1 x 10-6 cells per 24 hr per g tissue. Cell shedding rates of growing versus regressing tumors were not siginificantly different over a tumor size range of 2 to 4 g. The number of tumor cells in the arterial blood was 12-fold smaller than in the efferent tumor blood. It is concluded that: (ay cell shedding via blod probably plays only a minor role in the total cell loss by gtowing MTW9 carinomas; (b) hormone-induced tumor regression does not depend on increased cell shedding; (c) tumor cells are rapidly cleared from circulating blood; and (d) a 2-g MTW9 carcinoma pours enough cells into the host circulation to transplant the tumor every 24 hr.

Adenocarcinoma↗
PubMed2004

[Detection and clinic implication of circulating tumor cell in patients with lung cancer].

Micrometastasis may occur in the early stage of lung cancer and dissemination of lung cancer cells into blood circulation is pivotal for metastasis. Many approaches, such as polymerase chain reaction, magnetic activated cell sorting, flow cytometery, and rare event imaging system, have been developed rapidly. The detection of circulating tumor cells may renew the clinical stage and treatment of lung cancer.

Biomarkers, Tumor↗