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Results for “Neoplastic Cells, Circulating”

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PubMed2004

Quantification of disseminated tumor cells in the bloodstream of patients with hormone-refractory prostate carcinoma undergoing cytotoxic chemotherapy.

Only very limited data are available on the presence of circulating tumor cells during cytotoxic chemotherapy for hormone-refractory prostate cancer. We analyzed 241 blood samples from 32 patients with hormone-refractory PCa under a chemotherapy schedule. The etoposide, estramustine phosphate and paclitaxel scheme as well as the mitoxantrone and prednisone schedule were used to treat patients with advanced prostate cancer. The pre-therapy serum PSA values were in the range from 1.4 ng/ml to 2,870.9 ng/ml (median 74.5 ng/ml). We isolated the CD45-negative cell population by immunomagnetic depletion from 16 ml of peripheral blood samples. These cells were stained for pan-cytokeratin and evaluated. Patients were observed for an average of 67 weeks (range 16-120). In 77 (32%) samples originating from 27 (84%) patients, tumor cells were detected at least once. Twenty of these patients had shown an initial response to therapy as indicated by a >/=50% decrease of the pre-therapy PSA value. Of these, 14 patients experienced a biochemical and/or a clinical progression. For 13 (93%) of them, circulating tumor cells were detectable during the time of PSA response, i.e. during the PSA decline and before a biochemical or clinical progression. However, we could not correlate the amount of circulating tumor cells with the observed PSA levels. This study demonstrates that circulating tumor cells are detectable during chemotherapy for hormone-refractory prostate cancer regardless of the degree of PSA response.

Adenocarcinoma↗

PubMed2001

Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer.

BACKGROUND: Metastatic disease in colorectal cancer results from hematogenic dissemination of tumor cells. This dissemination can be explained by 2 concepts: (1) regional spread of tumor cells via portal venous drainage into the liver as the first site of metastasis and (2) early spread of tumor cells into central and peripheral venous blood as evidence of systemic hematogenic tumor cell dissemination. HYPOTHESIS: Tumor cell detection in different blood compartments could help to understand the predominant pattern of hematogenic tumor cell dissemination in colorectal cancer. DESIGN: Prospective consecutive series. SETTING: University hospital. PATIENTS AND METHODS: Mesenteric, central, and peripheral venous blood samples from 40 patients with colorectal cancer were examined by cytokeratin 20 reverse transcriptase polymerase chain reaction. MAIN OUTCOME MEASURES: Sensitivity and specificity of cytokeratin 20 reverse transcriptase polymerase chain reaction, and frequency of tumor cell detection in different blood compartments. RESULTS: Tumor cells were found in mesenteric venous blood of 20 of 40 patients, central venous blood of 6 of 40 patients, and peripheral venous blood of 2 of 19 patients. The detection rate in mesenteric venous blood was significantly higher than that in central and peripheral venous blood (P<.001). CONCLUSIONS: The significantly higher detection rate in mesenteric venous blood emphasizes the importance of the filter function of the liver for circulating tumor cells in portal venous blood. Tumor cell detection in central and peripheral venous blood, however, shows that this filtering process is limited and indicates early systemic hematogenic tumor cell dissemination in colorectal cancer.

Biomarkers, Tumor↗

PubMed1985

[Hemostatic mechanisms and malignant tumors].

The mutual relationships between malignant tumours and mechanisms of blood coagulation are presented in a brief survey. In this connection, the mechanisms of a tumour cell entering the circulation through the vessel well and its leaving into the tissues are discussed, the theory of microtrauma being used for explaining these processes. Subsequently, the alterations to be found in the count and function of thrombocytes after contact with a malignant cell and the impact on this cell by blood platelets are represented. As a third factor the activation of blood coagulation which is exercised by substances with a procoagulatory effect produced by the malignant tissue and the frequently observed thrombosis in the course of neoplastic diseases are dealt with in connection with blood level changes of some coagulation factors. In a fourth section the significance of fibrinolysis, its activation and inhibition as well as the production of fibrinolytic activators by neoplasms are discussed.

Animals↗

PubMed1999

The effects of transurethral resection and cystoprostatectomy on dissemination of epithelial cells in the circulation of patients with bladder cancer.

This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had different stages and grades of bladder cancer and two patients had benign bladder conditions. Twenty-five cancer patients required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1-G2: n = 19; pT1G2: n = 1) and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1) and one man received chemotherapy for metastatic disease. Venous blood (10 ml) was obtained from the antecubital fossa in each patient, before and 1-2 h after completion of surgery, and prior to treatment in the metastatic patient. An indirect immunocytochemical technique was used to detect circulating epithelial cells after centrifugation on Ficoll gradient and fixation of mononuclear cells on slides, using a monoclonal antibody directed against three cytokeratins: CK8, CK18 and CK19. Circulating epithelial cells were detected only in the patient with metastatic disease. None of the other patients had evidence of epithelial circulating cells before or after surgery. The results suggest that irrespective of disease stage and grade, neither endoscopic nor open bladder surgery leads to detectable dissemination of urothelial cells in the peripheral circulation. These procedures are therefore unlikely to increase the risk of progression and metastasis in transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗

PubMed1995

Unusual recurrence pattern in peritorcular meningioma--case report.

A 45-year-old female presented with a recurrent peritorcular meningioma. The recurrence was very unusual as the tumor arose from the confluens sinuum and extended to the left jugular bulb completely within the sinuses, obstructing the venous outflow. However, there were no clinical symptoms or neurological abnormalities, due to the development of collateral circulation. The possibility of intrasinus recurrence should always be considered in patients with tumor invasion to sinus walls, even if the patient has no clinical symptoms or neurological abnormalities.

Cranial Sinuses↗

PubMed1999

Comparison of immunocytochemistry, reverse transcriptase polymerase chain reaction, and nucleic acid sequence-based amplification for the detection of circulating breast cancer cells.

Detection of tumor cells in blood and bone marrow is increasingly used for the staging of patients with breast cancer and to evaluate the presence of tumor cells in peripheral blood progenitor cell collections to be used after high-dose therapy. We evaluated the sensitivity and specificity of three different methods for detection of tumor cells among non-tumor tissue. An immunocytochemical assay using antibodies directed against epitopes of the cytokeratin-19 (CK19) protein and two RNA-based methods: reverse transcriptase polymerase chain reaction (RT-PCR) and Nucleic Acid Sequence-Based Amplification (NASBA) for the same target gene were tested. With all the three methods, false-positive results were observed when peripheral blood mononuclear cells (PBMC) of healthy volunteers were tested. There was no concordance between the RNA-based assays and the immunocytochemical assay. The false-positive results in the RNA-based assays may be due to 'illegitimate expression' of epithelial genes in normal PBMC. The false-positive results in the immunocytochemical assay resulted from background staining of monocytes and granulocytes. This study demonstrates that CK19 is not a suitable target to detect the presence of breast tumor tells in PBMC. To reliably detect circulating tumor cells with RNA methods, the selection of suitable target genes is required, which are highly expressed in tumors but not at all in normal cells of blood and bone marrow. Genes with such characteristics may be identifiable with novel differential display techniques.

Breast Neoplasms↗

PubMed1997

[Molecular diagnostic detection of circulating tumor cells and their prognostic implications].

While not all circulating tumor cells survive, one could postulate that patients with circulating tumor cells might be candidates for adjuvant chemotherapy because of the risk of relapse. Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging of cancer. In malignant melanoma, the detection of circulating melanoma cells by tyrosinase RT-PCR correlated with the clinical stage of patients and was an independent prognostic factor for recurrence. A strong association was found between the detection of neuroblastoma cells in circulation by tyrosine hydroxylase RT-PCR with bone marrow micrometastasis. This method may be of use to identify early signs of relapse in disease-free patients. In prostatic cancer, the frequency of positivity for detection of circulating tumor cells in peripheral blood by PSA RT-PCR increased with tumor stages but a significant proportion of patients with metastatic disease were negative. The prognostic significance of the detection of tumor cell in blood in other epithelial tumors is not established and will require further long-term follow-up study.

Biomarkers, Tumor↗

PubMed2005

Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma.

We detected circulating plasma cells (PCs) by flow cytometry in 302 patients with newly diagnosed multiple myeloma (MM) by gating on CD38+CD45- cells. The number of circulating PCs per 50 000 mononuclear cells was reported. In 80 (27%) patients, no circulating PC were seen; 106 (35%) patients had 1 to 10 and 115 (38%) patients had more than 10 circulating PCs. Median overall survival for the 302 patients was 47 months. Patients with 10 or fewer circulating PCs had a median survival of 58.7 months, whereas patients with more than 10 circulating PCs had a median survival of 37.3 months (P = .001). On multivariate analysis, the prognostic value of circulating PCs was independent of beta2-microglobulin, albumin, and C-reactive protein. There was only a weak correlation between tumor mass and circulating PCs, suggesting that the appearance of circulating PCs may be a reflection of tumor biology. We conclude that the number of circulating PCs measured by flow cytometry in patients with newly diagnosed MM is an independent predictor of survival.

Adult↗

PubMed2001

Detection of tumor cells in the portal and peripheral blood of patients with colorectal carcinoma using competitive reverse transcriptase-polymerase chain reaction.

BACKGROUND: In spite of many reports, it remains unclear whether the presence of tumor cells in circulating blood flow predicts a poor prognosis. METHODS: Competitive seminested reverse transcriptase-polymerase chain reaction (RT-PCR), a technique for the quantitative detection of tumor cells, was applied to detect the presence of tumor cells in portal and peripheral blood samples from 121 patients with colorectal carcinoma and to clarify their clinical significance. This technique can detect one carcinoembryonic antigen (CEA) mRNA-expressing tumor cell in 1 x 10(5) normal lymphocytes. RESULTS: Six of 33 healthy volunteers (18%) demonstrated a positive reaction to this technique. CEA mRNA expression was detected in the portal blood in 51% of patients and in the peripheral blood in 42% of patients. The results from the two blood samples were consistent in 91% of patients. The positive expression rates for portal blood in patients with T1 tumors and those with TNM Stage I disease were 38% and 45%, respectively. The positive rate was significantly higher in patients with colon carcinoma and those with Stage III or IV disease. CEA mRNA expression, quantitatively measured (x 10(-8)/beta-actin), was 22.9 +/- 35.1 in the portal blood and 19.9 +/- 40.0 in the peripheral blood, with no statistically significant difference. A significant positive correlation was noted between portal and peripheral CEA mRNA expression levels according to Spearman correlation analysis (correlation coefficient = 0.78; P < 0.01). Multivariate analysis revealed that the positive rate and level of CEA mRNA expression in the portal and peripheral blood did not appear to be influenced by the established prognostic factors. CONCLUSIONS: The presence of circulating tumor cells might be of less value as a prognostic factor because they also can be detected in patients with early-stage colorectal carcinoma and appeared to be independent of the conventional prognostic factors.

Blood Specimen Collection↗

PubMed1997

Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation.

We sought to determine whether circulating tumor cells in the blood stem cell harvest from patients with multiple myeloma are associated with a shortened disease-free survival. Prospective analysis was performed in 33 patients of blood obtained at leukapheresis for future transplantation. An immunofluorescence microscopy procedure identified the tumor cells by their morphology and monotypic light chain staining. Eighteen patients had increased (> or = 0.2 x 10(6)/l) monoclonal plasma cells circulating in the blood at stem cell harvest. Fifteen of the 18 have relapsed, with a median relapse-free survival of 6.2 months. Of 15 patients with < 0.2 x 10(6) cells/l, seven have relapsed, with a median relapse-free survival of 22.5 months (P = 0.008). Patients with circulating plasma cells showed a trend toward shorter overall survival (P = 0.078). In a multivariate analysis using the bone marrow plasma cell labeling index and beta 2-microglobulin, the absolute number of plasma cells in the stem cell harvest achieved borderline significance for predicting relapse-free survival (P = 0.057). In conclusion, increased monoclonal plasma cells in the blood stem cell harvest are associated with a shortened relapse-free survival. This does not necessarily indicate that the circulating plasma cells were responsible for relapse. These results, however, have implications with regard to the timing of obtaining blood stem cells for patients who are candidates for ablative chemotherapy.

Adult↗

PubMed1987

Detection and characterization of circulating rat mammary tumor cells in buffy coat and correlation with metastasis.

A new method for detecting bloodborne TMT-081 rat mammary tumor cells in buffy coat has revealed dose-dependent variations in the latency period after inoculation of tumor cells, the concentration of circulating tumor cells, and the incidence of metastases. Cells isolated from buffy coat of right ventricular blood were more tumorigenic than tryptically dispersed cells from solid tumors. With the new method circulating tumor cells can be detected at concentrations as low as 3 cells/microliter of buffy coat, or approximately 60 cells/ml of whole blood. The morphologic and ultrastructural features of the primary tumor were generally retained in both the circulating and tryptically dispersed cells, as shown by light and electron microscopy. A sparse distribution of intermediate filaments was revealed by high-voltage electron microscopy, although the filaments were not evident in conventional transmission electron micrographs. They were identified as keratin by immunofluorescence studies.

Animals↗

PubMed2001

Methylation profiling of human cancers in blood: molecular monitoring and prognostication (review).

Cancer is a polygenetic and polyepigenetic disease. Circulating tumor cells in peripheral blood have been demonstrated to reflect the biological characteristics of tumors including the potential of metastasis development and tumor recurrence. Aberrant promoter methylation has emergingly become a fundamental molecular abnormality leading to transcriptional silencing of tumor suppressor genes, DNA repair genes and metastasis inhibitor genes, and is linked to the predisposition of genetic alterations of other cancer-associated genes. This epigenetic inheritance has significant biological implications for cancer progression and metastasis formation. Of significance, DNA hypermethylation of multiple genes successfully detected in circulating tumor cells from cancer patients may prove valuable for disease monitoring. A number of epigenetic markers may feasibly enable the detection of circulating tumor cells from patients with different cancer types. The prognostic and therapeutic implications of aberrant DNA methylation could eventually bring forth improved outcome of cancer patients. A growing body of evidence and future advances in understanding cancer epigenetics may fuel us to monitor and treat cancers in alternative ways.

DNA Methylation↗

PubMed2000

RT-PCR-based detection of occult disseminated tumor cells in peripheral blood and bone marrow of patients with solid tumors. An overview.

Despite recent progress in early detection and local curative therapy, patients with primary epithelial cancer quite frequently relapse with incurable metastasis. Early disseminated tumor cells that may be seminal for distant failure and are undetectable by current diagnostic methods have been identified by immunocytochemical techniques in bone marrow of cancer patients using monoclonal antibodies against cytokeratins. Recently, promising new molecular approaches, namely, reverse transcriptase--polymerase chain reaction (RT-PCR) assays, have been suggested as a potential technique for the detection of minimal residual tumor burden by targeting mRNA transcribed from epithelial genes in bone marrow, peripheral blood, or lymph nodes. Several studies using RT-PCR thus far indicate a highly sensitive and specific staging tool, although the prognostic value is still controversial. However, limitations may arise from ectopic expression of marker mRNA in hematopoietic cells and deficient expression in circulating tumor cells. The present review focuses on the relevant literature and demonstrates the range of current applications of RT-PCR-based assays for detecting disseminated tumor cells in peripheral blood and bone marrow of patients with solid tumors. We will both summarize technical evaluations of published molecular approaches and discuss the widely disparate results on PCR findings in clinical studies.

Bone Marrow↗

PubMed1962

Cancer cells in the circulating blood, with reference to cancer metastasis.

The author discusses the relation between the presence of cancer cells in the circulating blood and the development of metastasis, as demonstrated by studies on animals with experimentally induced tumours, by post-mortem studies on fatal human cases of cancer, and by studies on patients operated upon for stomach cancer. Although the correlation between the presence of tumour cells in the blood and the occurrence of metastatic lesions was found to be less close in the human cases of cancer than in the experimental animals, the author considers that it was sufficiently marked to justify the assumption that the appearance of tumour cells in the circulating blood is an important link in the chain of processes leading to cancer metastasis. In conclusion, the author puts forward the suggestion, based on the results of animal experiments, that chemotherapy might have an inhibitory effect on the liberated tumour cells in the blood, particularly if these cells are present only in small numbers, and thus be instrumental in halting the course of metastasis.

Animals↗

PubMed1993

Venous surgery in resection for abdominal malignancy.

Vascular surgical techniques were applied to the radical resection of carcinoma of the liver, biliary tract and pancreas. Distal and proximal portal vein reconstruction, respectively, was carried out in 16 patients with carcinoma of the pancreas and 16 with cancer of the liver and biliary tract. Hepatic vein trunks with tumour involvement were resected and reconstructed by various techniques in six patients. A suprarenal segment of the inferior vena cava was completely replaced by a prosthetic graft in three patients with retroperitoneal malignancy. Venous surgery increased the resectability of malignant tumours and preserved circulation in the organ remnant, although the long-term effect on survival is not yet clear. Vascular surgical techniques should be applied more widely in the field of general abdominal surgery.

Abdominal Neoplasms↗

PubMed1998

Ewing family tumors: potential prognostic value of reverse-transcriptase polymerase chain reaction detection of minimal residual disease in peripheral blood samples.

In more than 95% of patients, the Ewing family of tumors (ET) has chimeric transcripts caused by fusion of the EWS gene to either FLI1 or ERG. The presence of specific EWS-FLI1 or EWS-ERG transcripts in peripheral blood (PB) samples of patients being treated for ET was prospectively evaluated, and these data were correlated to their clinical status. The authors studied 113 PB samples from 28 patients with ET. Treatment included chemotherapy, radiotherapy, and surgical excision of tumor after induction therapy. PB samples were taken prospectively at least 2 weeks after resection of tumor. Nested reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot was performed in all samples. Resected tumors were reviewed for the degree of response to chemotherapy and volume. Seventy-seven PB samples from 28 patients had EWS-FLI1/ERG transcripts. In 11 patients, PB samples became negative with treatment, and, in 5 of them, the samples remained negative throughout the study. Samples taken during progression were always positive and, in 4 patients, became positive before progression was clinically evident. All patients with transcripts other than EWS-FLI1 type 1 (n = 3) died from tumor progression. This is a sensitive assay to monitor circulating tumor cells in Ewing tumors. The preliminary data suggest that progression is preceded by positive samples and may be related to specific transcript types.

Adolescent↗

PubMed1999

Detection of prostatic specific membrane antigen messenger RNA using immunobead reverse transcriptase polymerase chain reaction.

The present study was performed to detect circulating prostatic carcinoma (PC) cells using a novel three-step immunobead reverse transcriptase (RT) polymerase chain reaction (PCR) assay for prostatic specific membrane antigen (PSMA) messenger RNA (mRNA). The sensitivity and specificity of this technique was assessed and the incidence of immunobead RT-PCR positivity correlated with progressive metastatic disease and serum prostatic specific antigen (PSA) levels. Fifty peripheral blood (PB) samples from 46 patients with PC were incubated with magnetic beads coated with Ber-EP4 antibody directed against the human epithelial antigen a membrane antigen widely expressed by epithelial cells. The epithelial cell-enriched magnetic fraction was then subjected to mRNA isolation using oligo-deoxythymidine (dT) magnetic beads. Nested RT-PCR for PSMA was performed on the mRNA oligo-dT complex and the identity of the RT-PCR products was confirmed by Southern blotting. Twenty-one PB samples from 8 control subjects without PC were also evaluated. Three-step immunobead PSMA RT-PCR was able to detect one PC cell per 1 mL of PB. The positivity rate of the RT-PCR assay was significantly higher (11 of 25; 44%) in patients with metastatic tumor than in patients with non-metastatic disease (1 of 21; 5%) (P = 0.003). In patients with metastatic PC, RT-PCR positivity was much higher in patients with progressive disease (10 of 13; 77%) than in patients with responding or stable disease (1 of 12; 8%) (P = 0.001). There was a statistically significant correlation between immunobead PSMA PCR positivity and high levels of serum PSA (P = 0.005). All control subjects without PC tested negative for PSMA PCR. The three-step immunobead RT-PCR for PSMA can detect circulating PC cells with high specificity and sensitivity. Preliminary data show a strong correlation between immunobead PCR positivity, the presence of progressive metastatic disease, and high levels of serum PSA.

Antigens, Surface↗

PubMedDate not supplied

Perioperative detection of circulating cancer cells in patients with colorectal hepatic metastases.

BACKGROUND/AIMS: Surgical resection is the most effective therapy for metastatic colorectal cancer to the liver. However, the selection criteria for patients who may benefit from partial hepatectomy are not fully defined. The aim of this study was to evaluate the usefulness of perioperative molecular detection of circulating cancer cells in predicting clinical outcome in patients with colorectal metastatic liver cancer. METHODOLOGY: Blood samples were obtained perioperatively from the portal vein, peripheral artery, and superior vena cava in 16 consecutive patients with colorectal liver metastases who have undergone partial hepatic resection. We analyzed circulating cancer cells using a carcinoembryonic antigen-specific nested reverse transcriptase-polymerase chain reaction. RESULTS: Positive carcinoembryonic antigen-mRNA expression was detected in 7 (43.8%) of 16 patients. Six (85.7%) of those 7 patients had hematogenous rerecurrences during the 1- to 3-year follow-up period. None of 9 negative-patients showed re-recurrence (p < 0.01). Among the 9 of 16 patients receiving postoperative adjuvant chemotherapy, no clear effect was noted regarding re-recurrence in the positive carcinoembryonic antigen-mRNA patients. CONCLUSIONS: These results suggest that the molecular detection of circulating cancer cells at the time of surgery for colorectal liver metastases could be one measure of high-risk patients for hematogenous re-recurrence after partial hepatic resection.

Carcinoembryonic Antigen↗