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PubMed1993

[Successful interferon therapy of renal cell carcinoma with tumor thrombus extending into the inferior vena cava--a case report].

It is a fact that there are few effective drugs available except for interferon for that treatment of renal cell carcinoma, and the efficacy rate of interferon is less than 10% even if multiple drug regimens are included. We have experienced a case of renal cell carcinoma in whom interferon therapy was successful in reducing the primary lesion and tumor thrombus extending into the inferior vena cava. A 57-year-old man was admitted to our department with a complaint of macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a right renal tumor and the tumor thrombus. Because of the past history of his myocardial infarction, a radical operation was considered risky. So we started interferon therapy. Four months after the start of interferon therapy, the primary lesion and the tumor thrombus markedly reduced in their size, and the clinical response was evaluated as partial response by response criteria for urological cancer treatment. Therefore, radical nephrectomy and tumor thrombectomy were performed with extracorporeal circulation. Histopathologically, necrosis and lymphocyte infiltration into the cancer cell focus were seen, and these immunologic reactions were considered at the affection of interferon. In some case, interferon therapy is a useful and safe in the treatment of the primary lesion of renal cell carcinoma, and further investigation must be studied.

Carcinoma, Renal Cell↗

PubMed2003

Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma.

To detect circulating RCC cells, we established a nested RT-PCR system for cadherin-6 mRNA, which is specifically expressed in RCC. A total of 121 samples of peripheral blood (34 healthy volunteers and 87 patients with RCC) were analyzed in this study. Total RNA of the monocyte fraction of the blood was extracted, then nested RT-PCR using specific primers was performed to detect mRNA of N-cadherin or cadherin-6. Nested RT-PCR revealed that expression of cadherin-6 mRNA was not present in the blood of most healthy volunteers (absent in 32/34), but positive expression was observed in the blood at concentrations of 10 cells/ml or greater of the SKRC-33 RCC cell line, which is a strong expresser of cadherin-6. In peripheral blood from patients with metastatic disease, cadherin-6 mRNA was detected in 70.4% (19/27). Messenger RNA of cadherin-6 was detectable in 45.0% (27/60) of patients with localized tumors. The PCR-based detection system for peripheral blood samples from patients with metastatic disease could reveal the presence of circulating RCC cells in the blood. Detection of cadherin-6 mRNA in non-metastatic presurgical RCC patients suggests that careful follow-up study is necessary in these patients.

Adult↗

PubMed2001

Polymerase chain reaction in the detection of circulating tumour cells in peripheral blood of melanoma patients.

Conflicting results were obtained by various research groups using the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells circulating in peripheral blood. Whereas 100% positivity was initially reported for stage IV patients, more recent investigations reported positive detection rates between 30% and 50% in patients with disseminated melanoma. While the high detection rate initially reported in metastatic melanoma may be explained by contamination problems, methodological differences in different steps of the technical procedure of RT-PCR may account for the differences reported in more recent examinations. Major differences may result from the kind of blood preparation, the RNA isolation method, the kind of RT enzyme used, and the gene targeted by PCR primers. In our experience, blood purification by a Ficoll gradient increased melanoma cell detection rates compared to RNA extraction from total blood or after erythrocyte lysis. Amplification of MelanA in addition to tyrosinase resulted in a 30% enhanced sensitivity of melanoma cell detection compared to amplification to tyrosinase alone, whereas gp100/pMel17 and MUC18 gene products were already detected in blood from nonmelanoma patients. These findings are in agreement with those of other groups. Currently, an increase in the sensitivity for detection of circulating tumour cells to more than 50% of patients with disseminated melanoma seems to be unlikely. It is interesting that between 15% and 30% positive results and sometimes more have already been obtained from patients with primary melanoma. So far, there is no data for judging the prognostic significance of the detection of circulating tumour cells in patients without clinically recognisable metastases. Our limited experience shows that staging examinations in these patients reveal no proof of macrometastasis. Therefore, it is presently unclear whether these positive findings are associated with long-term prognosis or if they merely reflect false positive findings in this highly sensitive RT-PCR technique.

Biomarkers, Tumor↗

PubMed1987

Evaluation of circulating malignant cells provides prognostic information in cutaneous T cell lymphoma.

Peripheral blood lymphocyte morphology was evaluated prospectively by light microscopy of blood smears and E rosette preparations in 160 patients with cutaneous T cell lymphoma (CTCL). Blood involvement was related to the type of cutaneous T-stage, being present in 90% of patients with erythroderma (T4), 27% of those with cutaneous tumors (T3), 9% of those with generalized (T2), and 0% of those with limited skin plaques (T1). Untreated patients with blood involvement (38 of 105) had a higher frequency of CTCL in lymph nodes and viscera and survival inferior to that of patients with normal or nondiagnostic lymphocyte morphology (P less than .001). Multivariate analysis showed skin stage and age to be the most important pretreatment risk factors for survival. Although blood involvement was not an independent risk factor for the entire group, it appeared to have some adverse influence in the T2/T3 subsets (P = .051). Both lymphocytosis and size distribution of the circulating CTCL cells at initial diagnosis influenced survival. Patients with "mixed cell" cytology (greater than 20% large [greater than 11 microns] CTCL cells), had a worse survival than those with predominantly small circulating CTCL cells (P = .009). The former were more likely to have aggressive features, including lymph node effacement by tumor (P less than .001) and visceral disease (P = .074), than were "small cell" patients. Our data indicate that detailed review of the blood lymphocyte morphology in patients with diagnosed or suspected CTCL is helpful in predicting extent of disease and prognosis.

Age Factors↗

PubMed1976

[About tumor cell findings in the peripheral venous blood, blood-borne metastases and the incidence of thromboembolic episodes in patients with carcinoma of various localisations (author's transl)].

In a retrospective study the frequency distribution of positive screenings for free-floating cancer cells in the peripheral venous blood of patients with cancers of the larynx, the abdomen and the lung was related to the frequency of blood-borne metastases and the incidence of thromboembolic episodes within 5 years of observation. Carcinomas of the larynx which were characterized by a very low frequency of blood-borne metastases are related with a high level of free-floating cancer cells in the venous blood. In contrast abdominal and lung cancers have a high frequency of blood-borne metastases, but a lower level of circulating cancer cells in the peripheral venous blood. Also there is a significant correlation between the initial presence of circulating cancer cells and the incidence of thromboembolic episodes in patients with abdominal and lung cancers, in contrast to patient with cancers of the larynx who lack this coincidence. On the basis of our observation we assume that the circulating tumor cells of the patients with abdominal and lung cancers have a high stickiness, therefore displaying a strong tendency to attach to the vascular endothelium. Only lodged cancer cells are able to penetrate the vessel wall and to develop metastases in the interstitial tissue. Remote and more or less generalized effects of cancer on blood coagulation are observed. In certain instances a disseminated intravascular coagulation results, almost exclusively due to remote effects of clotting factors elaborated by cancer cells, sometimes leading to micro- or macrothrombosis.

Abdominal Neoplasms↗

PubMed2001

Molecular strategy for detecting metastatic cancers with use of multiple tumor-specific MAGE-A genes.

BACKGROUND: The human melanoma-associated antigen family A (MAGE-A) has high specificity and expression in various malignancies, but individual family members are expressed at low frequency in any one particular type of cancer. We therefore developed a method to detect mRNAs from multiple MAGE-A genes in a single reaction. METHODS: Universal MAGE-A (uMAGE-A) primers and probe were designed to reverse-transcribe, amplify, and detect by electrochemiluminescence (ECL) MAGE-A mRNAs on the Origen Analyzer. The assay was performed on total RNA of melanoma (n = 9 cell lines and 24 tumors), breast cancer (n = 7 and 26), and colorectal cancer (CRC; n = 5 and 12). We also evaluated blood from melanoma (n = 50), breast cancer (n = 16), and CRC (n = 21) patients. RESULTS: The uMAGE-A mRNA was detectable in 0.01-1 ng of cell line RNA. The identity of the uMAGE-A cDNA products was confirmed by sequencing and polyacrylamide gel electrophoresis. The uMAGE-A assay increased detection of melanoma, breast cancer, and CRC tumor by 13%, 31%, and 25%, respectively, compared with a MAGE-A1 assay, and by 17%, 19%, and 25%, respectively, compared with a MAGE-A3 assay. The uMAGE-A assay detected circulating tumor cells in the blood of melanoma (24%), breast cancer (25%), and CRC (29%) patients. CONCLUSIONS: The uMAGE-A reverse transcription-PCR/ECL assay provides a practical and sensitive approach for detection of various metastatic cancers in tissues and blood.

Antigens, Neoplasm↗

PubMed1990

[Metastasis in lung and pleura].

The Topography, extent and histopathology of lung and pleural metastases in 132 surgical resections were investigated with regard to primary tumours. The emphasis was on postmortaly obtained angiographic results of the neovascularisation of metastases, mainly by vessels of the functional pulmonary circulation with diameters of 20-60 microns. Different phases of metastatic spread were considered such as invasion, embolisation and implantation. The pathologic-anatomic investigation of metastases is becoming more and more important for morphological quantification of tumour regression following cytostatic therapy and for clarifying unknown primary tumours by the immunohistochemical examination of lung metastases.

Humans↗

PubMedDate not supplied

Arrest of metastatic cells: agents promoting and inhibiting instant non-specific adhesion by fibronectin.

A standard mechanical test was used to quantify instant non-specific adhesion provided in vitro by fibronectin and to demonstrate how this adhesive found on circulating tumour cells can be decreased in potency by 65% when the adherents are coated with dipalmitoyl phosphatidylcholine (DPPC). By comparison, the binding force is increased 97% by addition of sialic acid found on the more potent metastatic cells. The very tacky adhesive resulting from this mixture now fails to be inhibited by DPPC but not by phosphatidylethanolamine found in blood (1). These factors could determine whether a metastatic cell will arrest upon initial contact with a potential host tissue.

Cell Adhesion↗

PubMed2006

The measurement and therapeutic implications of circulating tumour cells in breast cancer.

Circulating tumours cells (CTCs) represent an important biologic link in the spread of breast cancer from primary to metastatic disease. CTCs are strong predictors of prognosis in patients with metastatic breast cancer. Research to date has focused on development of methods with adequate sensitivity and specificity to reproducibly identify these rare events. Future research will focus on the biologic phenotypes of these cells with goals to understand mechanisms of metastasis, to identify novel therapeutic targets, and to monitor response to therapy.

Breast Neoplasms↗

PubMed2000

[Does surgery promote the development of metastasis in melanoma?].

Surgery, which is currently the only curative treatment for malignant melanoma, is suspected, in particular presentations, to induce adverse effects such as an increase of metastasis spread. A literature review was performed in order to examine the alleged causes of such phenomena. A medline search covering the 1985-1999 period was performed first. The chosen articles and the study of the references of each of them produced additional articles. The hypothesis is based on the alleged existence of tumor dormancy as micrometastates at an early stage of the disease. Surgery could induce metastasis spread directly by increasing the rate of circulating tumor cells and indirectly above all by disturbing complex mechanisms of tumor regulation such as the balance between activating and inhibiting factors of tumor angiogenesis. Surgery itself as well as the surgical stress could also make easier metastasis spread owing to antitumor immune mechanisms disturbance. Currently, there is no adequate evidence to induce a modified approach in the management of cutaneous melanoma. Surgery remains the mainstay of treatment. However, basic research on angiogenesis and immunity must be carried on.

Humans↗

PubMed2005

Tumor cell and circulating markers in melanoma: diagnosis, prognosis, and management.

The search is on for biomarkers for use in the diagnosis, staging, prognosis, and management of patients with melanoma. As with many types of cancer, the hematogenous spread of melanoma is a bad prognostic sign, and many groups have attempted to detect circulating melanoma cells in patients with different stages of melanoma. Some studies have used direct extraction of intact tumor cells from the peripheral blood and others the detection of surrogate markers of circulating melanoma cells, such as tyrosinase or MART-1. However, a correlation between the detection of intact melanoma cells in the circulation and prognosis is controversial. Many other biomarkers have also been studied, including lactate dehydrogenase, S100, TA90, and C-reactive protein. Much progress has been made, and preliminary studies have shown promise with many of these markers. Finally, the detection of tumor-specific circulating DNA has shown promise as a prognostic and diagnostic marker of disease in melanoma as well. In this review we examine the most promising biomarkers for use in patients with cutaneous melanoma.

Antigens, Neoplasm↗

PubMed1977

Isolation and characterization of a neuroblastoma cell line from peripheral blood in a patient with disseminated disease.

Circulation in the blood stream of neuroblastoma cells was confirmed by establishment of a cell line from the peripheral blood of a child with disseminated disease. The morphologic, enzymatic, and chromosomal pattern of this cell line was similar to a cell line established from the primary tumor on a previous occasion. The peripheral blood smear did not demonstrate tumor cells but increased numbers of atypical monocytes; lymphoblasts were evident, which may have been unrecognized neuroblasts.

Acetylcholinesterase↗

PubMed1999

International Union Against Cancer. Classification of isolated tumor cells and micrometastasis.

BACKGROUND: Findings of isolated (disseminated or circulating) tumor cells (ITC) by immunocytochemistry and molecular pathology methods have led to varied interpretations and different applications of the TNM system. METHODS: An analysis of the relevant literature was undertaken. In addition, optional proposals for the classification of ITC, micrometastasis, and cytologic results in pleural and peritoneal washings are presented. RESULTS: Immunocytochemistry has a lower false-positive rate than nonmorphologic methods such as flow cytometry or the polymerase chain reaction; therefore the method(s) used always should be recorded. At the current time, the independent prognostic significance of ITC in regional lymph nodes and in the general circulation (blood, bone marrow, and other distant sites) is difficult to assess. To enable comparisons of treatment results and to avoid variation in staging, a finding of ITC should not be considered in the TNM and residual tumor (R) classifications, at least not at the current time. However, for future evaluation of their prognostic significance, the respective findings should be documented according to uniform criteria. CONCLUSIONS: ITC should be distinguished from micrometastasis. To investigate the independent prognostic significance of ITC and of positive lavage cytology, uniform data collection according to the proposed coding schema is recommended.

Ascitic Fluid↗

PubMed2001

Presence of aberrant tumor-reactive immunoglobulins in the circulation of patients with ovarian cancer.

OBJECTIVES: Cancer patients generally exhibit circulating tumor-reactive immunoglobulins; however, these antibodies fail to eradicate tumors or prevent their progression. This study identifies and characterizes an aberrant tumor-reactive IgG population present in women with ovarian cancer. METHODS: In this pilot study, IgG was isolated from the sera of women with advanced-stage ovarian cancer (stages III and IV, n = 62) and age-matched female volunteers (n = 50) by affinity chromatography. These IgGs were characterized on the basis on their aberrant binding to concanavalin A affinity columns. Subsequently, the concanavalin A-binding moiety was localized following IgG fragmentation, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and characterized by oligosaccharide profiling. RESULTS: The level of concanavalin A-binding IgG in our control population was 8.9 +/- 2.9%, whereas in ovarian cancer patients, the level of concanavalin A-binding IgG was 38.8 +/- 7.4%. In the patients with ovarian cancer, 87.5 +/- 5.7% of the tumor-reactive IgG was demonstrated to be concanavalin A-binding. Based on oligosaccharide profiling of the fragmented concanavalin A-binding IgG, the aberrant lectin binding appeared to be the consequence of altered glycosylation of one of the two Fc chains. CONCLUSIONS: While our previous studies have identified the presence of circulating IgG reactive with specific tumor-associated antigens and its association with poor prognosis, this report demonstrated the presence of an aberrantly glycosylated IgG population in cancer patients. This altered IgG appeared to be the primary class of tumor-reactive antibodies in these women.

Antibodies, Neoplasm↗

PubMed2004

Neck mass due to thrombosis of the jugular vein in patients with cancer.

The hypothesis that jugular thrombosis (JT) may cause a mass in the cervical region is usually overlooked. The objective of the present study was to identify the characteristics of neck masses resulting from JT in cancer patients and to analyze the possible reasons for their formation. A retrospective study was conducted on 8 patients with JT affected by 3 types of neoplasia, ie, carcinomas (3 cases), adenocarcinomas (3 cases), and lymphomas (2 cases) located in the breast, digestive apparatus, lymphatic system (2 cases each), lung and an undetermined site (1 case each), diagnosed over the last 12 years. The most frequent symptom of JT was the presence of a mass in the supraclavicular space (62.5% of cases) deeply located on the anterior margin of the sternocleidomastoid muscle and diagnosed by computed tomography and ultrasound. The masses were slightly hardened, with a clearly defined upper limit and an imprecise lower limit and with an irregular surface. The patients also presented with cough, hoarseness, pain during movements, facial edema, and collateral circulation. In one of the patients with a lung cancer, JT symptoms preceded the symptoms of cancer by 2 months. Hypercoagulation, compression, and invasion of a vessel possibly explain the occurrence of JT in these patients.

Adolescent↗

PubMed2006

The clinical significance of circulating tumor cells in the peripheral blood.

Tumors launch malignant cells into the circulation continuously. In early stages, the immune surveillance system eliminates these cells from the circulation, but at later times they may persist longer and be detected. The first recorded evidence of the presence of circulating tumor cells in the peripheral blood of cancer patients was documented in 1869. Now, modern molecular biologic and cell sorting techniques make their detection and characterization more practicable. This review will consider the methods currently available for their detection and characterization, and the clinical implications of their presence in various malignant conditions.

Animals↗

PubMed2004

Microsatellite analysis of serum DNA in patients with head and neck cancer.

We have shown previously that microsatellite alterations in serum DNA was predictive of distant metastasis in a study with 21 primary head and neck squamous cell carcinoma patients. To further investigate serum microsatellite alterations as a prognostic tool, we carried out microsatellite analysis of serum DNA with 10 markers on 152 patients with head and neck cancer. Forty-five percent (68/152) of patients had microsatellite alterations of serum DNA identical to corresponding tumor DNA. In 16 patients that had distant metastasis, 11 patients had a positive serum test (microsatellite alterations detectable in their serum DNA with one or more markers). The difference in distant metastasis rates between the negative and positive serum tests (6.0% [5/84] vs. 16.2% [11/68], RR = 2.7) was clinically significant and almost reached statistical significance (p = 0.06). When the analysis was restricted to patients with recurrent disease, a positive serum test correlated with those who developed distant metastasis (p = 0.04). Other parameters, such as development of recurrence, stage of the cancer, disease-free survival and overall survival, were not associated with a positive serum test. Detecting tumor DNA in serum by microsatellite analysis may help identify patients at risk for distant metastasis. Therefore, circulating tumor cells may contribute to the presence of tumor DNA in the serum. In the future if a serum test is positive, therapeutic approaches may by intensified, such as platinum-based chemoradiation, to reduce distant failures.

Carcinoma, Squamous Cell↗

PubMed2003

Increased circulating AC133+ CD34+ endothelial progenitor cells in children with hemangioma.

UNLABELLED: Hemangioma is the most common soft-tissue tumor of infancy. Despite the frequency of these vascular tumors, the origin of hemangioma-endothelial cells is unknown. Circulating endothelial progenitor cells (EPCs) have recently been identified as vascular stem cells with the capacity to contribute to postnatal vascular development. We have attempted to determine whether circulating EPCs are increased in hemangioma patients and thereby provide insight into the role of EPCs in hemangioma growth. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs) were isolated from hemangioma patients undergoing surgical resection (N = 5) and from age-matched controls (N = 5) undergoing strabismus correction surgery. PBMCs were stained with fluorescent-labeled antibodies for AC133, CD34, and VEGFR2/KDR. Fluorescent-labeled isotype antibodies served as negative controls. Histologic sections of surgical specimens were stained with the specific hemangioma markers Glut1, CD32, and merosin, to confirm the diagnosis of common hemangioma of infancy. EPCs harvested from healthy adult volunteers were stained with Glut1, CD32, and merosin, to assess whether cultured EPCs express known hemangioma markers. Hemangioma patients had a 15-fold increase in the number of circulating CD34 AC133 dual-staining cells relative to controls (0.78+/-0.14% vs.0.052+/-0.017%, respectively). Similarly, the number of PBMCs that stained positively for both CD34 and KDR was also increased in hemangioma patients (0.49+/-0.074% vs. 0.19+/-0.041% in controls). Cultured EPCs stained positively for the known hemangioma markers Glut1, CD32, merosin. CONCLUSIONS: This is the first study to suggest a role for EPCs in the pathogenesis of hemangioma. Our results imply that increased levels of circulating EPCs may contribute to the formation of this vascular tumor.

AC133 Antigen↗