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Results for “Neoplastic Cells, Circulating”

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PubMed2002

The molecular detection of circulating tumor cells in bladder cancer using telomerase activity.

PURPOSE: The detection of circulating tumor cells and micrometastases may have important prognostic and therapeutic implications. We investigated telomerase activity as a molecular marker for detecting bladder carcinoma cells in blood. MATERIALS AND METHODS: Peripheral blood mononuclear cells were isolated from whole blood using Ficoll/Hypaque. Immuno-magnetic beads labeled with an epithelial specific antibody were used to harvest epithelial cells from peripheral blood mononuclear cells. Telomerase activity was detected in this select population using the telomerase-polymerase chain reaction-enzyme-linked immunosorbent assay test based on the telomerase repeat amplification protocol method. The clinical applicability of this technique was explored by evaluating 30 patients with muscle invasive or metastatic bladder carcinoma and 17 healthy volunteers. RESULTS: Telomerase expression was detected in 27 of the 30 patients (90%) with high grade, muscle invasive or metastatic bladder cancer but in none of the 17 healthy controls. CONCLUSIONS: This test is a minimally invasive and specific approach for detecting circulating epithelial cells in patients with bladder cancer. This method may have great value for monitoring cancer progression.

Aged↗

PubMed1983

Recovery of malignant tumor cells from the right atrium during hepatic resection for hepatocellular carcinoma.

Tumor cells were recovered from the right atrium in three of five patients during hepatic resection for hepatocellular carcinoma. Mechanical factors during blunt mobilization and rotation of the hepatic tumor appeared to be responsible for tumor dislodgement into the venous circulation. Tumor embolization to the lungs may be one of the important reasons for the poor results of surgery in this disease. Two possible technical and therapeutic modifications are suggested to prevent or neutralize this phenomenon.

Blood↗

PubMed2005

Detection of cytokeratin 20 mRNA in the peripheral blood of patients with colorectal cancer by immunomagnetic bead enrichment and real-time reverse transcriptase-polymeras chain reaction.

BACKGROUND: Detection of circulating cancer cells is a useful indicator for the risk of recurrence of advanced carcinoma. The aim of the present study was to evaluate the potential value of a novel approach to detect the circulating cancer cells in patients with colorectal cancer. This method is based on a combination of isolation of epithelial cell by a combination of negative and positive immunomagnetic beads with detection of cytokeratin 20 (CK20) mRNA by reverse transcriptase-polymeras chain reaction (RT-PCR). METHODS: Peripheral blood samples were collected from 40 patients with colorectal carcinoma on the day before operation or chemical therapy. Mononuclear cells (MNC) were isolated by centrifugation through a Ficoll gradient. Each MNC sample was equally divided into three parts and then CD45 immunomagnetic beads and/or Ber-EP4 immunomagnetic beads were used to enrich colon cancer cells. Finally, the CK20 mRNA was detected by real-time quantitative RT-PCR. As a control, LS174T colon cancer cells were serially diluted with blood from healthy individuals. RESULTS: When CD45 and Ber-EP4 immunomagnetic beads were used successively, a significant correlation between CK20 mRNA levels and the initial cell concentrations was found in the control recovery experiment. The sensitivity of the assay was one cancer cell in 1 mL healthy blood. In the patient group, CK20 mRNA was detected in 80.0%, 82.5% and 72.5% of patients when CD45, Ber-EP4, and CD45/Ber-EP4 immunomagnetic beads were used, respectively. The positive detection rates of patients with colorectal carcinoma at Dukes A, B, C, and D stage were 0.0% (0/2), 33.3% (3/9), 86.7% (13/15), and 92.9% (13/14), respectively. The CK20 mRNA positive detection rate in peripheral blood was significantly correlated with tumor diameter (P < 0.01, chi(2)), lymphatic metastasis (P < 0.05) and hepatic metastasis (P < 0.05), but not with the differentiation of tumor cells. CONCLUSION: The combined use of negative and positive immunomagnetic beads followed by amplification of CK20 mRNA by means of RT-PCR is a non-invasive, sensitive, and specific assay for the detection of circulating colonic cancer cells.

Aged↗

PubMed1998

Detection of cancer cells in peripheral blood of breast cancer patients using reverse transcription-polymerase chain reaction for epidermal growth factor receptor.

The epidermal growth factor receptor (EGFR) has been reported to be expressed in high levels in primary breast cancer by immunohistochemistry. In the present study, a reverse transcription (RT)-PCR assay using EGFR primers was developed and evaluated for the detection of circulating micrometastases in the blood of breast cancer patients. Total RNA was extracted from breast cancer cell lines and from the blood of 23 control individuals and 37 breast cancer patients. After reverse transcription, outer and nested primers for EGFR were used for cDNA amplification. RNA integrity was confirmed with parallel RT-PCR amplification using beta2-microglobulin primers. PCR products were electrophoresed on agarose gels containing ethidium bromide and visualized by UV photography. Southern blotting was used to confirm EGFR specificity. The nested EGFR RT-PCR assay was capable of detecting a lower limit of 100 fg of total RNA from the A431 cell line. EGFR RNA was identified from the blood of 4 of 18 (22%) metastatic breast cancer patients, 0 of 6 locally recurrent breast cancer patients, 0 of 13 adjuvant breast cancer patients, and 0 of 23 controls (P = 0.03, metastatic versus control). The 18 metastatic breast cancer patients all had progressive disease at the time of blood sampling. The identity of the four EGFR-positive bands was confirmed by Southern blotting. The presence of RT-PCR positivity for EGFR was not a treatment-related phenomenon, because three of the four EGFR-positive patients were not receiving treatment at the time of blood collection. RT-PCR for EGFR is a sensitive and specific method for the detection of circulating micrometastases in a proportion of patients with metastatic breast cancer.

Biomarkers, Tumor↗

PubMed2004

Impact of circulating free tumor cells in the peripheral blood of colorectal cancer patients during laparoscopic surgery.

Despite widespread use of laparoscopic surgery for colorectal operations, its application for curative resection of colorectal cancer is still controversial. One of the major concerns is the impact of the laparoscopic procedure on dissemination of tumor cells. The main purpose of this study was to investigate the impact of laparoscopic surgery on circulating tumor cells in colorectal cancer patients. Quantitation of circulating free tumor cells (FTCs) was performed preoperatively, during the operation, and 14 days later by means of real-time quantitative reverse transcriptasepolymerase chain reaction (RT-PCR) targeting guanylyl cyclase C (GCC) mRNA in 42 colorectal cancer patients undergoing laparoscopic resections. Despite an increasing trend of FTC detection in patients with advancing stage, there is no significant difference in the preoperative FTC level by disease stage. No elevation in FTC level was found during the laparoscopic procedure in most patients compared with their preoperative FTC value. Patients with a persistently high FTC load [per nucleated blood cells (NBCs)] (> 10(2) FTCs/10(6) NBCs) 2 weeks postoperatively portends a poor prognosis regarding disease recurrence and tumor-related mortality when compared to those with an undetectable or low FTC load (< or = 10(2) FTCs/10(6) NBCs). We concluded that the laparoscopic procedure itself had no significantly deleterious effect on circulating FTCs and that the detection of FTCs by real-time qRT-PCR might be of clinical importance during the postoperative follow-up for colorectal cancer patients.

Adult↗

PubMed1999

Influence of sextant prostate needle biopsy or surgery on the detection and harvest of intact circulating prostate cancer cells.

PURPOSE: The feasibility of harvesting intact, circulating prostate cancer cells from the blood of men with advanced prostate cancer has previously been demonstrated. We studied the influence of sextant prostate needle biopsy and radical prostatectomy on harvesting intact circulating prostate cancer cells. MATERIALS AND METHODS: Via standard venipuncture 20 c.c. blood were obtained preoperatively, and 30 minutes and 3 days postoperatively from 23 men with clinically localized prostate cancer undergoing surgery. Similarly, blood was obtained before and after routine prostate biopsy from 13 men for an elevated prostate specific antigen level and/or abnormal digital rectal examination. The blood cells were removed via density centrifugation and magnetic cell sorting. The remaining prostate epithelial cells were characterized by indirect fluorescent immunocytochemical staining and fluorescent in situ hybridization using deoxyribonucleic acid probes. RESULTS: Sextant biopsy of the prostate induced circulating cells in 3 of 13 men (23%), only 1 of whom demonstrated cells with aneuploidy (Gleason score 3+4 = 7). Circulating cells were detected preoperatively, 30 minutes or 3 days postoperatively in 35% of radical prostatectomy cases. Of the patients 13% had detectable circulating cells 30 minutes postoperatively only and 9% had cells harvested on postoperative day 3. Persistence of circulating prostate cancer cells was noted in 13% of men on postoperative day 3. Serum prostate specific antigen level and pathological stage did not appear to be related to harvested cell number. CONCLUSIONS: Prostate cancer cells can be harvested from men with clinically localized disease undergoing sextant needle biopsy or radical prostatectomy. Routine prostate biopsy and surgery may influence the number of measurable circulating cells in the short term but the clinical significance and long-term prevalence of detectable circulating cells are unknown. Further studies are needed to evaluate the clinical usefulness of this assay for detecting, staging and monitoring prostate cancer.

Biopsy, Needle↗

PubMed1998

Effect of neoadjuvant androgen deprivation on circulating prostate cells in the bone marrow of men undergoing radical prostatectomy.

Our objective was to determine the effect of neoadjuvant hormonal therapy on the presence of circulating prostate cells in patients undergoing radical prostatectomy for prostate cancer. A total of 60 patients at high risk for extraprostatic disease were analyzed for the presence of circulating prostate cells using reverse transcriptase PCR (RTPCR) amplification of the prostate-specific antigen mRNA. Twenty-nine patients underwent radical prostatectomy for a clinical T2b-c tumor or a stage T1c-T2a tumor and a serum prostate-specific antigen level > or =10ng/ml (radical prostatectomy alone), and 31 similarly staged patients received neoadjuvant hormonal therapy before radical prostatectomy (neoadjuvant). Bone marrow samples were used for RTPCR analysis. Twenty-four percent and 58% of the radical-prostatectomy-alone patients and neoadjuvant patients had organ-confined disease, respectively (P = 0.007). In the radical-prostatectomy-alone group, 77% and 14% of patients with extraprostatic and organ-confined disease were RTPCR positive, respectively (P = 0.03). However, in the neoadjuvant group, 46% and 28% of patients with extraprostatic and organ-confined disease were RTPCR positive, respectively (P = 0.29). For patients that were RTPCR positive, 45 % of the neoadjuvant patients had organ-confined disease compared with 6% in the radical-prostatectomy-alone patients (P = 0.018). These data suggest that a subset of the neoadjuvant patients are converted to organ confined disease without eliminating the prostate cells in the bone marrow. Our data suggest that hormonal therapy before radical prostatectomy decreases the occurrence of extraprostatic disease but, to a lesser degree, the incidence of circulating prostate cells. This may partially explain why hormonal therapy before radical prostatectomy has not improved disease-free survival.

Androgen Antagonists↗

PubMed2003

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients.

We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P=0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P=0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral blood.

Antigens, Neoplasm↗

PubMed1983

Inhibition of the arrest of hematogenously disseminated tumor cells.

Most metastases in patients occur as a result of hematogenous dissemination of tumor cells. This process of metastasis is complex and consists of several steps, foremost of which is the arrest of circulating emboli in capillary beds and the formation of a thrombus at that site. Thrombus formation in the metastasis of human cancer was described first by Billroth in 1878. It was reported that the organization of tumor cell emboli, and the subsequent penetration of tumor cells into the capillary wall, was the first stage of metastasis. Since then, many investigations and observations have been made clinically as well as experimentally to clarify the process (or mechanisms) of tumor cell arrest and how to inhibit it. Coagulative and fibrinolytic pathways were believed to have a main role in thrombus formation. However, other factors responsible for the relationship between tumor cells and the host must be also considered. Elegant and extensive studies by Fidler and Kripke demonstrated that development of metastasis is not a random process, but a selection process of specialized subpopulations of highly metastatic cells within the primary tumors. Biochemical constituents and ionic properties on cell surfaces, deformability or locomotive activities of tumor cells, as well as thrombo-plastic-fibrinolytic activities, are also important factors determining the arrest patterns of circulating tumor cells. On the other hand, host defense factors against tumor cells in the bloodstream have been attracting much attention recently in tumor immunology. Host defense factors relating the arrest of tumor cells to the establishment of metastatic foci seemed difficult to define, since many studies showed contradictory data concerning the influence of immune response on tumor cell arrest. Hemodynamic abnormality may also influence the arrest of tumor cells in the circulation. Hypercoagulability induced from host tissues is greatly associated with the arrest patterns. Platelet activities might affect thrombus formation. Nevertheless, exact explanations of the process or mechanisms inhibiting or enhancing the arrest of tumor cells after hematogenous dissemination have not been obtained. In any event, for cancer treatment, it is important to determine which substances inhibit the arrest of circulating tumor cells and how to prevent hematogenous metastasis. In this review, we will focus upon coagulative and fibrinolytic processes and then upon substances that inhibit the arrest of circulating tumor cells. Furthermore, some comments on the possible clinical applications of inhibitory substances for prevention of cancer metastasis are added.

Animals↗

PubMed2005

Immunobead multiplex RT-PCR detection of carcinoembryonic genes expressing cells in the blood of colorectal cancer patients.

Circulating cell detection using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques has been studied as a new prognostic factor in colorectal cancer patients. With the view of enhancing detection sensitivity, we developed a new multiplex RT-PCR assay for circulating cell detection based on the expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5; formerly CEA) and CEACAM7 (formerly CGM2). Between November 2002 and December 2003, 45 stage III-IV, 39 stage I-II colorectal cancer patients, 32 non-colorectal cancer patients and 41 healthy individuals were included. Positive selection using HEA-125 immunobeads was applied to blood samples before mRNA extraction, cDNA synthesis and a multiplex CEACAM5/CEACAM7 RT-PCR assay. For both CEACAM5 and CEACAM7, the limit of detection was found to be as low as 1 expressing cell in 10(6) nucleated blood cells. The multiplex RT-PCR assay was negative for the 41 healthy individuals and the 32 non-colorectal cancer patients. The test was positive in 53/84 (63%) of the colorectal cancer patients for CEACAM5 and/or CEACAM7, whereas 32/84 (38%) were positive for both markers. Colorectal cancer patients were positive for one of the two markers in 80% of cases (36/45) for stage III-IV patients (CEACAM5 73%, CEACAM7 51%) and in 44% of cases (17/39) for stage I-II patients. This multiplex RT-PCR assay with two markers proved to be more sensitive than use of a single marker in detecting circulating tumour cells. The discrepant expression of CEACAM5 and CEACAM7 may label circulating tumour cells that have different levels of differentiation and subsequent aggressive behaviour.

Aged↗

PubMed1987

Cerebral infarction as a result of tumor emboli.

Autopsy records at Mayo Clinic were reviewed to determine the pattern of cerebral infarction occurring as a consequence of nonmyxomatous tumor emboli. Between 1951 and 1984, there were seven adult patients who fulfilled the criteria: focal or multifocal neurologic disease of abrupt onset; systemic cancer; and pathologic demonstration of tumor emboli in appropriate vessels. Tumors originated from the lung in four patients and from the colon and hypopharynx in one each; in one patient the primary source was unknown. Five patients had carotid and two had vertebrobasilar system strokes. Two patients had at least one antecedent transient ischemic attack (TIA). Three patients presented with cerebral infarction as the initial manifestation of their cancer. In two patients, it occurred immediately after pneumonectomy. In four patients, cerebral infarction occurred in a setting of widespread systemic, including pulmonary, metastases. At postmortem examination, one patient had a single large basilar artery tumor embolus. The others had multiple large and small vessel tumor embolic occlusions. The anterior circulation was affected in three patients, the posterior circulation in two, and both circulations were affected in two. Four patients had additional brain parenchymal metastases including one with diffuse leptomeningeal spread.

Aged↗

PubMedDate not supplied

Isolated organ perfusion does not result in systemic microembolization of tumor cells.

BACKGROUND: Isolated organ perfusion with hyperthermia and melphalan with or without tumor necrosis factor-alpha has been effectively used to treat regionally confined, unresectable malignancies of both the limb and liver. Many patients, however, will eventually relapse at distant sites. We used reverse transcription-polymerase chain reaction (RT-PCR) to determine whether significant tumor microembolization occurs in patients undergoing isolated limb perfusion (ILP), isolated hepatic perfusion (IHP), or hepatic resection. METHODS: Primers specific for the human tyrosinase gene or carcinoembryonic antigen gene were designed for RT-PCR to screen melanoma or colon adenocarcinoma, respectively. RNA from human melanoma lines (Pmel and 1286) and human colon adenocarcinoma lines (H508 and HT29) were used to generate positive control cDNA. Normal human blood was inoculated with tumor cells at concentrations that ranged from 10(-2) to 10(5) tumor cells/ml of blood to define the sensitivity. Systemic and perfusate blood samples were drawn from 15 patients (8 patients underwent IHP, 5 patients underwent ILP, and 2 patients underwent resection) before the start of the operation, immediately before and during the perfusion, and postoperatively. Mononuclear cell fractions were separated from the blood samples and RNA was extracted for the RT-PCR assay. Standard primers for human beta-actin were used to confirm that cDNA was generated after the RT reaction. RESULTS: RT-PCR assay sensitivity was determined to be 10 tumor cells/ml of whole blood. Of the 8 IHP patients, 6 had colon metastases and 2 had ocular melanoma metastases to the liver. All 5 ILP patients had in transit melanoma of the extremity. Two patients with colon metastases to the liver were found to have resectable disease. There were no detectable circulating tumor cells in the systemic circulation either preoperatively or postoperatively in all 15 patients that were screened. CONCLUSIONS: RT-PCR is a highly sensitive method of detecting tumor cells in perfusate or blood. Manipulation of the limb or liver followed by resection or isolated hyperthermic perfusion does not cause detectable release of circulating tumor cells. The late development of distant metastases observed in many of these patients does not correlate with the ability to measure circulating tumor cells during regional therapy.

Adenocarcinoma↗

PubMed2002

Clearance of circulating tumor cells after excision of primary colorectal cancer.

OBJECTIVE: To establish whether the prevalence of positive reverse transcriptase-polymerase chain reaction (RT-PCR) results decreased during the first 3 months after colorectal cancer excision, and to assess whether persistence of RT-PCR positivity after primary colorectal cancer excision was related to tumor stage or locally advanced and metastatic disease. METHODS: Systemic venous blood was collected from patients with colorectal cancer before and at intervals up to 12 weeks after surgery. RNA was extracted from the mononuclear cell fraction of the blood samples and subjected to RT-PCR using specific primers for carcinoembryonic antigen mRNA and cytokeratin-20 mRNA. Healthy individuals with no history of cancer were used as controls. RESULTS: The results of RT-PCR were positive in 81 of 116 patients with colorectal cancer before surgery, with no significant differences in preoperative prevalence by Dukes stage or presence of locally advanced or metastatic disease. There was a significant decrease in the prevalence of RT-PCR positivity at 24 hours after surgery compared with before surgery. On subgroup analysis by Dukes stage, only the decrease in Dukes A and B patients reached significance. Seven of the 143 controls were RT-PCR positive. CONCLUSIONS: Circulating tumor cells were present before treatment in most patients with colorectal cancer regardless of tumor stage or metastases. Clearance of circulating tumor cells within 24 hours of colorectal cancer excision was greatest in tumors with the best prognosis.

Adenocarcinoma↗

PubMed2003

Molecular detection of circulating cancer cells. Role in diagnosis, prognosis and follow-up of colon cancer patients.

BACKGROUND: The circulating tumor cells of solid tumors, especially in colorectal cancer has been of great interest in medical research in the last and new century. METHODS: A literature review of recent data for the preparation of a proposal for clinical applications. RESULTS: Starting with the detection of circulating cancer cells in histological sections, lymph nodes, bone marrow and peripheral blood have recently become the primary samples for these investigations. Following microscopic morphology, new methods were and are being developed continuously including rare cell enrichment and detection techniques like fluorescence microscopy, flow cytometry, RT-PCR and methylated DNA PCR. The sensitivity of these assays reaches down to the concentration of 1 tumor cell/ml blood. A lot of different epithelial markers were targeted with these techniques e.g. cytokeratins, EGFR, CEA, and EMA. Clinically, circulating tumor cells were found as independent prognostic factors in lymph nodes and bone marrow. In blood, their presence appears to be an early marker for recurrence and relapse. The change in their quantitative number is supposed to reflect the chemotherapeutic sensitivity and metastatic growth activity of the tumor. CONCLUSIONS: The detection of circulating tumor cells in bone marrow and lymph nodes is of clinical significance. Their presence in peripheral blood and therapeutic applications need further clarification.

Biomarkers, Tumor↗

PubMed1997

Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis.

PURPOSE: To determine the presence of cervical cancer cells in circulating peripheral blood of stage IVb cervical cancer patients with metastasis to distant organs. PATIENTS AND METHODS: Cervical cancer tissue from 15 stage IVb cervical cancer patients with metastasis were analyzed for the presence of human papillomavirus (HPV) type 16 DNA by nested polymerase chain reaction (PCR). The presence of transcriptional products of the HPV type 16 E6-transforming gene in the peripheral blood of the same 15 cancer patients was analyzed by reverse transcription and PCR. Cervical tissues and peripheral-blood specimens from 12 normal healthy individuals served as controls. RESULTS: Thirteen of 15 (86.7%) cervical cancer tissues from same number of patients were found to contain HPV type 16 DNA. Peripheral-blood specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were found to contain HPV-specific mRNA detectable by reverse transcription (RT) and PCR. Cervical tissues from all 12 normal controls were HPV-free. None of the peripheral-blood specimens from two cervical HPV-negative cancer patients and 12 normal controls contained detectable amounts of mRNA of HPV type 16 E6-transforming gene. CONCLUSION: The most likely source of the HPV-specific mRNA detected in the peripheral blood of cervical cancer patients with metastasis is the cervical cancer cells derived from or shed from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a sensitive indicator of circulating cervical cancer cells. If PCR positivity is proven to be able to predict disease progression reliably, these findings may have clinical applications in the treatment of cervical and many other cancers.

DNA, Viral↗

PubMed1985

Effect of leukocyte activation on the formation of heterotypic tumor-cell aggregates in vitro.

Walker tumor cell (1 x 10(6) cells/ml) were incubated at 37 degrees C in a stirred cuvette with rat peritoneal exudate cells (9 x 10(6) cells/ml) with or without the synthetic leukocyte chemo-attractant fMLP (2 x 10(6) M) or biologically active concentrations of the major endogenous chemo-attractant, C5a. Aggregation, induced by the chemo-attractants, was detected after 3 min by a platelet aggregometer and by studying cytocentrifuge preparations. The response was amplified in the presence of cytochalasin B (5 micrograms/ml). Tumor cells could be identified in the aggregates by their morphology or by autoradiography after labeling with 3H-thymidine. Although tumor cells were incorporated into the leukocyte aggregates, there was no appreciable change in the number of aggregates formed between tumor cells themselves. Levine III human breast tumor cells (1 x 10(6)/ml) in heparinized human blood were incorporated into leukocyte aggregates within 30 min of adding 50 U cobra venom factor to activate complement. Aggregation correlated with a decrease in complement hemolytic activity (CH50). The aggregation reaction was not cytotoxic to tumor cells when evaluated by Trypan blue exclusion or by 51Cr release. We conclude that local tumor cells can be incorporated into aggregates formed when leukocytes are stimulated by chemo-attractants. We postulate that intravascular activation of neutrophils might affect the localization of circulating tumor cells by incorporating them into microembolic cell aggregates and by causing damage to the pulmonary endothelium.

Animals↗

PubMed2004

Vaccination of prostatectomized prostate cancer patients in biochemical relapse, with autologous dendritic cells pulsed with recombinant human PSA.

This study was conducted in prostate cancer patients in biochemical relapse after radical prostatectomy, to assess the feasibility, safety, and immunogenicity of therapeutic vaccination with autologous dendritic cells (DCs) pulsed with human recombinant prostate-specific antigen (PSA) (Dendritophage-rPSA). Twenty-four patients with histologically proven prostate carcinoma and an isolated postoperative rise of serum PSA (>1 ng/ml to 10 ng/ml) after radical prostatectomy were included. The patients received nine administrations of PSA-loaded DCs by combined intravenous, subcutaneous, and intradermal routes over 21 weeks. Postbaseline blood tests were performed at months 1, 3, 6, 9, and 12 (PSA levels), at months 6 and 12 (circulating prostate cancer cells), at month 6 (anti-PSA IgG and IgM antibodies), and at up to eight time points before, during, and after immunization (PSA-specific T cells). Circulating prostate cancer cells detected in six patients at baseline were undetectable at 6 months and remained undetectable at 12 months. Eleven patients had a postbaseline transient PSA decrease on one to three occasions, predominantly occurring at month 1 (7 patients) or month 3 (2 patients). Maximum PSA decrease ranged from 6% to 39%. PSA decrease on at least one occasion was more frequent in patients with low Gleason score ( p=0.016) at prostatectomy and with positive skin tests at study baseline ( p=0.04). PSA-specific T cells were detected ex vivo by ELISpot for IFN-gamma in 7 patients before vaccination and in 11 patients after vaccination. Of the latter 11 patients, 5 had detectable T cells both before and during the vaccination period, 4 only during the vaccination period, while 2 patients could for technical reasons not be assessed prevaccination. No induction of anti-PSA IgG or IgM antibodies was detected. There were no serious adverse events or otherwise severe toxicities observed during the trial. Immunization with Dendritophage-rPSA was feasible and safe in this cohort of patients. An immune response specific for PSA could be detected in some patients. A notable effect was the disappearance of circulating prostate cells in all patients who were RT-PCR positive before vaccination.

Adenocarcinoma↗

PubMed1979

Entry of metastatic malignant cells into the circulation from a subcutaneously growing myelogenous tumor.

The initial stage of metastasis formation, i.e., the entry of metastatic cells from a malignant subcutaneously growing myelogenous tumor into the circulation, was observed by means of transmission electron microscopy and scanning electron microscopy in Long-Evans rats. The transmural passage of malignant cells occurred through the walls of intact venules within the tumor. The malignant cell penetrated the endothelial cell body by making a temporary migration pore. The migration pore closed after the malignant cell entered the vascular lumen. The endothelial vascular lining remained continuous. The entry of malignant cells into the circulation was not the result of the general invasive and destructive properties of malignant tumor cells, but the consequence of a specific action of the tumor cells on the abluminal plasma membrane of the endothelium.

Animals↗