PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Neoplastic Cells, Circulating”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed2005

Characterization of ocular and metastatic uveal melanoma in an animal model.

PURPOSE: To characterize, in detail, tumor development, malignant cell dissemination, and metastasis in a 10-week animal model of uveal melanoma. METHODS: One million 92.1 human primary uveal melanoma cells were injected into the suprachoroidal space of the right eye of 27 immunosuppressed albino rabbits. Intraocular tumor growth was monitored weekly by fundoscopy and by ultrasonography at the end of the experiment. To document the progression of the disease, one animal per week was killed. The enucleated eyes, lungs, and livers were macroscopically examined and histopathologically studied by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemistry. Mononuclear layers isolated from the rabbits' blood samples were cultured. RESULTS: Histopathology showed intraocular tumors in 89% of the animals. Tumor growth was found 1 week after cell inoculation, and by the end of the experiment large tumor masses were observed. Microscopic pulmonary metastatic foci were first observed 4 weeks after cell injection. By the end of the experiment, all the animals had metastasis to the lungs. Interestingly, 18% of the animals also had micrometastasis to the liver. Viable adherent uveal melanoma cells were successfully isolated from peripheral blood and grown in vitro. CONCLUSIONS: In this study, most rabbits developed intraocular tumors followed by lung metastasis, and some of these rabbits later developed liver micrometastases. This novel source of research material warrants a follow-up longer than 10 weeks to further explore the pathophysiologic bases of liver involvement commonly encountered in humans. The success in the isolation and culture of circulating malignant cells in this animal model suggests that it might be worthwhile to explore the application of this technique to the management of patients with primary uveal melanoma.

Animals↗
PubMed1981

In vivo isolation of a metastatic tumor cell variant involving selective and nonadaptive processes.

An investigation was done to determine whether spontaneous metastases that develop in a C3H mouse bearing the syngeneic UV-2237 fibrosarcoma are derived from specialized subpopulations of cells or represent an adaptation process to a local (organ) environment. Inbred C3H mice received sc injections of parent tumor and, 9 weeks later, 5 individual pulmonary metastases were harvested and established in culture. Cells from each of these metastases colonized in the lungs of normal recipient mice with significantly greater efficiency than did cells from the parent tumor. Mice received injections iv of cells from a cloned line of UV-2237 that produced few lung metastases. Cells from these metastases did not colonize in the lungs at a dramatically higher rate than did the parent clone. The growth per se of tumor cells into colonies in the lung is not sufficient by itself to endow cells with metastatic properties. The selection in vivo of cells with enhanced lung colonization does not require that the lung be used as a selective organ. A cell variant was selected for enhanced capacity to grow in the peritoneal cavity of normal recipients. This cell line was also found to have a high capacity to colonize in the lungs following introduction into the circulation. It was concluded that the growth of metastases in this murine tumor system was not due to adaptive processes but rather to selection by intrinsic properties of tumor cells.

Adaptation, Physiological↗
PubMed2005

Follow-up study of peripheral blood carcinoembryonic antigen mRNA using reverse transcription-polymerase chain reaction as an early marker of clinical recurrence in patients with curatively resected gastric cancer.

In this study, we evaluated the clinical significance of detecting carcinoembryonic antigen (CEA) mRNA in the peripheral blood samples of patients with gastric cancer. We analyzed the peripheral blood of 46 patients with gastric cancer who had undergone curative resection. The presence of CEA mRNA was serially monitored using a CEA-specific reverse transcription-polymerase chain reaction (RT-PCR) every 2 months. The clinical recurrence rates according to category were as follows: 100% (3 of 3) in the positive conversion, 0% (0 of 18) in the negative conversion, 50% (3 of 6) in the always-positive, and 10.5% (2 of 19) in the always-negative category. The recurrence rate was 66.7% (6 of 9) in the positive group and 5.4% (2 of 37) in the negative group (P < or =0.00022). Multiple logistic regression analysis demonstrated that only group variable had a significant effect on clinical recurrence (P = 0.015). We conclude that RT-PCR analysis of CEA mRNA in the peripheral blood seems to be a promising tool for the early detection of micrometastatic circulating tumor cells in gastric carcinoma patients and that it can be useful used to identify patients at risk for recurring.

Adult↗
PubMed2002

Tyrosinase mRNA in blood of patients with melanoma treated with adjuvant interferon.

PURPOSE: To evaluate the clinical significance of the detection of circulating melanoma cells in patients treated with adjuvant interferon and to determine their potential value as a marker of interferon response. PATIENTS AND METHODS: We prospectively analyzed 616 peripheral-blood samples from 120 melanoma patients with stage IIA (n = 33), IIB (n = 22), III (n = 50), or IV (surgically resected) (n = 15) disease receiving adjuvant interferon alfa-2b therapy. Tyrosinase mRNA was assayed by reverse transcriptase polymerase chain reaction (RT-PCR) as a marker of circulating melanoma cells before the start of interferon and every 2 to 3 months thereafter. RESULTS: With a median follow-up time of 32.3 months (range, 7.1 to 77.5 months), 47 patients (39.8%) relapsed and 31 (26%) died. During adjuvant interferon treatment, 76 patients (64%) had undetected circulating melanoma cells and 44 patients (36%) had a positive RT-PCR result in at least one sample. Actuarial 5-year disease-free survival was 62% in patients with persistently negative RT-PCR during interferon treatment and 38% for patients with positive RT-PCR during interferon (P =.02). Actuarial 5-year overall survival was 75% and 50%, respectively (P =.03). CONCLUSION: Patients with melanoma and tyrosinase mRNA detected in the blood during adjuvant interferon therapy had a worse prognosis compared with patients with undetected tyrosinase mRNA during treatment. Further investigation into the detection of circulating melanoma cells as a surrogate marker of response to adjuvant interferon therapy is warranted.

Actuarial Analysis↗
PubMedDate not supplied

Elective lymph node dissection for malignant melanoma: the tumor burden of nodal disease.

Many retrospective trials have demonstrated a survival benefit for elective lymph node dissection (ELND) in the treatment of clinical stage I malignant melanoma, but two randomized trials have found none. The relevant medical literature was reviewed with special attention devoted to the tumor burden of nodal disease. Following the lead of Handley, the biologic behavior of melanoma is compared to that of breast cancer. Patient survival appears to be determined by the volume of tumor cells circulating from the primary lesion or the regional nodes. A hypothesis is presented which suggests that metastatic disease develops only in those patients whose circulating tumor burden exceeds the host defense threshold of the patient--a threshold that is relatively stable throughout life. Some studies may have exaggerated the potential benefit of ELND, because some patients treated with delayed dissection were not closely followed and developed sizable nodal recurrence. Patients who decline ELND must be followed every one to three months. Investigators should precisely measure and report the volume of each patient's nodal disease. The debate over ELND can only be resolved with accurate data which begin to define the threshold at which nodal disease contributes to patient mortality.

Australia↗
PubMed1996

Metastasis. A primer for dermatologists.

BACKGROUND: Dermatologists often diagnose, treat, and manage patients who have cutaneous tumors that are potentially metastatic. While the fund of knowledge regarding metastasis is still quite incomplete, more and more is becoming understood about the mechanisms of carcinogenesis and metastasis. OBJECTIVE: To present in understandable terms what is known about carcinogenesis and metastasis and how this information can and should affect the clinician's approach to diagnosis, management, and follow-up of potentially metastatic cutaneous disease. METHODS: The recent literature pertaining to the current understanding of the mechanisms of carcinogenesis and metastasis are assimilated and reviewed. RESULTS: Carcinogenesis is fundamentally a three-step process comprised of initiation, promotion, and progression. One of the most dramatic results of progression is metastasis. Metastasis is the result of a complex set of cellular adaptations that enable the tumor cell to be able to separate from the primary tumor, invade, intravasate, circulate, implant at a distant site, extravasate, and lastly proliferate. CONCLUSION: A fundamental understanding of the mechanism of carcinogenesis and metastasis is important to the clinical dermatologist. Understanding these principles can affect the way in which the practitioner teaches and institutes preventative measures. It may also influence diagnostic and therapeutic approaches as well as subsequent management and follow-up of potentially metastatic or metastatic disease. There is little doubt that the best care for a patient with skin cancer can be given by the physician who knows the most about the integument. This behooves dermatologists to remain well informed about the present understanding of the development and progression of cancer.

Humans↗
PubMed1986

Conservation of epithelial cell phenotypes during hematogenous metastasis from mammary carcinomas.

The phenotypic heterogeneity of epithelial cells during hematogenous metastasis from primary mammary carcinomas of BALB/cfC3H mice was examined. Antisera to keratins were used in immunofluorescence assays to identify epithelial and myoepithelial cells. Both cell types were located in frozen sections of not only the primary lesions but also pulmonary metastases. Tumor cells disseminating to the lungs were recovered from the bloodstream of tumor-bearing mice with the use of a quantitative density gradient centrifugation procedure. Carcinoma cells were detected in the circulation of 62% of mice at the time of assay, but all tumors examined had released cells into the circulation at some point in their history. Epithelial cells and myoepithelial cells were detected simultaneously in 21% of mice, whereas other mice had only epithelial cells (16%) or myoepithelial cells (25%) in their circulation at the time of assay. Single cells and multicellular emboli of each cell type were disseminated, together with similar numbers of heterogeneous emboli containing both epithelial and myoepithelial cells. The evidence shows that the presence of both mammary epithelial and myoepithelial cells in pulmonary metastases from mouse mammary carcinomas can be accounted for by their hematogenous delivery as differentiated cells.

Animals↗
PubMed2005

Monoclonal anti-idiotype antibody 6G6.C4 fused to GM-CSF is capable of breaking tolerance to carcinoembryonic antigen (CEA) in CEA-transgenic mice.

Internal image anti-idiotypic antibodies are capable of mimicking tumor-associated antigens and thus may serve as surrogate for vaccination strategies in cancer patients. The monoclonal antibody (mAb) 6G6.C4 mimics an epitope specific for the human carcinoembryonic antigen (CEA) and generates a CEA-specific response (Ab3) in various experimental animals. In humans, however, 6G6.C4 only yields a very limited humoral anti-CEA reaction presumably due to tolerance against the CEA autoantigen. In this study, we investigated the CEA-specific Ab3 response in mice transgenic for the human CEA and tested whether the antigen tolerance could be overcome by fusing a recombinant single-chain variable fragment of 6G6.C4 (scFv6G6.C4) to the murine granulocyte macrophage colony-stimulating factor (GM-CSF). Like mAb 6G6.C4, the fusion protein (scFv6G6.C4/GM-CSF) retained binding to the CEA-specific idiotype mAb T84.66. Also, scFv6G6.C4/GM-CSF was biologically active as measured by proliferation of the GM-CSF-dependent murine FDC-P1 cells in vitro. After immunization with the scFv6G6.C4/GM-CSF fusion protein, CEA-transgenic animals showed significantly enhanced Ab3 antibody responses to scFv6G6.C4 (P=0.005) and to CEA (P=0.012) compared with the scFV6G6.C4 alone. Sera from mice immunized with the fusion protein specifically recognized CEA in Western blot analyses with no cross-reaction to CEA-related antigens. Finally, the Ab3 antisera detected single CEA-expressing tumor cells in suspension as shown by flow cytometry. Taken together, these data show in a model antigenically related to the human system that vaccination with scFv6G6.C4/GM-CSF improves vaccination against an endogenous tumor-associated antigen resulting in a highly specific humoral Ab3 response in vivo that is capable of bind single circulating CEA-positive tumor cells.

Animals↗
PubMed1995

Haematogenous dissemination of prostatic epithelial cells during radical prostatectomy.

Radical prostatectomy is one treatment for organ-confined prostatic adenocarcinoma. Dissemination of malignant prostatic cells after radical prostatectomy could be partly due to prostate manipulation during dissection. We confirmed by assay of prostate-specific membrane antigen by reverse-transcription nested PCR that prostate manipulation seeded prostatic epithelial cells in the general circulation in 12 of 14 consecutive patients operated on for organ-confined prostate adenocarcinoma. Our results suggest that surgeons should approach radical prostatectomy with care to avoid seeding from the prostate gland. Antiandrogen therapy might reduce the haematogenous spread of prostatic cells during radical prostatectomy.

Adenocarcinoma↗
PubMed2003

Detection of disseminated tumour cells in blood and bone marrow samples of patients undergoing hepatic resection for metastasis of colorectal cancer.

BACKGROUND: In 50-60 per cent of patients who undergo hepatic resection for metastasis of colorectal cancer the first site of tumour recurrence is extrahepatic, indicating the presence of more extensive disease at the time of resection. The aim of this study was to evaluate whether the presence of disseminated tumour cells in blood and bone marrow could predict extrahepatic tumour recurrence. METHODS: Cytokeratin 20 (CK20) reverse transcriptase-polymerase chain reaction was used to study the presence of tumour cells in preoperative peripheral blood and bone marrow samples from 41 patients with liver metastasis scheduled for surgical resection. RESULTS: CK20 expression was detected in six of 41 peripheral blood samples and in eight of 32 bone marrow samples. There was no correlation between CK20-positive samples and subsequent extrahepatic recurrence. Positive blood samples did, however, correlate with high serum carcinoembryonic antigen level and large tumour volume. None of the 14 patients previously treated with chemotherapy had CK20-positive samples, whereas six of 27 blood and eight of 20 bone marrow samples were positive in the chemotherapy-naive group. CONCLUSION: Although the number of patients in this study is limited, the presence of disseminated tumour cells did not predict subsequent extrahepatic recurrence. The results strongly suggest that the presence of circulating tumour cells in peripheral blood may reflect transient shedding of tumour cells related to large tumour volume.

Adult↗
PubMed1997

Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer.

The prognosis for patients with primary liver cancer (PLC) often depends on tumor recurrence and the development of extrahepatic metastases, particularly after liver transplantation. We have developed a sensitive test to detect both spontaneous circulation of tumor cells and the spread of liver cells due to chemoembolization and alcoholization. Reverse-transcription polymerase chain reaction was used to search for cells expressing alpha-fetoprotein (AFP) messenger RNA in the peripheral blood of 84 patients with PLC and 102 controls (55 patients with chronic hepatitis and/or cirrhosis, 10 patients with benign liver tumors or liver metastases from intestinal cancers, and 37 healthy individuals). By spiking the blood of healthy volunteers with HepG2 cells, we assessed the sensitivity limit: one HepG2 cell mixed with 10(7) leukocytes. All 102 controls tested negative. In contrast, 28 patients (33.3%) with PLC tested positive. Positivity for the test was significantly associated with portal thrombosis, tumor size, intravascular tumor emboli, serum AFP level, and extrahepatic metastases. Patients were followed up for a mean period of 39 +/- 51 weeks: the probability of developing extrahepatic metastases was significantly higher in positive than in negative patients. Eighteen negative patients with PLC were tested before, 1 hour after, and 24 hours after locoregional therapy: 9 tested positive either 1 or 24 hours after alcoholization or chemoembolization. In conclusion, we have developed a highly specific and sensitive test to detect circulating tumor cells in patients with PLC. This test is likely to be clinically useful in evaluating the risk of developing extrahepatic metastases and the possibility of iatrogenic spreading of liver-derived, possibly tumorous, cells.

Female↗
PubMed2004

Detection of circulating breast cancer cells in peripheral blood by a two-marker reverse transcriptase-polymerase chain reaction assay.

The aim of this study was to use a two-marker assay for the detection of breast cancer cells circulating in patients' blood. We have applied a PCR-based methodology to follow up the possibility of the development of metastatic disease in stage I and II patients who had undergone curative surgery. Since the number of circulating cancer cells in peripheral blood is very low, the technique for their detection needs to be not only highly sensitive, but also very specific. The reverse transcriptase-polymerase chain reaction (RT-PCR) technique may improve the sensitivity of breast cancer cell detection up to only a few cells per one million. The principle of the RT-PCR assay is to amplify a messenger RNA characteristic for breast epithelial cells in a blood sample. Since we do not expect such cells to be circulating in peripheral blood of healthy subjects, detection of the characteristic mRNA should indicate the presence of circulating breast cancer cells. We analyzed the usefulness of three mRNA markers: cytokeratin 19 (CK19), mammaglobin (hMAM) and beta subunit of human chorionic gonadotropin (beta-hCG) for this test. Blood samples (112) were obtained from 55 patients, in stages I and II, with or without metastasis to regional lymph nodes (N0 or N1). We found that a two-marker assay increases the sensitivity of detection of breast cancer cells in comparison with a single-marker one. Combination of two tumor-specific mRNA markers, hMAM/CK19 or beta-hCG/CK19, allowed the detection of circulating breast cancer cells in 65% of N1 patients and 38% of N0 patients. By comparison, the combination hMAM/beta-hCG allowed the detection of circulating breast cancer cells in the blood of 68% of N1 patients and 46% of N0 patients. Addition of the third marker did not significantly increase the detection sensitivity.

Base Sequence↗
PubMed2002

RT-PCR-based detection of circulating calcitonin-producing cells in patients with advanced medullary thyroid cancer.

In patients with medullary thyroid carcinoma (MTC) the clinical course of disease ranges from rapid tumor progression to long-lasting stable disease. The purpose of the present study was to investigate whether circulating tumor cells can be detected in the peripheral blood of patients with MTC by RT-PCR targeted to calcitonin (CT) mRNA and whether the results of this method are correlated with disease manifestation and metastatic potential. Blood samples from 19 consecutive patients with MTC and elevated CT levels were analyzed. Four had newly diagnosed MTC, and 15 patients had undergone total thyroidectomy. Six of 19 patients had detectable CT mRNA by RT-PCR. CT levels in the CT mRNA-positive patients were significantly higher than those in CT mRNA-negative patients [2,239-265,313 pg/ml; median 80,921 pg/ml (n = 6) vs. 70-46,787 pg/ml; median, 932 pg/ml (n = 13); P = 0.006]. CT mRNA was detectable in 5 of 8 patients with distant metastases, in 1 of 6 patients with local/regional lymph node metastases, but in none of the patients with newly diagnosed, organ-confined MTC (n = 2) or surgically treated MTC without tumor manifestation by various imaging studies (n = 3). In peripheral blood from 10 healthy volunteers and 21 patients with benign thyroid nodules, no CT RNA could be detected. In conclusion, an RT-PCR-based procedure was established to detect circulating CT-producing cells in the peripheral blood of patients with MTC. RT-PCR results seem to reflect tumor spread and aggressiveness and thus may help with early identification of patients with disseminated and rapidly progressive disease.

Adult↗
PubMed2005

Circulating nucleic acids in plasma or serum (CNAPS) as prognostic and predictive markers in patients with solid neoplasias.

It is now widely accepted that there is a need for the development of molecular markers of cancer that can be used for clinical prognostication and monitoring. Approximately a decade ago tumor-derived circulating nucleic acids in the plasma or serum (CNAPS) of cancer patients were introduced as a noninvasive tool for cancer detection. This review focuses on the various types of CNAPS of patients with solid neoplasias (genetic alterations in circulating DNA, microsatellites, methylated DNA, viral DNA, nucleosomes, mitochondrial DNA and cell-free mRNA) and their putative potential as prognostic or predictive parameter or even as a tool for therapy monitoring during follow-up. Additionally, this review aims to point out the difference between a prognostic and a predictive factor in patient bloodstream. However, with rapid technical improvement and well-designed studies we conclude that the next years will see CNAPS analysis integrated in the prognostication and monitoring of cancer patients, thus producing more specific treatment regimens for patients with various stages of neoplastic disease and ultimately longer survival and better quality of life.

Biomarkers, Tumor↗
PubMedDate not supplied

Surgery for hepatocellular carcinoma with tumor thrombus in the right atrium.

Three cases of tumor thrombus that originated from a hepatocellular carcinoma in the liver and extended into the right atrium are described. All patients had received both resection of the tumor thrombus and lobectomy of the liver either simultaneously or independently within a short interval. Surgical order and extracorporeal circulation system were varied depending on the thrombus extension. Two of the patients died within 4 months of surgery due to different reasons and the other is doing well at 24 months after surgery.

Aged↗
PubMed2004

Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer.

The clinical impact of circulating tumor cell (CTC) detection is controversial, mainly due to drawbacks of molecular approaches applied to this field. We sought to determine if the specific identification and counting of circulating tumor cells by cytomorphologic analysis has clinical usefulness. Peripheral blood (6 mL), treated using isolation by size of epithelial tumor cells, was obtained from 44 patients with primary liver cancer (PLC) and without metastases, 30 patients with chronic active hepatitis, 39 with liver cirrhosis, and 38 healthy individuals, and followed up for a mean period of 1 year. We searched for beta-catenin mutations in 60 single microdissected CTCs. One patient with liver cancer developed extrahepatic metastases during follow-up. CTCs and microemboli were found in 23 of the 44 patients with liver cancer and in none of the patients with chronic active hepatitis, patients with cirrhosis, or healthy subjects. Their presence was significantly associated with tumor diffusion (P =.0001) and portal tumor thrombosis (P =.006). Both the presence (P =.01) and number (P =.02) of CTCs and microemboli were significantly associated with a shorter survival. Beta-catenin mutations were found in 3 of 60 CTCs, arguing against their impact on the initial step of tumor cell invasion. In conclusion, the highly sensitive and specific detection of CTCs and microemboli may have clinical implications for cancer staging and outcome prediction. We also show the feasibility of molecular studies of individual circulating tumor cells, aimed at identifying gene mutations involved in tumor invasion.

Aged↗