• Title, Summary, Keyword: Circulating tumor cells

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Detection of Circulating Melanoma Cells by a Two-marker Polymerase Chain Reaction Assay in Relation to Therapy

  • Bitisik, Ozlem;Camlica, Hakan;Duranyildiz, Derya;Tas, Faruk;Kurul, Sidika;Dalay, Nejat
    • BMB Reports
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    • v.36 no.2
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    • pp.173-178
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    • 2003
  • Malignant melanoma is one of the most rapidly increasing cancer types, and patients with metastatic disease have a very poor prognosis. Detection of metastatic melanoma cells in circulation may aid the clinician in assessing tumor progression, metastatic potential, and response to therapy. Tyrosinase is a key enzyme in melanine biosynthesis. The gene is actively expressed in melanocytes and melanoma cells. Melan A is a differentiation antigen that is expressed in melanocytes. The presence of these molecules in blood is considered a marker for circulating melanoma cells. In this study, we analyzed the usefulness of this marker combination I evaluating the response to therapy in the blood of 30 patients with malignant melanoma. Circulating cells were detected by a reverse-transcriptase-polymerase-chain reaction. The tyrosinase expression was observed in 9 (30%) patients and Melan A in 19 (63.3%) patients before therapy. Following treatment, the tyrosinase mRNA was detected in only one patient, while Melan A transcripts were still present in 14 patients. We suggest that this molecular assay can identify circulating melanoma cells that express melanoma-associated antigens and may provide an early indication of therapy effectiveness.

Circulating Tumor Cells are Associated with Bone Metastasis of Lung Cancer

  • Cheng, Min;Liu, Lin;Yang, Hai-Shan;Liu, Gui-Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6369-6374
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    • 2014
  • Lung cancer (LC) is the leading cause of cancer mortality worldwide, predominantly due to the difficulty of early diagnosis and its high metastatic potential. Recently, increasing evidence suggests that circulating tumour cells (CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted interest in cancer metastasis detection and quantification. In present study, we collected blood samples from 67 patients with bone metastasis, and 30 patients without such metastasis, and searched for CTCs. Then the association of CTC numbers with bone metastasis and other clinico-pothological variants was analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the CTC number, there were significantly higher positivity of CTCs in the bone metastasis group than in the non-metastasis group. While the increase in CTC number was not significantly associated with any other clinicopathological factor, including age, gender, pathological type, intrapulmonary metastasis and lymph node metastasis, the CTC number in patients with positivity of the last above mentioned variants was obviously higher than in patients with negativity of the two variants. Taken together, the CTC number appears to be significantly associated with the bone metastasis from lung cancer.

Elevated Circulating CD19+ Lymphocytes Predict Survival Advantage in Patients with Gastric Cancer

  • Yu, Qi-Ming;Yu, Chuan-Ding;Ling, Zhi-Qiang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2219-2224
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    • 2012
  • Background: Circulating lymphocyte subsets reflect the immunological status and might therefore be a prognostic indicator in cancer patients. Our aim was to evaluate the clinical significance of circulating lymphocyte subset in gastric cancer (GC) cases. Methods: A retrospective study on a prevalent cohort of 846 GC patients hospitalized at Hospital from Aug 2006 to Jul 2010 was conducted. We calculated the patient's disease free survival (DFS) after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. Results: Our findings indicated a significantly decreased percentage of CD3+, and CD8+ cells, a significantly increased proportion of $CD4^+$, $CD19^+$, $CD44^+$, $CD25^+$, NK cells, and an increased $CD4^+/CD8^+$ ratio in GC patients as compared with healthy controls (all P < 0.05). Alteration of lymphocyte subsets was positively correlated with sex, age, smoking, tumor stage and distant metastasis of GC patients (all P<0.05). Follow-up analysis indicated significantly higher DFS for patients with high circulating $CD19^+$ lymphocytes compared to those with low $CD19^+$ lymphocytes (P=0.037), with $CD19^+$ showing an important cutoff of $7.91{\pm}2.98%$ Conclusion: Circulating lymphocyte subsets in GC patients are significantly changed, and elevated CD19+ cells may predict a favorable survival.

Diagnostic Yield of Primary Circulating Tumor Cells in Women Suspected of Breast Cancer: the BEST (Breast Early Screening Test) Study

  • Murray, Nigel P;Miranda, Roxana;Ruiz, Amparo;Droguett, Elsa
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1929-1934
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    • 2015
  • Purpose: To determine the diagnostic yield of primary circulating tumor cells in women with suspicion of breast cancer, detected as a result of an abnormal mammography. Materials and Methods: Consecutive women presenting for breast biopsy as a result of a mammogram BiRADs of 3 or more, had an 8ml blood sample taken for primary circulating tumor cell (CTC) detection. Mononuclear cells were obtained using differential gel centrifugation and CTCs identified using standard immunocytochemistry using anti-mammoglobin. A test was determined to be positive if 1 CTC was detected. Results: A total of 144 women with a mean age of $54.7{\pm}15.6$ years participated, 78/144 (53.0%) had breast cancer on biopsy, 65/140 (46.3%) benign pathologies and 1(0.7%) non-Hogkins lymphoma. Increasing BiRADs scores were associated with increased cancer detection (p=0.004, RR 1.00, 4.24, 8.50). CTC mammoglobin positive had a sensitivity of 81.1% and specificity of 90.9%, with positive and negative predictive values of 90.9% and 81.1% respectively. Mammoglobin positive CTCs detected 87% of invasive cancers, while poorly differentiated cancers were negative for mammoglobin. Only 50% of in situ cancers and none of the intraductal cancers had CTCs detected. Menopausal status did not affect the diagnostic yield of the CTC test, which was higher in women with BiRADS 4 mammograms. There was a significant trend (p<0.0001 Chi squared for trends) in CTC detection frequency from intraductal, in situ and invasive (OR 1.00, 8.00, 472.00). Conclusions: The use of primary CTC detection in women suspected of breast cancer has potential uses, especially with invasive cancer, but it failed to detect intra-ductal cancer and 50% of in situ cancer. There was no difference in the diagnostic yield between pre and post menopausal women. To confirm its use in reducing biopsies in women with BIRADs 4a mammagrams and in the detection of interval invasive breast cancer, larger studies are needed.

Possible Role of HER-2 in the Progression of Prostate Cancer from Primary Tumor to Androgen Independence

  • Murray, Nigel P;Reyes, Eduardo;Fuentealba, Cynthia;Jacob, Omar;Orellana, Nelson
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6615-6619
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    • 2015
  • Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.

Effects of Swainsonine on the Cell-mediated Immune Responses of Lipopolysaccharide (리포포리사카라이드의 세포성 면역반응에 미치는 스와인소닌의 영향)

  • Chae, Byeong-Suk;Ahn, Young-Keun;Kim, Joung-Hoon
    • YAKHAK HOEJI
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    • v.42 no.1
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    • pp.75-81
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    • 1998
  • Effects of swainsonine (SW: 8${\alpha}$, ${\beta}$-indolizidine-1alpha, 2${\alpha}$, 8${\beta}$-triol from Locoweed) on the cellular and nonspecific immune responses of lipopolysaccharide (LPS) wer e studied in ICR mice. Mice were divided into 4 groups (10mice/group), and LPS was given to each mouse 1 hr after i.p. injection with 3.7mg/kg of SW by i.p. injection twice a week for 14 days at a dose of 2mg/kg. Immune responses of the delayed-type hypersensitivity response (DTH) to sheep red blood cells (s-RBC), phagocytic activity and natural killer (NK) cell activity were evaluated. LPS treatment didn`t affect NK cell activity, phagocytic activity, DTH to s-RBC compared with those in controls, and phagocytic activity of sareoma 180 tumor bearing mice. However, circulating leukocytes were significantly decreased. Combinaton of LPS and SW increased circulating leukocytes significantly compared vath that in LPS alone, and DTH to s-RBC, NK cell activity and phagocytic activities of normal and sarcoma tumor bearing mice were not affected. These findings indicate that SW didn`t affected the cellular immune responses suppressed by LPS but significantly increased circulating leukocytes.

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Liquid Biopsy: Current Status and Future Perspective in Gastric Cancer and Helicobacter Infection (액체 생검(Liquid Biopsy): 위암 및 헬리코박터 감염증에서 적응과 전망)

  • Kang, Eun A;Han, Young Min;Park, Jong Min;Yoo, In Kyung;Hong, Sung Pyo;Hahm, Ki Baik
    • The Korean journal of helicobacter and upper gastrointestinal research
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    • v.18 no.3
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    • pp.150-156
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    • 2018
  • Precision medicine stands for 4Ps - precise, preventive, participatory, and personal; in which "precision" is important because the current modern medicine starts from "trial and error," and "one does not fit all". Current targeted therapies for cancer have changed treatment approaches and led the precision medicine; however, clinical use of liquid biopsy, using blood or other liquid specimens to characterize circulating tumor cells (CTC) or tumor genes instead of biopsies of tumor tissues, still awaits availability of more information regarding non-invasive cancer detection and characterization, prediction of treatment response, monitoring the disease course and relapse possibilities, identification of mechanisms of drug resistance, and newer pathogenesis. In this review, we will introduce the basic concept of CTC, circulating cell free DNA, and exosomes and their possible application for gastric cancer relevant with Helicobacter pylori infection.

Tumoral Accumulation of Long-Circulating, Self-Assembled Nanoparticles and Its Visualization by Gamma Scintigraphy

  • Cho, Yong-Woo;Kim, Yoo-Shin;Kim, In-San;Park, Rang-Woon;Oh, Seung-Jun;Moon, Dae-Hyuk;Kim, Sang-Yoon;Kwon, Ick-Chan
    • Macromolecular research
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    • v.16 no.1
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    • pp.15-20
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    • 2008
  • The enhanced permeability and retention (EPR) effect is used extensively for the passive targeting of many macromolecular drugs for tumors. Indeed, the EPR concept has been a gold standard in polymeric anticancer drug delivery systems. This study investigated the tumoral distribution of self-assembled nanoparticles based on the EPR effect using fluorescein and radio-labeled nanoparticles. Self-assembled nanoparticles were prepared from amphiphilic chitosan derivatives, and their tissue distribution was examined in tumor-bearing mice. The size of the nanoparticles was controlled to be 330 run, which is a size suited for opening between the defective endothelial cells in tumors. The long-circulating polymer nanoparticles were allowed to gradually accumulate in the tumors for 11 days. The amount of nanoparticles accumulated in the tumors was remarkably augmented from 3.4%ID/g tissue at 1 day to 25.9%ID/g tissue at 11 days after i.v. administration. The self-assembled nanoparticles were sustained at a high level throughout the 14 day experimental period, indicating their long systemic retention in the blood circulation. The ${\gamma}$-images provided clear evidence of selective tumor localization of the $^{131}I$-labeled nanoparticles. Confocal microscopy revealed the fluorescein-labeled nanoparticles to be preferentially localized in the perivascular regions, suggesting their extravasation to the tumors through the hyperpermeable angiogenic tumor vasculature. This highly selective tumoral accumulation of nanoparticles was attributed to the leakiness of the blood vessels in the tumors and their long residence time in the blood circulation.

Microchips and their Significance in Isolation of Circulating Tumor Cells and Monitoring of Cancers

  • Sahmani, Mehdi;Vatanmakanian, Mousa;Goudarzi, Mehdi;Mobarra, Naser;Azad, Mehdi
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.879-894
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    • 2016
  • In micro-fluid systems, fluids are injected into extremely narrow polymer channels in small amounts such as micro-, nano-, or pico-liter scales. These channels themselves are embedded on tiny chips. Various specialized structures in the chips including pumps, valves, and channels allow the chips to accept different types of fluids to be entered the channel and along with flowing through the channels, exert their effects in the framework of different reactions. The chips are generally crystal, silicon, or elastomer in texture. These highly organized structures are equipped with discharging channels through which products as well as wastes of the reactions are secreted out. A particular advantage regarding the use of fluids in micro-scales over macro-scales lies in the fact that these fluids are much better processed in the chips when they applied as micro-scales. When the laboratory is miniaturized as a microchip and solutions are injected on a micro-scale, this combination makes a specialized construction referred to as "lab-on-chip". Taken together, micro-fluids are among the novel technologies which further than declining the costs; enhancing the test repeatability, sensitivity, accuracy, and speed; are emerged as widespread technology in laboratory diagnosis. They can be utilized for monitoring a wide spectrum of biological disorders including different types of cancers. When these microchips are used for cancer monitoring, circulatory tumor cells play a fundamental role.