Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

Circulating tumor cell (CTC), as a novel tumor marker, has the characteristics of non-invasive, dynamic monitoring and high accuracy, and provides precise molecular characteristics of tumors and helps understand the changes in tumor development. Therefore, CTC has important clinical value in the dynamic monitoring of tumor progression. In order to standardize and guide the application of CTC detection in the diagnosis and treatment of gastrointestinal neoplasms, Gastric Cancer Group of Oncology Branch of Chinese Medical Association, Colorectal Cancer Professional Committee of Chinese Medical Doctor Association, Colorectal Cancer Professional Committee of Chinese Anti-Cancer Association, Gastric Cancer Professional Committee of Chinese Anti-Cancer Association, Digestive Tract Polyp and Precancerous Lesion Professional Committee of Chinese Anti-Cancer Association, jointly convened some domestic experts to discuss and formulate the Chinese expert consensus on the application of circulating tumor cell detection in the diagnosis and treatment of gastrointestinal neoplasms (2023 edition). The consensus provides opinions on the detection technology and clinical application of CTC detection in the diagnosis and treatment of gastrointestinal neoplasms, including the prediction of tumor prognosis, the monitoring of tumor recurrence and metastasis, the evaluation of treatment response, and the additional diagnostic value, providing guidance for clinical application.
Humans ; Stomach Neoplasms/therapy* ; Neoplastic Cells, Circulating/pathology* ; Consensus ; Neoplasm Recurrence, Local ; Colorectal Neoplasms/therapy*

Circulating tumor cells (CTCs) are frequently detected in patients with advanced-stage malignant tumors and could act as a predictor of poor prognosis. However, there is a paucity of data on the relationship between CTC number and primary tumor volume in patients with lung cancer. Therefore, our study aimed to evaluate the relationship between CTC number and primary tumor volume in patients with lung adenocarcinoma.METHODS: We collected blood samples from 21 patients with treatment-naive lung adenocarcinoma and 73 healthy individuals. To count CTCs, we used a CTC enrichment method based on fluid-assisted separation technology. We compared CTC numbers between lung adenocarcinoma patients and healthy individuals using propensity score matching, and performed linear regression analysis to analyze the relationship between CTC number and primary tumor volume in lung adenocarcinoma patients.RESULTS: CTC positivity was significantly more common in lung adenocarcinoma patients than in healthy individuals (p<0.001). The median primary tumor volume in CTC-negative and CTC-positive patients was 10.0 cm³ and 64.8 cm³, respectively. Multiple linear regression analysis showed that the number of CTCs correlated with primary tumor volume in lung adenocarcinoma patients (β=0.903, p=0.002). Further subgroup analysis showed a correlation between CTC number and primary tumor volume in patients with distant (p=0.024) and extra-thoracic (p=0.033) metastasis (not in patients with distant metastasis).CONCLUSION: Our study showed that CTC numbers may be associated with primary tumor volume in lung adenocarcinomas patients, especially in those with distant metastasis.]]>
Adenocarcinoma ; Humans ; Linear Models ; Lung Neoplasms ; Lung ; Methods ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Prognosis ; Propensity Score ; Tumor Burden

Cancer is a complex, heterogeneic, and dynamic disease involving multiple gene-environment interactions, and affecting numerous biological pathways. As such, the development of reliable and robust non-invasive platforms constitutes a vital step toward realizing the potential of precision medicine. Distant metastases harbor unique genomic characteristics that are not detectable in the corresponding primary tumor of the same patient, and metastases located at different sites show considerable intra-patient heterogeneity. Thus, the analysis of the resected primary tumor alone or, if possible, re-evaluation of tumor characteristics based on the biopsy of the most accessible metastasis, may not reveal sufficient information for treatment decisions. Here, we propose that this dilemma can be solved by a new diagnostic concept: liquid biopsy, that is, the analysis of therapeutic targets and drug resistance-conferring gene mutations in or on circulating tumor cells (CTCs). Finally, the analysis of the resected primary tumor alone may provide misleading information with regard to the characteristics of metastases, the key target for systemic anticancer therapy. Liquid biopsies are noninvasive tests using blood or fluids that detect CTCs or the products of tumors, such as fragments of nucleotides or proteins that are shed into biological fluids from the primary or metastatic tumors. Such biopsies are expected to be informative or easily accessible tools to provide comprehensive information regarding cancers beyond conventional biopsies. Thus, this review addresses the use of CTCs in cancer detection, diagnosis and monitoring and discusses the direction of its clinical application in cancer patient care.
Biopsy ; Diagnosis ; Early Detection of Cancer ; Gene-Environment Interaction ; Humans ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Nucleotides ; Patient Care ; Population Characteristics ; Precision Medicine

Early detection and accurate monitoring of cancer is important for improving clinical outcomes. Endoscopic biopsy and/or surgical resection specimens are the gold standard for diagnosing gastric cancer and are also useful for selecting therapeutic strategies based on the analysis of genomic/immune parameters. However, these approaches cannot be easily performed because of their invasiveness and because these specimens do not always reflect tumor dynamics and drug sensitivities during therapeutic processes, especially chemotherapy. Accordingly, many researchers have tried to develop noninvasive novel biomarkers that can monitor real-time tumor dynamics for early diagnosis, prognostic evaluation, and prediction of recurrence and therapeutic efficacy. Circulating tumor cells (CTCs) are metastatic cells that are released from the primary tumors into the blood stream and comprise a crucial step in hematogenous metastasis. CTCs, as a liquid biopsy, have received a considerable amount of attention from researchers since they are easily accessible in peripheral blood, avoiding the invasiveness associated with traditional biopsy techniques; they can also be used to derive clinical information for monitoring disease status. In this review, with respect to CTCs, we summarize the metastatic cascade, detection methods, clinical applications, and prospects for patients with gastric cancer.
Biomarkers ; Biopsy ; Drug Therapy ; Early Diagnosis ; Humans ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Recurrence ; Rivers ; Stomach Neoplasms

Prostate cancer is characterized by bone metastases and difficulty of objectively measuring disease burden. In this context, cell-free circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) quantitation and genomic profiling afford the ability to noninvasively and serially monitor the tumor. Recent data suggest that ctDNA and CTC quantitation are prognostic for survival. Indeed, CTC enumeration using the CellSearch^® platform is validated as a prognostic factor and warrants consideration as a stratification factor in randomized trials. Changes in quantities of CTCs using CellSearch also are prognostic and may be employed to detect a signal of activity of new agents. Molecular profiling of both CTCs and ctDNA for androgen receptor (AR) variants has been associated with outcomes in the setting of novel androgen inhibitors. Serial profiling to detect the evolution of new alterations may inform drug development and help develop precision medicine. The costs of these assays and the small quantities in which they are detectable in blood are a limitation, and novel platforms are required to address this challenge. The presence of multiple platforms to assay CTCs and ctDNA also warrants the consideration of a mechanism to allow comparison of data across platforms. Further validation and the continued development and standardization of these promising modalities will facilitate their adoption in the clinic.
Biomarkers, Tumor/blood* ; DNA, Neoplasm/blood* ; Humans ; Male ; Neoplastic Cells, Circulating/immunology* ; Prognosis ; Prostatic Neoplasms/pathology* ; Transcriptome

Cancer specimens obtained via surgical resection or biopsy are generally used to understand tumor-associated alterations; however, those approaches cannot always be performed because of their invasive nature, and they may fail to reflect current tumor dynamics and drug sensitivity, which may change during the therapeutic process. Therefore, many research groups have focused on developing a non-invasive biomarker with the ability to monitor tumor dynamics. Circulating tumor cells (CTCs) are metastatic cells released from the primary tumor into the bloodstream. Hematogenous spreading of CTCs is a crucial step in the metastatic cascade, which leads to the formation of overt metastases. CTCs have attracted considerable attention because of their easy accessibility and their superiority over conventional tumor markers. Detecting CTCs is considered a valuable modality to determine prognosis and monitor response to systemic therapies in patients with gastric cancer. Moreover, molecular analyses of CTCs may provide important biological information for individual patients with cancer, which may lead to the development of personalized cancer treatment. In this article, we review potential roles and clinical applications of CTCs in patients with gastric cancer.
Biomarkers, Tumor ; Biopsy ; Humans ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Prognosis ; Stomach ; Stomach Neoplasms

Although the incidence and mortality rate of gastric cancer have been steadily declining, gastric cancer is still the fourth most common cancer in the world and more than 50% of cases occur in Eastern Asia. In Korea, gastric cancer is the second most common cancer and third cause of cancer related death. The standard surgical procedure for resectable advanced gastric cancer is D2 lymphadenectomy with radical gastrectomy. Even though R0 resection was completed, recurrence is relatively common, and contributes to the limited survival of the patients in gastric cancer. As a clinically relevant factor for detection of the recurrence, the presence of isolating tumor cells has been introduced and it is so called as ‘micrometastasis’. Numerous immunohistochemistry and molecular studies have shown that micrometastasis can be demonstrated not only in lymph nodes but also in such body compartments as the bone marrow, peritoneal cavity and blood. Herein, we review the current knowledge and evidence of the prognostic significance of micrometastasis in peritoneal, lymph node, bone marrow. Also, we discuss the current state of research on the circulating tumor cell in peripheral blood.
Bone Marrow ; Far East ; Gastrectomy ; Humans ; Immunohistochemistry ; Incidence ; Korea ; Lymph Node Excision ; Lymph Nodes ; Mortality ; Neoplasm Micrometastasis* ; Neoplastic Cells, Circulating ; Peritoneal Cavity ; Prognosis ; Recurrence ; Stomach Neoplasms*

OBJECTIVETo assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC).

METHODSA total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrol(TM) CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed.

RESULTSs CTCs were detected in 64.5% (191/296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05).

CONCLUSIONPositive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.

Carcinoma, Hepatocellular ; blood ; diagnosis ; Case-Control Studies ; Humans ; Liver Neoplasms ; blood ; diagnosis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Portal Vein ; pathology ; Prognosis

The death of patients with gastric cancer is mainly due to its recurrence and metastasis, and circulating tumor cell (CTC) is the necessary condition of metastasis. As liquid biopsy, CTC detection has its certain clinical significance. The detection is required after enrichment because circulating tumor cells are rare. Many enrichment methods have been developed: methods based on physical characteristics of TCT, like density, size and dielectric properties and so on; immunogenicity, like Cell Search System; and microfluidic chip technology. The immunofluorescence is commonly used to identify CTC in gastric cancer and the isolated CTC can also be used for the following analysis on the level of nucleic acid, protein and gene regulation. Detection of CTC in gastric cancer is helpful to judge the prognosis, assess staging, monitor the curative effect and guide the development of drug. There are many challenges for clinical transformation of CTC: the lower enrichment efficiency, the less specific surface markers, the uncertain diagnostic efficiency and so on, but it also has the good research prospect because it is non-invasive, repeatable and can real-time monitor the condition and guide the clinical treatment compared with pathological biopsy. In this paper, the detection and identification methods, and clinical value of CTC in gastric cancer patients are reviewed.
Biomarkers, Tumor ; Biopsy ; Cell Separation ; methods ; Cytodiagnosis ; methods ; Flow Cytometry ; methods ; Fluorescent Antibody Technique ; methods ; Humans ; Microchip Analytical Procedures ; methods ; Neoplasm Recurrence, Local ; prevention & control ; Neoplasm Staging ; methods ; Neoplastic Cells, Circulating ; metabolism ; pathology ; Prognosis ; Secondary Prevention ; Stomach Neoplasms ; blood ; diagnosis ; genetics ; therapy ; Treatment Outcome