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*

AC133 Antigen ; Animals ; Antigens, CD ; metabolism ; Antigens, CD34 ; metabolism ; Antineoplastic Agents ; pharmacology ; Biomarkers, Tumor ; metabolism ; Glycoproteins ; metabolism ; Humans ; Neoplasms ; drug therapy ; metabolism ; pathology ; Neoplastic Cells, Circulating ; pathology ; Neoplastic Stem Cells ; drug effects ; metabolism ; pathology ; Peptides ; metabolism ; Receptors, Notch ; metabolism ; Signal Transduction ; Stem Cells ; drug effects ; metabolism ; pathology

OBJECTIVETo investigate the safety and tolerance of adjuvant dose-dense chemotherapy with paclitaxel and epirubicin for high-risk breast cancer.

METHODSFrom January 2004 to December 2006, 101 patients with high-risk breast cancer after surgical resection were enrolled into this study. The patients were divided into two groups: dose-dense and regular groups. Each patient received 6 cycles of chemotherapy with intravenous administration of paclitaxel (175 mg/m2, on D3) and epirubicin (60 mg/m2, on Dl and D2). The dose-dense group had repeated treatment every two weeks, while the regular group repeated it every three weeks. G-CSF was used in a dose of 3 microg/kg on D5-D9 during each cycle in the dose-dense group. While in the regular group, it was used only under the condition that grade II neutropenia occurred.

RESULTSThe toxicity could be evaluated in 101 patients. Major grade II-IV toxicities included: neutropenia, nausea, vomiting and alopecia. The incidence of grade III-IV neutropenia was 16.0% in the dose-dense group versus 54.9% in the regular group (P = 0.000); postponing of chemotherapy was 2.4% versus 6.0% (P = 0.027). Ninety-eight patients completed the chemotherapy as planed. After a median follow-up of 24 months, the median DFS and OS were not reached. The relapse-free rate and survival rate were 89.8% and 100% in the dose-dense group, which were 87.8% and 93.9% in the regular group. The relapse-free rate of the high-risk patients in the dose-dense group was 86.8% versus 81.3% in the regular group, and the corresponding survival rate was 100% versus 90.6%.

CONCLUSIONAdjuvant dose-dense chemotherapy with paclitaxel and epirubicin is safe, tolerable and promising for high-risk breast cancer.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; surgery ; Chemotherapy, Adjuvant ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Follow-Up Studies ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Humans ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; adverse effects ; Survival Rate ; Vomiting ; chemically induced ; Young Adult

OBJECTIVETo investigate the prognostic significance of micrometastasis (MM) in peripheral blood of patients with non-small cell lung cancer (NSCLC) treated by chemo-radiation therapy.

METHODSPeripheral blood was taken from 67 NSCLC patients before and after definitive chemo-radiation therapy. CK19 mRNA of the peripheral blood was measured by nested RT-PCR and both their relationship with clinicopathological features and prognostic significance were further investigated.

RESULTSThe micrometastasis-positive rates were 65.7% (44/67) and 32.8% (22/67), respectively, before and after the treatment. The micrometastasis-positive rate before treatment was closely in correlation with N-stage (P = 0.014). In contrast, it turned out to be more closely related with histological types (P = 0.019), weight loss (P = 0.01), KPS status (P = 0.027) as well as N-stage (P = 0.032) after chemo-radiation therapy. 4-yr distant metastasis rates (DMR) for micrometastasis-positive and -negative patients were 78.3% and 70.4%, respectively, before the treatment (P = 0.544) while they were 100% and 62.9%, respectively, after the chemoradiation (P < 0.001). The median survival time (MST) and 4-yr overall survival rate (OSR) for pretreatment micrometastasis-positive and -negative patients were 13.8 months and 17.6 months, and 18.2% and 17.4%, respectively (P = 0.619), while for post-treatment micrometastasis-positive and -negative patients they were 7.8 months and 27.6 months and 0 and 26.4%, respectively (P < 0.001). Multivariate analysis showed that the post-treatment positive micrometastasis was an independent unfavorable prognostic factor (P = 0.000).

CONCLUSIONDetection of micrometastasis in peripheral blood may possess a prognostic significance after definitive chemo-radiation therapy. Micrometastasis-negative patients have better prognosis compared to those with positive micrometastasis.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; therapy ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; drug effects ; radiation effects ; Humans ; Keratin-19 ; genetics ; Lung Neoplasms ; genetics ; pathology ; therapy ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplastic Cells, Circulating ; drug effects ; pathology ; radiation effects ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Radiotherapy, High-Energy ; methods ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Analysis