OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

Brain metastasis (BM) is the leading cause of mortality in lung cancer patients. The process of BM (from initial primary tumor development, migration and intravasation, dissemination and survival in the bloodstream, extravasation, to colonization and growth to metastases) is a complex process for which few tumor cells complete the entire process. Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment (TME) in assisting tumor cells in the completion of each BM step. This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer. The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.
Brain Neoplasms/pathology* ; Humans ; Lung Neoplasms/drug therapy* ; Neoplasm Metastasis ; Tumor Microenvironment

metastasis stage, differentiation, invasion depth, and lymph node metastasis (p< 0.005). ProGRP levels were significantly decreased after chemotherapy (p<0.001). Receiver operating characteristic curves revealed a sensitivity and specificity for serum ProGRP in GC of 85.9% and 81.2%, respectively. ProGRP levels were positively correlated with CA72-4 and CEA (r=0.792 and 0.688, p<0.05, respectively). Combined detection of ProGRP, CEA, and CA72-4 showed the best diagnostic power for GC.CONCLUSION: ProGRP may be useful as a potential biomarker for GC diagnosis and therapy.]]>
Carcinoembryonic Antigen ; Diagnosis ; Drug Therapy ; Humans ; Lymph Nodes ; Male ; Neoplasm Metastasis ; ROC Curve ; Sensitivity and Specificity ; Stomach Diseases ; Stomach Neoplasms

OBJECTIVE: To retrospectively evaluate the safety and efficacy of percutaneous radiofrequency ablation (RFA) in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma who had previously received curative surgery.MATERIALS AND METHODS: Between 2002 and 2017, percutaneous RFA was performed on 94 metachronous hepatic metastases (median diameter, 1.5 cm) arising from pancreatic cancer in 60 patients (mean age, 60.5 years). Patients were included if they had fewer than five metastases, a maximum tumor diameter of ≤ 5 cm, and disease confined to the liver or stable extrahepatic disease. For comparisons during the same period, we included 66 patients who received chemotherapy only and met the same eligibility criteria described.RESULTS: Technical success was achieved in all hepatic metastasis without any procedure-related mortality. During follow-up, local tumor progression of treated lesions was observed in 38.3% of the tumors. Overall median survival and 3-year survival rates were 12 months and 0%, respectively from initial RFA, and 14.7 months and 2.1%, respectively from the first diagnosis of liver metastasis. Multivariate analysis showed that a large tumor diameter of > 1.5 cm, a late TNM stage (≥ IIB) before curative surgery, a time from surgery to recurrence of < 1 year, and the presence of extrahepatic metastasis, were all prognostic of reduced overall survival after RFA. Median overall (12 months vs. 9.1 months, p = 0.094) and progression-free survival (5 months vs. 3.3 months, p = 0.068) were higher in the RFA group than in the chemotherapy group with borderline statistical difference.CONCLUSION: RFA is safe and may offer successful local tumor control in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma. Patients with a small diameter tumor, early TNM stage before curative surgery, late hepatic recurrence, and liver-only metastasis benefit most from RFA treatment. RFA provided better survival outcomes than chemotherapy for this specific group with borderline statistical difference.
Adenocarcinoma ; Catheter Ablation ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Liver ; Mortality ; Multivariate Analysis ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Recurrence ; Retrospective Studies ; Survival Rate

OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.
Acrylamides/therapeutic use* ; Adult ; Aged ; Aminoquinolines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/drug therapy* ; China ; Humans ; Middle Aged ; Neoplasm Metastasis ; Receptor, ErbB-2 ; Retrospective Studies ; Trastuzumab ; Treatment Outcome

PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84–0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837–0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.
Area Under Curve ; Breast Neoplasms ; Breast ; Calibration ; Discrimination (Psychology) ; Drug Therapy ; Humans ; Logistic Models ; Lymph Nodes ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Nomograms ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone

A 57-year-old male with periampullary duodenal mass was diagnosed as grade 3 duodenal neuroendocrine carcinoma with multiple liver metastasis. After nine cycles of cisplatin and etoposide, abdominal computed tomography (CT) findings showed complete regression of primary duodenal mass with marked size reduction of liver metastasis. Positron emission tomography findings showed metabolic complete response in both duodenal and liver mass. Pylorus-preserving pancreaticoduodenectomy was done and pathologic finding showed 5 mm sized remnant neuroendocrine tumor. The patient has remained alive with no evidence of disease for 43 months after initial diagnosis. This case suggests the possibility of heterogeneous nature of grade 3 neuroendocrine carcinoma and selected population may have extreme sensitivity to cisplatin and etoposide chemotherapy leading to complete response.
Carcinoma, Neuroendocrine ; Cisplatin ; Diagnosis ; Drug Therapy ; Etoposide ; Humans ; Liver ; Male ; Middle Aged ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Pancreaticoduodenectomy ; Positron-Emission Tomography

Gastric cancer involving the placenta during pregnancy is rare; however, we present 1 such case in this report. A 31-year-old Japanese woman was referred at 26 weeks of gestation for the evaluation of a swollen left supraclavicular lymph node. Biopsy revealed poorly differentiated adenocarcinoma, and esophagogastroduodenoscopy with biopsy of the stomach confirmed the diagnosis of gastric cancer. Her epigastric and back pain became more pronounced and her general status worsened, and we performed a cesarean delivery at 29 weeks. Microscopic examination of the placental specimen revealed poorly differentiated adenocarcinoma cells diffused into the intervillous space. Postpartum chemotherapy consisted of S-1 plus oxaliplatin. Unfortunately, this treatment was ineffective, and the patient died 3 months after delivery. The infant did well, without clinical or laboratory manifestations of metastasis. In patients with advanced gastric cancer during pregnancy, it is important to perform a microscopic examination of the placenta to evaluate for metastatic involvement.
Adenocarcinoma ; Adult ; Asian Continental Ancestry Group ; Back Pain ; Biopsy ; Diagnosis ; Drug Therapy ; Endoscopy, Digestive System ; Female ; Humans ; Infant ; Lymph Nodes ; Neoplasm Metastasis ; Placenta ; Postpartum Period ; Pregnancy ; Stomach ; Stomach Neoplasms

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031–3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.
Colorectal Neoplasms ; Drug Therapy ; Factor Xa Inhibitors ; Gastrointestinal Tract ; Hemorrhage ; Heparin, Low-Molecular-Weight ; Humans ; Incidence ; Mortality ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Rivaroxaban ; Stomach Neoplasms ; Venous Thromboembolism

With the advances in hepatocellular carcinoma (HCC) treatment, the lung metastasis of HCC is becoming increasingly important. In treating the lung metastasis of HCC, a multidisciplinary approach can lead to better results than systemic chemotherapy alone. Here, we report on a patient who presented with pulmonary masses, while the HCC was being controlled in the abdominal cavity. The presence of nontuberculous mycobacteria was identified during the diagnosis of the pulmonary masses. The pulmonary metastases of HCC were treated with a combination of angiotherapy, radiation therapy, and radiofrequency ablation. The patient showed a satisfactory progress with this multidisciplinary localized treatment. We report the clinical progress and review the recent literature regarding the treatment of pulmonary metastasis without intrahepatic HCC herein.
Abdominal Cavity ; Carcinoma, Hepatocellular ; Catheter Ablation ; Diagnosis ; Drug Therapy ; Humans ; Lung ; Neoplasm Metastasis ; Nontuberculous Mycobacteria