Research progress of cytokine release syndrome related to CAR-T immunotherapy / 国际肿瘤学杂志

Chimeric antigen receptor T-cell (CAR-T) immunotherapy is one of the new models of tumor targeted therapy. However, the presence of cytokine release syndrome (CRS) after CAR-T infusion is a key obstacle limiting its therapeutic effects. Macrophage activation and pyrosis of target tumor cells can trigger the release of interleukin-6 and other inflammatory factors, and excessive inflammatory factors can lead to excessive activation of endothelial cells, which is a key molecular mechanism for the escalation of CRS and the occurrence of serious adverse events. Intervention in multiple stages of cytokine production and structural optimization of chimeric antigen receptor molecules are effective strategies to reduce CRS.

Short-Term Outcomes and Safety of Computed Tomography-Guided Percutaneous Microwave Ablation of Solitary Adrenal Metastasis from Lung Cancer: A Multi-Center Retrospective Study

OBJECTIVE: To retrospectively evaluate the short-term outcomes and safety of computed tomography (CT)-guided percutaneous microwave ablation (MWA) of solitary adrenal metastasis from lung cancer. MATERIALS AND METHODS: From May 2010 to April 2014, 31 patients with unilateral adrenal metastasis from lung cancer who were treated with CT-guided percutaneous MWA were enrolled. This study was conducted with approval from local Institutional Review Board. Clinical outcomes and complications of MWA were assessed. RESULTS: Their tumors ranged from 1.5 to 5.4 cm in diameter. After a median follow-up period of 11.1 months, primary efficacy rate was 90.3% (28/31). Local tumor progression was detected in 7 (22.6%) of 31 cases. Their median overall survival time was 12 months. The 1-year overall survival rate was 44.3%. Median local tumor progression-free survival time was 9 months. Local tumor progression-free survival rate was 77.4%. Of 36 MWA sessions, two (5.6%) had major complications (hypertensive crisis). CONCLUSION: CT-guided percutaneous MWA may be fairly safe and effective for treating solitary adrenal metastasis from lung cancer.

A multicenter, randomized, controlled, phase Ⅲ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.</p><p><b>METHODS</b>According to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.</p><p><b>RESULTS</b>The duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).</p><p><b>CONCLUSIONS</b>In patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.</p>

3-Phosphoinositide-dependent protein kinase-1 in tumor genesis, development and treatment / 国际肿瘤学杂志

3-phosphoinositide dependent kinase-1 (PDK1) has been shown to be a critical regulator of the PI3K-Akt pathway.PDK1 can activate Akt and participates in the activation of PI3K-Akt signaling pathway to promote tumor development,invasion and metastasis.At present,it has been found that PDK1 is highly expressed in head and neck cancer,multiple myeloma,pancreatic cancer,esophageal cancer,colon cancer and other malignant tumors.Thereby inhibiting PDK1 overexpression may provide a new breakthrough for the treatment of malignant tumor.At present,many kinds of PDK1 inhibitors have been put into production,which plays an important role in tumor therapy.

The effect of p70S6K1 and 4EBP1 protein in colorectal cancer / 国际肿瘤学杂志

The phosphatidylinositide-3-kinase(PI3K)/ protein kinase B(Akt)/ mammalian target of rapamycin(mTOR)pathway is recognized to have an important role in the development and progression of colo-rectal cancer(CRC). The most extensively characterized downstream targets of mTORC1 are ribosomal protein S6 kinase 1(p70S6K1)and eukaryotic translation initiation factor(eIF)4E-binding protein 1(4EBP1),both of which are crucial to the regulation of protein synthesis. The abnormal expression of p70S6K1 and 4EBP1 in CRC has become the focus of attention.

Akt inhibitors in the treatment of colorectal cancer / 国际肿瘤学杂志

Protein kinase B( Akt)is an intermediate signal molecule in PI3K-Akt-mTOR signaling pathway which plays an important role in development and incidence of colorectal cancer when activated by phosphorylation. As target of drugs,Akt has become a focus in the treatment of colorectal cancer. Clinical trials research proves that many kinds of Akt inhibitors have good antitumor activity. In recent years,the Akt inhibi-tors are more and more be taken seriously in colorectal cancer treatment.

The progression of chimeric antigen receptor modified T cells in malignant tumor / 国际肿瘤学杂志

Recentyearshavewitnessedmuchprogressinbothbasicresearchandclinicaltrialsregar-ding cancer immunotherapy with chimeric antigen receptor (CAR)-engineered T cells.CAR combine the varia-ble regions of a specific monoclonal antibody (scFv)with the CD3ζendodomain.The extracellular domain of CAR-engineered T cells directly dock to the tumor-associated antigen (TAA).When T cells bind to target anti-gens,they mediated redirected cytotoxicity and secrete a series of cytokines such as Perforin,Granzyme,Inter-feron-γ(IFN-γ)and Tumor necrosis factor-α(TNF-α),which would eventually lead to the necrosis of tumor cells.Although the antitumor response of the CAR-engineered T cells is considered as successful and surpri-sing,it should be noted that some safety issues have been observed in other several basic researches and clinical trials.This overview focuses upon the utility and safety of the CAR-engineered T cells.

Docetaxel combined with intraperitoneal hyperthermic perfusion chemotherapy and hyperthermia to cure advanced ovarian cancer / 中国肿瘤临床

Objective:This study aimed to observe the curative effect and adverse reaction of docetaxel combined with intraperitoneal cisplatin chemotherapy and hyperthermia treatment of advanced ovarian cancer. Methods:A total of 83 patients with inoperable and recurrent advanced ovarian cancer were randomly divided into two groups:hyperthermia group and control group. The hyperthermia group consisted of 42 cases of docetaxel chemotherapy immediately treated with intraperitoneal cisplatin chemotherapy combined with abdominal local hyperthermia. The control group included 41 cases of docetaxel chemotherapy and intraperitoneal cisplatin chemotherapy treatment only. Results:The total efficiencies of the hyperthermia treatment group and the control group were 81%and 58.1%, respectively, which showed that the total efficiency significantly improved (P<0.05). The ascite control rates were 78.3%and 66.7%and CA125 decreased by 84.2%and 61.5%for the hyperthermia and control groups, respectively. The main adverse reactions were gastrointestinal reaction and bone marrow suppression. However, differences were not statistically significant. Conclusion:Docetaxel combined with cisplatin intraperitoneal perfusion hyperthermia significantly improved the curative effect on advanced ovarian cancer without increasing toxicity, which indicates that it is a treatment worth popularizing.

EGFR mutation in malignant pleural effusion of non-small cell lung cancer / 国际肿瘤学杂志

EGFR testing has become the consensus before epidermal growth factor-tyrosine kinase inhibitorrs (EGFR-TKIs) treatment in non-small cell lung cancer(NSCLC) patients.Malignant pleural effusion is the common clinical manifestation in NSCLC patients,and EGFR testing by using different methods in pleural effusion cells and free nucleic acids has good prospect for predicting the efficacy of EGFR-TKIs.