Metronomic chemotherapy (MCT) is defined as the rhythmic chemotherapy of low-dose cytotoxic drugs with short or no drug-free breaks over prolonged periods. MCT affects tumor cells and the tumor microenvironment. Particularly, the low-dose schedule impairs the repair process of endothelial cells, resulting in an anti-angiogenesis effect. By stimulating the immune system to eliminate tumor cells, MCT induces immunological activation. Furthermore, combined with targeted therapy, anti-angiogenic drugs enhance the efficacy of MCT. The present review is an overview of phase I, II and III clinical trials focusing on the efficacy, toxicity and mechanism of MCT in patients with non-small cell lung cancer (NSCLC). Furthermore, the prospects of MCT in NSCLC have been discussed. The present review indicated that MCT is an efficacious treatment for selected patients with NSCLC, with acceptable systemic side effects and economic viability for public health. Contents 1. Introduction 2. Preclinical studies of MCT 3. Clinical trials of MCT 4. Mechanism of MCT 5. Conclusion

BackgroundIn patients with metastatic colorectal cancer (mCRC) with an asymptomatic primary tumor, there is no consensus on the indication for resection of the primary tumor.MethodsThe PubMed, Embase and the Cochrane Library databases were searched from inception to November 30,2021. A meta-analysis was performed using RevMan (version 5.3.3; The Cochrane Collaboration) on the outcome of mCRC patients with or without resection of the primary tumor in 8 selected studies.ResultsThis meta-analysis included 2805 colorectal cancer patients with an asymptomatic primary tumor from 8 selected studies. Primary tumor resection (PTR) patients had longer overall survival (OS: MD =6.76 [3.39, 10.12], I2 = 77%, P < 0.0001), compared with non-primary tumor resection (NPTR) patients. In the subgroup, the randomized controlled trials (RCT) PTR group didn’t have longer overall survival (OS: MD =3.79 [-3.49, 11.08], I2 = 69%, P= 0.31); the Non-RCT PTR group had longer overall survival (OS: MD =8.42 [3.14, 13.70], I2 = 89%, P= 0.002). In the meanwhile, compared with NPTR group, the 2-year overall survival rate, the 3-year overall survival rate, 5-year overall survival rate in the PTR group is higher (OR=2.35 [1.74, 3.18], I2 = 0%, P < 0.00001; OR=3.61 [2.35, 5.54], I2 = 0%, P < 0.00001; OR=3.02 [1.72, 5.33], I2 = 48%, P= 0.0001, respectively).ConclusionsOur results from studies demonstrate that the resection of primary tumor is a prognostic factor for survival in mCRC patients. However, 2 RCTs showed the resection of primary tumor was not related with a significant survival benefit in subgroup. Therefore, a larger RCT in the era of modern chemotherapy and liver resection techniques would be helpful.

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. However, up to 40-50% of GISTs develop secondary resistance after an average of 24 months of imatinib treatment. It has been reported that autophagy can promote the survival of GIST cells and induce drug resistance. Presently, the specific mechanism of autophagy in GISTs with imatinib resistance is not clear. Materials and Methods: The cell-counting kit (CCK)-8 method and flow cytometry were used for in vitro drug sensitivity testing and autophagy level detection. Detection of the apoptosis level was by flow cytometry with the annexin V Kit. Western blotting was used to analyze the role of autophagy and apoptosis in GIST cells with CQ alone, imatinib alone, or in combination, and to analyze MAPK pathway expression. In vitro results were confirmed by in vivo experiments using the mice model. Hematoxylin and eosin and immunohistochemical staining were used to detect the pathological characteristics and immunophenotype of the transplanted tumor. Detection of KIT and PDGFRA gene mutations in the transplanted imatinib-resistant GIST was done by denaturing high performance liquid chromatography (DHPLC) and direct sequencing. ERK and KIT expression and regulation levels were detected by Western blotting. Results: In vitro and vivo experiments, the autophagy level of imatinib-resistant cells was higher than that of normal cells; CQ combined with imatinib can promote apoptosis by blocking autophagy of imatinib-resistant cells. In the meanwhile, we found that the phosphorylation level of ERK may be related to autophagy. Conclusion: Our data suggest that autophagy through the MAPK/ERK pathway may play a pivotal role in imatinib-resistant GIST proliferation. Moreover, combining an autophagy inhibitor with imatinib may be a potential valuable strategy in overcoming acquired resistance in GIST patients.

Introduction: Mature ovarian cystic teratoma is a cystic fatty tumor. Presence of floating fat balls in an ovarian cystic teratoma looking like a “sack of marbles” on magnetic resonance imaging (MRI) is a rare finding. Patient concerns: Herein, we report a 38-year old woman who was admitted to our hospital presenting with an abdominal mass and abdominal pain. Diagnosis: Ultrasonography revealed a giant cystic mass in the pelvis; T1-weighted MRI revealed multiple spherical signals in the lesion. Interventions: She underwent exploratory laparotomy and was histopathologically diagnosed with benign cystic teratoma. Outcomes: Finally, the patient recovered after operation. Until December 2018, she had been still healthy without recurrence of tumors. Conclusion: The aim of this case report was to present “sack of marbles” appearance on MRI, which will impress other doctors and improve the diagnosis of such diseases.

Rationale:Variant Philadelphia chromosome translocations involving chromosomes other than chromosomes 9 and 22 have been reported in 5% to 10% of patients with chronic myeloid leukemia (CML). Here, a case of CML with a t (9, 22, 16) (q34; q11; p13) translocation, which has never been described, is reported.Patient concerns:A 59-year-old female with dry cough, referred to our hospital, exhibited hepatosplenomegaly, high basophil count, and high platelet count at admission without any other known chronic diseases.Diagnoses:The patient was diagnosed with CML with the translocation t (9;22;16) (q34; q11; p13). The patient was treated with imatinib, a first-generation tyrosine kinase inhibitor (TKI), discontinuously, achieving a complete hematological response for 7 years. Since November 8, 2017, the patient had recurrent fever, and her platelet count rose to 1422 × 109/L. Subsequently, the E279K mutation in the BCR-ABL kinase region was detected.Outcomes:According to a previous report, this mutation confers sensitivity to nilotinib, a second-generation TKI. In the end, the patient received treatment with nilotinib and showed a complete hematological response.Lessons:The present study reports a rare case of CML with Ph chromosome and a t (9;22;16) (q34; q11; p13) translocation. For such cases about CML with variant Philadelphia chromosome translocations or BCR-ABL kinase region mutation, TKI may still be valuable.