BACKGROUND:Secreted protein acidic and rich in cysteine (SPARC) is always considered as a marker of poor prognosis. However, it helps to transport nab-paclitaxel and may lead better therapeutic ending. This meta-analysis was aimed to assess the relationship between SPARC expression level and clinical efficacy of nab-paclitaxel.METHODS:The PubMed and Embase databases were searched from inception to April 2020, and search terms included nanoparticle albumin-bound paclitaxel, nab-paclitaxel, nab-PTX, Abraxane, ABI-007, secreted protein acidic and rich in cysteine, SPARC, osteonectin, and BM-40. In addition, funnel plots were used to indicate the existence of publication bias.RESULTS:After further screening the full text, 5 studies that involved 336 patients were finally included in the study, of which, 3 studies concentrated on non-small cell lung cancer (NSCLC) and the other 2 on breast cancer and pancreatic cancer. SPARC status in tumor cells and stromal cells was taken into account. The HR for progression-free survival (PFS) between SPARC high and low groups was 1.25 (95% CI: 0.72-2.14, stromal cell) and 1.51 (95% CI: 0.93-2.46, tumor cell). The HR for OS between SPARC high and low groups was 1.07 (95% CI: 0.57-2.03, stromal cell) and 1.34 (95% CI: 0.74-2.43, tumor cell). It was revealed that SPARC expression level in tumor cells or stromal cells was not significantly correlated with the patient's survival outcomes. No significant publication bias was found in each analysis.CONCLUSIONS:SPARC expression level detected by immunohistochemistry (IHC) cannot predict the efficacy of nab-paclitaxel, while further large-scale clinical trials are required to confirm our findings.
Mitochondrial respiratory chain complex I deficiency is one of common mitochondrial disorders. However, the information is relatively little about the features of Chinese patients. In this study, the clinical, biological, and genetic analyses were performed in the children with respiratory chain complex I deficiency, in order to further understand the characteristics of the disease. Over a 3-year period, 67 patients (37 boys, 30 girls), presenting with unexplained multisystemic symptoms and signs were recruited. Clinical and laboratory data of the patients were summarized. Spectrophotometric assay was used for the analysis of mitochondrial complex I-V enzyme activity in peripheral leukocytes. The entire mitochondrial DNA (mtDNA) sequence was analysed for patients and their mothers. The children with respiratory chain complex I deficiency presented with multisystem dysfunction. Onset occurred before the third year of life in 96.9% patients without mtDNA mutation. Onset occurred before the third year of life in 76.5% of patients with mtDNA mutation (P = .03). About 51.5% of patients without mtDNA mutation had weakness, which is higher than 24% patients with mtDNA mutation (P = .02). Isolated complex I deficiency and combined complex I deficiency were found in 45 and 22 patients, respectively. The prevalence of isolated complex I deficiency was higher in the patients with mtDNA mutations (79.4%) than in the patients without mtDNA mutations (54.5%). Patients with nuclear DNA mutations are more likely to develop early onset in mitochondrial respiratory chain complex I deficiency. The patients with complex I deficiency of peripheral leukocytes may be more likely to be caused by mtDNA mutation.
Introduction: Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment.Areas covered: This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects.Expert opinion: Somatostatin analogs may control symptoms of hormone excess and tumor growth in patients with well-differentiated metastatic NETs, and biological therapies may improve progression-free survival for these patients. However, chemotherapy leads to higher objective response rates and symptom control by reducing tumor bulk. The low response rate and significant toxicities of conventional chemotherapy regimens limit their widespread use. Fortunately, some novel fluoropyrimidine-based treatment including fluorouracil, capecitabine, or S-1 based chemotherapy with or without antiangiogenic agents have been investigated in recent years. These treatments showed significant efficacy and less toxicity in pancreatic and non-pancreatic metastatic well-differentiated NETs. Additionally, non-pancreatic well-differentiated NETs have also achieved similar tumor response or survival comparable to pancreatic NETs. Moreover, some predictors of response to these treatment regimens have been evaluated.
The highest risk areas of gastric cancer are currently Japan, Korea and China; Qinghai, a high-altitude area, has one of the highest gastric cancer rates in China. The incidence of gastric cancer is higher in the Tibetan ethnic group compared to that in the Han ethnic group in Qinghai. This study was conducted to determine the clinical characteristics of mitochondrial DNA (mtDNA) mutations and copy numbers among Tibetans with gastric cancer residing at high altitudes and investigate the association between adaptations to hypoxic conditions and oncogenesis. A total of 23 Tibetan gastric cancer patients and 40 matched controls were recruited in this study. Leukocyte mtDNA genes and copy numbers were analyzed. The haplogroups were classified based on mitochondrial gene sequences. A total of 56.5% of the study participants had used alcohol at some point in their lives and 73.9% were positive for Helicobacter pylori (H. pylori). Eight mutations in 8 mitochondrial genes were identified in 43.4% of the Tibetan cancer patient group. There were no significant differences in leukocyte mtDNA copy number levels based on smoking status, alchohol consumption, obesity or H. pylori infection between the control and cancer groups. Statistical differences were also not found between gastric cancer patients with and those without mtDNA mutations. The majority of Tibetan patients with gastric cancer belonged to the mitochondrial haplogroup M9. In conclusion, Tibetans with gastric cancer residing at high altitudes exhibited a wide spectrum of mtDNA mutations. However, leukocyte mtDNA copy numbers in stage II gastric cancer were not statistically different compared to those in healthy Tibetans.