Bevacizumab in combination with anticancer drugs for previously treated advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Patients with NSCLC often have an advanced disease at the time of diagnosis, with a 1-year survival rate about 10-15% under the best support treatment. As therapeutic methods for lung cancer developed rapidly in recent years, the prognosis of stage IIIB or IV NSCLC also improve to a large extend. Bevacizumab is a monoclonal antibody against VEGFR which inhibits abnormal vascular growth in malignant tumors. In October 2006, bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for first-line use in advanced NSCLC. For patients with advanced NSCLC who failed in previously platinum-based chemotherapy, bevacizumab also showed enhancing efficacy to antitumor drugs recommended by the latest NCCN guideline. This review intends to present the recent progress and prospects of bevacizumab in second- or third-line treatment for patients with refractory NSCLC.

Comprehensive assessment of the association between XPD rs13181 polymorphism and lung cancer risk.

Xeroderma pigmentosum group D (XPD) rs13181 may reduce DNA repair capacity (DRC) through modifying XPD protein product. Reduced DRC is reportedly related to an increase in the risk of lung cancer. To precisely estimate the association between XPD rs13181 and lung cancer risk, we carried out the current meta-analysis. We searched multiple databases (up to 31 October 2013) for studies investigating the association of XPD rs13181 and lung cancer. Odds ratio (OR) was estimated with the fixed effect model to assess the association. Heterogeneity between studies was measured using Q test. Subgroup analyses were conducted by ethnicity, histological type, and sample size. Meta-analysis of 30 studies suggested that individuals carrying Gln/Gln genotype were more likely than the individuals with Lys/Lys or Lys/Gln + Lys/Lys genotypes (homozygous model, OR 1.18, 95 % confidence interval (CI) 1.07-1.31; recessive model, OR 1.17, 95 % CI 1.06-1.29) to develop lung cancer, without any substantial heterogeneity. This significantly increased risk was also revealed in the individuals harboring Gln/Gln + Lys/Gln genotypes (dominant model, OR 1.07, 95 % CI 1.01-1.12). Further stratification by histological type, ethnicity, and sample size yielded statistically significant estimates in subgroup of Caucasian subjects, non-small cell lung cancer, and relatively large studies, but borderline association in Asians. Our analyses demonstrate that XPD rs13181 may be associated with an increase in the risk of lung cancer among Caucasian populations.

Skeletal Muscle Change During Neoadjuvant Therapy and Its Impact on Prognosis in Patients With Gastrointestinal Cancers: A Systematic Review and Meta-Analysis.

Background: Gastrointestinal cancers are the most common malignant tumors worldwide. As the improvement of survival by surgical resection alone for cancers is close to the bottleneck, recent neoadjuvant therapy has been emphasized and applied in the treatment. Despite the advantage on improving the prognosis, some studies have reported neoadjuvant therapy could reduce skeletal muscle and therefore affect postoperative outcomes. However, the conclusions are still controversial. Methods: PubMed, CINAHL, Embase, and Cochrane Library were searched from inception to September 2, 2021. The inclusion criteria were observational studies, published in English, of individuals aged ≥18 years who underwent neoadjuvant therapy with gastrointestinal cancers and were assessed skeletal muscle mass before and after neoadjuvant therapy, with sufficient data on skeletal muscle change or the association with clinical outcomes. Meta-analysis was conducted by using the STATA 12.0 package when more than two studies reported the same outcome. Results: A total of 268 articles were identified, and 19 studies (1,954 patients) were included in the review. The fixed effects model showed that the risk of sarcopenia increased 22% after receiving neoadjuvant therapy (HR=1.22, 95% CI 1.14, 1.31, Z=4.286, P<0.001). In the random effects model, neoadjuvant therapy was associated with skeletal muscle loss, with a standardized mean difference of -0.20 (95% CI -0.31, -0.09, Z=3.49, P<0.001) and a significant heterogeneity (I2 = 62.2%, P<0.001). Multiple meta regression indicated that population, neoadjuvant therapy type, and measuring tool were the potential sources of heterogeneity. The funnel plot revealed that there was no high publication bias in these studies (Begg's test, P=0.544) and the sensitivity analysis showed stable results when separately excluding studies. For the postoperative outcomes, the results revealed that muscle loss during neoadjuvant therapy was significantly related to overall survival (HR=2,08, 95% CI =1.47, 2.95, Z=4.12, P<0.001, I2 = 0.0%), but not related to disease-free survival and other short-term outcomes. Conclusions: This systematic review and meta-analysis revealed that skeletal muscle decreased significantly during neoadjuvant therapy in patients with gastrointestinal cancers and skeletal muscle loss was strongly associated with worse overall survival. More high-quality studies are needed to update and valid these conclusions in a more specific or stratified way. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier PROSPERO (CRD42021292118).

Comparison of five sarcopenia screening tools in preoperative patients with gastric cancer using the diagnostic criteria of the European Working Group on Sarcopenia in Older People 2.

OBJECTIVES: The aim of this study was to compare the performance of five sarcopenia screening tools in preoperative patients with gastric cancer, including strength, assistance with walking, rise from a chair, climb stairs, and falls; strength, assistance with walking, rise from a chair, climb stairs, falls, and calf circumference (SARC-CalF); Ishii score chart; short version of the mini sarcopenia risk assessment; and full version of the mini sarcopenia risk assessment. METHODS: We conducted a cross-sectional study of consecutive patients undergoing a gastrectomy between May 2020 and October 2020. Sarcopenia was diagnosed per the diagnostic criteria proposed by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Data on the five sarcopenia screening tools, patient characteristics, nutrition risk screening 2002, and diagnostic indicators of sarcopenia were collected preoperatively, and pathological characteristics of the tumor were collected postoperatively. Based on the EWGSOP2 criteria, the clinical validity of the sarcopenia tools was measured using sensitivity, specificity, and predictive value. A receiver operator characteristic curve and area under curve were applied to compare the overall screening accuracy, and a Youden index was calculated to determine the optimal cutoff value of each tool. RESULTS: We included 260 participants age 62.38 ± 11.21 y. Based on the EWGSOP2 criteria, the prevalence of sarcopenia and severe sarcopenia were 8.46% and 4.62%, respectively. Moreover, the prevalence of sarcopenia risk ranged from 3.46% to 73.85% based on the five screening tools. Of these tools, SARC-CalF had the largest area under the curve (0.896) with moderate-to-high sensitivity (86.36%) and high specificity (92.86%). For SARC-CalF, the cutoff value of 10 reached the highest Youden index, and the corresponding sensitivity and specificity were 81.82% and 93.44%, respectively. CONCLUSION: Among the above five screening tools, SARC-CalF appeared to be the optimal choice to screen sarcopenia in preoperative patients with gastric cancer.

TFDP3 regulates the apoptosis and autophagy in breast cancer cell line MDA-MB-231.

Cancer/testis antigen TFDP3 belongs to the transcription factor DP(TFDP) family. It can bind to E2F family molecules to form a heterodimeric transcription factor E2F/TFDP complex. The complex is an important regulatory activator of cell cycle, involved in the regulation of cell proliferation, differentiation, apoptosis and other important physiological activities. In addition, TFDP3 has also been found to be a tumor-associated antigen that only expresses in malignant tumor tissue and normal testicular tissue; Thus, it is closely related to tumor occurrence and development. In this study, our group investigated the expression of TFDP3 in mononuclear cell samples from a variety of tissue-derived malignant tumors, breast cancer and benign breast lesions. The results show that TFDP3 is expressed in the malignant form of various tissues. Moreover, our recent research had focused on the ability of TFDP3 to influence the drug resistance and apoptosis of tumor cells. To further clarify the mechanisms involved in tumor resistance, this study also examined the expression of TFDP3 and tumor cell autophagy regulation; Autophagy helps cells cope with metabolic stress (such as in cases of malnutrition, growth factor depletion, hypoxia or hypoxia) removes erroneously folded proteins or defective organelles to prevent the accumulation of abnormal proteins; and removes intracellular pathogens. Our results showed that TFDP3 expression can induce autophagy by up-regulating the expression of autophagic key protein LC3(MAP1LC3) and increasing the number of autophagosomes during chemotherapy of malignant tumors. Then, DNA and organelles damage caused by the chemotherapy medicine are repaired. Thus, TFDP3 contributes toward tumor cell resistance. When siRNA inhibits TFDP3 expression, it can reduce cell autophagy, improving the sensitivity of tumor cells to chemotherapy drugs.

Targeted therapy of multiple liver metastases after resected solitary gastric metastasis and primary pulmonary adenocarcinoma.

Gastric metastases from lung adenocarcinoma are rare and usually asymptomatic. A 61-year-old woman was referred to our department because of a right lower pulmonary mass found on a chest X-ray film in August 2012. Right lower lobectomy was performed for pulmonary adenocarcinoma. Four months later, she developed epigastric discomfort. A fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) scan showed a malignancy at the cardias of the stomach. A biopsy diagnosed poorly differentiated carcinoma and a gastric carcinoma was suspected. She underwent a subtotal gastrectomy and part of esophagectomy. The histologic diagnosis was metastasis from the pulmonary adenocarcinoma. She visited us again for her increasing level of carcinoembryonic antigen (CEA) after two months. FDG-PET/CT showed multiple malignant lesions in her liver, considering metastases from pulmonary origin. As she harbored activating epidermal growth factor receptor (EGFR) mutation, she received erlotinib from April, 2013. She survives 4 years after the lung resection and is still on erotinib treatment with complete response. Although gastric metastasis from lung cancer is considered a late stage of the disease, a radical resection might provide survival in solitary metastasis. Moreover, systemic therapy was emphasized after local treatment in some late stage cases.

Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections.

Berberine is an isoquinoline alkaloid widely used in the treatment of microbial infections. Recent studies have shown that berberine can enhance the inhibitory efficacy of antibiotics against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA). However, the underlying mechanisms are poorly understood. Here, we demonstrated that sub-minimum inhibitory concentrations (MICs) of berberine exhibited no bactericidal activity against MRSA, but affected MRSA biofilm development in a dose dependent manner within the concentration ranging from 1 to 64 µg/mL. Further study indicated that berberine inhibited MRSA amyloid fibrils formation, which consist of phenol-soluble modulins (PSMs). Molecular dynamics simulation revealed that berberine could bind with the phenyl ring of Phe19 in PSMα2 through hydrophobic interaction. Collectively, berberine can inhibit MRSA biofilm formation via affecting PSMs' aggregation into amyloid fibrils, and thereby enhance bactericidal activity of antibiotics. These findings will provide new insights into the multiple pharmacological properties of berberine in the treatment of microbial-generated amyloid involved diseases.