Search

Background Recently for advanced gallbladder carcinoma, neoadjuvant chemotherapy has emerged as an important strategy in place of adjuvant chemotherapy with the hope that it will help to improve the resectability and survival. Aim and objective The goal was to conduct a systematic review of published publications on the benefits of neoadjuvant chemotherapy for advanced gallbladder cancer treatment. Materials and methods This systematic review followed the Meta-analysis Of Observational Studies in Epidemiology standards. The clinical benefit rate of neoadjuvant chemotherapy, curative resectability rate, and R0 resection were the major outcomes of interest. The secondary outcomes of interest were overall and disease-free survival. Results Six published papers were included (n = 420). One-hundred and twenty-eight cases (30.47%) despite receiving neoadjuvant chemotherapy had disease progression. Although 67.38% of patients (283 of 420) in this systematic review showed good response to the neoadjuvant chemotherapy, just 51.66% (217 of 420 cases) were operated, out of which only 171 cases were deemed to be feasible for surgical resection and had curative resection. Out of the cases that underwent curative surgery, 91.81% had R0 resection (157 out of 171 patients). The overall survival rate was found to be 18.5–50.1 months for patients in whom curative surgery was done and 5.0–10.8 months for nonsurgery patients. Conclusion No sufficient data exist to advocate the regular use of neoadjuvant chemotherapy in advanced gallbladder carcinoma, as data showed that only 1/3 of patients benefited and had a R0 resection. Further research should be the randomized controlled trials to further quantify the benefit of neoadjuvant chemotherapy in advanced gallbladder carcinoma. How to cite this article Naveed S, Qari H, Thau CM, et al. Neoadjuvant Chemotherapy for Advanced Gallbladder Cancer: Do We have Enough Evidence? A Systematic Review. Euroasian J Hepato-Gastroenterol 2021;11(2):87–94.

Ruiyun Zhang,1,* Jun Xia,2,* Yiqiu Wang,1,* Ming Cao,1 Di Jin,1 Wei Xue,1 Yiran Huang,1 Haige Chen1 1Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Cao; Haige ChenDepartment of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaEmail chowming2007@gmail.com; rjbladder@163.comObjective: Cancer cells with stemness and epithelial-to-mesenchymal transition (EMT) features display enhanced malignant and metastatic potential. This study aimed to introduce a new methodology developed in order to investigate the co-expression of a stemness (OCT4) and EMT markers on single circulating tumor cells (CTCs) of patients with localized urinary bladder cancer and their potential prognostic prediction value.Methods and Materials: Between April 2015 and July 2015, blood samples of 51 consecutive patients diagnosed with high risk bladder cancer (cT1-3N0M0) were prospectively investigated for CTCs. Peripheral blood (5 mL) was drawn before primary transurethral resection. Detection of CTCs was performed using the CanPatrolTM system. Nucleic acid probes were used to identify CTCs, and expression levels of epithelial and mesenchymal genes in CTCs were examined by situ hybridization assay.Results: All patients received radical cystectomy with pelvic lymph nodes dissection. CTCs were detected in 44 of 51 (86.3%) patients, respectively. The overall mean number of CTCs was 6.1 (range: 0∼ 29; median: 4). A total of 311 CTCs were detected in PB. High OCT4 expression (OCT4high) was detected more frequently in Epi−Mes+ cells (p=0.001). Patients with pathological confirmed muscle-invasive bladder cancer (MIBC) had higher Epi−Mes+ CTCs positive rates (p=0.001) and OCT4high CTCs positive rates (p=0.019) than pathological confirmed non muscle-invasive bladder cancer (NMIBC). Regarding co-expression of these markers, Epi−Mes+/OCT4high CTCs were more frequently evident in the MIBC setting (30.4% vs 3.6% of patients, p = 0.016).Conclusion: A differential expression pattern for these markers was observed both in NMIBC and MIBC disease. A subgroup of CTCs showed a CTCs expressing high OCT4, along with Mes were more frequently detected in patients with MIBC, suggesting that these cells may prevail during tumor muscle invasion and disease progression.Keywords: circulating tumor cells, epithelial-to-mesenchymal transition, OCT4, muscle-invasive bladder cancer

Muscle Specific Kinase myasthenia gravis (MuSK-MG) is an autoimmune disease that impairs neuromuscular transmission leading to muscle fatigability. No targeted medications are currently available, and non-specific immunotherapies are required. MuSK initiates a phosphorylation cascade regulating the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). SH2 domain-containing phosphatase (SHP2) negatively regulates the pathway inhibiting MuSK activation. In MuSK-MG, monovalent IgG4 autoantibodies block MuSK phosphorylation dispersing AChR clusters. The role of the smaller population of divalent MuSK IgG1, 2 and 3 antibodies is still undefined. The aims of the study were a) to test in vitro and in vivo SHP2 inhibition by NSC-87877 evaluating its efficacy in counteracting the effects of MuSK-Abs; b) to investigate the pathogenic contribution of MuSK IgG1-3-Abs. Protein phosphorylation and AChR clustering were studied in different cell lines exposed to NSC-87877, and to either patients’ purified MuSK-Ab subclasses or anti-MuSK monoclonals. NSC-87877 was tested for safety and efficacy in wild-type mice and a model of AChR deficiency syndrome. Effects of MuSK IgG1-3 were evaluated on impairment of the MuSK-Lrp4 interaction required for MuSK activation, and on the cytoskeleton activation necessary for cluster maturation. RNA transcriptomic analysis was performed to look for changes in intracellular pathways. In vitro, NSC-87877 increased MuSK phosphorylation protecting AChR clusters from dispersal in the presence of all MuSK-Ab subclasses. Functional MUSK was required for the effectiveness of the drug. In vivo, no side effects were observed but the available genetice myasthenic syndrome models did not improve. Divalent MuSK antibodies activated the phosphorylation cascade but failed to sustain cluster maturation, impairing MuSK-Lrp4 interaction and cytoskeleton rearrangements. Transcriptomic analysis did not detect specific changes that could inform on the mechanisms. In conclusion, SHP2 inhibition showed promising results in vitro, although more studies are needed in vivo to evaluate its potential effectiveness. Although the exact mechanisms of MuSK IgG1-3 antibodies were not identified, the work in this thesis confirms their potential pathogenic role in MuSK-MG that requires further investigation.

Traditional genome alignment methods based on dynamic programming are often a. computational expensive, b. unable to compare the genomes of distant species and c. unable to deal with low information regions. We are presenting an information-theoretic approach for pairwise genome local alignment. Our method, the expert model aligner, the XMAligner, relies on the expert model compression algorithm. To align two sequences, XMAligner first compresses one sequence to measure the information content at each position in the sequence. Then the sequence is compressed again but this time with the background knowledge from the other sequence to obtain the conditional information content. The information content and the conditional information content from the two compressions are examined. Similar regions in the compressed sequence should have the conditional information content lower than the individual information content. The method is applied to align the genomes of Plasmodium falciparum and Plasmodium knowlesi against other three Plasmodium genomes with different levels of diversity. Despite the differences in nucleotide composition of the reference sequences, the conserved regions found by XMAligner in three alignments are relatively consistent. A strong correlation was found between the similar regions detected by the XMAligner and the hypothetical annotation of Plasmodium species. The alignment results can be integrated into the DNAPlatform for visualisation.

This paper introduces a novel algorithm for biological sequence compression that makes use of both statistical properties and repetition within sequences by maintaining a panel of experts to predict the probability distribution of the next symbol in the sequence to be encoded. Expert probabilities are combined to obtain the final distribution. Experiments show that our algorithm outperforms existing compressors on typical DNA and protein sequence datasets while maintaining a practical running time. The resulting information sequence provides insight for further study of the biological sequence. We demonstrate a number pattern discovery tasks using our model.