The efficacy of low-power cumulative high-intensity focused ultrasound treatment for recurrent desmoid tumor.

BACKGROUND: Desmoid tumors are rare neoplasms that are locally invasive. However, optimal treatment strategies for recurrent desmoid tumors remain controversial. High-intensity focused ultrasound (HIFU) has been reported as a noninvasive modality for treating recurrent desmoid tumors. However, its efficacy against massive desmoid tumors or those with complex anatomies remains unclear. METHODS: We developed a new therapeutic strategy called low-power cumulative HIFU and applied it to treat recurrent desmoid tumors. RESULTS: We retrospectively collected data from 91 patients with recurrent desmoid tumors who underwent low-power cumulative HIFU treatment after surgical treatment failure. The mean ablation proportion of the HIFU treatment was 69.5%, and the objective response rate was 47.3%. The 5-year estimated progression-free survival rate for these patients was 69.3%. CONCLUSION: Low-power cumulative HIFU treatment could achieve significant efficacy and long-term control of recurrent desmoid tumors.

Successful treatment of metastatic colorectal cancer with synchronous BRAF V600E mutation and dMMR with BGB-A317.

Metastatic colorectal cancer with BRAF mutation is a type of highly invasive malignant tumor with poor prognosis and few treatment options. Here, we report a case of a BRAF-mutant and DNA mismatch-repair deficiency colorectal cancer patient with postoperative recurrence as well as abdominal cavity and pelvic metastasis, whose condition was relieved continuously after treatment with a new anti-PD-1 antibody, BGB-A317.

Left-sided primary tumor is a favorable prognostic factor for metastatic colorectal cancer patients receiving surgery.

OBJECTIVE: The role of surgery in metastatic colorectal cancer (mCRC) remains controversial. This study was performed to assess the impact of surgery on survival in metastatic colorectal cancer. MATERIALS AND METHODS: Information of mCRC patients diagnosed between January 1, 2004, and December 31, 2013, was retrieved from the Surveillance, Epidemiology, and End Results Program database. Patients were classified in three groups: patients undergoing resection of both primary and distant metastatic tumors (group 'PMTR'), patients receiving primary tumor resection alone (group 'PTR') and patients not undergoing any surgery (group 'No resection'). Kaplan-Meier method and multivariate Cox proportional hazard regression analysis were applied to estimate disease specific survival time (DSS) and determine prognostic factors. RESULTS: A total of 38,591 mCRC patients were eligible. Overall, median DSS of group 'PMTR' was significantly longer compared with group 'PTR' and group 'No resection' (28.0 vs 21.0 vs 11.0 months, P < 0.001). Stratified analysis observed that primary tumor in left-sided colorectal cancer (LCRC) was a favorable prognostic factor compared with right-sided colorectal cancer (RCRC) (median DSS of LCRC: PMTR, 34 months, PTR, 25 months, No resection, 13 months; median DSS of RCRC: PMTR, 20 months, PTR, 16 months, No resection, 8 months; P < 0.001). Multivariate analysis demonstrated that surgery was an independent prognostic factor for better survival (PMTR, HR = 0.403, 95% CI 0.384-0.423, P < 0.001; PTR, HR = 0.515, 95% CI 0.496-0.534, P < 0.001). Furthermore, in patients undergoing surgery, patients with younger age, female, married status, LCRC and lower CEA level were prone to receiving PMTR. CONCLUSIONS: This analysis demonstrated that surgery was an independent prognostic factor for improved survival in mCRC. Patients with LCRC had better survival than patients with RCRC after surgery.

Different treatment strategies and molecular features between right-sided and left-sided colon cancers.

The colon is derived from the embryological midgut and hindgut separately, with the right colon and left colon having different features with regards to both anatomical and physiological characteristics. Cancers located in the right and left colon are referred to as right colon cancer (RCC) and left colon cancer (LCC), respectively, based on their apparent anatomical positions. Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC, but molecular features also vary between them, not to mention the distinguishing clinical manifestations. Disease-free survival after radical surgery of both RCC and LCC are similar. In the treatment of RCC, the benefit gained from adjuvant FOLFIRI chemotherapy is superior, or at least similar, to LCC, but inferior to LCC if FOLFOX regimen is applied. On the other hand, metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting. For KRAS wild-type cancers, LCC benefits more from cetuximab treatment than RCC. Moreover, advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC. Significant varieties exist at the molecular level between RCC and LCC, which may serve as the cause of all apparent differences. With respect to carcinogenesis mechanisms, RCC is associated with known gene types, such as MMR, KRAS, BRAF, and miRNA-31, while LCC is associated with CIN, p53, NRAS, miRNA-146a, miRNA-147b, and miRNA-1288. Regarding protein expression, RCC is related to GNAS, NQO1, telomerase activity, P-PDH, and annexin A10, while LCC is related to Topo I, TS, and EGFR. In addition, separated pathways dominate progression to relapse in RCC and LCC. Therefore, RCC and LCC should be regarded as two heterogeneous entities, with this heterogeneity being used to stratify patients in order for them to have the optimal, current, and novel therapeutic strategies in clinical practice. Additional research is needed to uncover further differences between RCC and LCC.

Serum Protein Pattern Could Predict the Therapeutic Effect of First-Line Pemetrexed/Cisplatin Chemotherapy in Patients With Lung Adenocarcinoma.

BACKGROUND: In patients with advanced non-squamous non-small cell lung cancer (NSCLC), a pemetrexed/cisplatin (PP) regimen is considered as one of the preferred first-line treatments. However, only about half of the treated patients respond, and there is no clinically useful marker that can predict the response to the regimen. METHODS: We established a potential pattern for the prediction of efficacy of first-line PP chemotherapy in patients with lung adenocarcinoma, by using artificial neural networks (ANNs) analysis of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) in this preliminary study. RESULTS: The samples were randomly divided into training set and test set. From the test set, through cross-validation, the established protein pattern for PP separated the responders from the non-responders with a sensitivity of 95.8% and a specificity of 90.0%. CONCLUSION: It could be helpful for oncologists to select patients who could benefit from PP chemotherapy.

Special AT-rich sequence-binding protein 1 promotes cell growth and metastasis in colorectal cancer.

AIM: To evaluate the expression of special AT-rich sequence-binding protein 1 (SATB1) gene in colorectal cancer and its role in colorectal cancer cell proliferation and invasion. METHODS: Immunohistochemistry was used to detect the protein expression of SATB1 in 30 colorectal cancer (CRC) tissue samples and pair-matched adjacent non-tumor samples. Cell growth was investigated after enhancing expression of SATB1. Wound-healing assay and Transwell assay were used to investigate the impact of SATB1 on migratory and invasive abilities of SW480 cells in vitro. Nude mice that received subcutaneous implantation or lateral tail vein were used to study the effects of SATB1 on tumor growth or metastasis in vivo. RESULTS: SATB1 was over-expressed in CRC tissues and CRC cell lines. SATB1 promotes cell proliferation and cell cycle progression in CRC SW480 cells. SATB1 overexpression could promote cell growth in vivo. In addition, SATB1 could significantly raise the ability of cell migration and invasion in vitro and promote the ability of tumor metastasis in vivo. SATB1 could up-regulate matrix metalloproteases 2, 9, cyclin D1 and vimentin, meanwhile SATB1 could down-regulate E-cadherin in CRC. CONCLUSION: SATB1 acts as a potential growth and metastasis promoter in CRC. SATB1 may be useful as a therapeutic target for CRC.

Proteomic biomarker predicts therapeutical effects of oxaliplatin combining with fluoropyrimidine in metastatic gastric cancer patients by the SELDI-proteinchip platform.

BACKGROUND/AIMS: To evaluate potential protein markers for oxaliplatin-based first-line chemotherapy of metastatic gastric cancer (MGC), we have used proteomic analysis to compare the difference of serum proteomic spectra between responsive and non-responsive MGC patients. METHODOLOGY: Serum samples were collected before chemotherapy.Surface-enhanced laser desorption/ionisation time of-flight mass spectrometry (SELDI-TOF-MS) proteinchip array technology was applied to compare the differences of serous protein spectra between the twenty responsive patients and another fourteen non responsive patients. Cross validation was applied to identify the proper markers for an accurate judgment of prognosis. RESULTS: Fifty proteins were picked out for significantly increased or decreased expression(p<0.05, Student t-test). Among them, sixteen protein masses with 1081, 1267, 2941, 2985, 3148, 3165,3199, 3219, 3249, 3281, 4182, 4390, 4482, 4509,4533 and 5001 m/z were chosen as components of the best proteomic biomarker pattern for judgment of chemotherapy prognosis in MGC patients, achieving a sensitivity of 95% (19/20) and a specificity of 78.6%(11/14), respectively. CONCLUSIONS: SELDI-TOF-MS screens out the specific protein markers that help oncologists with judging the prognosis of oxaliplatin in combination with fluoropyrimidine, thus orientating first-line palliative chemotherapy for MGC patients.

Evaluation of therapeutic effect of tumor-targeted therapy.

The response evaluation criteria in solid tumors, which are based on tumor size alone, are the most frequently used and effective criteria by which to evaluate the tumor response to chemotherapy. However, the mechanism of tumor-targeted drugs is different from traditional cytotoxic drugs. Tumor-targeted drugs are designed to interfere with specific aberrant biological pathways involved in tumorigenesis. For this reason, the response evaluation in solid tumors is not adequate for the evaluation of targeted therapy. Molecular and functional imaging techniques such as dynamic contrast-enhanced perfusion computed tomography, dynamic contrast-enhanced magnetic resonance imaging, dynamic contrast-enhanced ultrasound, and fluorodeoxyglucose-positron emission tomography can reflect tumor blood flow and cellular metabolic changes directly, and are being used more frequently for the evaluation of targeted therapies. This article gives an overview of some of the new computed tomography criteria and the commonly used methods of targeted therapy evaluation.

Identification of the biomarkers for the prediction of efficacy in first-line chemotherapy of metastatic colorectal cancer patients using SELDI-TOF-MS and artificial neural networks.

BACKGROUND/AIMS: For patients with metastatic colorectal cancer, both FOLFOX regimen and FOLFIRI regimen are considered as first-line choices. There are no clinically useful markers that could predict the response to these regimens respectively. We aimed at identifying serum protein patterns which could predict the efficacy of chemotherapy. METHODOLOGY: Serum from 70 patients diagnosed as metastatic colorectal cancer before first-line chemotherapy were collected and analyzed for protein patterns using ANN analysis of SELDI-TOF-MS. Among the 70 cases, 44 patients received FOLFOX chemotherapy, while the other 26 patients received FOLFIRI chemotherapy. After four cycles of the treatment, RECIST criteria were used to define the responders (R) and non-responders (NR). RESULTS: A potential predicting pattern consisting of 6 biomarkers was identified in the patients receiving FOLFOX chemotherapy. Using this predicting pattern, the responders could be separated from the non-responders with a sensitivity of 92.9% and a specificity of 81.3%. Another potential predicting pattern that consisted of 7 bio-markers was identified in the patients who have received FOLFIRI chemotherapy. The sensitivity and the specificity of this predicting pattern were 92.3% and 92.3% respectively. CONCLUSIONS: Two potential pat-terns for the prediction of efficacy of FOLFOX or FOLFIRI chemotherapy were established in this preliminary study.

Genome-wide analysis of OCT4 binding sites in glioblastoma cancer cells.

OCT4, a member of the POU family of gene products, is an octamer motif-binding transcription factor. As it is known to play a crucial role in cancer processes including proliferation, invasion, and chemoradioresistance, it is important to identify the direct targets of OCT4 in living cancer cells. Here, chromatin immunoprecipitation-sequencing (ChIP-seq) was used to identify OCT4 binding sites in glioblastoma cancer cells. The results showed that 5438 OCT4 binding sites were localized in the glioblastoma cancer genome and that these sites contained a consensus sequence TTTkswTw (k=T or G, s=C or G, w=A or T), which occurred 3931 times in 2312 OCT4 binding regions. Furthermore, binding motifs of some other transcription factors were identified in OCT4 binding regions. Our results provide a valuable dataset for understanding gene regulation mechanisms underlying the function of OCT4 in glioblastoma cancer.

[Effects of different vectors and gene fragments on antigen expression of hepatitis E virus DNA immunization].

AIM: To investigate the effects of different vectors and gene fragments on antigen expression of hepatitis E virus (HEV) DNA immunization. METHODS: Gene fragments encoding p166 and p179, which contain the neutralization antigenic epitopes of a Chinese strain of HEV genotype IV, were cloned into two different eukaryotic expression vectors (pTR421 and pCDNA3.1), respectively. The in vitro expression level of p166 and p179 in HepG2 cells transfected by each of the recombinant plasmids with lipofectamine2000 was examined by means of immunofluorescence and Western blot. Meanwhile, the in vivo expression level in muscles of mice was examined with immunohistochemistry staining. RESULTS: Four recombinant plasmids, pTR421-166, pTR421-179, pCDNA3.1-166 and pCDNA3.1-179, were constructed successfully and confirmed correct with restriction endonuclease analysis and nucleotide sequencing. The antigen expression was only detected in HepG2 cells transfected by pTR421-179 and in myocytes of the mice injected with pTR421-179. Neither in vitro nor in vivo antigen expression was detected with pTR421-166 although p166 was only 13 amino acids shorter than p179 at N terminus. Neither pCDNA3.1-166 nor pCDNA3.1-179 was expressed in vitro and in vivo. CONCLUSION: Selection of the vectors and gene fragments is critical to HEV gene expression and HEV DNA vaccine.