Search

A three-descriptor quantitative structure–activity/toxicity relationship (QSAR/QSTR) model was developed for the skin permeability of a sufficiently large data set consisting of 274 compounds, by applying support vector machine (SVM) together with genetic algorithm. The optimal SVM model possesses the coefficient of determination R2 of 0.946 and root mean square (rms) error of 0.253 for the training set of 139 compounds; and a R2 of 0.872 and rms of 0.302 for the test set of 135 compounds. Compared with other models reported in the literature, our SVM model shows better statistical performance in a model that deals with more samples in the test set. Therefore, applying a SVM algorithm to develop a nonlinear QSAR model for skin permeability was achieved.

Jin Li,1 Yajun Li,2 Ruolan Zeng,2 Jingguan Lin,1 Meizuo Zhong,3 Xianling Liu,4 Yizi He,2 Junqiao He,2 Zhou Ouyang,2 Lijun Huang,2 Ling Xiao,5 Hui Zhou2 1Department of Comprehensive Chemotherapy/Daytime Chemotherapy, Hunan Cancer Hospital, Changsha, Hunan, People’s Republic of China; 2Department of Lymphoma and Hematology, Hunan Cancer Hospital, Changsha, Hunan, People’s Republic of China; 3Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Histology and Embryology, School of Basic Medical Science, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Hui ZhouDepartment of Lymphoma and Hematology, Hunan Cancer Hospital, Changsha, Hunan, People’s Republic of ChinaTel +86 731 89762281Email zhouhui9403@126.comPurpose: This retrospective study compared effectiveness between ≤ 4 cycles and ≥ 5 cycles of L-asparaginase/pegaspargase-based chemoradiation in newly diagnosed low-risk extranodal natural killer/T-cell lymphoma (ENKTL), nasal type classified according to the Prognostic Index of Natural Killer (PINK) lymphoma model.Patients and Methods: Patients were categorized into ≤ 4-cycle (2– 4 chemotherapy cycles, n = 166) and ≥ 5-cycle groups (5– 6 cycles, n = 86). Propensity score matching analysis was used to reduce potential confounding bias between the two groups. Treatment responses, adverse events, and survival outcomes between the two groups were analyzed.Results: No matter before or after matching (65 in the ≤ 4-cycle group, 65 in the ≥ 5-cycle group), response rates and survival outcomes were similar between the ≤ 4-cycle and ≥ 5-cycle groups. Incidences of grade 1– 2 anemia and transaminase elevation were higher in the ≥ 5-cycle group. After matching, for stage IE disease, there were no differences in response rates and survival outcomes between the two groups. For stage IIE disease, the complete response rate was higher in the ≥ 5-cycle group (72.4% vs 92.6%, p = 0.049), and the 3-year overall survival (65.5% vs 85.2%, p = 0.024) and 3-year progression-free survival (58.6% vs 81.5%, p = 0.027) rates were significantly extended in the ≥ 5-cycle group.Conclusion: When chemoradiotherapy strategies with L-asparaginase/pegaspargase-based regimens are applied to modern low-risk ENKTL patients classified according to the PINK model, it may be better to moderately extend chemotherapy courses in patients with stage IIE disease.Keywords: extranodal natural killer/T-cell lymphoma, nasal type, chemotherapy courses, low-risk

Background: This study aimed to investigate the association of circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) expression with disease risk, clinical characteristics, progression-free survival (PFS) and overall survival (OS) of multiple myeloma (MM), and to explore the influence of circ-ITCH overexpression on MM cell activities n vitro . Methods: Bone marrow samples from 92 MM patients and 30 healthy controls were collected, and circ- ITCH expression was detected by quantitative polymerase chain reaction. PFS and OS in MM patients were calculated. Circ-ITCH in human MM cell lines and normal bone marrow mononuclear cells (BMMCs) were detected. Circ-ITCH overexpression and control overexpression plasmids were transfected to U226 cell line, and cell proliferation as well as apoptosis were assessed. Results: Circ-ITCH expression was under-expressed in MM patients compared to healthy controls. And receiver operating characteristic curve displayed that circ-ITCH could distinguish MM patients from healthy controls [area under curve: 0.809 (95% CI: 0.722–0.895)]. Additionally, circ-ITCH high expression was associated with decreased International Staging System (ISS) stage in MM patients. Kaplan-Meier curves and Cox’s regression analysis displayed that circ-ITCH expression was positively correlated with PFS and OS. In vitro , circ-ITCH expression was lower in MM cell lines (including RPMI8226, U226 and NCI-H929) compared to normal BMMCs. In U226 cells, cell proliferation was decreased but apoptosis was elevated by circ-ITCH overexpression. Conclusions: Circ-ITCH might serve as a potential biomarker and treatment target for MM.

Yajun Li,1 Kailin Chen,2 Chaohui Zuo,3 Ruolan Zeng,1 Yizi He,1 Xiaoyan Chen,4 Ling Xiao,5 Hui Zhou1 1Department of Lymphoma and Hematology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 3Department of Gastroduodenal and Pancreatic Surgery, Translation Medicine Research Center of Liver Cancer, Laboratory of Digestive Oncology, Affiliated Cancer Hospital of Xiangya Medical School and Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Department of Pathology, Affiliated Cancer Hospital of Xiangya Medical School & Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 5Department of Histology and Embryology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, People’s Republic of ChinaCorrespondence: Hui ZhouDepartment of Lymphoma and Hematology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of ChinaFax +8673189762282Email zhouhui@hnca.org.cnChaohui ZuoDepartment of Gastroduodenal and Pancreatic Surgery, Translation Medicine Research Center of Liver Cancer, Laboratory of Digestive Oncology, Affiliated Cancer Hospital of Xiangya Medical School & Hunan Cancer Hospital, Central South University, 283 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of ChinaFax +8673189762142Email zuochaohui@hnca.org.cnPurpose: Hepatosplenic T cell lymphoma (HSTCL) is a rare tumor that lacks data to guide management decisions. To shed light on the nature and therapy of the entity, we conducted this study.Patients and Methods: We retrospectively reviewed patients diagnosed with HSTCL between 1975 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database to analyze the clinical characteristics and survival outcome compared with PTCL-NOS and ALK+ ALCL.Results: A total of 123 HSTCLs were included in the analysis. Most patients were aged ≤ 60 years (81.3%) and had a male predominance (69.1%). Organs with lymphoma infiltration of HSTCL were more common in the spleen (98.4%). The 1-year, 3-year, and 5-year overall survival (OS) rates in the entire HSTCL cohort were 56.9% (95% CI, 47.5– 66.3%), 37.6% (95% CI, 28.0– 47.2%), and 31.6.0% (95% CI, 22.2– 41.0%), respectively. The overall survival (OS) of HSTCL patients was similar to that of PTCL-NOS patients (P = 0.128) but worse than that of patients with ALK+ ALCL (P < 0.001). The disease-specific survival (DSS) of HSTCL patients was worse than that of PTCL-NOS and ALK+ ALCL patients (P < 0.05). The same tendency was found in the matched data set. Cox regression analyses indicated that the use of chemotherapy combined with topical treatment may improve the survival of patients with HSTCL.Conclusion: A higher proportion of young patients and a strong male predominance were found in HSTCL. Chemotherapy combined with topical treatment may be an optional regimen. Further studies are needed to intensify efforts in dealing with this rare but unfavorable disease.Keywords: hepatosplenic T cell lymphoma, survival, SEER, treatment

Huan Chen,1,* Yizi He,1,* Tao Pan,1 Ruolan Zeng,1 Yajun Li,1 Siwei Chen,2 Yufeng Li,2 Ling Xiao,2 Hui Zhou1 1Department of Lymphoma & Hematology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Histology and Embryology of School of Basic Medical Science, Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Zhou; Ling Xiao Email zhouhui9403@126.com; xiaolingcsu@csu.edu.cnPurpose: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease, which makes prognostic prediction challenging. The rapid development of research on ferroptosis provides the possibility of its use in prognosis in cancer patients. The aim of the current investigation was to perform a systematic study of ferroptosis and DLBCL prognosis to identify prognostic biomarkers in DLBCL.Materials and Methods: A total of 884 DLBCL patients from the Gene Expression Omnibus database were included in this study and were divided into a training set and a validation set. Univariate Cox regression analysis was used to investigate relationships between gene expression and prognostic values. Ferroptosis-related genes associated with overall survival in the training set were then extracted, and the least absolute shrinkage and selection operator Cox regression model was used to establish an eight-gene signature, comprising ZEB1, PSAT1, NGB, NFE2L2, LAMP2, HIF1A, FH, and CXCL2.Results: The signature exhibited significant independent prognostic value in both the training set and the validation set. It also exhibited strong prognostic value in subgroup analysis. A nomogram integrating the eight-gene signature and components of the International Prognostic Index facilitated reliable prognostic prediction.Conclusion: A novel and reliable ferroptosis-related gene signature that can effectively classify DLBCL patients into high-risk and low-risk groups in terms of survival rate was developed. It could be used for prognostic prediction in DLBCL patients. Targeting ferroptosis may be a therapeutic alternative in DLBCL.Keywords: diffuse large B-cell lymphoma, ferroptosis, Gene Expression Omnibus database, signature, prognostic

Diffuse large B-cell lymphoma (DLBCL) is an extremely heterogeneous tumor entity, which makes prognostic prediction challenging. The tumor microenvironment (TME) has a crucial role in fostering and restraining tumor development. Consequently, we performed a systematic investigation of the TME and genetic factors associated with DLBCL to identify prognostic biomarkers for DLBCL. Data for a total of 1,084 DLBCL patients from the Gene Expression Omnibus database were included in this study, and patients were divided into a training group, an internal validation group, and two external validation groups. We calculated the abundance of immune–stromal components of DLBCL and found that they were related to tumor prognosis and progression. Then, differentially expressed genes were obtained based on immune and stromal scores, and prognostic TME‐related genes were further identified using a protein–protein interaction network and univariate Cox regression analysis. These genes were analyzed by the least absolute shrinkage and selection operator Cox regression model to establish a seven-gene signature, comprising TIMP2, QKI, LCP2, LAMP2, ITGAM, CSF3R, and AAK1. The signature was shown to have critical prognostic value in the training and validation sets and was also confirmed to be an independent prognostic factor. Subgroup analysis also indicated the robust prognostic ability of the signature. A nomogram integrating the seven-gene signature and components of the International Prognostic Index was shown to have value for prognostic prediction. Gene set enrichment analysis between risk groups demonstrated that immune-related pathways were enriched in the low-risk group. In conclusion, a novel and reliable TME relevant gene signature was proposed and shown to be capable of predicting the survival of DLBCL patients at high risk of poor survival.

Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm. Although BL is relatively sensitive to chemotherapy, some patients do not respond to initial therapy or relapse after standard therapy, which leads to poor prognosis. The mechanisms underlying BL chemoresistance remain poorly defined. Here, we report a mechanism for the relationship between the phosphorylation of STAT3 on Tyr705 and BL chemoresistance. In chemoresistant BL cells, STAT3 was activated and phosphorylated on Tyr705 in response to the generation of the reactive oxygen species (ROS), which induced Src Tyr416 phosphorylation after multi-chemotherapeutics treatment. As a transcription factor, the elevated phosphorylation level of STAT3Y705 increased the expression of GPx1 and SOD2, both of which protected cells against oxidative damage. Our findings revealed that the ROS-Src-STAT3-antioxidation pathway mediated negative feedback inhibition of apoptosis induced by chemotherapy. Thus, the phosphorylation of STAT3 on Tyr705 might be a target for the chemo-sensitization of BL.

Breast cancer is one of the most common malignant tumors of women. Modern combinatorial therapeutic regimens can reduce patient tumor burdens to undetectable levels, yet in many cases these tumors will relapse. Understanding of breast cancer biology, developing more potent therapeutic approaches, and overcoming resistance are of great importance. WNT5A is a non-canonical signaling member of the WNT family. Its role in breast cancer still remains unclear. Most of the evidence shows that WNT5A is a suppressor in breast cancer and loss of its expression is associated with poor prognosis, while some evidence suggests the tumorigenicity of WNT5A. WNT signaling molecules are potent targets for treatment of cancer. Therefore, understanding the role of WNT5A in breast cancer may provide new ideas and methods for breast cancer treatment. We review the evidence concerning WNT5A and breast cancer involving the signaling pathways and the molecular-targeted therapy of WNT5A. Our results show that the role WNT5A plays depends on the availability of key receptors and intercellular interactions among different cell types.

Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma. The treatment of PCNSL is comprehensive, combining surgery, radiotherapy, and chemotherapy. However, the outcome is poor because of its high invasiveness and rate of recurrence. We analyzed 22 cases of PCNSL using next-generation sequencing (NGS) to detect 64 candidate genes. We used immunohistochemical methods to analyze gene expression in 57 PCNSL samples. NGS showed that recurrent mutations in KMT2D and CD79B, components of the NF-κB pathway, accounted for 65% of total mutations in PCNSL samples. The most frequent mutated gene was PIM1 (77.27%, 17/22), followed by MYD88 (63.64%, 14/22), CD79B (69.09%, 13/22), and KMT2D (50.00%, 11/22). Mutations of the CD79B gene were associated with an inferior progression-free survival (PFS), and GNA13 gene mutations were associated with a shorter PFS and overall survival (OS) in PCNSL patients (P

Peritoneal carcinomatosis (PC) is an important cause of morbidity and mortality among patients with gastric cancer. Thus, it is important to identify an ideal biomarker for PC.Plasma and ascites samples were collected from gastric cancer patients with PC and a control group. Lysophosphatidic acid (LPA) levels were tested and analyzed.The plasma LPA levels of gastric cancer patients with PC were significantly higher than those in gastric cancer patients after radical resection (p = 0.046) and healthy volunteers (p 0.001). Besides, plasma LPA levels were statistically lower after chemotherapy in gastric cancer patients with PC (p = 0.028). Furthermore, the ascites LPA levels were significantly higher in gastric cancer patients with peritoneal carcinomatosis than those in liver cirrhosis patients (p 0.001). Moreover, ascites LPA levels were statistically lower after intraperitoneal chemotherapy injection than before (p 0.001). In addition, the plasma LPA levels were significantly associated with serum CA125 levels (p = 0.032) and TNM stage in gastric cancer patients (p = 0.009). Individuals with plasma LPA levels20,000 ng/mL had significantly worse overall survival (OS) than those with plasma LPA levels20,000 ng/mL group (p = 0.006). In addition the group with ascites LPA levels24,000 ng/mL showed significantly worse progression-free survival (PFS) and OS (p 0.001 in PFS and OS).This study demonstrated that LPA levels in plasma and ascites may be useful diagnostic biomarkers for PC of gastric cancer and that higher levels are associated with poor prognosis.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Jinqiong Jiang, Yiping Liu, Youhong Tang, Li Li, Ruolan Zeng, Shan Zeng, Meizuo Zhong Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China Abstract: Increasing evidence has shown that aldehyde dehydrogenase 1A1 (ALDH1A1), a detoxifying enzyme, is responsible for chemoresistance in a variety of tumors. Although the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), chemoresistance is a common cause of treatment failure. This study aims to investigate the significance of ALDH1A1 expression and the mechanism by which ALDH1A1 is involved in the chemoresistance of DLBCL cells. ALDH1A1 expression was assessed in 88 DLBCL tissues by immunohistochemistry. The association between ALDH1A1 expression and outcome was evaluated. We also investigated the effect of ALDH1A1 on CHOP resistance in DLBCL cells using functional analysis. ALDH1A1 expression levels were upregulated in patients with stable or progressive disease after CHOP and its expression positively correlated with expression of STAT3 and p-STAT3. In keeping with these observations, ALDH1A1 expression was significantly associated with short survival of DLBCL patients who received CHOP chemotherapy. In functional assays in Pfeiffer cells, overexpression of ALDH1A1 conferred resistance to CHOP, while silencing of ALDH1A1 using short hairpin RNA had the opposite effect. Furthermore, we also observed that ALDH1A1 could regulate the JAK2/STAT3 pathway, while inhibition of the JAK2/STAT3 pathway by WP1066 negated the effect of ALDH1A1 overexpression. These observations reveal that ALDH1A1 induces resistance to CHOP through activation of the JAK2/STAT3 pathway in DLBCL, and its targeting provides a potential strategic approach for reversing CHOP resistance. Keywords: ALDH1A1, diffuse large B-cell lymphoma, CHOP, chemoresistance, JAK2/STAT3 pathway

Aim: To conduct a meta-analysis on the relationship between the usage of bisphosphonates and the risk of colorectal cancer. Methods: We searched PUBMED and EMBASE for studies assessing colorectal cancer incidence or prevalence in bisphosphonate users versus nonusers that were published before August 2012. We used the STATA software to calculate the pooled odds ratios (OR) and 95% confidence interval (CI) for the risk of colorectal cancer associated with exposure to bisphosphonates using a random-effects model. Results: Eight studies met our inclusion criteria, which comprised 5 cohort studies and 3 case-control studies, with a total of 22,291 colorectal cancer cases. The usage of bisphosphonates was associated with a statistically significant decrease in colorectal cancer risk, with a pooled OR of 0.89 (95% CI, 0.80-0.99). A statistically significant decrease in the risk of colorectal cancer was observed in the long-term exposure groups (pooled OR, 0.73; 95% CI, 0.57-0.93). Conclusions: These results indicate that the decrease in risk of colorectal cancer may be associated with the usage of bisphosphonates. More studies are needed to confirm the relationship.