Decoding transcriptomic signatures of cysteine string protein alpha-mediated synapse maintenance.

Synapse maintenance is essential for generating functional circuitry, and decrement in this process is a hallmark of neurodegenerative disease. Yet, little is known about synapse maintenance in vivo. Cysteine string protein α (CSPα), encoded by the Dnajc5 gene, is a synaptic vesicle chaperone that is necessary for synapse maintenance and linked to neurodegeneration. To investigate the transcriptional changes associated with synapse maintenance, we performed single-nucleus transcriptomics on the cortex of young CSPα knockout (KO) mice and littermate controls. Through differential expression and gene ontology analysis, we observed that both neurons and glial cells exhibit unique signatures in the CSPα KO brain. Significantly, all neuronal classes in CSPα KO brains show strong signatures of repression in synaptic pathways, while up-regulating autophagy-related genes. Through visualization of synapses and autophagosomes by electron microscopy, we confirmed these alterations especially in inhibitory synapses. Glial responses varied by cell type, with microglia exhibiting activation. By imputing cell-cell interactions, we found that neuron-glia interactions were specifically increased in CSPα KO mice. This was mediated by synaptogenic adhesion molecules, with the classical Neurexin1-Neuroligin 1 pair being the most prominent, suggesting that communication of glial cells with neurons is strengthened in CSPα KO mice to preserve synapse maintenance. Together, this study provides a rich dataset of transcriptional changes in the CSPα KO cortex and reveals insights into synapse maintenance and neurodegeneration.

Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence.

Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8+ T cell senescence, driven by atypical chemokine receptor 2 (ACKR2)+ CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2+ tumor cells are induced to produce transforming growth factor ß to drive CD8+ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8+ T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2+ tumor cells driving CD8+ T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8+ T cell senescence for chemoradiotherapy recurrence.

Decoding transcriptomic signatures of Cysteine String Protein alpha-mediated synapse maintenance.

Synapse maintenance is essential for generating functional circuitry and decrement in this process is a hallmark of neurodegenerative disease. While we are beginning to understand the basis of synapse formation, much less is known about synapse maintenance in vivo. Cysteine string protein α (CSPα), encoded by the Dnajc5 gene, is a synaptic vesicle chaperone that is necessary for synapse maintenance and linked to neurodegeneration. To investigate the transcriptional changes associated with synapse maintenance, we performed single nucleus transcriptomics on the cortex of young CSPα knockout (KO) mice and littermate controls. Through differential expression and gene ontology analysis, we observed that both neurons and glial cells exhibit unique signatures in CSPα KO brain. Significantly all neurons in CSPα KO brains show strong signatures of repression in synaptic pathways, while upregulating autophagy related genes. Through visualization of synapses and autophagosomes by electron microscopy, we confirmed these alterations especially in inhibitory synapses. By imputing cell-cell interactions, we found that neuron-glia interactions were specifically increased in CSPα KO mice. This was mediated by synaptogenic adhesion molecules, including the classical Neurexin1-Neuroligin 1 pair, suggesting that communication of glial cells with neurons is strengthened in CSPα KO mice in an attempt to achieve synapse maintenance. Together, this study reveals unique cellular and molecular transcriptional changes in CSPα KO cortex and provides new insights into synapse maintenance and neurodegeneration.

A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases.

Finding disease-relevant tissues and cell types can facilitate the identification and investigation of functional genes and variants. In particular, cell type proportions can serve as potential disease predictive biomarkers. In this manuscript, we introduce a novel statistical framework, cell-type Wide Association Study (cWAS), that integrates genetic data with transcriptomics data to identify cell types whose genetically regulated proportions (GRPs) are disease/trait-associated. On simulated and real GWAS data, cWAS showed good statistical power with newly identified significant GRP associations in disease-associated tissues. More specifically, GRPs of endothelial and myofibroblasts in lung tissue were associated with Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease, respectively. For breast cancer, the GRP of blood CD8+ T cells was negatively associated with breast cancer (BC) risk as well as survival. Overall, cWAS is a powerful tool to reveal cell types associated with complex diseases mediated by GRPs.

Massive prolapsed cervical lumps in cervical cancer treated with three-dimensional implant brachytherapy: a case report.

Background: Cervical cancer is one of the most common gynecological malignancies in developing countries. But the cervical cancer patients with tumor prolapse are very rare. The treatment principle of cervical cancer has been written into the guide, while the management of cervical lumps prolapse associated with cervical cancer is not standardized. Every doctor has different opinions on treatment strategies. Herein, we describe the three-dimensional brachytherapy treatment for massive prolapsed cervical lumps. Case Description: A 48-year-old woman diagnosed with cervical cancer developed a huge cervical mass prolapsed after defecation on the second day of chemotherapy. The mass surface was continuously bleeding and unable to return to the vagina. Therefore, uterine artery embolization interventional hemostasis was performed and then three-dimensional brachytherapy treatment was applied. The mass was necrotic and shedding and then retracted into the vagina on the 7th day after implantation treatment. Finally, the patient successfully received radical radiotherapy [pelvic and abdominal cavity external beam radiotherapy-PCTV 50.4 Gy/28 F, pelvic metastatic lymph nodes PGTVn 61.0 Gy/28 F, plus vaginal three-dimensional brachytherapy-HRCTV (D90) 27.25 Gy/4 F]. Conclusions: If cervical cancer combined with tumor prolapse is inoperable, three-dimensional implants brachytherapy seems to be an adequate therapeutic option.

Effects of Oncogene Neuregulin 1 on Breast Cancer Cells.

<b>Background and Objectives:</b> The NRG1 fusion protein is a driving factor for the occurrence and development of many tumours. We aimed to evaluate the effects of oncogene Neuregulin 1 (NRG1) on the proliferation and migration of breast cancer cells. <b>Materials and Methods:</b> Target gene NRG1 was transfected into breast cancer cells using the gene transfection technique and the migration ability of cells was observed by wound healing assay. The migration and invasion abilities of cells were further observed by Transwell assay and cell apoptosis was observed by TUNEL staining. The cell cycle distribution of breast cancer cells was detected by flow cytometry. <b>Results:</b> The wound healing assay exhibited that breast cancer cells overexpressing NRG1 exhibited stronger migration (p = 0.0047). More breast cancer cells of up-regulating NRG1 penetrated the transwell chamber, showing enhanced invasion ability (p = 0.0029). The TUNEL assay and flow cytometry demonstrated that NRG1 inhibited cell apoptosis and made them enter the active division stage. <b>Conclusion:</b> The NRG1 can promote the malignant function of breast cancer cells by augmenting migration and invasion abilities. High expression of NRG1 remarkably suppressed the apoptosis of breast cancer cells.

Circ-0036602 Acts As a Sponge of MiR-34a-5p and MiR-431-5p to Promote Cervical Cancer Proliferation and Invasion.

Background: Cervical cancer (CC) is one of the most common female malignancies worldwide. An increasing body of evidence suggests that circular RNAs (circRNAs) participate in the pathogenesis of various cancers, including CC. However, the expression profile and underlying molecular mechanisms remain largely unknown. Methods: In this study, high throughput sequencing was applied to identify circRNA in HPV-16 positive CC tissues. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression in CC tissues and cell lines. RNase R treatment, gel-electrophoresis, and RNA fluorescent in situ hybridization (FISH) were used to characterize the circRNAs. Subsequently, the Cell Counting Kit-8 assay (CCK8), transwell and wound healing assays were performed to assess circRNA function. Meanwhile, dual-luciferase reporter and western blot were used to clarify the associated molecular mechanisms. Results: Circ0036602 was upregulated in HPV-16 positive CC and correlated with a poor prognosis. Moreover, circ0036602 expression significantly correlated with the clinicopathologic characteristics. Knockdown of circ0036602 inhibited CC cell proliferation, migration, and invasion. Further studies showed that circ0036602 could bind to miR-34-5p and miR-431-5p to regulate the expression of the target gene HMGB1. Conclusions: Taken together, our findings suggest that circ0036602 is a tumor-promoting circRNA that promotes CC cells by sponging miR-34-5p and miR-431-5p to regulate HMGB1. Circ0036602 has huge prospects as a potential therapeutic target for CC patients.

Significance of ovarian transposition in the preservation of ovarian function for young cervical cancer patients undergoing postoperative volumetric modulated radiotherapy.

BACKGROUND: This paper aimed to evaluate the effectiveness of ovarian transposition (OT) and the dose constraint for preserving ovarian function in young cervical cancer patients who underwent postoperative volumetric modulated arc therapy (VMAT). METHODS: A retrospective analysis was conducted of young cervical cancer patients who accepted postoperative VMAT in the Affiliated Cancer Hospital of Nanjing Medical University from September 2015 to September 2018. VMAT plans for OT and non-OT patients were compared, and the patients' ovarian function was followed up. The transposed position of the ovaries and the radiation dose constraint were further explored using a receiver operator characteristic (ROC) curve. RESULTS: A total of 51 young patients (age ≤40 years) were included in the study, 32 of whom underwent OT and 19 of whom did not. For these OT and non-OT patients, the homogeneity index (HI), conformity index (CI), organs at risk (OARs), average number of monitor units (MUs), and mean treatment time were similar and showed no statistically significant difference (P≥0.05). Through follow-up studies, the number of patients with preserved ovarian function was found to be 22 (out of 32) and 0 (out of 19) in the OT and non-OT patients, respectively. The minimal distance for preserving ovarian function was determined as 2.1 cm between the center of a transposed ovary and the planning target volume (PTV) margin. The optimal limited radiation doses were estimated as maximum dose (Dmax) 9.8 Gy and mean dose (Dmean) 4.6 Gy, respectively. CONCLUSIONS: OT shows no negative effects on dose distribution, target region conformity, protection of OARs, or treatment efficacy and is therefore a reliable method in the preservation of ovarian function for young cervical cancer patients undergoing postoperative radiotherapy using the VMAT technique. Specifically, when the distance between the center of a transposed ovary and the PTV margin is more than 2.1 cm, and the radiation dose is limited to a Dmax of less than 9.8 Gy and a Dmean of less than 4.6 Gy, the function of transposed ovaries may be preserved.

MNX1 Promotes Malignant Progression of Cervical Cancer via Repressing the Transcription of p21cip1.

Motor neuron and pancreas homeobox 1 (MNX1) is a development-related genes and has been found to be highly expressed in several cancers. However, its biological function in cervical cancer remains largely unexplored. QRT-PCR, western blot, and IHC showed that MNX1 was abnormally overexpressed in cervical cancer tissues and cell lines. The high expression level of MNX1 correlated with poorer clinicopathologic characteristics in cervical cancer patients. Evaluated by RTCA (Real Time Cellular Analysis) proliferation assay, colony formation assay, EdU assay, transwell assay, and matrigel assay, we found that knockdown of MNX1 inhibited proliferation, migration and invasion of cervical cancer in vitro, while overexpression of MNX1 promoted malignant phenotype of cervical cancer. And subcutaneous xenograft model confirmed the malignant phenotype of MNX1 in vivo. Furthermore, flow cytometry, chromatin immunoprecipitation, and luciferase reporter assay indicated that MNX1 accelerated cell cycle transition by transcriptionally downregulating cyclin-dependent kinases p21cip1. In summary, our study revealed that MNX1 exerted an oncogenic role in cervical cancer via repressing the transcription of p21cip1 and thus accelerating cell cycle progression. Our results suggested that MNX1 was a potential diagnostic marker and therapeutic target for cervical cancer patients.

Ursolic acid promotes apoptosis and mediates transcriptional suppression of CT45A2 gene expression in non-small-cell lung carcinoma harbouring EGFR T790M mutations.

BACKGROUND AND PURPOSE: In non-small-cell lung carcinoma (NSCLC) patients, the L858R/T790M mutation of the epithelial growth factor receptor (EGFR) is a major cause of acquired resistance to EGFR-TKIs treatment that limits their therapeutic efficacy. Identification of drugs that can preferentially kill the NSCLC harbouring L858R/T790M mutation is therefore critical. Here, we have evaluated the effects of ursolic acid, an active component isolated from herbal sources, on erlotinib-resistant H1975 cells that harbour the L858R/T790M mutation. EXPERIMENTAL APPROACH: Gene expression omnibus (GEO) profiles analyses was applied to detect differentially expressed genes in NSCLC cells harbouring EGFR mutation. AnnexinV-FITC/PI, TUNEL staining, MTT, wound healing, RT-PCR, qRT-PCR, western blots, immunostaining, dual-luciferase reporters and ChIP-PCR were utilized to investigate the effects of ursolic acid in vitro and in vivo. KEY RESULTS: The cancer/testis antigen family 45 member A2 (CT45A2) was highly expressed in H1975 cells. Ectopic expression of CT45A2 in H1975 cells increased cell proliferation and motility in vitro. Silencing the CT45A2 expression strongly attenuated H1975 cells motility and growth. The anti-cancer effect of ursolic acid was critically dependent on CT45A2 expression in H1975 cells. Ursolic acid suppressed CT45A2 gene transcription mediated by transcriptional factor TCF4 and ß-catenin signalling. CONCLUSIONS AND IMPLICATIONS: CT45A2 is a novel oncogene for NSCLC with an EGFR T790 mutation. Ursolic acid induced apoptosis and inhibited proliferation of H1975 cells by negatively regulating the ß-catenin/TCF4/CT45A2 signalling pathway. Therefore, ursolic acid may be a potential candidate treatment for NSCLC harbouring the EGFR-L858R/T790M mutation.

DMBX1 promotes tumor proliferation and regulates cell cycle progression via repressing OTX2-mediated transcription of p21 in lung adenocarcinoma cell.

Lung adenocarcinoma (LUAD) was the predominant histological subtype of lung cancer, with poor prognosis. By analyzing the TCGA dataset, we found that DMBX1 (diencephalon/mesencephalon homeobox 1), a member of the bicoid sub-family of homeodomain-containing transcription factors, was overexpressed in LUAD and correlated with poorer prognosis and more advanced clinicopathological features of LUAD patients. Silencing of DMBX1 inhibited proliferation of LUAD and induced G1/S cell cycle arrest, whereas ectopic expression of DMBX1 enhanced tumor growth of LUAD and promoted G1/S cell cycle exit. Furtherly we found that the function of DMBX1 was dependent on p21 (CDKN1A), a key regulator of G1/S cell cycle progression. Co-IP assay revealed that DMBX1 directly bound to another homeobox transcription factor, OTX2. ChIP and luciferase reporter assay confirmed that OTX2 directly interacted with the promoter region of p21 to enhance its transcription, and DMBX1 repressed OTX2-mediated transcription of p21. Our study reveals that DMBX1 plays an oncogenic role in LUAD by repressing OTX2-mediated transcription of p21 and the results may provide new therapeutic targets for LUAD patients.

A comparative dosimetric study of cervical cancer patients with para-aortic lymph node metastasis treated with volumetric modulated arc therapy vs. 9-field intensity-modulated radiation therapy.

BACKGROUND: To compare the dosimetric characteristics between volumetric modulated arc therapy (VMAT) and 9-field intensity-modulated radiation therapy (9F-IMRT) for cervical cancer patients with para-aortic lymph node (PALN) metastasis. METHODS: We selected 20 patients who had received extended-field radiotherapy for cervical cancer with PALN metastasis. IMRT and VMAT plans were compared in terms of target, organs at risk (OARs), homogeneity index (HI), conformity index (CI), the number of monitor units (MUs) and treatment time (s). RESULTS: The CI and HI of VMAT plans were superior to those of IMRT plans (P<0.05). As for OARs, the mean maximum doses (Dmean) to the kidneys in the VMAT plans were all lower than those in IMRT plans (P<0.001). V40, V50 of the rectum, and V40 of the bladder in VMAT plans involved fewer doses than IMRT plans (P<0.001). Compared with IMRT plans, VMAT reduced the average number of MUs by 51% and the average treatment time by 31%. CONCLUSIONS: Both VMAT and IMRT plans can satisfy clinical dosimetric demands and protect OARs. VMAT has the best performance on CI and HI and can better protect the OARs. VMAT plans have fewer MUs and improve treatment efficiency.

A clinical, biologic and mechanistic analysis of the role of ZNF692 in cervical cancer.

OBJECTIVE: Cervical cancer (CC) is the most common malignancy in women. The zinc finger protein 692 (ZNF692) has been identified as a transcription factor and its aberrant expression participates in tumorigenesis of various cancers. However, its biological function and molecular mechanisms in cervical cancer remain unclear. METHODS: Microarrays were analysed by immunohistochemistry (IHC) to investigate the expression of ZNF692 in cervical cancer and its relationship with clinicopathologic characteristics. siRNAs and expression plasmids were used to reveal the biological function of ZNF692 in CC and subcutaneous xenograft model to examine the role of ZNF692 in vivo. Chromatin Immunoprecipitation and luciferase reporter assay were performed to ascertain whether ZNF692 binds to the promoter region of p27kip1. RESULTS: By analyzing The Cancer Genome Atlas (TCGA) dataset, we confirmed ZNF692 as a potential oncogene in CC. ZNF692 expression was up-regulated in CC tissues compared with that in adjacent normal tissues, and its overexpression was correlated with poor clinicopathologic characteristics. Moreover, ZNF692 promoted the proliferation, migration and invasion of CC cells both in vitro and in vivo. Regarding molecular mechanisms, up-regulation of ZNF692 was found to enhance the G1/S transition via regulating the p27kip1/PThr160-CDK2 signal pathway in CC cells. CONCLUSION: ZNF692 promotes CC cells proliferation and invasion through suppressing p27kip1 transcription by directly binding its promoter region, which suggests that ZNF692 may serve as an underlying therapeutic target and prognostic marker in CC.

SNAP23 suppresses cervical cancer progression via modulating the cell cycle.

OBJECTIVE: Cervical cancer (CC) is one of the most common gynecologic tumors in women worldwide, with poor prognosis and low survival rate. In this study, we identified SNAP23 as a potential tumor suppressor gene in CC. METHODS: The expression of SNAP23 in tissues and cell lines were measured by qRT-PCR, western blot and IHC. Knockdown of SNAP23 by siRNA and ectopic expression of SNAP23 by overexpression plasmid were performed to observe the biological function of SNAP23 in CC. Xenograft nude mice models were established to measure its function in vivo. RESULTS: SNAP23 was downregulated in CC tissues and had a negative correlation with advanced clinical characteristics. Ectopic expression of SNAP23 suppressed malignant phonotype of CC while knockdown of SNAP23 promoted the progression of CC in vitro. The flow cytometry analysis revealed that SNAP23 exerted its tumor suppressor activity via inducing G2/M cell cycle arrest. Moreover, xenograft tumor models showed that SNAP23 suppresses tumor growth in vivo. CONCLUSIONS: Our results revealed that SNAP23 suppressed progression of CC and induced cell cycle G2/M arrest via upregulating p21cip1 and downregulating CyclinB1.

KIF18B promotes tumor progression through activating the Wnt/ß-catenin pathway in cervical cancer.

BACKGROUND: KIF18B was identified as a potential oncogene by analysis of The Cancer Genome Atlas database. MATERIALS AND METHODS: We assessed KIF18B expression and explored its clinical significance in cervical cancer tissues. We have also evaluated the effects of KIF18B on cervical cancer cell proliferation, migration, and invasion both in vitro and in vivo. RESULTS: Our results show that KIF18B is overexpressed in cervical cancer tissues and is associated with a large primary tumor size, an advanced FIGO stage, and an advanced tumor grade. Knockdown of KIF18B induces cell cycle G1-phase arrest and inhibits the proliferation, migration, and invasion of cervical cancer cells, whereas its overexpression promotes proliferation, migration, and invasion in these cells. Moreover, silencing of KIF18B reduces expression of CyclinD1, ß-catenin, C-myc, and p-GSK3ß expression. CONCLUSION: These data suggest that KIF18B can serve as a novel oncogene that promotes the tumorigenicity of cervical cancer cells by activating Wnt/ß-catenin signaling pathway.

Dose Volume Effect of Acute Diarrhea in Post-Operative Radiation for Gynecologic Cancer.

BACKGROUND: Diarrhea is the primary symptom of concern in acute post-operative radiation-induced enteritis in gynecologic cancer. We retrospectively studied the correlation between the volume of irradiated small bowel and the development of acute diarrhea in these patients. MATERIALS AND METHODS: A total of 100 post-operative gynecologic cancer patients were analyzed. Pelvic computed tomography was performed to calculate the volume of irradiated small bowel. A dose-volume histogram was calculated from 5 to 40 Gy at 5 Gy intervals. Patients receiving conventional whole pelvic radiation therapy (RT) were assigned to Group I, and those who received intensity-modulated RT (IMRT) were assigned to Group II. A total dose of 40-50 Gy was delivered at 1.8-2.0 Gy per fraction daily. Acute diarrhea during treatment was scored. All data were expressed as a mean ± standard deviation. Different dose-volume parameters for small bowel in Grades 0-1 and Grades 2-3 diarrhea were calculated by the independent t-test. Univariate analysis of diarrhea risk factors was performed with the independent t-test or Chi-square/Fisher exact test. RESULTS: Of the 77 patients who received conventional RT, 44 (57.14%) experienced Grades 2-3 toxicities. Of the 23 patients who received IMRT, 9 (39.13%) experienced Grades 2-3 toxicities. Concurrent chemotherapy was slightly associated with a higher damage score in both groups (p = 0.028). None of the patient factors (weight, percentage depth dosage, dose fraction, distance from skin to tumor, lymph node metastasis, chemotherapy, block, brachytherapy, hypertension, or diabetes) were correlated with diarrhea in the two groups. The volumes of irradiated small bowel in patients who experienced Grades 2-3 diarrhea were significantly larger than those in patients who experienced Grades 0-1 diarrhea at all dose levels in Group I. V20 (372.19 ± 133.26 cm3, p = 0.004) was an independent factor for developing Grades 2-3 diarrhea in Group I. V25 (290.35 ± 130.22 cm3, p = 0.001) was an independent risk factor for all patients who developed higher score diarrhea. CONCLUSIONS: The volume of irradiated small bowel was an independent risk factor for all patients who developed diarrhea, especially those undergoing conventional RT.

ZNF692 promotes proliferation and cell mobility in lung adenocarcinoma.

By analyzing The Cancer Genome Atlas (TCGA) datasets, we discovered that the zinc finger protein 692 (ZNF692) were over-expressed in Lung adenocarcinoma (LUAD) tissues compared to adjacent non-tumor tissues (P < 0.0001). In this study, we investigated the function of ZNF692 in the progression of LUAD. We found that ZNF692 knockdown inhibited LUAD cells proliferation, migration, and invasion both in vitro and in vivo. And LUAD cell apoptosis was induced following the down-regulation of ZNF692. Our results show that ZNF692 is over-expressed in LUAD tissues compared to adjacent normal tissues, and hyper-expression of ZNF692 in LUAD is an independent risk factor for worse overall survival in LUAD patients (HR: 8.800, 95%CI: 1.082-71.560, P = 0.042) by Tissue Microarray stain assay (TMA). GO analysis indicated that most genes were enriched in metabolic process which were associated highly with ZNF692 levels. Collectively, our results suggested that ZNF692 may serve as a potential oncogene and biomarker in LUAD by influencing cell metabolism.

HBV Infection Status and the Risk of Cholangiocarcinoma in Asia: A Meta-Analysis.

Background. The inconsistent finding was between hepatitis B virus (HBV) infections and cholangiocarcinoma (CCA). This meta-analysis is to explore this relationship in Asia. Methods. A literature search was performed using PubMed, Web of Science, and Cochrane Library to October 30, 2015. Pooled incidence rate and OR with 95% CI were calculated using STATA 11.0. Results. Thirty-nine studies were included. The pooled incidence rate of CCA patients with HBV infection was 31% (95% CI 22%-39%). The pooled OR showed increased risk of CCA incidence with HBV infection (OR = 2.72, 95% CI 1.90-3.88), especially in ICC (OR = 3.184, 95% CI 2.356-4.302), while it showed no risk in ECC (OR = 1.407, 95% CI 0.925-2.141). Also, the pooled OR showed increased risk of ICC and ECC incidence (OR = 6.857, 95% CI 4.421-10.633 and OR = 1.740, 95% CI 1.260-2.404) in patients with HBsAg+/HBcAb+. The pooled OR showed increased risk of ICC incidence (OR = 1.410, 95% CI 1.095-1.816) in patients with HBsAg-/HBcAb+. Conclusion. It is suggested that HBV infection is associated with an increased risk of CCA in Asia. Two HBV infection models (HBsAg+/HBcAb+ and HBsAg-/HBcAb+) increase the risk of CCA, and patients with HBsAg-/HBcAb+ also had a risk of ICC. This trial is registered with PROSPERO CRD42015029264.

Correlation between bone marrow dose volumes and acute hematological toxicity in postoperative gynecological cancer patients.

OBJECTIVE: To identify the association between radiation dose volume and acute hematological toxicity (HT) in postoperative gynecological cancer patients receiving whole pelvic radiotherapy (RT) or intensity-modulated RT (IMRT), a principal component regression model was used to calculate HT. METHODS: Women (n=100) receiving with or without chemotherapy RT were retrospectively analyzed, 52 of whom received chemotherapy (paclitaxel and nedaplatin). The pelvis and lumbar vertebrae, defined as the prolong-pelvic bone marrow, were divided into the (1) combined ilium, ischium and pubis and the (2) lumbar vertebrae and the sacrum. The V5-V40 of subsides was calculated. The complete blood counts were recorded weekly. The principal component analysis was performed on volumes which generated the principal components (PCs), followed by using a logistic regression model. RESULTS: Forty-seven patients presented with grade 2-3 HT during RT. Chemotherapy increased the incidence of HT compared with RT alone (70.21% vs. 29.79%; p=0.001). Fifty-three patients with persistent HT developed more serious HT at an earlier stage of RT. The chemotherapy cycles and three PCs associated with grade 2-3 HT was identified to form the resulting principal logistic regression model. CONCLUSION: A new method to calculate the NTCP was achieved by PCs logistic regression.

Little association between the interleukin 10-3575T/A polymorphism and cancer risk: pooled analysis of 15608 cancer cases and 17539 controls.

The aim of the present work was to evaluate the association between the interleukin 10 (IL-10) -3575T/A (rs1800890) polymorphism and cancer risk. We performed a met-analysis based on 15 studies, including 15608 cancer cases and 17539 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association, and performed sensitivity analyses. In the stratified analyses by all included studies, no association between IL-10-3575T/A (rs1800890) polymorphism and cancer risk (OR=0.966, 95% CI=0.889-1.05, P=0.417 for A vs. T; OR=1.035, 95% CI=0.975-1.1, P=0.257 for AA vs. AT+TT; OR=1.008, 95% CI=0.964-1.054, P=0.723 for AA+AT vs. TT) was observed. In the stratified analyses by cancer type of lymphoma and non-lymphoma, no association between them was also detected (Lymphoma: OR=1.021, 95% CI=0.962-1.083, P=0.496 for A vs. T; OR=1.029, 95% CI=0.967-1.095, P=0.363 for AA vs. AT+TT; OR=1.017, 95% CI=0.952-1.086, P=0.626 for AA+AT vs. TT; Non-lymphoma: OR=0.966 95% CI=0.889-1.51, P=0.245 for A vs. T; OR=1.035, 95% CI=0.975-1.1, P=0.287 for AA vs. AT+TT; OR=1.017, 95% CI=0.948-1.091, P=0.967 for AA+AT vs. TT). The results were the same by sensitivity analyses. No publication bias was existed in the analysis. The interleukin 10-3575T/A polymorphism may have no association with cancer risk.