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Background. Although tumor size is regarded as the "T" stage of the tumor-node-metastasis (TNM) staging system for many solid tumors, its prognostic impact in gastric cancer remains uncertain and conflicting. Methods. We enrolled 6960 eligible patients from the Surveillance, Epidemiology, and End Results (SEER) database. The X-tile program was used to select the best cut-off value of tumor size. Then, the Kaplan–Meier method and the Cox proportional hazards model were applied to examine the efficacy of tumor size on prognostic prediction for overall survival (OS) and gastric cancer-specific survival (GCSS). The presence of nonlinear association was determined by the restricted cubic spline (RCS) model. Results. Tumor size was divided into 3 groups: small size (≤2.5 cm), medium size (2.6-5.2 cm), and large size (≥5.3 cm). After adjusting by covariates such as depth of tumor infiltration, the large and medium groups showed a worse prognosis than the small group; however, no survival difference in OS was suggested between the medium and large groups. Similarly, although there was a nonlinear relationship between tumor size and survival, increasing tumor size did not show an independent negative effect on prognosis in the RCS analysis. However, the stratified analyses proposed this 3-way cut of tumor size in prognostic prediction for patients with both inadequate lymphadenectomy and negative nodal metastasis. Conclusions. Tumor size as a prognostic predictor may not have good clinical applicability in gastric cancer. Otherwise, it was recommended for patients with both insufficient examinations of lymph nodes and stage N0 disease. [ABSTRACT FROM AUTHOR]

To investigate the impact of preoperative objective nutritional indices on the prognosis of patients with hepatocellular carcinoma (HCC) who underwent radical hepatectomy and to compare their predictive value for prognosis. The clinical data of 661 patients were retrospectively reviewed to analyze the risk factors associated with prognosis; explore the role of the prognostic nutritional index (PNI), nutritional risk index (NRI), and control nutritional status (CONUT) in HCC prognosis; and compare their predictive value. Several independent risk factors for overall survival (OS) were identified, including neutrophil count, prealbumin level, microvascular invasion (MVI), Barcelona Clinic Liver Cancer (BCLC) stage, and PNI. The following factors were confirmed to be associated with recurrence-free survival (RFS): alpha-fetoprotein (AFP) level, prothrombin time (PT), tumor size, tumor capsule, MVI, BCLC stage, and PNI. Compared with the corresponding subgroups, patients in the high PNI (>45) group and the high NRI (>100) group had better RFS and OS (P < 0.05). However, patients in the low CONUT score (≤3) group had a similar prognosis to patients in the high CONUT (>3) group (P = 0.050). Receiver operating characteristic (ROC) curve results showed that the area under the curve (AUC) of the PNI was significantly higher than that of the CONUT for RFS or OS but similar to that of the NRI. The predictive ability of the PNI for HCC prognosis was significantly better than that of the CONUT but similar to that of the NRI. [ABSTRACT FROM AUTHOR]

It was investigated that TP73-AS1(TP73 antisense RNA 1) could function as an oncogene in gastric cancer (GC). The expression and function of long noncoding RNAs (lncRNAs) could be impacted by single nucleotide polymorphisms (SNPs), which are related to cancer susceptibility and prognosis. This study was to reveal the association between lncRNAs TP73-AS1 polymorphisms (rs1181865 A > G, rs9800 G > C, rs3737589 A > G, rs2298222 G > A, rs7515164 C > A) and GC in 1000 GC cases and 1000 controls in a Chinese Han population. Rs3737589 G allele had significant associations with the increasing risk of GC (G vs. A: p =.005). Rs3737589 variant genotypes (AG + GG) were related to an increased risk of GC in the elder population (age ≥60), females, nonsmokers, nondrinkers, individuals living in urban, and individuals without family history of GC in stratified analyses. Rs3737589 variant genotypes (AG + GG) were related to the advanced depth of tumor invasion (T3 + T4). Besides, we found that GC patients with AG or GG genotype of rs3737589 had poorer overall survival (OS) than those with AA genotype (p <.05). Our findings showed that the lncRNA TP73-AS1 rs3737589 polymorphism might increase the risk of GC, and rs3737589 polymorphism could be a potential biomarker to predict the prognosis of GC patients. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate the oncologic influence of transurethral resection of the prostate (TURP) as a cytoreductive surgery in metastatic hormone sensitive prostate cancer (mHSPC), in the setting of continuous complete androgen blockade (CAB). Materials and methods: Medical histories of 146 consecutive Chinese males with newly diagnosed mHSPC, registered in our institution in 2006 and 2007, were reviewed. All of these patients received CAB as initial systematic therapy. Demographics and cancer control outcomes from 39 mHSPC patients who underwent TURP for a relief of bladder outlet obstruction were compared with those of the other 107 who received CAB only when they were still hormone-sensitive. Median follow-up was 15 months (3 to 27 months). Results: Age at diagnosis, baseline PSA, and biopsy Gleason score were comparable between the 2 groups. Patients who underwent a TURP had lower PSA nadir (median 0.15 ng/ml vs. 0.82 ng/ml, P = 0.015) and longer time to PSA nadir (11.2 months vs. 6.4 months, P < 0.001). More patients in the non-TURP group developed hormone refractory prostate cancer (P = 0.007). The TURP group had a tendency towards longer disease-specific survival and overall survival (24.4 months vs. 24.1 months and 24.4 months vs. 22.9 months, respectively), though this did not reach statistical significance. Conclusions: TURP resulted in a better and more prolonged response to hormone therapy in mHSPC, with a trend towards positive influence in disease specific survival and overall survival. To date, our preliminary report is the first study regarding long-term survival of cytoreductive surgery in mHSPC, and further investigations are warranted. [Copyright &y& Elsevier]

Background. Neoadjuvant chemotherapy (NAC) with subsequent radical surgery has become a popular treatment modality for advanced gastric cancer (AGC) worldwide. However, the survival benefit is still controversial, and prognostic factors remain undetermined. Aim. To identify clinical parameters that are associated with the survival of AGC patients after NAC and radical surgery and to establish a nomogram integrating multiple factors to predict survival. Methods. We reviewed the medical profiles of 215 AGC patients who received NAC and radical resection, and clinical parameters concerning NAC, surgery, pathological findings, and adjuvant chemotherapy were analyzed using a Cox regression model to determine their impact on survival. Based on these factors, a nomogram was developed and validated. Results. The overall 1-year and 3-year survival rates were 85.8% and 55.6%, respectively. Younger age (<60 years old), increased examined lymph nodes (exLNs), successful R0 resection, the achievement of pathological complete response (pCR), and acceptance of adjuvant chemotherapy were positive predictors of survival. The C-index of the established nomogram was 0.785. The area under receiver operating curve (ROC) at 1/3 years of prediction was 0.694/0.736, respectively. The model showed an ideal calibration following internal bootstrap validation. Conclusion. A nomogram predicting survival after NAC and surgery was established. Since this nomogram exhibited satisfactory and stable predictive power, it can be inferred that this is a practical tool for predicting AGC patient survival after NAC and radical surgery. [ABSTRACT FROM AUTHOR]

Background: Semaphorin 5A has been linked to tumor growth, invasion, and metastasis in pancreatic cancer. However, the role of semaphorin 5A in cervical cancer is not known. Our aim is to investigate the prognostic value of semaphorin 5A and its potential role in lymphangiogenesis and invasion in cervical cancer. Methods: In this study, pathological features and clinical data of 232 cervical cancer patients were retrospectively reviewed. Semaphorin 5A protein and mRNA expression was detected by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction, respectively. In vitro, we determined the role and mechanistic pathways of semaphorin 5A in tumor progression in cervical carcinoma cell lines. Results: Semaphorin 5A expression was significantly higher in stage IIb tumors than in stage Ia, Ib, and IIa tumors. High semaphorin 5A expression was significantly associated with pelvic lymph node metastasis, lymphovascular permeation, and poor survival. Semaphorin 5A induced lymphangiogenesis through a plexin-B/Met/vascular endothelial growth factor-C pathway. Semaphorin 5A also increased cervical cancer cell invasion by stimulating the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 via PI3K/AKT and plexin-B3. Conclusion: Our findings indicate that semaphorin 5A may represent a poor prognostic biomarker and anti-metastasis therapeutic target in cervical cancer. [ABSTRACT FROM AUTHOR]

Lipoprotein lipase (LPL), a crucial gene in lipid metabolism, has a significant role in the progression of malignant tumors. The purpose of this research was to investigate the impact of rs15285 found in the LPL gene's 3'UTR region on the risk, biological behavior, and gastric cancer (GC) prognosis as well as to examine its potential function. Genotyping of rs15285 in 888 GC cases and 874 controls was conducted by SNaPshot technology. We used bioinformatics analysis and in vitro experiments to study the role of rs15285. First, this study revealed for the first time that polymorphism rs15285 increases the risk of GC (OR = 1.48, 95%CI = 1.16–1.89, P = 0.002). Although no relationship was found between rs12585 and the pathological features of GC, the prognosis of individuals with the rs12585 TT genotype was poorer than that of patients with the CC or CC+CT genotype (HR = 2.39 for TT vs. CC, P = 0.025; HR = 2.38 for TT vs. CC+CT, P = 0.025). In addition, bioinformatics analysis showed rs12585 may affect the binding of miRNAs to LPL, resulting in an increase of LPL expression to promote cancer progression. Ultimately, in vitro tests revealed that the rs15285 T allele increased LPL expression on the mRNA as well as the protein levels, promoting GC cell proliferation, invasion, and metastasis. The LPL rs12528 TT genotype increased the risk of GC and predicted a poor prognosis. Mechanistically, the rs15285 T allele could improve the expression of LPL, and thus promotes the malignant phenotype of GC. Therefore, our study may provide new biological predictors and a theoretical basis for the prognosis and customized therapy of stomach cancer patients. Key points: • Rs15285 polymorphism is a risk factor for GC. • Rs12585 TT genotype predicts a bad outcome in GC individuals. • Rs15285 T allele enhances GC cells malignant biological behavior. [ABSTRACT FROM AUTHOR]

Background: Debates exist on the treatment decision of the stage II/III colorectal cancer (CRC) due to the insufficiency of the current TNM stage‐based risk stratification system. Epithelial–mesenchymal transition (EMT) and tumor microenvironment (TME) have both been linked to CRC progression in recent studies. We propose to improve the prognosis prediction of CRC by integrating TME and EMT. Methods: In total, 2382 CRC patients from seven datasets and one in‐house cohort were collected, and 1640 stage II/III CRC patients with complete survival information and gene expression profiles were retained and divided into a training cohort and three independent validation cohorts. Integrated analysis of 398 immune, stroma, and epithelial‐mesenchymal transition (ISE)‐related genes identified an ISE signature independently associated with the recurrence of CRC. The underlying biological mechanism of the ISE signature and its influence on adjuvant chemotherapy was further explored. Results: We constructed a 26‐gene signature which was significantly associated with poor outcome in Training cohort (p < 0.001, HR [95%CI] = 4.42 [3.25–6.01]) and three independent validation cohorts (Validation cohort‐1: p < 0.01, HR [95%CI] = 1.70 [1.15–2.51]; Validation cohort‐2: p < 0.001, HR [95% CI] = 2.30 [1.67–3.16]; Validation cohort‐3: p < 0.01, HR [95% CI] = 2.42 [1.25–4.70]). After adjusting for known clinicopathological factors, multivariate cox analysis confirmed the ISE signature's independent prognostic value. Subgroup analysis found that stage III patients with low ISE score might benefit from adjuvant chemotherapy (p < 0.001, HR [95%CI] = 0.15 [0.04–0.55]). Hypergeometric test and enrichment analysis revealed that low‐risk group was enriched in thr immune pathway while high‐risk group was associated with the EMT pathway and CMS4 subtype. Conclusion: We proposed an ISE signature for robustly predicting the recurrence of stage II/III CRC and help treatment decision by identifying patients who will not benefit from current standard treatment. [ABSTRACT FROM AUTHOR]

Objectives: The multicenter study aimed to explore the relationship between the growth pattern of liver metastases on preoperative MRI and early recurrence in patients with colorectal cancer liver metastases (CRCLM) after surgery.Methods: A total of 348 CRCLM patients from 3 independent centers were enrolled, including 130 patients with 339 liver metastases in the primary cohort and 218 patients in validation cohorts. Referring to the gross classification of hepatocellular carcinoma (HCC), the growth pattern of each liver metastasis on MRI was classified into four types: rough, smooth, focal extranodular protuberant (FEP), and nodular confluent (NC). Disease-free survival (DFS) curve was constructed using the Kaplan-Meier method.Results: In primary cohort, 42 (12.4%) of the 339 liver metastases were rough type, 237 (69.9%) were smooth type, 29 (8.6%) were FEP type, and 31 (9.1%) were NC type. Those patients with FEP- and/or NC-type liver metastases had shorter DFS than those without such metastases (p < 0.05). However, there were no significant differences in DFS between patients with rough- and smooth-type liver metastases and those without such metastases. The patients with FEP- and/or NC-type liver metastases also had shorter DFS than those without such metastases in two external validation cohorts. In addition, 40.5% of high-risk-type (FEP and NC) liver metastases converted to low-risk types (rough and smooth) after neoadjuvant chemotherapy.Conclusion: The FEP- and NC-type liver metastases were associated with early recurrence, which may facilitate the clinical treatment of CRCLM patients.Key Points: • In the primary cohort, patients with FEP- and NC-type metastases had shorter disease-free survival (DFS) and a higher intrahepatic recurrence rate than patients without such metastases in the liver. • In the primary cohort, there were no significant differences in DFS or intrahepatic recurrence rate between patients with rough- and smooth-type metastases and those without such metastases in the liver. • High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients in primary and external validation cohorts. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed. Methods: We performed whole-exome sequencing of matched tumor tissues and blood samples from 53 pGI-DLBCL patients. The exonic mutation profiles were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Results: A total of 6,588 protein-altering events were found and the five most frequent mutated genes in our pGI-DLBCL cohort were IGLL5 (47%), TP53 (42%), BTG2 (28%), P2RY8 (26%) and PCLO (23%). Compared to the common DLBCL, significantly less or absence of MYD88 (0%), EZH2 (0%), BCL2 (2%) or CD79B (8%) mutations were identified in pGI-DLBCL. The recurrent potential driver genes were mainly enriched in pathways related to signal transduction, infectious disease and immune regulation. In addition, HBV infection had an impact on the mutational signature in pGI-DLBCL, as positive HBsAg was significantly associated with the TP53 and LRP1B mutations, two established tumor suppressor genes in many human cancers. Moreover, IGLL5 and LRP1B mutations were significantly correlated with patient overall survival and could serve as two novel prognostic biomarkers in pGI-DLBCL. Conclusions: Our study provides a comprehensive view of the exonic mutation profile of the largest pGI-DLBCL cohort to date. The results could facilitate the clinical development of novel therapeutic and prognostic biomarkers for pGI-DLBCL. [ABSTRACT FROM AUTHOR]

BACKGROUND: Genetic polymorphisms are believed to represent a key aspect of predisposition to gastric cancer (GC). Therefore, considering the important role of Cathepsin B (CTSB) in promoting cancer onset and development, it could be very worthful to explore the function of CTSB-related genetic polymorphisms in GC. OBJECTIVE: In this study, we investigated the correlation of CTSB-related polymorphisms (rs9009A>T, rs6731T>C, rs1293303G>C, rs1874547C>T, rs3779659C>T, rs17814426C>T and rs148669985C>T) with GC risk and prognosis in a case-control study of 994 cases and 1000 controls. METHODS: All tag single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) sequencing technology. RESULTS: The results indicated rs9009, rs6731 and rs17814426 correlated with decreased risks of GC (HR = 0.97, p < 0.001; HR = 0.86, P = 0.019; HR = 0.85, P = 0.017; respectively). Stratification analysis further showed rs17814426 variant genotypes correlated with earlier T stage (p = 0.044). In addition, GC patients carrying the C allele of rs6371 had better overall prognosis (HR = 0.62, 95%CI = 0.44–0.88). CONCLUSION: Our results firstly suggested the importance of CTSB-related polymorphisms on GC which could predict GC risk and prognosis. [ABSTRACT FROM AUTHOR]

Background: Cancer-associated fibroblasts (CAFs) in the tumour microenvironment are associated with poor prognosis and chemoresistance in multiple solid tumours. However, there is a lack of universal measures of CAFs in colorectal cancer (CRC). The aim of this study was to assess the utility of a fibroblast-related gene signature (FRGS) for predicting patient outcomes and reveal its relevant mechanism. Methods: The GSE39582 dataset, which includes 316 CRC patients who did not receive adjuvant chemotherapy was used as a discovery cohort to identify the prognostic fibroblast-related genes (FRGs). A total of 1352 CRC patients were divided into one training cohort (GSE39582, n = 461) and two validation cohorts (TCGA, n = 338; meta-validation, n = 553) for the construction of the FRGS and the verification of its prognostic value in stage II/III CRC patients. Functional annotation and analysis were performed to explore the underlying mechanism. The ability of the FRGS to predict immunotherapy response was further tested in a clear cell renal cell carcinoma (ccRCC) cohort. Results: An 11-gene signature that had prognostic value for stage II/III CRC patients in both validation cohorts was developed (TCGA cohort: HR = 1.90, 95% CI 1.16–3.12, P < 0.01; meta-validation cohort: HR = 1.95, 95% CI 1.39–2.73, P < 0.001). A high level of CAFs was correlated with worse prognosis in CRC patients who did not receive adjuvant chemotherapy (HR = 3.63, 95% CI 2.24–5.88, P < 0.001). Importantly, patients in the low-risk group were found to be benefit from chemotherapy (P < 0.01), but not in the high CAF group (P > 0.05). Similar results were found in the TCGA cohort. Integrated with clinical characteristics, the FRGS was confirmed to be an independent prognostic factor in the multivariate analysis after adjustment for tumour TNM stage (GSE39582 cohort: HR = 3.19, 95% CI 1.88–5.41, P < 0.001; TCGA cohort: HR = 5.00, 95% CI 1.58–15.85, P = 0.007; meta-validation cohort: HR = 2.99, 95% CI 1.44–6.21, P = 0.003). Furthermore, the enrichment analysis found that the antitumour immune response was suppressed and the infiltration of CD4 T cells and M1 macrophages was depressed in the high CAF group. The FRGS was also found to have value in predicting for immunotherapy response in the ccRCC cohort. Conclusions: The 11-gene FRGS had independent prognostic value for CRC patients, as well as utility in the prediction of benefit from chemotherapy. CAFs in the tumour microenvironment might have an impact on the prognosis of CRC patients via inhibiting immune response. [ABSTRACT FROM AUTHOR]

aims to identify clinical features and prognostic factors of PT-DLBCL patients. Methods: Thirty-two patients were included in this retrospective study who were diagnosed as PT-DLBCL and treated in Fudan University Shanghai Cancer Center between November 2010 and May 2018. The demographic details, clinico-pathological characteristics of the patients were summarized, and the impact on progression-free survival (PFS) and overall survival (OS) was analyzed. Results: The median age of the patients was 57 (range 36–76) years old. All patients received rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 4–6 cycles and central nervous system (CNS) prophylaxis, with a CR rate 87.5% and an ORR 96.9%. Nineteen patients continued prophylactic contralateral testis radiation therapy (PCTRT) in our hospital. The 3-year PFS and OS rates were 79% and 92%, respectively. None of the 19 patients who received PCTRT experienced local recurrence. All three patients who suffered from CNS relapse were germinal center B-cell subtype. Kaplan–Meier analyses showed that PT-DLBCL patients with late-stage (Stage IV) (P =0.022), higher IPI score (IPI≥ 2) (P =0.017), B symptoms (P =0.004), and elevated LDH level (P =0.03) had a shorter PFS. More importantly, we found that patients with the ratio of the LDH level in serum to that in CSF ≥ 6.5 suffered from a worse PFS (P =0.028). Conclusion: Our work revealed that staging IV, IPI score ≥2, having B symptoms and elevated LDH level were risk factors for PT-DLBCL patients. Significantly, the PT-DLBCL patients with a high ratio of LDH level in serum to that in CSF were indicated to have a worse PFS. [ABSTRACT FROM AUTHOR]

Forkhead box (FOX) proteins constitute a huge family of transcriptional regulators, which are involved in a wide range of cancers. FOXK1 is a little studied member of FOXK subfamily. This study aimed to investigate the potential prognostic value of FOXK1 in human hepatocellular carcinoma (HCC) and explore potential underlying mechanisms. We performed bioinformatic analyses to evaluate the prognostic value of FOXK1 expression in human HCC and to reveal the underlying mechanism by which FOXK1 regulates HCC. RT-PCR, FACS analysis and sphere formation assay were carried out to investigate the role of FOXK1 in regulating liver cancer stem cells. Our results demonstrated that FOXK1 was overexpressed in human HCC and positively correlated with cancer progression. DNA hypomethylation and gene copy number variation contributed to the overexpression of FOXK1. Importantly, high FOXK1 expression was associated with both low overall survival probability (OS) and low relapse free survival probability (RFS) of HCC patients. Intriguingly, we found that high FOXK1 expression was correlated with activation of stem cell-regulating pathways in human HCC. Knockdown of FOXK1 resulted in downregulation of the cancer stem cell marker EpCAM and ALDH1 and decreased sphere-forming ability of hepatocellular carcinoma cells. Overall, our study identified FOXK1 as a new biomarker for prognosis of HCC patients and revealed its role in regulating stemness of hepatocellular carcinoma cells. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma is one of the predominant histological subtypes of primary gastric lymphomas. Factors that contribute to precise stratification and guide the treatment of this disease are still not well understood. We analyzed 73 primary gastric diffuse large B cell lymphoma patients retrospectively, and found that patients characterized by late stage, multiple localization, B symptoms, lower serum albumin level and elevated LDH level had a shorter overall survival through Univariate Cox regression analysis. Multivariate Cox regression analysis demonstrated that ALB ≤ 35g/L, staging ≥ IIE and multiple sites localization were independent adverse prognostic factors. Significantly, in 35 patients who received endoscopy at diagnosis, Kaplan–Meier analyses indicated that patients with large (≥3 cm) and deep lesions (≥11 mm) had an inferior OS (p =.01 and.039). These findings implicated that tumor size and depth are two indicators of prognosis under ultrasonography. Further randomized studies with large number of cases are needed. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the failure patterns and prognostic factors influencing survival in patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses. Materials and methods: Fifty-one patients were analysed retrospectively. Forty-eight, 33, 10, and 13 patients underwent surgery, radiotherapy, chemotherapy, and immunotherapy, respectively. Failure events, including local recurrence, regional relapse, distant metastases, and death, were examined. Results: During follow-up (median: 59.0 months), 36 patients experienced failure after treatment, including local (n = 17), regional (n = 8), and distant organ (n = 23) metastases. The median failure times for local, regional, and distant metastases were 13.0, 14.0, and 8.0 months, respectively. The median survival times from local, regional, and distant failure to death were 10.5, 8.0, and 4.0 months, respectively. The 5-year overall survival rates of patients with and without distant organ metastases were 14.4% and 72.6%, respectively (p <.001). Multivariate analyses showed that radiotherapy increased local recurrence-free and regional relapse-free survival. Patients with stage IV tumours had reduced distant metastasis-free and overall survival compared to patients with stage I–III tumours. Conclusions: Distant metastasis was mainly owing to failure. Radiotherapy and the disease stage were prognostic factors for survival. [ABSTRACT FROM AUTHOR]

Aim Elevated neutrophil-to-lymphocyte ratio ( NLR) has been demonstrated to be a poor prognostic factor in multiple types of malignancies, whereas the effect of NLR on the prognosis of epidermal growth factor receptor ( EGFR)-mutated advanced non-small-cell lung cancer ( NSCLC) patients treated with first-line EGFR tyrosine kinase inhibitors ( TKIs) is not fully addressed. Methods 81 metastatic NSCLC patients harboring EGFR mutation treated with first-line EGFR TKIs were retrospectively included. The associations between baseline clinical characteristics, including NLR, and tumor response, progression and survival were investigated. Results Elevated NLR (≥3.5) was observed in 33 of 81 patients. The progression-free and overall survival of the patients with increased NLR was significantly worse than that of the patients with decreased NLR (8.20 vs 10.60 months, P < 0.001 and 17.20 vs 23.20 months, P < 0.001, respectively). Elevated NLR was confirmed to be an independent prognostic factor for worse progression-free and overall survival in Cox multivariate analysis. Conclusion Elevated NLR is likely to be associated with poor outcome in EGFR-mutated advanced NSCLC patients treated with first-line EGFR TKIs. [ABSTRACT FROM AUTHOR]

FLT3-ITD mutations occur in approximately 30% of acute myeloid leukemia (AML) and are associated with a poor outcome. Currently available FLT3 inhibitors havein vitrobut limited clinical activity in FLT3-ITD AML. Reports have shown that an arsenic trioxide (ATO)/all-trans-retinoic acid (ATRA) combination improves prognosis in acute promyelocytic leukemia, especially with FLT3-ITD, and ATO or ATRA alone enhances apoptosis in FLT3-ITD AML cells treated with FLT3 inhibitors, providing a rationale to investigate the role of ATO/ATRA in FLT3-ITD AML. Here, we demonstrate that an ATO/ATRA combination selectively exerts synergistic cytotoxicity against FLT3-ITD AML cell lines (MV4;11/MOLM-13). The signaling pathways affected by ATO/ATRA include FLT3/STAT5/MYC, FLT3/STAT5/E2F1, FLT3/ERK/ATF5 and FLT3/AKT/ATF5.ATF5 may function as an oncogene in FLT3-ITD AML. Our findings provide experimental evidence that supports further exploration of ATO/ATRA in FLT3-ITD AMLin vivoand warrants a clinical evaluation of regimens comprising an ATO/ATRA combination. [ABSTRACT FROM PUBLISHER]

Vitiligo is a depigmentation disorder characterized by loss of functional melanocytes of the skin epidermis. The pathogenesis of vitiligo remains elusive. The purpose of this study is to investigate the effects of basic fibroblast growth factor (bFGF) on melanocyte migration, including its biochemical mechanism using transwell assay in vitro. We found that melanocyte treated with bFGF showed a significant increase in migration and cytoskeletal rearrangement. These changes were associated with increased activation of PI3K/Akt, Rac1, FAK, JNK, and ERK. Likewise, reduction of PI3K/Akt, Rac1, FAK, JNK, and ERK activity using selective inhibitors or siRNA was associated with impediment of bFGF-induced melanocyte migration. In addition, activity of Rac1, FAK, and JNK was reduced in cells in which PI3K/Akt was inhibited, activity of FAK and JNK was reduced in cells in which the Rac1 was inhibited, and activity of JNK was reduced in cells in which the FAK was inhibited. Collectively, these data demonstrate that bFGF facilitated melanocyte migration via PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways. © 2016 IUBMB Life, 68(9):735-747, 2016 [ABSTRACT FROM AUTHOR]

Objective: Esthesioneuroblastoma is a rare cancer. The purpose of this study was to review the long-term outcomes of patients with esthesioneuroblastomas (ENBs) who were treated at a single institution.Materials and Methods: One hundred thirteen patients with biopsy-proven ENBs between June of 1979 and November of 2014 were retrospectively reviewed. There was 1 patient at stage A, 23 stage B and 89 stage C according to Kadish classifications. The initial treatments included pre-operative radiotherapy (RT) followed by surgery in 11 patients, surgery followed by post-operative RT in 51, primary RT in 47, and surgery in 3, and only a single patient was treated with palliative chemotherapy alone.Results: The median follow-up was 75months, 5-year overall survival (OS), loco-regional control rate (LRC) and distant metastasis-free survival were 65%, 73% and 67%, respectively. The OSs at 5years were 91% in the pre-operative RT group, 82% in the post-operative RT group, and 50% in the primary RT group (p<0.001). Regarding the patients in early disease stages (Kadish A/B), no survival differences were observed between primary RT and combination treatment. Regarding the node-negative Kadish C disease patients, combination of surgery and RT elicited superior survival, and pre-operative RT yielded the best prognoses. Distant failure rate is over 60% for N-positive disease, chemotherapy may play a more important role.Conclusions: The optimal treatment policy for ENBs remains the combination of surgery and radiotherapy. When choosing the most adequate therapy for ENBs, disease stage, age and lymph nodes status should be taken into consideration. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcome and prognostic factors of recursive partitioning analysis (RPA) Class III brain metastatic patients treated with stereotactic radiotherapy (SRT).Materials and Methods: Fifty-six consecutive patients with metastatic brain tumors and Karnofsky performance scale (KPS) scores <70 treated with SRT from January 2008 to October 2013 were involved in the analysis. Twenty-five patients (44.6%) were with symptomatic extracranial lesions (SELs), and the other 31 patients (55.4%) were without SELs. The detailed follow-up data of KPS scores were available in 44 patients. The KPS score drop time (KDT) was calculated as the time between SRT and 10 points drop of KPS scores compared to the baseline. Kaplan-Meier and Cox proportional hazards regression analyses were performed for univariate and multivariate analyses.Results: The median overall survival time was 5.0 months (95% confidence interval [CI] 3.42-6.59) for the whole group. In multivariate analysis, the presence of SELs (P = 0.007, relative risk = 4.44, 95% CI 1.036-20.818) was the independent prognosis factor for survival. Median survival time was 3 months for the patients with SELs, 8 months for the patients without SELs. The median KDT of the 44 patients was 3.0 months (95% CI, 1.927-4.073 months). Again only the presence of SELs (P = 0.001, OR = 6.622, 95% CI, 2.108-20.801) was significantly related to KDT in multivariate analysis. The median KDT of the patients with SELs was 1.5 months, which was 5 months for the patients without SELs.Conclusion: The presence of SELs was a negative prognosis factor for the survival of RPA Class III brain metastatic patients. If RPA Class III brain metastatic patients were without SELs, SRT may be a reasonable treatment option, but if they had SELs, SRT may not be a reasonable treatment due to the short overall survival time and KDT. [ABSTRACT FROM AUTHOR]

The most studied genetic polymorphisms associated with gastric cancer (GC) risk are located in protein-coding genes. However, the localization of these in long non-coding RNAs (lncRNAs) has not been fully studied. We aim to investigate the associations of Long non-coding RNA macrophage migration inhibitory factor antisense RNA1(Lnc-MIF-AS1) five polymorphisms (rs755622, rs17004044, rs2070767, rs1007889, rs2000468) with the risk and prognosis of GC. A total of 844 GC patients and 871 controls were included in the study. Genotyping was carried out using polymerase chain reaction-ligase detection reaction (PCR-LDR) technology. Odds ratios (ORs) and 95% confidence intervals (CIs) generated from unconditional logistic regression, were applied to quantify the effects of MIF-AS1 gene SNPs on GC risk. Log-rank test and Cox regression analysis were fitted to estimate hazard ratios (HRs) to quantify the effects of MIF-AS1 gene SNPs on GC prognosis. Significant associations were identified between MIF-AS1 rs17004044 variants and GC group in the codominant, dominant and additive models (OR = 2.843, P = 0.010; OR = 1.370, P = 0.004; and OR = 1.386; P = 0.001). In addition, association between rs17004044 variants and survival of GC was extremely observed (TC HR = 2.02 (1.21–3.37) P = 0.007, CC HR = 5.61 (2.12–14.83), P = 0.001). MIF-AS1 polymorphism rs17004044 contributes to increased predisposition and prognosis to GC. [ABSTRACT FROM AUTHOR]

Summary Objective To evaluate the long-term survival outcomes and toxicity of a larger series of patients with non-metastatic T4 classification nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Materials and methods From March 2004 to June 2011, 335 non-metastatic T4 classification NPC patients treated by IMRT were analyzed retrospectively. Treatment induced toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0. Results With a median follow-up time of 53.6 months (range, 2.8–114.9 months), the 5-year local failure-free survival (LFFS), regional failure free survival (RFFS), distant failure-free survival (DFFS), and overall survival (OS) were 84.1%, 92.2%, 74.1%, and 63.0%, respectively. At their last follow-up visit, 118 patients (35.2%) had developed treatment failure. Distant metastasis was the major failure pattern after treatment. The most common toxicities were mainly in grade 1 or 2. Concurrent chemotherapy failed to improve survival rates for patients with T4 classification NPC. Conclusion The results of T4 classification NPC treated by IMRT were excellent, and distant metastasis was the most commonly failure pattern. Treatment-related toxicities were well tolerable. The role of concurrent chemotherapy for T4 classification NPC needs to be further investigated in the era of IMRT. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a primary malignancy of bone. Although new therapies continue to emerge, osteosarcoma-related morbidity and mortality remain high. Various studies have evaluated the prognostic value of VEGF levels in osteosarcoma patients, but they have yielded conflicting results. Methods: The 5-year survival of each study was aggregated following a methodological assessment, and a systematic review of eligible studies with meta-analysis and univariate analysis was performed to quantitatively review the correlation of VEGF overexpression with 5-year survival in patients with osteosarcoma. Results: A total of 387 patients in eleven papers were finally considered to be eligible for inclusion in our analysis. Aggregation of the 6 positive results in Kaplan-Meier curve showed a risk ratio of 2.84 (95% CI: 1.39-5.83, P = 0.004) associated with VEGF-positive conditions in comparison with VEGF-negative conditions, suggesting that there was significant association between VEGF positive and the 5-year mortality. But univariate analysis of eleven studies showed that there was a small inverse but not significant relationship between VEGF expression level and the 5-year survival of osteosarcoma patients, but stage III, neo-chemotherapy, the primary tumor location, osteoblastic histological subtype and the source of patients showed a significant impact on the 5-year survival of patients. Conclusions: The prognostic significance of VEGF expression in all its isoforms is still unknown based on the limited data available, but we find VEGF165 may play an important role. Future studies should examine the relationship between VEGF isoform expression and patients' survival and the relationship between VEGF isoform expression and EMMPRIN expression, which could be helpful for predicting the prognosis of patients with osteosarcoma. Once the conclusion of whether the VEGF and its isoforms playing a role in osteosarcoma were reached, it would help guide clinical decision-making regarding therapy and outcomes. In addition, we recommend a >25% positive staining of the cells as a VEGF-positive cut-off value in immunohistochemistry, since we find a relatively strict detecting method is likely to yield significant result in the 5-year survival of patients. [ABSTRACT FROM AUTHOR]

Purpose: To report on our experience in the treatment of nasopharyngeal carcinoma (NPC) by radical radiotherapy alone in our institution during the last decade. Methods and Materials: From January 1990 to May 1999, 905 NPC patients were treated and were studied retrospectively. Radical radiotherapy was given to this cohort by conventional technique in a routine dose of 70–72 Gy to the primary tumor and metastatic lymph nodes. In case of residual primary lesion, a boost dose of 8–24 Gy was delivered by either 192Ir afterloading brachytherapy, fractionated stereotactic radiotherapy, conformal radiotherapy, or small external-beam fields. Results: The 5-year and 10-year local-regional control, overall survival, and disease-free survival rates were 81.7% and 76.7%, 76.1% and 66.5%, 58.4% and 52.1%, respectively. In case of residual primary lesions after a dose of 70–72 Gy of conventional external-beam radiotherapy (EBRT), an additional boost was able to achieve a local control of 80.8%, similar to that obtained with primary lesions that completely disappeared at 70–72 Gy (82.6%, p = 0.892). Conclusions: The treatment results of radical EBRT followed by a boost dose to the residual primary tumor for nasopharyngeal carcinoma in our institution are promising. [Copyright &y& Elsevier]