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Hodgkin's lymphoma (HL) is a type of hematological neoplasm that generally appears alone, with a low incidence. The majority of cases histopathologically present as B-cell lymphoma. Multiple myeloma (MM) is defined as the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin (Ig). The coexistence of HL and MM is rare, however, the present study reports such a case. On May 31, 2012, a 45-year-old man was diagnosed with HL, stage III, 31 months ago. At the same time, computed tomography and magnetic resonance imaging showed osteolytic lesions, a significant increase in IgA λ chains, and multiple myeloma cells on bone marrow aspiration. Following 8 cycles of chemotherapy, the patient received maintenance treatment with thalidomide and dexamethasone. During 2 years of follow-up, the patient has maintained a complete response for HL and a stable disease state for MM. The coexistence of HL and MM is rare. Further study of such cases may explain the associations between these two tumors and aid the production of effective treatment options. [ABSTRACT FROM AUTHOR]

Colorectal cancer and throat cancer are the world's most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9) and phosphorylated extracellular signal-regulated kinases (ERK)1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to spare hematopoietical bone marrow (BM) identified by magnetic resonance (MR) radiation in order to alleviate acute hematologic toxicity (HT) for gastric cancer patients treated with postoperative chemoradiotherapy (CRT). Methods: A prospective, open-label, single-arm Phase II study (Clinicaltrials.gov; NCT 01863420) was conducted in 25 patients with gastric cancer who were eligible for postoperative concurrent CRT. The MR images of vertebral body T8-L4 were fused with images of simulating computed tomography. Hematopoietical BM was contoured according to the MR and spared in radiotherapy plan. The CRT regimen consisted of daily capecitabine (1600 mg/m2/d) and 45 Gy of radiation at 1.8 Gy per day. Primary endpoints were grade ≥3 HT that occurred within 2 months of initiation of CRT. The relationship between HT and dose-volume of BM was estimated by multivariable linear regression model. Results: Twenty four patients (96%) had T3-4 disease and 22 (88%) had disease with node positive. The median age was 53 years (range, 28-73 years). Before concurrent CRT, adjuvant chemotherapy was administered with a mean cycle of 4.3±0.5. Only five patients (20%) developed grade 3-4 HT during treatment, among whom two (8.0%) patients experienced grade 3-4 leucopenia, two (8.0%) experienced neutropenia, and two (8.0%) experienced thrombocytopenia, respectively. None of the patients showed grade 3-4 anemia. Multivariable linear regression revealed increased BM-V5 (P=0.03) and BM-V20 (P=0.002) were found to be significantly associated with decreased white blood cells nadirs in multivariable regression; increased BM-V20 (P<0.001) with decreased absolute neutrophil count nadirs, increased BM-V30 (P=0.002) and volume of BM (P=0.001) with decreased platelet count nadirs. Conclusion: Irradiation of active BM identified by MR is associated with HTs. Techniques to limit low-dose radiation, especially V20, to BM could reduce HT in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: To reduce acute hematologic toxicity (HT) in rectal cancer patients treated with neoadjuvant concurrent chemoradiotherapy by sparing the hematopoietical bone marrow (BM) indentified by magnetic resonance (MR). Materials and methods: A total of 35 staged II/III rectal cancer patients were prospectively enrolled. MR images of pelvis were fused with the simulating CT images. Active BM indentified by MR was contoured as an organ at risk in the treatment plan. The neoadjuvant treatment regimen consisted of 50 Gy of radiation delivered in 25 fractions, 5 days per week, with concurrent daily capecitabine (1650 mg/m/day, twice daily during RT course) and weekly oxiliplatin 50 mg/m/qw. Multivariable linear regression model is used to test correlation between HT and dose-volume of BM. Results: Thirty-one patients (88.6 %) had stage T3-4 disease, and 30 patients (85.7 %) had node-positive disease. The median age of cohort was 55 years (range 28-73 years). Only 9 (25.7 %), 6 (17.1 %), 1 (2.9 %) and 1 (2.9 %) experienced acute Grade 2-4 leukopenia, neutropenia, anemia and thrombocytopenia, respectively. Multivariable linear regression revealed increased BM-V5 was significantly associated with decreased WBC nadirs ( p = 0.005), decreased ANC nadirs ( p = 0.002), and decreased PLT nadirs ( p = 0.017). No dose-volume parameters of BM were found to be related with decreased Hb. Conclusions: The irradiated volume of pelvic BM identified by MR is associated with HT in rectal cancer patients undergoing neoadjuvant concurrent chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Totally implantable venous access port systems (TIVAPS) are widely used in breast cancer patients. However, complications are frequent and may necessitate device replacement or removal, resulting in additional patient stress and treatment delays. The aim of the present study was to investigate possible risk factors for complications. A total of 2,996 consecutive female breast cancer patients, with a median age of 50.2 years (range, 21.2-85.5 years) were enrolled in this observational, single-centre study between December, 2008 and April, 2014. TIVAPS implantation was principally performed using local anaesthesia and the blind puncture or Seldinger technique through internal jugular or subclavian vein access. A retrospective chart review was conducted to obtain information associated with TIVAPS and patient data. Insertion performed by blind puncture and Seldinger technique had a success ratio of 96.34 and 99.80%, respectively (χ²=29.905, P<0.001). However, the success ratio of the puncture technique group was 99.76% when the TIVAPS was implanted in the right internal jugular vein. The most common complications were late complications, with an overall incidence rate of 5.41% (162/2,996) during the entire device duration. The most common late complications included fibrin formation (1.84%, 55/2,996), port-related bacteraemia (1.44%, 43/2,996) and deep vein thrombosis (0.63%, 19/2,996). No patient died during the study. Our results demonstrated that insertion of TIVAPS by blind puncture or the Seldinger technique through internal jugular or subclavian vein access is convenient, and insertion by the Seldinger technique through the right internal jugular vein is the preferred method. Therefore, TIVAPS is safe for continuous infusional chemotherapy regimens for breast cancer patients. [ABSTRACT FROM AUTHOR]

The mitochondrial GTPase mitofusin-2 (Mfn2) gene is a novel gene characterized as a cell proliferation inhibitor. Mfn2 has previously been reported to play a role in regulating cell proliferation, apoptosis and differentiation in a number of cell types. However, there are no studies on the effect of Mfn2 in breast cancer. In this study, we aimed to elucidate the function and mechanism of Mfn2 in breast cancer. A plasmid encoding the complete Mfn2 open reading frame (pEGFP-Mfn2) was used to infect breast cancer cells. The effect of Mfn2 on proliferation was assessed by methyl thiazolyl tetrazolium and bromodeoxyuridine incorporation analyses. Flow cytometry, immunofluorescence and western blot analyses were used to test the effects of Mfn2 on cell cycle distribution and apoptosis. Additionally, the PI3K/Akt signaling pathway was analyzed after pEGFP-Mfn2 was transfected into MCF-7 cells. The results revealed that Mfn2 suppressed the proliferation of MCF-7 cells by regulating more cells at the G0/G1 phase and decreasing proliferating cell nuclear antigen and cyclin A expression. The results also demonstrated that the PI3K/Akt signaling pathway is involved in Mfn2-regulated proliferation and apoptosis. Taken together, this indicates that Mfn2 mediates MCF-7 cell proliferation and apoptosis via the PI3K/Akt signaling pathway. Mfn2 may thus be a significant therapeutic target in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy and toxicity of postoperative intensity-modulated radiation therapy (IMRT) for patients with soft tissue sarcomas (STSs) in the extremities and trunk wall. Patients and methods: Eighty patients with localized STSs in the extremities and trunk wall treated with function-conserving surgery and postoperative IMRT were analyzed. The primary locations were in the extremities in 51 patients and in the trunk wall in 29 patients. The margins were positive in nine patients and negative in 71 patients. The median dose of IMRT was 64 Gy. Results: At a median follow-up time of 38 months, eight patients developed local recurrences. The 5-year local control (LC) rate was 88.1%. The patients with negative margins exhibited much better LC than did those with positive margins (90% vs 64.8%, P=0.023). Multivariate analysis revealed that positive margin was an independent risk factor for LC. The 5-year distant metastasis-free survival, disease-free survival, and overall survival rates were 75.2%, 72.6%, and 83.6%, respectively. Large tumor size (.5 cm) was significantly associated with poor overall survival. Edema and joint stiffness were observed in 17.6% and 9.8% of patients with extremity STSs, respectively. Conclusion: IMRT provides excellent LC and low toxicity for patients with STSs in the extremities and trunk wall. [ABSTRACT FROM AUTHOR]

Background: Pim-1 kinase is a proto-oncogene and its dysregulation contributes to tumorigenesis and progression of a variety of malignancies. Pim-1 was suggested as a therapeutic target of cancers. The functional relevance of Pim-1 and the mechanism underlying its dysregulation in lung tumorigenesis remained unclear. This study aimed to investigate if Pim-1 has important functions in non-small-cell lung cancer (NSCLC) by: 1) evaluating the clinicopathologic significance of Pim-1 through analysing its expression in 101 human NSCLCs tissues using quantitative PCR, Western Blot and immunohistochemical studies, 2) determining its role in NSCLC and drug resistance using in vitro assays, and 3) investigating the regulatory mechanism of Pim-1 dysregulation in lung tumorigenesis. Results: Pim-1 was upregulated in 66.2% of the lung tumor tissues and its expression was significantly related to advanced stage (P = 0.019) and lymph node metastasis (P = 0.026). Reduced Pim-1 expression suppressed NSCLC cell growth, cell cycle progression and migration in vitro. Pim-1 was a novel target of miR-486-5p determined by luciferase report assay, and ectopic miR-486-5p expression in cancer cells reduced Pim-1 expression. Furthermore, eukaryotic translation initiation factor 4E (eIF4E) controlled the synthesis of Pim-1 in NSCLC cells, and its expression was positively associated with that of Pim-1 in NSCLC tissue specimens (r = 0.504, p < 0.001). The downregulated miR-486-5p and upregulated eIF4E in NSCLC cells led to the overexpression of Pim-1 by relieving the inhibitory effect of the 3′-UTR or 5′-UTR of Pim-1 mRNA, respectively. Moreover, Pim-1 knockdown sensitized NSCLC cells to cisplatin and EGFR tyrosine kinase inhibitor, gefitinib. Conclusions: Pim-1 kinase could be a critical survival signaling factor in NSCLC, and regulated by miR-486-5p and eIF4E. Pim-1 kinase may provide a potential target for diagnosis and treatment for lung cancer. [ABSTRACT FROM AUTHOR]

The fat mass and obesity-associated gene ( FTO) has previously been associated with human body mass index and porcine intramuscular fat content. In this study, the potential alternative splicing pattern of the FTO gene was investigated, and three novel splice variants were identified in Large White and indigenous Chinese Tibetan pigs. To explore the molecular effect of the FTO gene on the fat deposition caused by castration, 40 paired full-sibling male pigs were divided into intact and castrated groups, and the trait data showed that abdominal fat weight, percentage of abdominal fat weight, and backfat thickness in the intact group were significantly lower than in the castrated group ( p < 0.05). FTO mRNA expression in the hypothalamus was significantly increased in the castrated group compared with the intact group ( p < 0.05), but was not different in the abdominal fat or backfat tissues. Moreover, the relative expression of the FTO gene was shown to have a higher level in the hypothalamus when compared with expression in the fat tissues ( p < 0.05). Our results suggest that there are different patterns of alternative splicing and FTO expression among pig breeds. This study will provide clues for obtaining a better understanding of the porcine FTO gene function. [ABSTRACT FROM AUTHOR]

Background: To define the clinical target volume (CTV) for radiotherapy in patients with hepatocellular carcinoma (HCC). Methods: A prospective study was conducted to histologically evaluate the presence and the distance of microscopic extension (ME) for resected HCC on the basis of examination of whole-mount preparations of carcinoma tissue sections. Results: A total of 380 whole-mount slides prepared from tumor samples of 76 patients with HCC were examined. Patients with elevated pretreatment AFP levels exhibited higher risk of ME as compared to those with normal pretreatment AFP levels (93.9% vs. 69.8%, P < 0.01). ME positivity was 16.7% for Grade 1, 79.1% for Grade 2, and 96.3% for Grade 3 tumors (P < 0.01). The mean distance of ME was 0.0 ± 0.1 mm (range 0-0.2 mm) for Grade 1, 0.9 ± 0.9 mm (range 0-4.5 mm) for Grade 2, and 1.9 ± 1.9 mm (range 0-8.0 mm) for Grade 3 tumors (P < 0.01). Conclusions: The CTV margins for tumor Grades 1, 2, and 3 HCC, are recommended to be 0.2 mm, 4.5 mm, and 8.0 mm beyond the gross tumor margin, respectively, to account for possible ME of the tumors in all patients. [ABSTRACT FROM AUTHOR]

Objective: Small cell lung carcinoma (SCLC) is considered one of the most aggressive types of lung cancer due to its rapid growth and early metastasis. No tumor markers or therapeutic targets have been demonstrated to be specific or effective in SCLC to date. This study aims to evaluate the potential of Flotillin1 (Flot1) as a target of SCLC treatment. Methods: Flot1 expression level in the tissue of SCLC and other tissue of lung disease was detected using immunohistochemical staining. Transwell and Matrigel assays were employed to examine migration and invasion of cancer cells. Flow cytometry and xCELLigence system were used to evaluate cell apoptosis and cell viability, respectively. Expression levels of Flot1, epithelialmesenchymal transition (EMT) marker E-cadherin, vimentin, cyclinD1, TGF-β-Smad2/3, and p-AKT were examined using Western blot. Furthermore, xenograft tumor in nude mice was used to evaluate the growth and metastasis of NCI-H446 cells in vivo. Results: Our results demonstrated that Flot1 is highly expressed in SCLC samples and that its expression correlates strongly with clinical stage, distant metastasis, and poor survival. The knockdown of Flot1 decreased the growth, migration, and invasiveness of SCLC cells and reversed EMT phenotype in vitro and in vivo, while enhanced Flot1 expression exhibited the opposite behavior. Gene expression profile analysis demonstrated that Flot1-regulated genes frequently mapped to the AKT and TGF-β-Smad2/3 pathways. Our results further revealed that Flot1 affected the progression of SCLC via regulation of EMT progression. Conclusions: These findings indicated an oncogenic role of Flot1 via promoting EMT in SCLC and suggested its potential as a tumor marker and prognostic indicator. [ABSTRACT FROM AUTHOR]

Objective: The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment. This study determined the effects of genetic variations in genes involved in apoptosis, pyroptosis, and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy (CRT). Methods: The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT. The associations between genetic variations and overall survival (OS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs) computed using a Cox proportional regression model. Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase (ALOX5) gene and the ALOX5 rs702365 variant. Results: We detected 16 genetic polymorphisms in CASP3, CASP7, TRAILR2, GSDME, CASP4, HO-1, ALOX5, GPX4, and NRF2 that were significantly associated with OS in the additive model (P < 0.05). There was a substantial cumulative effect of three genetic polymorphisms (CASP4 rs571407, ALOX5 rs2242332, and HO-1 rs17883419) on OS. Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS. We demonstrated, for the first time, that rs702365 [G] > [C] represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response. Conclusions: Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment. [ABSTRACT FROM AUTHOR]

Salt stress significantly reduces the productivity of crop plants including maize (Zea mays). miRNAs are major regulators of plant growth and stress responses, but few studies have examined the potential impacts of miRNAs on salt stress responses in maize. Here, we show that ZmmiR169q is responsive to stress-induced ROS signals. After detecting that salt stress and exogenous H2O2 treatment reduced the accumulation of ZmmiR169q, stress assays with transgenic materials showed that depleting ZmmiR169q increased seedling salt tolerance whereas overexpressing ZmmiR169q decreased salt tolerance. Helping explain these observations, we found that ZmmiR169q repressed the transcript abundance of its target NUCLEAR FACTOR YA8 (ZmNF-YA8), and overexpression of ZmNF-YA8 in maize improved salt tolerance, specifically by transcriptionally activating the expression of the efficient antioxidant enzyme PEROXIDASE1. Our study reveals a direct functional link between salt stress and a miR169q-NF-YA8 regulatory module that plants use to manage ROS stress and strongly suggests that ZmNF-YA8 can be harnessed as a resource for developing salt-tolerant crop varieties. [ABSTRACT FROM AUTHOR]