Cancer by Sfakianakis Alexandros: 09/13/17

Τετάρτη 13 Σεπτεμβρίου 2017

Molecular profile of atypical hyperplasia of the breast

Abstract

Purpose

Atypical ductal and atypical lobular hyperplasia (AH) of the breast are important proliferative lesions which are associated with a significantly increased risk for breast cancer. The breast cancer which develops in association with AH may occur synchronously, representing local progression, or metachronously at a later date in either the ipsilateral or contralateral breast. These high-risk characteristics of AH suggest they contain significant genomic changes.

Methods

To define the genomic changes in AH, a comprehensive review of the literature was conducted to identify the numerical chromosomal and structural chromosomal changes, DNA methylation, and gene expression abnormalities in atypical ductal and atypical lobular hyperplasia.

Results

AHs are characterized by advanced genomic changes including aneuploidy, loss of heterozygosity, gross chromosomal rearrangements such as amplifications and large-scale deletions, DNA methylation of tumor suppressor and other genes, and gene expression differences between AH and surrounding normal breast tissue including significant estrogen receptor expression. Many of these changes are shared by an associated synchronous breast cancer, consistent with an important precursor role for AH. At the same time, many of the genomic changes of AHs are also shared by common sporadic breast cancer, consistent with a high risk for future development of metachronous breast cancer.

Conclusions

This molecular profile should help clarify the genomic characteristics and malignant predisposition of AH, and aid in the identification of new targets for the prevention of breast cancer

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Exome array analysis identifies ETFB as a novel susceptibility gene for anthracycline-induced cardiotoxicity in cancer patients

Abstract

Purpose

Anthracyclines are widely used chemotherapeutic drugs that can cause progressive and irreversible cardiac damage and fatal heart failure. Several genetic variants associated with anthracycline-induced cardiotoxicity (AIC) have been identified, but they explain only a small proportion of the interindividual differences in AIC susceptibility.

Methods

In this study, we evaluated the association of low-frequency variants with risk of chronic AIC using the Illumina HumanExome BeadChip array in a discovery cohort of 61 anthracycline-treated breast cancer patients with replication in a second independent cohort of 83 anthracycline-treated pediatric cancer patients, using gene-based tests (SKAT-O).

Results

The most significant associated gene in the discovery cohort was ETFB (electron transfer flavoprotein beta subunit) involved in mitochondrial β-oxidation and ATP production (P = 4.16 × 10⁻⁴) and this association was replicated in an independent set of anthracycline-treated cancer patients (P = 2.81 × 10⁻³). Within ETFB, we found that the missense variant rs79338777 (p.Pro52Leu; c.155C > T) made the greatest contribution to the observed gene association and it was associated with increased risk of chronic AIC in the two cohorts separately and when combined (OR 9.00, P = 1.95 × 10⁻⁴, 95% CI 2.83–28.6).

Conclusions

We identified and replicated a novel gene, ETFB, strongly associated with chronic AIC independently of age at tumor onset and related to anthracycline-mediated mitochondrial dysfunction. Although experimental verification and further studies in larger patient cohorts are required to confirm our finding, we demonstrated that exome array data analysis represents a valuable strategy to identify novel genes contributing to the susceptibility to chronic AIC.

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Early tumor shrinkage indicates a favorable response to bevacizumab-based first-line chemotherapy for metastatic colorectal cancer.

A close correlation between early tumor shrinkage (ETS) and overall survival (OS) has been shown in antiepidermal growth factor receptor antibody-based chemotherapies for metastatic colorectal cancer (mCRC), but the clinical impact of ETS in bevacizumab-based chemotherapy has not been adequately clarified. Clinical data of mCRC patients who started initial chemotherapy without antiepidermal growth factor receptor antibody from 2005 to 2010 were retrospectively evaluated. The relative change in tumor size after 8 weeks of chemotherapy expected from the first image assessment [estimated ETS (EETS)] and the relative change in the tumor size at the nadir compared with the baseline [depth of response (DPR)] were examined. Seventy-three patients were enrolled and 61 patients were evaluable for survival by simple regression analysis. Bevacizumab-based chemotherapies were administered to 40 (66%) patients. The median EETS, DPR, progression-free survival, and OS were 16.1%, 27.2%, 8.0 months, and 19.5 months, respectively. Progression-free survival showed a positive correlation with OS (R2=0.429), whereas EETS and DPR were less correlated with OS (R2=0.0682, 0.186). EETS was well correlated with DPR (R2=0.659). Patients with EETS greater than 16.12% were predicted to achieve tumor shrinkage of more than 30% at the maximum response. EETS in bevacizumab-treated mCRC showed a close correlation with DPR, which suggested that EETS might be useful, indicating a favorable response in treatment with bevacizumab-based chemotherapy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Early mobilization programme improves functional capacity after major abdominal cancer surgery: a randomized controlled trial

Abstract

Background: Major abdominal oncology surgery is associated with substantial postoperative loss of functional capacity, and exercise may be an effective intervention to improve outcomes. The aim of this study was to assess efficacy, feasibility and safety of a supervised postoperative exercise programme.Methods: We performed a single-blind, parallel-arm, randomized trial in patients who underwent major abdominal oncology surgery in a tertiary university hospital. Patients were randomized to an early mobilization postoperative programme based on supervised aerobic exercise, resistance and flexibility training or to standard rehabilitation care. The primary outcome was inability to walk without human assistance at postoperative day 5 or hospital discharge.Results: A total of 108 patients were enrolled, 54 into the early mobilization programme group and 54 into the standard rehabilitation care group. The incidence of the primary outcome was nine (16.7%) and 21 (38.9%), respectively (P=0.01), with an absolute risk reduction of 22.2% [95% confidence interval (CI) 5.9–38.6] and a number needed to treat of 5 (95% CI 3–17). All patients in the intervention group were able to follow at least partially the exercise programme, although the performance among them was rather heterogeneous. There were no differences between groups regarding clinical outcomes or complications related to the exercises.Conclusions: An early postoperative mobilization programme based on supervised exercises seems to be safe and feasible and improves functional capacity in patients undergoing major elective abdominal oncology surgery. However, its impact on clinical outcomes is still unclear.Clinical trial registration: NCT01693172.

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Prognostic significance of corticotroph staining in radiosurgery for non-functioning pituitary adenomas: a multicenter study

Abstract

Silent corticotroph staining pituitary adenoma (SCA) represents an uncommon subset of Non-Functioning adenomas (NFAs), hypothesized to be more locally aggressive. In this retrospective multicenter study, we investigate the safety and effectiveness of Stereotactic Radiosurgery (SRS) in patients with SCA compared with other non-SCA NFA's. Eight centers participating in the International Gamma-Knife Research Foundation (IGKRF) contributed to this study. Outcomes of 50 patients with confirmed SCAs and 307 patients with confirmed non-SCA NFA's treated with SRS were evaluated. Groups were matched. SCA was characterized by a lack of clinical evidence of Cushing disease, yet with positive immunostaining for corticotroph. Median age was 55.2 years (13.7–87). All patients underwent at least one trans-sphenoidal tumor resection prior to SRS. SRS parameters were comparable as well. Median follow-up 40 months (6-163). Overall tumor control rate (TCR) 91.2% (n = 280). In the SCA group, TCR were 82% (n = 41) versus 94.1% (n = 289) for the control-NFA (p = 0.0065). The SCA group showed a significantly higher incidence of new post-SRS visual deficit (p < 0.0001) assigned to tumor progression and growth, and post-SRS weakness and fatigue (p < 0.0001). In univariate and multivariate analysis, only the status of silent corticotroph staining (p = 0.005, p = 0.009 respectively) and margin dose (p < 0.0005, p = 0.0037 respectively) significantly influenced progression rate. A margin dose of ≥17 Gy was noted to influence the adenoma progression rate in the entire cohort (p = 0.003). Silent corticotroph staining represents an independent factor for adenoma progression and hypopituitarism after SRS. A higher margin dose may convey a greater chance of TCR.

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Questions about lower inner zone tumors in early-stage breast cancer

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Weight gain in hormone receptor-positive (HR+) early-stage breast cancer: is it menopausal status or something else?

Abstract

Purpose

This study investigates weight trajectories in pre- versus postmenopausal breast cancer (BC) survivors diagnosed with hormone receptor-positive tumors, with a specific focus on discerning menopausal status and type of endocrine treatment (ET) as risk factors for weight gain during ET.

Methods

We conducted a retrospective review of electronic medical records. Descriptive statistics and Chi-squared and t tests were used to compare pre- and postmenopausal women. Chi-squared tests and ANOVA were used for within-group associations between patient characteristics and weight trajectories. Log-binomial regression models were used to estimate relative risk for weight gain.

Results

The final sample was 32% premenopausal (n = 140) and 68% postmenopausal (n = 298). Relative risk (RR) for weight gain during ET was highest in women who were premenopausal (RR = 1.29, 1.03–1.52) and had Stage 3 BC (RR = 2.12, 1.59–2.82), mastectomy (RR = 1.49, 1.19–1.88), axillary node dissection (RR = 1.39, 1.11–1.73), and chemotherapy (RR = 1.80, 1.37–2.36). For each kg of weight gained between BC diagnosis and start of ET, and for each additional year of age, RR of gaining weight during ET decreased (RR = 0.98, 0.97–0.99, and RR = 0.99, 0.98–0.99, respectively). Menopausal status and type of ET were not significant predictors of weight gain. In multivariable analysis, only weight loss between BC diagnosis and start of ET was significant.

Conclusion

The association of weight loss prior to ET and subsequent substantial weight gain during ET warrants further investigation.

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Full Monte Carlo-based biological treatment plan optimization system for intensity modulated carbon ion therapy on GPU

Publication date: Available online 12 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Nan Qin, Chenyang Shen, Min-Yu Tsai, Marco Pinto, Zhen Tian, Georgios Dedes, Arnold Pompos, Steve B. Jiang, Katia Parodi, Xun Jia
PurposeOne of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to employ Monte Carlo (MC) methods to compute properties of each pencil-beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We have previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of this study is to build a biological treatment plan optimization system based on goCMC.Methods and MaterialsThe repair-misrepair-fixation model was implemented to compute spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We employed a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3-dimensional patient cases.ResultsOur system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions, while sparing critical structures. Using four NVidia GTX 1080 GPUs, total computation time including spot simulation, optimization, and final dose calculation was 0.6 hours for the prostate case (8282 spots), 0.2 hours for the pancreas case (3795 spots), and 0.3 hours for the brain case (6724 spots). The computation time was dominated by MC spot simulation.ConclusionsWe have built a biological treatment plan optimization system for IMCT that performs simulations by a fast MC engine, goCMC. To our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable timeframe.

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Introduction to special section on digital technology and cancer survivorship

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Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications

Summary

Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov, 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21–25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

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Eribulin in advanced breast cancer: safety, efficacy and new perspectives

Future Oncology, Ahead of Print.

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Superior properties of Fc-comprising scTRAIL fusion proteins

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered as a promising molecule for cancer treatment. However, clinical studies with soluble TRAIL failed to show therapeutic activity, which resulted in subsequent development of more potent TRAIL-based therapeutics. In the present study, we applied defined oligomerization and tumor targeting as strategies to further improve the activity of a single-chain version of TRAIL (scTRAIL). We compared three different formats of epidermal growth factor receptor (EGFR)-targeting dimeric scTRAIL fusion proteins (Diabody (Db)-scTRAIL, scFv-IgE heavy chain domain 2 (EHD2)-scTRAIL, scFv-Fc-scTRAIL) as well as two non-targeted dimeric scTRAIL molecules (EHD2-scTRAIL, Fc-scTRAIL) to reveal the influence of targeting and protein format on anti-tumor activity. All EGFR-targeted dimeric scTRAIL molecules showed similar binding properties and comparable cell death induction in vitro, exceeding the activity of the respective non-targeted dimeric format and monomeric scTRAIL. Superior properties were observed for the Fc fusion proteins with respect to production and in vivo half-life. In vivo studies using a Colo205 xenograft model revealed potent anti-tumor activity of all EGFR-targeting formats and Fc-scTRAIL and furthermore highlighted the higher efficacy of fusion proteins comprising an Fc part. Despite enhanced in vitro cell death induction of targeted scTRAIL molecules, however, comparable anti-tumor activities were found for the EGFR-targeting scFv-Fc-scTRAIL and the non-targeting Fc-scTRAIL in vivo.

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CCR5-dependent homing of T regulatory cells to the tumor microenvironment contributes to skin squamous cell carcinoma development

Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Tregs) have a critical role in the modulation of an anti- tumor immune response, and consequently the SCC development. Since the accumulation of Tregs at the tumor site is, in part, due to selective recruitment through CCR5 and CCR5-associated chemokines, we investigated the role of CCR5 in the SCC development. Our findings showed that CCR5-deficient mice (CCR5KO) were efficient in controlling papilloma's incidence when compared with wild-type mice. Analysis of tumor lesions in wild-type (WT) and CCR5KO mice revealed that lack of CCR5 lead to significant reduction in frequency of Treg cells and increased of CD4 T cells into the tumors. Moreover, the adoptive transfer of naturally occurring Tregs CD4+CD25+CCR5+, CD4+CD25-CCR5+ or CD8+CCR5+ conventional T cells to CCR5KO mice resulted in an increased papilloma incidence. Interestingly, adoptive transfer of WT CD4+CD25+CCR5+ cells to CCR5KO mice induced more undifferentiated SCC lesions, characterized by higher infiltration of macrophages and dendritic cells. In the present study, we also demonstrated that Treg migration to the tumor microenvironment is mediated by CCR5, and these cells are promoting tumor growth via inhibition of anti-tumor cells such as cytotoxic CD8+ T cells. Our findings reinforce the therapeutic potential of CCR5 inhibition for cancer treatment, and indicate an attractive approach for SCC treatment.

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Inhibition of the Receptor Tyrosine Kinase AXL Restores Paclitaxel Chemosensitivity in Uterine Serous Cancer

Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL in vitro and in vivo. We used small hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in vitro in the presence or absence of AXL. We also examined the role of the epithelial-mesenchymal transition in AXL-mediated paclitaxel resistance. Finally, we treated USC xenografts with paclitaxel, BGB324, or paclitaxel plus BGB324 and monitored tumor burden. AXL expression was higher in chemoresistant USC patient tumors and cell lines than in chemosensitive tumors and cell lines. Knockdown or inhibition of AXL increased sensitivity of USC cell lines to paclitaxel in vitro and increased cellular accumulation of paclitaxel. AXL promoted chemoresistance even in cells that underwent the epithelial-mesenchymal transition in vitro. Finally, in vivo studies of combination treatment with BGB324 and paclitaxel showed a greater than 51% decrease in tumor volume after 2 weeks of treatment when compared to no treatment or single agent treatments (P<0.001). Our results show that AXL expression mediates chemoresistance independent of EMT and prevents accumulation of paclitaxel. This study supports the continued investigation of AXL as a clinical target, particularly in chemoresistant USC.

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PD-1 status in CD8+ T cells associates with survival and anti-PD-1 therapeutic outcomes in head and neck cancer

Improved understanding of expression of immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency of PD-1+ TIL has been reported in human papillomavirus (HPV)+ HNC patients, despite the role of PD-1 in T cell exhaustion. This discordance led us to hypothesize that the extent of PD-1 expression more accurately defines T cell function and prognostic impact, since PD-1high T cells may be more exhausted than PD-1low T cells and may influence clinical outcome and response to anti-PD-1 immunotherapy. In this study, PD-1 expression was indeed upregulated on HNC patient TIL, and the frequency of these PD-1+ TIL was higher in HPV+ patients (p = 0.006), who nonetheless experienced significantly better clinical outcome. However, PD-1high CD8+ TIL were more frequent in HPV- patients and represented a more dysfunctional subset with compromised IFN-γ secretion. Moreover, HNC patients with higher frequencies of PD-1high CD8+ TIL showed significantly worse disease free survival (DFS) and higher hazard ratio for recurrence (p<0.001), while higher fractions of PD-1low T cells associated with HPV positivity and better outcome. In a murine HPV+ HNC model, anti-PD-1 mAb therapy differentially modulated PD-1high/low populations, and tumor rejection associated with loss of dysfunctional PD-1high CD8+ T cells and a significant increase in PD-1low TIL. Thus, the extent of PD-1 expression on CD8+ TIL provides a potential biomarker for anti-PD-1 based immunotherapy.

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ANGPTL1 interacts with integrin {alpha}1{beta}1 to suppress HCC angiogenesis and metastasis by inhibiting JAK2/STAT3 signaling

Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). Here we report that downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivo tumorigenicity, cell motility and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2 mediated anti-apoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG. Furthermore, ANGPTL1 inhibited angiogenesis by attenuating ERK and AKT signaling and interacted with integrin α1β1 receptor to suppress the downstream FAK/Src-JAK-STAT3 signaling pathway. Taken together, these results suggest ANGPTL1 as a prognostic biomarker and novel therapeutic agent in HCC.

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Structurally novel antiestrogens elicit differential responses from constitutively active mutant estrogen receptors in breast cancer cells and tumors

Many ERα-positive breast cancers develop resistance to endocrine therapy via mutation of estrogen receptors (ER) whose constitutive activation is associated with shorter patient survival. Because there is now a clinical need for new antiestrogens (AE) against these mutant ER, we describe here our development and characterization of three chemically novel AE that effectively suppress proliferation of breast cancer cells and tumors. Our AE are effective against wild type and Y537S and D538G ER, the two most commonly occurring constitutively active ER. The 3 new AE suppressed proliferation and estrogen target gene expression in WT and mutant ER-containing cells and were more effective in D538G than in Y537S cells and tumors. Compared to WT ER, mutants exhibited ~10 to 20-fold lower binding affinity for AE and a reduced ability to be blocked in coactivator interaction, likely contributing to their relative resistance to inhibition by AE. Comparisons between mutant ER-containing MCF7 and T47D cells revealed that AE responses were compound, cell-type and ERα-mutant dependent. These new ligands have favorable pharmacokinetic properties and effectively suppressed growth of WT and mutant ER-expressing tumor xenografts in NOD/SCID-gamma mice after oral or subcutaneous administration; D538G tumors were more potently inhibited by AE than Y537S tumors. These studies highlight the differential responsiveness of the mutant ER to different AE and make clear the value of having a toolkit of AE for treatment of endocrine therapy-resistant tumors driven by different constitutively active ER.

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Anti-Jagged immunotherapy inhibits MDSCs and overcomes tumor-induced tolerance.

Myeloid-derived suppressor cells (MDSCs) are a major obstacle to promising forms of cancer immunotherapy, but tools to broadly limit their immunoregulatory effects remain lacking. In this study, we assessed the therapeutic effect of the humanized anti-Jagged1/2 blocking antibody CTX014 on MDSC-mediated T cell suppression in tumor-bearing mice. CTX014 decreased tumor growth, impacted the accumulation and tolerogenic activity of MDSCs in tumors, and inhibited the expression of immunosuppressive factors arginase I and iNOS. Consequently, anti-Jagged therapy overcame tumor-induced T cell tolerance, increased the infiltration of reactive CD8+ T-cells into tumors, and enhanced the efficacy of T cell-based immunotherapy. Depletion of MDSC-like cells restored tumor growth in mice treated with anti-Jagged, whereas co-injection of MDSC-like cells from anti-Jagged-treated mice with cancer cells delayed tumor growth. Jagged1/2 was induced in MDSCs by tumor-derived factors via NFkB-p65 signaling, and conditional deletion of NFkB-p65 blocked MDSC function. Collectively, our results offer a preclinical proof of concept for the use of anti-Jagged1/2 to reprogram MDSC-mediated T cell suppression in tumors, with implications to broadly improve the efficacy of cancer therapy.

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Optical coherence tomography detects necrotic regions and volumetrically quantifies multicellular tumor spheroids

Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anti-cancer drug development. However, currently available imaging approaches employed in high-throughput screening drug discovery platforms e.g. bright field, phase contrast, and fluorescence microscopies, are unable to resolve 3D structures deep inside (>50 μm) tumor spheroids. In this study, we established a label-free, non-invasive optical coherence tomography (OCT) imaging platform to characterize 3D morphological and physiological information of multicellular tumor spheroids (MCTS) growing from ~250 μm up to ~600 μm in height over 21 days. In particular, tumor spheroids of two cell lines glioblastoma (U-87 MG) and colorectal carcinoma (HCT 116) exhibited distinctive evolutions in their geometric shapes at late growth stages. Volumes of MCTS were accurately quantified using a voxel-based approach without presumptions of their geometries. In contrast, conventional diameter-based volume calculations assuming perfect spherical shape resulted in large quantification errors. Furthermore, we successfully detected necrotic regions within these tumor spheroids based on increased intrinsic optical attenuation, suggesting a promising alternative of label-free viability tests in tumor spheroids. Therefore, OCT can serve as a promising imaging modality to characterize morphological and physiological features of MCTS, showing great potential for high-throughput drug screening.

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Whole-Genome Sequencing Reveals Breast Cancers with Mismatch Repair Deficiency

Mismatch repair (MMR)–deficient cancers have been discovered to be highly responsive to immune therapies such as PD-1 checkpoint blockade, making their definition in patients, where they may be relatively rare, paramount for treatment decisions. In this study, we utilized patterns of mutagenesis known as mutational signatures, which are imprints of the mutagenic processes associated with MMR deficiency, to identify MMR-deficient breast tumors from a whole-genome sequencing dataset comprising a cohort of 640 patients. We identified 11 of 640 tumors as MMR deficient, but only 2 of 11 exhibited germline mutations in MMR genes or Lynch Syndrome. Two additional tumors had a substantially reduced proportion of mutations attributed to MMR deficiency, where the predominant mutational signatures were related to APOBEC enzymatic activity. Overall, 6 of 11 of the MMR-deficient cases in this cohort were confirmed genetically or epigenetically as having abrogation of MMR genes. However, IHC analysis of MMR-related proteins revealed all but one of 10 samples available for testing as MMR deficient. Thus, the mutational signatures more faithfully reported MMR deficiency than sequencing of MMR genes, because they represent a direct pathophysiologic readout of repair pathway abnormalities. As whole-genome sequencing continues to become more affordable, it could be used to expose individually abnormal tumors in tissue types where MMR deficiency has been rarely detected, but also rarely sought. Cancer Res; 77(18); 1–8. ©2017 AACR.

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Tragedy, Perseverance, and Chance — The Story of CAR-T Therapy

In 2010, 5-year-old Emily Whitehead was diagnosed with acute lymphoblastic leukemia (ALL). Though her parents were told that if you had to have a kid with cancer, ALL was the best one to have, Emily's course was hardly typical. After two rounds of chemotherapy, necrotizing fasciitis developed in…

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Tragedy, Perseverance, and Chance — The Story of CAR-T Therapy

Novel inhibitors of lysine (K)-specific Demethylase 4A with anticancer activity

Summary

Lysine (K)-specific demethylase 4A (KDM4A) is a histone demethylase that removes methyl residues from trimethylated or dimethylated histone 3 at lysines 9 and 36. Overexpression of KDM4A is found in various cancer types. To identify KDM4A inhibitors with anti-tumor functions, screening with an in vitro KDM4A enzyme activity assay was carried out. The benzylidenehydrazine analogue LDD2269 was selected, with an IC₅₀ of 6.56 μM of KDM4A enzyme inhibition, and the binding mode was investigated using in silico molecular docking. Demethylation inhibition by LDD2269 was confirmed with a cell-based assay using antibodies against methylated histone at lysines 9 and 36. HCT-116 colon cancer cell line proliferation was suppressed by LDD2269, which also interfered with soft-agar growth and migration of HCT-116 cells. AnnexinV staining and PARP cleavage experiments showed apoptosis induction by LDD2269. Derivatives of LDD2269 were synthesized and the structure–activity relationship was explored. LDD2269 is reported here as a strong inhibitor of KDM4A in in vitro and cell-based systems, with anti-tumor functions.

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Long term outcome after resection of liver metastases from squamous cell carcinoma

Publication date: Available online 13 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Kiyohiko Omichi, Takashi Mizuno, Masayuki Okuno, Ching-Wei D. Tzeng, Claudius Conrad, Yun Shin Chun, Thomas A. Aloia, Jean-Nicolas Vauthey
BackgroundSquamous cell carcinoma (SCC) liver metastases still remains a difficult challenge and the effectiveness of resection for SCC liver metastases is unclear. The aim of this study was to analyze long-term outcomes of surgically treated patients with SCC liver metastases.MethodsThe clinicopathological characteristics, overall survival (OS), and recurrence free survival (RFS) of all patients with SCC liver metastases resected between 1998 and 2015, were analyzed.ResultsAmong 28 patients who met inclusion criteria, there were 19 patients with anal cancer metastases (68%), 2 (7%) with cervix cancer metastases, 2 (7%) with tonsil cancer metastases, 2 (7%) with lung cancer metastases, 2 (7%) with primary unknown cancer metastases and 1 (4%) with vulvar cancer metastases. Four (14%) patients underwent major hepatectomy. There were no liver insufficiency cases or 90-day mortality. Cumulative 3- and 5-year OS rates were 52% and 47%. Cumulative 1- and 3-year RFS rates were 50% and 25%.ConclusionsLong-term outcomes after resection of SCC liver metastases compare favorably with those of colorectal or neuroendocrine liver metastases. Liver resection can be an effective treatment option for SCC liver metastases in appropriately selected patients after systemic therapy.

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The effectiveness of the 8th American Joint Committee on Cancer TNM classification in the prognosis evaluation of gastric cancer patients: a comparative study between the 7th and 8th editions

Publication date: Available online 13 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Jun Lu, Chao-hui Zheng, Long-long Cao, Ping Li, Jian-wei Xie, Jia-bin Wang, Jian-xian Lin, Qi-yue Chen, Mi Lin, Chang-ming Huang
BackgroundThe 8^th edition of the AJCC TNM staging system for gastric cancer was released in 2016 and included major revisions, especially of stage III.Patients and MethodsData from 3,281 patients with GC who underwent R0 resection between December 2006 and November 2014 were reviewed. Of them, 1,579 patients with stage III according to the seventh edition were analyzed and the 7^th and 8^th TNM classifications were compared.ResultsThe most important tumor stages change observed in stage III GC. For stage III patients, the median number of lymph nodes (LNs) resected in stage III patients was 33 (range 5-112), and the optimal cut-off value for the number of LNs resected was 30. Although the 7^th edition classification had higher c-index, linear trend and likelihood ratioχ² scores, and smaller AIC values compared with those for the 8^th edition, which represented the optimum prognostic stratification, however, the differences between 7^th and 8^th edition seems to be not statistically significant, and AIC demonstrates similar trend as well. Further subgroup analysis found that the 8^th staging system generated the marginally better prognostic stratification only when LNs removed≥30.ConclusionThe 8^th TNM classification may provide better accuracy than 7^th edition in predicting the prognosis of stage III GC after R0 resection with LNs harvested≥30. However, further research in an external validation setting is warranted.

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An Audit Comparing The Reporting Of Staging MRI Scans For Rectal Cancer With The London Cancer Alliance (LCA) Guidelines

Publication date: Available online 13 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): M.R.S. Siddiqui, A.P. Shanmuganandan, S. Rasheed, P. Tekkis, G. Brown, A.M. Abulafi
BackgroundThis article focuses on the audit and assessment of clinical practice before and after introduction of MRI reporting guidelines. Standardised proforma based reporting may improve quality of MRI reports. Uptake of the use may be facilitated by endorsement from regional and national cancer organisations.MethodsThis audit was divided into 2 phases. MRI reports issued between April 2014 and June 2014 were included in the first part of our audit. Phase II included MRI reports issued between April 2015 and June 2015.Results14 out of 15 hospitals that report MRI scans in the LCA responded to our audit proposal. The completion rate of key MRI metrics/metrics was better in proforma compared to prose reports both before (98% vs 73%; p<0.05) and after introduction of the guidelines (98% vs 71%; p<0.05). There was an approximate doubling of proforma reporting after the introduction of guidelines and workshop interventions (39% vs 65%; p<0.05). Evaluation of locally advanced cancers (tumours extending to or beyond the circumferential resection margin) for beyond TME surgery was reported in 3% of prose reports vs. 42% in proformas.ConclusionsIncorporation of standardised reporting in official guidelines improved the uptake of proforma based reporting. Proforma based reporting captured more MRI reportable items compared to prose summaries, before and after the implementation of guidelines. MRI reporting of advanced cancers for beyond TME surgery falls short of acceptable standards but is more detailed in proforma based reports. Further work to improve completion especially in beyond TME reporting is required.

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Management of the Central Compartment in Differentiated Thyroid Carcinoma

Publication date: Available online 13 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Ryan P. Goepfert, Gary L. Clayman
Management of differentiated thyroid carcinoma (DTC) is gradually evolving with considerations of de-escalation of treatment and/or active surveillance in a significant proportion of patients on the basis of an improved understanding of the long-term disease and functional outcomes from both surgical and non-surgical approaches. This is fueled by improved risk stratification, which increasingly couples analysis of clinicopathologic prognostic factors as determined through high resolution ultrasound and fine needle aspiration cytology. This paper discusses general recommendations for preoperative decision-making in the management of the central compartment in DTC with particular reference to micropapillary thyroid carcinoma and encapsulated follicular variant papillary thyroid carcinoma. Given the multitude of specific factors that must be considered for each patient, therapeutic decisions should occur in a multidisciplinary setting weighing the risks of treatment morbidity against the risks of disease progression or recurrence. Recurrent/persistent disease merits special attention with regard to pre-operative planning and surgical risk, and should be managed by high-volume thyroid surgeons.

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The role of a new class of long noncoding RNAs transcribed from ultraconserved regions in cancer

Publication date: Available online 13 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Daniela Terracciano, Sara Terreri, Filomena de Nigris, Valerio Costa, George A. Calin, Amelia Cimmino
Ultraconserved regions (UCRs) represent a relatively new class of non-coding genomic sequences highly conserved between human, rat and mouse genomes. These regions can reside within exons of protein-coding genes, despite the vast majority of them localizes within introns or intergenic regions. Several studies have undoubtedly demonstrated that most of these regions are actively transcribed in normal cells/tissues, where they contribute to regulate many cellular processes. Interestingly, these non-coding RNAs exhibit aberrant expression levels in human cancer cells and their expression profiles have been used as prognostic factors in human malignancies, as well as to unambiguously distinguish among distinct cancer types. In this review, we first describe their identification, then we provide some updated information about their genomic localization and classification. More importantly, we discuss about the available literature describing an overview of the mechanisms through which some transcribed UCRs (T-UCR) contribute to cancer progression or to the metastatic spread. To date, the interplay between T-UCRs and microRNAs is the most convincing evidence linking T-UCRs and tumorigenesis. The limitations of these studies and the future challenges to be addressed in order to understand the biological role of T-UCRs are also discussed herein. We envision that future efforts are needed to convincingly include this class of ncRNAs in the growing area of cancer therapeutics.

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PP2A Regulates signaling through hormonal receptors in breast cancer with important therapeutic implications

Publication date: Available online 12 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Ion Cristóbal, Blanca Torrejón, Javier Martínez-Useros, Juan Madoz-Gurpide, Federico Rojo, Jesús García-Foncillas
The functional inhibition of protein phosphatase 2A (PP2A) has emerged in the last years as a common alteration in breast cancer that determines poor outcome and contributes to disease progression and aggressiveness. Furthermore, expression of estrogen receptor (ER) is a high relevant molecular event with key therapeutic implications in breast cancer, and androgen receptor (AR) signaling is involved in the pathogenesis of breast cancer and represents a novel target with crescent importance in this disease. In this review, we summarize the role of the tumor suppressor PP2A in modulating ER and AR signaling in breast cancer, the molecular mechanisms involved, and its biological and therapeutic impact.

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Outcomes after sofosbuvir-containing regimens for hepatitis C virus in patients with decompensated cirrhosis: a real-world study

Abstract

Background

Direct-acting antivirals have been used for decompensated cirrhotic patients with hepatitis C virus (HCV) infection. However, the benefits in Chinese patients with decompensated cirrhosis are unclear.

Methods

Thirty patients with HCV infection and decompensated cirrhosis were administered sofosbuvir-containing regimens at our hospital between April and December 2015. The efficacy and safety of the treatments was determined by sustained virological response at week 12 (SVR 12), change of liver function and adverse events.

Results

The cohort included 13 treatment-experienced and 17 treatment-naïve patients. A total of 27 patients (90%) achieved SVR 12. No baseline characteristics (sex, age, treatment-experience, genotype, viral load, liver function or splenectomy) was association with achievement of SVR 12. Patients achieved SVR 12 had significantly improved liver function by post-treatment week 12 (P < 0.05). Of the 30 patients, six developed anemia, one developed hepatic decompensation, two developed impaired renal function and one developed a severe upper respiratory tract infection during the treatment. There was no death or HCC development during 12 months of follow-up off-therapy. Two patients (7.4%) with SVR 12 experienced new decompensated episodes during the follow-up.

Conclusion

Sofosbuvir-containing regimens are effective in Chinese HCV patients with decompensated cirrhosis, regardless of baseline characteristics, as demonstrated by a high rate of SVR 12, as well as improvement in liver function. Although antiviral therapy is generally well tolerated, a vigilant monitoring of anemia and renal function should be mandatory.

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Liquid dynamic medicine and N-of-1 clinical trials: a change of perspective in oncology research

Abstract

The increasing use of genomics to define the pattern of actionable mutations and to test and validate new therapies for individual cancer patients, and the growing application of liquid biopsy to dynamically track tumor evolution and to adapt molecularly targeted therapy according to the emergence of tumor clonal variants is shaping modern medical oncology., In order to better describe this new therapeutic paradigm we propose the term "Liquid dynamic medicine" in the place of "Personalized or Precision medicine". Clinical validation of the "Liquid dynamic medicine" approach is best captured by N-of-1 trials where each patient acts as tester and control of truly personalized therapies.

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Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls

Abstract

Purpose

The fusion gene BRC–ABL has an important role to the progression of chronic myeloid leukemia (CML) and several signaling pathways have been characterized as responsible for the terminal blastic phase (BP). However, the initial phase, the chronic phase (CP), is long lasting and there is much yet to be understood about the critical role of BRC–ABL in this phase. This study aims to evaluate transcriptional deregulation in CD34+ hematopoietic cells (CD34+ cells) from patients with untreated newly diagnosed CML compared with CD34+HC from healthy controls.

Methods

Gene expression profiling in CML-CD34 cells and CD34 cells from healthy controls were used for this purpose with emphasis on five main pathways important for enhanced proliferation/survival, enhanced self-renewal and block of myeloid differentiation.

Results

We found 835 genes with changed expression levels (fold change ≥ ±2) in CML-CD34 cells compared with CD34 cells. These include genes belonging to PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways. Four of these pathways converge to MYC activation. We also identified five transcripts upregulated in CD34-CML patients named OSBPL9, MEK2, p90RSK, TCF4 and FZD7 that can be potential biomarkers in CD34-CML-CP.

Conclusion

We show several mRNAs up- or downregulated in CD34-CML during the chronic phase.

http://ift.tt/2xZywAb

SNH patients with brain metastases treated with SRS alone had fewer follow-up neuroimaging studies and were at higher risk for neurologic symptoms, hospitalization for brain metastases, and salvage neurosurgery in comparison with PH patients. Clinicians should consider the practice setting and patient access to follow-up care when they are deciding on the optimal strategy for the treatment of brain metastases. Cancer 2017;. © 2017 American Cancer Society.

http://ift.tt/2x1A7aW

Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls

Abstract

Purpose

Methods

Results

Conclusion

We show several mRNAs up- or downregulated in CD34-CML during the chronic phase.

http://ift.tt/2xZywAb

Sauna bathing reduces the risk of respiratory diseases: a long-term prospective cohort study

Abstract

Sauna bathing has been linked with numerous health benefits. Sauna bathing may reduce the risk of respiratory diseases; however, no prospective evidence exists to support this hypothesis. We aimed to assess the association of frequency of sauna bathing with risk of respiratory diseases (defined as chronic obstructive pulmonary disease, asthma, or pneumonia). Baseline sauna bathing habits were assessed in a prospective cohort of 1935 Caucasian men aged 42–61 years. During a median follow-up of 25.6 years, 379 hospital diagnosed incident cases of respiratory diseases were recorded. In adjustment for several major risk factors for respiratory conditions and other potential confounders, the hazard ratios (HRs) 95% confidence intervals (CIs) of respiratory diseases were 0.73 (0.58–0.92) and 0.59 (0.37–0.94) for participants who had 2–3 and ≥4 sauna sessions per week respectively compared with participants who had ≤1 sauna session per week. The multivariate adjusted HR (95% CI) for pneumonia was 0.72 (0.57–0.90) and 0.63 (0.39–1.00) for participants who had 2–3 and ≥4 sauna sessions per week respectively. Frequent sauna baths may be associated with a reduced risk of acute and chronic respiratory conditions in a middle-aged male Caucasian population.

http://ift.tt/2joBAmN

FOXP3 Is a HCC suppressor gene and Acts through regulating the TGF-β/Smad2/3 signaling pathway

Abstract

Background

FOXP3 has been discovered to be expressed in tumor cells and participate in the regulation of tumor behavior. Herein, we investigated the clinical relevance and biological significance of FOXP3 expression in human hepatocellular carcinoma (HCC).

Methods

Expression profile of FOXP3 was analyzed using real-time RT-PCR, western blotting and immunofluorescence on HCC cell lines, and immunostaing of a tissue microarray containing of 240 primary HCC samples. The potential regulatory roles of FOXP3 were dissected by an integrated approach, combining biochemical assays, analysis of patient survival, genetic manipulation of HCC cell lines, mouse xenograft tumor models and chromatin immunoprecipitation (ChIP) sequencing.

Results

FOXP3 was constitutively expressed in HCC cells with the existence of splice variants (especially exon 3 and 4 deleted, Δ3,4-FOXP3). High expression of FOXP3 significantly correlated with low serum α-fetoprotein (AFP) level, absence of vascular invasion and early TNM stage. Survival analyses revealed that increased FOXP3 expression was significantly associated with better survival and reduced recurrence, and served as an independent prognosticator for HCC patients. Furthermore, FOXP3 could potently suppress the proliferation and invasion of HCC cells in vitro and reduce tumor growth in vivo. However, Δ3,4-FOXP3 showed a significant reduction in the tumor-inhibiting effect. The inhibition of FOXP3 on HCC aggressiveness was acted probably by enhancing the TGF-β/Smad2/3 signaling pathway.

Conclusion

Our findings suggest that FOXP3 suppresses tumor progression in HCC via TGF-β/Smad2/3 signaling pathway, highlighting the role of FOXP3 as a prognostic factor and novel target for an optimal therapy against this fatal malignancy.

http://ift.tt/2fjeLMM

Can you un-ring the bell? A qualitative study of how affect influences cancer screening decisions

Abstract

Background

The belief that early detection is the best protection against cancer underlies cancer screening. Emerging research now suggests harms associated with early detection may sometimes outweigh the benefits. Governments, cancer agencies, and organizations that publish screening guidelines have found it is difficult to "un-ring the bell" on the message that "early detection is your best protection" because of its widespread communication and enduring resonance. This study explores affective factors—and their interplay with relevant analytical factors—in public/laypersons' decision making about cancer screening.

Methods

A total of 93 people (47 men, 46 women) attended focus groups about, respectively, prostate cancer screening and breast cancer screening in two Canadian cities.

Results

Affective factors were a major influence on many focus group participants' decision making about cancer screening, including fear of cancer and a generalized enthusiasm for prevention/screening, and they were often inspired by anecdotes about the cancer experiences of family and friends. Affect also existed alongside more analytical factors including assessments of reduced risk in the management of any cancer diagnosis if caught early, and, for men, the belief that an unreliable test is "better than nothing," and that men deserve prostate cancer screening because women have breast and cervical cancer screening. Affective factors were particularly noticeable in the sub-groups most supportive of screening and the "early detection" message: older women who felt that mammogram screening should begin at age 40 rather than 50, and older men who felt that prostate cancer screening should be expanded beyond its current unorganized, opportunistic usage. In contrast, younger participants displayed less affective attachments to "early detection" messages and had greater concerns about harms of screening and were more receptive to nuanced messages informed by evidence.

Conclusion

Policymakers attempting to communicate more nuanced versions of the "early detection" message need to understand the role of affect alongside other judgments brought into laypersons' decision making processes and anticipate how affective responses to their messages will be shaped, transformed, and potentially subverted by external forces beyond their control. Particularly overt external factors are campaigns by cancer advocacy organizations actively promoting breast and prostate cancer awareness and screening to younger women and men using affectively-charged messages.

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Time for crowd knowledge-based approach in SBRT planning

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Ultrawide field imaging and sonography of a radial buckle

Description

A 78-year-old male presented with blurring of vision in right eye (RE) since 2 months. He was diagnosed to have retinal detachment in RE 27 years ago, which had been successfully repaired with scleral buckling surgery. Retinal holes had been treated with laser prophylaxis in left eye (LE). On examination, visual acuity was 6/24 in RE and 6/9 in LE. Both eyes had posterior subcapsular cataract (RE>LE). The retina was attached in RE, while features of high myopia, like fundus tessellation and peripapillary crescent, were evident. Indent of a radial explant was noticeable in the inferior nasal quadrant along with indent of an encirclage band (figure 1). Lattice degeneration and adequately lasered retinal lesions were seen in both eyes. The posteriorly placed radial explant was noted as a raised and hyperechoic structure with corresponding acoustic shadow on ultrasound B scan of RE (figure 2)....

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Cranial fasciitis of childhood (CFC): an unusual clinical case of a rare disease.

Cranial fasciitis of childhood (CFC) is a very uncommon tumour of the scalp, which is almost exclusively observed in the first years of life. It is a benign proliferation of fibroblasts, but its rapid growth rate may resemble a malignant disease. This disease may be suspected from clinical and radiological features, but a definitive diagnosis may be achieved only by pathological examination. We report a case whose onset was in late childhood and whose clinical and radiological characteristics were atypical.

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Proximal avulsion rupture of the flexor digitorum longus tendon associated with a medial malleolus ankle fracture

Description

A 37-year-old man presented to the emergency department with right lower limb pain after being hit by an excavator. His right ankle was swollen, but no open wounds were observed. Radiography and CT of the right ankle revealed a medial malleolus ankle fracture (figure 1A,B).

Figure 1

(A) Radiograph revealing a medial malleolus ankle fracture. (B) CT scan revealing a medial malleolus ankle fracture.

During his treatment with osteosynthesis, a proximal avulsion rupture of the flexor digitorum longus (FDL) tendon from the musculotendinous attachment was discovered (figure 2). The flexor hallucis longus (FHL) tendon and posterior tibial neurovascular bundle were intact. The ruptured FDL tendon was interlaced through the FHL tendon and immobilised in a below-knee cast for 6 weeks. He showed a good functional outcome and had returned to work at the 5-month follow-up.

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Lactobacillus: the not so friendly bacteria

We present a 65-year-old diabetic patient with a complex liver abscess and bacteraemia from Lactobacillus paracasei. The abscess resulted in a prolonged hospital stay due to ongoing sepsis despite ultrasound-guided drainage and broad-spectrum antibiotics. Furthermore, the patient developed several secondary complications including a right-sided pleural effusion, an inferior vena cava thrombus and septic lung emboli. The abscess was eventually managed successfully with a prolonged course of antibiotics and multiple ultrasound-guided drainage procedures.

To our knowledge, this is the first reported case of probiotic consumption, confirmed by strain identification, as the likely source of a liver abscess. Probiotic products have been widely used for many years and are advocated to the general public for their health benefits with no warning of side effects. Lactobacilli are one group of bacteria commonly used in these products. Although rare, complications have been reported. Susceptible patients, such as those who are immunocompromised, should be advised against excessive consumption.

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Fine-needle aspiration of lipoblastoma: Cytological, molecular, and clinical features

BACKGROUND

Lipoblastomas are rare, benign adipocytic tumors that present mostly during infancy. In about 70% of cases, these tumors carry abnormalities in chromosome 8, mainly leading to rearrangements of the PLAG1 gene.

METHODS

We report a series of histologically proven lipoblastomas with previous fine-needle aspiration (FNA) cytology from 9 patients (n = 10 samples) and describe their clinical, cytological, and molecular features.

RESULTS

Our cohort included 5 boys and 4 girls (median age, 2.5 years [range, 10 months to 13 years]) who presented with soft tissue masses in the thorax (n = 3), abdomen (n = 2), axilla (n = 2), and thigh (n = 2). In 1 patient, the FNA diagnosis was inconclusive due to hypocellularity, and in another patient a diagnosis of benign lipomatous tumor was made. In the remaining 8 samples (one of which confirmed relapse), a correct preoperative FNA diagnosis was rendered. Smears were hypo- to moderately cellular and contained fragments of mature adipose tissue with thin branching vessels admixed with some lipoblasts in a myxoid matrix. Spindle cells and naked oval nuclei with no atypia were observed in the background. Of the 4 patients tested for PLAG1 rearrangement using FISH probes, 3 harbored this alteration (1 was made on a FNA smear and 1 was made in a tumor imprint). All the patients are alive and well, except for 1 patient with a retroperitoneal tumor who, after an initial incomplete excision, died of local disease progression.

CONCLUSION

FNA, especially if used together with molecular biology techniques (eg, PLAG1 FISH analysis), is a reliable and accurate diagnostic tool. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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A modified reporting approach for thyroid FNA in the NIFTP era: A 1-year institutional experience

BACKGROUND

The reclassification of noninvasive follicular variant of papillary thyroid carcinoma as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has created diagnostic and management issues for thyroid fine-needle aspiration (FNA). In response to these challenges, the authors' laboratory adopted a NIFTP policy including 1) stringent criteria (requiring pseudo-inclusions, papillae, and/or psammoma bodies) for a malignant diagnosis of papillary carcinoma to limit false-positive results due to NIFTP and 2) the use of explanatory notes in cases with cytomorphologic features suggestive of possible NIFTP to encourage lobectomy over thyroidectomy. This study examined the effects of this policy on FNA classification and subsequent surgical management.

METHODS

All thyroid FNAs performed at Brigham and Women's Hospital (n = 1300) during a 1-year period were evaluated for changes in the use of diagnostic categories, explanatory NIFTP notes, and surgical follow-up in comparison with historical controls.

RESULTS

The use of specific Bethesda categories did not significantly change. Only a single case of NIFTP was mistakenly classified as malignant. NIFTP was seldom suspected prospectively (17 of 1300; 1.3%); when NIFTP was suspected, cases were reported as suspicious for a follicular neoplasm/follicular neoplasm (n = 10) or suspicious for malignancy (SUS; n = 7). Five of the 7 SUS cases (71%) underwent partial thyroidectomy, compared to 19% of those classified as SUS without an explanatory NIFTP note (P < .02).

CONCLUSIONS

Thyroid FNA reporting modifications due to NIFTP affect only a small subset of specimens. When NIFTP is suspected, an explanatory note promotes limited surgical excision. More stringent criteria for malignancy affect few cases while potentially limiting false-positive diagnosis due to NIFTP. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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Genetic susceptibility in childhood acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and a leading cause of death due to disease in children. The genetic basis of ALL susceptibility has been supported by its association with certain congenital disorders and, more recently, by several genome-wide association studies (GWAS). These GWAS identified common variants in ARID5B, IKZF1, CEBPE, CDKN2A, PIP4K2A, LHPP and ELK3 influencing ALL risk. However, the risk variants of these SNPs were not validated in all populations, suggesting that some of the loci could be population specific. On the other hand, the currently identified risk SNPs in these genes only account for 19% of the additive heritable risk. This estimation indicates that additional susceptibility variants could be discovered. In this review, we will provide an overview of the most important findings carried out in genetic susceptibility of childhood ALL in all GWAS and subsequent studies and we will also point to future directions that could be explored in the near future.

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Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression

Abstract

The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect. The minimal effective dose was 10 μg each. The effect was dependent on CD8 T-cells. Intratumoral administration resulted in superior local and distant tumor control compared to systemic routes, supporting the in situ vaccine concept. In a single tumor A20 model, injection close to the tDLN resulted in similar efficacy as intratumoral and significantly better than targeting a non-tDLN, supporting the role of the tDLN as a viable immunotherapy target in addition to the tumor itself. Distribution studies confirmed expected concentration of antibodies in tumor and tDLN, in keeping with the anti-tumor results. Overall intratumoral or peri-tDLN administration of the novel combination of anti-CTLA4, anti-CD137, and anti-OX40, all agents in the clinic or clinical trials, demonstrates potent systemic anti-tumor effects. This immunotherapeutic combination is promising for future clinical development via both these safe and highly efficacious routes of administration.

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Downregulation of DEPTOR inhibits the proliferation, migration, and survival of osteosarcoma through PI3K/Akt/mTOR pathway

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Marketed drugs used for the management of hypercholesterolemia as anticancer armament

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Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression

Abstract

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International society for gastrointestinal hereditary tumours—InSiGHT

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Liposomal prednisolone phosphate potentiates the antitumor activity of liposomal 5-fluorouracil in C26 murine colon carcinoma in vivo

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Table of Content Volume 56, Number 11, November 2017

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Cancers, Vol. 9, Pages 124: MicroRNAs as Biomarkers in Colorectal Cancer

Cancers, Vol. 9, Pages 124: MicroRNAs as Biomarkers in Colorectal Cancer

Cancers doi: 10.3390/cancers9090124

Authors: Takaaki Masuda Naoki Hayashi Yosuke Kuroda Shuhei Ito Hidetoshi Eguchi Koshi Mimori

MicroRNAs (miRs) are small RNAs that repress mRNA translation, resulting in the degradation of mRNAs and regulation of the expression levels of various genes. Recent studies have shown that aberrant miR expression has a functional role in the initiation and progression of various malignancies, including colorectal cancer (CRC), which is one of the leading causes of cancer-related death worldwide. miRs have also been shown to have applications as diagnostic, prognostic, and predictive biomarkers because of their high tissue specificity, stability, and altered expression in tumor development. In this report, we examined the role of miRs as biomarkers in CRC through a review of meta-analyses and large-scale analyses having strong statistical confidence in the study outcomes. We also discuss current issues in the clinical application of these miRs.

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Paediatric anaesthesia for low-resource settings

1H022A033J02

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Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer

Suyang Guo, Bo Yang, Hongli Liu, Yuzhi Li, Shengze Li, Ling Ma, Jian Liu, Wei Guo

Journal of Cancer Research and Therapeutics 2017 13(4):689-692

Objective: The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Methods: Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. Results: The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21–33.20) mg/mL, 4.78 (0.22–175.20) mg/mL, and 11.56 (2.028–123.66) IU/mL for NRG and 5.64 (0.50–136.80) mg/mL, 22.41 (0.56–588.90) mg/mL, and 25.41 (3.658–3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= –0.13, P = 0.56) was found in the RG patients. Conclusion: Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.

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Expert consensus workshop report: Guideline for three-dimensional printing template-assisted computed tomography-guided 125I seeds interstitial implantation brachytherapy

Junjie Wang, Fujun Zhang, Jinhe Guo, Shude Chai, Guangjun Zheng, Kaixian Zhang, Anyan Liao, Ping Jiang, Yuliang Jiang, Zhe Ji

Journal of Cancer Research and Therapeutics 2017 13(4):607-612

Radioactive 125I seeds (RIS) interstitial implantation brachytherapy has been a first-line treatment for early-stage cancer of the prostate gland. However, its poor accuracy and homogeneity has limited its indication and hampered its popularization for a long time. Intriguingly, scholars based in China introduced computed tomography (CT)-guided technology to improve the accuracy and homogeneity of RIS implantation and broadened the indications. Then, they creatively designed and introduced three-dimensional printing coplanar template (3D-PCT) and 3D printing noncoplanar template (3D-PNCT) into the practice of RIS implantation. Use of such templates makes RIS implantation more precise and efficacious and aids preoperative planning, real-time dose optimization, and postoperative planning. However, studies on the standard workflow for 3D-PT-assisted CT-guided RIS implantation have not been published. Therefore, the China Northern Radioactive Seeds Brachytherapy Group organized multidisciplinary experts to formulate the guideline for this emerging treatment modality. This guideline aims at standardizing 3D-PT-assisted CT-guided RIS implantation procedures and criteria for selecting treatment candidates and assessing outcomes and for preventing and managing postoperative complications.

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Human epidermal growth factor receptor 2 amplification detection by droplet digital polymerase chain reaction in formalin-fixed paraffin-embedded breast and gastric cancer samples

Xingwen Wang, Yunyan Wu, Xueling Song, Chengtao Sun, Changshun Wu, Hong Feng

Journal of Cancer Research and Therapeutics 2017 13(4):730-734

Objective: Human epidermal growth factor receptor 2 (HER2) is an important biomarker for the precise individualized treatment including trastuzumab of HER2-positive breast and gastric cancer. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the routine analyses for formalin-fixed paraffin-embedded (FFPE) samples. However, IHC is variable and depends on the evaluator, and FISH is a labor intensive and expensive method. We evaluated the feasibility of droplet digital polymerase chain reaction (ddPCR) as a precise and quantitative method for HER2 amplification test. Materials and Methods: We used ddPCR to confirm HER2 amplification status in 24 breast cancer and 29 gastric cancer samples to validate the HER2 cutoff value in ddPCR. After setting cutoff value, all the above-mentioned samples were tested by IHC. Afterward, another 51 equivocal IHC 2+ gastric cancer samples were further determined by FISH and ddPCR, respectively, and the concordance between ddPCR and FISH was calculated. Results: We set the HER2 cutoff value at 1.8. The concordance rate of HER2 status between ddPCR and IHC was 94.4% (17 out of 18) in 24 breast cancer samples. In 29 gastric cancer specimens, the concordance rate of HER2 amplification between ddPCR and IHC was 100% (22 out of 22). At last, compared with FISH determined HER2 status, ddPCR HER2 scores correctly classified 44 of 51 cases with 86.3% concordance in 51 equivocal IHC 2+ gastric cancer samples. Conclusions: ddPCR was able to identify HER2 amplification status in breast and gastric cancers with precise correlation with IHC and FISH results. This method might become a standard method for testing FFPE samples. However, the technology requires further research.

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The clinical application of HPV E6/E7 mRNA testing in triaging women with atypical squamous cells of undetermined significance or low-grade squamous intra-epithelial lesion Pap smear: A meta-analysis

Li Yang, Yuanhang Zhu, Yang Bai, Xiaoan Zhang, Chenchen Ren

Journal of Cancer Research and Therapeutics 2017 13(4):613-620

Objective: The aim is to evaluate the clinical application value and correlation with cervical lesions' progression of human papillomavirus (HPV) E6/E7 mRNA test in women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intraepithelial lesions (LSILs/mild dyskaryosis) cytological abnormalities. Methods: A meta-analysis was conduct by searching China National Knowledge Infrastructure (1979–2016), Wanfang Date (1998–2016), VIP (1989–2016), PubMed (1950–2016), Web of Science (1950–2016) and Elsevier Science Direct (1998–2016), for studies on effect of HPV E6/E7 mRNA detection in women with ASCUS/LSIL/dyskaryosis. Study selection and appraisal were conducted independently by three authors, according to inclusive and exclusive criteria. Then, a meta-analysis was performed using the RevMan4.2 software. The subgroups analysis was conducted according to women's initial HPV DNA test results. Results: Six articles with a total of 1024 subjects were included in the study. It was concluded that a positive HPV E6/E7 mRNA tested result have a higher risk of progressing to CIN2+ in future 2 years than a negative result. The pooled relative risk (RR) is 3.08, (95% confidence interval [CI] = 1.57–6.07, P < 0.05). The same situation was also observed in the subgroup of HPV DNA tested positive group and HPV DNA tested unlimited group. The pooled RR value of the two subgroups was, respectively, 1.98, (95% CI = 1.19–1.19, P < 0.05) and 7.58, (95% CI = 3.64–3.64, P < 0.05). Conclusion: A positive HPV E6/E7 mRNA testing result suggested the women with ASCUS, or LSIL Pap smear was in a truly dangerous position, which is an adverse prognostic factor. It suggested that cervical lesions stay in a progressing status and these women should be referred for colposcopy and strengthen follow-up promptly. Whereas, women with a negative HPV E6/E7 mRNA testing result can increase follow-up interval, by comprehensively considering their situation, thus, avoiding unnecessary colposcopy and reducing the rate of colposcopy and biopsy.

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Expression and significance of Twist, estrogen receptor, and E-cadherin in human breast cancer cells and tissues

Ruizhi Tan, Li Wang, Jie Song, Jianchun Li, Tao He

Journal of Cancer Research and Therapeutics 2017 13(4):707-714

Objectives: Breast cancer is one of the most common malignancies in women, and the tumor cells' invasion and metastasis is the main cause of death. Recent reports showed that Twist, a transcription factor, plays multiple roles in breast cancer initiation, progress, and metastasis. However, the underlying mechanisms of Twist in tumor invasion and metastasis of breast cancer still remain unclear. Here, we examined the correlation between Twist, E-cadherin, and estrogen receptor (ER) in promoting invasion and metastasis in breast cancer cells and tissues. Materials and Methods: The mRNA and protein expression of Twist, E-cadherin, and ER in breast cancer cell lines (MCF-7, MDA-MB-435, MDA-MB-231, and ZR-75-30) and human invasive ductal carcinoma (IDC) tissues from 32 patients were detected by reverse transcription-polymerase chain reaction and immunohistochemistry (IHC), respectively. Results: Expression of Twist in cells with high ability of invasion and metastasis was higher than that in MCF-7 cell line which has low ability of invasion and metastasis, while the expression of ER and E-cadherin was much more higher in MCF-7 cell line than in other cells. IHC showed that the expression rate of Twist in IDC tissues and adjacent tissues was 84.38% and 31.25% and the positive expression of E-cadherin and ER was 21.88% and 40.63% in IDC tissues and 81.25% and 84.38% in adjacent tissues, respectively. Interestingly, overexpression of Twist promoted cellular invasion and metastasis and decreased the expression of E-cadherin, ER, AKT, and p-AKT in HEK-293 cells. Conclusions: Taken together, these findings demonstrated that Twist was upregulated in high invasion and metastasis cell lines as well as IDC tissues companioned with downregulated expression of E-cadherin and ER, which provides important clues for the deeper study of breast cancer.

http://ift.tt/2w7lkMW

Role of collagen triple helix repeat containing-1 in tumor and inflammatory diseases

Qian Wu, Qingrui Yang, Hongsheng Sun

Journal of Cancer Research and Therapeutics 2017 13(4):621-624

Initially, collagen triple helix repeat containing-1 (CTHRC1) is expressed mainly in adventitial fibroblasts and neointimal smooth muscle cells of balloon-injured vessels, and increases cell migration, promotes tissue repair in response to injury. A variety of studies demonstrated that over-expression of CTHRC1 in solid tumors results in enhancement of migration and invasion of tumor cells, and is associated with decreased overall survival and disease-free survival. CTHRC1 expression is elevated in hepatitis B virus-infected patients and highly correlated with hepatocellular carcinoma progression as well. Furthermore, CTHRC1 plays a pivotal role in a great many fields, including increases bone mass, prevents myelination, reverses collagen synthesis in keloid fibroblasts, and increases fibroblast-like synoviocytes migration speed and abundant production of arthritic pannus in rheumatoid arthritis. Therefore, it will provide new insight into the pathogenesis of tumor and autoimmune diseases, and will shed new light on the therapy of related clinical diseases.

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MicroRNA-30c inhibits metastasis of ovarian cancer by targeting metastasis-associated gene 1

Xia Wang, Li-Wei Qiu, Chen Peng, Shu-Ping Zhong, Lin Ye, Di Wang

Journal of Cancer Research and Therapeutics 2017 13(4):676-682

Background: It is important to find reliable molecular markers or biological targets that associate with ovarian cancer (OC) metastasis for diagnosis and treatment. In this study, researchers investigated the regulated chain of microRNA-30c (miR-30c) and metastasis-associated gene 1 (MTA1) in OC tissues and cells. Materials and Methods: Expression of miR-30c and MTA1 was detected with quantitative real-time polymerase chain reaction and immunohistochemistry in 33 OC and matched adjacent tissues. MiR-30c mimics were synthetized and transfected into SKOV3 cells to target MTA1. The wound healing and transwell assays were detected to observe migration and invasion of transfected OC cells. Results: Compared with matching normal ovarian tissues, the MTA1 expression was upregulated and localized in the cytoplasm, and the expression of miR-30c was significantly reduced. The expression intensity of MTA1 was correlated with the Federation of Gynecology and Obstetrics stage, tumor grade, and metastasis of OC. Transfecting miR-30c mimics could significantly reduce the expression of MTA1 in SKOV3 cells and obviously inhibit the migration and invasion of SKOV3 cells. Conclusion: MiR-30c and MTA1 abnormally expressed in OC, which may be related to metastasis of OC. In MiR-30c as a tumor suppressor gene, its expression in OC could lead to reduced expression of MTA1, which may be one of the mechanisms of metastasis of OC cells.

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Efficacy comparison of radiofrequency ablation and hepatic resection for hepatocellular carcinoma: A meta-analysis

E Changyong, Dan Wang, Yang Yu, Hongyu Liu, Hui Ren, Tao Jiang

Journal of Cancer Research and Therapeutics 2017 13(4):625-630

Objectives: The objective of this study is to compare the therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection (HR) for the treatment of hepatocellular carcinoma (HCC). Materials and Methods: A literature search was performed for comparative studies reporting outcomes of both RFA and HR for HCC. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results: A total of 4812 patients with HCC were included, with 2419 in the RFA group and 2393 in the HR group. The 3- and 5-year overall survival rates in the HR group were significantly higher than those in the RFA group (OR: 0.68, 95% CI: 0.58–0.79, P < 0.00001; OR: 0.57, 95% CI: 0.50–0.65, P < 0.00001, respectively). 1-, 3-, 5-year disease-free survival and correspond recurrence-free survival rates were all better in HR group. Conclusion: RFA gets promising clinical outcomes for HCC treatments but is not yet comparable to surgery. HR is still the first-line treatment for HCC.

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k-RAS mutation and resistance to epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with nonsmall cell lung cancer

Bin Zhou, Congrong Tang, Jie Li

Journal of Cancer Research and Therapeutics 2017 13(4):699-701

Objective: The aim of this study was to evaluate the relationship between k-RAS gene mutation and the resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in patients with nonsmall-cell lung cancer (NSCLC). Methods: Forty-five pathologies confirmed NSCLC patients who received EGFR-TKI (Gefitinib) treatment were retrospectively included in this study. The mutation of codon 12 and 13, located in exon1 and exon 2 of k-RAS gene were examined by polymerase chain reaction (PCR) and DAN sequencing in tumor samples of the included 45 NSCLC patients. The correlation between Gefitinib treatment response and k-RAS mutation status was analyzed in tumor samples of the 45 NSCLC patients. Results: Eight tumor samples of the 45 NSCLC patients were found to be mutated in coden 12 or 13, with an mutation rate of 17.8% (8/45); the objective response rate (ORR) was 29.7%(11/37) with 1 cases of complete response (CR) and 10 cases of partial response in k-RAS mutation negative patients. Furthermore, the ORR was 0.0% in k-RAS mutation positive patients with none CR. The ORR between k-RAS mutation and nonmutation patients were significant different (P < 0.05). Conclusion: k-RAS gene mutation status was associated with the response of Gefitinib treatment in patients with NSCLC.

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Transarterial embolization with N-butyl 2-cyanoacrylate for the treatment of arterioportal shunts in patients with hepatocellular carcinoma

Feng Duan, Yanhua Bai, Li Cui, Xiaohui Li, Jieyu Yan, Haiyan Zhu

Journal of Cancer Research and Therapeutics 2017 13(4):631-635

Aims: The aim of this study is to evaluate efficacy and safety of transarterial chemoembolization (TACE) with N-butyl 2-cyanoacrylate (NBCA) for the treatment of hepatocellular carcinoma (HCC) with arterioportal shunts (APS). Subjects and Methods: From January 2008 to June 2014, 36 cases of HCC with APS were treated by TACE with NBCA. NBCA-lipiodol mixture was superselective delivered before routine TACE in HCC patients with APS. Recanalization of shunt, objective response, clinical adverse events, and survival rates was retrospectively studied. Results: All interventional procedures were successful without any procedure relevant complications. The immediate APS improvement rate was 83.3% (30/36), and the APS improvement rate at first-time follow-up was 66.6% (20/30). Radiologically confirmed complete response (CR), partial response, stable disease, and progressive disease at 1 month after first chemoembolization were observed in 1 (2.7%), 19 (52.8%), 6 (16.7%), and 10 (27.8%) patients, respectively. Survival rates were 91.7% at 6 months, 47.2% at 1 year, and 13.9% at 2 years. The median survival time was 11 months. No severe adverse effects were noted. Conclusions: The preliminary experience indicates TACE with NBCA can be safely performed and may improve prognosis of HCC with arterioportal shunt.

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Supplemental conventional transarterial embolization/chemoembolization therapy via extrahepatic arteries for hepatocellular carcinoma

Yuanqan Huang, Zhongzhi Jia, Jianfei Tu, Tao Shen, Feng Tian, Guomin Jiang

Journal of Cancer Research and Therapeutics 2017 13(4):720-724

Purpose: To assess the value of conventional transarterial embolization/chemoembolization (cTAE/TACE) therapy via extrahepatic arteries for patients with unresectable hepatocellular carcinoma (HCC). Methods: Patients with unresectable HCC who underwent cTAE/TACE therapy via extrahepatic arteries between May 2008 and July 2016 across 4 medical centers were identified. The technical success, serum alpha-fetoprotein (AFP) levels changes, tumor response, disease control rate, survival rate, and major complication were analyzed. Results: A total of 185 patients (167 male and 18 female) were included in this study. A total of 401 procedures were performed of the 185 patients, with 2.2 ± 0.4 procedures for each patient. A total of 197 extrahepatic arteries were identified, including inferior phrenic artery (n = 80), omental artery (n = 39), gastric artery (n = 22), right renal capsular artery (n = 21), adrenal artery (n = 13), cystic artery (n = 11), and right internal mammary artery (n = 11). The technical success rate was 96.8% (179/185). The serum AFP levels were significantly reduced at 1 month after treatment in 71 patients whose AFP ≥400 ng/mL preprocedure (P < 0.01). The disease control rate was 93% (172/185) at 3 months after cTAE/TACE, with partial response, stable disease, or progressive disease of 115, 57, and 13 patients, respectively. The cumulative survival rate from the time of cTAE/TACE via extrahepatic arteries was 100% at 6 months. There were no embolization-related major complications. Conclusion: cTAE/TACE therapy via the extrahepatic arteries can reduce the incidence of presence of residual HCC, and improve the therapeutic efficacy of cTAE/TACE.

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Bronchial artery chemoembolization combined with radioactive iodine-125 seed implantation in the treatment of advanced nonsmall cell lung cancer

Yaoyong Chen, Yuwei Li, Yuming Jia, Kaijian Lei, Xinfeng Zhang, Yueyong Cao, Jun Zhu

Journal of Cancer Research and Therapeutics 2017 13(4):636-641

Objective: The aim of this study was to investigate the short-term efficacy and safety of bronchial artery chemoembolization (BACE) combined with radioactive iodine-125 seed implantation in the treatment of nonsmall cell lung cancer (NSCLC). Materials and Methods: Sixty-two Stage III–IV NSCLC patients were divided into Groups A and B. Thirty cases were treated with BACE combined with radioactive iodine-125 seed implantation in the Group A and 32 cases were treated with BACE alone in the Group B until disease progression. Efficacy, incidence rate of adverse drug reactions, and survival rate were compared between the two groups. Results: The local control rates and effective rates of Groups A and B were 90% and 59.3% and 74% and 40.6%, respectively, with P < 0.05 for each. The progression-free survival of the study group and the control group was 12.6 and 8.2 months, respectively; the median survival time of the Groups A and B was 644 and 544 days, and the difference was statistically significant (P = 0.034). Conclusion: BACE combined with radioactive iodine-125 seed implantation was safe and effective in the treatment of advanced NSCLC, with an efficacy superior to that of single BACE.

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Expert consensus workshop report: Guideline for three-dimensional-printing template-assisted computed tomography-guided 125I seeds interstitial implantation brachytherapy

Shiro Saito, Xin Ye

Journal of Cancer Research and Therapeutics 2017 13(4):605-606

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A retrospective analysis of the efficacy of microparticle-mediated chemoembolization in liver metastases arising from gastrointestinal tumors

Chuang Li, Ying Liu, Jun Zhou, Yue-Wei Zhang

Journal of Cancer Research and Therapeutics 2017 13(4):642-646

Purpose: We evaluated the clinical efficacy of gelatin sponge microparticle (GSM) -mediated chemoembolization for the treatment of patients with liver metastases following surgery for gastrointestinal tumors. Materials and Methods: In a retrospective analysis of 37 patients who were treated at our hospital with GSM-mediated chemoembolization for liver metastases over 13 years, we evaluated outcomes using a modified response evaluation criteria in solid tumors system and also assessed liver function and adverse effects. All patients had previously undergone surgery for gastrointestinal tumors. Results: Treatment produced various degrees of necrosis and shrinkage of lesions among our patients. Two patients achieved a complete response (CR), 27 showed a partial response (PR), five had stable disease, and three had progressive disease. The overall response rate (CR + PR) was 78%, and no severe adverse effects were observed. Conclusion: GSM-mediated chemoembolization showed good clinical efficacy in the treatment of liver metastases after gastrointestinal tumor surgery. However, larger cohort and clinical controlled studies are warranted.

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Repeated percutaneous microwave ablation for local recurrence of inoperable Stage I nonsmall cell lung cancer

Xia Yang, Xin Ye, Guanghui Huang, Xiaoying Han, Jiao Wang, Wenhong Li, Zhigang Wei, Min Meng

Journal of Cancer Research and Therapeutics 2017 13(4):683-688

Background: The safety and effectiveness of repeated computed tomography-guided percutaneous microwave ablation (MWA) in the management of local recurrence (LR) in patients with medically inoperable Stage I nonsmall cell lung cancer (NSCLC) were retrospectively evaluated. Materials and Methods: From February 2008 to August 2014, 104 patients with medically inoperable Stage I NSCLC received MWA. Patients with LR were given repeat MWA. The clinical outcomes and complications of repeat MWA for LR were evaluated. Results: At a median follow-up of 47 months, LR occurred in 24/104 (23.1%) patients within 12 ± 8 months after MWA. LR rates were higher in tumors >3.5 cm than that of tumors ≤3.5 cm (35.7% vs. 18.4%). Local control of the repeat MWA was achieved in 21 of 24 (87.5%) patients. Overall survival (OS) and progress-free survival (PFS) for patients without LR were similar to that of with LR and receiving repeat MWA (OS: 48 m vs. 41.5 m; PFS: 42 m vs. 32 m). The OS rates were 100%, 74.6%, 60.6%, and 27% for patients without LR at 1, 2, 3, and 5 years, and they were 96.4%, 69.5%, 60.6%, and 26.1% for patients with repeat MWA for LR. Repeat MWA for LR was not associated with more significant complications. Conclusion: The LR was higher in tumors >3.5 cm than that of in tumors ≤3.5 cm. For patients with LR, it was feasible and effective to use MWA repeatedly to achieve the similar OS and PFS as patients without LR. No additional complications were reported in the repeat MWA compared to the original MWA.

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