A qualitative insight into the self-management experience among Chinese breast cancer survivors

Abstract

Objective

With increasing awareness in the chronic nature of cancer, promoting the engagement of breast cancer survivors in self-management has become a priority of cancer care reform initiatives. This study aimed to reveal Chinese breast cancer survivors' views and experiences of self-management in extended survivorship.

Methods

Archived interview transcripts from 19 breast cancer survivors (<5 years since diagnosis) were subjected to a secondary analysis. Each transcript was re-examined through qualitative content analysis.

Results

Three categories were established to represent the perceptions of the participants on their self-management tasks related to health and well-being, emotions, and roles and relationships. Managing health and well-being covers modifying lifestyle, taking traditional Chinese medicine, attending regular follow-ups, relieving symptoms, and adhering to hormonal therapy. Managing emotions involves maintaining a positive attitude and utilizing supportive resources. Managing roles and relationships comprises adjusting to life as cancer survivors, maintaining marital relationships, and performing familial and other social roles.

Conclusions

The majority of the participants actively participated in various self-management tasks and behaviors that can help improve their health and prevent cancer recurrence. They may exhibit optimal self-management in their emotions and most health aspects but may exert limited efforts in managing their different roles during survivorship.

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Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target

Abstract

This study investigated the significance of La-related protein 1 (LARP1) in the development and progression of colorectal cancer (CRC). Quantitative real-time polymerase chain reaction and Western blot analyses were carried out to determine the mRNA and protein expression of LARP1 in CRC tumor tissues and paired adjacent normal mucosa. The expression of LARP1 was upregulated in CRC. Immunohistochemical analysis using tissue microarray was performed. A positive correlation between LARP1 and proliferating cell nuclear antigen (PCNA) in the area of proliferation was observed using the Spearman's correlation coefficient test (r = 0.332, P < 0.01). The elevated expression of LARP1 significantly correlated with T stage (P = 0.02), N stage (P = 0.006), M stage (P < 0.001), American Joint Committee on Cancer (AJCC) stage (P = 0.04), differentiation rank (P < 0.001), and PCNA level (P < 0.001). In addition, the inhibitory effect of LARP1 knockdown on CRC cell proliferation was demonstrated using Cell Counting Kit-8 (CCK8) and colony-forming cell (CFC) assays. Multivariate analysis showed that LARP1 was an independent prognostic factor for overall survival (OS; hazard rate (HR) = 0.244; 95 % confidence interval (CI), 0.078–0.769; P = 0.016) and disease-free survival (DFS; HR = 0.281; 95 % CI, 0.086–0.917; P = 0.035) in CRC patients. LARP1 plays an important role in the proliferation of colorectal cancer and represents a new prognostic indicator.

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Role of angiogenic factors of herbal origin in regulation of molecular pathways that control tumor angiogenesis

Abstract

The formation of blood capillaries to sustain development and growth of new tissues is referred to as angiogenesis. Angiogenesis is pivotal in both carcinogenesis and metastasis since capillaries are the sole source of supplying nutrients and oxygen to the proliferating tumor cells; therefore, this dependency of tumor growth on angiogenesis challenges researchers to halt tumor growth by targeting angiogenesis with the help of either synthetic or natural inhibitors. Many synthetic inhibitors of angiogenesis have not only come into force but also resulted in some severe adverse effects. Natural compounds may effectively fit into this condition and possibly decrease the time of treatment. In the recent past, literature is replete with evidences advocating the usefulness of natural compounds that target multiple biochemical pathways. The additional advantage of natural compounds is that their active principles interact with one another and work synergistically to give more meaningful and reliable effects than individual principle. Hence, if we are somehow able to combine more than two natural compounds, then it may be possible to enhance their potential by many folds, which shall prove to be very effective in combating tumor angiogenesis. This review shall discuss the concept of angiogenesis, molecular pathways, and angiogenic inhibitors and their specific targets and potential of natural compounds to greatly enhance the current knowledge of angiogenesis-inhibiting factors.

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NETs in cancer

Abstract

Many aspects of neutrophil hyperactivity and its role in numerous immune responses still remain a mystery. A new neutrophil mechanism was discovered recently, i.e., the formation of neutrophil extracellular traps (NETs). These structures, composed of DNA strands and neutrophil granule proteins, are an element of the non-specific immune response and bind pathogens to prevent their spread and ensure increased local concentrations of toxic factors. Research on this phenomenon shows that tumor-associated neutrophils (TANs) also form and release NETs. Reports on the role of NETs in the course of cancer are scarce, and the opinions on the involvement of extracellular traps in the disease are divided, indicating a dual function. There is speculation about the anti-cancer properties of NETs connected with direct killing of cancer cells or stimulation of the immune system. On the other hand, the trap structures might promote migration and immune escape of cancer cells or constitute a physical barrier between cancer cells and immune-competent cells. This article summarizes our knowledge about the proven roles of NETs in the course of cancer with particular focus on the significance of NETs as prognosis biomarkers in the course of the neoplastic process and their potential use in therapy.

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Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression

Abstract

Epithelial to mesenchymal transition (EMT) is a critical step in the metastasis of epithelial cancer cells. Butyrate, which is produced from dietary fiber by colonic bacterial fermentation, has been reported to influence EMT. However, some studies have reported that butyrate promotes EMT, while others have reported an inhibitory effect. To clarify these controversial results, it is necessary to elucidate the mechanism by which butyrate can influence EMT. In this study, we examined the potential role of annexin A1 (ANXA1), which was previously reported to promote EMT in breast cancer cells, as a mediator of EMT regulation by butyrate. We found that ANXA1 mRNA and protein were expressed in highly invasive melanoma cell lines (A2058 and A375), but not in SK-MEL-5 cells, which are less invasive. We also showed that butyrate induced ANXA1 mRNA and protein expression and promoted EMT-related cell invasion in SK-MEL-5 cells. Downregulation of ANXA1 expression using specific small interfering RNAs in butyrate-treated SK-MEL-5 cells resulted in increased expression of the epithelial marker E-cadherin and decreased cell invasion. Moreover, overexpressing ANXA1 decreased the expression of the E-cadherin. Collectively, these results indicate that butyrate induces the expression of ANXA1 in human melanoma cells, which then promotes invasion through activating the EMT signaling pathway.

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Signatures of prostate-derived Ets factor (PDEF) in cancer

Abstract

The Ets proteins are a family of transcription factors characterized by an evolutionarily conserved DNA-binding domain and have diverse biological functions including tumor suppressor as well as tumor promoter functions. They are regulated via a complex and diverse number of mechanisms and control key cellular processes. Prostate-derived Ets transcription factor (PDEF), a unique member of the ETS family, is present in tissues with high epithelial content are hormone-regulated, such as prostate, breast, salivary glands, ovaries, colon, airways, and stomach tissues. PDEF (prostate-derived Ets factor) is also referred to as SPDEF (SAM pointed domain containing Ets transcription factor), PSE (mouse homolog), or hPSE (human PSE) in the literature and is the sole member of the PDEF ETS sub-family. The role of PDEF in cancer development is still not fully elucidated though. The present article focuses on the key findings about the PDEF's biological functions, interacting proteins, and its target genes. There is a strong urge to focus on the clinical studies in larger cohort, which elucidate the regulation of PDEF and its target genes, to determine the potential of PDEF as biomarker. Based on the studies discussed in the present article, one can anticipate that PDEF offers a great potential for developing therapeutics against cancer.

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Role of miRNA dynamics and cytokine profile in governing CD44v6/Nanog/PTEN axis in oral cancer: modulating the master regulators

Abstract

Late diagnosis, low therapeutic response, and metastasis are accountable for poor 5-year survival rate of OSCC. These failures are attributed to the existence of "cancer stem cell (CSC)" subpopulation. Hence, it is necessary to identify and understand the mechanism of CSCs in tumor development, metastasis, and chemotherapeutic response. Propelling evidences suggest that microRNA (miRNA)-mediated regulation and cytokines of tumor microenvironment have the ability to modulate CSC signalling pathway; however, their exact mechanism needs to be elucidated. Thus, in this study, we characterized CSC markers and highlighted the miRNA dynamics and cytokine profile regulating these CSCs in a pathway-dependent manner. Our results demonstrated CD44+ subpopulation as tumor-initiating cells with self-renewal capability, tumorigenic growth potential and intrinsic chemoresistance. These tumors exhibited increased expression of CSC markers (CD44v3, CD44v6, Nanog, and Bmi1) and significantly reduced expression of PTEN and ATM in OSCC patients. Pathway analysis of these CSC markers demonstrated a prospective pathway regulated by miRNA and cytokine network. On analyzing these modulators, we observed decreased expression of miRNA542-3p, miRNA34a and miRNA9, and significant upregulation of miRNA21, thus forming an unexplored axis. Cytokine profiling revealed significantly increased levels of IL-6 and IL-8 compared to normals and demonstrated their strong association with CD44v6. Collectively, this study indicates that miR5423p and miR34a targets the CD44v6-Nanog-PTEN axis, thus playing a vital role in regulating the CSC properties. Furthermore, we speculate an impinging role of cytokines IL-6 and IL-8 in regulating this CSC-mediated pathway which can have prognostic and therapeutic implications.

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LINC00312 inhibits the migration and invasion of bladder cancer cells by targeting miR-197-3p

Abstract

To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.

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LncRNA and mRNA expression profiles of glioblastoma multiforme (GBM) reveal the potential roles of lncRNAs in GBM pathogenesis

Abstract

Glioblastoma multiforme (GBM) is the most common brain malignancy. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and are involved in their cell proliferation, apoptosis, angiogenesis, and invasion. The functional roles of lncRNAs in GBM are less known. We analyzed a cohort of exon microarray datasets from The Cancer Genome Atlas. The differently expressed lncRNAs and mRNA were subjected to construct lncRNA-mRNA co-expression network. Probable functions for lncRNAs were predicted according to lncRNA-mRNA network and genomic adjacency by GO and pathway analysis. The expression of lncRNAs and mRNAs in GBM tissues versus normal brain tissues was examined by quantitative reverse transcription polymerase chain reaction. The 398 lncRNAs and 1995 mRNAs were identified as distinctively expressed in GBM. Probable functional roles for 98 lncRNAs were involved in 30 pathways and 32 gene functions related to tumorigenesis, development, and metastasis. The identified sets of key lncRNAs specific to GBM were subsequently verified by experiment in GBM tissues. Our reports predict the biological functions of a multitude of lncRNAs in GBM that could be potential diagnostic and prognostic biomarkers as well as therapeutic targets. Moreover, our research provides a road map for the identification and analysis of lncRNAs in tumors.

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HSP90B1 overexpression predicts poor prognosis in NSCLC patients

Abstract

Non-small cell lung cancer (NSCLC) accounts for 85 % of lung cancer-related mortality worldwide. The heat shock protein 90B1 (HSP90B1) and DNA damage-inducible transcript 3 (DDIT3) are endoplasmic reticulum stress-related proteins that are associated with many malignancies. However, the roles of two proteins on NSCLC remain uncovered. To investigate the correlation between the expressions of HSP90B1 and DDIT3 and clinicopathological parameters of NSCLC as well as the significance of prognosis in NSCLC, a total of 143 NSCLC tissue samples and 45 control tissues samples were assessed. NSCLC patients were followed up from the day of surgery and ended by March 2014. The expressions of HSP90B1 and DDIT3 proteins were detected in all paraffin-embedded biopsy samples by immunochemistry. The HSP90B1 was highly expressed (65.2 %) in the 143 NSCLC patients, and its high expression was correlated with clinical stages (P = 0.001) and lymph node metastasis (P = 0.016). Similarly, DDIT3 was highly expressed in 43 (30.1 %) of 143 NSCLC patients, but only correlated with lymph node metastasis. Furthermore, Log-rank test suggested that high HSP90B1 expression may predict shorter survival (overall survival (OS)) and disease-free survival (DFS) for NSCLC patients. Cox model multivariate analyses indicated that HSP90B1 overexpression was an independent poor prognostic factor for both of OS and DFS. Therefore, HSP90B1 and DDIT3 may the potential biomarker to predict the NSCLC clinicopathological progress. Meanwhile, high HSP90B1 expression means poor prognosis, and HSP90B1 can be a promising prognosis factor for NSCLC.

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CAS (CSE1L) signaling pathway in tumor progression and its potential as a biomarker and target for targeted therapy

Abstract

CSE1L (chromosome segregation 1-like protein), also named as CAS (cellular apoptosis susceptibility protein), is highly expressed in most cancer types. CSE1L/CAS is a multiple functional protein that plays roles in apoptosis, cell survival, chromosome assembly, nucleocytoplasmic transport, microvesicle formation, and cancer metastasis; some of the functions are explicitly correlated. CSE1L is also a cancer serum biomarker. The phosphorylation of CAS is regulated by the extracellular signal-regulated kinase (ERK). The RAS/RAF/MAPK/ERK signaling pathways are the essential targets of most targeted cancer drugs, thus serum phosphorylated CSE1L may be a potential biomarker for monitoring drug resistance in targeted therapy. CSE1L can regulate Ras-induced ERK phosphorylation. CSE1L also regulates the expression and phosphorylation of CREB (cAMP response element binding protein) and MITF (microphthalmia-associated transcription factor) and is thus involved in the melanogenesis and progression of melanoma. CAS is an exosome/microvesicle membrane protein. Tumor cells consistently secrete microvesicles and tumor-derived microvesicles may be accumulated around tumors. Therefore, microvesicle membrane CSE1L may be a potential target for the development of high-efficacy antibody-drug conjugates (ADCs) for cancer therapy. This review will focus on CSE1L expression in cancers, its relationship to Ras/ERK and cAMP/PKA signaling pathways in melanoma development, its potential for the development of ADCs and tumor imaging reagents, and secretory phosphorylated CSE1L for monitoring the emergence of drug resistance in targeted cancer therapy.

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FBXO25 promotes cell proliferation, invasion, and migration of NSCLC

Abstract

FBXO25 is a recently discovered protein that belongs to the Fbx class of the F-box family of proteins, and F-box proteins play a crucial role in tumorigenesis. However, the function of FBXO25 in cancer was not revealed so far. As measured by immunohistochemical staining, FBXO25 was highly expressed in the cytoplasm and nucleus of lung cancer samples (64.2 %, 136/212), compared with adjacent normal lung tissues (23.3 %, 7/30, p < 0.01). In addition, its expression was positively correlated with TNM staging (p < 0.001) and lymph node metastasis (p = 0.017). The overall survival of non-small-cell lung cancer (NSCLC) patients with FBXO25-positive expression (40.646 ± 1.745 months) was significantly reduced compared with those with FBXO25-negative expression (46.548 ± 2.176 months, p = 0.023). Consistently, we found that the proliferation, invasion, and migration capacity of A549 cells transfected with FBXO25 were significantly greater than those of control cells, while interference of FBXO25 could significantly inhibit cell proliferation, invasion, and migration in H1299 cells. Furthermore, we demonstrated that FBXO25 could regulate the expression of β-catenin, YAP, some cyclins, and matrix metalloproteinases (MMPs). Collectively, these results indicate that FBXO25 may promote the tumorigenicity of lung cancer cells and might serve as a novel therapeutic target of NSCLC.

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Armillaridin induces autophagy-associated cell death in human chronic myelogenous leukemia K562 cells

Abstract

Armillaridin (AM) is an aromatic ester compound isolated from Armillaria mellea. Treatment with AM markedly reduced the viability of human chronic myelogenous leukemia K562, chronic erythroleukemia HEL 92.1.7, and acute monoblastic leukemia U937 cells, but not normal human monocytes, in a dose- and time-dependent manner. Treatment of K562 cells with AM caused changes characteristic of autophagy. Only a small amount of AM-treated K562 cells exhibited apoptosis. By contrast, AM treatment resulted in extensive apoptotic features in U937 and HEL 92.1.7 cells without evident autophagy. The autophagy of K562 cells induced by AM involved autophagic flux, including autophagosome induction, the processing of autophagosome-lysosome fusion and downregulation of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3). By bcr-abl knockdown, the growth inhibition of K562 cells caused by AM was partially blocked, suggesting that AM-induced cell death might be a bcr-abl-dependent mode of autophagy-associated cell death. In conclusion, AM is capable of inhibiting growth and inducing autophagy-associated cell death in K562 cells, but not in normal monocytes. It may have potential to be developed as a novel therapeutic agent against leukemia.

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Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer

Abstract

Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed hypermethylated in kidney cancer. Myopodin methylation status identified which patients showed a more aggressive clinical behavior and predicted antiangiogenic response. These observations support the clinical utility of an unmethylated myopodin as a prognostic and predictive biomarker in kidney cancer.

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Ganoderic acid targeting multiple receptors in cancer: in silico and in vitro study

Abstract

Receptor tyrosine kinases (RTKs) are transmembrane high-affinity surface receptors responsible for cell migration, adhesion, apoptosis, metabolism, and cell proliferation activities in various cancers. Minute aberration in the RTK signaling modulates the downstream signaling pathways that results in cancer. Ganoderic acid is a triterpene isolated from Ganoderma lucidum, which is renowned for its therapeutics effect, especially in cancer. The present study discusses receptor-based molecular docking of insulin receptor (IR), insulin-like growth factor receptor 1 (IGFR-1), vascular endothelial growth factor receptor-1 (VEGFR-1), vascular endothelial growth factor receptor-2 (VEGFR-2), and estrogen receptor (ER) with 50 isoforms of ganoderic acid along with natural inhibitors. These receptors were assessed for toxicity (ADMET) by using Maestro 9.6 (Schrödinger Inc). The calculated docking free energy yielded an excellent dock score for the ganoderic acid when docked with proteins IR, IGFR-1, VEGFR-1, VEGFR-2, and ER, suggesting its potential in combating cancer. Protein–ligand profile highlighted the binding interactions comprising lipophilic, hydrogen bonding, pi-pi stacking interactions, and noncovalent bonding which play a pivotal role in targeting cancer. In silico studies revealed structure of ganoderic acid A as best isoforms among 50 isoforms which exhibits biological activity in liver cancer cells. Ganoderic acids A significantly decrease the viability, proliferation, and oxidative stress in a dose-dependent manner in liver cancer cells.

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RK-33 functions as a radiosensitizer in prostate cancer

Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second-highest cause of cancer-related mortality in men. We identified an RNA helicase gene, DDX3 (DDX3X), which is over-expressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3. Functional studies indicated that RK-33 preferentially bound to DDX3 and perturbed its activity. Treatment of prostate cancer cell lines DU145, 22Rv1, and LNCaP (which have high DDX3 levels) with RK-33 decreased proliferation and induced a G1 phase cell cycle arrest. On the other hand, the low DDX3 expressing cell line, PC3, exhibited few changes following RK-33 treatment. Importantly, combination studies using RK-33 and radiation exhibited synergistic effects both in vitro and in a xenograft model of prostate cancer demonstrating the role of RK-33 as a radiosensitizer. Taken together, these results indicate that blocking DDX3 by RK-33 in combination with radiation treatment is a viable option for treating locally advanced prostate cancer.

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Transcriptional hallmarks of liver cancer

Integrative genomics helped characterize molecular heterogeneity in HCC, leading to targeted drug candidates for specific HCC subtypes. However, no consensus was achieved for genes and pathways commonly altered in HCC. Here we performed a meta-analysis of 15 independent datasets (n=784 human HCC) and identified a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared to the surrounding non-tumor tissue. In the HCC signature, up-regulated genes were linked to early genomic alterations in hepatocarcinogenesis, particularly gains of 1q and 8q. The HCC signature covered well-established cancer hallmarks, such as proliferation, metabolic reprogramming, and microenvironment remodeling, together with specific hallmarks associated with protein turnover and epigenetics. Subsequently, the HCC signature enabled us to assess the efficacy of signature-relevant drug candidates, including histone deacetylase inhibitors that specifically reduced the viability of six human HCC cell lines. Overall, this integrative genomics approach identified cancer hallmarks recurrently altered in human HCC that may be targeted by specific drugs. Combined therapies targeting common and subtype-specific cancer networks may represent a relevant therapeutic strategy in liver cancer.

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CCL22 to redirect Treg

T regulatory cells (Treg) avert autoimmunity but their increased levels in melanoma confer a poor prognosis. To explore the basis for Treg accumulation in melanoma, we evaluated chemokine expression in patients. A 5-fold increase was documented in the Treg chemoattractants CCL22 and CCL1 in melanoma-affected skin versus unaffected skin, as accompanied by infiltrating FoxP3+ T cells. In parallel, there was a ~2-fold enhancement in expression of CCR4 in circulating Treg but not T effector cells. We hypothesized that redirecting Treg away from tumors might suppress autoimmune side-effects caused by immune checkpoint therapeutics now used widely in the clinic. In assessing this hypothesis, we observed a marked increase in skin Treg in mice vaccinated with CCL22, with repetitive vaccination sufficient to limit Treg accumulation and melanoma growth in the lungs of animals challenged by tumor cell injection, whether using a prevention or treatment protocol design. The observed change in Treg accumulation in this setting could not be explained by Treg conversion. Overall, our findings offered a preclinical proof of concept for the potential use of CCL22 delivered by local injection as a strategy to enhance the efficacious response to immune checkpoint therapy while suppressing its autoimmune side-effects.

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Cancer immunotherapy by adoptive transfer of Th2 cells

Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+ T cells, however, the potential of CD4+ T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with interferon-γ (IFNγ)-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with Major Histocompatibility Complex (MHC) class II-negative myeloma. Th2 ACT efficiently eradicated subcutaneous myeloma in an antigen-specific fashion. Transferred Th2 cells persisted in vivo and conferred long-lasting immunity. Cancer eradication mediated by tumor-specific Th2 cells did not require B cells, natural killer T cells, CD8+ T cells, or IFNγ. Th2 ACT was also curative against B-cell lymphoma. Upon transfer, Th2 cells induced a type 2 inflammation at the tumor site with massive infiltration of M2-type macrophages producing arginase. In vivo blockade of arginase strongly inhibited Th2 ACT, consistent with a key role of arginase and M2 macrophages in myeloma elimination by Th2 cells. These results illustrate that cancer eradication may be achieved by induction of a tumor-specific Th2 inflammatory immune response at the tumor site. Thus, ACT with tumor-specific Th2 cells may represent a highly efficient immunotherapy protocol against cancer.

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Targeting acute myeloid leukemia with TP53-independent vosaroxin

Future Oncology Ahead of Print.


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Caring for cancer survivors: perspectives of oncologists, general practitioners and patients in Italy

Future Oncology Ahead of Print.


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Reversal of direct oral anticoagulants in hemophilia treatment

Summary

During the 57^th annual meeting of the American Society of Hematology 2015 in Orlando, Florida, various aspects in the field of hemostaseology were presented. The Choosing Wisely® campaign pointed out the importance of the critical use of diagnostic tools to rule out pulmonary embolism and questioned the relevance of thrombophilia testing in women undergoing routine infertility evaluation. Furthermore, the approval of idarucizumab, a specific antidote for the reversal of the anticoagulant effects of the direct thrombin inhibitor dabigatran, was highlighted. Finally, hemophilia specialists awaited the results of the SIPPET Trial, which were presented for the first time during the plenary session. Replacement therapy of previously untreated hemophilia A patients with plasma-derived factor VIII containing von Willebrand factor resulted in a lower incidence of inhibitors compared with patients treated with recombinant factor VIII.

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Reply to the letter to the editor 'Erroneous conclusions about the association between light alcohol drinking and the risk of cancer: comments on Bagnardi et al.'s meta-analysis, by S.-K. Myung

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Hematopoietic Cell Transplantation for Myelodysplastic Syndromes [Clinical Reviews]

Allogeneic hematopoietic cell transplantation (HCT) offers the only potential cure for patients with myelodysplastic syndromes (MDS). However, with current approaches to HCT, many older patients with comorbidities are poor HCT candidates, and treatment-related morbidity and mortality may offset benefit for patients with lower-risk disease. Consequently, selection of patients with MDS for HCT should take into consideration disease risk category including mutational status, HCT comorbidity index, functional status, donor options, and available institutional resources. Formal geriatric assessment may further guide use of HCT and, if HCT is chosen, selection of conditioning intensity. Patients with higher-risk MDS should be considered for HCT at the time of diagnosis, whereas expectant nontransplant management is more appropriate for those with lower-risk disease. A high blast burden at the time of HCT increases the risk of subsequent relapse; however, the role of pretransplant cytoreductive therapy and the regimen of choice remain controversial. Patients with MDS younger than 65 years and with an HCT comorbidity index ≤ 4 may benefit from more intense conditioning regimens. The presence of complex or monosomal karyotype or mutations in TP53, DNMT3A, or other genes identify patients with poorer outcomes following HCT. Patients with TP53 mutations have particularly poor survival, and should be enrolled in clinical trials whenever possible. Several important HCT studies are ongoing and will better define the role of HCT in MDS as well as the value of pretransplant cytoreductive therapy or post-transplant relapse-prevention strategies. Given the apparent underuse of HCT in eligible patients and low enrollment in MDS HCT clinical trials to date, timely referral of patients with MDS to such trials and HCT programs is critical.

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Communicating Value in Health Care Using Radar Charts: A Case Study of Prostate Cancer [CARE DELIVERY]

Purpose:

The transformation from volume to value will require communication of outcomes and costs of therapies; however, outcomes are usually nonstandardized, and cost of therapy differs among stakeholders. We developed a standardized value framework by using radar charts to visualize and communicate a wide range of patient outcomes and cost for three forms of prostate cancer treatment.

Materials and Methods:

We retrospectively reviewed data from men with low-risk prostate cancer who were treated with low-dose rate brachytherapy (LDR-BT), proton beam therapy, or robotic-assisted prostatectomy. Patient-reported outcomes comprised the Expanded Prostate Cancer Index Composite-50 domains for sexual function, urinary incontinence and/or bother, bowel bother, and vitality 12 months after treatment. Costs were measured by time-driven activity-based costing for the first 12 months of the care cycle. Outcome and cost data were plotted on a single radar chart for each treatment modality.

Results:

Outcome and cost data from patients who were treated with robotic-assisted prostatectomy (n = 381), proton beam therapy (n = 165), and LDR-BT (n = 238) were incorporated into the radar chart. LDR-BT seemed to deliver the highest overall value of the three treatment modalities; however, incorporation of patient preferences regarding outcomes may allow other modalities to be considered high-value treatment options.

Conclusion:

Standardization and visualization of outcome and cost metrics may allow more comprehensive and collaborative discussions about the value of health care services. Communicating the value framework by using radar charts may be an effective method to present total value and the value of all outcomes and costs in a manner that is accessible to all stakeholders. Variations in plotting of costs and outcomes will require future focus group initiatives.

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Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndromes: Where Are We Going With This? [COMMENTARIES]

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Defining High-Quality Palliative Care in Oncology Practice: An American Society of Clinical Oncology/American Academy of Hospice and Palliative Medicine Guidance Statement [CARE DELIVERY]

Purpose:

Integrated into routine oncology care, palliative care can improve symptom burden, quality of life, and patient and caregiver satisfaction. However, not all oncology practices have access to specialist palliative medicine. This project endeavored to define what constitutes high-quality primary palliative care as delivered by medical oncology practices.

Methods:

An expert steering committee outlined 966 palliative care service items, in nine domains, each describing a candidate element of primary palliative care delivery for patients with advanced cancer or high symptom burden. Using modified Delphi methodology, 31 multidisciplinary panelists rated each service item on three constructs: importance, feasibility, and scope within medical oncology practice.

Results:

Panelists endorsed the highest proportion of palliative care service items in the domains of End-of-Life Care (81%); Communication and Shared Decision Making (79%); and Advance Care Planning (78%). The lowest proportions were in Spiritual and Cultural Assessment and Management (35%) and Psychosocial Assessment and Management (39%). In the largest domain, Symptom Assessment and Management, there was consensus that all symptoms should be assessed and managed at a basic level, with more comprehensive management for common symptoms such as nausea, vomiting, diarrhea, dyspnea, and pain. Within the Appropriate Palliative Care and Hospice Referral domain, there was consensus that oncology practices should be able to describe the difference between palliative care and hospice to patients and refer patients appropriately.

Conclusion:

This statement describes the elements comprising high-quality primary palliative care for patients with advanced cancer or high symptom burden, as delivered by oncology practices. Oncology providers wishing to enhance palliative care delivery may find this information useful to inform operational changes and quality improvement efforts.

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Myelodysplastic Syndromes: Going Gently Into That Good Night [COMMENTARIES]

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Errata [Errata]

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Current and Evolving Therapies for Metastatic Pancreatic Cancer: Are We Stuck With Cytotoxic Chemotherapy? [Clinical Reviews]

At present, front-line therapy for metastatic pancreatic ductal adenocarcinoma is combination chemotherapy, most commonly FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) or gemcitabine and nanoparticle albumin-bound paclitaxel. Despite a better understanding of the genomic landscape and the importance of the tumor microenvironment, we have not made a seismic shift in the overall survival for this disease. Given our growing understanding of the biology of pancreatic ductal adenocarcinoma, the question remains whether novel, noncytotoxic agents will augment or even replace conventional chemotherapy. The thrust of ongoing efforts can be divided into broad categories, including exploiting the DNA damage repair phenotype, stroma and specific pathway–targeting agents, and enhancing immune destruction of pancreatic ductal adenocarcinoma. In this article, we review the current and evolving therapeutic landscape of metastatic pancreatic cancer.

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Access to Care in Vermont: Factors Linked With Time to Chemotherapy for Women With Breast Cancer--A Retrospective Cohort Study [FOCUS ON QUALITY]

Purpose:

In the rural United States, there are multiple potential barriers to the timely initiation of chemotherapy. The goal of this study was to identify factors associated with delays in the time from initial diagnosis to first systemic therapy (TTC) among women with breast cancer in Vermont.

Methods:

Using data from the Vermont Cancer Registry, we explored TTC for 702 female Vermont residents diagnosed with stage I to III breast cancer between 2006 and 2010 who received adjuvant chemotherapy. Multivariable linear regression was used to evaluate the associations between TTC and patient, tumor, treatment, and geographic variables.

Results:

Mean TTC was 10.2 weeks. Longer drive time (P < .001), more invasive surgery (P = .01), and breast reconstruction (P < .001) were each associated with longer TTC. Each additional 15 minutes of drive time was associated with a 0.34-week (95% CI, 0.22 to 0.46 weeks) increase in TTC. Participants age younger than 65 years whose primary payer was Medicare (n = 27) had significantly longer average TTC, by 2.37 weeks (P = .001), compared with those with private or military insurance. There was also substantial variation in TTC across hospitals (P < .001).

Conclusion:

Most female patients with stage I to III breast cancer in Vermont are receiving adjuvant chemotherapy within the National Comprehensive Cancer Network–recommended timeframe; however, improvements remain needed for certain subgroups. Novel approaches for women with long drive times need to be developed and evaluated in the community. Variation in TTC by hospital, even after adjusting for patient, tumor, and treatment factors, also suggests opportunities for process improvement.

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Is There Efficacy Beyond Cytotoxic Chemotherapy for Pancreatic Cancer? [COMMENTARIES]

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Improving Oral Oncolytic Patient Self-Management [Quality in Action]

Purpose:

Managing patients who are taking oral oncolytics is challenging because of the changing paradigm from frequent supervision during intravenous therapy to periodic observation with oral administration of drugs. We joined the Michigan Oncology Quality Consortium (MOQC) Oral Oncolytics Collaborative in 2013 to identify opportunities for improvement in this area.

Methods:

We completed MOQC's baseline self-assessment and performed an audit of medical records for 25 patients prescribed an oral oncolytic from May 2011 to July 2013. We implemented the following MOQC resources: a tracking system for patients taking oral oncolytics, patient education with drug-specific self-care guidelines, use of a modified Edmonton Symptom Assessment Scale, and a medication adherence questionnaire to be used on scheduled follow-up calls and return visits. We modified our workflow to include a standard teaching session and consistent follow-up phone calls. We conducted a retrospective postimplementation medical records audit from August 2013 to September 2014.

Results:

Baseline self-assessment revealed lack of start date documentation and lack of consistent follow-up. A baseline medical records audit showed that 48% of patients discontinued their medication without consulting their physician, and start date documentation was available for only 52% of patients. After participating in the quality initiative, 100% of patients sampled had a documented start date, and no patients discontinued their drug on their own. Seventeen percent had a dose reduction as a result of toxicity, as directed by the physician.

Conclusion:

The introduction of new office procedures to easily identify all patients receiving oral therapy and improvement in patients' ability to manage symptoms at home with the use of self-care guidelines contributed to an improvement in managing patients who are taking oral oncolytics.

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Adhering towards tumorigenicity: altered adhesion mechanisms in glioblastoma cancer stem cells

CNS Oncology Ahead of Print.


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Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L) mutation treated with everolimus therapy

CNS Oncology Ahead of Print.


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Quantitative analysis of plasma cell-free DNA and its DNA integrity in patients with metastatic prostate cancer using ALU sequence

Publication date: Available online 12 September 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Amal Fawzy, Karima M. Sweify, Hany M. El-Fayoumy, Nagwa Nofal
BackgroundProstate cancer (PC) is the most common cancer affecting men, it accounts for 29% of all male cancer and 11% of all male cancer related death. DNA is normally released from an apoptotic source which generates small fragments of cell-free DNA, whereas cancer patients have cell-free circulating DNA that originated from necrosis, autophagy, or mitotic catastrophe, which produce large fragments.Aim of workDifferentiate the cell free DNA levels (cfDNA) and its integrity in prostate cancer patients and control group composed of benign prostate hyperplasia (BPH) and healthy persons.Methodologycf-DNA levels were quantified by real-time PCR amplification in prostate cancer patients (n = 50), (BPH) benign prostate hyperplasia (n = 25) and healthy controls (n = 30) using two sets of ALU gene (product size of 115bp and 247-bp) and its integrity was calculated as a ratio of qPCR results of 247bp ALU over 115bp ALU.ResultsHighly significant levels of cf-DNA and its integrity in PC patients compared to BPH. Twenty-eight (56%) patients with prostate cancer had bone metastasis. ALU115 qpcr is superior to the other markers in discriminating metastatic patients with a sensitivity of 96.4% and a specificity of 86.4% and (AUC=0.981)ConclusionALU115 qpcr could be used as a valuable biomarker helping in identifying high risk patients, indicating early spread of tumor cells as a potential seed for future metastases.



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U/G SNP rs111904020 in 3′UTR of STAT3 regulated by miR-214 promotes hepatocellular carcinoma development in Chinese population

Abstract

STAT3 is an oncogene which mainly capable of regulating various biological characters by its transcriptional factor features driving thousands of genes. However, its upstream noncoding RNA-related regulations still remain unknown. In this study, we focused on the microRNA (miRNA)-associated single nucleotide polymorphisms (SNPs) in the 3′ unstranslated region (UTR) of STAT3 to investigate the further relationship of the SNPs with miRNAs among Chinese patients with hepatocellular carcinoma (HCC). We found that patients suffering from HBV infection indicated to be the susceptible population by comparing with controls. Besides, SNP rs111904020 (U/G) in STAT3, 3′UTR was involved in the occurrence of HCC by acting as tumor promoter factors. SNP rs111904020 (U/G) could be regulated by miR-214 which caused an upregulation of STAT3. Furthermore, the carriers of G genotype was related to high expression of STAT3, and larger tumor size as well as high probability of metastasis. Moreover, the SNP of U/G was associated with poor survival and high reoccurrence of HCC with a 5-year follow-up study. In conclusion, our findings have shown that the SNP rs111904020 (U/G) in STAT3 3′UTR acted as promotion factors in the HCC development through disrupting the regulatory role of miR-214 in STAT3 expression.

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Bone marrow-derived mesenchymal stem cells increase drug resistance in CD133-expressing gastric cancer cells by regulating the PI3K/AKT pathway

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited to primary tumours to compose the tumour microenvironment. In various cancers, CD133-positive cells have been shown to possess cancer stem cell properties that confer chemoresistance. This study aimed to investigate the role of BM-MSCs in the anti-tumour drug resistance of CD133-expressing gastric cancer cells and explore the underlying mechanisms that governing this role. We found that CD133⁺ gastric cancer cells displayed more resistance to chemotherapeutics than CD133⁻ cells. In addition, BM-MSCs increased the anti-apoptotic abilities and chemoresistance of CD133⁺ cells via upregulation of Bcl-2 and downregulation of BAX. Mechanistically, BM-MSCs triggered activation of the PI3K/Akt signalling cascade in CD133⁺ cells. Blocking the PI3K/Akt pathway inhibited the promotion of chemoresistance. Furthermore, BM-MSCs enhanced the drug resistance of CD133-overexpressing cells in vitro and in vivo, but not that of CD133-knockdown cells, which demonstrated the contribution of CD133 to this process. In conclusion, we demonstrated that BM-MSCs increased the anti-apoptotic abilities and drug resistance of CD133-expressing cells via activation of the PI3K/Akt pathway following Bcl-2 upregulation and BAX downregulation, in which CD133 played a significant role. Targeting this route may help improve the efficacy of chemotherapy in gastric cancer.

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MiR-429 is linked to metastasis and poor prognosis in renal cell carcinoma by affecting epithelial-mesenchymal transition

Abstract

MicroRNAs (miRNAs) have been proven to be important oncogenes and tumor suppressors in wide range of cancers, including renal cell carcinoma (RCC). In our study, we evaluated miRNA-429 as potential diagnostic/prognostic biomarker in 172 clear cell RCC patients and as a potential regulator of epithelial-mesenchymal transition (EMT) in vitro. We demonstrated that miR-429 is down-regulated in tumor tissue samples (P < 0.0001) and is significantly associated with cancer metastasis (P < 0.0001), shorter disease-free (P = 0.0105), and overall survival (P = 0.0020). In addition, ectopic expression of miR-429 in 786-0 RCC cells followed by TGF-β treatment led to increase in the levels of E-cadherin expression (P < 0.0001) and suppression of cellular migration (P < 0.0001) in comparison to TGF-β-treated controls. Taken together, our findings suggest that miR-429 may serve as promising diagnostic and prognostic biomarker in RCC patients. We further suggest that miR-429 has a capacity to inhibit loss of E-cadherin in RCC cells undergoing EMT and consequently attenuate their motility.

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Multiple imputation of cognitive performance as a repeatedly measured outcome

Abstract

Longitudinal studies of cognitive performance are sensitive to dropout, as participants experiencing cognitive deficits are less likely to attend study visits, which may bias estimated associations between exposures of interest and cognitive decline. Multiple imputation is a powerful tool for handling missing data, however its use for missing cognitive outcome measures in longitudinal analyses remains limited. We use multiple imputation by chained equations (MICE) to impute cognitive performance scores of participants who did not attend the 2011–2013 exam of the Atherosclerosis Risk in Communities Study. We examined the validity of imputed scores using observed and simulated data under varying assumptions. We examined differences in the estimated association between diabetes at baseline and 20-year cognitive decline with and without imputed values. Lastly, we discuss how different analytic methods (mixed models and models fit using generalized estimate equations) and choice of for whom to impute result in different estimands. Validation using observed data showed MICE produced unbiased imputations. Simulations showed a substantial reduction in the bias of the 20-year association between diabetes and cognitive decline comparing MICE (3–4 % bias) to analyses of available data only (16–23 % bias) in a construct where missingness was strongly informative but realistic. Associations between diabetes and 20-year cognitive decline were substantially stronger with MICE than in available-case analyses. Our study suggests when informative data are available for non-examined participants, MICE can be an effective tool for imputing cognitive performance and improving assessment of cognitive decline, though careful thought should be given to target imputation population and analytic model chosen, as they may yield different estimands.

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Issue Information - Ed Board

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MiR-106b promotes migration and invasion through enhancing EMT via downregulation of Smad 7 in Kazakh’s esophageal squamous cell carcinoma

Abstract

Accumulated evidence suggests that miR-106b played a key role in the promotion of the metastases of cancer; however, little is known about miR-106b in esophageal squamous cell carcinoma (ESCC). To investigate expression level of miR-106b in ESCC tissues, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-106b expression in 35 Kazakh's ESCC and paired normal adjacent tissues (NATs). To evaluate the role mediated by miR-106b in the proliferation, migration, and invasion, MTT, wound healing, and transwell assays were employed, respectively. Luciferase reporter assay was used to identify the downstream target through miR-106b. To understand the regulation between miR-106b and Smad 7, qRT-PCR and western blot were performed. The present study showed that miR-106b was pronouncedly upregulated in ESCC relative to paired NAT and that upregulated miR-106b was significantly associated with lymph node metastases. MiR-106b was found to be able to promote proliferation, migration, and invasion of ESCC cells in vitro. Smad 7 was confirmed as a downstream target of miR-106b in our experimental setting. Smad 7 was remarkably downregulated in ESCC compared with paired NAT. In addition, upregulation of miR-106b can promote epithelial mesenchymal transition (EMT) in ESCC cell in vitro. Our results indicated that miR-106b can promote migration and invasion of ESCC cells through enhancing EMT process via downregulation of Smad 7, suggesting that miR-106b can be a potential molecular phenotype in ESCC metastases.

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High expression of TRIM44 is associated with enhanced cell proliferation, migration, invasion, and resistance to doxorubicin in hepatocellular carcinoma

Abstract

Dysregulation of TRIM44 has been reported to be involved in tumorigenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the clinicopathological and biological significance of TRIM44 in HCC. We found that TRIM44 mRNA and protein expression was upregulated in HCC compared with matched normal tissues. Intriguingly, we also found that TRIM44 expression was significantly correlated with tumor size (P < 0.001), vascular invasion (P < 0.001), intrahepatic metastasis (P < 0.001), distant metastasis (P < 0.001), and Ki-67 expression (P < 0.001). Kaplan-Meier analysis showed that high TRIM44 staining was significantly correlated with shorter overall survival (P < 0.001). TRIM44 was an independent predictor of overall survival in patients with HCC. Furthermore, we found that ectopic expression of TRIM44 could promote cell proliferation via accelerating the G1/S-phase transition in HCC. Moreover, overexpression of TRIM44 could enhance the invasive and migratory capacity of HCC cells. Meanwhile, we found that high expression of TRIM44 could enhance resistance of HCC cells to doxorubicin via accelerating NF-κB activation. In conclusion, our results suggest that TRIM44 may be a novel prognostic indicator and potential therapeutic target of HCC.

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miR-214 inhibits invasion and migration via downregulating GALNT7 in esophageal squamous cell cancer

Abstract

Previous studies verified that miR-214 is of great significance in the invasion and migration of a variety of cancers. It has been demonstrated that UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7(GALNT7) is a putative target of miR-214. We performed this study to figure out how miR-214 and GALNT7 play their roles in the invasion and migration of esophageal squamous cell carcinoma (ESCC). The expression of miR-214 was significantly downregulated in tumors compared to the corresponding non-tumor tissues while GALNT7 showed an opposite tendency. The low expression of miR-214 and the high expression of GALNT7 were found positively correlated with poor tumor differentiation (P = 0.004), tumor invasion (P = 0.013), and lymph node metastasis (P = 0.012) in ESCC patients. Functional study demonstrated that overexpression of miR-214 or knockdown of GALNT7 could weaken invasive and migratory ability in Eca109, TE1, and KYSE150. Moreover, tumorigenicity assay showed us mice injected with cells containing miR-214 mimic or GALNT7 small interfering RNA formed substantially smaller tumors than that in miR-214 inhibitor group. Consequently, we concluded that miR-214 shows potential to be a diagnostic marker and therapeutic target in ESCC.

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Low rates of pregnancy screening in adolescents before teratogenic exposures in a national sample of children's hospitals

BACKGROUND

Adolescents with cancer engage in sexual behaviors and are exposed to teratogenic chemotherapy. There are no data regarding pregnancy screening patterns for adolescents before chemotherapy exposure.

METHODS

A cross-sectional study of leukemia and emergency room (ER) admissions in the Pediatric Health Information System from 1999 to 2011 was conducted. Females who were 10 to 18 years old and 1) had newly diagnosed acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) or 2) had ER visits with computed tomography (CT) of the abdomen/pelvis were included. The exposure was a hospital visit with either chemotherapy or an abdominal/pelvic CT scan. The main outcome was a pregnancy test billed on the same day or before the teratogenic exposure within the same index admission. Log-binomial regressions were used to compute prevalence ratios and 95% confidence intervals comparing pregnancy screening in the leukemia and ER cohorts.

RESULTS

A total of 35,650 admissions were identified. The proportion of visits with an appropriately timed pregnancy test was 35%, 64%, and 58% in the ALL (n = 889), AML (n = 127), and ER cohorts (n = 34,634), respectively. Patients with ALL were significantly less likely to have a pregnancy test than the ER cohort (adjusted prevalence ratio, 0.71; 95% confidence interval, 0.65-0.78), but there was no significant difference between the AML and ER cohorts (adjusted prevalence ratio, 1.12; 95% confidence interval, 0.99-1.27). There was substantial hospital-level variation in pregnancy screening patterns.

CONCLUSIONS

Adolescents with acute leukemia and ER visits have low rates of pregnancy screening before teratogenic exposures. Standardized practice guidelines for pregnancy screening among adolescents may improve screening rates. Cancer 2016. © 2016 American Cancer Society.

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Efficacy and safety of ibrutinib in Japanese patients with relapsed or refractory mantle cell lymphoma

Abstract

In this multicenter, single-arm, phase II study, efficacy and safety of ibrutinib were examined in Japanese patients with relapsed or refractory mantle cell lymphoma (MCL). Patients (age ≥ 20 years) with relapsed or refractory MCL who had progressed after receiving at least one prior treatment regimen, were enrolled. Patients were treated with oral ibrutinib (560 mg/once daily; 28-day cycle) until disease progression (or relapse), unacceptable toxicity, or study end. Primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Of the 16 patients who received treatment, 5 patients discontinued the study (progressive disease 4; sepsis 1). Median duration of ibrutinib exposure was 6.5 months (range, 2.8-8.3 months). The ORR was 87.5% (90% CI: 65.6-97.7; complete response =2 [12.5%]; partial response=12 [75.0%]). Median TTR for all responders (n=14) was 1.8 months (range, 0.7-5.3 months). The median DOR and PFS were not estimable due to censoring (range, DOR: 1.1 to 6.4+ months, PFS: 2.8 to 8.0+ months). OS data was immature due to the limited observation period. A total of 8/16 patients (50%) had at least one grade 3 adverse event (AE), and 5 (31.3%) patients reported serious AEs. The most commonly reported AEs were diarrhea and stomatitis (37.5% each), platelet count decreased (31.3%), and anemia (25%). Overall, orally administered single agent ibrutinib was efficacious with an acceptable safety profile in Japanese patients with relapsed or refractory MCL.

This article is protected by copyright. All rights reserved.

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Combined IKZF1 and IG markers as new tools for diagnosis and minimal residual disease assessment in Tunisian B-ALL.

Combined IKZF1 and IG markers as new tools for diagnosis and minimal residual disease assessment in Tunisian B-ALL.

Bull Cancer. 2016 Sep 7;

Authors: Besbes S, Hamadou WS, Boulland ML, Lefranc MP, Ben Youssef Y, Achour B, Khelif A, Fest T, Soua Z

Abstract
INTRODUCTION: The monitoring of minimal residual disease (MRD) approach in patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) allows an early detection of residual clones inducing relapses and therefore appropriate therapy strategy. The molecular markers may identify and quantify the residual blasts in B-ALL with normal cytology. In this study, we aimed to use combined IKZF1, IGH and IGK immunoglobulin genes for diagnosis and MRD monitoring in B-ALL sample using MLPA, multiplex PCR and real-time quantitative PCR.
MATERIAL: We showed that multiplex PCR and MLPA are necessary and complementary to detect IKZF1 deletions.
RESULTS: We have identified at the diagnosis clonal IGH rearrangement (VH3-JH5) and IKZF1 deletion (Δ4-7), which we have used it for MRD evaluation after induction chemotherapy. Despite the absence of chromosome abnormality, the patient may be classified in high-risk group with a relapse rate of residual blasts>10(-4) and sensitivity up to 10(-5). This molecular approach enabled the patient's stratification, which was overlooked by classical methods.
CONCLUSION: The combined IKZF1 and immunoglobulin genes will be used as appropriate molecular tools for diagnosis and MRD assessment of B-lineage leukemias and introduced as a routine tests in Tunisian clinical laboratories. They will be useful to stratify patients into risk groups leading to better treatment strategy.

PMID: 27614734 [PubMed - as supplied by publisher]

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[Radiotherapy in retroperitoneal sarcomas].

[Radiotherapy in retroperitoneal sarcomas].

Bull Cancer. 2016 Sep 7;

Authors: AlGhamdi H, Thariat J

PMID: 27614733 [PubMed - as supplied by publisher]

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Phase I and pharmacokinetic evaluation of the anti-telomerase agent KML-001 with cisplatin in advanced solid tumors

Abstract

Purpose

KML-001 (sodium metaarsenite) displaces hTERT from the nucleus and is synergistic with cisplatin. This phase I trial tested the tolerability, activity and pharmacology of this combination.

Methods

Patients with advanced solid tumors that were "platinum sensitive," PS 0-1, normal renal and hepatic function were eligible. Treatment was with cisplatin 75 mg/m² day 1 and KML-001 p.o. daily days 1–14 on a 21-day cycle. A standard 3 + 3 design was employed. Blood specimens for arsenic and platinum pharmacokinetics were obtained at 0, 1, 2, 3, 4, 5, 6, 24 h and days 8, 15 and 22.

Results

Eighteen patients (7 M, 11 F) were evaluable for the primary endpoint of toxicity. Patients were heavily pretreated for a variety of malignancies (mean number of prior regimens = 3). Sixteen had prior platinum therapy. The dose-limiting toxicity was prolongation of the QTc interval, seen in three patients in cohort 3 (20 mg) (two during cycle 1, one during cycle 2). A documented response was seen in a patient with heavily pretreated SCLC in cohort one. Several other patients had reduction in tumor burden. In addition to the dose-limiting toxicity of QTc prolongation, the most common toxicities observed were nausea and vomiting and cytopenias. Myelosuppression was primarily seen in patients who had undergone prior radiotherapy.

Conclusions

The combination of KML-001 and cisplatin was technically feasible and active. However, the occurrence of significant QTc prolongation led to discontinuation of the trial. This prolongation was likely a result of electrolyte abnormalities resulting from cisplatin superimposed on the known risks of arsenicals and QTc prolongation. Combinations with other platinum agents (e.g., carboplatin) should be considered. This is the first fully reported human trial of KML-001.

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Rectal melanoma: epidemiology, prognosis, and role of adjuvant radiation therapy

Abstract

Purpose

Rectal melanoma (RM) is a lethal malignancy which is not well understood. While cases are rising, data concerning effective management are limited. The present paper sought to elucidate the epidemiology and prognosis of RM, while also analyzing the role of adjuvant radiation therapy (RT).

Methods

We used the surveillance, epidemiology, and end results program to find all cases of RM diagnosed between 2004 and 2011. Patients 18 or older with non-metastatic disease who had undergone surgery were included. Data regarding the age, race, sex, marital status, stage, and radiation sequence with surgery were extracted from the database and analyzed. Disease-free (DFS) and overall survival (OS) was studied for the group overall and between subgroups.

Results

Median age at diagnosis was 69 years. RM is significantly more common in whites compared to nonwhites and occurs equally in males and females. Most patients are diagnosed at an early stage. Prognosis is poor with a median DFS of 27 months and median OS of 22 months. There were no differences in outcomes based on age, sex, marital status, or stage; however, OS was improved in nonwhites as compared to whites (P = 0.04). RT did not improve DFS (27 vs 28 months for surgery vs surgery and radiation, P = 0.82) or OS (19 vs 22 months for surgery vs surgery and radiation P=0.80) regardless of stage.

Conclusions

RM is an aggressive disease primarily affecting older, white patients. RT does not improve survival, regardless of stage. Optimal management of this lethal disease remains to be elucidated.

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Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines

Abstract

Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.

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Table of Content Volume 55, Number 11, November 2016

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Phase I and pharmacokinetic evaluation of the anti-telomerase agent KML-001 with cisplatin in advanced solid tumors

Abstract

Purpose

KML-001 (sodium metaarsenite) displaces hTERT from the nucleus and is synergistic with cisplatin. This phase I trial tested the tolerability, activity and pharmacology of this combination.

Methods

Patients with advanced solid tumors that were "platinum sensitive," PS 0-1, normal renal and hepatic function were eligible. Treatment was with cisplatin 75 mg/m² day 1 and KML-001 p.o. daily days 1–14 on a 21-day cycle. A standard 3 + 3 design was employed. Blood specimens for arsenic and platinum pharmacokinetics were obtained at 0, 1, 2, 3, 4, 5, 6, 24 h and days 8, 15 and 22.

Results

Eighteen patients (7 M, 11 F) were evaluable for the primary endpoint of toxicity. Patients were heavily pretreated for a variety of malignancies (mean number of prior regimens = 3). Sixteen had prior platinum therapy. The dose-limiting toxicity was prolongation of the QTc interval, seen in three patients in cohort 3 (20 mg) (two during cycle 1, one during cycle 2). A documented response was seen in a patient with heavily pretreated SCLC in cohort one. Several other patients had reduction in tumor burden. In addition to the dose-limiting toxicity of QTc prolongation, the most common toxicities observed were nausea and vomiting and cytopenias. Myelosuppression was primarily seen in patients who had undergone prior radiotherapy.

Conclusions

The combination of KML-001 and cisplatin was technically feasible and active. However, the occurrence of significant QTc prolongation led to discontinuation of the trial. This prolongation was likely a result of electrolyte abnormalities resulting from cisplatin superimposed on the known risks of arsenicals and QTc prolongation. Combinations with other platinum agents (e.g., carboplatin) should be considered. This is the first fully reported human trial of KML-001.

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Gene panel sequencing in familial Breast/Ovarian Cancer patients identifies multiple novel mutations also in genes others than BRCA1/2

Abstract

Breast and ovarian cancer (BC/OC) predisposition has been attributed to a number of high- and moderate to low-penetrance susceptibility genes. With the advent of next generation sequencing (NGS) simultaneous testing of these genes has become feasible. In this monocentric study we report results of panel-based screening of 14 BC/OC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, CHEK2, PALB2, ATM, NBN, CDH1, TP53, MLH1, MSH2, MSH6 and PMS2) in a group of 581 consecutive individuals from a German population with BC and/or OC fulfilling diagnostic criteria for BRCA1 and BRCA2 testing including 179 with a triple-negative tumor. Altogether we identified 106 deleterious mutations in 105 (18%) patients in 10 different genes, including 7 different exon deletions. Of these 106 mutations, 16 (15%) were novel and only six were found in BRCA1/2. To further characterize mutations located in or nearby splicing consensus sites we performed RT-PCR analysis which allowed confirmation of pathogenicity in 7 of 9 mutations analyzed. In PALB2 we identified a deleterious variant in six cases. All but one were associated with early onset BC and a positive family history indicating that penetrance for PALB2 mutations is comparable to BRCA2. Overall, extended testing beyond BRCA1/2 identified a deleterious mutation in further 6% of patients. As a downside, 89 variants of uncertain significance were identified highlighting the need for comprehensive variant databases. In conclusion, panel testing yields more accurate information on genetic cancer risk than assessing BRCA1/2 alone and wide-spread testing will help improve penetrance assessment of variants in these risk genes. This article is protected by copyright. All rights reserved.

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Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer-associated fibroblasts by paracrine activation of protease-activated receptor 2

Abstract

Cancer-associated fibroblasts (CAFs) are known to contribute to cancer progression. We have reported that cell surface expression of hepatocyte growth factor activator inhibitor 1 (HAI-1) is decreased in invasive oral squamous cell carcinoma (OSCC) cells. This study examined if HAI-1-insufficiency contributes to CAF recruitment in OSCC. Serum-free conditioned medium (SFCM) from a human OSCC line (SAS) stimulated the migration of 3 human fibroblast cell lines, NB1RGB, MRC5 and KD. SFCM from HAI-1-knockdown SAS showed an additive effect on the migration of NB1RGB and MRC5, but not KD. SAS SFCM induced protease-activated receptor-2 (PAR-2) expression in NB1RGB and MRC5, but not in KD, and a PAR-2 antagonist blocked the stimulatory effect of HAI-1 knockdown on migration of the PAR-2 expressing cell lines. Moreover, HAI-1-deficient SFCM showed additive stimulatory effects on the migration of wild-type but not PAR-2-deficient mouse fibroblasts. Therefore, the enhanced migration induced by HAI-1-insufficiency was mediated by PAR-2 activation in fibroblasts. This activation resulted from the deregulation of the activity of matriptase, a PAR-2 agonist protease. HAI-1 may thus prevent CAF recruitment to OSCC by controlling matriptase activity. When HAI-1 expression is reduced on OSCC, matriptase may contributed to CAF accumulation by paracrine activation of fibroblast PAR-2. Immunohistochemical analysis of resected OSCC revealed increased PAR2-positive CAFs in 35% (33/95) of the cases studied. The increased PAR-2 positive CAFs tended to correlate with infiltrative histology of the invasion front and shorter disease-free survival of the patients. This article is protected by copyright. All rights reserved.

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Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti-melanoma immune response

Abstract

Melanoma is a highly lethal cutaneous tumor, killing affected patients through development of multiple poorly immunogenic metastases. Suboptimal activation of immune system by melanoma cells is often due to molecular modifications occurring during tumor progression that prevent efficient recognition of melanoma cells by immune effectors. Statins are HMG-CoA reductase inhibitors, which block the mevalonate synthesis pathway, used by millions of people as hypocholesterolemic agents in cardiovascular and cerebrovascular diseases. They are also known to inhibit Rho GTPase activation and Rho dependent signaling pathways. Rho GTPases are regarded as molecular switches that regulate a wide spectrum of cellular functions and their dysfunction has been characterized in various oncogenic process notably in melanoma progression. Moreover, these molecules can modulate the immune response. Since ten years we have demonstrated that Statins and other Rho GTPases inhibitors are critical regulators of molecules involved in adaptive and innate anti-melanoma immune response. In this review we summarize our major observations demonstrating that these pharmacological agents stimulate melanoma immunogenicity and suggest a potential use of these molecules to promote anti-melanoma immune response. This article is protected by copyright. All rights reserved.

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Longitudinal fluctuation in mammographic percent density differentiates between interval and screen-detected breast cancer

Abstract

Interval breast cancer (IC) has a more aggressive phenotype and higher mortality than screen-detected cancer (SDC). In this case-case study, we investigated whether the size of longitudinal fluctuations in mammographic percent density (PD fluctuation) was associated with the ratio of IC vs. SDC among screened women with breast cancer. The primary study population consisted of 1,414 postmenopausal breast cancer cases, and the validation population of 1,241 cases. We calculated PD fluctuation as the quadratic mean of deviations between actual PD and the long-term trend estimated by a mixed effects model. In a logistic regression model we examined the association between PD fluctuation and interval vs. screen-detected cancer including adjustments for PD at last screening, age at diagnosis, BMI and hormone replacement therapy. All statistical tests were two-sided. There were 385 IC and 1029 SDC in the primary study population, with PD fluctuations of 0.44 and 0.41 respectively (p=0.0309). After adjustments, PD fluctuation was associated with an increased ratio of IC vs. SDC, with an estimated per-standard deviation odds ratio of 1.17 (95% CI = 1.03 to 1.33), compared to 1.19 (95% CI = 1.04 to1.38) in the validation population. In screened women with breast cancer, high fluctuation in mammographic percent density was associated with an increased ratio of IC vs. SDC. Whether this is entirely related to a reduced mammographic detectability or to a biological phenotype promoting faster tumor growth remains to be elucidated. This article is protected by copyright. All rights reserved.

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Recurrence-free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy

Abstract

The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence-free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non-)completion. Patients aged ≥70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non-academic hospitals were included. RFS and OS were analyzed with Kaplan-Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five-year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p=0.91), adjusted HR=0.99 (95%CI 0.68-1.44); OS: 66% vs. 66% (p=0.76), adjusted HR=0.93 (95%CI 0.64-1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three-year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p=0.21), adjusted HR=1.42 (95%CI 0.85-2.37); OS: 68% vs. 78% (p=0.41), adjusted HR=1.17 (95%CI 0.70-1.97)). Three-year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p=0.01), adjusted HR=2.07 (95%CI 1.11-3.84); OS: 65% vs. 80% (p=0.01), adjusted HR=2.00 (95%CI 1.12-3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients. This article is protected by copyright. All rights reserved.

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Mutant p53: A Novel Target for the Treatment of Patients with Triple-Negative Breast Cancer?

Abstract

The identification and validation of a targeted therapy for patients with triple-negative breast cancer (TNBC) is currently one of the most urgent needs in breast cancer therapeutics. One of the key reasons for the failure to develop a new therapy for this subgroup of breast cancer patients has been the difficulty in identifying a highly prevalent, targetable molecular alteration in these tumors. Recently however, the p53 gene was found to be mutated in approximately 80% of basal/TNBC, raising the possibility that targeting the mutant p53 protein product might be a new approach for the treatment of this form of breast cancer. In this study, we investigated the anti-cancer activity of PRIMA-1 and PRIMA-1^MET (APR-246), two compounds which were previously reported to reactivate mutant p53 and convert it to a form with wild-type (WT) properties. Using a panel of 18 breast cancer cell lines and 2 immortalized breast cell lines, inhibition of proliferation by PRIMA-1 and PRIMA-1^MET was found to be cell-line dependent, but independent of cell line molecular subtype. Although response was independent of molecular subtype, p53 mutated cell lines were significantly more sensitive to PRIMA-1^MET than p53 WT cells (p=0.029). Furthermore, response (measured as IC₅₀ value) correlated significantly with p53 protein level as measured by ELISA (p=0.0089, r=-0.57, n=19). In addition to inhibiting cell proliferation, PRIMA-1^MET induced apoptosis and inhibited migration in a p53 mutant-dependent manner. Based on our data, we conclude that targeting mutant p53 with PRIMA-1^MET is a potential new approach for treating p53-mutated breast cancer, including the subgroup with triple-negative (TN) disease. This article is protected by copyright. All rights reserved.

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Lipoxin A4 selectively programs the profile of m2 tumor-associated macrophages which favour control of tumor progression

Abstract

In tumor microenvironments, the macrophage population is heterogeneous, but some macrophages can acquire tumor-promoting characteristics. These tumor-associated macrophages (TAM) exhibit an M2-like profile, with deficient production of NO and ROS, characteristics of pro-inflammatory M1 cytotoxic macrophages. Lipoxins (LX) and 15-epi-lipoxins are lipid mediators which can induce certain features of M2 macrophages in mononuclear cells, but their effects on TAM remain to be elucidated. This study tested the hypothesis that ATL-1, a synthetic analogue of 15-epi-lipoxin A₄, could modulate TAM activity profile. We show that human macrophages (MΦ) differentiated into TAM-like cells after incubation with conditioned medium from MV3, a human melanoma lineage cell. Contrasting with the effects observed in other M2 subsets and M1 profile macrophages, ATL-1 selectively decreased M2 surface markers in TAM, suggesting unique behaviour of this particular M2 subset. Importantly, these results were replicated by the natural lipoxins LXA₄ and the aspirin induced 15-epi-LXA₄ (ATL). In parallel, ATL-1 stimulated TAM to produce NO by increasing the iNOS/arginase ratio and activated NADPH oxidase, triggering ROS production. These alterations in TAM profile induced by ATL-1 led to loss of the anti-apoptotic effects of TAM on melanoma cells and increased their cytotoxic properties. Finally, ATL-1 was found to inhibit tumor progression in a murine model in vivo, which was accompanied by alterations in TAM profile and diminished angiogenesis. Together, the results show an unexpected effect of lipoxin, which induces in TAM a change from an M2- to an M1-like profile, thereby triggering tumor cell apoptosis and down-modulating the tumor progression. This article is protected by copyright. All rights reserved.

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IFR4/MUM1-positive lymphoma in Waldeyer ring with co-expression of CD5 and CD10

Abstract

IRF4/MUM1-positive lymphoma is a new subgroup of germinal center-derived B-cell lymphoma, predominantly involving the Waldeyer ring (WR) in children. CD5 expression is rare in these lymphomas. We report a 7-year-old Chinese male with B-cell lymphoma. Evaluation of his specimen by morphology, immunohistochemistry, and FISH analysis demonstrated IRF4/MUM1-positive lymphoma with strong and extensive CD5 and CD10 positivity. Despite the lack of t(14;18)(q32;q21) rearrangement, BCL2 protein was expressed. Our report highlights the clinicopathologic features of IFR4/MUM1-positive lymphoma in WR with co-expression of CD5 and CD10, and thereby provides insight into this newly recognized disease entity.

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A novel immunomodulatory treatment involving mycophenolate mofetil and corticosteroids for pediatric autoimmune cytopenias

Abstract

Background

Successful treatment of both pediatric autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP), specifically those that are refractory to first-line therapies, remains unsatisfactory in terms of long-term remission and medication side effects. Here, we propose a novel combination therapy of mycophenolate mofetil (MMF), an adjunct immunosuppressive, and short-term corticosteroids for the treatment of persistent or chronic autoimmune cytopenias in children. This combination may allow for rapid decrease of steroid usage as well as prolonged count stabilization with minimal toxicity to the patient.

Procedure

Prospective case series of nine patients, six with persistent or chronic ITP and three with persistent or chronic AIHA, between the ages of 5 and 19 years who are being treated with combination therapy consisting of corticosteroids and MMF.

Results

All patients with ITP (Patients 4–9) and AIHA (Patients 1–3) met complete response (CR) criteria, as they all initially achieved platelet counts 100 × 10⁹ l^–1 or more or hemoglobin level greater than or equal to 10 g/dl, respectively, while on combination therapy and then maintained this level or higher while on MMF alone after steroids were discontinued.

Conclusions

Our results are very promising, as MMF appears to be an effective and well-tolerated adjunct immunosuppressant that allows for rapid weaning of steroid usage, minimal adverse side effects to the patients, and long-term stabilization of counts, a goal that has not been achieved successfully with other secondary treatment modalities. Therefore, this novel combination therapy may be an excellent alternative for the treatment of persistent or chronic autoimmune cytopenias in the pediatric population.

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It is time to address ambulatory central venous line infections in pediatric hematology/oncology patients

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A home-based physical activity intervention using activity trackers in survivors of childhood cancer: A pilot study

Abstract

Background

Over 70% of childhood cancer survivors develop late complications from therapy, many of which can be mitigated by physical activity. Survivors engage in exercise at similar or lower rates than their sedentary healthy peers. We piloted a novel home-based exercise intervention with a motivational activity tracker. We evaluated (i) feasibility, (ii) impact on activity levels and physical fitness, and (iii) barriers, preferences, and beliefs regarding physical activity.

Methods

Childhood cancer survivors currently 15 years or older and not meeting the Centers for Disease Control and Prevention physical activity guidelines were enrolled and instructed to wear the Fitbit One, a 4.8 cm × 1.8 cm motivational activity tracker, daily for 6 months. Baseline and follow-up evaluations included self-report surveys, an Actigraph accelerometer for 7 days, and a VO₂ maximum test by cardiac stress test.

Results

Nineteen participants were enrolled (13.4% participation rate) with a mean age of 24.3 ± 5.8 years (range 15–35). Four participants withdrew with a 79% retention rate. Participants wore the Fitbit an average of 19.0 ± 4.7 days per month during months 1–3 and 15.0 ± 7.9 days per month during months 4–6. Total weekly moderate to vigorous physical activity increased from 265.6 ± 117.0 to 301.4 ± 135.4 min and VO₂ maximum increased from 25.7 ± 7.7 to 27.2 ± 7.4 ml/kg/min. These changes were not statistically significant (P = 0.47 and 0.30, respectively). Survey responses indicated no change in barriers, preferences, and beliefs regarding physical activity.

Conclusions

This pilot study of a motivational activity tracker demonstrated feasibility as measured by participant retention, receptivity, and belief of utility. Future studies with a large sample size are needed to demonstrate the efficacy and sustainability of this intervention.

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