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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τρίτη 13 Σεπτεμβρίου 2016
The flavonoid apigenin from Croton betulaster Mull inhibits proliferation, induces differentiation and regulates the inflammatory profile of glioma cells.
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Lentivirus-mediated p21/Waf-1 short hairpin RNA enhances the cytotoxic effects and replicative potential of a bladder cancer-specific oncolytic adenovirus in vitro.
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Resolving Rivalries and Realigning Goals: Challenges of Clinical and Research Multiteam Systems [Original Contribution]
This article describes the care processes for a 64-year-old man with newly diagnosed advanced non–small-cell lung cancer who was enrolled in a first-line clinical trial of a new immunotherapy regimen. The case highlights the concept of multiteam systems in cancer clinical research and clinical care. Because clinical research represents a highly dynamic entity—with studies frequently opening, closing, and undergoing modifications—concerted efforts of multiple teams are needed to respond to these changes while continuing to provide consistent, high-level care and timely, accurate clinical data. The case illustrates typical challenges of multiteam care processes. Compared with clinical tasks that are routinely performed by single teams, multiple-team care greatly increases the demands for communication, collaboration, cohesion, and coordination among team members. As the case illustrates, the described research team and clinical team are separated, resulting in suboptimal function. Individual team members interact predominantly with members of their own team. A considerable number of team members lack regular interaction with anyone outside their team. Accompanying this separation, the teams enact rivalries that impede collaboration. The teams have misaligned goals and competing priorities that create competition. Collective identity and cohesion across the two teams are low. Research team and clinical team members have limited knowledge of the roles and work of individuals outside their team. Recommendations to increase trust and collaboration are provided. Clinical providers and researchers may incorporate these themes into development and evaluation of multiteam systems, multidisciplinary teams, and cross-functional teams within their own institutions.
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Reliability, Validity, and Feasibility of a Computer-Based Geriatric Assessment for Older Adults With Cancer [Focus on Quality]
Purpose:
The goal of this study was to evaluate the feasibility, reliability, and validity of a computer-based geriatric assessment via two methods of electronic data capture (SupportScreen and REDCap) compared with paper-and-pencil data capture among older adults with cancer.
Methods:Eligible patients were ≥ 65 years old, had a cancer diagnosis, and were fluent in English. Patients were randomly assigned to one of four arms, in which they completed the geriatric assessment twice: (1) REDCap and paper and pencil in sessions 1 and 2; (2) REDCap in both sessions; (3) SupportScreen and paper and pencil in sessions 1 and 2; and (4) SupportScreen in both sessions. The feasibility, reliability, and validity of the computer-based geriatric assessment compared with paper and pencil were evaluated.
Results:The median age of participants (N = 100) was 71 years (range, 65 to 91 years) and the diagnosis was solid tumor (82%) or hematologic malignancy (18%). For session 1, REDCap took significantly longer to complete than paper and pencil (median, 21 minutes [range, 11 to 44 minutes] v median, 15 minutes [range, 9 to 29 minutes], P < .01) or SupportScreen (median, 16 minutes [range, 6 to 38 minutes], P < .01). There were no significant differences in completion times between SupportScreen and paper and pencil (P = .50). The computer-based geriatric assessment was feasible. Few participants (8%) needed help with completing the geriatric assessment (REDCap, n = 7 and SupportScreen, n = 1), 89% reported that the length was "just right," and 67% preferred the computer-based geriatric assessment to paper and pencil. Test–retest reliability was high (Spearman correlation coefficient ≥ 0.79) for all scales except for social activity. Validity among similar scales was demonstrated.
Conclusion:Delivering a computer-based geriatric assessment is feasible, reliable, and valid. SupportScreen methodology is preferred to REDCap.
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Shared Goal Setting in Team-Based Geriatric Oncology [Original Contribution]
We present the case of a 92-year-old man, MH, who was given a diagnosis of colorectal cancer. His primary care physician, surgeon, geriatric oncologist, and family members all played important roles in his care. MH's case is an example of a lack of explicit shared goal setting by the health care providers with the patient and family members and how that impeded care planning and health. This case demonstrates the importance of explicitly discussing and establishing shared goals in team-based cancer care delivery early on and throughout the care process, especially for older adults. Each individual member's goals should be understood as they fit within the overarching shared team goals. We emphasize that shared goal setting and alignment of individual goals is a dynamic process that must occur several times at critical decision points throughout a patient's care continuum. Providers and researchers can use this illustrative case to consider their own work and contemplate how shared goal setting can improve patient-centered care and health outcomes in various team-based care settings. Shared goal setting among team members has been demonstrated to improve outcomes in other contexts. However, we stress, that little investigation into the impact of shared goal setting on team-based cancer care delivery has been conducted. We list immediate research goals within team-based cancer care delivery that can provide a foundation for the understanding of the process and outcomes of shared goal setting.
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Using Experience-Based Design to Improve the Care Experience for Patients With Pancreatic Cancer [Quality in Action]
Purpose:
Despite the importance of the patient care experience to quality and outcome, the literature detailing the care experience in patients with pancreatic cancer is limited.
Methods:To elicit the experience of patients with pancreatic cancer for care redesign, we deployed experience-based design, an emerging methodology based on identification of events of high emotional content, known as touch points, to delineate qualitatively what matters most to patients and families. We defined touch points through direct observations, interviews, and a focus group. We then used experience questionnaires to measure emotional content and develop an experience map to graphically display the fluctuating emotional journey through the care processes. Study subjects were patients with pancreatic cancer who were cared for at Virginia Mason Medical Center, family caregivers, and staff. Redesign was initiated through an all-day improvement event in September 2013.
Results:During 2013 and 2014, we cared for 485 new patients with pancreatic cancer, the majority of whom had local disease at diagnosis. The response rate for the experience questionnaire was 23% (117 of 500 questionnaires distributed). The experience-based design results were often contrary to staff preconceptions of the care experience for patients with pancreatic cancer, and contributed to redesign in three key areas: understanding and documenting patient goals and values, providing better resources for caregivers/families, and improving care coordination and support services.
Conclusion:Experience-based design enabled us to understand the care experience and associated emotional content for patients with pancreatic cancer and their caregivers. This knowledge then supported care redesign targeted at areas of high negative emotional content.
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"Winging It": How Older Breast Cancer Survivors Persist With Aromatase Inhibitor Treatment [Care Delivery]
Purpose:
Aromatase inhibitors (AIs) are an important and effective hormonal adjuvant treatment for early-stage breast cancer. Up to 50% of women stop AIs prematurely, missing a valuable therapeutic intervention.
Patients and Methods:We used grounded theory methodology to conduct in-depth, semistructured interviews and analyze data among patients with breast cancer diagnosed at age 65 years or older who were receiving an AI. The goal of the interviews was to understand decision making regarding persisting with AIs. Interview transcripts were systematically analyzed to identify emergent categories and relationships.
Results:Interviews were conducted with 27 women. After completion of primary treatment, women in our sample found themselves "winging it" as they faced substantial struggles with infrequent support during this new phase of the cancer trajectory. Self-management of AI adverse effects occurred in the contexts of older age and early survivorship. "Bearing it" emerged as another important management process regarding the impact of AIs on quality of everyday life. The complex decision to persist with the AI involved weighing the possibility of a cancer-free future against the burden of adverse effects. Women relied on informal networks for support, rather than oncology providers, highlighting the need for practical self-management strategies. The notion of a tipping point in persistence revealed their susceptibility to early discontinuation.
Conclusion:This study provides insight into potential decisional pathways leading to early discontinuation of AIs among older women with breast cancer. Better support is needed for these women.
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Facilitating Teamwork in Adolescent and Young Adult Oncology [Original Contribution]
A case of a young adult patient in the days immediately after a cancer diagnosis illustrates the critical importance of three interrelated core coordinating mechanisms—closed-loop communication, shared mental models, and mutual trust—of teamwork in an adolescent and young adult multidisciplinary oncology team. The case illustrates both the opportunities to increase team member coordination and the problems that can occur when coordination breaks down. A model for teamwork is presented, which highlights the relationships among these coordinating mechanisms and demonstrates how balance among them works to optimize team function and patient care. Implications for clinical practice and research suggested by the case are presented.
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BCR-ABL Testing by Polymerase Chain Reaction in Patients With Neutrophilia: The William Beaumont Hospital Experience and the Case for Rational Laboratory Test Requests [Care Delivery]
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from the fusion of the BCR-ABL genes, forming the Philadelphia chromosome. The diagnosis is often suspected when there is leukocytosis with left shift and basophilia. Confirmation of the diagnosis requires a demonstration of BCR-ABL by polymerase chain reaction. Using data from the William Beaumont laboratory data registry, we conducted a retrospective review of all the orders for BCR-ABL tests sent to the clinical pathology laboratory between March 11, 2014 and September 12, 2014. We concluded that the presence of concurrent neutrophilia and basophilia has a sensitivity of 100% (95% CI, 69.15% to 100%) and specificity of 100% (95% CI, 93.15% to 100%) in the initial diagnosis of CML. Our results suggest that the presence of both neutrophilia and basophilia should be used as a threshold for the placement of orders for BCR-ABL in the initial diagnosis of CML in patients with leukocytosis with left shift and provide a basis for a reduction in health care spending. Restricting BCR-ABL tests to this population would save approximately $198 million annually in national health care spending.
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Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment
Abstract
Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.
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Global methylation profiling to identify epigenetic signature of gallbladder cancer and gallstone disease
Abstract
Promoter methylation in various tumor suppressor genes is reported to influence gallbladder carcinogenesis. Here, we aimed to identify methylation status in gallbladder cancer (GBC) by performing a comprehensive genome-wide DNA methylation profiling. The methylation status of 485,577 CpG sites were investigated using Illumina's Infinium Human Methylation 450 BeadChip array in 24 tissues (eight each of tumor, adjacent non-tumor, and gallstone). About 33,443 differentially methylated sites (DMRs) were obtained in the whole human genome, of which 24,188 (72 %) were hypermethylated and 9255 (28 %) were hypomethylated. The data also revealed that majority of the DMRs are localized on the proximal promoter region [Transcription start sites (TSS200, TSS1500) and 5′ untranslated region (5′UTR)] and first exon. Exclusion of first exon detected a total of 10,123 (79 %) hypermethylated and 2703 (21 %) hypomethylated sites. Comparative analysis of the later with our differential proteomics data resulted in identification of 7 hypermethylated or down-regulated (e.g., FBN1, LPP, and SOD3) and 61 hypomethylated or up-regulated markers (e.g., HBE1, SNRPF, TPD52) for GBC. These genes could be further validated on the basis of their methylation/expression status in order to identify their utility to be used as biomarker/s for early diagnosis and management of GBC.
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Aberrant microRNA expression in tumor mycosis fungoides
Abstract
Herein, miRNA candidates relevant to mycosis fungoides were investigated to provide data on the molecular mechanisms underlying the pathogenesis of the disease. The miRNA expression profile of skin biopsies from patients with tumor stage MF (tMF) and normal donors was compared using miRNA microarrays. Overall, 154 miRNAs were found differentially expressed between tMF and the control cohort with the majority of them being up-regulated (57 %). Among the upregulated miRNAs, miR-3177, miR-514b-3p, miR-1267, and miR-1282 were exclusively detected in 70 % of tMF. Additional upregulated miRNAs included miR-34a, miR-29a, let-7a*, and miR-210, while miR-200c* was identified among the downregulated ones. Quantitative real-time polymerase chain reaction was used to further investigate the expression profiles of miR-34a and miR-29a and validated the overexpression of miR-34a. Enrichment studies revealed that the target genes of the differentially expressed miRNAs were important in several cancer-related signaling pathways. The overlapping relationship of the target genes among tMF, Sezary syndrome, and atopic dermatitis revealed several common and disease-specific genes. Collectively, our study modulated miR-34a as a candidate oncogenic molecule and miR-29a as a putative tumor suppressor highlighting their promising potential in the molecular pathogenesis of tMF.
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IGF-I receptor as an emerging potential molecular-targeted for hepatocellular carcinoma in vitro and in vivo
Abstract
Abnormal expression of insulin-like growth factor I receptor (IGF-IR) is associated with hepatocellular carcinoma (HCC) progression with largely unknown mechanisms. In this study, IGF-IR expression among different HCC cell lines and silencing its gene transcription on effects of HCC were investigated by short hairpin RNA (shRNA). Specific shRNA was successfully transfected into Bel-7404 or PLC/PRF/5 cells with 90 or 71 % efficiency. The inhibiting rate of IGF-IR at mRNA level were 54.9 % in Bel-7404 or 59.6 % in PLC/PRF/5 cells in accordance with its protein suppression, with the cell cycles at the G1 phase arrest and decreasing cyclinD1 via promoting apoptosis in vitro. With the xenograft models of PLC/PRF/5 cells inserted specific shRNA in vivo, the tumor-forming time (14.0 ± 1.1 days) or tumor volume (143 ± 24 mm3) in the shRNA group was significantly lengthened or smaller than those in the control group (7.2 ± 0.8 days or 372 ± 46 mm3, P < 0.001) or in the neg-shRNA group (7.5 ± 1.0 days or 350 ± 50 mm3, P < 0.001). Silencing the IGF-IR gene transcription inhibited cell proliferation or xenograft tumor growth of HCC, suggesting that IGF-IR might be a novel potential target for HCC gene therapy.
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Determination of a CD4 + CD25 − FoxP3 + T cells subset in tumor-draining lymph nodes of colorectal cancer secreting IL-2 and IFN-γ
Abstract
CD4+CD25−FoxP3+ cells are a newly recognized subset of T cells which was first reported in autoimmune diseases. In our previous study, this subset was detected in tumor-draining lymph nodes (TDLNs) of patients with breast cancer. As little is known about their function in TDLNs of cancer patients, in this study, their frequency as well as their ability to produce interleukin (IL)-2, IL-10, or interferon (IFN)-γ were investigated in TDLNs of colorectal cancer (CRC) patients. Mononuclear cells were isolated from lymph nodes of 13 patients with CRC using Ficoll-Hypaque gradient centrifugation. Cells were stimulated in vitro and stained with CD25, CD4, FoxP3, IFN-γ, IL-10, and IL-2 or isotype matched antibodies and subjected to flow cytometry. The frequency of CD4+CD25−FoxP3+CD127dim/− cells was significantly lower than CD4+CD25+FoxP3+CD127dim/− population in TDLNs of CRC patients. The percentage of CD127dim/− cells and also the MFI of FoxP3 expression was significantly lower in CD4+CD25−FoxP3+ in comparison with CD4+CD25+FoxP3+ population. Moreover, CD4+CD25−FoxP3+ cells contained higher percentages of IL-2- and IFN-γ-producing cells than CD4+CD25+FoxP3+ subpopulation. But, no difference was seen between two subsets in terms of IL-10 production. CD4+CD25−FoxP3+ cells in TDLNs of CRC patients had lower suppressive and higher effector properties in comparison with CD4+CD25+FoxP3+ conventional regulatory T cells.
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Cofilin activation inhibits centrosome clustering.
Centrosome amplification (CA) is a hallmark of virtually all types of cancers including solid tumors and hematological malignancies. Cancer cells with extra centrosomes use centrosome clustering (CC) to allow for successful division. Because normal cells do not rely on this mechanism, CC is regarded as a promising target to selectively eradicate cells harboring supernumerary centrosomes. To identify novel inhibitors of CC, we developed a cell-based high-throughput screen that reports differential drug cytotoxicity for isogenic cell populations with different centrosome contents. We identified CP-673451 and crenolanib, two chemically related compounds originally developed for inhibition of PDGFR-β, as robust inhibitors of CC with selective cytotoxicity for cells with extra centrosomes. We demonstrate that these compounds induce mitotic spindle multipolarity by activation of the actin severing protein cofilin, leading to destabilization of the cortical actin network, and provide evidence that this activation is dependent on slingshot phosphatases 1 and 2 but unrelated to PDGFR-β inhibition. More specifically, we found that although both compounds attenuated PDGF-BB-induced signaling, they significantly enhanced the phosphorylation of PDGFR-β downstream effectors, Akt and MEK, in almost all tested cancer cell lines under physiological conditions. In summary, our data reveal a novel mechanism of CC inhibition depending on cofilin-mediated cortical actin destabilization and identify two clinically relevant compounds interfering with this tumor cell specific target.
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Genetic evolution in metastatic lymph nodes of lung cancer
Tumor heterogeneity influences the clinical outcome of cancer patients, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six lung cancer patients using whole exome sequencing and RNA-seq. Although somatic single nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomical location of the tumors. Four out of six cases exhibited a branched clonal evolution pattern. Lymph nodes with acquired somatic variants demonstrated resistance to the cancer treatment. In this study, we demonstrated that multiple biopsies and sequencing strategies for different tumor regions are required for a comprehensive understanding of the landscape of genetic alteration and for guiding targeted therapy in advanced primary lung cancer.
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Symptom clusters and survival in Portuguese patients with advanced cancer
Abstract
This study aimed to identify clusters of symptoms, to determine the patient characteristics associated with identified, and determine their strength of association with survival in patients with advanced cancer (ACPs). Consecutively eligible ACPs not receiving cancer-specific treatment, and referred to a Tertiary Palliative Care Clinic, were enrolled in a prospective cohort study. At first consultation, patients rated 9 symptoms through the Edmonton Symptom Assessment System (0–10 scale) and 10 others using a Likert scale (1–5). Principal component analysis was used in an exploratory factor analysis to identify. Of 318 ACPs, 301 met eligibility criteria with a median (range) age of 69 (37–94) years. Three SCs were identified: neuro-psycho-metabolic (NPM) (tiredness, lack of appetite, lack of well−being, dyspnea, depression, and anxiety); gastrointestinal (nausea, vomiting, constipation, hiccups, and dry mouth) and sleep impairment (insomnia and sleep disturbance). Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter survival was observed for patients with the NPM cluster (58 vs. 23, P < 0.001), as well as for patients with two or more SCs (45 vs. 21, P = 0.005). In a multivariable model for survival at 30-days, age (HR: 0.98; 95% CI: 0.97–0.99; P = 0.008), hospitalization at inclusion (HR: 2.27; 95% CI: 1.47–3.51; P < 0.001), poorer performance status (HR: 1.90, 95% CI: 1.24–2.89; P = 0.003), and NPM (HR: 1.64; 95% CI: 1.17–2.31; P = 0.005), were associated with worse survival. Three clinically meaningful SC in patients with advanced cancer were identifiable. The NPM cluster and the presence of two or more SCs, had prognostic value in relation to survival.
Three clinically meaningful symptom clusters were identified in patients with advanced cancer. The neuro-psycho-metabolic cluster and the presence of two or more symptom clusters were associated with a poorer survival prognosis.
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New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma: a retrospective study
In patients with diffuse large B-cell lymphoma (DLBCL), central nervous system (CNS) relapse is uncommon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL pati...
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Pancreatic Cancer Cells May Obtain Nutrients from Neighboring Cells
Pancreatic cancer cells grow by instructing neighboring cells to provide them with nutrients, a new study published online August 10 in Nature has shown.
The researchers found that when grown together in culture, cancer cells prompted cells from the tumor microenvironment to degrade their own proteins and supply the cancer cells with the resulting amino acids. This external nutrient supply led to increased metabolism and growth in the pancreatic cancer cells. In separate experiments in mice, blocking the supply of nutrients from cells in the tumor microenvironment slowed pancreatic tumor growth.
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Blue Ribbon Panel Report: The Power of the Cancer Community Coming Together
Listening to the presentation of the Cancer Moonshot Blue Ribbon Panel report at the National Cancer Advisory Board (NCAB) meeting earlier this week, I was moved and inspired by this culmination of 5 months of work. The report demonstrates the power of the cancer community coming together as it never has before to deliver a promise of progress against cancer. The time, energy, dedication, and ideas that went into the report's creation have been nothing short of extraordinary, and I'd like to thank the cancer community for participating in this collaborative and important undertaking.
This report represents the collaboration of science, technology, advocacy, social science, and big data to solve some of cancer's greatest challenges. At the core of the report are 10 bold yet feasible initiatives that can benefit patients by changing the trajectory of our understanding of how cancer develops, how to prevent it, and how to treat it. I am honored to deliver this compelling report to Vice President Biden and my federal colleagues on the Cancer Moonshot Task Force for inclusion in their reports to the President later this fall.
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Powering Tumor Metastasis with Recycled Fuel
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Mien-Chie Hung, Riyao Yang, Yutong Sun
Receptor tyrosine kinase (RTK) recycling is of critical importance for RTK signaling and cancer, yet the process is poorly understood. In this issue, Ye et al. identify GOLM1 as a cargo adaptor that drives hepatocellular carcinoma metastasis by promoting EGFR recycling and provide insights into how this process is regulated.
Teaser
Receptor tyrosine kinase (RTK) recycling is of critical importance for RTK signaling and cancer, yet the process is poorly understood. In this issue, Ye et al. identify GOLM1 as a cargo adaptor that drives hepatocellular carcinoma metastasis by promoting EGFR recycling and provide insights into how this process is regulated.from Cancer via ola Kala on Inoreader http://ift.tt/2co0fC4
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T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Ilaria Marigo, Serena Zilio, Giacomo Desantis, Bernhard Mlecnik, Andrielly H.R. Agnellini, Stefano Ugel, Maria Stella Sasso, Joseph E. Qualls, Franz Kratochvill, Paola Zanovello, Barbara Molon, Carola H. Ries, Valeria Runza, Sabine Hoves, Amélie M. Bilocq, Gabriela Bindea, Emilia M.C. Mazza, Silvio Bicciato, Jérôme Galon, Peter J. Murray, Vincenzo Bronte
Effective cancer immunotherapy requires overcoming immunosuppressive tumor microenvironments. We found that local nitric oxide (NO) production by tumor-infiltrating myeloid cells is important for adoptively transferred CD8+ cytotoxic T cells to destroy tumors. These myeloid cells are phenotypically similar to inducible nitric oxide synthase (NOS2)- and tumor necrosis factor (TNF)-producing dendritic cells (DC), or Tip-DCs. Depletion of immunosuppressive, colony stimulating factor 1 receptor (CSF-1R)-dependent arginase 1+ myeloid cells enhanced NO-dependent tumor killing. Tumor elimination via NOS2 required the CD40-CD40L pathway. We also uncovered a strong correlation between survival of colorectal cancer patients and NOS2, CD40, and TNF expression in their tumors. Our results identify a network of pro-tumor factors that can be targeted to boost cancer immunotherapies.
Graphical abstract
Teaser
Marigo et al. show that nitric oxide produced by Tip-DCs, a subset of tumor-infiltrating myeloid cells, is important for tumor control by adoptive cell therapy (ACT). Tip-DCs require the CD40-CD40L pathway but not CSF-1R; CSF-1R blockade reduces immunosuppressive macrophages and improves tumor control by ACT.from Cancer via ola Kala on Inoreader http://ift.tt/2chRk8j
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Co-inhibition of CD73 and A2AR Adenosine Signaling Improves Anti-tumor Immune Responses
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Arabella Young, Shin Foong Ngiow, Deborah S. Barkauskas, Erin Sult, Carl Hay, Stephen J. Blake, Qihui Huang, Jing Liu, Kazuyoshi Takeda, Michele W.L. Teng, Kris Sachsenmeier, Mark J. Smyth
Preclinical studies targeting the adenosinergic pathway have gained much attention for their clinical potential in overcoming tumor-induced immunosuppression. Here, we have identified that co-blockade of the ectonucleotidase that generates adenosine CD73 and the A2A adenosine receptor (A2AR) that mediates adenosine signaling in leuokocytes, by using compound gene-targeted mice or therapeutics that target these molecules, limits tumor initiation, growth, and metastasis. This tumor control requires effector lymphocytes and interferon-γ, while antibodies targeting CD73 promote an optimal therapeutic response in vivo when engaging activating Fc receptors. In a two-way mixed leukocyte reaction using a fully human anti-CD73, we demonstrated that Fc receptor binding augmented the production of proinflammatory cytokines.
Graphical abstract
Teaser
Young et al. show that blockade of CD73 and A2AR, two components of the adenosinergic pathway, has more potent anti-tumor activity than blockade of either, partly due to increased CD73 expression in the absence of A2AR. Moreover, anti-CD73 antibodies require the FcR binding domain for optimal anti-tumor activity.from Cancer via ola Kala on Inoreader http://ift.tt/2chSIb7
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Tipping the Balancing ACT
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Shari Pilon-Thomas, Brian Ruffell
Adoptive cell transfer therapy has emerged as a powerful treatment for metastatic melanoma, but efficacy is limited by an inhospitable tumor microenvironment. In this issue of Cancer Cell, Marigo et al. demonstrate that therapy requires induced expression of nitric oxide synthase 2 in monocyte-derived dendritic cells.
Teaser
Adoptive cell transfer therapy has emerged as a powerful treatment for metastatic melanoma, but efficacy is limited by an inhospitable tumor microenvironment. In this issue of Cancer Cell, Marigo et al. demonstrate that therapy requires induced expression of nitric oxide synthase 2 in monocyte-derived dendritic cells.from Cancer via ola Kala on Inoreader http://ift.tt/2cJr7ea
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Physiologic Expression of Sf3b1K700E Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Esther A. Obeng, Ryan J. Chappell, Michael Seiler, Michelle C. Chen, Dean R. Campagna, Paul J. Schmidt, Rebekka K. Schneider, Allegra M. Lord, Lili Wang, Rutendo G. Gambe, Marie E. McConkey, Abdullah M. Ali, Azra Raza, Lihua Yu, Silvia Buonamici, Peter G. Smith, Ann Mullally, Catherine J. Wu, Mark D. Fleming, Benjamin L. Ebert
More than 80% of patients with the refractory anemia with ring sideroblasts subtype of myelodysplastic syndrome (MDS) have mutations in Splicing Factor 3B, Subunit 1 (SF3B1). We generated a conditional knockin mouse model of the most common SF3B1 mutation, Sf3b1K700E. Sf3b1K700E mice develop macrocytic anemia due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell (LT-HSC) expansion. Sf3b1K700E myeloid progenitors and SF3B1-mutant MDS patient samples demonstrate aberrant 3′ splice-site selection associated with increased nonsense-mediated decay. Tet2 loss cooperates with Sf3b1K700E to cause a more severe erythroid and LT-HSC phenotype. Furthermore, the spliceosome modulator, E7017, selectively kills SF3B1K700E-expressing cells. Thus, SF3B1K700E expression reflects the phenotype of the mutation in MDS and may be a therapeutic target in MDS.
Graphical abstract
Teaser
Obeng et al. generate knockin mice with Sf3b1K700E, a prevalent mutation in myelodysplastic syndrome (MDS). Sf3b1+/K700E mice display characteristics of MDS. Mouse and human MDS cells expressing SF3B1K700E exhibit aberrant 3′ splice-site selection, and SF3B1K700E sensitizes cells to a spliceosome modulator.from Cancer via ola Kala on Inoreader http://ift.tt/2ckunw0
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Lactate Dehydrogenase B Controls Lysosome Activity and Autophagy in Cancer
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Lucie Brisson, Piotr Bański, Martina Sboarina, Coralie Dethier, Pierre Danhier, Marie-Joséphine Fontenille, Vincent F. Van Hée, Thibaut Vazeille, Morgane Tardy, Jorge Falces, Caroline Bouzin, Paolo E. Porporato, Raphaël Frédérick, Carine Michiels, Tamara Copetti, Pierre Sonveaux
Metabolic adaptability is essential for tumor progression and includes cooperation between cancer cells with different metabolic phenotypes. Optimal glucose supply to glycolytic cancer cells occurs when oxidative cancer cells use lactate preferentially to glucose. However, using lactate instead of glucose mimics glucose deprivation, and glucose starvation induces autophagy. We report that lactate sustains autophagy in cancer. In cancer cells preferentially to normal cells, lactate dehydrogenase B (LDHB), catalyzing the conversion of lactate and NAD+ to pyruvate, NADH and H+, controls lysosomal acidification, vesicle maturation, and intracellular proteolysis. LDHB activity is necessary for basal autophagy and cancer cell proliferation not only in oxidative cancer cells but also in glycolytic cancer cells.
Graphical abstract
Teaser
Brisson et al. show that lactate dehydrogenase B (LDHB) is critical for lysosomal activity and autophagy in cancer cells. Silencing LDHB selectively inhibits the proliferation of both oxidative and glycolytic cancer cells over normal cells, suggesting inhibition of LDHB as a promising anticancer approach.from Cancer via ola Kala on Inoreader http://ift.tt/2ckulo5
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Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Hanlin Zeng, Jia Qu, Nan Jin, Jun Xu, Chenchu Lin, Yi Chen, Xinying Yang, Xiang He, Shuai Tang, Xiaojing Lan, Xiaotong Yang, Ziqi Chen, Min Huang, Jian Ding, Meiyu Geng
Histone deacetylase (HDAC) inhibitors have demonstrated clinical benefits in subtypes of hematological malignancies. However, the efficacy of HDAC inhibitors in solid tumors remains uncertain. This study takes breast cancer as a model to understand mechanisms accounting for limited response of HDAC inhibitors in solid tumors and to seek combination solutions. We discover that feedback activation of leukemia inhibitory factor receptor (LIFR) signaling in breast cancer limits the response to HDAC inhibition. Mechanistically, HDAC inhibition increases histone acetylation at the LIFR gene promoter, which recruits bromodomain protein BRD4, upregulates LIFR expression, and activates JAK1-STAT3 signaling. Importantly, JAK1 or BRD4 inhibition sensitizes breast cancer to HDAC inhibitors, implicating combination inhibition of HDAC with JAK1 or BRD4 as potential therapies for breast cancer.
Graphical abstract
Teaser
Zeng et al. show that HDAC inhibitors (HDACi) promote BRD4-mediated activation of LIFR, which in turn activates JAK1-STAT3 signaling and restrains the efficacy of HDACi in breast cancer. Concurrent inhibition of BRD4 or JAK sensitizes breast cancer, in particular the triple-negative subset, to HDACi.from Cancer via ola Kala on Inoreader http://ift.tt/2ckujfW
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Small-Molecule Targeting of E3 Ligase Adaptor SPOP in Kidney Cancer
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Zhong-Qiang Guo, Tong Zheng, Baoen Chen, Cheng Luo, Sisheng Ouyang, Shouzhe Gong, Jiafei Li, Liu-Liang Mao, Fulin Lian, Yong Yang, Yue Huang, Li Li, Jing Lu, Bidong Zhang, Luming Zhou, Hong Ding, Zhiwei Gao, Liqun Zhou, Guoqiang Li, Ran Zhou, Ke Chen, Jingqiu Liu, Yi Wen, Likun Gong, Yuwen Ke, Shang-Dong Yang, Xiao-Bo Qiu, Naixia Zhang, Jin Ren, Dafang Zhong, Cai-Guang Yang, Jiang Liu, Hualiang Jiang
In the cytoplasm of virtually all clear-cell renal cell carcinoma (ccRCC), speckle-type POZ protein (SPOP) is overexpressed and misallocated, which may induce proliferation and promote kidney tumorigenesis. In normal cells, however, SPOP is located in the nucleus and induces apoptosis. Here we show that a structure-based design and subsequent hit optimization yield small molecules that can inhibit the SPOP-substrate protein interaction and can suppress oncogenic SPOP-signaling pathways. These inhibitors kill human ccRCC cells that are dependent on oncogenic cytoplasmic SPOP. Notably, these inhibitors minimally affect the viability of other cells in which SPOP is not accumulated in the cytoplasm. Our findings validate the SPOP-substrate protein interaction as an attractive target specific to ccRCC that may yield novel drug discovery efforts.
Graphical abstract
Teaser
Using a structure-based design followed by hit optimization, Guo et al. report small-molecule inhibitors that disrupt oncogenic SPOP-mediated pathways by blocking SPOP-substrate interactions and suppress human clear-cell renal cell carcinoma in vitro and in vivo, suggesting the potential of SPOP-targeted therapy.from Cancer via ola Kala on Inoreader http://ift.tt/2cFuKTE
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Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Najoua Lalaoui, Kay Hänggi, Gabriela Brumatti, Diep Chau, Nhu-Y.N. Nguyen, Lazaros Vasilikos, Lisanne M. Spilgies, Denise A. Heckmann, Chunyan Ma, Margherita Ghisi, Jessica M. Salmon, Geoffrey M. Matthews, Elisha de Valle, Donia M. Moujalled, Manoj B. Menon, Sukhdeep Kaur Spall, Stefan P. Glaser, Jennifer Richmond, Richard B. Lock, Stephen M. Condon, Raffi Gugasyan, Matthias Gaestel, Mark Guthridge, Ricky W. Johnstone, Lenka Munoz, Andrew Wei, Paul G. Ekert, David L. Vaux, W. Wei-Lynn Wong, John Silke
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Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Haidong Tang, Yang Wang, Lukasz K. Chlewicki, Yuan Zhang, Jingya Guo, Wei Liang, Jieyi Wang, Xiaoxiao Wang, Yang-Xin Fu
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IDH1, Histone Methylation, and So Forth
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Virginie Penard-Lacronique, Olivier A. Bernard
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An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling
Publication date: 12 September 2016
Source:Cancer Cell, Volume 30, Issue 3
Author(s): Zoi Karoulia, Yang Wu, Tamer A. Ahmed, Qisheng Xin, Julien Bollard, Clemens Krepler, Xuewei Wu, Chao Zhang, Gideon Bollag, Meenhard Herlyn, James A. Fagin, Amaia Lujambio, Evripidis Gavathiotis, Poulikos I. Poulikakos
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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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Associations with intraocular pressure across Europe: The European Eye Epidemiology (E 3 ) Consortium
Abstract
Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analyzis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (−0.17 mmHg per 10 cm; 95 % CI –0.25, −0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.
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The limitations of opportunistic epidemiology, pseudopod epidemiology
Abstract
Epidemiology has been remarkably successful in the past in identifying the important agents of disease, the impact of the environment, both physical and social, and interrelationship with host susceptibility (genomics). Many of the advances in improving the health of individuals and populations have been the result of epidemiology studies that have identified the specific "agents" of disease and application of public health and preventive medicine. In recent years, large longitudinal studies have dominated epidemiology research, especially long incubation period chronic diseases. The initial hypotheses in these studies have been expanded by vertical extension studies using newer technologies to measure independent variables, vertical pseudopods, and additional studies of other diseases, horizontal pseudopods, of the original longitudinal study. Host susceptibility, i.e. genomics, has also become a prominent component of these longitudinal studies. The critical question addressed in this paper is whether these "pseudopod" epidemiology approaches have enhanced public health or generated a large number of studies of little impact.
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The Longitudinal Aging Study Amsterdam: cohort update 2016 and major findings
Abstract
The Longitudinal Aging Study Amsterdam (LASA) is an ongoing longitudinal study of older adults in the Netherlands, which started in 1992. LASA is focused on the determinants, trajectories and consequences of physical, cognitive, emotional and social functioning. The study is based on a nationally representative sample of older adults aged 55 years and over. The findings of the LASA study have been reported in over 450 publications so far (see www.lasa-vu.nl). In this article we describe the background and the design of the LASA study, and provide an update of the methods. In addition, we provide a summary of the major findings from the period 2011–2015.
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Smoking, physical exercise, BMI and late foetal death: a study within the Danish National Birth Cohort
Abstract
The aim of this paper was to estimate the effect of maternal and paternal smoking on foetal death (miscarriage and stillbirth) and to estimate potential interactions with physical exercise and pre-pregnancy body mass index. We selected 87,930 pregnancies from the population-based Danish National Birth Cohort. Information about lifestyle, occupational, medical and obstetric factors was obtained from a telephone interview and data on pregnancy outcomes came from the Danish population based registries. Cox regression was used to estimate the hazard ratios (adjusted for potential confounders) for predominantly late foetal death (miscarriage and stillbirth). An interaction contrast ratio was used to assess potential effect measure modification of smoking by physical exercise and body mass index. The adjusted hazard ratio of foetal death was 1.22 (95 % CI 1.02–1.46) for couples where both parents smoked compared to non-smoking parents (miscarriage: 1.18, 95 % CI 0.96–1.44; stillbirth: 1.32, 95 % CI 0.93–1.89). On the additive scale, we detected a small positive interaction for stillbirth between smoking and body mass index (overweight women). In conclusion, smoking during pregnancy was associated with a slightly higher hazard ratio for foetal death if both parents smoked. This study suggests that smoking may increase the negative effect of a high BMI on foetal death, but results were not statistically significant for the interaction between smoking and physical exercise.
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Does smoking influence the physical activity and lung cancer relation? A systematic review and meta-analysis
Abstract
Research suggests an inverse association between physical activity and lung cancer. However, whether the relation is modified by degree of smoking adjustment has not been summarized. We conducted a meta-analysis of physical activity and lung cancer focusing on evaluating whether smoking status and the degree of smoking adjustment influenced the association. Comparing high versus low physical activity levels from 25 observational studies yielded a lung cancer summary relative risk (RR) of 0.79 [95 % confidence interval (CI) = 0.72–0.87], with RRs of 0.87 (95 % CI = 0.80–0.94) for cohort studies and 0.57 (95 % CI = 0.46–0.71) for case–control studies. In further analyses restricted to cohort studies, physical activity was inversely related to lung cancer among former smokers (RR = 0.68, 95 % CI = 0.51–0.90) and current smokers (RR = 0.80, 95 % CI = 0.70–0.90), whereas the association was null among never smokers (RR = 1.05, 95 % CI = 0.78–1.40, p interaction = 0.26). The degree of smoking adjustment did not modify the association (p interaction = 0.73). Physical activity was unrelated to lung cancer among never smokers but it was inversely associated with lung cancer among former and current smokers. Although the physical activity and lung cancer relation was not modified by smoking status or degree of smoking adjustment, residual confounding by smoking remains a possible explanation for the relations observed.
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The prognostic impact of SYT-SSX fusion type and histological grade in pediatric patients with synovial sarcoma treated according to the CWS (Cooperative Weichteilsarkom Studie) trials
Abstract
Background
The aim of our analysis was the evaluation of the prognostic impact of SYT-SSX fusion status and histological grading in synovial sarcoma (SS) of children and adolescents in the context of the consistent multimodal treatment strategy of the CWS (Cooperative Weichteilsarkom Studie; Cooperative Soft Tissue Sarcoma Study Group) and in comparison with other risk factors.
Procedure
Between 1986 and 2006, out of 243 patients with SS, tumor samples from 84 patients with localized disease were available for RT-PCR analysis. Outcome depending on fusion status in the context with known clinical risk factors was analyzed.
Results
No prognostic significance was shown for SYT-SSX fusion status and for histological grade. Highest significance of negative prognostic impact was found for large tumor size in uni- and multivariate analysis (P < 0.01). Furthermore, male gender was shown to be an adverse prognostic factor in multivariate analysis (P = 0.01).
Conclusions
Based on our results, neither histological grading nor SYT-SSX fusion status seems to be suitable for outcome prediction and risk stratification in localized SS treated according to the CWS. This is in contrast to several other publications concerning more heterogeneous age groups including children and adults, and this indicates that prognostic factors should not be interpreted apart from the particular study population and the therapeutic context.
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Analysis of semen parameters in a young cohort of cancer patients
Abstract
Background
Infertility can be the result of some common cancer treatments and can significantly impact quality of life. Semen cryopreservation allows for fertility preservation. We analyzed the semen parameters of specimens collected from pubertal males from the Children's Hospital of Philadelphia (CHOP) in order to expand current knowledge on the quality of these specimens and inform a standard clinical practice.
Procedure
Males who were at least Tanner stage III and newly diagnosed with cancer at CHOP were approached regarding sperm banking. The success and quality of the samples collected were analyzed and compared in relation to prior treatment, age, and diagnosis.
Results
From 399 patients approached for semen collection, 339 (85%) attempted to bank sperm, of which 265 (78%) were successful and 60 (15%) refused to participate. Therapy prior to sperm banking significantly impacted a successful collection (P < 0.01). Only 16.9% of the untreated patients were azoospermic, whereas 84.0% of the treated subjects were azoospermic. Older patients were less likely to be azoospermic and have a greater quality collection when compared with younger patients (P < 0.01). However, 65% of our youngest patients still were able to cryopreserve semen. There was no difference in azoospermia across diagnostic groups (P = 0.35), though there were differences in quality of semen parameters across diagnoses.
Conclusion
Our data support that sperm banking pubertal males prior to the initiation of therapy is feasible. While there were differences in quality of semen parameters across age and diagnostic groups, most males, regardless of age or diagnosis, had adequate specimens for cryopreservation.
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Cranial epidural hematomas: A case series and literature review of this rare complication associated with sickle cell disease
Abstract
Background
Patients with sickle cell disease (SCD) may experience many complications of the central nervous system (CNS) including stroke, silent cerebral infarcts, and neuropsychological deficits. Cranial epidural hematoma is a rare but potentially serious complication.
Procedure
Case series of cranial epidural hematomas in children with SCD from three different institutions is considered, along with a literature review of cranial epidural hematomas in this population.
Results
Seven children with SCD with cranial epidural hematomas were identified from three different institutions. All patients were male and the age at presentation ranged from 10 to 18 years. Two patients presented with headache (28.6%), while the rest had no neurologic symptoms at presentation. Four patients required urgent neurosurgical intervention (57.1%) and one patient died (14.3%). A literature review identified 18 additional cases of cranial epidural hematomas in children with SCD. Of these, treatment ranged from supportive care to neurosurgical intervention. Twelve patients completely recovered (66.7%), one patient had long-term cognitive impairment (5.6%), and four patients died (22.2%). Combined with our data, cranial epidural hematomas have a mortality rate of 20.0%.
Conclusions
Although rare, cranial epidural hematoma can be fatal and should be considered in patients with acute neurological symptoms.
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Prognostic values of negative estrogen or progesterone receptor expression in patients with luminal B HER2-negative breast cancer
Abstract
Background
The luminal subtype of breast cancer is sensitive to anti-estrogen therapy and shows a better prognosis than that of human epidermal growth factor receptor2 (HER2)-enriched or triple-negative breast cancer. However, the luminal type of breast cancer is heterogeneous and can have aggressive clinical features. We investigated the clinical implications of single hormone receptor negativity in a luminal B HER2-negative group.
Methods
We collected luminal B HER2-negative breast cancer data that were estrogen receptor (ER) and/or progesterone receptor (PR) positive, Ki 67 high (>14 %), and HER2 negative and divided them into the ER- and PR-positive group and the ER- or PR-negative group. We analyzed the clinical and pathological data and survival according to ER or PR loss.
Results
There were no statistical differences in TNM stage, breast and axillary operative methods, or number of tumors between the ER- and PR-positive group and ER- or PR-negative group. However, the ER- or PR-negative group was associated with older age (≥45 years), higher histological grade, lower Bcl-2 expression, and far higher Ki 67 (>50 %). Disease-free survival (DFS) and overall survival (OS) were shorter in the ER- or PR-negative group than that in the ER- and PR-positive group (p = 0.0038, p = 0.0071).
Conclusions
ER- or PR-negative subgroup showed worse prognosis than ER- and PR-positive subgroup in the luminal B HER2-negative group. We could consider the negativity of ER or PR as prognostic marker in luminal B HER2-negative subtype of breast cancer.
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Early identification of DPAM in at-risk low-grade appendiceal mucinous neoplasm patients: a new approach to surveillance for peritoneal metastasis
Abstract
Background
Disseminated peritoneal adenomucinosis (DPAM) patients often have a history of appendectomy with identification of an incidental mucinous neoplasm (low-grade appendiceal mucinous neoplasm (LAMN)). The rate of developing DPAM is not well established.
Methods
Twenty-two patients with incidental LAMN were identified and monitored with cancer markers and CT every 4–6 months. Laparoscopy with peritoneal washing was performed in patients either in the event of radiographic disease or after 12 months in absence of radiographic disease. The rate of detecting peritoneal metastasis was determined for CT scan and laparoscopy.
Results
Peritoneal metastasis was detected in 5 (23 %) patients. Occult disease was detected in four patients at laparoscopy without a detectable disease on CT scan. One patient developed radiographic progression at 6 months confirmed with laparoscopy. Four patients were treated with cytoreductive surgery (CRS)/HIPEC and one with CRS only. The 17 patients with negative laparoscopy remain disease free with a median follow-up of 50 months.
Conclusions
The rate of peritoneal metastasis in incidental LAMN patients was 23 %. Laparoscopy was the primary screening tool identifying occult metastasis. The median PCI of 7 was low, and all the patients underwent R0/R1 resections. This study revealed 1 in every 4.4 patients with LAMN may develop PMP. Longer follow-up and further patient surveillance is warranted.
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