tbuckley/cabot-search huggingface dataset:
123I-FP-CIT and 99mTc-HMPAO in Pathologically Confirmed Progressive Supranuclear Palsy
Authors: Manuela Cristina Matesan, Saeed Elojeimy, Satoshi Minoshima
Journal: Clinical Nuclear Medicine (2016)

Molecular brain imaging I-FP-CIT SPECT is an important tool in evaluation of patients with parkinsonism. However, various neurodegenerative etiologies cannot be differentiated by I-FP-CIT SPECT alone. We present a case of progressive supranuclear palsy with abnormal I-FP-CIT SPECT and abnormal Tc-HMPAO SPECT depicted by quantitative analyses but unremarkable MRI 16 months after the onset of symptoms. Brain autopsy demonstrated presence of neuronal and glial tau pathology in both cortical and subcortical regions confirming the diagnosis of progressive supranuclear palsy. This case illustrates potential values of multimodal molecular brain imaging in conjunction with quantitative analysis in the evaluation of movement disorders.
Polymorphisms in the IL‐1 gene cluster influence systemic inflammation in patients at risk for acute‐on‐chronic liver failure
Authors: José Alcaraz‐Quiles, Esther Titos, Mireia Casulleras, Marco Pavesi, Cristina López‐Vicario, Bibiana Rius, Aritz Lopategi, Andrea de Gottardi, Ivo Graziadei, Henning Gronbaek, Pere Ginès, Mauro Bernardi, Vicente Arroyo, Joan Clària
Journal: Hepatology (2016)

Acute-on-chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrome characterized by acute decompensation, organ failure(s) and high short-term mortality. Recent findings suggest that an overexuberant systemic inflammation plays a primary role in ACLF progression. In this study, we examined whether genetic factors shape systemic immune responses in patients with decompensated cirrhosis. Six single-nucleotide polymorphisms (SNPs) in inflammation-related genes (interleukin [IL]-1 beta [IL-1β], rs1143623; IL-1 receptor antagonist [IL-1ra], rs4251961; IL-10, rs1800871; suppressor of cytokine signaling-3, rs4969170; nucleotide-binding oligomerization domain-containing protein 2, rs3135500; and chemerin chemokine-like receptor 1, rs1878022) were genotyped in 279 patients with cirrhosis with (n = 178) and without (n = 101) ACLF from the CANONIC study of the CLIF consortium. Among these SNPs, we identified two polymorphisms belonging to the IL-1 gene cluster (IL-1β and IL-1ra) in strong association with ACLF. Both SNPs were protective against ACLF; IL-1β (odds ratio [OR], 0.34, 95% confidence interval [CI], 0.13-0.89; P < 0.05) and IL-1ra (OR, 0.58; 95% CI, 0.35-0.95; P < 0.05) under the recessive and overdominant inheritance models, respectively. These protective SNPs translated into reduced circulating levels of IL-1β, IL-1α, IL-6, granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor, and C-reactive protein at enrollment as well as after 7-14 days of admission. These findings were confirmed in vitro in leukocytes incubated with plasma from patients with decompensated cirrhosis carrying the protective SNP genotypes. Notably, a higher frequency of the protective genotypes was observed in patients without (80%) than in those with (20%) ACLF. Consistently, patients carrying the combined protective genotypes showed a lower 28-day mortality rate. Conclusion: These data identify two common functional polymorphisms in the IL-1 gene cluster, which are associated with the inflammatory process related to development of ACLF. (Hepatology 2017;65:202-216).
Rate of clinical progression of neoadjuvant therapy (NAT) in triple-negative breast cancer: An updated analysis of response to NAT in locally advanced breast cancer (LABC) by tumor subtype.
Authors: S. Nasim
Journal: Journal of Clinical Oncology (2010)

e11035 Background: Neoadjuvant chemotherapy is considered standard of care in the treatment of LABC. It is recognized that subtypes of breast cancer may have differential benefit from the use of chemotherapy. The aim of this study was to determine clinical and pathologic response rates to NAT in these different subtypes. Methods: Patients with LABC (stage 2B/3) treated with NAT who were entered into the prospective database at the Sunnybrook Odette Cancer Center were included in the analysis. Patients were classified using immunohistochemical profiles as 1. Luminal A (ER+ and/or PR+, HER2-); 2. Luminal B (ER+ and/or PR+, HER2+; 3.HER2+ [HER2+ ER- PR-]); and 4. triple-negative (TN) (ER-, PR-, HER2-). Clinical and pathologic response to NAT was assessed and compared across the four subtypes. Pathologic complete response (pCR) was defined as no residual invasive disease in the breast or axilla. Results: Between Jan 2003 and Dec 2007, 143 patients received NAT and were included in the analysis. 69 (48%) were luminal A, 18 (13%) luminal B, 24 (17%) HER2-positive, and 32 (22%) were TN. All patients received an anthracycline and 63% received anthracycline and taxane. Median age at diagnosis was 57 and was not statistically different across subgroups. Clinical response rates were luminal A (81%) luminal B (83%), HER2+ (78%) and TN (48%). Patients in the TN group were more likely to progress while on NAT (25%) compared to other subgroups (3.4%) (p < 0.0001).25% of these patients were made operable by salvage radiation therapy. pCR rate for all patients was 10% but was not statistically different across subgroups (luminal A 5%, luminal B 19%, HER2+ 13% and TN 16%) (p = 0.312). Conclusions: Clinical and pathological response rates differ significantly between different tumor subtypes. The low pCR rate amongst the subgroups reflects the advanced stage of these patients. Clinicians treating patients with TN LABC need to watch patients closely given the high rate of clinical progression. Innovative strategies need to be developed if we are to continue to use CCR and pCR as surrogates for long-term benefits from systemic therapy. No significant financial relationships to disclose.
Serum ferritin and risk for new‐onset heart failure and cardiovascular events in the community
Authors: IJsbrand T. Klip, Adriaan A. Voors, Dorine W. Swinkels, Stephan J.L. Bakker, Jenny E. Kootstra‐Ros, Carolyn S. Lam, Pim van der Harst, Dirk J. van Veldhuisen, Peter van der Meer
Journal: European Journal of Heart Failure (2016)
Current Therapy for Hypoplastic Left Heart Syndrome and Related Single Ventricle Lesions
Authors: Richard G. Ohye, Dietmar Schranz, Yves D’Udekem
Journal: Circulation (2016)

Universally fatal only 4 decades ago, the progress in the 3-stage palliation of hypoplastic left heart syndrome and related single right ventricular lesions has drastically improved the outlook for these patients. Although the stage II operation (hemi-Fontan or bidirectional Glenn) and stage III Fontan procedure have evolved into relatively low-risk operations, the stage I Norwood procedure remains one of the highest-risk and costliest common operations performed in congenital heart surgery. Yet, despite this fact, experienced centers now report hospital survivals of &gt;90% for the Norwood procedure. This traditional 3-stage surgical palliation has seen several innovations in the past decade aimed at improving outcomes, particularly for the Norwood procedure. One significant change is a renewed interest in the right ventricle-to-pulmonary artery shunt as the source of pulmonary blood flow, rather than the modified Blalock-Taussig shunt for the Norwood. The multi-institutional Single Ventricle Reconstruction trial randomly assigned 555 patients to one or the other shunt, and these subjects continue to be followed closely as they now approach 10 years postrandomization. In addition to modifications to the Norwood procedure, the hybrid procedure, a combined catheter-based and surgical approach, avoids the Norwood procedure in the newborn period entirely. The initial hybrid procedure is then followed by a comprehensive stage II, which combines components of both the Norwood and the traditional stage II, and later completion of the Fontan. Proponents of this approach hope to improve not only short-term survival, but also potentially longer-term outcomes, such as neurodevelopment, as well. Regardless of the approach, traditional surgical staged palliation or the hybrid procedure, survivals have vastly improved, and large numbers of these patients are surviving not only through their Fontan in early childhood, but also into adolescence and young adulthood. As this population grows, it becomes increasingly important to understand the longer-term outcomes of these Fontan patients, not only in terms of survival, but also in terms of the burden of disease, neurodevelopmental outcomes, psychosocial development, and quality of life.
Outcome in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with CHOP-R Can Be Predicted by Stage and Serum Lactate Dehydrogenase (LDH) Level.
Authors: Laurie H. Sehn, Mukesh Chhanabhai, Karamjit Gill, Paul Hoskins, Richard Klasa, Kerry J. Savage, Tamara Shenkier, Judy Sutherland, Randy D. Gascoyne, Joseph M. Connors
Journal: Blood (2006)
The cytogenetic features of Chinese patients with myeloproliferative diseases
Authors: L. Duan, S. Zhang, J. Li
Journal: Journal of Clinical Oncology (2007)

17533 Background: To investigate the cytogenetic features in Chinese patients with myeloproliferative diseases(MPD). Methods: The chromosomal abnormalities of 98 newly diagnosed essential thrombocytosis(ET) patients and 50 newly diagnosed polycythemia vera(PV) patients were studied by conventional cytogenetics (CC) and R-banding technique. Interphase fluorescence in situ hybridization (FISH) were used to detect trisomy 8 in 50 ET cases and detect trisomies 8 and 9 in 50 PV and 8 normal individuals. Results: CC showed 6.12% (6/98) of ET patients had chromosomal abnormalities including 1 case with 13q-, 2 with 5q-, 1 with 7q-, 1 with der(14)t(1;14) and 1 with Rob(13;14). FISH detected 1 case with trisomy 8 among 50 cases. CC showed 6% (3/50) of PV patients had chromosomal abnormalities including trisomy 8, deletion of chromosome Y and inversion of chromosome 11. FISH detected two cases of trisomy 8, including the confirmed one by CC technique, and one case of trisomy 9 neglected by CC technique. Conclusions: In our study, the incidence of chromosomal abnormalities in MPD by CC was rare. The frequency of trisomies 8 and 9was low in untreated MPD. No significant financial relationships to disclose.
Pharmacological Blockade of NF-kB with AS602868, a Potent Small Molecule Inhibitor of IKK2 Leads to Apoptosis of Sensitive and Resistant Chronic Myeloid Leukemia Cells.
Authors: Veronique Imbert, Nadege Gonthier, Catherine Frelin, Nicolas Sirvent, Michael Hummelsberger, Anne Sirvent von Bueltzingsloewen, Jill-Patrice Cassuto, Francois-Xavier Mahon, Philippe Rousselot, Michel Dreano, Jean-Francois Peyron
Journal: Blood (2005)
The impact of waist-to-hip ratio (WHR) on survival in metastatic breast cancer patients treated with aromatase inhibitors (AIs)
Authors: M. Artac, M. Samur, H. Bozcuk, B. Afacan, M. Ozdogan
Journal: Journal of Clinical Oncology (2007)

1070 Background: Aromatase inhibitors represent a novel hormonal therapy for breast cancer. Aromatase is expressed in the ovaries, brain, bone and, adipose and breast tissue. Elevated WHR, representing a higher abdominal fat distribution, has been associated with both the development of and mortality from breast cancer. Therefore, we aimed to identify whether abdominal fat distribution could affect the outcome in metastatic breast cancer patients treated with AIs. Methods: A total of 46 metastatic breast cancer patients treated with first line hormonal therapy were enrolled in this study. Pretreatment body weight, height, BMI and WHR were measured. Estrogen, progesteron and c- erb-B2 receptor status were also evaluated in analyses. Univariate and multivariate Cox regression analyses, and Kaplan Meier survival curves subjected to log rank testing were utilized for the survival analyses. Forward likelihood ratio was used for the multivariate selection process. A P value &lt; 0.05 was considered to be significant. Results: Median age was 51 years (range 28 - 75). 36 patients were treated with letrozole and 10 patients with anastrozole. Median body weight, height, WHR and BMI were found to be 68.5 kg (range 46 - 115), 156 cm (range 137 - 167), 0.91 (range 0.7 - 1.2), and 28.7 (range 18 - 45), respectively. Factors associated with overall survival in the univariate analysis were age, c-erb-B2 expression intensity (+++ versus others by immunohistochemistry), and WHR, whereas only WHR retained significance in the multivariate analysis. Likewise, predictors of progression free survival were c-erb-B2 expression intensity and WHR. However, none of these factors was significant in the multivariate analysis. Median overall survival figures were 472 days versus unreached for patients with a WHR of &lt;0.92 and =0.92 (Log rank statistic = 9.76, P = 0.002). Similarly, the corresponding progression free survival figures for patients with a WHR of &lt;0.92 and =0.92 were 423 versus 1,004 days (Log rank statistic = 6.37, P = 0.012). Conclusions: This is the first report examining and suggesting the value of abdominal fat distribution in relation with benefit from AIs in metastatic breast cancer. Our results should be validated in larger series. No significant financial relationships to disclose.
Unanswered Questions Concerning Locoregional Irradiation in Breast Cancer—Reply
Authors: Philip M. P. Poortmans, Charlotte Coles, Jacques Bernier
Journal: JAMA Oncology (2016)

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Topical administration of cryopreserved living micronized amnion accelerates wound healing in diabetic mice by modulating local microenvironment
Authors: Yongjun Zheng, Shizhao Ji, Haibin Wu, Song Tian, Yunqing Zhang, Li Wang, He Fang, Pengfei Luo, Xingtong Wang, Xiaoyan Hu, Shichu Xiao, Zhaofan Xia
Journal: Biomaterials (2016)
TCR diversity – a universal cancer immunotherapy biomarker?
Authors: Douglas G. McNeel
Journal: Journal for ImmunoTherapy of Cancer (2016)

Sipuleucel-T was approved as a treatment for men with advanced metastatic, castration-resistant prostate cancer on the basis of improved survival in randomized clinical trials. A major challenge for this therapy, as well as other newer cancer immunotherapy agents, has been to identify markers that can identify patients who benefit from these therapies. In a recent manuscript by Sheikh and colleagues, the investigators evaluated changes in T cell clonality in the peripheral blood and tumors of patients treated with sipuleucel-T using next generation sequencing of T cell receptor Vß CDR3 sequences. Their findings are discussed in the context of this trial and other cancer immunotherapies.
Abstract IA14: Breaking bad: Cancer-associated fibroblasts are reprogrammed from growth inhibitory to pro-inflammatory and tumor promoting in breast cancer
Authors: Yoray Sharon, Nour Ershaid, Yael Raz, Noam Cohen, Metsada Pasmanik-Chor, Tamar Geiger, Neta Erez
Journal: Cancer Research (2016)

Abstract Breast tumors are characterized by an extensive desmoplastic stroma, abundantly populated by fibroblasts. We previously demonstrated that Cancer-Associated Fibroblasts (CAFs) orchestrate tumor-enhancing inflammation in multiple mouse and human malignancies, including breast cancer. Although breast cancer is one of the major tumor types where CAFs were shown to be tumor promoting, there is no detailed analysis of the dynamic changes in CAFs characteristics and function in correlation with tumor progression. We therefore set out to characterize the dynamic changes in CAFs during progression of mammary carcinogenesis, in a transgenic mouse model of human breast cancer. We profiled the transcriptome of fibroblasts isolated from normal mammary glands, or from mammary glands of transgenic mice at defined tumorigenic stages. Data analysis revealed unique CAF gene signatures that correspond to distinct tumor stages, with only partial overlap between the stages, suggesting co-evolution of the microenvironment with tumorigenic progression. Interestingly, the gene signature of fibroblasts isolated from hyperplastic lesions is inverse to that in CAFs from neoplastic stages, and has a growth inhibitory phenotype, while CAFs from mammary tumors express pro-inflammatory and tumor promoting gene signatures. Moreover, we functionally demonstrate that CAFs isolated from late carcinoma express a gene signature that links tissue damage with tumor-promoting inflammation. To identify tumor-secreted factors capable of reprogramming normal mammary fibroblasts to pro-inflammatory CAFs, we performed a proteomic screen of breast cancer cells secretome, and identified Osteopontin (OPN). Knockdown of OPN in tumor cells in vivo resulted in attenuated stromal activation, reduced immune cell recruitment and inhibition of tumor growth. Taken together, our findings reveal reciprocal crosstalk between fibroblasts and cancer cells which drives CAF reprogramming, to facilitate tumor progression in breast cancer. Citation Format: Yoray Sharon, Nour Ershaid, Yael Raz, Noam Cohen, Metsada Pasmanik-Chor, Tamar Geiger, Neta Erez. Breaking bad: Cancer-associated fibroblasts are reprogrammed from growth inhibitory to pro-inflammatory and tumor promoting in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA14.
Correlation of COX2 expression with tumor-induced osteoclastic lesions in breast cancer bone metastasis
Authors: C. Schem, Z. Li, N. Maass, W. Jonat, D. Medina, Y. H. Shi, M. Zhang
Journal: Journal of Clinical Oncology (2008)

1116 Background: Metastatic dissemination is complicated and depends largely on the interaction of primary tumors and the local host environment. In this study we have established a new mouse model to mimic the process of tumor metastasis in breast cancer patients and revealed the enhancing influence of COX2 expression on bone metastases in breast cancer. Methods: TM40D-MB mouse mammary tumor cells were transplanted to the mammary glands of syngeneic mice, causing a local tumor and were metastatic to bone. We compared the expression profile of high (TM40D-MB) versus low metastatic (TM40D) tumor cells using the Affymetrix microarray platform. Differentially expressed genes were confirmed by Northern-blot analysis. The COX2 gene was selected for further functional studies. TM40D-COX2 and TM40D-C controle cells were injected to mouse femur and the effect was analysed by microcomputed tomography (μCT) scanning for trabecular bone volume. Shown effects were challenged by selective COX2 inhibition (NS-398) in an osteoclast formation assay. Results: Mammary tumors developed in the glands in situ and were metastatic to bone with over 53% efficiency. Microarray analysis revealed a list of genes that were consistently up-/down-regulated in TM40D-MB tumor cells. Various differentially expressed genes (e.g. PTX3, FGF7, COX2) were confirmed using Northern-blot analysis. Injection of TM40D-COX2 cells to mouse femur caused a significant increase in bone destruction compared to TM40D-C as measured by the micro-computed tomography. In vitro assays showed that COX2 significantly increased the rate of osteoclast formation, and this effect was reversible by the specific COX2 inhibitor. Conclusions: These data indicate that COX2 expression can influence bone metastasis in this new breast cancer model. The availability of this mouse model and the comparative study of gene expression signatures between TM40D and other bone metastasis models will likely generate important information about common pathways for breast cancer bone metastasis. Further functional studies of metastasis signature genes should help to develop means to curb the metastasis process. Clinical evaluation of specific COX2 inhibitors will clarify the use of these drugs in adjuvant and advanced disease treatment. No significant financial relationships to disclose.
PET-CT as an Alternative to Fiducial Markers Guidance in Liver Metastasis Treatment
Authors: Fernanda Granato, Andre C. Felicio, Lilian Yuri Itaya Yamaga, Solange Amorim Nogueira, Taise Vitor
Journal: Clinical Nuclear Medicine (2016)

The liver is the organ most commonly affected by colorectal cancer metastasis. Currently, liver resection is the treatment of choice, but in cases where it is not possible, intensity-modulated radiation therapy is an alternative. We report the case of a 57-year-old woman whose colorectal carcinoma metastasized to the liver. She was referred for implantation of fiducial markers for intensity-modulated radiation therapy planning. PET-CT stands out as an additional tool for distinguishing metabolically active tumor tissue from other tissues, ensuring effective introduction of percutaneous fiducial markers, especially in cases where use of conventional imaging techniques is limited.
Lack of CD34 Expression in Acute Myeloid Leukemia (AML) Is a Favorable Prognostic Factor in Patients Treated with Stem Cell Transplant Irrespective of the Cytogenetic Risk
Authors: Fahed Almhareb, Claudia Ulrike Walter, Randa Nounou, Salem Khalil, Nasir Bakshi, Tarek Owaidah, Naeem A. Chaudhri, Hazzaa Al Zahrani, Said Mohamed, Walid Rasheed, Fahad Alsharif, Mahmoud Aljurf, Maher Albitar
Journal: Blood (2011)
Prospective Study of 168 Infants with Transient Abnormal Myelopoiesis with Down Syndrome: Japan Pediatric Leukemia/Lymphoma Study Group, TAM-10 Study
Authors: Hideki Muramatsu, Tomoyuki Watanabe, Daisuke Hasegawa, Park Myoung-ja, Shotaro Iwamoto, Takashi Taga, Etsuro Ito, Tsutomu Toki, Kiminori Terui, Ryu Yanagisawa, Katsuyoshi Koh, Akiko M. Saito, Keizo Horibe, Yasuhide Hayashi, Souichi Adachi, Shuki Mizutani, Kenichiro Watanabe
Journal: Blood (2015)
Molecular Pathways That Determine the Activation State of Macrophages within the Myeloma Niche
Authors: Chelsea Hope, Ellen Hebron, Jaehyup Kim, Jeff Jensen, Claire Flanagan, Neehar Bhatia, Catherine Leith, Ioanna Maroulakou, Constantine S. Mitsiades, Shigeki Miyamoto, Natalie Callander, Peiman Hematti, Fotis Asimakopoulos
Journal: Blood (2012)