tbuckley/cabot-search huggingface dataset:
Impact of Glutathione S-transferase (GST) P1, M1 and T1 polymorphisms on clinical outcome to Cisplatin/5-Fluorouracil chemotherapy in patients with advanced gastric cancer
Authors: Eray Goekkurt, Stephan Hoehn, Christine Wolschke, Corinna Wittmer, Christian Stüber, Jan Stoehlmacher
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

6166 

Purpose: The purpose of our study was to analyse the predictive value of Glutathione S-transferase (GST) P1, M1 and T1 polymorphisms on clinical outcome to cisplatin/5-FU chemotherapy in patients with advanced gastric cancer. Methods: Between 2001 and 2003 54 patients with advanced gastric cancer were treated with 5-FU/cisplatin chemotherapy. Tumor specimen of 52 patients were available for genotype analyses. GSTP1-105 polymorphism was determined using a PCR based RFLP technique. GSTM1 and GSTT1 polymorphisms, consisting of presence or absence of the gene, were determined using a multiplex PCR with BCL as an internal control. DNA was extracted from paraffin-embedded tumors. Results: Thirteen out of 52 patients (25%) showed response to chemotherapy. The majority of patients (36/52, 69%) demonstrated stable disease or disease progression. Three patients (6%) were not eligible for response due to missing of radiological tumor re-evaluation. Genotypes could be determined as follows: GSTP1 50/52 (96%), GSTM1 and GSTT1 52/52 (100%). Patients homozygous for the GSTP1-105 Valine (Val) genotype showed a significant superior response rate of 67% compared to 22% in patients harboring at least one GSTP1-105 Isoleucin (Ile) allele (p=0.037, Fishers Exact Test). In fact, all patients possessing the homozygous GSTP1-105 Valine genotype demonstrated control of the disease. Furthermore, patients with two Val alleles showed a superior median survival of 14,9 months (95% CI 7.8, 21,9) compared to patients with at least one GSTP1-105 Ile allele with only 6.0 months (95% CI 5.0, 7.0) (p=0.029, Logrank Test). There was no association between GSTM1 or GSTT1 polymorphism and response to chemotherapy or overall survival in this group of patients. Conclusion: The less active GSTP1-105 Val variant may lead to accumulation of the cisplatin and hereby contribute to superior response to this chemotherapy and survival in patients harbouring this genotype. Our data suggest that testing patients for this GSTP1 polymorphism may become a promising tool predicting clinical outcome to cisplatin/5-FU chemotherapy in patients with advanced gastric cancer.
Frequency, determinants, and temporal trends in lymph node assessment in women with ductal carcinoma in situ
Authors: J. J. Griggs, M. E. Sorbero, G. M. Ahrendt, A. Stark, A. W. Dick
Journal: Journal of Clinical Oncology (2007)

11050 Background: This study examined factors associated with lymph node (LN) assessment in women with ductal carcinoma in situ (DCIS) at two sites in the U.S. Methods: Detailed clinical, pathologic, and radiographic information was collected through medical record review for 1090 patients with pure DCIS treated between 1985 and 2000 in Monroe County, New York and the Henry Ford Health System (HFHS), Detroit, Michigan. Sociodemographic, clinical, pathologic, and radiologic factors associated with LN assessment were examined using logistic regression models. Covariates were interacted with a site indicator; models were tested down to include only interactions with treatment and year. Results: 395 (36.2%) women had LN assessment; 43 of these were sentinel node dissections. Of the 438 women who had a mastectomy, 341 (86.3%) had LN assessment compared with 54 (13.7%) of the 598 women who had breast conserving surgery (p = 0.0001). In multivariate logistic regression, factors positively associated with LN assessment were mastectomy (OR, 45.5 95% CI 23.9, 86.5), private insurance (OR 2.3, 95% CI 1.2, 4.4), and high nuclear grade (OR 3.7, 95% CI 1.5, 9.2). Smoking was negatively associated with LN assessment (OR 0.5, 95% CI .3, .9). Age, race, method of detection (palpable mass vs. mammography), histologic subtype, and presence of multifocal disease were not associated with LN assessment. Statistically significant downward trends over time existed and did not differ between the two sites. LN assessment rates differed by treatment by site. Women who had mastectomy at HFHS were more likely to have LN assessment than women who had mastectomy in Monroe County (OR 5.0, 95% CI 1.5, 16.7), but women at HFHS who had autogenous reconstruction following mastectomy were substantially less likely to have LN assessment than their counterparts in Monroe County (OR 0.2, 95% CI .04, .65). Conclusions: The finding that LN assessment rates in women with DCIS vary according to non-clinical factors, such as treatment site and insurance type, suggests uncertainty about the role of LN assessment exists. Local treatment culture and financial incentives may play a role in the variations in LN assessment patterns. No significant financial relationships to disclose.
Germline Sequence Variants and Ovarian Cancer
Authors: Elena M. Stoffel, Eric R. Fearon
Journal: JAMA Oncology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time
Authors: S.A.A. Kooijmans, L.A.L. Fliervoet, R. van der Meel, M.H.A.M. Fens, H.F.G. Heijnen, P.M.P. van Bergen en Henegouwen, P. Vader, R.M. Schiffelers
Journal: Journal of Controlled Release (2016)
Fatigue in older adults with acute myeloid leukemia (AML): Predictors and impact on quality of life (QOL) and functional status
Authors: S. M. Alibhai, M. Leach, J. Brandwein, M. D. Minden
Journal: Journal of Clinical Oncology (2006)

6565 Background: Fatigue is one of the most common and important symptoms in patients with cancer, yet little is known about predictors of fatigue or its impact on either QOL or functional status in older adults with AML. Methods: Patients aged 60 or older presenting with AML to an AML referral centre were enrolled at diagnosis. Fatigue and QOL were evaluated at baseline and at 1, 4, and 6 months. Questionnaires included the Functional Assessment of Cancer Therapy Anemia and Fatigue subscale (FACT-An) and the European Organization for the Research and Treatment of Cancer QLQ-C30. Correlations between FACT-An scores, predictor variables, and QOL domains were examined with Pearson correlation. Mixed effects modeling was used to examine changes in fatigue over time. Results: Between June 2003 and December 2005, 63 patients (mean age 72) were enrolled. Fatigue was the most common symptom and was of moderate severity in the majority of patients. Fatigue scores at baseline did not correlate with age, hemoglobin level, white blood cell count, or bone marrow blast percentage but correlated positively with depression scores. There were strong correlations (r=0.56 to 0.70, p&lt;0.01) between fatigue scores and depression scores over time, and moderate to strong correlations (r=0.36 to 0.67, p&lt;0.01) with both global QOL and all 5 QOL domains of the QLQ-C30 over time. Correlations were slightly weaker with functional status measures (r=0.25 to 0.76). There was a weak but inconsistent relationship between fatigue scores and change in hemoglobin over time. Fatigue scores did not improve over time regardless of treatment intent and were not better by 6 months among those achieving complete remission. Conclusions: Fatigue is the most common symptom in older adults with AML and is negatively correlated with QOL and functional status. There is a weak relationship with anemia but not with other markers of disease severity. Fatigue does not improve by 6 months even in those who achieve remission. Further studies are needed to identify potential intervention targets to improve fatigue in this population. No significant financial relationships to disclose.
Absence of WASp Enhances Hematopoietic and Megakaryocytic Differentiation in a Human Embryonic Stem Cell Model
Authors: Miguel G Toscano, Pilar Muñoz, Almudena Sánchez-Gilabert, Marién Cobo, Karim Benabdellah, Per Anderson, Verónica Ramos-Mejía, Pedro J Real, Olaf Neth, Agueda Molinos-Quintana, Philip D Gregory, Michael C Holmes, Francisco Martin
Journal: Molecular Therapy (2015)

The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene and characterized by severe thrombocytopenia. Although the role of WASp in terminally differentiated lymphocytes and myeloid cells is well characterized, its role in early hematopoietic differentiation and in platelets (Plts) biology is poorly understood. In the present manuscript, we have used zinc finger nucleases targeted to the WAS locus for the development of two isogenic WAS knockout (WASKO) human embryonic stem cell lines (hESCs). Upon hematopoietic differentiation, hESCs-WASKO generated increased ratios of CD34+CD45+ progenitors with altered responses to stem cell factor compared to hESCs-WT. When differentiated toward the megakaryocytic linage, hESCs-WASKO produced increased numbers of CD34+CD41+ progenitors, megakaryocytes (MKs), and Plts. hESCs-WASKO-derived MKs and Plts showed altered phenotype as well as defective responses to agonist, mimicking WAS patients MKs and Plts defects. Interestingly, the defects were more evident in WASp-deficient MKs than in WASp-deficient Plts. Importantly, ectopic WAS expression using lentiviral vectors restored normal Plts development and MKs responses. These data validate the AND-1_WASKO cell lines as a human cellular model for basic research and for preclinical studies for WAS. The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene and characterized by severe thrombocytopenia. Although the role of WASp in terminally differentiated lymphocytes and myeloid cells is well characterized, its role in early hematopoietic differentiation and in platelets (Plts) biology is poorly understood. In the present manuscript, we have used zinc finger nucleases targeted to the WAS locus for the development of two isogenic WAS knockout (WASKO) human embryonic stem cell lines (hESCs). Upon hematopoietic differentiation, hESCs-WASKO generated increased ratios of CD34+CD45+ progenitors with altered responses to stem cell factor compared to hESCs-WT. When differentiated toward the megakaryocytic linage, hESCs-WASKO produced increased numbers of CD34+CD41+ progenitors, megakaryocytes (MKs), and Plts. hESCs-WASKO-derived MKs and Plts showed altered phenotype as well as defective responses to agonist, mimicking WAS patients MKs and Plts defects. Interestingly, the defects were more evident in WASp-deficient MKs than in WASp-deficient Plts. Importantly, ectopic WAS expression using lentiviral vectors restored normal Plts development and MKs responses. These data validate the AND-1_WASKO cell lines as a human cellular model for basic research and for preclinical studies for WAS.
A Preclinical Model of Malignant Peripheral Nerve Sheath Tumor-like Melanoma Is Characterized by Infiltrating Mast Cells
Authors: Michael Hölzel, Jennifer Landsberg, Nicole Glodde, Tobias Bald, Meri Rogava, Stefanie Riesenberg, Albert Becker, Göran Jönsson, Thomas Tüting
Journal: Cancer Research (2015)

Human melanomas exhibit considerable genetic, pathologic, and microenvironmental heterogeneity. Genetically engineered mice have successfully been used to model the genomic aberrations contributing to melanoma pathogenesis, but their ability to recapitulate the phenotypic variability of human disease and the complex interactions with the immune system have not been addressed. Here, we report the unexpected finding that immune cell-poor pigmented and immune cell-rich amelanotic melanomas developed simultaneously in Cdk4R24C-mutant mice upon melanocyte-specific conditional activation of oncogenic BrafV600E and a single application of the carcinogen 7,12-dimethylbenz(a)anthracene. Interestingly, amelanotic melanomas showed morphologic and molecular features of malignant peripheral nerve sheath tumors (MPNST). A bioinformatic cross-species comparison using a gene expression signature of MPNST-like mouse melanomas identified a subset of human melanomas with a similar histomorphology. Furthermore, this subset of human melanomas was found to be highly associated with a mast cell gene signature, and accordingly, mouse MPNST-like melanomas were also extensively infiltrated by mast cells and expressed mast cell chemoattractants similar to human counterparts. A transplantable mouse MPNST-like melanoma cell line recapitulated mast cell recruitment in syngeneic mice, demonstrating that this cell state can directly reconstitute the histomorphologic and microenvironmental features of primary MPNST-like melanomas. Our study emphasizes the importance of reciprocal, phenotype-dependent melanoma-immune cell interactions and highlights a critical role for mast cells in a subset of melanomas. Moreover, our BrafV600E-Cdk4R24C model represents an attractive system for the development of therapeutic approaches that can target the heterogeneous tumor microenvironment characteristic of human melanomas.
Molecular basis of the immunogenicity of cell death during chemotherapy
Authors: Laurence Zitvogel, Lionel Apetoh, Francois Ghiringhelli, Antoine Tesniere, Carla Ortiz, Nathalie Chaput, Theo Panaretakis, Jean Kanelopoullos, Guido Kroemer
Journal: Cancer Research (2008)

SY29-04   Conventional therapies of cancer rely upon cytotoxic agents such as radio- and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. We reported that anthracyclin, X-Rays and platinum based-therapies mediate optimal antitumor efficacy against established mouse tumors in immunocompetent but not immunocomprised littermates. Dying tumor cells or locally irradiated tumor beds prime naive T cells in their draining lymph nodes and induce Th1 differentiation. This finding paved the way to the demonstration that dendritic cells (DC) are pivotal in the immunogenicity of cell death triggered by anticancer drugs.  First, phagocytosis of dying tumor cells by DC requires translocation of calreticulin to the tumor cell surface (Obeid et al. Nat. Med. Jan. 2007).  Second, dying tumor cells release high mobility group box 1 protein from their nuclei which will trigger TLR4 receptors harboured on DC. TLR4 signaling is indeed mandatory for the immunogenicity of cell death to promote the efficient processing of tumor cells by DC (Apetoh et al. Nat. Med. Aug. 2007). TLR4 deficient mice failed to respond to X-Rays or anthracyclins or oxaliplatinum. However, cotreatment with TLR9 or TLR3 agonists or with chloroquine (a drug regulating lysosomal pH) could compensate for the TLR4 defects in antigen processing and presentation (Apetoh, Immunol; Rev. 2007).  We recently delineated additional molecular pathways critical for the polarization of the T cell immune responses that will be further discussed at the meeting.  The clinical relevance of these preclinical findings has been evaluated in patients receiving anticancer chemotherapy. The TLR4 status could predict the therapeutic outcome in breast cancer females treated with systemic anthracyclins. Patients carrying a TLR4 loss-of-function allele (Asp299Gly) manifested a higher incidence of metastases at ten years (50% versus 37.4% in non mutated patients) after surgery (Log rank test, p = 0.03). Similar trends were found in colon cancer patients treated with 5FU and/or oxaliplatinum-based regimen. These results delineate a clinically relevant immunoadjuvant pathway triggered by tumor cell death that could be exploited to ameliorate the efficacy of current therapies in defined cohorts of patients.
Impact of low-lipid environment on de novo lipid synthesis pathways in cancer cells
Authors: Nousheen Zaidi
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Increased lipogenesis is a hallmark of a wide variety of cancers and is under intense investigation as potential anti-neoplastic target. Although brisk lipogenesis is observed in the presence of exogenous lipids, evidence is mounting that these lipids may adversely affect the
High concordance of HER-2/neu gene amplification and overexpression in hematogeneous breast cancer metastases
Authors: R. Simon, A. Kaur, P. Schraml, H. Novotny, M. Mirlacher, G. Sauter
Journal: Journal of Clinical Oncology (2005)

626 Background: Recently, HER2 amplification was described in disseminated tumor cells from HER2 negative primary tumors, raising the question of the HER2 status in hematogenous metastases. Methods: To study heterogeneity of HER2 expression in primary breast cancers and their hematogenous metastases, a tissue microarray (TMA) was constructed. Four tissue samples were analyzed, each from 58 primary tumors and 657 hematogenous metastases from autopsy tissue of 160 patients by fluorescence in situ hybridization (FISH; PathVysion, Vysis-Abbott) and immunohistochemistry (IHC; HercepTest, DAKO). IHC 2+ and /3+ cases were classified as HER2 positive. Results: An overall concordance of FISH and IHC was found with 94.3% amplification in samples with 3+ and 40.0% amplification in samples with 2+ IHC. Minimal Heterogeneity was seen between different tissue samples from one tumor block in 2.1%, between different metastases in 6.2% and no heterogeneity was found between primary tumors and their metastases (interpretable results of 18 patients). All cases with discrepant FISH data had borderline FISH results. They were judged differently in different tissue samples and did not reflect true heterogeneity. The IHC findings showed more heterogeneity: within one tumor block in 5.1%, between different metastases in 12.8% and between primary tumors and their metastases in 17.4% (interpretable results of 46 patients). This was due to equivocal IHC2+ cases and IHC artifacts. FISH data of IHC heterogeneous cases never provided evidence for any genomic heterogeneity, suggesting technical issues on autopsy material as a major cause for IHC heterogeneity. Conclusion: These results suggest a low frequency of true HER2 heterogeneity in primary and metastatic breast cancer. The most of cases with conflicting results are either due to borderline FISH findings or to equivocal or false IHC. We thus conclude that HER2 testing on primary tumors is reflective of the HER2 status of all hematogenous metastases of a patient, and is reliable to determine treatment regimens in the adjuvant and metastatic setting. No significant financial relationships to disclose.
Identification of tumor tissue origin by a microRNA-based molecular assay
Authors: S. Rosenwald, H. Gibori, S. Gilad, L. Cohen, I. Leizerman, I. Barshack, D. Nonaka, A. Tobar, R. Aharonov, N. Rosenfeld
Journal: Journal of Clinical Oncology (2009)

11036 Background: Hundreds of thousands of patients are diagnosed each year with metastatic cancer. For ∼10% of these, the tumor primary site is never identified, and they are defined as Cancer of Unknown Primary (CUP). Identification of tumor tissue-of- origin has significant therapeutic implications and presents a major diagnostic challenge. In previous work we showed that by combining expression profiles of tissue-specific microRNAs with a biologically-motivated classification scheme, tumor tissue-of-origin can be identified with high accuracy. Here we describe the development of this approach into a practical diagnostic assay. Methods: We developed protocols for extraction of high-quality RNA that retain the microRNA fraction from FFPE archival tissue samples. Proprietary, highly specific qRT-PCR was used to profile microRNA expression levels in hundreds of samples. Results: A training set of nearly 400 primary and metastatic tumors samples with known primary sites, representing 25 different tumor types, was used to define a standardized diagnostics assay (miRview mets). The assay uses a qRT-PCR protocol to measure a panel of 48 microRNA biomarkers. The assay was validated on a test set of nearly 200 primary and metastatic tumors whose primary sites were blinded. The classification protocol identifies either a single, high-confidence origin or two possible low-confidence predictions. Overall, correct primary site was identified for 83% of the tumors. For 70% of the cases a single high-confidence prediction was made; these cases had a higher accuracy: 90% of the primary sites predicted with high confidence were accurately identified. Conclusions: Previous studies highlighted the tissue-specificity of microRNA expression. We developed this potential into a diagnostic assay that identifies tumor origins with high accuracy. This assay provides an important new tool for diagnosing tumor tissue origin. [Table: see text]
Abstract P399: Development of a Claims-Based Algorithm to Identify a Coronary Heart Disease Free Population in Medicare
Authors: Shia T Kent, Monika M Safford, Hong Zhao, Emily B Levitan, Jeff R Curtis, Meredith L Kilgore, Paul Muntner
Journal: Circulation (2014)

Introduction: There is increasing interest in using claims data to study risk for incident coronary heart disease (CHD). However, claims-based algorithms for identifying a population without a history of CHD are not well established. Objective: To develop a claims-based algorithm for identifying a population without previous myocardial infarction (MI) or coronary revascularization. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is a national cohort that included a baseline study visit in 2003-2007. Participants linked to Medicare claims were used to identify cohorts with continuous 6 month, 1 year, 2 year, or 3 year coverage prior to the REGARDS baseline (“look-back” periods). History of CHD at baseline was defined as a self-report of a previous MI or cardiac revascularization. We examined Medicare claims prior to baseline to identify evidence of CHD. Approaches used fixed-window look-back periods (e.g., claims within a 1 year window prior to baseline) and all available look-back (e.g. requiring a minimum of 1 year of Medicare coverage, but using all claims available prior to baseline). Among those without CHD claims in Medicare, we calculated the percent who self-reported CHD for the different look-back periods. Results: There were 8,104 participants with 6 months of look-back and no CHD claims. Requiring 1, 2 or 3 year look back periods reduced the number of participants by 1,001 (5%), 2,237 (16%) and 3,157 (26%), respectively. Using fixed-window look-back periods, the percent without CHD claims who self-reported CHD was lower with longer look-back periods (Table). Requiring 6 months of look-back and using all available claims resulted in a lower percent self-reporting CHD than any fixed-window look-back period. The percent self-reporting CHD was only modestly lower when requiring longer all available look-back periods. Conclusion: We found that a 6 month minimum look-back period is adequate for identifying a CHD-free population in Medicare when all available claims data are used.