tbuckley/cabot-search huggingface dataset:
Urinary 8-oxoguanine as a predictor of survival in patients undergoing radiotherapy.
Authors: Krzysztof Roszkowski, Ryszard Olinski
Journal: Journal of Clinical Oncology (2013)

e22197 Background: Despite several factors with prognostic value which are available for conventional cancer therapy, there is no test of the outcome of radiotherapy for individual prediction. Usually a certain dose level is prescribed for a whole group of cancer patients with similar diagnosis. This dose is set empirically taking into consideration the most sensitive patients. However, development of a prognostic test would allow to predict in advance which patients may be treated with even a higher dose while in the other case to find another more successful modality. The aim of this work was to investigate whether fractionated radiotherapy of cancer patients (n=99) is responsible for oxidative DNA damage on the level of the whole organism and whether the biomarkers of the damage such as 8-oxo-dG (8-oxo-7,8-dihydro-2’-deoxyguanosine) and its modified base (8-oxo-Gua) in urine and DNA may be used as a predictor of radiotherapy success. Methods: All the aforementioned modifications were analyzed using techniques which involve HPLC/EC or HPLC/GC/MS. Results: Of all analysed parameters only patients with significantly elevated urinary excretion of the 8-oxo-Gua with concomitant unchanged level of 8-oxo-dG in leukocytes DNA in the samples collected 24 h after the first fraction in comparison to the initial level have significantly increased survival time (60 mo. after the treatment, survival of 50% of the patients who fulfill the above mentioned criteria, in comparison with 10% of the patients who did not). Conclusions: Results of our work suggest that patients with higher urinary 8-oxo-Gua and concomitant stable level of 8-oxo-dG in leukocytes DNA, after 24h of the first dose should be regarded as better responder to radiotherapy as being at lower risk of mortality. Impact: The above mentioned statement could make it possible to use these parameters as a markers to predict the clinical success.
Feasibility to obtain a chemogram in circulating tumorigenic cells to guide further treatments in refractory solid tumors.
Authors: Antonio Cubillo, Antonio Calles, Pedro P. López-Casas, Mark Ricigliano, Emiliano Calvo, Ignacio Duran, Fernando López-Ríos, Margarita Rodriguez, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2012)

3066 Background: Circulating tumorigenic cells (CTCs) may be responsible for tumor progression, represent a new source of information of tumor biology, avoiding unnecessary biopsies. Gene-expression analysis (GEA) of CTCs could guide anti-cancer therapies in patients with refractory solid tumors. Methods: Pts &gt;18y ECOG PS 0-2 with advanced refractory solid tumors were recruited. Twelve ml blood samples were collected from each pt and processed for isolation of CTCs using a novel cell adhesion assay (Vita-Cap, Vitatex Inc., Stony Brook, NY) following the manufacturer protocol. Total RNA was extracted with RNeasy Mini Kit (Qiagen Inc.) and GEA was performed with Affymetrix GeneChip Human Genome U133 Plus 2.0 array. The CEL file obtained for each pt sample was used in a gene-set expression analysis (GSEA) to determine the enrichment profile of the pt sample to a pre-determined set of 12 PGx-modeled drugs created from the GI50 data of the NCI-60 cell lines. The drug with the highest Normalized Enrichment Score (NES) obtained from the GSEA was selected as the most sensitive. The NES for each drug was standardized and rank-ordered according to Sensitive/Intermediate/Resistant categories to generate a nominal chemo-sensitivity profile for the pt. This generates a comprehensible report called chemogram (ChG). We assessed preliminary efficacy in pts treated based on ChG. Results: ChG was obtained in 74/75 pts (57% male/43% female, median age 57y [20-81]) Tumor’s type was GI 67% (CRC n=18; pancreatic n=18; gastric n=6; cholangiocarcinoma n=7), NSCLC 14%, breast 8%, sarcoma 8%, others 3%. Median of 2 previous lines of therapy [range 1-12]. ECOG PS was 1 in 56%. Average RNA/pt 2.4 ng/µl (95% CI 1.5-3.4) Median time to obtain the report from blood extraction was 4 wks [range 2-7] Pts treated after the ChG were 37 (49%), of them 25 (69%) based on ChG recommended drug. In patients treated with ChG sensitive drugs, PFSratio ≥ 1.3 (PFS on therapy after ChG/PFS on prior therapy) was 24%, and 3 partial responses (12%) were observed. Conclusions: It is feasible to generate a sensitivity drug profiling on CTCs which shows preliminary activity and merits further studies.
CORRELATION BETWEEN ECHOCARDIOGRAPHIC MEASURES AND HS-CTNT LEVELS PRE- AND POST-BARIATRIC SURGERY
Authors: Carine Hamo, Amelia Wallace, Amil M. Shah, Roberta Florido, Justin Echouffo Tcheugui, Kunihiro Matsushita, Gary Gerstenblith, Ron Hoogeveen, Christie M. Ballantyne, Elizabeth Selvin, Josef Coresh, Chiadi Ndumele
Journal: Journal of the American College of Cardiology (2020)
Trefoil factor 1 as a predictive factor of bone metastases in breast cancer.
Authors: Laura Mercatali, Yibin Kang, Michele Zanoni, Chiara Liverani, Elisa Carretta, Marianna Ricci, Nada Riva, Sebastiano Calpona, Alberto Bongiovanni, Wainer Zoli, Dino Amadori, Toni Ibrahim
Journal: Journal of Clinical Oncology (2013)

11022 Background: Patients with breast cancer frequently develop bone metastases, which are responsible for high morbidity and reduced quality of life. The early identification of patients with a high probability of relapsing in this site could be used to select candidates for tailored therapy with bone-specific drugs such as bisphosphonates or RANK-L inhibitors. We aimed to identify a pattern of tissue markers in primary breast cancer that could predict bone metastatization. Methods: Expression of different markers was retrospectively analyzed in frozen breast cancer tissue samples from 90 patients comprising 30 cases with no evidence of disease (NEDP), 30 with bone metastases (BMP) and 30 with visceral metastases (VMP). Eight transcripts were analyzed by Quantitative Real time PCR: trefoil factor 1(TFF1), bone sialoprotein (IBSP), heparanase (HPSE), secreted protein acidic and rich in cysteine (SPARC), connective tissue growth factoe (CTGF), B2 microglobulin (B2M) and receptor activator of Nf-kB (RANK). Immunohistochemistry of TFF1 was performed on a part of the case series. Results: Marker expression analysis in the 3 different subgroups showed at least twofold higher median values of all markers in NEDP and VMP subgroups than in BMP. In particular, TFF1, B2M and CXCR4 levels showed statistically significant values. Median TFF1 value in BMP patients was 430.64 compared to 115.83 and 32.79 in VMP and NEDP, respectively (p=0.0043). Considering markers as dichotomous variables, TFF1 expression in BMP reached 59% compared to 21% and 23 % in NEDP and VMP, respectively (p=0.0022). Univariate analysis confirmed that TFF1 predicted the relapse and also the site of relapse. Immunohistochemistry data on TFF1 revealed that this protein was expressed only by cancer cells. Furthermore, the accuracy of the marker did not change at RNA or protein level, thus excluding a post transcriptional control of the RNA. Conclusions: In this preliminary study we identified a gene expression pattern in primary breast cancer that can identify patients destined to relapse to the bone. In particular, TFF1 would seem to be a suitable marker for bone metastatization and a possible target for the development of new drugs.
Nomogram for survival after primary surgery for bulky stage IIIC ovarian carcinoma
Authors: D. S. Chi, Y. Sonoda, N. R. Abu-Rustum, C. S. Awtrey, J. Huh, R. R. Barakat, M. W. Kattan
Journal: Journal of Clinical Oncology (2006)

5058 Background: Nomograms have been developed for numerous malignancies to predict a specific individual’s probability of long-term survival based on known prognostic factors. To date, no prediction model has been developed for patients with ovarian cancer. The objective of this study was to develop a nomogram to predict the probability of 4-year survival after primary cytoreductive surgery for bulky stage IIIC ovarian carcinoma. Methods: Nomogram predictor variables included age, tumor grade, histologic type, preoperative platelet count, the presence or absence of ascites, and residual disease status after primary cytoreduction. Disease-specific survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used for multivariable analysis. The Cox model was the basis for the nomogram. The concordance index was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. Results: A total of 462patients with bulky stage IIIC ovarian carcinoma underwent primary cytoreductive surgery at our institution during the study period of 1/89 to 12/03, of whom 397 were evaluable for inclusion in the study. The median age of the study population was 60 years (range 22–87). The primary surgeon in all cases was an attending gynecologic oncologist. Postoperatively, all patients received platinum-based systemic chemotherapy. Ovarian cancer-specific survival at 4 years was 51%. A nomogram was constructed on the basis of a Cox regression model and the 6 predictor variables. This nomogram was internally validated using bootstrapping and shown to have excellent calibration with a bootstrap-corrected concordance index of 0.67. Conclusions: A nomogram was developed to predict 4-year disease-specific survival after primary cytoreductive surgery for bulky stage IIIC ovarian carcinoma. The nomogram utilizes 6 predictor variables that are readily accessible, assigns a point value to each variable, and then predicts the probability of 4-year survival based on the total point value for an individual patient. This tool should be useful for patient counseling, clinical trial eligibility determination, postoperative management, and follow-up. No significant financial relationships to disclose.
Mediation of Cartilage Matrix Degeneration and Fibrillation by Decorin in Post‐traumatic Osteoarthritis
Authors: Qing Li, Biao Han, Chao Wang, Wei Tong, Yulong Wei, Wei‐Ju Tseng, Li‐Hsin Han, X. Sherry Liu, Motomi Enomoto‐Iwamoto, Robert L. Mauck, Ling Qin, Renato V. Iozzo, David E. Birk, Lin Han
Journal: Arthritis & Rheumatology (2020)

To elucidate the role of decorin, a small leucine-rich proteoglycan, in the degradation of cartilage matrix during the progression of post-traumatic osteoarthritis (OA).Three-month-old decorin-null (Dcn-/- ) and inducible decorin-knockout (DcniKO ) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post-traumatic OA. The OA phenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy-nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro-computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild-type and Dcn-/- mice were stimulated with the inflammatory cytokine interleukin-1β (IL-1β) in vitro (n = 6 mice per group). The resulting chondrocyte response to IL-1β and release of sGAGs were quantified.In both Dcn-/- and DcniKO mice, the absence of decorin resulted in accelerated sGAG loss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P < 0.05). Also, Dcn-/- mice developed more salient osteophytes, illustrating more severe OA. In cartilage explants treated with IL-1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion of sGAGs was released to the media from Dcn-/- mouse explants, in both live and devitalized conditions (P < 0.05).In post-traumatic OA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.
N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE IN THE PREDICTION OF REDUCED CORONARY FLOW VELOCITY RESERVE IN ASYMPTOMATIC TYPE 2 DIABETIC PATIENTS
Authors: Tamara Kovacevic-Preradovic, Bojan Stanetic, Ljiljana Kos, Gabrijela Malesevic, Snjezana Popovic-Pejicic, Ana Djordjevic-Dikic, Nathan Wong, Miodrag Ostojic
Journal: Journal of the American College of Cardiology (2020)
Simplified gemcitabine and platin regimen for NSCLC to be used in the neoadjuvant setting
Authors: G. Cartei, S. Binato, C. Sacco, S. Scalone, R. Ceravolo, U. Fantoni, S. Cingarlini, A. Palamidese, A. Iop, E. Colombrino
Journal: Journal of Clinical Oncology (2006)

17155 Background: Platin (P) salts and Gemcitabine (G) are used for NSCLC. GP regimens frequently included G on day 1, 8 and 15; P on day 2; every 28 days. However, the third G dose often is omitted because of myelo-toxicity, with a consistent no respect of the intended drugs’ doses. We devised a simplified regimen, based on two Day-Hospital admissions per cycle (c), with G on day 1 and 8; P after G on day 8; every 21 days. Aim of study: a high RR within the first 3 c.s for a GP regimen for neoadjuvant therapy. Methods: This prospective, multi-centre investigation included G (1500 mg/m 2 ) on day 1 and 8, and P (100 mg/m 2 ) on day 8 immediately following G, on a 3-weeks-c. Eligible criteria: age 18 to 75 years, NSCLC histologically, no previous chemotherapy, KPS 50%, WBC ≥ 4.0 × 10 9 /L, platelet ≥100 × 10 9 /L and normal kidney-liver function. QoL evaluation: 46 out of 95 valuable patients. Restaging procedures: repeated 3 and 6 c.s. Results: Out of 105 patients, 95 had at least 3 c.s and 59 of them had further 3 c.s. Myelo-toxicity ≥ G3 was mainly neuthropoenia, easily amenable with symptomatic and GCSF therapies; PNS toxicity occurred in 17.9% of patients. QoL was ameliorated (p &lt; 0.05). Therapy was tolerable; gave RR was 52.3% after 3 c.s (Intention-to-treat analysis) and 57.9% in 95 valuable patients after at least 3 therapy c.s. In the 95 valuable patients over the first 42 days, i.e. after 2 c.s and just before the third c., 10 c.s out of 190 were delayed by one week, with a dose intensity reduction of 5.29%. Conclusions: This two Day-Hospital admissions regimen is at least as good as more complex GP regimens, with an appreciable RR after 3c.s; it may be proponed in the neoadjuvant setting. Acknowledgments: Present work was part of studies program of, and partly supported by, AOI (Associazione Oncologia Italiana, Padova, Italy). No significant financial relationships to disclose.
Simultaneous inhibition of CXCR1/2, TGF-β, and PD-L1 remodels the tumor and its microenvironment to drive antitumor immunity
Authors: Lucas A Horn, Jeffrey Riskin, Heidi A Hempel, Kristen Fousek, Hanne Lind, Duane H Hamilton, Kristen K McCampbell, Dean Y Maeda, John A Zebala, Zhen Su, Jeffrey Schlom, Claudia Palena
Journal: Journal for ImmunoTherapy of Cancer (2020)

Despite the success of immune checkpoint blockade therapy in the treatment of certain cancer types, only a small percentage of patients with solid malignancies achieve a durable response. Consequently, there is a need to develop novel approaches that could overcome mechanisms of tumor resistance to checkpoint inhibition. Emerging evidence has implicated the phenomenon of cancer plasticity or acquisition of mesenchymal features by epithelial tumor cells, as an immune resistance mechanism.
Gender-concordant identity documents and mental health among transgender adults in the USA: a cross-sectional study
Authors: Ayden I Scheim, Amaya G Perez-Brumer, Greta R Bauer
Journal: The Lancet Public Health (2020)

Transgender (trans) people experience profound mental health disparities compared with the general population, attributable in part to the psychological effects of gender non-affirmation. Despite the barriers to legal gender affirmation for trans people, little is known about its association with mental health. We therefore sought to determine whether having gender-concordant identity documents (IDs) is associated with mental health among trans adults in the USA. We hypothesised that having an ID that reflects one's preferred name and gender marker would be associated with reduced psychological distress and suicide risk.In this cross-sectional observational study, we obtained data from the 2015 US Transgender Survey, the largest cross-sectional survey of trans adults in the USA, with 27 715 participants. Eligible participants were adults (≥18 years), residing in a US state, territory, or overseas US military base; and considered themselves transgender, trans, genderqueer, non-binary, or similar. We excluded participants not living day-to-day in a different gender to the sex they were assigned at birth, participants who identified as crossdressers, and those missing data. The primary exposure of interest was whether all or some (vs none) of a respondent's IDs reflected their preferred name and gender marker. We examined associations with psychological distress (measured with the Kessler 6 scale) and suicide ideation, planning, and attempts in the past year, which we analysed using linear and modified Poisson regression models to examine associations with respondents' IDs.Of 22 286 respondents included in our analytic sample, 10 288 (weighted percentage 45·1%) had their preferred name and gender marker on none, 9666 (44·2%) on some, and 2332 (10·7%) on all of their IDs. Compared with those with no gender-concordant ID, respondents for whom all IDs were concordant had lower prevalence of serious psychological distress (adjusted prevalence ratio 0·68, 95% CI 0·61-0·76), suicidal ideation (0·78, 0·72-0·85), and suicide planning (0·75, 0·64-0·87), adjusting for potential confounders. Having some versus no concordant ID was generally associated with smaller reductions in distress and suicidality. Gender-concordant ID was not associated with suicide attempts (eg, adjusted prevalence ratio for all vs no IDs was 0·92, 95% CI 0·68-1·24).Possession of gender-concordant IDs might improve mental health among trans persons. Gender recognition policies should be considered structural determinants of transgender health.None.
Absence of MHC class II on cDC1 dendritic cells triggers fatal autoimmunity to a cross-presented self-antigen
Authors: Christian Wohn, Valentin Le Guen, Odessa Voluzan, Frédéric Fiore, Sandrine Henri, Bernard Malissen
Journal: Science Immunology (2020)

Conventional dendritic cells expressing the XCR1 chemokine receptor (cDC1s) excel at cross-presentation. Here, we developed and used a mouse model in which a Cre recombinase is expressed under the control of the Xcr1 gene while preserving XCR1 expression. We used it to generate mice with conditional deletion of MHC class II (MHCII) molecules on cDC1s. By preventing cDC1s to receive suppressive regulatory T cell inputs via MHCII-restricted interactions, the objective of the present study was to gauge whether MHCII-deficient cDC1s lose their capacity of tolerizing autoreactive CD8+ T cells. Whereas MHCII+ cDC1 readily cross-tolerized strongly autoreactive CD8+ T cells specific for a keratinocyte-derived self-antigen, MHCII-deficient cDC1s converted them into potent effectors capable of triggering a fast-onset lethal autoimmunity associated with severe skin histopathological manifestations. Preventing egress of such pathogenic self-reactive CD8+ T cell effectors from the cutaneous draining lymph nodes abrogated the autoimmune condition. Therefore, our results revealed that the cross-tolerizing capacity of cDC1s is not a property fully acquired at the time they undergo homeostatic maturation but needs to be enforced via MHCII-restricted, suppressive interactions with regulatory T cells.
CLO20-035: Real-World Minimal Residual Disease (MRD) Assessment and Trends Using clonoSEQ in B-Cell Acute Lymphoblastic Leukemia and Multiple Myeloma
Authors: Audrey Demaree, Anthony Hewitt, Ben Eckert, Lik Wee Lee
Journal: Journal of the National Comprehensive Cancer Network (2020)

"CLO20-035: Real-World Minimal Residual Disease (MRD) Assessment and Trends Using clonoSEQ in B-Cell Acute Lymphoblastic Leukemia and Multiple Myeloma" published on 20 Mar 2020 by National Comprehensive Cancer Network.
Role of glutathione S-transferase and cytochrome P-450 polymorphisms in the clinical outcome of osteosarcoma patients.
Authors: Alini Trujillo-Paolillo, Carolina Salinas-Souza, Indhira Dias-Oliveira, Antonio Sergio Petrilli, Silvia R. C. Toledo
Journal: Journal of Clinical Oncology (2013)

10535 Background: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Glutathione S-transferase (GST) and Cytochrome P-450 (CYP) family genes are involved in almost all anticancer drugs metabolism. The polymorphisms in these genes are associated with anticancer drugs resistance and toxicity events. This study aims to investigate the genotype frequencies of GSTM1, GSTT1, GSTM3, CYP1A2, CYP2C9 and CYP3A5 genes in OS patients and the influence of these polymorphisms in their clinical outcome. Methods: We investigated the peripheral blood DNA of 70 OS patients (25 metastatic and 45 nonmetastatic at diagnosis), following the GLATO - Latin American Group of Osteosarcoma Treatment - 2006. GSTM1 and GSTT1 deletion polymorphisms were examined through a multiplex-PCR and the GSTM3 polymorphism of three base pair-deletion using PCR-RFLP method. CYP1A2, CYP2C9 and CYP3A5 single nucleotide polymorphisms (SNPs) were investigated through real time PCR using TaqMan probe. Results: We found that GSTM1 null genotype was correlated with relapse occurrence (p=0,031) in patients that received high doses of chemotherapy. The CYP1A2*F allele was associated with lung metastasis (p=0,032), lung relapse (p=0,018) and high grade of ototoxicity (p=0,039). The CYP3A5*3 allele was associated with high grade of hepatotoxicity (p=0,010). The presence of at least one GSTM3*B allele was associated with better overall survival (p=0,045). The presence of CYP3A5*3 homozygous genotype was associated with better overall survival (p=0,043) in metastatic patients at diagnosis. The genotype GSTM3*B/ GSTM1 present, GSTM3*B/ GSTT1 present and GSTM3*B/CYP3A5*3 in metastatic patients at diagnosis were associated with better survival (p=0,048; p=0,004; p=0,012, respectively). Conclusions: The findings of this study suggest that GST and CYP polymorphisms may have a role in treatment response and may be an important marker in the future to personalized therapy in OS. Furthermore, CYP1A2*F allele is correlated with risk of lung metastasis and GSTM3*B homozygous genotype in combination with GSTM1 present, GSTT1 present and CYP3A5*3 were associated with better survival.
FAMILY HISTORY OF SUDDEN CARDIAC DEATH IN BRUGADA SYNDROME: A SYSTEMIC REVIEW AND META-ANALYSIS
Authors: Pattara Rattanawong, Jakrin Kewcharoen, Chanavuth Kanitsoraphan, Timothy Barry, Anusha Shanbhag, Nway L. Ko Ko, Wasawat Vutthikraivit, Win-Kuang Shen
Journal: Journal of the American College of Cardiology (2020)