tbuckley/cabot-search huggingface dataset:
Abstract PS16-27: Small extracellular vesicle-mediated intercellular TGF-β1 transferring promotes adriamycin-resistant transmission in breast cancer cells
Authors: Zhi Xu, JInhai Tang
Journal: Cancer Research (2021)

Abstract Chemotherapeutic resistance is a major obstacle to control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we demonstrate that sEV-TGF-involves in intercellular drug-resistant transmission from adriamycin-resistant cells to adriamycin-sensitive cells. sEVs were isolated and characterized form the both sensitive and resistant cells. sEVs derived from the resistant cells were incubated with the sensitive cells and resulted in transmitting the resistant phenotype to the recipient cells. Cytokine antibody microarray revealed that most metastasis associated cytokines present at the high levels in sEVs from the resistant cells compared to their levels in sEVs from the sensitive cells, particularly TGF-β1. The sEV-TGF-β1 led to phosphorylation of Smad2/3 and remarkably changed the phenotypes of the recipient cells by suppressing apoptosis and enhancing cell movability. Finally, the sEV-TGF-mediated drug-resistance transmission was validated using a zebrafish xenograft tumor model. The results from this study elaborated that sEV-TGF-β1 intercellular transfer contributes to adriamycin resistance in BCa. Citation Format: Zhi Xu, JInhai Tang. Small extracellular vesicle-mediated intercellular TGF-β1 transferring promotes adriamycin-resistant transmission in breast cancer cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-27.
Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study
Authors: Huiqiang Huang, Jun Zhu, Ming Yao, Tae Min Kim, Dok Hyun Yoon, Seok-Goo Cho, Hyeon Seok Eom, Soon Thye Lim, Su-peng Yeh, Yuqin Song, Yok Lam Kwong, Jin Seok Kim, Jie Jin, Yuankai Shi, HyeJin Kim, Min Qing, Tianyuan Zhou, Grace Gao, Zongqi Dong, Ming Qi, Won Seog Kim
Journal: Journal of Hematology & Oncology (2021)

Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL.This phase 2 study with Simon's two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification).In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5-43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29-339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43-106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94-438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab.In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016.
Increased lysosomal burden correlates with the metastatic potential of human breast cancer xenografts
Authors: Kristine Glunde, Catherine A. Foss, Tiffany Greenwood, Zaver M. Bhujwalla
Journal: Cancer Research (2006)

3446  β1,6-N-acetylgulcosaminyltransferase V (GnT-V) expression, assessed via β1,6-branched oligosaccharide formation, is common in human cancer and is correlated with metastasis and poor survival. GnT-V has multiple glycoprotein substrates and thereby exerts global effects on cancer progression, characteristic of a master regulator of metastasis. Yet little is known of GnT-V expression within tumors at the tissue and cellular levels. Here we report histochemical analyses comparing GnT-V and β1,6-branched oligosaccharides in malignant melanoma (n = 24 cases). We were surprised to find distinct patterns of GnT-V expression that differed between cases. Methods. GnT-V and β1,6-branched oligosaccharides were compared in formalin-fixed, paraffin-embedded tumor specimens. Tumor sections were stained with anti-GnT-V, with the lectin LPHA (β1,6-branched oligosaccharides), and in some cases with antibodies to the Golgi complex. Stains were analyzed by light microscopy. Results. All tumors stained with GnT-V. On the cellular level GnT-V stained large perinuclear structures consistent with the Golgi complex and also showed cytoplasmic staining. Thus although GnT-V is known to be enzymatically active in the Golgi complex, the protein was not localized solely to this structure. On the tissue level three staining patterns were seen. 1) The most common was uniform GnT-V staining throughout the tumor with a correspondence between GnT-V protein and β1,6-branched oligosaccharides. Thus in this pattern most if not all tumor cells were induced for GnT-V synthesis and enzymatic activity. 2) In a second pattern GnT-V protein was restricted to certain nests or areas of the tumor where again there was a correspondence with β1,6-branched oligosaccharides. This pattern indicated different tumor cell phenotypes for GnT-V synthesis or degradation. 3) In a third pattern, GnT-V stained throughout the tumor but in this case β1,6-branched oligosaccharides were restricted to certain nests or areas. This indicted selective activation or inhibition of GnT-V enzymatic activity. Conclusions. These findings reveal for the first time that GnT-V synthesis and enzymatic activity are subject to multiple levels of regulation. This information should help pave the way to a fuller understanding of GnT-V expression —a key factor in tumor invasion and metastasis.
Dynamics of SARS-CoV-2 shedding in the respiratory tract depends on the severity of disease in COVID-19 patients
Authors: Dieter Munker, Andreas Osterman, Hans Stubbe, Maximilian Muenchhoff, Tobias Veit, Tobias Weinberger, Michaela Barnikel, Jan-Niclas Mumm, Katrin Milger, Elham Khatamzas, Sarah Klauss, Clemens Scherer, Johannes C. Hellmuth, Clemens Giessen-Jung, Michael Zoller, Tobias Herold, Stephanie Stecher, Enrico N. de Toni, Christian Schulz, Nikolaus Kneidinger, Oliver T. Keppler, Jürgen Behr, Julia Mayerle, Stefan Munker
Journal: European Respiratory Journal (2021)

A fraction of COVID-19 patients progress to a severe disease manifestation with respiratory failure and the necessity of mechanical ventilation. Identifying patients at risk is critical for optimised care and early therapeutic interventions. We investigated the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding relative to disease severity. We analysed nasopharyngeal and tracheal shedding of SARS-CoV-2 in 92 patients with diagnosed COVID-19. Upon admission, standardised nasopharyngeal swab or sputum samples were collected. If patients were mechanically ventilated, endotracheal aspirate samples were additionally obtained. Viral shedding was quantified by real-time PCR detection of SARS-CoV-2 RNA. 45% (41 out of 92) of COVID-19 patients had a severe disease course with the need for mechanical ventilation (severe group). At week 1, the initial viral shedding determined from nasopharyngeal swabs showed no significant difference between nonsevere and severe cases. At week 2, a difference could be observed as the viral shedding remained elevated in severely ill patients. A time-course of C-reactive protein, interleukin-6 and procalcitonin revealed an even more protracted inflammatory response following the delayed drop of virus shedding load in severely ill patients. A significant proportion (47.8%) of patients showed evidence of prolonged viral shedding (&gt;17 days), which was associated with severe disease courses (73.2%). We report that viral shedding does not differ significantly between severe and nonsevere COVID-19 cases upon admission to the hospital. Elevated SARS-CoV-2 shedding in the second week of hospitalisation, a systemic inflammatory reaction peaking between the second and third week, and prolonged viral shedding are associated with a more severe disease course.
Evolution of epitope-specific IgE and IgG4 antibodies in children enrolled in the LEAP trial
Authors: Mayte Suarez-Farinas, Maria Suprun, Henry T. Bahnson, Rohit Raghunathan, Robert Getts, George duToit, Gideon Lack, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2021)
Reply: Matters Arising ‘Investigating sources of inaccuracy in wearable optical heart rate sensors’
Authors: Brinnae Bent, Oana M. Enache, Benjamin Goldstein, Warren Kibbe, Jessilyn P. Dunn
Journal: npj Digital Medicine (2021)

This is a response to the Matters Arising (MA) that examines our original article, 'Investigating inaccuracies in wearable optical heart rate sensors' 1 .We performed this original study to address the concern that there was inadequate published research on the potential effect of skin tone on wearable device accuracy.The central hypothesis tested in the original study was that darker skin tones have decreased photoplethysmography-based heart rate measurement accuracy as compared with lighter skin tones.The MA suggests improvements surrounding two aspects of the original study: the sample size and the use of the Fitzpatrick skin tone (FP) scale to categorize skin tones.The original study was designed and powered according to the above hypothesis.We acknowledge that visual skin tone scales are imperfect, and that a study can never prove the null hypothesis to be true.We, too, encourage more work examining wearable device accuracy across skin tones.In this reply, we aim to address questions surrounding the sample size, covariates, and choice of skin tone scale in the original article.The two overarching analyses planned for the original study were an Analysis of Variance (ANOVA) to test for a difference in means of heart rate accuracy between FP skin tone groups, and a mixed effects regression model to explore potential effects of wearable device type and activity type during wear.To achieve 80% power to reject the null hypothesis that there is no difference in heart rate accuracy between the six FP groups (∝ = 0.5), we concluded that 48 participants were needed overall, with eight participants in each of the skin tone categories for the ANOVA and 46 needed for the mixed effects model (f2 = 0.15).We acknowledge that power analyses are imperfect sample size calculation tools and that domain-knowledge based decisions must be made to define the parameters of the power analysis.Here, a medium effect size of 0.3 was chosen based on a pilot study examining differences in green light absorption across skin tones on the FP scale 2 .In this study, we recruited and enrolled an approximately equal distribution of skin tones to meet our power requirements (with 7, 8, 10, 9, 9, and 10 participants, respectively, for FP groups 1-6).In the MA it is suggested that there should be an increased number of participants in FP6.Addressing concerns raised in the MA of greater heterogeneity in darker skin tone groups, we did not find differences in variance of heart rate measurements or their errors across skin tone groups (Fig. 2).Overall, we recommend a statistically-based justification for all sample size choices.Given established effects of movement on PPG heart rate accuracy [3][4][5][6] , in the original study we comprehensively explored potential interaction between skin tone and level of activity (Fig 2).No interaction effects were found that could not be directly
A novel balloon-attached endoscopy-assisted reduction technique for an acute strangulated stoma prolapse
Authors: Takaya Shimura, Takanori Ozeki, Hajime Ushigome, Takahisa Hirokawa, Kazuyoshi Shiga, Hiroki Takahashi, Hiromi Kataoka
Journal: Endoscopy (2021)

Stoma prolapse is a common late complication that occurs in 2–26 % of colostomies [1]. Prolapse is most frequently seen after loop colostomies [2] and often involves the distal limb [3]. Prolapsed stoma is rarely incarcerated or strangulated; however, such cases require emergency surgery [3] [4].
Targeting the HuR Oncogenic Role with a New Class of Cytoplasmic Dimerization Inhibitors
Authors: Natalia Filippova, Xiuhua Yang, Subramaniam Ananthan, Jennifer Calano, Vibha Pathak, Larry Bratton, Rakesh H. Vekariya, Sixue Zhang, Edward Ofori, Emily N. Hayward, David Namkoong, David K. Crossman, Michael R. Crowley, Peter H. King, James Mobley, Louis B. Nabors
Journal: Cancer Research (2021)

Abstract The development of novel therapeutics that exploit alterations in the activation state of key cellular signaling pathways due to mutations in upstream regulators has generated the field of personalized medicine. These first-generation efforts have focused on actionable mutations identified by deep sequencing of large numbers of tumor samples. We propose that a second-generation opportunity exists by exploiting key downstream “nodes of control” that contribute to oncogenesis and are inappropriately activated due to loss of upstream regulation and microenvironmental influences. The RNA-binding protein HuR represents such a node. Because HuR functionality in cancer cells is dependent on HuR dimerization and its nuclear/cytoplasmic shuttling, we developed a new class of molecules targeting HuR protein dimerization. A structure–activity relationship algorithm enabled development of inhibitors of HuR multimer formation that were soluble, had micromolar activity, and penetrated the blood–brain barrier. These inhibitors were evaluated for activity validation and specificity in a robust cell-based assay of HuR dimerization. SRI-42127, a molecule that met these criteria, inhibited HuR multimer formation across primary patient-derived glioblastoma xenolines (PDGx), leading to arrest of proliferation, induction of apoptosis, and inhibition of colony formation. SRI-42127 had favorable attributes with central nervous system penetration and inhibited tumor growth in mouse models. RNA and protein analysis of SRI-42127–treated PDGx xenolines across glioblastoma molecular subtypes confirmed attenuation of targets upregulated by HuR. These results highlight how focusing on key attributes of HuR that contribute to cancer progression, namely cytoplasmic localization and multimerization, has led to the development of a novel, highly effective inhibitor. Significance: These findings utilize a cell-based mechanism of action assay with a structure–activity relationship compound development pathway to discover inhibitors that target HuR dimerization, a mechanism required for cancer promotion.
Abstract PS6-40: Clinical risk criteria and recurrence index for distant recurrence for patients with early stage luminal breast cancer
Authors: Skye Hung-Chun Cheng, Liang-Chih Liu, Ling-Ming Tseng, Chuan-Hsun Chang, Chiun-Sheng Huang, Ji-An Liang, Yu-Chen Hsu, Chia-Ming Hsieh, Jun-Ru Wei
Journal: Cancer Research (2021)

Abstract Background:Clinical risk criteria (CRC) has been used in two well-known gene-expression trials (TAILORX and MINDACT) to predict the risk of distant recurrence (DR). The definition of clinical low-risk patients was (1) node-negative associated with (grade 1 with tumor ≤3cm, grade 2 with tumor≤2cm, or grade 3 with tumor ≤1cm) and N1 with grade 1 and tumor ≤2cm. Recurrence Index for distant recurrence (RI-DR) is a clinical-genomic model, based on genomic profiling derived from Asian women. The primary purpose of this study is to access the clinical utility of RI-DR and CRC in Asian breast cancer patients. Methods:A total of 208 patients (N0 70.2%, N1 29.8%) with luminal-like breast cancer were enrolled in a retrospective study across Taiwan medical centers. Kaplan-Meier method was used to calculate the survival rates and the log rank test was applied for the survival difference between two or more independent groups. The primary endpoint was the recurrence-free interval (RFI). Results:With a median follow-up of 49.05 [IQR 29.72-71.96], the 5-year RFI was significantly poorer in the high-risk group than the low-risk group (87.2% [95% CI, 80.0-95.0] versus 95.2% [89.75-100] by the RI-DR, p = 0.011; and 86.9% [79.8-94.6] versus 97.0% [92.9-100] by the clinical risk, p = 0.03). Combined the CRC and RI-DR together, clinical high (CH) and RI-DR high (RH)had the poorest 5-year RFI (85.2%, [76.6-94.8]); clinical low (CL) and RI-DR low (RL) had the best 5-year RFI (98.0% [94.08, 100]). Among CL-risk patients, RL group has a trend towards less recurrence than RH group (1/66 [1.51%] versus 2/19 [10.52%], p= 0.15). Similar trend was observed in CH-risk patients (RL: 2/41 (4.88%) versus RH: 12/82 [14.63%], p = 0.17) (Table 1). Conclusions:The present study provides robust evidences that clinical-risk criteria and RI-DR testing could partition patients into good and poor prognosis in early-stage luminal breast cancer. RI-DR has a trend to identify low- and high-risk patients if clinical risk criteria have been applied in clinical practice. Analyses of Clinical Risk Criteria and Recurrence Index TogetherNo. of PatientsNo. of Events5-year RFI % (95% CI)Log rank, P valueClinical-Clinical-HighRI-DR high821285.20 [76.55, 94.81]0.17RI-DR low41291.30 [80.15, 100]Clinical-LowRI-DR high19294.12 [83.57, 100]0.15RI-DR low66197.96 [94.08, 100] Citation Format: Skye Hung-Chun Cheng, Liang-Chih Liu, Ling-Ming Tseng, Chuan-Hsun Chang, Chiun-Sheng Huang, Ji-An Liang, Yu-Chen Hsu, Chia-Ming Hsieh, Jun-Ru Wei. Clinical risk criteria and recurrence index for distant recurrence for patients with early stage luminal breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-40.
CLINICAL OUTCOME OF PATIENTS TREATED WITH HEPATIC ARTERIAL INFUSION OF OXALIPLATIN AND L-FOLINIC ACID MODULATED 5-FLUOROURACIL FOR INOPERABLE COLORECTAL CANCER LIVER METASTASES, A SINGLE CENTER EXPERIENCE
Authors: M.k. Van Bael, Jacques De Greve, Georges Delvaux, Bart Neyns
Journal: Annals of Oncology (2010)
A Clinically Applicable 24-Protein Model for Classifying Risk Subgroups in Pancreatic Ductal Adenocarcinomas using Multiple Reaction Monitoring-Mass Spectrometry
Authors: Minsoo Son, Hongbeom Kim, Dohyun Han, Yoseop Kim, Iksoo Huh, Youngmin Han, Seung-Mo Hong, Wooil Kwon, Haeryoung Kim, Jin-Young Jang, Youngsoo Kim
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) subtypes have been identified using various methodologies. However, it is a challenge to develop classification system applicable to routine clinical evaluation. We aimed to identify risk subgroups based on molecular features and develop a classification model that was more suited for clinical applications. Experimental Design: We collected whole dissected specimens from 225 patients who underwent surgery at Seoul National University Hospital [Seoul, Republic of Korea (South)], between October 2009 and February 2018. Target proteins with potential relevance to tumor progression or prognosis were quantified with robust quality controls. We used hierarchical clustering analysis to identify risk subgroups. A random forest classification model was developed to predict the identified risk subgroups, and the model was validated using transcriptomic datasets from external cohorts (N = 700), with survival analysis. Results: We identified 24 protein features that could classify the four risk subgroups associated with patient outcomes: stable, exocrine-like; activated, and extracellular matrix (ECM) remodeling. The “stable” risk subgroup was characterized by proteins that were associated with differentiation and tumor suppressors. “Exocrine-like” tumors highly expressed pancreatic enzymes. Two high-risk subgroups, “activated” and “ECM remodeling,” were enriched in terms such as cell cycle, angiogenesis, immunocompetence, tumor invasion metastasis, and metabolic reprogramming. The classification model that included these features made prognoses with relative accuracy and precision in multiple cohorts. Conclusions: We proposed PDAC risk subgroups and developed a classification model that may potentially be useful for routine clinical implementations, at the individual level. This clinical system may improve the accuracy of risk prediction and treatment guidelines. See related commentary by Thakur and Singh, p. 3272