tbuckley/cabot-search huggingface dataset:
Correlation of statin use with breast random periareolar fine needle aspiration (RPFNA) cytomorphology in high risk postmenopausal women
Authors: P. Sharma, B. F. Kimler, T. Kennedy, E. J. Smith, Q. J. Khan, C. J. Fabian
Journal: Journal of Clinical Oncology (2006)

1031 Background: In vitro studies have demonstrated that statins (HMG CoA reductase inhibitors) suppress tumor growth and proliferation in breast cancer cell lines. Published clinical data on the chemoprotective role of statins in breast cancer are conflicting. Moreover, there are no published studies specifically examining the impact of statin use on breast cancer risk biomarkers in high risk women. We have previously demonstrated that cytologic atypia detected by RPFNA is associated with a 5 fold increase in short term risk of breast cancer in high risk women. The aim of this study was to explore the effect of statin use on breast RPFNA cytomorphology in postmenopausal women at high risk of developing breast cancer (based on personal and family history). Methods: Thehigh risk breast clinic database at the University of Kansas Medical Center was queried from April 2002 to September 2005 for statin use in postmenopausal women. We first identified postmenopausal women who underwent RPFNA while on a statin (cases). Postmenopausal women who underwent RPFNA while not on a statin (controls) were then identified and matched with statin users for known breast cancer risk factors (age, 5 year Gail risk and BMI). Frequencies of categorical variables were assessed using chi-square analysis. Continuous variables were assessed using Mann-Whitney non parametric test. Results: 504 postmenopausal women were identified. Thirty five of these 504 women underwent RPFNA while on statin therapy. For statin users (cases), the median age was 56 years, median 5 year Gail risk was 3.6%, median BMI was 28 and the median duration of statin use was 1.4 years (range 0.3 to 13 yrs). Sixty nine controls were identified. There was no difference between cases and controls with respect to HRT use (54% vs 40%, p=0.22), duration of HRT use (p=0.30) and visual breast density (p=0.80). RPFNA atypia was detected in 11% of cases and 26% of controls (p=0.13). Conclusion: Although prevalence of RPFNA atypia was less frequent among statin users, this difference was not statistically significant in this small cohort of high risk women with relatively short duration of statin use. Larger studies are warranted to investigate this further. No significant financial relationships to disclose.
Augmentation of the cytotoxicity of ibandronate by y-27632, a rho kinase inhibitor, in prostate cancer cells.
Authors: Alper Ata, Ata Ozcimen, Hakan Kurt, Nalan Tiftik, Ali Arican, Kansu Buyukafsar
Journal: Journal of Clinical Oncology (2012)

e15104 Background: Bisphosphonates, which have been used for the treatment of breast and prostate cancers (Epplen et al., 2011) inhibit mevalonate pathway that results in the reduction of Ras prenylation, which eventually inhibits tumor growth (Luckman et al., 1998). Rho/Rho kinase signaling has a fundamental role in cancer cell proliferation, migration and metastasis (Vega et al., 2008) Therefore, in this study, we aimed to investigate effects of Y-27632, which inhibits Rho-kinase, ibandronate, which inhibits farnesyl transferase and their combination on cell proliferation in prostate cell lines, PC-3. Methods: The adherent prostate cell line, PC-3 (ATCC) was grown in RPMI-1640 supplemented with 10 % fetal bovine serum, 1 % L-glutamine, 1 % penicillin (10.000U/ml) and streptomycin (10.000 mg/ml) in a humidified atmosphere of 5 % CO 2 at 37 o C for confluency. The cells were seeded in the wells of E-plates (24,000 cells/well) that allowed a real-time-monitoring of the cell index reflected cell growth and proliferation (xCELLigence, Roche). The cell index was evaluated at the different points of time (post-treatment 12, 24, 36, 48, 60 and 72 h) in the groups of ibandronate, Y-27632, the combination and time-course control. Results: Ibandronate (10-100 mM), Y-27632 (50-100 mM) markedly decreased cell index. The combination of Y-27632 with ibandronate resulted in potentiation of cytotoxicity in PC-3 cells. Conclusions: Rho kinase inhibitors, biphosphonates and their combination may be beneficial for the treatment of prostate cell cancers.
COMPARISON OF SENSITIVITY AND SPECIFICITY OF DELTA CALCIUM SCORE, POOLED COHORT RISK ASSESSMENT, AND FRAMINGHAM RISK SCORE FOR PREDICTING MYOCARDIAL INFARCTION OR CLINICAL REVASCULARIZATION
Authors: Chirag Desai, Phillip Petrasko, Terezia Petraskova, Tomasz Kozlowski, Adu Solomon, Tomasz Stys
Journal: Journal of the American College of Cardiology (2020)
ICOS Is an Indicator of T-cell–Mediated Response to Cancer Immunotherapy
Authors: Zunyu Xiao, Aaron T. Mayer, Tomomi W. Nobashi, Sanjiv S. Gambhir
Journal: Cancer Research (2020)

Immunotherapy is innovating clinical cancer management. Nevertheless, only a small fraction of patient's benefit from current immunotherapies. To improve clinical management of cancer immunotherapy, it is critical to develop strategies for response monitoring and prediction. In this study, we describe inducible T-cell costimulator (ICOS) as a conserved mediator of immune response across multiple therapy strategies. ICOS expression was evaluated by flow cytometry, 89Zr-DFO-ICOS mAb PET/CT imaging was performed on Lewis lung cancer models treated with different immunotherapy strategies, and the change in tumor volume was used as a read-out for therapeutic response. ImmunoPET imaging of ICOS enabled sensitive and specific detection of activated T cells and early benchmarking of immune response. A STING (stimulator of interferon genes) agonist was identified as a promising therapeutic approach in this manner. The STING agonist generated significantly stronger immune responses as measured by ICOS ImmunoPET and delayed tumor growth compared with programmed death-1 checkpoint blockade. More importantly, ICOS ImmunoPET enabled early and robust prediction of therapeutic response across multiple treatment regimens. These data show that ICOS is an indicator of T-cell-mediated immune response and suggests ICOS ImmunoPET as a promising strategy for monitoring, comparing, and predicting immunotherapy success in cancer. SIGNIFICANCE: ICOS ImmunoPET is a promising strategy to noninvasively predict and monitor immunotherapy response.See related commentary by Choyke, p. 2975.
Nimotuzumab with concurrent chemoradiotherapy in patients with locally advanced head and neck cancer (LASCCHN).
Authors: Naresh Somani, Karandikar SM, Kamlesh Bokil, Kumar Tapash Bhowmik, Shyam Agarwal
Journal: Journal of Clinical Oncology (2013)

6084 Background: Nimotuzumab is a humanized monoclonal antibody targeting EGFR receptors. Unlike other anti-EGFR monoclonal antibodies, it has demonstrated to be safe and effective when combined with chemotherapy or/and radiotherapy. We evaluated safety and efficacy of concurrently administrating nimotuzumab with chemo-radiotherapy in patients with locally advanced inoperable squamous cell carcinomas of head and neck region in a usual health care setting. Methods: Open-label single-arm study. Patients of age 18 years and above with histologically confirmed squamous cell cancer of head and neck region in an inoperable stage (stage III &amp; IV) having an ECOG ≤ 2 were included in the study. Informed consent was obtained from all the patients. The patient were administered injection cisplatin (30 mg/m 2 IV) and nimotuzumab (200 mg IV) weekly for six weeks along with radiotherapy of 6600cGy over 33 fractions. Patients were evaluated based on RECIST criteria 24 weeks after the last cycle of chemotherapy. Results: Fifty seven patients were enrolled in the study. Mean age of the patients was 51yr (29 yr-79 yr). Most common site of cancer was oral cavity 32 (56.14%). Fourty six (80.70%) patients completed 6 cycles of therapy. ORR was 80.7%, 34 with CR (59.6%), 12 with PR (21%), 8 with SD (14%), 3 with PD (5.2%). Most common adverse event seen was mucositis (33%) but there was no grade III or IV adverse event. Conclusions: Addition of anti-EGFR monoclonal antibody (nimotuzumab) is safe and efficacious based on the loco-regional response and confirms the available phase II data. The long-term survival benefits based on this encouraging response rate needs to be further evaluated especially in patients with inoperable LASCCN.
Identification and evaluation of outcome measurement instruments in pyoderma gangrenosum: a systematic review*
Authors: J.D. Lu, M.M. Hobbs, W.W. Huang, A.G. Ortega‐Loayza, A. Alavi
Journal: British Journal of Dermatology (2020)

Pyoderma gangrenosum (PG) is a rare autoinflammatory skin condition that causes tissue destruction and subsequent painful ulcers. To date, there are no core domains or instruments for assessing PG severity in clinical trials, and current treatment paradigms rely on outcome measurements that have not been well characterized in the literature.To perform two systematic reviews that (i) identify the outcome measurement instruments used in PG clinical trials and their corresponding domains and (ii) identify any associated validation studies and evaluate their measurement properties and methodological quality.We systematically searched the MEDLINE and Embase databases for PG outcome measurement instruments. We also systematically searched for PG instrument validation studies. We evaluated the measurement properties and methodological quality of validation studies using the 2018 COSMIN Risk of Bias checklist.In total, seven clinical trials were included. These studies utilized a total of 20 different instruments, including 11 physician-reported instruments, eight patient-reported instruments and one composite instrument. Among these, 85% of the instruments lacked any validation data. Of the remaining three validated instruments (speed of healing, physician global assessment and resolution of inflammation), methodological quality was not available for half of the COSMIN categories.We identified 17 non-validated outcome measurement instruments used in PG clinical trials. We conclude that PG validation studies are required for existing instruments, and new instruments need to be developed to inform the consensus process for the development of a core outcome set for PG. What is already known about this topic? Pyoderma gangrenosum (PG) is a rare autoinflammatory skin condition that has been characterized by multiple outcome measurement instruments in clinical trials. However, there is no consensus on the most validated and appropriate outcome measurement instruments. What does this study add? This study identifies and evaluates 20 unique outcome measurement instruments for PG in the literature. Of these 20, 17 lack any instrument validation data, highlighting the need for future studies. What are the clinical implications of this work? Despite the current use of several outcome measurement instruments, future studies should explore the validation surrounding these instruments, as no instruments can currently be recommended.
The role of surgical cytoreduction before imatinib therapy in patients with advanced GIST.
Authors: Hojung An, Min-Hee Ryu, Baek-Yeol Ryoo, Byeong Seok Sohn, Ki-Hun Kim, Sung Tae Oh, Chang Sik Yu, Jeong Hwan Yook, Byung Sik Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2012)

10093 Background: Despite dramatic improvement of survival with introduction of imatinib mesylate, resistance to imatinib eventually develops in most of patients with advanced gastrointestinal stromal tumor (GIST). It is well known that baseline tumor size is an important factor related to imatinib resistance. We hypothesize that decreasing tumor size by surgery before starting imatinib may delay the emergence of resistance and improve prognosis in patients with advanced GIST. Methods: From 2001 to 2010, 102 patients with initially metastatic GIST and 147 patients with recurrent GIST were enrolled in this analysis. Patients with local relapse only were excluded because they were potentially curable by surgery alone. Patients were categorized into two groups according to the extent of cytoreduction; i.e., patients whose initial tumor bulk reduced &gt;75% surgically before starting imatinib (group A) and the others (group B). Results: Among total 249 patients, 62 patients received initial surgery. 35 (14%) patients whose tumor bulk reduced &gt; 75% were categorized into group A, and the remaining 214 (86%) were in group B. In group A, the median age was younger; more patients were initially metastatic; peritoneal metastases were more frequent; but liver metastases were less. The total tumor size was significantly reduced from median 122 mm before cytoreduction to 0 mm after on CT scans in group A. With a median follow-up of 42.7 months, progression-free survival (PFS) tended to be better in group A than in group B in univariate analysis (HR=0.60; 95% CI, 0.36-1.02; p=0.061), but PFS was not statistically different between the two groups in multivariate analysis (p=0.488). Meanwhile, absence of KIT exon 11 mutation (p=0.007), baseline total tumor size &gt; 150mm (p=0.043), and granulocyte count &gt; 5000/mm 3 (p=0.009) remained independent poor prognostic factors. Conclusions: Despite marked decrease of total tumor size, the outcomes were not significantly improved in patients receiving initial cytoreduction more than 75% of baseline tumor bulk before starting imatinib. These results suggest that initial cytoreduction does not have beneficial role in advanced GIST, so imatinib should be still the first treatment of choice in this population.
ECG-DERIVED AGE AND SURVIVAL: VALIDATING THE CONCEPT OF PHYSIOLOGIC AGE DETECTED BY ECG USING ARTIFICIAL INTELLIGENCE
Authors: Adetola Ladejobi, Jose Medina-Inojosa, Michal Shelly, Zachi Itzhak Attia, Christopher Scott, Bernard J. Gersh, Peter Noseworthy, Paul Friedman, Suraj Kapa, Francisco Lopez-Jimenez
Journal: Journal of the American College of Cardiology (2020)
A Network-Based “Phenomics” Approach for Discovering Patient Subtypes From High-Throughput Cardiac Imaging Data
Authors: Jung Sun Cho, Sirish Shrestha, Nobuyuki Kagiyama, Lan Hu, Yasir Abdul Ghaffar, Grace Casaclang-Verzosa, Irfan Zeb, Partho P. Sengupta
Journal: JACC. Cardiovascular imaging (2020)
TILs in metastatic melanoma tumors: A biomarker for immunotherapy?
Authors: Sunandana Chandra, Yi Ding, Michelle W. Ma, Michael Bannan, Farbod Darvishian, Russell S. Berman, Richard Shapiro, Michelle Krogsgaard, Iman Osman, Anna C. Pavlick
Journal: Journal of Clinical Oncology (2012)

8589 Background: Increased tumor infiltrating lymphocytes (TILs) in primary (P) and locoregional melanoma tissue correlate with improved clinical outcome. Our recent data have suggested that matrix metalloproteinase 23 (MMP 23) expression (exp) in P result in lower prevalence of TILs and correlate with poor clinical outcome. On this basis, we examined P and metastatic (M) melanoma tissues to assess for concordance between the presence of TILs, MMP 23 protein levels and clinical response(resp) to anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) therapy (tx). Methods: 21 melanoma patients (pts) with M specimens were analyzed. 17 matched P specimens were also evaluated. Immunohistochemical (IHC) staining for TILs of the pre-anti-CTLA4 specimens were conducted and confirmed by 2 pathologists. IHC TILs were graded- 2+: &gt;10% TILs present in multiple foci in both peri- and through the tumor; 1+: 1-10% TILs present in one or more foci in the tumor and predominantly peri-tumor; 0: no TILs were present or if the lymphocytes did not infiltrate the tumor. TILs in P and M were analyzed for concordance and potential for predictability of resp to anti-CTLA4 tx. Staining to identify lymphocyte subtypes and MMP 23 exp in M is being completed. Results: 20 pts received anti-CTLA4 tx. M analysis- 6 pts with 0 TILs in M (5 no response [NR], 1 partial response[PR]); 8 pts with 1-2+ TILs in M (1 complete response [CR], 5 PR, 2 progressive disease [PD]); 6 pts with 2+ TILs in M ( 3 CR, 2 PR, 1PD). 1 pt with 2+ TILs in M resected, no tx and 4 years disease free. TILs present in 13 P, absent in 4 P and not evaluable in 4 pts with unknown P melanoma. MMP 23 protein scores in P (range 2-4) correlated with melanoma recurrence. MMP 23 exp in M will be reported. Conclusions: TILs in P do not appear to correlate with TILs in M or predict for resp to anti-CTLA4 tx. TILs in M may be an indicator of responsiveness to anti-CTLA4 tx. Identification of the type of M TIL subsets may further refine tx recommendations.
TGFb expression as predictor of outcome in EGFR wild type (WT) metastatic non-small cell lung cancer (NSCLC) patients (PTS) treated with EGFR tyrosine kinase inhibitors (TKIs).
Authors: Giovanna Finocchiaro, Luca Toschi, Letizia Gianoncelli, Barbara Canal, Luca Rubino, Chiara Lo Russo, Laura Giordano, Anna Destro, Isabella Garassino, Licia Siracusano, Raffaele Cavina, Massimo Roncalli, Antonino Carbone, Armando Santoro
Journal: Journal of Clinical Oncology (2012)

e18104 Background: Gefitinib and erlotinib have shown to be highly effective in pts harboring EGFR mutations, while the majority of EGFR wt pts does not respond to treatment.Preclinical data suggested that TGFb and HGF could affect response to TKIs. Aim of the present study is to investigate molecular predictors for primary resistance to TKIs in metastatic NSCLC pts. Methods: This retrospective study included 120 metastatic NSCLC patients treated with gefitinib (68/56.7%) or erlotinib (52/43.3%) in first line (20/16.7%) or after prior chemotherapy (100/83.4%) with at least one measurable lesion and availability of paraffin-embedded tumour tissue from primary cancer. Analyses included presence of mutations in EGFR and KRAS genes, assessment of ALK rearrangement by fluorescence in situ hybridization (FISH) and protein expression of HGF and TGFb by immunohistochemistry (IHC). Pts were grouped in IHC+ and IHC- according to staining intensity. Results: In the whole study cohort response rate (RR) was 9.2%, median progression free survival (PFS) 2.5 months, and overall survival (OS) 7.8 months. EGFR mutations were observed in 9.2% of pts and were significantly associated with better pts outcome. KRAS was mutated in 23.3% of pts without any correlation with clinical end points. ALK translocations were observed in 5 pts (4.2%), and none responded to treatment. IHC was successfully performed for HGF and TGFb in 95 and 75 pts respectively. No difference was seen in HGF+ (9/9.5%) vs HGF- pts in terms of RR, PFS and OS. TGFb+ pts (41/54.7%) had a significantly shorter OS than TGFb- pts (6.7 vs 10.3 months, p=0.020) although no difference in terms of RR and PFS was observed. When restricting survival analysis to EGFR wt/KRAS wt pts (n=80) TGFb+ subjects had a significantly worse PFS (1.9 vs 2.9 months, HR 2.16, CI 95% 1.18;3.95, p=0.013) and OS (5.3 vs 8.8 months, HR 2.07, CI 95% 1.10;3.91, p=0.025) when compared with the TGFb- group. Conclusions: Overexpression of TGFb is associated with a poor outcome in EGFR and KRAS wt pts treated with gefitinb or erlotinib. Prospective validation of the role of TGFb as a mediator of intrinsic resistance to EGFR TKIs in NSCLC is warranted.
Abstract 20803: Conditional Knockout of Heme Oxygenase-1 in Lysozyme M Positive Cells Attenuates Angiotensin II-Induced Vascular Inflammation
Authors: Moritz Brandt, Jeremy Lagrange, Sabine Kossmann, Thomas Münzel, Philip Wenzel
Journal: Circulation (2017)

Introduction: Heme oxygenase-1 (HO-1) protects vascular function in hypertension, presumably by anti-inflammatory effects on monocytes. The purpose of this study was to explore the role of HO-1 in ...
Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era
Authors: Gaurav Goyal, Mark L. Heaney, Matthew Collin, Fleur Cohen-Aubart, Augusto Vaglio, Benjamin H. Durham, Oshrat Hershkovitz-Rokah, Michael Girschikofsky, Eric D. Jacobsen, Kazuhiro Toyama, Aaron M. Goodman, Paul Hendrie, Xin-xin Cao, Juvianee I. Estrada-Veras, Ofer Shpilberg, André Abdo, Mineo Kurokawa, Lorenzo Dagna, Kenneth L. McClain, Roei D. Mazor, Jennifer Picarsic, Filip Janku, Ronald S. Go, Julien Haroche, Eli L. Diamond
Journal: Blood (2020)
HSR20-106: Quantifying Patient Preferences for Attributes Associated With First-Line Treatment of Metastatic Non-Small Cell Lung Cancer
Authors: Brian Seal, Candice Yong, M. Janelle Cambron-Mellott, Oliver Will, Martine C. Maculaitis, Kelly Clapp, Emily Mulvihill, Ion Cotarla, Ranee Mehra
Journal: Journal of the National Comprehensive Cancer Network (2020)

"HSR20-106: Quantifying Patient Preferences for Attributes Associated With First-Line Treatment of Metastatic Non-Small Cell Lung Cancer" published on 20 Mar 2020 by National Comprehensive Cancer Network.
ACTIVE SMOKING IS ASSOCIATED WITH DECREASED RATES OF WOUND HEALING AFTER ENDOVASCULAR TREATMENT OF CRITICAL LIMB ISCHEMIA
Authors: Damianos Kokkinidis, Stefanos Giannopoulos, Moosa Haider, Timothy Jordan, Anita Sarkar, Gagan Singh, Eric Secemsky, Jay S. Giri, Joshua Beckman, Ehrin J. Armstrong
Journal: Journal of the American College of Cardiology (2020)
Adjuvant cancer peptide vaccine treatment with intravesical BCG therapy for non-muscle-invasive bladder cancer.
Authors: Wataru Obara
Journal: Journal of Clinical Oncology (2013)

e15587 Background: We previously reported safety and high immunogenicity of peptide vaccine treatment using two novel peptides derived from oncoantigens, M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1), for patients with advanced bladder cancer. We further conducted a multi-center phase II clinical trial using the same peptides to investigate the effectiveness to prevent recurrence after TURBt for patients with non-muscle invasive bladder cancer (NMIBC). Methods: The key eligibility criteria were patients with intermediate or high risk for NMIBC, with tumors having expression of MPHOSPH1 and/or DEPDC1, and with HLA class I expression on tumor cells. HLA-A24-restricted MPH and/or DEP derived peptide were subcutaneously administered in combination with intravesical BCG therapy after TUR-Bt. All enrolled patients had received the vaccination without knowing HLA-A status, and the HLA genotypes were used for a key-open marker. The primary endpoint was to examine effect on recurrence free survival (RFS) and secondary endpoint was induction of peptide-specific CTL response, injection site of reaction (ISR) and adverse effect. Results: A total of 133 patients were enrolled. RFS rates at 2 years in all patients were 74.4 %. Although the difference in RFS between the A24(+) and A24(-) groups (77.2% vs. 70.4%) was not statistically significant (p=0.24), that in the ISR-positive group was significantly better than that in the ISR-negative group (81.6% vs. 54.3%, p=0.0004). The peptide vaccine treatment was well-tolerated without any treatment- associated severe adverse events, while the bladder irritability caused by BCG treatment was observed in 64 cases (48.1%). The MPHOSPH1 and DEPDC1 peptide-specific CTL responses in the 24(+) group were observed in 82 % and 83 % of patients, respectively. Four (7.4%) cases in the 24(-) group revealed the peptide-specific CTL response, indicating some cross-reactivity against the vaccinated peptides on other HLA allele(s). Conclusions: Combination immunotherapy of intravesical BCG and cancer peptide vaccine demonstrated the promising clinical effect on recurrence prevention for NMIBC as well as good immunogenicity and safety. Clinical trial information: 00633204.
THE INCIDENCE, RISK FACTORS AND OUTCOMES WITH 5-FU (FLUOROURACIL)-ASSOCIATED CORONARY VASOSPASM
Authors: Amna Zafar, Ramya Mosarla, Zsofia Drobni, Raza Alvi, Matthew Lei, Uvette Y. Lou, Sean Murphy, Maeve Jones-O'Connor, Vineet K. Raghu, Adam Rokicki, Dahlia Banerji, Colin D. Weekes, John R. Clark, Jeffrey Clark, Lawrence S. Blaszkowsky, Erica Tavares, Tomas G. Neilan
Journal: Journal of the American College of Cardiology (2020)