tbuckley/cabot-search huggingface dataset:
Clinically relevant gene sequencing in gynecologic cancers.
Authors: Giuseppe Del Priore, Maurie Markman, Kim Kramer, Justin Chura, John Farley, Sybilann Williams, Herbert Beck, Donald Peter Braun, Madappa N. Kundranda
Journal: Journal of Clinical Oncology (2014)

e16506 Background: Individualized cancer therapy is a long held goal for patients and clinicians. We report the results of a commercially available precision medicine assay in recurrent gyn cancers. Methods: Prospective cohort of all tumors sent for next-generation sequencing as part of clinical decision making from a network of tertiary care centers during 2013. Results: Approximately 1,062 new recurrent cancers (endometrial, ovarian, cervical) were seen from all sites. Of these 103 (9.7%) formalin fixed paraffin embedded tissue were sent for genomic testing with 103 yielding results. Overall median age was 54 yrs (range 26–78), uterine 59 yrs, ovarian 53 yrs, and cervix 49 yrs. Median number of prior chemotherapy cycles was 4 (range 0-9). There were a total of 381 genomic alterations detected (107 in 23 uterine, 30 in 10 ovarian and 28 in 8 cervical specimens). Recurrent ovarian clear cell and mucinous tumors (n=8) had 29 unique alterations vs 16 in 11 SCT (X2p=0.16). Granulosa cell results indicated 7/9 had FOXL2C134W alteration; ovarian mucinous results indicated 3/3 included KRAS alteration and ovarian clear cell results indicated 4/5 included ARID1A alteration. 99 specimens (96%) contained at least 1 identified genomic alteration associated with treatment options including TP53 in 56/99 results (56%); 63 test results (61%) indicated a genomic alteration associated with an FDA approved drug; 91 test results (88%) indicated at least one intervention available on ClinicalTrial.gov; 32 of the 63 test results (51%) included more than one actionable mutation. Conclusions: Genomic testing indicates a potential role for specific FDA approved drugs in the majority of highly pretreated selected recurrent gynecologic cancers.
Psoriasis and depression
Authors: A. Egeberg, J.P. Thyssen, J.J. Wu, L. Skov
Journal: British Journal of Dermatology (2019)

Psoriasis is a common skin disease affecting approximately 5‐10 percent of people in the Nordic countries, and more than 125 million people worldwide. The disease has been associated with low treatment adherence, meaning people don't stick with their treatment, and unhealthy lifestyle (e.g. smoking, alcohol consumption, decreased physical activity) and, in turn, cardiometabolic disease. Patients with psoriasis have a higher frequency of depression, but little is known about whether this is due to psoriasis itself, or whether this is predominantly due to patients' comorbidities, meaning the diseases they suffer alongside their psoriasis. This study therefore examined the risk of depression in 247,755 patients with psoriasis compared with the general population. Using registry data from Denmark, this study found a slightly increased risk of developing depression in patients with psoriasis, independent of other risk factors such as comorbidity. Overall, the risk was modest, but a somewhat higher risk was seen in those people requiring a stronger type of treatment called biologic therapy, i.e. those with more severe psoriasis, and especially among patients aged 40 to 50 years. Notably, the highest occurrence of depression was among people with a prior history of depression, suggesting that these patients may represent a particularly vulnerable group in which increased awareness may be needed. Collectively, these results may help clinicians identify which patients are at particularly high risk of depression in whom pre‐emptive measures may be needed to reduce the future risk of depression.
The relationship between platelet-lymphocyte ratio, neutrophil-lymphocyte ratio, and survival in metastatic gastric cancer.
Authors: Mutlu Dogan, Nuriye Ozdemir, Tulay Eren, Ozan Yazici, Nurullah Zengin
Journal: Journal of Clinical Oncology (2014)

e15045 Background: Platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) might affect survival in some malignancies. Our aim was to evaluate the basal PLR and NLR effect on survival in metastatic gastric cancer (MGC). Methods: MGC patientsfollowed between2006 and 2013 were included. The cut-off values for PLR were 160 and 2,5 for NLR. PFS and OS were estimated for group I (PLR >160), group II (PLR <160), group III (NLR > 2,5), group IV (NLR<2,5), group V (PLR >160 & NLR > 2,5), group VI (PLR <160 and NLR <2,5). Results: 109 MGC patients were evaluated for basal hemogram parameters and survival analysis, retrospectively. Most of the patients were male with grade III adenocarcinoma (50,5 %), corpus localization ( 45,3%) and liver metastasis (38,9%). They had 1st line mDCF (cisplatin 60 mg/m2 (day 1), 5FU 600 mg/m2(days 1-5), docetaxel 60 mg/m2(days 1-5), q3w). Results are summarized in the Table. There was no difference for MPV (median 7,9 for both; ranges: 6-11,6 and 6-9,7) between groups I and II. Conclusions: Patients with PLR >160 and/or NLR >2,5 had significantly shorter OS. PFS was also shorter in them but unsignificant between groups V and VI. Patient characteristics and survival analysis. Group I Group II Group III Group IV Group V Group VI Age (median, range) 52 (30-73) 54 (32-76) 54 (38-76) 54 (30-74) 54 (32-76) 58 (30-74) Male/female 2 3,8 3,53 1,93 3,3 2,31 Grade 3/4 toxicity Thrombocytopenia (%) Neutropenia (%) FEN (%) 2,8 23,9 0 2,6 28,9 0 5,9 25 0 2,4 29,2 0 1,8 16 1,8 1,9 17 1,9 PFS (median, months) 7,6 vs 11,2 (p=0,04) 7,6 vs 11,8 (p=0,01) 7 vs 10,4 (p=0,1) OS (median, months) 10,2 vs 17,1 (p=0,003) 10,5 vs 19,1 (p=0,002) 10,5 vs 17,7 (p=0,009)
Pronostic value of maximum standardized uptake value in recurrent epithelial ovarian cancer.
Authors: Aranzazu Fernandez, Maria Mayoral, Pilar Paredes, Francisco Aya, Manuel Selvi, Pedro Gascon, Laura Vidal Boixader
Journal: Journal of Clinical Oncology (2014)

e16518 Background: Metabolic tumor parameters for preoperative [18F]FDG PET/TC imaging may be a useful predictor of recurrence in patients with epithelial ovarian cancer (EOC). The aim of this study is to evaluate if the Maximum Standardized Uptake Value (SUVmax) has prognostic value in those patients with suspected recurrence of EOC. Methods: 39 patients who have previously shown positive histology studies for EOC and were suspected to disease recurrence were subjected to a total of 41 PET/TC image studies from April 2007 to December 2012. 29 of this PET/TC studies were positive and it was the first disease recurrence for 14 patients. SUVmax was calculated one hour after intravenous injection of 0.11 mCi/kg of [18F]FDG. Recurrence sites, mean SUVmax by region and the highest SUVmax were recorded for each patient. The primary endpoint of this study was the correlation between the highest SUVmax and progression-free survival (PFS). PFS was defined as the time elapsed between PET/CT image and progression or death from any cause. Secondary endpoints were the correlation between the highest SUVmax and CA-125 levels. Results: The most frequent recurrence site was peritoneum (48.3%), followed by visceral-bone metastasis (24.1%) and retroperitoneal lymph nodes (24.1%). Mean SUVmax by region were: 5.1 for pelvic lymph nodes; 5.9 for mediastinal lymph nodes; 4.9 for retroperitoneal lymph nodes; 6 for peritoneal disease and 7.4 for visceral-bone metastasis. With a median follow-up of 39.3 months, median PFS was 12.4 with 24 events reported. No significant correlation was found between highest SUVmax and PFS. Significant positive correlation was found between the highest SUVmax and CA-125 level for 14 patients with first recurrence of EOC. Conclusions: Results shown in this study cannot prove the prognostic value of PET for recurrent EOC. However, a positive correlation between SUVmax and CA-125 has been found for first recurrent EOC. Further analyses are ongoing and data will be presented.
Characterization of a lung cancer growth factor, LASEP1, as a serologic and prognostic biomarker and a therapeutic target.
Authors: Atsushi Takano, Yusuke Nakamura, Yataro Daigo
Journal: Journal of Clinical Oncology (2013)

11104 Background: Identification and evaluation of oncoproteins are an effective approaches to develop novel diagnostic/prognostic biomarkers or therapeutic targets. Methods: We established a strategy as follows. i)To identify up-regulated genes in non-small cell lung cancers (NSCLCs) using the cDNA microarray, ii) To verify the candidate genes for their no or low expression in 23 normal tissues by northern-blot, iii)To validate clinicopathological significance of their protein expression by tissue microarray, iv)To verify whether they are essential for the growth of cancer cells by siRNA, and v)To measure their serum protein levels by ELISA. Results: We identified LASEP1 (Lung cancer Associated Serum Protein 1) as a candidate target molecule. Immunohistochemical staining using tumor tissue microarrays consisting of 374 NSCLC confirmed positive staining of LASEP1 was observed in 210 (56.1%) of 374 NSCLC. In addition, a high level of LASEP1 expression was associated with poor prognosis of NSCLC patients. Serum LASEP1 levels were higher in NSCLC than in healthy volunteers. The proportion of serum LASEP1-positive cases was 127 (38.6%) of 329 lung cancers, while 4 (3.9%) of 102 healthy volunteers were falsely diagnosed. Furthermore, treatment of lung cancer cells with siRNAs against LASEP1 suppressed its expression and resulted in growth suppression of the lung cancer cells; on the other hand, induction of exogenous expression of LASEP1 conferred growth-promoting activity in vitro. We found its 50-kDa receptor (LASEPR) which interacts with LASEP1 on lung cancer cell surface. Suppression of LASEPR expression by siRNAs inhibited the growth of cancer cells. The LASEP1-LASEPR interaction promoted the cell growth in an autocrine manner. In addition, the growth activity of the LASEP1-positive cells was neutralized by the addition of originally developed anti-LASEP1 monoclonal antibodies into their culture media. The systemic administration of the anti-LASEP1 antibody to tumor-implanted mice significantly suppressed tumor growth without any adverse events. Conclusions: We have identified LASEP1 as potential targets for development of biomarkers and therapeutic target for lung cancer.
Venetoclax and Navitoclax in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Authors: Thomas Alexander, Norman J. Lacayo, Vinod A. Pullarkat, Elias J. Jabbour, Seong Lin Khaw, Charles G. Mullighan, Ashish Bajel, Jessica Leonard, Robin Norris, Jeffrey Rubnitz, Susan I. Vear, Michelle Schmidt, Bo Tong, Ying Zhou, Jeremy A. Ross, Lindsey Rosenwinkel, Amanda Jacobson, Su Young Kim, Wendy Stock
Journal: Blood (2018)
Phase IB trial of cisplatin (C), gemcitabine (G), and veliparib (V) in patients with known or potential BRCA or PALB2-mutated pancreas adenocarcinoma (PC).
Authors: Eileen Mary O'Reilly, Maeve Aine Lowery, Michal Fani Segal, Sloane C. Smith, Malcolm J. Moore, Hedy Lee Kindler, Talia Golan, Amiel Segal, Erin E. Salo-Mullen, Ellen Hollywood, Andrew S. Epstein, Marinela Capanu, Mary Ellen Moynahan, Anne Fusco, Zsofia Kinga Stadler, Richard Kinh Gian Do, Alice P. Chen, Kenneth H. Yu, Laura H. Tang, David Paul Kelsen
Journal: Journal of Clinical Oncology (2014)

4023 Background: 5% to 8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish with PC (10-15%). Pre-clinical data demonstrates that DNA-damaging drugs (C) and poly-ADP ribose polymerase inhibitors (PARPi) have significant activity in BRCA mut PC models. This trial evaluates the optimal dose of V with fixed doses of C and G in PC. Methods: Primary endpoints: Determination of dose-limiting toxicity (DLT) and Recommended Phase II Dose (RP2D), safety (NCI CTCAE 4.0). Secondary endpoints: RECIST 1.1 response rate (RR), duration of response, progression-free survival, overall survival and correlatives involving tumor biopsies to evaluate mechanisms of sensitivity, resistance to platinum and PARPi. Eligibility: Untreated BRCA, PALB2 mut PC or strong personal/family history of pancreas or BRCA-related malignancy; measurable stage III/IV PC; ECOG 0-1. Treatment Plan: C 25mg/m2 IV, G 600mg/m2 IV, both d3, 10, q 3 weeks and V PO BID day 1- X. Results: Between 02/12– 10/13, N= 33 screened, 17 enrolled. Male = 10, Female = 7. Median age = 60 years (range 42- 72). BRCA = 9. Non-BRCA = 8. Four dose levels of V evaluated; 2 DLT's at V 80 mg PO BID continuous dosing (Table). Grade 3-4 toxicities: Anemia, neutropenia, thrombocytopenia, fatigue. 1 fatal bowel perforation tumor/diverticulitis*. For N= 9 BRCA patients: 5 (56%) partial responses (PR), 4 (44%) stable disease. For N= 8 non-BRCA: 5 stable, 2 progression. N= 5 BRCA patients continue on study and 7 of 9 BRCA patients are alive. Tissue analyses on BRCA subset will be presented. Conclusions: The RP2D of veliparib is 80 mg PO BID day 1-12 q 3 weeks with fixed dose C + G. Main grade 3-4 toxicities are hematologic, fatigue. The combination of C, G + V shows high activity in BRCA mut PC. A randomized phase II trial evaluating C, G +/- V is underway in BRCA/PALB2 mut PC (NCT01585805). Funding and acknowledgements: National Cancer Institute CTEP, Lustgarten Foundation, AbbVie. Clinical trial information: NCT01585805. Veliparib PO BID N DLT BRCA subgroup 20 mg, day 1-12 3 - N= 2, 1 PR, 1 SD* 40 mg, day 1-12 3 - N= 1, 1 PR 80 mg, day 1-12 6 - N= 5, 2 PR, 3 SD 80 mg, day 1-21 5 2 (grade 4 platelets, ANC) N= 1, 1 PR
Abstract P245: Sleep Variability and Cardiac Autonomic Modulation in Adolescents - Penn State Child Cohort (PSCC) Study
Authors: Duanping Liao, Fan He, Sol M Rodriguez-Colon, Alexandros N Vgontzas, Julio Fernandez-Mendoza, Edward O Bixler
Journal: Circulation (2013)

Objectives: To assess the relationship between habitual sleep time and its variability and cardiac autonomic modulation (CAM) in a population-based sample of adolescents. Methods: We used available data from the first 300 adolescents who have completed the follow up examinations in the population-based PSCC study. We used actigraphy to assess sleep time for 8 consecutive nights. Excluding the first night, we calculated each participant’s 7-night mean sleep time, and its standard deviation. The latter was used as a measure of sleep time variability. CAM was assessed by heart rate variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-hour high resolution Holter ECG. The HRV indices in frequency domain [high frequency power (HF), low frequency power (LF), and LF/HF ratio] and time domain [standard deviation of normal RR intervals (SDNN), and the square root of the mean squared difference of successive normal RR intervals (RMSSD), and heart rate (HR)] were calculated on a 30-minute basis (...
Outcome of patients with chronic lymphocytic leukemia and acute kidney injury: Single-center experience (2000-2012).
Authors: Ankit Anand, Hussam Al-Sharif, Karthika raya Linga, Ali Al-Ameri
Journal: Journal of Clinical Oncology (2014)

e18012 Background: Chronic lymphocytic leukemia is a B cells neoplasia that commonly affects lymph nodes, liver, spleen and bone marrow. Acute Kidney injury (AKI) in CLL is difficult to review since major published evidence is limited to case reports. There are reports of AKI secondary to leukemic infiltration of kidney, but this is extremely rare. Nevertheless chemotherapy related AKI is much more common. Aim: To study effects of AKI on long term survival of patients with CLL. Methods: A retrospective study on CLL pts from 2000- 2012 was conducted at Akron General Medical Center, Ohio, US. After IRB approval, 123 pts were identified from hospital database with the established diagnosis of CLL. Laboratory values were assessed before and after diagnosis of CLL. AKI was identified by Acute Kidney injury network (AKIN) criteria. Patients were followed for 400 weeks, at which point 34 (28%) pts were lost to follow up. 24 pts (20%) did not have sufficient laboratory data and had to be removed from the study. 65(53%) pts were studied and data analyzed. Kaplan Meier survival analysis was done for pts who had AKI compared to pts who did not. Results: Of 123 pts with CLL we were able to analyze only 65 pts (53%). Of those 65 pts, 27pts (42%) were females and 38 (58%) pts were males. Three pts (5%) were African American and 59 (90%) pts were Caucasian. Three (5%) pts did not have this information on the records reviewed.12 (18%) pts had AKI and 53 (72%) had no evidence of AKI. Of those who had AKI, 11 (92%) pts were caucasian and one (8%) was of African American origin. Nine (75%) pts were males and three (25%) pts were females.Median survival in pts with AKI was 104 weeks as compared to 263 weeks in pts without AKI. Mean survival in pts with AKI was 168 weeks as compared to 300 weeks in pts without AKI. P value was significant at 0.03. Standard error (SE) for pts with AKI was 41.74 and 31.78 for pts without AKI. 95% CI of mean was 86.52 - 250.14. 95% CI of median for pts with AKI was 30-308 and 154-334 for pts without AKI. Conclusions: According to our study, survival is compromised in CLL pts if they develop AKI at anytime during disease course. Furthermore, AKI in our study was more common in caucasian male pts. More data and studies are needed to verify these findings.
Differences in hormonal receptor status and Ki67 expression between primary breast cancer and metastasis: Is variation related to previous therapy?
Authors: Lorenzo Gerratana, Elena Poletto, Marta Bonotto, Alessandro Minisini, Elena Ongaro, Claudia Bozza, Marika Cinausero, Carla Di Loreto, Gianpiero Fasola, Fabio Puglisi
Journal: Journal of Clinical Oncology (2014)

e22006 Background: Several studies have reported discordances between primaries and recurrences in breast cancer (BC). However, little is known about the relationship between therapy, immunophenotype (IP) variation and prognosis. Aim of this study was to explore how anticancer treatments influence IP and to evaluate the prognostic impact of discordance between paired primaries and recurrences. Methods: The study included 201 consecutive patients with advanced BC that underwent biopsy of metastatic lesions at the University Hospital of Udine, Italy, between 2004 and 2013. Estrogen (ER) and progesterone receptors (PgR) were dichotomized at 1%, the cut-off point of Ki67 was set at 14%. IP variation was tested through McNemar test. Association between treatment and IP changes was investigated through logistic regression. Cox regression was performed. Results: The distribution of ER, PgR and Ki67 was significantly different between primaries and recurrences (P= 0.0007, P<0.0001 and P<0.0001, respectively). On univariate analysis, previous treatment with aromatase inhibitors (AI) was associated with a decrease in ER and PgR expression (OR 4.68, P=0.004 and OR 2.51, P=0.006, respectively), while antiestrogen therapy (AE) lead to a decrease in PgR levels (OR 4.01, P<0.0001). Exposure to anthracycline-based regimens or taxanes led to a lower probability in Ki67 increase (OR 0.305, P=0.01 and OR 0.25, P=0.01, respectively). An inverse association was observed with AE (OR 3.84, P=0.007). On multivariate analysis, exposure to both AI and AE retained its significance relatively to PgR expression (OR 0.35, P=0.0035 and OR 0.23, P<0.0001, respectively), while only AE was associated with Ki67 variation (OR 0.2, P=0.009). Prognostic impact of ER and Ki67 on overall survival (OS) was noticed in case of relative decrease of ER (34.98 months vs 57.73 months, HR=2.11, P=0.006) or increase of Ki67 (42.41 months vs 24.07 months, HR=0.55, P=0.02). Conclusions: Our results suggest that ER, PgR and Ki67 expression may be influenced by previous treatments. Although counterintuitive, patients affected by metastatic lesions with higher Ki67 than in the primary tumor experienced longer OS.
Abstract 13697: Direct Effects of C-Type Natriuretic Peptide on Left Ventricular Contractile Performance in Heart Failure: Assessment by Left Ventricular Pressure-Volume Analysis
Authors: Zhi Zhang, Heng-Jie Cheng, Tiankai Li, Xiaowei Zhang, Guowei Zhou, Nobuyuki Ohte, Che Ping Cheng
Journal: Circulation (2017)

Background: Emerging evidence supports C-type natriuretic peptide (CNP), a potent endogenous vasodilating and natriuretic peptide as a new therapeutic option for the treatment of HF. Both circulating and cardiac levels of CNP are increased in patients with congestive heart failure (HF), which may alter left ventricular(LV) functional response to CNP and suggest it is released as a cytoprotective mechanism. However, the direct cardiac effects of CNP, independent of the alterations in loading conditions, remain controversial. We test the hypothesis that CNP has a direct positive inotropic effect on LV contractile performance in HF, which is independent of altered heart rate, load or baroreflexes. Methods: We assessed the cardiac effects of CNP (2 μg/kg plus 0.4 μg/kg/min, iv, 20 min) in 11 chronically-instrumented conscious dogs with pacing-induced HF by using pressure (P)-volume (V) analysis. Results: With reflexes intact, CNP administration significantly reduced LV end-systolic pressure (PES, 94±20 vs 106...
Ibrutinib for the Treatment of Bing-Neel Syndrome
Authors: Gilad Itchaki, Jonas Paludo, Maria Lia Palomba, Marzia Varettoni, Dipti Talaulikar, Julio C. Chavez, Christian Buske, Alessandra Tedeschi, David Simpson, Constantine S. Tam, Samar Issa, Stephen M. Ansell, Steven P Treon, Jorge J. Castillo
Journal: Blood (2018)
Activation of Estrogen Receptor Alpha by Decitabine Inhibits Osteosarcoma Growth and Metastasis
Authors: Maria Angeles Lillo Osuna, Jesus Garcia-Lopez, Ikbale El Ayachi, Iram Fatima, Aysha B. Khalid, Jerusha Kumpati, Alexandria V. Slayden, Tiffany N. Seagroves, Gustavo A. Miranda-Carboni, Susan A. Krum
Journal: Cancer Research (2018)

Abstract Osteosarcoma is a malignant tumor in the bone, which originates from normal osteoblasts or osteoblast precursors. Normal osteoblasts express estrogen receptor alpha (ERα); however, osteosarcomas do not express ERα due to promoter DNA methylation. Here we show that treatment of 143B osteosarcoma cells with decitabine (DAC, 5-Aza-2′-deoxycytidine) induces expression of ERα and leads to decreased proliferation and concurrent induction of osteoblast differentiation. DAC exposure reduced protein expression of metastasis-associated markers VIMENTIN, SLUG, ZEB1, and MMP9, with a concurrent decrease in mRNA expression of known stem cell markers SOX2, OCT4, and NANOG. Treatment with 17β-estradiol (E2) synergized with DAC to reduce proliferation. Overexpression of ERα inhibited proliferation and induced osteoblast differentiation, whereas knockout of ERα by CRISPR/Cas9 prevented the effects of DAC. In an orthotopic model of osteosarcoma, DAC inhibited tumor growth and metastasis of 143B cells injected into the tibia of NOD SCID gamma mice. Furthermore, ERα overexpression reduced tumor growth and metastasis, and ERα knockout prevented the effects of DAC in vivo. Together, these experiments provide preclinical evidence that the FDA-approved DNA methylation inhibitor DAC may be repurposed to treat patients with osteosarcoma based on its efficacy to decrease proliferation, to induce osteoblast differentiation, and to reduce metastasis to visceral organs. Significance: These findings describe the effects of DNA methyltransferase inhibition on ERα and its potential role as a tumor suppressor in osteosarcoma. See related commentary by Roberts, p. 1034 See related article by El Ayachi and colleagues; Cancer Res 79(5);982–93.