tbuckley/cabot-search huggingface dataset:
DNA microarray analysis of tumors in versipelostatin (VST)-administered MKN74-xenograft nude mice
Authors: Tadashi Nakamura, Masami Okabe, Yasunari Kashihara, Shigeo Sato, Aki Furuno, Sakae Saitoh, Naomi Haga, Takashi Tsuruo, Akihiro Tomida
Journal: Cancer Research (2007)

4830  Versipelostatin (VST), a macrocyclic compound, was isolated from Streptomyces versipellis 4083-SVS6 by Park et al (Tetrahedron Lett. 43:6941, 2002). VST has been found to suppress gene activation of molecular chaperon GRP78 during glucose deprivation, a microenvironmental stress condition commonly seen in poorly vasculized solid tumors (JNCI 96:1300, 2006). Consistent with inhibition of GRP78 induction, VST showed a selective cytotoxicity to glucose-deprived cancer cells. Moreover, VST can inhibit tumor growth of stomach adenocarcinoma MKN74 xenografts in nude mice and is a potential therapeutic agent against solid tumors. However, little is known about the mechanisms of VST action in tumor growth inhibition. In this study, we conducted DNA microarray analysis to investigate changes in gene expression of xenografted tumors with or without VST treatment.  We prepared MKN74-xenografted Balb/c nu/nu mice and treated them with VST intravenously at 6 or 9 mg/kg for three days after the tumor volumes reached about 100 mm³. Eight hours after administering the VST, the tumors were excised to isolate mRNA for gene expression analysis with Human Genome U133 Plus 2.0 Array™ (Affymetrix Co. Ltd). DNA microarray data were extracted on the basis of the criteria of signal intensity and signal log ratio.  VST treatment (9 mg/kg/day, 3 days/week for 3 weeks) for MKN74-xenografted nude mice suppressed tumor growth compared with vehicle-treated control mice. Then, we screened the gene expression pattern in the tumors in the first round of VST treatment (the first week) using the DNA microarray technique. On the whole, no drastic changes in gene expression could be detected, but some interesting changes were observed. For example, increased expression was seen in vascular endotherial growth factor (VEGF) and prostaglandin-endoperoxide synthase 2 (COX-2), while decreased expression was seen in metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), fibronectin 1, and cyclin E2. Interestingly, the expression signature was detected significantly in tumors treated with 9 mg/kg of VST, but less significantly in tumors treated with 6 mg/kg of VST, a dose that showed marginal tumor growth inhibition. To validate the expression signature, we are examining gene expression pattern in xenograft models of pancreatic cancer cells as well as MKN74 cells in greater detail.  We identified changes in gene expression pattern that are associated with tumor growth inhibition by VST. Our present results, together with further analysis in other xenograft models, will be useful in understanding the antitumor action mechanisms of VST and in identifying biomarkers for clinical trials of this new type of antitumor drug.
Insurance status and cholangiocarcinoma: A NCDB analysis.
Authors: Hibah Ahmed, Nathan Law, Katrina Wolfe, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2020)

500 Background: There is an increasing rise of cholangiocarcinoma though the cause is unclear. Cholangiocarcinoma is more often than not incurable at diagnosis and associated with a high mortality rate. Our goal was to compare survival of patients with differing insurance types diagnosed with cholangiocarcinoma identified in the National Cancer Database (NCDB). Methods: We identified 5,638 patients with cholangiocarcinoma in the NCDB diagnosed between 2004-2014. Patients included were categorized as having no insurance, private insurance, Medicaid, or Medicare were included. Between-insurance survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p &lt; .05 indicated statistical significance. Results: Statistically significant survival differences were indicated between all insurance groups (all adjusted p &lt; 0.05), such that privately insured patients had the highest median survival. The discrepancy in survival between uninsured and privately insured patients was the largest (6.5 months vs 13.1 months, respectively). Medicaid patients on average had a survival of 7.5 months, while Medicare patients had a median survival of 7.8 months. 2.8% of uninsured patients presented with stage I cholangiocarcinoma, whereas 34% of privately insured patients presented with stage I cholangiocarcinoma. More Medicare patients were treated at community cancer programs compared to privately insured patients (56.7% vs 30.7%, respectively). Likewise, more Medicare patients were treated at academic/research programs compared to those with private insurance, Medicaid, or those who were uninsured (44.7% vs 38.7% vs 7.2% vs 3.7%, respectively). Conclusions: Our study shows the discrepancies in survival between patients with differing insurance statuses. Of all insurances, those privately insured had the largest median survival. [Table: see text]
Topical 5% minoxidil versus topical 0.2% glyceryl trinitrate in treatment of chronic anal fissure: A randomized clinical trial
Authors: Sameh Hany Emile, Mohamed Anwar Abdel-Razik, Ayman Elshobaky, Samy Abbas Elbaz, Wael Khafagy, Mostafa Shalaby
Journal: International Journal of Surgery (2020)
Personalized ANtibodies for GastroEsophageal Adenocarcinoma (PANGEA): Primary efficacy analysis of the phase II platform trial (NCT02213289).
Authors: Daniel V.T. Catenacci, Samantha Lomnicki, Leah Chase, Bryan Peterson, Kelly Moore, Ugne Markevicius, Lindsay Alpert, Namrata Setia, John Hart, Chih-Yi Liao, Uzma Siddiqui, Kiran Turaga, Mitchell C. Posner, Kristen Kipping-Johnson, Sunil Narula, Murtuza M. Rampurwala, Yuan Ji, Theodore Karrison, Blase N. Polite, Hedy L. Kindler
Journal: Journal of Clinical Oncology (2020)

356 Background: 1-yr OS is ~40% for HER2- &amp; ~55% for HER2+ advanced (aGEA). Targeted therapies (tx) have had limited benefit due to molecular heterogeneity. Methods: This phase 2a study of a personalized tx strategy (PTS) enrolled newly diagnosed aGEA pts who then received up to 3 cytotoxic (cx) lines: first line (1L) 5FU + oxaliplatin, 2L 5FU + irinotecan &amp; 3L 5FU + docetaxel. Baseline biomarker profiling (BP) was mandated on primary &amp; metastatic tumors (PT/MT) &amp; progressive disease points (PD1, PD2). Assigned antibody (AN) was added to cx by a predefined prioritized tx algorithm (PTA) (Table) based on the MT BP. At PD1, pts went to 2L cx + initial AN. Upon results of PD1 BP, pts changed AN only if BP evolved per PTA. The same was done at PD2. If AN was unavailable (MET/FGFR2), these pts were tx’d with cx alone (not ITT). The 1 0 endpt was 1-yr OS of the PTS. Assuming historical 50% 1-yr OS for all aGEA pts, 68 pts tx’d per protocol PTS provided 80% power to detect an HR=0.67, corresponding to a 1-yr OS rate of 63% (under exponential survival), using a 1-sided test at the 0.10 alpha level. 2 0 endpts: safety, feasibility, PT/MT BP discordance at baseline &amp; over tx line, &amp; OS/PFS/ORR by tx line &amp; BP group. Results: Between 6/2015-5/2019, 80 consecutive pts enrolled at 3 sites: ECOG PS 0-2 40/33/7; Male 80%; median age 60, range 28-81, peritoneal disease 36%. AN assigned by PTA at 1L &amp; 1-yr OS are shown (Table). PT/MT discordance was 37%. Of 68 pts treated by PTS ITT, the 1-yr OS was 69.4% (p&lt;0.001). The mOS was 16.4m [95%CI 13.8-20.8]. Any grade &gt;3 tox thru all 3 tx lines was seen in 32% of pts. 2 0 analyses will be presented. Conclusions: PANGEA was feasible &amp; met its 1 0 efficacy objective with observed 1-yr OS of 69.4%, meriting a randomized study. Clinical trial information: NCT02213289 . U.S. National Institutes of Health.[Table: see text]
大きなウィルヒョウ・ロビン腔:機能的磁気共鳴画像法およびトラクトグラフィー | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Wong Sui Hsien, Das Kumar, Puthuran Mani, Lecky Bryan, White Richard
Journal: JAMA Neurology (2010)
The General Factor of Psychopathology
Authors: Gregory T. Smith, Emily A. Atkinson, Heather A. Davis, Elizabeth N. Riley, Joshua R. Oltmanns
Journal: Annual Review of Clinical Psychology (2020)

An important advance in understanding and defining mental disorders has been the development of empirical approaches to mapping dimensions of dysfunction and their interrelatedness. Such empirical approaches have consistently observed intercorrelations among the many forms of psychopathology, leading to the identification of a general factor of psychopathology (the p factor). In this article, we review empirical support for p, including evidence for the stability and criterion validity of p. Further, we discuss the strong relationship between p and both the general factor of personality and the general factor of personality disorder, substantive interpretations of p, and the potential clinical utility of p. We posit that proposed substantive interpretations of p do not explain the full range of symptomatology typically included in p. The most plausible explanation is that p represents an index of impairment that has the potential to inform the duration and intensity of a client's mental health treatment.
FIGHT-302: Phase III study of first-line (1L) pemigatinib (PEM) versus gemcitabine (GEM) plus cisplatin (CIS) for cholangiocarcinoma (CCA) with <i>FGFR2</i> fusions or rearrangements.
Authors: Tanios S. Bekaii-Saab, Juan W. Valle, Eric Van Cutsem, Lorenza Rimassa, Junji Furuse, Tatsuya Ioka, Davide Melisi, Teresa Macarulla, John A. Bridgewater, Harpreet Singh Wasan, Mitesh J. Borad, Christine F. Lihou, Huiling Zhen, Luis Féliz, Ekatherine Asatiani, Ping Jiang, Arndt Vogel
Journal: Journal of Clinical Oncology (2020)

TPS592 Background: For advanced CCA, standard of care 1L systemic treatment is GEM + CIS. Genetic alterations in intrahepatic CCA provide potential therapeutic targets. Fibroblast growth factor receptor (FGFR) 2 gene rearrangements driving CCA tumorigenesis were identified almost exclusively in intrahepatic CCA patients (pts) (incidence, 10–16%). In phase 2, PEM (INCB054828), a selective, potent, oral FGFR1–3 inhibitor elicited an objective response rate (ORR) of 35.5% and median progression-free survival (PFS) of 6.9 months (mo) in previously treated, locally advanced or metastatic CCA with FGFR2 rearrangements (NCT02924376). FIGHT-302, a randomized, open-label, phase 3 study will evaluate efficacy and safety of 1L PEM vs GEM + CIS in unresectable/metastatic CCA with FGFR2 fusions or rearrangements (NCT03656536). Methods: Eligible pts are adults with confirmed unresectable/metastatic CCA; no prior systemic therapy for advanced disease &lt; 6 mo before enrollment; radiographically measurable/evaluable disease (per RECIST v1.1); ECOG PS ≤1; documented FGFR2 fusions or rearrangements. Exclusions include clinically significant corneal or retinal disorder; history of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic soft tissue calcification; untreated CNS metastases or history of uncontrolled seizures. Pts will be randomized (1:1; stratified by region and tumor burden) to PEM 13.5 mg QD on a 21-day (d) cycle or GEM (1000 mg/m 2 ) + CIS (25 mg/m 2 ) on D1 and D8 of 21-d cycles (max 8). Crossover to PEM allowed after confirmed progression. PEM titration to 18 mg from cycle 2 allowed for pts without hyperphosphatemia (serum phosphate &gt; 5.5 mg/dL) and Grade ≥2 treatment-related adverse events during cycle 1. Hyperphosphatemia will be managed with diet modifications, phosphate binders, diuretics, or dose adjustments. Treatment will continue until progression or unacceptable toxicity. Primary endpoint is PFS (by independent review). Secondary endpoints are ORR, overall survival, duration of response, disease control rate, safety, and quality of life. Four pts (target N = 432) are enrolled as of Sep 25, 2019. Clinical trial information: NCT03656536.
A real-world observational study of somatostatin analogue use and costs in Canada.
Authors: Winson Y. Cheung, Marion Feuilly, Callahan Laforty, Anna Liovas, Heather McKechnie, Jonathan M. Loree
Journal: Journal of Clinical Oncology (2020)

608 Background: Somatostatin analogue (SSA) use is indicated in acromegaly and neuroendocrine tumours for symptomatic relief and tumour control. Two long-acting SSAs (lanreotide and octreotide) are currently available, but comparative real-world data on their use are limited. This study evaluated SSA use and costs in Canada. Methods: Claims data from the IQVIA Private Drug Plan (PDP), Ontario Drug Benefit (ODB) program and Régie de l’assurance-maladie du Québec (RAMQ) were compiled. Injection burden, rescue medication use and costs were compared (using unpaired t-test or Wilcoxon test) over a 12-month period from first SSA prescription. Patients (pts) were eligible if the first prescription was dispensed Sept. 2015–Jun. 2018. Results: 908 pts were included: lanreotide 120 mg, N=375; octreotide long-acting release (LAR) 30 mg, N=533. Lanreotide treatment was associated with a lower weighted average injection burden for 12 months when compared to octreotide (12.54 vs 13.44 injections/pt, respectively; p&lt;0.0001). Pts receiving lanreotide also had lower mean use of rescue medications than those treated with octreotide (0.01 vs 0.05 claims/pt/year), although this difference was greatest during the first month of treatment (mean difference: 0.19; p&lt;0.0001), after which differences in rescue medication use were only significant (p&lt;0.05) at Months 5 and 6. Mean total annual costs (rescue medication + LAR) were lower for lanreotide than octreotide ($27,829.35/pt [N=373] vs $31,255.49/pt [N=530], respectively, p&lt;0.0001). Conclusions: In the absence of clinical trials directly comparing the SSAs, factors driving treatment selection are unclear. Findings from our real-world observational study suggest treatment with lanreotide to be less burdensome and costly than octreotide and may inform treatment discussions with pts. References1. Ipsen Biopharmaceuticals. Somatuline Autogel Product Monograph. 2018. Available at: https://cnetscanada.org/wp-content/uploads/2018/06/Somatuline-Product-Monograph.pdf; 2. Novartis Pharmaceuticals Canada Inc. Sandostatin LAR Product Monograph. 2018. Available at: http://www.ask.novartispharma.ca/download.htm?res=sandostatin_scrip_e.pdf&amp;resTitleId=789.
Biliary tract cancer (BTC) in the elderly: A real-world tertiary cancer center experience.
Authors: Massimiliano Salati, Francesco Caputo, Krisida Cerma, Andrea Spallanzani, Fabio Gelsomino, Chiara Santini, Alessandro Bocconi, Maria Laura Riggi, Gabriele Luppi, Andrea Casadei Gardini, Massimo Dominici
Journal: Journal of Clinical Oncology (2020)

492 Background: Although BTC is mostly a disease of the elderly, only limited data ara available on the optimal management of this patient (pt) population. In fact, older pts are underepresented in clinical trials and results are seldom reported by age group. In this study, we aimed at evaluating pattern of care and treatment outcome in BTC aged ≥ 70 years and comparing them with their younger counterparts. Methods: Medical records of BTC followed at the Modena Cancer Centre from 2007 and 2019 were retrospectively reviewed.. Overall survival (OS) was estimated with the Kaplan-Meier curves and compared by log-rank test. Differences between categorical variables were assessed using the chi square test. Univariate and multivariate analyses were performed to assess the impact of covariates on survival. Results: A total of 120 BTC patients (49%) ≥ 70 were included in the analysis. 54% (64) were female, 47% (56) had iCCA, 41% (49) GBC, and 12% (15) eCCA. 68% (81) had unresectable locally advanced or metastatic disease. 32% (39) underwent surgical resection, 60% (72) were treated with first-line chemotherapy (1L), while 29% (21) of them went on to receive second-line (2L). No differences in terms of both chance to receive surgery (p=0.59) and survival (p=0.25) were recorded compared to youngers. In the advanced-disease setting, median OS was 8 months and was significantly worse than that of the younger counterparts (p&lt;0.001). Older patients were less likely to receive 1L (p&lt;0.001) and 2L (p&lt;0.001) chemotherapy and doublet regimens (p&lt;0.001). Female gender (p=0.031), ECOG PS 0 (p&lt;0.001), stage III (p&lt;0.001) and NLR&gt;3 (p&lt;0.001) were independently associated with a better prognosis in older BTC receiving 1L, with 1-year OS of 82% (95%CI 68-91, p=0.031). Conclusions: In this real-world study, no survival difference was found between older and non-older surgically-treated patients. Contrariwise, elderly BTC were less frequently treated with chemotherapy for advanced disease and their outcome is poorer than youngers. However, clinical and biochemical prognostic have been identified that may assist in selecting older pts more likely to benefit from systemic treatment, both in clinical trials and daily practice.
S-1+oxaliplatin with pembrolizumab for advanced gastric cancer: The cohort 1 in a phase IIb KEYNOTE-659 study.
Authors: Hisateru Yasui, Akihito Kawazoe, Kensei Yamaguchi, Yuji Negoro, Mizutomo Azuma, Kenji Amagai, Hiroki Hara, Hideo Baba, Masahiro Tsuda, Hisashi Hosaka, Hisato Kawakami, Takashi Oshima, Yasushi Omuro, Nozomu Machida, Taito Esaki, Kazuhiro Yoshida, Tomohiro Nishina, Yoshito Komatsu, Shi Rong Han, Kohei Shitara
Journal: Journal of Clinical Oncology (2020)

382 Background: The KEYNOTE-059 study showed the preliminary antitumor activity and tolerability of chemotherapy with pembrolizumab (P) for advanced gastric cancer (AGC). In Japan, S-1 + platinum regimen is a standard chemotherapy for AGC. The KEYNOTE-659 study (NCT03382600) investigated the efficacy and safety of S-1 + oxaliplatin (SOX; cohort 1) or cisplatin (SP; cohort 2) with P as the first line treatment in patients (pts) with human epidermal growth factor receptor 2 (HER2)-negative, programmed death-ligand 1 (PD-L1)-positive AGC. Here, we report the results of cohort 1. Methods: The key inclusion criteria were as follows: age ≥18 to ≤75 years; an ECOG performance status of 0 or 1; and chemotherapy-naïve, HER2-negative and PD-L1-positive AGC. PD-L1 positivity was defined as a combined positive score of ≥1 using the IHC 22C3 PharmDx assay. An S-1 dose of 40-60 mg per dose was orally administered, twice daily, for the first 2 weeks of a 3-week cycle. P (200 mg) and oxaliplatin (OX; 130 mg/m 2 ) were administered on day 1 of each cycle. The primary endpoint was overall response rate (ORR) that was assessed by a blinded independent central review (BICR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety. Results: From April to September 2018, 54 pts were enrolled at 25 sites in Japan. The median follow-up time was 10.1 months. The median number of P doses and cycles in SOX were 9 (range, 2-18) and 6 (range, 2-13), respectively. The relative dose intensities of S-1 and OX were 73% and 60%, respectively. The ORR and DCR assessed by BICR were 72.2% (95% CI 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. The median PFS was 9.4 months (95% CI 6.6-NR). Median DOR and OS were not reached. Grade ≥3 adverse events (AEs) were reported in 31 pts (57.4%). The most common treatment-related AEs of grade ≥3 were thrombocytopenia (14.8%), neutropenia (13.0%), colitis (7.4%), and adrenal insufficiency (5.6%). There were no treatment-related deaths. Conclusions: This study showed the encouraging efficacy and manageable safety of SOX with P therapy as a first line in pts with HER2-negative, PD-L1-positive AGC. Clinical trial information: NCT03382600.
Prospective observational cohort study of second-line chemotherapy administration after first-line platinum-based chemotherapy for patients with advanced NSCLC in Japan (SAPPHIRE study).
Authors: Kiyotaka Yoh, Yasushi Goto, Yoichi Naito, Kazuma Kishi, Yasuo Ohashi, Hideo Kunitoh
Journal: Journal of Clinical Oncology (2013)

8058 Background: Maintenance therapy after first-line platinum-based chemotherapy (first-CT) is reported to be beneficial to patients with advanced non-small cell lung cancer (NSCLC). However, its impact on overall survival appears to be marginal or negligible, if those without maintenance receive active second-line chemotherapy (second-CT), which is initiated at disease progression. The purpose of this study is to investigate the proportion of second-CT administration after first-CT for patients with advanced NSCLC. Methods: From April 2010 to September 2011, 865 patients with advanced NSCLC who were initiated on first-CT at 30 institutions in Japan were enrolled in this prospective observational study. Baseline characteristics, regimens and responses to first-CT, whether or not they received second-CT, and if not, reasons for non-administration were recorded. This report describes from patients with at least 6 months of follow up. This study was supported by the Public Health Research Center Foundation CSPOR. Results: A total of 865 eligible patients with advanced NSCLC provided patient characteristics and details of first-CT. Of all patients, 70% had adenocarcinoma, 20% had squamous cell carcinoma, and 10% were positive for the EGFR mutation. At this data cut off, 225 patients were excluded from the analysis due to disease progression and loss of follow-up during first-CT, and 194 (22%) patients received maintenance therapy after first-CT. Among the 508 patients who were followed up for at least 6 months, 131 patients (26%) could not receive second-CT; the reasons were as follows: declined PS, 79 (60%); patient refusal, 28 (21%); death of any cause, 6 (5%); others, 18 (14%). Conclusions: Preliminary results of this large observational study in Japan suggested that around 20% of patients missed an opportunity to receive appropriate second-CT despite the follow-up of advanced NSCLC patients after first-CT. Further investigation is needed to elucidate the selection criteria of patients that may benefit the most from maintenance therapy, not second-CT at disease progression.