tbuckley/cabot-search huggingface dataset:
A phase II trial of biweekly pemetrexed (P) and gemcitabine (G) in the first-line treatment (tx) of patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: N. W. Peacock, D. R. Spigel, J. D. Hainsworth, D. A. Yardley, H. A. Burris, J. H. Barton, J. F. Patton, D. L. Shipley, L. Simons, F. A. Greco
Journal: Journal of Clinical Oncology (2006)

17054 Background: P and G are active and well-tolerated non-platinum agents used in the tx of NSCLC. Previous trials have combined P and G in the first-line NSCLC setting using a 21D schedule. This trial examined the safety and activity of biweekly P/G. Methods: Theprimary endpoints of this single center community-based phase II study were toassess the safety and response rate (RR) of P/G in pts with previously untreated stage III (unresectable) or IV NSCLC. Tx included: P 500mg/m 2 IV D1 and G 1500mg/m 2 IV D1 Q 14D for 8–12 cycles. Pts also received folate and B12 prophylaxis. Pts were restagedafter 4 cycles. Eligibility included:measurable disease, ECOG PS 0–2, adequate organ function, informed consent, and no active brain metastases. Analysis was by intent to treat. Results: Thirty-five pts were enrolled between 5/05 and 8/05. The median follow-upis 6 months (3.5–7.5 months). Baseline characteristics include: medianage 65 years (41–85); male/female, 71%/29%; ECOG PS 0,1,2:17%/71%/12%; and histology, adenocarcinoma (34%), large cell (29%), squamous (11%), mixed or not specified (26%). The median number of cycles delivered was 8 (1–12). Grade (G)3/4 non-hematologic toxicity included:chest pain (6%), constipation (6%), fatigue (17%), hypercalcemia (6%), dyspnea (9%), and tachyarrhythmia (9%). G3/4 hematologic toxicity included: neutropenia(51%), anemia (8%), and thrombocytopenia (3%). G3/4 febrile neutropenia occurred in 14%. There were notx-related deaths. Response data are availablefor 35 pts. Complete/partial responses for all pts were observed in 0 pts/7pts, respectively, for an overall RR of 20% (95% CI 10%-36%, 1 pt unconfirmed by RECIST criteria). Fifty-four percentof pts had stable disease, and 14% had disease progression(4 pts were unevaluable.) Six-month progression-free survival (PFS) andoverall survival (OS) were 51% and 67%, respectively. Median PFS and OS have not been reached. Conclusions: Biweekly P/G is a safe and well-tolerated regimen with RRsimilar to other standard first-line regimens for the tx of pts with advanced NSCLC, and further study is warranted. Median and 1-year PFSand OS endpoints have not been reached in this trial. [Table: see text]
Consequential administration of intralesional (intratumoral) GM-CSF and IL-2 in the management of metastatic and primary invasive cutaneous melanoma.
Authors: E. George Elias, Bhuvnesh K Sharma
Journal: Journal of Clinical Oncology (2013)

e20052 Background: Patients with dermal and subdermal metatases as well as invasive primary melanoma allow a great opportunity to evaluate the local and systemic response to intralesional therapy. Methods: Ten patients were studied and completed 2½ years of of follow-up. Four had multiple small intransit metastases each measured 3mm-1cm with 3 to &gt;100 lesions per patient, three had large coalesced sclerotic lesions, and two had distant metastases with palpable subcutaneous nodules. Each received intralesional GM-CSF 500 μg weekly, and in case of failure, IL-2 was substituted at 18 million IU weekly. One patient with invasive primary melanoma and a satellite lesion received both cytokines at the skin lesions one week preoperatively. All the patients had flow cytometric analysis of the peripheral blood before and during therapy. All resected tissues were examined histopathologically and by immunohistochemistry. Results: This was safe and nontoxic program. Three of the four patints with small lesions had complete response (CR) to GM-CSF and one failed but had CR to IL-2. All four patients are alive free of disease for 31-45 months. The three patients with sclerotic lesions failed to respond to either agents. One of the two patients with distant metastases had CR for 6 months. The resected tissues from the patient with primary and satellite lesions revealed complete tumor necrosis with massive histiocytosis and overexpression of CD8+, CD83+ and CD25+ cells at the injection sites and regional lymph nodes and is alive free of disease for over 32 months. The flow cytometric analysis showed no significant changes in white cell differentiation and no dendritic cells were identified before or during therapy. Conclusions: Consequential intralesional administration of GM-CSF and IL-2 seems to have a role in the management of some high-risk patients. While GM-CSF can stimulate autologous dendritic cells, IL-2 activates T cells in the presence of patient own tumor. Such combination can activate a strong antitumor response specific to the patient, which is taken-up by the lymphatics.
Reproducibility of in‐hospital worsening heart failure event adjudication in the RELAX‐AHF‐EU trial
Authors: Jonas Hallén, Aldo P. Maggioni, Esteban Lopez‐De‐Sa, Fabio M. Turazza, Klaus Witte, Erland Erdmann, Ulf Dahlström, Georg Ertl, Olav W. Nielsen, Jose Lopez Sendon, Thomas Holbro, Chien‐Wei Chen, Claudio Gimpelewicz, Martin R. Cowie
Journal: European Journal of Heart Failure (2019)
Abstract 2061: A novel small molecule inhibitor of MDM2-p53 (APG-115) has antitumor activity in gastric adenocarcinoma
Authors: Lin Zhang, Luo Qiuyun, Yan Xianglei, Xueping Wan, Luping Yuan, Yuxing Zhang, Suna Zhou, Wentao Pan, Mengxian Pan, Miaozhen Qiu, Shijuan Mai, Dajun Yang
Journal: Cancer Research (2019)

Abstract Background: The amplification of Murine Double Minute 2 (MDM2) and mutation of P53 are significant processes in the incidence of gastric cancer. APG-115, a small molecular inhibitor of MDM2-P53, is a novel potential anticancer agent. We aim to investigate the anticancer effect of APG-115 in gastric cancer. Methods: We selected 87 pairs of gastric cancer tissues (primary tumors and metastatic tissues). Using Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH), we examined the expression and amplification of MDM2 and P53. Using MTS, we examined the anti-proliferation activity of APG-115 in five gastric cancer cell lines (AGS, MKN-45, BGC-823, NCI-N87, NUGC-3) by CCK-8 assay. We used western blot analysis and siRNA interference for mechanism exploration to examine the anti-cancer activity of APG-115 in p53 wild type gastric cancer cell lines. Gastric cancer cell xenograft nude mice models were used for in vivo efficacy evaluation. Results: We examined 87 pairs of gastric cancer tissues in IHC. The results suggested that the primary tumors and metastatic tissues with high expression of MDM2 and P53 have shortened survival. The proliferation inhibition of APG-115 on p53 wild-type gastric cancer cells of AGS and MKN45 was concentration and time dependent. APG-115 induced apoptosis in gastric cancer cells. APG-115 can induced cell-cycle arrest in G1/G0 phase in the p53 wild-type of gastric cancer cells. APG-115 exhibited potent antitumor activity against established human gastric cancer xenografts. Conclusions: APG-115 can inhibitor tumor growth in p53 wild-type gastric cancer cells by inducing apoptosis and cell cycle arrest both in vitro and vivo. APG-115 can serve as an effective and precise therapeutic strategy for gastric cancer. Citation Format: Lin Zhang, Luo Qiuyun, Yan Xianglei, Xueping Wan, Luping Yuan, Yuxing Zhang, Suna Zhou, Wentao Pan, Mengxian Pan, Miaozhen Qiu, Shijuan Mai, Dajun Yang. A novel small molecule inhibitor of MDM2-p53 (APG-115) has antitumor activity in gastric adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2061.
James Malpas: pioneer of medical oncology who developed combination chemotherapy
Authors: Alan Craft
Journal: BMJ (2019)

Before the 1960s the only modalities of therapy for cancer were surgery and radiotherapy, and these could be successful only if the cancer was localised. There were no treatments for disseminated diseases, including leukaemia. 

It was during a junior registrar post at Barts that James Malpas was encouraged by Ronald Bodley Scott to take an interest in oncology. Gordon Hamilton Fairley was senior to him, and he went off to the US to look at combination chemotherapies that were being developed for lymphomas and leukaemia. 

Previously the advice from pharmacologists had been that to avoid resistance of cancer cells, only one drug at a time should be given. Responses were seen, but few were sustained.

Combining drugs seemed to produce much better response rates, but the drugs were toxic, with unpleasant side effects. The Barts team modified the drugs used to make them less toxic and remarkable results were seen. Their game changing paper showed that when the combination of mustine, vinblastine, prednisolone, and procarbazine (MVPP) was used, two thirds of patients who had received no previous treatment for …
Abstract 20134: Similar Heparin Dosing in Uninterrupted Anticoagulation Treatment With Dabigatran Etexilate versus Warfarin in Catheter Ablation of Atrial Fibrillation: The Re-Circuit Study
Authors: Hugh Calkins, Stephan Willems, Richard Schilling, Stefan H Hohnloser, Ken Okumura, Matias Nordaby, Edward P Gerstenfeld
Journal: Circulation (2017)

Background: The RE-CIRCUIT study showed significantly fewer International Society on Thrombosis and Haemostasis major bleeding events (ISTH MBEs) in patients undergoing AF catheter ablation with un...
Lysine acetyltransferase Tip60 is required for hematopoietic stem cell maintenance
Authors: Akihiko Numata, Hui Si Kwok, Qi-Ling Zhou, Jia Li, Roberto Tirado-Magallanes, Vladimir Espinosa Angarica, Rebecca Hannah, Jihye Park, Chelsia Qiuxia Wang, Vaidehi Krishnan, Deepa Rajagopalan, Yanzhou Zhang, Siqin Zhou, Robert S. Welner, Motomi Osato, Sudhakar Jha, Stefan K. Bohlander, Berthold Göttgens, Henry Yang, Touati Benoukraf, John W. Lough, Deepak Bararia, Daniel G. Tenen
Journal: Blood (2020)
The differences in sexual satisfaction, quality of life, and social support between patients with prostate cancer and cervical cancer after radiotherapy.
Authors: Anna Kieszkowska-Grudny, Monika Rucinska, Sergiusz Nawrocki
Journal: Journal of Clinical Oncology (2013)

e20666 Background: Cervical cancer (CxCa) and prostate cancer (PRCa) have a major impact on sexuality, quality of life (QoL) and patients (pts) require social support(SS). Study aim was to compare sexual satisfaction and activity,QoL and level of required and received SS in group of CxCa and PRCa pts min.3 months after radical radiotherapy (RTH). Methods: 97pts were included to the study:50 non-metastatic PRCa pts (54-83y, M=68,8) and47 CxCa pts (27-69y,M=54,4) after RTH. Subjects filled out:QLQ-C30,PR25,CX24, Berlin Social Support Scales (BSSS) and demographic data.The Chi 2 ,t-Student test,and linear regression analyses were used (p&lt;0,5). Results: However sexual activity and satisfaction in both cancer groups is significantly lower (p&lt;0,05) than in healthy population, no differences were observed between CxCa and PRCa pts. No difference were found between general and any subscale of QoL in both groups, although men needed significantly more help with eating, dressing, washing or using the toilet. However,men felt less male than women less feminine because of cancer (p&lt;0,001). Predictors to better femininity evaluation (R 2 =0,650;p&lt;0,05)were: higher appetite, emotional functioning, perceived available instrumental support and marital status. Predictors of poor masculinity evaluation (R 2 =0,346;p&lt;0,05)were: shortness of breath, age, lower perceived available emotional support. The most significant differences (p&lt;0,05) were observed between groups in the evaluation of SS: perceived available emotional SS was higher in pts with CxCa than with PRCa, while protective-buffering SS, currently received emotional SS and general SS were higher in the group of PRCa than CxCa pts. Conclusions: QoL was similar in both groups, in some areas men needed more help that women. Sexual activity and satisfaction is lower in cancer pts in comparison with general population, but no differences were observed between CxCa and PRCa pts, however emotional SS was crucial for better sexual satisfaction. The more visible difference were found in SS, and even men with PRCa have been receiving more SS,women with CxCa perceived particular SS higher than in fact such support had experienced.
Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score
Authors: Kristen M. Sanfilippo, Suhong Luo, Tzu‐Fei Wang, Mark Fiala, Martin Schoen, Tanya M. Wildes, Joseph Mikhael, Nicole M. Kuderer, David C. Calverley, Jesse Keller, Theodore Thomas, Kenneth R. Carson, Brian F. Gage
Journal: American Journal of Hematology (2019)

Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending primary thromboprophylaxis, in those identified at high-risk of VTE by the presence of risk factors. The National Comprehensive Cancer Network (NCCN) has adopted these guidelines; however, they lack validation. We sought to develop and validate a risk prediction score for VTE in MM and to evaluate the performance of the current IMWG/NCCN guidelines. Using 4446 patients within the Veterans Administration Central Cancer Registry, we used time-to-event analyses to develop a risk score for VTE in patients with newly diagnosed MM starting chemotherapy. We externally validated the score using the Surveillance, Epidemiology, End Results (SEER)-Medicare database (N = 4256). After identifying independent predictors of VTE, we combined the variables to develop the IMPEDE VTE score (Immunomodulatory agent; Body Mass Index ≥25 kg/m2 ; Pelvic, hip or femur fracture; Erythropoietin stimulating agent; Dexamethasone/Doxorubicin; Asian Ethnicity/Race; VTE history; Tunneled line/central venous catheter; Existing thromboprophylaxis). The score showed satisfactory discrimination in the derivation cohort, c-statistic = 0.66. Risk of VTE significantly increased as score increased (hazard ratio 1.20, P = <.0001). Within the external validation cohort, IMPEDE VTE had a c-statistic of 0.64. For comparison, when evaluating the performance of the IMWG/NCCN guidelines, the c-statistic was 0.55. In summary, the IMPEDE VTE score outperformed the current IMWG/NCCN guidelines and could be considered as the new standard risk stratification for VTE in MM.
Case of early Barrett cancer following peroral endoscopic myotomy
Authors: Yervant Ichkhanian, Petros Benias, Mouen A Khashab
Journal: Gut (2019)

Peroral endoscopic myotomy (POEM) offers an effective and a minimally invasive approach for the management of patients with achalasia and is now considered the standard of care at many centres around the world. Despite its excellent outcomes, the high incidence of postoperative GORD remains its major limitation. Unlike laparoscopic Heller myotomy (LHM), no concomitant fundoplication is performed during POEM, which can increase the incidence of GORD and its long-term consequences. Recently, we diagnosed a case of de novo Barrett’s oesophagus (BE) with oesophageal adenocarcinoma in a patient, 4 years after POEM was performed for achalasia, highlighting the possible long-term consequences of postprocedural GORD.

Since it was first clinically described,1 POEM has gained worldwide acceptance as an endoscopic technique for the management of achalasia. Despite its well-established efficacy and safety, the development of GORD post-POEM remains a major concern.2 Of particular concern is that up to two-thirds of patients have asymptomatic and unrecognised GORD.3 The effectiveness of our current management and monitoring strategies for GORD following POEM is not well established. In addition, long-term data pertinent to chronic oesophageal acid exposure after POEM are lacking.

The following case is of a 69-year-old man who initially presented at the age of 64 with a 15-year history of dysphagia, regurgitation, microaspiration and intermittent chest pain, and high-resolution oesophageal manometry (HREM) was consistent with type III achalasia. Impedance-pH study was negative for underlying gastro-oesophageal reflux (GER), and the patient had no additional pertinent medical, surgical or family history.

POEM was performed with a 17 cm oesophageal myotomy and 2 cm gastric myotomy with no adverse events. Postprocedure, the distensibility index increased from a baseline value of 1.7 mm2/mm Hg to 6.3 mm2/mm Hg using the endoluminal functional lumen imaging probe (EndoFLIP), and oesophagram revealed proper lower oesophagus emptying with no …
Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy
Authors: Rong Fan, Bin Zhou, Min Xu, Deming Tan, Junqi Niu, Hao Wang, Hong Ren, Xinyue Chen, Maorong Wang, Qin Ning, Guangfeng Shi, Jifang Sheng, Hong Tang, Xuefan Bai, Shi Liu, Fengmin Lu, Jie Peng, Jian Sun, Qing Xie, Jinlin Hou, Mobin Wan, Shijun Chen, Yanyan Yu, Hong Ma, Jun Cheng, Hongfei Zhang, Huimin Liu, Zhiliang Gao, Xiaoguang Dou
Journal: Clinical Gastroenterology and Hepatology (2019)

There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment.We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old; 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers.After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35; 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102; 31.4%; P = .018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13; 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27; 33.3%; P = .286) CONCLUSIONS: In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.
HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy
Authors: William R. McManus, Michael J. Bale, Jonathan Spindler, Ann Wiegand, Andrew Musick, Sean C. Patro, Michele D. Sobolewski, Victoria K. Musick, Elizabeth M. Anderson, Joshua C. Cyktor, Elias K. Halvas, Wei Shao, Daria Wells, Xiaolin Wu, Brandon F. Keele, Jeffrey M. Milush, Rebecca Hoh, John W. Mellors, Stephen H. Hughes, Steven G. Deeks, John M. Coffin, Mary F. Kearney
Journal: Journal of Clinical Investigation (2019)

To investigate the possibility that HIV-1 replication in lymph nodes sustains the reservoir during antiretroviral therapy (ART), we looked for evidence of viral replication in 5 donors after up to 13 years of viral suppression. We characterized proviral populations in lymph nodes and peripheral blood before and during ART, evaluated the levels of viral RNA expression in single lymph node and blood cells, and characterized the proviral integration sites in paired lymph node and blood samples. Proviruses with identical sequences, identical integration sites, and similar levels of RNA expression were found in lymph nodes and blood samples collected during ART, and no single sequence with significant divergence from the pretherapy population was detected in either blood or lymph nodes. These findings show that all detectable persistent HIV-1 infection is consistent with maintenance in lymph nodes by clonal proliferation of cells infected before ART and not by ongoing viral replication during ART.
Identification of Coding and Long Noncoding RNAs Differentially Expressed in Tumors and Preferentially Expressed in Healthy Tissues
Authors: Juan P. Unfried, Guillermo Serrano, Beatriz Suárez, Paloma Sangro, Valeria Ferretti, Celia Prior, Loreto Boix, Jordi Bruix, Bruno Sangro, Víctor Segura, Puri Fortes
Journal: Cancer Research (2019)

Abstract The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets allow unprecedented gene expression analyses. Here, using these datasets, we performed pan-cancer and pan-tissue identification of coding and long noncoding RNA (lncRNA) transcripts differentially expressed in tumors and preferentially expressed in healthy tissues and/or tumors. Pan-cancer comparison of mRNAs and lncRNAs showed that lncRNAs were deregulated in a more tumor-specific manner. Given that lncRNAs are more tissue-specific than mRNAs, we identified healthy tissues that preferentially express lncRNAs upregulated in tumors and found that testis, brain, the digestive tract, and blood/spleen were the most prevalent. In addition, specific tumors also upregulate lncRNAs preferentially expressed in other tissues, generating a unique signature for each tumor type. Most tumors studied downregulated lncRNAs preferentially expressed in their tissue of origin, probably as a result of dedifferentiation. However, the same lncRNAs could be upregulated in other tumors, resulting in "bimorphic" transcripts. In hepatocellular carcinoma (HCC), the upregulated genes identified were expressed at higher levels in patients with worse prognosis. Some lncRNAs upregulated in HCC and preferentially expressed in healthy testis or brain were predicted to function as oncogenes and were significantly associated with higher tumor burden, and poor prognosis, suggesting their relevance in hepatocarcinogenesis and/or tumor evolution. Taken together, therapies targeting oncogenic lncRNAs should take into consideration the healthy tissue, where the lncRNAs are preferentially expressed, to predict and decrease unwanted secondary effects and increase potency. Significance: Comprehensive analysis of coding and noncoding genes expressed in different tumors and normal tissues, which should be taken into account to predict side effects from potential coding and noncoding gene-targeting therapies.