tbuckley/cabot-search huggingface dataset:
Interleukin-32α Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis
Authors: Dong Ju Son, Yu Yeon Jung, Young Sik Seo, Heonyong Park, Dong Hun Lee, Sanghyeon Kim, Yoon-Seok Roh, Sang Bae Han, Do Young Yoon, Jin Tae Hong
Journal: Theranostics (2017)

Interleukin-32 (IL-32) is a multifaceted cytokine that promotes inflammation and regulates vascular endothelial cell behavior. Although some IL-32 isoforms have been reported to contribute to vascular inflammation and atherosclerosis, the functional role of IL-32α in vascular inflammation and atherogenesis has not been studied. Methods: IL-32α function was assessed in cells with transient IL-32α overexpression or treated with recombinant human IL-32α by western blotting and mRNA expression analysis. Vascular smooth muscle cell (VSMC) proliferation and migration was examined by BrdU incorporation and wound healing assays, respectively. In addition, the participation of IL-32α on vascular inflammation, arterial wall thickening, and atherosclerosis in vivo was monitored in human IL-32α transgenic (hIL-32α-Tg) mice with or without ApoE knockout (ApoE -/- /hIL-32α-Tg). Results: Our analyses showed that IL-32α suppresses genes involved in the inflammatory and immune responses and cell proliferation, and by limiting matrix metalloproteinase (MMP) function. In vivo, administration of hIL-32α inhibited vascular inflammation and atherosclerosis in hIL-32α-Tg and ApoE -/- /hIL-32α-Tg mice. Subsequent microarray and in silico analysis also revealed a marked decreased in inflammatory gene expression in hIL-32α-Tg mice. Collectively, our studies demonstrated that IL-32α upregulates the atheroprotective genes Timp3 and Reck by downregulating microRNA-205 through regulation of the Rprd2-Dgcr8/Ddx5-Dicer1 biogenesis pathway. Conclusion: Our findings provide the first direct evidence that IL-32α is an anti-inflammatory and anti-atherogenic cytokine that may be useful as a diagnostic and therapeutic protein in atherosclerosis.
Chapter V: Chemical Methods and Procedures
Journal: Circulation (1968)

Serum cholesterol was centrally determined by a modified, semi-automated Abell-Kendall method at the Lipid Standardization Laboratory of the Communicable Disease Center, U.S. Public Health Service, Atlanta, Georgia. The standard error of measurement for blind duplicates, randomized over six days, ranged from 2.7 to 3.0 mg./dl., after repeating the analysis of samples whose duplicates differed by more than 9 mg./dl. Serial analyses of specimens from stock serum pools showed a pooled standard deviation of 3.5 mg./dl., and no systematic trend over time. These data demonstrate the feasibility of obtaining consistent high quality serum cholesterol analyses in a national cooperative study through a central laboratory. Fatty acid composition of red blood cells, adipose tissue, and cholesterol esters was analyzed locally in three participating laboratories by gas liquid chromatography. At all three laboratories, analyses were confined to the peaks corresponding to palmitate, stearate, oleate, and linoleate; these were calibrated by comparing with N.I.H. standard mixture D chromatographed on the same day. Triglycerides were measured locally in two participating laboratories, on fasting plasma or randomly collected serum "clarified" by preliminary centrifugation. Inter-laboratory comparison of analyses of fasting serum yielded a mean difference of 2.8 mg./dl., and a standard error of measurement between the laboratories of 14 mg./dl. Diet-Heart foods were analyzed by the Woodson-Tenent Laboratories, Memphis, Tennessee, for water, total fat, protein, ash, cholesterol, and fatty acid distribution.
Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors
Authors: Netta Mäkinen, Kati Kämpjärvi, Norma Frizzell, Ralf Bützow, Pia Vahteristo
Journal: Molecular Cancer (2017)

Uterine smooth muscle tumors range from benign leiomyomas to malignant leiomyosarcomas. Based on numerous molecular studies, leiomyomas and leiomyosarcomas mostly lack shared mutations and the majority of tumors are believed to develop through distinct mechanisms. To further characterize the molecular variability among uterine smooth muscle tumors, and simultaneously insinuate their potential malignant progression, we examined the frequency of known genetic leiomyoma driver alterations (MED12 mutations, HMGA2 overexpression, biallelic FH inactivation) in 65 conventional leiomyomas, 94 histopathological leiomyoma variants (18 leiomyomas with bizarre nuclei, 22 cellular, 29 highly cellular, and 25 mitotically active leiomyomas), and 51 leiomyosarcomas. Of the 210 tumors analyzed, 107 had mutations in one of the three driver genes. No tumor had more than one mutation confirming that all alterations are mutually exclusive. MED12 mutations were the most common alterations in conventional and mitotically active leiomyomas and leiomyosarcomas, while leiomyomas with bizarre nuclei were most often FH deficient and cellular tumors showed frequent HMGA2 overexpression. Highly cellular leiomyomas displayed the least amount of alterations leaving the majority of tumors with no known driver aberration. Our results indicate that based on the molecular background, histopathological leiomyoma subtypes do not only differ from conventional leiomyomas, but also from each other. The presence of leiomyoma driver alterations in nearly one third of leiomyosarcomas suggests that some tumors arise through leiomyoma precursor lesion or that these mutations provide growth advantage also to highly aggressive cancers. It is clinically relevant to understand the molecular background of various smooth muscle tumor subtypes, as it may lead to improved diagnosis and personalized treatments in the future.
Abstract 151: Cell-based Therapies for Heart Failure: Changes in Cytokine Expression From Mesenchymal Stem Cells and Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: Amitabh C Pandey, Jordan Lancaster, David Harris, Steven Goldman, Elizabeth Juneman
Journal: Circulation Research (2015)

Mesenchymal stem cells (MSCs) use paracrine signaling to modulate the cellular microenvironment via expression of cytokines, chemokines, and adhesion molecules to aid and promote endogenous repair. Induced pluripotent stem cell derived cardiomyocyte (iPSC-CMs) and mesenchymal stem cells (MSCs) together may play a synergistic role in changing the microenvironment milieu to allow for endogenous cellular repair through paracrine signaling. Cytokine expression is involved in the progression of heart failure (HF). Using a rat model of HF, cell based therapies with a fibroblast embedded patch only, iPSC-CM patch, and MSCs via tail vein (IV) or intracardiac injections (IC) to the left ventricle (LV) were administered, and RNA was subsequently isolated, and real-time polymerase chain reaction (PCR) was performed for analysis of gene expression. Evaluation of gene expression revealed significant increases in the expression of connexin 43 with iPSC-CMs (p&lt;0.05). Expression of MMP9 was decreased with MSCs alone (p&lt;0.05) but with the use of the patch with both cell types, its levels were significantly increased (p&lt;0.05). Myosin heavy chain was seen to increase significantly with increasing cell numbers in iPSC-CM therapy (p&lt;0.05). Markers of angiogenesis including vascular endothelial growth factor, angiopoietin, and insulin like growth factor were significantly increased with iPSC-CM patch therapy (p&lt;0.05). Up-regulation of angiogenic cytokines and cardio-protective cytokines may help in slowing progression of HF. Interestingly, we also observed an increase in some markers, which were associated with HF. In conclusion, both iPSC-CM patch and MSCs altered signaling in the setting of HF, perhaps leading to improvement of at the cellular level. An iPSC-CM-based patch and MSCs as an adjuvant therapy may be able to play a role in the setting of HF as cellular therapeutic approach.
Colonic Parasitic Infection Mimicking Peritoneal Seeding on 18F-FDG PET/CT
Authors: Beong Woo Kim, Hae Won Kim, Kyoung Sook Won, Yu-Na Kang, Byung-Wook Choi
Journal: Clinical Nuclear Medicine (2017)

A 77-year-old man with anorexia and weight loss for 6 months received a diagnosis of gastric cancer by endoscopy and referred for 18F-FDG PET/CT for initial staging. 18F-FDG PET/CT showed multiple foci of increased FDG uptake with diffuse wall thickening and multiple diverticula. The differential diagnoses were peritoneal seeding and multiple diverticulitis. The patient underwent curative total gastrectomy, and the lesion was diagnosed as poorly differentiated adenocarcinoma by histological examination. He underwent anterior resection of the sigmoid colon for exploration. The nodular lesions of the sigmoid colon were diagnosed by histopathologic examination as chronic diverticulitis caused by a parasitic infection.
Arylamine N -acetyltransferase 2 genotype-dependent N -acetylation of isoniazid in cryopreserved human hepatocytes
Authors: Mark A. Doll, Raúl A. Salazar-González, Srineil Bodduluri, David W. Hein
Journal: Acta Pharmaceutica Sinica B (2017)

Cryopreserved human hepatocytes were used to investigate the role of arylamine N-acetyltransferase 2 (NAT2; EC 2.3.1.5) polymorphism on the N-acetylation of isoniazid (INH). NAT2 genotype was determined by Taqman allelic discrimination assay and INH N-acetylation was measured by high performance liquid chromatography. INH N-acetylation rates in vitro exhibited a robust and highly significant (P<0.005) NAT2 phenotype-dependent metabolism. N-acetylation rates in situ were INH concentration- and time-dependent. Following incubation for 24 h with 12.5 or 100 µmol/L INH, acetyl-INH concentrations varied significantly (P = 0.0023 and P = 0.0002) across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. The clear association between NAT2 genotype and phenotype supports use of NAT2 genotype to guide INH dosing strategies in the treatment and prevention of tuberculosis.
In Reply:
Authors: Reshma Jagsi, Thomas F. DeLaney, Karen Donelan, Nancy J. Tarbell
Journal: Journal of Clinical Oncology (2005)

debated.Hyperfractionated radiation, to reduce normal tissue complications, and dose escalation, has unfortunately not improved the prognosis. 6The only reference to the value of proton therapy in the article is a 1989 article describing a series of patients who were treated for chordomas and chondrosarcomas of the base of the skull. 7There is therefore a presumption of clinical benefit of proton therapy in this case, which is not justified on the facts presented-level 5 evidence or extrapolation from basic principles.Future clinical reports evaluating the benefit of proton therapy in this situation, with the help of modeling of physical parameters of cases, will be most useful.The selection of patient for a program or the evaluation of eligibility criteria for a formalized study would be more apt contexts for decision making regarding therapies of uncertain gain.Patients, or their relatives, who are given to understand that they will not receive a form of treatment because of rationing will understand that they are deprived, which may not be factual.There are gentler phrases, such as "resource allocation" or "priority setting," though these may have very much the same meaning.These terms should be used with circumspection when the evidence indicates that the benefits are only potentially present or clinically insignificant when compared with other widely available modalities.
A Look Inside of the Complex Pathogenesis of B-RAF(V600E)-Driven Cancer
Authors: Emilia Caputo
Journal: Theranostics (2017)

Cancer is a very complex disease, where cell alterations (i.e. gene mutations, dysregulated signaling pathway(s) and epigenetic modifications) contribute to its development and progression.Elucidating the connections among these cell modifications is a critical challenge, in order to understand the mechanisms which are activated from cancer cells to survive and proliferate.Interesting, Prof. Peng Hou and colleagues, at the First Affiliated Hospital of Xi'an Jiaotong University in China, identified unknown epigenetic mechanisms and their involvement in the tumorigenesis of B-RAF(V600E)-driven cancer.
Complementary medicine use during adjuvant radiotherapy of breast cancer.
Authors: Rebecca Buecker, Ulrich Schafer
Journal: Journal of Clinical Oncology (2017)

e12088 Background: Complementary medicine (CM) is used widely in cancer patients, mostly in palliative treatment regimes or during chemotherapy. In contrast, the use of CM during curative Radiotherapy (RT) is less frequent.The aim of this study was to evaluate the influence of CM with regard to toxicity and recurrence during postoperative radiotherapy for breast cancer. Methods: Between 2010 and 2013 all patients intended for adjuvant radiotherapy for breast cancer received a questionnaire concerning the use of CM e.g. Vitamins, trace elements, enzymes, natural herbs etc. (yes / no) and if yes what kinds. Radiotherapy was applied with 50.4 Gy to the whole breast and a Boost of 10.8 Gy in 6.5 weeks.6 weeks after radiotherapy the side effects were analyzed. Follow up for progression rates was done yearly. Results: A total number of 879 patients with breast cancer completed the questionnaire, 641 (73%) did not take any CM and 238 (27%) took CM. There were almost 40 different products mentioned and the most common were magnesium (n=71) and selenium (n=38). The RT side effects (Dermatitis RTOG grade 0, I, II, III/IV) 6 weeks after completion of RT were as follow: in the non CM group 53% grade 0, 41% grade I, and 6% grade II, 0% grade III/IV. And in the CM group 54%, 39%, 9%, and 0% respectively. The corresponding side effects for the group taking magnesium were 35% 42%, 6% and 1% and for the selenium group 47%, 47%, 5% and 0%. There was no significant difference in side effects between the non CM and CM patients, respectively magnesium and selenium group . The sum of all registered disease progression (0 years – 5 years) were in the non CM group 6.4%, in the CM group 6.3%, in the magnesium group 5.6% and in the selenium group 7.9%, no significant difference could be detected between all groups. Conclusions: In this cohort, 27 % of patients used CM during adjuvant radiotherapy of breast cancer. The most commonly product is magnesium followed by selenium. A measurable influence of CM on RT side effects or disease progression could not be identified.
Similar outcome of elderly patients in intergroup trial 0096: Cisplatin, etoposide, and thoracic radiotherapy administered once or twice daily in limited stage small cell lung carcinoma.
Authors: R Livingston, W Sause, R Komaki, Darren A. Yuen, Matthew D. Johnson, G Zou, A Turrisi, Ulrich H. Wagner, R R Blum, S C Aisner
Journal: The Lancet (2000)
Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine
Authors: Martin Pool, H. Rudolf de Boer, Marjolijn N. Lub-de Hooge, Marcel A.T.M. van Vugt, Elisabeth G.E. de Vries
Journal: Theranostics (2017)

Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.
A long way to go after the initial experience with balloon pulmonary angioplasty
Authors: Hiromi Matsubara, Aiko Ogawa
Journal: European Respiratory Journal (2017)

To date, the standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH) has been surgical pulmonary endarterectomy (PEA) followed by life-time anticoagulation therapy [1]. However, excellent results with PEA have been limited to select centres with experience and expertise; many patients who are possible candidates for PEA at expert centres would be considered ineligible in many countries [2]. Medical treatment has shown little or no improvement in haemodynamic parameters in patients with CTEPH who are ineligible for PEA [3, 4]. Thus, despite partial success of balloon pulmonary angioplasty (BPA) in the USA [5], attempts to treat patients with CTEPH by BPA have increased in several countries where PEA is not widely performed [6–8]. Before starting a BPA programme, two main problems in the initial report [5] need to be resolved: its low efficacy and high incidence of complication. To improve efficacy and safety of balloon pulmonary angioplasty, accumulation of experience and knowledge is needed <http://ow.ly/lVSj30bFFNh>
Incidence of febrile neutropenia with use of docetaxel plus cyclophosphamide (TC) for breast cancer.
Authors: Kiran Patel, Brenda Diergaarde, Adam Brufsky, Rachel Catherine Jankowitz, Barry C. Lembersky, Priya Rastogi, Shannon Leigh Huggins-Puhalla
Journal: Journal of Clinical Oncology (2017)

e12073 Background: Incidence of febrile neutropenia (FN) is reported as 5% in breast cancer patients receiving TC (Jones et al., JCO 2006), which would not justify the usage of prophylactic granulocyte colony stimulating factors (G-CSF). We previously showed that the incidence of FN may be as high as 23% in a small study. (N = 130, Soni et al., ASCO 2011). In the current study, we determined the incidence of FN in a larger cohort (N = 415), and evaluated the usage of G-CSF and its relation to FN, age, stage, and hormonal status. Methods: We retrospectively reviewed the electronic medical records from patients diagnosed with breast cancer who received at least one standard dose cycle of adjuvant TC between 2010-2016 at a university-based breast oncology practice. Chi-square or Fisher’s exact tests were used to assess differences between groups. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multiple logistic regression models. Results: We identified in total 415 patients who received adjuvant TC. Median age at diagnosis was 58 (range: 25-86), the majority had stage I or II (N = 382; 92.1%) disease, and 315 (75.9%) were ER+, 277 (66.8%) PR+, 42 (10.1%) HER2+, 22 (5.3%) triple-positive, and 81 (19.5%) triple-negative. Prophylactic G-CSF was utilized in 247 patients (59.5%), and unknown for 43 (10.4%). Overall 39 (9.4%) patients experienced febrile neutropenia. Incidence of FN among those receiving G-CSF was 4.5% versus 17.6% among those who did not (p &lt; 0.001). Use of G-CSF significantly lowered risk of FN, OR (95%CI): 0.20 (0.10-0.43) adjusted for age at diagnosis and stage. Use of G-CSF on incidence of FN did not differ significantly by age, stage, or hormonal status. Conclusions: Our data confirms a high rate of FN in patients receiving TC without G-CSF prophylaxis. Our institutional high rate of G-CSF use ( &gt; 50%) reduced the incidence of FN to 4.5% and the observed significant difference in FN incidence between the non G-CSF group and G-CSF group suggests that prophylaxis may be considered when administering TC. Age, stage, and hormonal status do not seem to affect the usage of G-CSF or incidence of FN in our population.
A Phase 1/2 Study of the Second Generation Selective Inhibitor of Nuclear Export (SINE) Compound, KPT-8602, in Patients with Relapsed Refractory Multiple Myeloma
Authors: R. Frank Cornell, Adriana C Rossi, Rachid Baz, Craig C Hofmeister, Chaim Shustik, Joshua R. Richter, Christine Chen, Dan T. Vogl, Sharon Shacham, Erkan Baloglu, William Senapedis, Joel Ellis, Sharon Friedlander, Cassandra Choe-Juliak, Christopher L Cubitt, Joel G Turner, Daniel Sullivan, Michael Kauffman
Journal: Blood (2016)
High-dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) for recurrent/progressive CNS lymphoma.
Authors: Mary Roberta Welch, Craig Steven Sauter, Matthew J. Matasar, Craig Moskowitz, Antonio Marcilio Padula Omuro
Journal: Journal of Clinical Oncology (2012)

2089 Background: In two reports by Soussain et al, promising efficacy was observed in recurrent primary CNS lymphoma with induction cytarabine/VP-16 (CYVE) followed by HDC-ASCT (busulfan, thiotepa and cyclophosphamide [BTC]), but significant toxicity, mainly from CYVE, has limited widespread use. We report our experience with HDC-ASCT with alternative induction regimens. Methods: Retrospective review of pts with recurrent/refractory non-Hodgkin lymphoma (NHL) with CNS involvement treated with HDC-ASCT (2000-present). Results: Seventeen pts met inclusion criteria: med age= 58 (41-65); 9 were women; med KPS prior to transplant= 90 (range 70-100). At initial presentation, 10 had primary CNS lymphoma (ocular: 1); 7 had systemic NHL without CNS involvement; 1 had both systemic and CNS disease. Pts had been heavily pre-treated. Among those with PCNSL, high dose MTX was used in all pts and WBRT in 4. Two pts had received a previous HDC-ASCT. Among systemic NHL pts, various regimens were used, mostly R-CHOP(4), but also R-EPOCH (1), CVP (1), ICE (1) and CODOX-M (1). At CNS recurrence, pts received various induction regimens prior to HD-ASCT: high-dose methotrexate (MTX)-based chemotherapy (N= 13), cytarabine-based regimens (N=2), and other (N= 2). All pts achieved a CR or near CR prior to HDC-ASCT. Harvesting was obtained with G-CSF alone in 9 pts; 8 required plerixafor. Two pts failed mobilization N=15 received HDC-ASCT. The HDC consisted of BTC (N=13); 1 received BEAM and 1 received reduced intensity fludarabine, melphalan and alemtuzumab. Eight pts experienced a grade III or IV toxicity – most commonly fatigue, febrile neutropenia, and infection. One previously transplanted pt died from sepsis. With a med follow-up of 11 months, post-transplant med-PFS has not been reached. The 12m PFS was 92% (95% CI 56-98). Because no patient has progressed, the OS was identical to PFS. Conclusions: HDC-ASCT was a highly effective salvage approach in this population of recurrent/refractory CNS lymphoma. To reduce the risk of harvesting failure at the time of recurrence, harvesting stem cells at the time of initial treatment could be considered in pts with high risk for relapse.