gebhart/patrepeval huggingface dataset:
Antibodies to watch in 2018 (2018)

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody therapeutics (ibalizumab, burosumab, tildrakizumab, caplacizumab, erenumab, fremanezumab, galcanezumab, romosozumab, mogamulizumab) were in regulatory review in the EU or US, and regulatory actions on their marketing applications are expected by the end of 2018. Based on company announcements and estimated clinical study primary completion dates, and assuming the study results are positive, marketing applications for at least 12 antibody therapeutics that are now being evaluated in late-stage clinical studies may be submitted by the end of 2018. Of the 12 candidates, 8 are for non-cancer indications (lanadelumab, crizanlizumab, ravulizumab, eptinezumab, risankizumab, satralizumab, brolucizumab, PRO140) and 4 are for cancer (sacituzumab govitecan, moxetumomab pasudotox, cemiplimab, ublituximab). Additional antibody therapeutics to watch in 2018 include 19 mAbs undergoing evaluation in late-stage studies with primary completion dates in late 2017 or during 2018. Of these mAbs, 9 are for non-cancer indications (lampalizumab, roledumab, emapalumab, fasinumab, tanezumab, etrolizumab, NEOD001, gantenerumab, anifrolumab) and 10 are for cancer indications (tremelimumab, isatuximab, BCD-100, carotuximab, camrelizumab, IBI308, glembatumumab vedotin, mirvetuximab soravtansine, oportuzumab monatox, L19IL2/L19TNF). Positive clinical study results may enable marketing application submissions in 2018. Brief summaries of these antibody therapeutics are provided in this installment of the 'Antibodies to watch' article series.
Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C (2014)

Objective: Mounting clinical and experimental evidence has demonstrated that even advanced fibrosis and cirrhosis are reversible. Thus, there is a considerable imperative to develop antifibrotic strategies that are applicable to liver fibrosis. In the present study, the attenuation of carbon tetrachloride (CCl 4 )-induced hepatic fibrosis in rats through the co-treatment with antioxidant vitamins C and E or glycine alone was investigated. Materials and Methods: Sixty male Sprague-Dawley were divided randomly into control, CCl 4 , vitamin E+C, and glycine groups. Except for the control group, all rats in the other groups received orally 2 ml/kg CCl 4 dissolved in olive oil (1:1, v/v) twice a week; antioxidant vitamins were supplemented orally (p.o.) at a dose of 200 IU/kg/day vitamin E and 50 mg/kg/day vitamin C. Glycine dose was 0.6 g/Kg/day (p.o.). After 9 weeks, all rats were sacrificed for biochemical and histopathological investigations. Results: Serum levels of hepatic transaminases, alkaline phosphatase, gamma glutamyl transferase, and β-glucuronidase strikingly increased in CCl 4 group. As a biomarker of fibrinogenesis, hyaluronic acid was significantly elevated. These were associated with drastic significant decline in serum albumin concentration level, blood glutathione (GSH) content, GSH peroxidase, catalase and superoxide dismutase enzymatic activities, as well as a striking significant increase in the concentration of serum malondialdehyde. A significant increase in the mean serum concentration levels of tumor necrosis factor-a and transforming growth factor-b1 has been observed in CCl 4 -treated rats. Histopathological examination highlighted and confirmed the biochemical results. Conclusion: The results of this study confirmed the ameliorative effects of vitamin E plus C combination and glycine supplements against liver fibrosis in rats induced by CCl 4 .
Adeno-Associated Viral Vectors for CF Gene Therapy (2003)

AAV is a nonpathogenic human parvovirus that has a natural mechanism for long-term persistence in human cells. Wild-type AAV is unique in that it undergoes stable integration of its DNA into a specific region of human chromosome 19, the AAVS1 site (1–4), a process that our group has also recently described in vivo in rhesus macques (5). This site specificity appears to be mediated by specific interactions between the nonstructural protein, Rep, and the sequence-specific binding elements within the AAVS1 site (6). AAV vectors have been developed by deleting the two AAV genes, rep and cap from the viral genome, and substituting transgenes such as CFTR (7,8). Since the rep gene is deleted, these vectors generally do not integrate in a site-specific manner, yet they do persist long-term in mammalian cells through a complicated process that involves both episomal persistence and random-site integration (9–11).
Tongue and tonsil carcinoma (2005)

The increase in tonsil SCC incidence from 1973 to 2001 paralleled the increase in tongue SCC, whereas SCC in all other oral and pharyngeal sites remained constant or decreased. This may suggest similar etiologic factors for SCC affecting the palatine tonsils and tongue in younger populations.
Phenotypic mixing between human immunodeficiency virus and vesicular stomatitis virus or herpes simplex virus. (1990)

Superinfection of H9 cells persistently infected with human immunodeficiency virus (HIV) with thermolabile vesicular stomatitis virus (VSV) or herpes simplex virus (HSV) led to the synthesis of hybrid progeny. These phenotypic mixtures were able to infect HeLa or Chinese hamster ovary cell lines, leading to the production of HIV p24 antigen and infectious HIV. This production was abrogated by prior incubation of the phenotypic mixtures with antiserum against VSV or HSV, as well as by incubation of the mixtures at 39 degrees C for 10 h. These results demonstrate that during coinfection of cells with either a RNA or DNA virus, HIV forms hybrid virions composed of the genetic information of HIV and the envelope glycoproteins of the coinfecting viruses.
Oncolysis of human ovarian cancers by echovirus type 1 (2005)

A small number of enteroviruses possess the capacity to induce rapid and marked lytic infections in cells of various human malignancies. During screening of representative human enteroviruses for their oncolytic capacity, we observed that echovirus type 1 (EV1) displayed a high level of tropism for human ovarian cancer cells. EV1 is an enterovirus which largely causes asymptomatic infections in humans and whose tissue tropism is primarily regulated via interactions with the I domain of the alpha subunit of cell surface-expressed integrin alpha2beta1. We evaluated the capacity of wild-type EV1 to act as an oncolytic agent of ovarian cancers propagated as cell monolayers, multicellular spheroids or xenografts in SCID mice. EV1 infection of in vitro propagated ovarian cell lines expressing high levels of integrin alpha2beta1 was assessed for specific viral attachment, antibody blockade, induction of cytopathic effect and production of progeny virions. EV1 lytically infected all 8 human ovarian cancer cell lines tested (2008, DOV13, JAM, OVCA-429, OVCAR-3, OVHS-1, OAW-42 and IGROV-1) but not the immortalized normal ovarian surface epithelial cell line (HOSE) or human PBMCs. EV1 challenge was equally effective in the oncolysis of human ovarian cancer cells whether in monolayer or spheroidal environments. The therapeutic efficacy of EV1 was demonstrated by rapid reduction of tumor burden by a single viral intratumoral injection in SCID mice bearing multiple preformed s.c. xenografts. Using an in vivo i.p. human ovarian cancer xenograft model, administration of EV1 was further shown to significantly inhibit the formation and burden of ascites tumors. These findings demonstrate an important proof of principle for employing wild-type EV1 as a potential oncolytic agent in the control of human ovarian cancers.
RGD‐based PET tracers for imaging receptor integrin αvβ3 expression (2013)

Positron emission tomography (PET) imaging of receptor integrin αv β3 expression may play a key role in the early detection of cancer and cardiovascular diseases, monitoring disease progression, evaluating therapeutic response, and aiding anti-angiogenic drugs discovery and development. The last decade has seen the development of new PET tracers for in vivo imaging of integrin αv β3 expression along with advances in PET chemistry. In this review, we will focus on the radiochemistry development of PET tracers based on arginine-glycine-aspartic acid (RGD) peptide, present an overview of general strategies for preparing RGD-based PET tracers, and review the recent advances in preparations of (18) F-labeled, (64) Cu-labeled, and (68) Ga-labeled RGD tracers, RGD-based PET multivalent probes, and RGD-based PET multimodality probes for imaging receptor integrin αv β3 expression.
Brain Cytoplasmic and Flagellar Outer Arm Dyneins Share a Highly Conserved Mr 8,000 Light Chain (1996)

Sequence comparisons with the Mr 8,000 light chain from Chlamydomonas outer arm dynein revealed the presence of highly conserved homologues (up to 90% identity) in the expressed sequence tag data base (King, S. M. & Patel-King, R. S. (1995a) J. Biol. Chem. 270, 11445-11452). Several of these homologous sequences were derived from organisms and/or tissues that lack motile cilia/flagella, suggesting that these proteins may function in the cytoplasm. In Drosophila, lack of the homologous protein results in embryonic lethality (Dick, T., Ray, K., Salz, H. K. & Chia, W.(1996) Mol. Cell. Biol., 16, 1966-1977). Fractionation of mammalian brain homogenates reveals three distinct cytosolic pools of the homologous protein, one of which specifically copurifies with cytoplasmic dynein following both ATP-sensitive microtubule affinity/sucrose density gradient centrifugation and immunoprecipitation with a monoclonal antibody specific for the 74-kDa intermediate chain (IC74). Quantitative densitometry indicates that there is one copy of the Mr 8,000 polypeptide per IC74. Dual channel confocal immunofluorescent microscopy revealed that the Mr 8,000 protein is significantly colocalized with cytoplasmic dynein but not with kinesin in punctate structures (many of which are associated with microtubules) within mammalian oligodendrocytes. Thus, it appears that flagellar outer arm and brain cytoplasmic dyneins share a highly conserved light chain polypeptide that, at least in Drosophila, is essential for viability.
Murine model of cutaneous infection with gram-positive cocci (1992)

Staphylococcus aureus has remained an important cause of nosocomial wound infections, but standardized or reproducible systems for analyzing cutaneous infections caused by S. aureus do not exist. A variety of foreign materials, variable inocula, and skin traumas have been used to promote infection. To minimize these variables and ensure reproducibility, we chose a model using subcutaneous injections of a fixed quantity of dextran microbeads (Cytodex) as the foreign material added to standardized broth suspensions of S. aureus. Suspensions (0.2 ml) injected into an outbred strain of immunocompetent hairless mice generated reproducible, measurable lesions. With S. aureus Smith Diffuse, fluctuant, erythematous lesions with a peak diameter of 15 mm were observed; these lesions yielded purulent material containing gram-positive cocci and neutrophils and yielded growth of S. aureus on culture. Lesion size was proportional to the bacterial inoculum size. Histologic examination of excised lesions revealed typical abscesses. A second strain of S. aureus (SLC3) produced dermonecrosis instead of abscesses at an inoculum size of 10(7) CFU. Control injections with a sterile Cytodex suspension regularly produced nondraining, nonerythematous nodules with maximum diameters of less than or equal to 5 mm. Streptococcus pyogenes produced late-onset necrotic lesions and abscesses. Using a foreign substance, this model generates easily observed and reproducible cutaneous infection with S. aureus and streptococci that can potentially discriminate between inter- and intrastrain differences. Such a model could be used to test the pathogenicity of isogeneic strains of these bacterial species and to evaluate the efficacy of antimicrobial agents.
Viral induction of AID is independent of the interferon and the Toll-like receptor signaling pathways but requires NF-κB (2007)

Activation-induced cytidine deaminase (AID) is expressed in germinal centers of lymphoid organs during immunoglobulin diversification, in bone marrow B cells after infection with Abelson murine leukemia retrovirus (Ab-MLV), and in human B cells after infection by hepatitis C virus. To understand how viruses signal AID induction in the host we asked whether the AID response was abrogated in cells deficient in the interferon pathway or in signaling via the Toll-like receptors. Here we show that AID is not an interferon responsive gene and abrogation of Toll-like receptor signaling does not diminish the AID response. However, we found that NF-kappaB was required for expression of virally induced AID. Since NF-kappaB binds and activates the AID promoter, these results mechanistically link viral infection with AID transcription. Thus, induction of AID by viruses could be the result of several signaling pathways that culminate in NF-kappaB activation, underscoring the versatility of this host defense program.
Transplacental transfer of human antinuclear antibodies in mice by injection of lupus IgG in pregnant animals. (1990)

Pregnant female Balb/c mice were injected with IgG fractions from patients with systemic lupus erythematosus, in order to study the in vivo passage of antinuclear antibodies (ANA) across the placenta. After injection of monospecific sera directed against nDNA, Sm, nRNP, Ro(SSA) and La(SSB), ANA were found in fetal circulation and trapped in the liver, spleen kidney and skin of fetus. Also, ANA were demonstrated in placental tissue and cord. The placental IgG-Fc receptors apparently played a major role in ANA entry into the fetus. Our study demonstrates that human ANA can be passively transferred into experimental animals to study their kinetics during pregnancy.
Human Skin Storage Techniques (1983)

The nude mouse model is an excellent technique for studying the viability of stored human skin. In this study Roswell Park Memorial Institute (RPMI) tissue culture medium provided reliable storage of viable human skin for 20 days. Antibiotic concentration plays a role in stored skin viability with low concentrations of penicillin and streptomycin providing adequate bacterial control and improved viability when compared to identical media with high concentrations of the same antibiotics. Addition of fetal calf serum to the storage medium did not improve human skin viability in this experiment.
Expression of MDA-7/IL-24 and Its Clinical Significance in Resected Non–Small Cell Lung Cancer (2005)

MDA-7/IL-24 status was a significant prognostic factor in lung adenocarcinoma, not in lung squamous cell carcinoma.
Aerobic exercise + weight loss decreases skeletal muscle myostatin expression and improves insulin sensitivity in older adults (2013)

Exercise and weight loss results in a downregulation of myostatin mRNA and an improvement in insulin sensitivity in obese older men and women.
Cubé Resin Insecticide:  Identification and Biological Activity of 29 Rotenoid Constituents (1999)

Cubé resin, the root extract from Lonchocarpus utilis and urucu, is an important insecticide, acaricide, and piscicide. The four major active ingredients are rotenone, deguelin, rotenolone, and tephrosin, totaling 77 wt %. As a commercial pesticide, the minor constituents are also of chemical interest and toxicological relevance. This study identifies 25 minor rotenoids in cubé resin "brittle" of which 12 are new compounds, the most unusual being 7'-chloro-5'-hydroxy-4',5'-dihydrodeguelin (the first chlororotenoid from a plant extract) and four isomers of 4',5'-dihydro-4', 5'-dihydroxytephrosin. Several of the minor rotenoids may be decomposition products from free radical processes during sample preparation, extraction with trichloroethylene, and processing the resin. Assays of the 29 rotenoids as inhibitors of NADH:ubiquinone oxidoreductase activity (primary target for toxicity) and phorbol ester-induced ornithine decarboxylase activity (indicator of cancer chemopreventive action) and for cytotoxicity establish similar structure-activity relationships in each system and the importance of the overall molecular conformation and the E-ring substituents.
Monocyte chemotactic protein 1 is a potent activator of human basophils. (1992)

Cytokines belonging to the RANTES/SIS family are highly induced in a number of pathophysiological processes such as autoimmune disorders, cancers, atherosclerosis, and chronic inflammation. However, apart from their chemotactic activity on monocytes and particular lymphocyte types, the biological activities in the human system of this recently discovered cytokine family are largely unknown. Here we report that one family member, described as monocyte chemotactic protein 1 (MCP-1), strongly activates mature human basophils in a pertussis toxin-sensitive manner. MCP-1 causes a rise in the cytosolic free calcium level in basophils and monocytes, but not in other blood leukocyte types, and triggers basophil degranulation at low concentrations (ED50 = 3-10 nM). Thus, MCP-1 is a cytokine capable of directly inducing histamine release by basophils. Furthermore, MCP-1 promotes the formation of leukotriene C4 by basophils pretreated with interleukin 3 (IL-3), IL-5, or granulocyte/macrophage colony-stimulating factor. MCP-1-induced basophil mediator release may play an important role in allergic inflammation and other pathologies expressing MCP-1.
New PET Imaging Agent for the Serotonin Transporter:  [18F]ACF (2-[(2-Amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine) (2002)

A new F-18-labeled phenylthiophenyl derivative specific for imaging of serotonin transporters (SERT) in the brain by positron emission tomography (PET) is described. Fluorinated phenylthiophenyl derivative, ACF, 2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine, was prepared by first coupling 2,5-dichloro-4-nitroaniline with 2-mercapto-N,N-dimethylbenzamide. The amino group of the coupled adduct was converted to a fluoro group through a Schiemann reaction. Subsequently, a one pot reduction of both nitro and amide groups by BH(3)-tetrahydrofuran yielded the nonradioactive ACF (yield 25%). In vitro binding assays using cell membrane homogenates of LLC cells expressing SERT, dopamine transporters (DAT), or norepinephrine transporters (NET) showed excellent binding affinity and selectivity for SERT (K(i) = 0.05, 3020, and 650 nM for SERT, DAT, and NET, respectively). For preparation of the [(18)F]ACF, the NH(2) group of the initially coupled adduct was converted to the trimethylammonium salt, which was replaced by [(18)F]fluoride in the presence of Kryptofix 222 and potassium carbonate. The final product, [(18)F]ACF, was obtained after a borane and stannous chloride reduction reaction. The combined two step reaction gave a radiochemical yield of 10-15% (EOB) and a radiochemical purity of >99%. Synthesis of the novel PET tracer, [(18)F]ACF, as a probe for binding to SERT in the brain was successfully achieved. The new tracer [(18)F]ACF showed excellent brain penetration and selective localization after an iv injection in rats (brain uptake at 2, 30, 60, 120, and 240 min was 3.27, 1.28, 0.69, 0.21, and 0.06% dose/organ, respectively). The hypothalamus/cerebellum ratio at 60 min post iv injection was 3.55. This specific localization in the hypothalamus was blocked by pretreatment of (+)McN5652. This novel ligand is a potential PET tracer for in vivo evaluation of SERT in the brain.
Pacing for adult patients with left atrial isomerism: efficacy and technical considerations (2003)

Adults with LAI benefit from pacemaker implantation, which reduces recurrence of supraventricular tachycardia and maintains atrioventricular synchrony. Future studies need to determine the preferred pacemaker mode and optimal timing for pacing.
Realizing the Promise of Reverse Phase Protein Arrays for Clinical, Translational, and Basic Research: A Workshop Report (2014)

Reverse phase protein array (RPPA) technology introduced a miniaturized "antigen-down" or "dot-blot" immunoassay suitable for quantifying the relative, semi-quantitative or quantitative (if a well-accepted reference standard exists) abundance of total protein levels and post-translational modifications across a variety of biological samples including cultured cells, tissues, and body fluids. The recent evolution of RPPA combined with more sophisticated sample handling, optical detection, quality control, and better quality affinity reagents provides exquisite sensitivity and high sample throughput at a reasonable cost per sample. This facilitates large-scale multiplex analysis of multiple post-translational markers across samples from in vitro, preclinical, or clinical samples. The technical power of RPPA is stimulating the application and widespread adoption of RPPA methods within academic, clinical, and industrial research laboratories. Advances in RPPA technology now offer scientists the opportunity to quantify protein analytes with high precision, sensitivity, throughput, and robustness. As a result, adopters of RPPA technology have recognized critical success factors for useful and maximum exploitation of RPPA technologies, including the following: preservation and optimization of pre-analytical sample quality, application of validated high-affinity and specific antibody (or other protein affinity) detection reagents, dedicated informatics solutions to ensure accurate and robust quantification of protein analytes, and quality-assured procedures and data analysis workflows compatible with application within regulated clinical environments. In 2011, 2012, and 2013, the first three Global RPPA workshops were held in the United States, Europe, and Japan, respectively. These workshops provided an opportunity for RPPA laboratories, vendors, and users to share and discuss results, the latest technology platforms, best practices, and future challenges and opportunities. The outcomes of the workshops included a number of key opportunities to advance the RPPA field and provide added benefit to existing and future participants in the RPPA research community. The purpose of this report is to share and disseminate, as a community, current knowledge and future directions of the RPPA technology.