gebhart/patrepeval huggingface dataset:
Activation of retinoic acid receptor alpha is sufficient for full induction of retinoid responses in SK-BR-3 and T47D human breast cancer cells. (2000)

Retinoid signaling via retinoic acid (RA) and retinoid X receptors (RARs and RXRs) regulates mammary epithelial cell growth and differentiation. Loss of RAR-beta might represent an early event during breast carcinogenesis. Higher differentiated, estrogen-dependent, estrogen receptor (ER)-positive (ER+) mammary carcinoma cells have been found to contain relatively high levels of RAR-alpha and to be responsive to retinoids, whereas most undifferentiated, estrogen-independent, ER-negative (ER-) cells are characterized by low RAR-alpha expression and by retinoid resistance. In contrast, RAR-gamma is detectable at equal levels in both ER+ and ER- cells. In the present investigation, we directly examined the relative contribution of the distinct retinoid receptors to the retinoid response of breast cancer cells by comparing the effects of low concentrations of specific retinoids, which selectively activate individual receptor subtypes, on growth, cell cycle distribution, apoptosis, and on the autoregulation of RAR-alpha and RAR-gamma in ER- SK-BR-3 and ER+ T47D breast cancer cells. In vitro growth activity was determined by using a colorimetric cell viability assay and analysis of cell cycle distribution, and apoptosis was performed by flow cytometry of propidium iodide-stained or fluorescent Annexin V-labeled cells, respectively, whereas expression of RAR-alpha and RAR-gamma was determined by Northern blotting. Both cell lines are retinoid sensitive and express high amounts of RAR-alpha, RAR-gamma, and RXR-alpha. RAR-alpha-selective compounds (AM80 and AM580) inhibit cell growth, induce G1 arrest, stimulate apoptosis, and up-regulate RAR-alpha and RAR-gamma mRNA as efficiently as RAR/RXR-pan-reactive (9-cis RA) and RAR-pan-reactive retinoids (all-trans RA, TTNPB). Remarkably, an RAR-alpha antagonist (Ro 41-5253) not only blocks the RAR-alpha-selective agonists but also the pan-reactive compounds. In contrast, RAR-13-selective (CD417), RAR-gamma-selective (CD437/AHPN), and RXR-alpha-selective (Ro 25-7386) retinoids exert no effects on the examined parameters. Thus, our results support the idea that RAR-alpha is the crucial receptor mediating the biological effects during retinoid signaling in both ER- SK-BR-3 and ER+ T47D human breast cancer cells.
Juxtapapillary choroidal neovascular membrane in a patient with Paget's disease and lattice corneal dystrophy. (1989)

Paget's disease (osteitis deformans) is a relatively common metabolic bone disease characterized by the gradual development of bony deformities. These deformities lead to cranial and peripheral neuropathies from nerve and blood vessel impingement. Angioid streaks are associated with Paget's disease and are the result of linear breaks in Bruch's membrane caused by the calcification and degeneration of this elastic tissue layer. A case report of a patient with Paget's disease with angioid streaks and a secondary choroidal neovascular membrane is presented. The membrane was treated with argon laser photocoagulation. The patient also had an incidental finding of lattice corneal dystrophy which required penetrating keratoplasty.
Injectable and Biodegradable pH-Responsive Hydrogels for Localized and Sustained Treatment of Human Fibrosarcoma (2015)

Injectable hydrogels are an important class of biomaterials, and they have been widely used for controlled drug release. This study evaluated an injectable hydrogel formed in situ system by the reaction of a polyethylene glycol derivative with α,β-polyaspartylhydrazide for local cancer chemotherapy. This pH-responsive hydrogel was used to realize a sol-gel phase transition, where the gel remained a free-flowing fluid before injection but spontaneously changed into a semisolid hydrogel just after administration. As indicated by scanning electron microscopy images, the hydrogel exhibited a porous three-dimensional microstructure. The prepared hydrogel was biocompatible and biodegradable and could be utilized as a pH-responsive vector for drug delivery. The therapeutic effect of the hydrogel loaded with doxorubicin (DOX) after intratumoral administration in mice with human fibrosarcoma was evaluated. The inhibition of tumor growth was more obvious in the group treated by the DOX-loaded hydrogel, compared to that treated with the free DOX solution. Hence, this hydrogel with good syringeability and high biodegradability, which focuses on local chemotherapy, may enhance the therapeutic effect on human fibrosarcoma.
Enhanced purification of carbon nanotubes by microwave and chlorine cleaning procedures (2016)

A new two-step purification method of carbon nanotubes (CNTs) involving a microwave treatment followed by a gas-phase chlorination process is reported.
Receptor-mediated gene delivery employing lectin-binding specificity. (1994)

Selective targeting of malignant cells will be necessary to implement many of the gene therapy strategies being designed to combat cancer. Targeting can be achieved by transductional or transcriptional approaches. Transductional targeting can be accomplished by exploiting differences in the molecules or receptors expressed on the cell surface of malignant versus normal cells. Given that malignant cells can be distinguished from normal by differences in the expression of cell surface carbohydrates, we hypothesized that transductional targeting would be feasible by molecular conjugate vectors which achieve cell binding by virtue of lectins directed against the cell surface glycocalyx. We have shown that gene transfer can be accomplished by these novel lectin-targeted molecular conjugate vectors and that lectin binding specificities may serve as a means for potential targeting of cancer cells for the purposes of gene therapy.
Blood T-cell receptor chain transcriptome in multiple sclerosis. Characterization of the T cells with altered CDR3 length distribution (2004)

Multiple sclerosis is an inflammatory demyelinating disease of the CNS associated with T cells autoreactive for myelin components. In this study, we analysed the T-cell receptor (TCR) usage of the variable beta (Vbeta) chain transcriptome in the blood of multiple sclerosis patients at various stages of the disease using a global and quantitative comparison of the complementarity-determining region 3 length distribution (CDR3-LD) of transcripts of the 26 Vbeta genes. We investigated 35 patients: 12 with a high risk of multiple sclerosis, 10 with clinically definite multiple sclerosis, 13 with a relapsing-remitting worsening and active multiple sclerosis and 13 healthy individuals. Cells bearing the TCR transcripts with altered CDR3-LD were sorted and studied for CD4 or CD8 phenotype, cytokine transcript accumulation and response to human myelin basic protein (MBP). We show that patients from all the groups have a significantly skewed blood T-cell repertoire. Vbeta transcriptome patterns were more altered in patients from the clinically definite multiple sclerosis group and the worsening and active multiple sclerosis group than in the high risk group. The T cells sorted from Vbeta families with altered CDR3-LD concerned both CD4 and CD8 T cells, with a more pronounced skewing in the CD8 compartment. These cells displayed a significantly increased level of interferon-gamma, interleukin-2 and tumour necrosis factor-alpha transcripts compared with their counterparts from the healthy individual group. Furthermore, using interferon-gamma enzyme-linked immunospot (ELISPOT) assays, T cells from four out of seven altered Vbeta families tested from multiple sclerosis patients responded to human MBP, whereas no response was observed with human albumin or with altered Vbeta families from healthy individuals. Our data support the concept of an early autoimmune component in the disease and emphasize the possible involvement of CD8-positive T cells in multiple sclerosis.
Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation (2014)

Inflammation is an important component of various cancers and its inflammatory cells and mediators have been shown to have prognostic potential. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. In earlier studies, we demonstrated that immunoglobulin free light chains (FLC) can trigger mast cells in an antigen-specific manner. Increased expression of FLC was observed within stroma of various human cancers including those of breast, colon, lung, pancreas, kidney and skin, and FLC expression co-localized with areas of mast cell infiltration. In a large cohort of breast cancer patients, FLC expression was shown associated with basal-like cancers with an aggressive phenotype. Moreover, lambda FLC was found expressed in areas of inflammatory infiltration and its expression was significantly associated with poor clinical outcome. Functional importance of FLCs was shown in a murine B16F10 melanoma model, where inhibition of FLC-mediated mast cell activation strongly reduced tumor growth. Collectively, this study identifies FLCs as a ligand in the pro-tumorigenic activation of mast cells. Blocking this pathway may open new avenues for the inhibition of tumor growth, while immunohistochemical staining of FLC may be helpful in the diagnosis and prognosis of cancer.
Gain of Nrf2 Function in Non-Small-Cell Lung Cancer Cells Confers Radioresistance (2010)

Nuclear factor erythroid-2 related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates the expression of antioxidant enzymes and several anti-apoptotic proteins, which confer cytoprotection against oxidative stress and apoptosis. Constitutive activation of Nrf2 in lung cancer cells promotes tumorigenicity and contributes to chemoresistance by upregulation of glutathione, thioredoxin, and the drug efflux pathways involved in detoxification of electrophiles and broad spectrum of drugs. In this study, we show that RNAi-mediated lowering of Nrf2 levels in non-small-cell lung cancer (NSCLC) cell lines (A549 and H460) led to a dramatic increase in endogenous reactive oxygen species (ROS) levels. Similarly, γ-irradiation-induced formation of protein carbonyls were significantly higher in Nrf2-depleted lung cancer cells, suggesting increased lethality of ionizing radiation in the absence of Nrf2. Radiation-induced protein oxidation in Nrf2shRNA cells correlated with reduced survival as measured by clonogenic assay. Radiation-induced cell death was abrogated by pretreatment with antioxidants such as N-acetyl-L-cysteine, glutathione, and vitamin-E, highlighting the importance of antioxidants in conferring protection against radiation injury. Using genetically-modified gain and loss of function models of Nrf2, in mouse embryonic fibroblasts, we establish that constitutive activation of Nrf2 protects against ionizing radiation toxicity and confers radioresistance. Thus, targeting Nrf2 activity in radioresistant tumors could be a promising strategy to circumvent radioresistance.
Gardner syndrome in a man with an interstitial deletion of 5q (1986)

Chromosome analysis of blood cells from a 42-year-old white male with mental retardation, colon carcinoma, horseshoe kidney, absence of left lobe of the liver, agenesis of the gallbladder, and possible Gardner syndrome revealed a constitutional marker chromosome due to del(5)(q13q15) or del(5)(q15q22). A polymorphic chromosome #22 with enlarged satellites was inherited from the father, who is phenotypically normal, and was probably unrelated to the congenital malformations. This is the first report of a Gardner syndrome patient with an interstitial deletion of 5q.
The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle (2003)

In the mammalian ovary, great interest in the expression and function of the bone morphogenetic protein (BMP) family has been recently generated from evidence of their critical role in determining folliculogenesis and female fertility. Despite extensive work, there is a need to understand the cellular sites of expression of these important regulatory molecules, and how their gene expression changes within the basic ovary cell types through the cycle. Here we have performed a detailed in situ hybridization analysis of the spatial and temporal expression patterns of the BMP ligands (BMP-2, -3, -3b, -4, -6, -7, -15), receptors (BMPR-IA, -IB, -II), and BMP antagonist, follistatin, in rat ovaries over the normal estrous cycle. We have found that: i) all of the mRNAs are expressed in a cell-specific manner in the major classes of ovary cell types (oocyte, granulosa, theca interstitial, theca externa, corpora lutea, secondary interstitial, vascular and ovary surface epithelium); and ii) most undergo dynamic changes during follicular and corpora luteal morphogenesis and histogenesis. The general principle to emerge from these studies is that the developmental programs of folliculogenesis (recruitment, selection, atresia), ovulation, and luteogenesis (luteinization, luteolysis) are accompanied by rather dramatic spatial and temporal changes in the expression patterns of these BMP genes. These results lead us to hypothesize previously unanticipated roles for the BMP family in determining fundamental developmental events that ensure the proper timing and developmental events required for the generation of the estrous cycle.
EVIDENCE THAT ANTIHUMAN TUMOR NECROSIS FACTOR MONOCLONAL ANTIBODY PREVENTS OKT3-INDUCED ACUTE SYNDROME (1992)

We have used an antihuman tumor necrosis factor monoclonal antibody, CB006 (murine IgG1), to prevent the OKT3-induced acute clinical syndrome. This syndrome is due to the massive, although transient release in the circulation of various cytokines (TNF, interferon gamma, interleukin 2, interleukin 6) and represents one important side effect linked to in vivo use of OKT3. Fourteen kidney allograft recipients undergoing prophylactic OKT3 therapy were treated with CB006 in a single i.v. injection of either 0.4 mg/kg (group I, 7 patients) or 2 mg/kg (group II, 7 patients), 1 hr before the first OKT3 administration. Nineteen consecutive patients formed a historical control group. None of the CB006-pretreated patients showed any of the common, severe OKT3-associated symptoms (hypotension, respiratory distress, or neurotoxicity), which were observed in 10% of the historical controls. In addition, CB006-treated patients showed a lower frequency of pyrexia (> or = 39 degrees C) and gastrointestinal symptoms. None of the CB006-treated patients presented severe vomiting or diarrhea, defined as repeated episodes inducing significant fluid and electrolyte loss. Two out of the 7 patients in group I and group II had mild transitory diarrhea. Mild single vomiting episodes occurred in 2 group I patients and 3 group II patients. At variance in all controls, gastrointestinal symptoms were long lasting and associated with major prostration due to electrolyte and fluid loss. Importantly, CB006-treated patients who presented mild symptoms had detectable bioactive circulating TNF, showing incomplete inactivation of OKT3-induced TNF by CB006. CB006 was perfectly well tolerated, did not induce xenosensitization, and did not affect the biological or clinical effectiveness of OKT3.
Growth and Physical Properties of LPCVD Polycrystalline Silicon Films (1984)

Undoped LPCVD silicon films have been deposited at five temperatures between 560° and 620°C. The films were characterized as grown and after thermal annealing at 900°, 950°, and 1000°C. We used x‐ray diffraction, TEM, SEM, Raman and elastic light scattering, optical absorption and reflection, and other techniques in order to obtain information on the grain size, structure, structural perfection, and surface roughness. We found that polysilicon films of good structural perfection, low strain, and small surface roughness are obtained when the films are deposited in the amorphous phase and subsequently crystallized at 900°–1000°C. Such films are superior in all investigated material aspects to films grown in the crystalline phase.
Retroviral integration sites in transgenic Mov mice frequently map in the vicinity of transcribed DNA regions (1990)

Transcription of cellular sequences flanking proviral insertion sites was studied in several Mov mouse strains, each of which carried one copy of the Moloney murine leukemia virus in its germ line. In three out of five randomly chosen Mov strains, the provirus had integrated in the vicinity of DNA regions transcribed in the embryonal stem cell line CCE and the embryonal carcinoma cell line F9. Assuming that CCE and F9 cells are developmentally equivalent to the early embryonic cells that were infected to establish the Mov strains, our results suggest that retroviruses integrate preferentially into actively transcribed DNA regions.
PDGF, TGF-β, and Heterotypic Cell–Cell Interactions Mediate Endothelial Cell–induced Recruitment of 10T1/2 Cells and Their Differentiation to a Smooth Muscle Fate (1998)

We aimed to determine if and how endothelial cells (EC) recruit precursors of smooth muscle cells and pericytes and induce their differentiation during vessel formation. Multipotent embryonic 10T1/2 cells were used as presumptive mural cell precursors. In an under-agarose coculture, EC induced migration of 10T1/2 cells via platelet-derived growth factor BB. 10T1/2 cells in coculture with EC changed from polygonal to spindle-shaped, reminiscent of smooth muscle cells in culture. Immunohistochemical and Western blot analyses were used to examine the expression of smooth muscle (SM)-specific markers in 10T1/2 cells cultured in the absence and presence of EC. SM-myosin, SM22alpha, and calponin proteins were undetectable in 10T1/2 cells cultured alone; however, expression of all three SM-specific proteins was significantly induced in 10T1/2 cells cocultured with EC. Treatment of 10T1/2 cells with TGF-beta induced phenotypic changes and changes in SM markers similar to those seen in the cocultures. Neutralization of TGF-beta in the cocultures blocked expression of the SM markers and the shape change. To assess the ability of 10T1/2 cells to contribute to the developing vessel wall in vivo, prelabeled 10T1/2 cells were grown in a collagen matrix and implanted subcutaneously into mice. The fluorescently marked cells became incorporated into the medial layer of developing vessels where they expressed SM markers. These in vitro and in vivo observations shed light on the cell-cell interactions that occur during vessel development, as well as in pathologies in which developmental processes are recapitulated.
Tissue-Specific Activity of Two Manganese Superoxide Dismutase Promoters in Transgenic Tobacco (1996)

In eukaryotes, manganese superoxide dismutase is a nuclear-encoded protein that scavenges superoxide radicals in the mitochondrial matrix. We have isolated two manganese superoxide dismutase genes from Nicotiana plumbaginifolia L. and fused the 5' upstream regulatory region of these genes to the beta-glucuronidase reporter gene. The two gene fusions displayed a differential tissue specificity in transgenic tobacco (Nicotiana tabacum). Promoter activity of the SodA1 gene fusion was found in the pollen, middle layer, and stomium of anthers, but was usually undetectable in vegetative organs of mature plants. The SodA2 gene fusion was expressed in the leaves, stems, roots, and flowers. SodA2 promoter activity was most prominent in the vascular bundles, stomata, axillary buds, pericycle, stomium, and pollen. Histochemical analysis of succinate dehydrogenase activity suggested that the spatial expression of the two gene fusions is generally correlated with mitochondrial respiratory activity.
Evaluation of the effect of TRU-016, an anti-CD37 directed SMIP in combination with other therapeutic drugs in models of non-Hodgkin's lymphoma (2009)

8571 Background: TRU-016, a single chain anti-CD37 Fc fusion molecule has been shown to display pro-apoptotic and Fc-dependent cellular cytotoxicity activities against primary CLL cells and NHL cell lines. The pro-apoptotic signal generated by TRU-016 binding to CD37 on CLL cells has been shown to be caspase-independent and distinct from the signal generated by many other therapeutics including rituximab. We have tested drug combinations using the mantle cell lymphoma line Rec-1 and diffuse large B-cell lymphoma line SU-DHL-6 in vitro and extended these results to in vivo settings using the follicular lymphoma cell line DOHH2 treated with the combination of TRU-016 and bendamustine. Methods: To determine TRU-016 interactions with the established therapeutics rituximab, doxorubicin, rapamycin, and bendamustine, drugs were tested alone or in combination with TRU-016 and the anti-proliferative effects on cell lines measured after 96 hours. Combination index analysis was performed for drug combinations over the 20–90% effect levels using the Calcusyn software package. To determine if in vitro synergy could be recapitulated in vivo, SCID mice were implanted with DOHH2 cells and therapeutic treatment was initiated when tumor volumes reached 200 mm 3 . Treatments consisted of TRU-016, bendamustine, or the combination of TRU-016 and bendamustine. Results: Combination index analyses determined that TRU-016 is synergistic with rituximab, bendamustine, or rapamycin and additive with doxorubicin in NHL models. In vivo results show that treatment with the combination of TRU-016 and bendamustine resulted in increased efficacy compared to the efficacy attained with the individual drugs. This demonstrates that the in vitro synergy results were extendable to a more complex in vivo disease model. Conclusions: TRU-016 in combination with rituximab, rapamycin, or bendamustine increases cell killing of NHL cells. Furthermore, the combination of TRU-016 and bendamustine displayed greater in vivo anti-tumor activity than either agent alone against a follicular lymphoma tumor model. [Table: see text]
Dynamic response of colliding-pulse mode-locked quantum-well lasers (1995)

The colliding-pulse mode-locked scheme, using quantum-well semiconductor lasers, has been reported to be useful for the generation of short optical pulses with a high repetition rate. In this paper, the large signal dynamic process of a monolithic colliding-pulse mode-locked laser diode is simulated using a large signal laser model. The refractive index changes induced by variations of the carrier density and the standing wave effect in the saturable absorber have been taken into account in the simulation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>