抗人肺癌细胞单克隆抗体的制备及其特性的研究

用人肺鳞癌细胞LTEP-78细胞系免疫Blab/c小鼠获得3株抗人肺癌细胞的单克隆抗体杂交瘤系。其中BLTI-01株经六次克隆化培养,体外传代8个月以上。BLTI-01与白细胞抗原及血型抗原基本上无交叉反应;与骨髓细胞无交叉反应;与癌胚抗原和胎甲球蛋白不相关;与肺鳞癌、肺腺癌细胞系及部分其它肿瘤细胞呈阳性反应。     

Intrapleural and intravenous Corynebacterium parvum in patients with resected stage I and II non-small cell carcinoma of the lung

Summary A prospective randomized trial compared the administration of intrapleural plus intravenous Corynebacterium parvum (C. parvum) versus placebo in patients with resected Stage I and Stage II non-small cell bronchogenic carcinoma. Treatment consisted of 7 mg C. parvum injected into the pleural space and 7 mg C. parvum intravenously once between days 6 and 12 postoperatively and 7 mg intravenously every 3rd month during the 1st year. Intrapleural administration of 35 cc of saline served as the placebo and the flush after intrapleural C. parvum.Of the 303 patients entered into this study, 286 were evaluable, with an average follow-up time of 3.5 years. More complications, especially fever, were observed in patients receiving C. parvum. A fever greater than 38 °C was observed in 9% of the patients assigned to placebo and 76% of the patients assigned to C. parvum. There was no significant difference between the treatments with respect to disease-free interval or survival.M. Kaufmann, J. Stjernswärd**, A. Zimmermann (Ludwig Institute for Cancer Research, Bern Branch); K. Stanley**, M. Isley, M. Zelen (Frontier Science & Tech. Research Foundation, Brookline, MA, USA); C. Mouritzen, P. Paulsen, U. Henriques (Dept. of Thoracic and Cardiovascular Surgery and Institute of Pathology, Kommunehospital, Aarhus, Denmark); N. Konietzko, W. Maassen, W. Hartung, W. Wierich (Ruhrland Clinic, Essen-Heidhausen, and Pathology Institute, Ruhr-University, Bochum, FRG); P. Oehl (Innere Klinik und Poliklinik Tumorforschung, Essen, FRG); J. Vogt-Moykopf, H. Toomes, W. Hofmann (Rohrbach Hospital, Clinic for Thoracic Medicine and Pathology Institute, Heidelberg, FRG); F. Krause, R. Rios, R. Spanel (Klinik Löwenstein, Löwenstein, and Pathology Institute, Ulm, FRG); J. Orel, B. Hrabar, D. Ferluga, T. Rott (University Medical Center, Thoracic Surgery and Pathology, Ljubljana, Yugoslavia); H. A. Rostad, J. R. Vale, P. Lexow (Rikshospital, Oslo, Norway); S. Hagen, S. Birkeland (Ulleval Hospital, Oslo, Norway); T. Harbitz, R. Nissen-Meyer (Aker Hospital, Oslo, Norway); E. Aspevik, H. Engedal, A. Mykin (Haukeland Hospital, Bergen, Norway); V. O. Björk, L. Rodriguez, K. Böök, J. Willems (Karolinska Sjukhuset, Thoracic Surgical Clinic and Pathology Department, Stockholm, Sweden); E. Grädel, J. Hasse, P. Dalquen (Kantonsspital, Dept of Surgery, Div. of Cardiac & Thoracic Surgery & Pathology Institute, Basel, Switzerland); L. Eckmann, K. Hänni, K. Zimmermann (Tiefenauspital Surg. Clinic, Univ. of Bern, Switzerland); B. Nachbur, H. U. Würsten, H. Cottier, A. Zimmermann (Inselspital Dept. of Thoracic and Cardiovascular Surg. and Pathology Institute, Bern, Switzerland); W. Maurer, M. Kaufmann (Bürgerspital, Surgical Department, Solothurn, Switzerland); H. Denck, E. Zwintz, St. Wuketich (Krankenhaus der Stadt Wien-Lainz, I. Chir. Dept., and Path. Inst., Vienna, Austria); N. Pridun, H. Hackl (Pulmonologisches Zentrum der Stadt Wien, and Path. Inst., Vienna, Austria); E. Moritz, W. Schlick, H. Holzner (II. Chir. University Clinic and Path. Inst., Vienna, Austria); K. Karrer (Institute for Cancer Research, Vienna, Austria); R. G. Crispen (ITR-Biomedical Research, University of Illinois, Chicago, USA); D. S. Freestone, R. Bomford, M. T. Scott, T. Priestman, L. Toy (The Wellcome Research Laboratories, Beckenham, England)** Present address: Cancer Unit, World Health Organization, Geneva, Switzerland Offprint requests to: K. Stanley, Ludwig Institute for Cancer Research, Inselspital, CH-3010 Bern, SwitzerlandLudwig Lung Cancer Study Group:     

Search for the possible role of ‘immunotherapy’ in operable bronchial non-small cell carcinoma (stage I and II): A phase I study with Corynebacterium parvum intrapleurally

Summary The possibility of giving C. parvum intrapleurally (i.p.) was investigated. C. parvum was given post-operatively either i.p. only or i.p. and intravenously (i.v.) simultaneously. The dose varied from 0.1–10 mg i.p. All patients had been operated for a bronchial carcinoma. Results: (1) Subjective complaints of either dyspnoea, thoracic pain, chills or nausea occured in 31 of 63 patients. No clear dose relation was found. A feeling of discomfort and fever could occur for another 3–4 days after the above more acute symptoms had disappeared. (2) Increased fever (0.5° C) occurred in 71% of the patients injected i.p. only. (3) No anaphylactic reaction was observed. (4) Increased total white blood cell counts (<20%) occurred in 38 patients. The WBC increase was mainly due to higher number of neutrocytes and granulocytes. Total lymphocyte, monocyte, eosinophilic, and basophilic granulocytes values per mm³ circulating blood remained unchanged, except at the dose of 7 mg C. parvum i.p. when monocyte values were increased significantly from 576±247 to 1100±578/mm³. (5) Moderate to severe effusions were observed radiologically in three patients after C. parvum intrapleurally.The study group is: M. Kaufmann, J. Stjernswärd (Ludwig Institut for Cancer Research, Lausanne Branch, Switzerland), M. Zelen, K. Stanley (Frontier Science and Technology Research Foundation, Inc. Amherst, New York, USA), D. S. Freestone, R. Bomford, M. T. Scott, T. Priestman (The Wellcome Research Laboratory, Beckenham, England), C. Mouritzen, G. Ahlbom (Dept. of Thoracic and Cardiovascular Surgery, Aarhus Kommunehospital, Aarhus, Denmark), N. Konietzko, D. Greschuchna (Ruhrland Klinic, Essen-Haidhausen, Germany), P. Hilgard (Innere Klinik und Poliklinik [Tumorforschung] Essen, Germany), J. Vogt-Moykopf, D. Zeidler, H. Toomes (Thoraxchirurgische Spezial-Klinik, Heidelberg-Rohrbach, Germany), F. Krause, R. Rios (Thoraxchirurgische Abt., Fachkrankenhaus für Lungen- und Bronchialerkrankungen, Löwenstein, Germany), J. Orel, M. Benedik, B. Hrabar (Clinical Center, Dept. of Thoracic Surgery, Ljubljana, Yugoslavia), S. Plesnicar (The Institute of Oncology, Ljubljana, Yugoslavia), H. A. Rostad, J. R. Vale (Rikshospital, Oslo, Norway), S. Hagen, S. Birkeland, (Ulleval Hospital, Oslo, Norway), T. Harbitz, R. Nissen-Meyer (Aker Hospital, Oslo, Norway), L. Rodriguez, V. O. Björk, K. Böök (Karolinska Sjukhuset, Thoracic Clinic, Stockholm, Sweden), E. Gradel, J. Hasse, P. Holbro (Kantonsspital, Thoraxchirurgische Klinik, Basel, Switzerland), L. Eckmann (Tiefenauspital, Chir. Univ.-Klinik, Bern, Switzerland), B. Nachbur, T. Liechti (Inselspital, Dept. of Thoracic and Cardiovascular Surgery, Bern, Switzerland), H. Cottier (Inst. of Pathology, Inselspital, Bern, Switzerland), W. Maurer, M. Kaufmann, P. Froelicher (Bürgerspital, Surgical Dept., Solothurn, Switzerland), H. Denck, N. Pridun (Krankenhaus der Stadt Wien-Lainz, Chir. Abt., Vienna, Austria), K. Karrer (Institute for Cancer Research, University of Vienna, Austria) Reprint requests should be addressed to any of the members listed above, or to the Ludwig Lung Cancer Trial, Operation Office, LICR, CH-1066 Epalinges, Switzerland. (For Current Contents, etc., please use above address)     

Highly Efficient Flexible Hybrid Nanocrystal‐Cu(In,Ga)Se2 (CIGS) Solar Cells

A novel scheme for hybridizing inkjet‐printed thin film Cu(In,Ga)Se₂ (CIGS) solar cells with self‐assembled clusters of nanocrystal quantum dots (NQDs), which provides a 10.9% relative enhancement of the photon conversion efficiency (PCE), is demonstrated. A non‐uniform layer of NQD aggregates is deposited between the transparent conductive oxide and a CdS/CIGS p‐n junction using low cost pulsed‐spray deposition. Hybridization significantly improves the external quantum efficiency of the hybrid devices in the absorption range of the NQDs and in the red to near‐IR parts of the spectrum. The low wavelength response enhancement is found to be induced by luminescent down‐shifting (LDS) from the NQD layer, while the increase at longer wavelengths is attributed to internal scattering from NQD aggregates. LDS is demonstrated using time‐resolved spectroscopy, and the morphology of the NQD layer is investigated in fluorescence microscopy and cross‐sectional transmission electron microscopy. The influence of the NQD dose on the PCE of the hybrid devices is investigated and an optimum value is obtained. The low costs and limited material consumptions associated with pulsed‐spray deposition make these flexible hybrid devices promising candidates to help push thin‐film photovoltaic technology towards grid parity.     

Life cycles,phenology and genetic structure of endangered Megacrania tsudai Shiraki (Phasmatodea: Phasmatidae): Male individuals from a geographic parthenogenesis species

Megacrania tsudai, a peripherally distributed member of Megacrania, requires conservation in Taiwan; it has limited distribution in Taiwan and its eastern offshore islands. It feeds on screw pines (Pandanus odoratissimus) in nature and has demonstrated a specific defensive mechanism involving actinidine secretion from the prothoracic gland. However, details of its distribution area, life cycle and developmental phenology remain largely unknown. In this study, a field survey and review of published works revealed M. tsudai distribution in coastal zones and along river shores near estuaries. At room temperature, the egg period was 128 days. The development of the first to sixth instars required 17, 26, 27, 26, 34 and 43 days, respectively, on average; and a generation cycle required approximately 204 days. The phenology of the mesonotal granules was recorded. Moreover, genetic analysis of the mitochondrial cytochrome oxidase I (COI), 16S ribosomal DNA (16S rDNA) and the nuclear ribosomal spacer indicated the occurrence of genetic drift. Therefore, the rearing procedures proposed in this study for the primary and last instars of M. tsudai can facilitate its conservation. Megacrania tsudai was previously recorded as parthenogenetic; however, two male individuals were fostered unexpectedly. The male body length was 91 mm, which is shorter than the female length (120 mm). During mating, the male climbs onto the female's back and protrudes its genitalia downward. Geographical parthenogenesis is likely the reproductive strategy among peripheral M. tsudai; however, the rarely found M. tsudai male could be an intermediate link of reproductive strategy in the transition from tychoparthenogenesis to parthenogenesis.     

Repression of lignin biosynthesis promotes cellulose accumulation and growth in transgenic trees.

Because lignin limits the use of wood for fiber, chemical, and energy production, strategies for its downregulation are of considerable interest. We have produced transgenic aspen (Populus tremuloides Michx.) trees in which expression of a lignin biosynthetic pathway gene Pt4CL1 encoding 4-coumarate:coenzyme A ligase (4CL) has been downregulated by antisense inhibition. Trees with suppressed Pt4CL1 expression exhibited up to a 45% reduction of lignin, but this was compensated for by a 15% increase in cellulose. As a result, the total lignin-cellulose mass remained essentially unchanged. Leaf, root, and stem growth were substantially enhanced, and structural integrity was maintained both at the cellular and whole-plant levels in the transgenic lines. Our results indicate that lignin and cellulose deposition could be regulated in a compensatory fashion, which may contribute to metabolic flexibility and a growth advantage to sustain the long-term structural integrity of woody perennials.     

Sensitivity of the S1 neuronal calcium network to insulin and Bay‐K 8644 in vivo: Relationship to gait,motivation, and aging processes

Neuronal hippocampal Ca²⁺ dysregulation is a critical component of cognitive decline in brain aging and Alzheimer''s disease and is suggested to impact communication and excitability through the activation of a larger after hyperpolarization. However, few studies have tested for the presence of Ca²⁺ dysregulation in vivo, how it manifests, and whether it impacts network function across hundreds of neurons. Here, we tested for neuronal Ca²⁺ network dysregulation in vivo in the primary somatosensory cortex (S1) of anesthetized young and aged male Fisher 344 rats using single‐cell resolution techniques. Because S1 is involved in sensory discrimination and proprioception, we tested for alterations in ambulatory performance in the aged animal and investigated two potential pathways underlying these central aging‐ and Ca²⁺‐dependent changes. Compared to young, aged animals displayed increased overall activity and connectivity of the network as well as decreased ambulatory speed. In aged animals, intranasal insulin (INI) increased network synchronicity and ambulatory speed. Importantly, in young animals, delivery of the L‐type voltage‐gated Ca²⁺ channel modifier Bay‐K 8644 altered network properties, replicating some of the changes seen in the older animal. These results suggest that hippocampal Ca²⁺ dysregulation may be generalizable to other areas, such as S1, and might engage modalities that are associated with locomotor stability and motivation to ambulate. Further, given the safety profile of INI in the clinic and the evidence presented here showing that this central dysregulation is sensitive to insulin, we suggest that these processes can be targeted to potentially increase motivation and coordination while also reducing fall frequency with age.     

Identification of Alkaloid Compounds Arborinine and Graveoline from Ruta angustifolia (L.) Pers for their Antifungal Potential against Isocitrate lyase (ICL1) gene of Candida albicans

Mycopathologia - Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised...     

Gain-of-function hot spot mutant p53R248Q regulation of integrin/FAK/ERK signaling in esophageal squamous cell carcinoma

PurposeTP53, encoding the protein p53, is among the most frequently mutated genes in all cancers. A high frequency of 60 – 90% mutations is seen in esophageal squamous cell carcinoma (ESCC) patients. Certain p53 mutants show gain-of-function (GoF) oncogenic features unrelated to its wild type functions.MethodsThis study functionally characterized a panel of p53 mutants in individual ESCC cell lines and assayed for GoF oncogenic properties.ResultsThe ESCC cell line with endogenous p53^R248Q expression showed suppressed tumor growth in an immunocompromised mouse model and suppressed colony growth in in vitro three-dimensional culture, when depleted of the endogenous p53 protein expression. This suppression is accompanied by suppressed cell cycle progression, along with reduced integrin expression and decreased focal adhesion kinase and extracellular-regulated protein kinase signaling and can be compensated by expression of a constitutively active mitogen-activated protein. P53^R248Q enhances cell proliferation upon glutamine deprivation, as compared to other non-GoF mutants.ConclusionsIn summary, study of the functional contributions of endogenous p53 mutants identified a novel GoF mechanism through which a specific p53 mutant exerts oncogenic features and contributes to ESCC tumorigenesis.     

Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a difficult to treat cancer characterized by poor tumor immunity with only one approved systemic drug, sorafenib. If novel combination treatments are to be developed with immunological agents, the effects of sorafenib on tumor immunity are important to understand. In this study, we investigate the impact of sorafenib on the CD4+CD25? effector T cells (Teff) and CD4+CD25+ regulatory T cells (Tregs) from patients with HCC. We isolated Teff and Treg from peripheral mononuclear cells of HCC patients to determine immune reactivity by thymidine incorporation, ELISA and flow cytometry. Teff cultured alone or with Treg were supplemented with different concentrations of sorafenib. The effects of sorafenib on Teff responses were dose-dependent. Pharmacologic doses of sorafenib decreased Teff activation by down regulating CD25 surface expression. In contrast, sub-pharmacologic concentrations of sorafenib resulted in Teff activation. These low doses of sorafenib in the Teff cultures led to a significant increase in Teff proliferation, IL2 secretion and up-regulation of CD25 expression on the cell surface. In addition, low doses of sorafenib in the suppression Teff/Treg cocultures restored Teff responses by eliminating Treg suppression. The loss of Treg suppressive function correlated with an increase in IL2 and IL6 secretion. Our findings show that sub-pharmacologic doses of sorafenib impact subsets of T cells differently, selectively increasing Teff activation while blocking Treg function. In conclusion, this study describes novel immune activating properties of low doses of sorafenib by promoting immune responsiveness in patients with HCC.