Current and Emerging Pharmacotherapies for the Treatment of Relapsed Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a very aggressive cancer with poor outcome if left untreated, but it is also one of the most chemotherapy responsive cancers. Overall it has a very poor prognosis especially if it is chemotherapy resistant to first line treatment. Second line chemotherapy has not been very beneficial in SCLC as opposed to breast cancer and lymphoma. In the last few years topotecan is the only drug that has been approved by the food and drug administration (FDA) for the second line treatment of SCLC but in Japan another drug, amrubicin is approved. There are many combinations of different chemotherapies available in moderate to high intensity, in this difficult to treat patient to overcome the chemo resistance, but many of these studies are small or phase II trials. In this article we have reviewed single agent and multidrug regimens that were studied in both chemo sensitive and refractory setting, including the most recent clinical trials

Nanobacteria Are Mineralo Fetuin Complexes

“Nanobacteria” are nanometer-scale spherical and ovoid particles which have spurred one of the biggest controversies in modern microbiology. Their biological nature has been severely challenged by both geologists and microbiologists, with opinions ranging from considering them crystal structures to new life forms. Although the nature of these autonomously replicating particles is still under debate, their role in several calcification-related diseases has been reported. In order to gain better insights on this calciferous agent, we performed a large-scale project, including the analysis of “nanobacteria” susceptibility to physical and chemical compounds as well as the comprehensive nucleotide, biochemical, proteomic, and antigenic analysis of these particles. Our results definitively ruled out the existence of “nanobacteria” as living organisms and pointed out the paradoxical role of fetuin (an anti-mineralization protein) in the formation of these self-propagating mineral complexes which we propose to call “nanons.” The presence of fetuin within renal calculi was also evidenced, suggesting its role as a hydroxyapatite nucleating factor

Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0–2. Treatment was vinorelbine 25 mg m−2 i.v. weekly and cisplatin 100 mg m−2 i.v. every 4 weeks with hydration and standard prophylactic antiemetic treatment. Patients gave written informed consent. Characteristics of 54 consecutive patients were: males 85%, epithelial subtype 74%, IMIG stages III and IV 35 and 46%, performance status 0, 1, and 2, 26, 69, and 6%, and median age 63 years (31–78 years). CTC grade 3 or 4 toxicity occurred with respect to leukocytopenia (48% of patients, grade 4 in 13%), nausea (13%), neurotoxicity (11%), nephrotoxicity (4%), and other toxicities (9%). There were no toxic deaths. The median number of cycles was four. The fraction of patients alive at 1-, 2-, and 3-years were 61, 31, and 4%, respectively, and median survival and median time to progression were 16.8 months (0.5 to 46.4 +months) and 7.2 months (1.6 to 40.6 + months). There were two CRs and 14 PRs (response rate 29.6%). Cisplatin and intravenous vinorelbine is a highly active regimen in MPM with a response rate and survival comparable to the most active regimens so far reported

Pseudonocardia hispaniensis sp. nov., a novel actinomycete isolated from industrial wastewater activated sludge

A novel actinomycete, designated PA3T, was isolated from an oil refinery wastewater treatment plant, located in Palos de la frontera, Huelva, Spain, and characterized taxonomically by using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate formed a distinct subclade in the Pseudonocardia tree together with Pseudonocardia asaccharolytica DSM 44247T. The chemotaxonomic properties of the isolate, for example, the presence of MK-8 (H4) as the predominant menaquinone and iso-C16:0 as the major fatty acid are consistent with its classification in the genus Pseudonocardia. DNA:DNA pairing experiments between the isolate and the type strain of P. asaccharolytica DSM 44247T showed that they belonged to separate genomic species. The two strains were readily distinguished using a combination of phenotypic properties. Consequently, it is proposed that isolate PA3T represents a novel species for which the name Pseudonocardia hispaniensis sp. nov. is proposed. The type strain is PA3T (= CCM 8391T = CECT 8030T).Cuesta Amat, G.; Soler Hernández, A.; Alonso Molina, JL.; Ruvira, M.; Lucena, T.; Arahal, D.; Goodfellow, M. (2013). Pseudonocardia hispaniensis sp. nov., a novel actinomycete isolated from industrial wastewater activated sludge. Antonie van Leeuwenhoek. 103(1):135-142. doi:10.1007/s10482-012-9792-1S1351421031Alonso JL, Cuesta G, Ramírez GW, Morenilla JJ, Bernácer I, Lloret RM (2009) Manual de técnicas avanzadas para la identificación y control de bacterias filamentosas. Epsar-Generalitat Valenciana, España, p 21–36Ara I, Tsetseg B, Daram D, Suto M, Ando K (2011) Pseudonocardia mongoliensis sp. nov. and Pseudonocardia khuvsgulensis sp. nov., isolated from soil. 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Eur J Biochem 12:133–142Duangmal K, Thamchaipenet A, Matsumoto A, Takahashi Y (2009) Pseudonocardia acaciae sp. nov., isolated from roots of Acacia auriculiformis A. Cunn. ex Benth. Int J Syst Evol Microbiol 59:1487–1491Gordon RE, Barnett DA, Handerhan JE, Pang CH-N (1974) Nocardia coeliaca, Nocardia autotrophica, and the nocardin strain. Int J Syst Bacteriol 24:54–63Hamid ME, Minnikin DE, Goodfellow M, Ridell M (1993) Thin-layer chromatographic analysis of glycolipids and mycolic acids from Mycobacterium farcinogenes, Mycobacterium senegalense and related taxa. Zbl Bakt 279:354–367Hasegawa T, Takizawa M, Tanida S (1983) A rapid analysis for chemical grouping of aerobic actinomycetes. J Gen Microbiol 29:319–322Henssen A (1957) Beiträge zur Morphologie und Systematik der thermophilen Actinomyceten. Arch Mikrobiol 26:373–414Huang,Y, Goodfellow M (2012) Genus Pseudonocardia Hennsen 1957, 408VP emend. In: Goodfellow M, Kämpfer P, Busse H-J, Trujillo M, Suzuki KE, Ludwig W, Whitman WB (eds) Bergey’s manual of systematic bacteriology, 2nd edn, vol 5, part B. Springer, New YorkHuang Y, Wang L, Lu Z, Hong L, Liu Z, Tan GYA, Goodfellow M (2002) Proposal to combine the genera Actinobispora and Pseudonocardia in an emended genus Pseudonocardia, and description of Pseudonocardia zijingensis sp. nov. Int J Syst Evol Microbiol 52:977–982Huss VAR, Festl H, Schleifer KH (1983) Studies on the spectrophotometric determination of DNA hybridization from renaturation rates. Syst Appl Microbiol 4:184–192Kaewkla O, Franco CMM (2010) Pseudonocardia adelaidensis sp. nov., an endophytic actinobacterium isolated from the surface-sterilized stem of a grey box tree (Eucalyptus microcarpa). Int J Syst Evol Microbiol 60:2818–2822Kaewkla O, Franco CMM (2011) Pseudonocardia eucalypti sp. nov., an endophytic actinobacterium with a unique knobby spore surface, isolated from roots of a native Australian eucalyptus tree. Int J Syst Evol Microbiol 61:742–746Kämpfer P, Kohlweyer U, Thiemer B, Andreesen JR (2006) Pseudonocardia tetrahydrofuranoxydans sp. nov. Int J Syst Evol Microbiol 56:1535–1538Labeda DP, Goodfellow M, Chun J, Zhi XY, Li WJ (2011) Reassessment of the systematics of the suborder Pseudonocardineae: transfer of genera within the family Actinosynnemataceae Labeda and Kroppenstedt 2000 emend. Zhi et al. 2009 into an emended family Pseudonocardiaceae Embley et al. 1989 emend. Zhi et al. 2009. Int J Syst Evol Microbiol 61:1259–1264Lane DJ (1991) 16S/23S rRNA sequencing. In: Stackebrandt E, Goodfellow M (eds) Nucleic acid techniques in bacterial systematics. Wiley, Chichester, pp 115–148Lechevalier MP, Lechevalier H (1970) Chemical composition as a criterion in the classification of aerobic actinomycetes. Int J Syst Bacteriol 20:435–443Lechevalier MP, Stern AER, Lechevalier HA (1981) Phospholipids in the taxonomy of actinomycetes. Zbl Bakt Suppl 11:111–116Li J, Zhao GZ, Huang HY, Zhu WY, Lee JC, Kim CJ, Xu LH, Zhang LX, Li WJ (2010) Pseudonocardia rhizophila sp. nov., a novel actinomycete isolated from a rhizosphere soil. Antonie Van Leeuwenhoek 98:77–83Liu ZP, Wu JF, Liu ZH, Liu SJ (2006) Pseudonocardia ammonioxydans sp. nov., isolated from coastal sediment. Int J Syst Evol Microbiol 56:555–558Lucena T, Pascual J, Garay E, Arahal DR, Macián MC, Pujalte MJ (2010) Haliea mediterranea sp. nov., a new marine gammaproteobacterium. Int J Syst Evol Microbiol 60:1844–1848Ludwig W et al (2004) ARB: a software environment for sequence data. Nucleic Acids Res 32:1363–1371Mahendra S, Alvarez-Cohen L (2005) Pseudonocardia dioxanivorans sp. nov., a novel actinomycete that grows on 1,4-dioxane. Int J Syst Evol Microbiol 55:593–598Mesbah M, Premachandran U, Whitman WB (1989) Precise measurement of the G+C content of deoxyribonucleic acid by high-performance liquid chromatography. Int J Syst Bacteriol 39:159–167MIDI (2008) Sherlock microbial identification system operating manual, version 6.1. MIDI Inc., NewarkMinnikin DE, O’Donnell AG, Goodfellow M, Alderson G, Athalye M, Schaal A, Parlett JH (1984) An integrated procedure for the extraction of isoprenoid quinones and polar lipids. J Microbiol Methods 2:233–241Nam S-W, Chun J, Kim S, Kim W, Zakrzewska-Czerwinska J, Goodfellow M (2003) Tsukamurella spumae sp. nov., a novel actinomycete associated with foaming in activated sludge plants. Syst Appl Microbiol 26:367–375Okoh A, Ajisebutu S, Babalola G, Trejo-Hernandez MR (2001) Potential of Burkholderia cepacia RQ1 in the biodegradation of heavy crude oil. Int Microbiol 4:83–87Park SW, Park ST, Lee JE, Kim YM (2008) Pseudonocardia carboxydivorans sp. nov., a carbon monoxide-oxidizing actinomycete, and an emended description of the genus Pseudonocardia. Int J Syst Evol Microbiol 58:2475–2478Pruesse E, Quast C, Knittel K, Fuchs B, Ludwig W, Peplies J, Glöckner FO (2007) SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res 35:7188–7196Qin S, Su YY, Zhang YQ, Wang HB, Jiang CL, Xu LH, Li WJ (2008) Pseudonocardia ailaonensis sp. nov., isolated from soil in China. Int J Syst Evol Microbiol 58:2086–2089Qin S, Zhu WY, Jiang JH, Klenk HP, Li J, Zhao GZ, Xu LH, Li WJ (2010) Pseudonocardia tropica sp. nov., an endophytic actinomycete isolated from the stem of Maytenus austroyunnanensis. Int J Syst Evol Microbiol 60:2524–2528Qin S, Xing K, Fei SM, Lin Q, Chen XM, Li WJ, Jiang JH (2011) Pseudonocardia sichuanensis sp. nov., a novel endophytic actinomycete isolated from the root of Jatropha curcus L. Antonie Van Leeuwenhoek 99:395–401Rehfuss M, Urban J (2005) Rhodococcus phenolicus sp. nov., a novel bioprocessor isolated actinomycete with the ability to degrade chlorobenzene, dichlorobenzene and phenol as sole carbon sources. Syst Appl Microbiol 28:695–701Reichert K, Lipski A, Pradella S, Stackebrandt E, Altendorf K (1998) Pseudonocardia asaccharolitica sp. nov. and Pseudonocardia sulfidoxidans sp. nov., two new dimethyl disulfide-degrading actinomycetes and emended description of the genus Pseudonocardia. Int J Syst Bacteriol 48:441–449Sakiyama Y, Thao NKN, Vinh HV, Giang NM, Miyadoh S, Hop DV, Ando K (2010) Pseudonocardia babensis sp. nov., isolated from plant litter. Int J Syst Evol Microbiol 60:2336–2340Sasser M (1990) Identification of bacteria by gas chromatography of cellular fatty acids. MIDI Tech Note 101:1–7Schäfer J, Busse HJ, Kämpfer P (2009) Pseudonocardia parietis sp. nov., from the indoor environment. Int J Syst Evol Microbiol 59:2449–2452Seviour RJ, Kragelund C, Kong Y, Eales K, Nielsen JL, Nielsen PH (2008) Ecophysiology of the actinobacteria in activated sludge systems. Antonie Van Leeuwenhoek 94:21–33Shirling EB, Gottlieb D (1966) Methods for characterization of Streptomyces species. Int J Syst Bacteriol 16:313–340Staneck JL, Roberts GD (1974) Simplified approach to identification of aerobic actinomycetes by thin-layer chromatography. 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Syst Appl Microbiol 33:291–299Zhao GZ, Li J, Zhu WY, Li XP, Tian SZ, Zhao LX, Xu LH, Li WJ (2011a) Pseudonocadia bannaensis sp. nov., a novel actinomycete isolated from the surface-sterilized roots of Artemisiae annua L. Antonie Van Leeuwenhoek 100:35–42Zhao GZ, Li J, Huang HY, Zhu WY, Zhao LX, Tang SK, Xu LH, Li WJ (2011b) Pseudonocardia artemisiae sp. nov., isolated from surface-sterilized Artemisia annua L. Int J Syst Evol Microbiol 61:1061–1065Zhao GZ, Li J, Huang HY, Zhu WY, Park DJ, Kim CJ, Xu LH, Li WJ (2011c) Pseudonocardia kunmingensis sp. nov., an actinobacterium isolated from surface-sterilized roots of Artemisia annua L. Int J Syst Evol Microbiol 61:2292–229

Digitalization or flexibilization? The changing role of technology in the political economy of Japan

We are increasingly surrounded by talk of digitalization. Yet, we remain unsure about what impact this digitalization will have upon socio-economic institutions, how the introduction of this digitalization will be contested, the likely role of the state in managing the adoption of digital technology, and the likely consequences for the broader political economy if and when it is introduced. This article examines the process of digitalization as it has unfolded in the service sector in Japan. Based on qualitative interviews with managers in the hospitality industry and union officials, the paper depicts a process that contrasts starkly with the more optimistic view adopted by some commentators, according to which digitalization has the potential to improve working conditions and contribute to a more stable form of growth. Instead, the paper draws on Regulation Theory to argue that the introduction of digitalization is part of a wider process of neoliberalization. As such, digitalization has contributed to deskilling, the fragmentation of work tasks, a digital divide, the intensification of work, and higher levels of workplace surveillance. This represents a further dismantling of the social compromise that underpinned Japan’s earlier period of economic growth

Saccharopolyspora ghardaiensis sp. nov., an extremely halophilic actinomycete isolated from Algerian Saharan soil

A novel halophilic actinomycete, strain designated H53T, was isolated from a Saharan soil sample collected from Chaâbet Ntissa, Béni-isguen, Ghardaïa (South of Algeria) and was characterized taxonomically by means of polyphasic approach. Optimal growth was found to occur at 30–35 °C, pH 6–7 and in the presence of 15–25% (w/v) NaCl. The strain was observed to produce abundant aerial mycelium, which formed long chains of rod-shaped spores at maturity, and well developed and fragmented substrate mycelium. The cell wall was determined to contain meso-diaminopimelic acid; the diagnostic whole-cell sugars were arabinose and galactose. The predominant menaquinones were found to be MK-9(H4) and MK-9(H6). The predominant cellular fatty acids were determined to be iso- and anteiso-C17:0, iso-C15:0, and cis9 iso-C17:1. The diagnostic phospholipid detected was phosphatidylcholine. The morphological and chemotaxonomic characteristics of the strain were consistent with those of members of the genus Saccharopolyspora. Phylogenetic analyses on the basis of the 16S ribosomal RNA (rRNA) gene sequence showed that this strain formed a distinct phyletic line within the radiation of the genus Saccharopolyspora. The 16S rRNA sequence similarities between strain H53T and other members of the genus Saccharopolyspora ranged from 92.1 to 94.3%. The DNA G+C content of strain H53T was 72.6%. The genotypic and phenotypic data showed that the strain H53T represents a novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora ghardaiensis sp. nov. is proposed, with the type strain H53T (=DSM 45606T=CCUG 63370T=CECT 8304T)

Streptomyces aridus sp. nov., isolated from a high altitude Atacama Desert soil and emended description of Streptomyces noboritoensis Isono et al. 1957.

A polyphasic study was undertaken to determine the taxonomic status of a Streptomyces strain which had been isolated from a high altitude Atacama Desert soil and shown to have bioactive properties. The strain, isolate H9(T), was found to have chemotaxonomic, cultural and morphological properties that place it in the genus Streptomyces. 16S rRNA gene sequence analyses showed that the isolate forms a distinct branch at the periphery of a well-delineated subclade in the Streptomyces 16S rRNA gene tree together with the type strains of Streptomyces crystallinus, Streptomyces melanogenes and Streptomyces noboritoensis. Multi-locus sequence analysis (MLSA) based on five house-keeping gene alleles showed that isolate H9(T) is closely related to the latter two type strains and to Streptomyces polyantibioticus NRRL B-24448(T). The isolate was distinguished readily from the type strains of S. melanogenes, S. noboritoensis and S. polyantibioticus using a combination of phenotypic properties. Consequently, the isolate is considered to represent a new species of Streptomyces for which the name Streptomyces aridus sp. nov. is proposed; the type strain is H9(T) (=NCIMB 14965(T)=NRRL B65268(T)). In addition, the MLSA and phenotypic data show that the S. melanogenes and S. noboritoensis type strains belong to a single species, it is proposed that S. melanogenes be recognised as a heterotypic synonym of S. noboritoensis for which an emended description is given. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10482-017-0838-2) contains supplementary material, which is available to authorized users

Actinomycete integrative and conjugative elements

This paper reviews current knowledge on actinomycete integrative and conjugative elements (AICEs). The best characterised AICEs, pSAM2 of Streptomyces ambofaciens (10.9 kb), SLP1 (17.3 kb) of Streptomyces coelicolor and pMEA300 of Amycolatopsis methanolica (13.3 kb), are present as integrative elements in specific tRNA genes, and are capable of conjugative transfer. These AICEs have a highly conserved structural organisation, with functional modules for excision/integration, replication, conjugative transfer, and regulation. Recently, it has been shown that pMEA300 and the related elements pMEA100 of Amycolatopsis mediterranei and pSE211 of Saccharopolyspora erythraea form a novel group of AICEs, the pMEA-elements, based on the unique characteristics of their replication initiator protein RepAM. Evaluation of a large collection of Amycolatopsis isolates has allowed identification of multiple pMEA-like elements. Our data show that, as AICEs, they mainly coevolved with their natural host in an integrated form, rather than being dispersed via horizontal gene transfer. The pMEA-like elements could be separated into two distinct populations from different geographical origins. One group was most closely related to pMEA300 and was found in isolates from Australia and Asia and pMEA100-related sequences were present in European isolates. Genome sequence data have enormously contributed to the recent insight that AICEs are present in many actinomycete genera. The sequence data also provide more insight into their evolutionary relationships, revealing their modular composition and their likely combined descent from bacterial plasmids and bacteriophages. Evidence is accumulating that AICEs act as modulators of host genome diversity and are also involved in the acquisition of secondary metabolite clusters and foreign DNA via horizontal gene transfer. Although still speculative, these AICEs may play a role in the spread of antibiotic resistance factors into pathogenic bacteria. The novel insights on AICE characteristics presented in this review may be used for the effective construction of new vectors that allows us to engineer and optimise strains for the production of commercially and medically interesting secondary metabolites, and bioactive proteins