bluuebunny/crossref_metadata_2025 huggingface dataset:
DDRE-13. INHIBITION OF EXTRACELLULAR CARBONIC ANHYDRASES INHIBITS GLIOBLASTOMA CELL INVASION
Authors: Proescholdt Martin , Zhenwei Qiu , Annette Lohmeier , Nils-Ole Schmidt , Marsha Merrill
Published: March 2021

OBJECTIVE

Malignant gliomas metabolize glucose preferably by glycolysis which is in accordance with the Warburg effect. This induces a high demand of glucose combined with a significant lactic acid load. The hypoxia-inducible carbonic anhydrase (CA) IX has been shown to moderate the extrusion of hydrogen ions into the extracellular space. Since the acidification of the extracellular environment contributes to host tissue invasion due to activation of proteolytic enzymes, we hypothesized that CA IX plays an important role in malignant glioma Recently, specific small molecule inhibitors of this enzyme have been developed and may provide an innovative strategy for anti – invasive treatment.

METHODS

Two established and 4 primary GBM cell lines (2 with mesenchymal and 2 with proneural transcriptional profile) were exposed to the CAIX inhibitor U104 under normoxic and hypoxic conditions. Cell toxicity was measured by ATP and crystal violet assay. For invasion assessment, a matrigel invasion chamber system with 8 µm pore size polycarbonate filter was used. CAIX expression was analyzed by quantitative RTPCR and Western Blot.

RESULTS

Hypoxia significantly induced CAIX expression in all cell lines. Invasiveness increased significantly under hypoxic conditions in the mesenchymal cells (p < 0.01). Regardless of oxygenation status, the mesenchymal group displayed significantly higher invasiveness compared to the proneural group (p = 0.006). Looking at all cell lines, invasion is significantly inhibited by U104, both under normoxic and hypoxic conditions (p < 0.01). However, while the mesenchymal group showed the highest susceptibility to CAIX inhibition followed by the proneurally differentiated group, the established cell lines were entirely refractory to CAIX inhibition.

CONCLUSION

Our data demonstrate that CAIX inhibition can effectively inhibit invasion in malignant glioma cells independent from oxygenation status, however the effects are significantly influenced by cell type specific biological features.
DDRE-32. THERAPEUTIC TARGETING OF A NOVEL METABOLIC ADDICTION IN DIFFUSE MIDLINE GLIOMA
Authors: Pal Sharmistha , Kaplan Jakub P , Stopka Sylwia A , Regan Michael S , Hunsel Bradley R , Kann Benjamin H , Agar Nathalie Y R , Stiles Charles D , Cooney Tabitha M , Mueller Sabine , Chowdhury Dipanjan , Kaelin William G , McBrayer Samuel K , Haas-Kogan Daphne
Published: March 2021

Diffuse midline glioma (DMG) is a uniformly fatal pediatric cancer that is in need of urgent “outside the box” therapeutic approaches. Recent studies show that tumor cells adapt to stresses created by oncogenic mutations and these oncogene-induced adaptations create vulnerabilities that can be exploited to therapeutic ends. To uncover these oncogene-induced vulnerabilities in DMGs we conducted a genome-wide CRIPSR knockout screen in three DMG lines. The top common DMG dependency pathway that we discovered is de novo pyrimidine biosynthesis. Under normal conditions pyrimidine nucleotide needs are met through the salvage pathway. However, in DMG tumorigenesis, pyrimidine nucleotide synthesis is rewired such that the cells become dependent on the de novo biosynthesis pathway. De novo pyrimidine synthesis is catalyzed by CAD, DHODH and UMPS; all three genes are identified as dependencies in our screen and have been validated using shRNA mediated gene knockdown. Interestingly, DMG cells did not exhibit a dependency on the de novo purine biosynthesis pathway. Using a small molecule inhibitor of DHODH, BAY2402234 [currently studied in phase I trial for myeloid malignancies (NCT03404726)], we have demonstrated and validated, (i) efficacy and specificity of de novo pyrimidine synthesis inhibition in vitro in DMG cells; (ii) de novo pyrimidine addiction is not attributable to cell proliferation; (iii) DHODH inhibition induces apoptosis by hindering replication and inciting DNA damage; (iv) DHODH and ATR inhibition act synergistically to induce DMG cell death; and (v) critical in vivo efficacy. The in vivo experiment documents that BAY2402234 crosses the blood-brain barrier, is present in the brain at therapeutically relevant concentrations, suppresses de novo pyrimidine biosynthesis in intracranial DMG tumors in mice, and prolongs survival of orthotopic DMG tumor bearing mice. Taken together, our studies have identified a novel metabolic vulnerability that can be translated for the treatment of DMG patients.
DDRE-33. MELATONIN AS A MASTER METABOLIC SWITCH FOR GLIOBLASTOMA
Authors: Fernandez-Gil Beatriz Irene , Vazquez-Ramos Carla , Bechtle Alexandra , Suarez-Meade Paola , Qosja Neda , Schiapparelli Paula , Sarabia-Estrada Rachel , Escames Germaine , Quinones-Hinojosa Alfredo
Published: March 2021

Glioblastoma (GBM) is the most common form of malignant primary brain cancer in adults with a median survival of only 15 months. Therefore, new therapies to suppress malignant brain cancer are needed. Brain Tumor Initiating Cells (BTICs) are a GBM subpopulation of cells with a highly glycolytic profile that are thought to be responsible of the resistance of GBM to treatments. Metabolic reprogramming allows tumor cells to survive in unsupportive microenvironments. Manipulating tumor metabolism to counteract GBM resistance arises as a powerful approach with minimum effects in normal counterparts. At pharmacological concentrations, melatonin displays oncostatic properties. This is thought to be due to an increase in mitochondrial oxidative phosphorylation through the effects of melatonin in mitochondria, key organelle in metabolic homeostasis. We hypothesize that melatonin could alter BTIC metabolism, by inducing an anti-Warburg effect and as consequence, melatonin will decrease the viability of GBM cells and tumor growth. We found that treatment of GBM cell lines with 3mM melatonin significantly altered tumor cell metabolism. We observed that melatonin downregulated the lactate symporter MCT4 (p<0.002), inducing a significant intracellular accumulation of lactate (p<0.002) while decreasing it in the extracellular media (p<0.001). This was followed by a decrease in the internal pH (p<0.002). These effects were compensated by an increase in the oxygen consumption rate (OCR) followed by decay that leaded to an increase in ROS production (p<0.001). All these changes result in a depletion of cellular ATP (p<0.001) and eventually drove to a decrease in the proliferation (p<0.001) and cell death (p<0.001). When applied in vivo we observed a significant reduction in the tumor growth (p<0.001), volume (p<0.002) and weight (p<0.002), as well as a drop in the proliferation marker ki67 (p<0.001) and a fibrosis increase in treated tumors. These results position melatonin as a strong therapeutic candidate for GBM therapy.
ETMM-06. ELEVATED MITOCHONDRIAL TOM20 EXPRESSION SUPPRESSES GLIOMA MALIGNANCY BY ENHANCING OXIDATIVE PHOSPHORYLATION
Authors: Li Mao , Zhang Shuxin , Yang Wanchun , Yang Yuan , Pang Dejiang , Mao Qing , Chen Mina , Liu Yanhui
Published: March 2021

BACKGROUND

Malignant glioma display a metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation (OXPHOs). However, the underlying mechanism for this metabolic switch in glioma is not well elucidated. Mitochondrial translocases of the outer/inner membrane (TOMs/TIMs) import proteins into mitochondria, and could thereby regulate OXPHOs. The objective of this study is to investigate the expression of TOM/TIM members in glioma, as well as their functional and therapeutic implications.

METHODS

Transcriptome sequencing (RNA-seq), real-time PCR, Western blot, and immunohistochemistry were used to identify Tom20 as a significantly downregulated TOM/TIM protein in 20 paired glioma/Peritumoral tissues. To study the biological function of Tom20 in glioma, we interrogated metabolic alterations in Tom20 overexpressed glioma cells by GC-MS metabolomics, acetyl-CoA assay, and Seahorse assay. We compared the cell proliferation and viability profiles between Tom20 overexpressed and control cells in vitro and in vivo. To investigate the therapeutic implication of Tom20 expression, we tested OXPHOs inhibitor metformin in Tom20 overexpressed cells and xenograft mouse models.

RESULTS

We find that Tom20, a critical component of the mitochondrial outer membrane translocases, is downregulated in malignant gliomas. Using an integrative approach spanning bioinformatic analysis, metabolomics, and functional approaches, we reveal that Tom20 elevation activates mitochondrial OXPHOs in glioma cells and reduces tumor malignancy. We also find that Tom20 upregulation sensitizes glioma cells to metformin in vitro, and improves the therapeutic efficacy of metformin in glioma in vivo.

CONCLUSION

Our work defines Tom20 as a glioma suppressor and an indicator of metformin treatment in glioma.
FSMP-11. TARGETING CHOLESTEROL HOMEOSTASIS DYSREGULATION FOR THE TREATMENT OF GLIOBLASTOMA
Authors: Han Mingzhi
Published: March 2021

Dysregulated cholesterol metabolism is a hallmark of many cancers, including glioblastoma (GBM), but its role in disease progression is not well understood. Here, we identified cholesterol 24-hydroxylase (CYP46A1), a brain-specific enzyme responsible for elimination of cholesterol through conversion of cholesterol to 24(S)-hydroxycholesterol (24OHC), as one of the most dramatically dysregulated cholesterol metabolism genes in GBM. CYP46A1 was significantly decreased in GBM samples compared to normal brain tissue. In gliomas, a reduction in CYP46A1 expression was associated with increasing tumour grade and poor prognosis. Functionally, ectopic expression of CYP46A1 suppressed cell proliferation and in vivo tumour growth by increasing 24OHC levels. RNA-seq revealed that treatment of GBM cells with 24OHC suppressed tumour growth through regulation of LXR and SREBP signaling. Efavirenz (EFV), an activator of CYP46A1 that is known to penetrate the blood-brain barrier (BBB), inhibited GBM growth in vivo. Our findings demonstrate that CYP46A1 is a critical regulator of cellular cholesterol in GBM and that the CYP46A1/24OHC axis is a potential therapeutic target.
FSMP-12. A ROLE FOR PROLINE BIOSYNTHESIS IN HYPOXIC GLIOBLASTOMA
Authors: Vettore Lisa , Westbrook Rebecca , Roberts Jennie , Escribano-Gonzalez Cristina , Cuozzo Federica , Hodson David , Watts Colin , Nixon Colin , Tennant Daniel
Published: March 2021

Hypoxia is a common feature of glioblastoma, and a known driver of therapy resistance in brain tumours. Understanding the metabolic adaptations to hypoxia is key to develop new effective treatments for patients. A recent screening study highlighted Pyrroline-5-carboxylate reductase-like (PYCRL) as one of the top three genes that allowed tumour survival in hypoxia. PYCRL is one of the three enzymes involved in proline biosynthesis along with the mitochondrial pyrroline-5-carboxylate reductase 1 and 2 (PYCR1/2). The latter use glutamine as the carbon source to fuel the pyrroline-5-carboxylate (P5C)-to-proline reaction, whereas the cytosolic PYCRL is known to use ornithine to produce proline. Our investigations have shown that PYCRL differs from PYCR1 and 2 in the impact on cellular redox, which is a critical factor in hypoxic survival. Our data suggest that PYCRL activity is required for normal regulation of glioblastoma cell growth and the ability to deal with cellular stress, and that this enzyme may therefore represent a novel target in the treatment of these devastating tumours. Importantly, our study also begins to provide much-needed clarity over the network surrounding proline metabolism and redox maintenance.
FSMP-13. HYPOXIC REGULATION OF LACTATE DEHYDROGENASE GENES (LDHA/B) IN T98 GLIOBLASTOMA MULTIFORME CELLS
Authors: White Brian E , Buono Russell J
Published: March 2021

Glioblastoma multiforme (GBM) is the most common primary brain cancer and carries a poor prognosis. GBM cells exhibit extensive metabolic alterations that enhance survival and proliferation in the mixed normoxic-hypoxic tumor microenvironment. Lactate dehydrogenase (LDH) enzymes are critical mediators of the normoxic to hypoxic transition in cells. Two LDH genes (A/B) encode monomers that combine to form five isoenzymes (LDH1-5) with different properties for pyruvate to lactate interconversion. Hypoxic induction of LDHA in all cells appears to occur via HIF-1 mediated transcription. However, little is known about hypoxic regulation of LDHB in cancer. We report on hypoxic regulation of LDHA/B in T98G, a rare cell line that has both normal and neoplastic features. Human T98 GBM cell lines were cultured in a humidified incubator at 37° C and 5% CO2 and were grown in normoxia (21% O2) or hypoxia (95% N2, 5% C02) for 72 hours. Relative expression of LDH isoforms 1-5 was assessed using native gel electrophoresis. Expression of the LDHA and LDHB genes was measured using qRT-PCR. LDHA-dominant isoforms (4/5) were detected in T98G cells subjected to normoxia and hypoxia via gel electrophoresis, however, LDHB-dominant isoforms (1/2) were not. The LDHA/B-equimolar isoform (3) was decreased in T98G cells subjected to hypoxia. LDHA gene expression was over two-fold greater than LDHB in normoxia (p = .00256 by one-tailed Mann-Whitney U test), and over nine-fold greater in hypoxia (p = .00256). LDHA:LDHB expression in hypoxia compared to normoxia was significantly different (p = .00256). LDHA expression increased three-fold in hypoxia (p = .00256), while LDHB expression decreased 0.3-fold in hypoxia (p = .03288). We document LDHB dysregulation in T98G cells as the gene is minimally responsive to oxygen. Therapeutic strategies aimed at promoting LDHB expression may complement inhibition of LDHA and reduce GBM survival in hypoxia.
FSMP-15. EVALUATING THE ROLE OF LONG-CHAIN FATTY ACID METABOLISM IN PROMOTING GLIOBLASTOMA GROWTH
Authors: Ravi Divya , del Genio Carmen , Ghiasuddin Haider , Gaur Arti
Published: March 2021

Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.
Seasons of Coronavirus Disease 2019
Authors: Macnofsky Robin , Chow Eric J
Published: March 2021

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality. Although much of the focus has been on the management and treatment of acute COVID-19, some patients have experienced prolonged symptoms after their acute infection had resolved. In this perspective, a patient shares her experience of postacute COVID-19, highlighting a journey of a revolving door of symptoms. Her infectious disease physician summarizes the next steps required to better care for this growing group of patients.
Institutional Architecture
Authors: Schillig Michael
Published: March 2021

Recovery and resolution planning and early intervention constitute an integral part of an enhanced and strengthened framework for regulation and supervision with a focus on resolution planning and resolvability assessment. As an institution’s financial position deteriorates, the supervisory process may naturally lead on to crisis management and resolution. As a result of the global financial crisis and the eurozone crisis, the jurisdictions under consideration here have restructured their institutional frameworks for regulation, supervision, and resolution. This chapter seeks to provide an overview of these institutional changes and developments. From an institutional perspective, it contextualizes the discussion in the following chapters.
Remedies for Torts, Breach of Contract, and Equitable Wrongs
Authors: Burrows Andrew
Published: March 2021

The fourth edition of Andrew Burrows' seminal work Remedies for Torts, Breach of Contract, and Equitable Wrongs (previously Remedies for Torts and Breach of Contract), updates and extends coverage of judicial remedies for civil wrongs in English law. Since the release of the previous edition in 2004, the scope of discussion in the book has developed to include many contemporary case studies. Examples of these include Morris-Garner v One Step Ltd on negotiating damages, Milner v Carnival on quantum of mental distress damages, Forsyth Grant v Allen on restitution for torts, to name but a few, as well as crucial Supreme Court decisions on penalty clauses (Cavendish v Makdessi) and injunctions (LauritzenCool, Araci v Fallon and Coventry v Lawrence). In addition to comprehensive updating to take account of new developments in the law, this book includes two new chapters. Unique to the fourth edition, the first explores damages under the Human Rights Act of 1998; the second examines negotiating damages. Remedies for Torts, Breach of Contract, and Equitable Wrongs by leading scholar Andrew Burrows is a popular work amongst students and practitioners due to its broad coverage, factual detail, insightful application of academic context and enduring subject matter.
Compensating advantages
Authors: Burrows Andrew
Published: March 2021

The compensatory aims require the courts to assess not only the position the claimant would have been in if the breach of contract or tort had not been committed but also its actual position as a result of the tort or breach of contract, so that damages can make up the difference. Where the claimant’s actual position has been, or will be, improved by benefits acquired subsequent to and as a result of the tort or breach of contract, one might expect (in accordance with the compensatory aims) that such benefits would be taken into account—if they are ignored the claimant will be left in a better position than if the contract had been performed or if no tort had been committed. In a nutshell, one might expect ‘compensating advantages’ to be deducted or, as it is sometimes alternatively expressed, that losses mitigated would not be compensated. But in fact compensating advantages are often not deducted. Our concern here is to indicate when this is so.
Equitable (compensatory) damages
Authors: Burrows Andrew
Published: March 2021

Prior to 1858 there was probably some power, albeit very restricted, to award damages in equity in addition to specific performance. But this is of merely historical interest, because by the Chancery Amendment Act 1858, s 2 (Lord Cairns’s Act) the Court of Chancery was given power to award damages ‘in addition to or in substitution for [an] injunction or specific performance’. This power to award what are commonly referred to as ‘equitable damages’ is now vested in the courts by the Senior Courts Act 1981, s 50. As regards damages in addition, the power is self-explanatory—whenever an injunction or specific performance is granted, damages can be added. But when may damages in substitution be awarded?
Punitive damages
Authors: Burrows Andrew
Published: March 2021

Punitive or exemplary damages are damages whose purpose is to punish the defendant for his or her wrongful conduct. In Broome v Cassell Lord Hailsham said that he preferred the term ‘exemplary damages’ to ‘punitive damages’ as better expressing the policy of the law. English courts have subsequently followed Lord Hailsham’s preference. But in its Report on this area in 1997, the Law Commission recommended that the pre-Broome v Cassell terminology of ‘punitive damages’ was clearer and more straightforward and did not accept that this label deflected attention from the deterrence and disapproval aims of such damages. As the Law Commission said, ‘When one uses the term “punishment” in the criminal law, one does not thereby indicate that deterrence is not an important aim.’ Although nothing of substantive importance should turn on which label is adopted, the Law Commission’s approach is persuasive and the term ‘punitive damages’ is therefore preferred in this chapter and book.
The award of an agreed sum
Authors: Burrows Andrew
Published: March 2021

The award of an agreed sum is a remedy which protects the promisee’s expectations by enforcing the defendant’s contractual promise to pay a sum of money. As such, its justification ultimately rests on the morality of promise-keeping. The remedy can be regarded as a hybrid, being like damages in that it is common law and monetary but like specific performance in that its function is to compel performance of a positive contractual obligation.
Definitions
Authors: Stone David
Published: March 2021

The Regulation establishes on an EU-wide basis two distinct design rights: Much of the law relating to design rights applies to both of the above, and to national (and Benelux) registered designs by virtue of the Directive.
Exclusions from Protection
Authors: Stone David
Published: March 2021

Not every feature of a product can be protected by design rights within the European Union. The Regulation and Directive expressly exclude from design protection: This chapter deals with each in turn.
Grounds for Invalidity
Authors: Stone David
Published: March 2021

Article 25 of the Regulation sets out all the grounds for invalidity for RCDs and unregistered Community designs. Article 11 of the Directive sets out relevantly identical provisions in relation to national (and Benelux) registered designs, although some are not mandatory: see para 24.35.
Invalidity Proceedings before the Office
Authors: Stone David
Published: March 2021

The validity of an RCD can be tested either before the Office or in a counterclaim in infringement proceedings before a Community design court. It is not possible to commence proceedings for invalidity of an RCD directly before a Community design court (or indeed, any court).
Identity Disclosure
Authors: Riordan Jaani
Published: March 2021

Internet intermediaries frequently acquire information about tortious activity which is relevant to a claim against a third party. Such information can be relevant in two ways: first, it may reveal the identity of an anonymous user who is alleged to have committed a wrong; and second, it may supply evidence of the acts carried out by that user and the rights which the claimant says have been infringed. Obtaining access to this information is often essential for a claim to proceed, since without it the true tortfeasor may remain unknown. However, disclosure is unlike many other remedies because it is available without proof of wrongdoing by the disclosing party.
Defamation
Authors: Riordan Jaani
Published: March 2021

Fuelled by the scale, ubiquity, and persistence of internet content, and by the public’s appetite for scandal and intrigue, online defamatory statements possess unparalleled potential to harm a person’s reputation indelibly. Necessarily, when such statements are promulgated, it is an internet intermediary which processes, stores, and transmits them. This chapter considers when such a party is liable to pay damages to the claimant.
Data Protection
Authors: Riordan Jaani
Published: March 2021

This chapter examines the liability of internet intermediaries for contraventions of the data protection regime. Data protection duties, like those upholding rights of privacy and confidentiality, can impose significant burdens upon internet intermediaries. This is because much of the information in which these services deal will contain ‘personal data’, and in some cases sensitive personal data, while almost all of the activities undertaken by them will involve some form of ‘processing’ of those data.
Parallel Imports
Authors: Mühlendahl Alexander , Botis Dimitris , Maniatis Spyros , Wiseman Imogen
Published: March 2021

Free movement of goods, one of the ‘four freedoms’ together with free movement of persons, services, and capital covered in the Treaties, is a fundamental principle with two purposes. The first is purely economic; a customs union and common market comprising individual Member States cannot be established unless goods from all the Member States are sold freely and compete effectively in all the Member States. The second is political, if there is to be a single common market then goods must flow freely within its borders. The effect of national measures that block the importation of goods from one Member State to another, make their marketing more difficult, or raise their price, is the distortion of the free flow of goods and competition. Inevitably, in a single market such measures have to be eliminated.
Provision Of Information For Creditors And Lodgement Of Their Claims
Authors: Lenzig Katja
Published: March 2021

Any foreign creditor may lodge claims in insolvency proceedings by any means of communication, which are accepted by the law of the State of the opening of proceedings. Representation by a lawyer or another legal professional shall not be mandatory for the sole purpose of lodging of claims.
The Nature of the Re Hastings-Bass Duty
Authors: Ashdown Michael
Published: March 2021

Lord Walker’s analysis in Pitt v Holt in the Supreme Court accords in all essential respects with the reasons put forward in Chapter 3 to prefer a duty (‘weak’) rather than results-oriented (‘strong’) account of the Re Hastings-Bass rule, as does the approach adopted by Lloyd LJ in the Court of Appeal, which Lord Walker expressly endorses. Yet Lord Walker’s judgment does not yet provide a wholly comprehensive basis for the future development of the law. There remain a number of loose ends, arising predominantly from issues not specifically before the court in Pitt, but which have been matters of concern in earlier Re Hastings-Bass cases, including: how a ‘relevant consideration’ is defined; the significance of establishing that the trustees ‘would’ or ‘might’ have acted differently, in view of Lord Walker’s refusal to choose between these two alternatives; the specific problems arising from the use of professional advisers, and in cases concerning tax liability and pension trusts. These matters are addressed in detail in chapters 5 to 8. But in order to do this it is first necessary to clarify the juridical nature of the ‘duty of consideration’ upon which Lord Walker’s analysis depends.
Introduction
Authors: Bork Reinhard , Mangano Renato
Published: March 2021

This chapter is an introduction to the issues involved in cross-border insolvency cases and their regulation as covered by the EIR, which recast the OR. It also provides a view-from-the-cathedral of EU Regulation 2015/848; a concise description of its history, aims, and principles; as well as a list of the other relevant sources of law, including those of soft law such as the UNCITRAL Model Law and the European Communication and Cooperation Guidelines for Cross-border Insolvency (the so-called ‘CoCo Guidelines’). Finally, the role of the Court of Justice of the European Union (CJEU) for the interpretation of European insolvency law and its judicial activism are analysed.
Secondary Insolvency Proceedings
Authors: Bork Reinhard , Mangano Renato
Published: March 2021

The European Insolvency Regulation permits the opening of territorial proceedings conducted parallel to main proceedings, thereby modifying the concept of universality through the existence of so-called secondary proceedings. Secondary proceedings serve different purposes and are characterized by the fact that they are limited in their scope, as they only affect assets within the Member State in which the secondary proceedings have been opened. While the requirements for the opening of secondary proceedings as well as their effects are largely governed by the lex fori concursus secundarii, the EIR not only modifies some of these requirements but also contains an entire set of rules concerning the coordination of secondary and main proceedings to ensure efficient administration of the debtor’s assets. This chapter will therefore examine the principles of secondary proceedings, the requirements for and the effects of the opening of such proceedings, and the relationship between main and secondary proceedings.
Austria
Authors: Gassner Gottfried , Schirmer Thomas
Published: March 2021

The material contained herein is intended as a general guide only and is not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and authors bear no responsibility for any errors or omissions contained therein.
The Republic of Korea
Authors: Han Min , Choi Woo Young
Published: March 2021

The material contained herein is intended as a general guide only. The information and opinions which it contains are not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and authors bear no responsibility for any errors or omissions contained therein.
Singapore
Authors: Jeremiah Herman , Xue Joan
Published: March 2021

The material contained herein is intended as a general guide only and is not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and authors bear no responsibility for any errors or omissions contained therein.
The Settlor: Reserved Powers and Private Trust Companies
Authors: Panico Paolo
Published: March 2021

The development of trust law in Victorian England, which led to many of the rules of equity still in force today, followed a social and economic evolution where the typical settlors were no longer members of the landed gentry but professionals and businessmen living in the cities and settling movable wealth, mainly financial assets, rather than landed estates. A similar development is taking place in the first decades of the twenty-first century, where the typical settlors are successful business people from various areas of the world, whose background is not the Anglo-American legal system and who have often accumulated an impressive wealth by running their own business. Their families may have interests in various parts of the world and succession planning is required in order to hand over the business to the next generation.
Trustee Liability to Third Parties
Authors: Panico Paolo
Published: March 2021

Trusts are not corporate entities: they have no legal personality and so are capable neither of owning property in their own right nor of suing or being sued. Title to the trust property vests in the trustees, who in turn have standing to sue or to be sued in their capacity as such. Of course, this is a basic notion in trust law, yet it entails some intractable consequences for trustees contracting with third parties.
Protectors
Authors: Panico Paolo
Published: March 2021

This chapter deals with the office of trust protectors. The widespread use of protectors is a relatively new practice that has grown in popularity in parallel with the development of the offshore trust industry since the last quarter of the twentieth century. However, the practice of conferring certain functions to a non-trustee has been recorded for centuries.
Asset Protection Trusts
Authors: Panico Paolo
Published: March 2021

The phrase ‘asset protection trust’ is generally used to describe a set of statutory provisions intended to enhance a settlor’s ability to ringfence assets and place them beyond the reach of his or her creditors. Instances of asset protection trust legislation have been enacted in a number of offshore centres since the mid-1980s and in some US states since the late 1990s.
Appointment Of Directors
Authors: Griffiths Martin
Published: March 2021

This chapter deals with directors who are formally appointed to the role (including cases where the formal process is defective). It does not consider de facto or shadow directors. It describes the rules relating to the required numbers of directors, their eligibility for appointment, the appointment process, and the publicity rules relating to the appointment. Appointed directors may be either executive or non-executive directors. The relevant statutory provisions are now found in Part 10 of the Companies Act. The sections about the appointment of directors are ss 154–61. The sections about publicity, concerning the register of directors and directors’ residential addresses, are ss 162–7 and 240–6. Reference should also be made to the company’s own constitution.
Taxation of Directors’ Earnings and Benefits
Authors: Chacko Thomas
Published: March 2021

This chapter outlines the tax issues that arise in the context of directorships. The great majority of these concern the director’s income tax liability, which is in most circumstances the same as that of any other employee. However, there are a number of more elaborate ways of remunerating employees which are likely to be encountered in the context of directors, both because they are often among the higher-paid employees of a business and because their employers often wish to link their remuneration to performance. This chapter therefore covers ‘golden hellos’ and termination payments, other ways of benefiting an employee (including the reimbursement of expenses and making them loans), and pension contributions, before outlining the tax implications of various share schemes that might be used. More complex remuneration planning is mentioned in Section D, but the wider area of remuneration structures is outside the scope of this work.
Duty Not To Accept Benefits From Third Parties
Authors: Haywood Marcus
Published: March 2021

The duty of a director not to accept benefits from a third party, now stated in the 2006 Act, s 176, is part of the broader duty not to profit from his position as a director without the company’s consent.
Duty Not To Accept Benefits From Third Parties
Authors: Lloyd Tamlyn , Marcus Haywood
Published: March 2021

One of the consequences of the common law principle that a director must avoid conflicts of interest was that a director could not have an interest in a transaction with the company unless he had disclosed all material facts about the interest to the members and they had approved or authorized his having the interest. Authorization by the board was not sufficient. If the other party to the transaction had notice of the irregularity, the company might rescind the contract. The director might also be liable for breach of duty and under a duty to account for profits obtained by reason of such dealings.
The Company’s Remedies for Breach of Directors’ General Duties
Authors: Zacaroli Antony
Published: March 2021

The Companies Act 2006 has effected no change to the remedies which lie against a director for breach of duty. Section 178(1) provides that ‘the consequences of breach (or threatened breach) of s 171–7 are the same as would apply if the corresponding common law rule or equitable principle applied’, and s 178(2) provides that the duties set out in ss 171–3 and 175–7 ‘are, accordingly, enforceable in the same way as any other fiduciary duty owed to a company by its directors’. No separate express provision is made in respect of the duty to exercise reasonable care, skill, and diligence (set out in s 174), but it is clear that the remedies for breaches of that duty are those provided by the common law.
Pension Schemes
Authors: Legge Henry
Published: March 2021

The first decade of the new millennium saw a huge increase in the cost to companies of providing pensions for their current and former employees. Schemes which had previously been assessed as well funded and in surplus became underfunded and in deficit. The costs of funding this deficit and the accruing liabilities of the scheme can often be a very significant drain on a company’s cash flow and resources.
Investigations and Public Interest Winding-Up Petitions
Authors: Davis Glen
Published: March 2021

Serious misconduct, or breaches of duty by a company or its directors affecting the company’s relationships with members of the public, may trigger an investigation by the Secretary of State into the manner in which the company’s business has been conducted, or even the appointment of inspectors and publication of a formal report. In an appropriate case, the Secretary of State or a regulatory authority may petition the court to wind the company up on the basis that it is ‘just and equitable’ to do so in the public interest. Such a liquidation need not be predicated on insolvency. A winding-up order terminates the directors’ powers of management and is the logical response to misconduct or mismanagement by directors which is revealed by an inspector’s report.
Introduction
Authors: Mallon Christopher , Waisman Shai Y , Schrock Ray C
Published: March 2021

As we said in the introduction to the first edition, and as continues to be the case, two systems of law dominate the world debt markets—English law and New York law. Any company of any size, from pretty well anywhere in the world that is looking to raise finance, will find itself heading either to London or New York capital markets and the debt instruments that it then enters into will be governed by the laws of one or other of these jurisdictions.
Giving Effect to Debt Compromise Arrangements–Binding The Minority or out of The Money Classes of Creditors
Authors: Mallon Christopher , Waisman Shai Y , Schrock Ray C
Published: March 2021

When it comes to remedies at a pre-insolvency proceeding stage, it can be said that England and the US are two countries separated by a common law. In particular, the hardening of common law and equitable rules into clear statements that could be set out in a text book in the nineteenth century in England does not appear to have been replicated to the same extent in the US. England has a strict system of precedent and very clear notions of equitable doctrines and statutory interpretation, whereas the US has a looser approach.
Venue and Forum Selection in the US and UK
Authors: Mallon Christopher , Waisman Shai Y , Schrock Ray C
Published: March 2021

Most bankruptcy cases in the US are heard by specialized bankruptcy courts, which are vested with authority to hear such cases by the US district courts. The United States Congress granted US district courts original and exclusive jurisdiction over—that is, the authority to hear—US bankruptcy cases. However, district courts may (and uniformly do) refer such cases and proceedings to the bankruptcy courts in their respective districts, often pursuant to standing referral orders (in other words, the referral to the bankruptcy courts is automatic).
Employees and Trade Unions
Authors: Mallon Christopher , Waisman Shai Y , Schrock Ray C
Published: March 2021

At first blush, the UK and US case law and statutory regimes that are applicable in insolvency to employees and the unions that represent them appear to be quite different. However, a more thorough review reveals that the goal in both jurisdictions is the same: to reduce the harsh impact of insolvency on those who are usually the least at fault for the subject company’s predicament’its employees. Indeed, among other similarities, both systems provide for priority in right of payment for a portion of the compensation due employees, have stringent notice requirements in the event of termination or rejection of collective bargaining agreements, and require information sharing and good faith negotiations. The underlying objective of each system is to level the playing field and to incentivize the employer and the employees to reach a consensual solution to avoid the risks and burdens mandated by each regime. Whether the legislators, administrators, and jurists in either jurisdiction have gone too far or not far enough in developing tools for one side or the other will depend on the reader’s perspective.
Report on the operation of this Regulation
Authors: Tilmann Winfried
Published: March 2021

Para 1 sets out the Commission’s general reporting obligation customary in regulations of the Union. The first time limit is short (three years) because, based on experience, it is in the initial phase when defects in functioning are more likely to arise or are more obvious, and because they may be quickly remedied. The second and following reports must be prepared at five-year intervals. With the report, the Commission must make proposals to amend the Regulation ‘where necessary’. Under the TFEU the Commission has the exclusive right to make amendment proposals to the European Parliament and the Council (‘right of proposal’, Art 17(2) TEU). The reports are obligatory. The making of amendment proposals is left to the discretion of the Commission (‘where necessary’).
Entry into force and application
Authors: Tilmann Winfried
Published: March 2021

Para 1 determines the entry into force of the EPUE Reg in the manner customary for regulations of the Union: 20 days from the date of publication. The Regulation entered into force together with the EPUET Reg on 21 January 2013. It was not possible to link the provision on entry into force to the entry into force of the UPCA because the entry into force of a Union act must be temporally specific and may not be made conditional on an event outside the Union.
Translation in the event of a dispute
Authors: Keussen Christoph
Published: March 2021

Given that the language regime for EPUEs is restricted to the three official languages of the EPO, third parties having no or only a limited understanding of the respective language of proceedings may find it difficult to understand the relevant patent specifications. To facilitate access to the content of a relevant patent specification for the defendant in the case of a dispute, the patent proprietor in such cases may be required to submit additional translations.
Scope of application
Authors: Tilmann Winfried
Published: March 2021

Art 3 refers to the patents, patent applications, and protection certificates subject to the Agreement in any way, that is, for which the UPC has exclusive jurisdiction in respect of the actions referred to in Art 32 UPCA. The first main area of ‘application’ of the Agreement to an IP right or an application is the enforcement or contestation of that right by way of a legal action within the scope of the Court’s exclusive jurisdiction pursuant to Art 32(1)(a), (b), (c), (f), (g), (h), and (i) UPCA. The second main area is an independent revocation proceedings pursuant to Art 32(1)(d) UPCA and a revocation counterclaim pursuant to Art 32(1)(e) UPCA.
The Court of First Instance
Authors: Büttner Tilmann
Published: March 2021

Pursuant to Art 6 UPCA, the Court is construed as a unitary entity and comprises at first instance three types of divisions: the central division, the regional divisions, and the local divisions. These divisions may differ in the details of their staff and their competences, however they are on an equal footing in terms of the competence of their panels.
The Court of Appeal
Authors: Büttner Tilmann
Published: March 2021

The Court of Appeal, competent for deciding appeals and being the only admissible legal remedy within the UPC system, has the task of supervising and unifying the jurisdiction of the divisions of first instance. The procedures and decisions of the first instance, although exercised by panels of a common court, may diverge considerably as they will probably be affected by the different cultures of legal proceedings of the CMS from which the judges come. Therefore, and because of the lack of any further admissible legal remedy against decisions of the Court of Appeal, the Court of Appeal will not follow the legal tradition of one of the CMSs within the UPC. Consequently, to achieve this it is necessary to provide for a multinational composition of the panels of the Court of Appeal with judges who are, even above the level necessary in any event for the office of a judge at the UPC, qualified, experienced, and acknowledged as such by patent practice.
Eligibility criteria for the appointment of judges
Authors: Tilmann Winfried
Published: March 2021

For a court deciding exclusively on patent matters and being in particular competent to reverse the decisions of the technically qualified patent examiners of the EPO in the case of revoking a patent, the need for both legally and technically qualified persons is obvious. However, despite the great importance of technical knowledge, the case must still be decided on the basis of legal criteria. There are no examples of the involvement of technically qualified judges in the jurisdictions of most CMSs, hence, the cooperation of lawyers and technical experts on a Court’s panel will be a new experience for many prospective legally or technically qualified UPC judges. The model of the Swiss Federal Patent Court may help and, also, some CMSs do have experience with such cooperation.
Judicial independence and impartiality
Authors: Büttner Tilmann
Published: March 2021

The status of UPC judges is determined exclusively by the UPCA. It differs in several respects from the status of German judges.
Sources of law
Authors: Tilmann Winfried
Published: March 2021

Union law is mentioned in the first position in lit a of para 1. When is the UPC required to apply Union law? The UPC was established by the UPCA which is a piece of international law and is not part of Union law. That makes the UPC an international court. However, the Member States established it—at the level of international law—as a court common to them which, pursuant to Arts 1(2) and 21 UPCA, is part of their respective national judicial systems. As part of the judicial system (Art 21 UPCA) of the CMSs—by an order under international law—and by reason of an express provision in Art 20 UPCA, the Court fulfils the obligation of the CMSs to apply Union law. Since the Court is a ‘court common to a number of Member States’, ‘it is situated within the judicial system of the European Union’, which is why ‘its decisions’ are subject to ‘mechanisms capable of ensuring the full effectiveness of Union law’. This wording—used in Opinion C-1/09 of the Court of Justice with reference to the Benelux Court of Justice—is also appropriate with reference to the UPC. Although it is integrated into the judicial systems of the Member States in a different way compared with the Benelux Court of Justice, it is a ‘court common to the Member States’, and it is only based on that connecting factor that the Benelux Court of Justice is ‘situated within the judicial system of the European Union’. The ‘mechanisms capable’ are expressly confirmed in Arts 21–23 UPCA.