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To understand how much or how little progress is made in democratising higher education, an examination of transformation in the sector needs to be undertaken. Such an examination will reveal best practice, the sharing of which can move the process of transformation forward by inspiring those further beyond in the process. This article serves to fulfil that purpose. It comprises an assessment of equity and diversity in selected higher education institutions in the country that may be regarded as "best practice". The study focussed on the university as an equity employer and thus staff equity is examined. The article reports the South African component of a five-country study undertaken in late 2004. (Contains 2 figures.)

The prevalence of overweight and obesity, particularly in children, raises serious attention to its causes and possible interventions. Food marketing to children has in recent years come under scrutiny as one of the putative factors responsible for the rising rates of obesity among children. This article addresses the global evidence base on the issue and explores policy interventions practised in the more developed world as well as the local challenges in dealing with the issue in South Africa. South African policymakers have a wide range of policy options based on international practice in committing to the health and well-being of its children. [ABSTRACT FROM AUTHOR]

Equity and diversity have become part of the dialogue, debate, policy and scholarship at higher education institutions in South Africa. These have appeared through the transformation agendas at institutions, focussing on a number of different issues: student access and development, staff equity, institutional climate or culture etc. This paper reflects on the issues of equity and diversity in higher education institutions through the development of a framework of domains into which existing research may be classified. The organising framework incorporates the variables that impact the development of equity and diversity, documents the research and practice, and identifies areas for further research in the field of equity and diversity in higher education institutions. [ABSTRACT FROM AUTHOR]

Aim: To explore the views of general practitioners (GPs) and nurses on type 2 diabetes (T2D) management, including the use of recently funded T2D medications in New Zealand (NZ) and their perceived barriers to providing optimal care., Background: T2D is a significant health concern in NZ, particularly among Māori and Pacific adults. Characterised by prolonged hyperglycaemia, T2D is generally a progressive condition requiring long-term care., Methods: Semi-structured interviews were conducted between July and December 2022 with 21 primary care clinicians (10 GPs and 11 nurses/nurse prescribers) from nine different general practice clinics across the Auckland and Waikato regions of NZ. Framework analysis was conducted to identify common themes in clinicians' perceptions and experiences with T2D management., Findings: Three themes were identified: health-system factors, new medications, and solution-based approaches. Lack of clinician time, healthcare funding, staff shortages, and burn-out were identified as barriers to T2D management under health-system factors. The two newly funded medications, empagliflozin and dulaglutide, were deemed to be a positive change for T2D care in that they improved patient satisfaction and clinical outcomes, but several clinicians were hesitant to prescribe these medications. Participants suggested that additional education and specialist diabetes support would be helpful to inform optimal medication prescribing and that better use of a multi-disciplinary team (clinical and support staff) could support T2D care by reducing workload, addressing cultural gaps in healthcare delivery, and reducing burnout. An improved primary care work environment, including appropriate professional development to support prescribing of new medications and the value of collaboration with a non-regulated workforce, may be required to facilitate optimal T2D management in primary care. Future research should focus on interventions to increase support for both clinical teams and patients while adopting a culturally appropriate approach to increase patient satisfaction and improve health outcomes.

Introduction In Aotearoa New Zealand (NZ), type 2 diabetes (T2D) is predominantly managed in primary care. Despite established guidelines, patients are often suboptimally managed, with inequitable health outcomes. To date, few NZ studies have evaluated the primary care management of T2D at the time of diagnosis. Aim This study aims to explore patients' the provision of education and delivery of care to patients at the time of diagnosis, which is a crucial time in the disease trajectory. Methods Participants were recruited from a Māori health provider in the Waikato District, and diagnosed with T2D after January 2020. Patients were texted a link to opt into a survey (larger study) and then registered interest by providing contact details for an interview (current study). Semi-structured interviews were conducted and were audio recorded, transcribed, and thematically analysed. Results In total, 11 participants aged 19-65 years completed the interviews (female n  = 9 and male n  = 20); the comprised Māori (n  = 5), NZ European (n  = 5) and Asian (n  = 1) participants. Three overarching themes were identified, including: (1) ineffective provision of resources and education methods; (2) poor communication from healthcare practitioners; and (3) health system barriers. Discussion Evidently, there are difficulties in primary care diabetes mellitus diagnosis and management. Improvements could include locally relevant resources tailored to patients' experiences and cultural identities. Utilising whānau support and a non-clinical workforce, such as health navigators/kaiāwhina, will drastically address current workforce issues and assist patient self-management. This will allow improved diagnosis experiences and better health outcomes for patients and whānau.

Background: Pharmacist prescribers have comprehensive pharmacotherapy knowledge that can be useful for management of complex health conditions such as type 2 diabetes, yet the number of pharmacist prescribers working in New Zealand primary care is low., Aim: To explore the experiences of pharmacist prescribers in supporting type 2 diabetes management in New Zealand primary care., Methods: Qualitative research design using semi-structured interviews with six pharmacist prescribers working in NZ primary care. Thematic analysis guided this study and themes were finalised with the wider research team., Results: Three major themes were identified: team approach, health inequity and the role of a pharmacist prescriber. This study found that pharmacist prescribers may improve health equity by providing advanced pharmacotherapy knowledge within a wider primary care team to support complex patient needs and understanding the wider social determinants of health that impact effective diabetes management. Participants reportedly had more time to spend with patients (than GPs or nurses) and could also contribute to improving health outcomes by directly educating and empowering patients., Conclusion: The views of pharmacist prescribers have seldom been explored and this study suggests that their role may be under-utilised in primary care. In particular, pharmacist prescribers can provide specialist prescribing (and often mobile) care, and may contribute to improving health outcomes and reducing inequity when used as part of a multi-disciplinary team., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aotearoa New Zealand has been commended for the overarching effectiveness of its Covid-19 response. Yet, the lockdowns challenged the health of whānau Māori (Māori families) alongside their social, cultural and financial well-being. However, Māori have repeatedly demonstrated innovative means of resilience throughout the pandemic. This review aimed to document the local grassroots, community-level responses to Covid-19 lockdowns by Māori. Three sources for searching for evidence were used: academic, websites and media, and Māori community networks. A total of 18 records were reviewed. Four of these records comprised published academic literature, 13 comprised news, online and media articles, and one was a situation report. Findings were grouped into three categories: distributive networks, well-being and resource support. The findings of this review provide an exemplar for the strength of Māori leadership and agency, alongside value-driven holistic approaches to health and well-being that could positively impact the health of all., Competing Interests: Shemana Cassim (PhD) is a Lecturer at Te Kura Hinengaro Tangata School of Psychology, Massey University. Shemana has an interest in the cultural, historical and social contexts and societal structures that influence the everyday life-worlds of peoples of colour. Recently, Shemana has been involved in multiple community health research projects aimed at promoting equitable health outcomes for Māori as well as Muslim migrant communities. Shemana has held a Research Fellowship with Ngā Pae o te Māramatanga and was also a Research Fellow on multiple externally funded research projects based at the University of Waikato. Shemana is a co-convenor of the Aotearoa Migration Research Network, an executive council member of CEAD (Contemporary Ethnographies Across Disciplines), and on the Editorial Board of the Journal of Community and Applied Social Psychology. Teorongonui Josie Keelan (PhD) is a contractor who works some of her time with Ngā Pae o te Māramatanga as a Senior Research Fellow and some of her time on other projects. These include research with Ngāti Whakaue kaumātua (elders from the Ngāti Whakaue iwi) contributing to understanding of the lives, concerns and dreams of kaumātua. In addition, she is working with the Joint Research Committee of the Mana Wāhine Waitangi Tribunal Claim and is the Interim Kōmiti Māori representative on the Council of Te Pūkenga, the New Zealand Institute of Technology and Polytechnics. Josie has an interest in the application of the mātauranga contained in traditional stories and whakataukī (proverbs) in contemporary contexts. The authors declared no potential conflicts of interest with respect to the research, authorship and publication of this article., (© The Author(s) 2022.)

Static cold storage (SCS) is currently the most widely used method for organ preservation, but a number of limitations are associated including tissue damage and restricted opportunity for organ repair. Thus, the development of improved hypothermic storage solutions is an urgent need. Herein, using a renal epithelial cell model (LLC-PK1), we tested the benefits of ADD10, a novel clinical grade antioxidant product, in reducing damages associated with ischemia-reperfusion (IR). Cells were stored up to 24h at 4 °C in University of Wisconsin (UW) solution without or in the presence of 1% ADD10 with following reperfusion up to 24h at 37 °C. The presence of ADD10 significantly decreased cells damages, cell death, and the level of reactive oxygen species (ROS) (P < 0.05). Concomitantly, ADD10 supplementation also favored an increased oxygen consumption rate (OCR) and improved bioenergetics of LLC-PK1 cells (P < 0.05). Finally, preliminary in vivo studies suggested a benefit of ADD10 on the renal function post-transplantation. In conclusion, these results demonstrate that the addition of ADD10 to the preservation solution not only efficiently protects renal cells during SCS, but also improves the functionality of cold-stored organs during transplantation., Competing Interests: Declaration of competing interest Shamir Cassim and Emanuelle Pascolo-Rebouillat are employees of Addmedica, and importantly, the funding body had no influence on data acquisition. Pierre-Yves Martin was a former employee of Addmedica., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Glutathione peroxidase 4 (GPX4) has been reported as one of the major targets for ferroptosis induction, due to its pivotal role in lipid hydroperoxide removal. However, recent studies pointed toward alternative antioxidant systems in this context, such as the Coenzyme Q-FSP1 pathway. To investigate how effective these alternative pathways are in different cellular contexts, we used human colon adenocarcinoma (CRC) cells, highly resistant to GPX4 inhibition. Data obtained in the study showed that simultaneous pharmacological inhibition of GPX4 and FSP1 strongly compromised the survival of the CRC cells, which was prevented by the ferroptosis inhibitor, ferrostatin-1. Nonetheless, this could not be phenocopied by genetic deletion of FSP1, suggesting the development of resistance to ferroptosis in FSP1-KO CRC cells. Considering that CRC cells are highly glycolytic, we used CRC Warburg-incompetent cells, to investigate the role metabolism plays in this phenomenon. Indeed, the sensitivity to inhibition of both anti-ferroptotic axes (GPx4 and FSP1) was fully revealed in these cells, showing typical features of ferroptosis. Collectively, data indicate that two independent anti-ferroptotic pathways (GPX4-GSH and CoQ10-FSP1) operate within the overall physiological context of cancer cells and in some instances, their inhibition should be coupled with other metabolic modulators, such as inhibitors of glycolysis/Warburg effect.

This study aimed to explore refugee women's experiences of interpreters in healthcare in Aotearoa, New Zealand (NZ). Semi-structured interviews were conducted with nine women who arrived in NZ as refugees. Analysis involved a 'text in context' approach. An iterative and interpretive process was employed by engaging with participant accounts and field notes. The various meanings behind participants' experiences were unpacked in relation to the literature and the broader socio-cultural contexts in which these experiences occurred. Findings highlighted issues with professional and informal interpreters. These issues included cost, discrepancies in dialect, translation outside appointments, and privacy. Findings indicate ethical and practical implications of using interpreters in healthcare for refugee women. A step to achieving equitable healthcare for refugee women in New Zealand entails putting in place accessible and robust communicative infrastructure.

Background: In 2014 the New Zealand Ministry of Health implemented a universal program of screening for gestational diabetes mellitus (GDM) in pregnancy; however, data suggest that only half of all women are being screening according to the guidelines. This study aimed to explore women's views and experiences of GDM screening and to determine what the main screening barriers are., Methods: Eighteen women were recruited from the Waikato region of New Zealand, who were either pregnant (>28 weeks of gestation) or had given birth in the last 6 months. These women participated in a semi-structured interview about their experience of GDM screening and the transcripts were thematically analyzed. Of these women, 14 had been screened for gestational diabetes (three were screened late) and four had not been screened at all., Results: Multiple barriers to screening for GDM were identified, with two overarching themes of "confusion, concerns, and access to information for screening," and "challenges to accessing and completing the screening test." Specific barriers included the preference of risk-based assessments for GDM by their leading health professional (usually a registered midwife); negative perceptions of "sugar drink test"; needing time off work and childcare; travel costs for rural women; previous negative screening experiences; and reduced health literacy., Conclusion: There appear to be both woman-, midwife-, and system-level barriers to screening for GDM. While screening is ultimately a woman's choice, there does appear to be capacity to increase screening rates by improving awareness of the updated guidelines, and making the test environment more accessible and comfortable., Competing Interests: No competing financial interests exist., (© Lynne Chepulis et al., 2022; Published by Mary Ann Liebert, Inc.)

Competing Interests: Nil.

Pancreatic ductal adenocarcinoma (PDAC), accounting for 90-95% of all pancreatic tumors, is a highly devastating disease associated with poor prognosis. The lack of accurate diagnostic tests and failure of conventional therapies contribute to this pejorative issue. Over the last decade, the advent of theranostics in nuclear medicine has opened great opportunities for the diagnosis and treatment of several solid tumors. Several radiotracers dedicated to PDAC imaging or internal vectorized radiotherapy have been developed and some of them are currently under clinical consideration. The functional information provided by Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) could indeed provide an additive diagnostic value and thus help in the selection of patients for targeted therapies. Moreover, the therapeutic potential of β - - and α-emitter-radiolabeled agents could also overcome the resistance to conventional therapies. This review summarizes the current knowledge concerning the recent developments in the nuclear medicine field for the management of PDAC patients.

Background: Despite the fact that there is an increasingly effective armoury of medications to treat diabetes, many people continue to have substantially elevated blood glucose levels. The purpose of this study was to explore what the barriers to diabetes management are in a cohort of people with diabetes and poor glycaemic control., Methods: Qualitative semistructured interviews were carried out with 10 people with diabetes who had known diabetes and a recent HbA1c of >11.3% (100 mmol/mol) to explore their experiences of barriers to diabetes self-management and glycaemic control., Results: Barriers to diabetes management were based around two key themes: biopsychosocial factors and knowledge about diabetes. Specifically, financial concerns, social stigma, medication side effects, and cognitive impairment due to hyperglycaemia were commonly reported as barriers to medication use. Other barriers included a lack of knowledge about their own condition, poor relationships with healthcare professionals, and a lack of relevant resources to support diet and weight loss., Conclusion: People with diabetes with poor glycaemic control experience many of the same barriers as those reported elsewhere, but also experience issues specifically related to their severe hyperglycaemia. Management of diabetes could be improved via the increased use of patient education and availability of locally relevant resources., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Lynne Chepulis et al.)

Objective: The objective of this research was to document the barriers to early presentation and diagnosis of lung cancer within primary healthcare, identified by Māori whānau (families) and primary healthcare providers in the Midland region of Aotearoa New Zealand., Methods: This project used a kaupapa Māori approach. Nine community hui (focus groups) and nine primary healthcare provider hui were carried out in five rural localities in the Midland region. Each community hui included cancer patients, whānau, and other community members. Each healthcare provider hui comprised staff members at the local primary healthcare centre, including General Practitioners and nurses. Hui data were thematically analysed., Results: Barriers and enablers to early diagnosis of lung cancer were categorised into three key themes: GP relationship and position in the community, health literacy and pathways to diagnosis., Conclusion: This study demonstrates that culturally responsive, patient-centred healthcare, and positive GP-patient relationships are significant factors for Māori patients and whānau serving as barriers and enablers to early diagnosis of lung cancer., (© 2020 John Wiley & Sons Ltd.)

Background: Lung Cancer is the leading cause of cancer deaths in Aotearoa New Zealand. Māori communities in particular have higher incidence and mortality rates from Lung Cancer. Diagnosis of lung cancer at an early stage can allow for curative treatment. This project aimed to document the barriers to early diagnosis and treatment of lung cancer in secondary care for Māori communities., Methods: This project used a kaupapa Māori approach. Nine community hui (focus groups) and nine primary healthcare provider hui were carried out in five rural localities in the Midland region. Community hui included cancer patients, whānau (families), and other community members. Healthcare provider hui comprised staff members at the local primary healthcare centre, including General Practitioners and nurses. Hui data were thematically analysed., Results: Barriers and enablers to early diagnosis of lung cancer were categorised into two broad themes: Specialist services and treatment, and whānau journey. The barriers and enablers that participants experienced in specialist services and treatment related to access to care, engagement with specialists, communication with specialist services and cultural values and respect, whereas barriers and enablers relating to the whānau journey focused on agency and the impact on whānau., Conclusions: The study highlighted the need to improve communication within and across healthcare services, the importance of understanding the cultural needs of patients and whānau and a health system strategy that meets these needs. Findings also demonstrated the resilience of Māori and the active efforts of whānau as carers to foster health literacy in future generations.

Most healthcare providers (HCPs) work from ethical principles based on a Western model of practice that may not adhere to the cultural values intrinsic to Indigenous peoples. Breaking bad news (BBN) is an important topic of ethical concern in health research. While much has been documented on BBN globally, the ethical implications of receiving bad news, from an Indigenous patient perspective in particular, is an area that requires further inquiry. This article discusses the experiences of Māori (Indigenous peoples of New Zealand) lung cancer patients and their families, in order to investigate the ethical implications of receiving bad news. Data collection occurred through 23 semistructured interviews and nine focus groups with Māori lung cancer patients and their families in four districts in the Midland Region of New Zealand: Waikato, Bay of Plenty, Lakes and Tairāwhiti. The findings of this study were categorised into two key themes: communication and context. Avenues for best practice include understanding the centrality of the HCP-patient relationship and family ties in the healthcare journey, and providing patients with the full range of viable treatment options including hope, clear advice and guidance when the situation calls for it. Overall, the findings of this study hold implications for providing culturally safe and humanistic cancer care when BBN to Māori and Indigenous patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a dismal 5-year survival rate of 5% and very limited efficacy of the current therapeutic regimens. The lethality of PDAC stems from asymptomatic early stage of the disease, its propensity to rapidly disseminate, as well as unusual, dense and highly active surrounding stroma. Fortunately, promising literature data suggests that exploiting newly contextualized type of cell death, termed "ferroptosis", has great potential for overcoming the major problems regarding PDAC treatment. A major player in this type of cell death is Glutamate/Cystine antiporter - xCT, which is responsible for the uptake of oxidized form of cysteine, and thus maintenance of intracellular amino acid and redox homeostasis. xCT seems to fulfill all requirements of the solid and specific molecular target for ferroptosis-based anti-cancer therapy. In this chapter we summarized mounting literature data supporting this hypothesis, but also, we pointed out some of the underexamined aspects of xCT-dependent (patho)physiology of the cancer cell, which have to be addressed in future studies. The abstract could be used as "informative abstract" for the online version., (© 2021. Springer Nature Switzerland AG.)

Background: New Zealand (NZ) has high rates of colorectal cancer but low rates of early diagnosis. Due to a lack of understanding of the pre-diagnostic experience from the patient's perspective, it is necessary to investigate potential patient and health system factors that contribute to longer diagnostic intervals. Previous qualitative studies have discussed delays using The Model of Pathways to Treatment, but this has not been explored in the NZ context. This study aimed to understand the patient experience and perception of their general practitioner (GP) through the diagnostic process in the Waikato region of NZ. In particular, we sought to investigate potential barriers and facilitators that contribute to longer diagnostic intervals., Methods: Ethical approval for this study was granted by the New Zealand Health and Disability Ethics Committee. Twenty-eight participants, diagnosed with colorectal cancer, were interviewed about their experience. Semi-structured interviews were audio recorded, transcribed verbatim and analysed thematically using The Model of Pathways to Treatment framework (intervals: appraisal, help-seeking, diagnostic)., Results: Participant appraisal of symptoms was a barrier to prompt diagnosis, particularly if symptoms were normalised, intermittent, or isolated in occurrence. Successful self-management techniques also resulted in delayed help-seeking. However if symptoms worsened, disruption to work and daily routines were important facilitators to seeking a GP consultation. Participants positively appraised GPs if they showed good technical competence and were proactive in investigating symptoms. Negative GP appraisals were associated with a lack of physical examinations and misdiagnosis, and left participants feeling dehumanised during the diagnostic process. However high levels of GP interpersonal competence could override poor technical competence, resulting in an overall positive experience, even if the cancer was diagnosed at an advanced stage. Māori participants often appraised symptoms inclusive of their sociocultural environment and considered the impact of their symptoms in relation to family., Conclusions: The findings of this study highlight the importance of tailored colorectal cancer symptom communication in health campaigns, and indicate the significance of the interpersonal competence aspect of GP-patient interactions. These findings suggest that interpersonal competence be overtly displayed in all GP interactions to ensure a higher likelihood of a positive experience for the patient.

Contextualisation of the new type of cell death called "ferroptosis" opened a completely new avenue for the development of anti-cancer therapies. Cumulative fundamental research dating back to the mid-20th century, crowned by the extraordinary work of the group led by Dr. Stockwell from Columbia University in 2012, finally got its candidature to be applied in the clinical settings. Although the potential for clinical importance is undoubtedly growing every day, as showed by the increasing number of papers dealing with ferroptosis and its applications, long experience of cancer research and treatment taught us that caution is still necessary. The plasticity of the tumour cells, particularly acute, along with its involvement in the resistance mechanisms, that have been seen, to greater or lesser extent, for almost all currently used therapies, represents the biggest fascinations in biomedical research field and also the biggest challenge to achieving cures in cancer patients. Accordingly, the main features of fundamental research have to be vigilance and anticipation. In this review, we tried to summarize the literature data, accumulated in the past couple of years, which point out the pitfalls in which "ferroptosis inducers" can fall if used prematurely in the clinical settings, but at the same time can provide a great advantage in the exhausting battle with cancer resistance. This is the first comprehensive review focusing on the effects of the cell-to-cell contact/interplay in the development of resistance to ferroptosis, while the contribution of cell-born factors has been summarized previously so here we just listed them.

Māori experience poorer health statistics in terms of cancer incidence and mortality compared to non-Māori. For prostate cancer, Māori men are less likely than non-Māori men to be diagnosed with prostate cancer, but those that are diagnosed are much more likely to die of the disease than non-Māori men resulting in an excess mortality rate in Māori men compared with non-Māori. A review of the literature included a review of the epidemiology of prostate cancer; of screening; of access to healthcare and of treatment modalities. Our conclusion was that there are a number of reasons for the disparity in outcomes for Māori including differences in staging and characteristics at diagnosis; differences in screening and treatment offered to Māori men; and general barriers to healthcare that exist for Māori men in New Zealand. We conclude that there is a need for more culturally appropriate care to be available to Māori men., Competing Interests: Nil.

Background/aim: Nearly all mammalian tumors of diverse tissues are believed to be dependent on fermentative glycolysis, marked by elevated production of lactic acid and expression of glycolytic enzymes, most notably lactic acid dehydrogenase (LDH). Therefore, there has been significant interest in developing chemotherapy drugs that selectively target various isoforms of the LDH enzyme. However, considerable questions remain as to the consequences of biological ablation of LDH or upstream targeting of the glycolytic pathway., Materials and Methods: In this study, we explore the biochemical and whole transcriptomic effects of CRISPR-Cas9 gene knockout (KO) of lactate dehydrogenases A and B [LDHA/B double KO (DKO)] and glucose-6-phosphate isomerase (GPI KO) in the human colon cancer cell line LS174T, using Affymetrix 2.1 ST arrays., Results: The metabolic biochemical profiles corroborate that relative to wild type (WT), LDHA/B DKO produced no lactic acid, (GPI KO) produced minimal lactic acid and both KOs displayed higher mitochondrial respiration, and minimal use of glucose with no loss of cell viability. These findings show a high biochemical energy efficiency as measured by ATP in glycolysis-null cells. Next, transcriptomic analysis conducted on 48,226 mRNA transcripts reflect 273 differentially expressed genes (DEGS) in the GPI KO clone set, 193 DEGS in the LDHA/B DKO clone set with 47 DEGs common to both KO clones. Glycolytic-null cells reflect up-regulation in gene transcripts typically associated with nutrient deprivation / fasting and possible use of fats for energy: thioredoxin interacting protein (TXNIP), mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), PPARγ coactivator 1α (PGC-1α), and acetyl-CoA acyltransferase 2 (ACAA2). Other changes in non-ergometric transcripts in both KOs show losses in "stemness", WNT signaling pathway, chemo/radiation resistance, retinoic acid synthesis, drug detoxification, androgen/estrogen activation, and extracellular matrix reprogramming genes., Conclusion: These findings demonstrate that: 1) The "Warburg effect" is dispensable, 2) loss of the LDHAB gene is not only inconsequential to viability but fosters greater mitochondrial energy, and 3) drugs that target LDHA/B are likely to be ineffective without a plausible combination second drug target., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of all pancreatic tumors, is a highly devastating disease with poor prognosis and rising incidence. The lack of available specific diagnostics tests and the limited treatment opportunities contribute to this pejorative issue. Over the last 10 years, a growing interest pointing towards mesothelin (MSLN) as a promising PDAC-associated antigen has emerged. The limited expression of MSLN in normal tissues (peritoneum, pleura and pericardium) and its overexpression in 80 to 90% of PDAC make it an attractive candidate for therapeutic management of PDAC patients. Moreover, its role in malignant progression related to its involvement in tumor cell proliferation and resistance to chemotherapy has highlighted the relevance of its targeting. Hence, several clinical trials are investigating anti-MSLN efficacy in PDAC. In this review, we provide a general overview of the different roles sustained by MSLN during PDAC progression. Finally, we also summarize the different MSLN-targeted therapies that are currently tested in the clinic.

Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is subdivided according to the cell-of-origin (COO) classification into germinal centre B-cell (GCB) and activated B-cell (ABC) subtypes, each with different molecular profiles and clinical behaviour. This study aims to describe the pattern of the COO subtypes, the proportion of Epstein-Barr virus (EBV) co-infection, and their influence on survival outcomes in a setting of high HIV prevalence. This retrospective cohort study included patients diagnosed with de novo DLBCL NOS at our tertiary academic centre in Cape Town, South Africa over a 14-year period. Immunohistochemical stains were performed for COO classification, according to the Hans algorithm. Tumour EBV co-infection was established by EBV-encoded ribonucleic acid in situ hybridisation (EBER-ISH) staining. The effect of the COO subtypes and EBV co-infection on overall survival were described by means of univariate, bivariate and multivariate analyses. A total of 181 patients with DLBCL NOS were included, which comprised 131 HIV-uninfected and 50 HIV-infected patients. There was an equal distribution of GCB and ABC subtypes in the HIV-infected and HIV-uninfected groups. EBV co-infection was detected in 16% of the HIV-infected cases and in 7% of the HIV-uninfected cases (p=0.09). There was no significant difference in the incidence of EBV co-infection between the GCB and ABC subtypes (p=0.67). HIV-infected patients with CD4 ≥150 cells/mm 3 had similar survival to HIV-uninfected patients (p=0.005). Multivariate regression analysis showed that in the HIV-infected group with marked immunosuppression (CD4 <150 cells/mm 3 ), there was significantly poorer overall survival compared to the HIV-uninfected group (HR 2.4, 95% CI 1.3-4.1). There were no statistically significant differences in overall survival by DLBCL COO subtype. There was no difference in the proportion of DLBCL COO subtypes, regardless of HIV status. EBV co-infection was more common in the HIV-infected group, but less than described in the literature. Unexpectedly, there were no significant differences in survival outcomes between the GCB and ABC subtypes. Higher CD4 counts in the HIV-infected group had good survival outcomes, while lower CD4 counts predicted adverse survival outcomes. Further research is needed to explore the genetic mutational landscape of HIV-associated DLBCL., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

A defining hallmark of tumor phenotypes is uncontrolled cell proliferation, while fermentative glycolysis has long been considered as one of the major metabolic pathways that allows energy production and provides intermediates for the anabolic growth of cancer cells. Although such a vision has been crucial for the development of clinical imaging modalities, it has become now evident that in contrast to prior beliefs, mitochondria play a key role in tumorigenesis. Recent findings demonstrated that a full genetic disruption of the Warburg effect of aggressive cancers does not suppress but instead reduces tumor growth. Tumor growth then relies exclusively on functional mitochondria. Besides having fundamental bioenergetic functions, mitochondrial metabolism indeed provides appropriate building blocks for tumor anabolism, controls redox balance, and coordinates cell death. Hence, mitochondria represent promising targets for the development of novel anti-cancer agents. Here, after revisiting the long-standing Warburg effect from a historic and dynamic perspective, we review the role of mitochondria in cancer with particular attention to the cancer cell-intrinsic/extrinsic mechanisms through which mitochondria influence all steps of tumorigenesis, and briefly discuss the therapeutic potential of targeting mitochondrial metabolism for cancer therapy.

Immune cells survey and patrol throughout the body and sometimes take residence in niche environments with distinct cellular subtypes and nutrients that may fluctuate from those in which they matured. Rooted in immune cell physiology are metabolic pathways and metabolites that not only deliver substrates and energy for growth and survival, but also instruct effector functions and cell differentiation. Unlike cancer cells, immune cells are not subject to a "Darwinian evolutionary pressure" that would allow them to adapt to developing tumors but are often irrevocably affected to local nutrient deprivation. Thus, immune cells must metabolically adapt to these changing conditions in order to perform their necessary functions. On the other hand, there is now a growing appreciation that metabolic changes occurring in cancer cells can impact on immune cell functionality and contribute to tumor immune evasion, and as such, there is a considerable and growing interest in developing techniques that target metabolism for immunotherapy. In this review, we discuss the metabolic plasticity displayed by innate and adaptive immune cells and highlight how tumor-derived lactate and tumor acidity restrict immunity. To our knowledge, this review outlines the most recent insights on how tumor microenvironment metabolically instructs immune responsiveness.

Mesothelin is a membrane-associated protein overexpressed in pancreatic ductal adenocarcinoma (PDAC). Some mesothelin-targeted therapies are in clinical development but the identification of patients eligible for such therapies is still challenging. The objective of this study was to perform the imaging of mesothelin in mice models of PDAC with a technetium-labeled anti-mesothelin single-domain antibody ( 99m Tc-A1)., Methods: The Cancer Genomic Atlas (TCGA) database was used to determine the prognostic role of mesothelin in PDAC. 99m Tc-A1 was evaluated both in vitro in PDAC cells (SW1990 and AsPC-1) and in vivo in an experimental model of mesothelin-expressing PDAC (AsPC-1) in mice., Results: TCGA analysis showed that PDAC patients with high mesothelin expression had a shorter overall survival (P = 0.00066). The binding of 99m Tc-A1 was 2.1-fold greater in high-mesothelin-expressing AsPC-1 cells when compared to moderate-mesothelin-expressing SW1990 cells ( p < 0.05). In vivo, the 99m Tc-A1 uptake was 3.5-fold higher in AsPC-1-derived tumors as compared to a technetium-labeled irrelevant antibody ( 99m Tc-Ctl) ( p < 0.01)., Conclusions: 99m Tc-A1 accurately allows imaging of mesothelin-expressing experimental PDAC tumors. Our experiments paved the way for the development of a companion test for mesothelin-targeted therapies.