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The development of an effective combined vaccine represents a crucial strategy for preventing outbreaks of infectious diseases and reducing the burden on healthcare resources. Developing a combined vaccine against both influenza and the coronavirus is a promising approach, but it is still in the early stages of development. This paper reports on a novel combined pentavalent candidate vaccine that has shown promising results in mice, with statistically significant differences in mean antibody titer against the coronavirus and the influenza antigens compared to placebo. We have shown that the coronavirus antigen is capable of inducing an immune response autonomously, regardless of the presence of the influenza antigens in a combined vaccine. On the other hand, the presence of the coronavirus antigen in a combined vaccine showed to enhance the immune response against some of the studied influenza antigens, suggesting that these antigens may act in synergy and elicit an enhanced immune response. The absence of dose-dependent difference in mean antibody titer within the same antigenic groups of vaccine preparations suggested that even small amounts of the coronavirus and the influenza antigens could induce an immune response just as good as high-dose vaccine preparations, which certainly has important safety and cost implications. The vaccine is soon to be ready for clinical trials and mass production. [ABSTRACT FROM AUTHOR]

Lutein is the main component of macular and retinal pigment so that it is essential for eye health. In addition, lutein is also related to various metabolic processes in the human body with strong antioxidant properties. The green extraction of lutein in wet microalgae is critical for the further applications as nutraceuticals and pharmaceuticals. Ionic liquid-based aqueous two-phase system (ATPS) is a green approach for multiple product extraction from microalgae. In this study, the extraction performances of ATPS composed of four different cholinium-based compounds (choline geranate, choline chloride, choline dihydrogen citrate and choline bitartrate) and polyethylene glycol 400 (PPG400) were compared. The choline dihydrogen citrate (Ch DHcit) showed a better extraction ability of lutein than other cholinium-based ILs. After optimizing the addition of cholinium-based ILs and PPG400, the ATPS with the best composition (PPG400: Ch Dhcit: water: algal suspension = 42:26:22:10 wt%) was applied to the extraction of lutein from wet Chlorella sp. Six imidazolium-based ionic liquids (1-ethyl-3-methylimidazole chloride, 1-ethyl-3-methylimidazolium bromide, 1-butyl-3-methylimidazolium bromide, 1-butyl-3-methylimidazole chloride, 1-hexyl-3-methylimidazole chloride and 1-hexyl-3-methylimidazolium bromide) were compared as an adjuvant for the lutein extraction from wet Chlorella sp. The introduction of a small amount of 1-ethyl-3-methylimidazole chloride ([C 2 mim]Cl) improved the extraction efficiency of lutein increased by 9.98 %. In the multiple-times extraction process, the total extraction efficiency of three times distribution reached 102.61 %. This paper provides a new approach to the extraction of lutein from algal biomass. [Display omitted] • An ionic liquid-based aqueous two-phase system was used for lutein extraction. • ATPS was composed of PPG400 and dihydrocholine citrate. • About 5 % [C 2 mim]Cl was added into ATPS as an adjuvant. • The extraction efficiency was improved for ATPS with adjuvant. • The extraction efficiency of ATPS with adjuvant was better than acetone. [ABSTRACT FROM AUTHOR]

In conjugate, inactivated, recombinant, and toxoid vaccines, adjuvants are extensively and essentially used for enhanced and long-lasting protective immune responses. Depending on the type of diseases and immune responses required, adjuvants with different design strategies are developed. With aluminum salt-based adjuvants as the most used ones in commercial vaccines, other limited adjuvants, e.g. , AS01, AS03, AS04, CpG ODN, and MF59, are used in FDA-approved vaccines for human use. In this paper, we review the uses of different adjuvants in vaccines including the ones used in FDA-approved vaccines and vaccines under clinical investigations. We discuss how adjuvants with different formulations could affect the magnitude and quality of adaptive immune response for optimized protection against specific pathogens. We emphasize the molecular mechanisms of various adjuvants, with the aim to establish structure-activity relationships (SARs) for designing more effective and safer adjuvants for both preventative and therapeutic vaccines. [ABSTRACT FROM AUTHOR]

Potent adjuvants are highly demanded for most protein and peptides based vaccine candidates in clinical development. Recognition of viral single stranded (ss)RNA by innate toll-like receptors 7/8 in dendritic cells results in a cytokine environment supportive to the establishment of long lasting antibody responses and Th1 oriented T cell immunity. To fully exploit the immunestimulatory properties of ssRNA, it needs to be adequately formulated to ensure its optimal delivery to dendritic cells in the vaccine draining lymph nodes. In the present paper, we report on the design of ssRNA nanocomplexes formed by complexation of the cationic poly(carbonic acid 2-dimethylamino-ethyl ester 1-methyl-2-(2-methacryloylamino)-ethyl ester) (pHPMA-DMAE) based polymeric carrier and ssRNA. The resulting ssRNA nanocomplexes were subsequently PEGylated through copper-free click chemistry using PEG-bicyclo[6.1.0]nonyne (PEG-BCN) and cross-linked via disulfide bonds to increase their stability. The obtained near-neutral charged PEGylated ssRNA nanocomplexes (~150 nm) combined ssRNA protection with highly efficient delivery of ssRNA to DCs in the vaccine draining lymph nodes after subcutanuously administration. When co-administrated with a model antigen (soluble ovalbumin (OVA)), ssRNA nanocomplexes were far more efficient at inducing CD8 cytolytic T cells when compared to OVA co-adminstarted with naked ssRNA. Furthermore, IgG2c antibody titers, indicative of Th1 skewed T cell responses, were >10 times increased by complexing ssRNA into the PEGylated nanocomplexes. This study highlights the potential of post-functionalizing ssRNA nanocomplexes by copper-free click chemistry and these findings indcate that this potent ssRNA adjuvant may profoundly improve the efficacy of a variety of vaccines requiring Th1-type immunity. [ABSTRACT FROM AUTHOR]

Very interesting issues regarding RCC treatment have been raised during 2017. We analysed the main news that may potentially modified clinical practice. Conflicting data came from trials testing targeted therapies in the adjuvant setting, supporting the necessity of further investigations. One of the key goals of RCC research is focused on the first-line therapy, with particular interest focus on immunotherapy combinations. Redefine the standard of care with the aim of improving patients' survival represents an imperative need. Enhancing immunotherapy antitumor activity by combining immune checkpoint inhibitors with anti-angiogenetic therapies is a noteworthy research field, with promising results. In addiction, we analysed in the metastatic setting data about the role of cytoreductive nephrectomy and the possibility of delay the start of first-line therapy after an active surveillance period. Based on recent developments, the paper outlines future prospective of RCC research. [ABSTRACT FROM AUTHOR]

H7N9 influenza infection in humans would result in severe respiratory illness. Vaccination is the best way to prevent influenza virus. In this paper, we investigated the effect of early protection provided by inactivated whole-virion H7N9 influenza vaccine in a mouse model. Mice were immunized intramuscularly once with different doses of inactivated whole-virion H7N9 influenza vaccine alone or in combination with MF59 adjuvant. Specific IgM and IgG antibody titers in sera of mice were detected by ELISA 3, 5 and 7days after immunization. To evaluate the early protection provided by the vaccine, mice were challenged with lethal dose (40LD 50 ) of homologous virus 3, 5 and 7 days after immunization respectively. The survival rate and body weight change of mice during 21 days after challenge and the residual lung virus titer on 3rd day after challenge were determined. The results demonstrated that mice could obtain effective protection 3 days after immunization with the vaccine at a high dose, and 5–7 days after immunization even at a low dose. Thus early immune responses induced by inactivated whole-virion H7N9 vaccine could provide effective protection. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a blood-borne pathogen which has chronically infected people worldwide. Therefore, it is of utmost importance to design prophylactic and therapeutic vaccine in order to control HCV infection. To date, several researchers have attempted to improve the efficiency of HCV vaccine by using different adjuvants. However, a few studies have focused on the synthetic immunomodulatory drugs as adjuvants for HCV vaccine. Recently, researchers have shown that lenalidomide, which is used to treat the patients with multiple myeloma, is capable of improving the immune system factors. In this paper, two doses of lenalidomide along with pcDNA3.1 + NS3 as HCV DNA vaccine were administrated in mice models and the percentage of regulatory T cells (Treg cells) and the cells with PD-1 + expression in spleen of mice model were investigated by flow cytometry method. Additionally, activities of CTL cells and NK cells were evaluated in spleen of prophylactic and therapeutic mice models via LDH method. Results of the Treg and PD-1 analysis showed that low dose of lenalidomide along with pcDNA3.1 + NS3 can noticeably decrease the percentage of Treg cells and the cells with PD-1 + expression, while lenalidomide can significantly increase the CTL and NK activity in mice models. Also, results of the therapeutic mice model, in which SP2/0 cells- challenged mice were treated with 5 mg/kg lenalidomide in combination with pcDNA3.1 + NS3, reasonably agreed with those of the prophylactic model. Finally, it was found that lenalidomide can reduce the level of Treg cells which results in lower the cells with PD-1 + expression and subsequently higher CTL and NK cell activities. This study concluded that lenalidomide possess the characteristics of an ideal adjuvant candidate for use in combination with HCV DNA vaccine in order to promote the immune response and vaccine efficiency. [ABSTRACT FROM AUTHOR]

[Display omitted] • TME and glycolysis promote the occurrence and metastasis of tumors. • The mRNA vaccine activates CTL, cooperative NK, and M1 cells to improve the TIME. • Using vectors enhances the anti-tumor effect of the mRNA vaccine by improving TIME. • An mRNA vaccine combined with adjuvants or ICIs inhibits tumor metastasis. With the increasing threat of tumors to humans, mRNA vaccine-based immunotherapy has received extensive attention; however, the killing effect is sometimes unsatisfactory. The occurrence of tumors is closely related to the abnormality of the tumor immune microenvironment, including the increase in the number of immunosuppressive cells, the anomaly of some cells with tumor-killing function, and the increase in the glycolysis pathway, all of which will affect the anti-tumor effect of mRNA vaccines. Furthermore, delivery in the body and successful escape from lysosome are also essential steps that involve the result of killing. Starting from inhibiting tumor growth and metastasis by mRNA vaccines, this paper summarizes the tumor microenvironment constructed by immunosuppressive cells and cytokines, which inhibit immune cells from exerting anti-tumor effects, emphasizing the increase of glycolytic pathway after tumor formation, which makes tumors have a high probability of metastasis. In the present study, mRNA vaccines adjust the number of immune cells by combining adjuvants or immune checkpoint inhibitors (ICIs), thereby improving the tumor immune microenvironment (TIME) and tilting the balance in favor of immune-potent cells can achieve better anti-tumor effects. All efforts to understand the relationship between TIME and mRNA vaccine will provide a basis for tumor treatment in the future. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria, viruses, fungi, parasites, and other microbes constantly change to ensure survival. Several pathogens have adopted strict and intricate strategies to fight medical treatments. Many drugs, frequently prescribed to treat these pathogens, are becoming obsolete and ineffective. Because pathogens have gained the capacity to tolerate or resist medications targeted at them, hence the term antimicrobial resistance (AMR), in that regard, many natural compounds have been routinely used as new antimicrobial agents to treat infections. Thus, plant lectins, the carbohydrate-binding proteins, have been targeted as promising drug candidates. This article reviewed more than 150 published papers on plant lectins with promising antibacterial and antifungal properties. We have also demonstrated how some plant lectins could express a synergistic action as adjuvants to boost the efficacy of obsolete or abandoned antimicrobial drugs. Emphasis has also been given to their plausible mechanism of action. The study further reports on the immunomodulatory effect of plant lectins and how they boost the immune system to curb or prevent infection. • Pathogenic bacteria, viruses, fungi and parasites frequently change to ensure survival. • Several microbes have adopted strict and intricate strategies to fight drugs that are made to kill them. • These strategic changes in microbes lead to microbes' resistance. • Plant lectins are carbohydrates-binding proteins which could recognize microbes' outer membrane glycans and may kill them. • This review discusses the possible future applications of plant lectins as antimicrobial. [ABSTRACT FROM AUTHOR]

Self-amplifying replicon RNA (RepRNA) are large molecules (12-14 kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) – absolute requirements for vaccine design – were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo , inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines. From the Clinical Editor The use of self-amplifying replicon RNA (RepRNA) to increase vaccine antigen payloads can potentially be useful in effective vaccine design. Nonetheless, its use is limited by the degradation during the uptake process. Here, the authors attempted to solve this problem by packaging RepRNA using polyethylenimine (PEI)-polyplex delivery vehicles. The efficacy was confirmed in vivo by the appropriate humoral and cellular immune responses. This novel delivery method may prove to be very useful for future vaccine design. [ABSTRACT FROM AUTHOR]

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ⩾2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18 000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients. [ABSTRACT FROM AUTHOR]

Recombinant subunit vaccines in general are poor immunogens likely due to the small size of peptides and proteins, combined with the lack or reduced presentation of repetitive motifs and missing complementary signal(s) for optimal triggering of the immune response. Therefore, recombinant subunit vaccines require enhancement by vaccine delivery vehicles in order to attain adequate protective immunity. Particle-based delivery platforms, including particulate antigens and particulate adjuvants, are promising delivery vehicles for modifying the way in which immunogens are presented to both the innate and adaptive immune systems. These particle delivery platforms can also co-deliver non-specific immunostimodulators as additional adjuvants. This paper reviews efforts and advances of the Particle-based delivery platforms in development of vaccines against malaria, a disease that claims over 600,000 lives per year, most of them are children under 5 years of age in sub-Sahara Africa. [ABSTRACT FROM AUTHOR]

The persistent incidence of high levels of multidrug-resistant (MDR) bacteria seriously endangers global public health. In response to MDR-associated infections, new antibacterial drugs and strategies are particularly needed. Screening to evaluate a potential compound to reverse antibiotic resistance is a good strategy to alleviate this crisis. In this paper, using high-throughput screening methods, we identified that oxyclozanide potentiated tetracycline antibiotics act against MDR bacterial pathogens by promoting intracellular accumulation of tetracycline in resistant bacteria. Furthermore, mechanistic studies demonstrated that oxyclozanide could directly kill bacteria by disrupting bacterial membrane and inducing the overproduction of bacterial reactive oxygen species. Oxyclozanide effectively reduced the production of virulence proteins in S. aureus and neutralized the produced α-hemolysin, thereby effectively alleviating the inflammatory response caused by bacteria. Finally, oxyclozanide significantly reversed tetracycline resistance in animal infection assays. In summary, these results demonstrated the capacity of oxyclozanide as a novel antibiotic adjuvant, antibacterial and anti-virulence multifunctional compound to circumvent MDR bacteria and improve the therapeutic effect of persistent infections caused by MDR bacteria worldwide. [Display omitted] • The discovery of a novel type of antibacterial and anti-virulence multifunctional antibacterial agent. • Oxyclozanide remarkably potentiated the activity of tetracycline against MDR bacteria. • Oxyclozanide eliminated the activity of hemolysin and biofilm while inhibiting the production of MRSA toxins. • Oxyclozanide reversed tetracycline resistance against MDR bacteria in vivo. [ABSTRACT FROM AUTHOR]

The development of efficient and cheap vaccines against several aquatic viruses is necessary for a sustainable fish farming industry. Toll-like receptor (TLR) ligands have already been used as good adjuvants in human vaccines. With more understanding of TLR expression, function, and ligand specificity in fish, more efficient adjuvants for fish viral vaccines can be developed. In this paper, we examine all known TLRs in Atlantic salmon ( Salmo salar ) and demonstrate that head kidney and spleen are the main organs expressing TLRs in salmon. We also show that adherent head kidney leucocytes from salmon are able to respond to many of the known agonists for human TLRs, and that viral infection can induce up-regulation of several TLRs. These findings substantiate these receptors’ role in immune responses to pathogens in salmonids making their ligands attractive as vaccine adjuvant candidates. [ABSTRACT FROM AUTHOR]

Abstract: Alum (or aluminum-containing) adjuvants are key components of many vaccines currently on the market. The immuno-potentiation effect of alum adjuvants is presumably due to their interaction with antigens, leading to adsorption on the alum particle surface. Understanding the mechanism of antigen adsorption/desorption and its influencing factors could provide guidance on formulation design and ensure proper in-vivo immuno-potentiation effect. In this paper, surface adsorption of several model proteins on two types of aluminum adjuvants (Alhydrogel® and Adjuphos®) are investigated to understand the underlying adsorption mechanisms, capacities, and potential influencing factors. It was found that electrostatic interactions are the major driving force for surface adsorption of all the model proteins except ovalbumin. Alhydrogel has a significantly higher adsorption capacity than Adjuphos. Several factors significantly change the adsorption capacity of both Alhydrogel and Adjuphos, including molecular weight of protein antigens, sodium chloride, phosphate buffer, denaturing agents, and size of aluminum particles. These important factors need to be carefully considered in the design of an effective protein antigen-based vaccine. [Copyright &y& Elsevier]

Abstract: The generation of both antibody and CD8+ T cell responses against pathogens is considered important for many advanced vaccines for diseases including tuberculosis, HIV and malaria. However, most current vaccines are delivered into muscle by the needle and syringe method and induce protection via humoral (antibody) immune responses. In this paper, we test the hypothesis that delivering a model subunit protein antigen (ovalbumin) to the skin''s abundant immune cell population using a densely packed microprojection array (Nanopatch) enhances CD8+ T cell responses. We found that the Nanopatch significantly enhanced the CD8+ T cell responses when compared to intramuscular delivery of both antigen-only and adjuvanted cases (Quil-A and CpG; separately). To our knowledge, this is the first published study demonstrating significantly improved CD8+ T cell responses achieved by delivering subunit vaccines to the skin''s abundant immune cell population. Successfully replicating these findings in humans could significantly advance the reach of vaccines. [Copyright &y& Elsevier]

Abstract: Induction of CD8+ T-cell responses is critical for the immunological control of a variety of diseases upon vaccination. Modern subunit vaccines are based on highly purified recombinant proteins. The high purity represents a major advancement in terms of vaccine safety compared to previous vaccination strategies with live attenuated or whole killed pathogens, but typically renders vaccine antigens poorly immunogenic and insufficient in mobilizing protective immunity. Adjuvants are therefore needed in vaccine formulations to enhance, direct and maintain the immune response to vaccine antigens. However, a weakness of many adjuvants is the lack of induction of CD8+ T-cell responses against protein antigens, which are required for protection against challenging and difficult infectious diseases such as AIDS and for therapeutic cancer vaccination. Within the last decade, adjuvant systems that can induce CD8+ T-cell responses have been developed and the first clinical trials demonstrating the clinical relevance of such formulations have been performed. This paper reviews the current status of lipid- and polymer-based particulate antigen delivery systems capable of stimulating CD8+ T-cell immunity with special focus on mechanisms of priming and pharmaceutical requirements for optimal activation of cytotoxic T-lymphocytes that can kill virus-infected or abnormal (cancer) cells. [Copyright &y& Elsevier]

Abstract: Recently we reported that reacetylation of N,N,N-trimethyl chitosan (TMC) reduced the adjuvant effect of TMC in mice after intranasal (i.n.) administration of whole inactivated influenza virus (WIV) vaccine. The aim of the present study was to elucidate the mechanism of this lack of adjuvanticity. Reacetylated TMC (TMC-RA, degree of acetylation 54%) was compared with TMC (degree of acetylation 17%) at six potentially critical steps in the induction of an immune response after i.n. administration in mice. TMC-RA was degraded in a nasal wash to a slightly larger extent than TMC. The local i.n. distribution and nasal clearance of WIV were similar for both TMC types. Fluorescently labeled WIV was taken up more efficiently by Calu-3 cells when formulated with TMC-RA compared to TMC and both TMCs significantly reduced transport of WIV over a Calu-3 monolayer. Murine bone-marrow derived dendritic cell activation was similar for plain WIV, and WIV formulated with TMC-RA or TMC. The inferior adjuvant effect in mice of TMC-RA over that of TMC might be caused by a slightly lower stability of TMC-RA–WIV in the nasal cavity, rather than by any of the other factors studied in this paper. [Copyright &y& Elsevier]

Abstract: This paper provides an overview of the legislations and regulatory approaches currently applied to the nonclinical safety assessment of human preventive vaccine products in three ICH regions, i.e., the EU, USA, and Japan. Perspectives of the three regions with regard to the various types of toxicity studies currently considered to assess the nonclinical safety of preventive vaccines are compared and described in more detail than in published guidelines. In addition, the common issues and current challenges in nonclinical safety assessment of preventive vaccines are discussed. [Copyright &y& Elsevier]

Background: Trastuzumab-based adjuvant therapy has become the standard of care for human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (EBC). Both anthracycline- and non-anthracycline-containing trastuzumab regimens are approved in the United States, but cardiotoxicity is increased with anthracycline-containing regimens.Design: This paper reviews published and reported efficacy and cardiac safety data from the adjuvant trastuzumab trials [National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31/North Central Cancer Treatment Group (NCCTG) N9831, Breast Cancer International Research Group (BCIRG) 006, Herceptin Adjuvant (HERA), FinHer, and Programme Adjuvant Cancer Sein (PACS) 04].Results: The addition of trastuzumab to adjuvant chemotherapy significantly improved disease-free survival (from 24% to 58%) in five of the six trials. Overall survival was significantly improved (23%–35%) in the large trials. In NSABP B-31/ NCCTG N9831, 5.0%–6.6% of patients who received doxorubicin and cyclophosphamide (AC) were unable to receive trastuzumab. Cardiac event rate was highest in the anthracycline-containing trastuzumab arms (1.9%–3.8%) and lowest with the regimen of docetaxel, carboplatin, and trastuzumab (TCH) (0.4%).Conclusions: Incorporation of trastuzumab into anthracycline and non-anthracycline adjuvant chemotherapy regimens has substantially improved outcomes in HER2-postive EBC. The TCH regimen has the lowest rates of cardiac dysfunction, but uncertainty exists regarding the relative efficacy of TCH compared with anthracycline-containing trastuzumab regimens. Cardiac risk factor assessment can aid in selection of trastuzumab-based adjuvant therapy regimens. [ABSTRACT FROM PUBLISHER]

Abstract: Traditionally, the role of hormonal therapy (HT) for prostate cancer (PCa) has been the palliative treatment of advanced and metastatic disease. Recently, advances in the development of androgen-deprivation therapy (ADT) with luteinising hormone-releasing hormone (LHRH) agonists have made LHRH agonists the standard of care for 90% of men with advanced or metastatic PCa. Although the role of ADT is historically well defined, recent studies demonstrate that the treatment of advanced or metastatic PCa with ADT can be tailored to the needs of the patient. This may be achieved by the immediate or deferred initiation of ADT (orchiectomy or LHRH agonist treatment) depending upon the nature of the disease and the patient''s age. Patients who are likely to die of non-PCa-related causes prior to an indication for treatment initiation, for example, may benefit from deferred treatment, which may spare them the burden of treatment-related adverse events. In contrast, patients who are likely to die of PCa-related causes may benefit from immediate treatment because this option may delay disease progression and reduce symptom burden. Additionally, recent studies have shown that prognostic disease markers such as prostate-specific antigen (PSA) and PSA doubling time (PSA DT) can be used as indicators of who may receive the greatest benefit from treatment. Patients with a high baseline PSA level or a short PSA DT (markers of aggressive and/or advanced disease), for example, are more likely to die of disease-related causes than patients with low baseline PSA levels or long PSA DT. Furthermore, recent studies have shown that HT may be used successfully in adjuvant settings for patients in earlier stages of the disease and/or who require radical treatment. This paper reviews which patients can benefit from HT in terms of treatment timing, baseline prognostic indicators, disease stage, and adjuvant use. [Copyright &y& Elsevier]

Abstract: Subunit vaccines are generally safer, but often less effective than live attenuated vaccines as they lack the necessary co-stimulatory factors. The formulation of an adjuvant like N-trimethyl chitosan (TMC) with an antigen can overcome its poor immunogenicity. Recent data suggest the importance of incorporating the antigen and the adjuvant into one entity for maximum immunostimulatory effect, e.g. by using (nano)particles. In the present paper we introduce the conjugation of an antigen, ovalbumin (OVA), to TMC as an alternative to nanoparticles for subunit vaccination. OVA was covalently linked to TMC using thiol chemistry (SPDP method). The uptake of the resulting TMC–OVA conjugate by dendritic cells (DC) and its effect on DC maturation was assessed in vitro and its immunogenicity was investigated in mice. We found that with the SPDP method a reducible covalent bond between TMC and OVA could be introduced, without disrupting the protein''s antigenicity and structure. Uptake of TMC–OVA conjugate by dendritic cells was similar to the uptake of TMC/OVA nanoparticles, over 5-fold increased compared to a solution of OVA and TMC. Mice immunized with TMC–OVA conjugate produced 1000-fold higher OVA specific IgG titers than mice immunized with either OVA or a physical mixture of TMC and OVA. Moreover, these antibody titers were slightly elevated compared to the titers obtained with TMC/OVA nanoparticles. Conjugation of the antigen to an adjuvant is therefore a viable strategy to increase the immunogenicity of subunit vaccines and may provide an alternative to the use of particles. [Copyright &y& Elsevier]

Abstract: Adjuvant use of nutritional and herbal medicines has potential to increase the efficacy of synthetic pharmaceuticals, and perhaps also decrease their side-effects by allowing lower doses to be prescribed. We evaluated current evidence for adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines; and explored novel future areas of research. The paper also critiques current evidence for co-administration of St. John’s wort with synthetic antidepressants. We performed a systematic search of MEDLINE, CINAHL, PsycINFO, The Cochrane database, China National Knowledge Infrastructure and the Chinese Science Citation Database. Search results were supplemented by a review of reference lists and a forward search using the Web of Science. Where possible we calculated effect sizes. Encouraging evidence exists for the use of omega-3 fatty acids, SAMe, folic acid and l-tryptophan adjuvantly with antidepressants to enhance response and improve efficacy. Various nutrients also have emerging evidence as effective adjuncts with antipsychotics and mood stabilizers. While some evidence supports nutritional adjuvancy with various psychopharmacotherapies, adjuvant use of herbal therapies has not been sufficiently studied to warrant standard clinical application. This remains a promising area of research via robust, safety-conscious studies. [Copyright &y& Elsevier]

Abstract: Squalene is a natural lipid belonging to the terpenoid family and a precursor of cholesterol biosynthesis. It is synthesized in humans and also in a wide array of organisms and substances, from sharks to olives and even bran, among others. Because of its significant dietary benefits, biocompatibility, inertness, and other advantageous properties, squalene is extensively used as an excipient in pharmaceutical formulations for disease management and therapy. In addition, squalene acts as a protective agent and has been shown to decrease chemotherapy-induced side-effects. Moreover, squalene alone exhibits chemopreventive activity. Although it is a weak inhibitor of tumor cell proliferation, it contributes either directly or indirectly to the treatment of cancer due to its potentiation effect. In addition, squalene enhances the immune response to various associated antigens, and it is therefore being investigated for vaccine delivery applications. Since this triterpene is well absorbed orally, it has been used to improve the oral delivery of therapeutic molecules. All of these qualities have rendered squalene a potentially interesting excipient for pharmaceutical applications, especially for the delivery of vaccines, drugs, genes, and other biological substances. This paper is the first review of its kind and offers greater insight into squalene''s direct or indirect contribution to disease management and therapy. [Copyright &y& Elsevier]

Abstract: Markers that predict the sensitivity of tumours to chemotherapy must address two questions: (a) which tumours are more likely to respond to chemotherapy? and (b) what is the optimal chemotherapy regimen for a specific tumour or group of tumours? To answer these questions will require markers of general chemosensitivity and drug-specific chemosensitivity, respectively. Beyond these fundamental questions lies an important practical question: are the predictive markers in the current literature ready for routine clinical use? The focus of this paper is to address this practical question. We will first review retrospective trials that have reported promising chemotherapy signatures, presenting in a comprehensive manner for the non bio-informatician the different methods used so far. In addition, we will summarise prospective trials (either ongoing or under development) designed to test the multigene classifiers currently thought to predict chemosensitivity. Finally, we will discuss why microarray studies have so far failed to identify new targets, and how we might be able to improve on these results through large-scale genotyping of tumours. [Copyright &y& Elsevier]

Summary: Several randomized trials investigating the benefit of adjuvant chemotherapy after surgery in non-small cell lung cancer (NSCLC) have provided conflicting results. With over 7000 patients included, we analyzed results of 13 reports over the past 10 years in which patients received either platinum-containing chemotherapy or not. The major endpoint was to assess the magnitude of the benefit of adjuvant chemotherapy in terms of the absolute benefit. All phase III randomized trials and meta-analyses published as peer-reviewed papers or as abstracts from 1994 to 2007 were eligible. A literature-based meta-analysis was performed; event-based overall- and disease-free survival (OS/DFS) and Relative Risks (RRs) with 95% confidence intervals (CIs) were derived. Magnitudes of benefit were evaluated with: absolute benefit and the number of patients treated for one patient to benefit. Seven sub-populations were examined. Combined effect estimation was computed with fixed- and random-effect models; a heterogeneity test was also applied. Twelve trials plus an individual patient meta-analysis (7334 patients) were gathered; the trials were designed to determine if cisplatin- or carboplatin-based chemotherapy improves survival over surgery. When data were pooled and plotted, significant differences in favor of chemotherapy were seen in OS in all seven sub-population, with a relative benefit of 7–12% and an absolute benefit ranging from 2.5% to 4.1%. A more significant trend for chemotherapy was found in DFS. No significant heterogeneity was observed for all outcomes and sub-populations. The absolute benefit of adjuvant chemotherapy remains essentially the same regardless of how data are screened. While significant differences are clearly found in this analysis, the small magnitude of benefit seen with this large population, especially when considering the number of patients needed for one to benefit, raises important issues when weighing risks and benefits of treatment for individual patients. [Copyright &y& Elsevier]

[Display omitted] While classic vaccines have proved greatly efficacious in eliminating serious infectious diseases, innovative vaccine platforms open a new pathway to overcome dangerous pandemics via the development of safe and effective formulations. Such platforms play a key role either as antigen delivery systems or as immune-stimulators that induce both innate and adaptive immune responses. Liposomes or lipid nanoparticles, virus-like particles, nanoemulsions, polymeric or inorganic nanoparticles, as well as viral vectors, all belong to the nanoscale and are the main categories of innovative vaccines that are currently on the market or in clinical and preclinical phases. In this paper, we review the above formulations used in vaccinology and we discuss their connection with the development of safe and effective prophylactic vaccines against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Abstract: The need to enhance the immunogenicity of purified subunit antigens has prompted the development of new adjuvants. The adjuvant emulsion MF59™ has been tested in animals in combination with different antigens and finally evaluated in humans. It was licensed after the successful outcome of preclinical and clinical testing. This paper summarizes the main characteristics of the MF59™ adjuvant, including animal testing, clinical experience with various vaccines, and information from current postmarketing surveillance data. This review supports the hypothesis that MF59™ is a safe adjuvant for human use. [Copyright &y& Elsevier]

Abstract: Objectives: This paper reviews the latest technologic developments in the field of external-beam radiation therapy (RT) for prostate cancer (PCa) and their clinical applications in the postprostatectomy setting and in conjunction with hormonal manipulation. Methods: This review is based on a presentation during the New Horizons in Urology 2007 meeting held in Monte Carlo, Monaco, and includes relevant data from recently published literature. Results: Modern computer imaging, for example, computer tomography or magnetic resonance imaging, allows three-dimensional treatment planning techniques and a better definition and delineation of the target (prostate with or without seminal vesicles) and of the organs at risk (rectum, bladder, and penile bulb). Intensity-modulated RT and image-guided RT approaches are now available for the RT of PCa. Several phase 3 randomized clinical trials have demonstrated that immediate adjuvant RT after radical prostatectomy (RP) for patients at high risk for local relapse is associated with improved biochemical-free survival and clinical progression-free survival, compared to salvage RT. Furthermore, for high-risk, locally advanced PCa, androgen-deprivation therapy (ADT) combined with RT has shown better overall survival, compared to RT alone and recent data have revealed that 3 yr of adjuvant ADT after RT is superior to 6 mo for this subgroup of patients. Conclusions: Technologic progress has contributed to improved RT results in clinically localized and locally advanced PCa. Immediate, adjuvant RT should be considered for patients with high-risk pathologic features after RP. For patients with locally advanced PCa, ADT combined with RT yields better outcomes than RT alone. [Copyright &y& Elsevier]

Summary: The 2003 St. Gallen consensus panel divided the many available adjuvant chemotherapy (CT) regimens into those with “standard efficacy” (AC×4, CMF×6) and those with “superior efficacy” (FA(E)C×6, CA(E)F×6, A(E)→CMF, TAC×6, AC×4→ paclitaxel (P)×4 or docetaxel (D)×4) but also greater complexity, toxicity and cost. This paper will summarize the latest information on long-term side effects of the “superior” regimens and 5-year benefits reported in taxane trials, including those of a “new” sequential regimen, FEC×3→ docetaxel×3. Rapidly expanding evidence of marked heterogeneity in the magnitude of CT benefits according to the tumour oestrogen receptor (ER) status, a claim made for many years by IBCSG investigators, will be reviewed; it will lead to the conclusion that a revolution needs to take place in the way oncologists think about the CT added value and design adjuvant clinical trials. The conclusions proposed to the 2005 St. Gallen consensus panel are that: adequately dosed anthracycline-based CT regimens remain an acceptable standard for many women; a lower threshold for using taxanes in sequence or combination with anthracyclines (A) is justified in the presence of an ER-negative or low-ER tumour status, other aggressive biologic features (such as HER-2 overexpression), fear about A-induced cardiotoxicity; no recommendation can yet be made as far as the optimal taxane-A regimen, the best taxane or the best taxane schedule. [Copyright &y& Elsevier]

Abstract: Colorectal adenocarcinoma ranks second as a cause of death due to cancer in the Western world. In Europe, 40% of patients with this disease is over 70 years old and only 52% of them with positive nodes usually receive an adjuvant chemotherapy. Despite early reports to the contrary, these patients tolerate cancer treatment and surgical resections as well as their younger counterparts but as a result of exclusion criteria, those receiving an adjuvant therapy are very few. This paper examines the factors pertinent to the small number of clinical trials designed for adjuvant colorectal cancer in the elderly. [Copyright &y& Elsevier]

Abstract: Advances in molecular biology and biotechnology, coupled with an increased understanding of disease processes and mechanisms of protective immunity have facilitated the development of new rationally-designed vaccines utilising recombinant proteins, naked DNA, live vectors, genetically-modified toxins and whole dendritic and tumour cells for both prophylaxis and therapy of a wide range of indications. These new vaccine technologies coupled with novel adjuvants, delivery systems, formulations, dosing routes and regimes present many unique and difficult challenges in demonstrating product safety and efficacy to support clinical testing. This paper aims to review these novel vaccine and adjuvant technologies and to highlight the key safety issues potentially associated with them. Approaches taken to demonstrate vaccine safety by assessing systemic and local toxicity, biodistribution and persistence, immunogenicity and immunotoxicity, reproductive toxicology, safety pharmacology and genotoxicity within the current regulatory framework are presented. [Copyright &y& Elsevier]

Current attempts at active immunization of patients to their adenocarcinomas have heretofore met with a curiously little success. The carrier antigens, viral vector proteins, and other co-administered antigens typically elicit strong cell-mediated or humoral responses while the relevant cancer antigen elicits undetectable or feeble responses and often minimal if any retardation of malignant tissue growth is seen. There are exceptions but clearly more effective cancer antigen immunization strategies are needed. Adenylate cyclase, AC, catalyses the conversion of ATP to cyclic adenosine monophosphate (cAMP). Increased cAMP down regulates tumor necrosis factor-alpha, TNF, and decreased cAMP reliably up-regulates synthesis and release of TNF. TNF enhances dendritic cell (DC) maturation processes started by other stimuli. TNF promotes antigen responding CD4+ and CD8+ lymphocytes’ proliferation, and suppresses suppressor T cells during primary immunization. Tenofovir is an oral antiviral drug currently used in anti-HIV treatments. It is an acyclic nucleoside analogue of adenosine monophosphate that also happens to increase TNF. The mechanism has not been established but antagonism of cAMP’s inhibition of TNF is the likely path. Prostaglandin E (PGE) is a stimulatory allosteric modifier of AC and thus suppresses TNF via the resultant increase of cAMP. Since cyclooxygenase, COX, is the rate-controlling enzyme in PGE production, COX inhibitors, otherwise known as non-steroidal anti-inflammatory drugs (NSAID), increase TNF synthesis and release by depriving AC of PGE. Indomethacin, diclofenac and ketorolac are COX inhibitors that have been on the market for many years that would be well suited for use to increase TNF levels. This paper reviews the data on TNF up-regulation by tenofovir and COX inhibitors and the consequent augmented antigen driven lymphocyte proliferation secondary to increased TNF and suggests exploration of tenofovir and COX inhibitors like indomethacin, diclofenac or ketorolac in augmentation of current cancer immunotherapy attempts. Profound COX inhibition can lead to a compensatory leukotriene increase and leukotrienes have been identified as growth and survival factors in various gastrointestinal cancers. Therefore, zileuton, an orally active 5-lipooxygenase inhibitor that prevents leukotriene synthesis, should be added whenever profound COX inhibition is undertaken in cancer immunotherapies. [Copyright &y& Elsevier]

A recombinant form of the outer membrane protein (A-layer protein) associated with atypical Aeromonas salmonicida was expressed, fused to a cellulose binding domain (CBD) isolated from Clostridium cellulovorans. The resultant chimerical protein was bound to either Sigmacell 20® or Orbicell™ cellulose particles. Common goldfish were injected intraperitoneally with the cellulose–protein complex and blood serum antibody levels produced against A-protein were examined weekly by means of ELISA. These titers were compared to those induced by immunization of goldfish with the same protein, with or without Freund’s incomplete adjuvant, as well as to a standard bacterin-adjuvant system. Small Orbicell beads (1–10 μM) induced antibody levels that were equal to the titers produced by the adjuvanted protein and bacterin formulae. In comparison, the larger Sigmacell particles (10–20 μM) proved to be poor immunopotentiators. The long-term titer elicited from a single injection of A-protein bound to Orbicell beads was equivalent to that induced by two injections. All the vaccinated fish demonstrated memory to the A-layer protein after exposure to a pathogenic load of atypical A. salmonicida with Orbicell treated fish displaying the highest titer. No direct correlation was found between the presence of anti-A-protein antibodies and protection against infection. The paper describes a simple and safe method to increase the potential immunogenicity of soluble recombinant proteins by employing relatively inexpensive cellulose particles. [Copyright &y& Elsevier]

Most mammalian immune systems and parasites have co-evolved over the millennia, interacting within a common environment and communicating through a common language. This language is comprised of copious dialects in which a variety of host innate and acquired immune pathways actively interact with a multitude of parasite-specific survival strategies. Nonetheless, a simplified language is likely present since the same basic molecular and cellular mechanisms are associated with resistance or susceptibility to parasite infection. Protective immunity against protozoa within the phylum Apicomplexa (e.g. Cryptosporidia, Eimeria, Neospora, Plasmodia and Toxoplasma) is generally CD4+ T cell-dependent and elicited along the IL-12/IFN-γ/iNOS effector axis. This simplified language can be decoded in part by significant advances in understanding naı¨ve T cell activation, differentiation and generation of immunologic memory. Vaccine adjuvants and new immunisation strategies for generation of more potent immunity can also be viewed through this common language lens. The aim of this paper is to summarise recently published fundamental immunology studies, their relevance through examples in specific coccidian-host immune dialects, and how this simplified language can be used for the more rationale design of parasite vaccine control strategies. [Copyright &y& Elsevier]

Dendritic cells (DCs) are recognized as the sole professional antigen-presenting cells capable of priming naive T cells of the helper and cytotoxic phenotypes. This property is presently exploited with success in vaccinal strategies against pathogens or tumor cells that otherwise escape immune recognition, but the repeated infusions of ex vivo expanded and sensitized DCs are usually required to achieve protection. In this paper, we demonstrate that liposomal antigens can efficiently relay and propagate the action of DCs, inducing a strong long-term response against their associated antigen. Their effect is mainly achieved by improving the ex vivo loading of DCs and by efficiently channeling the activation stimulus into the induction of effector function. This is demonstrated by the sustained immunoglobulin production as well as by the sustained lymphoproliferation and the increased cytokine secretion that can be achieved upon restimulation of DC-primed immune cells with limited amount of liposomal antigenic material. Being well-tolerated and easily prepared, liposomal antigens could therefore be expected to significantly contribute to the efficiency and to a more general utilization of the highly promising but rather cumbersome DC-based immunotherapies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Liposomes self-assembled from lipids are excellent targeted transport carrier materials. • Lipids have the role of immune stimulation, which can stimulate the effect of innate immunity. • Liposomes combined with targeted transport and immunostimulatory effects have great advantages in cancer vaccines. Cancer is still a major threat for human life, and the cancer immunotherapy can be more optimized to prolong life. However, the effect of immunotherapy is not encouraging. In order to achieve outstanding immune effect, it is necessary to strengthen antigens uptake of antigen presenting cells. Adjuvants were added to vaccines to achieve this purpose, which could be divided into two types: as an immunostimulatory molecule, the innate immunities of the body were triggered; or as a delivery carrier, and antigens were cross-delivery through the "cytoplasmic pathway" and released at a specific location. This paper reviewed the relevant research status of tumor vaccine immune adjuvants in recent years. Among the review, the function, combination strategies and derivatives of lipid A were discussed in detail. In addition, some suggestions on the existing problems and research direction of lipids as tumor vaccine adjuvants were put forward. [ABSTRACT FROM AUTHOR]

• Discusses the importance of adjuvants in the development of a vaccine against SARS-CoV-2. • Summarizes the results of clinical vaccine studies on similar coronaviruses with various adjuvants. • Discusses the current progress in the development of adjuvanted vaccines against COVID-19. The extensive efforts around the globe are being made to develop a suitable vaccine against COVID-19 (Coronavirus Disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). An effective vaccine should be able to induce high titers of neutralizing antibodies to prevent the virus from attaching to the host cell receptors. However, to elicit the protective levels of antibodies, a vaccine may require multiple doses or assistance from other immunostimulatory molecules. Further, the vaccine should be able to induce protective levels of antibodies rapidly with the least amount of antigen used. This decreases the cost of a vaccine and makes it affordable. As the pandemic has hit most countries across the globe, there will be an overwhelming demand for the vaccine in a quick time. Incorporating a suitable adjuvant in a SARS-CoV-2 vaccine may address these requirements. This review paper will discuss the experimental results of the adjuvanted vaccine studies with similar coronaviruses (CoVs) which might be useful to select an appropriate adjuvant for a vaccine against rapidly emerging SARS-CoV-2. We also discuss the current progress in the development of adjuvanted vaccines against the disease. [ABSTRACT FROM AUTHOR]

• Adjuvant CV13 could prepare stable W/O/W emulsion by one-step emulsification. • Adjuvant CV13 containing GSLS had shown a good immune synergistic effect. • FMD vaccine prepared with CV13 containing GSLS induced high level of immune response. There has been an increasing interest in finding new formulations that qualify as vaccine adjuvants, which must be safe, stable, and have the capacity to stimulate a strong immune response. In this study, a basic formulation of a water-in-oil-in-water (W/O/W) adjuvant CV13 was developed, and ginseng stem-leaf saponins (GSLS) were added as an immune booster into oil phase. The physicochemical properties of the adjuvant were tested. Furthermore, the immune activity and the adjuvant effects, as indicated by the foot-and-mouth disease virus (FMDV) antigen were evaluated. The results showed that CV13 was similar in appearance to ISA 206 and could package FMDV antigen into a stable W/O/W emulsion. The FMD vaccine prepared with CV13 alone or CV13 containing GSLS achieved pharmaceutical characteristics comparable to a vaccine prepared with ISA 206, moreover the structural stability of the CV 13 vaccine was found to be better. Mice that were immunized with the FMD vaccine prepared with CV13 containing GSLS presented a significantly higher LPBE antibody titer and splenocyte proliferation rate than those immunized with a vaccine prepared with CV13 alone (p < 0.05). In addition, there was no significant difference between the groups that were immunized with FMD vaccine prepared with CV13 containing GSLS and ISA206 in terms of cellular and humoral immune response. In this paper, CV13 containing GSLS shows excellent immunologic adjuvant effect in mice model, and this new adjuvant may provide a potential choice for FMD vaccine production in the future. [ABSTRACT FROM AUTHOR]

6,6 ′ -Aryl trehalose derivatives have been synthesized with a view towards identifying novel Th-17-inducing vaccine adjuvants based on the high affinity Mincle ligand Brartemicin. The initial structure-activity relationships of these novel trehalose-based compounds were investigated. All compounds have been evaluated for their ability to engage the Mincle receptor and induce a potential pro-Th17 cytokine profile from human peripheral blood mononuclear cells based on IL-6 production in human peripheral blood mononuclear cells. The preliminary biological characterization of the designed analogs presented in this paper should aid in the future design and testing of more affine ligands that may foster the discovery of novel adjuvants with improved pharmacological properties. [ABSTRACT FROM AUTHOR]

Most pathogens enter the body through mucosal surfaces. Therefore, vaccination through the mucosal route can greatly enhance the mucosal immune response. Vaccination via the mucosal surface is the most effective way to trigger a protective mucosal immune response, but the vast majority of vaccines used are administered by injection. Strategies to enhance the mucosal immunity have been developed by using vaccine adjuvants, delivery systems, bacterial or viral vectors, and DNA vaccines. Appropriate vaccine adjuvants and drug delivery systems can improve the immunogenicity of antigens, induce a stronger immune response, and reduce the vaccine dose and production cost. In recent years, many studies have focused on finding safe and effective vaccine adjuvants and drug delivery systems to formulate the mucosal vaccines for solving the above problems. Great progress has also been made in vaccine adjuvants and drug delivery systems based on biodegradable polymer nanoparticles. In this paper, the research progress of the mucosal vaccine and its related adjuvants and drug delivery systems in recent years was reviewed, and the application of polymers as adjuvants and drug delivery system in vaccine was prospected. This review provides a fundamental knowledge for the application of biodegradable polymer nanoparticles as adjuvants and carriers in mucosal vaccines and shows great application prospects. [ABSTRACT FROM AUTHOR]

Dr. R.K. Gherardi presented two papers at the symposium, detailing his researches into a proposed new clinical entity which he has entitled Macrophagic Myofasciitis (MMF). In his first paper he described the histopathologic and immunologic characteristics of the condition, and in the second, the clinical and serologic features. Dr. Gherardi believes that MMF, a syndrome of ascending myalgias, fatigue and diffuse musculoskeletal pain, may be related to a chronic immune response to aluminum granulomas persisting at the sites of prior immunization with aluminum adjuvated vaccines. [Copyright &y& Elsevier]

Luminal breast cancers demonstrate significant molecular and clinical heterogeneity, despite the commonality of shared expression of the estrogen receptor (ER). To date, no clinical trial has prospectively investigated the optimal chemotherapy regime according to luminal type, highlighting a paucity of data furthermore required to guide treatment decisions. Current methods of predicting advantage from adjuvant chemotherapy lack refinement and can over-estimate the risk of relapse, inevitably leading to a proportion of patients being unnecessarily exposed to chemotherapy. This paper will explore the evidence behind modalities which may add further value to existing known clinicopathological and molecular profiling techniques in predicting clinical benefit from chemotherapy. Adjuvant chemotherapy regime choice in the context of early luminal breast cancer types will be discussed, and areas for further research and debate identified. [ABSTRACT FROM AUTHOR]

The molecular subtypes of breast cancer have individual patterns of behaviour, prognosis and sensitivity to treatment, with subsequent implications for the choice of, or indeed role for adjuvant therapy. The luminal A and B subtypes make up the majority of breast cancers, but despite sharing expression of the oestrogen receptor (ER), they are molecularly distinct. It follows then that they would have different sensitivities to chemotherapy. Clinically, luminal A disease has a better prognosis than luminal B, and may not derive significant benefit from adjuvant chemotherapy. However no prospective trials have specifically investigated the benefit of adjuvant chemotherapy in each subtype, nor do we know if certain agents are more or less effective. This paper will briefly summarise the role of molecular profiles in assessing the need for chemotherapy and predicting its effectiveness, followed by an assessment of the relative value of newer anthracycline- or taxane-containing regimes in the luminal-like subtypes, providing a review of retrospective analyses. [ABSTRACT FROM AUTHOR]

There is growing evidence that obesity is associated with poor outcomes in early stage breast cancer. This paper addresses four current areas of focus: 1. Is obesity associated with poor outcomes in all biologic subtypes of breast cancer? 2. Does obesity effect AI efficacy or estrogen suppression in the adjuvant setting? 3. What are the potential biologic underpinnings of the obesity-breast cancer association? 4. Are intervention studies warranted? If so, which interventions in which populations? Research is needed to resolve these questions; intervention trials involving lifestyle interventions or targeting the biology postulated to link obesity and cancer are recommended. [ABSTRACT FROM AUTHOR]

A safety signal around Pandemrix, an AS03 adjuvanted influenza A(H1N1) pdm09 vaccine potentially causing narcolepsy in children and adolescents became public in August 2010, long after cessation of the influenza A(H1N1) pdm09 campaigns in Europe. The signal originated from Finland and Sweden, two countries with school based pandemic vaccination campaigns, with high vaccine coverage, and vaccinations being provided at the peak of the circulating wild virus. Since the announcement awareness grew in Europe, with extensive public media dissemination and regulatory actions. This resulted in a steep increase in the spontaneous reports of exposed cases, a decrease in diagnostic lag times of this rare, underdiagnosed disease and finally victim compensation. The signaling countries conducted rapid risk assessment studies to quantify the signal to the best of their abilities, in the midst of the public awareness, most of which could not distinguish between a vaccine and an awareness effect. Due to the strong but variable associations from the epidemiological studies, the search for biological mechanisms started. Currently it is not yet understood how Pandemrix might cause narcolepsy, and whether it would be specific to Pandemrix. The paper describes the current evidence and puts forward the questions that remain to be answered, which are relevant for future pandemic preparedness when adjuvants may be used for dose sparing. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the outcome of patients with head and neck adenoid cystic carcinoma (ACC) treated using pencil beam scanning proton therapy (PBS PT) at our institution.Materials and Methods: Thirty-five patients who underwent treatment with PBS PT for ACC between 2001 and 2017 were included. Local control (LC), distant control (DC), progression-free survival (PFS), overall survival (OS) and their prognostic factors were evaluated. Adverse effects were prospectively assessed.Results: The median patient follow-up was 30 months. Prior to PT, 26 patients (74.3%) underwent surgery with R0/R1/R2 outcome in 5, 13 and 8 cases, respectively. Nine patients (25.7%) presented with inoperable disease. The 2-year LC, DC, PFS and OS was 92.2%, 77.8%, 74.3% and 88.8%, respectively. LC was influenced by patient age (p = 0.002) with a significant difference between local and distant failure (median 61.3 vs. 42.3 years, p = 0.005). Tumor T stage was a significant risk factor for PFS (p = 0.045) and tumor prognostic group affected OS (p = 0.049). No significant survival advantage for operable vs. inoperable disease could be identified. The acute and late grade 3 toxicity rates were 14.3% and 6.1%, respectively. No acute or late grade 4/5 toxicities were observed.Conclusions: PBS PT is an effective and safe treatment for patients with head & neck ACC in both definitive and adjuvant setting. Distant metastases are the main pattern of failure. Age, tumor stage and clinical stage had a significant negative impact on LC, OS and PFS. [ABSTRACT FROM AUTHOR]