Assessment of Cancer-Related Fatigue,Pain, and Quality of Life in Cancer Patients at Palliative Care Team Referral: A Multicenter Observational Study (JORTC PAL-09)

Introduction

Cancer-related fatigue greatly influences quality of life in cancer patients; however, no specific treatments have been established for cancer-related fatigue, and at present, no medication has been approved in Japan. Systematic research using patient-reported outcome to examine symptoms, particularly fatigue, has not been conducted in palliative care settings in Japan. The objective was to evaluate fatigue, pain, and quality of life in cancer patients at the point of intervention by palliative care teams.

Materials and Methods

Patients who were referred to palliative care teams at three institutions and met the inclusion criteria were invited to complete the Brief Fatigue Inventory, Brief Pain Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative.

Results

Of 183 patients recruited, the majority (85.8%) were diagnosed with recurrence or metastasis. The largest group (42.6%) comprised lung cancer patients, of whom 67.2% had an Eastern Cooperative Oncology Group Performance Status of 0–1. The mean value for global health status/quality of life was 41.4, and the highest mean European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative symptom item score was for pain (51.0). The mean global fatigue score was 4.1, and 9.8%, 30.6%, 38.7%, and 20.8% of patients’ fatigue severity was classified as none (score 0), mild (1–3), moderate (4–6), and severe (7–10), respectively.

Discussion

Cancer-related fatigue, considered to occur more frequently in cancer patients, was successfully assessed using patient-reported outcomes with the Brief Fatigue Inventory for the first time in Japan. Results suggested that fatigue is potentially as problematic as pain, which is the main reason for palliative care.     

2-Cys peroxiredoxin of Plasmodium falciparum is involved in resistance to heat stress of the parasite

In the cytoplasm of Plasmodium falciparum, two peroxiredoxins: PfTPx-1 and Pf1-Cys-Prx, are expressed at different time-points of the parasite cell cycle during the intraerythrocytic stage. In the present study, to gain insight into the functions of Prxs in the cytoplasm of P. falciparum, we investigated the heat stress sensitivity of the previously established PfTPx-1 KO line and found that PfTPx-1 disruption renders the parasite hypersensitive to heat stress. In addition, we established Pf1-Cys-Prx knockout (KO) parasite lines. The phenotypes of Pf1-Cys-Prx KO lines were different to those of the PfTPx-1 KO line and did not show hypersensitivity to reactive oxygen species, reactive nitrogen species, chloroquine or heat stress. These results suggest that the function of Pf1-Cys-Prx in the parasite cytoplasm is independent from that of PfTPx-1. The hyperthermal protective function of the PfTPx-1 is obviously important for the parasite physiology in the human patient body, in which it must survive repeated incidences of fever.     

Cephalic lateral line canal system of the golden venus chub, <Emphasis Type="Italic">Hemigrammocypris rasborella</Emphasis> (Teleostei: Cypriniformes)

We investigated the cephalic lateral line canal system of the golden venus chub, Hemigrammocypris rasborella. The cephalic lateral line canal system consists of the infraorbital canal (IOC), the preopercular canal (POC), the mandibular canal (MC), the supraorbital canal (SOC), the temporal canal (TC), and the supratemporal canal (STC), and is characterized by the following pedomorphic features: disjunction of IOC and SOC, of TC and POC, and of POC and MC. We also discuss the phylogenetic significance of the cephalic lateral line canal system of H. rasborella.     

The two actin-interacting protein 1 genes have overlapping and essential function for embryonic development in Caenorhabditis elegans

Disassembly of actin filaments by actin-depolymerizing factor (ADF)/cofilin and actin-interacting protein 1 (AIP1) is a conserved mechanism to promote reorganization of the actin cytoskeleton. We previously reported that unc-78, an AIP1 gene in the nematode Caenorhabditis elegans, is required for organized assembly of sarcomeric actin filaments in the body wall muscle. unc-78 functions in larval and adult muscle, and an unc-78-null mutant is homozygous viable and shows only weak phenotypes in embryos. Here we report that a second AIP1 gene, aipl-1 (AIP1-like gene-1), has overlapping function with unc-78, and that depletion of the two AIP1 isoforms causes embryonic lethality. A single aipl-1-null mutation did not cause a detectable phenotype. However, depletion of both unc-78 and aipl-1 arrested development at late embryonic stages due to severe disorganization of sarcomeric actin filaments in body wall muscle. In vitro, both AIPL-1 and UNC-78 preferentially cooperated with UNC-60B, a muscle-specific ADF/cofilin isoform, in actin filament disassembly but not with UNC-60A, a nonmuscle ADF/cofilin. AIPL-1 is expressed in embryonic muscle, and forced expression of AIPL-1 in adult muscle compensated for the function of UNC-78. Thus our results suggest that enhancement of actin filament disassembly by ADF/cofilin and AIP1 proteins is critical for embryogenesis.     

Metabolic engineering for the production of prenylated polyphenols in transgenic legume plants using bacterial and plant prenyltransferases

Prenylated polyphenols are secondary metabolites beneficial for human health because of their various biological activities. Metabolic engineering was performed using Streptomyces and Sophora flavescens prenyltransferase genes to produce prenylated polyphenols in transgenic legume plants. Three Streptomyces genes, NphB, SCO7190, and NovQ, whose gene products have broad substrate specificity, were overexpressed in a model legume, Lotus japonicus, in the cytosol, plastids or mitochondria with modification to induce the protein localization. Two plant genes, N8DT and G6DT, from Sophora flavescens whose gene products show narrow substrate specificity were also overexpressed in Lotus japonicus. Prenylated polyphenols were undetectable in these plants; however, supplementation of a flavonoid substrate resulted in the production of prenylated polyphenols such as 7-O-geranylgenistein, 6-dimethylallylnaringenin, 6-dimethylallylgenistein, 8-dimethylallynaringenin, and 6-dimethylallylgenistein in transgenic plants. Although transformants with the native NovQ did not produce prenylated polyphenols, modification of its codon usage led to the production of 6-dimethylallylnaringenin and 6-dimethylallylgenistein in transformants following naringenin supplementation. Prenylated polyphenols were not produced in mitochondrial-targeted transformants even under substrate feeding. SCO7190 was also expressed in soybean, and dimethylallylapigenin and dimethylallyldaidzein were produced by supplementing naringenin. This study demonstrated the potential for the production of novel prenylated polyphenols in transgenic plants. In particular, the enzymatic properties of prenyltransferases seemed to be altered in transgenic plants in a host species-dependent manner.     

Linkage Mapping of Toll-Like Receptors (TLRs) in Japanese Flounder, <Emphasis Type="Italic">Paralichthys olivaceus</Emphasis>

Toll-like receptors (TLRs) are responsible for the recognition of specific pathogen-associated molecular patterns and consequently activate signal pathways leading to inflammatory and interferon responses. The region surrounding several TLRs was previously found to be associated with resistance to specific disease. Hence, we determined the location of 11 TLRs in Japanese flounder (Paralichthys olivaceus) using polymorphic microsatellite markers. TLR1 and TLR3 were located on linkage group (LG) 21 and 7, respectively. Membrane TLR5 and soluble TLR5 were mapped to LG22. TLR7 and TLR8 were mapped to LG3. TLR9 was found on LG1 and TLR14 and TLR21 were located on the same linkage group, LG10. TLR22 was found on LG8. Interestingly, TLR2 was mapped with the previously reported Poli9-8TUF microsatellite marker which is tightly associated with lymphocystis virus disease resistance. Therefore, TLR2 is a candidate gene for resistance to lymphocystis disease. These results imply that the location of a TLR associated with a particular disease may be valuable for the research on the relationship between host immune response and disease resistance.     

Genetic analysis of barrage line formation during mycelial incompatibility in Rosellinia necatrix

When mycelia of Rosellinia necatrix encounter mycelia of a different genetic strain, distinct barrage lines are formed between the two. These barrages have variable features such as pigmented pseudosclerotia structures, a clear zone, fuzzy hair-like mycelia, or tuft-like mycelia, suggesting that mycelial incompatibility triggers a number of cellular reactions. In this study, to evaluate cellular reactions we performed genetic analysis of mycelial incompatibility of R. nectarix, using 20 single ascospore isolates from single perithecia. Mycelial interaction zones were removed by spatula and cellular reactions studied on oatmeal agar media. The interaction zones were categorized into types such as sharp or wide lines, with or without melanin, and combinations of these. Although various reaction types were observed, we were able to identify a single genetic factor that appears to be responsible for the barrage line formation within oatmeal agar medium. DNA polymorphism analysis identified parental isolates and revealed that R. necatrix has a heterothallic life cycle.     

Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations

Hirschsprung disease (HSCR) is thought to result as a consequence of multiple gene interactions that modulate the ability of enteric neural crest cells to populate the developing gut. However, it remains unknown whether the single complete deletion of important HSCR-associated genes is sufficient to result in HSCR disease. In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrb(sl) mutations. Moreover, we found that this mutation results in serious congenital sensorineural deafness, and these strains may be used as ideal models of Waardenburg Syndrome Type 4 (WS4). Furthermore, we evaluated how the same changed genetic background modifies three features of WS4 syndrome, aganglionosis, hearing loss, and pigment disorder in these congenic strains. We found that the same genetic background markedly changed the aganglionosis, but resulted in only slight changes to hearing loss and pigment disorder. This provided the important evidence, in support of previous studies, that different lineages of neural crest-derived cells migrating along with various pathways are regulated by different signal molecules. This study will help us to better understand complicated diseases such as HSCR and WS4 syndrome.     

Screening of protein kinase inhibitors and knockdown experiments identified four kinases that affect mitochondrial ATP synthesis activity

Mitochondrial ATP synthase, a major ATP supplier in respiring cells, should be regulated in amount and in activity to respond to the varying demands of cells for ATP. We screened 80 protein kinase inhibitors and found that HeLa cells treated with four inhibitors exhibited reduced mitochondrial ATP synthesis activity. Consistently, knockdown of their target kinases (PKA, PKCδ, CaMKII and smMLCK) resulted in a decrease in mitochondrial ATP synthesis activity. Among them, mitochondria of smMLCK-knockdown cells contained only a small amount of ATP synthase, while the α- and β-subunits of ATP synthase were produced normally, suggesting that smMLCK affects assembly (or decay) of ATP synthase.