[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia â ¡ (J-EPOCC â ¡)-Disease Awareness and Issues Related to Cancer Cachexia Among Healthcare Professionals].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC)was conducted among cancer patients, their families and healthcare professionals in Japan, and it showed that the term"cancer cachexia"was highly recognized among health care professionals, whereas the staging and criteria for cancer cachexia defined by European Palliative Care Research Collaborative( EPCRC)was less understood. Also, many healthcare professionals tended to consider the term"cancer cachexia" as the terminal stage of cancer, and most of them lacked the knowledge that cancer cachexia is a disease complication which is potentially developed from the early stage of cancer. Since anamorelin was approved in 2021 for"Cancer cachexia in unresectable advanced or recurrent of non-small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCC Ⅱ) was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their families and healthcare professionals1). The results for healthcare professionals showed that the awareness of the staging and criteria has increased among doctors in 2022 compared with 2019, and an increasing number of doctors considered"cancer cachexia"was associated with loss of muscle mass, totally body weight loss, appetite loss and systemic inflammation that may occur in early stages of cancer. On the other hand, awareness of staging and diagnostic criteria for cancer cachexia has not remarkably changed among medical staff since 2019, with levels of awareness varying among those with different job categories. Therefore, in order to achieve early detection and intervention of cancer cachexia, it is necessary to raise the awareness of cancer cachexia among not only doctors but also medical staff by increasing their opportunities to get to know the disease condition, diagnosis, and treatment of cancer cachexia.

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexiaâ ¡ (J-EPOCCâ ¡)-Challenges in Early Detection and Early Intervention for Appetite Loss and Weight Loss During Cancer Treatment].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC), conducted among cancer patients, their families and healthcare professionals in Japan showed that nearly half of patients who had experienced appetite loss or weight loss during cancer treatment had not consulted with healthcare professionals about their symptoms, and it meant that patients missed the opportunity to receive medical intervention. Since anamorelin was approved in 2021 fo"r Cancer cachexia in non- small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCCⅡ)was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their family and healthcare professionals. The results showed that there was no apparent change in awareness of appetite loss and weight loss, suggesting many patients may miss treatment opportunities. Further disease awareness is required among patients and their families to enhance the understanding of the significance of therapeutic interventions for appetite loss or weight loss, and to call their attention for early detection and treatment.

A matched-filter technique with an objective threshold.

We propose an objective threshold determination method for detecting outliers from the empirical distribution of cross-correlation coefficients among seismic waveforms. This method is aimed at detecting seismic signals from continuous waveform records. In our framework, detectability is automatically determined from Akaike's Information Criterion (AIC). We applied the method of seismic signal detection to continuous records collected over two years. The results show that the maximum value of network cross-correlation coefficients sampled from each constant interval can be approximated by the theory of extreme value statistics, which provides a parametric probability density function of maxima. By using the function, outliers can be considered with a reasonable criterion.

Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study.

BACKGROUND: To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice. METHODS: This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records. RESULTS: Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1-27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2-12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141. CONCLUSIONS: The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141. TRIAL REGISTRATION NUMBER: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436).

Re-challenge of Platinum-based Chemotherapy for Platinum-refractory Patients with Recurrent or Metastatic Head and Neck Cancer: Claims Data Analysis in Japan.

BACKGROUND: The role of platinum rechallenge in head and neck cancer (HNC) has not yet been fully evaluated. OBJECTIVES: It is our goal to assess the real-world treatment patterns and usefulness of platinum rechallenge in patients with platinum-refractory recurrent or metastatic HNC receiving platinum rechallenge. METHODS: This is a retrospective study using data from a Japanese hospital claims database stored in electronic hospital information systems. Patients with HNC or undefined histology with an HNC diagnosis using the disease code, between January 1, 2013 and September 30, 2016, were included. Patients diagnosed with other malignancies on or before the initial diagnosis of HNC and those without cancer stage information in the database were excluded from the study. RESULTS: A total of 43 994 patients were identified from the database as HNC patients. Of those, in patients who had cancer progression within 6 months after platinum-based chemotherapy administered for primary or recurrent disease (N=842), the median treatment duration of platinum rechallenge for platinum refractory patients was only 1 cycle. The second-line treatment continuation rate at 6 months was 20.1% for patients who received platinum rechallenges and 32.8% for those who received non-platinum-based regimens. CONCLUSIONS: The findings from this study of data from routine clinical practice suggest that the benefit of platinum rechallenge in a platinum-refractory setting would be limited.

Identification of Novel D-Aspartate Oxidase Inhibitors by in Silico Screening and Their Functional and Structural Characterization in Vitro.

D-Aspartate oxidase (DDO) is a degradative enzyme that is stereospecific for acidic D-amino acids, including D-aspartate, a potential agonist of the N-methyl-D-aspartate (NMDA) receptor. Dysfunction of NMDA receptor-mediated neurotransmission has been implicated in the onset of various mental disorders, such as schizophrenia. Hence, a DDO inhibitor that increases the brain levels of D-aspartate and thereby activates NMDA receptor function is expected to be a useful compound. To search for potent DDO inhibitor(s), a large number of compounds were screened in silico, and several compounds were identified as candidates. They were then characterized and evaluated as novel DDO inhibitors in vitro (e.g., the inhibitor constant value of 5-aminonicotinic acid for human DDO was 3.80 µM). The present results indicate that some of these compounds may serve as lead compounds for the development of a clinically useful DDO inhibitor and as active site probes to elucidate the structure-function relationships of DDO.

Identification of novel D-amino acid oxidase inhibitors by in silico screening and their functional characterization in vitro.

D-amino acid oxidase (DAO) is a degradative enzyme that is stereospecific for D-amino acids, including D-serine and D-alanine, which are potential coagonists of the N-methyl-D-aspartate (NMDA) receptor. Dysfunction of NMDA receptor-mediated neurotransmission has been implicated in the onset of various mental disorders such as schizophrenia. Hence, a DAO inhibitor that augments the brain levels of D-serine and/or D-alanine and thereby activates NMDA receptor function is expected to be an antipsychotic drug, for instance, in the treatment of schizophrenia. In the search for potent DAO inhibitor(s), a large number of compounds were screened in silico, and several compounds were estimated as candidates. These compounds were then characterized and evaluated as novel DAO inhibitors in vitro. The results reported in this study indicate that some of these compounds are possible lead compounds for the development of a clinically useful DAO inhibitor and have the potential to serve as active site probes to elucidate the structure-function relationships of DAO.

The spermine-bisaryl conjugate as a potent inducer of B- to Z-DNA transition.

DNA containing alternating purine and pyrimidine repeats has the potential to adopt the Z-DNA structure, one of the well-studied structures besides A- and B-DNA. Despite a number of molecular models that have been proposed to explain the mechanism for B→Z transition, there is continued discussion on the mechanism and physiological role of this transition. In this study, we have found that the bis(2-naphthyl)-maleimide-spermine conjugate (3c) exhibits a remarkable ability to cause the B→Z transition of d(CGCGCG)(2) at low salt concentrations. Using isothermal titration calorimetry (ITC) we show that the B→Z transition induced by 3c is both enthalpically and entropically favorable. The ligand might effect the dehydration of B-DNA, which leads to the B→Z transition. Interestingly, an intermediate CD between the B and Z forms was observed in the pH-dependent transition in the presence of the ligand. The unique structure and characteristics of the ligand designed in this investigation will be useful for the study of Z-DNA.

Selective protein modification by the hydroperoxide intermediate in a photoprotein, aequorin.

During the course of protein modification program, we employed a recombinant aequorin, the apo-protein reconstituted with coelenterazine, and found out that the photolytic hyperperoxide modified three -S-SCH2CHOHCHOHCH2SH groups to -S-SCH2CHOHCH=CH-S=O)H or -S-SCH2CHOHCH=CH-S(=O)OH of terminal DTT connected to cysteine residues of the C145, C152 and C180, which turned out to locate near the chromophore.

Determination of solvent-trapped products obtained by photolysis of aryl azides in 2,2,2-trifluoroethanol.

A series of nonfluorinated and fluorinated aryl azides with varied functionality patterns were irradiated in 2,2,2-trifluoroethanol with either a high-pressure or a low-pressure mercury lamp. Interestingly, one of the major products in these reactions was the result of the recombination of anilino and alkyl radicals to form the corresponding hemiaminal compounds. The structure of the recombination products was assigned unambiguously after proton/deuterium exchange experiments followed by MS and MS/MS analysis.