[Evaluation of the Leftover Capecitabine Tablets in Adjuvant CAPOX Chemotherapy for Gastric Cancer].

Since it is important that patients take their oral anticancer therapy as prescribed, pharmacists need to assess adherence. In addition, oral anticancer drugs are expensive, and reuse of leftover drugs at outpatient pharmacy clinics is useful in reducing drug costs. The present study aimed to clarify when and why patients have leftover capecitabine tablets, and the cost of leftover capecitabine tablets reused at an outpatient pharmacy clinic, focusing on adjuvant capecitabine plus oxaliplatin (CAPOX) chemotherapy for gastric cancer. We retrospectively studied patients who received adjuvant CAPOX chemotherapy for gastric cancer between November 1, 2015, and April 30, 2021, at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The cost of leftover capecitabine reused by pharmacists was calculated based on the National Health Insurance drug price standard for the study period. This study included 64 patients who received adjuvant CAPOX chemotherapy. Thirty-seven patients had 152 leftover capecitabine tablets. The most common reasons for leftover capecitabine tablets were nausea and vomiting (21.7%), missed doses (18.4%), and diarrhea (13.2%). The leftover capecitabine tablets for 25 patients were reused at the outpatient pharmacy clinic at a cost of JPY 604142.8 (JPY 24165.7 per patient). The study results suggest that evaluating capecitabine adherence and the reasons for leftover capecitabine tablets at outpatient pharmacy clinics as well as reusing leftover medication can contribute to reducing drug costs.

[Effect of the Antiemetic Drug Olanzapine on Blood Sugar Levels in Patients Treated with Adjuvant or Neoadjuvant Chemotherapy for Breast Cancer].

This retrospective study aimed to evaluate the effect of the antiemetic drug olanzapine(OLZ)on blood sugar levels in patients treated with adjuvant or neoadjuvant chemotherapy(AC: doxorubicin plus cyclophosphamide or CEF: cyclophosphamide plus epirubicin plus fluorouracil) for breast cancer. Here, we evaluated the frequency of diabetes(postprandial blood sugar: PBS≥200 mg/dL)and the change in PBS in 149 patients who were prescribed OLZ between September 2016 and August 2017 at our hospital. No diabetic patients were identified during the observation period(median: 3 cycles of chemotherapy). Among the 95 patients with more than 2 PBS readings, no difference was observed in the incidence of increased PBS, regardless of the diabetic risk, before and after OLZ administration. This study therefore found that the short term use of OLZ as an antiemetic had little effect on PBS, suggesting that it can be used safely during treatment with AC or CEF.

Impact of Primary Pegfilgrastim Prophylaxis on Relative Dose Intensity in Neoadjuvant/Adjuvant FEC-100 Chemotherapy.

BACKGROUND/AIM: This study aimed was to clarify the impact of pegfilgrastim (PEG) 3.6 mg primary prophylaxis of febrile neutropenia (FN) on the average relative dose intensity (ARDI) of neoadjuvant/adjuvant FEC-100 for breast cancer. MATERIALS AND METHODS: This retrospective, single-centre cohort study including 296 patients who received FEC-100 compared PEG and non-PEG groups. The PEG group received PEG 3.6 mg as a single subcutaneous injection in each study cycle. The primary endpoint was the ARDI of FEC-100. The secondary endpoints were patient percentage of ARDI≥85%, factors associated with ARDI≥85%, and reasons for reduced ARDI. RESULTS: The PEG group showed significantly higher mean ARDI (95.6% versus 90.7%, p<0.001) and patient percentage of ARDI≥85% (93.0% versus 79.9%, p=0.001). PEG was significantly associated with ARDI≥85% (p=0.009). Neutropenia and FN, the main reasons for reduced ARDI, were significantly lower in the PEG group (p<0.05). CONCLUSION: Primary PEG 3.6 mg prophylaxis increased the ARDI of FEC-100.

Comparison of cisplatin-induced nephrotoxicity when using conventional versus short hydration in gastric cancer-a retrospective study.

Although a short hydration protocol for cisplatin has been recently developed for use in lung cancer, this has yet to be established for gastric cancer. This study reviewed medical records of patients with gastric cancer who received XPT(capecitabine/cisplatin/trastuzumab) therapy containing cisplatin. Patients received either the conventional or short hydration regimen. Nephrotoxicity was compared between these two regimens by monitoring the serum creatinine. Out of the 26 total patients, 19 received the conventional regimen while 7 received the short hydration regimen. There was a higher nephrotoxicity was observed in the group receiving the conventional regimen (42.1%, 8/19) as compared to the short hydration regimen (0%, 0/7). There was a statistically significant difference in nephrotoxicity between the regimens (P = 0.039). Study results suggest that short hydration may be a feasible regimen for XPT therapy in gastric cancer patients.

Self-Reported Adherence to Capecitabine on XELOX Treatment as Adjuvant Therapy for Colorectal Cancer.

Adherence has become an important issue in modern oncology treatment. Most studies have included heterogeneous target tumor types, regimens, and therapy settings. Our study focused on capecitabine during capecitabine plus oxaliplatin (XELOX) treatment as an adjuvant therapy for colorectal cancer. The main aims of this study were to evaluate real-life adherence to capecitabine and to investigate candidate factors that might decrease adherence. We studied 338 consecutive patients who received XELOX treatment between December 1, 2011, and April 30, 2015, at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. Our study assessed adherence to capecitabine through patient-reported treatment diaries and interviewed nonadherents to determine the reasons for not taking capecitabine at a pharmaceutical outpatient clinic. We calculated the adherence rate in a cycle as: number of times the patient took capecitabine/28. Relative dose intensities and factors associated with deteriorating adherence to capecitabine were retrospectively surveyed from electronic patient records. Uni- and multivariate logistic regression analyses were used to investigate factors associated with optimal adherence. The study covered 282 patients who received 2,055 cycles of XELOX. Median adherence rate was 94.0% in the first cycle, and median relative dose intensity of capecitabine was 77.8%. The most common reasons for nonadherence were nausea/vomiting and diarrhea. The presence of the following factors was not significantly associated with adherence: ECOG performance status ≥1 (p = 0.715), clinical stage (p = 0.408), primary tumor site (p = 0.576), age ≥70 years at study entry (p = 0.757), female gender (p = 0.504), and not living alone (p = 0.579). The adherence rate from this study was significantly higher than the adherence from metastatic settings. Adherence-enhancing interventions for capecitabine in XELOX treatment as adjuvant therapy comprised management of nausea/vomiting and diarrhea.

Burkholone, a new cytotoxic antibiotic against IGF-I dependent cells from Burkholderia sp.

In the course of our screening program for new inhibitors of IGF-I signaling, we isolated a new cytotoxic antibiotic, burkholone, from the culture broth of Burkholderia sp. QN15488. The structure of burkholone was determined to be (E)-3-methyl-2-(2-octenyl)-4-quinolone by a series of NMR analyses. Burkholone induced cell death 32D/GR15 cells with an IC50 value of 160 nM in IGF-I containing medium, while no cell death was observed in IL-3 containing medium even at the concentration of 37 microM.

Characterization of histone lysine-specific demethylase in relation to thyroid hormone-regulated anuran metamorphosis.

The thyroid hormone receptor (THR) is a member of the nuclear transcription factor and plays a central role in regulating anuran metamorphosis. Previous studies with mammalian cells have suggested that THR is involved in chromatin remodeling through histone methylation. In the present study, we cloned cDNA of lysine-specific demethylase gene, xLSD1, from Xenopus laevis and examined its expression in relation to metamorphosis. Overexpression of xLSD1 in A6 cells, a Xenopus laevis cell line, resulted in the decrease of methylation status of lysine residues of histone H3, indicating that the protein of cloned xLSD1 was functionally active. The expression of LSD1 at mRNA levels was up-regulated in the body skin and the intestine during natural and thyroid hormone-induced metamorphosis. Larval epidermal basal cells and intestinal epithelial cells at the premetamorphic stage were identified as the xLSD1-expressing cells. At the metamorphic climax stage the progenitor cells of adult epidermal basal cells also expressed xLSD1, whereas those of the adult intestinal epithelial cells did not. We propose that LSD1 participates in the regulation of metamorphosis through THR- or another transcriptional factor-induced chromatin remodeling.

A novel oligoalginate lyase from abalone, Haliotis discus hannai, that releases disaccharide from alginate polymer in an exolytic manner.

We previously reported the isolation and cDNA cloning of an endolytic alginate lyase, HdAly, from abalone Haliotis discus hannai [Carbohydr. Res.2003, 338, 2841-2852]. Although HdAly preferentially degraded mannuronate-rich substrates, it was incapable of degrading unsaturated oligomannuronates smaller than tetrasaccharide. In the present study, we used conventional chromatographic techniques to isolate a novel unsaturated-trisaccharide-degrading enzyme, named HdAlex, from the digestive fluid of the abalone. The HdAlex showed a molecular weight of 32,000 on SDS-PAGE and could degrade not only unsaturated trisaccharide but also alginate and mannuronate-rich polymers at an optimal pH and temperature of 7.1 and 42 degrees C, respectively. Upon digestion of alginate polymer, HdAlex decreased the viscosity of the alginate at a slower rate than did HdAly, producing only unsaturated disaccharide without any intermediate oligosaccharides. These results indicate that HdAlex degrades the alginate polymer in an exolytic manner. Because HdAlex split saturated trisaccharide producing unsaturated disaccharide, we considered that this enzyme cleaved the alginate at the second glycoside linkage from the reducing terminus. The primary structure of HdAlex was deduced with cDNAs amplified from an abalone hepatopancreas cDNA library by the polymerase chain reaction. The translational region of 822 bp in the total 887-bp sequence of HdAlex cDNA encoded an amino-acid sequence of 273 residues. The N-terminal sequence of 16 residues, excluding the initiation methionine, was regarded as the signal peptide of this enzyme. The amino-acid sequence of the remaining 256 residues shared 62-67% identities with those of the polysaccharide lyase family-14 (PL14) enzymes such as HdAly and turban-shell alginate lyase SP2. To our knowledge, HdAlex is the first exolytic oligoalginate lyase belonging to PL14.

Recruitment of fusiform face area associated with listening to degraded speech sounds in auditory-visual speech perception: a PET study.

For the fast and accurate cognition of external information, the human brain seems to integrate information from multi-sensory modalities. We used positron emission tomography (PET) to identify the brain areas related to auditory-visual speech perception. We measured the regional cerebral blood flow (rCBF) of young, normal volunteers during the presentation of dynamic facial movement at vocalization and during a visual control condition (visual noise), both under the two different auditory conditions of normal and degraded speech sounds. The subjects were instructed to listen carefully to the presented speech sound while keeping their eyes open and to say what they heard. The PET data showed that elevation of rCBF in the right fusiform gyrus (known as the "face area") was not significant when the subjects listened to normal speech sound accompanied by a dynamic image of the speaker's face, but was significant when degraded speech sound (filtered with a 500 Hz low-pass filter) was presented with the facial image. The results of the present study confirm the possible involvement of the fusiform face area (FFA) in auditory-visual speech perception, especially when auditory information is degraded, and suggest that visual information is interactively recruited to make up for insufficient auditory information.

YM-202204, a new antifungal antibiotic produced by marine fungus Phoma sp.

A new antifungal antibiotic, YM-202204 (1), was found in the culture broth of marine fungus Phoma sp. Q60596. The structure of 1 was determined by several spectroscopic experiments as a new lactone compound. This antibiotic exhibited potent antifungal activities against Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, and also inhibited glycosyl-phosphatidyl-inositol (GPI)-anchoring in yeast cells.