BACKGROUND: To overcome the unfavorable issues associated with conventional anti-adhesive HA/CMC film, we developed an anti-adhesive thermally cross-linked gelatin film. OBJECTIVE: We tried to clarify the re-attachability of the film and the required properties concerning the film thickness, stiffness and anti-adhesion effect. METHODS: To determine the optimal thickness, 5 kinds of the thickness of gelatin film and the conventional film were analyzed by the tensile test, shearing test, buckling test and tissue injury test. Finally, using the optimal film thickness, we tried to clarify the anti-adhesion effect of the reattached film. RESULTS: The tensile and shearing test showed gelatin films ≥30 μm thick had greater tensile strength and a smaller number of film fractures, than the conventional film. The buckling and tissue injury test showed gelatin films ≥60 μm thick had higher buckling strength and worse injury scores than the conventional film. The anti-adhesive effect of re-attached gelatin film using optimal thickness (30–40 μm) found the anti-adhesion score was significantly better than that of the control. CONCLUSIONS: Provided it has an optimal thickness, gelatin film can be reattached with enough physical strength not to tear, safety stiffness not to induce tissue injury, and a sufficient anti-adhesion effect.
ABSTRACTABSTRACTIntroduction At present, the combination of immune checkpoint inhibitors (ICIs) or an ICI and a tyrosine kinase inhibitor (TKI) are the main treatment options as first-line therapy for metastatic renal cell cancer (mRCC). Among them, pembrolizumab plus lenvatinib was recently launched in Japanese clinical practice.Area covered In this review, the efficacies and safety profiles of pembrolizumab plus lenvatinib for mRCC between Japanese and global populations are compared. In addition, lenvatinib is currently available for the treatment of not only mRCC but also of endometrial, thyroid, thymic, and hepatocellular cancers. We briefly summarized the characteristics of pembrolizumab plus lenvatinib or lenvatinib monotherapy for these malignancies. Finally, the characteristics of pembrolizumab plus lenvatinib for mRCC in the Japanese population are briefly elucidated.Expert opinion In order to develop optimal personalized treatment for mRCC patients, it is necessary for physicians who treat mRCC patients to possess in-depth knowledge of not only the efficacy and safety profile of the respective therapies but also of the interpatient heterogeneities between Japanese and global populations.KEYWORDS: Immune checkpoint inhibitor (ICI)tyrosine kinase inhibitor (TKI)combination therapypembrolizumab plus lenvatinibmetastatic renal cell cancer (mRCC)interpatient heterogeneity Article highlights At present, combinations of ICIs or TKI/ICI are the standard treatment options as first-line therapy for mRCC.Among the combination therapies, pembrolizumab plus lenvatinib just launched in 2022 Japanese clinical practice.We compare the efficacy and safety profile of pembrolizumab plus lenvatinib between Japanese and global populations.Efficacies, which include progression-free survival (PFS) and overall survival (OS) periods, complete response (CR) rates, objective response rates (ORRs), and disease control rates (DCRs), are comparable between these populations. The long PFS period (22.1 months), high CR rates (19.0%), high ORR (69.0%), and high DCR (95.2%) are attractive in the Japanese population.The incidences of specific adverse events, which include palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hypothyroidism, and hypertension, appear to be higher in Japanese patients than in the overall population.As a result of the treatment-related dose reduction for these adverse events, the relative dose intensities (RDIs) of lenvatinib appear to be lower in Japanese patients than in the overall population.Nonetheless, due to the significance of the initial RDI of lenvatinib, its starting dose of 20 mg should not be reduced.Declaration of interestT Yuasa received remuneration for a lecture from Eizai (Tokyo, Japan) and MSD Japan (Tokyo, Japan).The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Supplemental dataSupplemental data for this article can be accessed online at https://doi.org/10.1080/14737140.2023.2200170.Additional informationFundingThis work was partly supported by JSPS KAKENHI Grant Number 21K09342 (S.K).
A 28-year-old male presented with a small painless lump in his left hemiscrotum. A physical examination revealed a non-tender mass that was palpable on the tail of left epididymis, and the testis and spermatic cord were normal. Ultrasonography showed an isoechoic round shaped tumor, 16 mm in diameter. An exploration of the scrotum was performed, based on a preoperative diagnosis of a left epididymal tumor. The tumor was located below the tail of epididymis, and had a whitish capsule, which looked similar to tunica albuginea testis. A frozen section revealed testicular tissue without any malignant change, and therefore polyorchidism was diagnosed. The accessory testis was resected because there was no connection with the epididymis and vas deferens. Polyorchidism is a rare congenital anomaly with 24 cases reported in the Japanese literature. The indications for the resection of an accessory testis are controversial. Patients with intrascrotal polyorchidism might be recommended to undergo a resection of the accessory testes if there are signs of dysplasia during an intraoperative biopsy. Patients must be followed up with regular clinical and ultrasonic examinations when accessory testes are preserved. However, extrascrotal supernumerary testes should be managed by an orchiectomy because of the increased risk of malignancy.
Abstract Fibrosis is an important pathological mechanism in heart failure (HF) and is associated with poor prognosis. We analyzed fibrosis in HF patients using transcriptomic data. Genes differentially expressed between normal control and congestive HF (CHF) dogs included P3H1 , P3H2 , P3H4 , P4HA2 , PLOD1 and PLOD3 , which belong to the 2-oxoglutarate-dependent dioxygenases (2OGD) superfamily that stabilizes collagen during fibrosis. Quantitative polymerase chain reaction analysis demonstrated 2OGD gene expression was increased in CHF samples compared with normal left ventricle (LV) samples. 2OGD gene expression was repressed in angiotensin converting enzyme inhibitor-treated samples. These genes, activated the hydroxylation of proline or lysin residues of procollagen mediated by 2-oxoglutaric acid and O 2, produce succinic acid and CO 2 . Metabolic analysis demonstrated the concentration of succinic acid was significantly increased in CHF samples compared with normal LV samples. Fibrosis was induced in human cardiac fibroblasts by TGF-ß1 treatment. After treatment, the gene and protein expressions of 2OGD, the concentration of succinic acid, and the oxygen consumption rate were increased compared with no treatment. This is the first study to show that collagen-related 2OGD genes contribute to HF during the induction of fibrosis and might be potential therapeutic targets for fibrosis and HF.
Spermatogenesis is controlled by hormonal secretions from the hypothalamus and pituitary gland, by factors produced locally in the testis, and by direct interaction between germ cells and Sertoli cells in seminiferous tubules. Although the mammalian testis contains high levels of d-aspartate (d-Asp), and d-Asp is known to stimulate the secretion of testosterone in cultured Leydig cells, its role in testis is unclear. We describe here biochemical, immunohistochemical, and flow cytometric studies designed to elucidate developmental changes in testicular d-Asp levels and the direct effect of d-Asp on germ cells. We found that the concentration of d-Asp in mouse testis increased with growth and that fluctuations in d-Asp levels were controlled in part by its degradative enzyme, d-aspartate oxidase expressed in Sertoli cells. In vitro sperm production studies showed that mitosis in premeiotic germ cells was strongly inhibited by the addition of d-Asp to the culture medium. Moreover, immunohistochemical analysis demonstrated that d-Asp accumulated in the differentiated spermatids, indicating either transport of d-Asp to spermatids or its de novo synthesis in these cells. Such compartmentation seems to prevent premeiotic germ cells in mouse testis from being exposed to the excess amount of d-Asp. In concert, our results indicate that in mouse testis, levels of d-Asp are regulated in a spatiotemporal manner and that d-Asp functions as a modulator of spermatogenesis.
The present study evaluated the impact of nedaplatin‑containing chemotherapy on renal function in 35 patients with urothelial carcinoma (UC) between 2001 and 2014 who were unfit for cisplatin treatment. As comparative controls, the present study also examined 35 patients with the same disease who underwent cisplatin‑containing chemotherapy during the same period. The changes in the estimated glomerular filtration rate (eGFR) prior to and following the administration of nedaplatin during each cycle of chemotherapy was investigated. The present study also reported the overall response rates and adverse events in each group. A total of 31 cycles of the gemcitabine/nedaplatin regimen and 66 cycles of the methotrexate/epirubicin/nedaplatin regimen were administered. In the nedaplatin group, the mean eGFRs prior to and following chemotherapy were 45.4 and 47.8 ml/min/1.73 m2, respectively. The eGFR of the post‑chemotherapy group was significantly increased (P<0.001). On the other hand, in the cisplatin group, the eGFR following chemotherapy was significantly lower than the rate prior to chemotherapy (P<0.001). The overall response rates were 30.4 and 66.7% in the nedaplatin and cisplatin groups, respectively. In the two groups, myelosuppression was the most common side effect, but the occurrence rates in both groups were similar, and these adverse events were manageable. With regard to nephrotoxicity, nedaplatin‑containing chemotherapy for cisplatin‑unfit patients with UC is a safe treatment modality.
A 56-year-old male presented with fever of unknown origin and subacute dementia which progressed to death with seizure, coma and acute deterioration of general conditions. He had splenomegaly but not skin eruption or lymph node swelling. Autopsy findings showed that mononuclear tumor cells were widespread within the lumens of small blood vessels, indicating the features of neoplastic angioendotheliosis. The involved organs were shown to be brain, lung, adrenal grand, testis, bone marrow, heart and thyroid gland. To determine the origin of tumor cells, an immunohistochemical study was carried out using a panel of monoclonal antibodies. The results indicated that the tumor cells were of B-lymphocyte origin. These findings support the possibility that neoplastic angioendotheliosis is a lymphoma with proliferation in small blood vessels throughout the body.
