Early uptake and continuous accumulation of thallium-201 chloride in a benign mixed tumor of soft tissue: Case Report

A case of benign mixed tumor of the soft tissue in a 64-year-old Japanese male is presented. He noticed a painless, elastic hard mass sized 3 cm in the right knee, which gradually grew larger and harder in the last 5 years. Magnetic resonance imaging demonstrated a mass lesion embedded in the subcutaneous tissue with low and high signal intensity at T1- and T2-weighted images, respectively. Tl-201 scintigraphy showed an early uptake of Tl-201 within the lesion at 10 minutes after injection, which was slightly decreased but still continued at 2 hours later. The patient underwent a resection of tumor, and the pathological diagnosis was a benign mixed tumor of soft tissue without high vascularity, characterized by histological features similar to pleomorphic adenomas in the salivary glands. Immunohistochemical study proved expression of Na(+)/K(+)-ATPase of tumor cells. Overexpression of Na(+)/K(+)-ATPase of the tumor might be responsible for the early uptake of Tl-201, and poor vascular structure in this tumor might lead to continuous accumulation. The Tl-201 scintigraphic features of mixed tumor of soft tissue are assessed to resemble those of malignant soft tissue tumors

Effect of Fertilization on the Severity of Attack by the Defoliator Caterpillar (Noorda blitealis Walker, 1859) and on the Yield of Moringa (Moringa oleifera Lam, 1785)

Purpose: Moringa, which is increasingly grown pure in semi-intensive and intensive systems, requires adequate fertilization to produce well. In some cases, this operation can inhibit the development of its bioaggressors. The aim of this study was to determine the effect of different types of fertilization on the defoliator caterpillar (Noorda blitealis) and moringa production. Methodology: The trial was conducted on the Kalapaté experimental station belonging to the Institut ational de la recherche agronomique du Niger over two seasons. The experimental design was a split-plot with 4 replications in which the main plots were represented by fertilizer types (NPK, cattle, poultry and compost). The elementary plots were made up of fertilizer doses (0, 0, 5, 1 and 1.5 kg/ha for organic fertilizers, and 0, 3, 6 and 9 g/package for NPK). The severity of the caterpillar attack and moringa yield were recorded. Findings: The results showed that NPK acted faster than other fertilizers in reducing the severity of attack by N. blitealis.  The reduction rate was 28.40% in the first season compared with cattle manure, which is the most attacked. In the second season, compost had a similar effect to NPK. Both reduced this parameter by over 45% each compare to cattle and poultry manure. Their action consequently increased moringa yield compared with cattle manure and poultry droppings. Also, a negative linear relationship was noted between manure dose and severity of attack, while the dose-yield relationship was of the second-degree polynomial type. Unique Contribution to Theory, Practice and Policy: Compost can therefore be used to minimize attacks by Noorda blitealis and can enable sustainable production without any risk of toxicity from synthetic pesticides. In view of these results, moringa growers must compost cattle and poultry manure, and all other organic sources of fertilization, before any application

AURKA/PLK1/CDC25C Axis as a Novel Therapeutic Target in INI1-Deficient Epithelioid Sarcoma

Inoue A., Outani H., Imura Y., et al. AURKA/PLK1/CDC25C Axis as a Novel Therapeutic Target in INI1-Deficient Epithelioid Sarcoma. Cancer Science , (2025); https://doi.org/10.1111/cas.16438.Effective therapeutic strategies for epithelioid sarcoma (EpS), a high-grade soft tissue sarcoma characterized by loss of integrase interactor 1 (INI1), have not yet been developed. The present study therefore investigated the association between INI1 loss and upregulation of the aurora kinase A (AURKA)/polo-like kinase 1 (PLK1)/cell division cycle 25C (CDC25C) axis, as well as the therapeutic relevance of this axis in EpS. Notably, our findings showed that the reintroduction of INI1 in VA-ES-BJ cells significantly reduced proliferation, mitigated tumorigenicity, and negatively regulated the expression of AURKA and its downstream effectors, as well as the activation of PLK1 and CDC25C. These results suggest that INI1 deficiency enhanced EpS growth by upregulating the AURKA/PLK1/CDC25C axis. AURKA silencing using siRNAs inhibited VA-ES-BJ and Asra-EPS cell proliferation by inactivating PLK1 and CDC25C. Alisertib, a selective AURKA inhibitor, exerted markedly greater antiproliferative effects on EpS cells than on normal human dermal fibroblasts, and these effects were dependent on INI1 deficiency. Inhibition of AURKA activity by alisertib induced G2/M cell cycle arrest and apoptosis via the inactivation of AURKA downstream effectors in EpS cells. Alisertib also significantly decreased VA-ES-BJ xenograft tumor growth. Taken together, our findings revealed that INI1 loss in EpS cells enhances the expression of AURKA and its downstream effectors and persistently activates PLK1 and CDC25C mediated by AURKA, making the cells reliant on the AURKA/PLK1/CDC25C axis. Therefore, the AURKA/PLK1/CDC25C axis activated by INI1 deficiency could serve as a novel therapeutic target for this devastating disease

Age-related genomic alterations and chemotherapy sensitivity in osteosarcoma: insights from cancer genome profiling analyses

The version of record of this article, first published in International Journal of Clinical Oncology, is available online at Publisher’s website: https://doi.org/10.1007/s10147-024-02673-2.Background: Osteosarcoma, the most common primary bone malignancy, has a complex genetic basis and two incidence peaks. In younger patients, the standard treatment involves wide surgical resection combined with adjuvant chemotherapy; however, the role of chemotherapy in elderly patients remains controversial. The aims of this study were to investigate genetic differences between younger and elderly patients with osteosarcoma and to identify genetic signatures associated with chemotherapy response. Methods: Genetic alterations were analyzed using cancer genome profiling data for 204 patients with osteosarcoma obtained from the Center for Cancer Genomics and Advanced Therapeutics. Results: The mutation spectrum was consistent with previous results for osteosarcoma. CCNE1, MCL1, MYC, and RB1 alterations were significantly associated with a younger age, while CDK4, CDKN2A, CDKN2B, H3F3A, KMT2D, MDM2, RAC1, and SETD2 alterations were significantly associated with an older age. Age, unsupervised clustering of gene alterations, and MYC amplifications were significantly associated with the response to ifosfamide. Notably, both clustered mutation signatures and MYC amplification were correlated with age. Conclusions: These findings suggest that distinct oncogenic mechanisms contribute to differential sensitivity to chemotherapy in younger and elderly patients. Cancer genome profiling may aid in chemotherapy selection, and its early implementation is recommended to optimize treatment strategies

Clinical outcomes for patients with synovial sarcoma of the hand

PURPOSE: Soft tissue sarcoma of the hand is rare, and one of the most common histological diagnosis is synovial sarcoma. We report the clinical outcomes of patients with synovial sarcoma of the hand and discuss treatment strategies. METHODS: We reviewed five patients with synovial sarcoma of the hand treated at our institutions from 1983 to 2013. The mean patient age at the time of diagnosis was 36.6 years (range, 20–62 years). Two patients underwent marginal excision after neoadjuvant chemotherapy, followed by radiation therapy, one underwent wide local excision and two received chemotherapy and radiation therapy. RESULTS: The average duration of follow-up for all patients was 88.2 months (range, 14–218 months). Two patients continuously remained disease free, two experienced local recurrence requiring additional surgery and then showed no evidence of disease, and one who had distant metastasis at diagnosis died of the disease. No patients developed lymph node metastasis. The estimated 5-year overall survival was 80%. CONCLUSIONS: Our case series suggests that patients with localised synovial sarcoma of the hand may have favourable outcomes. Wide excision or marginal excision, followed by radiation therapy combined with chemotherapy, represent acceptable treatment strategies for synovial sarcoma of the hand. Regional lymph node dissection does not seem to be essential for synovial sarcoma of the hand

小・中・高校生の作文に見る家族意識の学校段階別比較--「家族・家庭生活」領域の授業実践のために

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GDF15 propeptide promotes bone metastasis of castration-resistant prostate cancer by augmenting the bone microenvironment

Yamamichi Gaku, Kato Taigo, Arakawa Noriaki, et al. GDF15 propeptide promotes bone metastasis of castration-resistant prostate cancer by augmenting the bone microenvironment. Biomarker Research 12, 147 (2024); https://doi.org/10.1186/s40364-024-00695-6.Background: Bone metastasis (BM) is a common and fatal condition in patients with castration-resistant prostate cancer (CRPC). However, there are no useful blood biomarkers for CRPC with BM, and the mechanism underlying BM is unclear. In this study, we investigated precise blood biomarkers for evaluating BM that can improve the prognosis of patients with CRPC. Methods: We comprehensively examined culture supernatants from four prostate cancer (PCa) cell lines using Orbitrap mass spectrometry to identify specific proteins secreted abundantly by PCa cells. The effects of this protein to PCa cells, osteoblasts, osteoclasts were examined, and BM mouse model. In addition, we measured the plasma concentration of this protein in CRPC patients for whom bone scan index (BSI) by bone scintigraphy was performed. Results: A total of 2,787 proteins were identified by secretome analysis. We focused on GDF15 propeptide (GDPP), which is secreted by osteoblasts, osteoclasts, and PCa cells. GDPP promoted the proliferation, invasion, and migration of PC3 and DU145 CRPC cells, and GDPP aggravated BM in a mouse model. Importantly, GDPP accelerated bone formation and absorption in the bone microenvironment by enhancing the proliferation of osteoblasts and osteoclasts by upregulating individual transcription factors such as RUNX2, OSX, ATF4, NFATc1, and DC-STAMP. In clinical settings, including a total of 416 patients, GDPP was more diagnostic of BM than prostate-specific antigen (PSA) (AUC = 0.92 and 0.78) and the seven other blood biomarkers (alkaline phosphatase, lactate dehydrogenase, bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, osteocalcin, procollagen I N-terminal propeptide and mature GDF15) in patients with CRPC. The changes in BSI over time with systemic treatment were correlated with that of GDPP (r = 0.63) but not with that of PSA (r = -0.16). Conclusions: GDPP augments the tumor microenvironment of BM and is a novel blood biomarker of BM in CRPC, which could lead to early treatment interventions in patients with CRPC

Combined targeting of mTOR and c-MET signaling pathways for effective management of epithelioid sarcoma

BACKGROUND: Epithelioid sarcoma (EpS) is a high-grade malignant soft-tissue sarcoma characterized by local recurrences and distant metastases. Effective treatments for EpS have not been established and thus novel therapeutic approaches against EpS are urgently required. mTOR inhibitors exert antitumor effects on several malignancies but AKT reactivation by mTOR inhibition attenuates the antitumor effects of mTOR inhibitors. This reactivation is receptor tyrosine kinase (RTK)-dependent due to a release of negative feedback inhibition. We found that c-MET was the most highly activated RTK in two human EpS cell lines, Asra-EPS and VAESBJ. Here we investigated the functional and therapeutic relevance of mTOR and/or c-MET signaling pathways in EpS both in vitro and in vivo. METHODS: We first examined the effects of an mTOR inhibitor, RAD001 (everolimus), on cell proliferation, cell cycle, AKT/mTOR signaling, and xenograft tumor growth in EpS cell lines. Next, we determined whether RAD001-induced AKT reactivation was blocked by silencing of c-MET or treatment with a selective c-MET inhibitor, INC280. Finally, we evaluated the antitumor effects of RAD001 combined with INC280 on EpS cell lines compared with either single agent or control in vitro and in vivo. RESULTS: Constitutive AKT phosphorylation was observed in Asra-EPS and VAESBJ cells. RAD001 suppressed EpS cell growth by inducing cell cycle arrest but enhanced AKT phosphorylation, which resulted in intrinsic resistance to mTOR inhibitors. In both EpS cell lines, RAD001-induced AKT phosphorylation was dependent on c-MET signaling. INC280 inhibited phosphorylation of c-MET and its downstream molecules, and decreased RAD001-induced phosphorylation of both AKT and ERK in EpS. Compared with a single agent or control, the combination of RAD001 and INC280 exerted superior antitumor effects on the growth of EpS cell lines in vitro and in vivo. CONCLUSIONS: Targeting of mTOR and c-MET signaling pathways significantly abrogates the growth of EpS in preclinical models and may be a promising therapeutic approach for patients with EpS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1476-4598-13-185) contains supplementary material, which is available to authorized users

Clinical Outcome of Patients with Pelvic and Retroperitoneal Bone and Soft Tissue Sarcoma : A Retrospective Multicenter Study in Japan

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan