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Abstract Germ cells preferentially induce apoptosis in response to DNA damage to avoid genomic mutations. Apoptosis of germ cells is closely related to cancer development and chemotherapy resistance; however, its regulatory mechanism is unclear. Here, we suggest that testis-specific lncRNA LINC03074 is involved in male germ cell apoptosis by regulating the expression of the proto-oncogene MDM2. LINC03074 is highly expressed in the sperm of healthy adult testes and cancer cells of testes with testicular germ cell tumors (TGCTs). LINC03074 binds to MDM2 mRNA via an Alu element, thereby reducing MDM2 protein levels. LINC03074 stimulates STAU1-mediated nuclear export of MDM2 mRNA by increasing STAU1 binding to MDM2 mRNA in the cell nucleus, thereby promoting PKR-mediated translational repression in the cytoplasm. The induction of apoptosis in TGCT cells and their responsiveness to the anticancer drug cisplatin is enhanced by LINC03074. Notably, LINC03074 increased E2F1 expression without increasing p53, the primary target of MDM2, and upregulated the apoptotic gene p73, the target gene of E2F1. LINC03074-mediated regulation of apoptosis contributes to the responsiveness of TGCTs to anticancer drug-induced DNA damage.

Introduction Small‐cell carcinoma of the urinary bladder has a poor prognosis, and no standard treatment has been established. We encountered a case of a patient with metastasis in which complete response and long‐term survival were obtained by treating the primary lesion with a combination of irinotecan, carboplatin chemotherapy, and radiation therapy. Case presentation An 83‐year‐old man was diagnosed with a bladder tumor with liver metastasis. Small‐cell carcinoma was diagnosed via transurethral resection. Second‐line chemotherapy with irinotecan and carboplatin and irradiation of the primary lesion were significantly effective. The imaging evaluation showed a complete response. The therapeutic effect was maintained for 1 year, even after the discontinuation of chemotherapy. Conclusion Irinotecan and carboplatin should be considered for the treatment of small‐cell carcinoma of the bladder. Irradiation of the primary lesion may also be useful if the extent of metastasis is low.

An increased number of patients with syphilis was recently reported in Japan and the United States. Syphilitic orchitis, a late complication of syphilis, is a rare disease that presents as testicular swelling. In most cases, a diagnostic orchiectomy is performed because of the possibility of testicular cancer. We report a case treated conservatively with antibiotics considering the possibility of syphilitic orchitis based on the blood test results and describe long-term changes observed in the imaging findings.

Abstract To compare gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with ultrahypofractionated radiotherapy (UHF) or brachytherapy [BT; low dose rate, LDR or high dose rate (HDR) with or without external beam radiotherapy (EBRT)]. We compared 253 UHF and 1664 BT ± EBRT groups. The main outcomes were the incidence and severity of acute and late GU and GI toxicities. The secondary endpoint was biochemical control rate. Cumulative late actuarial GU toxicity did not differ for grade ≥ 2 (8.6% at 5-years in UHF and 13.3% in BT ± EBRT, hazard ratio [HR], 0.7066; 95% CI, 0.4093–1.22, p = 0.2127). Actuarial grade ≥ 2 late GI toxicity was higher in UHF (5.8% at 5-years, HR: 3.619; 95% CI, 1.774–7.383, p

Plasmacytoid dendritic cells (pDCs) perform dual proinflammatory and immunosuppressive roles. We recently reported the potential of pDC therapy for treatment of intractable acute liver failure. However, establishment of efficient methods to deliver pDCs to the liver is essential for future clinical therapeutic applications. The present study demonstrates a higher abundance of liver and peripheral blood pDCs in mice lacking C-C motif chemokine receptor 9 (CCR9), a pDC gut-homing receptor, than in WT mice. Adoptive transfer of Ccr9–/– pDCs resulted in a higher efficiency of migration to the liver than WT pDCs did, while WT pDCs migrated efficiently to the original target organ, the small intestine. Further, Ccr9–/– pDCs consistently migrated efficiently to livers with concanavalin A–induced inflammation, and exerted a more effective immunosuppressive effect, resulting in better protection against acute liver inflammation than that demonstrated by WT pDCs. These findings highlight the therapeutic potential of the manipulation of the CCR9 axis as an approach to improve migration of immunosuppressive pDCs to the liver in order to exploit their beneficial effects in acute liver disease.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer death worldwide despite recent advances in surveillance and therapeutic management. The outcomes for HCC patients remain poor, often as a result of late diagnosis or lack of effective treatments. Early detection and precise diagnosis are evidently crucial in improving the prognosis of HCC. However, HCC is a highly heterogeneous cancer with various clinical backgrounds and altered molecular pathways; these factors make its precise diagnosis more difficult. Approximately 25% of HCCs harbor actionable mutations, which are yet to be translated into clinical practice. In the era of precision medicine, molecular or genomic information are indispensable for HCC diagnosis and prognosis. Exploring genomic alterations has become a requirement for identifying the molecular subtypes of HCC. Recent studies have introduced molecular markers to help identify early HCC and to clarify its multistep process of carcinogenesis. The subclassification of tumors into proliferation class and nonproliferation class HCCs gives pointers to the HCC phenotype and facilitates the selection of appropriate treatments. In this review, we broadly summarize some of the latest insights into HCC subclassification from the perspective of molecular pathology. Immunohistochemistry-based subclassification allows improved characterization of HCC in daily clinical practice. Moreover, analysis of the immune microenvironment, intra-tumoral morphological heterogeneity, and imaging features gives additional information regarding the classification of HCC. Combinations of these approaches are expected to inform and advance the precision diagnosis and management of HCC.

Introduction: Many studies have reported a poor prognosis for eosinophilic granulomatosis with polyangiitis (EGPA) patients with cardiac involvement. Case study: a woman developed eGpa at 37 years of age, with weight loss, numbness in the right upper and lower extremities, muscle weakness, skin rash, abdominal pain, chest pain, an increased peripheral blood eosinophil count (4165/µL), and necrotizing vasculitis on peroneal nerve biopsy. the patient was treated with prednisolone, immunosuppressants, intravenous immune globulin, and mepolizumab, but she experienced many relapses, with chest pain, abdominal pain, numbness, and paralysis, over a long period. the patient died from aspiration pneumonia at 71 years of age after undergoing left total hip arthroplasty for left hip neck fracture. Results: autopsy showed bronchopneumonia in the lower lung lobes on both sides, as well as infiltration of inflammatory cells, including neutrophils and lymphocytes. there was no evidence of active vasculitis in either the lung or colon. at autopsy the heart showed predominantly subendocardial fibrosis and fatty infiltration, but no active vasculitis or eosinophilic infiltration. Conclusion: to our knowledge, there have been no autopsy reports of EGPA patients who have survived for 34 years with recurrent cardiac lesions. In this case, the cardiac involvement (active vasculitis and eosinophilic infiltration) had improved by the time of death. [ABSTRACT FROM AUTHOR]