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Lactate dehydrogenase (LDH) catalyses the conversion of pyruvate to lactate and NADH to NAD + ; it has two isoforms, LDHA and LDHB. LDHA is a promising target for cancer therapy, whereas LDHB is necessary for basal autophagy and cancer cell proliferation in oxidative and glycolytic cancer cells. To the best of our knowledge, selective inhibitors for LDHB have not yet been reported. Here, we developed a high-throughput mass spectrometry screening system using an LDHB enzyme assay by detecting NADH and NAD + . As a result, we identified a small-molecule LDHB selective inhibitor AXKO-0046, an indole derivative. This compound exhibited uncompetitive LDHB inhibition (EC 50  = 42 nM). X-ray crystallography revealed that AXKO-0046 bound to the potential allosteric site away from the LDHB catalytic active site, suggesting that targeting the tetramerisation interface of the two dimers is critical for the enzymatic activity. AXKO-0046 and its derivatives can be used to validate LDHB-associated pathways in cancer metabolism.

Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B‐NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy‐resistant advanced‐stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti‐PD‐1 antibody immunotherapy group did not show tumor suppression. Only the B‐NIT group showed strong tumor growth inhibition at both BNCT‐treated and shielded distant sites. Intratumoral CD8+ T‐cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B‐NIT group. Analysis of CD8+ T cells in tumor‐infiltrating lymphocytes (TILs) showed that CD62L‐ CD44+ effector memory T cells and CD69+ early‐activated T cells were predominantly increased in the B‐NIT group. Administration of CD8‐depleting mAb to the B‐NIT group completely suppressed the augmented therapeutic effects. This indicated that B‐NIT has a potent immune‐induced abscopal effect, directly destroying tumors with BNCT, inducing antigen‐spreading effects, and protecting normal tissue. B‐NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy‐resistant malignancies, B‐NIT can become a new treatment candidate for advanced‐stage cancers. Boron neutron capture therapy leads to new treatment option to overcome cancer immunotherapy resistance.

Background While magnetic resonance imaging (MRI) is well-established for local assessment of prostate cancer, its prognostic utility in the metastatic setting remains poorly defined. We investigated whether pretreatment MRI findings can predict survival and disease progression in prostate cancer patients with bone metastases. Methods Of the 2,314 patients with pathologically proven prostate cancer between 2014 and 2021 in our hospital, this retrospective study finally included 19 patients with bone metastases who underwent prostate MRI within six months before diagnosis. Clinical and radiological parameters were analyzed, including Gleason score, prostate-specific antigen (PSA) density, clinical T stage, maximum tumor diameter (MTD), and normalized mean apparent diffusion coefficient (nADCmean). Time-dependent receiver operating characteristic curve analysis was used to determine the optimal cut-points for continuous variables with p-values <0.2. Univariate survival and disease progression analyses were performed using the Kaplan-Meier method and the log-rank test. Univariate Cox proportional hazards regression analyses were performed to estimate the hazard ratio. Results The median age was 69 years (range, 54-91 years). Gleason scores were 4 +4 = 8, 4 + 5 = 9, 5 + 4 = 9, and 5 + 5 = 10 in 12, three, three, and one patients, respectively. Median follow-up duration was 45 months. Seven patients died, and 12 experienced disease progression. MTD ≥49 mm was significantly associated with shorter overall survival compared to MTD <49 mm (median survival, 51 vs 95 months; p = 0.015). A higher nADCmean (≥0.19) was a significant prognostic factor for disease progression (p = 0.031). Gleason score, PSA density, and clinical T stage did not significantly discriminate outcomes in this metastatic cohort. Conclusions In prostate cancer patients with bone metastases, larger maximum tumor diameter on pretreatment MRI predicts poorer overall survival and may be more useful than clinical T stage for prognostic stratification. Higher normalized apparent diffusion coefficient (ADC) was associated with disease progression. Histopathological characteristics that raise ADC despite high Gleason score such as relatively low cell density, heterogeneous morphology, and cribriform pattern might have led to this result. These MRI-derived parameters could help guide treatment planning and risk assessment in metastatic prostate cancer. However, further studies are necessary to validate these findings due to the limitation of small sample size in this study.

Background Boron neutron capture therapy (BNCT) is a molecularly targeted chemoradiation modality that relies on boron delivery agents such as p-borophenylalanine (BPA), which require LAT1 (L-type amino acid transporter 1) for tumor uptake. However, the limited efficacy of BPA in LAT1-low tumors restricts its therapeutic scope. To address this limitation, we developed a tumor marker–guided BNCT strategy targeting cancers overexpressing the clinically validated glycan biomarker CA19-9. Methods We conducted transcriptomic analyses using The Cancer Genome Atlas (TCGA) datasets to identify LAT1-low cancers with high CA19-9 expression. These analyses revealed elevated expression of fucosyltransferase 3 (FUT3), which underlies CA19-9 biosynthesis, in pancreatic, biliary, and ovarian malignancies. Based on this, we synthesized a novel boron compound, fucose-BSH, designed to selectively accumulate in CA19-9–positive tumors. We evaluated its physicochemical properties, pharmacokinetics, biodistribution, and antitumor efficacy in cell lines and xenograft models, comparing its performance to that of BPA. Results Fucose-BSH demonstrated significantly greater boron uptake in CA19-9–positive cell lines (AsPC-1, Panc 04.03, HuCCT-1, HSKTC, OVISE) compared to CA19-9–negative PANC-1. In HuCCT-1 xenografts, boron accumulation reached 36.2 ppm with a tumor/normal tissue ratio of 2.1, outperforming BPA. Upon neutron irradiation, fucose-BSH–mediated BNCT achieved > 80% tumor growth inhibition. Notably, fucose-BSH retained therapeutic efficacy in LAT1-deficient models where BPA was ineffective, confirming LAT1-independent targeting. Conclusions This study establishes a novel precision BNCT approach by leveraging CA19-9 as a tumor-selective glycan marker for boron delivery. Fucose-BSH offers a promising platform for expanding BNCT to previously inaccessible LAT1-low malignancies, including pancreatic, biliary, and ovarian cancers. These findings provide a clinically actionable strategy for tumor marker–driven chemoradiation and lay the foundation for translational application in BNCT. This strategy has the potential to support companion diagnostic development and precision stratification in ongoing and future BNCT clinical trials. Translational Relevance Malignancies with elevated CA19-9 expression, such as pancreatic, biliary, and ovarian cancers, are associated with poor prognosis and limited response to current therapies. This study presents a tumor marker–guided strategy for boron neutron capture therapy (BNCT) by leveraging CA19-9 glycan biology to enable selective tumor targeting via fucose-BSH, a novel boron compound. Through transcriptomic data mining and preclinical validation, fucose-BSH demonstrated LAT1-independent boron delivery, potent BNCT-mediated cytotoxicity, and tumor-specific accumulation in CA19-9–positive models. These findings support a precision chemoradiation approach that addresses a critical gap in BNCT applicability, offering a clinically actionable pathway for patient stratification and therapeutic development in CA19-9–expressing cancers. Graphical Abstract

Introduction Xanthogranulomatous prostatitis is a very rare benign inflammatory lesion of the prostate that may be similar to prostatic carcinoma in clinical presentation and radiological characteristics. Case presentation A 77‐year‐old man was admitted to our hospital because of high prostate‐specific antigen level. Magnetic resonance imaging showed a 6.5 cm in diameter multifocal mass with hemorrhage at the base of the left lobe of the prostate. Biopsy was performed. Histopathological examination revealed no evidence of malignancy. After biopsy, he developed recurring fever, so the patient was treated with open suprapubic tumor resection to control infection. Pathological examination revealed xanthogranulomatous prostatitis. Conclusion It is necessary to diagnose xanthogranulomatous prostatitis by cooperation between urologists and pathologists, and consider xanthogranulomatous prostatitis as a differential diagnosis. Treatment should be conservative in principle; however, surgical intervention may be necessary.

Soft tissue sarcomas (STSs) are rare heterogeneous malignancies of mesenchymal origin. Pulmonary metastases develop in approximately 50% of the patients with high-grade STS, being the major cause of mortality in patients with metastatic STS. Pulmonary metastasectomy has been reported to contribute to long-term survival; however, an appropriate treatment has not been established. We aimed to identify factors associated with post-metastasis survival in STS patients with pulmonary metastasis and determine the appropriate treatment for each patient. We retrospectively reviewed the records of metastatic STS patients treated between 2000 and 2017 and analyzed the clinico-pathologic variables to identify factors associated with the survival. The median survival after pulmonary metastasis was 20.6 months, and the 1-, 3-, and 5-year survival rates were 68.6%, 36.0%, and 25.1%, respectively. The survival was significantly greater in patients who underwent pulmonary metastasectomy than in those without surgery (38.9 months vs. 10.5 months; p < 0.0001). Among those who did not undergo surgery, the survival was significantly greater in patients who received chemotherapy than in those without chemotherapy (19.1 months vs. 6.3 months, p = 0.037). Multivariate analysis identified pulmonary metastasectomy as the most important prognostic factor for post-metastasis survival (Hazard ratio 5.623; 95% Confidence Interval 2.733–11.572; p < 0.0001). In conclusion, pulmonary metastasectomy was the most important prognostic factor for post-metastasis survival in patients with metastatic STS. In addition, chemotherapy could prolong survival in patients who were not eligible for pulmonary resection. Although we should carefully weigh the risks and benefits, appropriate treatment for pulmonary metastases could contribute to long-time survival.

Background This study aimed to investigate the association between the Fc-gamma receptor IIIA (FCGR3A) 158 polymorphism and clinical outcomes in kidney transplantation (KTx) patients. Specifically, we focused on late-onset neutropenia (LON) in ABO-incompatible (ABOi) or HLA-incompatible (HLAi) KTx recipients who underwent rituximab (RTx) desensitization therapy. Methods FCGR3A 158F/V polymorphisms were identified in 85 ABOi or HLAi KTx recipients who underwent RTx desensitization at our institution between April 2008 and October 2021. We analyzed these polymorphism groups in relation to their preoperative background and incidence of LON, infection, and rejection. In addition, we examined the risk factors for LON development. Results The following FCGR3A 158F/V polymorphisms were identified: FF genotype ( n  = 45); FV genotype ( n  = 36), and VV genotype ( n  = 4). LON occurred in 25 out of 85 recipients within 1 year after KTx, significantly more frequently in patients with the FCGR3A FV + VV genotype (17/40) than in those with the FF genotype (8/45) ( p  = 0.01). A multivariate analysis identified the V-allele as an independent risk factor for LON (OR, 4.03; 95% CI, 1.38—11.73, p  = 0.01). However, there were no significant differences in the incidence rates of post-transplant infection and rejection between the FF and FV + VV genotypes. Conclusion Recipients with the FCGR3A 158 V-allele were identified as having a higher risk of developing LON following KTx with RTx desensitization therapy. However, the presence of this V-allele did not affect the safety or efficacy of RTx desensitization before KTx.

Introduction Leydig cell tumors (LCTs), constituting 1%–3% of testicular tumors, are mostly benign, but malignant cases present treatment challenges. We report a malignant LCT case with a notable response to mitotane. Case Presentation A 43‐year‐old male presented with a right testicular induration and was diagnosed with a Leydig cell tumor following orchiectomy. BEP chemotherapy was initiated for the liver metastases, but after four cycles, new lymph node and bone lesions appeared. Mitotane was started, which markedly reduced liver and nodal metastases. However, due to fatigue, anorexia, and nipple discomfort, mitotane was discontinued. The disease progressed, and the patient died 4 years post‐diagnosis and 14 months after starting mitotane. Conclusion Mitotane shows promise in treating malignant LCTs, but careful management of adverse effects is necessary.

Background The selection of radiation therapy dose fractionation schedules for bone metastases is often based on the estimation of life expectancy. Therefore, accurate prognosis prediction is an important issue. It is reported that the Katagiri scoring system can be used to predict the survival of patients with bone metastases. We aimed to assess prognostic factors and validate the Katagiri scoring system in patients who were treated with radiation therapy for bone metastases. Materials/Methods We retrospectively reviewed data of all patients who were treated with radiation therapy for bone metastases between 2004 and 2013. Age, sex, Karnofsky performance status (KPS), Eastern Cooperative Oncology Group performance status (ECOG PS), primary site (lesions and characteristics), visceral metastases, laboratory data, previous chemotherapy, and multiple bone metastases were analyzed for associations with overall survival (OS). Katagiri scores were calculated for each patient and were used to compare OS. Results Out of the 616 patients included in this analysis, 574 had died and 42 remained alive. The median follow-up time for survivors was 42 months. Univariate analysis revealed that age ( P  = 0.604) and multiple bone metastases ( P  = 0.691) were not significantly associated with OS. Multivariate analysis revealed that sex, ECOG PS, KPS, primary characteristics, visceral metastases, laboratory data, and previous chemotherapy were significantly associated with OS. The survival rates at 3, 6, 12, and 24 months, categorized by Katagiri score, were as follows: score 0–3, 94.4, 77.8, and 61.1%, respectively; score 4–6, 67.7, 48.7, and 31.2%, respectively; and score 7–10, 39.1, 22.1, and 9.0%, respectively ( P  < 0.001). Conclusion Sex, ECOG PS, KPS, primary characteristics, visceral metastases, laboratory data, and previous chemotherapy were significant predictors of survival in patients with bone metastases. The Katagiri scoring system was significantly correlated with OS and can help us select the optimal dose-fractionation.

Proximal-type epithelioid sarcoma is an aggressive malignant soft-tissue neoplasm, a “proximal” variant of epithelioid sarcoma, resistant to multimodal therapy and involved in early tumor-related death. Pertinent treatments are, therefore, continually being explored. A 24-year-old woman with nonmetastatic proximal-type epithelioid sarcoma, originating subcutaneously on the right side of the vulva, underwent surgical resection; the lesion recurred, however, leading to death 3 months after the second surgery. Here described is a case of proximal-type epithelioid sarcoma expressing L-type amino acid transporter 1 (LAT1) that transports essential amino acids and p-borono-L-phenylalanine (BPA)—the chemical compound used in boron neutron capture therapy (BNCT)—and is highly expressed in many malignant tumors. Recently, LAT1 has drawn attention, and relevant treatments have been studied—LAT1 inhibitor and BNCT. LAT1 expression in proximal-type epithelioid sarcoma may lead to cogent treatments for the disease.