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1.
Article in English | MEDLINE | ID: mdl-38805108

ABSTRACT

INTRODUCTION: Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. METHODS: Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. RESULTS: Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2 ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2 ng/ml (n = 28). Patients with postoperative CEA > 6.2 ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. CONCLUSION: The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2 ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.

2.
Sci Rep ; 14(1): 12001, 2024 05 25.
Article in English | MEDLINE | ID: mdl-38796538

ABSTRACT

The current study aimed to establish an experimental model in vitro and in vivo of urinary crystal deposition on the surface of ureteral stents, to evaluate the ability to prevent crystal adhesion. Non-treated ureteral stents were placed in artificial urine under various conditions in vitro. In vivo, ethylene glycol and hydroxyproline were administered orally to rats and pigs, and urinary crystals and urinary Ca were investigated by Inductively Coupled Plasma-Optical Emission Spectrometer. in vitro, during the 3- and 4-week immersion periods, more crystals adhered to the ureteral stent in artificial urine model 1 than the other artificial urine models (p < 0.01). Comparing the presence or absence of urea in the composition of the artificial urine, the artificial urine without urea showed less variability in pH change and more crystal adhesion (p < 0.05). Starting the experiment at pH 6.3 resulted in the highest amount of crystal adhesion to the ureteral stent (p < 0.05). In vivo, urinary crystals and urinary Ca increased in rat and pig experimental models. This experimental model in vitro and in vivo can be used to evaluate the ability to prevent crystal adhesion and deposition in the development of new ureteral stents to reduce ureteral stent-related side effects in patients.


Subject(s)
Stents , Animals , Rats , Swine , Male , Hydrogen-Ion Concentration , Calcium/urine , Crystallization , Ureter , Ethylene Glycol/chemistry , Hydroxyproline/urine , Urine/chemistry , Rats, Sprague-Dawley
3.
PLoS One ; 19(5): e0292628, 2024.
Article in English | MEDLINE | ID: mdl-38748746

ABSTRACT

Hepatic ischemia-reperfusion injury causes liver damage during surgery. In hepatic ischemia-reperfusion injury, the blood coagulation cascade is activated, causing microcirculatory incompetence and cellular injury. Coagulation factor Xa (FXa)- protease-activated receptor (PAR)-2 signaling activates inflammatory reactions and the cytoprotective effect of FXa inhibitor in several organs. However, no studies have elucidated the significance of FXa inhibition on hepatic ischemia-reperfusion injury. The present study elucidated the treatment effect of an FXa inhibitor, edoxaban, on hepatic ischemia-reperfusion injury, focusing on FXa-PAR-2 signaling. A 60 min hepatic partial-warm ischemia-reperfusion injury mouse model and a hypoxia-reoxygenation model of hepatic sinusoidal endothelial cells were used. Ischemia-reperfusion injury mice and hepatic sinusoidal endothelial cells were treated and pretreated, respectively with or without edoxaban. They were incubated during hypoxia/reoxygenation in vitro. Cell signaling was evaluated using the PAR-2 knockdown model. In ischemia-reperfusion injury mice, edoxaban treatment significantly attenuated fibrin deposition in the sinusoids and liver histological damage and resulted in both anti-inflammatory and antiapoptotic effects. Hepatic ischemia-reperfusion injury upregulated PAR-2 generation and enhanced extracellular signal-regulated kinase 1/2 (ERK 1/2) activation; however, edoxaban treatment reduced PAR-2 generation and suppressed ERK 1/2 activation in vivo. In the hypoxia/reoxygenation model of sinusoidal endothelial cells, hypoxia/reoxygenation stress increased FXa generation and induced cytotoxic effects. Edoxaban protected sinusoidal endothelial cells from hypoxia/reoxygenation stress and reduced ERK 1/2 activation. PAR-2 knockdown in the sinusoidal endothelial cells ameliorated hypoxia/reoxygenation stress-induced cytotoxicity and suppressed ERK 1/2 phosphorylation. Thus, edoxaban ameliorated hepatic ischemia-reperfusion injury in mice by protecting against micro-thrombosis in sinusoids and suppressing FXa-PAR-2-induced inflammation in the sinusoidal endothelial cells.


Subject(s)
Factor Xa Inhibitors , Liver , MAP Kinase Signaling System , Pyridines , Receptor, PAR-2 , Reperfusion Injury , Thiazoles , Animals , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Factor Xa Inhibitors/pharmacology , Receptor, PAR-2/metabolism , Pyridines/pharmacology , Thiazoles/pharmacology , Thiazoles/therapeutic use , Mice , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver/blood supply , MAP Kinase Signaling System/drug effects , Male , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Mice, Inbred C57BL , Disease Models, Animal , Mitogen-Activated Protein Kinase 3/metabolism
4.
CEN Case Rep ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750297

ABSTRACT

Tertiary lymphoid tissue (TLT) develops at sites of chronic immune stimulation, including infection, autoimmune disease, transplant rejection, and cancer. Recently, TLT has been focused on an indicator for poor renal prognosis in various kidney diseases. In cryoglobulinemic vasculitis (CV), specific glomerular and vascular lesions are seen; however, tubulointerstitial lesions are usually nonspecific. We herein report the case of a 74-year-old man with idiopathic CV with rare tubulointerstitial lesions, such as tubulointerstitial nephritis (TIN) with IgG4-positive plasma cell infiltration and TLT. To our knowledge, this is the first report identifying TLT in the kidney biopsy in a patient with CV. Glucocorticoid improved the renal outcome. The association between CV and TIN with TLT remains unknown.

5.
Int J Urol ; 31(5): 459-463, 2024 May.
Article in English | MEDLINE | ID: mdl-38239011

ABSTRACT

Prostatitis is a major urological disease affecting 25%-50% of men over their lifetime. However, prostatitis is often overlooked in nonurologic departments due to its sometimes indeterminate symptoms. In this review, we describe how to recognize and treat acute bacterial prostatitis, which manifests as a clinical problem in other departments as well as urology, to help prevent this disease from being overlooked. There are several possible negative effects of not recognizing acute bacterial prostatitis (ABP). First, initial treatment can fail. In the hyperacute phase, common antibiotics are often effective, but in rare cases, such antibiotics may not be effective. In addition, once ABP progresses to form a prostate abscess, potentially avoidable surgical interventions are often needed. A second issue is the transition to chronic prostatitis. If chronic bacterial prostatitis progresses, treatment requires long-term antibiotic administration and the response rate is not high. Some patients may have to deal with urinary tract infections for the rest of their lives. Finally, there is the problem of overlooking the underlying disease. ABP is rare in healthy adult men without underlying disease, including sexually transmitted diseases as well as benign prostatic hyperplasia, urinary stones, and malignant tumors, and may not be obvious. When examining patients with fever of unknown origin, it is necessary to exclude not only infectious diseases but also collagen diseases and malignant tumors. If there are any doubts, we recommend a rectal exam and consultation with a urologist.


Subject(s)
Anti-Bacterial Agents , Prostatitis , Humans , Male , Prostatitis/complications , Prostatitis/microbiology , Prostatitis/diagnosis , Acute Disease , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/diagnosis , Bacterial Infections/complications , Chronic Disease
6.
J Biochem ; 175(3): 299-312, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38030385

ABSTRACT

Extracellular vesicles (EVs) are important mediators of intercellular communication. However, the methods available for distinguishing the heterogeneity of secreted EVs and isolating and purifying them are limited. This study introduced a HiBiT-tag to detect various EV markers, including CD63, CD9, Epidermal Growth Factor Receptor (EGFR), Flotilin1, and Syndecan-1, and investigated whether these marker-containing vesicles were capable of binding to differently charged column carriers. Four column carriers, Diethylaminoethyl (DEAE), Capto Adhere, Blue and Heparin, showed affinity for CD63 containing EVs, but their elution patterns varied. Furthermore, we observed that the elution patterns of the EV markers differed among vesicles with distinct surface charges when a DEAE column was used. This suggests that the incorporation of EV markers varied between these vesicles. The markers showed different subcellular localizations, indicating that the site of vesicle formation may contribute to the production of vesicles with varying charges and marker incorporation. These findings may have implications for the development of methods to purify homogeneous EVs, which could be useful in EV-mediated drug delivery systems.


Subject(s)
Ethanolamines , Extracellular Vesicles , Extracellular Vesicles/metabolism , Cell Communication , Biological Transport
7.
Case Rep Oncol ; 16(1): 1558-1567, 2023.
Article in English | MEDLINE | ID: mdl-38089732

ABSTRACT

Introduction: C-ros oncogene 1 (ROS1) translocation is an oncogenic driver-mutation identified in 1-2% of non-small-cell lung cancer (NSCLC) cases. Although crizotinib, a tyrosine kinase inhibitor (TKI) against ALK/ROS1, is known to be effective against ROS1-fusion-positive NSCLC, such cases sometimes progress with brain metastases. The most frequently reported crizotinib-resistance mutation is ROS1 G2032R, and some studies have found that even newly developed ROS1 TKIs, such as entrectinib and lorlatinib, show a decreased efficacy against it. The optimal therapies for ROS1-fusion-positive NSCLC and how such cases can be sequenced have not yet been established. Case Presentation: We herein report a patient with ROS1-fusion-positive NSCLC diagnosed at 34 years old. Crizotinib was started at the diagnosis and switched after 25 months to cisplatin/pemetrexed/bevacizumab once the disease progressed with multiple brain metastases that were resistant to stereotactic radiation therapy. The cytotoxic chemotherapy stabilized the patient's condition for 17 months until he developed leptomeningeal metastasis (LM). He underwent lumboperitoneal shunting and whole-brain radiotherapy, followed by crizotinib re-administration. Despite crizotinib treatment, his neurological symptoms, such as double vision, headache, weakness in the legs, and walking difficulties, progressed. Eventually, subsequent entrectinib treatment was initiated, which resolved all of the symptoms mentioned above. Regrettably, liquid next-generation sequencing had failed to detect the resistance mechanism due to minimal ctDNA in this case. Conclusion: These findings imply that sequential entrectinib administration may be effective in patients with disease progression limited to central nervous system metastases during crizotinib administration.

8.
J Virol ; 97(10): e0042623, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37830820

ABSTRACT

IMPORTANCE: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has caused a global public health crisis. The E protein, a structural protein found in this virus particle, is also known to be a viroporin. As such, it forms oligomeric ion channels or pores in the host cell membrane. However, the relationship between these two functions is poorly understood. In this study, we showed that the roles of E protein in virus particle and viroporin formation are distinct. This study contributes to the development of drugs that inhibit SARS-CoV-2 virus particle formation. Additionally, we designed a highly sensitive and high-throughput virus-like particle detection system using the HiBiT tag, which is a useful tool for studying the release of SARS-CoV-2.


Subject(s)
Coronavirus Envelope Proteins , SARS-CoV-2 , Humans , COVID-19 , Lysosomes/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Viroporin Proteins/metabolism , Coronavirus Envelope Proteins/metabolism , Amino Acid Motifs , Virus Release
9.
Langenbecks Arch Surg ; 408(1): 297, 2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37548783

ABSTRACT

BACKGROUND: The study aimed at retrospectively assessing the impact of spleen volume (SpV) on the development of posthepatectomy liver failure (PHLF) in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). METHODS: 152 patients with primary HCC who underwent hepatectomy (sectionectomy or more) were classified into PHLF and non-PHLF groups, and then the relationship between PHLF and SpV was assessed. SpV (cm3) was obtained from preoperative CT and standardized based on the patient's body surface area (BSA, m2). RESULTS: PHLF was observed in 39 (26%) of the 152 cases. SpV/BSA was significantly higher in the PHLF group, and the postoperative 1-year survival rate was significantly worse in the PHLF group than that in the non-PHLF group (p = 0.044). Multivariable analysis revealed SpV/BSA as a significant independent risk factor for PHLF. Using the cut-off value (160 cm3/m2), the 152 cases were divided into small SpV and large SpV groups. The incidence of PHLF was significantly higher in the large SpV group (p = 0.002), the liver failure-related mortality rate was also significantly higher in the large SpV group (p = 0.007), and the 1-year survival rate was significantly worse in the large SpV group (p = 0.035). CONCLUSION: These results suggest SpV as a predictor of PHLF and short-term mortality in patients who underwent hepatectomy for HCC. Moreover, SpV measurement is a simple and potentially useful method for predicting PHLF in patients with HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Failure , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Spleen , Retrospective Studies , Liver Failure/etiology , Liver Failure/surgery , Hepatectomy/adverse effects , Postoperative Complications/epidemiology
10.
J Infect Chemother ; 29(12): 1132-1136, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37611743

ABSTRACT

INTRODUCTION: Retrograde pyelography (RP) is performed for examination of upper urinary tract cancers and hydronephrosis. Although urinary tract infections (UTI) are known to be complicated by the examination, there are few reports on the frequency of occurrence and prophylactic antibiotics. METHODS: The incidence of UTI and febrile UTI (f-UTI) and patient background information were compared in 388 patients who underwent RP at our hospital from January 2018 to December 2022. We also examined the administration of pre-RP antibiotics. RESULTS: Of the 388 patients who underwent RP, 27 (6.9%) had UTI and 17 (4.4%) had f-UTI. Of the 27 UTI cases, 25 (92.6%) were pyelonephritis; 20 (74.0%) were hospitalized and 2 (7.4%) presented with septic shock and were managed in the intensive care unit. When comparing the background of patients with UTI, no significant differences were found in the present study, but when limited to the 17 cases of f-UTI, the presence of hydronephrosis before RP and not prescribing antibiotics before RP were associated with significantly higher incidence of f-UTI (p = 0.019, p = 0.036, respectively). Especially for patients without pyuria and bacteriuria before RP, prescribing antibiotics before RP resulted in 0 cases of f-UTI (p = 0.020). CONCLUSION: This retrospective study showed that the presence of hydronephrosis before RP and not prescribing prophylactic antibiotics before RP are risk factors for f-UTI.

11.
Int J Pharm ; 644: 123297, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37574114

ABSTRACT

DNA nanostructures are promising delivery carriers because of their flexible structural design and high biocompatibility. Selectivity in cellular uptake is an important factor in the development of DNA-nanostructure-based delivery carriers. In this study, DNA nanotubes were selected as the DNA structures, and their selectivity for cellular uptake and the mechanisms involved were investigated. Unlike DNA nanostructures such as polypod-like nanostructured DNA or DNA tetrahedrons, which are easily taken up by macrophages, the formation of DNA nanotubes increases uptake by fibroblasts and fibroblast-like cells. We focused on the collagen expressed in cells as a factor in this process, and found DNA nanotube formation increased the affinity for type I collagen compared with that of single-stranded DNA. Collagenase treatment removes collagen from fibroblasts and reduces the uptake of DNA nanotubes by fibroblasts. We directly observed DNA nanotube uptake by fibroblasts using transmission electron microscopy, whereby the nanotubes were distributed on the cell surface, folded, fragmented, and taken up by phagocytosis. In conclusion, we demonstrated a novel finding that DNA nanotubes are readily taken up by fibroblasts and myoblasts.


Subject(s)
Nanostructures , Nanotubes , Nanotubes/chemistry , Collagen , Nanostructures/chemistry , DNA/chemistry , Fibroblasts
12.
HPB (Oxford) ; 25(10): 1268-1277, 2023 10.
Article in English | MEDLINE | ID: mdl-37419780

ABSTRACT

BACKGROUND: T category classification for pancreatic ductal adenocarcinoma (PDAC) in the Classification of Pancreatic Cancer by the Japan Pancreas Society (JPS) is quite different from that of the American Joint Committee on Cancer (AJCC). The JPS classification focuses on extrapancreatic extension, while the AJCC focuses mainly on tumor size. This study aimed at identifying prognostic factors in PDAC patients undergoing chemoradiotherapy (CRT) by comparing the differences of T categories in these two classifications. METHODS: This retrospective study involved 344 PDAC patients who underwent CRT from 2005 to 2019 and their T-category variables were re-evaluated on computed tomography (CT) images. Disease-specific survival (DSS) was compared based on the JPS and AJCC T categories, while multivariate analysis was performed to identify prognostic factors. RESULTS: Based on the AJCC, 5-year DSS of T3 was better than those of T1 and T2 (57.1% vs. 47.7% and 37.4%). In multivariate analysis, performance status, CEA, the involvement of superior mesenteric vein and superior mesenteric artery, the JPS stage before CRT, and regimen of chemotherapy were identified as independent prognostic factors. CONCLUSIONS: In localized PDAC patients treated with chemoradiotherapy, extrapancreatic extension, as while as biological, conditional and therapeutic factors, is a better prognostic factor than tumor size.


Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Prognosis , Japan , Retrospective Studies , Neoplasm Staging , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/therapy , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/therapy , Pancreas/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/therapy , Chemoradiotherapy , Pancreatic Neoplasms
13.
Langenbecks Arch Surg ; 408(1): 261, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37392289

ABSTRACT

PURPOSE: Neoadjuvant chemotherapy (NAC) is not commonly used for perihilar cholangiocarcinoma (PHC). This study evaluated the safety and efficacy of NAC for PHC. METHODS: Ninety-one PHC patients without metastases were treated at our department. Patients were classified as resectable (R), borderline resectable (BR), or locally advanced unresectable (LA). Upfront surgery (US) was performed for R-PHC patients without regional lymph node metastases (LNM) or those unable to tolerate NAC. The NAC regimen comprised two courses of gemcitabine-based chemotherapy for advanced PHC: R-PHC with LNM, BR, and LA. RESULTS: US and NAC were performed on 32 and 59 patients, respectively. For US, 31 patients underwent curative intent surgery (upfront-CIS). NAC caused adverse effects in 10/59 (17%), allowed 36/59 (61%) to undergo curative intent surgery (NAC-CIS) without impairing liver function, and spared 23/59 (39%) from undergoing resection (NAC-UR). Overall survival was better in the upfront-CIS and NAC-CIS groups than in the NAC-UR group (MST: 74 vs 57 vs 17 months, p < 0.001). In 59 NAC patients, tumour size response occurred in 11/11 (100%) of R, 22/33 (66.7%) of BR, and 9/15 (60.0%) of LA patients. The un-resection rate was the highest in the LA group (27% [3/11] than in R, 30% [10/33] in BR, and 67% [10/15] in LA, p = 0.039). Multivariate analyses revealed that LA and age were independent risk factors for non-resection after NAC. CONCLUSION: was safe and contributed to improving survival in advanced PHC patients. R-PHC was responsive to NAC, but LA remains a risk factor for non-resection through NAC.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Klatskin Tumor , Humans , Klatskin Tumor/drug therapy , Klatskin Tumor/surgery , Neoadjuvant Therapy , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic
14.
Cancers (Basel) ; 15(10)2023 May 10.
Article in English | MEDLINE | ID: mdl-37345021

ABSTRACT

Since castration-resistant prostate cancer (CRPC) acquires resistance to molecularly targeted drugs, discovering a class of drugs with different mechanisms of action is needed for more efficient treatment. In this study, we investigated the anti-tumor effects of nanaomycin K, derived from "Streptomyces rosa subsp. notoensis" OS-3966. The cell lines used were LNCaP (non-CRPC), PC-3 (CRPC), and TRAMP-C2 (CRPC). Experiments included cell proliferation analysis, wound healing analysis, and Western blotting. In addition, nanaomycin K was administered intratumorally to TRAMP-C2 carcinoma-bearing mice to assess effects on tumor growth. Furthermore, immuno-histochemistry staining was performed on excised tissues. Nanaomycin K suppressed cell proliferation in all cell lines (p < 0.001) and suppressed wound healing in TRAMP-C2 (p = 0.008). Nanaomycin K suppressed or showed a tendency to suppress the expression of N-cadherin, Vimentin, Slug, and Ras in all cell lines, and suppressed the phosphorylation of p38, SAPK/JNK, and Erk1/2 in LNCaP and TRAMP-C2. In vivo, nanaomycin K safely inhibited tumor growth (p = 0.001). In addition, suppression of phospho-Erk1/2 and increased expression of E-cadherin and cleaved-Caspase3 were observed in excised tumors. Nanaomycin K inhibits tumor growth and suppresses migration by inhibiting epithelial-mesenchymal transition in prostate cancer. Its mechanism of action is related to the inhibition of phosphorylation of the MAPK signaling pathway.

16.
Anticancer Res ; 43(7): 3003-3013, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37351958

ABSTRACT

BACKGROUND/AIM: Dendritic cells (DCs) are difficult to evaluate in lung regional lymph nodes because of region-specific structures, such as abundant trabeculae connecting the medullary and subcapsular sinuses, the latter of which contains few anthracotic macrophages. Therefore, DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DCsign)-positive DCs and CD68-positive macrophages are unlikely to show a typical distribution. The present study therefore explored quantitative factors connecting the nodal DC morphology to the patient outcome. MATERIALS AND METHODS: Lymph nodes from 34 non-small-cell lung cancer patients who underwent complete resection were used for immunohistochemical assessments of DCsign and CD68 and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Preoperative patient blood samples were used for the quantitative evaluation of monocytes. RESULTS: The nodal DCs showed a complementary distribution with macrophages, thus few DCs were seen in clusters of macrophages. DCs often presented as a mesh-like rosette that was solitary or connected to a DC cluster. DCs disappeared, and some macrophages were apoptotic when surrounded by cancer cells that have metastasized to lymph nodes. The proportional area of a DC cluster was significantly associated with the histological differentiation of cancer (p=0.013), with a higher ratio tending to lead to a better overall survival (p=0.059), and significantly so in adenocarcinoma (p=0.007). The rosette number was significantly correlated with the smoking index and blood monocyte number (p=0.013 and p=0.005, respectively). CONCLUSION: The nodal DC morphology appears useful as a prognostic factor and may lead to a new phase of clinicopathological studies of solid cancers.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Clinical Relevance , Macrophages/metabolism , Monocytes/pathology , Lymph Nodes/pathology , Transforming Growth Factor beta/metabolism , Dendritic Cells/metabolism
17.
Oncology ; 101(10): 645-654, 2023.
Article in English | MEDLINE | ID: mdl-37364538

ABSTRACT

INTRODUCTION: Prostate cancer (PCA) is one of the most common cancers in the world, and current therapies are debilitating to patients. To develop a novel modality for the treatment of PCA, we evaluated the efficacy of intralesional administration of the Sirt3 activator Honokiol (HK) and the NADPH oxidase inhibitor Dibenzolium (DIB). METHODS: We used a well-established transgenic adenocarcinoma mouse prostate (TRAMP-C2) model of hormone-independent PCA. MTS assay, apoptosis assay, wound healing assay, transwell invasion assay, RT-qPCR, and Western blotting were conducted in vitro, and HK and DIB were intratumorally administered to mice bearing TRAMP-C2 tumors. Tumor size and weight were observed over time. After removing tumors, H-E staining and immunohistochemistry (IHC) staining were conducted. RESULTS: Treatment by HK or DIB showed an inhibitory effect on cell proliferation and migration in PCA cells. Poor ability to induce apoptosis in vitro, insufficient expression of caspase-3 on IHC staining, and increased necrotic areas on H-E staining indicated that necrosis plays an important role in cell death in treating groups by HK or DIB. RT-PCR, Western blotting, and IHC staining for epithelial mesenchymal transition (EMT) markers suggested that EMT was suppressed by HK and DIB individually. In addition, HK induced activation of CD3. Mouse experiments showed safe antitumor effects in vivo. CONCLUSIONS: HK and DIB suppressed PCA proliferation and migration. Further research will explore the effects of HK and DIB at the molecular level to reveal new mechanisms that can be exploited as therapeutic modalities.


Subject(s)
Prostatic Neoplasms , Male , Humans , Mice , Animals , Cell Line, Tumor , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Immunohistochemistry , Epithelial-Mesenchymal Transition , Cell Proliferation , Cell Movement
18.
Prostate ; 83(12): 1217-1226, 2023 09.
Article in English | MEDLINE | ID: mdl-37221965

ABSTRACT

BACKGROUND: Ultrasound (US) can induce cell injury, and we have previously reported that adjusting the pulse repetition frequency (PRF) of ultrasound output can induce prostate cancer cell destruction without causing a rise in the temperature of the irradiated area. In this study, we examined the mechanism of nonthermal ultrasound cell destruction, which was not fully clarified in our previous reports. METHODS: In vitro, we evaluated postirradiation cells immediately after treatment and examined membrane disruption by proliferation assay, LDH assay, and apoptosis assay. In vivo, we injected mice with human LNCaP and PC-3 prostate cancer cells and evaluated the therapeutic effects of US irradiation by H-E staining and immunostaining. RESULTS: Proliferation assays showed inhibition at 3 h postirradiation independently of PRF and cell line (p < 0.05). Quantitative assessment of apoptosis/necrosis by flow cytometry showed widely varying results depending on cell type. LNCaP showed an increase in late apoptosis at 0 h independent of PRF (p < 0.05), while PC-3 showed no significant difference at 0 h. The LDH assay showed an increase in LDH independent of PRF in LNCaP (p < 0.05 respectively), but no significant difference in PC-3. In vivo, tumor volume was compared and a significant reduction was observed at 10 Hz for LNCaP (p < 0.05) and 100 Hz for PC-3 (p < 0.001) at 3 weeks after the start of irradiation. The excised tumors were evaluated with Ki-67, Caspase-3, and CD-31 and showed a significant treatment effect independent of cell type and PRF (p < 0.001 respectively). CONCLUSION: Examining the mechanism behind the therapeutic effect of US irradiation revealed that the main effect was achieved by apoptosis induction rather than necrosis.


Subject(s)
Prostatic Neoplasms , Male , Humans , Animals , Mice , Mice, Nude , Prostatic Neoplasms/metabolism , Prostate/pathology , Apoptosis , Disease Models, Animal , Necrosis , Cell Line, Tumor
19.
Surg Today ; 53(8): 917-929, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36943448

ABSTRACT

PURPOSE: Radical antegrade modular pancreatosplenectomy (RAMPS) is a standard procedure for patients with pancreatic body and tail cancer. There are two types of RAMPS: anterior and posterior, but their indications and surgical outcomes remain unclear. We compared the surgical outcomes, postoperative course, and prognosis between anterior and posterior RAMPS. METHODS: Between 2007 and 2020, 105 consecutive patients who underwent RAMPS for pancreatic body and tail cancers were divided into an anterior RAMPS group (n = 30) and a posterior RAMPS group (n = 75). To adjust for differences in preoperative characteristics and intraoperative procedures, an inverse probability of treatment weighting (IPTW) analysis was done, using propensity scores. RESULTS: After IPTW adjustment, the postoperative body temperature of the posterior RAMPS group and the amount of drain discharge in the anterior RAMPS group were significantly lower, from postoperative days (PODs) 1 to 3, but there were no differences in postoperative complications, recurrence patterns, or prognosis between the two groups. Regarding the diagnostic ability of multidetector-row computed tomography (MD-CT) for direct tumor involvement of the left adrenal gland, the sensitivity and specificity were 100% and 90.0%, respectively. CONCLUSION: Pancreatic body and tail cancer without apparent preoperative direct tumor involvement of the left adrenal gland on MD-CT may be sufficient indication for anterior RAMPS.


Subject(s)
Laparoscopy , Pancreatic Neoplasms , Humans , Pancreatectomy/methods , Pancreatic Neoplasms/pathology , Splenectomy/methods , Survival Analysis , Probability
20.
Rinsho Ketsueki ; 64(2): 125-129, 2023.
Article in Japanese | MEDLINE | ID: mdl-36990732

ABSTRACT

A 59-year-old-woman complained of weight loss and abdominal pain. A CT scan revealed a 20 cm large retroperitoneal mass, and she was diagnosed with diffuse large B-cell lymphoma via biopsy of the mass. After 75% CHP therapy, she developed an acute abdomen and CT revealed generalized peritonitis. Amylase in the ascites fluid was elevated, and infiltration into the pancreas was suspected on CT before treatment, suggesting a pancreatic fistula caused by tumor shrinkage. Enterobacteria were found in ascites fluid culture, suggesting a gastrointestinal perforation complication. The patient was refractory to treatment, and death was confirmed due to progression of the primary disease. The pathological autopsy revealed diffuse pancreatic infiltration, suggesting that the pancreatic fistula was caused by pancreatic injury. Pancreatic fistula is a known complication of surgical procedures but is rarely caused by tumor shrinkage due to chemotherapy. Since there is no preventive method for pancreatic injury caused by tumor shrinkage, early diagnosis and early treatment of pancreatic fistula are critical, and ascites fluid analysis, including amylase, was thought to be useful for the diagnosis.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Peritonitis , Female , Humans , Middle Aged , Pancreatic Fistula/complications , Ascites , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Peritonitis/complications , Amylases/therapeutic use
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