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1.
Oncol Lett ; 28(4): 458, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39114573

ABSTRACT

The association of computed tomography (CT)-derived skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) with postoperative prognosis in patients with gastric cancer (GC) remains unknown. Therefore, the present study aimed to assess the association between SMI and SMD with 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with GC. SMI and SMD were measured preoperatively in patients who underwent gastrectomy. Patients were categorized into Groups 1 (high SMI and SMD), 2 (high SMI or SMD) and 3 (low SMI and SMD). OS and RFS rates were assessed using Kaplan-Meier analysis and the log-rank test. Among 459 patients, OS and RFS rates were significantly lower in the low-SMD group than in the high-SMD group (OS, 83.4% vs. 88.8%, respectively; P=0.04 and RFS, 80.5% vs. 87.2%, respectively; P=0.02). OS and RFS rates were also significantly lower in Group 3 than in Groups 2 and 1 (P=0.006). Multivariate analysis revealed that a low SMI and SMD (Group 3) was a significant independent prognostic factor for OS [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.17-4.59; P=0.016] and RFS (HR, 2.28; 95% CI, 1.19-4.37; P=0.013). In summary, low SMI and SMD values may be useful postoperative prognostic indicators for patients with GC.

2.
Anticancer Res ; 44(8): 3515-3524, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39060072

ABSTRACT

BACKGROUND/AIM: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex. PATIENTS AND METHODS: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis. RESULTS: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females. CONCLUSION: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival.


Subject(s)
Gastrectomy , Intra-Abdominal Fat , Stomach Neoplasms , Subcutaneous Fat , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnostic imaging , Male , Female , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/pathology , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Middle Aged , Aged , Gastrectomy/mortality , Prospective Studies , Sex Factors , Prognosis , Preoperative Period , Adult , Postoperative Period , Aged, 80 and over , Kaplan-Meier Estimate , Tomography, X-Ray Computed
3.
Heliyon ; 10(12): e32973, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38988571

ABSTRACT

Hypertrophic pachymeningitis (HP) is a rare inflammatory disease characterized by thickening of the dura mater. HP develops with several inflammatory diseases. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and IgG4 related disease are reported as 2 major causes. With hematologic diseases, only 3 cases have been reported. We report the case of myelodysplastic syndrome (MDS) developing HP. Our case provides a thought-provoking hypothesis regarding the potential relationship between MDS and HP.

4.
Chem Sci ; 15(27): 10402-10407, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38994432

ABSTRACT

Non-canonical terpene synthases (TPSs) with primary sequences that are unrecognizable as canonical TPSs have evaded detection by conventional genome mining. This study aimed to prove that novel non-canonical TPSs can be efficiently discovered from proteins, hidden in genome databases, predicted to have 3D structures similar to those of class I TPSs. Six types of non-canonical TPS candidates were detected using this search strategy from 268 genome sequences from actinomycetes. Functional analyses of these candidates revealed that at least three types were novel non-canonical TPSs. We propose classifying the non-canonical TPSs as classes ID, IE, and IF. A hypothetical protein MBB6373681 from Pseudonocardia eucalypti (PeuTPS) was selected as a representative example of class ID TPSs and characterized. PeuTPS was identified as a diterpene synthase that forms a 6/6/6-fused tricyclic gersemiane skeleton. Analyses of PeuTPS variants revealed that amino acid residues within new motifs [D(N/D), ND, and RXXKD] located close to the class I active site in the 3D structure were essential for enzymatic activity. The homologs of non-canonical TPSs found in this study exist in bacteria as well as in fungi, protists, and plants, and the PeuTPS gene is not located near terpene biosynthetic genes in the genome. Therefore, structural-model-based genome mining is an efficient strategy to search for novel non-canonical TPSs that are independent of biological species and biosynthetic gene clusters and will contribute to expanding the structural diversity of terpenoids.

5.
Surg Endosc ; 38(8): 4236-4244, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38858251

ABSTRACT

INTRODUCTION: Indocyanine green fluorescence imaging (ICG-FI) reduces anastomotic leakage (AL) in rectal cancer surgery. However, no studies investigating risk factors for anastomotic leakage specific to the group using ICG-FI have ever previously been conducted. The purpose of this retrospective multicenter study was to ascertain the risk factors for AL in the group using ICG-FI. METHODS: A total of 638 patients who underwent laparoscopic or robotic anterior resection for rectal cancer between April 2018 and March 2023 were included in this study. Patients were divided into two groups: the ICG-FI group (n = 269) and the non-ICG-FI group (n = 369) for comparative analysis. The effects of clinicopathological and treatment-related factors on AL in the ICG-FI group were evaluated using both univariate and multivariate analyses. RESULTS: The incidence of AL in the ICG-FI group was 4.8%. Although there was no significant difference in the incidence of AL between the two groups, it was observed to be lower in the ICG-FI group. A multivariate analysis revealed a preoperative C-reactive protein-to-albumin ratio (CAR) ≥ 0.049 (odds ratio, 3.73; 95% confidence interval, 1.01-13.70; p = 0.048) as an independent risk factor for AL in the ICG-FI group. CONCLUSIONS: In this study, CAR was the only identified risk factor for AL in the ICG-FI group. It was suggested that CAR could be a criterion for early surgical intervention, prior to the escalation of risks, or for considering interventions such as diverting stoma creation.


Subject(s)
Anastomotic Leak , C-Reactive Protein , Indocyanine Green , Optical Imaging , Rectal Neoplasms , Humans , Anastomotic Leak/etiology , Anastomotic Leak/epidemiology , Rectal Neoplasms/surgery , Male , Female , Retrospective Studies , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Risk Factors , Middle Aged , Aged , Optical Imaging/methods , Laparoscopy/methods , Laparoscopy/adverse effects , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Coloring Agents , Serum Albumin/analysis , Serum Albumin/metabolism
7.
Langenbecks Arch Surg ; 409(1): 189, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896303

ABSTRACT

PURPOSE: Although there have been many reports on learning curves for robotic surgery, it is unclear how surgeons' conventional laparoscopic surgical skills influence their ability in performing robotic surgery for colorectal cancer (CRC). The aim of this study was to determine the surgical outcomes of robotic surgery for CRC during the induction phase by skilled laparoscopic surgeons. METHODS: Surgical outcomes of consecutive CRC cases between January 2021 and March 2023 following the skilled phase of laparoscopic surgery and introductory phase of robotic surgery performed by three skilled laparoscopic surgeons were compared. RESULTS: Overall, 77 consecutive patients diagnosed with sigmoid colon or rectosigmoid cancer were analysed, including 50 in the laparoscopy group (LAP) and 27 in the robotic group (Ro). Patient characteristics, including age, sex, body mass index, and tumour progression, did not differ between the groups. The median operation time was 204 min in the robotic group and 170 min in the laparoscopic group (p < 0.001). Blood loss was significantly lower in the robotic group (p = 0.0059). The incidence of grade 2 or higher complications did not differ between the two groups (LAP, 10.0% vs. Ro, 7.4%, p = 1). In the robotic group, the time required for lymph node dissection had a greater impact on operative duration. CONCLUSION: Skills acquired from performing conventional laparoscopic surgery may contribute to the safe and reliable performance of robotic surgery for CRC. TRIAL REGISTRATION: UMIN000050923.


Subject(s)
Clinical Competence , Colorectal Neoplasms , Laparoscopy , Robotic Surgical Procedures , Humans , Male , Female , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Aged , Middle Aged , Operative Time , Learning Curve , Retrospective Studies , Treatment Outcome , Aged, 80 and over
8.
Methods Enzymol ; 699: 477-512, 2024.
Article in English | MEDLINE | ID: mdl-38942515

ABSTRACT

Large terpene synthases (large-TSs) are a new family of TSs. The first large-TS discovered was from Bacillus subtilis (BsuTS), which is involved in the biosynthesis of a C35 sesquarterpene. Large-TSs are the only enzymes that enable the biosynthesis of sesquarterpenes and do not share any sequence homology with canonical Class I and II TSs. Thus, the investigation of large-TSs is promising for expanding the chemical space in the terpene field. In this chapter, we describe the experimental methods used for identifying large-TSs, as well as their functional and structural analyses. Additionally, several enzymes related to the biosynthesis of large-TS substrates have been described.


Subject(s)
Alkyl and Aryl Transferases , Bacillus subtilis , Alkyl and Aryl Transferases/metabolism , Alkyl and Aryl Transferases/chemistry , Alkyl and Aryl Transferases/genetics , Bacillus subtilis/enzymology , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Terpenes/metabolism , Terpenes/chemistry , Substrate Specificity
9.
Diagn Pathol ; 19(1): 89, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943126

ABSTRACT

BACKGROUND: Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and comprises > 95% of all LPL cases. Rituximab-based regimens have been predominant in the management of WM. Infusion-related reactions (IRRs) are a primary concern with rituximab, although it is generally better tolerated with less toxicity than conventional anticancer agents. Here, we present an autopsy case of an elderly man who died suddenly after receiving the initial infusion of rituximab for WM/LPL. CASE PRESENTATION: An 84-year-old man was found dead in his bedroom. He had undergone the initial intravenous rituximab infusion for progressive anemia related to Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) approximately 15 h before death. Although the protocol for rituximab administration and additional medication was considered appropriate, he exhibited several symptoms consistent with infusion-related reactions (IRRs) during the infusion. Autopsy revealed monotonous proliferation of small-to-medium-sized lymphocytic cells in the bone marrow, consistent with the premortem diagnosis of WM/LPL. Additionally, immunoglobulin λ-light chain-derived amyloid (ALλ) deposition was identified in all organs other than the brain. Although ALλ deposition and LPL infiltration were found in the heart, they were not severe enough to cause severe functional impairment. Severe congestion and/or edema were observed in the lungs, liver, and brain. Although significant inflammatory cell infiltration was not found in any organs, laboratory tests revealed elevated serum levels of inflammatory cytokines, including interleukin-1ß, interleukin-6, tumor necrosis factor-α and the presence of IgM-λ monoclonal protein. CONCLUSION: Acute IRRs associated with the initial rituximab infusion were the major contributing factor to his sudden unexpected death. The autopsy findings of present case suggest the necessity for thorough monitoring of older patients with WM/LPL undergoing rituximab treatment, particularly when pronounced IRRs occur during the first administration, in addition to investigating complications of WM/LPL before infusion.


Subject(s)
Autopsy , Rituximab , Waldenstrom Macroglobulinemia , Humans , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/pathology , Waldenstrom Macroglobulinemia/complications , Rituximab/adverse effects , Rituximab/administration & dosage , Male , Aged, 80 and over , Death, Sudden/etiology , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/administration & dosage , Bone Marrow/pathology , Fatal Outcome , Infusions, Intravenous
10.
Colorectal Dis ; 26(5): 1047-1052, 2024 May.
Article in English | MEDLINE | ID: mdl-38566354

ABSTRACT

AIM: Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) is rapidly spreading. The robotic surgical techniques to approach lateral invasion, such as that of the pelvic plexus, have not yet been established. In this technical note, we present a video illustrating a surgical technique for lateral invasion using our novel technique and discuss its pitfalls. METHOD: We present the case of a 65-year-old man with LARC. Robotic surgery was performed after TNT using the da Vinci Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). The surgical procedure was as follows: (1) D3 lymph node dissection around the inferior mesenteric artery using a medial-to-lateral approach; (2) rectal mobilization; (3) dissection of the ureterohypogastric fascia and ureter; and (4) combined resection of the hypogastric nerve and pelvic plexus. The key surgical point for sidewall invasion is the resection extent. Dividing the resection extent into three areas is important: zone A, which contains the pelvic plexus and is closest to the tumour; zone B, which contains the iliac vessels; and zone C, the most lateral zone, which contains the obturator nerves. This allows organ and function preservation by resecting only the smallest organ that truly requires R0 resection. RESULTS: The operating time was 333 min, console time was 232 min, and blood loss was 0 mL. The circumferential resection margin was 10 mm, and an R0 resection was achieved. CONCLUSION: We introduced a novel approach for robotic surgery after TNT for LARC with sidewall invasion. This technique can be performed safely and may help standardize 'beyond total mesorectal excision'.


Subject(s)
Neoadjuvant Therapy , Neoplasm Invasiveness , Rectal Neoplasms , Robotic Surgical Procedures , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Male , Neoadjuvant Therapy/methods , Aged , Robotic Surgical Procedures/methods , Rectum/surgery , Proctectomy/methods , Lymph Node Excision/methods , Hypogastric Plexus/surgery
11.
In Vivo ; 38(3): 1509-1511, 2024.
Article in English | MEDLINE | ID: mdl-38688637

ABSTRACT

BACKGROUND/AIM: Immune checkpoint inhibitors can induce immune-related adverse events in various organs, thus careful observation is required. CASE REPORT: A 69-year-old man was diagnosed with advanced lung adenocarcinoma and treated with combined therapy of carboplatin plus pemetrexed plus pembrolizumab. After two cycles of treatment, anemia was noted. Myelosuppression due to cytotoxic anticancer agents was suspected and the cytotoxic agents were discontinued, followed by three courses of pembrolizumab monotherapy. However, the anemia persisted, requiring red blood cell transfusions. A bone marrow biopsy revealed erythroblast hypoplasia and chromosomal abnormalities, resulting in a diagnosis of pure red cell aplasia. These adverse events were considered immune-related because of the treatment history with an immune checkpoint inhibitor, and 60 mg/day (1 mg/kg/day) of prednisolone was initiated. Anemia improved, and it did not recur during the tapering of prednisolone. CONCLUSION: Immune-related pure red cell aplasia should be considered for patients presenting anemia during treatment with immune checkpoint inhibitors.


Subject(s)
Adenocarcinoma of Lung , Antibodies, Monoclonal, Humanized , Chromosome Aberrations , Immune Checkpoint Inhibitors , Lung Neoplasms , Red-Cell Aplasia, Pure , Humans , Red-Cell Aplasia, Pure/chemically induced , Red-Cell Aplasia, Pure/drug therapy , Male , Aged , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Immune Checkpoint Inhibitors/adverse effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
12.
Gan To Kagaku Ryoho ; 51(3): 334-335, 2024 Mar.
Article in Japanese | MEDLINE | ID: mdl-38494823

ABSTRACT

Desmoid-type fibromatosis is a relatively rare disease, often associated with familial adenomatous polyposis and a history of abdominal surgery. A 43-year-old male patient presented with abdominal pain and contrast-enhanced CT showed a mass in the lower abdomen. The mass was a 4×4×3 cm white, dense tumor with a wreath-like arrangement of eosinophilic spindle-shaped cells. Immunostaining showed KIT(-), CD34(-), desmin(-), ß-catenin(+), SMA(few+), and the diagnosis was desmoid-type fibrosis. Six months after surgery, there was no apparent recurrence.


Subject(s)
Adenomatous Polyposis Coli , Fibromatosis, Abdominal , Fibromatosis, Aggressive , Male , Humans , Adult , Fibromatosis, Aggressive/surgery , Fibromatosis, Aggressive/diagnosis , Adenomatous Polyposis Coli/surgery , Adenomatous Polyposis Coli/complications , Mesentery/surgery , Mesentery/pathology , Abdominal Pain , Intestine, Small/surgery , Intestine, Small/pathology , Fibromatosis, Abdominal/surgery
13.
Environ Geochem Health ; 46(2): 64, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38319371

ABSTRACT

This study explored the legacy impact of Zinc plant residues (ZPRs) in Kabwe, Zambia, on the environment and human health, particularly in light of the town's reputation for Pb pollution. ZPRs solid samples and groundwater within and around ZPRs zone were collected from the legacy mine, along with soils in a 10 km radius from the mine site. Bioaccessible fractions of Pb and Zn were elucidated by Japanese leaching test (JLT) and simple bioaccessibility extraction test (SBET). Cationic speciation of Pb and Zn from inhalable and ingestible ZPRs particles was investigated via sequential extraction. Groundwater in the ZPRs area showed higher Zn levels (1490 mg/L) compared to Pb (1.7 mg/L). Elevated Zn concentration were facilitated by the presence of soluble Zn sulfates while Pb was constrained due to its precipitation as anglesite. Groundwater sampled outside the ZPRs area was within the Zambia regulatory limits (< 0.5 mg/L for Pb and < 1 mg/L for Zn). Inhalation exposure to < 30 µm dust particles from ZPRs and soils near the mine indicated negligible risk, with < 3% of bioaccessible Pb in artificial lysosomal fluid. Meanwhile, oral intake of ZPRs particles < 250 µm revealed elevated bioaccessible fractions (36% for Pb and 70% for Zn). ZPRs cationic speciation of ingestible particles < 30 µm, 30-75 µm, 75-150 µm and 150-250 µm indicated that the bioaccessible Pb predominantly emanated from labile Pb fractions under gastric conditions with pH < 1. This was due to the dissolution of Pb associated with the exchangeable phase, carbonates and iron/manganese oxides; however, only exchangeable/carbonate Pb was bioaccessible at pH < 2. Hazard quotients indicated increased risks of Pb intoxication through the ingestion of ZPRs and soils near the legacy mine, with higher risks observed in children, emphasizing the need to remediate legacy mine wastes to reduce health risks and protect groundwater through monitoring in mining-affected regions.


Subject(s)
Groundwater , Lead , Child , Humans , Zinc , Manganese , Dust
14.
Int J Mol Sci ; 25(3)2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38338848

ABSTRACT

Multiple myeloma (MM) is a cancer of plasma cells. Normal (NL) cells are considered to pass through a precancerous state, such as monoclonal gammopathy of undetermined significance (MGUS), before transitioning to MM. In the present study, we acquired Raman spectra at three stages-834 NL, 711 MGUS, and 970 MM spectra-and applied the dynamical network biomarker (DNB) theory to these spectra. The DNB analysis identified MGUS as the unstable pre-disease state of MM and extracted Raman shifts at 1149 and 1527-1530 cm-1 as DNB variables. The distribution of DNB scores for each patient showed a significant difference between the mean values for MGUS and MM patients. Furthermore, an energy landscape (EL) analysis showed that the NL and MM stages were likely to become stable states. Raman spectroscopy, the DNB theory, and, complementarily, the EL analysis will be applicable to the identification of the pre-disease state in clinical samples.


Subject(s)
Monoclonal Gammopathy of Undetermined Significance , Multiple Myeloma , Paraproteinemias , Humans , Multiple Myeloma/diagnosis , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Spectrum Analysis, Raman , Paraproteinemias/diagnosis , Biomarkers , Disease Progression
15.
Sci Rep ; 14(1): 1419, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38228813

ABSTRACT

Onoceroids are a rare family of triterpenes. One representative onoceroid is ambrein, which is the main component of ambergris used as a traditional medicine. We have previously identified the onoceroid synthase, BmeTC, in Bacillus megaterium and succeeded in creating ambrein synthase by introducing mutations into BmeTC. Owing to the structural similarity of ambrein to vitamin D, a molecule with diverse biological activities, we hypothesized that some of the activities of ambergris may be induced by the binding of ambrein to the vitamin D receptor (VDR). We demonstrated the VDR binding ability of ambrein. By comparing the structure-activity relationships of triterpenes with both the VDR affinity and osteoclastic differentiation-promoting activity, we observed that the activity of ambrein was not induced via the VDR. Therefore, some of the activities of ambergris, but not all, can be attributed to its VDR interaction. Additionally, six unnatural onoceroids were synthesized using the BmeTC reactions, and these compounds exhibited higher VDR affinity than that of ambrein. Enzymatic syntheses of onoceroid libraries will be valuable in creating a variety of bioactive compounds beyond ambergris.


Subject(s)
Ambergris , Triterpenes , Ambergris/chemistry , Receptors, Calcitriol , Triterpenes/pharmacology , Naphthols/chemistry , Vitamin D
16.
J Pharmacol Sci ; 154(1): 30-36, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38081681

ABSTRACT

Overexpression of inhibitor of apoptosis (IAP) proteins is associated with poor prognosis. In multiple myeloma (MM), the IAP inhibitors (IAPi), LCL161, have been evaluated in preclinical and clinical settings but are not fully effective. Among IAPs, XIAP has the strongest anti-apoptotic function with direct binding activity to caspases and cIAP1 and cIAP2 are positive regulator of NF-κB signaling. Prior IAPi such as LCL161 has high affinity to cIAP1 and cIAP2 resulting in inferior inhibiting activity against XIAP. A novel dimeric IAPi, AZD5582 (C58H78N8O8), have high binding potency to XIAP with EC50 dose of 15 nM, enabling to simultaneous inhibit XIAP and cIAP1/2. AZD5582 monotherapy showed cell growth inhibition for all MM cell lines, MM1S, RPMI8226, U266 and KMS-5 and induced apoptosis. AZD5582 further showed anti-proliferation effect under the IL-6 additional condition and inhibited JAK-STAT signaling triggered by IL-6. AZD5582 combined with carfilzomib therapy showed a synergistic effect. Enhanced apoptosis was also observed in combination therapy. Synergistic effect was further observed with other conventional therapeutics. Simultaneous XIAP and cIAP1/2 inhibition by the dimeric IAPi AZD5582 is promising. This study provides a rationale of AZD5582 as a new treatment strategy in monotherapy and in combination therapy.


Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/drug therapy , Interleukin-6 , Cell Line, Tumor , Apoptosis , Inhibitor of Apoptosis Proteins/metabolism , Inhibitor of Apoptosis Proteins/pharmacology , X-Linked Inhibitor of Apoptosis Protein/metabolism , X-Linked Inhibitor of Apoptosis Protein/pharmacology
17.
Eur J Oncol Nurs ; 67: 102461, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37976753

ABSTRACT

PURPOSE: Health literacy (HL) is pivotal in managing patients with abdominal cancer and is associated with treatment outcomes and care experience. However, detailed characteristics of HL and their associations with clinical features remain uncertain in the population. Therefore, we aimed to comprehensively investigate HL and its associations with clinical characteristics in older patients with abdominal tumours. METHODS: We analysed 103 older patients with abdominal tumours prescribed perioperative rehabilitation programs in an acute care hospital. The Japanese version of the European Health Literacy Survey Questionnaire was used to measure comprehensive HL. Multivariate ordinal or linear regression analyses were used to explore the associations between HL and the following clinical characteristics: physical status, physical function, cardiopulmonary function, levels of activities of daily living (ADL), physical activity level, and health-related quality of life (HR-QoL). All regression analyses included patient demographics as covariates. RESULTS: Approximately 50%-70% of the participants had difficulty accessing and appraising health-related information, and 20%-45% thought it was difficult to understand and apply the information. The percentage of limited HL levels in general HL, three health-relevant domains, and four competencies ranged from 62% to 83%. Moreover, regression analyses revealed that lower HL was associated with worse physical status/function, lower ADL, and poorer HR-QoL. CONCLUSION: Most older patients with abdominal tumours have limited HL, which may lead them to make treatment decisions without fully understanding what healthcare providers advise. Furthermore, patients with lower HL are at a higher risk of poor treatment outcomes because of their worse clinical characteristics.


Subject(s)
Abdominal Neoplasms , Health Literacy , Humans , Aged , Quality of Life , Cross-Sectional Studies , Activities of Daily Living , Surveys and Questionnaires
18.
Anticancer Res ; 43(12): 5663-5670, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38030195

ABSTRACT

BACKGROUND/AIM: Ramucirumab plus paclitaxel has been widely used as a second-line chemotherapy for treating advanced gastric cancer. However, the real-world data of this regimen for older patients with gastric cancer (GC) remains unrevealed. The aim of this study was to clarify the feasibility and efficacy of this regimen for older patients with GC in a single-arm, phase II study. PATIENTS AND METHODS: Patients aged ≥70 years having unresectable or recurrent GC who met the eligible criteria were enrolled. Paclitaxel was administered at a dose of 80 mg/m2 on days 1, 8, and 15, and ramucirumab was administered at a dose of 8 mg/kg on day 1 and day 15 of a 4-week cycle. Primary endpoint was the incidence of adverse events and secondary endpoints were response rate, progression-free survival, and overall survival. A total of 25 patients were enrolled in the full-set analysis. RESULTS: Grade 3 or more adverse events were observed in 21 patients (84.0%). Neutropenia was most frequently observed (68.0%), followed by peripheral sensory neuropathy (12.0%), and febrile neutropenia (12.0%). Median progression-free survival and overall survival were 6.9 months and 13.4 months, respectively. Disease control rate was 88.0%, and response rate of patients with measurable lesions was 52.9%. Notably, no treatment-related deaths occurred. CONCLUSION: Ramucirumab plus paclitaxel as a second-line chemotherapy demonstrated acceptable oncological outcomes, despite the occurrence of frequent adverse events. It is necessary to carefully select patients and adjust treatment regimens in older patients with GC to safely administer chemotherapy and subsequently achieve satisfactory long-term outcomes.


Subject(s)
Adenocarcinoma , Stomach Neoplasms , Humans , Aged , Paclitaxel/therapeutic use , Stomach Neoplasms/pathology , Adenocarcinoma/pathology , Neoplasm Recurrence, Local/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Ramucirumab
19.
Cells ; 12(16)2023 08 14.
Article in English | MEDLINE | ID: mdl-37626869

ABSTRACT

Chimeric-antigen-receptor (CAR) T-cell therapy for CD19-expressing B-cell malignancies is already widely adopted in clinical practice. On the other hand, the development of CAR-T-cell therapy for T-cell malignancies is in its nascent stage. One of the potential targets is CD26, to which we have developed and evaluated the efficacy and safety of the humanized monoclonal antibody YS110. We generated second (CD28) and third (CD28/4-1BB) generation CD26-targeted CAR-T-cells (CD26-2G/3G) using YS110 as the single-chain variable fragment. When co-cultured with CD26-overexpressing target cells, CD26-2G/3G strongly expressed the activation marker CD69 and secreted IFNgamma. In vitro studies targeting the T-cell leukemia cell line HSB2 showed that CD26-2G/3G exhibited significant anti-leukemia effects with the secretion of granzymeB, TNFα, and IL-8, with 3G being superior to 2G. CD26-2G/3G was also highly effective against T-cell lymphoma cells derived from patients. In an in vivo mouse model in which a T-cell lymphoma cell line, KARPAS299, was transplanted subcutaneously, CD26-3G inhibited tumor growth, whereas 2G had no effect. Furthermore, in a systemic dissemination model in which HSB2 was administered intravenously, CD26-3G inhibited tumor growth more potently than 2G, resulting in greater survival benefit. The third-generation CD26-targeted CAR-T-cell therapy may be a promising treatment modality for T-cell malignancies.


Subject(s)
Lymphoma, T-Cell , Receptors, Chimeric Antigen , Animals , Mice , T-Lymphocytes , CD28 Antigens , Dipeptidyl Peptidase 4 , Antibodies, Monoclonal , Cell- and Tissue-Based Therapy
20.
Digestion ; 104(6): 460-467, 2023.
Article in English | MEDLINE | ID: mdl-37647880

ABSTRACT

INTRODUCTION: Endoscopic full-thickness resection (EFTR) without laparoscopic assistance (pure EFTR) is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been performed outside China because of concerns regarding pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing. This study aimed to evaluate the efficacy and safety of endoscopic resection with one-port placement (EROPP) for gastric GISTs. METHODS: This retrospective study included 17 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2022. One camera port was inserted in the umbilicus before initiating the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layers around the lesion was performed by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection was made using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect was performed with an over-the-scope clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety. RESULTS: All procedures were completed successfully without conversion to laparoscopic surgery. The median size of the resected tumors was 23 mm (range, 8-35 mm), the median resection time was 36 min (range, 22-95 min), and closure time was 18 min (range, 10-45 min). The rates of en bloc and complete resection were 100% and 88%, respectively. In 2 cases, another port was added to aspirate the leaking fluid or check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful, and no adverse events were reported. CONCLUSIONS: EROPP is a safe and minimally invasive treatment for gastric GISTs and appears to be suitable for introducing EFTR procedures.


Subject(s)
Endoscopic Mucosal Resection , Gastrointestinal Stromal Tumors , Laparoscopy , Stomach Neoplasms , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Retrospective Studies , Gastroscopy/adverse effects , Gastroscopy/methods , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Laparoscopy/adverse effects , Endoscopic Mucosal Resection/methods , Treatment Outcome
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