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Burkitt lymphoma (BL) is a highly aggressive form of non-Hodgkin's B-cell lymphoma. Currently, multi-agent chemotherapy regimens are being used to significantly improve cure rates and achieve complete remissions in BL patients. However, drug resistance can often occur within 6 months in BL patients, contributing to poor prognosis. Mounting evidence suggests that cell adhesion-mediated drug resistance (CAM-DR), caused by the interaction between the bone marrow microenvironment and tumour cells may play an important role in drug resistance to chemotherapy. However, the molecular mechanism underlying CAM-DR in BL has not been identified yet. In this study, we investigated the molecular mechanism responsible for CAM-DR in BL cells. We also examined the therapeutic targets of CAM-DR in BL cells and found CD49d and CD49e to be the important adhesion molecules involved. However, CD49a, CD49b, CD11a, CD29, CD18, and CD61 were not found to be associated with CAM-DR in BL cells. Furthermore, we clarified that CD49d- and CD49e-mediated CAM-DR could be attributed to an increase in the expression of B cell leukemia-xL (Bcl-xL) and survivin proteins, and a decrease in the expression of Bcl-2 associated X (Bax), Bcl-2 interacting mediator (Bim) and p53 upregulated modulator of apoptosis (PUMA) proteins via nuclear factor kappaB (NF-κB) activation. In addition, bortezomib was found to overcome CAM-DR in BL cells by inhibiting NF-κB. Thus, bortezomib may have potential clinical applications in the treatment of CD49d- and CD49e-mediated CAM-DR in BL patients. [ABSTRACT FROM AUTHOR]

The tumor-killing activity of radiotherapy and chemotherapy for cancer is closely associated with the production of active oxygen, and the relation between therapeutic resistance and active oxygen scavengers produced by the tumor itself is gaining more attention. It is considered that manganese superoxide dismutase (MnSOD) protects host cells from oxidative stress, in synergy with other antioxidant enzymes. In this study, we used a quantitative polymerase chain reaction assay to measure MnSOD mRNA in resected specimens from patients with esophageal and gastric cancers. In both esophageal and gastric cancers, the level of MnSOD mRNA was significantly elevated in cancer tissue compared to non-cancer tissue (P < 0.01). In gastric cancer tissue, the MnSOD mRNA level was significantly higher than in esophageal cancer tissue (P < 0.01). The significance of MnSOD in cancer tissue was investigated further by measuring MnSOD content in resected specimens using an enzyme-linked immunosorbent assay, and by examining its location by an immunohistochemical method. Upregulation of MnSOD in cancer tissue most likely serves as a protective mechanism against anti-cancer therapies known to produce superoxide radicals as a key component of their tumor-killing activity. [ABSTRACT FROM AUTHOR]

Abstract Background Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis. The inhibition of this key enzyme in the mevalonate pathway leads to suppression of cell proliferation and induction of apoptosis. However, the molecular mechanism of apoptosis induction by statins is not well understood in glioblastoma. In the present study, we attempted to elucidate the mechanism by which statins induce apoptosis in C6 glioma cells. Methods The cytotoxicity of statins toward the C6 glioma cells were evaluated using a cell viability assay. The enzyme activity of caspase-3 was determined using activity assay kits. The effects of statins on signal transduction molecules were determined by western blot analyses. Results We found that statins inhibited cell proliferation and induced apoptosis in these cells. We also observed an increase in caspase-3 activity. The apoptosis induced by statins was not inhibited by the addition of farnesyl pyrophosphate, squalene, ubiquinone, and isopentenyladenine, but by geranylgeranyl-pyrophosphate (GGPP). Furthermore, statins decreased the levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt. Conclusions These results suggest that statins induce apoptosis when GGPP biosynthesis is inhibited and consequently decreases the level of phosphorylated ERK1/2 and Akt. The results of this study also indicate that statins could be used as anticancer agents in glioblastoma.

Introduction: This study aimed to evaluate the efficacy of perioperative dysphagia rehabilitation in older adult patients diagnosed with gastric cancer who underwent gastrectomy., Materials and Methods: This retrospective study included 149 patients over 80 years who underwent gastrectomies between January 2000 and December 2020. The patients were divided into two groups based on the intervention of the dysphagia rehabilitation team (DRT group: n = 101) and the non-intervention control group (C group: n = 48). Inverse probability weighting (IPW) analysis was used to reduce bias caused by potential confounding., Results: The incidence of overall complications was significantly lower in the DRT group (odds ratio [OR]; 0.27[0.08-0.93]), among which the incidence of postoperative pneumonia (OR; 0.07[0.01-0.43]) and aspiration pneumonia (OR; 0.05[0.01-0.44] was significantly reduced. Ten patients developed postoperative pneumonia; seven were in the C group, and three were in DRT group. Sixty percent of these patients had preoperative comorbidities related to the respiratory system. Regarding the time of onset of aspiration pneumonia, two patterns were observed: onset within a short period after surgery and onset after the start of eating. In contrast, five patients underwent preoperative dysphagia rehabilitation in the DRT group. Among them, postoperative aspiration pneumonia was prevented in four patients, and the others were prevented from severe pneumonitis by the intervention of the dysphagia rehabilitation team., Discussion: Perioperative intervention in dysphagia rehabilitation is not only associated with reduced postoperative pneumonia but also creates awareness in the medical staff and promotes careful observation of swallowing in patients, thereby controlling the incidence of postoperative pneumonia. The perioperative intervention of the dysphagia rehabilitation team is useful for older adult patients with gastric cancer., Competing Interests: Declaration of Competing Interest Atsushi Yasuda, Yutaka Kimura, Takushi Yasuda, Yoko Hiraki, Takaomi Hagi, Hiroaki Kato, Osamu Shiraishi, Masayuki Shinkai, Motohiro Imano, and Haruhiko Imamoto declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd., Methods: Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs)., Results: Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected., Conclusions: T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice., Clinical Trial Registration: UMIN000049032., Competing Interests: Declarations. Conflict of interest: Hisato Kawakami has been a consultant for Astellas Pharma Inc., and Daiichi Sankyo; received honoraria from Bristol-Myers Squibb Co. Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd, Otsuka Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Bayer Yakuhin Ltd, MSD K.K., Chugai Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd., Yakult Pharmaceutical Industry, Taiho Pharmaceutical Co. Ltd. and Nippon Kayaku Co. Ltd; and received research funding from Bristol-Myers Squibb Co. Ltd., Taiho Pharmaceutical Co. Ltd, Daiichi Sankyo, Eisai and Kobayashi Pharmaceuticals. Koki Nakanishi has received honoraria from Taiho Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo and Bristol-Myers Squibb. Akitaka Makiyama has been a consultant for Lilly Japan and received honoraria from Lilly Japan, Chugai Pharma, Takeda, Daiichi Sankyo, Taiho Pharmaceutical, Ono Pharmaceutical and Bristol-Myers Squibb Japan. Satoshi Morita reports honoraria from AstraZeneca Japan, Bristol-Myers Squibb, Chugai Pharma, Lilly Japan, Merck Sharp & Dohme, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer and Eisai, research funding from Eisai and is one of the statistical editors for Gastric Cancer. Yukiya Narita has been a consultant for Daiichi Sankyo/AstraZeneca; been on the speakers’ bureau of Ono Pharmaceutical, Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb and Daiichi Sankyo/AstraZeneca; and research funding from Ono Pharmaceutical, Daiichi Sankyo/AstraZeneca and Astellas Pharma. Naotoshi Sugimoto reports research funding from MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Lilly Japan, Daiichi Sankyo, Sumitomo Dainippon Pharma, Chugai Pharma, BeiGene, Solasia Pharma, Astellas Pharma and Eisai. Keiko Minashi reports research funding from Ono Pharmaceutical, MSD, Astellas Pharma, BeiGene, Amgen and Daiichi Sankyo/UCB Japan. Yasuhiro Kodera has been a consultant for Daiichi Sankyo; received honoraria from Chugai Pharma, Yakult Honsha, Taiho Pharmaceutical, Ono Pharmaceutical, MSD K.K, Tsumura & Co., Daiichi Sankyo, Nippon Kayaku, Lilly Japan, Miyarisan Pharmaceutical, Olympus, AbbVie, Amgen, Bristol-Myers Squibb, Edwards Lifesciences and Covidien; research funding from Chugai Pharma, Daiichi Sankyo, Taiho Pharmaceutical, Abbott Japan, Lilly Japan, Kaken Pharmaceutical, Tsumura & Co., Covidien, Nippon Kayaku, Shionogi, Johnson & Johnson, Bayer, TOA Pharmaceuticals, AbbVie, EA Pharma, Pfizer and Otsuka and is the Editor-in-Chief of Gastric Cancer. Hiroki Kume, Keita Yamaguchi and Wataru Hashimoto are employees of Daiichi Sankyo Co. Ltd., Japan. Kei Muro has been a consultant or served as an adviser for Chugai Pharma, AstraZeneca, Ono Pharmaceutical, Amgen, Solasia Pharma; has received honoraria from Takeda, Chugai Pharma, Taiho Pharmaceutical, Lilly, Ono Pharmaceutical, Bayer, Sanofi, Bristol-Myers Squibb, Daiichi Sankyo/UCB Japan, Ono Pharmaceutical, MSD, Daiichi Sankyo, Pfizer, Sanofi, Taiho Pharmaceutical, Astellas Pharma, Eisai, Chugai Pharma, Amgen, Novartis and Merck KGaA. Hirotaka Konishi, Motohiro Imano and Rin Inamoto have nothing to disclose. Ethics approval: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. The study protocol was approved by Nagoya University Bioethics Review Board (approval no. 2022–0170). Consent to participate: Informed consent was obtained from all patients; however, opt-out registration was permitted for patients from whom it was difficult to obtain written informed consent for a variety of reasons., (© 2024. The Author(s).)

We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs. The efficacy index (EI), calculated from the frequency of LN metastases and survival rates, was used as prognostic value of each LN station dissection for patient survival. Risk factors for #104 LN metastasis were determined by multivariable logistic regression. The frequency of #104 LN metastasis was 11.6% overall, 31.7% in upper and 8.3% in middle/lower third lesion. Neoadjuvant chemotherapy was administered to 71% of patients and chemo-radiation to 11%. The 5-year overall survival was 45.8%. The EI for #104 LNs (5.3) was similar to that for #101 LNs. Risk factors were age < 65 years, upper third lesion, clinical N2-3, #101/106rec LN metastasis and poorly differentiated carcinoma. The 5-year overall survival of patients with middle/lower lesions was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs. The prognosis of patients with #104 LN metastases is similar to that of patients with metastases in other regional LN stations. Therefore, we recommend 3FL exclusively for patients at a high risk of #104 LN metastasis due to the overall metastatic rate not being high., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Primary squamous cell carcinoma of the kidney is rare, with only a few cases reported to date., Case Presentation: A right renal mass was detected in a 73-year-old asymptomatic man. Dynamic contrast-enhanced computed tomography showed a hypodensity mass extending from the upper pole of the kidney to the right lobe of the liver. Renal biopsy revealed that this tumor was squamous cell carcinoma. One month later, computed tomography showed rapid tumor growth. Radical nephrectomy and partial hepatic resection were performed. Pathological analysis indicated that this tumor originated from the tubular epithelium, and the patient was diagnosed with primary squamous cell carcinoma of the kidney.Following up without adjuvant therapy, he developed retroperitoneal recurrence and multiple lung metastases and expired., Conclusion: In this case, squamous cell carcinoma of the kidney invaded the liver and progressed rapidly. Considering these observations, surgical resection should be promptly performed in suspected cases., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Background: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC., Methods: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival., Results: The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors., Conclusions: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery., (© 2024. Society of Surgical Oncology.)

Recent reports have described the practicality of laparoscopic intragastric surgery (l-IGS) as an alternative for resecting submucosal tumors (SMTs) near the esophagogastric junction (EGJ), where excision using an exogastric approach would be difficult. However, even using IGS to perform a full-thickness resection of SMTs that are in or extremely close to the EGJ is very difficult to do safely and avoid disrupting or causing stenosis of the EGJ, without advanced experience. This study retrospectively examined the usefulness of l-IGS for gastric SMTs located in or extremely close to the EGJ. Fourteen patients with gastric SMTs < 2 cm of the EGJ and underwent l-IGS were eligible for this study. We examined the tumor location, operative time, intraoperative hemorrhage, degree of deformation, gastroesophageal reflux disease, perioperative complications, and recurrence. Furthermore, we compared patients with tumors in the EGJ with those with tumors near the EGJ and patients in whom three-port l-IGS was performed with those who underwent single-incision laparoscopic surgery. The average tumor size, operative time, intraoperative hemorrhage, and postoperative hospitalization of the 14 patients were 30.9 ± 21.3 mm, 125.2 ± 31.1 min, 30.7 ± 103.3 mL, and 9.2 ± 3.1 d, respectively. No differences in these parameters according to the type of l-IGS or tumor location were observed. All patients underwent l-IGS without complications and were free from EGJ deformation or esophagitis. We believe that l-IGS is useful for gastric SMTs located < 2 cm of the EGJ as it can be safely performed for difficult tumor locations and does not cause deformation of the EGJ., (© 2024. Italian Society of Surgery (SIC).)