Search

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. Published by Elsevier Ltd.)

Background: Malignant melanoma is among the deadliest forms of skin cancers, and its incidence has been increasing over the past decades. In malignant melanoma, activation of the nuclear factor kappa B (NF-κB) promotes survival, migration, and invasion of cancer cells. Anti-NF-κB agents for treating metastatic melanoma would be beneficial, but no such drug is approved as either monotherapy or adjuvant therapy. Dimethyl fumarate (DMF) is an approved anti-inflammatory drug already in clinical use for psoriasis and multiple sclerosis., Objective: We investigated the anti-tumour effect of DMF treatment in metastatic melanoma in vitro and in vivo., Methods: The cell viability was assessed via trypan blue exclusion assay. The migration and invasion was analyzed in a Boyden chamber assay. The anti-metastatic effects and anti-tumour activity of DMF was determined in an in-vivo model. The expressions of NF-κB pathway and NF-κB regulatory proteins were detected via western blotting., Results: DMF decreased the cell viability, migration and invasion in vitro. In addition, DMF inhibited spontaneous metastasis and tumour growth. Mechanistically, DMF prevented the nuclear translocation of NF-κB, whereas no changes were observed in the phosphorylation levels of inhibitor of kappa B (IκB). In addition, DMF inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs). Furthermore, DMF treatment decreased the expression of Survivin and Bcl-extra large (Bcl-XL) proteins., Conclusion: Our results suggest that DMF as a novel inhibitor of NF-κB may be a potential therapeutic agent for metastatic melanoma., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Mangiferin is a naturally occurring glucosyl xanthone, which induces apoptosis in various cancer cells. However, the molecular mechanism underlying mangiferin-induced apoptosis has not been clarified thus far. Therefore, we examined the molecular mechanism underlying mangiferin-induced apoptosis in multiple myeloma (MM) cell lines. We found that mangiferin decreased the viability of MM cell lines in a concentration-dependent manner. We also observed an increased number of apoptotic cells, caspase-3 activation, and a decrease in the mitochondrial membrane potential. In addition, mangiferin inhibited the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated inhibitor kappa B (IκB) and increased the expression of IκB protein, whereas no changes were observed in the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase 1/2 (JNK1/2), and mammalian target of rapamycin (mTOR). The molecular mechanism responsible for mangiferin-induced inhibition of nuclear translocation of NF-κB was a decrease in the expression of phosphorylated NF-κB-inducing kinase (NIK). Moreover, mangiferin decreased the expression of X-linked inhibitor of apoptosis protein (XIAP), survivin, and Bcl-xL proteins. Knockdown of NIK expression showed results similar to those observed with mangiferin treatment. Our results suggest that mangiferin induces apoptosis through the inhibition of nuclear translocation of NF-κB by suppressing NIK activation in MM cell lines. Our results provide a new insight into the molecular mechanism of mangiferin-induced apoptosis. Importantly, since the number of reported NIK inhibitors is limited, mangiferin, which targets NIK, may be a potential anticancer agent for the treatment of MM., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: We performed short-term neoadjuvant chemotherapy (s-NAC) to examine whether anticancer drugs can change the proliferative ability of cancer cells in gastric cancer patients., Methods: Chemotherapy was performed for 72 h before gastrectomy in 63 gastric cancer patients. Patients were classed into four groups: Group F, 16 cases who received a single administration of 5-fluorouracil (5-FU); Group C, 15 cases who received a single administration of cis-diamminedichloroplatinum (CDDP; cisplatin); Group FC, 16 cases who received both 5-FU+CDDP; and a Control group, 16 cases who did not receive chemotherapy. We reviewed neoadjuvant biopsy tissue and gastric cancer tissue delivered by operation in these cases. The TUNEL method and immunohistochemistry with an anti-MIB-1 antibody were used to evaluate cellular apoptosis and proliferative ability, respectively. The apoptotic index (AI) and an MIB-1 index (MI) were also calculated., Results: There were no differences in AI or MI in biopsy tissue between the groups. The AI of gastric cancer tissue in Group FC was significantly higher than in the other groups (P < 0.01). The MI of Group FC was significantly lower than in the other groups (P < 0.05). In addition, after s-NAC operation there was a significant inhibition of proliferative potency and an induction of apoptosis in Group FC., Conclusion: Combination of CDDP and 5-FU reduced proliferative potency and increased cellular apoptosis in gastric cancer cells., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background/aims: The regeneration after liver injury is regulated by the release and activation of several growth factors. The role of the plasmin/alpha(2)-antiplasmin (alpha(2)-AP) system in liver regeneration was investigated., Methods: CCl(4) was injected intraperitoneally into the mice deficient (-/-) in fibrinolytic factors: alpha(2)-AP-/-, plasminogen (Plg) -/-, and Plg-/-.alpha(2)-AP-/-, and wild-type (WT) mice. The liver tissue was examined for its microscopic appearance, fibrinolytic activity, and fibronectin levels., Results: In the gene deficient and WT mice, the livers exhibited the same extent of necrosis 2 days after the CCl(4) injection. The livers of the WT mice normalized after 7 days, and the alpha(2)-AP-/- mice normalized after 5 days. In contrast, the livers of the Plg-/- and Plg-/-.alpha(2)-AP-/- mice remained in the damaged state until 14 days after the liver injury. The injection of anti-alpha(2)-AP antibody in the WT mice improved the regeneration after the liver injury, and the injection of tranexamic acid in the alpha(2)-AP-/- mice reduced., Conclusions: These results suggest that the plasmin/alpha(2)-AP system played an important role in hepatic repair via clearance from the injury area.

The purpose of this study was to examine whether the increased sensitivity of cancer cells to adriamycin (ADM), which is known to produce superoxide radicals, was brought through suppressed manganese superoxide disumutase (MnSOD) expression in the presence of transforming growth factor beta1 (TGFbeta1). T.T., MKN28, and MKN45 cell lines were treated with TGFbeta1 before exposure to ADM. Athymic female mice bearing the MKN28 cells were treated with TGFbeta1, ADM, or TGFbeta1 + ADM. Pretreatment of T.T., MKN28, and MKN45 cell lines with TGFbeta1 resulted in increased sensitivity to ADM. In contrast, simultaneous exposure to TNFalpha, which increased MnSOD expression, decreased sensitivity of cancer cells to ADM. In vivo studies demonstrated that the combined administration of TGFbeta1 and ADM delayed tumor growth better than either treatment alone. Our results suggest that the synergistic antitumor effects of TGFbeta1 and ADM may be due to decreased MnSOD expression in cancer cells. Thus, combined administration of TGFbeta1 and ADM might prove useful for treatment of malignant disease.

Human liver cells (Chang liver) were exposed to 5 micrograms Zn, 2.5 micrograms Cu or 1 microgram Cd/ml in cultured medium. These exogeneous heavy metals were accumulated by the cells and induced de novo synthesis of metallothionein after a 3-h incubation period. The production of Zn-, Cu- or Cd-thionein started in the cells with accumulation of 1 nmol Zn, 0.3 nmol Cu and 0.1 nmol Cd/mg cytosol protein and subsequently the amounts of metal-binding thioneins increased in agreement with the relative amount of metal accumulated in the cytosol over a 24-h period. When cells containing Zn- or Cu-thionein were placed in metal free medium, 70% or 25% of the zinc or copper bound to each original metallothionein was released after 3 h; bound metals decreased to 85% and 65% respectively after 24 h. The disappearance of metal from metallothionein correlated with increases of metal in the medium. On the other hand, 35S-counts incorporated into Zn- and Cu-thionein decreased only to 40% and 15% of the levels in the original metallothionein after 3 h; 35S-counts decreased to 65% and 45%, respectively, after 24 h, indicating that metals bound to metallothionein decreased more quickly than 35S-counts. These results suggest that metals were released from metallothionein and were excreted into the medium. However, 35S- and 109Cd-counts in Cd-thionein changed very little, if at all, in the cells even after a 24-h incubation period. Our data strongly suggest that Zn- and Cu-thionein are degraded in the cells, but that Cd-thionein remains longer than either Zn- or Cu-thionein. When cells containing Zn-thionein were incubated in metal-free medium, Zn-thionein was digested in the cells and peptide fragments ranging about 200-400 daltons were excreted from the cells.