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1.
Ann Coloproctol ; 40(2): 89-113, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38712437

ABSTRACT

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

2.
Research (Wash D C) ; 7: 0365, 2024.
Article in English | MEDLINE | ID: mdl-38654733

ABSTRACT

Neutrophils are primed for neutrophil extracellular trap (NET) formation during diabetes, and excessive NET formation from primed neutrophils compromises wound healing in patients with diabetes. Here, we demonstrate that trained immunity mediates diabetes-induced NET priming in neutrophils. Under diabetic conditions, neutrophils exhibit robust metabolic reprogramming comprising enhanced glycolysis via the pentose phosphate pathway and fatty acid oxidation, which result in the accumulation of acetyl-coenzyme A. Adenosine 5'-triphosphate-citrate lyase-mediated accumulation of acetyl-coenzyme A and histone acetyltransferases further induce the acetylation of lysine residues on histone 3 (AcH3K9, AcH3K14, and AcH3K27) and histone 4 (AcH4K8). The pharmacological inhibition of adenosine 5'-triphosphate-citrate lyase and histone acetyltransferases completely inhibited high-glucose-induced NET priming. The trained immunity of neutrophils was further confirmed in neutrophils isolated from patients with diabetes. Our findings suggest that trained immunity mediates functional changes in neutrophils in diabetic environments, and targeting neutrophil-trained immunity may be a potential therapeutic target for controlling inflammatory complications of diabetes.

3.
Ann Coloproctol ; 40(1): 62-73, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38414122

ABSTRACT

PURPOSE: This study aimed to evaluate the long-term clinical outcomes based on the ligation level of the inferior mesenteric artery (IMA) in patients with rectal cancer. METHODS: This was a retrospective analysis of a prospectively collected database that included all patients who underwent elective low anterior resection for rectal cancer between January 2013 and December 2019. The clinical outcomes included oncological outcomes, postoperative complications, and functional outcomes. The oncological outcomes included overall survival (OS) and relapse-free survival (RFS). The functional outcomes, including defecatory and urogenital functions, were analyzed using the Fecal Incontinence Severity Index, International Prostate Symptom Score, and International Index of Erectile Function questionnaires. RESULTS: In total, 545 patients were included in the analysis. Of these, 244 patients underwent high ligation (HL), whereas 301 underwent low ligation (LL). The tumor size was larger in the HL group than in the LL group. The number of harvested lymph nodes (LNs) was higher in the HL group than in the LL group. There were no significant differences in complication rates and recurrence patterns between the groups. There were no significant differences in 5-year RFS and OS between the groups. Cox regression analysis revealed that the ligation level (HL vs. LL) was not a significant risk factor for oncological outcomes. Regarding functional outcomes, the LL group showed a significant recovery in defecatory function 1 year postoperatively compared with the HL group. CONCLUSION: LL with LNs dissection around the root of the IMA might not affect the oncologic outcomes comparing to HL; however, it has minimal benefit for defecatory function.

4.
J Yeungnam Med Sci ; 41(2): 61-73, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38351610

ABSTRACT

Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.

5.
Ann Coloproctol ; 39(6): 502-512, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38145898

ABSTRACT

PURPOSE: Minimally invasive surgery (MIS) is currently the standard treatment for rectal cancer. However, its limitations include complications and incomplete total mesorectal resection (TME) due to anatomical features and technical difficulties. Transanal TME (TaTME) has been practiced since 2010 to improve this, but there is a risk of local recurrence and intra-abdominal contamination. We aimed to analyze samples obtained through lavage to compare laparoscopic TME (LapTME) and TaTME. METHODS: From June 2020 to January 2021, 20 patients with rectal cancer undergoing MIS were consecutively and prospectively recruited. Samples were collected at the start of surgery, immediately after TME, and after irrigation. The samples were analyzed for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) through a quantitative real-time polymerase chain reaction. The primary outcome was to compare the detected amounts of CEA and CK20 immediately after TME between the surgical methods. RESULTS: Among the 20 patients, 13 underwent LapTME and 7 underwent TaTME. Tumor location was lower in TaTME (7.3 cm vs. 4.6 cm, P=0.012), and negative mesorectal fascia (MRF) was more in LapTME (76.9% vs. 28.6%, P=0.044). CEA and CK20 levels were high in 3 patients (42.9%) only in TaTME. There was 1 case of T4 with incomplete purse-string suture and 1 case of positive MRF with dissection failure. All patients were followed up for an average of 32.5 months without local recurrence. CONCLUSION: CEA and CK20 levels were high only in TaTME and were related to tumor factors or intraoperative events. However, whether the detection amount is clinically related to local recurrence remains unclear.

6.
Immune Netw ; 23(5): e38, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37970234

ABSTRACT

Neutrophils are professional phagocytes that provide defense against invading pathogens through phagocytosis, degranulation, generation of ROS, and the formation of neutrophil extracellular traps (NETs). Although long been considered as short-lived effector cells with limited biosynthetic activity, recent studies have revealed that neutrophils actively communicate with other immune cells. Neutrophils employ various types of soluble mediators, including granules, cytokines, and chemokines, for crosstalk with immune cells. Additionally, ROS and NETs, major arsenals of neutrophils, are utilized for intercellular communication. Furthermore, extracellular vesicles play a crucial role as mediators of neutrophil crosstalk. In this review, we highlight the extracellular mechanisms of neutrophils and their roles in crosstalk with other cells.

7.
Int J Colorectal Dis ; 38(1): 167, 2023 Jun 10.
Article in English | MEDLINE | ID: mdl-37300565

ABSTRACT

PURPOSE: Endoscopic resection (ER) is a reliable treatment for early colorectal cancer without lymph node metastasis. We aimed to examine the effects of ER performed prior to T1 colorectal cancer (T1 CRC) surgery by comparing long-term survival after radical surgery with prior ER to that after radical surgery alone. METHODS: This retrospective study included patients who underwent surgical resection of T1 CRC at the National Cancer Center, Korea, between 2003 and 2017. All eligible patients (n = 543) were divided into primary and secondary surgery groups. To ensure similar characteristics between the groups, 1:1 propensity score matching was used. Baseline characteristics, gross and histological features, along with postoperative recurrence-free survival (RFS) between the two groups were compared. Cox proportional hazard model was used to identify the risk factors affecting recurrence after surgery. Cost analysis was performed to examine the cost-effectiveness of ER and radical surgeries. RESULTS: No significant differences were observed in 5-year RFS between the two groups in matched data (96.9% vs. 95.5%, p = 0.596) and in the unadjusted model (97.2% vs. 96.8%, p = 0.930). This difference was also similar in subgroup analyses based on node status and high-risk histologic features. ER before surgery did not increase the medical costs of radical surgery. CONCLUSION: ER prior to radical surgery did not affect the long-term oncologic outcomes of T1 CRC or significantly increased the medical costs. Attempting ER first for suspected T1 CRC would be a good strategy to avoid unnecessary surgery without concerns of worsening cancer-related prognosis.


Subject(s)
Colorectal Neoplasms , Humans , Retrospective Studies , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Prognosis , Lymphatic Metastasis , Treatment Outcome
8.
Ann Coloproctol ; 39(6): 467-473, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37105525

ABSTRACT

PURPOSE: Most predictive factors for lymph node metastasis in rectal neuroendocrine tumors (NETs) have been based on local and endoscopic resection. We aimed to evaluate the risk factors for lymph node metastasis in patients who underwent radical resection for rectal NETs and stratify the risk of lymph node metastasis. METHODS: Sixty-four patients who underwent radical resection for rectal NETs between January 2001 and January 2018 were included. We investigated the risk factors of lymph node metastasis using clinicopathologic data. We also performed a risk stratification for lymph node metastases using the number of previously known risk factors. For oncologic outcomes, the 5-year overall survival and recurrence-free survival were evaluated in both groups. RESULTS: Among the patients who underwent radical surgery, 32 (50.0%) had lymph node metastasis and 32 (50.0%) had non-lymph node metastasis. In the multivariable analysis, only the male sex was identified as a risk factor for lymph node metastasis (odds ratio, 3.695; 95% confidence interval, 1.128-12.105; P=0.031). When there were 2 or more known risk factors, the lymph node metastasis rate was significantly higher than when there were one or no risk factors (odds ratio, 3.667; 95% confidence interval, 1.023-13.143; P=0.046). There was also no statistical difference between the 2 groups in 5-year overall survival (P=0.431) and 5-year recurrence-free survival (P=0.144). CONCLUSION: We found that the rate of lymph node metastasis increased significantly when the number of known risk factors is 2 or more.

9.
Nat Commun ; 14(1): 1631, 2023 03 24.
Article in English | MEDLINE | ID: mdl-36959217

ABSTRACT

Acid sphingomyelinase (ASM) has been implicated in neurodegenerative disease pathology, including Alzheimer's disease (AD). However, the specific role of plasma ASM in promoting these pathologies is poorly understood. Herein, we explore plasma ASM as a circulating factor that accelerates neuropathological features in AD by exposing young APP/PS1 mice to the blood of mice overexpressing ASM, through parabiotic surgery. Elevated plasma ASM was found to enhance several neuropathological features in the young APP/PS1 mice by mediating the differentiation of blood-derived, pathogenic Th17 cells. Antibody-based immunotherapy targeting plasma ASM showed efficient inhibition of ASM activity in the blood of APP/PS1 mice and, interestingly, led to prophylactic effects on neuropathological features by suppressing pathogenic Th17 cells. Our data reveals insights into the potential pathogenic mechanisms underlying AD and highlights ASM-targeting immunotherapy as a potential strategy for further investigation.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Mice , Animals , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Alzheimer Disease/pathology , Amyloid beta-Peptides , Mice, Transgenic , Sphingomyelin Phosphodiesterase/genetics , Disease Models, Animal , Immunotherapy , Amyloid beta-Protein Precursor
10.
Front Microbiol ; 13: 988522, 2022.
Article in English | MEDLINE | ID: mdl-36225352

ABSTRACT

Most clinical isolates of Acinetobacter baumannii, a nosocomial pathogen, are multidrug-resistant (MDR), fueling the search for alternative therapies. Bacteriophage-derived endolysins have potent antibacterial activities and are considered as alternatives to antibiotics against A. baumannii infection. Gram-negative bacteria possess outer lipid membrane that prevents direct contact between the endolysins and the cell wall. We hypothesized that the fusion of antimicrobial peptide (AMP) with endolysin could help to reduce bacterial endolysin resistance and increase antimicrobial activity by membrane permeability action. Accordingly, we fused cecropin A, a commonly used AMP, with the N-terminus of AbEndolysin, which enhances the bactericidal activity of the chimeric endolysin. The bactericidal activity of cecropin A-fused AbEndolysin increased by at least 2-8 fold for various MDR A. baumannii clinical isolates. The in vitro bactericidal activity results also showed higher bacterial lysis by the chimeric endolysin than that by the parental lysin. The engineered AbEndolysin (eAbEndolysin) showed synergistic effects with the beta-lactam antibiotics cefotaxime, ceftazidime, and aztreonam, and an additive effect with meropenem and imipenem. eAbEndolysin had no cytotoxic effect on A549 cell line and rescued mice (40% survival rate) from systemic A. baumannii infection. Together, these findings suggest the potential of lysin therapy and may prompt its use as an alternative to antibiotics.

11.
Ann Surg Treat Res ; 103(2): 96-103, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36017141

ABSTRACT

Purpose: Oral sulfate tablets are abundantly used for bowel preparation before colonoscopy. However, their efficiency and safety for bowel preparation before colorectal surgery remain ill-defined. Herein, we aimed to compare the surgical site infection rates and efficiency between oral sulfate tablets and sodium picosulfate. Methods: We designed a prospective, randomized, phase 2 clinical trial. Patients with colorectal cancer aged 19-75 years who underwent elective bowel resection and anastomosis by minimally invasive surgery were administered oral sulfate tablets or sodium picosulfate. Eighty-three cases were analyzed from October 2020 to December 2021. Surgical site infection within 30 days after surgery was considered the primary endpoint. Postoperative morbidities, the degree of bowel cleansing, and tolerability were the secondary endpoints. Results: Surgical site infection was detected in 1 patient (2.5%) in the oral sulfate tablet group and 2 patients (4.7%) in the sodium picosulfate group, indicating no significant difference between the 2 groups. Postoperative morbidity and the degree of bowel cleansing bore no statistically significant differences. Furthermore, none of the investigated tolerability criteria, namely bloating, pain, nausea, vomiting, and discomfort, differed significantly between the 2 groups. The patients' willingness to reuse the drug was also not significantly different between the 2 groups. Conclusion: Although we could not establish the noninferiority of oral sulfate tablets to sodium picosulfate, we found no evidence suggesting that oral sulfate tablets are less safe or tolerable than sodium picosulfate in preoperative bowel preparation.

12.
Gastrointest Endosc ; 96(6): 1036-1046.e1, 2022 12.
Article in English | MEDLINE | ID: mdl-35863516

ABSTRACT

BACKGROUND AND AIMS: This study aimed to assess the long-term survival of patients with T1 colorectal cancer (CRC) after local or surgical resection considering the type and number of risk factors for lymph node metastasis. METHODS: This study included patients with high-risk T1 CRC who underwent therapeutic resection at the National Cancer Center, Korea between January 2001 and December 2014. Risk factors included positive resection margin, high-grade histology, deep submucosal invasion, vascular invasion, budding, and no background adenoma (BGA). We statistically divided the population into favorable or unfavorable subpopulations. The favorable subpopulation included the following 5 combinations of risk factors: positive margin only or unconditional for margin status, deep submucosal invasion only, budding only, no BGA only, and budding + no BGA. We analyzed the survival rate according to the resection type (local or surgical) in the total cohort and in each subpopulation. RESULTS: Eighty-one and 466 patients underwent local and surgical resections, respectively. The distant recurrence-free survival (DRFS) and overall survival (OS) rates were significantly high in the surgical group (hazard ratio [HR], .20; 95% confidence interval [CI], .06-.61; P = .0045 and HR, .41; 95% CI, .25-.70; P = .0010, respectively). In the favorable subpopulation, both DRFS and OS rates were not significantly different between the surgical and local groups (HR, .26; 95% CI, .02-4.19; P = .3431 and HR, .58; 95% CI, .27-1.23; P = .1534, respectively). CONCLUSIONS: Intensive surveillance without additional surgery may be another option in selected cases after of high-risk T1 CRC endoscopic resection.


Subject(s)
Adenoma , Colorectal Neoplasms , Humans , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Retrospective Studies , Lymphatic Metastasis , Adenoma/surgery , Endoscopy , Risk Factors , Margins of Excision , Neoplasm Recurrence, Local/epidemiology
13.
Korean J Physiol Pharmacol ; 26(4): 229-238, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35766001

ABSTRACT

Severe bacterial infections are frequently accompanied by depressed neutrophil functions. Thus, agents that increase the microbicidal activity of neutrophils could add to a direct antimicrobial therapy. Lysophosphatidylcholine augments neutrophil bactericidal activity via the glycine (Gly)/glycine receptor (GlyR) α2/TRPM2/p38 mitogen-activated protein kinase (MAPK) pathway. However, the direct effect of glycine on neutrophil bactericidal activity was not reported. In this study, the effect of glycine on neutrophil bactericidal activity was examined. Glycine augmented bactericidal activity of human neutrophils (EC50 = 238 µM) in a strychnine (a GlyR antagonist)-sensitive manner. Glycine augmented bacterial clearance in mice, which was also blocked by strychnine (0.4 mg/kg, s.c.). Glycine enhanced NADPH oxidase-mediated reactive oxygen species (ROS) production and TRPM2-mediated [Ca2+]i increase in neutrophils that had taken up E. coli . Glycine augmented Lucifer yellow uptake (fluid-phase pinocytosis) and azurophil granule-phagosome fusion in neutrophils that had taken up E. coli in an SB203580 (a p38 MAPK inhibitor)-sensitive manner. These findings indicate that glycine augments neutrophil microbicidal activity by enhancing azurophil granule-phagosome fusion via the GlyRα2/ROS/calcium/p38 MAPK pathway. We suggest that glycine could be a useful agent for increasing neutrophil bacterial clearance.

14.
Ann Coloproctol ; 38(3): 262-265, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34696537

ABSTRACT

PURPOSE: Anastomotic bleeding after colorectal surgery is a rare, mostly self-limiting, postoperative complication that could lead to a life-threatening condition. Therefore, prompt management is required. This study aimed to evaluate the efficacy and safety of endoscopic clipping for acute anastomotic bleeding after colorectal surgery. METHODS: We retrospectively reviewed the data of patients pathologically diagnosed with colorectal cancer at National Cancer Center, Korea from January 2018 to November 2020, which presented with anastomotic bleeding within the first postoperative week and were endoscopically managed with clips. RESULTS: Nine patients had anastomotic bleeding, underwent endoscopic management, and, therefore, were included in this study. All patients underwent laparoscopic (low/ultralow) anterior resection with mechanical double-stapled anastomosis. Anastomotic bleeding was successfully managed through a colonoscopy with clips on the first trial in all patients. Hypovolemic shock occurred in one patient, following anastomotic breakdown. CONCLUSION: Endoscopic clipping seems to be an effective and safe treatment for anastomotic bleeding with minimal physiologic stress, easy accessibility, and scarce postoperative complications. However, a surgical backup should always be considered for massive bleeding.

15.
Br J Pharmacol ; 179(5): 998-1016, 2022 03.
Article in English | MEDLINE | ID: mdl-34524687

ABSTRACT

BACKGROUND AND PURPOSE: There is a scarcity of information regarding the role of prothrombin kringle-2 (pKr-2), which can be generated by active thrombin, in hippocampal neurodegeneration and Alzheimer's disease (AD). EXPERIMENTAL APPROACH: To assess the role of pKr-2 in association with the neurotoxic symptoms of AD, we determined pKr-2 protein levels in post-mortem hippocampal tissues of patients with AD and the hippocampi of five familial AD (5XFAD) mice compared with those of age-matched controls and wild-type (WT) mice, respectively. In addition, we investigated whether the hippocampal neurodegeneration and object memory impairments shown in 5XFAD mice were mediated by changes to pKr-2 up-regulation. KEY RESULTS: Our results demonstrated that pKr-2 was up-regulated in the hippocampi of patients with AD and 5XFAD mice, but was not associated with amyloid-ß aggregation in 5XFAD mice. The up-regulation of pKr-2 expression was inhibited by preservation of the blood-brain barrier (BBB) via addition of caffeine to their water supply or by treatment with rivaroxaban, an inhibitor of factor Xa that is associated with thrombin production. Moreover, the prevention of up-regulation of pKr-2 expression reduced neurotoxic symptoms, such as hippocampal neurodegeneration and object recognition decline due to neurotoxic inflammatory responses in 5XFAD mice. CONCLUSION AND IMPLICATIONS: We identified a novel pathological mechanism of AD mediated by abnormal accumulation of pKr-2, which functions as an important pathogenic factor in the adult brain via blood brain barrier (BBB) breakdown. Thus, pKr-2 represents a novel target for AD therapeutic strategies and those for related conditions.


Subject(s)
Alzheimer Disease , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Disease Models, Animal , Hippocampus/metabolism , Humans , Kringles , Mice , Mice, Transgenic , Prothrombin/metabolism , Prothrombin/therapeutic use , Thrombin
16.
Surg Endosc ; 36(5): 2861-2868, 2022 05.
Article in English | MEDLINE | ID: mdl-34046714

ABSTRACT

BACKGROUND: Since the introduction of Enhanced Recovery After Surgery (ERAS), early diet after surgery has been emphasized and clinical outcomes have improved, though vomiting has been reported frequently. We defined diet failure based on clinical manifestation and images after colon cancer surgery and attempted to analyze underlying risk factors by comparing the early diet group with the conventional diet group. METHODS: All consecutive patients underwent colectomy with curative intent at a single institution between August 2015 and July 2017. The early diet group was started on soft diet on the second day after surgery, while the conventional group started the same after flatulence. The primary outcome was the difference in the incidence of diet failure between the two groups. Secondary outcomes were analyzed to determine risk factors for diet failure and readmission due to ileus. RESULTS: Overall, 293 patients were included in the conventional diet group and 231 in the early diet group. There were no significant differences between the two groups, except for shorter hospital stays in the early diet group (median 8 days, p < 0.001). A total of 46 patients (early diet, n = 20; conventional diet, n = 26, p = 1.000) had diet failure. Multivariate analysis showed that operation time (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.33-2.32) and side-to-side anastomosis compared with the end-to-end method (OR 4.41, 95% CI 2.10-9.24) were independent risk factors for diet failure. Sixteen patients were readmitted due to ileus that occurred within 2 months after surgical operation. Diet resumption time was not a risk factor for both diet failure and ileus. CONCLUSIONS: Early diet resumption does not increase diet failure and can reduce hospital stay. Anastomosis and operation time may be related to diet failure. Our study suggests that evaluation of surgical factors is important for postoperative recovery, and well-designed follow-up studies are needed.


Subject(s)
Colonic Neoplasms , Ileus , Colectomy/adverse effects , Colectomy/methods , Colonic Neoplasms/complications , Colonic Neoplasms/surgery , Diet , Humans , Ileus/epidemiology , Ileus/etiology , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Recovery of Function
17.
J Bone Miner Res ; 37(3): 505-514, 2022 03.
Article in English | MEDLINE | ID: mdl-34812548

ABSTRACT

The differentiation and activity of bone-resorbing osteoclasts are tightly regulated to maintain the homeostasis of healthy bones. In this study, the role of protein tyrosine phosphatase 1B (PTP1B) during osteoclastogenesis was studied in myeloid-specific Ptpn1-deficient (conditional knockout [cKO]) mice. The mRNA and protein expression of PTP1B increased during the formation of mature osteoclasts from mouse bone macrophages on stimulation with macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). The Ptpn1 cKO mice exhibited increased femoral trabecular bone volume with a decreased number and activity of osteoclasts compared with control mice. The in vitro culture of osteoclast precursors corroborated the inhibition of osteoclastogenesis in cKO cells compared with control, with concomitantly decreased RANKL-dependent proliferation, lower osteoclast marker gene expression, reduced nuclear expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), diminished intracellular Ca2+ oscillations, and increased phosphorylation of proto-oncogene tyrosine-protein kinase Src on inhibitory tyrosine residue. In a ligature-induced periodontitis model, Ptpn1 cKO mice exhibited attenuated osteoclastogenesis and alveolar bone loss following the induction of inflammation. The Ptpn1-deficient mice were similarly protected from ovariectomy-induced bone loss compared with control mice. These results provide a novel regulatory role of PTP1B in osteoclastogenesis and suggest a potential as a therapeutic target for bone-lytic diseases. © 2021 American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Bone Resorption , Osteogenesis , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Animals , Bone Resorption/metabolism , Cell Differentiation , Female , Inflammation/metabolism , Mice , Mice, Inbred C57BL , NFATC Transcription Factors/metabolism , Osteoclasts/metabolism , Ovariectomy , Phosphoric Monoester Hydrolases/metabolism , RANK Ligand/metabolism , Tyrosine/metabolism
18.
Free Radic Biol Med ; 176: 322-334, 2021 11 20.
Article in English | MEDLINE | ID: mdl-34637923

ABSTRACT

Strategies for cancer treatment have traditionally focused on suppressing cancer cell behavior, but many recent studies have demonstrated that regulating the tumor microenvironment (TME) can also inhibit disease progression. Macrophages are major TME components, and the direction of phenotype polarization is known to regulate tumor behavior, with M2-like polarization promoting progression. It is also known that reactive oxygen species (ROS) in macrophages drive M2 polarization, and M2 polarization promote lung cancer progression. Lung cancer patients with lower expression of the antioxidant enzyme peroxiredoxin 5 (Prx5) demonstrate poorer survival. This study revealed that Prx5 deficiency in macrophages induced M2 macrophage polarization by lung cancer. We report that injection of lung cancer cells produced larger tumors in Prx5-deficit mice than wild-type mice independent of cancer cell Prx5 expression. Through co-culture with lung cancer cell lines, Prx5-deficient macrophages exhibited M2 polarization, and reduced expression levels of the M1-associated inflammatory factors iNOS, TNFα, and Il-1ß. Moreover, these Prx5-deficient macrophages promoted the proliferation and migration of co-cultured lung cancer cells. Conversely, suppression of ROS generation by N-acetyl cysteine (NAC) inhibited the M2-like polarization of Prx5-deficient macrophages, increased expression levels of inflammatory factors, inhibited the proliferation and migration of co-cultured lung cancer cells, and suppressed tumor growth in mice. These findings suggest that blocking the M2 polarization of macrophages may promote lung cancer regression.


Subject(s)
Lung Neoplasms , Peroxiredoxins , Animals , Cell Line, Tumor , Humans , Lung Neoplasms/genetics , Macrophage Activation , Macrophages , Mice , Peroxiredoxins/genetics , Reactive Oxygen Species , Tumor Microenvironment
19.
ANZ J Surg ; 91(10): 2067-2073, 2021 10.
Article in English | MEDLINE | ID: mdl-34476891

ABSTRACT

BACKGROUNDS: In cancer patients, the optimal appendicitis treatment has not been established. Therefore, we aimed to determine the ideal treatment option for appendicitis in cancer patients. METHODS: This retrospective study included 185 cancer patients with acute appendicitis who were divided into the early surgical group (n = 152) involving surgery performed within 48 h following the appendicitis diagnosis or the conservative group (n = 33) involving intravenous antibiotics. We compared the appendicitis treatment efficacy between the groups. RESULTS: In the early surgical group, the antibiotic duration [5.5 days (4.0-8.0) vs. 17.0 days (12.5-25.0), p < 0.001] and hospital stay length [7.0 days (5.0-11.75) vs. 10.0 days (8.0-32.0), p < 0.001] were significantly shorter. Regarding pathology, 16/171 (9.4%) patients who underwent surgery exhibited appendiceal tumours. During the 1-year follow-up period, one recurrence occurred in each group [1/152 (0.7%) vs. 1/33 (3.0%), p = 0.326]. The 1-year treatment success rate was higher in the early surgical group [99.3% (151/152) vs. 42.4% (14/33), p < 0.001]. CONCLUSION: Early surgical treatment yielded a significantly higher success rate than conservative treatment for appendicitis in cancer patients. Surgery for appendicitis in cancer patients should be considered not only for treatment but also for pathologic confirmation.


Subject(s)
Appendicitis , Acute Disease , Anti-Bacterial Agents/therapeutic use , Appendectomy , Appendicitis/complications , Appendicitis/drug therapy , Appendicitis/surgery , Conservative Treatment , Humans , Length of Stay , Neoplasm Recurrence, Local , Retrospective Studies , Treatment Outcome
20.
Ann Surg Treat Res ; 101(2): 111-119, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34386460

ABSTRACT

PURPOSE: This study was performed to evaluate the risk of readmission in the first year after low anterior resection (LAR) for patients with rectal cancer and to identify the contributing factors for readmission related to dehydration specifically. METHODS: This was a retrospective analysis of 570 patients who underwent LAR for rectal cancer at National Cancer Center, Republic of Korea. A diverting loop ileostomy was performed in 357 (62.6%) of these patients. Readmission was defined as an unplanned visit to the emergency room or admission to the ward. The reasons for readmission were reviewed and compared between the ileostomy (n = 357) and no-ileostomy (n = 213) groups. The risk factors for readmission and readmission due to dehydration were analyzed using multivariable logistic and Cox proportional hazard model. RESULTS: Dehydration was the most common cause of readmission in both groups (ileostomy group, 6.7%, and no-ileostomy group, 4.7%, P = 0.323). On multivariable analysis, risk factors for readmission were an estimated intraoperative blood loss of ≥400 mL (odds ratio [OR], 1.757; 95% confidence interval [CI], 1.058-2.918; P = 0.029), and postoperative chemotherapy (OR, 2.914; 95% CI, 1.824-4.653; P < 0.001). On multivariable analysis, postoperative chemotherapy, and not a diverting loop ileostomy, was an independent risk factor for dehydration-related readmission (OR, 5.102; 95% CI, 1.772-14.688; P = 0.003). CONCLUSION: The most common cause of readmission after LAR for rectal cancer was dehydration, as reported previously. Postoperative chemotherapy, not the creation of a diverting ileostomy, was identified as the risk factor associated with readmission related to dehydration.

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