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2.
Front Surg ; 10: 1255929, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795145

RESUMO

Objectives: To compare the usefulness and safety of off-clamp microwave scissors-based sutureless partial nephrectomy (MSPN) with on-clamp conventional partial nephrectomy (cPN) in dogs. Methods: We performed off-clamp MSPN using microwave scissors (MWS) in six dogs, and on-clamp cPN in three dogs, in two-stage experiments. The bilateral kidney upper poles were resected via a midline incision under general anesthesia. After 14 days of follow-up, the lower pole resections were performed. The renal calyces exposed during renal resections were sealed and transected using MWS in off-clamp MSPN and were sutured in on-clamp cPN. In the off-clamp MSPN group, the generator's power output of MWS was set as either 50 W or 60 W for each kidney side. We compared the procedure time (PT), ischemic time (IT), blood loss (BL), and normal nephron loss (NNL) between the two techniques using the Mann-Whitney U-test. Results: We successfully performed 24 off-clamp MSPNs and 12 on-clamp cPNs. The off-clamp MSPN was significantly superior to on-clamp cPN in avoiding renal ischemia (median IT, 0 min vs. 8.6 min, p < 0.001) and reducing PT (median PT, 5.8 min vs. 11.5 min, p < 0.001) and NNL (median NNL, 5.3 mm vs. 6.0 mm, p = 0.006) with comparable BL (median BL, 20.9 ml vs. 23.2 ml, p = 0.804). No bleeding and major urine leakage were noted during the reoperations. Conclusions: Off-clamp MSPN outperforms on-clamp cPN in lowering the risks of postoperative renal function impairment in dogs.

3.
Pathol Res Pract ; 246: 154498, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37207529

RESUMO

BACKGROUND: The histology of the cardiac mucosa at the esophagogastric junction (EGJ) at birth is still a controversy. We conducted a histopathological study of the EGJ to clarify the morphology, and to determine the presence or absence of cardiac mucosa at birth. SUBJECTS: We examined 43 Japanese neonates and infants that are born prematurely or at full term. Death had occurred between 1 and 231 days after birth. RESULTS: Cardiac mucosa without parietal cells showing positivity for anti-proton pump antibody, adjacent to the most distal squamous epithelium, was observed in 32 (74%) of the 43cases. Such mucosa was evident in neonates that were full-term and had died within 14 days after birth. On the other hand, cardiac mucosa with parietal cells adjacent to squamous epithelium was noted in 10 cases (23%); the remaining one (2%) had columnar-lined esophagus. Squamous and columnar islands were observed in a single histological section from the EGJ in 22 (51%) of the 43 cases. Parietal cells were sparsely or densely present in the gastric antral mucosa. CONCLUSIONS: On the basis of these histological findings, we consider that cardiac mucosa exists in neonates and infants and can be defined as such, irrespective of the presence or absence of parietal cells (so-called oxyntocardiac mucosa). Neonates born prematurely or at full-term have cardiac mucosa in the EGJ just after birth, as is the case for Caucasian neonates.


Assuntos
Esôfago de Barrett , Carcinoma de Células Escamosas , Recém-Nascido , Humanos , Mucosa/patologia , Junção Esofagogástrica/patologia , Esôfago de Barrett/patologia , Epitélio/patologia , Carcinoma de Células Escamosas/patologia , Mucosa Gástrica/patologia
4.
Surg Innov ; 30(4): 419-427, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36961743

RESUMO

OBJECTIVES: To assess the feasibility of off-clamp laparoscopic partial nephrectomy using microwave scissors. METHODS: We performed transperitoneal laparoscopic partial nephrectomy, without hilar clamping or renorrhaphy, using only microwave scissors for renal resection in a porcine model. For each kidney, 2 types of procedures were performed: a middle pole resection excising an area of 2-cm diameter and approximately 1-cm depth and a lower pole resection at the level of the lower polar line. The renal calyces exposed during renal resection were sealed and transected using microwave scissors. After 3 days of follow-up, the pigs were reoperated to inspect for postoperative complications. Euthanasia was performed to collect the remaining kidneys for histopathological examination. RESULTS: Ten procedures were successfully performed, without hilar clamping or suturing of the renal calyces and parenchyma, in 5 kidneys from 3 pigs. The median resecting time, blood loss, and lateral thermal injury were 23.2 min, 47.1 mL, and 6.8 mm in the middle pole resection, and were 15.1 min, 26.5 mL, and 6.9 mm in the lower pole resection, respectively. No complications were noted during reoperation, such as postoperative hemorrhage and major urine leakage. Extravasation occurred in 2 middle pole resections and 3 lower pole resections during retrograde pyelogram. Hematoxylin and eosin staining revealed thermal injury characterized by tissue microwave fixation in the near zone and acute coagulative necrosis in the intermediate zone. CONCLUSIONS: Microwave scissors-based off-clamp laparoscopic partial nephrectomy is feasible in pigs and can be used for clinical applications.


Assuntos
Neoplasias Renais , Laparoscopia , Suínos , Animais , Micro-Ondas/uso terapêutico , Estudos de Viabilidade , Nefrectomia/métodos , Rim/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Constrição
5.
BMC Gastroenterol ; 22(1): 289, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672698

RESUMO

BACKGROUND: Pancreatic acinar cell metaplasia (PACM) has been rarely reported in the gastric mucosa. In the present study, we aimed to elucidate the clinical and pathological characteristics of PACM associated with Helicobacter pylori (H. pylori). METHOD: 5930 patients who underwent five- or two-point gastric biopsy according to the updated Sydney system (USS) by upper gastrointestinal endoscopy were enrolled. The patients were categorized into current H. pylori infection (CHI), post-H. pylori eradication (PHE), and non-H. pylori infection (NHI) groups according to the H. pylori infection status, and the frequency and location of PACM were compared. Additionally, a case-control study was performed to compare the USS scores between patients with CHI and PACM and those with CHI but not PACM. RESULT: The frequencies of PACM were 0.49% (10/2039), 0.75% (25/3332), and 0% (0/559) in the CHI, PHE, and NHI groups, respectively. PACM was found in the greater curvature of the antrum in 33 of the 35 patients with PACM. Among the patients with CHI, the inflammation scores in the greater curvature of the antrum and the greater curvature of the corpus were lower in patients with PACM than in those without PACM. CONCLUSION: Although rarely reported in the gastric mucosa, PACM was closely related to H. pylori infection, especially in the antrum, and was associated with relatively mild inflammation.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Células Acinares/patologia , Estudos de Casos e Controles , Mucosa Gástrica/patologia , Gastrite/complicações , Gastrite/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Inflamação/patologia , Metaplasia/patologia
6.
Gut ; 71(8): 1488-1514, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35725291

RESUMO

OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.


Assuntos
Esôfago de Barrett , Refluxo Gastroesofágico , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/epidemiologia , Esôfago de Barrett/etiologia , Consenso , Junção Esofagogástrica , Humanos , Inflamação , Metaplasia
7.
Exp Anim ; 71(2): 161-172, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34789616

RESUMO

In oral surgery, tissue loss may occur in some cases, resulting in bone exposure and subsequent wound infection and possible scar formation during secondary healing. In this study, Terudermis® Artificial Dermis (AD-T), a dermal defect graft made from processed bovine dermis collagen and gelatin sponge (GS) were used as dressings on 100-mm2 wounds with exposed bone on the heads of rats. For the control group, the wound was left exposed. The wound-healing efficacy of the treatment was compared macroscopically and histologically among the three groups at 1, 2, and 4 weeks after surgery. Complete wound healing was achieved faster in the AD-T group than in the GS group, and osteoblasts appeared on the bone surface, indicating accelerated bone remodeling. Furthermore, in the AD-T group, there was an increased production of newly formed blood vessels, fibroblasts and osteoblasts positive for anti-cortactin antibodies, which are believed to contribute to wound healing. Our findings suggest that AD-T is better than GS as a wound dressing material.


Assuntos
Gelatina , Cicatrização , Animais , Bandagens , Bovinos , Colágeno , Derme , Ratos
8.
Cardiovasc Intervent Radiol ; 44(11): 1790-1797, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34231011

RESUMO

PURPOSE: This animal experimental study evaluated how hepatic artery and portal vein transient occlusion affects the ablation zone of hepatic radiofrequency ablation (RFA). MATERIAL AND METHODS: Twenty-one rabbits were divided into three groups of seven each: (1) control, (2) hepatic artery occlusion, and (3) portal vein occlusion by a balloon catheter. For each rabbit, two or three RFA sessions were performed using an electrode needle. Ablation time, temperature around the tip of RFA needle at the end of RFA, ablation volume on fat-suppressed T1-weighted image in the hepatobiliary phase, and coagulative necrosis area on histopathology were measured and compared between the three groups using the Kruskal-Wallis paired Mann-Whitney U tests. RESULTS: In 43 RFA sessions (group 1, 15; group 2, 14; group 3, 14), mean tissue temperature in group 3 (77.0 °C ± 7.7 °C) was significantly higher compared to groups 1 (59.2 °C ± 18.8 °C; P = 0.010) and 2 (67.5 °C ± 9.9 °C; P = 0.010). In addition, mean ablation volume and coagulative necrosis in group 3 (2.10 ± 1.37 mm3 and 0.86 ± 0.28 mm2, respectively) were larger compared to groups 1 (0.84 ± 0.30 mm3; P < 0.001 and 0.55 ± 0.26 mm2; P = 0.020, respectively) and 2 (0.89 ± 0.59 mm3; P = 0.002 and 0.60 ± 0.22 mm2; P = 0.024, respectively). CONCLUSION: Portal vein occlusion potentially boosts tissue temperature, ablation volume, and area of histopathologically proven coagulative necrosis during hepatic RFA in the non-cirrhotic liver.


Assuntos
Experimentação Animal , Ablação por Cateter , Ablação por Radiofrequência , Animais , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Coelhos
9.
Int J Oncol ; 59(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33982789

RESUMO

The phosphorylation of pyruvate dehydrogenase (PDH) by pyruvate dehydrogenase kinase (PDK) 4 inhibits its ability to induce a glycolytic shift. PDK4 expression is upregulated in various types of human cancer. Because PDK4 regulation is critical for metabolic changes in cancer cells, it is an attractive target for cancer therapy given its ability to shift glucose metabolism. It was previously shown that a novel PDK4 inhibitor, cryptotanshinone (CPT), suppressed the three­dimensional (3D)­spheroid formation of pancreatic and colorectal cancer cells. In the present study, the effects of CPT on the invasiveness of bladder cancer cells were investigated. CPT significantly suppressed the invasiveness and 3D­spheroid formation of T24 and J82 bladder cancer cells. CPT also suppressed the phosphorylation of PDH and ß­catenin, as well as the expression of N­cadherin, which are all critical for inducing epithelial­mesenchymal transition (EMT). The knockdown of ß­catenin or PDK4 using specific small interfering RNAs suppressed N­cadherin expression and invasiveness in T24 cells. An mTOR inhibitor also suppressed the phosphorylation of ß­catenin and N­cadherin expression. Furthermore, CPT injection significantly suppressed pancreatic tumor growth and peritoneal dissemination of highly metastatic SUIT­2 pancreatic cancer cells in a mouse orthotopic pancreatic cancer model, without evident toxicity. Moreover, immunohistochemistry analyses demonstrated decreased ß­catenin expression in CPT­treated pancreatic tumors compared with control tumors. Taken together, these results indicate that CPT reduced the invasiveness and metastasis of bladder cancer cells by suppressing EMT via the mTOR/ß­catenin/N­cadherin pathway.


Assuntos
Antineoplásicos/farmacologia , Fenantrenos/farmacologia , Piruvato Desidrogenase Quinase de Transferência de Acetil/antagonistas & inibidores , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
10.
Anticancer Res ; 41(3): 1327-1339, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788724

RESUMO

BACKGROUND: Colonic cancer is associated with a low incidence of peritoneal metastasis compared with gastric cancer; however, the reason for this remains unclear. In this study, a model of peritoneal dissemination using the CT26 murine colon cancer cell line was used to analyze the physiological roles of cancer-derived exosomes. MATERIALS AND METHODS: Exosomes were collected from the supernatant of CT26 cell culture by ultracentrifugation. The number of peritoneal disseminations in two mouse models of colonic cancer pre-administered exosomes or phosphate-buffered saline were compared. RESULTS: Cancer-derived exosomes suppressed peritoneal dissemination compared to phosphate-buffered saline. After administration of exosomes, the number of intraperitoneal macrophages and the expression of inducible nitric oxide synthase increased. Furthermore, cancer-derived exosomes increased activated natural killer cells and interferon-γ expression. CONCLUSION: Tumor-derived exosomes from colonic cancer may suppress peritoneal metastasis via an immunological mechanism.


Assuntos
Neoplasias do Colo/imunologia , Exossomos/imunologia , Vigilância Imunológica/imunologia , Neoplasias Peritoneais/imunologia , Animais , Linhagem Celular Tumoral , Movimento Celular/imunologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Exossomos/metabolismo , Feminino , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Óxido Nítrico Sintase Tipo II/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Neoplasias Peritoneais/secundário , Células RAW 264.7
11.
Int J Mol Sci ; 22(4)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670390

RESUMO

The conventional two-dimensional (2D) culture is available as an in vitro experimental model. However, the culture system reportedly does not recapitulate the in vivo cancer microenvironment. We recently developed a tissueoid cell culture system using Cellbed, which resembles the loose connective tissue in living organisms. The present study performed 2D and three-dimensional (3D) culture using prostate and bladder cancer cell lines and a comprehensive metabolome analysis. Compared to 3D, the 2D culture had significantly lower levels of most metabolites. The 3D culture system did not impair mitochondrial function in the cancer cells and produce energy through the mitochondria simultaneously with aerobic glycolysis. Conversely, ATP production, biomass (nucleotides, amino acids, lipids and NADPH) synthesis and redox balance maintenance were conducted in 3D culture. In contrast, in 2D culture, biomass production was delayed due to the suppression of metabolic activity. The 3D metabolome analysis using the tissueoid cell culture system capable of in vivo cancer cell culture yielded results consistent with previously reported cancer metabolism theories. This system is expected to be an essential experimental tool in a wide range of cancer research fields, especially in preclinical stages while transitioning from in vitro to in vivo.


Assuntos
Técnicas de Cultura de Células , Metabolismo Energético , Neoplasias da Próstata/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Humanos , Masculino , Células PC-3
12.
Virchows Arch ; 479(1): 169-178, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33515301

RESUMO

There are two types of pyloric gland-like metaplasia in the corpus of stomach: pyloric and pseudopyloric metaplasias. They show the same morphology as the original pyloric glands in H&E staining. Pseudopyloric metaplasia is positive for pepsinogen (PG) I immunohistochemically, whereas pyloric metaplasia is negative. Recently, spasmolytic polypeptide-expressing metaplasia (SPEM) is proposed for pyloric gland-like metaplasia mainly in animal experiments. SPEM expresses trefoil factor family 2 (TFF2) and is often considered synonymous with pseudopyloric metaplasia. We reviewed consecutive 22 Japanese patients with autoimmune gastritis (AIG) to investigate TFF2 expression in pyloric and pseudopyloric metaplasias by counting all pyloric gland-like glands in biopsy specimens taken from greater curvature of the middle corpus according to the Updated Sydney System. Pyloric metaplasia was seen in all the 22 cases, and pseudopyloric metaplasia was found in 15 cases. Of 1567 pyloric gland-like glands in all the cases, 1381 (88.1%) glands were pyloric metaplasia glands, and the remaining 186 (11.9%) glands were pseudopyloric metaplasia glands. TFF2 expression was observed in pyloric or pseudopyloric metaplasia glands in 20 cases. TFF2 expression was recognized in 409 of 1381 (26.9%) pyloric metaplasia glands and 27 of 186 (14.5%) pseudopyloric metaplasia glands (P<0.01, chi-square test). In conclusion, SPEM was not always the same as pseudopyloric metaplasia in human AIG, and the majority of metaplasia in AIG was not pseudopyloric but pyloric metaplasia.


Assuntos
Doenças Autoimunes/metabolismo , Mucosa Gástrica/química , Gastrite/metabolismo , Fator Trefoil-2/análise , Doenças Autoimunes/patologia , Biomarcadores/análise , Biópsia , Feminino , Mucosa Gástrica/patologia , Gastrite/patologia , Humanos , Imuno-Histoquímica , Japão , Masculino , Metaplasia , Estudos Retrospectivos
13.
Dig Dis Sci ; 66(4): 1072-1079, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32440745

RESUMO

BACKGROUND: We previously reported the development of pancreatic acinar cell metaplasia (PACM) in the glandular stomach of a duodenal contents reflux model (reflux model). AIMS: We aimed to investigate the characteristics and histogenesis of PACM using a reflux model. METHODS: A reflux model was created using 8-week-old male Wistar rats, which were killed up to 30 weeks postoperatively. Histological examination was performed to analyze the glandular stomach-jejunal anastomosis. Furthermore, electron microscopic images of PACM samples were compared with pancreatic and gastric glands removed from rats that had not undergone surgery. Immunostaining for α-amylase, HIK1083, TFF2, and Ki-67 was performed, and double fluorescent staining was carried out using antibodies against α-amylase and HIK1083, or α-amylase and TFF2. RESULTS: In all reflux model rats, PACM was observed proximal to the glandular stomach-jejunal anastomosis, surrounded by pseudopyloric metaplasia. The number of chief cells was decreased in the deep part of the gland, where PACM occurred. Electron microscopy showed that PACM cells had greater numbers of rough endoplasmic reticulum tubules than chief cells, and exhibited pancreatic acinar cell morphology. Upon immunochemical staining, the regenerative foveolar epithelium and part of the pseudopyloric glands stained strongly positive for TFF2, whereas PACM cells were only weakly positive. Double fluorescent staining identified early lesions of PACM in the neck, which were double positive for α-amylase and TFF2, but negative for HIK1083. CONCLUSIONS: PACM could be induced by duodenal contents reflux. PACM originates from stem cells located in the neck of oxyntic glands during gastric mucosal regeneration.


Assuntos
Refluxo Duodenogástrico , Jejuno/cirurgia , Metaplasia , Pâncreas , Suco Pancreático/metabolismo , Estômago , Células Acinares/patologia , Anastomose Cirúrgica/métodos , Animais , Ácidos e Sais Biliares/metabolismo , Refluxo Duodenogástrico/complicações , Refluxo Duodenogástrico/metabolismo , Mucosa Gástrica/patologia , Metaplasia/etiologia , Metaplasia/patologia , Modelos Teóricos , Pâncreas/metabolismo , Pâncreas/patologia , Ratos , Ratos Wistar , Estômago/patologia , Estômago/cirurgia
14.
Ann Surg ; 273(6): e206-e213, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31290765

RESUMO

OBJECTIVE: The aim of the study was to investigate whether inhibition of Sonic Hedgehog (SHH) pathway would prevent progression of Barrett's Esophagus (BE) to esophageal adenocarcinoma. BACKGROUND: The hedgehog signaling pathway is a leading candidate as a molecular mediator of BE and esophageal adenocarcinoma (EAC). Repurposed use of existing off-patent, safe and tolerable drugs that can inhibit hedgehog, such as itraconazole, could prevent progression of BE to EAC. METHODS: The efficacy of itraconazole was investigated using a surgical rat reflux model of Barrett's Metaplasia (BM). Weekly intraperitoneal injections of saline (control group) or itraconazole (treatment group; 200 mg/kg) were started at 24 weeks postsurgery. Esophageal tissue was harvested at 40 weeks. The role of the Hh pathway was also evaluated clinically. Esophageal tissue was harvested after 40 weeks for pathological examination and evaluation of the SHH pathway by immunohistochemistry. RESULTS: BM was present in control animals 29 of 31 (93%) versus itraconazole 22 of 24 (91%). EAC was significantly lower in itraconazole 2 of 24 (8%) versus control 10 of 31 (32%), respectively (P = 0.033). Esophageal SHH levels were lower in itraconazole vs control (P = 0.12). In esophageal tissue from humans with recurrent or persistent dysplastic BE within 24 months of ablative treatment, strong SHH and Indian Hedgehog expression occurred in distal BE versus proximal squamous epithelium, odds ratio = 6.1 (95% confidence interval: 1.6, 23.4) and odds ratio = 6.4 (95% confidence interval: 1.2, 32.8), respectively. CONCLUSION: Itraconazole significantly decreases EAC development and SHH expression in a preclinical animal model of BM. In humans, BE tissue expresses higher SHH, Indian Hedgehog, and bone morphogenic protein levels than normal squamous esophageal epithelium.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/etiologia , Esôfago de Barrett/complicações , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/etiologia , Proteínas Hedgehog/antagonistas & inibidores , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Adenocarcinoma/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Neoplasias Esofágicas/patologia , Masculino , Invasividade Neoplásica , Ratos , Ratos Sprague-Dawley
15.
Cancer Sci ; 112(2): 918-931, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33244783

RESUMO

Metabolic programming of cancer cells is an essential step in transformation and tumor growth. We established two-dimensional (2D) monolayer and three-dimensional (3D) cultures, the latter called a "tissueoid cell culture system", using four types of tongue cancer cell lines. We also undertook a comprehensive metabolome analysis of three groups that included xenografts created by transplanting the cell lines into nude mice. In addition, we undertook a functional analysis of the mitochondria, which plays a key role in cancer metabolism. Principal component analysis revealed the plots of the four cell lines to be much narrower in 2D culture than in 3D culture and xenograft groups. Moreover, compared to xenografts, the 2D culture had significantly lower levels of most metabolites. These results suggest that the unique characteristics of each cell disappeared in 2D culture, and a type of metabolism unique to monolayer culture took over. Conversely, ATP production, biomass synthesis, and maintenance of redox balance were shown in 3D culture using sufficient nutrients, which closely resembled the metabolic activity in the xenografts. However, there were several differences between the metabolic activity in the 3D culture and xenografts. In vivo, the cancer tissue had blood flow with stromal cells present around the cancer cells. In the xenografts, we detected metabolized and degraded products in the liver and other organs of the host mice. Furthermore, the 3D system did not show impairment of mitochondrial function in the cancer cells, suggesting that cancer cells produce energy simultaneously through mitochondria, as well as aerobic glycolysis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Organoides/metabolismo , Esferoides Celulares/metabolismo , Neoplasias da Língua/metabolismo , Animais , Carcinoma de Células Escamosas/patologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Organoides/patologia , Esferoides Celulares/patologia , Neoplasias da Língua/patologia
16.
Pathobiology ; 87(5): 291-301, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966983

RESUMO

BACKGROUND: We developed a 3-dimensional (3D) culture system using a high-purity silica fiber scaffold of unwoven sheets called CellbedTM. METHODS: We used adherent colon and esophagogastric junction adenocarcinoma cells, tongue squamous cell carcinoma (SqCC) cells, and nonadherent gastric cancer cells. These cells were subjected to staining with various substances and observed by electron microscopy. To evaluate the effects of extracellular matrix in carcinoma tissues, SqCC cells were cultured in Cellbed coated with collagens I, III, and IV. RESULTS: Especially well-differentiated carcinoma cells cultured in this 3D system showed their own unique characteristics: luminal formation in adenocarcinoma cells and cell stratification and keratinization in SqCC cells. Scanning electron microscopy revealed the proliferation of cancer cells with cytoplasm entwined in Cellbed. Intercellular desmosomes in squamous epithelia were detected by transmission electron microscopy of vertical cross sections. SqCC cells cultured in Cellbed coated with collagen IV showed enhanced invasive and proliferative abilities. CONCLUSION: Because the morphology of cancer cells cultured in this 3D culture system is similar to that in living organisms, we called the system a "tissueoid cell culture system." Coating with collagen IV enables the modification of cell-matrix interactions as well as recapitulation of the in vivo microenvironment.


Assuntos
Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Silicatos/química , Alicerces Teciduais/química , Adenocarcinoma , Carcinoma de Células Escamosas , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Matriz Extracelular/metabolismo , Humanos , Microscopia Eletrônica de Varredura , Neoplasias Gástricas , Neoplasias da Língua
18.
J Forensic Sci ; 65(5): 1557-1562, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32501618

RESUMO

To evaluate the usefulness of forensic autopsies in determining latent prostate cancer (PC) prevalence, we examined latent PC prevalence from autopsies and compared our findings between decedents with and without cancer. Data from forensic autopsies performed in Japan from 2004 to 2014 were obtained. For each prostate, histopathological examinations were performed in both the base and the apex sections. Three hundred and seventeen Japanese decedents were selected for analysis. The mean age of decedents was 56.4 ± 17.8 years (range, 14-94 years). Among this population, 39.4% died suddenly of disease and 60.6% died of external causes. Latent PC was identified in 45 (14.2%) decedents, who ranged from 27 to 93 years old (mean, 71.1 ± 12.9 years). The prevalence of clinically significant PC with a Gleason score of 7 or more was 8.8%, and the rate increased with age. Fifteen males had cancers other than PC. The prevalence of overall latent PC was significantly higher for those with cancer compared with those without (40.0% vs. 12.9%; P = 0.003). In this study, the use of forensic autopsy materials provided the opportunity to obtain a more accurate natural history of PC, as the decedents in this situation would have been more likely to have died suddenly while behaving as normal prior to death, and less likely to have been impacted by long-term medical interventions.


Assuntos
Neoplasias da Próstata/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Autopsia , Causas de Morte , Morte Súbita/epidemiologia , Patologia Legal , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prevalência
19.
Clin Exp Dent Res ; 6(4): 420-427, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32281236

RESUMO

BACKGROUND: Ezrin, ERK, STAT3, and AKT are proteins that are overexpressed in various types of cancer, although their expressions in tongue cancer has received less focus. This study aimed to address associations between the expression levels of these proteins and with characteristics of the tumor and patient survival. METHODS: We performed immunohistochemical staining of ezrin, ERK, STAT3, and AKT in tumors from patients with tongue carcinoma in situ (CIS, n = 17) and tongue squamous cell carcinoma (SCC, n = 46). Statistical differences between the SCC versus the CIS cohorts were estimated by calculations of bivariate odds ratios of low versus high expression of the proteins. Fisher's exact tests were used to appraise interassociations between the proteins, as well as expression levels versus patient and tumor characteristics. Survival based on Kaplan-Meier statistics in combination log-rank tests were used to address potential effects of the patient and tumor characteristics versus 5-year survival rate. RESULTS: The relative high: low expression of all four proteins in the two cohorts differed, and particularly ERK was markedly overexpressed in the SCC versus the CIS cohort (odds ratio = 45.3, p < .01). The relative high: low expression each protein versus patient and tumor characteristics; showed associations between AKT expression and T stage (p = .002) plus node metastases (p = .12), and between ERK expression and drinking (p = .01) and smoking history (p = .01). There was no significant difference observed between ERK and the three other molecules, nor any significant difference between the degree of expression of each protein and the 5-year disease-specific survival rate. CONCLUSION: Ezrin, ERK, STAT3, and AKT appear to be involved in the progress from carcinoma in situ in the tongue into squamous cell carcinoma. ERK in particular is overexpressed, suggesting that ERK may be a novel therapeutic target for preventing tongue cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias da Língua/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Neoplasias da Língua/cirurgia
20.
Magn Reson Med Sci ; 19(2): 125-134, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31061268

RESUMO

PURPOSE: This study assessed the MRI findings of strangulated small bowel obstruction (SBO) and mesenteric venous occlusion (MVO) in a rabbit model using 3T MRI. MATERIALS AND METHODS: Twenty rabbits were included in this study. The strangulated SBO and MVO models were generated via surgical procedures in nine rabbits, and sham surgery was performed in two rabbits. The success of generating the models was confirmed via angiographic, macroscopic, and microscopic findings after the surgical procedure. MRI was performed before and 30 min after inducing mesenteric ischemia. T1-weighted images (T1WIs), T2-weighted images (T2WIs), and fat-suppressed T2WIs (FS-T2WIs) were obtained using the BLADE technique, and fat-suppressed T1WIs (FS-T1WIs) were obtained. The signal intensities of the affected bowel before and after the surgical procedures were visually categorized as high, iso, and low intense compared with the findings for the normal bowel wall on all sequences. Bowel wall thickness was measured, and the signal intensity ratio (SI ratio) was calculated using the signal intensities of the bowel wall and psoas muscle. RESULTS: Angiographic, macroscopic, and microscopic findings confirmed that all surgical procedures were successful. The ischemic bowel wall was thicker than the normal bowel. The bowel wall was thicker in the MVO model (3.17 ± 0.55 mm) than in the strangulated SBO model (2.26 ± 0.46 mm). The signal intensity and SI ratio of the bowel wall were significantly higher after the procedure than before the procedure on all sequences in both models. The mesentery adjacent to the ischemic bowel loop exhibited a high signal intensity in all animals on FS-T2WIs. CONCLUSION: Non-contrast MRI can be used to evaluate mesenteric ischemia caused by strangulated SBO and MVO. FS-T2WIs represented the best modality for depicting the high signal intensity in the bowel wall and mesentery caused by ischemia.


Assuntos
Obstrução Intestinal/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Isquemia Mesentérica/diagnóstico por imagem , Oclusão Vascular Mesentérica/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Coelhos
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