The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum

Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.

Blastic plasmacytoid dendritic cell neoplasm:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions are usually the first manifestation of BPDCN,although the tumor may also invade the bone marrow,lymph nodes,peripheral blood,and other parts of the body,leading to several other manifestations,requiring further differentiation through skin biopsy and immunohistochemistry.CASE SUMMARY In the present paper,the cases of 2 patients diagnosed with BPDCN are discussed.The immunohistochemistry analysis of these 2 patients revealed positivity for CD4,CD56,and CD123.Currently,no standard chemotherapy regimen is available for BPDCN.Therefore,intensive therapy for acute lymphoblastic leukemia was applied as the treatment method for these 2 cases.CONCLUSION Although allogeneic bone marrow transplantation could be further effective in prolonging the median survival the ultimate prognosis was unfavorable.Future treatment modalities tailored for elderly patients will help prolong survival.

Endoscopic submucosal tunnel dissection for largesuperficial esophageal squamous cell neoplasms

Endoscopic submucosal dissection(ESD)is a wellestablished treatment for superficial esophageal squamous cell neoplasms(SESCNs)with no risk of lymphatic metastasis.However,for large SESCNs,especially when exceeding two-thirds of the esophageal circumference,conventional ESD is time-consuming and has an increased risk of adverse events.Based on the submucosal tunnel conception,endoscopic submucosal tunnel dissection(ESTD)was first introduced by us to remove large SESCNs,with excellent results.Studies from different centers also reported favorable results.Compared with conventional ESD,ESTD has a more rapid dissection speed and R0 resection rate.Currently in China,ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique,as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria.However,not all patients with SESCNs are candidates for ESTD,and postoperative esophageal strictures should also be taken into consideration,especially for lesions with a circumference greater than three-quarters.In this article,we describe our experience,review the literature of ESTD,and provide detailed information on indications,standard procedures,outcomes,and complications of ESTD.

Short term results of endoscopic submucosal dissection in superficial esophageal squamous cell neoplasms

AIM: To evaluate the efficacy of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. METHODS: Between July 2007 and March 2009, 27 consecutive superficial esophageal squamous cell neoplasms in 25 enrolled patients were treated by endoscopic submucosal dissection. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The mean size of the lesions was 21 ± 13 mm (range 2-55 mm); the mean size of the resection specimens was 32 ± 12 mm (range 10-70 mm). The enblock resection rate was 100% (27/27), and en block resection with tumor-free lateral/basal margins was 88.9% (24/27). Perforation occurred in 1 patient who was managed by conservative medical treatments. None of the patients developed local recurrence or distant metastasis in the follow-up period. CONCLUSION: Endoscopic submucosal dissection is applicable to superficial esophageal squamous cell neoplasms with promising results.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua,China:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.

Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm:Insights from recent case studies

We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.

Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature

BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.

Underwater endoscopic mucosal resection for neoplasms in the pyloric ring of the stomach: Four case reports

BACKGROUND Tumors located in the pylorus are technically more complex to resect by endoscopic resection,as the anatomical characteristics of this region can affect the adequate assessment of margins and performance of the procedure.We reported the results of underwater endoscopic mucosal resection(UEMR)of benign mucosal neoplasms located in the pyloric ring.CASE SUMMARY This case series describes 4 patients with 4 mucosal neoplasms located in the pyloric ring.The diameter of each neoplasm was less than 15 mm.We performed UEMR for the lesions.Water immersion enabled slight floating of the lesions,resulting in easy identification.We achieved en bloc resection with a snare and electrosurgical unit.All procedure were performed within 3 min without adverse events.Pathologic examination showed low-grade dysplasia with clear resection margins in one case and hyperplastic polyps in three cases.CONCLUSION UEMR can be an effective and safe treatment method for neoplasms in the gastric pyloric ring.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Plasma Cell Neoplasms, Clinicopathological Characteristics and Immunophenotype of 21 Patients

Introduction: Plasma cell neoplasms are monoclonal proliferations characterized by the secretion of an immunoglobulin product known as component "M" or monoclonal. The World Health Organization (WHO 2008) defines as plasma cell neoplasms the following: plasma cell myeloma, plasmacytoma and those syndromes defined by immunoglobulin deposits and primary amyloidosis, The objective of the present work was to correlate their clinical, morphological and phenotype characteristics in 21 patients. Material and Methods: A 2-year retrospective review was performed of the files of the surgical pathology laboratory and of the hematology service of the General Hospital of Mexico, searching for patients with a diagnosis of plasma cell neoplasm. We analyzed the following variables: age, gender, clinical symptoms, evolution, localization, laboratory tests, morphology, and expression of immunohistochemical markers. Of the 21 patients, 12 (57.1%) corresponded to plasma cell myelomas and 9 (42.8%) were plasmacytomas (seven extraosseous and two solitary bone plasmacytoma);women predominated with 61.4% and age ranged between 22 and 84 years. Mass and epistaxis were observed in the patients with plasmacytomas, and symptoms of medullary compression and anemia were observed in those patients with plasma cell myeloma. The time of symptomatology varied from 3 to 12 months. Laboratory tests revealed that lactate dehydrogenase (LDH), beta 2 microglobulin, C-reactive protein were altered and that hypercalcemia and anemia were present more in the systemic form of the disease. Treatment depended on the clinical staging and laboratory data. Mature forms predominated morphologically. Immunohistochemical stain revealed a constant expression for CD 138, six patients expressed CD 56, and expression of the Kappa and Lambda light chains was while.

Endoscopic submucosal dissection for superficial esophageal neoplasms

Endoscopic submucosal dissection(ESD) is currently accepted as the major treatment modality for superficial neoplasms in the gastrointestinal tract including the esophagus.An important advantage of ESD is its effectiveness in resecting lesions regardless of their size and severity of fibrosis.Based on excellent outcomes for esophageal neoplasms with a small likelihood of lymph node metastasis,the number of ESD candidates has increased.On the other hand,ESD still requires highly skilled endoscopists due to technical difficulties.To avoid unnecessary complications including perforation and postoperative stricture,the indications for ESD require careful consideration and a full understanding of this modality.This article,in the highlight topic series,provides detailed information on the indication,procedure,outcome,complications and their prevention in ESD of superficial esophageal neoplasms.

Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: Implications on chemoprevention

AIM: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group.This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism.METHODS: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining.RESULTS: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P＜0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P＜0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development.CONCLUSION: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression.

Granular cell tumor of stomach: A case report and review of literature

Granular cell tumor （GCT） was described for the first time by Abrikosoff in 1926. It is a relatively rare neoplasm that may occur at many sites, but most commonly in the skin or soft tissues. The occurrence of GCT in the gastrointestinal tract is rare, accounting approximately for 8% of all tumors, among which the most common site is the esophagus, whereas gastric localization is very rare. Gastric GCTs can be solitary or, more frequently, associated with other gastrointestinal localization. Although GCTs are usually clinically and histologically benign, some malignant cases have been reported. Histologically, these tumors consist of polygonal and fusiform cells disposed in compact ＂nests＂ and immunohistochemical staining for S-100 protein supports the proposed derivation from Schwann cells. A correct preoperative diagnosis of this tumor can only be made in 50% of all patients and it is always based on endoscopic biopsy. Laparoscopic or conventional wedge resection represents the treatment of choice. In this study, the authors reported a case of a 49-year-old woman with a solitary granular cell tumor of the stomach with infiltrative pattern, successfully treated with surgical resection. A review of literature is also presented with emphasis on diagnostic criteria concerning the malignant form.

A perivascular epithelioid cell tumor of the stomach:An unsuspected diagnosis

Perivascular epithelioid cell tumor(PEComa) is a rare mesenchymal neoplasia and currently well recognized as a distinct entity with characteristic morphological,immunohistochemical and molecular findings.We report a case of PEComa arising in the antrum of a 71-year-old female with melena.The tumor,located predominantly in the submucosa as a well delimited nodule,measured 3.0 cm in diameter and was completely resected,with no evidence of the disease elsewhere.Histologically,it was composed predominantly of eosinophilic epithelioid cells arranged in small nests commonly related to variably sized vessels,with abundant extracellular material,moderate nuclear variation and discrete mitotic activity.No necrosis,angiolymphatic invasion or perineural infil-tration was seen.Tumor cells were uniformly positive for vimentin,smooth muscle actin,desmin and melan A.Although unusual,PEComa should be considered in the differential diagnosis of gastric neoplasia with characteristic epithelioid and oncocytic features and prominent vasculature.

Enhanced expression of epidermal growth factor receptor gene in gastric mucosal cells by the serum derived from rats treated with electroacupuncture at stomach meridian acupoints

AIM: To investigate the effect of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expression of epidermal growth factor receptor (EGFR) gene in gastric mucosal cells. METHODS: The stress-induced gastric mucosal injury in rat model was established by water-immersion and restrained stress methods. 52 rats were randomly divided into: normal group (n = 8), model group (n = 8), model serum group (n = 12), stomach serum group (n = 12), and gallbladder serum group (n = 12). The gastric mucosal cells were separated by pronase-EDTA digestion method and incubated with serum. The EGFR gene expression in gastric mucosal cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Compared with normal group (0.6860 ± 0.0594), the serum derived from rats of the stomach group (1.2272 ± 0.0813, P = 0.00 < 0.01) and gallbladder group (0.9640 ± 0.0387, P = 0.00 < 0.01) had a tendency to enhance the EGFR gene expression in gastric mucosal cells. Such tendency existed in the model group (0.7104 ± 0.0457) but with no signifi cant difference (P = 0.495 > 0.05) and in model serum group (0.8516 ± 0.0409) with an extremely obvious difference (P = 0.001 < 0.01). Furthermore, the EGFR gene expression in stomach serum group was significantly higher than that in gallbladder serum group (P = 0.00 < 0.01). CONCLUSION: The present study shows that serumderived from rats treated with electroacupuncture at stomach meridian acupoints can distinctly increase the EGFR gene expression of gastric mucosal cells. Therefore, there is certain meridian specificity in the serum, which could provide a proof for the TCM theory “particular relation between meridian and internal organ”.

Blastic Plasmacytoid Dendritic Cell Neoplasm:Progress in Cell Origin,Molecular Biology,Diagnostic Criteria and Therapeutic Approaches

Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.

Profiling cellular bioenergetics, glutathione levels, and caspase activities in stomach biopsies of patients with upper gastrointestinal symptoms

AIM: To measure biochemical parameters in stomach biopsies and test their suitability as diagnostic biomarkers for gastritis and precancerous lesions.METHODS: Biopsies were obtained from the stomachs of two groups of patients(n = 40) undergoing fiberoptic endoscopy due to upper gastrointestinal symptoms. In the first group(n = 17), only the corpus region was examined. Biopsies were processed for microscopic examination and measurement of mitochondrial O2 consumption(cellular respiration), cellular adenosine triphosphate(ATP), glutathione(GSH), and caspase activity. In the second group of patients(n = 23), both corpus and antral regions were studied. Some biopsies were processed for microscopic examination, while the others were used for measurements of cellular respiration and GSH level.RESULTS: Microscopic examinations of gastric corpus biopsies from 17 patients revealed normal mucosae in 8 patients, superficial gastritis in 7 patients, and chronic atrophic gastritis in 1 patient. In patients with normal histology, the rate(mean ± SD) of cellular respiration was 0.17 ± 0.02 μmol/L O2 min-1 mg-1, ATP content was 487 ± 493 pmol/mg, and GSH was 469 ± 98 pmol/mg. Caspase activity was detected in 3 out of 8 specimens. The values of ATP and caspase activity were highly variable. The presence of superficial gastritis had insignificant effects on the measured biomarkers. In the patient with atrophic gastritis, cellular respiration was high andATP was relatively low, suggesting uncoupling oxidative phosphorylation. In the second cohort of patients, the examined biopsies showed either normal or superficial gastritis. The rate of cellular respiration(O2. μmol/L min-1 mg-1) was slightly higher in the corpus than the antrum(0.18 ± 0.05 vs 0.15 ± 0.04, P = 0.019). The value of GSH was about the same in both tissues(310 ± 135 vs 322 ± 155, P = 0.692).CONCLUSION: The corpus mucosa was metabolically more active than the antrum tissue. The data in this study will help in understanding the pathophysiology of gastric mucosa.

Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells

AIM:To determine the cytological and molecular effects of peroxisome proliferation-activated receptor(PPAR)-γ and PPAR-γ agonists on stomach cancer cells.METHODS:To determine the proliferation-suppressive effects of troglitazone and ciglitazone,SNU-216 and SNU-668 stomach cancer cells were plated in media containing 40 μmol/L troglitazone and ciglitazone at a density of 1 × 104 cells/well.After 3,5 and 7 d,the cells were counted with a hemocytometer.To assess the appearance of PPAR-γ,a reverse-transcription polymerase chain reaction analysis was performed.On day 7,Western blotting was used to determine the effects of troglitazone and ciglitazone on the expression of p21 and phosphorylated-ERK(pERK) genes.Flow cytometry analysis was used to determine which portion of the cell cycle was delayed when troglitazone was used to suppress cell proliferation.In order to clarify the mechanism underlying the activity of troglitazone,microarray analysis was conducted.RESULTS:PPAR-γ was manifested in both SNU-216 and SNU-668 cells.Ciglitazone and troglitazone suppressed cell growth,and troglitazone was a stronger suppressor of stomach cancer cells than ciglitazone,an inducer of cell cycle arrest in the G1 phase.SNU-668 cells were also determined to be more sensitive to ciglitazone and troglitazone than SNU-216 cells.When troglitazone and ciglitazone were administered to stomach cancer cells,levels of p21 expression were increased,but ERK phosphorylation levels were reduced.When GW9662,an antagonist of PPAR-γ,was applied in conjunction with ciglitazone and troglitazone,the cell growth suppression effect was unaffected.The gene transcription program revealed a variety of alterations as the consequence of troglitazone treatment,and multiple troglitazone-associated pathways were detected.The genes whose expression was increased by troglitazone treatment were associated with cell development,differentiation,signal transmission between cells,and cell adhesion,and were also associated with reductions in cell proliferation,the cell cycle,nuclear metabolism,and phosphorylation.CONCLUSION:Troglitazone and ciglitazone suppress the proliferation of stomach cancer cells via a PPAR-γ-independent pathway.