Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact

Abstract The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

Histomorphological spectrum of gastrointestinal stromal tumors: an institutional experience

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the abdominal area. They can involve any portion of the gastrointestinal (GI) tract, omentum, mesentery, retroperitoneum, and other sites. They form 1-2% of the histologic types of gastrointestinal tract tumors. Aims and objectives were to analyze and correlate morphological, clinical and histomorphology features of gastrointestinal tumors presenting at different sites. Methods: This was a retrospective observational study for six years. Medical records of the histopathologically diagnosed GIST cases were reviewed for patient demographics and clinical presentation, and tumor findings were noted. Results: Of the 28 patients, ages ranged from 28 to 80 years. Symptoms ranged from abdominal pain, epigastric discomfort, mass, upper/lower gastrointestinal bleeding, rectal bleeding, anemia, weight loss, and small bowel obstruction. Sites involved were the small bowel, stomach, mesentery, rectum, duodenum, greater omentum, and retroperitoneum. Of 28 cases of GIST, 25 cases showed both c-KIT and DOG-1 positivity, 1 case showed only c-KIT positivity, 1 case showed only DOG-1 positivity, and 1 case was both c-KIT and DOG-1 negative. Conclusions: GISTS are unpredictable mesenchymal tumors. Common sites are the stomach and small gut. Mesenteric and omental GIST are rare. Spindle cell morphology was more commonly present.

Venetoclax combined with avapritinib for treatment of refractory/relapsed acute myeloid leukemia with KIT gene mutation: report of 2 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the therapeutic efficacy of venetoclax combined with avapritinib in treatment of refractory/relapsed acute myeloid leukemia (AML) with KIT gene mutation.Methods:The clinical data of 2 AML patients with KIT gene mutation who received venetoclax combined with avapritinib admitted to Canglang Hospital of Suzhou in October 2022 and November 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:Both patients with high-risk relapsed/refractory AML and KIT gene mutation were females; the one was 53 years and the other was 17 years. Case 1 was diagnosed with AML-M 2, and genetic testing revealed positive mutations in ASXL1, KIT, and RUNX1. The patient relapsed after transplantation and then was treated with venetoclax combined with avapritinib achieving morphologic leukemia-free status (MLFS). Case 2 was diagnosed with AML, and RUNX1-RUNX1T1 (AML1-ETO) fusion gene and KIT and DX15 gene mutations were detected. The patient was treated with venetoclax combined with avapritinib regimen after relapse, and the treatment regimen significantly reduced the tumor load. Complete remission was achieved after bridging to allogeneic hematopoietic stem cell transplantation. Conclusions:AML with KIT gene mutation is heterogeneous and some patients are difficult to treat with very poor prognosis. Bridging (secondary) hematopoietic stem cell transplantation can be the better treatment choice for relapsed patients achieving MLFS or complete remission after venetoclax combined with avapritinib treatment regimen.

Interferon, interleukin 2 combined with lenalidomide for elderly acute myeloid leukemia with minimal residual disease-positive: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the effect of interferon, interleukin 2 (IL-2) combined with lenalidomide in the treatment of acute myeloid leukemia (AML) with minimal residual disease (MRD)-positive.Methods:The clinical data of 1 elderly AML patient with persistent MRD positive treated with interferon, IL-2 combined with lenalidomide in the Affiliated Cancer Hospital of Zhengzhou University in December 2019 were retrospectively analyzed, and the relevant literature was reviewed.Results:The 72-year-old male patient was diagnosed as AML-M 2b with c-kit mutation, the low-risk group according to laboratory related examinations, flow cytometry, genetic testing. The patient did not achieve remission after 1 cycle of standard VA (venetoclax + azacitidine) regimen, and achieved complete remission (CR) after another 1 cycle of IA (idarubicin + cytarabine) induction regimen, followed by consolidation therapy with medium dosage cytarabine and D-CAG (decitabine + cytarabine + aclarubicin + granulocyte colony-stimulating factor) regimen, during which the AML1-ETO fusion gene progressively increased. After programmed death receptor 1 (PD-1) inhibitor-based combination therapy, the AML1-ETO fusion gene remained negative for more than 1 month, and then increased again; subsequently, the patient was treated with the ITI (interferon, thalidomide, and interleukin-2) regimen, and the AML1-ETO fusion gene remained negative for more than 7 months; thalidomide was changed to lenalidomide after the increase again, and AML1-ETO fusion gene remained negative again for 2 years until May 2023. Conclusions:Interferon, IL-2 combined with lenalidomide have a significant therapeutic efficacy in reversing MRD positive and have mild adverse reactions, which can be used as a new option for refractory AML.

Effects of emodin on proliferation, adhesion, migration and c-kit mRNA and protein expression of human epidermal melanocytes / 中华医学美学美容杂志

Objective:To investigate the effects of emodin on proliferation, adhesion, migration, c-kit mRNA and protein expression of human epidermal melanocytes.Methods:Human epidermal melanocytes cultured in vitro were treated with different concentrations of emodin, a blank control group (containing medium + human epidermal melanocytes) and an experimental group (containing medium + human epidermal melanocytes + different concentrations of emodin) were set up. Cell proliferation was measured by CCK-8 method, cell adhesion was measured by microplate assay, cell migration was measured by Transwell membrane assay, and c-kit mRNA expression was measured by reverse transcription-polymerase polymerase chain reaction; Western blot was used to detect the expression of c-kit protein.Results:Compared with the blank control group, emodin decreased the proliferation, adhesion and migration of human epidermal melanocytes, the difference was statistically significant ( F=391.48, P<0.0001; F=10.93, P=0.003; F=7.75, P=0.009). Compared with the blank control group, emodin in the experimental group had a bidirectional effect on the expression of c-kit mRNA and protein. High concentration of emodin inhibited the expression of c-kit mRNA and protein, and the expression of c-kit mRNA and protein was significantly increased by Emodin ( F=11.491, P=0.003; F=2155.11, P<0.001). Conclusions:Emodin inhibits the proliferation, adhesion and migration of human epidermal melanocytes, high concentration of emodin inhibits the expression of c-kit mRNA and protein, and low concentration of emodin promotes the expression of c-kit mRNA and protein, and the results provide a basis for the clinical application of emodin in pigmented dermatosis.

Clinicopathological analysis of primary nasopharyngeal melanomas in elderly patients / 中华老年医学杂志

Objective:To investigate the clinicopathologic features and molecular genetics characteristics of sinonasal tract mucosal malignant melanomas(STMMMs)in elderly patients.Methods:The clinicopathological features, immunohistochemical features and BRAF, C-KIT, NRAS mutations of STMMM in ten elderly patients were retrospectively analyzed.Results:Among the 10 patients, 5 were female and 5 were male.The patients were aged 65-81 years, with an average age of(72.5 ± 8.5)years.The lesions in 7 cases were located in the nasal cavity and paranasal sinuses, and in the other 3 cases were located in the nasopharynx.The morphologies of tumor cells under microscope was complex and diverse, showing plasma cell-like, rhabdomyoblast-like, small cell-like, epithelial-like, and spindle cell-like morphologies.Immunohistochemically, HMB-45 and S-100 were generally positive in 10 cases, and the positive rate of Melan A was 70.0%.The genes detection data showed no mutations in BRAF or NRAS genes in all the 10 cases, while C-KIT exon 11 c. 1666_1667insA mutation was found in one case, and the remaining 9 cases were wild-type for C-KIT.All the 10 cases were followed up for 4~50 months.Three cases survived so far.Conclusions:STMMM in elderly patients are rare and easy to be misdiagnosed.Immunohistochemistry and genetic testing provide guidance for accurate diagnosis and targeted therapy.

Effect of C-KIT gene mutation on the prognosis of acute myeloid leukemia associated with core-binding factor in children: a Meta-analysis / 白血病·淋巴瘤

Objective:To systematically evaluate the relationship between C-KIT gene mutation and the prognosis of childhood core-binding factor-related acute myeloid leukemia (CBF-AML).Methods:The PubMed database was searched with "KIT" "Acute Myeloid Leukemia" and "Children"; the Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM), VIP database and Wanfang database were also searched with "KIT" "Acute Myeloid Leukemia" and "Children", and the search time was from the establishment of the database to October 1, 2020. After strict screening, the literature was included in the analysis; according to the presence or absence of genetic changes, the included cases was divided into C-KIT mutation group and wild group, and the complete remission (CR) rate, event-free survival (EFS) rate, and overall survival (OS) rate of the two groups were analyzed.Results:Six articles were collected, including 4 articles in English and 2 articles in Chinese, with a total of 667 patients. There was a statistically significant difference in the EFS rate between the C-KIT mutation group and wild group in children with CBF-AML ( HR = 2.40, 95% CI 1.47-3.89, P = 0.001); there was no significant difference in the CR rate and OS rate ( OR = 0.93, 95% CI 0.48-1.80, P = 0.830; HR = 1.92, 95% CI 0.96-3.83, P = 0.065) between the two groups. Conclusions:C-KIT gene mutation may be a risk factor for poor prognosis in children with CBF-AML.

Electroacupuncture can alter bladder c-Kit expression in rats with urination disorders after a spinal cord injury / 中华物理医学与康复杂志

Objective:To observe any effects of electroacupuncture (EA) on urodynamics and bladder c-Kit expression in rats with urination disorders after spinal cord injury (SCI).Methods:Complete spinal cord injury models were created in female Sprague-Dawley rats by transecting the spine at the thoracic or sacral level. On day 22 after the injury, the rats with successful modeling were randomized into a thoracic spinal cord injury (TSCI) group, a TSCI+ EA group, a sacral spinal cord injury (SSCI) group and an SSCI+ EA group, each of 10. Both EA groups were given 15 minutes of EA at the Guanyuan (CV4) and Sanyinjiao (SP6) points daily for 14 days. After the intervention, urination function was evaluated using bladder volume, compliance and residual urine volume. Hematoxylin and eosin staining was used to observe any morphological changes in bladder tissues. The gene and protein expression of c-Kit in bladder tissues were detected using real-time quantitative polymerase chain reactions and western blotting.Results:Compared with the sham group, the bladder volume and compliance of the TSCI group decreased significantly, while the average residual urine volume increased significantly. In the SSCI group the average residual urine volume, bladder volume and compliance all increased significantly. The modeling altered the morphology of the bladder in all of the SCI rats. The average expression of c-Kit mRNA and protein increased significantly in TSCI group, but both decreased significantly in the SSCI group. EA improved the histological structure of the SCI rats′ bladders.Conclusions:EA can bi-directionally regulate bladder c-Kit expression, and that is a possible mechanism for improving urinary incontinence and urine retention after an SCI.

Prevalence of CKIT and PDGFRA mutation in gastrointestinal stromal tumors among Filipinos

Background@#Gastrointestinal stromal tumors (GIST) is defined as specific, typically kit (CD117)-positive and CKIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation-driven mesenchymal tumors that can occur anywhere in the GI tract. GIST diagnosis relies heavily on immunohistomorphology. However, with the advent of molecular testing, the classification, diagnosis and targeted-therapy for gastrointestinal mesenchymal tumors have been greatly improved. In the Philippines, molecular testing is not yet readily available as in other countries. The local molecular profile of gastrointestinal stromal tumors is a point of investigation as treatment may be more tailored to the patients’ needs.@*Objective@#This study aims to determine the prevalence of CKIT and PDGFRA mutations among formalin-fixed and paraffin embedded gastrointestinal stromal tumors and other gastrointestinal mesenchymal tumors in St. Luke’s Medical Center – Quezon City.@*Methods@#A retrospective cross-sectional study of formalin fixed and paraffin embedded tumor samples diagnosed as Gastrointestinal Stromal Tumor from January 1, 2009 to December 31, 2017 will be analyzed for KIT and PDGFRA mutations. @*Result@#The epidemiology of GIST remains constant in that mean age group is the 5th to 6th decade, with equal gender distribution, and stomach followed by small bowel are the most common sites. Mutational analysis of the GISTs showed predominantly KIT Exon 11 (47.83%) followed by CKIT Exon 9 (13.04%) and PDGFRA Exon 18 (10.87%). For KIT Exon 11, deletion is the most common mutations followed by point mutations. No mutation is detected in 47.83% of GISTs. @*Conclusion@#Mutational analysis for CKIT-PDGFRA is warranted among GIST patients, as it may significantly influence treatment protocol in our patients.

Rare and unknown canine systemic mastocytosis: clinical and laboratory features of an aberrant c-Kit mutation neoplasia / A rara e desconhecida mastocitose sistêmica canina: características clínicas e laboratoriais de uma neoplasia aberrante na mutação c-Kit

Systemic mastocytosis (SM) pathology is extremely rare in canine practice, with insufficient reported data. The knowledge of the clinical behavior of this pathology is scarce. In human medicine, SM has been widely investigated, being defined as a rare hematopoietic disorder by the World Health Organization (2016), within the type of myeloproliferative neoplasms. Herein, we describe a systemic mastocytosis case in a Portuguese Serra-da-Estrela dog, where a cutaneous grade III/high-grade MCT was also diagnosed. The clinical decline of the animal and owner's insistence throughout anamnesis that the dog was markedly different after the cytologic exam performed in another clinic, along with both severe eosinophilia and hepatomegaly, led to the clinical suspicion of SM. The animal passed away 7 days later. Post-morteminvestigation confirmed SM pathology, and a deletion of 15 base pairs change on c-Kit gene exon 11 was identified. Contemplating the low number of cases described in the literature, this publication aims to disclose clinical and laboratory features of rare and poorly described canine SM, taking into consideration human outcomes described in the literature.(AU)

A patologia da mastocitose sistêmica (SM) é extremamente rara na prática clínica canina, com escassos casos descritos na literatura científica. O conhecimento do comportamento clínico desta patologia é mínimo. Na medicina humana, a SM tem sido amplamente investigada, sendo definida como uma doença hematopoiética rara pela Organização Mundial da Saúde (2016), dentro do tipo de neoplasias mieloproliferativas. Descrevemos aqui um caso de mastocitose sistêmica num cão Serra-da-Estrela português, diagnosticado também com um mastocitoma cutâneo grau III / alto grau. O declínio clínico do animal e a insistência do proprietário durante a anamnese de que o cão estava marcadamente diferente após o exame citológico realizado em outra clínica, juntamente com eosinofilia e hepatomegalia graves, levantaram a suspeita clínica de SM. O animal faleceu 7 dias depois. A investigação post-mortem confirmou a patologia SM, e o estudo molecular revelou uma deleção de 15 pares de bases no exon 11 do gene c-Kit. Contemplando o baixo número de casos descritos na literatura, o objetivo desta publicação é divulgar características clínicas e laboratoriais de SM canina, levando em consideração informações clínicas descritas em humanos.(AU)

Cardiac differentiation of bone-marrow-resident c-kit+ stem cells by L-carnitine increases through secretion of VEGF, IL6, IGF-1, and TGF-β as clinical agents in cardiac regeneration

The idea of regenerating lost myocardium via cell-based therapies remains as highly considerable. C-kit? stem/progenitor cells are represented to be suitable candidates for cardiac regeneration compared to other stem cells.A multitude of cytokines from these cells are known to give such multifunctional properties; however, theassociated mechanisms of these factors are yet to be totally understood. The aim of the present study was toinvestigate the in vitro effect of L-carnitine (LC) on cardiac differentiation of c-kit? cells using a cytokinessecretion assay. For this purpose, bone-marrow-resident-c-kit? cells were enriched by MACS method, andwere differentiated to cardiac cells using cardiomyocyte differentiation medium in the absence (control group)and presence of LC (experimental group). Also, characterization of enriched c-kit? cells was performed usingflow cytometry and immunocytochemistry. In the following, the cells were subjected to real-time PCR andWestern blotting assay for gene and protein assessment, respectively. Afterward, culture medium was collectedfrom both control (-LC) and experimental groups (? LC) for cytokine measurement. It was found that 0.2mM LC significantly increased the mRNA and protein expression of cardiac markers of Ang-1, Ang-2, C-TnI,VEGF, vWF, and SMA in c-kit?-cardiomyogenic-differentiated cells. Also, the significant presence of IL-6,IGF-1, TGF-b, and VEGF were obvious in the cultured media from the experimental group compared with thecontrol group. It can be concluded that the mentioned in vitro effects of LC on cardiac differentiation of c-kit?cells could have resulted from the secreted cytokines IL-6, IGF-1, TGF-b, and VEGF.

Aging-associated Morphological Changes of Myenteric Plexus in Colon / 胃肠病学

Background: The high incidence of gastrointestinal motility disorders in the elderly may be related to the aging of myenteric plexus (MP). Aims: To investigate the aging-associated morphological changes of colonic MP in rats. Methods: Fourteen male Sprague-Dawley (SD) rats were divided into 6-, 18- and 25-month-old groups. HE staining was used to evaluate the morphological changes of MP and its neurons; immunohistochemistry was used to detect the amount of protein gene product 9.5 (PGP9.5), acetylcholine esterase (AChE), neuronal nitric oxide synthase (nNOS) and c-kit positive cells. Results: There were significant differences in area of ganglions (H=8.14, P=0.02), density of ganglions (F=4.12, P=0.046), area of neuronal cell bodies (F=9.60, P=0.00), area of neuronal cell nucleus (H=9.29, P=0.01), number of neurons per ganglion (F=7.60, P=0.01) and numbers of PGP9.5 positive neurons (F=26.11, P=0.00), AChE positive neurons (H=11.83, P=0.00), nNOS positive neurons (F=20.77, P=0.00) and c-kit positive cells (F=14.25, P=0.00) among the three groups. Compared with 6-month-old group, area of ganglions, area of cell bodies, area of cell nucleus in 18-, 25-months-old groups were significantly increased (P<0.05), while density of ganglions, number of neurons per ganglion and numbers of PGP9.5 positive neurons, AChE positive neurons, nNOS positive neurons and c-kit positive cells were significantly decreased (P<0.05). Conclusions: There are obvious signs of MP ageing (or degeneration) and compensation associated with aging, which may be closely related with the decline in gastrointestinal motility and high incidence of gastrointestinal motility disorders in the elderly.

Homoharringtonine synergy with oridonin in treatment of t(8; 21) acute myeloid leukemia / 医学前沿

Collaboration of c-KIT mutations with AML1-ETO (AE) has been demonstrated to induce t(8; 21) acute myeloid leukemia (AML). Targeted therapies designed to eliminate AE and c-KIT oncoproteins may facilitate effective treatment of t(8; 21) AML. Homoharringtonine (HHT) features activity against tumor cells harboring c-KIT mutations, whereas oridonin can induce t(8; 21) AML cell apoptosis and AE cleavage. Therefore, studies should explore the efficacy of combination therapy with oridonin and HHT in t(8; 21) AML. In this study, we investigated the synergistic effects and mechanism of oridonin combined with HHT in t(8; 21) AML cell line and mouse model. The two drugs synergistically inhibited cell viability and induced significant mitochondrial membrane potential loss and apoptosis. Oridonin and HHT induced significant downregulation of c-KIT and its downstream signaling pathways and promoted AE cleavage. HHT increased intracellular oridonin concentration by modulating the expressions of MRP1 and MDR1, thus enhancing the effects of oridonin. The combination of oridonin and HHT prolonged t(8; 21) leukemia mouse survival. In conclusion, oridonin and HHTexert synergistic effects against t(8; 21) leukemia in vivo and in vitro, thereby indicating that their combination may be an effective therapy for t(8; 21) leukemia.

A comparison between cDNA and DNA samples for the detection of c-KIT exon 17 mutation in acute myeloid leukemia patients / 中华检验医学杂志

Objective To investigate the impact of sample typeon the detection of c-KIT exon 17 mutation in acute myeloid leukemia (AML) patients. Methods A retrospective study was conducted on 51 bone marrow samples collected from 37 AML patients [17 maleand 20 female, with a median age of 33 (range from 1 to 82)] at diagnosis or after treatment from June 2016 to August 2018. Of the 37 cases of AML, 24 were t(8; 21) AML, 11 were inv(16)/t(16;16) AML and 2 were non-CBF-AML. RNA and DNA were simultaneously extracted from every sample. PCR followed by Sanger sequencing were used to screen c-KIT exon 17 mutation, and the comparisons were made between paired cDNA and DNAsamples. Results (1) Of the 51 paired samples, 14 pairs were simultaneously detected positive for c-KITmutation in both of cDNA and DNA samples, but 17 pairs were detected negative in both, and the remaining 20 pairswere only detected positive for the mutation in cDNA but not in DNA, with an inconsistency rate of 39.2％. The positive rate of detecting c-KITmutation was significantly higher in cDNA than in DNA samples (66.7％vs 27.5％,P=0.000073). (2)Inconsistent mutation results between paired cDNA and DNA samples occurred in t(8;21)AML, inv(16)AML and non-CBF-AML patients with the inconsistency rate of 36.4％(12/33), 27.2％(3/11) and 71.4％ (5/7), respectively. (3)The inconsistency rate was significantly higher in samples collected after treatment compared with those collected at diagnosis (72.7％vs 13.8％, P=0.00003). (4) All 5 serially monitored patients with c-KITmutation had inconsistency in mutation detection between cDNA and DNA samples during follow up. Conclusion cDNA improves the detection of c-KIT exon 17 mutation in AML patients compared with DNA, which is especially common after treatment.

Phenotypic changes of interstitial cells of Cajal after intestinal obstruction in rat model

The objective was to study the effect of mechanical intestinal obstruction in rats on the phenotype of interstitial cells of Cajal (ICC). Healthy Wistar rats were randomly divided into sham-operation group (C), one day obstruction group (M1), two days obstruction group (M2), and three days obstruction group (M3), with 10 rats in each group. The expression of SCF mRNA and c-Kit protein in intestinal tissue was investigated by RT-PCR and immunohistochemistry. Compared with the sham-operation group, the relative expression of SCF mRNA and the expression of c-Kit protein in intestinal tissue were significantly decreased in both obstruction groups. Levels decreased gradually with the prolongation of obstruction time, and significantly decreased on the 3rd day after obstruction (P<0.05). Immunohistochemical staining of the small intestine showed that the number of ICC in the sham-operation group was the highest, and they were gradually decreased with the extension of obstruction time in the M1 to M3 groups. There was a significant difference between groups (P<0.05). Intestinal obstruction caused a decrease in the concentrations of SCF mRNA and c-Kit protein in ICC. With the prolongation of intestinal obstruction, the number of ICCs gradually decreased.

No detection of c-kit gene mutations in exons 9, 11, 13 and 17 and low CD117 expression in plaque-stage mycosis fungoides

Abstract: The growth factor receptor c-kit (CD117) is expressed in immature T-cells and in some advanced forms of mycosis fungoides. c-kit gene mutation results in unrestricted neoplastic proliferation. We aimed to detect by PCR the most frequent exon mutations in seventeen plaque-stage MF patients, in their perilesional skin and in healthy skin donors. We secondarily evaluated CD117 expression by immunohistochemistry in plaque-stage and tumor-stage MF. We detected no mutation in c-kit gene and low CD117 expression was confirmed on atypical cells in one patient. Complete c-kit exon and intron sequences should be assessed and more sensitive sequencing method could be also applied.

Progress in the study of stem cell factor receptor c-kit in skin melanin metabolism / 中华整形外科杂志

Skin melanin metabolism is a complex and fine regulation process, which is controlled by multiple genes, many enzymes and proteins. With the in-depth study of the factors affecting the skin melanin metabolism, scientists have found that the signaling pathway initiated by the combination of stem cell factor receptor c-kit and its ligand stem cell factor plays an important role in the metabolism of skin melanin.The paper summarizes the recent research progress on the role of c-kit receptor in the skin melanin metabolism, including the molecular mechanism and the clinical application.

Relationship between c-kit mRNA expression and prognosis in patients with rectal carcinoma / 中华肿瘤杂志

Objective@#To investigate the correlation between c-kit mRNA expression and prognosis in patients with rectal carcinoma.@*Methods@#The expression of c-kit mRNA in rectal carcinoma tissues(n=66) was detected by multiplex branched-DNA liquid chip method. According to the expression level, the patients were classified into the c-kit mRNA high expression group and the low group. We analyzed the relationship between the c-kit mRNA expression and the clinicopathological characteristics of patients, as well as the factors affecting patients′prognosis.@*Results@#Of the 66 rectal carcinoma patients, 18(27.3%)cases were c-kit mRNA high expression. No significant correlation was found between the c-kit mRNA expression and gender, age, preoperative carcinoembryonic antigen, preoperative hemoglobin, distance to verge, lymph node metastasis, tumor thrombus, T stage, TNM stage and tumor differentiation (P>0.05). In follow-up, 34 patients died, 32 patients and 36 patients were recurrence or metastasis. The 1-, 3-, 5-year overall survival(OS) of c-kit mRNA high expression group were 100.0%, 77.8%, 77.8%, respectively, while those of the low one were 93.8%, 56.3%, 45.8%, respectively. The difference was statistically significant(P=0.025). Lymph node metastasis, T stage and TNM stage were also significant associated with OS(P<0.05). The 1-, 3-, 5-year disease free rate (DFS)of the c-kit mRNA high expression group were 100.0%, 77.8% and 77.8%, respectively, while those of the low one were 77.1%、43.8% and 41.7%, respectively, and the difference between the two groups was significant (P=0.044). As a reslut, c-kit mRNA expression (P=0.038) and TNM stage (P=0.039) were the independent prognostic factors affecting the OS in rectal cancer patients.@*Conclusions@#Low expression of c-kit was associated with poor prognosis of rectal carcinoma. And the mechanism underlying this phenomenon deserves further exploration.

Inosine protects bladder structure and function in rats with diabetic cystopathy / 医学研究生学报

Objective At present,there is still a lack of effective means for the treatment of diabetic cystopathy,and to find natural antioxidants for this purpose has become a hot spot in research. This study is to investigate the protective effect of inosine on the bladder of diabetic rats and its antioxidative stress mechanisms. Methods A total of 60 adult male Sprague-Dawley rats were ran-domly divided into three groups of equal number:normal control,diabetes mellitus(DM) model control,and inosine intervention. The DM model was made by intraperitoneal injection of streptozotocin at 60 mg/kg. The DM model controls were injected with saline while the model rats in the intervention group with inosine, all at 75 mg/kg, ip,bid. After 4 and 8 weeks of treatment, the bladder tissues were collected from the rats for examination of the structural changes by HE staining,determination of the expressions of c-kit and nerve growth factor (NGF) by immunofluorescence assay, and observation of the ultrastructure of the bladder tissue under the electron microscope,de-tection of the cell apoptosis by TUNEL,and measurement of the con-tents of malondialdehyde (MDA),superoxide dismutase (SOD),and glutathione (GSH). Results HE staining indicated signifi-cant mucosal hyperplasia, disordered arrangement, loose structure, fracture, expanded intervals and collagen fiber filling of muscle bundles,muscular atrophy,lymphocytes infiltration,vascular hyperplasia and congestion,and few muscle bundles,while electron mi-croscopy manifested disordered arrangement, interrupted connection, mitochondrial vacuolation in muscular and interstitial cells, shrinkage of nuclear membrane,disappearance of nucleoli,and irregular chromatin margination and condensation in the bladder tissues of the DM rat models. Immunofluorescence assay showed that the signals of c-kit and NGF were reduced in the DM models as compared with those in the normal controls. After 4 and 8 weeks of intervention,the cell apoptosis rate was significantly higher in the DM model control ([1.68±3.04]% and [10.51±0.90]%) and inosine-treated rats ([7.00±1.72]% and [7.24±1.66]%) than in the normal controls ([4.65±3.04]% and[5.48±2.00]%),but remarkably lower in the inosine-treated than in the DM model controls(P<0.01). The contents of SOD and GSH were increased(P<0.05) while that of MDA decreased markedly in the DM models(P<0.05),but the former decreased (P<0.05) while the latter increased significantly in the inosine intervention group as compared with the DM model control group (P<0.05). At 8 weeks,the contents of SOD and GSH were remarkably lower in the DM model than in the normal con-trols (P<0.01),while that of MDA markedly higher than in both the normal control and inosine intervention groups (P<0.01). The wet weight of the bladder was significantly increased in the DM model and inosine intervention groups in comparison with that of the nor-mal controls(P<0.01). Conclusion Oxidative stress plays an important role in the development and progression of diabetic cystopa-thy. Inosine can protect the bladder structure and function of the DM rat by reducing oxidative stress and injury to the bladder tissue.

Effect of PI3K/Akt/mTOR signal pathway-mediated N822K mutation on apoptosis induced by c-KIT inhibitor in AML cells / 中国免疫学杂志

Objective:To investigate the effect of c-KIT N822K mutation on the apoptosis of AML cells induced by c-KIT inhibitor and to explore the underlying molecular mechanisms.Methods: Kasumi-1 cells that carry the c-KIT N822K mutation were used as experimental group,and HL-60 and NB4 cells with non-c-KIT N822K mutation were used as control group.These AML cells were treated with 0,0.04,0.16 and 0.64 μmol/L c-KIT inhibitor sunitinib for 24 h,respectively.Apoptosis-related proteins and PI3K/Akt/mTOR pathway proteins were detected by Western blot,compared the changes of cell-related signal pathway proteins in each group.Results: With the increase of sunitinib concentration,the expression of apoptosis-related proteins Bax,CytoC,Caspase-9, Actived-Caspase-3 and PARP in HL-60 and NB4 cells were increased (P<0.05),and the expression of anti-apoptotic protein Bcl-2 was down-regulated (P<0.01).However,the trend of this change was obviously weakened in Kasumi-1 cells with N822K mutation.In Kasumi-1 cells,the phosphorylation levels of PI3K/Akt/mTOR pathway proteins such as PI3K,Akt,4EBP1 and mTOR were down-regulated in a dose-dependent manner(P<0.05),but not in HL-60 cells and NB4 cells.Conclusion:The constitutive activation of c-KIT induced by N822K mutation may affect the apoptosis induction of c-KIT inhibitor sunitinib to Kasumi-1 cells,which may be related to the inhibition of PI3K/Akt/mTOR pathway.