BACKGROUND Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions,including colorectal adenoma.Screening colonoscopy frequently reveals chicken skin mucosa(CSM;white or yellow-white speckled muc...BACKGROUND Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions,including colorectal adenoma.Screening colonoscopy frequently reveals chicken skin mucosa(CSM;white or yellow-white speckled mucosa)surrounding colo-rectal polyps,caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors.CSM-positive colorectal polyps are associated with various diseases;however,their prognosis varies greatly.Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps.Improved imaging is required to diagnose and treat CSM-positive colorectal polyps.METHODS This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy.All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system.Based on the pathological results,patients were classified as non-neoplastic polyps(five juvenile polyps),neoplastic polyps,non-invasive high-grade neoplasia(NHGN),or submucosal invasive carcinoma(SM stage cancer).We analyzed and compared the clinical features,suspected risk factors for malignant transformation of neoplastic polyps,and early infiltration of sub-mucosal carcinoma.RESULTS The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps.Most NHGN polyps had a deeper red mucosal color.On logistic regression analyses,diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps.Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM;type 2 CSM was more common in neoplastic polyps.Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer.Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal cancer disappeared within 12 months.No tumor recurrence was found during either partial or complete endoscopic resection of the CSM.CONCLUSION CSM-positive colorectal polyps>1 cm in diameter or with deeper red mucosa may be related to NHGN.Resection of CSM surrounding colorectal adenomas did not affect tumor recurrence.展开更多
BACKGROUND Bronchiolar adenoma(BA)and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer.Diagnosis is difficu...BACKGROUND Bronchiolar adenoma(BA)and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer.Diagnosis is difficult because of the limited knowledge of these tumors and their morphological similarities to malignant tumors,including invasive mucinous adenocarcinoma,especially based on the histopathology of intraoperative frozen sections.These tumors are now considered to be benign neoplasms,with malignant transformation reported in only a few cases.CASE SUMMARY A 57-year-old woman presented with a 17.0 mm×7.0 mm nodule in the lower lobe of the left lung.Hematoxylin-eosin staining and immunohistochemistry of a surgical specimen were performed.The tumor consisted of a BA area and a mucinous adenocarcinoma(MA)area.In the BA area,the tumor had a bilayered structure of luminal cells and basal cells.The basal cells were positive for CK5/6 and p40,but the MA area was negative for these biomarkers.The Ki-67 proliferation index was low(1%-2%).The patient was diagnosed with BA accompanied by MA,and had a favorable outcome.CONCLUSION The present study indicated that BA may be carcinogenic,and suggests that clinicians should be aware of its potential for malignant transformation.展开更多
Objective:To investigate the effect of mir-3168 on the malignant transformation and cisplatin resistance of AGS and AGS/DDP gastric cancer cells,and to verify its target gene.Methods:The expression of mir-3168 in AGS ...Objective:To investigate the effect of mir-3168 on the malignant transformation and cisplatin resistance of AGS and AGS/DDP gastric cancer cells,and to verify its target gene.Methods:The expression of mir-3168 in AGS and AGS/DDP gastric cancer cells was detected by qPCR,and mir-3168 mimic,inhibitor and negative control were synthesized.They were transfected into AGS and AGS/DDP gastric cancer cells,respectively.The expression of mir-3168 and TP53 mRNA was detected by qPCR.Cell viability was detected by CCK8 under gradient cisplatin treatment and non treatment,apoptosis was detected by flow cytometry,cell invasion was detected by Transwell,and TP53 protein expression was detected by western blot,The database predicted the binding sites of mir-3168 and TP53.According to the binding sites,the double luciferase experiment was used to verify the binding of mir-3168 and TP53.Results:Compared with cisplatin sensitive gastric cancer cell AGS,mir-3168 was significantly overexpressed in cisplatin resistant gastric cancer cell AGS/DDP;mir-3168 mimic promotes cisplatin resistance,proliferation and invasion of AGS and AGS/DDP gastric cancer cells,and inhibits apoptosis of AGS and AGS/DDP gastric cancer cells;mir-3168 inhibitor inhibits cisplatin resistance,proliferation and invasion of AGS and AGS/DDP gastric cancer cells,and promotes apoptosis of AGS and AGS/DDP gastric cancer cells;mir-3168 mimic inhibits the expression of TP53 mRNA and protein,and mir-3168 inhibitor promotes the expression of TP53 mRNA and protein;Targetscan database predicted that there was a binding point between mir-3168 and TP53,and the double luciferase experiment suggested that mir-3168 was bound to TP53 through the predicted binding site.Conclusion:mir-3168 may promote the malignant transformation of AGS and AGS/DDP gastric cancer cells and cisplatin resistance by targeting TP53.展开更多
BACKGROUND Adenomyoepithelioma(AME)of the breast is a rare type of benign breast tumor.Many AMEs show benign behavior,but reports of the malignant type are rare.We present the case of a patient with AME with repeated ...BACKGROUND Adenomyoepithelioma(AME)of the breast is a rare type of benign breast tumor.Many AMEs show benign behavior,but reports of the malignant type are rare.We present the case of a patient with AME with repeated local recurrences and further malignant transformation.CASE SUMMARY A 53-year-old woman visited our hospital with a 16-mm palpable mass in the right breast.A core needle biopsy was performed.The pathological diagnosis was AME.Lumpectomy with a safety margin was performed without axillary lymph node dissection(ALND).Two years later,local recurrence developed,and the patient again underwent lumpectomy with a safety margin.The pathology showed malignant AME,and the margin was negative.Eight months later,local recurrence developed again in the same location,and a total mastectomy was performed without ALND.The pathological diagnosis was malignant AME.The patient was disease-free for three years posttreatment.CONCLUSION The treatment of AME requires caution,as it may exhibit repeated recurrences after local excision as well as malignant transformation.展开更多
Objective:Traditional Chinese medicine(TCM)and modern medicine have both been used in arresting malignant transformation of chronic atrophic gastritis(CAG)in China with good therapeutic effect.However,no studies have ...Objective:Traditional Chinese medicine(TCM)and modern medicine have both been used in arresting malignant transformation of chronic atrophic gastritis(CAG)in China with good therapeutic effect.However,no studies have been undertaken to assess the risk of malignant transformation in CAG patients using both modern medicine and TCM features.Our study aimed to develop risk assessment models for malignant transformation of CAG combining indicators of both TCM and modern medicine.These models will facilitate early warning and control of malignant transformation of CAG from the perspective of evidence-based integrative medicine.Methods:In the proposed registry study,a total of 1000 eligible CAG patients will be recruited from four hospitals in China.A 10-year follow-up study will be conducted both on-site and off-site to track the events of malignant transformation.Frequency analysis and chi-squared tests will be used to perform the comparative analysis on the prevalence of malignant transformation events and indicators in TCM or modern medicine in different groups.A multivariate Cox proportional hazard model will be used to perform correlation analyses of malignant transformation events and factors of TCM or modern medicine.Conclusion:The proposed study has been designed with a large sample size and long follow-up period,in which wide-ranging modern medicine and TCM indicators can be gathered over the whole process of malignant transformation of CAG.Based on this study,risk assessment models for malignant transformation ofCAGmaybe constructed fromthe perspective of integrative medicine.This may provide clinicians and patients with an optimized early warning system as well as prevention strategies for malignant transformation of CAG.展开更多
BACKGROUND O_(6)-methylguanine-DNA methyltransferase(MGMT)is a suicide enzyme that repairs the mispairing base O_(6)-methyl-guanine induced by environmental and experimental carcinogens.It can transfer the alkyl group...BACKGROUND O_(6)-methylguanine-DNA methyltransferase(MGMT)is a suicide enzyme that repairs the mispairing base O_(6)-methyl-guanine induced by environmental and experimental carcinogens.It can transfer the alkyl group to a cysteine residue in its active site and became inactive.The chemical carcinogen N-nitroso compounds(NOCs)can directly bind to the DNA and induce the O_(6)-methylguanine adducts,which is an important cause of gene mutation and tumorigenesis.However,the underlying regulatory mechanism of MGMT involved in NOCs-induced tumorigenesis,especially in the initiation phase,remains largely unclear.AIM To investigate the molecular regulatory mechanism of MGMT in NOCs-induced gastric cell malignant transformation and tumorigenesis.METHODS We established a gastric epithelial cell malignant transformation model induced by N-methyl-N’-nitro-N-nitrosoguanidine(MNNG)or N-methyl-N-nitroso-urea(MNU)treatment.Cell proliferation,colony formation,soft agar,cell migration,and xenograft assays were used to verify the malignant phenotype.By using quantitative real-time polymerase chain reaction(qPCR)and Western blot analysis,we detected the MGMT expression in malignant transformed cells.We also confirmed the MGMT expression in early stage gastric tumor tissues by qPCR and immunohistochemistry.MGMT gene promoter DNA methylation level was analyzed by methylation-specific PCR and bisulfite sequencing PCR.The role of MGMT in cell malignant transformation was analyzed by colony formation and soft agar assays.RESULTS We observed a constant increase in MGMT mRNA and protein expression in gastric epithelial cell malignant transformation induced by MNNG or MNU treatment.Moreover,we found a reduction of MGMT gene promoter methylation level by methylation-specific PCR and bisulfite sequencing PCR in MNNG/MNU-treated cells.Inhibition of the MGMT expression by O_(6)-benzylguanine promoted the MNNG/MNU-induced malignant phenotypes.Overexpression of MGMT partially reversed the cell malignant transformation process induced by MNNG/MNU.Clinical gastric tissue analysis showed that MGMT was upregulated in the precancerous lesions and metaplasia tissues,but downregulated in the gastric cancer tissues.CONCLUSION Our finding indicated that MGMT upregulation is induced via its DNA promoter hypomethylation.The highly expressed MGMT prevents the NOCs-induced cell malignant transformation and tumorigenesis,which suggests a potential novel approach for chemical carcinogenesis intervention by regulating aberrant epigenetic mechanisms.展开更多
Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignan...Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of IDHmutant LGGs.Methods:We screened data for 108 patients with sAIDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from IDH-mutant LGGs to sAIDHmut/G4,and associated risk factors and outcomes.Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with IDH-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;P<0.0001)in patients with IDH-mutant gliomas.Conclusions:Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDHmutant gliomas.展开更多
BACKGROUND Mature teratoma is a common benign ovarian germ cell tumor,accounting for about 20%of ovarian tumors.The malignant transformation of this tumor is less than 2%.The most common type is squamous cell carcinom...BACKGROUND Mature teratoma is a common benign ovarian germ cell tumor,accounting for about 20%of ovarian tumors.The malignant transformation of this tumor is less than 2%.The most common type is squamous cell carcinoma,followed by adenocarcinoma.Malignant transformation of colonic mature teratoma is extremely rare.We here report a case of malignant transformation of primary mature teratoma of the colon.The type of malignant transformation was adenocarcinoma.CASE SUMMARY A 63-year-old woman was admitted to our hospital due to persistent pain in her right lower abdomen for 1 mo,and she had no nausea,vomiting,blood in the stools,or other symptoms.Preoperative colonoscopy showed uplift of the sigmoid colon mucosa and submucosa.The biopsy showed squamous epithelium.However,contrast-enhanced computed tomography of abdomen and pelvis showed a localized thickening of the sigmoid wall,suggesting colon cancer.Endoscopic ultrasonography(EUS)revealed that the structure of the intestinal wall at the base of the lesion was destroyed,and the boundary between the lesion and the surroundings was unclear.According to the findings of the EUS,the patient did not undergo endoscopic submucosal dissection,but underwent radical resection of the tumor.Histologically,squamous epithelium was seen on the mucosal surface of the colon wall,cartilage and glands were seen under the epithelium,and adenocarcinoma was seen on the muscular layer and serous surface.The final pathological diagnosis was malignant teratoma of the colon.We have followed up the patient for 2 mo since the operation,and the patient recovered well.CONCLUSION This case suggests the possibility of mature teratoma in the colon and recognition of malignant types,and it should not be considered as an exclusively ovarian tumor.展开更多
BACKGROUND Biliary adenofibromas(BAFs)are rare primary hepatic neoplasms,some of which can potentially undergo malignant transformation.Here,we describe a rare case of malignant transformation of BAF.CASE SUMMARY A 51...BACKGROUND Biliary adenofibromas(BAFs)are rare primary hepatic neoplasms,some of which can potentially undergo malignant transformation.Here,we describe a rare case of malignant transformation of BAF.CASE SUMMARY A 51-year-old female was referred to our hospital with epigastric pain.Computed tomography showed a solitary liver mass combined with the enlargement of multiple mediastinal and cervical lymph nodes,clinically mimicking a liver carcinoma with extensive lymph node metastasis.However,core needle biopsy suggested BAF with malignant transformation.Finally,the patient underwent curative resection of the neoplasm and was recurrence-free for 12 mo.CONCLUSION Our case serves as an example of a rare manifestation of BAF.Our report and the previously published experience,reinforce that curative resection should be considered the primary treatment for BAFs with malignant transformation,leading to a favorable prognosis.展开更多
BACKGROUND In rare cases,odontogenic keratocysts(ODs)transform into squamous cell carcinoma.Intervals between the first attendance of a patient and the diagnosis of OD with malignant transformation vary from weeks to ...BACKGROUND In rare cases,odontogenic keratocysts(ODs)transform into squamous cell carcinoma.Intervals between the first attendance of a patient and the diagnosis of OD with malignant transformation vary from weeks to years.In this article,we report a case of malignancy derived from OD with a five-day delay in diagnosis.CASE SUMMARY A 54-year-old woman was referred to Tongji Hospital in Wuhan,China with complaints of moderate pain,recurrent swelling,and pus discharge around her left maxillary lateral incisor for over 10 years.Physical examination revealed a fistula at the palatine-side mucoperiosteum of the left maxillary lateral incisor and enlarged lymph node in the left neck.Cone beam computed tomography revealed a cystic lesion with massive bone destruction from the left maxillary central incisor to the left secondary maxillary premolar and local bony destruction in the left first mandibular molar.The patient was clinically diagnosed with OD.Enucleation rather than marsupialization was performed given the risk factors of long history,recent aggravated pain,and massive bony destruction.Malignant transformation of OD was confirmed by pathologists 3 d after the operation.Radical surgery was performed,and lymph node metastasis was observed.The patient was subjected to postoperative radiotherapy and synchronous chemotherapy,and no local recurrence or distant metastasis was noted at one-year follow-up.CONCLUSION Our case suggests that clinicians should be aware of the malignant transformation of OD,especially when patients present with a long history,massive cyst,chronic inflammation,recent persistent infections,aggravated pain,numbness around the cystic lesion,and lymph node enlargement.展开更多
Malignant transformation of hamsterembryo cells was induced in vitro by rareearth iron mineral dusts(MP),naturalthorium(Th02) and MP plus Th02.Dusts of MP,MP plus Th02 or Th02 were added into themedium with the final ...Malignant transformation of hamsterembryo cells was induced in vitro by rareearth iron mineral dusts(MP),naturalthorium(Th02) and MP plus Th02.Dusts of MP,MP plus Th02 or Th02 were added into themedium with the final concentration of 17.0,展开更多
<strong>Background:</strong> Inverted Papilloma (IP) is the most common benign neoplasms arising from the mucosal lining of the of the Sino-Nasal tract with single or multifocal attachment sites. The high ...<strong>Background:</strong> Inverted Papilloma (IP) is the most common benign neoplasms arising from the mucosal lining of the of the Sino-Nasal tract with single or multifocal attachment sites. The high propensity to recur, local aggressive behavior and possibility of malignant transformation attract considerable interest. <strong>Objective:</strong> To assess the factors affecting Sino-nasal IP, malignant transformation rate, and post-operative recurrence rate. <strong>Methods:</strong> A retrospective study was carried out on all cases diagnosed as Sino-Nasal Papilloma between January 2010 and December 2020 at Salmaniya Medical Complex, Bahrain. Data gathered from medical records were analyzed using SPSS. A total of 49 Sino-Nasal Papilloma cases were recorded of which 37 were IP. Factors affecting Sino-Nasal IPs are presented. <strong>Results:</strong> Sino-Nasal IP was recorded in 37 cases, composed of 28 males and 9 females with first presentation average age of 45.86 years. These involved 20 cases in the left side, 14 in the right side and 3 were bilateral. Recurrence in males and females was found to be 35.7% and 33%, respectively, with an average of 12.6 months. The symptoms include nasal blockage (97.3%), epistaxis and postnasal drip (13.5% each), headache (8.1%) and hyposmia and rhinorrhea (5.4%, each). The main recurrence was at stage T2 (60.5%), while in smokers (26.7%) and non-smokers (50%). Malignant transformation occurred in one patient only (2.6%). <strong>Conclusion:</strong> IP is the most common type of SNP with male predominance. The recurrence rate is high with an average of a year and the malignant transformation occurred in 2.6 % of the cases.展开更多
Retrorectal cystic hamartomas are rare congenital lesions that can undergo malignant transformation, and adenocarcinoma is the most frequently described histological type. The authors describe a case of a 53-year-old ...Retrorectal cystic hamartomas are rare congenital lesions that can undergo malignant transformation, and adenocarcinoma is the most frequently described histological type. The authors describe a case of a 53-year-old female patient with a localized well-differentiated adenocarcinoma that developed in a retrorectal cystic hamartoma. The patient was submitted to surgery (a Kraske procedure), with an R1 resection, followed by adjuvant radio-chemotherapy. After 23 months of follow up, the patient remains free from disease recurrence. Given the rarity of this entity, this case allows us to reflect on the differential diagnosis, therapeutic approach and patients’ follow-up.展开更多
The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.Howev...The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.However,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood.In the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer elements.We found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)gene.Furthermore,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model.Subsequently,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency.Consistently,KLF4 expression also decreased in lung cancer tissues and cell lines.It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells.Collectively,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function.Therefore,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.展开更多
Inflammatory myofibroblastic tumor(IMT) is an uncommon benign neoplasm with locally aggressive behavior but malignant change is rare.We report an unusual case of pelvic-abdominal inflammatory myofibroblastic tumor wit...Inflammatory myofibroblastic tumor(IMT) is an uncommon benign neoplasm with locally aggressive behavior but malignant change is rare.We report an unusual case of pelvic-abdominal inflammatory myofibroblastic tumor with malignant transformation in a 14-year-old boy presenting with abdominal pain and 9 kg body weight loss in one month.Computed tomography revealed a huge pelvi-abdominal mass(30 cm),possibly originating from the pelvic extraperitoneal space,protruding into the abdomen leading to upward displacement of the bowel loops,downward displacement of the urinary bladder,massive central necrosis,a well-enhanced peripheral solid component with prominent peritumoral vascularity.Subsequent examination confirmed the computed tomographic findings.Histopathologic examination revealed proliferative epitheloid and spindle cells,inflammatory cell infiltration and high mitotic counts.Immunohistochemistry was strongly positive for anaplastic lymphoma kinase and revealed a high proliferative index(ki-67 = 40%).DNA sequencing and electronic microscopy further confirmed the primitive fibroblastic cell phenotype of the tumor and a final diagnosis of inflammatory myofibroblastic tumor with malignant transformation was established.Rapid tumor recurrence was noted 20 d after radical tumor resection.To our knowledge,this is the largest documented case of IMT in a pediatric patient and the first report of IMT with malignant transformation originating from the pelvic extraperitoneal space.展开更多
Objective: To investigate the mechanism of carcinogenesis, invasion and metastasis. Methods: The expressions of adhesive molecule and adhesive structure in v-k-ras transformed normal rat kidney cells (KNRK) were d...Objective: To investigate the mechanism of carcinogenesis, invasion and metastasis. Methods: The expressions of adhesive molecule and adhesive structure in v-k-ras transformed normal rat kidney cells (KNRK) were detected with a variety of molecular biological techniques, including cell culture, immunofluorescence labeling, electron microscopy, polyacrylamide gel electrophoresis, and protein blotting, and compared with normal rat kidney (NRK) cells. Results: The significantly shortened doubling time, remarkably active proliferation ability in soft agar, and invasive growth in the abdomen of nude rat, demonstrated the malignant biological behaviors of KNRK cells. In KNRK cells, the adhesive molecules, P-cadherin, α and β catenin, actin, and adhesive structures, the adhesive junction and gap junction, were all abnormally expressed. And cell aggregation was significantly decreased. The aggregation ability disappeared at 20℃, and became active with a suitable amount of calcium solution. Conclusion: Following the transfection of virus K-ras gene, normal cells were transformed into malignant cells. In early stage of cancer, the variation of adhesive ability may be one of the vital factors underlying tumorigenesis, invasion and metastasis.展开更多
Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and qual...Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management.As a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral leukoplakia.In this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside.Although no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.展开更多
Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseas...Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ)on inner mitochondrial membrane(IMM)regulates long chain fatty acidβ-oxidation,and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD.The sequences of its peptide chain and DNA nucleotides have been identified,and the catalytic activity of CPT-Ⅱ is affected on its gene mutations,deficiency,enzymatic thermal instability,circulating carnitine level and so on.Recently,the CPT-Ⅱ dysfunction has been discovered in models of liver lipid accumulation.Meanwhile,the malignant transformation of hepatocyte-related CD44^(+) stem T cell activation,high levels of tumor-related biomarkers(AFP,GPC3)and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.This review focuses on some of the progress of CPT-Ⅱ inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.展开更多
Objective To screen miRNA profiles of malignantly transformed human bronchial epithelial cells, 16HBE-T, induced by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide (anti-BPDE), and to analyze putative miR-10a target...Objective To screen miRNA profiles of malignantly transformed human bronchial epithelial cells, 16HBE-T, induced by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide (anti-BPDE), and to analyze putative miR-10a targets in 16HBE-T. Methods A novel microarray platform was employed to screen miRNA profiles of 16HBE-T cells transformed by anti-BPDE. Microarray data for miR-10a and miR-320 were validated using quantitative real time polymerase chain reaction (QRT-PCR). The expression of a putative target for miR-10a, HOXA1, was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and QRT-PCR. Results In comparison with the vehicle-treated cells (16HBE-N), 16HBE-T exhibited differential expression of 54 miRNAs, in which, 45 were over-expressed and 9 were down-regulated. The five most highly expressed miRNAs were miR-494, miR-320, miR-498, miR-129, and miR-106a. The lowest expressed miRNAs were miR-10a, miR-493-5p, and miR-363*. Three members of miR-17-92 cluster, miR-17-5p, miR-20a, and miR-92, showed significantly higher abundance in 16BHE-T as miR-21, miR-141, miR-27a, miR-27b, miR-16 and miRNAs of the let-7 family. The putative target for miR-10a, HOXA1 mRNA was up-regulated 3-9-fold in 16HBE-T, as compared with 16HBE-N. Conclusion The findings of the study provide information on differentially expressed miRNA in malignant 16HBE-T, and also suggest a potential role of these miRNAs in cell transformation induced by anti-BPDE. HOXA1 is similarly up-regulated, suggesting that miR-10a is associated with the process of HOXA 1-mediated transformation.展开更多
AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal...AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.展开更多
基金the Science and Technology Plan Project of Chengdu Municipal Health Commission,No.2019007.
文摘BACKGROUND Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions,including colorectal adenoma.Screening colonoscopy frequently reveals chicken skin mucosa(CSM;white or yellow-white speckled mucosa)surrounding colo-rectal polyps,caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors.CSM-positive colorectal polyps are associated with various diseases;however,their prognosis varies greatly.Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps.Improved imaging is required to diagnose and treat CSM-positive colorectal polyps.METHODS This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy.All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system.Based on the pathological results,patients were classified as non-neoplastic polyps(five juvenile polyps),neoplastic polyps,non-invasive high-grade neoplasia(NHGN),or submucosal invasive carcinoma(SM stage cancer).We analyzed and compared the clinical features,suspected risk factors for malignant transformation of neoplastic polyps,and early infiltration of sub-mucosal carcinoma.RESULTS The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps.Most NHGN polyps had a deeper red mucosal color.On logistic regression analyses,diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps.Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM;type 2 CSM was more common in neoplastic polyps.Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer.Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal cancer disappeared within 12 months.No tumor recurrence was found during either partial or complete endoscopic resection of the CSM.CONCLUSION CSM-positive colorectal polyps>1 cm in diameter or with deeper red mucosa may be related to NHGN.Resection of CSM surrounding colorectal adenomas did not affect tumor recurrence.
基金Supported by the Science and Technology Plan Project of Wenzhou,China,No.Y20190117the Natural Science Foundation of Zhejiang Province,China,No.LQ21H090017。
文摘BACKGROUND Bronchiolar adenoma(BA)and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer.Diagnosis is difficult because of the limited knowledge of these tumors and their morphological similarities to malignant tumors,including invasive mucinous adenocarcinoma,especially based on the histopathology of intraoperative frozen sections.These tumors are now considered to be benign neoplasms,with malignant transformation reported in only a few cases.CASE SUMMARY A 57-year-old woman presented with a 17.0 mm×7.0 mm nodule in the lower lobe of the left lung.Hematoxylin-eosin staining and immunohistochemistry of a surgical specimen were performed.The tumor consisted of a BA area and a mucinous adenocarcinoma(MA)area.In the BA area,the tumor had a bilayered structure of luminal cells and basal cells.The basal cells were positive for CK5/6 and p40,but the MA area was negative for these biomarkers.The Ki-67 proliferation index was low(1%-2%).The patient was diagnosed with BA accompanied by MA,and had a favorable outcome.CONCLUSION The present study indicated that BA may be carcinogenic,and suggests that clinicians should be aware of its potential for malignant transformation.
基金This study was supported by National Natural Science Foundation of China(81960303)Youjiang Medical College for Nationalities Affiliated Hospital(R202011710)+6 种基金Youjiang Medical College for Nationalities Affiliated Hospital,Youjiang Key Talents Research Project(Y20212603)Guangxi Key Laboratory of Molecular Pathology of Hepatobiliary Diseases,Affiliated Hospital of Youjiang Medical College for Nationalities(GxZDSYs-009)Scientific Research and Technology Development Program of Baise City(Baike 20213301)Scientific Research and Technology Development Program of Baise City(Baike 20213242)Self-funded research project of Health Commission of Guangxi Zhuang Autonomous Region(20190953)Self-funded research Project of Administration of Traditional Chinese Medicine of Guangxi Zhuang Autonomous Region(GXZYL20220304)Guangxi University Young and Middle-aged Teachers Basic Research Ability Improvement Project(2021KY0538)。
文摘Objective:To investigate the effect of mir-3168 on the malignant transformation and cisplatin resistance of AGS and AGS/DDP gastric cancer cells,and to verify its target gene.Methods:The expression of mir-3168 in AGS and AGS/DDP gastric cancer cells was detected by qPCR,and mir-3168 mimic,inhibitor and negative control were synthesized.They were transfected into AGS and AGS/DDP gastric cancer cells,respectively.The expression of mir-3168 and TP53 mRNA was detected by qPCR.Cell viability was detected by CCK8 under gradient cisplatin treatment and non treatment,apoptosis was detected by flow cytometry,cell invasion was detected by Transwell,and TP53 protein expression was detected by western blot,The database predicted the binding sites of mir-3168 and TP53.According to the binding sites,the double luciferase experiment was used to verify the binding of mir-3168 and TP53.Results:Compared with cisplatin sensitive gastric cancer cell AGS,mir-3168 was significantly overexpressed in cisplatin resistant gastric cancer cell AGS/DDP;mir-3168 mimic promotes cisplatin resistance,proliferation and invasion of AGS and AGS/DDP gastric cancer cells,and inhibits apoptosis of AGS and AGS/DDP gastric cancer cells;mir-3168 inhibitor inhibits cisplatin resistance,proliferation and invasion of AGS and AGS/DDP gastric cancer cells,and promotes apoptosis of AGS and AGS/DDP gastric cancer cells;mir-3168 mimic inhibits the expression of TP53 mRNA and protein,and mir-3168 inhibitor promotes the expression of TP53 mRNA and protein;Targetscan database predicted that there was a binding point between mir-3168 and TP53,and the double luciferase experiment suggested that mir-3168 was bound to TP53 through the predicted binding site.Conclusion:mir-3168 may promote the malignant transformation of AGS and AGS/DDP gastric cancer cells and cisplatin resistance by targeting TP53.
文摘BACKGROUND Adenomyoepithelioma(AME)of the breast is a rare type of benign breast tumor.Many AMEs show benign behavior,but reports of the malignant type are rare.We present the case of a patient with AME with repeated local recurrences and further malignant transformation.CASE SUMMARY A 53-year-old woman visited our hospital with a 16-mm palpable mass in the right breast.A core needle biopsy was performed.The pathological diagnosis was AME.Lumpectomy with a safety margin was performed without axillary lymph node dissection(ALND).Two years later,local recurrence developed,and the patient again underwent lumpectomy with a safety margin.The pathology showed malignant AME,and the margin was negative.Eight months later,local recurrence developed again in the same location,and a total mastectomy was performed without ALND.The pathological diagnosis was malignant AME.The patient was disease-free for three years posttreatment.CONCLUSION The treatment of AME requires caution,as it may exhibit repeated recurrences after local excision as well as malignant transformation.
基金This study will be supported by grants from the National Natural Science Foundation of China(No.81630080,91129714,81270466,81173424 and 81373796)the Science Research Foundation of BUCM(No.2014-JYBZZ-XS-134)+1 种基金the Research Foundation of the Doctoral Program of Higher Education of China(No.20120013110014)the National Undergraduates Innovating Experimentation Project of the Ministry of Education of China(No.081002609).
文摘Objective:Traditional Chinese medicine(TCM)and modern medicine have both been used in arresting malignant transformation of chronic atrophic gastritis(CAG)in China with good therapeutic effect.However,no studies have been undertaken to assess the risk of malignant transformation in CAG patients using both modern medicine and TCM features.Our study aimed to develop risk assessment models for malignant transformation of CAG combining indicators of both TCM and modern medicine.These models will facilitate early warning and control of malignant transformation of CAG from the perspective of evidence-based integrative medicine.Methods:In the proposed registry study,a total of 1000 eligible CAG patients will be recruited from four hospitals in China.A 10-year follow-up study will be conducted both on-site and off-site to track the events of malignant transformation.Frequency analysis and chi-squared tests will be used to perform the comparative analysis on the prevalence of malignant transformation events and indicators in TCM or modern medicine in different groups.A multivariate Cox proportional hazard model will be used to perform correlation analyses of malignant transformation events and factors of TCM or modern medicine.Conclusion:The proposed study has been designed with a large sample size and long follow-up period,in which wide-ranging modern medicine and TCM indicators can be gathered over the whole process of malignant transformation of CAG.Based on this study,risk assessment models for malignant transformation ofCAGmaybe constructed fromthe perspective of integrative medicine.This may provide clinicians and patients with an optimized early warning system as well as prevention strategies for malignant transformation of CAG.
基金Supported by National Natural Science Foundation of China,No.81472543 and No.81772919Zhejiang Provincial Natural Science Foundation of China,No.LY18H160024 and No.LY20H160040
文摘BACKGROUND O_(6)-methylguanine-DNA methyltransferase(MGMT)is a suicide enzyme that repairs the mispairing base O_(6)-methyl-guanine induced by environmental and experimental carcinogens.It can transfer the alkyl group to a cysteine residue in its active site and became inactive.The chemical carcinogen N-nitroso compounds(NOCs)can directly bind to the DNA and induce the O_(6)-methylguanine adducts,which is an important cause of gene mutation and tumorigenesis.However,the underlying regulatory mechanism of MGMT involved in NOCs-induced tumorigenesis,especially in the initiation phase,remains largely unclear.AIM To investigate the molecular regulatory mechanism of MGMT in NOCs-induced gastric cell malignant transformation and tumorigenesis.METHODS We established a gastric epithelial cell malignant transformation model induced by N-methyl-N’-nitro-N-nitrosoguanidine(MNNG)or N-methyl-N-nitroso-urea(MNU)treatment.Cell proliferation,colony formation,soft agar,cell migration,and xenograft assays were used to verify the malignant phenotype.By using quantitative real-time polymerase chain reaction(qPCR)and Western blot analysis,we detected the MGMT expression in malignant transformed cells.We also confirmed the MGMT expression in early stage gastric tumor tissues by qPCR and immunohistochemistry.MGMT gene promoter DNA methylation level was analyzed by methylation-specific PCR and bisulfite sequencing PCR.The role of MGMT in cell malignant transformation was analyzed by colony formation and soft agar assays.RESULTS We observed a constant increase in MGMT mRNA and protein expression in gastric epithelial cell malignant transformation induced by MNNG or MNU treatment.Moreover,we found a reduction of MGMT gene promoter methylation level by methylation-specific PCR and bisulfite sequencing PCR in MNNG/MNU-treated cells.Inhibition of the MGMT expression by O_(6)-benzylguanine promoted the MNNG/MNU-induced malignant phenotypes.Overexpression of MGMT partially reversed the cell malignant transformation process induced by MNNG/MNU.Clinical gastric tissue analysis showed that MGMT was upregulated in the precancerous lesions and metaplasia tissues,but downregulated in the gastric cancer tissues.CONCLUSION Our finding indicated that MGMT upregulation is induced via its DNA promoter hypomethylation.The highly expressed MGMT prevents the NOCs-induced cell malignant transformation and tumorigenesis,which suggests a potential novel approach for chemical carcinogenesis intervention by regulating aberrant epigenetic mechanisms.
基金supported bygrants from the Beijing Hospitals Authority Youth Programme(Grant No.QML20190506)the Capital Health Development Research Project(Grant No.2020-2-1072).
文摘Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of IDHmutant LGGs.Methods:We screened data for 108 patients with sAIDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from IDH-mutant LGGs to sAIDHmut/G4,and associated risk factors and outcomes.Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with IDH-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;P<0.0001)in patients with IDH-mutant gliomas.Conclusions:Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDHmutant gliomas.
文摘BACKGROUND Mature teratoma is a common benign ovarian germ cell tumor,accounting for about 20%of ovarian tumors.The malignant transformation of this tumor is less than 2%.The most common type is squamous cell carcinoma,followed by adenocarcinoma.Malignant transformation of colonic mature teratoma is extremely rare.We here report a case of malignant transformation of primary mature teratoma of the colon.The type of malignant transformation was adenocarcinoma.CASE SUMMARY A 63-year-old woman was admitted to our hospital due to persistent pain in her right lower abdomen for 1 mo,and she had no nausea,vomiting,blood in the stools,or other symptoms.Preoperative colonoscopy showed uplift of the sigmoid colon mucosa and submucosa.The biopsy showed squamous epithelium.However,contrast-enhanced computed tomography of abdomen and pelvis showed a localized thickening of the sigmoid wall,suggesting colon cancer.Endoscopic ultrasonography(EUS)revealed that the structure of the intestinal wall at the base of the lesion was destroyed,and the boundary between the lesion and the surroundings was unclear.According to the findings of the EUS,the patient did not undergo endoscopic submucosal dissection,but underwent radical resection of the tumor.Histologically,squamous epithelium was seen on the mucosal surface of the colon wall,cartilage and glands were seen under the epithelium,and adenocarcinoma was seen on the muscular layer and serous surface.The final pathological diagnosis was malignant teratoma of the colon.We have followed up the patient for 2 mo since the operation,and the patient recovered well.CONCLUSION This case suggests the possibility of mature teratoma in the colon and recognition of malignant types,and it should not be considered as an exclusively ovarian tumor.
基金Supported by Innovative Project of Medical and Health Science,Zhejiang Province,No.2021RC002。
文摘BACKGROUND Biliary adenofibromas(BAFs)are rare primary hepatic neoplasms,some of which can potentially undergo malignant transformation.Here,we describe a rare case of malignant transformation of BAF.CASE SUMMARY A 51-year-old female was referred to our hospital with epigastric pain.Computed tomography showed a solitary liver mass combined with the enlargement of multiple mediastinal and cervical lymph nodes,clinically mimicking a liver carcinoma with extensive lymph node metastasis.However,core needle biopsy suggested BAF with malignant transformation.Finally,the patient underwent curative resection of the neoplasm and was recurrence-free for 12 mo.CONCLUSION Our case serves as an example of a rare manifestation of BAF.Our report and the previously published experience,reinforce that curative resection should be considered the primary treatment for BAFs with malignant transformation,leading to a favorable prognosis.
基金Supported by the National Natural Science Foundation of China,No.81600911.
文摘BACKGROUND In rare cases,odontogenic keratocysts(ODs)transform into squamous cell carcinoma.Intervals between the first attendance of a patient and the diagnosis of OD with malignant transformation vary from weeks to years.In this article,we report a case of malignancy derived from OD with a five-day delay in diagnosis.CASE SUMMARY A 54-year-old woman was referred to Tongji Hospital in Wuhan,China with complaints of moderate pain,recurrent swelling,and pus discharge around her left maxillary lateral incisor for over 10 years.Physical examination revealed a fistula at the palatine-side mucoperiosteum of the left maxillary lateral incisor and enlarged lymph node in the left neck.Cone beam computed tomography revealed a cystic lesion with massive bone destruction from the left maxillary central incisor to the left secondary maxillary premolar and local bony destruction in the left first mandibular molar.The patient was clinically diagnosed with OD.Enucleation rather than marsupialization was performed given the risk factors of long history,recent aggravated pain,and massive bony destruction.Malignant transformation of OD was confirmed by pathologists 3 d after the operation.Radical surgery was performed,and lymph node metastasis was observed.The patient was subjected to postoperative radiotherapy and synchronous chemotherapy,and no local recurrence or distant metastasis was noted at one-year follow-up.CONCLUSION Our case suggests that clinicians should be aware of the malignant transformation of OD,especially when patients present with a long history,massive cyst,chronic inflammation,recent persistent infections,aggravated pain,numbness around the cystic lesion,and lymph node enlargement.
文摘Malignant transformation of hamsterembryo cells was induced in vitro by rareearth iron mineral dusts(MP),naturalthorium(Th02) and MP plus Th02.Dusts of MP,MP plus Th02 or Th02 were added into themedium with the final concentration of 17.0,
文摘<strong>Background:</strong> Inverted Papilloma (IP) is the most common benign neoplasms arising from the mucosal lining of the of the Sino-Nasal tract with single or multifocal attachment sites. The high propensity to recur, local aggressive behavior and possibility of malignant transformation attract considerable interest. <strong>Objective:</strong> To assess the factors affecting Sino-nasal IP, malignant transformation rate, and post-operative recurrence rate. <strong>Methods:</strong> A retrospective study was carried out on all cases diagnosed as Sino-Nasal Papilloma between January 2010 and December 2020 at Salmaniya Medical Complex, Bahrain. Data gathered from medical records were analyzed using SPSS. A total of 49 Sino-Nasal Papilloma cases were recorded of which 37 were IP. Factors affecting Sino-Nasal IPs are presented. <strong>Results:</strong> Sino-Nasal IP was recorded in 37 cases, composed of 28 males and 9 females with first presentation average age of 45.86 years. These involved 20 cases in the left side, 14 in the right side and 3 were bilateral. Recurrence in males and females was found to be 35.7% and 33%, respectively, with an average of 12.6 months. The symptoms include nasal blockage (97.3%), epistaxis and postnasal drip (13.5% each), headache (8.1%) and hyposmia and rhinorrhea (5.4%, each). The main recurrence was at stage T2 (60.5%), while in smokers (26.7%) and non-smokers (50%). Malignant transformation occurred in one patient only (2.6%). <strong>Conclusion:</strong> IP is the most common type of SNP with male predominance. The recurrence rate is high with an average of a year and the malignant transformation occurred in 2.6 % of the cases.
文摘Retrorectal cystic hamartomas are rare congenital lesions that can undergo malignant transformation, and adenocarcinoma is the most frequently described histological type. The authors describe a case of a 53-year-old female patient with a localized well-differentiated adenocarcinoma that developed in a retrorectal cystic hamartoma. The patient was submitted to surgery (a Kraske procedure), with an R1 resection, followed by adjuvant radio-chemotherapy. After 23 months of follow up, the patient remains free from disease recurrence. Given the rarity of this entity, this case allows us to reflect on the differential diagnosis, therapeutic approach and patients’ follow-up.
基金the National Natural Science Foundation of China(Grant No.82072580).
文摘The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.However,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood.In the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer elements.We found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)gene.Furthermore,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model.Subsequently,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency.Consistently,KLF4 expression also decreased in lung cancer tissues and cell lines.It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells.Collectively,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function.Therefore,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.
文摘Inflammatory myofibroblastic tumor(IMT) is an uncommon benign neoplasm with locally aggressive behavior but malignant change is rare.We report an unusual case of pelvic-abdominal inflammatory myofibroblastic tumor with malignant transformation in a 14-year-old boy presenting with abdominal pain and 9 kg body weight loss in one month.Computed tomography revealed a huge pelvi-abdominal mass(30 cm),possibly originating from the pelvic extraperitoneal space,protruding into the abdomen leading to upward displacement of the bowel loops,downward displacement of the urinary bladder,massive central necrosis,a well-enhanced peripheral solid component with prominent peritumoral vascularity.Subsequent examination confirmed the computed tomographic findings.Histopathologic examination revealed proliferative epitheloid and spindle cells,inflammatory cell infiltration and high mitotic counts.Immunohistochemistry was strongly positive for anaplastic lymphoma kinase and revealed a high proliferative index(ki-67 = 40%).DNA sequencing and electronic microscopy further confirmed the primitive fibroblastic cell phenotype of the tumor and a final diagnosis of inflammatory myofibroblastic tumor with malignant transformation was established.Rapid tumor recurrence was noted 20 d after radical tumor resection.To our knowledge,this is the largest documented case of IMT in a pediatric patient and the first report of IMT with malignant transformation originating from the pelvic extraperitoneal space.
基金This work was supported by the National Natural Sciences Foundation of China (No. 30371624).
文摘Objective: To investigate the mechanism of carcinogenesis, invasion and metastasis. Methods: The expressions of adhesive molecule and adhesive structure in v-k-ras transformed normal rat kidney cells (KNRK) were detected with a variety of molecular biological techniques, including cell culture, immunofluorescence labeling, electron microscopy, polyacrylamide gel electrophoresis, and protein blotting, and compared with normal rat kidney (NRK) cells. Results: The significantly shortened doubling time, remarkably active proliferation ability in soft agar, and invasive growth in the abdomen of nude rat, demonstrated the malignant biological behaviors of KNRK cells. In KNRK cells, the adhesive molecules, P-cadherin, α and β catenin, actin, and adhesive structures, the adhesive junction and gap junction, were all abnormally expressed. And cell aggregation was significantly decreased. The aggregation ability disappeared at 20℃, and became active with a suitable amount of calcium solution. Conclusion: Following the transfection of virus K-ras gene, normal cells were transformed into malignant cells. In early stage of cancer, the variation of adhesive ability may be one of the vital factors underlying tumorigenesis, invasion and metastasis.
基金supported by the National Natural Science Foundation of China(Nos.81671006 and 81300894)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-038)+2 种基金the National Clinical Key Discipline Construction Project(No.PKUSSNKP-202102)the Program for New Clinical Techniques and Therapies of Peking University Hospital of Stomatology(No.PKUSSNCT-22A14)the Innovation Fund for Outstanding Doctoral Candidates of Peking University Health Science Center(No.BMU2022BSS001),China.
文摘Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management.As a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral leukoplakia.In this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside.Although no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.
基金Supported by the National Natural Science Foundation of China,No.81873915 and No.31872738the Key Plan of Nantong S&T Development,No.MS12020021the S&T Program of Medical School of Nantong University,No.TDYX2021010.
文摘Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ)on inner mitochondrial membrane(IMM)regulates long chain fatty acidβ-oxidation,and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD.The sequences of its peptide chain and DNA nucleotides have been identified,and the catalytic activity of CPT-Ⅱ is affected on its gene mutations,deficiency,enzymatic thermal instability,circulating carnitine level and so on.Recently,the CPT-Ⅱ dysfunction has been discovered in models of liver lipid accumulation.Meanwhile,the malignant transformation of hepatocyte-related CD44^(+) stem T cell activation,high levels of tumor-related biomarkers(AFP,GPC3)and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.This review focuses on some of the progress of CPT-Ⅱ inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.
基金supported by the National Natural Science Foundation of China(No.30571546,30771780)the Scientific Research Foundation of the State Education Ministry for Returned Overseas Chinese Scholars(2007-24)+1 种基金the Natural Science Foundation of Guangdong Province(No.07117550)the Natural Science Key Program of Higher Education Institutions of Guangdong Province,China(No.06Z021).
文摘Objective To screen miRNA profiles of malignantly transformed human bronchial epithelial cells, 16HBE-T, induced by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide (anti-BPDE), and to analyze putative miR-10a targets in 16HBE-T. Methods A novel microarray platform was employed to screen miRNA profiles of 16HBE-T cells transformed by anti-BPDE. Microarray data for miR-10a and miR-320 were validated using quantitative real time polymerase chain reaction (QRT-PCR). The expression of a putative target for miR-10a, HOXA1, was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and QRT-PCR. Results In comparison with the vehicle-treated cells (16HBE-N), 16HBE-T exhibited differential expression of 54 miRNAs, in which, 45 were over-expressed and 9 were down-regulated. The five most highly expressed miRNAs were miR-494, miR-320, miR-498, miR-129, and miR-106a. The lowest expressed miRNAs were miR-10a, miR-493-5p, and miR-363*. Three members of miR-17-92 cluster, miR-17-5p, miR-20a, and miR-92, showed significantly higher abundance in 16BHE-T as miR-21, miR-141, miR-27a, miR-27b, miR-16 and miRNAs of the let-7 family. The putative target for miR-10a, HOXA1 mRNA was up-regulated 3-9-fold in 16HBE-T, as compared with 16HBE-N. Conclusion The findings of the study provide information on differentially expressed miRNA in malignant 16HBE-T, and also suggest a potential role of these miRNAs in cell transformation induced by anti-BPDE. HOXA1 is similarly up-regulated, suggesting that miR-10a is associated with the process of HOXA 1-mediated transformation.
基金Supported by the National Natural Science Foundation,No.81673241,No.81200634,No.81370982the program of Jiangsu Key Research Plan,No.BE2016698the International Science and Technology Cooperation Program of China,No.2013DFA32150
文摘AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.