Thirty-year overview of Japanese autopsy cases of Takayasu arteritis - Results of analysis of Japanese autopsy reports.

OBJECTIVE: The objective of the study was to analyse the trends in Takayasu arteritis (TAK) in Japan during three recent decades based on autopsy reports. METHODS: We extracted TAK cases from the Japanese Pathological Autopsy Reports published during three decades (1991-2000, 2001-10, and 2011-20) and compared the data for the number of cases, age, gender, malignant tumour complication rate, and cause of death. RESULTS: 322 TAK cases were reported during the 30 years. They represented 0.04-0.06% of the total autopsies, with little variation among the three decades. The peak age at autopsy increased: from the 60s for 1991-2010 to the 70s for 2011-20. The malignant tumour complication rate increased to 12.2%, 18.5%, and 22.7% during the three decades. However, about half of those cases had no metastases, and malignant tumours were rarely directly involved in a TAK patient's death. TAK-associated cardiovascular lesions accounted for most deaths. CONCLUSIONS: Although the age at TAK onset showed little change during the 30 years, the age at autopsy has increased, suggesting that the long-term prognosis has improved. Although the malignant tumour complication rate increased with age, the most common causes of death were cardiovascular lesions.

Role of tRNA-derived small RNAs(tsRNAs) in the diagnosis and treatment of malignant tumours.

Malignant tumours area leading cause of death globally, accounting for approximately 13% of all deaths. A detailed understanding of the mechanism(s) of the occurrence and development of malignant tumours and identification of relevant therapeutic targets are therefore key to tumour treatment. tsRNAs(tRNA-derived small RNAs)-also known as TRFs (tRNA-derived fragments), tiRNAs (tRNA-derived stress-induced RNAs), tRNA halves, etc.-are a recently identified class of small noncoding RNAs that are generated from mature tRNA or tRNA precursors through cleavage by enzymes such as angiogenin, Dicer, RNase Z, and RNase P. Several studies have confirmed that dysregulation of tsRNAs is closely related to the tumorigenesis of breast cancer, nasopharyngeal cancer, lung cancer, and so on. Furthermore, research indicates that tsRNAs can be used as clinical diagnostic markers and therapeutic targets for cancer. In our review, we summarized the recent research progress on the role and clinical application of tsRNAs in tumorigenesis and progression. Video Abstract.

Research progress of circRNA in malignant tumour metabolic reprogramming.

Cancer is a multi-factor systemic malignant disease, which has seriously threatened human health and created a heavy burden on the world economy. Metabolic reprogramming, one of the important signs of malignant tumours, provides necessary nutrition for tumorigenesis and cancer development; thus, it has recently become a research hot spot, even though the metabolic mechanism is quite intricate. Circular RNA (circRNA) affects cancer cell metabolism through various molecular mechanisms, playing an important role in promoting or suppressing cancer. Because of the structure characteristics, circRNA is quite stable, and can be utilized as biomarkers. In this review, we analysed and summarized the characteristics and biological functions of circRNA and comprehensively reviewed and discussed the important role of circRNA in cancer metabolic reprogramming. This review will provide new ideas for developing new anti-cancer therapeutic targets, mining cancer diagnostic and prognostic markers, and will provide guidance for other researchers to design circRNA-related experiments and develop anti-tumour drugs.

Value of contrast-enhanced ultrasound in the differential diagnosis of ureteral tuberculosis from ureteral malignant tumour in women.

This study aimed to evaluate the contrast-enhanced ultrasound (CEUS) features of ureteral tuberculosis (UTB) and ureteral malignant tumour and to explore its application value in the differentiation of UTB from ureteral tumour. The ultrasound (US) and CEUS imaging features of 33 and 12 cases of pathologically confirmed UTB and ureteral malignant tumour, respectively, were retrospectively evaluated, and echo of the ureteral wall, abnormal echo of the lumen, degree of ureteral dilation and CEUS patterns of the two diseases were statistically analysed. The results revealed that the lumen echo of UTB was hyperechoic or anechoic, whereas that of ureteral tumour lesions was hypoechoic (χ2 = 28.22, P < 0.001). The wall echo of the obstruction site differed between the two diseases; in UTB, the ureteral wall was thickened but the outer wall remained intact, whereas in ureteral tumour, both the malignant tumour wall and outer wall were irregular (χ2 = 30.25, P < 0.001). CEUS of UTB revealed nonenhancement or heterogeneous enhancement in the lumen, whereas that of ureteral tumours revealed significant homogeneous enhancement (χ2 = 30.25, P < 0.001). Thus, CEUS can reveal lesion microcirculation and be used to evaluate blood supply characteristics in the lesion, indicating that it has high potential for differentiating the two diseases.

Limited parotid surgery as sole form of treatment for carefully selected malignant tumours of the parotid gland: Still sufficient on the long-term?

BACKGROUND: The aim of the study was to investigate the oncological and functional outcome following extracapsular dissection as the sole form of treatment in locally limited low-grade malignant parotid tumours in the long term. METHODS: The records of all patients treated for T1-T2 low-grade malignant tumours of the parotid gland solely by means of extracapsular dissection between 2005 and 2017 were studied retrospectively. RESULTS: A total of 16 cases formed our study sample (7 men, 9 women). Their mean age was 50.2 years (21-84 years). Mean follow-up was 107 months (60-201 months). In 6 cases the tumour was an acinic cell carcinoma, in 9 cases a mucoepidermoid carcinoma and in one case a basal cell adenocarcinoma. Regarding the T category, the tumour was Tis in one case, T1 in 12 cases and T2 in three cases. The five-year disease-specific survival rate was 100 %, as was local disease control. Facial nerve function was House-Brackmann grade I without exception. CONCLUSIONS: Our study showed very encouraging long-term results following primary extracapsular dissection as the sole surgical therapy for carefully selected low-stage, low-grade, inferiorly located lesions in patients with high compliance. LAY SUMMARY: The "one-size-fits-all" strategy of complete parotidectomy with neck dissection might be tantamount to overtreatment by less aggressive cases of parotid cancer. Extracapsular dissection seems to be oncologically sufficient for carefully selected T1-T2 low-grade cases in the long-term in patients with ensured follow-up.

Investigation of standardized training of radiation oncology residents for gynaecological tumours in China.

BACKGROUND: Radiotherapy standardized training (ST) has been conducted for 7 years in China. This investigation evaluated the difficulties of and need for ST of radiation oncology residents (RORs) for gynaecological tumours (GYN) in China. METHODS: An anonymous online survey was conducted on the "Questionnaire Star" platform. The questionnaire contained 30 questions, including the basic information of the students, their knowledge of radiotherapy theory, training on GYN, the difficulties and needs they faced, and possible solutions. RESULTS: A total of 469 valid questionnaires were collected, resulting in a valid response rate of 85.3%. During the ST, only 58-60% of RORs received training in GYN, with a median clinical rotation time of 2-3 months. Among the RORs surveyed, 50.1% knew the physical characteristics of brachytherapy (BRT), and 49.2% could choose the appropriate BRT for patients. At the end of ST, 75.3% were able to complete the target delineation in GYN independently, and 56% were able to complete the BRT operation independently. The scarcity of GYN patients, insufficient teaching awareness of superior doctors, and lack of interest are the main reasons why ST cannot meet the standard. CONCLUSION: In China, the ST of RORs in GYN should be strengthened, the teaching awareness of specialist trainers should be increased, and the curriculum should be optimized, especially the curriculum for specialist operation and a strict assessment system.

Preservation of the left colic artery in modified laparoscopic anterior rectal resections without auxiliary abdominal incisions for transanal specimen retrieval.

BACKGROUND: Laparoscopic low anterior rectal resection is the most widely used surgical procedure for middle and low rectal cancer. The aim of this study was to investigate the feasibility and safety of the extracorporeal placement of the anvil in preserving the left colic artery in laparoscopic low anterior rectal resection without auxiliary incisions for transanal specimen retrieval in this research. METHODS: Clinical data and follow-up data of patients undergoing laparoscopic low anterior rectal resection from January 2017 to October 2020 were collected. The resections were modified such that the resisting nail holder was extracorporeally placed for the transanal exenteration of the specimen without using auxiliary abdominal incisions while preserving the left colic artery. By analyzing the data of anastomotic stenosis, anastomotic bleeding and anastomotic fistulas after surgery, the advantages and disadvantages of this surgical method for patients were clarified. RESULTS: A total of 22 patients were enrolled. Five of 22 patients simultaneously underwent double-barrel terminal ileostomy. The postoperative exhaust time was 2-7 (median, 3) days. Postoperative anastomotic bleeding occurred in one patient, postoperative anastomotic fistula occurred in four patients, and postoperative anastomotic stenosis occurred in six patients. There were four patients with postoperative distant metastasis, of which three had concomitant local recurrence. Seventeen patients had no obvious symptoms or signs of recurrent metastases during follow-up appointments, and one died of liver failure. CONCLUSIONS: Modified laparoscopic low anterior rectal resection, which resects the specimen through anus eversion by inserting the anvil extracorporeally while preserving the left colic artery, is safe and feasible for patients with low rectal cancer.

Vaginal tumours in childhood: a descriptive analysis from a large paediatric medical centre.

PURPOSE: Malignant tumours of the vagina are very rare in children. The purpose of this study was to retrospectively analyse the clinical presentation, treatment, and outcome of vaginal tumours in children treated in a single institution. METHODS: This study retrospectively analysed the clinical data of children diagnosed with vaginal malignant tumours who were admitted to the Beijing Children's Hospital of Capital Medical University from January 2007 to December 2020 and followed these patients to observe their prognoses and outcomes. RESULTS: During 13 years, a total of 33 children were included in this study, including 13 children with rhabdomyosarcoma and 20 children with endodermal sinus tumours. The average age at diagnosis was 20.4 months. The main clinical manifestations were vaginal bleeding and protruding masses. Of the 13 children with vaginal rhabdomyosarcoma, 12 were treated with multidrug chemotherapy combined with conservative tumour resection, and their tumours completely resolved; only one child underwent vaginectomy and hysterectomy. Twenty children with vaginal endodermal sinus received PEB chemotherapy. Among these patients, the tumour disappeared after chemotherapy in 12 children, and the remaining nodular tumour foci in 8 children were confirmed to be necrotic tissue by pathology. CONCLUSION: Our research confirms that chemotherapy combined with conservative surgical treatment is effective for treating children with vaginal malignancies.

Sebaceous carcinoma of forehead: A rare malignant lesion.

Sebaceous carcinoma is an uncommon malignant tumour of the sebaceous glands. This lesion typically occurs as painless and slow growing nodule in the eyelid region. In rarity, it can develop on buccal mucosa, head and neck, and other regions of the body in people in their 60s and 70s. Sebaceous carcinoma is locally aggressive and carries the potential of regional and distant spread. We present the case of a 15-year-old male who was diagnosed with sebaceous carcinoma over the forehead. After discussing the case in the board meeting, surgery was performed to remove the tumour with 1 cm margin. Outer table of the frontal bone was also removed and intraoperative frozen section was done for margin clearance. After the excision, soft tissue coverage was done with free Anterolateral thigh flap and the patient received six cycles of post-operative radiation therapy.

Long-term safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis: 3-year follow-up of a postmarketing surveillance.

OBJECTIVES: To analyse the long-term safety and effectiveness of abatacept for rheumatoid arthritis using real-world, Japanese, postmarketing surveillance data, focusing on serious infections and malignancies as priority events. METHODS: This 3-year, multicentre surveillance registered patients undergoing abatacept treatment by intravenous infusion between July 2011 and October 2012. RESULTS: The safety and effectiveness analysis sets included 647 and 596 patients, respectively. The total observation period for the safety analysis was 1280 patient-years. Over the 3-year follow-up, the incidence rates of adverse drug reactions (ADRs) and serious ADRs were 19.92 per 100 patient-years (22.87% of patients) and 4.06 per 100 patient-years (6.65% of patients), respectively. Infections and infestations were the most common ADRs (14.68%), followed by respiratory, thoracic, and mediastinal disorders (3.09%). Incidence rates of serious infections as ADRs and malignancy as adverse events were 1.95 and 1.02 per 100 patient-years, respectively. Retention rates at 1 and 3 years were 67.4% and 43.9%, respectively. Significant decreases from baseline were observed in Disease Activity Score (DAS) 28-erythrocyte sedimentation rate and DAS28-C-reactive protein, as well as Health Assessment Questionnaire-Disability Index (HAQ-DI) and modified HAQ scores. CONCLUSIONS: No new safety signals were detected during the 3-year observation period and effectiveness was maintained over time.

Efficacy of argon-helium cryoablation and its effects on immune function of patients with neck malignant tumours.

OBJECTIVES: Our study aimed to investigate the clinical efficacy of argon-helium cryoablation and its effects on the immune function of patients with neck malignant tumours. DESIGN: Retrospective study. SETTING: Single-institution academic tertiary care centre. METHODS: Totally, 180 patients harbouring head and neck malignant tumours were divided into the argon-helium cryoablation group (n = 150) and the radiotherapy group (n = 50). The efficacy of the two groups was compared, and the immune function was observed. RESULTS: The short-term clinical effect of the argon-helium cryoablation group was significantly higher than that of the radiotherapy group (P < .05). After treatment, the CD3+, CD4+, CD8+ and CD4+/CD8+ of the argon-helium cryoablation group were significantly better than those of the radiotherapy group (P < .001). The results of TNF-α, IL-1 ß and CRP in the argon-helium cryoablation group were significantly better than that in the radiotherapy group (P < .001). CONCLUSION: Argon-helium cryoablation could effectively improve the immune function, 5-year survival rate and local remission rate.

Non-Hodgkin's lymphoma of the appendix and distal ileum. A rare case report.

Primary gastrointestinal (GI) tract lymphomas constitute 1%-4% of all GI malignancies. Primary lymphomas of appendix are even more rare and are seen in 0.015% of all appendicectomy specimens. Here, we report a rare case of non-Hodgkin's lymphoma tumours in the appendix and distal ileum in a non-immune compromised young male patient who presented with intermittent intussusception and pain in the right iliac fossa. A laparoscopic right hemicolectomy was performed and the patient recovered uneventfully. Adjuvant chemotherapy (CHOP) in the form of CHOP regimen has been further advised.

Malignant tumours of temporomandibular joint.

BACKGROUND: Malignant tumours of the temporomandibular joint (MTTMJ) are extremely rare. Studies describing its unique epidemiology, clinicopathological features, treatment and prognosis comprehensively are limited. To address these issues, current investigation was performed. METHODS: A retrospective research was carried out by using population-based data from the Surveillance, Epidemiology, and End Results database (1973-2016). RESULTS: Data for a total of 734 patients, including 376 men and 358 women, was found. The median age was 47 years. The 5-year and 10-year disease specific survival (DSS) rates were 69.2 and 63.6%, respectively. Significant differences in DSS were found according to age, race, tumour type, AJCC/TNM stage, surgery, radiotherapy, chemotherapy and different treatment modalities (P < 0.05). In the multivariate survival analysis, age > 44 years and AJCC stage III and IV were associated with poor DSS. CONCLUSION: MTTMJ was mostly found in white people with a median age of 47 years without any sex predominance. Patient's age and AJCC stage was independent predictor of DSS.

Genome-wide transcriptional analysis of Aristolochia manshuriensis induced gastric carcinoma.

Context: Aristolochia manshuriensis Kom (Aristolochiaceae) (AMK) is known for toxicity and mutagenicity.Objective: The tumorigenic role of AMK has yet to be understood.Materials and methods: AMK extracts were extracted from root crude drug. SD (Sprague Dawley) rats underwent gavage with AMK (0.92 g/kg) every other day for 10 (AMK-10) or 20 (AMK-20) weeks. Stomach samples were gathered for histopathological evaluation, microarray and mRNA analysis.Results: The gastric weight to body weight ratio (GW/BW) is 1.7 in the AMK-10 cohort, and 1.8 in AMK-20 cohort compared to control (CTL) cohort. Liver function was damaged in AMK-10 and AMK-20 rats compared to CTL rats. There were no significant changes of CRE (creatinine) in AMK-10 and AMK-20 rats. Histopathological analysis revealed that rats developed dysplasia in the forestomach in AMK-10 rats, and became gastric carcinoma in AMK-20 rats. Genes including Mapk13, Nme1, Gsta4, Gstm1, Jun, Mgst2, Ggt6, Gpx2, Gpx8, Calml3, Rasgrp2, Cd44, Gsr, Dgkb, Rras, and Amt were found to be critical in AMK-10 and AMK-20 rats. Pik3cb, Plcb3, Tp53, Hras, Myc, Src, Akt1, Gnai3, and Fgfr3 worked in AMK-10 rats, and PDE2a and PDE3a played a pivotal role in AMK-20 rats.Discussion and conclusions: AMK induced benign or malignant gastric tumours depends on the period of AMK administration. Genes including Mapk13, Nme1, Gsta4, Gstm1, Jun, Mgst2, Ggt6, Gpx2, Gpx8, Calml3, Rasgrp2, Cd44, Gsr, Dgkb, Rras, Amt, Pik3cb, Plcb3, Tp53, Hras, Myc, Src, Akt1, Gnai3, Fgfr3, PDE2a, and PDE3a were found to be critical in aristolochic acid-induced gastric tumour process.

Caspase-3, p53 and Bcl-2 expression in basal cell carcinoma of the eyelid.

INTRODUCTION: Eyelid tumours mostly originated from skin and its appendeges. External carcinogens like UV radiation causes cell damages in the eyelid skin and contributes to carcinogenesis. Apoptosis is a very important mechanism to prevent these damage and probable neoplatic change. AIM: To compare caspase-3, p53 and Bcl-2 levels between patients with basal cell carcinoma (BCC) of the eyelid and healthy individuals. MATERIAL AND METHODS: Pathology archives from October 2012 to April 2015 were scanned for BCC biopsies of the eyelid and tissue removed during blepharoplasty and entropion procedures. A total of 36 specimens were found. The specimens were divided into two groups: BCC group and controls (consisting of eyelid tissue removed during routine blepharoplasty). The pathology specimens were then stained using p53, Bcl-2 and caspase-3 stains and the intensity of staining was graded on a 0-3 scale. RESULTS: Samples from a total of 36 patients were included in the study. Eighteen (50.0%) patients were female. There were 13 patients in the BCC group and 23 patients in the control group. The mean age was 66.0 ±10.8 years in the BCC group, and 65.61 ±11.22 years in the control group. The caspase-3 staining was lower in the BCC group than in the control group. No significant differences were found between the BCC group and the control group in terms of p53 levels or Bcl-2 levels (both of them, p = 1.000). CONCLUSIONS: The caspase-3 level was lower in the BCC group. This result suggests that these enzymes can play a significant role in carcinogenesis of eyelid BCC.

Anterolateral thigh free flap in reconstruction of lateral skull base defects after oncological resection.

PURPOSE: Evaluation of the utility of the free anterolateral thigh flap reconstruction of the defects resulting from radical temporal bone resection in the management of lateral skull base malignancies in a single institution. METHODS: An analysis of 17 en bloc subtotal petrosectomies for removal of malignant tumours was performed. There were 12 squamous cell carcinomas, 4 basal cell carcinomas and 1 adenoid cystic carcinoma. The tumours were staged with the University of Pittsburgh TNM system. In all patients, the lateral temporal bone with the preservation of the petrous apex and carotid artery was performed. All patients had parotid gland resection. The post-resection defect was reconstructed with an ALT free flap. RESULTS: Tumour radical resection and defect reconstruction with an ALT flap was achieved in all patients without intraoperative complications. The transplants were harvested as fasciocutaneous flaps, 11 perfused by musculocutaneous and 6 by septocutaneous perforators. The ALT flaps had a mean pedicle length of 8 cm (6-12 cm), and the flap size ranged between 6 × 15 cm and 15 × 30 cm. The flaps were supplied by nine facial, five occipital and three maxillary arteries. Recipient-site veins included eight internal jugular, seven facial, one retromandibular and one external jugular vein. All arterial pedicles were anastomosed in an end-to-end manner. The veins were anastomosed with interrupted sutures and in 11 cases with Synovis-Coupler® devices. All the flap transfers were performed successfully. Three patients experienced postoperative complications. CONCLUSIONS: The ALT flap proved to be effective for covering large temporal skull base defects resulting from the radical removal of temporal bone malignancies. The functional and cosmetic results were acceptable with a low complication rate.

Clinical behaviours and prognoses of high- and low-risk parotid malignancies based on histology.

PURPOSE: To report 5-year survival in patients with primary parotid malignant tumours and assess the impact of various factors on survival or local control among diverse histologic groups. METHODS: A total of 65 patients with primary parotid malignant tumours who had surgery between 2003 and 2014 were identified. Demographic characteristics including age, T stage, N stage and clinical or pathological performance were analysed. According to risk stratification (based on pathology), 65 primary parotid malignant tumours were divided into high-risk (23, 35.38%) and low-risk (35, 53.85%) groups. Overall survival (OS) and disease-free survival (DFS) were recorded by the Kaplan-Meier methods. RESULTS: The 5-year overall survival rate for primary parotid malignant tumours was 70.9%. Patients older than 60 years with fixed mass, pain, facial-nerve palsy and high-grade N stage had adverse OS and DFS. Upon multivariable analysis, facial-nerve palsy (HR 24.59; 95% CI 2.338-178.446; P = 0.002) was the only independent predictive factor for OS. Patients with high-risk parotid malignant types were more likely to have tumour pain, facial-nerve palsy (Chi-square test: < 0.0001 and 0.02), lymphatic metastasis and local/regional recurrence (Chi-square test: 0.008 and 0.012). CONCLUSIONS: Compared with low-risk parotid carcinoma, tumours with high-risk histological features tend to need aggressive surgical extirpation, neck dissection and postoperative radiotherapy.

The mRNA-binding protein Serbp1 as an auxiliary protein associated with mammalian cytoplasmic ribosomes.

While transcription plays an obviously important role in gene expression, translation has recently been emerged as a key step that defines the composition and quality of the proteome in the cell of higher eukaryotes including mammals. Selective translation is supposed to be regulated by the structural heterogeneity of cytoplasmic ribosomes including differences in protein composition and chemical modifications. However, the current knowledge on the heterogeneity of mammalian ribosomes is limited. Here, we report mammalian Serbp1 as a ribosome-associated protein. The translated products of Serbp1 gene, including the longest isoform, were found to be localized in the nucleolus as well as in the cytoplasm. Subcellular fractionation indicated that most of cytoplasmic Serbp1 molecules were precipitated by ultracentrifugation. Proteomic analysis identified Serbp1 in the cytoplasmic ribosomes of the rodent testis. Polysome profiling suggested that Serbp1, as a component of the small 40S subunit, was included in translating ribosomes (polysomes). Cosedimentation of Serbp1 with the 40S subunit was observed after dissociation of the ribosomal subunits. Serbp1 was also included in the ribosomes of human cancer cells, which may lead to a mechanistic understanding of an emerging link between Serbp1 and tumour progression. SIGNIFICANCE OF THE STUDY: In mammalian cells, the final protein output of their genetic program is determined not only by controlling transcription but also by regulating the posttranscriptional events. Although mRNA-binding proteins and the cytoplasmic ribosome have long been recognized as central players in the posttranscriptional regulation, their physical and functional interactions are still far from a complete understanding. Here, we describe the intracellular localization of Serbp1, an mRNA-binding protein, and the inclusion of this protein in actively translating ribosomes in normal and cancer cells. These findings shed a new light into molecular mechanisms underlying Serbp1 action in translational gene regulation and tumour progression.

Influences of Allee effects in the spreading of malignant tumours.

A recent study by Korolev et al. [Nat. Rev. Cancer, 14:371-379, 2014] evidences that the Allee effect-in its strong form, the requirement of a minimum density for cell growth-is important in the spreading of cancerous tumours. We present one of the first mathematical models of tumour invasion that incorporates the Allee effect. Based on analysis of the existence of travelling wave solutions to this model, we argue that it is an improvement on previous models of its kind. We show that, with the strong Allee effect, the model admits biologically relevant travelling wave solutions, with well-defined edges. Furthermore, we uncover an experimentally observed biphasic relationship between the invasion speed of the tumour and the background extracellular matrix density.

Constitutive ERK1/2 activation contributes to production of double minute chromosomes in tumour cells.

Double minute chromosomes (DMs) are extrachromosomal cytogenetic structures found in tumour cells. As hallmarks of gene amplification, DMs often carry oncogenes and drug-resistance genes and play important roles in malignant tumour progression and drug resistance. The mitogen-activated protein kinase (MAPK) signalling pathway is frequently dysregulated in human malignant tumours, which induces genomic instability, but it remains unclear whether a close relationship exists between MAPK signalling and DMs. In the present study, we focused on three major components of MAPK signalling, ERK1/2, JNK1/2/3 and p38, to investigate the relationship between MAPK and DM production in tumour cells. We found that the constitutive phosphorylation of ERK1/2, but not JNK1/2/3 and p38, was closely associated with DMs in tumour cells. Inhibition of ERK1/2 activation in DM-containing and ERK1/2 constitutively phosphorylated tumour cells was able to markedly decrease the number of DMs, as well as the degree of amplification and expression of DM-carried genes. The mechanism was found to be an increasing tendency of DM DNA to break, become enveloped into micronuclei (MNs) and excluded from the tumour cells during the S/G2 phases of the cell cycle, events that accompanied the reversion of malignant behaviour. Our study reveals a linkage between ERK1/2 activation and DM stability in tumour cells.