Clinical features and survival of patients with multiple primary malignancies

BACKGROUND Multiple primary malignancies(MPM)are characterized by two or more primary malignancies in the same patient,excluding relapse or metastasis of prior cancer.We aimed to elucidate the clinical features and survival of MPM patients.AIM To elucidate the clinical features and survival of MPM patients.METHODS A retrospective study of MPM patients was conducted in our hospital between June 2016 and June 2019.Overall survival(OS)was calculated using the Kaplan-Meier method.The log-rank test was used to compare the survival of different groups.RESULTS A total of 243 MPM patients were enrolled,including 222 patients with two malignancies and 21 patients with three malignancies.Of patients with two malignancies,51(23.0%)had synchronous MPM,and 171(77.7%)had metachronous MPM.The most common first cancers were breast cancer(33,14.9%)and colorectal cancer(31,14.0%).The most common second cancers were non-small cell lung cancer(NSCLC)(66,29.7%)and gastric cancer(24,10.8%).There was no survival difference between synchronous and metachronous MPM patients(36.4 vs 35.3 mo,P=0.809).Patients aged>65 years at diagnosis of the second cancer had a shorter survival than patients≤65 years(28.4 vs 36.4 mo,P=0.038).Patients with distant metastasis had worse survival than patients without metastasis(20.4 vs 86.9 mo,P=0.000).Following multivariate analyses,age>65 years and distant metastasis were independent adverse prognostic factors for OS.CONCLUSION During follow-up of a first cancer,the occurrence of a second or more cancers should receive greater attention,especially for common concomitant MPM,to ensure early detection and treatment of the subsequent cancer.

Overexpression of IQGAP1 in human pancreatic cancer

BACKGROUND:Pancreatic cancer is a highly aggressive malignant tumor with the lowest survival rate.A better understanding of the molecular mechanisms which contribute to pancreatic cancer occurrence and progression will aid in the development of new approaches to the early diagnosis,prevention,and treatment of this deadly disease.The scaffold protein IQGAP1 shows elevated levels in a variety of cancer types.Currently,we investigated whether or not IQGAP1 is also overexpressed in pancreatic cancer.METHODS:IQGAP1 expression was examined in pancreatic cancer and normal tissues adjacent to cancerous tissues(adjacent tissues)by Western blotting and real-time RT-PCR as well as in paraffin sections of tissue microarray by immunohistochemistry.The correlations between IQGAP1 expression and various clinicopathological characteristics were analyzed.RESULTS:Western blotting and real-time RT-PCR revealed that the levels of IQGAP1 protein and mRNA expression in pancreatic cancer tissues were significantly increased compared with adjacent tissues.Immunohistochemistry analysis on tissue microarray showed that IQGAP1 protein expression was significantly higher in pancreatic cancer(80.0%,48/60)compared with adjacent tissues(18.3%,11/60)(P【0.001).Moreover,overexpression of IQGAP1 was shown to be associated with the grades of tumor differentiation(P【0.05).CONCLUSION:The overexpression of IQGAP1 may play an important role in pancreatic cancer occurrence and progression,and IQGAP1 may serve as a novel molecular target for the diagnosis and treatment of pancreatic cancer.

Comparative analysis of constitutes and metabolites for traditional Chinese medicine using IDA and SWATH data acquisition modes on LC-Q-TOF MS

Identification of components and metabolites of traditional Chinese medicines(TCMs)employing liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF MS)techniques with information-dependent acquisition(IDA)approaches is increasingly frequent.A current drawback of IDA-MS is that the complexity of a sample might prevent important compounds from being triggered in IDA settings.Sequential window acquisition of all theoretical fragment-ion spectra(SWATH)is a dataindependent acquisition(DIA)method where the instrument deterministically fragments all precursor ions within the predefined m/z range in a systematic and unbiased fashion.Herein,the superiority of SWATH on the detection of TCMs’components was firstly investigated by comparing the detection efficiency of SWATH-MS and IDA-MS data acquisition modes,and sanguisorbin extract was used as a mode TCM.After optimizing the setting parameters of SWATH,rolling collision energy(CE)and variable Q1 isolation windows were found to be more efficient for sanguisorbin identification than the fixed CE and fixed Q1 isolation window.More importantly,the qualitative efficiency of SWATH-MS on sanguisorbins was found significantly higher than that of IDA-MS data acquisition.In IDA mode,18 kinds of sanguisorbins were detected in sanguisorbin extract.A total of 47 sanguisorbins were detected when SWATH-MS was used under rolling CE and flexible Q1 isolation window modes.Besides,26 metabolites of sanguisorbins were identified in rat plasma,and their metabolic pathways could be deduced as decarbonylation,oxidization,reduction,methylation,and glucuronidation according to their fragmental ions acquired in SWATH-MS mode.Thus,SWATH-MS data acquisition could provide more comprehensive information for the component and metabolite identification for TCMs than IDA-MS.

Durable response to pulsatile icotinib for central nervous system metastases from EGFR-mutated non-small cell lung cancer: A case report

BACKGROUND Central nervous system(CNS) metastases are a catastrophic complication of nonsmall cell lung cancer(NSCLC), including brain and leptomeningeal carcinomatosis, and are always accompanied by a poor prognosis. Despite the continuous development of existing treatments, the therapy of CNS metastases remains challenging.CASE SUMMARY We report a patient who was definitively diagnosed with brain and leptomeningeal metastases from NSCLC with a targeted mutation in epidermal growth factor receptor(EGFR). A standard dosage of icotinib(125 mg three times daily) was implemented but ineffective. CNS lesions developed despite stable systemic control, so pulsatile icotinib(1125 mg every 3 d) was administered. This new strategy for administration has lasted 25 mo so far, and resulted in complete remission of neurological symptoms, almost vanished lesions, and longer survival with no notable side effects.CONCLUSION This is the first successful example of pulsatile icotinib for treating isolated CNS progression from EGFR mutation-positive NSCLC, providing a new alternative for the local treatment of CNS metastases.

Pathological changes in the brain after peripheral burns

Brain injuries are common complications in patients with thermal burns and are associated with unpleasant outcomes.In clinical settings,it was once believed that brain injuries were not major pathological processes after burn,at least in part due to the unavailability of specific clinical manifestations.Burn-related brain injuries have been studied for more than a century,but the underlying pathophysiology has not been completely clarified.This article reviews the pathological changes in the brain following peripheral burns at the anatomical,histological,cytological,molecular and cognitive levels.Therapeutic indications based on brain injury as well as future directions for research have been summarized and proposed.

Meiotic nuclear divisions 1(MND1)fuels cell cycle progression by activating a KLF6/E2F1 positive feedback loop in lung adenocarcinoma

Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD.Methods:The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus(GEO)datasets and The Cancer Genome Atlas(TCGA)data were combined,and a promising risk biomarker called meiotic nuclear divisions 1(MND1)was selectively acquired.Cell viability assays and subcutaneous xenograftmodelswere used to validate the oncogenic role ofMND1 in LUADcell proliferation and tumor growth.Aseries of assays,including mass spectrometry,co-immunoprecipitation(Co-IP),and chromatin immunoprecipitation(ChIP),were performed to explore the underlying mechanism.Results:MND1 up-regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis.In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle.The results of the Co-IP,ChIP and dual-luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel-like factor 6(KLF6),and thereby protecting E2F transcription factor 1(E2F1)from KLF6-induced transcriptional repression.Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner.Conclusions:MND1,KLF6,and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD.MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.