Hexazinone is a post-emergence herbicide/arboricides, and its acute poisoning has rarely been reported. Hexazinone is low-toxic to humans, but mass intake of hexazinone would still lead to organ impairment. This article analyzes a case of acute hexazinone poisoning from the poisoning treatment center of our hospital, and summarizes the symptoms and treatment effects of hexazinone poisoning, which is aimed at improving the comprehension, diagnosis and treatment of the disease.
Administration, Oral ; Herbicides ; Humans ; Poisoning ; Triazines

OBJECTIVE: To investigate the antileukemia activity of phosphatidylinositol-3 kinase (PI3K) inhibitor ZSTK474 on human leukemia cell line U937. METHODS: MTT, soft agar assay, flow cytometric analysis and western blot were used to detect the effect of ZSTK474 on U937 cell proliferation, tumorigenicity, cell cycle, cell apoptosis and phosphorylation levels of the key factor of PI3K/AKT pathway. Chou-Talalay method was used to evaluate the combination of ZSTK474 with Cytarabine or Homoharringtonine. RESULTS: PI3K inhibitor ZSTK474 could inhibit the proliferation and tumorigenicity of U937 cell, induce G CONCLUSION ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Glycogen Synthase Kinase 3 beta ; Humans ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Triazines ; U937 Cells

Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1∶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P=0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P=0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use* ; China ; Female ; Gastrointestinal Stromal Tumors/genetics* ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local ; Prognosis ; Proto-Oncogene Proteins c-kit/genetics* ; Pyrazoles ; Pyrroles ; Receptor, Platelet-Derived Growth Factor alpha/genetics* ; Retrospective Studies ; Triazines

OBJECTIVE: To study the effects of the overexpression of autophagy-related gene 3 (ATG3) on autophagy and salinomycin-induced apoptosis in breast cancer cells and explore the underlying mechanisms. METHODS: We used the lentivirus approach to establish a breast cancer cell line with stable overexpression of ATG3. Western blotting, immunofluorescence staining and transmission electron microscopy were used to analyze the effect of ATG3 overexpression on autophagy in breast cancer MCF-7 cells. Using the AKT/mTOR agonists SC79 and MHY1485, we analyzed the effect of AKT/mTOR signal pathway activation on ATG3 overexpression-induced autophagy. Western blotting and flow cytometry were used to analyze the effect of autophagy on apoptosis of the ATG3-overexpressing cells treated with salinomycin and 3-MA (an autophagy inhibitor). RESULTS: In ATG3-overexpressing MCF-7 cells, ATG3 overexpression obviously promoted autophagy, inhibited the AKT/mTOR signaling pathway, significantly weakened salinomycin-induced apoptosis ( < 0.01), caused significant reduction of the levels of the pro-apoptotic proteins cleaved-caspase 3 ( < 0.01) and Bax ( < 0.05), and enhanced the expression of the anti-apoptotic protein Bcl-2 ( < 0.05). The inhibition of autophagy obviously weakened the inhibitory effect of ATG3 overexpression on salinomycin-induced apoptosis. CONCLUSIONS ATG3 overexpression promotes autophagy possibly by inhibiting the AKT/mTOR signaling pathway to decrease salinomycin-induced apoptosis in MCF-7 cells, suggesting that autophagy induction might be one of the mechanisms of drug resistance in breast cancer cells.
Acetates ; pharmacology ; Apoptosis ; drug effects ; genetics ; Autophagy ; drug effects ; Autophagy-Related Proteins ; metabolism ; Benzopyrans ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation ; Humans ; MCF-7 Cells ; Morpholines ; pharmacology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; metabolism ; Pyrans ; pharmacology ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism ; Triazines ; pharmacology ; Ubiquitin-Conjugating Enzymes ; metabolism

Prostate cancer is the second most common cancer in men worldwide. There are many occupational factors that have been suggested to cause prostate cancer. Our aim was to evaluate the evidence for causality by a literature review of occupational factors. We searched literature in Medline and SCOPUS from 1966 to June 30, 2015 to identify occupational risk factors for prostate cancer. The following risk factors were selected: farmers/agricultural workers, pesticides – whole group, and separately organophosphate and organochlorine pesticides, carbamates and triazines, cadmium, chromium, cutting fluids, acrylonitrile, rubber manufacturing, whole body vibration, shift work, flight personnel, ionizing radiation, and occupational physical activity. For each factor a literature search was performed and presented as meta-analysis of relative risk and heterogeneity (Q and I² index). A total of 168 original studies met the inclusion criteria with 90,688 prostate cancer cases. Significantly increased risks were observed for the following occupational exposures: pesticides (metaRR = 1.15, 95% confidence interval [CI] = 1.01–1.32; I² = 84%), and specifically group of organochlorine pesticides (meta relative risk [metaRR] = 1.08, 95% CI = 1.03–1.14; I² = 0%), chromium (metaRR = 1.19, 95% CI = 1.07–1.34; I² = 31%), shift work (metaRR = 1.25, 95% CI = 1.05–1.49; I² = 78%) and pilots (metaRR = 1.41, 95% CI = 1.02–1.94; I² = 63%) and occupational physical activity in cohort studies (metaRR = 0.87, 95% CI = 0.81–0.94; I² = 0%). The literature review supports a causal association for a few of the previously suggested factors.
Acrylonitrile ; Cadmium ; Carbamates ; Chromium ; Cohort Studies ; Epidemiologic Studies ; Humans ; Male ; Motor Activity ; Occupational Exposure ; Pesticides ; Population Characteristics ; Prostate ; Prostatic Neoplasms ; Radiation, Ionizing ; Risk Factors ; Rubber ; Triazines ; Vibration

A case of a 17-year-old nulligravid with onset of seizure episodes since menarcheis reported. She was diagnosed with Seizure Disorder treated with Phenobarbital and was seizure free for 2 years. Two years prior to consult, seizure recurrences were noted to coincide with menstruation, hence, was diagnosed with Catamenial Epilepsy. Patient was shifted to Lamotrigine but seizure exacerbations were still observed, prompting referral to the Reproductive Medicine service for adjunctive hormonal therapy. Depot medroxyprogesterone acetate was added to the antiepileptic drug which provided seizure control. Adjunctive hormonal therapy proved to be helpful in the management of intractable seizures in this patient.

The report aims to give a better understanding of the neuroactive properties of estrogen and progesterone and its role in the development of Catamenial Epilepsy. Gender-related and psychosocial issues in the treatment of Epilepsy in the child-bearing years up to the menopause are also discussed.

Human ; Female ; Adolescent ; Anticonvulsants ; Seizures ; Progesterone ; Lamotrigine ; Medroxyprogesterone Acetate ; Menstruation ; Epilepsy ; Triazines ; Phenobarbital ; Menopause ; Estrogens ; Reproductive Medicine

A case of a 17-year-old nulligravid with onset of seizure episodes since menarcheis reported. She was diagnosed with Seizure Disorder treated with Phenobarbital and was seizure free for 2 years. Two years prior to consult, seizure recurrences were noted to coincide with menstruation, hence, was diagnosed with Catamenial Epilepsy. Patient was shifted to Lamotrigine but seizure exacerbations were still observed, prompting referral to the Reproductive Medicine service for adjunctive hormonal therapy. Depot medroxyprogesterone acetate was added to the antiepileptic drug which provided seizure control. Adjunctive hormonal therapy proved to be helpful in the management of intractable seizures in this patient.

The report aims to give a better understanding of the neuroactive properties of estrogen and progesterone and its role in the development of Catamenial Epilepsy. Gender-related and psychosocial issues in the treatment of Epilepsy in the child-bearing years up to the menopause are also discussed.

Human ; Female ; Adolescent ; Anticonvulsants ; Seizures ; Progesterone ; Lamotrigine ; Medroxyprogesterone Acetate ; Menstruation ; Epilepsy ; Triazines ; Phenobarbital ; Menopause ; Estrogens ; Reproductive Medicine

OBJECTIVETo investigate the efficacy and safety of lamotrigine monotherapy in children with epilepsy via a systematic review.

METHODSPubMed, Cochrane, CNKI, VIP, CBM, Wanfang Data were searched for randomized controlled trials (RCTs) of lamotrigine monotherapy in children with epilepsy. Literature screening, data extraction, and quality assessment were performed according to the method recommended by Cochrane Collaboration. RevMan 5.2 software was used to conduct the Meta analysis.

RESULTSA total of 9 RCTs involving 1 016 participants were included. Lamotrigine yielded a significantly lower complete control rate of seizure than ethosuximide, but the complete control rate of seizure showed no significant differences between lamotrigine and carbamazepine/sodium valproate. Patients treated with lamotrigine had a significantly lower incidence rate of adverse events than those treated with carbamazepine, but the incidence rate of adverse events showed no significant differences between patients treated with lamotrigine and sodium valproate/carbamazepine. The drop-out rate showed no significant differences between the three treatment groups.

CONCLUSIONSLamotrigine is an ideal alternative drug for children who do not respond to traditional antiepileptic medication or experience significant adverse reactions; however, more high-quality RCTs with a large sample size and a long follow-up time are needed to confirm these conclusions.

Anticonvulsants ; therapeutic use ; Epilepsy ; drug therapy ; Humans ; Randomized Controlled Trials as Topic ; Triazines ; adverse effects ; therapeutic use

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. RESULTS: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.
Adult ; Aged ; *Alleles ; Allopurinol/adverse effects/*pharmacology ; Anticonvulsants/*adverse effects ; Asian Continental Ancestry Group/*genetics ; Carbamazepine/adverse effects/*pharmacology ; Case-Control Studies ; Drug-Related Side Effects and Adverse Reactions/*genetics/immunology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; HLA-B Antigens/*genetics ; Humans ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Stevens-Johnson Syndrome/ethnology/etiology/*genetics ; Triazines/adverse effects/*pharmacology

UNLABELLEDObjetive: To investigate the effects of PKF118-310 on cell cycle and proliferation of K562 cell lines and its mechanism.

METHODSAfter treatment of PKF118-310 with different concentration, the proliferation inhibition on K562 cell lines was detected by MTT, the existance of β-catenin and TCF-4 in the cells was observed by immunohistochemistry. The change of the cell cycle was detected by flow cytometry. The expressions of caspase-3, β-catenin, TCF and BCL-9 were detected by Western blot.

RESULTSPKF118-310 can inhibit the proliferation of K562 cell line by S phase blocking. The β-catenin and TCF in the cells were observed by immunohistochemistry. After treating this cell line with PKF118-310 of different concentrations for 72 h, the expression level of caspase-3 increased, the expression levels of β-catenin, TCF and BCL-9 significantly decreased.

CONCLUSIONPKF118-310 induces cycle arest of K562 cells at the S phase and inhibits the proliferation of these cells through decreasing β-catenin/TCF/BCL-9 thrascriptional activity.

Caspase 3 ; Cell Cycle ; Cell Proliferation ; Humans ; K562 Cells ; Pyrimidinones ; Triazines ; beta Catenin