Effect of propofol on sensitivity of glioma cells to temozolomide and the role of lncRNA-GAS5 / 中华麻醉学杂志

Objective:To evaluate the effect of propofol on the sensitivity of glioma cells to temozolomide and the role of long noncoding RNAs (lncRNAs)-growth arrest-specific transcript 5 (GAS5) in it.Methods:Human glioma cell line U251 were cultured in vitro and seeded in 6-, 24- or 96-well plates at a density of 1×10 5 cells/ml, and were divided into 5 groups ( n=30 each) using a random number table method: control group (group C), temozolomide group (group T), propofol + temozolomide group (group PT), negative-siRNA + propofol + temozolomide group (group NPT) and GAS5-siRNA + propofol + temozolomide group (group GPT). The U251 cells in group C were cultured in the common culture medium.In group T, temozolomide 400 μmol/L was added to the culture medium.In group PT, the cells were cultured with propofol 8 μg/ml first and then with temozolomide 400 μmol/L.In group NPT and group GPT, U251 cells were transfected with negative-siRNA and GAS5-siRNA, respectively, and then cultured in the same way as previously described in group PT.The expression of lncRNA-GAS5 in U251 cells was detected by quantitative real-time polymerase chain reaction, the cell survival rate was measured by CCK-8 assay, the apoptosis rate was determined by flow cytometry, cell invasion was determined by Transwell invasion assay, and the expression of c-Myc, glutathione S-transferase mu 3 (GSTM3) and P21 was detected by Western blot. Results:Compared with group C, the cell survival rate was significantly decreased, the apoptosis rate was increased, the number of invasive cells was decreased, the expression of c-Myc and GSTM3 was down-regulated, and the expression of P21 and lncRNA-GAS5 was up-regulated in the other four groups ( P<0.05). Compared with group T, the cell survival rate was significantly decreased, the apoptosis rate was increased, the number of invasive cells was decreased, the expression of c-Myc and GSTM3 was down-regulated, and the expression of P21 and lncRNA-GAS5 was up-regulated in group PT and group NPT ( P<0.05). Compared with group PT, the cell survival rate was significantly increased, the apoptosis rate was decreased, the number of invasive cells was increased, the expression of c-Myc and GSTM3 was up-regulated, and the expression of P21 and lncRNA-GAS5 was down-regulated in group GPT ( P<0.05), and no significant change was found in the parameters mentioned above in group NPT ( P>0.05). Conclusions:Propofol can enhance the sensitivity of glioma cells to temozolomide, and the expression of lncRNA-GAS5 is involved in the process.

Chinese expert consensus on bendamustine for the treatment of lymphoma (2020 version) / 白血病·淋巴瘤

Bendamustine, a bifunctionnal molecule with alkylating agent and antimetabolites properties, has shown a better efficacy in many pathological types of lymphomas. Many studies have shown the better efficacy of bendamustine with or without other agents in the treatment of lymphomas including indolent non-Hodgkin lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma. In 2008, bendamustine was approved by Food and Drug Administration of the United States for the treatment of patients with rituximab-resistant indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia. However, bendamustine was not approved for the treatment of lymphomas in China unitil 2018, and most physicians had little clinical experience on the use of this agent. Based on the results of clinical trials of bendamustine in China and the relevant domestic and foreign literatures, the Chinese hematologists and oncologists developed the Chinese expert consensus on bendamustine for the treatment of lymphomas (2020 version).

Marine drugs for cancer: surfacing biotechnological innovations from the oceans

This review will discuss the contributions of marine natural molecules, a source only recently found to have pharmaceutical prospects, to the development of anticancer drugs. Of the seven clinically utilized compounds with a marine origin, four are used for the treatment of cancer. The development of these drugs has afforded valuable knowledge and crucial insights to meet the most common challenges in this endeavor, such as toxicity and supply. In this context, the development of these compounds will be discussed herein to illustrate, with successful examples provided by cytarabine, trabectedin, eribulin and brentuximab vedotin, the steps involved in this process as well as the scientific advances and technological innovation potential associated with developing a new drug from marine resources.

Differences between NMRI and DBA/2J mice in the development of somites and susceptibility to methylnitrosourea-induced skeleton anomalies

ABSTRACT The development of DBA/2J mouse strain embryos is nearly 12 h - or 6 somite pairs - delayed as compared to the outbred NMRI mouse embryos of the same age on gestation days (GD) 8-12. To evaluate inter-strain differences in susceptibility to teratogens, dams were treated with methylnitrosourea (MNU, 5 mg/kg body weight i.p.) on defined gestation days (NMRI: GD 9, 91/2 or 10; DBA/2J: GD 10 or 101/2). Skeletal anomalies produced by MNU on both mouse strains varied with the GD of treatment. The pattern of anomalies produced by MNU on a given GD markedly differed between the two mouse strains, yet they were similar -with a few exceptions- when exposures at equivalent embryonic stages are compared. Findings from this study indicated that strain-dependent differences in the developmental stage of mouse embryos of the same gestational age occur, a possibility that has been often neglected when inter-strain differences in susceptibility to developmental toxicants are interpreted.

Avaliação da expressão do gene MGMT nos tecidos normal e neoplásico de doentes com câncer colorretal / Evaluation of the expression of the MGMT gene in normal and neoplastic tissue of patients with colorectal cancer

OBJETIVO: Avaliar a expressão tecidual do gene de reparo MGMT comparando a mucosa cólica normal e neoplásica em doentes com câncer colorretal. MÉTODOS: Foram estudados 44 portadores de adenocarcinoma colorretal confirmado por estudo histopatológico. Foram excluídos doentes suspeitos de pertencerem a famílias com câncer colorretal hereditário (HNPCC e PAF) e os portadores de câncer do reto médio e inferior submetidos a tratamento quimioradioterápico neoadjuvante. A expressão do gene MGMT foi avaliada pela técnica da reação de polimerase em cadeia em tempo real (RT-PCR). A comparação dos resultados encontrados para expressão do gene MGMT entre tecidos normais e neoplásicos foi feita pelo teste t de Student pareado, adotando-se nível de significância de 5% (p <0,05). RESULTADOS: A expressão tecidual do gene MGMT em todos os doentes foi menor no tecido neoplásico quando comparada a do tecido normal (p=0,002). CONCLUSÃO: O gene de reparo MGMT encontra-se menos expresso no tecido neoplásico quando comparados aos tecidos normais em portadores de CCR esporádico.

OBJECTIVE: To evaluate the expression of tissue repair gene MGMT by comparing normal and neoplastic colonic mucosa in patients with colorectal cancer (CRC). METHODS: We studied 44 patients with colorectal cancer confirmed by histopathology. We excluded patients suspected of belonging to families with hereditary colorectal cancer (HNPCC and FAP) and patients with cancer of the lower or medium rectum treated with neoadjuvant chemoradiotherapy. The MGMT gene expression was assessed by the technique of polymerase chain reaction in real time (RT-PCR). The comparison of results for MGMT gene expression between normal and neoplastic tissues was made by paired Student's t test, adopting a significance level of 5% (p <0.05). RESULTS: Tissue expression of the MGMT gene in all patients was lower in tumor tissue when compared to normal tissue (p = 0.002). CONCLUSION: The repair gene MGMT is less expressed in tumor tissue compared to normal tissues in patients with sporadic CRC.

Therapy related myelodysplastic syndrome: A case report and review of literature.

Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS) 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

A Case of Therapy-related Myeloid Neoplasm after Successful Treatment of Acute Promyelocytic Leukemia

Acute promyelocytic leukemia (APL) is considered as a curative disease after combined chemotherapy based on all-trans retinoic acid (ATRA) and anthracycline. However, as long-term survivors continue to increase, reports on sporadic cases of therapy-related myeloid neoplasm (t-MN) after successful APL treatment are also increasing. Recently, we have experienced one patient who developed t-MN 7 yr after APL diagnosis. Even though he had not been exposed to alkylating agents at all, he showed alkylating agents-associated features such as long latency period (>5 yr), first presentation as myelodysplatic phase (multilineage dysplasia with increased blasts), and complex karyotype including monosomy 5 and 7. He received only supportive care and expired 3 months after the diagnosis of t-MN (6 months of survival after the onset of cytopenias). t-MN after complete remission of APL is a rare but fatal complication, and patients with complex karyotypes show ominous prognosis in particular. For the early diagnosis of t-MN, long-term and close monitoring of the patient is needed. One should suspect this late complication whenever any unknown cytopenia develops, and should perform bone marrow biopsy and cytogenetic analysis.

Tratamiento del síndrome nefrótico idiopático / Treatment of the idiopathic nephrotic syndrome

A pesar de los años transcurridos desde la descripción del síndrome nefrótico, del desarrollo de la industria farmacéutica y de los medicamentos con que se cuenta para enfrentar esta glomerulopatía, todavía existen pacientes de muy difícil tratamiento, que obligan a utilizar diferentes fármacos sin que se pueda asegurar con exactitud la respuesta en cada caso. Los pacientes que no responden a los esteroides constituyen un grupo especial y de difícil control, pero los que presentan recaídas frecuentes o corticodependencia también obligan en muchas ocasiones al empleo de otros medicamentos con toxicidad especial y respuesta no precisa. Por tal motivo se considera de interés esta revisión sobre los fármacos que con mayor frecuencia se pueden utilizar y sobre la indicación de cada uno de ellos. Sin pretender agotar el tema, se trata de llevar al pediatra una posible guía para el tratamiento de los casos de difícil control.

Despite the years passed from the description of nephrotic syndrome, the development of pharmaceutical industry and of the drugs available to face this glomerulopathy, still there are patients very difficult to treat, who oblige us to use different drugs without achieve exactly the response in each case. Patients non-respondent to steroids are a special group and of difficult control, but those having frequent relapses or cortico-dependent also oblige us to use another drugs with a special toxicity and non-precise response. Thus, this is considered an interesting review on drugs more frequent used and on prescription of each of them. Without exhaust the subject, we try to offer the pediatricians a possible guide for treatment of cases of difficult control.

A Case of Therapy-related Acute Myeloid Leukemia associated with inv(16) / 대한진단검사의학회지

The inv(16)(p13q22) is found in de novo AML and is closely associated with the FAB subtype M4eo. The inv(16) is rarely reported in therapy-related AML (t-AML) patients. Herein, we report a case of t-AML with inv(16) after combination chemotherapy using antimitotic agent and alkylating agent (cis-platin-paclitaxel) for ovarian serous cystadenocarcinoma.

The Effect of Gadd Genes Expression in Surveillance of DNA Damage Induced by Nitrogen Mustard / 环境与健康杂志

Objective To study the effect of Gadd genes expression in surveillance of DNA damage. Methods The human liver tumor cells were treated with alkylating agent(nitrogen mustard) and total RNA was extracted, the expression levels of Gadd genes were determined by RT-PCR. Results Treated with 1 ng/?l nitrogen mustard for 3 h, 24 h, 48 h respectively and with 1 ng/?l, 5 ng/?l nitrogen mustard for 24 h respectively, the expression levels of Gadd genes increased at first (P0.05). Conclusion Gadd genes expression can be used as the indexes in the surveillance of DNA damage induced by nitrogen mustard.

Low concentration MNNG inhibition of JNK/SAPK is independent of a nuclear signal while MNNG activation of p38MAPK may depend on a nuclear signal* / 中国病理生理杂志

AIM: To identify the effect of alkylating agent N-methyl-N'- nitro-N-nitrosoguanidine (MNNG) with low concentration on JNK/SAPK and p38MAPK and the origins of JNK/SAPK and p38MAPK cascade.METHODS: p38 and JNK kinase activity were detected by immunoprecipitation and Western immunoblotting in intact and enucleated Vero cells.RESULTS: With the same experimental conditions, low concentration of MNNG inhibited JNK kinase in both intact cell and enucleated Vero cell. MNNG activated p38 kinase in intact cell while no effect on p38 kinase in enucleated cell was observed.CONCLUSION: Inhibition of JNK/SAPK by low concentration of MNNG was independ of a nuclear signal while MNNG activation of p38MAPK may depend on a nuclear signal.

Establishment of cell lines whose hREV3 gene expression was inhibited by transfection of antisense RNA expression plasmids and their biological characteristics / 中国病理生理杂志

AIM: to establish the cell lines whose hREV3 gene expression was blocked by antisense RNA and observe their characteristis of cell growth rate and N - methyl - N' - nitrosoguanidine (MNNG) sensitivi- ty . METHODS: With modified calcium phosphate - DNA coprecipitation method the eukaryocytic expression plasmid expressing antisense fragment of hREV3,pBK - RSV - hREV3- and pMAMneo - amp hREV3 were transfected into human embryo kidney cell line of HEK - 293. After G418 selection, cell lines of 293 - B - hREV3- and 293 - M hREV3- were established. By cell counting method, the cell growth rate and MNNG sensitivity of these cell lines were characterized. RESULTS: No change of cell growth rates of these cell lines was observed whether hREV3 gene expres- sion was blocked by either the persistent or induced expression of the antisense hREV3 RNA. While the sensitivity of these cell lines to MNNG was somewhat elevated, as compared with their parent cell line 293 and the cell lines trans- fected with vector DNAs. CONCLUSION: The gene product of hREV3 was not essential for the cell growth, but it may play a role in the DNA repair functions of the cells after exposure to DNA damaging agents.