Exosome-derived non-coding RNA-mediated chemotherapy resistance in cancer: research advances / 国际药学研究杂志

The drugresistance caused by the long-term application of chemotherapeutic drugs is still the obstacle and problem of current tumor treatment. Therefore, elucidating the mechanism of tumor drug resistance to establish strategies to overcome or reverse tumor drug resistance has always been an urgent issue in tumor treatment. Exosome is one of the research hotspots in recent years. Exosome carries a variety of biologically active substances, such as non-coding RNA(ncRNA), DNA, and protein, and is an important medium of signal transmission between cells, which regulates a variety of physiological processes and pathological activities in the body. Particularly, the ncRNA in exosomes secreted by tumor cells affects the tumor angiogenesis, immune escape and metastasis phenotypes, and also mediates tumor cell resistance. This article reviews recent studies on exosomes-derived ncRNA-mediated antineoplastic drug resistance to clarify the role of exosomes in tumor resistance, aiming to provide a reference for the development of antitumor drugs and the improvement of efficacy of tumor chemotherapy.

Advances in research on anti-tumor drug-related renal injury / 医学研究生学报

Novel antineoplastic drugs have significantly prolonged the survival time of cancer patients. Meanwhile, nephrotoxicity of antineoplastic drugs and its adverse effects on the prognosis of cancer patients have received increasing attention. Conventional chemotherapy causes kidney injury mainly through direct renal toxicity, while new anti-tumor drugs can induce a number of kidney damage, including acute renal tubular injury, thrombotic microangiopathy, interstitial nephritis, and glomerular diseases through multiple mechanisms. Clinicians must be knowledgeable in the renal toxicity of antineoplastic drugs to minimize the nephrotoxicity of the drugs and diagnose early, especially in patients with underlying kidney disease. This article focuses on the risk factors, clinical and histological patterns, pathogenesis, prevention and treatment of renal injury associated with the antineoplastic drugs, especially novel targeted antineoplastic drugs.

O sofrimento e espiritualidade de pacientes com câncer em tratamento quimioterápico: sistematização da assistência de enfermagem na dimensão espiritual / The suffering and spirituality of cancer patients in chemotherapy treatment: systematization of nursing care in the spiritual dimension

Introdução: O sofrimento dos pacientes com câncer tem múltiplas dimensões e envolve aspectos físicos, sociorrelacionais, espirituais, psicológicos e emocionais. A atuação do enfermeiro nesta área deve, portanto, transcender o simples objetivo de controle dos efeitos tóxicos. Objetivo: Desvelar o significado de sofrimento vivenciado por pacientes em tratamento quimioterápico no INCA; identificar as associações existentes entre as Experiências Subjetivas de Sofrimento mensuradas no Inventário IESSD, varáveis clínicas, sociodemográficas e o Coping Religioso/Espiritual adotado pelos participantes por meio da escala CRE-Breve. Método: Trata-se de um estudo misto, segundo a estrutura paralela convergente descrita por Creswell, em que os dados quantitativos e qualitativos são coletados simultaneamente, para depois serem comparados com o objetivo de determinar convergências, diferenças e combinações. O presente estudo se baseou em uma amostra de 100 pacientes, dentre os quais, 18 integraram a entrevista qualitativa. Foram incluídos pacientes com indicação de quimioterapia antineoplásica (QTA), boa orientação temporoespacial, ausência de patologia psiquiátrica diagnosticada e boa capacidade cognitiva. Foram excluídos indivíduos com Performance Status maior que 3. Para compreensão do sofrimento, foi utilizado o referencial fenomenológico de Merleau-Ponty. Resultados: Da análise qualitativa emergiram 13 categorias temáticas. No que tange aos achados quantitativos, o Sofrimento Global apresentou uma correlação significativa muito fraca e positiva com o CREN. Este estilo de enfrentamento, por sua vez, teve uma correlação significativa muito fraca com o Sofrimento Psicológico, Sofrimento Existencial e Sofrimento Físico. O Sofrimento Global não se correlacionou ao CREP total, e o mesmo apresentou uma correlação significativa negativa com a Experiência Positiva de Sofrimento. A Experiência Positiva de Sofrimento foi dimensão com maiores médias no inventário IESSD, sendo o Sofrimento Sociorrelacional a causa de maior angústia para os pacientes que responderam ao referido instrumento. Considerações finais: Foi possível obter, na interpretação final desta investigação, metainferências derivadas da fusão dos dois bancos de dados. Ficou claro que os pacientes nutrem um nível de esperança alto, enquanto realizam o tratamento quimioterápico, independente de seus objetivos e duração. A presença de dor e fadiga aumenta a percepção de sofrimento durante o tratamento, levando a sentimentos de inutilidade e de isolamento social, quando de sua coexistência. Os resultados qualitativos e quantitativos também corroboraram para o entendimento de que os pacientes se encontram mais vulneráveis ao sofrimento no início do tratamento, devido à desinformação, ao medo, aos sinais e sintomas exacerbados da doença, e uma longa jornada para o diagnóstico. Como produto final, foi proposta uma nova intervenção de enfermagem, denominada "Aconselhamento espiritual e emocional". Esta intervenção é mais específica e derivada da intervenção "Aconselhamento", já descrita na classificação NIC desde 1992. As atividades sugeridas foram elaboradas a partir dos resultados quantitativos e das categorias fenomenológicas encontradas, contribuindo desta forma, para com uma abordagem diferenciada e sitematizada dirigida à pacientes em QTA

Introduction: The cancer patients´ suffering has multiple dimensions, and involves physical, social-relational, spiritual, psychological and emotional aspects. The nurse performance in this area should therefore go beyond the simple objective to control the toxic effects of the treatment. Objective: To reveal the meaning of the suffering experienced by patients undergoing chemotherapy at the INCA; identify the associations existing among the Subjective Experiences of Suffering measured in the IESSD Inventory, clinical, social-demographical variables and the Religious/Spiritual Coping adopted by the participants using the RSC-Brief Scale. Method: This is a mixed study according to the convergent parallel described by Creswell, in which the quantitative and qualitative data are collected simultaneously, being then compared with the aim of determining convergences, differences and combinations. The current study was based on a sample of 100 patients, of which, 18 integrated the qualitative interview. We included patients with indication for chemotherapy, good orientation in time and space, absence of diagnosed psychiatric pathology and good cognitive ability. Individuals with Performance Status greater than 3 were excluded. For understanding the suffering, we used the phenomenological referential of Merleau-Ponty. Results: From the qualitative analysis, 13 thematic categories emerged. With regard to the quantitative findings, the Global Suffering presented a significant very weak correlation with NRSC. This coping style, in turn, presented a significant very weak correlation with the Psychological Suffering, Existential Suffering and Physical Suffering. The Global Suffering not correlated with total PRSC; and the same presented a negative significant correlation with the Positive Experience of Suffering. The Positive Experience of Suffering was the dimension with the highest averages in the IESSD inventory, being the Social-Relational Suffering the main distress cause for the patients who responded to this tool. Final considerations: It was possible to obtain meta-inferences derived from the fusion of the two database. It became clear that patients foster a high level of hope while submit to chemotherapy, independent of their objectives and duration. The presence of pain and fatigue increase the perception of suffering during the treatment, leading to feelings of uselessness and social isolation when they coexist. The qualitative and quantitative results also corroborated to understand that patients are more vulnerable to the suffering at the beginning of treatment, due to the disinformation, fear, exacerbated signs and symptoms of the disease, and a long journey to the diagnosis. As a final product, a new nursing intervention, called "Spiritual and Emotional Counseling", was proposed. This intervention is more specific and derived from the "Counseling" intervention, already described in the NIC classification since 1992. The suggested activities were elaborated from the quantitative results and from the phenomenological categories found, thus contributing to a differentiated and systemized approach directed to the patients on antineoplastic chemotherapy

Introducción: El sufrimiento de los pacientes con cáncer tiene múltiples dimensiones, y implica aspectos físicos, socio-relacionales, espirituales, psicológicos e emocionales. La actuación del enfermero en esta área debe, por lo tanto, trascender el simples objetivo de controle de los efectos tóxicos del tratamiento. Objetivo: Desvelar el significado de sufrimiento experimentado por pacientes en tratamiento quimioterápico en el INCA; identificar las asociaciones existentes entre las Experiencias Subjetivas de Sufrimiento mensuradas en el Inventario IESSD, variables clínicas, sociodemográficas y el Coping Religioso/Espiritual adoptado por los participantes a través de la escala CRE-Breve. Método: Se trata de un estudio mixto según la estructura paralelo-convergente descrita por Creswell, en que los datos cuantitativos y cualitativos son recogidos simultáneamente, para después ser comparados con el objetivo de determinar convergencias, diferencias y combinaciones. El presente estudio se basó en una muestra de 100 pacientes, entre los cuales, 18 integraron la entrevista cualitativa. Se incluyeron pacientes con indicación de quimioterapia, buena orientación tempo-espacial, ausencia de patología psiquiátrica diagnosticada y buena capacidad cognitiva. Se excluyeron individuos con Performance Status mayor que 3. Para la comprensión del sufrimiento, fue utilizado el referencial fenomenológico de Merleau-Ponty. Resultados: Del análisis cualitativo emergieron 13 categorías temáticas. En lo que respecta a los hallados cuantitativos, el Sufrimiento Global presentó una correlación significativa muy débil y positiva con el CREN. Este estilo de enfrentamiento, a su vez, tuve una correlación significativa muy débil con el Sufrimiento Psicológico, Sufrimiento Existencial y Sufrimiento Físico. El Sufrimiento Global no se correlacionó con el CREP total; y el mismo presentó una correlación significativa negativa con la Experiencia Positiva de Sufrimiento. La Experiencia Positiva de Sufrimiento fue la dimensión con mayores medias en el inventario IESSD, siendo el Sufrimiento Socio - relacional la causa de mayor angustia para los pacientes que respondieron al referido instrumento. Consideraciones finales: Se pudo obtener en la interpretación final de esta investigación, metainferencias derivadas de la fusión de los dos bancos de datos. Quedó claro que los pacientes nutren un nivel de esperanza alto mientras realizan la quimioterapia, independiente de sus objetivos y duración. La presencia de dolor y fatiga aumentan la percepción de sufrimiento durante el tratamiento, llevando a sentimientos de inutilidad y aislamiento social en cuanto su coexistencia. Los resultados cualitativos y cuantitativos también confirmaron el entendimiento de que los pacientes se encuentran más vulnerables al sufrimiento en el inicio del tratamiento, debido a la desinformación, medo, signos y síntomas exacerbados por la enfermedad, y una longa jornada para el diagnóstico. Como producto final, se propuso una nueva intervención de enfermería, llamada "Asesoramiento Espiritual y Emocional". Esta intervención es más específica y derivada de la intervención "Asesoramiento", ya descrita en la clasificación NIC desde 1992. Las actividades sugeridas fueron elaboradas a partir de los resultados cuantitativos y de las categorías fenomenológicas encontradas, contribuyendo de esta forma a un enfoque diferenciado y sitematizado dirigido a la orientación del pacientes en quimioterapia antineoplásica

Analysis of 15 183 Cases of ADR Caused by Antineoplastic Drugs / 中国药房

OBJECTIVE: To investigate the characteristics and regularity of ADR induced by antineoplastic drugs and provide reference for safe drug use in clinic. METHODS: ADR reports induced by antineoplastic drugs reported by 108 hospitals during Jan. 2009-Dec. 2016 were collected from PLA ADR Monitoring Center. ADR reports were analyzed respectively in respects of types of ADR reports, patients ' gender and age, administration route, occurrence time, types of antineoplastic drug, the situation of patients suffering tumor, systems/organs involved in ADR, clinical manifestations, outcome, etc. RESULTS: Among 15 183 ADR reports, there were 462 cases of new ADR and 2 873 cases of severe ADR; there were 8 039 male (52. 95％) and 7 144 female (47. 05％). The proportion of severe ADR in female (20. 00％) was significantly higher than male (17. 96％), with statistical significance (P=0. 001). ADR was mainly induced by intravenous administration (90. 53％), and mainly occurred 2-＜7 d after medication (23. 00％). Top 3 drug categories in the list of ADR were platinum antineoplastic drugs (25. 63％), plant-derived antineoplastic drugs and its derivative (24. 42％) and anti-metabolism drugs (18. 50％). Male patients mainly suffered from lung cancer, colorectal cancer and gastric cancer; female patients mainly suffered from breast cancer, lung cancer and colorectal cancer. Systems/organs involved in ADR were gastrointestinal system, hematological system and systemic damage. Main clinical manifestations were nausea, vomiting, myelosuppression, skin rash and fever. Totally 92. 57％ of ADR cases were cured and recovered after treatment, and 5 cases died. CONCLUSIONS: Antineoplastic drugs have high incidence of ADR with serious damage. Clinic should strengthen the monitoring of key population and key drugs so as to reduce the occurrence of ADR.

Small molecule 3-phosphoinositide-dependent protein kinase-1 inhibitors / 国际药学研究杂志

3-phosphoinositide-dependent protein kinase-1 (PDK1) is a member of the AGC kinase family. It can activate a variety of other AGC family kinases. It is also an important member of the PI3K / Akt signaling pathway. PDK1 plays an important role in cell growth, proliferation and metabolism, and its abnormal activation is closely related with tumor formation. Thus, PDK1 inhibitors play a certain role in promoting the development of a therapy for cancer. This review describes recent developments of small molecule kinase inhibitors targeting on PDK1.

Analysis of the Application of Antineoplastic Drugs in Patients with Colorectal Cancer in Our Hospital during 2011-2014 / 中国药房

OBJECTIVE:To provide reference for medication and chemotherapy in patients with colorectal cancer. METH-ODS:Through retrospective study,case histories and doctor’s advice of the colorectal cancer patients receiving chemotherapy in our hospital during 2011-2014 were consulted to analyze the chemotherapy,medication and irrational drug use. RESULTS:A total of 593 cases of colorectal cancer patients with chemotherapy frequency of 1 940 times were collected to analyze the choice of che-motherapy regimen mainly from the following aspects:indications of chemotherapy,choice of chemotherapy regimen,chemothera-py process and chemotherapy period. There was 409 cases of irrational drug use according to the analysis of drug dosage,selection of solvents and drug concentration,the unqualified rate was 21.08% . CONCLUSIONS:The medication and chemotherapy in pa-tients with colorectal cancer in our hospital are basically rational,but there are still certain problems and shortcomings. In future clinical applications,the medication and chemotherapy need to be improved.

The efficacy evaluation of common antineoplastic drugs in TACE for primary hepatic carcinoma / 实用肿瘤学杂志

Transarterial chemoembolization is an important treatment for advanced primary hepatic carci -noma.Along with the development of TACE therapy , more and more antineoplastic drugs have been used in transarterial chemoembolization .However,the side effects and the efficacy of the drugs are still not very clear . Therefore,we summarize and compare the mechanism of actions ,efficacies and side effects of these drugs in this paper .

The progress of study on methods to assess occupational exposure to antineoplastic agents / 中国药学杂志

OBJECTIVE: To make a summary evaluation of methods for monitoring occupational exposure to antineoplastic drugs. METHODS: Recent literatures were reviewed, and the key information was extracted, classified and summarized. RESULTS: So far biological monitoring and environmental monitoring are the main sensitive and specific methods to assess occupational exposure to antineoplastic agents. CONCLUSION: It is inevitable for many healthcare workers being exposed to antineoplastic drugs which are mostly cytostatic. Owing to the potential occupational hazard, it is critical to assess this kind of risk precisely. This article is to review the progress of studies on nowadays related assessing methods.

Using thermosensitive chemotherapy agent to improve the effect of radiofrequency ablation for liver tumors：an animal experiment / 介入放射学杂志

Objective To investigate the pathologic mechanism of radiofrequency ablation ( RFA ) combined with intravenous infusion of thermosensitive liposome encapsulated vinorelbine (TL-Vin) in treating liver tumors, and to analyze the effect of combination therapy on the long-term survival rate. Methods H22 liver adenocarcinoma tissue was subcutaneously implanted into ICR mice to establish the animal models. At the first experimental period, 40 mice were randomly and equally divided into 5 groups to receive different therapeutic scheme (using different TL-Vin concentrations). Twenty-four hours after the treatment the tumor specimens were collected, the necrotic areas were measured separately, and the optimal TL-Vin concentration was determined. At the second experimental period, 13 mice were randomly selected to receive treatment. Half an hour after the treatment the tumor tissues were collected and the TL-Vin concentration within the tumor was determined. At the third experimental period, 32 mice were randomly and equally divided into 4 groups, and 90 days after treatment the tumor growth curve was drawn. The survival rate was compared between each other of the groups. Results Compared with pure RFA group, TL-Vin + RFA significantly increased tumor coagulation extent (P0.05). Tumor coagulation area in TL-Vin + RFA group was bigger than that in free-VIN + RFA group at the concentration of 10 mg/kg [(341.8 ± 65.4)mm2 vs (225.3 ± 25.4)mm2, P < 0.01]. In TL-Vin group the coagulation margin was clear. The mean intratumoral Vinorelbine accumulation in TL-Vin + RFA group was 10 folds of that in free-Vin group [(1 156.5 ± 158.3)ng/ml vs (194.5 ± 52.3)ng/ml, P = 0.005]. TL-Vin +RFA had better survival result than that of RFA alone (37.6 ± 20.1 days vs. 23.4 ± 5.0 days, P=0.015), as well as than that of free-Vin + RFA [(37.6 ± 20.1)days vs (23.3 ± 1.2)days, P = 0.016]. Conclusion Thermosensitive liposomal chemotherapies (Vinorelbine) can be selectively delivered at the edge of RFA coagulation area and thus effectively increase RFA-induced tumor coagulation and prolong the end-point survival in experimental mice.

Inhibitory effect of baicalin on fluorouracil resistant HCC cell line BEL-7402/5-Fu and its possible mechanism / 第二军医大学学报

Objective: To investigate the inhibitory effect of baicalin on the fluorouracil (Fu) resistant hepatocarcinoma cell (HCC) BEL-7402/5-Fu and its possible mechanism. Methods: Hepatocarcinoma cell line BEL-7402 and Fu-resistant hepatocarcinoma cell line BEL-7402/5-Fu were cultured in vitro. The inhibitory effect of baicalin on the BEL-7402/5-Fu cells was assessed by MTT assay; the intracellular rhodamine fluorescence intensity was observed by flow cytometry; the expression of MDR1 gene was detected by RT-PCR; and the expression of protein P-glycoprotein (P-gp) was analyzed by Western blotting assay. Adhesion assay was conducted using Matrigel model. Expression of beta 1-integrin and E-CD protein was detected by immuno-fluorescence technique. Results: Baicalin inhibited the proliferation of both BEL-7402 and BEL-7402/5-Fu cells, with IC50 of baicalin being 34.2 mg/L and 36.6 mg/L, respectively. Baicalin (5 mg/L and 10 mg/L) partially reversed the resistance of BEL-7402/5-Fu to Fu, with the reversal folds being 28.6 and 46.7, respectively. Baicalin (5 mg/L and 10 mg/L) increased the sensitivity of BEL-7402 cells to Fu, with the sensitivity-enhancing folds being 1.4 and 2.1, respectively. Baicalin also increased the concentration of rhodamine and expression of integrin β1, inhibited the expression of MDR1 gene and P-gp, E-CD protein, and reduced the adhesion capacity, with the effect of 10 mg/L baicalin significantly effective than that of 5 mg/L baicalin (all P<0.05). Conclusion: Baicalin can inhibit the proliferation of BEL-7402/5-Fu in vitro, and partially reverse the resistance to Fu, which is attributable to the increased accumulation of intracellular drug concentration, inhibited expression of MDR1 gene.

The chemotherapy tolerance of gemcitabine and cisplatin in old patients with advanced pancreatic cancer / 中华胰腺病杂志

Objective To investigate the tolerance of chemotherapy based on gemcitabine and cisplatin in elderly patients (> 70 years old) with advanced pancreatic cancer. Methods Retrospective analysis in 34 elderly patients with advanced pancreatic cancer between January 2004 and January 2009 was performed. Results 6 patients had partial remission (PR) and 16 patients had stable diaease (SD). The clinical benefit response (CBR) rate was 64.7%. 18 patients reduced their analgesics dose exceeding 50% , as well as pain intensity descended exceeding 35% , 22 patients had the weight increased more than 7% and had improved general well-being. The incidence rate of nausea and vomiting was 38. 2% (13/34) , 4 patients had worsened liver function and aggravated skin and sclera stained yellow. Incidence of Ⅲ- Ⅳ myelosuppressive was 34. 6% , and there were decrease in the number of white blood cell, hemoglobin, platelets to some extent, the rate of thrombocytopenia was 28. 3% (12/34) , blood routine normalized after using G-CSF. There was no occurrence of peripheral neurotoxicity or chemotherapy-related death. Conclusions Chemotherapy of gemcitabine in combination with cisplatin was tolerable for elderly patients with advanced pancreatic cancer who were in good condition of behavior.