Bizarre presentation of choriocarcinoma: A case report / Philippine Journal of Obstetrics and Gynecology

@#Choriocarcinoma is a malignant subtype of gestational trophoblastic disease that follows any type of pregnancy. It is characterized by rapid hematogenous spread to multiple organs, associated with high human chorionic gonadotropin levels with good response to chemotherapy. We present the case of a 31‑year‑old Filipina who initially presented with severe headaches and blurring of vision 3 years after an unremarkable term pregnancy. The transvaginal ultrasound was normal. After a series of diagnostic tests, the initial working impression was a primary brain tumor with metastases to the lungs, adrenal, kidney, and vulva. Emergency craniotomy was done due to deteriorating status secondary to an intracranial hemorrhage. The histopathology report showed choriocarcinoma. Chemotherapy using Etoposide‑Methotrexate‑Actinomycin D‑Cyclophosphamide‑Vincristine with high‑dose methotrexate and concomitant whole‑brain irradiation was then instituted with good response. This case highlights the importance of having a high index of suspicion for gestational trophoblastic neoplasia to prevent the performance of unnecessary procedures, leading to a delay in diagnosis and the institution of the appropriate treatment.

A cohort study of vincristine-induced peripheral neuropathy in children / 中国当代儿科杂志

OBJECTIVES@#To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN.@*METHODS@#The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups.@*RESULTS@#A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05).@*CONCLUSIONS@#There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.

Linfoma de células B de alto grado de malignidad con morfología blastoide durante el embarazo: reporte de un caso / High-grade malignant B-Cell lymphoma with blastoid during pregnancy: a case report

Resumen ANTECEDENTES: Durante el embarazo es más común el linfoma de Hodking que el no Hodking; afecta, en promedio, a mujeres de 30 años (18-44 años) y más. Suele diagnosticarse alrededor de las 28 semanas de embarazo y está documentado que puede llegarse al término. Los esquemas de tratamiento pueden iniciarse en el posparto inmediato o, incluso, antes. La incidencia mundial del linfoma no Hodking es de 0.8 por cada 100,000 mujeres; se desconoce la supervivencia durante el embarazo. CASO CLINICO: Paciente de 34 años, con antecedentes obstétricos de tres embarazos, una cesárea y un aborto y el embarazo actual en curso de las 29 semanas, referida de la ciudad de Colima debido a un reporte de BI-RADS 3 en el ultrasonido de mama y un nódulo mamario palpable, con evidencia de múltiples tumoraciones en la zona hepática, esplénica y peripancreática. La biopsia tomada de las zonas de la lesión reportó: linfoma de células B de alto grado de malignidad, con morfología blastoide y expresión de C-MYC y BCL2. Además, la paciente se encontró con: anemia, dolor abdominal, múltiples nódulos hepáticos y adenopatías abdominales. Se decidió la interrupción del embrazo a las 30 semanas, con la obtención de un recién nacido, sin complicaciones. Enseguida se inició el tratamiento con rituximab-etopósido-prednisolona-vincristina-ciclofosfamida-doxorrubicina (R-EPOCH) con adecuada adaptación por la paciente. CONCLUSION: Puesto que la información bibliográfica de linfoma y embarazo es escasa el caso aquí reportado es relevante por su aporte. La atención multidisciplinaria favorecerá siempre el pronóstico de las pacientes.

Abstract BACKGROUND: Hodking's lymphoma is more common during pregnancy than non-Hodking's lymphoma; it affects, on average, women aged 30 years (18-44 years) and older. It is usually diagnosed around 28 weeks of pregnancy and is documented to be carried to term. Treatment regimens can be initiated in the immediate postpartum period or even earlier. The worldwide incidence of non-Hodking's lymphoma is 0.8 per 100,000 women; survival during pregnancy is unknown. CLINICAL CASE: 34-year-old patient, with obstetric history of three pregnancies, one cesarean section and one abortion and the current pregnancy in progress at 29 weeks, referred from the city of Colima due to a report of BI-RADS 3 on breast ultrasound and a palpable breast nodule, with evidence of multiple tumors in the hepatic, splenic and peripancreatic area. Biopsy taken from the lesion areas reported: high grade malignant B-cell lymphoma, with blastoid morphology and expression of C-MYC and BCL2. In addition, the patient was found to have: anemia, abdominal pain, multiple hepatic nodules and abdominal adenopathies. It was decided to terminate the pregnancy at 30 weeks, with the delivery of an uncomplicated newborn. Rituximab-Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (R-EPOCH) therapy was started immediately with adequate adaptation by the patient. CONCLUSION: Since bibliographic information on lymphoma and pregnancy is scarce, the case reported here is relevant for its contribution. Multidisciplinary care will always favor the prognosis of patients.

Effect of Hypoxia Inducible Factor-1α on Chemosensitivity of B-ALL Cells to Vincristine and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of hypoxia on the chemosensitivity of B-acute lymphoblastic leukemia （B-ALL） cells to Vincristine (VCR) and the mechanisms.@*METHODS@#B-ALL cells SUP-B15, Nalm-6 and RS4;11 were selected as the research objects. The cells were divided into the control group and the hypoxia mimic group (CoCl2 pretreatment). The two groups were treated with VCR at different concentrations for 24 hours, CCK-8 was used to detect cell viability, flow cytometry was used to detect cell apoptosis, and Western bolt method was used to detect hypoxia inducible factor (HIF-1α), BAX, Bcl-2 and β-actin protein expression. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect BAX and β-actin mRNA levels.@*RESULTS@#CoCl2 could simulate hypoxic environment to induce the expression of HIF-1α. The cells SUP-B15 and RS4;11 of the hypoxia mimic group were lower sensitivity to VCR as compared with the control group; the apoptosis rate of the hypoxia mimic group was lower than that of the control group after 80 nmol/L VCR treatment. The expression levels of BAX protein and mRNA in the hypoxia mimic group were lower than those of the control group, and there was no significant difference in the expression levels of Bcl-2 protein between two groups.@*CONCLUSION@#Under hypoxic conditions, HIF-1α may mediate VCR resistance in B-ALL cells by downregulating the pro-apoptotic protein BAX.

Dehydroabietic acid chemosensitizes drug-resistant acute lymphoblastic leukemia cells by downregulating survivin expression

Objective: To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells. Methods: Acute lymphoblastic leukemia cells REH and CCRF- CEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay, human active caspase-3 Quantikine ELISA kit, and flow cytometry. Vincristine-resistant REH cells (REH-R), survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance. Additionally, in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine. Results: Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells. Survivin expression was upregulated in REH-R cells compared with REH cells. Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine. Akt phosphorylation was also increased in REH-R cells compared to REH cells. In addition, LY294002, a PI3k/Akt pathway blocker, inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells. Dehydroabietic acid effectively reduced survivin expression in REH-R cells, thereby enhancing the therapeutic effect of vincristine on drug-resistant cells. Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine. Moreover, the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia, compared with vincristine treatment alone. Conclusions: Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.

Analysis of clinical characteristics and risk factors associated with incomplete intestinal obstruction in children with medulloblastoma / 中华实用儿科临床杂志

Objective:To analyze the clinical characteristics of children with medulloblastoma (MB) complicated with incomplete intestinal obstruction, and to explore the possible pathogenesis of intestinal obstruction in children with MB.Methods:A total of 409 children with MB admitted to the Department of Pediatrics of Beijing Shijitan Hospital, Capital Medical University from October 2014 to January 2019 were recruited into this study, and the clinical data of children with incomplete intestinal obstruction were collected and analyzed retrospectively.A comparison was performed between these children and those without intestinal obstruction who were treated at the same time.The chi- squared test and Logistic regression analysis were adopted to explore the pathogenesis of intestinal obstruction.The overall survival (OS) rate was calculated with the Kaplan-Meier method. Results:There were 11 cases of 409 children with MB complicated with incomplete intestinal obstruction in total, with the morbidity of 2.7%, they were all over 3 years old, with the median age of 8.7 years, and a male-to-female ratio of 4.5∶1.The incomplete intestinal obstruction in all cases occurred during the first cycle of maintenance chemotherapy after radiotherapy.All these patients could be reco-vered after conservative treatment, and no incomplete intestinal obstruction occurred in the subsequent chemotherapy.The results of Logistic regression analysis showed that there was a correlation between age and the development of incomplete intestinal obstruction ( P<0.05). The 2-year OS rate of MB patients complicated with incomplete intestinal obstruction was (87.5±11.7)%, and that of patients without incomplete intestinal obstruction during the same period was (92.8±1.6)%, which showed that the difference between the two group was not statistically significant ( P>0.05). Conclusions:Incomplete intestinal obstruction would occur in all MB patients within 2 months after radiotherapy, and children more than 3 years old are more prone to suffer from this disease.Therefore, it can be supposed that gastrointestinal mucosa was damaged under the double attack of radiotherapy and Vincristine, which slowed down the intestinal peristalsis, thus inducing intestinal obstruction.

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor

ABSTRACT: This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p 0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.

RESUMO: Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p 0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor / Comparação entre as alterações hematológicas e bioquímicas ocasionadas pela quimioterapia convencional e quimioterapia metronômica no tratamento do tumor venéreo transmissível canino

This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p<0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.(AU)

Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p<0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.(AU)

An Optimization Of Sterically Stabilized Liposome Using Design Of Experiment Approach

Purpose: Recently, drug delivery system with controlled and targeted drug release at the tumor sites emerged as an attractive option for improving anticancer therapeutics. Advanced Nano therapeutics must not be limited to nano scale but should find their way to target the solid tumor via direct or indirect way. Pegylation on the surface of liposome helps to become liposome as long circulating and indirect or passive targeting to tumor. Purpose of this study is to develop and optimize the critical process parameters which plays important role in the quality pegylated liposome. Design of experiment (DOE) was used to study the impact of critical process variables like hydration temperature, extrusion process temperature, ethanol concentration, drug loading temperature and drug loading time.

Effect of Arrabidaea chica extract against chemically induced breast cancer in animal model

Abstract Purpose: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. Methods: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. Results: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. Conclusion: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.

Downregulation of DBN1 is related to vincristine resistance in colon cancer cells

Objective: This study was aimed to investigate the relationship between the expression of drebrin (DBN1) gene and resistance in colon cancer to reveal the mechanism of tumor drug resistance and provide a basis for the reversal of this drug resistance in tumor cells. Materials and Methods: The human colon carcinoma cell line HCT-8 was used, and vincristine (VCR)-resistant colon cancer cell line HCT-8/V was established by gradually increasing the concentration of VCR. Polymerase chain reaction (PCR) primers were designed for DBN1 gene. The DBN1 differential expression in colon cancer sensitive and resistant cell lines was detected by fluorescence quantitative PCR. Western blot analysis was used to study DBN1 expression in the resistant cells further. Results: VCR resistance of HCT-8/V cell line was established. Quantitative PCR and Western blot results showed that DBN1 expression in the resistant cell line was significantly lower, the difference being statistically significant (P < 0.05). Conclusion: Low DBN1 gene expression may be associated with colon cancer cell resistance to VCR.

Sub-chronic administration of vincristine sulfate induces renal damage and apoptosis in rats via induction of oxidative stress and activation of Raf1-MEK1/2-Erk1/2 signal transduction / La administración subcrónica de sulfato de vincristina induce daño renal y apoptosis en ratas por inducción de estrés oxidativo y activación de la transducción de señales Raf1-MEK1/2-Erk1/2

SUMMARY: In spite of being one of the most powerful anti-cancer drug, the nephrotoxicity of Vincristine (VCR) is not well established in either animals or humans. Hence, this study evaluates the nephrotoxic effect of VCR in rats after sub-chronic long-term administration. Rats were divided into 2 groups (n=10/group) of either control and VCR treated rats (50 mg/kg). Treatments were carried out for 30 consecutive days, after which a series of biochemical and molecular experiments related to kidney function were evaluated. VCR administration significantly decreased the survival rate (69.8 %) and impaired renal function as evidenced by lowered creatinine (Cr) clearance (Ccr), high serum levels of urea and Cr, increased urinary protein levels and resulted in sever cortex pathological alterations, including glomerulus congestion and damage as well as vascular degenerations up to necrosis of both proximal and distal convoluted tubules. Mechanistically, VCR lowered renal antioxidant potential and ATP levels, enhanced lipid peroxidation and induced inflammation. In addition, VCR induced activation of Raf-1-MEK1/2-ERK1/2 signaling pathway leading to downregulation of Bcl2 and upregulation of P53, Bax, and cleaved caspase-3. In conclusion, these findings show a nephrotoxic effect of VCR sulfate in rats after sub-chronic administration and such effect was mediated by activation of ERK1/2 induced apoptosis.

RESUMEN: A pesar de ser uno de los medicamentos de mayor eficacia contra el cáncer, aún no se ha establecido la nefrotoxicidad de la vincristina (VCR) en animales y humanos. Por lo tanto, este estudio evalúa el efecto nefrotóxico de la VCR en ratas después de la administración subcrónica a largo plazo. Las ratas se dividieron en 2 grupos (n = 10 / grupo) de control y ratas tratadas con VCR (50 mg / kg). Los tratamientos se llevaron a cabo durante 30 días consecutivos, después de los cuales se evaluaron una serie de experimentos bioquímicos y moleculares relacionados con la función renal. La administración de VCR disminuyó significativamente la tasa de supervivencia (69,8 %), dificultó la función renal, lo que se observó además en los bajos niveles de creatinina (Cr) (Ccr), los niveles séricos elevados de urea y Cr, un nivel más alto de proteína urinaria, los que dieron lugar a alteraciones patológicas severas de la corteza, incluido el glomérulo congestión y daño, como también degeneraciones vasculares, incluyendo la necrosis de los túbulos contorneados proximales y distales. Mecánicamente, el VCR redujo el potencial antioxidante renal y los niveles de ATP, mejoró la peroxidación lipídica y la inflamación inducida. Además, la VCR indujo la activación de la vía de señalización Raf-1-MEK1 / 2-ERK1 / 2 que conduce a la regulación negativa de Bcl-2 y la regulación positiva de P53, Bax y la caspasa-3. En conclusión, estos hallazgos muestran un efecto nefrotóxico del sulfato de VCR en ratas después de la administración subcrónica. Dicho efecto fue mediado por la activación de la apoptosis inducida por ERK1 / 2.

Experimental study of a novel photosensitizer mediated photodynamic therapy on resistant gastric cancer / 中国药理学通报

Aim To investigate the therapeutic efficacy of DTP-mediated photodynamic therapy (PDT) on SGC7901/VCR human vincristine ( VCR )-resistant gastric cancer cells, and to reveal the relationship between DTP-PDT and P-gp. Methods MTT assay was employed to evaluate the cytotoxicity of DTP-PDT and combination treatment with DTP-PDT and VCR. A SGC7901/VCR-bearing nude mouse model was established, and the tumor volume was measured to draw the growth curve. Cell apoptosis was detected by flow cytometry, and the yield of intracellular singlet oxygen (O2) was determined after DTP-PDT. The expression of MDR1 mRNA and P-gp was determined by qPCR and flow cytometry, respectively. Results DTP-PDT demonstrated significant cytotoxicity on SGC7901/VCR cells and the nude mice transplanted tumor. DTP-PDT could induce the apoptosis of SGC7901/VCR cells and the generation of intracellular O2. DTP-PDT could inhibit the expression of MDR1 mRNA and P-gp, which could be reduced by a-tocopherol. Combined treatment with DTP-PDT and VCR demonstrated synergistic efficacy on resistant cells, which could be reduced by or-tocopherol. Conclusions O2 generated by DTP-me-diated PDT could inhibit the growth of SGC7901/VCR cells and induce cell apoptosis. Meanwhile, it inhibits the over-expression of P-gp on cell membranes, leading to reduced efflux of VCR and synergistic efficacy with DTP-PDT and VCR eventually.

Efeitos de sulfato de vincristine sobre os testículos de ratos albinos, tratados na fase pré-púbere / Effects of vincristine sulphate on albino rat testis treated in the prepuberal phase

Este trabalho visou avaliar os efeitos de sulfato de vincristine sobre os testículos de ratos tratados na fase pré púbere, sobretudo quanto às alterações das células de Sertoli e das células germinativas. Foram utilizados 30 animais controles e 30 tratados com sulfato de vincristine. As aplicações da droga ocorreram aos 15 dias de vida, e a eutanásia aos 40, 64 e 127 dias de vida para possibilitar a avaliação em diferentes estágios de desenvolvimento reprodutivo. Foram realizadas medidas biométricas (pesos corpóreos e testiculares), medidas morfométricas testiculares, (eixos testiculares maiores e menores, diâmetros testiculares de túbulo e lúmen seminíferos, e altura do epitélio seminífero) e estereológicas (volumes testiculares e as densidades de volume do tecido tubular e do tecido intersticial testicular). As medidas biométricas foram feitas em todos os animais do experimento, e as avaliações morfométricas e estereológicas foram realizadas em 200 túbulos seminíferos. Os resultados demonstraram que sulfato de vincristine reduz parâmetros biométricos como peso corpóreo, peso testicular e volume testicular total. Variáveis morfométricas e estereológicas como diâmetro dos túbulos seminíferos, altura do epitélio seminífero e volume dos túbulos seminíferos também foram reduzidos. Os tipos celulares mais atingidos foram as espermatogônias, espermátides tardias e células de Sertoli.(AU)

This study evaluated the vincristine sulfate effect on rat testes treated in pre pubertal stage, especially regarding the changes of Sertoli cells and germ cells. Thirty control rats and 30 rats treated with vincristine sulfate were used. The drug application occurred at 15 days of life, and euthanasia at 40, 64 and 127 days of life to enable evaluation at different stages of reproductive development. Biometric measurements were performed (body and testicular weights), testicular morphometric measures (major and minor testicular axis and of seminiferous tubule and seminiferous lumen) and stereological (testicular volumes and volume densities of the tubular and testicular interstitial tissue). The biometric measurements were made on all rats in the experiment, and morphometric and stereological analysis was carried out in 200 seminiferous tubules. The results demonstrate that vincristine sulfate reduces biometric parameters such as body weight, testicular weight and the total testicular volume. Morphometric and stereological variables as diameter of the seminiferous tubules, height of the seminiferous epithelium and volume of the seminiferous tubules were also reduced. The most affected cell types were spermatogonia, late spermatids and Sertoli cells.(AU)

Preparation of vincristine loaded low density lipoprotein nanoparticles modified by T7 peptide and evaluation of therapeutic effect on glioma / 药学学报

The purpose of this study was to prepare T7 peptide modified vincristine loaded low density lipoprotein (T7-LDL-VCR) nanoparticles to penetrate through blood brain barrier for targeting the brain tumor cells. Firstly, the low density lipoprotein (LDL) nanoparticles were extracted and separated from human serum by density gradient centrifugation method, and then was loaded into the nanoparticle's lipid core by the dry film method, T7 peptide was covalent modified on the surface of the nanoparticles. T7-LDL-VCR was characterized by particle size, entrapment efficiency and peptide attachment efficiency. The fluorescent probe DiR was used to track the brain biodistribution of T7-LDL-VCR in mice bearing intracranial C6 glioma by means of in vivo imaging. The therapeutic effect of nanoparticles was observed with magnetic resonance imaging (MRI). Finally, relative tumor volume and survival curve were determined in mice. The results showed that the mean size of the prepared T7-LDL-VCR nanoparticle was about 30 nm, encapsulation efficiency was 30.1%, and peptide attachment efficiency was 63.88%. As expected, the prepared preparation has good brain targeting and good effect on the treatment of glioma in mice:the relative tumor volumes of T7-VCR-LDL, LDL-VCR and VCR were 30%, 51.50% and 79.25%, respectively; the median survival time (36 days), which was 2, 1.85 and 1.38 fold higher than that of physiological saline, free VCR and LDL-VCR, respectively. This study suggests that dual modified hposomes possessed a better ability penetrating the blood brain barrier to target the brain tumor with significant antitumor activities.

EMA/CO regimen for chemotherapy 24 patients with ultra high-risk gestational trophoblastic neoplasia / 中华妇产科杂志

Objective To evaluate etoposide,methotrexate and dactinomycin (EMA)/ cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk gestational trophoblastic neoplasia (GTN).Methods A total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics (FIGO) prognostic scores greater or equal to 12 with liver,brain,or extensive metastases did poorly when treated with primary chemotherapy admitted in Women's Hospital,School of Medicine,Zhejiang University from January 2001 to December 2015.All of the patients were treated by EMA/CO regimen and followed up to death or December 2017.The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated.Results All of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 (ranged 12-18,median 13.0).Twenty patients (83％,20/24) received EMA/CO regimen as primary treatment and 4 patients (17％,4/24) had a history of failed chemotherapy.Seven patients (29％,7/24) had metastasis of liver or brain and 17 patients (71％,20/24)had no metastasis of liver and brain.Twenty-four patients received totally 167 courses of EMA/CO regimen (average 7.0 courses).Sixteen patients achieved complete remission and 8 patients showed drug-resistant.The complete remission rate was 67％ (16/24) and the resistance rate was 33％ (8/24).Of the 16 patients who got complete remission,6 cases were treated with EMA/CO regimen alone,and 10 cases were treated by chemotherapy combined with surgery.For the 8 patients who showed drug-resistant to EMA/CO,5 cases of them received EMA/etoposide and cisplatin (EP) regimen and 3 cases got remission,1 case received methotrexate,dactinomycin and cyclophosphamide (MAC) regimen and got remission,2 cases gave up treatment because of economic factors.The side effects of EMA/CO mainly included Ⅲ-Ⅳ degree neutropenia,anemia and alopecia.The incidence of Ⅲ-Ⅳ degree neutropenia during the treatment of EMA/CO was 21.6％ (36/167),the incidence of anemia was 96.4％ (161/167),and the incidence of alopecia was 60.5％ (101/167).In these 24 ultra high-risk GTN patients,4 patients died during follow-up.In the 20 patients who got complete remission,no recurrence or secondary tumor by chemotherapy were occurred.Conclusion EMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.

Clinical Study on Prevention and Treatment of CIPN Induced by Vincristine Through TCM Prescription of Peripheral Neuropathy Hand-food Soaking Combined with Mecobalamin / 中国中医药信息杂志

Objective To observe the clinical efficacy of prevention and treatment of chemotherapy induced peripheral neurpathy (CIPN) by vincristine via using TCM prescription of peripheral neuropathy hand-food soaking combined with mecobalamin. Methods Totally 120 patients with non-Hodgkin's lymphoma who all received chemotherapy drugs including vincristine were randomly divided into treatment group (36 cases), control group (36 cases) and combined treatment group (36 cases). All groups received routine treatment (all used CHOP, R-CHOP and H-CAVD plans for the first time), for 6 cycles of chemotherapy. The control group was given mecobalamin at the same time, 0.5 mg each time, oral administration, three times a day. The treatment group was given TCM prescription of peripheral neuropathy hand-foot soaking at the same time, hands first and feet later, 20 minutes each time, twice a day. The combined treatment group was given TCM prescription of peripheral neuropathy and mecobalamin at the same time, the same as the former method. 7 days were set as one treatment course, and all the treatment lasted for 6 cycles of chemotherapy. The incidence and degree of CIPN were evaluated in 2, 4, and 6 cycles of chemotherapy, and the satisfaction was compared. 50 patients of CIPN degree ≥Ⅱ were screened, paused chemotherapy, and participated in consolidation treatment research. The 50 patients were assigned into treatment group (25 cases) and control group (25 cases). The control group took oral mecobalamin, and the treatment group used TCM prescription of peripheral neuropathy hand-foot soaking; the methods were the same as former methods, for 20 d. Clinical efficacy and satisfaction of both groups were evaluated. Results After the second cycle of chemotherapy, the incidence of CIPN in the treatment group and the combined treatment group were obviously lower than the control group (P<0.05). After the fourth cycle of chemotherapy, the incidence of CIPN in the combined treatment group were obviously lower than the control group (P<0.01); the incidence of CIPN degree ≥Ⅱ in the treatment group and combined treatment group were obviously lower than the control group (P<0.05). After the sixth cycle of chemotherapy, the incidence of CIPN degree ≥Ⅱ in the treatment group and combined treatment group were obviously lower than the control group (P<0.01). The satisfaction rate of the treatment group was higher than the control group (P<0.01). For the consolidation therapy to patients of CIPN degree ≥Ⅱ, there was no statistical significance in clinical efficacy between the treatment group and the control group (P>0.05), but the satisfaction rate of the treatment group was higher than the control group (P<0.01). Conclusion TCM prescription of peripheral neuropathy hand-food soaking combined with mecobalamin can obviously relieve CIPN degree induced by vincristine, and improve the life quality of patients.

Curcumin reverses resistance of human esophageal cancer Eca-109/VCR cells to vincristine by inhibiting Notch1 signaling pathway / 肿瘤

Objective: To investigate the reversal effect of curcumin (Cur) on the resistance of human esophageal cancer Eca-1 09/vincristine (VCR) cells to VCR, and to explore its possible mechanism. Methods: MTT method was used to detect the effect of different concentrations of Cur on the proliferation of Eca-1 09/VCR cells and the reversal effect of Cur (25 μmol/L) on the resistance of Eca-109/VCR cells to VCR. The Eca-109/VCR cells were treated with Cur (25 μmol/L) alone, VCR (2 μg/mL) alone or Cur (25 μmol/L) combined with VCR (2 μg/mL) for 24 h, respectively. Then the apoptosis was analyzed by FCM and Hoechst 33258 fluorescence staining. The expression levels of Notch1, Jagged1, and hairy and enhancer of split 1 (Hes1) mRNAs were detected by real-time fuorescent quantitative PCR. The expressions of Notch1, Jagged1, Hes1 and P-glycoprotein (P-gp) proteins were measured by Western blotting. Results: The proliferation inhibitory rate of Eca-1 09/VCR cells was (8.82±0.80) % after the treatment with 25 μmol/L Cur. After the treatment with Cur (25 μmol/L) and various concentrations of VCR for 24 h, the half maximal inhibitory concentration (IC50) of VCR on Eca-1 09/VCR cells is decreased from (7.70±0.63) μg/mL to (2.55± 0.12) μg/mL. The reversal fold of Cur was 3.02. After the treatment with Cur (25 μmol/L) and VCR (2 μg/mL) for 24 h, the apoptosis rate of Eca-1 09/VCR cells was significantly higher than those in Cur (25 μmol/L) group and VCR (2 μg/mL) group (both P < 0.05), the expression levels of Notch1, Jagged1 and Hes1 mRNAs were significantly lower than those in Cur (25 μmol/L) group and VCR (2 μg/mL) group (all P < 0.01), and the expressions of Notch1, Jagged1, Hes1 and P-gp proteins were significantly down-regulated in Eca-1 09/VCR cells (all P < 0.05). Conclusion: Cur can obviously reverse the resistance of esophageal cancer Eca-109/VCR cells to VCR. The mechanism may be related to the inhibition of Notch1 signaling pathway and the down-regulation of P-gp expression.

Model establishment of skin damage and molecular mechanism on transgenic zebrafish embryos / 中国药理学通报

Aim To establish a new model of skin damage by u-sing vincristine to transgenic zebrafish (krt4:NTR-hKikGR).Methods Skin fluorescent transgenic zebrafish embryos after 24 h fertilization were treated with the 0.01~0.04 mmol·L-1 vincristine,and zebrafish skin cell ablation was investigated un-der fluorescence microscope after 24 h,at same time skin death cells were detected with TUNEL assay and image processed, then the protein expressions of KRT4, caspase-3 and p53 were assessed with Western blot. Results 0.02 mmol·L-1and 0.04 mmol·L-1vincristine could obviously induce zebrafish skin cell apoptosis(P<0.01) with statistically significant differ-ence compared with the control, and the same result could be accomplished in TUNEL assay. Results of Western bolt showed that vincristine could increase the embryos caspase-3 and p53 expression(P <0.01), while vincristine in high concentration might decrease KRT4 markedly(P<0.01). Conclusion Vin-cristine can induce damage on zebrafish skin with suppression KTR4,which can be used as a new skin damage model.

Vincristine combined with glucocorticoids for the treatment of 11 cases of infantile Kasabach-Merritt syndrome / 中华皮肤科杂志

Objective To explore effective therapy for Kasabach-Merritt syndrome (KMS).Methods Clinical data were collected from 11 infants with KMS in the Department of Dermatology,Beijing Children's Hospital affiliated to Capital Medical University between 2015 and 2017,and the efficacy of vincristine combined with glucocorticoids for the treatment of KMS was evaluated.Results Of the 11 patients,4 were male and 7 were female.Their average age at the first clinic visit was 87.91 ± 72.01 days (range,1-212 days).Most of the hemangiomas manifested as hard violaceous plaques,and skin purpura occurred around the hemangiomas in 5 patients.The initial blood platelet counts of the 11 patients ranged from 4 × 109/L to 32 × 109/L.All the patients were treated with oral prednisone at doses of (2-5) mg· kg 1· d1 combined with intravenous injection of vincristine at a dose of 0.05 mg/kg every week.Among 10 patients treated with glucocorticoids and vincristine,the blood platelet counts became normal after (1.8± 1.23) weeks of treatment,the fibrinogen levels returned to normal after (3.6 ± 1.26) weeks of treatment,and the hemangiomas started to become softer and smaller after (3.9 ± 0.74) weeks.The blood platelet count still did not return to normal in 1 patient after 5 weeks of vincristine treatment.After the treatment with venous embolization,the blood platelet count gradually became normal and remained stable.Conclusion Vincristine combined with glucocorticoids can control the development of hemangioma in infants with KMS,and improve the recovery of blood platelet count.