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2.
Lett Appl Microbiol ; 74(4): 564-576, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34958703

RESUMO

Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50 ) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug-resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae-related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin-17A (IL-17A); however, the levels of interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL-17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC.


Assuntos
Candidíase Vulvovaginal , Materia Medica , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Feminino , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Materia Medica/farmacologia , Materia Medica/uso terapêutico , Camundongos
3.
Zhonghua Wai Ke Za Zhi ; 57(9): 666-672, 2019 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-31474058

RESUMO

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ(2) test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ(2)=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions: It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , China , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Hipertermia Induzida , Laparoscopia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
4.
Zhonghua Zhong Liu Za Zhi ; 41(2): 118-123, 2019 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-30862141

RESUMO

Objective: To investigate the therapeutic effect of Jin Long Capsule (JLC) combined with neoadjuvant chemotherapy on the invasive breast cancer, and to explore the mechanism of JLC in inhibiting multidrug resistance of breast cancer. Methods: 200 patients were divided into experimental group and control group (100 cases per group). The control group used TEC regimen for neoadjuvant chemotherapy. And the experimental group was treated with TEC regimen combined with oral JLC. According to the Miller & Payne grading system (MP), the efficacy of neoadjuvant chemotherapy was evaluated based on histopathological changes of breast cancer after neoadjuvant chemotherapy. Adverse effect was evaluated according to the classification criteria of the National Cancer Institute of the United States-The Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The expression of P-glycoprotein (P-gp), glutathione thiol transferase (GST)-π and topoisomerase Ⅱα (TopoⅡα) in breast cancer tissues before and after neoadjuvant chemotherapy were detected by immunohistochemical staining. Results: There were 83 effective cases (83%) in the experimental group, which was higher than that in the control group (65.0%, P<0.05). The incidence of leukopenia, gastrointestinal reactions and alopecia in grade 3 to 4 of the experimental group were lower than those of the control group (all P<0.05). The positive rates of P-gp, GST-π and TopoⅡα expression in the control group were 65.0% (65/100), 61.0% (61/100) and 69.0% (69/100), respectively, and they were 80.6% (75/93), 78.5% (73/93) and 37.6% (35/93) after chemotherapy. The positive rates of P-gp and GST-π expression were significantly higher than those before chemotherapy (both P<0.05), whereas the positive rate of TopoⅡα expression was significantly lower than that before chemotherapy (P<0.05). In the experimental group, the positive rates of P-gp, GST-π and TopoⅡα expression before chemotherapy were 62.0% (62/100), 63.0% (63/100) and 69.0% (69/100), respectively, while after chemotherapy, they were 68.2% (60/88), 67.0% (59/88) and 63.6% (56/88). There was no significant difference in the positive rates and expression intensity of P-gp, GST-π and TopoⅡα before and after the chemotherapy (P>0.05). Conclusion: Jin Long Capsule (JLC) can inhibit multidrug resistance, improve the efficacy of neoadjuvant chemotherapy, and reduce adverse reactions of breast cancer.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Medicamentos de Ervas Chinesas/uso terapêutico , Terapia Neoadjuvante , Subfamília B de Transportador de Cassetes de Ligação de ATP , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Cápsulas , Quimioterapia Adjuvante/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , DNA Topoisomerases Tipo II/metabolismo , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Glutationa Transferase/metabolismo , Humanos , Terapia Neoadjuvante/efeitos adversos , Taxoides/administração & dosagem , Taxoides/efeitos adversos
5.
Blood Cancer J ; 4: eXX, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25303370

RESUMO

Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r(2)=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4(+) T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.


Assuntos
Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Infecções por Helicobacter , Helicobacter pylori , Interleucinas , Linfoma de Zona Marginal Tipo Células B , Proteínas de Neoplasias , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas , Linfócitos T CD4-Positivos/metabolismo , Linhagem Celular Tumoral , Feminino , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/terapia , Humanos , Interleucinas/biossíntese , Interleucinas/genética , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/terapia , Masculino , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/terapia , Interleucina 22
6.
Transplant Proc ; 45(10): 3546-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24314955

RESUMO

OBJECTIVES: Renal ischemia and reperfusion (I/R) injury frequently leads to acute renal failure (ARF) and multiple-organ injury with a substantial morbidity rate. The primary cause of ARF-associated death is, however, cardiac failure instead of renal failure itself, and the pathogenesis of renal I/R-induced cardiac injury is still poorly understood. We evaluated the efficacy of curcumin pretreatment on cardioprotection. METHODS: Thirty Sprague-Dawley rats were evenly divided into 3 groups of sham-operated control, renal I/R injury, and a curcumin pretreatment group. Renal ischemia was conducted by bilateral occlusions of pedicles for 45 minutes, followed by 3 hours of reperfusion. The cardiac function was assessed by the left ventricular end-systolic-pressure-volume-relation (ESPVR), systolic pressure (SP), ejection fraction (EF), and stroke volume (SV). Myocardial injury was assessed based on creatine kinase muscle brain fraction (CK-MB) and Troponin I (cTnI), and kidney injury was assessed based on blood urea nitrogen (BUN) and creatinine. We also assessed the levels of tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) in the heart tissues. RESULTS: SV, EF, and SP reduced moderately during the ischemic phase with no major change in ESPVR. During reperfusion, SV, SP, and ESPVR initially increased, and then steadily decreased. Myocardial and kidney injury were marked by the increases in serum CK-MB and cTnI, and creatinine and BUN level. Curcumin pretreatment ameliorated ESPVR and attenuated injuries of both the heart and kidney resulting from I/R insult. CONCLUSIONS: Curcumin pretreatment improved cardiac contractility and attenuated myocardial and renal injury through reducing inflammatory response in the kidney and heart and oxidative stress in the myocardium.


Assuntos
Injúria Renal Aguda/prevenção & controle , Curcumina/farmacologia , Cardiopatias/prevenção & controle , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/sangue , Injúria Renal Aguda/fisiopatologia , Animais , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Creatina Quinase Forma MB/sangue , Creatinina/sangue , Citoproteção , Modelos Animais de Doenças , Coração/fisiopatologia , Cardiopatias/sangue , Cardiopatias/fisiopatologia , Mediadores da Inflamação/metabolismo , Rim/irrigação sanguínea , Rim/metabolismo , Malondialdeído/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Troponina I/sangue , Fator de Necrose Tumoral alfa/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos
7.
Opt Express ; 20(1): A119-24, 2012 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-22379672

RESUMO

Vertical GaN-based light-emitting diodes (LEDs) were fabricated with a Si substrate using the wafer-bonding technique. Lapping and dry-etching processes were performed for thinning the sapphire substrate instead of removing this substrate using the laser lift-off technique and the thinning process associated with the wafer-bonding technique to feature LEDs with a sapphire-face-up structure and vertical conduction property. Compared with conventional lateral GaN/sapphire-based LEDs, GaN/Si-based vertical LEDs exhibit higher light output power and less power degradation at a high driving current, which could be attributed to the fact that vertical LEDs behave in a manner similar to flip-chip GaN/sapphire LEDs with excellent heat conduction. In addition, with an injection current of 350 mA, the output power (or forward voltage) of fabricated vertical LEDs can be enhanced (or reduced) by a magnitude of 60% (or 5%) compared with conventional GaN/sapphire-based LEDs.


Assuntos
Óxido de Alumínio/química , Gálio/química , Índio/química , Iluminação/instrumentação , Semicondutores , Desenho de Equipamento , Análise de Falha de Equipamento
8.
Eur J Clin Nutr ; 60(1): 136-41, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16234843

RESUMO

Infant formulas are often heat sterilized in hospitals where water contamination or nosocomial infection is a concern, but there are few studies of the effect of high heat on the nutritional value of infant formula. In particular, the effect of heat sterilization on free amino acid (FAA) concentrations is seldom discussed. In view of the importance of these nutrients for infant growth, we investigated the FAA concentrations of infant formula after heat sterilization. Powdered infant formulas were reconstituted with hot water (80 degrees C) in glass bottles and placed in an autoclave for 5 min at 105 degrees C and 5600 kg/m2 of pressure. Additional samples of formula were prepared by conventional methods to serve as controls. After autoclaving, we measured the FAA concentrations with ion exchange chromatography. The results were compared with those obtained after conventional preparation. We found a 19.5% lower amount of total protein after autoclaving compared with conventional preparation. Concentrations of total FAA were significantly lower after autoclaving (696.5 +/- 101.4 vs 899.4 +/- 152.2 micromol/l, P = 0.01). The concentrations of individual amino acids were also lower in autoclaved infant formulas, with differences ranging from -4.1 to 71.5% (mean 22.6%). Concentrations of certain amino acids were more than 30% lower, such as valine (71.5%), citrulline (61.1%), glutamine (60.6%), ethanolamine (54%), and lysine (39.2%). Both essential and nonessential amino acids were similarly affected by autoclaving, 28.17 and 27.13%, respectively, lower than in controls (P = 0.37). The concentration of ammonia was significantly higher after autoclaving (645.2 +/- 76.2 vs 393.2 +/-140.7 micromol/l, P = 0.0003). However, the urea level was significantly lower after autoclaving than after conventional preparation (1110.8 +/- 162.7 vs 1426.5 +/- 209.5 micromol/l, P = 0.0004). The accumulation of ammonia may reflect degradation of protein and amino acids. Autoclaving clearly results in decreased concentrations of FAA in infant formula. The increased concentration of ammonia after autoclaving is of concern if it leads to deleterious effects.


Assuntos
Aminoácidos/análise , Manipulação de Alimentos , Temperatura Alta/efeitos adversos , Fórmulas Infantis/química , Fenômenos Fisiológicos da Nutrição do Lactente , Amônia/efeitos adversos , Amônia/análise , Cromatografia por Troca Iônica/métodos , Humanos , Lactente , Fórmulas Infantis/normas , Recém-Nascido , Valor Nutritivo
9.
Eye (Lond) ; 18(5): 470-3, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15131676

RESUMO

BACKGROUND AND PURPOSE: Patients are increasingly well informed about the availability of antioxidant products and the claims made for their benefits in age-related macular degeneration (AMD). Consequently, their use is becoming widespread. The purpose of this study is to conduct a survey of the commonly encountered products, and to compare their ingredients with the current Age-Related Eye Disease Study (AREDS) recommendations. METHODS: A search was undertaken for products sold as 'eye nutrients' at local pharmacies and health food shops, and for products advertised via the Internet. Information about these products was collated and analysed. RESULTS: We identified 22 eye nutrient products. Analysis of their constituents showed that, although over 75% contained all the constituents used in AREDS, only two matched the dosage profiles recommended in the study. CONCLUSION: The authors draw no conclusion on the efficacy of nutritional supplements in the prevention of AMD. In order to advise their patients, ophthalmologists should be familiar with these products. The compiled list in this paper should provide a useful reference for them.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Degeneração Macular/prevenção & controle , Antioxidantes/química , Antioxidantes/provisão & distribuição , Ácido Ascórbico/administração & dosagem , Cobre/administração & dosagem , Suplementos Nutricionais/análise , Humanos , Degeneração Macular/dietoterapia , Vitamina E/administração & dosagem , Zinco/administração & dosagem , beta Caroteno/administração & dosagem
10.
J Glaucoma ; 7(6): 413-6, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9871864

RESUMO

PURPOSE: To assess the influence of adrenaline and hyaluronidase on pulsatile ocular blood flow and intraocular pressure changes during retrobulbar anesthesia. METHOD: Patients undergoing cataract surgery under local anesthesia received a 5-mL retrobulbar injection of lignocaine with either adrenaline, hyaluronidase, or no addition. Continuous pneumotonometry was performed using the OBF tonograph (OBF Labs, Chippenham, UK), which automatically derives pulsatile ocular blood flow values. Measurements were taken before and one minute after injection, and changes were compared between groups to evaluate the effects of changing the constituents of the injection. RESULTS: There was a marked decrease in pulsatile ocular blood flow during injection in all groups. In the group receiving lignocaine with hyaluronidase, the decrease in pulsatile ocular blood flow (mean -141 microL/min) was significantly less than in either the group receiving lignocaine and adrenaline (mean -249 microL/min) or the group receiving lignocaine alone (mean -245 microL/min). There was no significant change in intraocular pressure in any group. CONCLUSION: Hyaluronidase appears to lessen the reduction in pulsatile ocular blood flow. Injection volumes of 5 mL need not cause significant intraocular pressure change.


Assuntos
Anestésicos Locais/administração & dosagem , Epinefrina/administração & dosagem , Olho/irrigação sanguínea , Hialuronoglucosaminidase/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Lidocaína/administração & dosagem , Anestesia Local , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Extração de Catarata , Combinação de Medicamentos , Sinergismo Farmacológico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Injeções , Órbita , Fluxo Pulsátil , Tonometria Ocular
11.
Zhongguo Yao Li Xue Bao ; 14 Suppl: S28-30, 1993 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-8010069

RESUMO

A semi-solid cell culture technique was used to study the sensitivity of K562, HL-60, and Raji leukemic cell lines to the inhibitory effect of psoralen plus ultraviolet irradiation. Results indicated that: 1) the inhibition rate of K562, HL-60, and Raji cell lines were 86%, 35%, and 36%, respectively; and 2) K562, HL-60, and Raji cell lines were treated with psoralen (20 micrograms.ml-1) for 1 h, then irradiated with ultraviolet (1 J/cm2) for 10 min, none of the leukemic cell lines showed colony or cluster formation. These suggested that the cytocidal effect of psoralen plus ultraviolet might be useful to eradicate the residual leukemic cells in the bone marrow transplantation.


Assuntos
Leucemia Eritroblástica Aguda/patologia , Terapia PUVA , Ficusina/farmacologia , Humanos , Leucemia de Células B/patologia , Leucemia Promielocítica Aguda/patologia , Células Tumorais Cultivadas/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco
12.
Zhongguo Yao Li Xue Bao ; 13(1): 69-71, 1992 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-1605039

RESUMO

The effects of silybin (Sil) on myocardial infarction size and ischemia- and reperfusion-induced arrhythmias were studied in anesthetized open chest Sprague-Dawley rats. It was found that pretreatment with Sil 20, 50, and 80 mg.kg-1 iv reduced significantly infarct size by 34.7%, 35.0%, and 50.6% respectively at 4 h after ligation. Sil prevented ischemic arrhythmia only at the dose of 80 mg.kg-1. In reperfusion experiment, pretreatment with Sil 20 mg.kg-1 decreased significantly reperfusion-induced arrhythmia.


Assuntos
Arritmias Cardíacas/prevenção & controle , Infarto do Miocárdio/tratamento farmacológico , Silimarina/uso terapêutico , Animais , Arritmias Cardíacas/etiologia , Masculino , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/complicações , Ratos , Ratos Endogâmicos
15.
Adv Exp Med Biol ; 163: 101-14, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6613723

RESUMO

A variety of quinazoline analogues of folic acid (5,8-dideazafolates) are of interest as potential antineoplastic agents, biochemical probes, and/or affinity ligands for the purification of folate requiring enzymes. Chief among these are 5,8-dideazaisopteroylglutamate, 5,8-dideazaisoPteGlu, (IAHQ), a compound with proven activity against the growth of human colon adenocarcinoma cells in vitro, and 10-formyl-5,8-dideazapteroylglutamic acid, which serves as a substrate for glycinamide ribonucleotide transformylase and is also an effective inhibitor of mammalian thymidylate synthase. New methods for preparing these compounds in excellent purity as determined by high performance liquid chromatography (HPLC) have been developed. In each case the carboxyl groups of L-glutamic acid are protected with t-butyl ester groups, since these can subsequently be removed readily using trifluoroacetic acid without decomposition or racemization of the final product. This approach has proven to be of particular value in the formation of gamma-L-glutamyl derivatives of IAHQ containing 1-3 additional glutamyl residues.


Assuntos
Ácido Fólico/análogos & derivados , Ácidos Pteroilpoliglutâmicos/síntese química , Quinazolinas/síntese química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Neoplasias do Colo/fisiopatologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Indicadores e Reagentes , Ácidos Pteroilpoliglutâmicos/toxicidade , Quinazolinas/toxicidade , Relação Estrutura-Atividade
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