Bordetella bronchiseptica is a potent and safe adjuvant that enhances the antigen-presenting capability of dendritic cells

We previously demonstrated that Bordetella bronchiseptica (B. bronchiseptica) antigen (Ag) enhances the Mycoplasma hyopneumoniae Ag-specific immune response. The focus of this study was whether acellular bacterin of B. bronchiseptica could be used as an adjuvant to increase antigen-presenting capability of dendritic cells (DCs) by increasing the level of activation. The metabolic activity of DCs was increased by B. bronchiseptica, similar to lipopolysaccharide (LPS). Flow cytometry analysis revealed that B. bronchiseptica increases the expression of major histocompatibility complex class-2, cluster of differentiation (CD)40, CD54, and CD86 which are closely related to DC-mediated immune responses. B. bronchiseptica enhanced the production of cytokines related to adaptive immune responses. Furthermore, the survival rate of B. bronchiseptica-injected groups was 100% at 15 and 20 mg/kg doses, whereas that of LPS-injected groups was only 20%, 0% at 15 and 20 mg/kg doses respectively, and so B. bronchiseptica is likely to be safer than LPS. Taken together, these results indicate that B. bronchiseptica can be used as an adjuvant to enhance the antigen-presenting capability of DCs. B. bronchiseptica is a candidate for producing vaccines, especially in case of DC-mediating efficacy and safety demands. This study provides researchers and clinicians with valuable information regarding the usage of B. bronchiseptica as a safe bacteria-derived immunostimulating agent for developing efficient vaccines.

Extracranial systemic antitumor response through the abscopal effect induced by brain radiation in a patient with metastatic melanoma

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain’s distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient’s tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms such as headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient’s CNS metastases improved significantly within weeks of her therapy. The patient’s non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

Evaluation of herb extracts and germanium oxide as immunological adjuvants in quails ( Coturnix coturnix japonica ) / Evaluación de extractos de hierbas y el óxido de germanio como adyuvantes inmunológicos en codornices ( Coturnix coturnix japonica )

ABSTRACT Objective. The aim of present investigation was to assess the immunostimulatory activity of herb extracts from Allium sativum, Aloe arborescens and germanium oxide. Materials and methods. Quails were immunized three times orally with bovine serum albumin (BSA) in combination with the crude plant extracts and the inorganic substance which was indicated above. BSA-specific IgA antibodies in saliva and IgY antibodies in egg yolk were tested by ELISA. Results. It was discovered that the birds treated with BSA in combination with either Allium sativum or Aloe arborescens extracts or germanium oxide had higher titers of BSA-specific IgA antibodies in the saliva at the 42 day of monitoring, while the quails administered with BSA and Allium sativum or Aloe arborescens extracts or germanium oxide demonstrated higher levels of BSA-specific IgY antibodies in the egg yolk at the end of observation. Furthermore, the birds immunised with BSA alone had significantly lower immune responses to BSA than quails immunised with BSA supplemented with the herb extracts and germanium oxide. Conclusions. These data suggest that medicinal plant extracts and germanium oxide can be applied as oral adjuvants or as immunomodulators for quails.

RESUMEN Objetivo. Evaluar la actividad inmunoestimulante de extractos de hierbas de Allium sativum, Aloe arborescens y óxido de germanio. Materiales y métodos. Las codornices se inmunizaron tres veces por vía oral con albúmina de suero bovino (BSA) en combinación con los extractos vegetales crudos y la sustancia inorgánica antes indicada. Los anticuerpos IgA específicos de la BSA en la saliva y los anticuerpos IgY en la yema de huevo se analizaron mediante ELISA. Resultados. Se encontró que las aves tratadas con BSA en combinación con extractos de Allium sativum o Aloe arborescens o con óxido de germanio tenían títulos más altos de anticuerpos IgA específicos de BSA en la saliva a los 42 días de seguimiento, mientras que las codornices administradas con BSA y Allium sativum o extractos de Aloe arborescens u óxido de germanio demostraron niveles más altos de anticuerpos IgY específicos de BSA en la yema de huevo al final de la observación. Además, las aves inmunizadas sólo con BSA tuvieron respuestas inmunitarias significativamente más bajas a la BSA que las codornices inmunizadas con BSA complementadas con extractos de hierbas y óxido de germanio. Conclusiones. Estos datos sugieren que los extractos de plantas medicinales y el óxido de germanio pueden aplicarse como adyuvantes orales o como inmunomoduladores para las codornices.

Phytochemical bioprospecting, antioxidant, antimicrobial and cytotoxicity activities of saline extract from Tithonia diversifolia (Hemsl) A. Gray leaves

Objective: To evaluate antimicrobial and antioxidant properties of saline extract from Tithonia diversifolia leaves by phytochemical bioprospecting, and investigate its safety against animal cells. Methods: The saline extract was prepared, with NaCl (0.15 M), by constant stirring of the dried and pulverized leaves, followed by volume reduction by lyophilization. The extract was phytochemical characterized using ultra-performance liquid chromatography, and total phenol and flavonoid analysis also was performed. The antioxidant capacity was determined through DPPH· radical, the antimicrobial property was evaluated against standard bacteria and fungi, and the viability assays were performed against mice splenocytes. Results: Fifteen compounds were identified belonging to two main classes terpenoids and phenolics. The extract showed 22.185 mg GAE/g of total phenolic compounds and 3.220 mg QE/g of flavonoid. Moreover, extract showed higher antioxidant ability similar to butylated hydroxytoluene a standard molecule [(3.042±0.019) mg AAE/g and (4.12±0.10) mg AAE/g to saline extract and butylated hydroxytoluene, respectively]. The antimicrobial assays demonstrated that the extract had a significant antifungal potential against Candida species and could be used with safety against mice splenocytes, in concentrations lower than 50 μg/mL, promoting higher proliferation in these cells. Conclusions: Saline extract from Tithonia diversifolia leaves presents potential antioxidant, antifungal properties and induces immunostimulation in mice splenocytes.

Phytochemical bioprospecting, antioxidant, antimicrobial and cytotoxicity activities of saline extract from Tithonia diversifolia (Hemsl) A. Gray leaves

Objective: To evaluate antimicrobial and antioxidant properties of saline extract from Tithonia diversifolia leaves by phytochemical bioprospecting, and investigate its safety against animal cells. Methods: The saline extract was prepared, with NaCl (0.15 M), by constant stirring of the dried and pulverized leaves, followed by volume reduction by lyophilization. The extract was phytochemical characterized using ultra-performance liquid chromatography, and total phenol and flavonoid analysis also was performed.The antioxidant capacity was determined through DPPH? radical, the antimicrobial property was evaluated against standard bacteria and fungi, and the viability assays were performed against mice splenocytes. Results: Fifteen compoundswereidentifiedbelongingtotwomainclassesterpenoidsandphenolics.Theextract showed 22.185 mg GAE/g of total phenolic compounds and 3.220 mg QE/g of flavonoid. Moreover, extract showed higher antioxidant ability similar to butylated hydroxytoluene a standard molecule [(3.042±0.019) mg AAE/g and (4.12±0.10) mg AAE/g to saline extract and butylated hydroxytoluene, respectively].The antimicrobial assays demonstrated that the extract had a significant antifungal potential against Candida species and could be used with safety against mice splenocytes, in concentrations lower than 50 μg/mL, promoting higher proliferation in these cells. Conclusions: Saline extract from Tithonia diversifolia leaves presents potential antioxidant, antifungal properties and induces immunostimulation in mice splenocytes.

Preclinical immunotoxicity evaluation of implantable medical devices / 医疗卫生装备

The preclinical immunotoxicity evaluation of implantable medical devices was described.Firstly,the guidelines and regulations about the immunotoxicity evaluation of medical devices were summarized.These documents directed the immunotoxicity evaluation of implantable medical devices.Secondly,various aspects concerning the design of the immunotoxicity evaluation experiments were discussed here,including the hazardous effect of potential degradation products,the risk management of medical devices,the tests for interactions,the tests for in vitro cytotoxicity,the tests for local effects after implantation,the tests for irritation and delayed-type hypersensitivity,the tests for systemic toxicity.Thirdly,different types of immune responses with regard to immunotoxicity evaluation were listed and introduced here.In the end,the evaluation of implantable medical devices was expected to be more rigorous in the future.

Preclinical immunotoxicity evaluation of implantable medical devices / 医疗卫生装备

The preclinical immunotoxicity evaluation of implantable medical devices was described.Firstly,the guidelines and regulations about the immunotoxicity evaluation of medical devices were summarized.These documents directed the immunotoxicity evaluation of implantable medical devices.Secondly,various aspects concerning the design of the immunotoxicity evaluation experiments were discussed here,including the hazardous effect of potential degradation products,the risk management of medical devices,the tests for interactions,the tests for in vitro cytotoxicity,the tests for local effects after implantation,the tests for irritation and delayed-type hypersensitivity,the tests for systemic toxicity.Thirdly,different types of immune responses with regard to immunotoxicity evaluation were listed and introduced here.In the end,the evaluation of implantable medical devices was expected to be more rigorous in the future.

Selenium and vitamin E enriched diet increases NK cell cytotoxicity in cattle / Dieta enriquecida com selênio e vitamina E aumenta a citotoxicidade de células NK em bovinos

A number of studies has shown that antioxidants, fatty acids and trace minerals may modulate different immune cell activities, and that their deficiency may be associated with diseases and impaired immune responses. In innate immunity, natural killer (NK) cells have a central role, killing virally infected and cancerous cells, and also secreting cytokines that shape adaptive immune responses. Thus, the aim of this study was to evaluate the effect of enriched diets in selenium plus vitamin E and/or canola oil on complete blood count and on NK cell cytotoxicity from blood lymphocytes of Nellore bulls. Bulls that received selenium plus vitamin E had (P=0.0091) higher NK cell cytotoxicity than control bulls. This result positively correlated with serum selenium levels. To the best of our knowledge, this is the first study that showed immunostimulatory effects of selenium plus vitamin E on NK cell cytotoxicity of Nellore bulls.(AU)

Vários estudos demonstraram que antioxidantes, ácidos graxos e minerais podem modular a atividade de diferentes células do sistema imunológico e que as suas carências podem estar associadas a doenças e a respostas imunes comprometidas. Na imunidade inata, os linfócitos natural killer (NK) têm um papel central matando células infectadas por vírus e células cancerígenas, ao mesmo tempo em que também secretam citocinas que modulam as respostas imunes adaptativas. Assim, o objetivo deste estudo foi avaliar o efeito de dietas enriquecidas em selênio e vitamina E e/ou óleo de canola no hemograma e na citotoxicidade das células NK do sangue de bovinos da raça Nelore. Os animais que receberam selênio e vitamina E tiveram (P = 0,0091) maior citotoxicidade das células NK do que os animais do grupo controle. Este resultado foi positivamente correlacionado com os níveis de selênio no sangue. Para o melhor do nosso conhecimento, este é o primeiro estudo que mostrou efeitos imunoestimulatórios do selênio e vitamina E sobre a citotoxicidade das células NK de bovinos Nelore.(AU)

Screening of biological amniotic immunization safety / 国际药学研究杂志

Objective: To evaluate the immunity efficacy of human amniotic membranes on rats. Methods: One hundred and fifty Wistar rats were randomly divided into five groups: biological amnion group, immunosuppression group, immunostimulation group, sham-operated group and blank control group. According to the study period, each group of thirty rats would be randomly divided into five experimental operation subgroups: the 1st week, the 2nd week, the 4th week, the 8th week group and the 12th week groups. The rats were implanted subcutaneously, then intramuscular injection of gentamicin sulfate for 3 days to resist the infection, and the immune organ coefficient, and the killing abilities of NK cell, IL-1β, IL-6 and TNF-αserum levels were detected according to the study period. Results: At 1st, 2nd, 4th, 8th and 12th week after amniotic membrane implantation in rats, compared with the sham-operated and blank control groups, the biological amnion group had nonsignificant differences(P>0.05). At 1st week after amniotic membrane implantation in rats, immunosuppression group showed different levels of the immunosuppressive effect, such as the analysis of immune organ coefficient, which had significant differences compared with other groups(P<0.01). At 1st week after amniotic membrane implantation in rats, the imunostimulation group showed a certain degree of the immunostimulant effect, such as the killing abilities of NK cell, which had marked differences compared with other groups(P<0.05). Conclusion: The amniotic membranes have satisfactory immune safety with implantation in rats and do not cause significant adverse immune reactions.

Screening of biological amniotic immunization safety / 国际药学研究杂志

Objective To evaluate the immunity efficacy of human amniotic membranes on rats. Methods One hundred and fifty Wistar rats were randomly divided into five groups:biological amnion group,immunosuppression group,immunostimulation group, sham-operated group and blank control group. According to the study period,each group of thirty rats would be randomly divided into five experimental operation subgroups:the 1st week,the 2nd week,the 4th week,the 8th week group and the 12th week groups. The rats were implanted subcutaneously,then intramuscular injection of gentamicin sulfate for 3 days to resist the infection ,and the immune organ coefficient,and the killing abilities of NK cell ,IL-1β,IL-6 and TNF-αserum levels were detected according to the study period.Results At 1st ,2nd ,4th ,8th and 12th week after amniotic membrane implantation in rats,compared with the sham-operated and blank control groups,the biological amnion group had nonsignificant differences (P>0.05). At 1st week after amniotic membrane implantation in rats, immunosuppression group showed different levels of the immunosuppressive effect,such as the analysis of immune organ coefficient , which had significant differences compared with other groups (P<0.01). At 1st week after amniotic membrane implantation in rats,the imunostimulation group showed a certain degree of the immunostimulant effect,such as the killing abilities of NK cell,which had marked differences compared with other groups (P<0.05). Conclusion The amniotic membranes have satisfactory immune safety with implantation in rats and do not cause significant adverse immune reactions.

Bacterial strains isolated from Jeotgal (salted seafood) induce maturation and cytokine production in mouse bone marrow-derived dendritic cells / 대한수의학회지

Jeotgal (salted seafood) has been one of major fermented foods in Korea for long time. Although there are many studies about Jeotgal in various aspects of food, its immunological importance on hosts has not been elucidated yet. In this study, we investigated if several bacteria isolated from Jeotgal may modulate the function of dendritic cells (DCs), powerful antigen-presenting cells equipped with special immunological capabilities. 4 Jeotgal bacteria were selected as representatives and used for experiments. To treat viable DCs, those bacteria were killed at 60degrees C for 30 min. The viability of DCs treated with Jeotgal bacteria was verified and two isolates significantly induced high production of interleukin-12, a representative cell-mediated cytokine of DCs. Surface activation and maturation markers (MHC class II, CD40, CD86) of DCs were analyzed by flow cytometer. In addition, the treated DCs showed significantly high lymphocyte stimulatory capability compared to control DCs based on allogeneic mixed lymphocyte reactions. These observations suggest that Jeotgal isolates can function as immunostimulating bacteria in hosts, like Lactobacillus. Taken together, these experimental evidences may broaden the use of Jeotgal isolates in immunological fields in addition to as a fermented food.

Mucosal Vaccination against Enteric Pathogens in the Developing World.

Of the approximately 9 million children under the age of 5 yr that die annually in developing nations, about 5.1 million will die from preventable infectious diseases. This disastrous human and economic loss is caused in large part by three types of acute diarrhea and attendant respiratory tract infections that are responsible for approximately 2.6 million of these deaths. Thus, enteric pathogens remain a major factor contributing to persistent poverty and poor health in developing nations. Novel mucosal vaccination strategies are emerging that can protect epithelial surfaces and therefore promise a simple, effective and safe interventional therapy to overcome the mortality generated by these debilitating infectious diseases. Before the full potential for mucosal vaccination against enteric diseases can be realized, the innate immune system must be strengthen by addressing secondary problems such as malnutrition, malabsorption and gastrointestinal tract impairment. Here we describe the major enteric pathogens responsible for childhood morbidity and mortality in developing and resource-limited countries. We also discuss the development of mucosal vaccination strategies that when combined with modern principles of nutritional therapy may help improve the health and socio-economic status of developing nations.

Efecto protector de Petiveria alliacea L. (Anamú) sobre la inmunosupresión inducida por 5-fluoruracilo en ratones Balb/c / Protecting effect of Petiveria Alliacea (Anamu) on the immunosuppression induced by 5-fluoruracil in Balb/c mice

A preclinical study was carried out to determinate the protective properties of Petiveria alliacea Linn on 5-Fluoruracilo (5-FU)-immunosuppressed animals, a cytostatic drug often used in cancer treatment. Were use five groups of female Balb/c mice (5 mice/group).Two groups were treated with 400 and 1200 mg/kg of P. alliacea leaves and stems powder respectively, and a third group was treated with carboxymethyl cellulose as vehicle. Two additional control groups were set up: a 5-FU treated group, as immunosuppression control, and a NaCl solution (0.9 percent treated group. Animals were treated daily for five days and then a unique dose of 150 mg/kg of 5-FU was administered and the treatment continued for another four days. At termination blood and tissue samples were collected for leukocyte total count, analysis of bone marrow cellularity, thymus weight and total IgG antibody forming cells. Our results show that the group treated with the highest dose of P. alliacea, was less affected by 5-FU-induced immunosupresion compared with the other treated groups. The results derived from this study suggest that P. alliacea, a medicinal plant product, could be used in patients under antineoplasic regimens to avoid the deleterious adverse effects of the immunosuppressive drugs.

Se realizó un estudio preclínico para la determinación de las propiedades protectoras de la planta Petiveria alliacea Linn sobre la inmunosupresión inducida por la droga citostática 5- Fluoruracilo (5-FU), la cual se utiliza muy frecuentemente en la terapia contra el cáncer. Se utilizaron cinco grupos de ratones hembras Balb/c (5 ratones por grupo) que incluyeron dos grupos de tratamiento con dos niveles de dosis del polvo de las hojas y tallos de la planta: 400 y 1200 mg/kg, así como grupos controles con solución de NACl y con el vehículo (solución de carboximetil celulosa) por vía oral, aplicados durante 5 días, luego una administración única de 150 mg/kg de 5-FU y la continuación del tratamiento en los restantes 5 días. En las variables: conteo global y diferencial de leucocitos, celularidad de la médula ósea, peso del timo y Células Formadoras de Anticuerpos (CFA) IgG totales, se pudo observar que el grupo de mayor dosis de P. alliacea tuvo una menor afectación por la inmunosupresión inducida por 5-FU, en comparación con el resto de los grupos tratados. Estos resultados apoyan el uso de formulaciones de esta planta en pacientes que reciben tratamientos antineoplásicos para la protección contra la inmunosupresión.

Effect of probiotic supplemented diet on marine shrimp survival after challenge with vibrio harveyi / Efeito do uso de dieta suplementada com o probiótico sobre a sobrevivência de camarões marinhos após o desafio com vibrio harveyi

The effect of a Lactobacillus plantarum-supplemented diet on shrimp growth, digestive tract bacterial microbiota, survival, and some hemato-immunological parameters after an experimental challenge with Vibrio harveyi was studied. No difference (P>0.05) was observed in shrimp survival (80±6 percent) and final weight (6.63±0.56g) after 60 days feeding trial. Total bacteria count and Vibrio spp. count in the digestive tract were not diferent (P>0.05) until day 40, but they were lower (P<0.05) in the probiotic-supplemented group on day 60. Total lactic bacteria in the shrimp digestive tract was higher after day 20 in the probiotic-supplemented group. Ten hours after V. harveyi challenge, survival of the probiotic-supplemented group (65.7±2.9 percent) was higher (P>0.05) than the control group (39.9±4.4 percent). Bacterial counts in hemolymph and hepatopancreas was lower (P<0.05) in the probiotic-supplemented group than in the control group after V. harveyi challenge. Total hemocyte count and serum agglutination activity were higher (P>0.05) in the probiotic-supplemented group after challenge with V. harveyi. Probiotic-supplemented diet modifies shrimp digestive tract bacterial microbiota, increasing resistance to V. harveyi infection.

Avaliou-se o efeito de uma dieta suplementada com Lactobacillus plantarum na engorda de Litopenaeus vannamei sobre a microbiota bacteriana do trato digestivo, a sobrevivência e alguns parâmetros hematoimunológicos após desafio com Vibrio harveyi. Não foi observada diferença significativa na sobrevivência (80±6 por cento) e no peso final dos camarões (6,63±0,56g) durante a engorda (60 dias). A população de bactérias totais e Vibrio spp. no intestino não diferiu até o 40º dia de cultivo, mas foi inferior nos camarões alimentados com dieta suplementada com probiótico no 60º dia de cultivo. A população de bactérias lácticas foi superior no intestino de camarões alimentados com dieta suplementada com probióticos após o 20º dia de cultivo. Dez horas após o desafio, a sobrevivência dos camarões alimentados com dieta suplementada com probiótico foi superior (65,7±2,9 por cento) a dos camarões do controle (39,9±4,4 por cento). Camarões alimentados com dieta suplementada com probióticos e desafiados com V. harveyi apresentaram menor contagem de bactérias na hemolinfa e hepatopâncreas. A contagem total de hemócitos e a atividade aglutinante da hemolinfa foram superiores nos camarões inoculados com V. harveyi alimentados com dieta suplementada com probióticos. A suplementação da dieta com probióticos modifica a microbiota bacteriana intestinal dos camarões aumentando sua resistência ao desafio com V. harveyi.

Effect of mucilage from yam on activation of lymphocytic immune cells

The immunostimulating activities of mucilage fraction from yam were investigated. The proliferation of BSA-primed lymph node cells was enhanced between 4.1- to 10.9-fold compare to control, when cultured with 1 to 25 microgram/mL of yam-mucilage fraction. It showed strong immunopotentiating activity than ginseng extract and as remarkable as Bifidobacterium adolescentis M101-4 known as a positive immunostimulator. Mitogenicity to lymph node cells was fully induced by concanavalin A and lipopolysaccharide. The proliferation of splenocytes and Peyer's patch cells was enhanced between 5.0- to 14.1-fold and 2.4- to 6.4-fold, respectively, when cultured with 1 to 25 microgram/mL of yam-mucilage fraction. It enhanced the production of cytokines such as tumor necrosis factor-alpha and IL-6 in the culture of RAW 264.7 macrophage cells. In the culture of lipopolysaccharide-stimulated RAW 264.7 cells, production of cytokines was as similar as compared to controls. In unstimulated RAW 264.7 cells, both tumor necrosis factor-alpha and IL-6 production were enhanced between 15.6- to 60.1-fold and 2.3- to 9.1-fold, respectively. Mucilage fraction from yam is expected to be a safe immunopotentiator to maintain the host immunity and develop a physiologically functional food.

Antitumor and Antioxidant Activities of the Extracts from Fruiting Body of Phellinus linteus

Fruiting bodies of Phellinus linteus were extracted by hot water and alkali methods. Sugar contents of PL-H (hot water extract) and PL-A (alkali water extract) were 81.1%, 37.4% and protein contents were 6.2%, 21.8%, respectively. Amino acid pattern showed that two extracts contained large amount of aspartic acid and alanine. Two extracts showed characteristic IR absorption pattern for glycosidic bond at 890 cm(-1). PL-H was divided two fractions by gel filtration chromatography and the molecular weights of each fraction were estimated to be about 10 kD and 225 kD, respectively and also PL-A was estimated 10 kD. Two extracts showed strong antitumor, immunomodulating and antioxidant activities, and were compared with commercialized glycopeptide anticancer drugs.