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BACKGROUND: Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. OBJECTIVES: To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200â mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. RESULTS: At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded. CONCLUSIONS: Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.
Psoriasis is a skin disease characterized by scaly and raised patches of skin on any part of the body. The condition can be caused by a combination of how a person's immune system works, their genes and their environment. A cytokine is a substance secreted by certain cells of the immune system that have an effect on other cells. One such cytokine, called IL-17A, has been associated with different inflammatory diseases, including psoriasis. We conducted a large trial in Chinese people with moderate-to-severe psoriasis to look at the efficacy (ability to produce the intended result) and safety of a medicine called xeligekimab (known as a 'monoclonal antibody') which works by targeting IL-17A. We randomly assigned 420 Chinese patients to receive 200â mg of xeligekimab every 2 weeks or a 'placebo' (no active medicine) for the first 12 weeks. We extended the treatment schedule of xeligekimab to every 4 weeks for a further 40 weeks. To assess how the medicine worked, we measured people's psoriasis symptoms and severity. To assess how safe the medicine was, we looked at the side-effects (or 'adverse events'). The results of this trial showed that xeligekimab improved people's psoriasis and itching starting at week 4 of receiving treatment, and more than 60% of people achieved improvement or remission by week 6, which was sustained up to week 52. The safety of xeligekimab was similar to another medicine classed as a monoclonal antibody (called secukinumab) and there were no new or unexpected adverse events reported. Overall, our findings suggest that xeligekimab is a safe and effective medicine for the treatment of psoriasis in Chinese people.
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Anticorpos Monoclonais Humanizados , Psoríase , Humanos , Psoríase/tratamento farmacológico , Masculino , Método Duplo-Cego , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Esquema de Medicação , Interleucina-17/antagonistas & inibidores , Índice de Gravidade de Doença , Idoso , Adulto JovemRESUMO
BACKGROUND: There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. METHODS: In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. RESULTS: At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician's Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs . 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs . 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. CONCLUSION: Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05108766.
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Anticorpos Monoclonais Humanizados , Psoríase , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , População do Leste Asiático , Psoríase/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Verruca plana is a benign proliferation of the skin caused by human papilloma virus (HPV) infection. Fresh garlic can serve as an alternative therapy, and it has shown considerable effectiveness as a topical treatment for verruca plana. However, topical garlic treatment for verruca plana triggered Koebner phenomenon (KP), which has not been previously reported. AIM: The aim of our report is to explore the possible causes of this adverse reaction. METHOD: We here describe a 20-year-old female patient who developed a beaded rash after garlic treatment for facial wart plana, known as autoinoculation or KP. RESULTS: Garlic may have caused damage to the surrounding normal skin through primary irritation or allergic reactions. Then, the HPV virus on the primary verruca plana took the opportunity to spread to the surrounding skin injured by garlic stimulation, triggering the KP. CONCLUSION: When using garlic to treat verruca plana, the operator needs to precisely apply the mashed garlic to the warts, and this treatment is strictly prohibited for patients who are allergic to garlic. Avoid such adverse reactions.
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Alho , Infecções por Papillomavirus , Verrugas , Feminino , Humanos , Adulto Jovem , Adulto , Infecções por Papillomavirus/complicações , Verrugas/tratamento farmacológico , Papillomavirus Humano , Administração TópicaRESUMO
OBJECTIVES: Syphilis is a sexually transmitted infection (STI) caused by treponema pallidum. Its rash usually affects the trunk and limbs extensively, including the palms and soles of the feet. Secondary syphilis confined to the face is extremely rare. METHODS: We report a case of annular rupioid secondary syphilis, which was misdiagnosed as verruca vulgaris. RESULTS: The patient's lesions were confined to the face and resembled oyster shells. Her serological tests results were positive for treponema pallidum particle agglutination assay (TPPA) and rapid plasma reagin (RPR) (1:64). CONCLUSION: According to epidemiological history, clinical presentation, non-treponemal tests, treponemal tests, and effective benzathine penicillin G treatment, confirmed secondary syphilis.
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Sífilis , Feminino , Humanos , Penicilina G Benzatina/uso terapêutico , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sorodiagnóstico da Sífilis/métodos , Treponema pallidumRESUMO
2',4'-dihydroxy-6'-methoxychalcone (cardamonin) is a natural compound with anti-proliferative effects on several cancer types including nasopharyngeal carcinoma. The effects of cardamonin on melanoma cells are unknown. The present study investigated the anti-proliferative effect of cardamonin on human melanoma cell lines (M14 and A375), and the underlying apoptosis inducing mechanisms. MTS assay showed that cardamonin inhibited M14 cells viability, and a reduction of the M14 cell density was also observed. Flow cytometry showed that cardamonin induced M14 cells apoptosis in a dose-dependent manner. Western blot analysis showed protein expression in M14 and A375; the pro-apoptotic protein BAX was upregulated, while the anti-apoptotic protein B-cell lymphoma-2 was downregulated. The protein expression of cleaved caspase-8, -9 and cleaved poly (ADP-ribose) polymerase was increased, whereas P65 was decreased. Furthermore, cardamonin inhibited M14 cell migration. These findings suggest that cardamonin may be a novel anticancer treatment for human melanoma.
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OBJECTIVE: To establish cisplatin (CDDP)-resistant melanoma B16F10 (CDDP-R B16F10) cell line with stable expression of T-cadherin, and to study its biological characteristics.â© Methods: CDDP-R B16F10 cell line was exposure to high and gradually increased dose of CDDP. 3-(4.5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) was used to test the proliferation of CDDP-R B16F10 cell line, and the sensitivity of CDDP-R B16F10 cell line to CDDP and paclitaxel was examined. The pEGFP-N1-T-cadherin, a plasmid vector encoding human T-cadherin, was generated by inserting T-cadherin cDNA into a pEGFP-N1 vector. The pEGFP-N1-T-cadherin was transfected into CDDP-R B16F10 cell line. The expression of T-cadherin mRNA and protein were measured by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry SP method, respectively. The effect of T-cadherin combined with CDDP on proliferation of CDDP-R B16F10 cell line was determined by MTT assay. The sensitivity of CDDP-R B16F10 cell line with stably transfected T-cadherin to paclitaxel was examined by MTT assay.â© Results: The CDDP-R B16F10 cell line was established successfully. There was no difference in proliferation between the CDDP-R B16F10 cell line and B16F10 cell line (P>0.05). The IC50 of CDDP-R B16F10 cell line and B16F10 cell line to CDDP were 268.706 and 19.748 mg/L, respectively, and the resistance index was 13.61. The IC50 of CDDP-R B16F10 cell line and B16F10 cells to paclitaxel were 11.415 and 7.799 mg/L, respectively, and the resistance index was 1.46. The expression vector pEGFP-N1-T-cadherin was constructed successfully. RT-PCR, Western blotting and immunohistochemistry SP method showed that T-cadherin could be transcribed and expressed. MTT assay showed that T-cadherin combined with CDDP could inhibit the proliferation of CDDP-R B16F10 cell line (P<0.05). Factorial analysis showed that there was interaction between T-cadherin and CDDP in inhibiting the proliferation of CDDP-R B16F10 cell line (P<0.05). T-cadherin combined with paclitaxel could inhibit the proliferation of CDDP-R B16F10 cell line (P<0.05). Factorial analysis showed that there was no interaction between T-cadherin and paclitaxel in inhibiting the proliferation of CDDP-R B16F10 cell line (P>0.05). â© Conclusion: The CDDP-R B16F10 cell line with stable expression of T-cadherin is established successfully. T-cadherin can reverse the CDDP resistance to CDDP-R B16F10 cell line, and promote its sensitivity to paclitaxel.
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Melanoma , Antineoplásicos , Caderinas , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino , Resistencia a Medicamentos Antineoplásicos , HumanosRESUMO
Ganoderma lucidum (Fr.) Karst (Ganodermataceae) is a medicinal mushroom that has been extensively used in China for centuries to promote longevity and improve vigor without significant adverse effects. There is continuous interest in the bioactive properties of G. lucidum in view of its newly developed popularity in other regions besides Asia, such as Europe. Glycopeptide derived from G. lucidum (Gl-PS) is one of the main effective components isolated from this mushroom. The Gl-PS has been demonstrated pleiotropic with many bioactivities including immunomodulatory and antitumor effects. Macrophages are important cells involved in innate and adaptive immunity. Classically activated macrophages (M1) and alternatively activated macrophages (M2), with their different roles, display distinct cytokine profiles: M1 preferentially produces TNF-α, IL-6, and IL-12; conversely, M2 generates more IL-10 and arginase. Gl-PS might have the potential to promote macrophage M1 polarization by lipopolysaccharide (LPS). In this study, LPS was used to induce the M1 polarization. It was shown that the level of the TNF-α, IL-6, and IL-12 were increased and the IL-10 and arginase I were decreased in the polarized M1 macrophages after application of Gl-PS compared to the control. The results indicated the potential of Gl-PS to promote M1 polarization vs M2, with the health beneficial understanding of the bioactivities of Gl-PS.
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Antígenos de Plantas/farmacologia , Glicopeptídeos/farmacologia , Macrófagos Peritoneais/imunologia , Animais , Arginase/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Reishi/imunologiaRESUMO
Some cytokines, such as interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), produced by lymphocytes might play an important role in anti-tumor immunity and their production is possibly suppressed by cancer. Amelioration of the suppression of cytokine production might contribute to cancer control. Ganoderma lucidum polysaccharides (Gl-PS), a versatile group of a component of G. lucidum and one with various bioactivities, might have this potential. In this study, analyses including reverse transcription and the polymerase chain reaction (RT-PCR), immunocytochemistry and Western blot were used to test the effects of Gl-PS on the production of IL-2, IFN-γ and TNF-α in mononuclear lymphocytes by incubating Gl-PS with mouse splenic mononuclear lymphocytes in the presence of B16F10 cell culture supernatant following activation by phytohemagglutinin. The RT-PCR, immunocytochemistry and Western blot assays showed that the production of IL-2, IFN-γ and TNF-α in mononuclear lymphocytes was suppressed by B16F10 cell culture supernatant at both the mRNA and protein levels, whereas the suppression was fully or partially ameliorated by Gl-PS. The amelioration by Gl-PS against the suppression of the production of IL-2, IFN-γ and TNF-α in mononuclear lymphocytes by B16F10 cell culture supernatant might contribute to cancer control.
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Citocinas/imunologia , Polissacarídeos Fúngicos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/imunologia , Melanoma/imunologia , Reishi/química , Animais , Linhagem Celular Tumoral , Polissacarídeos Fúngicos/química , Melanoma/patologia , CamundongosRESUMO
Transforming growth factor ß (TGF-ß), interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF) are three of the commonly studied cytokines playing an important role in tumor initiation and progression. Besides their promotional effects on tumor progression, the three cytokines have immunosuppressive effects that facilitate tumor initiation and progression as well. Ganoderma lucidum polysaccharides (Gl-PS) with multiple bioactivities may have the effect on B16F10 melanoma cells to induce stronger antitumor immune response that has been demonstrated. Gl-PS may have the suppressive effects on the production of these three cytokines, which has yet to be demonstrated. In this study, we tested these effects of Gl-PS by incubating Gl-PS with malignant tumor cells such as B16F10 cells, a melanoma cell line, and LA795 cells, a lung carcinoma cell line. RT-qPCR and enzyme-linked immunosorbent assay showed that the production of TGF-ß1, IL-10, and VEGF in B16F10 melanoma cells and LA795 lung carcinoma cells was suppressed by Gl-PS at both mRNA and protein levels, suggesting that the suppression on production of TGF-ß, IL-10, and VEGF in B16F10 melanoma cells and LA795 lung carcinoma cells by Gl-PS may contribute to the therapy on melanoma and lung carcinoma along with the induction of stronger antitumor immune response.
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Interleucina-10/antagonistas & inibidores , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Polissacarídeos/farmacologia , Reishi/química , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Carcinoma/metabolismo , Linhagem Celular Tumoral , Interleucina-10/biossíntese , Interleucina-10/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Melanoma Experimental/genética , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/genética , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND/AIMS: This study was conducted to determine the potential of Ganoderma lucidum polysaccharides (Gl-PS) in protection against lung cancer patient plasma-induced suppression of lymphocytes. Lung cancer is a major cause of disease and loss of life in the United States and worldwide. Cancer cells release immunosuppressive mediators, such as PGE2, TGF-ß, IL-10, and VEGF, to inhibit the immune response to escape from immune surveillance. Gl-PS has been shown to counteract this immune inhibition in an animal cell culture model, and thus to facilitate tumor control. The present study explored whether or not such an effect could also be demonstrated in human lung cancer patients. METHODS: Immunofluorescence, flow cytometry, MTT, immunocytochemistry, and western blot analysis were used to assess lymphocyte activation with PHA. RESULTS: The plasma of lung cancer patients suppressed proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA, effects that were partially of fully reversed by Gl-PS. CONCLUSION: Lung cancer patient plasma-induced suppression of lymphocyte activation by phytohemagglutinin may be antagonized fully or partially by Gl-PS, an observation suggesting the potential of Gl-PS in cancer therapy.
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Proliferação de Células/efeitos dos fármacos , Polissacarídeos Fúngicos/farmacologia , Neoplasias Pulmonares/sangue , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/metabolismo , Reishi/química , Idoso , Animais , Citocinas/sangue , Citocinas/imunologia , Feminino , Polissacarídeos Fúngicos/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
It is well-documented that macrophages have the functions to regulate antitumor immune response. Antitumor response can be launched by a series of events, starting with inflammation mediated by monocyte/macrophages, which stimulates natural killer and dendritic cells and finally activates the cytotoxic lymphoid system. Monocytes/macrophages may be the first line of defense in tumors. However, specific and nonspecific immunotherapy for human cancer has shown no success or limited success in clinical trials. Part of the reasons attribute to tumor-derived soluble factors that suppress functions of immune cells or induce apoptosis of these cells, including macrophages. Therefore, antagonism of the suppression on the macrophages is an important goal for tumor immunotherapy. To achieve this purpose, Ganoderma lucidum polysaccharides (Gl-PS) with multiple bioactivities were used on mouse peritoneal macrophages incubating with culture supernatants of B16F10 melanoma cells (B16F10-CS). It was shown that the viability, phagocytic activity, NO production, TNF-α production and activity in peritoneal macrophages after activation by lipopolysaccharide were suppressed by B16F10-CS, while the suppressions were fully or partially antagonized by Gl-PS. In conclusion, B16F10-CS is suppressive to the viability, phagocytic activity, NO production, TNF-α production and activity in peritoneal macrophages while Gl-PS had the antagonistic effects against this suppression, suggesting this potential of Gl-PS to facilitate cancer immunotherapy.
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Meios de Cultura/química , Macrófagos Peritoneais/efeitos dos fármacos , Melanoma Experimental/química , Polissacarídeos/farmacologia , Reishi/química , Animais , Sobrevivência Celular , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Fagocitose/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Melanoma is one of the most deadly skin cancers. T-cadherin is an atypical member of the cadherin superfamily as it lacks the transmembrane and cytoplasmic domains and is anchored to cell membranes through glycosylphosphatidylinositol (GPI) anchors. T-cadherin downregulation is associated with a poorer prognosis in various carcinomas, such as lung, ovarian, cervical and prostate cancer, while in the majority of cancer cell lines, T-cadherin re-expression inhibits cell proliferation and invasiveness, increases susceptibility in apoptosis and reduces tumor growth in in vivo models. The functional relevance of T-cadherin gene expression in melanoma progression remains to be clarified. The present study was designed for this purpose. The T-cadherin gene was transfected into B16F10 melanoma cells to express T-cadherin in the cells which were originally deficient in T-cadherin expression. The proliferation, invasiveness, apoptosis and cell cycle of the transfected B16F10 melanoma cells were analyzed. The present study showed that the expression of T-cadherin in B16F10 melanoma cells markedly reduced cell proliferation and permeation through Matrigel-coated membranes, representing invasiveness. The percentage of early apoptotic cells and cells in the G2/M phase of the cell cycle was markedly increased compared with either parental B16F10 (without transfection) or empty pEGFP-N1 (without T-cadherin gene)-transfected B16F10 cells, suggesting G2/M arrest, with similarity between the parental and empty pEGFP-N1-transfected B16F10 cells. T-cadherin is important in melanoma progression and may be a possible target for therapy in melanoma and certain other types of cancer.
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Immune responses to tumor-associated antigens are often detectable in tumor-bearing hosts, but they fail to eliminate malignant cells or prevent development of metastases. Tumor cells produce factors such as interleukin-10, transforming growth factor-ß1 and vascular endothelial growth factor (VEGF) that suppress the function of immune cells or induce apoptosis of immune cells. Culture supernatant of tumor cells may contain these immunosuppressive factors which suppress lymphocyte activation. CD71 and FasL are two important molecules that are expressed upon lymphocyte activation. Counteraction against suppression CD71 and FasL expression upon lymphocyte activation may benefit tumor control. A potential component with this effect is Ganoderma lucidum polysaccharides (Gl-PS). In this study, Gl-PS was used on lymphocytes incubating with culture supernatant of B16F10 melanoma cells (B16F10-CS) in the presence of phytohemagglutinin. Following induction with phytohemagglutinin, B16F10-CS suppressed CD71 expression in lymphocytes (as detected by immunofluorescence and flow cytometry), proliferation in lymphocytes (as detected by MTT assay), and FasL expression in lymphocytes (as detected by immunocytochemistry and western blot analysis), while Gl-PS fully or partially counteracted these suppressions. Gl-PS showed counteractive effects against suppression induced by B16F10-CS on CD71 and FasL expression upon lymphocyte activation, suggesting the potential of Gl-PS to facilitate cancer immunotherapy.
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Urticaria is one of the most frequent dermatoses and its prevalence in the general population is estimated to be ~20%, whereas a substantial percentage of the cases may be classified as chronic idiopathic urticaria (CIU). The inflammatory response presenting with spontaneous wheals exhibits pro-inflammatory characteristics, involving a prominent role for lymphocytes with a mixed Th1/Th2 response in which interleukin (IL)-2 and IL-10 are prominently secreted by Th1 and Th2 cells, respectively. In CIU patients, it was demonstrated that IL-10 production was elevated and IL-2 reduced compared to controls. Therefore, inhibition of IL-10 and promotion of IL-2 production by the lymphocytes, indicating Th2 inhibition and Th1 promotion, may facilitate the treatment of CIU. Whether the polysaccharide nucleic acid fraction of bacillus Calmette-Guérin (BCG-PSN), which possesses multiple immunomodulatory properties, has that potential, remains to be elucidated. In this study, BCG-PSN was used on lymphocytes isolated from CIU patients, with healthy donors used as controls. Immunocytochemistry and ELISA were used to detect IL-2 and IL-10 production. It was demonstrated that the IL-2 production by the lymphocytes in the CIU group was significantly lower compared to that in the healthy control group and it increased sequentially with the increase of the concentration of BCG-PSN used. By contrast, the IL-10 production by the lymphocytes in the CIU group was significantly higher compared to that in the healthy control group and decreased sequentially with the increase of the concentration of BCG-PSN used. Thus, it may be concluded that the BCG-PSN has the potential to promote IL-2 and inhibit IL-10 production in the lymphocytes of CIU patients, facilitating the treatment of CIU.
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PURPOSE: It is obvious that malignant cells evade from immune system in patients with manifest malignancy. Deficient major histocompatibility complex (MHC) class I and costimulatory molecules on malignant cells partially consist of evasion strategy since antigen bond MHC and costimulatory molecules provide two signals necessary for T cell activation. Therefore, enhancement of MHC-I and costimulatory molecules may favor restraint of the evasion. For this purpose, Ganoderma lucidum Polysaccharides (Gl-PS) was used on B16F10 melanoma cells in this study. METHODS: Immunocytochemistry and flowcytometry were used to determine the H-2K(b) and H-2D(b) (two prominent MHC class I molecules in C57BL mouse) as well as B7-1 and B7-2 (two prominent costimulatory molecules) expression on B16F10 cells after incubation with Gl-PS, while messenger ribonucleic acid (mRNA) of these molecules was detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The H-2K(b) and H-2D(b), and B7-1 and B7-2 on B16F10 cells and mRNAs of these molecules were enhanced by Gl-PS, and more efficient antitumor cytotoxicity was induced by the Gl-PS treated cells. CONCLUSIONS: The MHC class I molecules and costimulatory molecules may be enhanced by Gl-PS, and more efficient immune cell mediated cytotoxicity against these B16F10 cells may be induced, which may favor cancer therapy.
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Antineoplásicos Fitogênicos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes MHC Classe I/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Polissacarídeos/uso terapêutico , Reishi/química , Animais , Antineoplásicos Fitogênicos/química , Antígeno B7-1/biossíntese , Antígeno B7-2/biossíntese , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Genes MHC Classe I/genética , Antígenos H-2/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/químicaRESUMO
OBJECTIVES: Tumour cells produce factors such as interleukin 10 (IL-10), transforming growth factor ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) that suppress the function of immune cells or induce apoptosis of immune cells. One of the most important goals of tumour immunotherapy is to antagonize this suppression on immune cells. Ganoderma lucidum polysaccharides (Gl-PS) may have this potential. The purpose of this study was to determine the antagonistic effects of Gl-PS on the suppression induced by B16F10 melanoma cell culture supernatant (B16F10-CS) on lymphocytes. METHODS: Gl-PS was used on lymphocytes incubated with B16F10-CS. Enzyme-linked immunosorbent assay was used to determine the levels of IL-10, TGF-ß1 and VEGF in B16F10-CS. The MTT assay was used to determine the proliferation of lymphocytes. Immunocytochemistry and Western blot assay were used to determine perforin and granzyme B production in lymphocytes. KEY FINDINGS: There were elevated levels of IL-10, TGF-ß1 and VEGF in B16F10-CS. The lymphocyte proliferation, and perforin and granzyme B production in lymphocytes after induction with phytohemagglutinin, as well as lymphocyte proliferation in the mixed lymphocyte reaction, were suppressed by B16F10-CS. This suppression was fully or partially antagonized by Gl-PS. CONCLUSIONS: B16F10-CS suppressed lymphocyte proliferation and perforin and granzyme B production in lymphocytes after induction with phytohemagglutinin, as well as lymphocyte proliferation in the mixed lymphocyte reaction. This suppression may be associated with elevated levels of immunosuppressive IL-10, TGF-ß1 and VEGF in B16F10-CS. Gl-PS had antagonistic effects on the immunosuppression induced by B16F10-CS, suggesting the potential for Gl-PS in cancer immunotherapy.
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Produtos Biológicos/farmacologia , Tolerância Imunológica/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Melanoma Experimental/imunologia , Polissacarídeos/farmacologia , Reishi/química , Animais , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Granzimas/biossíntese , Interleucina-10/metabolismo , Contagem de Linfócitos , Linfócitos/metabolismo , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Perforina/biossíntese , Lectinas de Plantas , Polissacarídeos/uso terapêutico , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The immune system in patients with cancer often fails to control tumour growth because of deficient immunogenicity of tumour cells. Ganoderma lucidum polysaccharides (Gl-PS) are believed to have anti-tumour effects by boosting host immune function. Additionally, Gl-PS may have some direct effects on tumour cells in the activation of lymphocytes, thus enhancing the immunogenicity of tumour cells. We tested the effects of Gl-PS in lymphocyte activation by incubating Gl-PS with a tumour cell line deficient in antigen presentation. Our study showed that Gl-PS can promote B16F10 melanoma cells to induce lymphocyte proliferation, CD69 and FasL expression and IFN-γ production, indicating that Gl-PS can improve the nature of B16F10 cells to activate lymphocytes. Furthermore, H-2D(b) [a major histocompatibility (MHC) class I molecule], and B7-1 and B7-2 (two prominent co-stimulatory molecules expressed on B16F10 cells) were enhanced by Gl-PS, suggesting that these molecules may at least partially be involved in the process of Gl-PS on B16F10 cells to activate lymphocytes.