RESUMO
The whitefly, Bemisia tabaci (Gennadius), is responsible for significant yield losses in many crops, including potato, by sucking the phloem sap and transmitting a number of plant viruses. B. tabaci is a complex of cryptic species which is commonly designated as genetic groups. The B. tabaci genetic groups differ biologically with respect to host plant preference, insecticidal resistance, reproduction capacity, and ability to transmit begomoviruses. Therefore, understanding genetic variation among populations is important for establishing crop-specific distribution profile and management. We sequenced the mitochondrial cytochrome oxidase I (mtCOI) gene of B. tabaci collected from major potato growing areas of India. BLAST analysis of the 24 mtCOI sequences with reference Gene Bank sequences revealed four B. tabaci genetic groups prevailing in this region. mtCOI analysis exhibited the presence of Asia II 1, Asia II 5, Asia 1, and MEAM1 B. tabaci genetic groups. Our study highlighted that a new genetic group Asia II 5 has been detected in Indo-Gangetic Plains. Further virus-vector relationship study of ToLCNDV with Asia II 5 B. tabaci revealed that females are efficient vector of this virus as compared to males. This behavior of females might be due to their ability to acquire more virus titer than males. This study will help in better understanding of whitefly genetic group mediated virus diseases.
RESUMO
The tumor antigen (TA)-targeted monoclonal antibodies (mAb) cetuximab and panitumumab target the human epidermal growth factor receptor and have been integrated into treatment regimens for advanced squamous cell carcinoma of the head and neck (SCCHN). The therapeutic efficacy of these mAbs has been found to be enhanced when combined with radiotherapy and chemotherapy. However, clinical trials indicate that these findings are limited to fewer than 20% of treated patients. Therefore, identifying patients who are likely to benefit from these agents is crucial to improving therapeutic strategies. Interestingly, it has been noted that TA-targeted mAbs mediate their effects by contributing to cell-mediated cytotoxicity in addition to inhibition of downstream signaling pathways. Here, we describe the potential immunogenic mechanisms underlying these clinical findings, their role in the varied clinical response and identify the putative biomarkers of antitumor activity. We review potential immunological biomarkers that affect mAb therapy in SCCHN patients, the implications of these findings and how they translate to the clinical scenario, which are critical to improving patient selection and ultimately outcomes for patients undergoing therapy.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Antígenos de Neoplasias/imunologia , Biomarcadores , Carcinoma de Células Escamosas/radioterapia , Cetuximab , Terapia Combinada , Receptores ErbB/imunologia , Neoplasias de Cabeça e Pescoço/radioterapia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Macrófagos/imunologia , Panitumumabe , Infecções por Papillomavirus , Receptores de IgG/genética , Fator de Transcrição STAT3/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linfócitos T Reguladores/imunologia , Evasão Tumoral/imunologiaRESUMO
BACKGROUND: Although regulatory T cells (Treg) are highly enriched in human tumours compared with peripheral blood, expression of the immune-checkpoint receptors, immunosuppressive molecules and function of Treg in these two sites remains undefined. METHODS: Tumour-infiltrating lymphocytes and peripheral blood lymphocytes were isolated from a cohort of head and neck squamous cell carcinoma (HNSCC) patients. The immunosuppressive phenotypes and function of intratumoral Treg were compared with those of peripheral blood Treg. RESULTS: The frequency of immune-checkpoint receptor-positive cells was higher on intratumoral FOXP3(+)CD25(hi) Treg compared with circulating Treg (CTLA-4, P=0.002; TIM-3, P=0.002 and PD-1, P=0.002). Immunosuppressive effector molecules, LAP and ectonucleotidase CD39 were also upregulated on intratumoral FOXP3(+) Treg (P=0.002 and P=0.004, respectively). CTLA-4 and CD39 were co-expressed on the majority of intratumoral FOXP3(+)CD4(+) Treg, suggesting that these molecules have a key role in regulatory functions of these cells in situ. Notably, intratumoral Treg exhibited more potently immunosuppressive activity than circulating Treg. CONCLUSION: These results indicate that intratumoral Treg are more immunosuppressive than circulating Treg and CTLA-4 and CD39 expressed can be potential target molecules to inhibit suppressive activities of intratumoral Treg in situ.
Assuntos
Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Imunossupressores/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T Reguladores/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Apirase/metabolismo , Antígeno CTLA-4/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/metabolismo , Citocinas/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Tolerância Imunológica/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismoRESUMO
A series of substituted N-arylphthalamic acids 3a-i has been synthesized by the reaction of phthalic anhydride 1 and aryl- or heterocyclic amines 2a-i, in the absence of solvents, in a domestic microwave oven. The formation of nine N-arylphthalamic acids was accomplished in 1-3 min giving excellent yields for compounds 3a-g, but moderate yield of compounds 3h and 3i, respectively. Compounds 3h and 3i are new. Interestingly, N-arylphthalamic acids 3a-i induced hyperlipidemia in Swiss white mice and also increased animals' body weight.
Assuntos
Hipolipemiantes/síntese química , Ácidos Ftálicos/síntese química , Animais , Peso Corporal/efeitos dos fármacos , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/metabolismo , Hipolipemiantes/química , Hipolipemiantes/toxicidade , Camundongos , Micro-Ondas , Modelos Animais , Ácidos Ftálicos/química , Ácidos Ftálicos/toxicidadeRESUMO
A facile synthesis of anomerically pure phthalimidomethyl 2,3,4,6-tetra-O-acetyl- and phthalimidomethyl 2,3-di-O-acetyl-4,6-di-O-benzoyl-alpha-D-mannopyranosides (6 and 9b) starting from N-hydroxymethylphthalimide and tri-O-acetyl-D-glucal is described. Compounds 3, 6, 8, 9a and 9b have been tested for their hypolipidemic activity in mice. All these compound showed significant reduction of plasma cholesterol and triglyceride levels. Compound 9b has been found to possess the highest activity.
Assuntos
Hipolipemiantes/síntese química , Manosídeos/farmacologia , Animais , Colesterol/sangue , Hipolipemiantes/farmacologia , Masculino , Manosídeos/síntese química , Camundongos , Ftalimidas/síntese química , Ftalimidas/farmacologia , Triglicerídeos/sangueRESUMO
A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin. Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms.
Assuntos
Anti-Infecciosos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Oxidiazóis/química , Animais , Antibacterianos , Bactérias/efeitos dos fármacos , Carragenina , Edema/induzido quimicamente , Edema/prevenção & controle , Fungos/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Oxidiazóis/farmacologia , Ratos , Ratos WistarRESUMO
Seven new phthalimide derivatives (9a-g) with 1,2,4-oxadiazol-5-yl methyl group attached to nitrogen have been synthesized from N-phthaloylglycine 6 and arylamidoximes 7a-g. All of these showed potent analgesic effect with acetic acid induced "writhing" test in mice. One of the better compounds (ID50 = 2.2 mg/Kg i.p.) has been found to be 9a which also demonstrates analgesic activity against inflammatory pain.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Ftalimidas/síntese química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Camundongos , Ftalimidas/farmacologiaRESUMO
Significant local analgesic and anti-inflammatory activity has been observed after oral administration of 3-[3-(phenyl)-1,2,4-oxadiazol-5-yl] propionic acid (POPA). Doses of 150 and 300 mg/kg body weight administered orally by gavage to adult (25-35 g) albino mice of both sexes can inhibit acetic acid-induced writhing by 31.0% and 49.5%, respectively (mean +/- SEM writhing numbers during 20 min were 52.0 +/- 6.0 and 38.3 +/- 7.2 vs 75.8 +/- 6.6 for control group which received saline; N = 6). Carrageenin-induced inflammation in the female Wistar rat (200-250 g) can be reduced by 43.3% and 42.2% 3 h after oral administration (gavage) of 75 and 150 mg/kg of POPA (mean +/- SEM, 30.0 +/- 1.3% and 30.6 +/- 2.4% vs 52.9 +/- 3.7% for control group which received saline; N = 5). In the hot plate test on adult albino mice (25-35 g) of both sexes, POPA (150 and 300 mg/kg, po) was totally ineffective (N = 10). Our results indicate that POPA appears to offer potential safety and efficacy as a local analgesic and anti-inflammatory agent with no central nervous system involvement
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Inflamação/tratamento farmacológico , Oxidiazóis/uso terapêutico , Dor/tratamento farmacológico , Administração Oral , Animais , Anti-Inflamatórios , Feminino , Masculino , Camundongos , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Significant local analgesic and anti-inflammatory activity has been observed after oral administration of 3-[3-(phenyl)-1,2,4-oxadiazol-5-yl] propionic acid (POPA). Doses of 150 and 300 mg/kg body weight administered orally by gavage to adult (25-35 g) albino mice of both sexes can inhibit acetic acid-induced writhing by 31.0 and 49.5, respectively (mean +/- SEM writhing numbers during 20 min were 52.0 +/- 6.0 and 38.3 +/- 7.2 vs 75.8 +/- 6.6 for control group which received saline; N = 6). Carrageenin-induced inflammation in the female Wistar rat (200-250 g) can be reduced by 43.3 and 42.2 3 h after oral administration (gavage) of 75 and 150 mg/kg of POPA (mean +/- SEM, 30.0 +/- 1.3 and 30.6 +/- 2.4 vs 52.9 +/- 3.7 for control group which received saline; N = 5). In the hot plate test on adult albino mice (25-35 g) of both sexes, POPA (150 and 300 mg/kg, po) was totally ineffective (N = 10). Our results indicate that POPA appears to offer potential safety and efficacy as a local analgesic and anti-inflammatory agent with no central nervous system involvement
Assuntos
Animais , Masculino , Feminino , Camundongos , Ratos , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides , Inflamação/tratamento farmacológico , Oxidiazóis/uso terapêutico , Dor , Administração Oral , Anti-Inflamatórios , Ratos Wistar , Fatores de TempoRESUMO
The Diels-Alder product from the reaction of methyl 2,3,6-trideoxy-alpha-D-glycero-hex-2-enopyranosid-4-ulose (1b) with trans-1-methoxy-3-tert-butyl-dimethylsilyloxy-1,3-butadiene is 3b (93%). Reaction of 3b wih sodium borohydride causes reduction of the C-4 carbonyl group only, but, with lithium aluminum hydride, further reactions occur which can be rationalized by fragmentation brought about by hydride cleavage on the silicon-oxygen bond, with simultaneous ejection of the beta-methoxyl group complexed to a trivalent aluminum species. The enone resulting from this fragmentation also reacts further with lithium aluminum hydride, and several products result. The behavior of postulated intermediates, which have been prepared separately and subjected to the reaction conditions, supports the proposed reaction mechanisms. The "second generation" enone (methyl 2,3,6-trideoxy-alpha-D-talopyranosido)-[3,2-d]-2-cyclohexenone+ ++ (10a), arising from the first generation precursors 1b, has been prepare by two routes.