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1.
Proc Natl Acad Sci U S A ; 121(4): e2317283121, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38227666

RESUMO

Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.


Assuntos
Neoplasias Pancreáticas , Receptores de Antígenos Quiméricos , Feminino , Humanos , Linhagem Celular Tumoral , Proteínas Ligadas por GPI/metabolismo , Mesotelina , Neoplasias Pancreáticas/tratamento farmacológico , Linfócitos T/metabolismo
2.
Dtsch Tierarztl Wochenschr ; 114(10): 388-93, 2007 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-17970338

RESUMO

Respiratory diseases play an important role in reptiles kept in captivity. Microbiological examinations are described as an essential part of the diagnostic possibilities. Therefore the aim of this study was to collect data on the usefulness of results obtained after aerobic culture (sheepblood, brilliantgreen, sabouraud's agar) of swabs and tracheal lavages following standardized sampling. Respiratory symptoms were found in 24.3% of the snakes, 16.5% of the tortoises/turtles and 1.6% of the lizards presented in the clinic for birds and reptiles at the university Leipzig. Altogether, 52% of the examined samples were found to be bacteriologically and 31% mycologically of pathologic significance. The tracheal lavage proved to be more sensitive in comparison to swabs taken from the pharynx. The bacteria most often found in the samples were Pseudomonas aeruginosa, Klebsiella pneumoniae and Stenotrophomonas maltophila. Mycologic culture revealed Aspergillus sp. and yeast most often. In boids and pythons, the highest number of bacteriologic results assessed to be of pathological significance were found (75%). Mycologically, samples from tortoises were found most often to have a result of pathological significance (48%). To summarize the aerobic cultivation on standard media (in this study: Columbia-Agar with sheep blood, brilliant-green-, Sabouraud-Agar) can be recommended as an initial diagnostic measure in reptiles presented with respiratory symptoms; further pathogens (eg, viral examination, Mycoplasma) should be checked additionally.


Assuntos
Infecções Bacterianas/veterinária , Técnicas de Diagnóstico do Sistema Respiratório/veterinária , Micoses/veterinária , Répteis/microbiologia , Infecções Respiratórias/veterinária , Animais , Bactérias Aeróbias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/fisiopatologia , Micoses/diagnóstico , Micoses/fisiopatologia , Faringe/microbiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia , Traqueia/microbiologia
3.
J Hum Lact ; 15(1): 35-9, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10578773

RESUMO

This pilot study evaluated how the scores from each of two breastfeeding assessment tools correlated with breastfeeding satisfaction and problems. A convenience sample of 30 first-time breastfeeding mothers participated. Mothers were randomly assigned to use either the LATCH or Infant Breastfeeding Assessment Tool (IBFAT). The Maternal Breastfeeding Evaluation Scale (MBFES) and Potential Early Breastfeeding Problem Tool (PEBPT) were used to evaluate the association of the scores of each assessment tool with breastfeeding satisfaction and breastfeeding problems. As scores on the both the LATCH and IBFAT increased, maternal satisfaction scores tended to increase, but not significantly, and breastfeeding problem scores tended to decrease (r = -0.5, p = 0.06 and r = -0.49, p = 0.06; respectively.


Assuntos
Atitude Frente a Saúde , Aleitamento Materno/efeitos adversos , Aleitamento Materno/psicologia , Transtornos da Lactação/etiologia , Transtornos da Lactação/psicologia , Mães/psicologia , Avaliação em Enfermagem/métodos , Satisfação Pessoal , Adulto , Feminino , Humanos , Projetos Piloto , Reprodutibilidade dos Testes
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