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1.
Clin Cancer Res ; 13(11): 3339-46, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17545541

RESUMO

PURPOSE: To evaluate the expression levels of claudin-3 and claudin-4, the low- and high-affinity receptors, respectively, for the cytotoxic Clostridium perfringens enterotoxin (CPE) in uterine carcinosarcomas and explore the potential for targeting these receptors in the treatment of this aggressive uterine tumor. EXPERIMENTAL DESIGN: We analyzed claudin-3 and claudin-4 receptor expression at mRNA and protein levels in flash frozen and formalin-fixed, paraffin-embedded carcinosarcoma specimens. Recombinant CPE was used as a novel therapy against chemotherapy-resistant carcinosarcoma cell lines in vitro. The therapeutic effect of sublethal doses of CPE was studied in severe combined immunodeficient mouse xenografts harboring large s.c. carcinosarcomas. RESULTS: All flash-frozen carcinosarcoma biopsies (12 of 12) and short-term carcinosarcoma cell lines evaluated overexpressed claudin-3 and claudin-4 by quantitative reverse transcription-PCR. Membranous immunoreactivity for claudin-4 protein expression was documented in 80% (20 of 25) of primary tumors and 100% (6 of 6) of the metastatic carcinosarcomas, whereas negligible staining was found in normal endometrial cells. Regardless of their resistance to chemotherapeutic agents, all short-term carcinosarcoma cell lines tested died within 1 h of exposure to 3.3 microg/mL of CPE in vitro. Intratumoral injections of well-tolerated doses of CPE in large s.c. carcinosarcoma xenografts led to large areas of tumor cell necrosis and tumor disappearance in all treated animals. CONCLUSIONS: Claudin-3 and claudin-4 receptors are highly overexpressed in carcinosarcoma. These proteins may offer promising targets for the use of CPE as a novel type-specific therapy against this biologically aggressive variant of endometrial cancer.


Assuntos
Carcinossarcoma/metabolismo , Carcinossarcoma/microbiologia , Clostridium perfringens/metabolismo , Enterotoxinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/biossíntese , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/microbiologia , Idoso , Idoso de 80 Anos ou mais , Animais , Claudina-3 , Claudina-4 , Feminino , Humanos , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Transplante de Neoplasias
2.
J Natl Cancer Inst ; 58(6): 1795-806, 1977 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-864756

RESUMO

We characterized two human cell lines (Hs578T and Hs578Bst), which provide several unique features that should be useful in the study of breast disease. Hs578T, derived from a carcinosarcoma, is epithelial in origin. Hs578Bst, established from normal tissue peripheral to the tumor, is myoepithelial in origin. This is the first report of companion cell lines, one malignant and one normal, established from the same organ.


Assuntos
Neoplasias da Mama/patologia , Mama , Carcinossarcoma/patologia , Linhagem Celular , Aneuploidia , Mama/citologia , Mama/metabolismo , Mama/microbiologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/microbiologia , Carcinossarcoma/genética , Carcinossarcoma/metabolismo , Carcinossarcoma/microbiologia , Aberrações Cromossômicas , Diploide , Células Epiteliais , Epitélio/microbiologia , Epitélio/patologia , Feminino , Humanos , Receptores de Estrogênio
3.
Cancer Res ; 36(1): 181-8, 1976 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-174806

RESUMO

Repeated injections of urethan into suckling BALB/c mice induced multiple papillary adenocarcinomas in the lungs and kidneys. When the pulmonary tumors were transplanted i.p. by cell graft into 6 suckling BALB/c mice, they induced disseminated carcinosarcomas within the peritoneal cavity in all inoculated animals. Tumors resulting from the transplantation of tumor cells were used for preparation of filtered extracts. The filtrates were inoculated into 6 suckling BALB/c mice and induced generalized malignant lymphomas in all animals. The primary urethan-induced pulmonary and renal tumors, the carcinosarcomas that resulted from i.p. cell transfer, and also the generalized malignant lymphomas induced by inoculation of filtered extracts contained C-type virus particles. Theoretically, it could be assumed that both the primary urethan-induced pulmonary and renal tumors, as well as the cell-graft-induced peritoneal carcinosarcomas, contained the C-type virus particles as passengers, not necessarily related etiologically to the tumors in which they were found. It is quite likely, however, that these virus particles were etiologically related to the filtrate-induced malignant lymphomas in which they were also found.


Assuntos
Neoplasias Experimentais/microbiologia , Retroviridae/isolamento & purificação , Uretana , Adenocarcinoma Papilar/induzido quimicamente , Adenocarcinoma Papilar/microbiologia , Animais , Carcinossarcoma/etiologia , Carcinossarcoma/microbiologia , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/microbiologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/microbiologia , Linfoma/etiologia , Linfoma/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Neoplasias Peritoneais/etiologia , Neoplasias Peritoneais/microbiologia
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