Growth arrest by sulfasalazine (SASP) of subrenal capsule prostate cancer xenografts in immuno-deficient mice is coupled to a decrease in the number of tumor-associated macrophages
Notice bibliographique
Résumé
5865 SASP is an established anti-inflammatory drug which at low levels (0.2 mM) specifically inhibits cellular cystine uptake mediated by the xc- plasma membrane cystine transporter. As such, SASP can be used to arrest proliferation of cancer cells which critically depend for growth on extracellular cystine (or cysteine, the reduced form). We have previously shown that SASP can arrest growth of lymphoma cells via cyst(e)ine starvation by inhibiting (i) their uptake of cystine via the xc- transporter and (ii) secretion of cysteine, an xc--mediated process, by fibroblasts in their environment acting as cysteine suppliers. Notably, intraperitoneal administration of SASP to rats markedly inhibited growth of lymphoma transplants (Anti-Cancer Drugs 14:21, 2003). Further studies aimed at prostate cancer showed that DU-145 and PC3 human prostate cancer cells have a critical requirement for extracellular cystine, in contrast to LNCaP cells capable of synthesizing cysteine. As expected, LNCaP cells were much less sensitive in vitro to SASP-induced growth arrest than DU-145 and PC3 cells. In the present study, the response of LNCaP xenografts in immuno-deficient mice to treatment with SASP was compared with that of DU-145 and PC3 tumors. Groups of male, testosterone-supplemented Rag-2M mice were used, carrying established LNCaP cell xenografts (about 80 mm3) under the kidney capsules. Every 12 h they received i.p. injections of saline (controls; n=4) or SASP (250 mg/kg body wt; n=7) for 8 days. Animals were then sacrificed and tumors harvested for volume measurement and histological analysis (H&E and macrophage staining, using biotinylated, rat antimouse macrophage antibodies). It was found that LNCaP xenografts were surprisingly sensitive to SASP treatment, showing growth arrests of about 70% (relative to controls), comparable to growth arrests found for DU-145 and PC3 tumors. Immunohistochemical analysis revealed presence in control mice of numerous mouse macrophages lining tumor-kidney boundaries. In contrast, the numbers of such tumor-associated macrophages (TAMs) were markedly reduced in SASP-treated mice. Administration of SASP (i.p.) has been reported to decrease numbers of mouse macrophages. Taken together, the results suggest that the growth arrest of LNCaP tumors by SASP may be due to a reduction in the number of TAMs and consequently their tumor growth-promoting activity, recently recognized as an important factor in cancer development. In the case of DU-145 and PC3 tumors, a reduction in immunologically activated TAMs would likely also lead to decreased cysteine supply. SASP, an old drug, may be useful in prostate cancer therapy for targeting tumor growth-promoting macrophages. Supported by CIHR and DOD US Army.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».