In vitro studies on the lymphoma growth-inhibitory activity of sulfasalazine
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Bibliographic record
Abstract
Sulfasalazine (SASP) is a novel, potent inhibitor of cellular cystine uptake mediated by the x(c)- cystine/glutamate antiporter. Lymphoid cells cannot synthesize cyst(e)ine and depend for growth on its uptake from their micro-environment. We previously showed that SASP (0.2 mM) can abrogate lymphoma cell proliferation in vitro by specifically inhibiting x(c)- -mediated cystine uptake. Intraperitoneal administration of SASP to Noble rats markedly suppressed Nb2-U17 rat lymphoma transplant growth, notably without major toxicity to the hosts. Since Nb2-U17 cells are x(c)- -deficient, the growth arrest was apparently not due to SASP-tumor cell interaction, but possibly to interference with x(c)- -mediated cysteine secretion by somatic cells. In this study we found that replication of x(c)- -deficient Nb2-11 lymphoma cells can be sustained in vitro, in the absence of cystine uptake enhancers, by co-culturing with IMR-90 fibroblasts known to secrete cysteine. SASP, at 0.15 and 0.2 mM, arrested replication of fibroblast-driven Nb2-11 cells by 93 and 100%, respectively, without impeding fibroblast proliferation. Addition of 2-mercapto-ethanol (60 microM), a cystine uptake enhancer, almost completely prevented this growth arrest, indicating that SASP specifically inhibited cysteine secretion by the fibroblasts, a process based on x(c)- -mediated cystine uptake. It is proposed that the lymphoma growth-inhibitory activity of SASP in vivo involves inhibition of cysteine secretion by tumor-associated somatic cells (macrophages, dendritic cells), leading to cysteine starvation of the tumor cells and apoptosis. The difference between the lymphoma cells and fibroblasts in sensitivity to SASP treatment is consistent with the marked antitumor effect of SASP lacking significant side effects.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it