Potential use for sulfasalazine in lung cancer therapy
Bibliographic record
Abstract
3844 The amino acid, cystine, or its reduced form, cysteine, is essential for cell growth and metabolism. While cyst(e)ine is nutritionally a non-essential amino acid, certain tissues cannot synthesize it, rendering their growth critically dependent on uptake of cyst(e)ine from their micro-environment. Sulfasalazine (SASP), a drug used for treatment of rheumatoid arthritis and Crohn’s disease, was previously shown to inhibit the xc- cystine/glutamate antiporter, a common plasma membrane cystine transporter. At patient-tolerated levels (about 0.2 mM), SASP can inhibit both xc--mediated cellular uptake of cystine and supply of cysteine by somatic cells, an xc--mediated process; intraperitoneal administration of SASP to rats markedly inhibited growth of lymphoma transplants (Gout et al., Anti-Cancer Drugs 14:21, 2003). In the present study we investigated the growth dependencies on extracellular cystine of a variety of cultured human lung cancer cell lines, including the H460 (large cell carcinoma), H226 (squamous cell carcinoma) and H82 (small cell lung cancer (SCLC)). The cells were tested by culturing them in RPMI-1640 medium supplemented with dialyzed fetal bovine serum (10%) and antibiotics, in the absence and presence of cystine. Tumor growth-inhibitory activity of SASP was examined using SCID-Rag2M mice carrying growing SCLC tissue xenografts (from a patient designated AB79) grafted under the renal capsules; notably, these xenografts were markedly resistant to a 7-day conventional treatment with cisplatin and etoposide, as shown by continuing, but reduced growth. In vitro it was found that the growth of the H460 large cell carcinoma cell line in the absence of cystine was about 5% of that of the control, increasing to approximately 50% when cystathionine (0.15 mM), an immediate precursor of cysteine, was added. This indicates that these cells contained gamma-cystathionase for production of cysteine via cleavage of cystathionine. Similar results were obtained with the H226 squamous cell carcinoma and H82 SCLC cells. In vivo, intraperitoneal administration of SASP at 250 mg/kg b.i.d. for 7 days markedly inhibited growth of the AB79 xenografts relative to controls, i.e. by 51% (p
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".