DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lymph node disorder — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLymph node disorder maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
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ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside lymph node disorder in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of EphA4 kinase domain — Dasatinib has a real, experimentally solved structure in complex with this target (PDB 2Y6O, 1.543 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 1n1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6O · 1.543 Å · ligand Dasatinib (1N1). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 multi-institutional study of 4254 patients with oral cavity squamous cell carcinoma found that lymph node density (the number of positive nodes divided by the total number of excised nodes) predicted survival. Five-year overall survival was 49% for patients with a density of 0.07 or less, compared with 35% for those with a density above 0.07. Disease-specific survival was 60% versus 41%. The authors concluded that lymph node density stratified risk within individual N subgroups and that a modified TNM staging system based on this ratio was superior to the traditional system. They proposed that the measure could identify patients who need more aggressive adjuvant treatment.
A 2008 article cautioned that although lymph node count is easy to measure and correlates with survival for many cancers, no study has yet shown that increasing the number of nodes removed improves patient outcome. The authors warned against using lymph node count as a quality indicator without evidence that interventions to raise the count actually benefit patients.
A 2020 study of 625 patients with papillary thyroid cancer who had surgery without prophylactic central neck dissection reported favourable long-term outcomes. After a median follow-up of 104 months, the 10-year disease-specific survival was 99.7% and the 10-year recurrence-free survival was 90.2%. The 10-year lymph node recurrence rate in the central compartment was only 2.7%. The authors concluded that patients with clinically negative central compartment lymph nodes do well without prophylactic dissection.
A 1994 report on laparoscopic pelvic lymphadenectomy in 10 patients with genitourinary malignancy found that the procedure altered staging in three patients (one upstaged, two downstaged), with significant therapeutic implications. Operative times ranged from 2 to 3 hours, and the median number of lymph nodes removed was five. Two patients suffered thromboembolic complications soon after the procedure. The authors considered the technique valuable for identifying suitable candidates for radical therapy and for excluding patients with lymph node involvement.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Cancer · 2013 · 196 citations · open access
Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research
AbstractBACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.
Journal of Surgical Oncology · 2008 · 49 citations · open access
Is lymph node count an ideal quality indicator for cancer care?
AbstractAlthough lymph node count has substantial appeal as a quality indicator because of the ease of measurement, the presence of variation in the population, the association with survival for many cancers, and the previous success of quality intervention programs, improvements in patient outcome by increasing lymph node counts have not yet been demonstrated. This article discusses potential pitfalls in the use of lymph node count as a quality indicator.
Therapy program for patients with advanced stages of chronic lymphocytic leukemia. Chlorambucil, splenectomy, and total lymph node irradiation
AbstractBACKGROUND: The clinical course of chronic lymphocytic leukemia (CLL) is variable. Staging systems define high risk groups, such as patients with Rai's Stage III and IV and Binet's stage C disease, as having a poor overall median survival. Most combination therapy programs have resulted in similar results. Chlorambucil remains the most commonly used drug, and new drugs, such as fludarabine, are promising. METHODS: Fifty-three patients with poor prognosis CLL (Stage III and IV) underwent chlorambucil treatment at a high intermittent dose. When Stage 0 was obtained, patients were considered responders and kept under surveillance. When the patients stopped responding after one or several courses of chlorambucil, further therapy was performed, including splenectomy (29 patients) and total lymph node irradiation (9 of the 29 splenectomized patients). RESULTS: The overall median survival was 60 months. Thrombocytopenia and anemia were resolved in 55% and 82% of the patients, respectively, after chlorambucil therapy and in 85% and 100%, respectively, after splenectomy. Complications occurred in 34% of the splenectomized population. Total lymph node irradiation was poorly tolerated in 66% of the patients. When this analysis was performed, 24 patients were classified as having Stage 0 disease with no disease progression for a mean of 21 months. CONCLUSIONS: Therapy programs allowing the selection of responders by the successive use of high intermittent dose chlorambucil and splenectomy may be beneficial in treating patients with advanced stage CLL. Because of its toxicity, total lymph node irradiation has no significant therapeutic effect.
Journal of Cancer Research and Therapeutics · 2020 · 9 citations · open access
Long-term outcomes of patients with papillary thyroid cancer who did not undergo prophylactic central neck dissection
AbstractAIMS: The role of prophylactic central neck dissection (CND) in the management of papillary thyroid carcinoma (PTC) is controversial. This study reports outcomes of an observational approach in PTC patients without clinical evidence of lymph node metastasis. MATERIALS AND METHODS: Patients with PTC who had surgery (without prophylactic CND) between January 2000 and December 2008 were included in this study. Recurrence-free survival (RFS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. Cox regression was used in multivariable models. RESULTS: Out of 625 patients, 486 (77.8%) were female, 144 (23%) were aged 55 years or more, 73 (11.7%) had macroscopic extrathyroidal extension, and 79 (12.7%) had pT3 or pT4 disease. Samples were collected from 12 (1.9%) patients with lymph node metastasis in the perithyroidal tissue and 2 (0.3%) patients with lymph node metastasis in the lateral neck lymph tissue for frozen section examination. After a median follow-up of 104 months, the 10-year DSS and RFS rates were 99.7% and 90.2%, respectively. The 10-year lymph node recurrence rate in the central compartment was 2.7%. pT3/4 stage was an independent predictive factor for RFS (P < 0.001, hazard ratio 1.966, 95% confidence interval 1.446-2.673). CONCLUSION: The outcomes of patients with clinically negative lymph nodes in the central compartment were favorable without prophylactic CND.
Translational Lung Cancer Research · 2023 · 8 citations · open access
Distinct metastatic spread and progression patterns in patients treated with crizotinib for ROS1- and ALK-rearranged non-small cell lung cancer: a single-center retrospective study
AbstractBackground: Crizotinib has been approved for C-ros oncogene 1 (ROS1)- and anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients. Few studies have examined the differences in crizotinib treatment outcomes between these patients and the progression sites during treatment. We investigated the metastatic spread, crizotinib efficacy, and progression patterns during crizotinib treatment in ROS1- and ALK-rearranged NSCLC patients. Methods: We retrospectively reviewed crizotinib-treated ROS1- and ALK-rearranged NSCLC patients between January 2011 and March 2021. Patient characteristics, clinical outcomes, and progression patterns during treatment were collected from medical records. The metastasis extent, crizotinib response, and progression patterns between the groups were compared. Results: We identified 26 patients with ROS1- and 42 with ALK-positive NSCLC. The baseline proportion of central nervous system (CNS) metastases did not differ between the groups (12% vs. 29%, P=0.10), but the proportion of extrathoracic metastases, including CNS metastases, was significantly higher in ALK-positive than in ROS1-positive NSCLC patients (35% vs. 71%, P=0.003). Regarding the response to crizotinib, the objective response rate (ORR), progression-free survival (PFS), or overall survival (OS) did not significantly differ between the groups (ROS1 vs. ALK, ORR: 69% vs. 69%, P=0.987; PFS: median 10.9 vs. 10.7 months, P=0.232; median OS: not reached vs. 67.7 months, P=0.495). The CNS was the most common metastasis site in both groups [ROS1 vs. ALK, 69% (11/16) vs. 46% (17/37), P=0.127], and the cumulative incidence of CNS metastasis did not differ between the groups (P=0.914). Conclusions: Crizotinib treatment outcomes, including progression patterns, were similar between ROS1- and ALK-positive NSCLC patients.
Laparoscopic pelvic lymphadenectomy – early results
AbstractOBJECTIVE: To report our initial experience and early results of laparoscopic pelvic lymphadenectomy (LPL). PATIENTS AND METHODS: Between May 1991 and April 1992, 10 patients with genitourinary malignancy (eight prostate, one bladder carcinoma, one penile melanoma) underwent LPL. Following biopsy, initial staging was carried out using computed tomography (CT), a bone scan and the prostate specific antigen level (prostate cancer). Six patients underwent unilateral laparoscopic dissection, three patients bilateral dissection and one patient required conversion to an open procedure. Operative times ranged from 2 to 3 h, and the number of lymph nodes removed ranged from three to nine (median five). RESULTS: Three patients had their staging altered following LPL (one patient was upstaged and two patients were downstaged), with significant therapeutic implications. Two patients suffered thromboembolic complications while undergoing definitive therapy soon after LPL. CONCLUSION: Our early results suggest that LPL is valuable in identifying suitable patients for radical therapy as well as excluding patients with lymph node involvement, thereby reducing morbidity.
TURKISH JOURNAL OF MEDICAL SCIENCES · 2020 · 5 citations · open access
Impact of low molecular weight heparin administration on the clinical course of the COVID-19 disease
AbstractBackground: Lymphopenia is the most important criterion of mortality and discharging feature for patients infected with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical impact of a low molecular weight heparin (LMWH) treatment on the clinical course of COVID-19. Materials and methods: Patients’ clinical symptoms, radiologic outcomes, hematologic, biochemical, D-dimer, and C-reactive protein (CRP) results were obtained from their medical records. Participants were separated into 2 groups: one was treated with LMWH and the other was not. Improvement in the patients was compared before and after treatment. Results: Ninety-six patients who were diagnosed with COVID-19 between April and May 2020 were retrospectively analyzed. The multivariable analysis showed that the count of lymphocytes, D-dimer, and CRP levels were significantly improved in the LMWH group, as compared to the control group (OR, (95% CI) 0.628 (0.248–0.965), P < 0.001); OR, (95% CI) 0.356 (0.089–0.674), P < 0.001, respectively). The area under the receiver operating characteristic (ROC) curve analysis was AUC: 0.679 ± 0.055, 0.615 ± 0.058, and 0.633 ± 0.057, respectively; the β-value was found to be –1.032, –0.026, and –0.465, respectively. Conclusion: The LMWH treatment group demonstrated better laboratory findings, including recovery in the lymphocyte count, CRP, and D-dimer results.
OncoTargets and Therapy · 2021 · 4 citations · open access
Hodgkin Lymphoma as a Secondary Neoplasm During Therapy for Chronic Myeloid Leukaemia: Case Report and Review of the Literature
AbstractINTRODUCTION: Incidences of chronic myeloid leukaemia (CML) after treatment of Hodgkin lymphoma (HL) are well described. Here, we report a case of secondary HL in a patient with CML treated with dasatinib as a third-line treatment. PATIENT INFORMATION: A 64-year-old male was diagnosed with CML and initially treated with imatinib and then with nilotinib due to resistance. Finally, the patient experienced cardiovascular complications, and dasatinib was introduced. After 19 months of treatment, the patient experienced enlargement of lymph nodes that formed packs on the neck. INTERVENTIONS: Based on histopathological examination of the lymph nodes, a diagnosis of classical Hodgkin lymphoma - mixed cellularity was established. The patient was successfully treated with 4 cycles of AVD (adriamycin, vinblastine, dacarbazine) chemotherapy. OUTCOMES: Complete metabolic remission of Hodgkin lymphoma is currently sustained, and the molecular response to dasatinib at a reduced dose of 50 mg daily corresponds with a deep molecular response. CONCLUSION: In this report, we demonstrate the efficacy and safety of the combination of dasatinib and AVD regimens in coexisting CML and HL. This case report emphasizes the importance of insightful evaluation and differential diagnosis in cases of lymphadenopathy during CML treatment.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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