Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the management of photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR) (syn. chronic actinic dermatitis), a chronic and often severe photodermatosis, there has been concern that patients may be predisposed to the development of lymphoreticular malignancy. A follow-up study of 231 patients with PD/AR who had been investigated at the Photobiology Unit, Ninewells Hospital, Dundee, between 1971 and 1991, was undertaken to determine (i) the incidence and type of malignancies (ii) the causes of any deaths. This information was obtained from three sources: (a) National Cancer Registry data, (b) death certificates, (c) when possible or practical, by casenote review. Thirty-eight malignancies had occurred (in 37 of the 231 patients). Although six of the 38 malignancies were lymphoma registrations, it emerged from a review of casenotes, pathology reports and death certificates that five of the six were incorrect: two were labelled 'mycosis fungoides' prior to diagnosis of PD/AR; a case of dermatopathic lymphadenopathy was initially reported as Hodgkin's disease; clerical errors had occurred in two cases. The remaining case was a true B-cell lymphoma. The occurrence of one lymphoreticular malignancy is not significantly different from the number expected in a normal population (0.96), when applying 5-year age-, sex-, and site-specific incidence rates to the cumulative patient years of risk [standardized incidence ratio 1.04 (95% CI 0.03-5.79)]. There was also no significant increase in the risk of non-lymphoma malignancies in the PD/AR subjects. Since diagnosis, 83 patients have died, the majority from cardiorespiratory or cerebrovascular diseases, or the reported malignancies, a pattern expected in an elderly population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The photosensitivity dermatitis and actinic reticuloid syndrome: no association with lymphoreticular malignancy. 791 84

RNA polymerase I (Pol I) transcription of ribosomal RNA genes (rDNA) is tightly regulated downstream of oncogenic pathways, and its dysregulation is a common feature in cancer. We evaluated CX-5461, the first-in-class selective rDNA transcription inhibitor, in a first-in-human, phase I dose-escalation study in advanced hematologic cancers. Administration of CX-5461 intravenously once every 3 weeks to 5 cohorts determined an MTD of 170 mg/m2, with a predictable pharmacokinetic profile. The dose-limiting toxicity was palmar-plantar erythrodysesthesia; photosensitivity was a dose-independent adverse event (AE), manageable by preventive measures. CX-5461 induced rapid on-target inhibition of rDNA transcription, with p53 activation detected in tumor cells from one patient achieving a clinical response. One patient with anaplastic large cell lymphoma attained a prolonged partial response and 5 patients with myeloma and diffuse large B-cell lymphoma achieved stable disease as best response. CX-5461 is safe at doses associated with clinical benefit and dermatologic AEs are manageable. SIGNIFICANCE: CX-5461 is a first-in-class selective inhibitor of rDNA transcription. This first-in-human study establishes the feasibility of targeting this process, demonstrating single-agent antitumor activity against advanced hematologic cancers with predictable pharmacokinetics and a safety profile allowing prolonged dosing. Consistent with preclinical data, antitumor activity was observed in TP53 wild-type and mutant malignancies.This article is highlighted in the In This Issue feature, p. 983.
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PMID:First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematologic Cancers: Results of a Phase I Dose-Escalation Study. 3109 2