BACKGROUND: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain.
OBJECTIVE: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort.
METHODS: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms \"systemic sclerosis\" and \"NOR90\" across three databases: Medline via PubMed, Scopus, and Thomson Reuters\' Web of Science Core Collection, from inception to November 1st, 2023.
RESULTS: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %.
CONCLUSIONS: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.

Acridine derivatives have been thoroughly investigated and discovered to have multitarget qualities, inhibiting topoisomerase enzymes that regulate topological changes in DNA and interfering with DNA\'s vital biological function. This article discusses current progress in the realm of novel 9-substituted acridine heterocyclic compounds, including the structure and structure- activity connection of the most promising molecules. The IC50 values of the new compounds against several human cancer cell lines will also be presented in the publication. The review also looks into the inhibition of topoisomerase by polycyclic aromatic compounds.
Acridine rings can be found in molecules used in many different areas, including industry and medicine. Nowadays, acridines with anti-bacterial activity are of research interest due to decreasing bacterial resistance. Some acridine derivatives showed antimalarial or antiviral activity. Acridine derivatives were also investigated for anti-tumor activity due to the interaction with topoisomerase II and DNA base pairs. Considering these possible uses of acridine derivatives, this work overviewed all significant structure performances for the specific action of these compounds.
The objective of this study is to review the activity of acridines as anti-proliferative agents.
This review is designed as acridines acting as topoisomerase I and II inhibitors/ poison, Acridines on the G-quadraplux interaction, Acridines with metal complexes, Acridines with quinacrine scaffold, Acridines with sulphur moiety.
Although introduced in the 19th century, acridine derivatives are still of scientific interest. In this review, acridine derivatives with various biological activities (antiparasitic, antiviral, anti-bacterial, and antiproliferative) and their structure-activity relationship analyses are presented. Although several mechanisms of their action are known, the only important are discussed here. It can be concluded that the dominant mechanisms are DNA intercalation and interaction with enzymes.

UNASSIGNED: Topoisomerases are important targets for therapeutic improvement in the treatment of some diseases, including cancer. Inhibitors and poisons of topoisomerase I can limit the activity of this enzyme in its enzymatic cycle. This fact implies an anticancer effect of these drugs, since most cancer cells are characterized by both a higher activity of topoisomerase I and a higher replication rate compared to non-cancerous cells. Clinically approved inhibitors include camptothecin (CPT) and its derivatives. However, their limitations have encouraged different research groups to prepare new compounds, proof of which are the numerous research works and patents, some of them in the last five years.
UNASSIGNED: This review covers patent literature on topoisomerase I inhibitors and their application published between 2016-present.
UNASSIGNED: The highest contribution toward patent development has been obtained from academics or small biotechnology companies. The most important fields of innovation include the preparation of prodrugs or inhibitors combined with other agents, as biocompatible polymers or antibodies. A promising development of topoisomerase I inhibitors is expected in the next years, directed to the treatment of diverse diseases, specifically toward different types of cancer and infectious diseases, among others.

Liposomal irinotecan (nal-IRI; Onivyde®; also known as pegylated liposomal irinotecan) has been developed with the aim of maximising anti-tumour efficacy while minimising drug-related toxicities compared with the conventional (non-liposomal) formulation of this topoisomerase 1 inhibitor. In combination with 5-fluorouracil and leucovorin (5-FU/LV), nal-IRI is the first agent to be specifically approved for use in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy. In the pivotal, phase III NAPOLI-1 trial, intravenous administration of nal-IRI + 5-FU/LV to gemcitabine-pretreated patients with mPDAC (as a second-line treatment in approximately two-thirds of cases) was associated with a significant ≈ 2-month median overall survival advantage compared with 5-FU/LV alone. Moreover, adding nal-IRI to 5-FU/LV extended survival with a manageable safety profile and without adversely affecting health-related quality of life, thereby producing significant and clinically meaningful gains in quality-adjusted survival relative to 5-FU/LV alone. Complementing the observed efficacy and safety of nal-IRI in NAPOLI-1 are an increasing number of real-world studies, which provide evidence of the effectiveness of this combination therapy in the treatment of mPDAC that has progressed following gemcitabine-based therapy in contemporary clinical practice in Europe, the USA and East Asia. Thus, nal-IRI, in combination with 5-FU/LV, is the first regimen specifically approved for use as a second- or subsequent-line therapy in gemcitabine-pretreated patients with mPDAC and, as such, represents a valuable treatment option in this setting.

BACKGROUND: Patients with systemic sclerosis (SSc) have an increased risk of malignancy. In this study, we aimed to analyze the prevalence of cancer, the risk factors and the impact on overall survival.
METHODS: We analyzed clinical (history of cancer, toxic exposition, organ involvement), immunological and treatment data in a monocentric cohort of SSc patients followed between January 2004 and December 2017.
RESULTS: Two hundred and ten patients with SSc were included. During the follow-up, twenty-one patients (10 %) were diagnosed with malignancies. The underlying malignancies were breast adenocarcinoma (n=6, 28%), lung cancer (n=6, 28%), colorectal (colic adenocarcinoma, carcinoid tumor of the appendix), ovarian and cervix uteri, melanoma, kidney and papillary thyroid carcinoma (one of each). The median time between the first visit and the diagnosis of cancer was 4 [2-10] years. The overall survival in SSc patients with cancer was not significantly different from patients without cancer, with median survival during the first quartile (75%) at 12 years for patients with cancer and 11.6 years for those without cancer (P=0.9). The history of renal scleroderma crisis (HR 10.99, IC95% [1.95-62.07]; P=0.006) and the presence of anti-topoisomerase I antibodies (HR 5.5, IC95% [1.40-21.67]; P=0.01) were associated with an increased risk of cancer, whereas the presence of gastroesophageal reflux was inversely associated with the cancer occurrence (HR 0.22, IC95% [0.056-0.867]; P=0.03).
CONCLUSIONS: The history of renal scleroderma crisis and the positivity of anti-topoisomerase I antibodies were associated with an increased risk of cancer in SSc patients in this monocentric study.

In this review, we describe a detailed investigation about the structural variations and relative activity of 1,8-naphthalimide based intercalators and anticancer agents. The 1,8-naphthalimides binds to the DNA via intercalation, and exert their antitumor activities through Topoisomerase I/II inhibition, photoinduced DNA damage or related mechanism. Here, our discussion focused on works published over the last ten years (2007-2017) related to therapeutic applications, in the order of cancer treatment followed by other properties of 1,8-naphthalimides. In preparing for this review, we considered that several seminal reviews have appeared over the last fifteen years and focused on closely related subjects, however, none of them is exhaustive.

Moyamoya disease and syndrome constitute two distinct pathological entities with a primary finding of progressive distal internal carotid artery occlusion, which results in either an ischemic or hemorrhagic sequela. While the disease entity stands as a primary arterial vasculopathy, moyamoya syndrome represents a secondary vasculopathy associated with a systemic inflammatory process. We describe a patient with an ischemic stroke and angiographic findings of moyamoya in the setting of positive antinuclear antibodies and anti-Scl-70 antibodies with clinical features of scleroderma on exam. A review of current literature identified three similar cases where immunosuppression in addition to secondary stroke prevention led to reduced frequency of neurological sequelae. These cases plus our own demonstrate that patients with moyamoya vasculopathy in association with anti-Scl 70 antibodies exist on a spectrum with either predominant scleroderma features or neurological symptoms. There are a limited number of cases reported of moyamoya vasculopathy in association with anti-Scl 70 antibodies. This case report demonstrates that not only may the association be more common than we think, but that it exists on a dynamic spectrum with variable clinical presentation and course.

暂无摘要。

Sarcoidosis and systemic sclerosis (SSc) rarely coexist. Here, we report a Japanese female SSc patient who developed systemic sarcoidosis. Her SSc was a limited type negative for anti-Scl-70 antibody and positive for anticentromere antibody (ACA). Moreover, we performed a review of the English-language published work that described cases of concurrent SSc and sarcoidosis. Then, we found that most SSc and sarcoidosis concurrent patients positive for anti-Scl-70 antibody were male (77.8%). On the other hand, most patients positive for ACA were female (87.5%). These results suggest some relationships between autoantibody profiles and sex in SSc and sarcoidosis concurrence.

Following treatment with anthracyclines and taxanes, few established options exist for the treatment of metastatic breast cancer (MBC). Although the topoisomerase 1 inhibitors irinotecan, etirinotecan, and topotecan have been used in clinical trials on MBC, the drugs have never been introduced as standard treatment for the disease. We performed a systematic review on topoisomerase 1 inhibitors in MBC and found 22 prospective trials and three retrospective ones. No phase III trials were identified. Only one study was randomized, and generally studies were small. Response rates (RR) for irinotecan monotherapy varied from 5 to 23 %, whereas RRs for etirinotecan were 26-32 %. Only four trials on topotecan monotherapy were reported with RRs of 6-31 %. Combination therapy with irinotecan and various chemotherapeutics resulted in RRs ranging from 14 to 64 %, whereas irinotecan combined with biologic agents showed very limited effect. Topotecan was studied in combination with either another chemotherapeutic or a biologic agent in two trials, both studies failing to show any effect of topotecan. The most common grade 3 and 4 adverse events (AE) for irinotecan were neutropenia, diarrhea, and nausea/vomiting. The dosing schedule appears to affect the toxicity profile of the drug. Hematologic AEs are most frequently reported for topotecan. Conclusively, topotecan does not seem to be efficient in the treatment of MBC. Irinotecan seem to be effective in some patients previously treated with anthracyclines and taxanes. RRs of 23 % for irinotecan and 32 % for etirinotecan are comparable to some of the more commonly used treatments for MBC. However, a large proportion of patients do not respond, thus emphasizing the need for a biomarker predictive of response to irinotecan in order to introduce this drug as the standard treatment for MBC.