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  • Aromatization of the pyrrole ring

    2024-04-02

    Aromatization of the pyrrole ring after anion capturing, using acceptor atoms with electron deficiency (B & Be), and substitution of strong electron withdrawing groups such as CN were three strategies used to design a new class of anion receptors. Comparison of the anion affinities of these anion receptors with those reported in literature show that they are among the strongest anion receptors reported so far. Because of larger values of SO affinities compared to other anion affinities, these compounds can be considered as selective SO receptors. Nowadays the organoboron compounds are easily synthesized [,], hence, attempts to synthesize some of these anion receptors are highly recommended.
    Introduction The St. Gallen surrogate classification for intrinsic breast cancer subtypes defines four entities: luminal-A-like, luminal-B-like, HER2-positive and basal-like [1]. They are assessed by the immunohistochemical evaluation of estrogen receptor α (ERα – later also referred to as ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2) and Ki-67. Triple-negative breast cancer is closely related to the basal intrinsic phenotype and is characterized by lack of expression of ER, PgR and no overexpression of HER2. Luminal tumors are defined as ER and/or PgR positive, therefore, such tumors may have three distinct profiles: ER(+)/PgR(+), ER(+)/PgR(−), ER(−)/PgR(+). Luminal A-like tumors are characterized by a high expression of ER and/or PgR, whereas luminal B-like cases demonstrate a lower expression of hormone receptors and a higher proliferation rate. Prat et al. suggested the cut-off of >20% PgR expressing Caspase-9 Colorimetric Assay Kit synthesis best correlates with luminal-A phenotype. Until the 2015 edition, the ER(−)/PgR(+) phenotype had not been included in the surrogate definitions of intrinsic subtypes of breast cancer proposed by the St. Gallen consensus and in the 2017 guidelines the subtype allocation of ER(−)/PgR(+) cancers between luminal A-like and luminal B-like phenotype is still not clearly defined [2]. The use of the reference method, gene-expression profiling (Prediction Analysis of Microarray 50, PAM50) showed that these tumors are mostly basal-like (50–60%) and luminal-A (15–30%), suggesting a significant molecular heterogeneity within the group [3], [4], [5]. Extensive research has shown that PgR expression is dependent on ER activity [6]. Therefore, the ER(−)/PgR(+) profile in breast cancer is hard to explain on biological grounds and for this reason some pathologists and oncologists put its existence into question. On the other hand, in recent years there is growing body of evidence that such cancers create a unique group with distinct molecular and clinical features. In 2004 Olivotto started a debate on the significance of PgR expression evaluation in breast cancer patients. He declared that PgR testing in breast cancer management should be discontinued, due to its negligible role in altering therapeutic decisions [7]. This article has aroused many controversies and initiated worldwide discussion. In response, some authors have raised an important issue: PgR status in ER(−) tumors may provide an important predictive information and PgR positivity may indicate which patients are more likely to respond to adjuvant endocrine treatment [8]. Others pointed out the prognostic value of PgR expression in breast cancer, especially if determined by appropriate immunohistochemical methods [9].
    Materials and methods A MEDLINE search was performed to identify all original and review articles addressing ER(−)/PgR(+) breast cancer. The following keywords were included: breast cancer, estrogen receptor, progesterone receptor. The analysis was restricted to the time period between 1990 and 2017. Bibliographies, references and related articles were also reviewed. Relevant papers were selected by one author (MK) with the agreement of the expert panel of coauthors. The main findings reported by these studies are shown in Table 1.