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Breast cancer causes a high rate of mortality all over the world. Therefore, the present study focuses on the anticancer activity of new lower rim-functionalized calix[4]arenes integrated with isatin and the p-position of calixarenes with 1,4-dimethylpyridinium iodine against various human cancer cells such as MCF-7 and MDA-MB-231 breast cancer cell lines, as well as the PNT1A healthy epithelial cell line. It was observed that compound 6c had the lowest values in MCF-7 (8.83 µM) and MDA-MB-231 (3.32 µM). Cell imaging and apoptotic activity studies were performed using confocal microscopy and flow cytometry, respectively. The confocal imaging studies with 6c showed that the compound easily entered the cell, and it was observed that 6c accumulated in the mitochondria. The Comet assay test was used to detect DNA damage of compounds in cells. It was found that treated cells had abnormal tail nuclei and damaged DNA structures compared with untreated cells. In vitro human aromatase enzyme inhibition profiles showed that compound 6c had a remarkable inhibitory effect on aromatase. Compound 6c displayed a significant inhibition capacity on aromatase enzyme with the IC50 value of 0.104 ± 0.004 µM. Thus, not only the anticancer activity of the new fluorescent derivatives, which are the subject of this study, but the aromatase inhibitory profiles have also been proven., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: Noscapine, a naturally occurring alkaloid obtained from opium poppy, is a microtubule-targeting agent. This study is aimed to investigate the effects of noscapine on human breast cancer cell lines by comparing them with those of tamoxifen and docetaxel., Methods: MCF-7 and MDA MB-23 cell lines were used to observe the effects of docetaxel, tamoxifen, and noscapine on cell proliferation. For each drug, cell blocks were prepared from cultured cells treated with IC50 dose of each drug and these were examined histologically. The expressions of Ki-67, Bcl-2, BAX, and cyclin-D1 were assessed immunohistochemically., Results: Although noscapine showed cytotoxic effects on both cell lines in a time and dose dependent manner, MDA-MB-231 cells were more susceptible to its effects. Noscapine inhibited MCF-7 and MDA-MB-231 cells proliferation in vitro with IC50 value of 29 µM and 69 µM, respectively, which was comparable with IC50 of tamoxifen (40 µM and 50 µM) and docetaxel (43 nM and 32 nM). Noscapine showed anti-proliferative effects by decreasing Ki-67, cyclin-D1 and apoptotic effects by increasing BAX/Bcl-2 ratio in both breast cancer cells. Its effect was comparable with tamoxifen and docetaxel., Conclusion: Noscapine may be a good chemotherapeutic agent for the treatment of breast cancer, especially in estrogen receptor‑negative breast cancer (Tab. 2, Fig. 7, Ref. 40).

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. In this way they might influence whether a cell is sensitive or resistant to a certain drug. So far, only a limited number of relatively small scale studies comprising few cell lines and/or drugs have been performed. To obtain a broader view on miRNAs and their association with drug response, we investigated the expression levels of 411 miRNAs in relation to drug sensitivity in 36 breast cancer cell lines. For this purpose IC50 values of a drug screen involving 34 drugs were associated with miRNA expression data of the same breast cancer cell lines. Since molecular subtype of the breast cancer cell lines is considered a confounding factor in drug association studies, multivariate analysis taking subtype into account was performed on significant miRNA-drug associations which retained 13 associations. These associations consisted of 11 different miRNAs and eight different drugs (among which Paclitaxel, Docetaxel and Veliparib). The taxanes, Paclitaxel and Docetaxel, were the only drugs having miRNAs in common: hsa-miR-187-5p and hsa-miR-106a-3p indicative of drug resistance while Paclitaxel sensitivity alone associated with hsa-miR-556-5p. Tivantinib was associated with hsa-let-7d-5p and hsa-miR-18a-5p for sensitivity and hsa-miR-637 for resistance. Drug sensitivity was associated with hsa-let-7a-5p for Bortezomib, hsa-miR-135a-3p for JNJ-707 and hsa-miR-185-3p for Panobinostat. Drug resistance was associated with hsa-miR-182-5p for Veliparib and hsa-miR-629-5p for Tipifarnib. Pathway analysis for significant miRNAs was performed to reveal biological roles, aiding to find a potential mechanistic link for the observed associations with drug response. By doing so hsa-miR-187-5p was linked to the cell cycle G2-M checkpoint in line with this checkpoint being the target of taxanes. In conclusion, our study shows that miRNAs could potentially serve as biomarkers for intrinsic drug resistance and that pathway analyses can provide additional information in this context., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: The drug screening referenced in this study was funded by Janssen Pharmaceutica (Beerse, Belgium) and has been described in detail earlier (Uhr et al., 2015). JWMM and JAF received for the referenced study funding from Janssen Pharmaceutica, representing a financial competing interest. AJ is collaborating with AbbVie (North Chicago, IL, USA) in clinical trials with the drug Veliparib and other drugs, not used in this study. AJ and JM received Veliparib to be used in this earlier study free of charge, representing a non-financial competing interest. Besides these detailed competing interests, AJ and JM have no further relevant declarations regarding these two commercial sources. KU, WJCPvdS, AAJH, BO, MS, EACW, AWMB and MTMvJ declare that they have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Tyrosine kinase inhibitors (TKIs) are targeted treatments for various cancers. Skin toxicities are one of the most common nonhematological side-effects of TKIs. We report an imatinib mesylate (IM) induced hyperpigmented acne rosacea (AR) and sunitinib-induced palmar hyperkeratosis in the case with gastrointestinal stromal tumor. AR was arisen due to the discontinuation of IM. To the best of our knowledge, this kind of cutaneous side-effect with IM has not been documented previously.

Aims: To evaluate preoperative concomitant chemoradiation using cisplatin plus docetaxel followed by consolidation chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (NSCLC)., Patients and Methods: Medical records of patients with locally advanced unresectable NSCLC (stage IIIA and IIIB) treated with concomitant chemoradiotherapy using cisplatin + docetaxel combination followed by consolidation chemotherapy were retrospectively evaluated. All the patients were consecutively treated. Chemotherapy consisted of weekly cisplatin 20 mg/m(2) and docetaxel 20 mg/m(2) during radiotherapy. Radiotherapy dose was 58-66 Gy given in 2 Gy fractions, 5 days per week. The patients were subsequently referred to surgery if adequately downstaged. Consolidation chemotherapy using cisplatin and docetaxel both at doses 75 mg/m(2) every 3 weeks followed local therapy in all patients., Results: A total of 54 patients were evaluated (49 males, 5 females with a median age of 58 years; 41 [75.9%] stage IIIB and 13 [24.1%] IIIA). Twelve patients (22.2%) achieved pathologic complete response and 20 (37%) partial response. Downstaging was possible in 32 patients (59.3%). Twenty-six patients (48.1%) were operated after concomitant chemoradiotherapy (pneumonectomy [n = 2], lobectomy [n = 12], and wedge resection [n = 12]). Toxicity was tolerable. Median progression-free survival and overall survival (OS) for the entire cohort were 14 and 22 months, respectively. In resected patients (n = 26), median PFS and OS have not been reached with a median follow-up duration of 24 months., Conclusion: Preoperative concomitant chemoradiation using weekly cisplatin and docetaxel followed by surgery and consolidation chemotherapy is effective and well tolerated in patients with unresectable locally advanced NSCLC.

Objective: To investigate the impact of c-erb2 status on survival after high-dose chemotherapy., Methods: Between March 1997 and June 2004, a total of 54 women with breast cancer who has at least 8 metastatic lymph nodes underwent high-dose chemotherapy with hematopoietic stem cell transplantation in Gulhane Military Medical School, Ankara, Turkey. Archival specimens were analyzed by fluorescent in situ hybridization to determine the impact of c-erb2 status after peripheral blood stem cell transplantation on survival. The patients were divided into c-erb2 negative (n=20) and positive (n=11) groups., Results: No statistically significant differences were detected between c-erb2 negative and positive groups regarding 5-year disease-free survival (41 and 27%, log rank p=0.11), and overall survival (60 and 45%, p=0.33). Transplant related mortality did not differ between groups., Conclusion: We found no differences between c-erb2 negative and positive groups regarding disease-free and overall survival. To clarify the value of the c-erb2 status in predicting outcome after high-dose chemotherapy, prospective randomized studies are needed.

Background: Nephrotoxicity is one of the most frequent dose-limiting factors of high-dose chemotherapy to create tolerance of autologous peripheral blood stem-cell transplantation (PBSCT) for the treatment of malignant diseases. The relative importance of factors that may be responsible for the development of nephrotoxicity varied in different trials., Methods: The factors affecting nephrotoxicity in the early period of high-dose ifosfamide, carboplatin and etoposide treatment (ICE) followed by autologous PBSCT was investigated in 47 patients. ICE was given as a conditioning regimen for 6 days. Nephrotoxicity was defined as an increase in the serum creatinine concentration of 0.5 mg/dl or more over individual baseline levels., Results: Eleven patients developed nephrotoxicity (23.4%). There was no significant difference in baseline renal function between patients with nephrotoxicity and those without. No differences were found between the two groups in terms of average total doses of ICE, infections and antibiotic use. The age of patients was higher in those with nephrotoxicity (37+/-3.7 vs 26+/-1.7 years, P=0.019). The cumulative cisplatin dose administered prior to this regimen was higher in the group that developed nephrotoxicity (470 vs 227 mg/m(2), P=0.02). The overall mortality rate was 17%, but the transplant-related deaths were higher in the presence of nephrotoxicity (54.5 vs 5.5%, P=0.001)., Conclusions: The cumulative dose of cisplatin is a strong risk factor for the development of nephrotoxicity in patients who receive high doses of ICE followed by PBSCT. Nephrotoxicity may occur with much lower doses than the currently recommended maximum doses.

DNA topoisomerases are essential enzymes that regulate the conformational changes in DNA topology by catalyzing the concerted breakage and rejoining of DNA strands during normal cellular growth. During the past few years, there has been considerable pharmacological interest in these enzymes because the inhibitors of DNA topoisomerases represent a major class of anticancer drugs. In this study, we investigated the effects of the extracts, prepared from a number of Helichrysum taxa, on mammalian DNA topoisomerase I via in vitro supercoil relaxation assays using plasmid substrate, pBR322. Cytotoxic alkaloid, camptothecin, an inhibitor of eukaryotic topoisomerase I, was used as reference compound throughout the assays. Quantitative comparisons of the supercoiled and relaxed DNA band intensities on agarose gels suggested that the extracts from H. pallasii (Sprengel) Ledeb., H. armenium DC subsp. araxinum (Kirp.) Takht, and H. plicatum DC subsp. plicatum manifested a considerable inhibition on the enzyme in a dose-dependent manner. The inhibition of mammalian DNA topoisomerase I by Helichrysum extracts is a significant result because they can be potential sources of anticancer drugs. [ABSTRACT FROM AUTHOR]

Although 5-fluorouracil (5-FU)-related cardiotoxicity is well known, atrial arrhythmia, as a potentially serious complication has not been studied in detail. The aim of this study was to determine the P max and Pd in the electrocardiograms (ECG) of patients receiving 5-FU treatment. Twenty-five patients (mean age: 62 years) receiving a 5-FU bolus plus continuous infusion with calcium leucovorin over 48 h and with normal pre-treatment cardiac physical examinations, ECG and echocardiography were enrolled. P maximum (P max), P minimum (P min) and P dispersion (Pd) (maximum minus minimum P wave duration) were measured from the 12-lead ECG at the 0th and 48th hour of the first chemotherapy cycle. Echocardiography was also obtained in all patients at the same times. Clinical cardiotoxicity was observed in two patients. P max and Pd were both significantly longer after 5-FU treatment at the 48th hour ( P < 0·001). P min did not change ( P > 0·05). Treatment with 5-FU based regimens may increase Pd and prolong the P max in cancer patients. These alterations may be predictive of patients at risk of atrial arrhythmias during 5-FU treatment. [ABSTRACT FROM AUTHOR]