Metastasis is the leading cause of breast cancer-related mortality and involves cells from a primary tumor invading into adjacent tissue by using the circulatory system.During the process of metastasis, several dynamic and reciprocal interactions between cancer cells and inflammatory cells occur in the surrounding tumor microenvironment via the secretion of several cytokines, including tumor necrosis factor-α, and transforming growth factor-β.The present study aimed to investigate the functional role of recombinant apurinic apyrimidinic endonuclease 1(APE1)/Redox factor-1 (Ref-1) with reducing activity, [APE1/Ref-1-(SH)2] in the regulation of metastatic migration in cytokine-stimulated MDA-MB-231 breast cancer cells.The results reveal that [APE1/Ref-1-(SH)2], but not the oxidized form of recombinant APE1/Ref-1, attenuated migration, and invasion of cytokines-stimulated MDA-MB-231 cells.These effects were induced by the oxidative conformational changes due to the thiol-disulfide exchange reaction targeting disulfide bonds in extracellular domain of the cytokine receptors.Blocking of the binding of the cytokines to the corresponding receptors also reversed epithelial-to-mesenchymal transition (EMT) in cytokine-stimulated MDA-MB-231 cells.The reversal of EMT was accompanied by changes in the expression levels of representative EMT markers, E-cadherin, N-cadherin, vimentin, and snail.Remarkable phenotypic changes were also observed in MDA-MB-231 cells, as the cells adopted an epithelial like globular shape, with regular dimension, a reorganized cytoskeleton, and collapsing filopodia and lamellipodia.In conclusion, although devising a stable form of recombinant [APE1/Ref-1-(SH)2] requires further study, its ability to target cytokine receptors and to inhibit their intracellular signaling suggests the use of [APE1/Ref-1-(SH)2] as a promising agent for regulating metastatic cancer cells.
In the case of invasive breast carcinomas (BC) there are extremely rare late nonregional retroperitoneal lymph node recurrences, occurring after 10 years of disease diagnosis .We present a 32-year-old woman, who was diagnosed in 2010 with left HER2 positive invasive ductal BC-pT2N1M0.Complex treatment involving radical mastectomy with axillary dissection and complex adjuvant treatment (chemotherapy, radiotherapy, targeted therapy with trastuzumab, endocrine therapy with LHRH agonist plus tamoxifen) was conducted.After 4 years, disease progression with left supraclavicular lymph node enlargement has been manifested.After surgical resection of supraclavicular lymph node, the patohistological analysis establishes lymph metastasis from HER2 positive invasive ductal carcinoma.After 6 years of multimodal treatment, including eight chemotherapy cycles docetaxel, bilateral adnexectomy, 2 targeted agents trastuzumab/pertuzumab and endocrine therapy with aromatase inhibitor, PET/ CT visualizes a nonregional lymph recurrence of left retroperitoneal lymph nodes.Isolated involvement of distant nodal regions is extremely uncommon.Complex therapy, including a definitive radiotherapy of retroperitoneal para-aortic lymph nodes combined with targeted therapy achieved complete remission in nonregional abdominal lymph recurrence.
Received: January 03, 2021; Accepted: January 26, 2021; Published: January 29, 2021 It has been reported that a so-called clean colon procedure, in which all precancerous lesions, colorectal tubular adenomas / colorectal tubulovillous adenomas, are endoscopically resection treatment is extremely useful for preventing colorectal carcinogenesis and death from colorectal cancer [1-4]. The effectiveness of chemopreventive measures to take the antidiabetic drugs metformin and low-dose aspirin has also been reported [5-7]. Recently, there have been reports suggesting the involvement of intestinal microorganisms such as Fusobacterium nucleatum (F. nucleatum) in colorectal carcinogenesis [8-13], and there is a possibility that a strategy targeting intestinal microorganisms will be taken as future methods for preventing colorectal carcinogenesis. This review describes the prospects for new strategies on colorectal carcinogenesis prevention targeting intestinal microbiome such as F. nucleatum.
