Matrix metalloproteinases as therapeutic targets in breast cancer

Matrix metalloproteinases (MMPs) are the most prominent proteinases involved in tumorigenesis. They were initially recognized to promote tumor progression by remodeling the extracellular matrix through their proteolytic activity. However, accumulating evidence has revealed that some MMPs have protective roles in cancer progression, and the same MMP can exert opposing roles depending on the cell type in which it is expressed or the stage of cancer. Moreover, studies have shown that MMPs are involved in cancer progression through their roles in other biological processes such as cell signaling and immune regulation, independent of their catalytic activity. Despite the prognostic significance of tumoral or stromal expression of MMPs in breast cancer, their roles and molecular mechanisms in breast cancer progression remain unclear. As the failures of early clinical trials with broad-spectrum MMP inhibitors were mainly due to a lack of drug specificity, substantial efforts have been made to develop highly selective MMP inhibitors. Some recently developed MMP inhibitory monoclonal antibodies demonstrated promising anti-tumor effects in preclinical models of breast cancer. Importantly, anti-tumor effects of these antibodies were associated with the modulation of tumor immune microenvironment, suggesting that the use of MMP inhibitors in combination with immunotherapy can improve the efficacy of immunotherapy in HER2-positive or triple-negative breast cancer. In this review, the current understanding of the roles of tumoral or stromal MMPs in breast cancer is summarized, and recent advances in the development of highly selective MMP inhibitors are discussed

Epigenetic Regulation of Cancer-Associated Genes in Ovarian Cancer

The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except for the DNA hypomethylation of some genes. Recently, we reported that the overexpression of cancer-promoting genes in ovarian cancer is associated with the loss of repressive histone modifications. This discovery suggested that epigenetic derepression may contribute to ovarian tumorigenesis by constituting a possible mechanism for the overexpression of oncogenes or cancer-promoting genes in tumors. The emerging importance of epigenetic aberrations in tumor initiation and in the regulation of cancer-initiating cells, suggests that epigenetically regulated genes may be promising therapeutic targets and biomarkers. Given that the current challenges in ovarian cancer include the identification of biomarkers for early cancer detection and the discovery of novel therapeutic targets for patients with recurrent malignancies undergoing chemotherapy, understanding the epigenetic changes that occur in ovarian cancer is crucial. This review looks at epigenetic mechanisms involved in the regulation of cancer-associated genes, including the contribution of epigenetic derepression to the activation of cancer-associated genes in ovarian cancer. In addition, possible epigenetic therapies targeting epigenetically dysregulated genes are discussed. A better understanding of the epigenetic changes in ovarian cancer will contribute to the improvement of patient outcomes

Fishbone-Associated Actinomycosis of the Anterior Cervical Space: A Diagnostic Dilemma

We report the imaging and pathologic findings of fishbone-associated actinomycosis of the anterior cervical space in a 57-year-old man, misdiagnosed preoperatively as a malignancy originating from thyroglossal duct cyst. CT revealed an enhancing mass containing a small abscess pocket and two sharp linear calcifications within it, which infiltrated into the strap muscle. Pathologic examination demonstrated two fishbones within the actinomycotic abscess. Fishbone-associated actinomycosis should be considered when a cervical mass contains sharp linear calcifications

Overexpression of Cancer-Associated Genes via Epigenetic Derepression Mechanisms in Gynecologic Cancer

Like other cancers, most gynecologic cancers are caused by aberrant expression of cancer-related genes. Epigenetics is one of the most important gene expression mechanisms, which contribute to cancer development and progression by regulating cancer-related genes. Since the discovery of differential gene expression patterns in cancer cells when compared with normal cells, extensive efforts have been made to explore the origins of abnormal gene expression in cancer. Epigenetics, the study of inheritable changes in gene expression that do not alter DNA sequence is a key area of this research. DNA methylation and histone modification are well-known epigenetic mechanisms, while microRNAs and alternative splicing have recently been identified as important regulators of epigenetic mechanisms. These mechanisms not only affect specific target gene expression but also regulate the functioning of other epigenetic mechanisms. Moreover, these diverse epigenetic regulations occur simultaneously. Epigenetic regulation of gene expression is extraordinarily complicated and all epigenetic mechanisms to be studied at once to determine the exact gene regulation mechanisms. Traditionally, the contribution of epigenetics to cancer is thought to be mediated through the inactivation of tumor suppressor genes expression. But recently, it is arising that some oncogenes or cancer-promoting genes (CPGs) are overexpressed in diverse type of cancers through epigenetic derepression mechanism, such as DNA and histone demethylation. Epigenetic derepression arises from diverse epigenetic changes, and all of these mechanisms actively interact with each other to increase oncogenes or CPGs expression in cancer cell. Oncogenes or CPGs overexpressed through epigenetic derepression can initiate cancer development, and accumulation of these abnormal epigenetic changes makes cancer more aggressive and treatment resistance. This review discusses epigenetic mechanisms involved in the overexpression of oncogenes or CPGs via epigenetic derepression in gynecologic cancers. Therefore, improved understanding of these epigenetic mechanisms will provide new targets for gynecologic cancer treatment

Exposure to sound vibrations lead to transcriptomic, proteomic and hormonal changes in Arabidopsis

Sound vibration (SV) is considered as an external mechanical force that modulates plant growth and development like other mechanical stimuli (e.g., wind, rain, touch and vibration). A number of previous and recent studies reported developmental responses in plants tailored against SV of varied frequencies. This strongly suggests the existence of sophisticated molecular mechanisms for SV perception and signal transduction. Despite this there exists a huge gap in our understanding regarding the SV-mediated molecular alterations, which is a prerequisite to gain insight into SV-mediated plant development. Herein, we investigated the global gene expression changes in Arabidopsis thaliana upon treatment with five different single frequencies of SV at constant amplitude for 1 h. As a next step, we also studied the SV-mediated proteomic changes in Arabidopsis. Data suggested that like other stimuli, SV also activated signature cellular events, for example, scavenging of reactive oxygen species (ROS), alteration of primary metabolism, and hormonal signaling. Phytohormonal analysis indicated that SV-mediated responses were, in part, modulated by specific alterations in phytohormone levels; especially salicylic acid (SA). Notably, several touch regulated genes were also up-regulated by SV treatment suggesting a possible molecular crosstalk among the two mechanical stimuli, sound and touch. Overall, these results provide a molecular basis to SV triggered global transcriptomic, proteomic and hormonal changes in plant

Hanja alexia with agraphia after left posterior inferior temporal lobe infarction: a case study.

Korean written language is composed of ideogram (Hanja) and phonogram (Hangul), as Japanese consists of Kanji (ideogram) and Kana (phonogram). Dissociation between ideogram and phonogram impairment after brain injury has been reported in Japanese, but few in Korean. We report a 64-yr-old right-handed man who showed alexia with agraphia in Hanja but preserved Hangul reading and writing after a left posterior inferior temporal lobe infarction. Interestingly, the patient was an expert in Hanja; he had been a Hanja calligrapher over 40 yr. However, when presented with 65 basic Chinese letters that are taught in elementary school, his responses were slow both in reading (6.3 sec/letter) and writing (8.8 sec/letter). The rate of correct response was 81.5% (53 out of 65 letters) both in reading and writing. The patient's performances were beyond mean-2SD of those of six age-, sex-, and education-matched controls who correctly read 64.7 out of 65 and wrote 62.5 out of 65 letters with a much shorter reaction time (1.3 sec/letter for reading and 4.0 sec/letter for writing). These findings support the notion that ideogram and phonogram can be mediated in different brain regions and Hanja alexia with agraphia in Korean patients can be associated with a left posterior inferior temporal lesion