Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of $80{\mu}M$, $21{\mu}M$, and $82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.
Background: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2-overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. Materials and Methods: Fifty-four HER2-positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. Results: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). Conclusions: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.
Conventionally, immunotoxins have been produced as a single polypeptide from fused genes of an antibody fragment and a toxin. In this study, we adopted a unique approach of chemical conjugation of a toxin protein and an antibody fragment. The two genes were separately expressed in Escherichia coli and purified to high levels of purity. The two purified proteins were conjugated using a chemical linker. The advantage of this approach is its ability to overcome the problem of low recombinant immunotoxin production observed in some immunotoxins. Another advantage is that various combinations of immunotoxins can be prepared with fewer efforts, because the chemical conjugation of components is relatively simpler than the processes involved in cloning, expression, and purification of multiple immunotoxins. As a proof of concept, the scFv of trastuzumab and the PE24 fragment of Pseudomonas exotoxin A were separately produced using E. coli and then chemically crosslinked. The new immunotoxin was tested on four breast cancer cell lines variably expressing HER2. The chemically crosslinked immunotoxin exhibited cytotoxicity in proportion to the expression level of HER2. In conclusion, the present study revealed an alternative method of generating an immunotoxin that could effectively reduce the viability of HER2-expressing breast cancer cells. These results suggest the effectiveness of this method of immunotoxin crosslinking as a suitable alternative for producing immunotoxins.
The premise of the intentional model of split-ticket voting is that some voters split their tickets simply because they prefer divided government and believe in constant "checks and balances." This article examines whether this premise stands firm in an emerging democracy like Taiwan. That is, by using survey data in Taiwan, we explore whether one's attitude toward divided or unified government is "real." We hypothesize that a citizen's attitude toward "checks and balances" is subject to change, and conditional on whether her preferred party is in power. Specifically, we speculate that a citizen would tend to hold the balancing perspective or favor divided government, if her preferred party is in opposition. However, if her preferred party becomes the ruling party, she would be more likely to oppose (hold) the balancing (non-balancing) perspective or favor unified government. We then utilize panel survey data embedded in Taiwan's Election and Democratization Studies (TEDS) to verify our hypothesis.
Enuresis nocturia is more prevalent in children than in adults. Using polysomnography (PSG), we investigated the causes of adult enuresis nocturia in a 20-year-old female patient with nighttime bedwetting. In spite of normal urological examinations, her detailed medical history disclosed frequent sleep paralysis and urination during dreams. During PSG, two electromyograms were attached to her anus to assess the tone of her bladder's sphincter while she slept. During REM sleep, the EMG tone of the mandible decreased, but the anal and bladder sphincter tones did not. The polysomnogram revealed moderate obstructive sleep apnea. Consequently, she was diagnosed with adult parasomnia (nocturnal enuresis) overlap syndrome with OSA. This study demonstrates the value of PSG with simultaneous anal tone EMG for diagnosing NREM parasomnia and nocturnal enuresis.
Kim, Hye-Jung;Ahn, Hye-Jin;Kang, Hyeweon;Park, Jaehui;Oh, Seul gi;Choi, Saehae;Lee, Won-Kyu;Nam, Ho-Woo
Parasites, Hosts and Diseases
/
제58권3호
/
pp.249-255
/
2020
Toxoplasma gondii, a ubiquitous, intracellular parasite of the phylum Apicomplexa, infects an estimated one-third of the human population as well as a broad range of warm-blooded animals. We have observed that some tyrosine kinase inhibitors suppressed the growth of T. gondii within host ARPE-10 cells. Among them, afatinib, human epithermal growth factor receptor 2 and 4 (HER2/4) inhibitor, may be used as a therapeutic agent for inhibiting parasite growth with minimal adverse effects on host. In this report, we conducted a proteomic analysis to observe changes in host proteins that were altered via infection with T. gondii and the treatment of HER2/4 inhibitors. Secreting proteins were subjected to a procedure of micor basic reverse phase liquid chromatography, nano-liquid chromatography-mass spectrometry, and ingenuity pathway analysis serially. As a result, the expression level of heterogeneous nuclear ribonucleoprotein K, semaphorin 7A, a GPI membrane anchor, serine/threonine-protein phosphatase 2A, and calpain small subunit 1 proteins were significantly changed, and which were confirmed further by western blot analysis. Changes in various proteins, including these 4 proteins, can be used as a basis for explaining the effects of T. gondii infections and HER2/4 inhibitors.
Purpose: The purpose of this study was to investigate the recurrence pattern and characteristics of patients based on the 2013 St. Gallen surrogate molecular subtypes after breast-conserving surgery (BCS) in Chinese women. Methods: This retrospective analysis included 709 consecutive breast cancer patients undergoing BCS from 1999-2010 at our institution. Five different surrogate subtypes were created using combined expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates were calculated. Results: The 5-year LRRFS, DMFS, and DFS rates were 90.5%, 88.2%, and 81.5%, respectively. Multivariate analysis revealed that young age, node-positive disease, and HER2 enrichment were independent prognostic factors in LRRFS patients. There was also an independent prognostic role of lymph node-positive disease in DMFS and DFS patients. Patients with luminal A tumors had the most favorable prognosis, with LRRFS, DMFS, and DFS rates of 93.2%, 91.5%, and 87.4% at 5 years, respectively. Conversely, HER-2-enriched tumors exhibited the highest rate of locoregional recurrence (20.6%). Conclusion: Surrogate subtypes present with significant differences in RFS, DMFS, and LRRFS. Luminal A tumors have the best prognosis, whereas HER2-enriched tumors have the poorest.
This study is done to assist in the limit of stage dress design research considering the sense of the times and the sympathy of spectators for actual stage. For the base research, to visualize the image which the spectators are feeling from Shakespeare's Hamlet, the evaluators had to analyze the whole image and color tone of the figures. First of all, 2 clothing for Hamlet, Gertrude and Ophelia had to be designed, and following conclusion has drawn. Hamlet A corresponds with passive looks which is a combination of loneliness, sadness and the unstable mental state of not adapting to and hiding from the reality. Hamlet B has more of matured looks which make Hamlet more free and comfortable from life and death as he overcame a crisis of death. Gertrude A corresponds with the image of coming right out of the funeral of late king. Gertrude B shows more of her sadness as she hears of her son Hamlet's despair and resentment and her maternal return degradation which is a special situations emphasizing her unstable and dizzy image. Ophelia A shows her usual and normal looks of a livelihood and femininity. She congratulates the wedding and coronation, and falls in love with Hamlet which shows a lot of her girlish image. Ophelia B shows dismantled rationality and violated virginity which is a very complex and unstable state showing a completely different image. Based on the above research. It was proposed their clothing through the next study of the characters, and personally make them for 2003 Yeonheedan Street Group's performance Hamlet.
The main objective of the present study is to examine the traditional concepts of women's virtues which originated mainly from Confucian ethical thoughts. According to Naefoon, a moral text for women which was highly respected in the Yangban society of Yi dynasty, the main virtues for women were as follows : 1. Fidelity ; A woman had to be faithful for life to only one man who was, or was going to be, her husband. 2. Filial piety ; Sons and daughters were supposed to dedicate their hearty love and respect to their parents, parents in law, and whole ancestors. 3. Obedience ; A woman was required to be completly obedient to her husband as well as to her father. She was also supposed to be obident even to her sons when she was old. 4. Diligence and Thrift ; It was highly advisable for a woman to work hard for household matters. 5. Hospitality ; Hearty hospitality for domestic guests was one of the main duties of women in traditional Korean society. 6. Maternal wisdom ; a mother was supposed to be both stern and merciful to her children. 7. Kindness to relatives ; Special Kindness to her husband's relatives was required as a duty to a married woman. The above mentioned seven main virtues cannot be said to be fit , as such to the contemporary Korean society. Many of them are unacceptable when we evaluate them form the democratic viewpoint . But we still find some valuable ideas at the bottom of the concepts of these virtues. If we properly modify them so that they fit to our own age, they might become a source of wisdom even for the contemporary moral life. It's tried to give some suggestions concerning how to modify the concepts of women's virtues in question, and them gave a sketch of an ideal figure of women in this industrial society.
Purpose: Mycobacterium abscessus belongs to the group of rapid-growing atypical mycobacterium. The organism is ubiquitous and is found in soil, dust, and water. Although it rarely causes disease in humans, Mycobacterium abscessus has been associated with soft tissue infection. To the best of our knowledge, this is the first case report of facial soft tissue Mycobacterium abscessus infection in a healthy child in Korea. Methods: A 12-year-old girl presented with an erythematous skin lesion with serous discharge on her chin, which had been present for 3 weeks. On her history, she had a laceration wound on her chin at public bath and the lesion was repaired at emergency department immediately. Although conventional soft tissue infecton treatment, her lesion remains unhealed state and had serous discharge for 2 months. Moreover, we found a 1 cm sized nodular mass on her chin. Therefore we performed excision operation and referred the specimen to the laboratory for microbial and histopathologic study. Results: Pathology report confirmed the mass was enlarged lymph node with chronic necrotizing granulomatous inflammation with central microabscess. Non-Tuberculous mycobacterium identification test through tissue specimen resulted Mycobacterium abscessus. We prescribed clarithromycin for three weeks by oral administration as well as performed wound debridement and mass excision via previous wound. This way, her lesion appeared to be complete healing with minimal scarring. There were no evidence of inflammation sign or palpable mass. Conclusion: Although the prevalence is rare, Mycobacterium abscessus infections of soft tissue should be considered even in a healthy child with a lesion caused by trauma or which fails to respond to conventional treatment.
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