• Archives of Pharmacal Research
• /
• 제26권11호
• /
• pp.892-897
• /
• 2003

Anticancer drugs have serious side effects arising from their poor malignant cells selectivity, Since insulin receptors highly express on the cytomembrane of some kind of tumor cells, using insulin as the vector was expected to reduce serious side effects of the drugs. The objective of this study was to evaluate the tumor targeting effect of the newly synthesized mitoxantrone-insulin conjugate (MIT-INS) with the drug loading of 11.68%. In vitro stability trials showed MIT-INS were stable in buffers with different pH (2-8) at $37^{\circ}C$ within 120 h (less than 3% of free MIT released), and were also stable in mouse plasma within 48 h (less than 1 % of free MIT released). In vivo study on tumor-bearing mice showed that, compared with MIT [75.92 $\mu g \cdot$ h/g of the area under the concentration-time curve (AUC) and 86.85 h of mean residence time (MRT)], the conjugates had better tumor-targeting efficiency with enhanced tumor AUC of 126.53 1l9 h/g and MTR of 151.95 h. The conjugate had much lower toxicity to most other tissues with targeting indexes ($TI^c$) no larger than 0.3 besides good tumor targeting efficiency with $TI^c$ of 1.67. The results suggest the feasibility to promote the curative effect in ca.ncer chemotherapy by using insulin as the vector of anti-cancer drugs.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제29권5호
• /
• pp.405-416
• /
• 2007

Objective : Lots of papers have revealed that tumor growth related factors such as EGF, EGFR, c-erbB-2 play an important role in tumorigenesis and proliferation. These factors are found in most tumors of ectodermal origin. But, documentations of tumor growth related factors on salivary gland tumors were rare. Therefore, we determined expressions of tumor growth related factors; PCNA, p53, EGF, EGFR, cerbB2(HER-2), Maspin, DMBT-1, N-Ras in representative salivary gland tumors. Materials and methods : A few types of salivary tumors were examined by immunohistochemical assays. Each antibody was applied to specimens of tumors. Specimens were composed of 5 pleomorphic adenomas (PA), 3 mucoepidermoid carcinomas (MEC), 2 adenoid cystic carcinomas (ACC) and 2 squamous cell carcinomas (SCC) from 12 patients. One specimen was selected randomly as negative control. For evaluation of staining intensity, each stained sample was divided into 5 grade; no staining, obscure, weak staining, moderate staining, strong staining. Results : Strong expressions of PCNA were found in all tumors except of PA. EGF was expressed strongly in SCC, ACC sequently. But in both PA and MEC, EGF expression was weak. EGFR and c-erbB-2 expression showed similar patterns in all salivary gland tumor tissues. P53 showed weak expression generally in all salivary gland tumors. DMBT-1 was expressed in SCC rather than in ACC or in MEC. N-Ras showed weak expressions in all salivary gland tumors except of squamous cell carcinoma. Conclusion : Taken together, tumor growth related factors were expressed in salivay tumors as well as mucosal squamous cell carcinoma. Especially EGFR and c-erbB-2 could be candidates as diagnostic markers for estimating clinical grade of salivary gland tumors. But further studies with reliable methods will be needed to confirm the results of this study.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권2호
• /
• pp.157-165
• /
• 2023

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and current therapeutic strategies are limited in their effectiveness. The expressions of Rab5 and the M2 tumor-associated macrophage marker CD163 in tissues were detected by Western blot. The migration and invasion of cells were determined using a Transwell assay. The expressions of the exosome markers were evaluated by Western blot. The polarization of human macrophages (THP-1) was determined by incubation of THP-1 cells with conditioned medium or exosomes collected from MDA-MB-231 cells with indicated transfections or by a coculture system of THP-1 and MDA-MB-231 cells. The M1 and M2 macrophage markers were evaluated by qRT-PCR. The expression of Rab5 in TNBC was significantly higher than that in normal breast tissue. Rab5 expressions in triple-negative and luminal A breast cancer were higher than those in other molecular subtypes. Higher CD163 expression was observed in triple-negative breast cancer and in triple-negative and luminal B subtypes. Rab5 knockdown suppressed but Rab5 overexpression promoted the migration and invasion capacity of MDA-MB-231 cells. The levels of CD63 and CD9 in the medium of Rab5 knockdown cells were lower than those in control cells, whereas higher levels of CD63 and CD9 were observed in Rab5 overexpression cells. Rab5 knockdown decreased the excretion but did not alter the diameter of the exosomes. Knockdown of Rab5 facilitated the anti-tumor polarization of macrophages, which was partially reversed by Rab5 overexpression. Therefore, Rab5 is expected to be a potential therapeutic target for triple-negative breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권3호
• /
• pp.1171-1176
• /
• 2014

Objective: The tumor suppressor gene, Ras-association domain family (RASSF)2A, is inactivated by promoter hypermethylation in many cancers. The current study was performed to evaluate the methylation status of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and correlations with gene expression and clinicopathologic characteristics. Method: We detected methylation of the RASSF2A gene in tissues and corresponding plasma samples from 47 EOC patients and 14 patients with benign ovarian tumors and 10 with normal ovarian tissues. The methylation status was determined by methylation-specific PCR while gene expression of mRNA was examined by RT-PCR. The EOC cell line, SKOV3, was treated with 5-aza-2'-deoxycytidine (5-azadC). Results: RASSF2A mRNA expression was significantly low in EOC tissues. The frequency of aberrant methylation of RASSF2A was 51.1% in EOC tissues and 36.2% in corresponding plasma samples, whereas such hypermethylation was not detected in the benign ovarial tumors and normal ovarian samples. The expression of RASSF2A mRNA was significantly down-regulated or lost in the methylated group compared to the unmethylated group (p<0.05). After treatment with 5-aza-dC, RASSF2A mRNA expression was significantly restored in the Skov3 cell line. Conclusion: Epigenetic inactivation of RASSF2A through aberrant promoter methylation may play an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be a valuable molecular marker for the early detection of EOC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권18호
• /
• pp.7799-7803
• /
• 2014

Background: To determine the imprinting status of the IGF2 in Chinese patients with primary lung cancer and to analyze the clinical significance of the loss of imprinting (LOI) of IGF2. Materials and Methods: PCRRFLP and RT-PCR-RFLP were carried out to select heterozygous cases for the ApaI polymorphism within exon 9 of the IGF2 gene and further analyze IGF2 LOI in 64 lung cancer patients, respectively. Results: Of 64 lung cancer patients, 31 were heterozygous for IGF2. The positive rates of IGF2 LOI of lung cancer foci, matched paracancer tissues, and normal lung tissues were 77.4% (24/31), 61.3% (19/31), and 29.0% (9/31), respectively. The LOI differences for IGF2 among the three groups were statistically significant (${\chi}^2=15.267$, p=0.000), and the LOI frequency of IGF2 in normal lung tissue was significantly lower than that in lung cancer foci and paracancer tissues (${\chi}^2=14.577$, p=0.000; ${\chi}^2=6.513$, p=0.011). No statistical difference was observed between the lung tumor group and the matched paracancer group (${\chi}^2=1.897$, p=0.168). The prevalence of advanced clinical stages (${\chi}^2=2.379$; p=0.017) and lymph node metastasis (${\chi}^2=5.552$; p=0.018) was significantly higher for LOI-positive paracancer tissues than for LOI-negative paracancer tissues. Conclusions: IGF2 LOI is highly frequent in Chinese primary lung cancer patients, especially those with increased risk of lymph node metastasis and advanced clinical stages. IGF2 LOI may be an early epigenetic event in human lung carcinogenesis.

• BMB Reports
• /
• 제50권12호
• /
• pp.621-627
• /
• 2017

We previously reported the involvement of zinc-finger protein 143 (ZNF143) on cancer cell motility in colon cancer cells. Here, ZNF143 was further characterized in breast cancer. Immunohistochemistry was used to determine the expression of ZNF143 in normal tissues and in tissues from metastatic breast cancer at various stages. Notably, ZNF143 was selectively expressed in duct and gland epithelium of normal breast tissues, which decreased when the tissue became malignant. To determine the molecular mechanism how ZNF143 affects breast cancer progression, it was knocked down by infecting benign breast cancer cells with short-hairpin (sh) RNA-lentiviral particles against ZNF143 (MCF7 sh-ZNF143). MCF7 sh-ZNF143 cells showed different cell-cell contacts and actin filament (F-actin) structures when compared with MCF7 sh-Control cells. In migration and invasion assays, ZNF143 knockdown induced increased cellular motility in breast carcinoma cells. This was reduced by the recovery of ZNF143 expression. Taken together, these results suggest that ZNF143 expression contributes to breast cancer progression.

• BMB Reports
• /
• 제48권3호
• /
• pp.147-152
• /
• 2015

Small interfering RNA (siRNA) functions through pairing with specific mRNA sequences and results in the mRNA's degradation. It is a potential therapeutic approach for many diseases caused by altered gene expression. The delivery of siRNA is still a major problem due to its rapid degradation in the circulation. Various strategies have been proposed to help with the cellular uptake of siRNA and short or small hairpin RNA (shRNA). Here, we reviewed recently published data regarding local applications of siRNA. Compared with systemic delivery methods, local delivery of siRNA/shRNA has many advantages, such as targeting the specific tissues or organs, mimicking a gene knockout effect, or developing certain diseases models. The eye, brain, and tumor tissues are 'hot' target tissues/organs for local siRNA delivery. The siRNA can be delivered locally, in naked form, with chemical modifications, or in formulations with viral or non-viral vectors, such as liposomes and nanoparticles. This review provides a comprehensive overview of RNAi local administration and potential future applications in clinical treatment.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권1호
• /
• pp.165-171
• /
• 2013

The aim of the present study was to analyze the expression of FHIT and WWOX in nasopharyngeal carcinoma (NPC) and correlations with clinical pathologic features. mRNA expression of the FHIT and WWOX was assessed by real-time fluorescent relatively quantitative PCR in 61 NPC tissues and 45 non-cancerous nasopharyngeal tissues. As a result, mRNA expression levels of both FHIT and WWOX were significantly lower in NPC patients than in control samples (P=0.049 and 0.045, respectively). Moreover, the mRNA expression of both had an inverse relation with larger invasive range (P=0.035 and 0.048, respectively), poor histologic differentiation (P=0.012 and 0.016) and advanced clinical stage (P=0.026 and 0.038). Consistency was found between expression of FHIT and WWOX in the same NPC tissues (r=0.681, P=0.00). In conclusion, synergy between FHIT and WWOX may exist in the development of NPC so that the two factors may be considered as important genetic markers. Detecting the expression of FHIT and WWOX should provide clinically significant information relevatn to tumor diagnosis, progression and treatment modalities for NPC.

• Current Optics and Photonics
• /
• 제3권2호
• /
• pp.150-153
• /
• 2019

Larynx cancer is a potentially terminal and severe type of neck and head cancer in which malignant cells start to grow and spread upwards in the larynx, or voice box. Smoking tobacco, drinking hot beverages and drinking alcohol are the main risk factors for these tumors. In this study, we aimed to develop a precise, accurate and rapid chemometrics assisted Raman spectroscopy method for diagnosis of larynx cancer in deparaffinized tissue samples. In the proposed method, samples were deparaffinized and 20 microns of each tissue were located on a coverslip. Both healthy (n = 13) and cancerous tissues (n = 13) were exposed to a Raman laser (785 nm) and excitations were recorded between wavenumbers of $50{\sim}1500cm^{-1}$. An Orthogonal Partial Least Square algorithm was applied to evaluate the Raman spectrum obtained. Sensitivity and specificity of the proposed method is high enough with the aid of Principal Component Analysis (PCA) to test the whole model. Healthy and cancerous tissues were accurately and precisely clustered. A rapid, easy and precise diagnosis algorithm was developed for larynx cancer. By this method, some useful data about differences in biomolecules of each group (phospholipids, amides, tyrosine, phenylalanine collagen etc.) was also obtained from the spectra. It is claimed that the optimized method has a great potential for clustering and separating tumor tissues from healthy ones. This novel, rapid, precise and objective diagnosis method may be an alternative for the conventional methods in literature for diagnosis of larynx cancer.

• 대한치과의사협회지
• /
• 제11권8호
• /
• pp.525-530
• /
• 1973

True collagenolytic enzymes in animal tissues were first demonstrated by Gross and Lapiere (1962), who showed the ability of such an enzyme in the culture medium of living explants of tadpole tissue to degrade a specific substrate of undenatured collagen under physiological conditions. Recently, tumor-associated collagenolytic activity has been demonstrated in human neoplasm and in ascites V Carcinoma. This investigation have been peforme to determine whether or not a collagen lytic enzyme could e found in isolated solid Tawa sarcoma of Donryu female rat obtained the culture medium. The results were as follows. 1. 11.5mg% of hydroxyproline contained in Donryu rat skin collagen, which was extracted by 0.5M acetic acid. 2. Cultivation of solid Tawa sarcoma tissues on reconstituted rat skin collagen gels showed lysis of adjacent gel after 18 hours, and much more extensive lysis after 5 days. 3. Collagen substrate was not attacked by the common proteolytic enzymes, trypsin, pepsin, and pronase.