• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2229-2234
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• 2012

Purpose: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). Materials: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. Results: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 $LI{\leq}25%$, VEGF $scoring{\leq}8$), mG2 (Ki67 LI>25%, VEGF $scoring{\leq}8$; or Ki67 $LI{\leq}25%$, VEGF scoring > 8), and mG3 (Ki67 LI > 25%, VEGF scoring > 8), which can indicate favorable, intermediate and poor prognosis, respectively. Conclusions: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3539-3548
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• 2012

The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2729-2734
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• 2012

Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects. Oroxylum indicum (L.) Vent. is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties. In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA-MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay. All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells. PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells. Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects. Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity. Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.313-319
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• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

• Radiation Oncology Journal
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• v.36 no.3
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• pp.172-181
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• 2018

Successful anticancer strategies require a differential response between tumor and normal tissue (i.e., a therapeutic ratio). In fact, improving the effectiveness of a cancer therapeutic is of no clinical value in the absence of a significant increase in the differential response between tumor and normal tissue. Although radiation dose escalation with the use of intensity modulated radiation therapy has permitted the maximum tolerable dose for most locally advanced cancers, improvements in tumor control without damaging normal adjacent tissues are needed. As a means of increasing the therapeutic ratio, several new approaches are under development. Drugs targeting signal transduction pathways in cancer progression and more recently, immunotherapeutics targeting specific immune cell subsets have entered the clinic with promising early results. Radiobiological research is underway to address pressing questions as to the dose per fraction, irradiated tumor volume and time sequence of the drug administration. To exploit these exciting novel strategies, a better understanding is needed of the cellular and molecular pathways responsible for both cancer and normal tissue and organ response, including the role of radiation-induced accelerated senescence. This review will highlight the current understanding of promising biologically targeted therapies to enhance the radiation therapeutic ratio.

• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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• pp.319-331
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• 2011

Purpose: The purpose of this study is to evaluate current criteria for insurance coverage by Health Insurance Review & Assessment Service (HIRA) on the systemic therapy used in the treatment of advanced or metastatic renal cell carcinoma (RCC), by reviewing all available clinical evidences including a variety of clinical practice guidelines. Methods: We searched clinical databases and collected data from published phase 1 through 3 randomized clinical trials on all systemic therapies used in RCC, including novel targeted therapies. Additionally, current clinical practice guidelines on the management of kidney cancer or RCC were reviewed. Based on the collected data we evaluated the appropriateness of the HIRA criteria for insurance coverage on the systemic therapy of RCC whether they are evidence-based and up to date. Results: On the basis of the collected data we concluded that there was a need for a revision in HIRA criteria for systemic therapy of RCC. Despite recent emerging therapeutic advances and changes in therapeutic strategies of management of RCC, some of anticancer regimens were inappropriately listed even though they were not proven to provide efficacy or safety superior to those of other therapies. We thus proposed an updated recommendation based on current clinical evidences. Conclusion: Systemic therapy of RCC is being rapidly changed with the advancement of understanding of the molecular biology of cancer. Consequently newly developed targeted therapies are becoming the standard therapy in the management of medically or surgically unresectable advanced or metastatic RCC. To provide effective and safe therapy to patients with RCC, the criteria for insurance coverage should be made carefully taking into consideration of most up-to-date and high-quality clinical evidences, and should be continuously reviewed so as to reflect evidence-based clinical practice.

• Radiation Oncology Journal
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• v.35 no.4
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• pp.325-331
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• 2017

Purpose: There is controversy regarding the cosmetic outcome after accelerated partial breast radiation (APBR). We report the cosmetic outcome from a single-arm prospective clinical trial of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I breast cancer (BC), using a novel fractionation schedule. Materials and Methods: Forty-two patients aged ${\geq}65$, with Stage I BC who underwent breast-conserving surgery were enrolled in a phase I/II study evaluating a 2-week course of APBR. Thirty eligible patients received 40 Gy in 4 Gy daily fractions. Cosmetic outcome was assessed subjectively by physician/patient and objectively by using a computer program (BCCT.core) before APBR, during, and after completion of the treatment. Results: The median age was 72 years, the median tumor size was 0.8 cm, and the median follow-up was 50.5 months. The 5-year locoregional control in this cohort was 97% and overall survival 87%. At the last follow-up, patients and physicians rated cosmesis as 'excellent' or 'good' in 100% and 91 %, respectively. The BCCT.core program scored the cosmesis as 'excellent' or 'good' in 87% of the patients at baseline and 81% at the last follow-up. The median $V_{50}$ (20 Gy) of the whole breast volume (WBV) was 37.2%, with the median WBV $V_{100}$ (40 Gy) of 10.9%. Conclusion: An excellent rate of tumor control was observed in this prospective trial. By using multiple assessment techniques, we are showing acceptable cosmesis, supporting the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5191-5197
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• 2015

A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

• Bulletin of the Korean Chemical Society
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• v.34 no.1
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• pp.154-158
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• 2013

Development of dual functional liposome has been studied for cancer theragnostics. Therefore, we focused on ultrasound-sensitive liposomes with doxorubicin (DOX) and gadolinium (Gd) as a theragnostic carrier having a potential for cancer therapy and diagnosis. In this study, Gd(III)-DOTA-modified sonosensitive liposomes (GL) was developed using chemically synthesized Gd(III)-DOTA-DPPE lipid. Sonosensitivity of GL to 1 MHz ultrasound induced 25% of DOX release. The relaxivities ($r_1$) of GL were $7.33-10.34\;mM^{-1}s^{-1}$, which was higher than that of MR-bester$^{(R)}$. Intracellular delivery of DOX from GL by ultrasound irradiation was evaluated according to ultrasound intensity, resulting in increase of uptake of DOX released from ultrasound-triggered GLs compared to GL3 or Doxil$^{(R)}$ without ultrasound. Taken together, this study shows that the paramagnetic and sonosensitive liposomes, GL, is a novel and highly effective delivery system for drug with the potential for broad applications in human disease.

• Radiation Oncology Journal
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• v.35 no.1
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• pp.1-15
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• 2017

Locoregional failure is the most frequent pattern of failure in locally advanced head and neck cancer patients and it leads to death in most of the patients. Second primary tumors occurring in the other head and neck region reach up to almost 40% of long-term survivors. Recommended and preferred retreatment option in operable patients is salvage surgical resection, reporting a 5-year overall survival of up to 40%. However, because of tumor location, extent, and underlying comorbidities, salvage surgery is often limited and compromised by incomplete resection. Reirradiation with or without combined chemotherapy is an appropriate option for unresectable recurrence. Reirradiation is carefully considered with a case-by-case basis. Reirradiation protocol enrollment is highly encouraged prior to committing patient to an aggressive therapy. Radiation doses greater than 60 Gy are usually recommended for successful salvage. Despite recent technical improvement in intensity-modulated radiotherapy (IMRT), the use of concurrent chemotherapy, and the emergence of molecularly targeted agents, careful patient selection remain as the most paramount factor in reirradiation. Tumors that recur or persist despite aggressive prior chemoradiation therapy imply the presence of chemoradio-resistant clonogens. Treatment protocols that combine novel targeted radiosensitizing agents with conformal high precision radiation are required to overcome the resistance while minimizing toxicity. Recent large number of data showed that IMRT may provide better locoregional control with acceptable acute or chronic morbidities. However, additional prospective studies are required before a definitive conclusion can be drawn on safety and effectiveness of IMRT.