Vol 2-5 Review Article

Functional Imaging-guided Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: Review

Xiao Wang*, Yin Zhang, Ning Yue, Ke Nie

Department of Radiation Oncology, Rutgers-Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA

In treating locally advanced non-small-cell lung cancer (NSCLC), radio-tolerance of the normal lung often limits the amount of dose that can be delivered to the primary cancer site. Radiation-related pneumonitis (RP) and other normal lung tissue complications have a significant impact on clinical outcome and patient quality of life. How to minimize treatment side effects while achieving desirable local control of lung cancers has been a continuous challenge.

Functional imaging-guided radiotherapy, which can achieve a local boost of primary cancer site or functional avoidance of normal organs, has been increasingly utilized in clinics. Various imaging approaches have been employed to achieve functional imaging guidance and implemented in different treatment regimens. There are several on-going clinical trials aiming to evaluate the clinical outcomes that are utilizing functional imaging-guided photon radiation to spare the high functioning portions of the lungs. The main applications of functional imaging-guided radiotherapy in the management of NSCLC patients will be discussed in this review.

DOI: 10.29245/2578-2967/2018/5.1150 View / Download Pdf View Full Text
Vol 2-5 Mini Review

Pyrrole indolin-2-One Based Kinase Inhibitor as Anti-Cancer Agents

Ting-Hsuan Yang1,2, Ren-Jun Hsu2, Wen-Hsin Huang1, An-Rong Lee1*

School of Pharmacy, National Defense Medical Center, No. 161, Section 6, Mingchuan East Road, Taipei 11490, Taiwan

Tri-Service General Hospital Biobank, No.325, Sec. 2, Chenggong Rd. Taipei 11490, Taiwan

Cancer cells are characterized by uncontrolled proliferation after escaping from inherent physiological constraints on growth and survival and by destructive invasion of the healthy surrounding tissues. Many kinases involved in signal transduction are overactive in malignant tumor cells. Thus, pharmacotherapeutic interventions targeting kinases responsible for signal transduction of cancer hallmarks have become promising in developing novel anticancer agents. Pyrrole indolin-2-one (or pyrrole oxindole, 1), a lead scaffold of kinase inhibitors, is used for anti-angiogenesis via inhibiting vascular endothelial growth factor receptors (VEGFs) and platelet-derived growth factor receptors (PDGFRs). The kinase selectivity and inhibitory activity of pyrrole indolin-2-one 1 can be significantly influenced through structural modifications. This mini-review provides a detailed overview of structural modification of pyrrole indolin-2-one derivatives for the development of novel kinase inhibitors.

DOI: 10.29245/2578-2967/2018/5.1153 View / Download Pdf View Full Text
Vol 2-5 Review Article

Constitutive Aryl Hydrocarbon Receptor Signaling in Prostate Cancer Progression

Maryam Ghotbaddini, Vivian Moultrie, Joann B. Powell*

Clark Atlanta University- Center for Cancer Research and Therapeutic Development 223 James P. Brawley Drive Atlanta, Georgia, USA

Research on the aryl hydrocarbon receptor (AhR) has largely focused on its activation by various environmental toxins. Consequently, only limited inferences have been made regarding its constitutive activity in the absence of an exogenous ligands. Evidence has shown that AhR is constitutively active in advanced prostate cancer cell lines which model castration resistant prostate cancer (CRPC). CRPC cells can thrive in an androgen depleted environment. However, AR signaling still plays a major role. Although several mechanisms have been suggested for the sustained AR signaling, much is still unknown. Recent studies suggest that crosstalk between constitutive AhR and Src kinase may sustained AR signaling in CRPC. AhR forms a protein complex with Src and plays a role in regulating Src activity. Several groups have reported that tyrosine phosphorylation of AR protein by Src leads to AR activation, thereby promoting the development of CRPC. This review evaluates reports that implicate constitutive AhR as a key regulator of AR signaling in CRPC by utilizing Src as a signaling intermediate.

DOI: 10.29245/2578-2967/2018/5.1136 View / Download Pdf View Full Text
Vol 2-5 Review Article

Recent Development of Bio-Reducible Polymers for Efficient Gene Delivery System

Sung Wan Kim1,2*, Joung-Pyo Nam1,2, Soyoung Kim1,2, Yong Kiel Sung1,2,3

Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA

Center for Chemically Controlled Delivery, University of Utah, Salt Lake City, Utah 84112, USA

Department of Chemistry, Dongguk University, Phildong-ro 1 Gil, Chung-gu, Seoul 04620, Korea

The design of a gene delivery system requires a complete understanding of the interaction between targeting cell and delivery systems. The poly(cystaminebis- (acrylamide)-diaminohexane) (poly(CBA-DAH)) has been confirmed as a bio-reducible efficient delivery carrier among the various systems. Poly(ethylenimine) (PEI, 1.8?kDa) was conjugated to poly(CBA-DAH) via a disulfide bond. The PEI conjugated poly(CBA-DAH) (PCDP) was able to bind with pDNA at a very low molecular weight ratio and form the polyplexes with nano-size and positive surface charge. To confirm the transfection efficiency, the plasmid DNA encodes with the luciferase reporter gene and green fluorescent protein reporter gene have made to use a bio-reducible efficient gene delivery. The PCDP polyplexes show 10 times higher gene transfection efficiency than Lipofectamine® polyplexes in bio-mimic in vivo condition. It has been reviewed that the bio-reducible PEI(1.8kDa) conjugated poly(CBA-DAH) is finally concluded as an efficient gene delivery carrier.

DOI: 10.29245/2578-2967/2018/5.1145 View / Download Pdf View Full Text
Vol 2-5 Mini Review

MicroRNA-181a Suppresses Progestin-Stimulated Breast Cancer Cell Growth

Xue Li1, Chun Yang2, Xiangyan Ruan1, Stéphane Croteau2, Pierre Hardy2*

1Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China

2Departments of Medicine, Pediatrics, Pharmacology and Physiology, University of Montreal, Montreal, Quebec, Canada

Despite all our efforts, breast cancer remains a major public health problem threatening women’s health all around the world. The morbidity of breast cancer is rising in most countries and is going to rise further over the next 20 years. Hormone treatment is widely used and it is the most efficient method of reducing menopausal symptoms or preventing abortion and pregnancy. However, multiple studies have demonstrated that hormones, especially synthetic progesterone, remain an indisputable risk factor for breast cancer. MicroRNAs are a group of endogenous small non-coding single strand RNAs which play regulatory roles in the initiation, development, and progression of different types of cancer. Evidence from multiple sources indicates that microRNA-181a exerts anti-breast cancer effects by inducing cancer cell death and preventing tumor invasion, infiltration and metastasis, etc. Our recent studies revealed that microRNA-181a not only suppresses breast cancer MCF-7 cell growth but also abrogates progestin-provoked cell growth. In this review, several interesting aspects of hormone replacement therapy and the role of microRNA-181a during progestin treatment are discussed.

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