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https://read.qxmd.com/read/30774867/the-anti-apoptotic-proteins-naf-1-and-iaspp-interact-to-drive-apoptosis-in-cancer-cells
#1
Anat Iosub-Amir, Fang Bai, Yang-Sung Sohn, Luhua Song, Sagi Tamir, Henri-Baptiste Marjault, Guy Mayer, Ola Karmi, Patricia A Jennings, Ron Mittler, José N Onuchic, Assaf Friedler, Rachel Nechushtai
Suppression of apoptosis is a key Hallmark of cancer cells, and reactivation of apoptosis is a major avenue for cancer therapy. We reveal an interaction between the two anti-apoptotic proteins iASPP and NAF-1, which are overexpressed in many types of cancer cells and tumors. iASPP is an inhibitory member of the ASPP protein family, whereas NAF-1 belongs to the NEET 2Fe-2S protein family. We show that the two proteins are stimulated to interact in cells during apoptosis. Using peptide array screening and computational methods we mapped the interaction interfaces of both proteins to residues 764-778 of iASPP that bind to a surface groove of NAF-1...
January 21, 2019: Chemical Science
https://read.qxmd.com/read/30774378/establishing-a-detection-method-for-ccny-a-potentially-significant-clinical-investigative-marker-in-nsclc-patients
#2
Li Ma, Meng Gu, Yu Teng, Weiying Li
Background: CCNY, a novel cyclin family member, plays an increasingly important role in the progression of tumor invasion and metastasis, including lung cancer. However, the clinical significance of CCNY in non-small-cell lung cancer (NSCLC) patients is unknown. Patients and methods: We prepared CCNY monoclonal antibodies, validated specific peptides by a peptide array, and established a double-antibody sandwich ELISA detection method. Then, we measured CCNY levels in 100 NSCLC patients and 50 healthy controls...
2019: OncoTargets and Therapy
https://read.qxmd.com/read/30771730/recent-advances-of-anti-cancer-therapies-including-the-use-of-cell-penetrating-peptides
#3
REVIEW
Annika Klimpel, Tamara Lützenburg, Ines Neundorf
Cancer is one of the major growing public health problems making the development of new anti-cancer treatment strategies still compulsory. Conventionally used chemotherapies are quite often associated with severe side effects. One reason is limited cell-permeability of the used drugs resulting in only poor overall bioavailability. During the last thirty years, cell-penetrating peptides (CPPs) have extensively been studied as efficient vehicles for several classes of cargos, and the development of novel therapeutic applications including CPPs has gained a major role in current cancer research...
February 13, 2019: Current Opinion in Pharmacology
https://read.qxmd.com/read/30771535/advances-in-immunotherapy-delivery-from-implantable-and-injectable-biomaterials
#4
REVIEW
David G Leach, Simon Young, Jeffrey D Hartgerink
Macroscale biomaterials, such as preformed implantable scaffolds and injectable soft materials, possess powerful synergies with anti-cancer immunotherapies. Immunotherapies on their own typically have poor delivery properties, and often require repeated high-dose injections that result in serious off-tumor effects and/or limited efficacy. Rationally designed biomaterials allow for discrete localization and controlled release of immunotherapeutic agents, and have been shown in a large number of applications to improve outcomes in the treatment of cancers via immunotherapy...
February 13, 2019: Acta Biomaterialia
https://read.qxmd.com/read/30769871/novel-ran-rcc1-inhibitory-peptide-loaded-nanoparticles-have-anti-cancer-efficacy-in-vitro-and-in-vivo
#5
Yusuf A Haggag, Kyle B Matchett, Robert A Falconer, Mohammad Isreb, Jason Jones, Ahmed Faheem, Paul McCarron, Mohamed El-Tanani
The delivery of anticancer agents to their subcellular sites of action is a significant challenge for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have significant potential to be utilised as cancer therapeutics due to their selectivity, high potency and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1 (Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid) PEG-PLGA polymeric nanoparticles (NPs)...
February 14, 2019: Cancers
https://read.qxmd.com/read/30769238/peptide-vaccines-in-early-breast-cancer
#6
Carmen Criscitiello, Giulia Viale, Giuseppe Curigliano
The immune system plays a dual role of host-protecting and tumor-promoting, as elegantly expressed by the 'cancer immunoediting' hypothesis. Although breast cancer has not been traditionally considered to be immunogenic, recently there is accumulating and solid evidence on the association between immune system and breast cancer. To mount an effective anti-tumor response, host immunosurveillance must recognize tumor-specific epitopes, thus defining the antigenicity of a tumor. Neoantigens are mutant cancer peptides that arise as terminal products of the expression of somatic cancer mutations...
February 7, 2019: Breast: Official Journal of the European Society of Mastology
https://read.qxmd.com/read/30769131/ratiometric-co-encapsulation-and-co-delivery-of-doxorubicin-and-paclitaxel-by-tumor-targeted-lipodisks-for-combination-therapy-of-breast-cancer
#7
Chunlai Feng, Haisheng Zhang, Jiaming Chen, Siqi Wang, Yuanrong Xin, Yang Qu, Qi Zhang, Wei Ji, Fumiyoshi Yamashita, Mengjie Rui, Ximing Xu
Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro, combination treatment requires improvement in vivo due to uncontrolled ratiometric delivery. In this study, a tumor-targeting lipodisk nanoparticle formulation was developed for ratiometric loading and the transportation of two hydrophobic model drugs, doxorubicin (DOX) and paclitaxel (PTX), in one single platform. Furthermore, a slightly acidic pH-sensitive peptide (SAPSP) incorporated into lipodisks effectively enhanced the tumor-targeting and cell internalization...
February 12, 2019: International Journal of Pharmaceutics
https://read.qxmd.com/read/30765725/enhanced-anti-tumor-activity-of-the-multi-leu-peptide-pace4-inhibitor-transformed-into-an-albumin-bound-tumor-targeting-prodrug
#8
Anna Kwiatkowska, Frédéric Couture, Samia Ait-Mohand, Roxane Desjardins, Yves L Dory, Brigitte Guérin, Robert Day
The proprotein convertase PACE4 has been validated as a potential target to develop new therapeutic interventions in prostate cancer (PCa). So far, the most effective compound blocking the activity of this enzyme has been designed based on the structure of a small peptide Ac-LLLLRVKR-NH2 known as the Multi-Leu (ML) peptide. Optimization of this scaffold led to the synthesis of compound C23 (Ac-[DLeu]LLLRVK-amidinobenzylamide) with a potent in vivo inhibitory effect on the tumor growth. However, further developments of PACE4 inhibitors may require additional improvements to counter their rapid renal clearance and to increase their tumor targeting efficiency...
February 14, 2019: Scientific Reports
https://read.qxmd.com/read/30763811/functional-expression-of-mucin1-in-human-duodenal-adenocarcinoma
#9
Satomi Shiba, Atsushi Miki, Hideyuki Ohzawa, Takumi Teratani, Yasunaru Sakuma, Alan Kawarai Lefor, Joji Kitayama, Naohiro Sata
OBJECTIVE: Mucin1 (MUC1), a member of the mucin family, is a glycoprotein which is often expressed in malignant cells. However, the expression and function of MUC1 in human duodenal adenocarcinoma (DAC) has not yet been characterized because of its low frequency. Here, we examined the functional roles of core protein (MUC1-C) in DAC. MATERIALS AND METHODS: Using a human duodenal cancer cell line, HuTu80, proliferation, migration, invasion, ALDH activity was assessed by cell counting kit-8, scratch wound healing, matrigel invasion, and ALDEFUOR assays, respectively...
February 11, 2019: Journal of Surgical Research
https://read.qxmd.com/read/30763634/core-matched-nanoassemblies-for-targeted-co-delivery-of-chemotherapy-and-photosensitizer-to-treat-drug-resistant-cancer
#10
Di Jiang, Minjun Xu, Yuanyuan Pei, Yukun Huang, Yu Chen, Fenfen Ma, Huiping Lu, Jun Chen
Emergence of drug resistance in tumors causes therapeutic failure or tumor relapse. Combination of chemotherapy and photodynamic therapy holds significant promise to treat drug-resistant tumors. However, stubborn hydrophobicity of photosensitizer (PS), low encapsulation efficiency and leaking problem of PS in organic carrier, and disparate physicochemical properties of PS and chemotherapeutics make the combination unachievable. Thus how to efficiently co-deliver the two functional agents to enable photo-chemotherapy seems to be one of the key challenges...
February 11, 2019: Acta Biomaterialia
https://read.qxmd.com/read/30763603/emerging-roles-for-the-relaxin-rxfp1-system-in-cancer-therapy
#11
REVIEW
Thatchawan Thanasupawat, Aleksandra Glogowska, Sai Nivedita-Krishnan, Brian Wilson, Thomas Klonisch, Sabine Hombach-Klonisch
A role for the hormone relaxin in cancer was described well before the receptor was identified. Relaxin predominantly increases the growth and invasive potential in cancers of different origins. However, relaxin was also shown to promote cell differentiation and to act in a dose-and time-dependent manner in different cancer cell models used. Following the discovery of the relaxin like family peptide receptor 1 (RXFP1) as the cellular receptor for RLN1 and RLN2, research has focussed on the ligand interaction with the large extracellular domain of RXFP1 and resulting molecular signaling mechanisms...
February 11, 2019: Molecular and Cellular Endocrinology
https://read.qxmd.com/read/30759373/what-doesn-t-kill-you-makes-you-stranger-dipeptidyl-peptidase-4-cd26-proteolysis-differentially-modulates-the-activity-of-many-peptide-hormones-and-cytokines-generating-novel-cryptic-bioactive-ligands
#12
Ahmed M Elmansi, Mohamed E Awad, Nada H Eisa, Dmitry Kondrikov, Khaled A Hussein, Alexandra Aguilar-Pérez, Samuel Herberg, Sudharsan Periyasamy-Thandavan, Sadanand Fulzele, Mark W Hamrick, Meghan E McGee-Lawrence, Carlos M Isales, Brian F Volkman, William D Hill
Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand...
February 10, 2019: Pharmacology & Therapeutics
https://read.qxmd.com/read/30758022/probing-a-dipeptide-based-supramolecular-assembly-as-an-efficient-camptothecin-delivering-carrier-for-cancer-therapy-computational-simulations-and-experimental-validations
#13
Mengchi Sun, Xiangyu Zhang, Zisen Gao, Tian Liu, Cong Luo, Yongshan Zhao, Yun Liu, Zhonggui He, Jian Wang, Jin Sun
Short peptide-based supramolecular assemblies have drawn much attention in the field of drug delivery. However, the progress still remains limited owing to the inefficient drug loading capacity of conventional short peptide-based materials. In this study, based on coordinated intramolecular π-π stacking, we customize a dipeptide-based rhein derivative (rhein-diphenylalanine peptide, RDP), which could spontaneously form spherical nanoassemblies for drug delivery. A structure-based virtual screening of a library of small molecules is conducted to identify the suitable compounds which could be effectively delivered by this nanocarrier...
February 13, 2019: Nanoscale
https://read.qxmd.com/read/30755156/significance-of-serum-antibodies-against-hpv-e7-hsp27-hsp20-and-hp91-in-iranian-hpv-exposed-women
#14
Amitis Ramezani, Arezoo Aghakhani, Sepehr Soleymani, Anahita Bavand, Azam Bolhassani
BACKGROUND: Among different types of human papillomavirus (HPV), types 16 and 18 were known to be high-risk agents causing mainly cervical cancer. Up to now, the potential of HPV E7 protein has been proved as a diagnostic marker of cervical cancer. Moreover, the levels of anti-heat shock protein (Hsp) and anti-high mobility group box-1 (HMGB1) antibodies in cancer patients have been useful in tumor diagnosis. The goal of the present study was to determine the efficiency of the potential serologic markers including HPV E7, Hsp20, Hsp27 proteins and Hp91 peptide in Iranian HPV-exposed women, for the first time...
February 12, 2019: BMC Infectious Diseases
https://read.qxmd.com/read/30744071/mechanism-and-potential-of-egg-consumption-and-egg-bioactive-components-on-type-2-diabetes
#15
REVIEW
Xiaofeng Wang, Myoungjin Son, Chalamaiah Meram, Jianping Wu
Type-2 diabetes (T2D) is one of the major global health challenges and a substantial economic burden. Egg and egg-derived components have been indicated to possess antioxidant, anti-inflammatory, anti-hypertensive, immunomodulatory, and anti-cancer activities. However, the scientific evidence about the benefits of egg on T2D is debatable. The relationship between egg consumption and the risk of T2D from observational epidemiological studies is not consistent. Interventional clinical studies, however, provide promising evidence that egg consumption ameliorates the risk of T2D...
February 8, 2019: Nutrients
https://read.qxmd.com/read/30743204/prevention-and-treatment-of-cervical-cancer-by-a-single-administration-of-human-papillomavirus-peptide-vaccine-with-cpg-oligodeoxynucleotides-as-an-adjuvant-in-vivo
#16
Yang Yang, Yuxin Che, Yan Zhao, Xuelian Wang
No licensed therapeutic human papillomavirus (HPV) vaccine is currently available, so it remains a high priority to develop a therapeutic HPV vaccine or prophylactic/therapeutic HPV vaccine for cervical cancer. In this current study, we designed an HPV vaccine including CpG oligodeoxynucleotides 1826 as an adjuvant and HPV16 E7 43-77 peptide as antigen, which contains a CD8 T cell epitope (E7 49-57), and two CD4 T cell epitopes (E7 43-77 and E7 50-62). The prophylactic and therapeutic effect on cervical cancer induced by a single administration of vaccine, were comprehensively evaluated by examining the tumor size and the percentage of tumor-free/bearing mice...
February 8, 2019: International Immunopharmacology
https://read.qxmd.com/read/30743049/nucleus-targeted-nano-delivery-system-eradicates-cancer-stem-cells-by-combined-thermotherapy-and-hypoxia-activated-chemotherapy
#17
Hongjuan Li, Weixiao Yan, Xiaomin Suo, Haotong Peng, Xinjian Yang, Zhenhua Li, Jinchao Zhang, Dandan Liu
Many efforts have focused on the cancer stem cell (CSC) targeting nano delivery system, however, the anticancer therapy efficacy is relative low due to the highly drug-resistance and drug efflux. Nucleus-targeted drug delivery is a promising strategy for reverse the drug resistance and drug efflux of CSCs, but in vivo nucleus-targeted drug delivery has been challenging. Herein, we designed a mesoporous silica nanoparticle (MSN)-based nucleus-targeted system, which could directly target the CSCs and further enter the nucleus by the surface modification of anti-CD133 and thermal-triggered exposure of TAT peptides under an alternating magnetic field (AMF)...
February 6, 2019: Biomaterials
https://read.qxmd.com/read/30740611/the-year-s-new-drugs-and-biologics-2018-part-i
#18
A I Graul, P Pina, E Cruces, M Stringer
Sixty-four new drugs and biologics reached their first global markets in 2018, the greatest number in at least a decade. In addition, 19 important new line extensions (new indications, new combinations or new formulations of previously marketed drugs) were introduced over the course of 2018. Twenty-three other new products and new line extensions were approved but not launched before December 31. As has been the trend in recent years, oncology was the most active therapeutic area in terms of new launches, with cancer drugs accounting for 25% of all novel drugs and biologics introduced worldwide last year...
January 2019: Drugs of Today
https://read.qxmd.com/read/30735705/preparation-and-characterization-of-humanized-nanobodies-targeting-the-dimer-interface-of-epidermal-growth-factor-receptor-egfr
#19
He Zhu, Lin Zhao, Zemin Li, Biyan Wen, Chuangnan Qiu, Mengmiao Liu, Zhimin Xu, Shuzhuang Hu, Huangjin Li
Epidermal growth factor receptor (EGFR) is an effective target for the treatment of many epithelial cancers. However, EGFR inhibitors have low clinical response rates and are prone to drug resistance arising from mutations and heterodimerization of EGFR. Therefore, targeting the highly conserved dimer interface of EGFR may be an effective strategy for improving the clinical response of anti-EGFR therapies. Nanobodies have significant advantages over conventional antibodies in terms of size, solubility, stability and cost-effectiveness...
February 5, 2019: Protein Expression and Purification
https://read.qxmd.com/read/30723585/a-non-functional-neoepitope-specific-cd8-t-cell-response-induced-by-tumor-derived-antigen-exposure-in-vivo
#20
Mathias Vormehr, Katharina Reinhard, Renata Blatnik, Kathrin Josef, Jan David Beck, Nadja Salomon, Martin Suchan, Abderraouf Selmi, Fulvia Vascotto, Johannes Zerweck, Holger Wenschuh, Mustafa Diken, Sebastian Kreiter, Özlem Türeci, Angelika B Riemer, Ugur Sahin
Cancer-associated mutations, mostly single nucleotide variations, can act as neoepitopes and prime targets for effective anti-cancer T-cell immunity. T cells recognizing cancer mutations are critical for the clinical activity of immune checkpoint blockade (ICB) and they are potent vaccine antigens. High frequencies of mutation-specific T cells are rarely spontaneously induced. Hence, therapies that broaden the tumor specific T-cell response are of interest. Here, we analyzed neoepitope-specific CD8+ T-cell responses mounted either spontaneously or after immunotherapy regimens, which induce local tumor inflammation and cell death, in mice bearing tumors of the widely used colon carcinoma cell line CT26...
2019: Oncoimmunology
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