scholarly journals Ablation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis

2018 ◽  
Vol 115 (16) ◽  
pp. 4228-4233 ◽  
Author(s):  
He Xu ◽  
Min-Sik Lee ◽  
Pei-Yun Tsai ◽  
Ashley S. Adler ◽  
Natasha L. Curry ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Amino Acids ◽  
Insulin Receptor ◽  
Tumor Cells ◽  
Proteasome Inhibitors ◽  
Essential Amino Acids ◽  
Tumor Burden ◽  
Lung Tumorigenesis ◽  
Insulin Receptor Substrates ◽  
Effective Therapeutic Strategy

Non–small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, with 25% of cases harboring oncogenic Kirsten rat sarcoma (KRAS). Although KRAS direct binding to and activation of PI3K is required for KRAS-driven lung tumorigenesis, the contribution of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in the context of mutant KRAS remains controversial. Here, we provide genetic evidence that lung-specific dual ablation of insulin receptor substrates 1/2 (Irs1/Irs2), which mediate insulin and IGF1 signaling, strongly suppresses tumor initiation and dramatically extends the survival of a mouse model of lung cancer with Kras activation and p53 loss. Mice with Irs1/Irs2 loss eventually succumb to tumor burden, with tumor cells displaying suppressed Akt activation and strikingly diminished intracellular levels of essential amino acids. Acute loss of IRS1/IRS2 or inhibition of IR/IGF1R in KRAS-mutant human NSCLC cells decreases the uptake and lowers the intracellular levels of amino acids, while enhancing basal autophagy and sensitivity to autophagy and proteasome inhibitors. These findings demonstrate that insulin/IGF1 signaling is required for KRAS-mutant lung cancer initiation, and identify decreased amino acid levels as a metabolic vulnerability in tumor cells with IR/IGF1R inhibition. Consequently, combinatorial targeting of IR/IGF1R with autophagy or proteasome inhibitors may represent an effective therapeutic strategy in KRAS-mutant NSCLC.

scholarly journals Contribution of LAT1-4F2hc in Urological Cancers via Toll-like Receptor and Other Vital Pathways

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 229
Author(s):  
Xue Zhao ◽  
Shinichi Sakamoto ◽  
Maihulan Maimaiti ◽  
Naohiko Anzai ◽  
Tomohiko Ichikawa
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Essential Amino Acids ◽  
Amino Acid Transporter ◽  
Tumor Cell Growth ◽  
Transporter Protein ◽  
Urological Cancers

Tumor cells are known for their ability to proliferate. Nutrients are essential for rapidly growing tumor cells. In particular, essential amino acids are essential for tumor cell growth. Tumor cell growth nutrition requires the regulation of membrane transport proteins. Nutritional processes require amino acid uptake across the cell membrane. Leucine, one of the essential amino acids, has recently been found to be closely associated with cancer, which activate mTOR signaling pathway. The transport of leucine into cells requires an L-type amino acid transporter protein 1, LAT1 (SLC7A5), which requires the 4F2 cell surface antigen heavy chain (4F2hc, SLC3A2) to form a heterodimeric amino acid transporter protein complex. Recent evidence identified 4F2hc as a specific downstream target of the androgen receptor splice variant 7 (AR-V7). We stressed the importance of the LAT1-4F2hc complex as a diagnostic and therapeutic target in urological cancers in this review, which covered the recent achievements in research on the involvement of the LAT1-4F2hc complex in urinary system tumors. In addition, JPH203, which is a selective LAT1 inhibitor, has shown excellent inhibitory effects on the proliferation in a variety of tumor cells. The current phase I clinical trials of JPH203 in patients with biliary tract cancer have also achieved good results, which is the future research direction for LAT1 targeted therapy drugs.

scholarly journals Dynamic BH3 profiling identifies active BH3 mimetic combinations in non-small cell lung cancer

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Danielle S. Potter ◽  
Ruochen Du ◽  
Patrick Bhola ◽  
Raphael Bueno ◽  
Anthony Letai
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Tumor Burden ◽  
Small Cell ◽  
Targeted Agents ◽  
Small Cell Lung ◽  
Conventional Chemotherapy ◽  
Bh3 Mimetic

AbstractConventional chemotherapy is still of great utility in oncology and rationally constructing combinations with it remains a top priority. Drug-induced mitochondrial apoptotic priming, measured by dynamic BH3 profiling (DBP), has been shown in multiple cancers to identify drugs that promote apoptosis in vivo. We therefore hypothesized that we could use DBP to identify drugs that would render cancers more sensitive to conventional chemotherapy. We found that targeted agents that increased priming of non-small cell lung cancer (NSCLC) tumor cells resulted in increased sensitivity to chemotherapy in vitro. To assess whether targeted agents that increase priming might enhance the efficacy of cytotoxic agents in vivo as well, we carried out an efficacy study in a PC9 xenograft mouse model. The BH3 mimetic navitoclax, which antagonizes BCL-xL, BCL-w, and BCL-2, consistently primed NSCLC tumors in vitro and in vivo. The BH3 mimetic venetoclax, which electively antagonizes BCL-2, did not. Combining navitoclax with etoposide significantly reduced tumor burden compared to either single agent, while adding venetoclax to etoposide had no effect on tumor burden. Next, we assessed priming of primary patient NSCLC tumor cells on drugs from a clinically relevant oncology combination screen (CROCS). Results confirmed for the first time the utility of BCL-xL inhibition by navitoclax in priming primary NSCLC tumor cells and identified combinations that primed further. This is a demonstration of the principle that DBP can be used as a functional precision medicine tool to rationally construct combination drug regimens that include BH3 mimetics in solid tumors like NSCLC.

ATB0,+ transporter-mediated targeting delivery to human lung cancer cells via aspartate-modified docetaxel-loading stealth liposomes

2017 ◽  
Vol 5 (2) ◽  
pp. 295-304 ◽  
Author(s):  
Qiuhua Luo ◽  
Bin Yang ◽  
Wenhui Tao ◽  
Jia Li ◽  
Longfa Kou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Amino Acids ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Rapid Growth ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Stealth Liposomes ◽  
Human Lung Cancer Cells ◽  
Targeting Delivery

Tumor cells have an increased demand for amino acids to support their rapid growth and malignant metastasis.

Pengoptimalan Air Leri dalam Pembuatan Sabun Pembersih Wajah Alami yang Ekonomis

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Rahmawati Rahmawati ◽  
Trimayasari Trimayasari ◽  
Ghozali Akhmad Mustaqim ◽  
Wening Dwi Prastiwi ◽  
Emas Agus Prastyo Wibowo
Keyword(s):  
Amino Acids ◽  
Fine Particles ◽  
Hard Water ◽  
Essential Amino Acids ◽  
Ultraviolet Rays ◽  
Starch Granules ◽  
Facial Skin ◽  
Skin Cells ◽  
The Face ◽  
Made In

AbstractSoap facial cleanser is needed to keep the facial skin to keep them clean and healthy. The purpose of this study to make soap cleanser with natural materials such as hard water deposits leri. This is because the use of leri water starch or starch granules of fine particles contained in water leri dansel dust can shed the dead skin on the face because of the essential amino acids contained can regenerate skin cells. In addition, water leri can brighten the face because the leri water oryzanol contain substances that can update the development and formation of the pigment melanin, which is effectively to ward off ultraviolet rays. The process of making soap using the principle of saponification reaction, namely the reaction between the oil and the KOH/NaOH. Facial cleansing soap made in this study is solid soap. Based on the results of quality test, soap solid leri water has a pH of 11.1, saponification number is 33, the water content of 46% as well as respondents to the test aspects of aroma and foam shows good results so this water leri treatment can be an alternative solution to prevent the use of soap facial cleansers that contain harmful chemicals. Keywords: air leri, soap cleanser, saponification  AbstrakSabun pembersih wajah sangat diperlukan untuk menjaga kulit wajah agar tetap bersih dan sehat. Tujuan dari penelitian ini untuk membuat sabun pembersih wajah dengan bahan alami berupa endapan air leri. Penggunaan air leri ini dikarenakan butiran partikel starch atau pati halus yang terdapat dalam air leri dapat merontokkan debu dansel kulit mati pada wajah karena asam amino esensial yang terkandung dapat meregenerasi sel-sel kulit. Selain itu, air leri dapat mencerahkan wajah karena air leri mengandung zat oryzanol yang dapat memperbarui perkembangan dan pembentukan pigmen melanin, yang efektif guna menangkal sinar ultraviolet. Proses pembuatan sabun menggunakan prinsip reaksi saponifikasi, yaitu reaksi antara minyak dan KOH/NaOH. Sabun pembersih wajah yang dibuat dalam penelitian ini ialah sabun padat. Berdasarkan hasil uji mutu, sabun air leri padat memiliki pH 11,1, angka penyabunan sebesar 33 kadar air 46 kadar air 46 % serta uji responden terhadap aspek aroma dan busa yang menunjukkan hasil cukup baik sehingga pengolahan air leri ini dapat menjadi solusi alternative untuk mencegah penggunaan sabun pembersih wajah yang mengandung bahan kimia berbahaya. Kata kunci: air leri, sabun pembersih wajah, saponifikasi 

ADAPTIVE CAPACITY OF EINKORN HUSKLESS IN THE SECOND, THIRD AND SEVENTH RUSSIAN FEDERATION REGIONS

1970 ◽  
pp. 34-38
Author(s):  
S. K. Temirbekova ◽  
M. Sh. Begeulov ◽  
Yu. V. Afanaseva ◽  
I. M. Kulikov ◽  
N. E. Ionova
Keyword(s):  
Amino Acids ◽  
Biochemical Analysis ◽  
Chemical Properties ◽  
First Grade ◽  
Essential Amino Acids ◽  
Wheat Grain ◽  
Volume Yield ◽  
Class 1 ◽  
Group B ◽  
Field And Laboratory Conditions

Biochemical, immunological and physico-chemical properties of an ancient wheat grain – hulless spelt cultivar Gremme are investigated. Biochemical analysis of grain revealed a high content of protein, fiber, macro-and microelements, a rich composition of essential amino acids, which is characteristic of ancient wheat species. Evaluated milling and baking properties of spelt flour. Physical and chemical parameters of spelt grain met the requirements for soft wheat grain class 1: the mass fraction of gluten-38.7 %, the nature of the grain-795 g / l, the number of drops-416 C, the total vitreousness-70 %. However, gluten had an increased stickiness, which is obviously due to the increased content of fiber and gliadin fraction. Grinding of spelt grain was carried out on the aggregate mill installation "Miller 100 Lux" to obtain baking flour of various cultivars. The overall yield of flour of the first grinding was 59.7 %. The highest volume yield (359 cm3) and the best organoleptic properties (total baking score – 3.6 points) were observed in a sample of bread baked from spelt flour that meets the requirements for wheat baking flour of the first grade. Studies have confirmed the possibility of using flour produced from the spelt grain of the Gremme variety for the production of bakery products of increased biological, therapeutic and prophylactic, nutritional value and with a high organoleptic rating. Cereals and flour are very rich in trace elements-manganese, selenium, zinc, potassium, iron, phosphorus, vitamins from group B and B, essential amino acids (biochemical analysis was carried out by the Cherkizovo Center). The cultivar is resistant to drought, heat, excessive moisture. Proved immunological properties to several diseases in the field and laboratory conditions-resistant to enzyme-mycotic seed depletion (EMIS), various types of rust, powdery mildew.

Value of quantitative and qualitative assessment of protein in workers’ diet

2019 ◽  
pp. 97-103
Author(s):  
S. E. Dubenko ◽  
T. V. Mazhaeva ◽  
G. M. Nasybullina
Keyword(s):  
Amino Acids ◽  
Physical Exertion ◽  
Qualitative Evaluation ◽  
Essential Amino Acids ◽  
Qualitative Assessment ◽  
Health State ◽  
Occupational Hazards ◽  
Occupational Groups ◽  
Branched Chain ◽  
Amino Acid Contents

Th e authors reviewed literature on methodic evaluations of human requirements of protein, based on Russian and foreign data bases (Scopus, Web of Science, MedLine, RINTs, eLIBRA RY) via key words in article headings, and evaluated quality and quantity of protein in diets of workers exposed to occupational hazards. Average requirements of amino acids and their additional intake for bett er health state in certain occupational groups remains a topical problem. Th e article covers list of methods for quantitative and qualitative evaluation of proteins in foods and diets. Findings are diff erences in approaches to protein quantity regulation in Russian Federation and WHO/FAO/UNU (protein normal level in RF is higher, depends on physical exertion, with lower quantity of amino acids with branched chain in structure of essential amino acids). Th erapeutic and prophylactic diet corresponding to Order N46 of Russian Health Ministry for main occupations of metallurgic workshops can be considered as high-proteous and balanced in amino acid contents. Necessity is to study adequate intake of amino acids in workers exposed to occupational hazards, for improving protective and adaptative body mechanisms, and prevention of occupational and occupationally conditioned diseases.

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