Targeting the Proline-Glutamine-Asparagine Axis in Cancer Therapy |Chapter 5 | Pharmaceutical Research: Recent Advances and Trends Vol. 2

 

The present study targets the Proline-Glutamine-Asparagine-Arginine Metabolic Axis in Amino Acid Starvation Cancer Therapy. The study also reviewed the interactive regulatory mechanisms that control cellular levels of these amino acids for amino acid starvation therapy and how drug resistance is evolved underlying treatment failure. The non-essential amino acids such as proline (Pro), glutamine (Gln), asparagine (Asn) and arginine (Arg) support this promise. While these amino acids can be synthesized endogenously in normal cells, however many human tumors, ranging from leukemia to solid cancers, do not produce sufficient amounts of these amino acids to support their growth. Our bodies are capable of producing the conditionally non-essential amino acids proline, glutamine, asparagine, and arginine. Nonetheless, they are necessary for the development of highly proliferative cells, including malignancies. These amino acids are expressed in lower quantities in many malignancies, necessitating their importation from the environment. While the biosynthesis of these amino acids is inter-connected but can be intervened individually through inhibition of key enzymes of the biosynthesis of these amino acids, resulting in amino acid starvation and cell death. Amino acid starvation strategies have been in various stages of clinical applications. Targeting asparagine using asparaginase has been approved for treating acute lymphoblastic leukemia. Targeting glutamine and arginine starvations are in various stages of clinical trials and targeting proline starvation is in pre-clinical development. The most important obstacle of these therapies is drug resistance, mostly due to the reactivation of the key enzymes involved in the biosynthesis of the targeted amino acids and reprogramming of compensatory survival pathways, via transcriptional, epigenetic, and posttranscriptional mechanisms. This study provided a broader scope of targeting amino acid starvation beyond the current individual one. Perhaps it is time to think globally when designing strategies to target amino acid starvation therapy. This may eventually lead to the development of effective strategies in cancer treatment.

 

Author(s)details:-

 

Macus Tien Kuo
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

 

Helen H. W. Chen
Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.

 

Lynn G. Feun
Department of Medicine, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

 

Niramol Savaraj
Division of Hematology and Oncology, Miami Veterans Affairs Heaithcare System, Miami, FL 33136, USA.

 

Please See the book here :- https://doi.org/10.9734/bpi/prrat/v2/391

Determining the Effect of Preoperative Administration of Oral Arginine and Glutamine in Patients with Enterocutaneous Fistula Subjected to Definitive Surgery: A Prospective Randomized Trial | Chapter 4 | Advancement and New Understanding in Medical Science Vol. 7

Background: Management of enterocutaneous fistulas (ECFs) is a complex and challenging problem commonly found by general and specialized surgeons. Recently, some nutrients have been used to improve the immune system of patients who are subjected to gastrointestinal surgery. The use of glutamine and arginine has shown several advantages in postoperative outcomes in patients after gastrointestinal surgery.

The objective of this study was to determine the effect of the preoperative administration of enteral glutamine and arginine in patients submitted to surgical repair of their ECF regarding recurrence, inflammatory cytokines, and infectious complications.

Patients and Methods: Forty patients with enterocutaneous fistula were randomly assigned to one of two groups. The control group received the standard medical care while the patients of the experimental group were supplemented with enteral administration of 4.5 g of arginine and 10 g of glutamine per day for 7 days prior to 3the surgery. All the collected data was analyzed using GraphPad Prism and SPSS. The primary outcome variable was the recurrence of the fistula and the secondary outcomes were preoperative and postoperative serum concentrations of interleukin 6 and C-reactive protein and postoperative infectious complications.

Results: Twenty patients were assigned to each group. The fistula recurred in two patients (10%) of the experimental group and in nine patients (45%) of the control group (P < 0.001). We found a total of 13 infectious complications in six patients of the control group (all with fistula recurrence) and none in the experimental group. Mean preoperative serum concentrations of interleukin 6 and C-reactive protein were lower in patients from the experimental group. In addition, these levels were lower in patients who had recurrence if compared to patients who did not recur. The results of this study show that the preoperative use of oral arginine and glutamine in patients with ECF has positive effects about fistula recurrence, postoperative inflammatory markers, and infectious complications after definitive surgery (fistula resection and primary anastomosis).

Conclusion: Most patients with ECF require definitive surgical treatment for its closure. Preoperative administration of oral arginine and glutamine could be valuable in the postoperative recovery of patients with enterocutaneous fistulas submitted to definitive surgery.

Author(s) Details:

José L. Martínez,
Department of General and Gastrointestinal Surgery, UMAE Hospital de Especialidades – Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Mexico City, Mexico and Programa de Doctorado en Ciencias Biológicas, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico.

Ilka Bosco-Garate,
Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades – Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Av. Cuauhtémoc 330, 3er Piso, Colonia Doctores, Delegación Cuauhtémoc, 06720 Mexico City, Mexico.

Luis Manuel Souza-Gallardo,
Department of General and Gastrointestinal Surgery, UMAE Hospital de Especialidades – Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Mexico City, Mexico.

José D. Méndez,
Unidad de Investigación Médica en Enfermedades Metabólicas, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Mexico City, Mexico.

Marco A. Juárez-Oropeza,
Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Rubén Román-Ramos,
División Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico.

Eduardo Ferat-Osorio,
Department of General and Gastrointestinal Surgery, UMAE Hospital de Especialidades – Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Mexico City, Mexico and Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades – Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Av. Cuauhtémoc 330, 3er Piso, Colonia Doctores, Delegación Cuauhtémoc, 06720 Mexico City, Mexico.

Please see the link here: https://stm.bookpi.org/ANUMS-V7/article/view/13420

Role of Green Tea in Brain Aging | Chapter 7 | Current Topics on Chemistry and Biochemistry Vol. 2

 Green tea use has been shown in epidemiological research to be helpful in lowering the risk of dementia. However, it's unclear which green tea components and how they work to minimise that risk. The most significant risk factor for dementia is the ageing of the brain. As a result, we focused our research on the impact of green tea in preventing brain ageing. Green tea's most important component is epigallocatechin gallate (EGCG). Although both EGCG and epigallocatechin (EGC) have been found to cross the blood–brain barrier and reach the brain parenchyma, EGCG has been shown to promote neuronal differentiation more effectively than EGC. It's also been suggested that the gut microbiota's products of EGCG decomposition aid nerve cell growth. indicating that both EGCG and its breakdown products, although with a temporal lag, operate on nerve cells Green tea, on the other hand, contains the free amino acids theanine and arginine, which have stress-relieving properties. While long-term stress increases brain ageing, the anti-stress effects of theanine and arginine slow this down. Because EGCG and caffeine counteract this effect, the ratio of these green tea components is critical for anti-stress effects. Green tea's suppression of brain ageing through stimulation of neurons by EGCG and its breakdown products, as well as the decrease of stress by theanine and arginine, are considered to be involved in lowering the incidence of dementia, according to these studies.

Author(s) Details:

Keiko Unno,
Tea Science Center, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

Yoriyuki Nakamura,
Tea Science Center, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

Please see the link here: https://stm.bookpi.org/CTCB-V2/article/view/7134