Characterization of low active ghrelin ratio in patients with advanced pancreatic cancer

Miura, Tomofumi; Mitsunaga, Shuichi; Ikeda, Masafumi; Ohno, Izumi; Takahashi, Hideaki; Suzuki, Hidetaka; Irisawa, Ai; Kuwata, Takeshi; Ochiai, Atsushi

doi:10.1007/s00520-018-4248-4

Cited by 5 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We are also conducting a translational study to investigate new biomarkers for the diagnosis of cachexia. There is increasing evidence of a close link between cancer cachexia and plasma free amino acid (PFAA) or ghrelin levels [20, 21]. Cancer cachexia is characterized by skeletal muscle loss and anorexia [22].…”

Section: Introductionmentioning

confidence: 99%

A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background Most advanced elderly cancer patients experience fatigue, anorexia, and declining physical function due to cancer cachexia, for which effective interventions have not been established. We performed a phase I study of a new nonpharmacological multimodal intervention called the nutritional and exercise treatment for advanced cancer (NEXTAC) program and reported the excellent feasibility of and compliance with this program in elderly patients with advanced cancer who were at risk for cancer cachexia. We report here the background, hypothesis, and design of the next-step multicenter, randomized phase II study to evaluate the efficacy of the program, the NEXTAC-TWO study. Methods Patients with chemo-naïve advanced non-small cell lung cancer or pancreatic cancer, age ≥ 70 years, performance status ≤2, with adequate organ function and without disability according to the modified Katz index will be eligible. In total, 130 participants will be recruited from 15 Japanese institutions and will be randomized into either the intervention group or a control group. Computer-generated random numbers are allocated to each participant. Stratification factors include performance status (0 to 1 vs. 2), site of primary cancer (lung vs. pancreas), stage (III vs. IV), and type of chemotherapy (cytotoxic vs. others). Interventions and assessment will be performed 4 times every 4 ± 2 weeks from the date of randomization. Interventions will consist of nutritional counseling, nutritional supplements (rich in branched-chain amino acids), and a home-based exercise program. The exercise program will include low-intensity daily muscle training and lifestyle education to promote physical activity. The primary endpoint is disability-free survival. It is defined as the period from the date of randomization to the date of developing disability or death due to any cause. This trial also plans to evaluate the improvements in nutritional status, physical condition, quality of life, activities of daily living, overall survival, and safety as secondary endpoints. Enrollment began in August 2017. The study results will demonstrate the efficacy of multimodal interventions for elderly cancer patients and their application for the maintenance of physical and nutritional conditions in patients with cancer cachexia. This work is supported by a grant-in-aid from the Japan Agency for Medical Research and Development. Discussion This is the first randomized trial to evaluate the efficacy and safety of a multimodal intervention specific for elderly patients with advanced cancer. Trial registration Registered at August 23, 2017. Registry number: UMIN000028801 . Electronic supplementary material The online version of this article (10.1186/s12885-019-5762-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Body weight, Karnofsky performance status (KPS), Eastern Cooperative Oncology Group performance status (ECOG-PS), laboratory tests, severity of symptoms (the Japanese version of the MD Anderson Symptom Inventory; MDASI-J) [ 28 ] and a blood sample were collected before anti-cancer treatment. MDASI-J is a 13-item symptom scale (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, memory, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness or tingling) rated numerically from 0 (“not present”) to 10 (“as bad as you can imagine”) based on symptoms present over the preceding 24 h. Severe appetite loss was defined as MDASI-J ≥ 2, as per our previous study [ 29 ]. The cut-off for serum levels of C-reactive protein (CRP) was determined as 2.0 mg/dL in accordance with our previous study [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

Suzuki

Mitsunaga

Ikeda

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.

show abstract

“…The summary long-term clinical role of systemic ghrelin should be a trade-off between these two contrary effects. Ratio of systemic acetylated/total ghrelin showed no significant association with survival of advanced pancreas cancer patients (110).…”

Section: Other Cancersmentioning

confidence: 99%

Attribution of Ghrelin to Cancer; Attempts to Unravel an Apparent Controversy

et al. 2019

View full text Add to dashboard Cite

Ghrelin is an endogenous peptide hormone mainly produced in the stomach. It has been known to regulate energy homeostasis, stimulate secretion of growth hormone, and mediate many other physiologic effects. Various effects attributed to ghrelin contribute to many aspects of cancer development and progression. Accordingly, a large body of evidence has emerged about the association of ghrelin with several types of cancer in scales of cell-line, animal, and human studies. However, existing data are controversial. This controversy occurs in two main domains: one is the controversial results in local effects of ghrelin on different types of human cancer cell-lines; the second is the apparent disagreement in the results of in-vitro and clinical studies that investigated ghrelin association to one type of cancer. These inconsistencies have hampered the indications to consider ghrelin as a potential tumor biomarker or therapeutic agent in cancer patients. Previous studies have reviewed different parts of current literature about the ghrelin-cancer relationship. Although they have highlighted these controversial results in various ways, no specific recommendations have been given to address it. In this study, we comprehensively reviewed in-vitro, in-vivo, and clinical studies and attempted to use the following approaches to unravel the inconsistencies detected: (a) to distinguish local and systemic effects of ghrelin in interpreting its summary clinical role in each cancer; (b) scrutinizing factors that regulate local effects of ghrelin and could justify different effects of ghrelin on different cancer cell-lines. These approaches could have notable implications for future in-vitro and clinical studies.

show abstract

Characterization of low active ghrelin ratio in patients with advanced pancreatic cancer

Abstract: Low active ghrelin ratio was related to lack of appetite and low cholinesterase and tended to be related to anorexia grade 2 or higher in patients with treatment-naïve advanced pancreatic cancer.

Cited by 5 publications

References 34 publications

A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol

A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol

Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

Attribution of Ghrelin to Cancer; Attempts to Unravel an Apparent Controversy

Contact Info

Product

Resources

About