scholarly journals Preclinical Models for Studying the Impact of Macrophages on Cancer Cachexia

2020 ◽  
Vol 91 (1) ◽  
Author(s):  
Spas Dimitrov Markov ◽  
Daisy Gonzalez ◽  
Kamiya Mehla
Keyword(s):  
Cancer Cachexia ◽  
Preclinical Models ◽  
The Impact

scholarly journals Polypharmacy and Malnutrition Management of Elderly Perioperative Patients with Cancer: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1961
Author(s):  
Eiji Kose ◽  
Hidetaka Wakabayashi ◽  
Nobuhiro Yasuno
Keyword(s):  
Side Effects ◽  
Cancer Cachexia ◽  
Drug Effects ◽  
Drug Efficacy ◽  
Nutritional Management ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Drug Induced ◽  
Anabolic Resistance ◽  
Patients With Cancer ◽  
The Impact

Malnutrition, which commonly occurs in perioperative patients with cancer, leads to decreased muscle mass, hypoalbuminemia, and edema, thereby increasing the patient’s risk of various complications. Thus, the nutritional management of perioperative patients with cancer should be focused on to ensure that surgical treatment is safe and effective, postoperative complications are prevented, and mortality is reduced. Pathophysiological and drug-induced factors in elderly patients with cancer are associated with the risk of developing malnutrition. Pathophysiological factors include the effects of tumors, cachexia, and anorexia of aging. Metabolic changes, such as inflammation, excess catabolism, and anabolic resistance in patients with tumor-induced cancer alter the body’s ability to use essential nutrients. Drug-induced factors include the side effects of anticancer drugs and polypharmacy. Drug–drug, drug–disease, drug–nutrient, and drug–food interactions can significantly affect the patient’s nutritional status. Furthermore, malnutrition may affect pharmacokinetics and pharmacodynamics, potentiate drug effects, and cause side effects. This review outlines polypharmacy and malnutrition, the impact of malnutrition on drug efficacy, drug–nutrient and drug–food interactions, and intervention effects on polypharmacy or cancer cachexia in elderly perioperative patients with cancer.

Impact of Cancer Cachexia on Treatment With PD-1/PD-L1 Inhibitors Plus Chemotherapy in Advanced Non-small-Cell Lung Cancer

2021 ◽  
Author(s):  
Taichi Miyawaki ◽  
Tateaki Naito ◽  
Michitoshi Yabe ◽  
Hiroaki Kodama ◽  
Naoya Nishioka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cancer Cachexia ◽  
Advanced Nsclc ◽  
Group Performance ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
The Impact

Abstract PurposeProgrammed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors plus chemotherapy has become the standard first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). However, few studies have explicitly focused on the impact of cancer cachexia on the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy. Thus, we evaluated the clinical implications of cancer cachexia on the survival outcomes in patients who received this treatment.MethodsWe conducted a retrospective review of medical records of patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors plus chemotherapy from December 2018 to December 2020. Cancer cachexia was diagnosed as an unintentional weight loss of 5% or more over six months. We evaluated the progression-free survival (PFS) and overall survival (OS) for patients with or without cancer cachexia who received PD-1/PD-L1 inhibitors plus chemotherapy.ResultsAmong the 80 included patients, 37 (46%) had cancer cachexia. Cachectic patients had a lower objective response rate (30 vs 51%, P <0.05), poorer PFS (2.3 vs 12.0 months, P <0.05), and poorer OS (10.8 vs 23.9 months, P <0.05) than non-cachectic patients. The Cox proportional-hazard ratios (95% confidence interval) of cancer cachexia were 1.77 (1.01–3.10) for PFS and 2.90 (1.40–6.00) for OS, with adjustments for Eastern Cooperative Oncology Group performance status, PD-L1 tumour proportion score, histology, and central nervous system metastases. ConclusionPre-treatment cancer cachexia may reduce treatment efficacy and shorten survival time in patients receiving PD-1/PD-L1 inhibitors plus chemotherapy. Early evaluation and intervention for cancer cachexia might improve oncological outcomes in patients with advanced NSCLC.

Cancer Cachexia: Beyond Weight Loss

2016 ◽  
Vol 12 (11) ◽  
pp. 1163-1171 ◽  
Author(s):  
Andrew R. Bruggeman ◽  
Arif H. Kamal ◽  
Thomas W. LeBlanc ◽  
Joseph D. Ma ◽  
Vickie E. Baracos ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Composition ◽  
Clinical Practice ◽  
Physical Functioning ◽  
Early Identification ◽  
Cancer Cachexia ◽  
Psychosocial Support ◽  
Investigational Agents ◽  
Pharmacologic Agents ◽  
The Impact

Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in clinical practice, prevention, early identification, and intervention remain challenging. The impact of cancer cachexia on quality of life, treatment-related toxicity, physical function, and mortality are well established; however, establishing a clinically meaningful definition has proven challenging because of the focus on weight loss alone. Attempts to more comprehensively define cachexia through body composition, physical functioning, and molecular biomarkers, while promising, are yet to be routinely incorporated into clinical practice. Pharmacologic agents that have not been approved by the US Food and Drug Administration but that are currently used in cancer cachexia (ie, megestrol, dronabinol) may improve weight but not outcomes of interest such as muscle mass, physical activity, or mortality. Their routine use is limited by adverse effects. For the practicing oncologist, early identification and management of cachexia is critical. Oncologists must recognize cachexia beyond weight loss alone, focusing instead on body composition and physical functioning. In fact, becoming emaciated is a late sign of cachexia that characterizes its refractory stage. Given that cachexia is a multifactorial syndrome, it requires early identification and polymodal intervention, including optimal cancer therapy, symptom management, nutrition, exercise, and psychosocial support. Consequently, oncologists have a role in ensuring that these resources are available to their patients. In addition, in light of the promising investigational agents, it remains imperative to refer patients with cachexia to clinical trials so that available options can be expanded to effectively treat this pervasive problem.

Impact of pretreatment serum creatinine on outcomes in pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15749-e15749
Author(s):  
Taha Alrifai ◽  
Faisal Ali ◽  
Zimu Gong ◽  
Phyo Thazin Myint ◽  
Karan Nijhawan ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Pancreatic Adenocarcinoma ◽  
Cancer Cachexia ◽  
Statistical Significance ◽  
Surrogate Marker ◽  
Cost Effective ◽  
Prognostic Indicator ◽  
Kaplan Meier ◽  
The Impact ◽  
Pretreatment Serum

e15749 Background: Pancreatic Adenocarcinoma (PA) is an aggressive malignancy with an estimated 5-year survival of 8.5%. PA was responsible for 7.3% of all cancer deaths in 2018 in the US. We aimed to evaluate the impact of pretreatment serum creatinine (SCr) level on Overall Survival (OS) in patients with PA. Methods: A retrospective review of electronic health records of patients with PA seen at our institution between 01/2014 and 01/2018 was done. We collected patients’ SCr at the time of diagnosis, and excluded patients with a glomerular filtration rate (GFR) below 60 mL/min per 1.73 m2 or SCr > 1.3 mg/dL. Patients were dichotomized around a SCr of 0.5 mg/dL. Kaplan-Meier survival estimate was performed to evaluate statistical significance. Results: A total of 83 patients, including 37 females and 46 males, with a median age at diagnosis of 67 years, were included. SCr of < 0.5 mg/dL was associated with a lower median OS as compared to a SCr of ≥0.5 mg/dL, (253 days versus 364 days; P = 0.035). There were more female patients in the low SCr group (71% vs 39%, P = 0.027). Patients with SCr of < 0.5 mg/dL had a lower mean BMI compared to patients with a SCr of ≥0.5 mg/dL, however this was not statistically significant (BMI = 22.45 versus 25.72; P = 0.49). Conclusions: Low SCr is predictive of a lower median OS in patients with PA. SCr has been suggested as a surrogate marker for muscle mass, which is closely associated with the degree of cancer cachexia. Our finding emphasizes the need for future larger studies to evaluate the utility of SCr as a prognostic indicator, as well as a cost-effective surrogate for measuring cancer cachexia. [Table: see text]

ONC201 in previously irradiated pediatric H3 K27M-mutant glioma or newly diagnosed DIPG.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3619-3619
Author(s):  
Sharon L. Gardner ◽  
Carl Johannes Koschmann ◽  
Rohinton Tarapore ◽  
Jeffrey C. Allen ◽  
Wafik Tharwat Zaky ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Single Agent ◽  
High Grade Glioma ◽  
Biologically Active ◽  
High Grade ◽  
Newly Diagnosed ◽  
Preclinical Models ◽  
Open Label ◽  
The Impact

3619 Background: ONC201 is a first-in-class DRD2 antagonist and ClpP agonist that has demonstrated promising activity in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 in recurrent H3 K27M-mutant glioma patients . The recommended phase 2 dose (RP2D) of 625mg ONC201 orally once a week has been established in adult patients as well tolerated and biologically active. ONC201 efficacy has been shown in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 have been reported in adult recurrent H3 K27M-mutant glioma patients. We report results from the first Phase I pediatric clinical trial of ONC201. Methods: This open-label, multi-center trial for pediatric H3 K27M-mutant glioma or non-biopsied DIPG employed a 3+3 dose-escalation and dose-expansion design with 6 arms. Arms A and E, which have completed accrual, determined the RP2D of ONC201 using oral capsule and liquid formulations in post-radiation pediatric H3 K27M-mutant glioma patients ONC201, respectively. Arm B aims to determine the RP2D for ONC201 in combination with radiotherapy in patients with newly diagnosed DIPG. Arms C and D aim to measure intratumoral ONC201 concentrations in midline glioma patients and the impact of ONC201 on H3 K27M DNA levels in CSF, respectively. Arm F was recently opened to study ONC201 as a single agent in patients with progressive H3 K27M-mutant tumors (excluding DIPG and spinal cord tumors) following radiotherapy. After determining the RP2D, a dose-expansion cohort will evaluate the safety, radiographic response, and activity of ONC201. Results: An RP2D of weekly 625mg ONC201 scaled by body weight as a capsule or in liquid formulation was established in the primary endpoints of arms A, B and E alone or in combination with radiation, without incidence of dose-limiting toxicity (DLT). Pharmacokinetic profiles were similar to those observed in adults (T1/2: 8.4h; Tmax: 2.1h; Cmax: 2.3ug/mL; AUC0-tlast: 16.4ug/mL), with similar exposure across body weights. Conclusions: ONC201 was well tolerated without DLTs at the same adult RP2D scaled by body weight as monotherapy or in combination with radiotherapy in pediatric H3 K27M-mutant glioma patients. Further investigation of ONC201 to treat H3 K27M-mutant glioma and DIPG is warranted. Clinical trial information: NCT03416530 .

Differential impact of obesity on the pathogenesis of RA or preclinical models is contingent on the disease status

2016 ◽  
Vol 76 (4) ◽  
pp. 731-739 ◽  
Author(s):  
Seung-jae Kim ◽  
Zhenlong Chen ◽  
Abdul B Essani ◽  
Hatem A Elshabrawy ◽  
Michael V Volin ◽  
...  
Keyword(s):  
Disease Onset ◽  
Disease Status ◽  
Joint Inflammation ◽  
Preclinical Models ◽  
M1 Macrophages ◽  
Adipose Tissues ◽  
Monocyte Migration ◽  
M1 Macrophage ◽  
Established Disease ◽  
The Impact

ObjectiveStudies were performed to uncover the significance of obesity in rheumatoid arthritis (RA) and preclinical models.MethodsPreclinical arthritis models were used to examine the impact of obesity on disease onset and remission. Conditioned media from RA adipose tissues were used to investigate the mechanism contributing to joint neutrophil influx and M1 macrophage differentiation observed in early and remission phases of arthritis.ResultsWe report that mice fed with high fat diet (HFD) have an earlier onset of collagen-induced arthritis (CIA) compared with mice on regular diet. However, the differences in CIA joint swelling between the two diet groups are lost once disease is established. We found that early arthritis triggered by obesity is due to elevated joint MIP2/interleukin-8 levels detected in CIA as well as in the RA and mouse adipose tissues and the effect of this chemokine on neutrophil recruitment. Although active disease progression is similarly affected in both diet groups, arthritis resolution is accelerated in lean mice while joint inflammation is sustained in obese mice. We document that HFD can prolong toll-like receptor (TLR)4-induced arthritis by increasing joint monocyte migration and further remodelling the recruited cells into M1 macrophages. Consistently, we show that adipose condition media can transform RA and wild-type naïve myeloid cells into M1 macrophages; however, this function is impaired by TLR4 blockade or deficiency.ConclusionsWe conclude that despite established disease being unaffected by obesity, the early and the resolution phases of RA are impacted by obesity through different mechanisms.

scholarly journals Cancer Vaccines, Adjuvants, and Delivery Systems

2021 ◽  
Vol 12 ◽  
Author(s):  
Samantha J. Paston ◽  
Victoria A. Brentville ◽  
Peter Symonds ◽  
Lindy G. Durrant
Keyword(s):  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
18Th Century ◽  
Checkpoint Inhibitors ◽  
Early Cancer ◽  
Delivery Systems ◽  
Preclinical Models ◽  
Current Vaccine ◽  
Therapeutic Cancer Vaccines ◽  
The Impact

Vaccination was first pioneered in the 18th century by Edward Jenner and eventually led to the development of the smallpox vaccine and subsequently the eradication of smallpox. The impact of vaccination to prevent infectious diseases has been outstanding with many infections being prevented and a significant decrease in mortality worldwide. Cancer vaccines aim to clear active disease instead of aiming to prevent disease, the only exception being the recently approved vaccine that prevents cancers caused by the Human Papillomavirus. The development of therapeutic cancer vaccines has been disappointing with many early cancer vaccines that showed promise in preclinical models often failing to translate into efficacy in the clinic. In this review we provide an overview of the current vaccine platforms, adjuvants and delivery systems that are currently being investigated or have been approved. With the advent of immune checkpoint inhibitors, we also review the potential of these to be used with cancer vaccines to improve efficacy and help to overcome the immune suppressive tumor microenvironment.

scholarly journals The Impact of IgA and the Microbiota on CNS Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Annie Pu ◽  
Dennis S. W. Lee ◽  
Baweleta Isho ◽  
Ikbel Naouar ◽  
Jennifer L. Gommerman
Keyword(s):  
Immune Cells ◽  
Preclinical Models ◽  
Potential Therapeutic Target ◽  
Cns Disease ◽  
Mechanistic Insight ◽  
Circulating Lymphocytes ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
The Impact ◽  
Insight Into

Although anatomically distant from the central nervous system (CNS), gut-derived signals can dynamically regulate both peripheral immune cells and CNS-resident glial cells to modulate disease. Recent discoveries of specific microbial taxa and microbial derived metabolites that modulate neuroinflammation and neurodegeneration have provided mechanistic insight into how the gut may modulate the CNS. Furthermore, the participation of the gut in regulation of peripheral and CNS immune activity introduces a potential therapeutic target. This review addresses emerging literature on how the microbiome can affect glia and circulating lymphocytes in preclinical models of human CNS disease. Critically, this review also discusses how the host may in turn influence the microbiome, and how this may impact CNS homeostasis and disease, potentially through the production of IgA.

Designing Relevant Preclinical Rodent Models for Studying Links Between Nutrition, Obesity, Metabolism, and Cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Elaine M. Glenny ◽  
Michael F. Coleman ◽  
Erin D. Giles ◽  
Elizabeth A. Wellberg ◽  
Stephen D. Hursting
Keyword(s):  
Treatment Options ◽  
Annual Review ◽  
Publication Date ◽  
Rodent Models ◽  
Cancer Model ◽  
Preclinical Models ◽  
Cancer Models ◽  
The Impact ◽  
The Relationship ◽  
Insight Into

Diet and nutrition are intricately related to cancer prevention, growth, and treatment response. Preclinical rodent models are a cornerstone to biomedical research and remain instrumental in our understanding of the relationship between cancer and diet and in the development of effective therapeutics. However, the success rate of translating promising findings from the bench to the bedside is suboptimal. Well-designed rodent models will be crucial to improving the impact basic science has on clinical treatment options. This review discusses essential experimental factors to consider when designing a preclinical cancer model with an emphasis on incorporating these models into studies interrogating diet, nutrition, and metabolism. The aims of this review are to ( a) provide insight into relevant considerations when designing cancer models for obesity, nutrition, and metabolism research; ( b) identify common pitfalls when selecting a rodent model; and ( c) discuss strengths and limitations of available preclinical models. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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