CDK4/6 Inhibition on Glucose and Pancreatic Beta Cell Homeostasis in Young and Aged Rats

Genetic deletion of cyclin-dependent kinase 4 (Cdk4) is associated with pancreatic beta cell loss and glucose dysregulation in rodents. Palbociclib, one of the first selective CDK4/6 inhibitors approved for the treatment of advanced breast cancer, is currently being investigated as an adjuvant treatment in patients with early-stage breast cancer and in a variety of cancers covering a wide-range of patient populations. Hence, longer chronic toxicity studies were necessary to further examine its safety profile. The effects of different doses and duration of palbociclib administration on glucose and beta cell homeostasis in young (two months) versus aged (12 months) rats was compared. Glucose dysregulation, due to pancreatic beta cell degeneration, was observed in young rats administered the highest dose of palbociclib for 6 months. Abnormal pancreatic islet histology and activation of the endoplasmic reticulum stress response in beta cells were detected after shorter administration with high-dose palbociclib in young rats. To test the hypothesis that palbociclib-associated inhibition of beta cell proliferation will more profoundly affect younger animals that have not achieved replicative quiescence, we administered high-dose palbociclib to aged rats for 6 months. In contrast to the young rats, despite equivalent exposures to palbociclib, no evidence of impaired glucose tolerance, hypoinsulinemia, beta cell vacuolization, or beta cell loss was seen in aged rats. Palbociclib admi...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Metabolism Source Type: research

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Conclusion: The data demonstrated that an MRM-based proteomic assay that measures plasma levels of three specific peptides can be a useful tool for breast cancer screening and its accuracy is cancer-type specific. PMID: 31897331 [PubMed]
Source: Journal of Breast Cancer - Category: Cancer & Oncology Tags: J Breast Cancer Source Type: research
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Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
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Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
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Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research
UCLA began observing its 100th birthday this year and delivered new  advances in research, health care, the arts, community service and teaching. These are some of the top stories from UCLA Newsroom in 2019 — those which made news and engaged the community of Bruins and beyond.UCLA Newsroom will resume publishing on Jan. 2, 2020. For more, be sure toperuse the archives and to followUCLA Newsroom on Twitter. UCLA turns 100UCLA ArchiveUCLA from overhead in the 1930s.Founders of UCLA would marvel at their creationIn just 100 years, UCLA has grown into a respected center of learning, research and health ca...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
AbstractObjectivesPaeoniflorin, a representative pinane monoterpene glycoside in plants ofPaeoniaceae family, possesses promising anticancer activities on diverse tumours. This paper summarized the advance of Paeoniflorin on cancersin vivo andin vitro, discussed the related molecular mechanisms, as well as suggested some perspectives of the future investigations.Key findingsAnticancer activities of paeoniflorin have been comprehensively investigated, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, glioma, bladder cancer and leukaemia. Furthermore, the potential mole...
Source: Journal of Pharmacy and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Review Source Type: research
Miller Biswas Acharyya Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type in which the mortality rate approaches the incidence rate. More than 85% of PDAC patients experience a profound loss of muscle mass and function, known as cachexia. PDAC patients with this condition suffer from decreased tolerance to anti-cancer therapies and often succumb to premature death due to respiratory and cardiac muscle wasting. Yet, there are no approved therapies available to alleviate cachexia. We previously found that upregulation of the metal ion transporter, Zip14, and altered zinc homeostasis are critical me...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ek Zdeňka Rottnerová Vojtěch Spiwok Pavel Drašar Tomáš Ruml Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake,...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
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Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research
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Source: Plastic and Reconstructive Surgery Global Open - Category: Cosmetic Surgery Tags: Original Article Source Type: research
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