Publications by authors named "Rubinek T"

Article Synopsis
  • Patients with metastatic breast cancer often develop resistance to endocrine therapies, and in some cases, this is linked to mutations in the estrogen receptor-α (ESR1) that can lead to worse outcomes.
  • Research using MCF-7 cells with common ESR1 mutations showed that these cells are more resistant to chemotherapy drugs, as evidenced by higher survival rates and lower levels of cell death compared to cells with wild-type ESR1.
  • The study identified that the JNK/c-Jun/MDR1 pathway is involved in this chemoresistance, indicating that targeting this pathway may provide new treatment strategies for breast cancer patients with ESR1 mutations.
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Breast cancer (BC) is associated with type 2 diabetes mellitus (T2DM) and obesity. Glucagon-like peptide (GLP)-1 regulates post-prandial insulin secretion, satiety, and gastric emptying. Several GLP-1 analogs have been FDA-approved for the treatment of T2DM and obesity.

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Klotho, a 1012 amino acid transmembrane protein, is a potent tumor suppressor in different cancer types. Klotho is composed of two internal repeats KL1 and KL2, and the tumor suppressor activity is primarily attributed to the KL1 domain. Despite its significant role in regulating various cancer-related pathways, the precise mechanism underlying its tumor suppressor activity remains unresolved.

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Background And Objectives: Antileucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis was first described in 2010 and is today the most common type of limbic encephalitis. During the course of the disease, 60%-88% of the patients develop hyponatremia. The etiology of the sodium disorder is unclear, often presumed to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

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Unlabelled: Multiple studies have identified metabolic changes within the tumor and its microenvironment during carcinogenesis. Yet, the mechanisms by which tumors affect the host metabolism are unclear. We find that systemic inflammation induced by cancer leads to liver infiltration of myeloid cells at early extrahepatic carcinogenesis.

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Background: The use of medical cannabis has rapidly increased among cancer patients worldwide. Cannabis is often administered concomitantly with cancer medications, including immune checkpoint inhibitors (ICIs). As the cannabinoid receptors are abundantly expressed and modulate immune cells, it has been hypothesised that cannabis may attenuate the activity of ICIs.

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Background: An effect of non-oncology medications on cancer outcome has been proposed. In this study, we aimed to systematically examine the impact of commonly prescribed non-oncology drugs on clinical risk and on the genomic risk [based on the Oncotype DX recurrence score (RS)] in early breast cancer (BC).

Experimental Design: We collected data on clinical risk (stage and grade), genomic risk (Oncotype DX RS), and on non-oncology medications administered to 1423 patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative BC during the month of their surgery.

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Klotho is a well-established longevity hormone. Its most prominent function is the regulation of phosphate homeostasis. However, klotho possesses multiple pleiotropic activities, including inhibition of major signaling pathways, reducing oxidative stress and suppressing inflammation.

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Background: While side-effects and health-related quality of life (QoL) are routinely assessed in clinical trials, commonly used tools do not measure patients' ability to maintain normal daily activities. QoL can be severely affected directly by the disease, the treatment side-effects and by personal and societal misconceptions promoting avoidance from activities perceived as dangerous for cancer patients. We examined practices of actively treated patients with cancer.

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Metastases are often the direct cause of death from pancreatic ductal adenocarcinoma (PDAC). The role of genomic alterations (GA) in mediating tropism and metastasis formation by PDAC cells is currently unknown. We aimed to identify GAs predisposing colonization of PDAC cells to the liver and decipher mechanisms enabling this process.

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Klotho is an anti-aging transmembrane protein, which can be shed and can function as a hormone. Accumulating data indicate that klotho is a tumor suppressor in a wide array of malignancies, and designate the subdomain KL1 as the active region of the protein towards this activity. We aimed to study the role of klotho as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC).

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Background: Estrogen receptor α (ESR1) plays a critical role in promoting growth of various cancers. Yet, its role in the development of pancreatic cancer is not well-defined. A less studied region of ESR1 is the hinge region, connecting the ligand binding and DNA domains.

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Klotho is a transmembrane protein, which can be shed and act as a circulating hormone and is involved in regulating cellular calcium levels and inhibition of the PI3K/AKT pathway. As a longevity hormone, it protects normal cells from oxidative stress, and as a tumor suppressor it inhibits growth of cancer cells. Mechanisms governing these differential activities have not been addressed.

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Background: Klotho is a transmembrane protein that can be shed and can act as a circulating hormone in three forms: soluble klotho (KL1 + KL2), KL1, and KL2. Klotho was discovered as a gene implicated in aging through inhibition of the IGF-I pathway. Our laboratory discovered the role of klotho as a tumor suppressor in breast cancer and other malignancies.

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Background: Klotho, a single-pass transmembrane protein associated with premature aging, acts as a tumor suppressor gene by inhibiting insulin/insulin-like growth factor-1 and fibroblast growth factor pathways. Downregulated Klotho expression is reported in melanoma, mesothelioma, bladder, breast, gastric, cervix, lung, and kidney cancers and is associated with a poor prognosis. Klotho expression and Klotho promoter hypermethylation are predictive factors for patient prognosis.

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Purpose: Mutations in the ligand-binding domain (LBD) of estrogen receptor α (ER) confer constitutive transcriptional activity and resistance to endocrine therapies in patients with breast cancer. Accumulating clinical data suggest adverse outcome for patients harboring tumors expressing these mutations. We aimed to elucidate mechanisms conferring this aggressive phenotype.

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Klotho is an anti-aging transmembrane protein, which can be shed and function as a hormone. Accumulating data indicate klotho as a tumor suppressor in a wide array of malignancies and indicate the subdomain KL1 as the active region of the protein. We aimed to study the role of klotho as a tumor suppressor in colorectal cancer.

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Pancreatic cancer poorly responds to available drugs, and finding novel approaches to target this cancer type is of high significance. Here, based on a common property of pancreatic cancer cells to express somatostatin receptors (SSTR), we designed drug conjugates with novel somatostatin-derived cyclic peptides (SSTp) with broad selectivity towards SSTR types to facilitate drug targeting of the pancreatic cancer cells specifically. Uptake of our newly designed SSTps was facilitated by SSTRs expressed in the pancreatic cancers, including SSTR2, SSTR3, SSTR4 and SSTR5.

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Klotho was first discovered as an aging-suppressor gene. Mice that do not express klotho die prematurely with multiple symptoms of aging, several of which are also characteristic of decreased GH/IGF-1 axis activity. Klotho is highly expressed in the brain, the kidney, and parathyroid and pituitary glands, but can also serve as a circulating hormone by its shedding, forming soluble klotho (sKlotho) that can be detected in blood, cerebrospinal fluid and urine.

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Context: Klotho is an aging-modulating protein expressed mainly in the kidneys, which can be cleaved and shed to act as a circulating hormone. Several lines of evidence suggest a tight interaction between klotho and the GH-IGF-I axis. We showed previously that klotho levels are decreased in pediatric patients with growth hormone deficiency (GHD).

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The klotho gene is implicated in many physiological activities, among them aging, glucose metabolism, and phosphate and calcium metabolism. Many cellular activities of klotho were implicated in promoting these activities. Two of them, inhibition of the insulin-like growth factor-1 pathway and of the Wnt signaling pathway, are also major pathways associated with cancer development and progression.

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The growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is pivotal for many metabolic functions, including proper development and growth of bones, skeletal muscles, and adipose tissue. Defects in the axis' activity during childhood result in growth abnormalities, while increased secretion of GH from the pituitary results in acromegaly. In order to keep narrow physiologic concentration, GH and IGF-1 secretion and activity are tightly regulated by hypothalamic, pituitary, endocrine, paracrine, and autocrine factors.

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Background & Aims: Klotho is a trans-membrane protein which can be shed to act as a hormone; its blood levels may be regulated by the GH/IGF-1 axis. Klotho deficient mice exhibit short lifespan and characteristics of aging and malnutrition, including decreased fat and muscle mass, osteopenia, and impaired fertility. As anorexia nervosa (AN) is characterized by malnutrition and GH resistance, we hypothesized klotho levels would be altered in AN, and aimed to assess klotho levels in undernourished AN patients and changes in klotho following weight rehabilitation.

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Aims: Klotho is a trans-membrane protein that serves as a tumour suppressor in a wide array of malignancies. Recent data suggest it as an epigenetically silenced tumour suppressor in cervical cancer. Yet, the expression pattern of klotho in cervical cancer has not been determined.

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Unlabelled: Klotho is a transmembrane protein containing two internal repeats, KL1 and KL2, both displaying significant homology to members of the β-glycosidase family. Klotho is expressed in the kidney, brain, and various endocrine tissues, but can also be cleaved and act as a circulating hormone. Klotho is an essential cofactor for binding of fibroblast growth factor 23 (FGF23) to the FGF receptor and can also inhibit the insulin-like growth factor-1 (IGF-1) pathway.

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