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* Context.--Although several neuroendocrine cell types constitute gastroenteropancreatic neuroendocrine tumors (NETs), the clinical and prognostic implications of the expression of multiple peptide hormones have not been comprehensively evaluated in rectal NETs. Objective.--To identify the clinicopathologic characteristics and prognostic impact of peptide hormone expression. Design.--We evaluated the expression of peptide YY (PYY), glucagon, somatostatin, serotonin, insulin, and gastrin using immunolabeling in 446 endoscopically or surgically resected rectal NETs. Results.--PYY, glucagon, serotonin, somatostatin, insulin, and gastrin were expressed in 261 of 389 (67.1%), 205 of 446 (46.0%), 36 of 446 (8.1%), 33 of 446 (7.4%), 2 of 446 (0.4%), and 1 of 446 cases (0.2%), respectively. Immunoreactivity to any peptide hormone was present in 345 of 446 cases (77.4%). Tumors expressing serotonin or somatostatin were associated with lymphovascular invasion, chromogranin A expression, and shorter disease-free survival (DFS). Rectal NETs were classified as L-cell, enterochromaffin-cell, D-cell, null-expression, or mixed-expression type based on peptide hormonal expression status. Patients with D-cell Net had the shortest DfS (10-year DFS, 54.5%), followed by those with enterochromaffin-cell NET (89.5%), null expression (97.0%), L-cell NET (99.6%), and mixed-expression NET (100%; P < .001). Multivariable analyses revealed that somatostatin expression was an independent indicator of poor prognosis with respect to DFS in rectal NETs (P = .001). Conclusions.--Somatostatin expression is a poor prognostic indicator in patients with rectal NETs. Therefore, additional peptide hormonal immunolabeling, including somatostatin, serotonin, and PYY, in rectal NETs can provide more information regarding DFS. (Arch Pathol Lab Med. 2023;147:797-807; doi: 10.5858/ arpa.2022-0032-OA), The incidence of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) has increased substantially during the past few decades. They are currently the second most common digestive system tumor, after colorectal cancer. (1,2) [...]

Silencing of aberrantly expressed microRNAs (miRNAs or miRs) has emerged as one of the strategies for molecular targeted cancer therapeutics. In particular, miR-21 is an oncogenic miRNA overexpressed in many tumors, including ovarian cancer. To achieve efficient administration of anti-miR therapeutics, delivery systems are needed that can ensure local accumulation in the tumor environment, low systemic toxicity, and reduced adverse side effects. In order to develop an improved anti-miR therapeutic agent for the treatment of ovarian cancer, a nanoformulation is engineered that leverages biodegradable porous silicon nanoparticles (pSiNPs) encapsulating an anti-miR-21 locked nucleic acid payload and displaying a tumor-homing peptide for targeted distribution. Targeting efficacy, miR-21 silencing, and anticancer activity are optimized in vitro on a panel of ovarian cancer cell lines, and a formulation of anti-miR-21 in a pSiNP displaying the targeting peptide CGKRK is identified for in vivo evaluation. When this nanoparticulate agent is delivered to mice bearing tumor xenografts, a substantial inhibition of tumor growth is achieved through silencing of miR-21. This study presents the first successful application of tumor-targeted anti-miR porous silicon nanoparticles for the treatment of ovarian cancer in a mouse xenograft model.

This study investigated the effects of Lycium chinense Mill (LCM) extract on obesity and diabetes, using both in vitro and high-fat diet (HFD)-induced obesity mouse models. We found that LCM notably enhanced glucagon-like peptide-1 (GLP-1) secretion in NCI-h716 cells from 411.4 ± 10.75 pg/mL to 411.4 ± 10.75 pg/mL compared to NT (78.0 ± 0.67 pg/mL) without causing cytotoxicity, implying the involvement of Protein Kinase A C (PKA C) and AMP-activated protein kinase (AMPK) in its action mechanism. LCM also decreased lipid droplets and lowered the expression of adipogenic and lipogenic indicators, such as Fatty Acid Synthase (FAS), Fatty Acid-Binding Protein 4 (FABP4), and Sterol Regulatory Element-Binding Protein 1c (SREBP1c), indicating the suppression of adipocyte differentiation and lipid accumulation. LCM administration to HFD mice resulted in significant weight loss (41.5 ± 3.3 g) compared to the HFD group (45.1 ± 1.8 g). In addition, improved glucose tolerance and serum lipid profiles demonstrated the ability to counteract obesity-related metabolic issues. Additionally, LCM exhibited hepatoprotective properties by reducing hepatic lipid accumulation and diminishing white adipose tissue mass and adipocyte size, thereby demonstrating its effectiveness against hepatic steatosis and adipocyte hypertrophy. These findings show that LCM can be efficiently used as a natural material to treat obesity and diabetes, providing a new approach for remedial and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua Cham. et Schltdl tubers. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrate that ACN inhibited c-Myc expression through CNOT2 and MID1IP1, and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer. [ABSTRACT FROM AUTHOR]

Bitter taste receptors (TAS2Rs) are G protein-coupled receptors localized in the taste buds of the tongue. They may also be present in non-lingual organs, including the brain, lung, kidney, and gastrointestinal (GI) tract. Recent studies on bitter taste receptor functions have suggested TAS2Rs as potential therapeutic targets. The human bitter taste receptor subtype hTAS2R50 responds to its agonist isosinensetin (ISS). Here, we demonstrated that, unlike other TAS2R agonists, isosinensetin activated hTAS2R50 as well as increased Glucagon-like peptide 1 (GLP-1) secretion through the Gβγ-mediated pathway in NCI-H716 cells. To confirm this mechanism, we showed that ISS increased intracellular Ca2+ and was suppressed by the IP3R inhibitor 2-APB as well as the PLC inhibitor U73122, suggesting that TAS2Rs alters the physiological state of enteroendocrine L cells in a PLC-dependent manner. Furthermore, we demonstrated that ISS upregulated proglucagon mRNA and stimulated GLP-1 secretion. ISS-mediated GLP-1 secretion was suppressed in response to small interfering RNA-mediated silencing of Gα-gust and hTAS2R50 as well as 2-APB and U73122. Our findings improved the understanding of how ISS modulates GLP-1 secretion and indicates the possibility of using ISS as a therapeutic agent in the treatment of diabetes mellitus. [ABSTRACT FROM AUTHOR]