Mitochondrial unfolded protein response-dependent β-catenin signaling promotes neuroendocrine prostate cancer.

The mitochondrial unfolded protein response (UPR) maintains mitochondrial quality control and proteostasis under stress conditions. However, the role of UPR in aggressive and resistant prostate cancer is not clearly defined. We show that castration-resistant neuroendocrine prostate cancer (CRPC-NE) harbored highly dysfunctional oxidative phosphorylation (OXPHOS) Complexes.

The mitochondrial unfolded protein response (UPR): shielding against toxicity to mitochondria in cancer.

Mitochondria are essential for tumor growth and progression. However, the heavy demand for mitochondrial activity in cancer leads to increased production of mitochondrial reactive oxygen species (mtROS), accumulation of mutations in mitochondrial DNA, and development of mitochondrial dysfunction. If left unchecked, excessive mtROS can damage and unfold proteins in the mitochondria to an extent that becomes lethal to the tumor.

A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60.

Mitochondrial proteostasis, regulated by the mitochondrial unfolded protein response (UPRmt), is crucial for maintenance of cellular functions and survival. Elevated oxidative and proteotoxic stress in mitochondria must be attenuated by the activation of a ubiquitous UPRmt to promote prostate cancer (PCa) growth. Here we show that the 2 key components of the UPRmt, heat shock protein 60 (HSP60, a mitochondrial chaperonin) and caseinolytic protease P (ClpP, a mitochondrial protease), were required for the development of advanced PCa.

Small-Molecule MMRi62 Induces Ferroptosis and Inhibits Metastasis in Pancreatic Cancer via Degradation of Ferritin Heavy Chain and Mutant p53.

High frequency of KRAS and TP53 mutations is a unique genetic feature of pancreatic ductal adenocarcinoma (PDAC). TP53 mutation not only renders PDAC resistance to chemotherapies but also drives PDAC invasiveness. Therapies targeting activating mutant KRAS are not available and the outcomes of current PDAC treatment are extremely poor.

Assessing Oligomerization Status of Mitochondrial OXPHOS Complexes Via Blue Native Page.

Mitochondrial metabolism plays key roles in pathologies such as cancer. The five complexes of the oxidative phosphorylation (OXPHOS) system are crucial for producing ATP and maintaining cellular functions and are particularly exploited in cancer cells. Understanding the oligomeric state of these OXPHOS complexes will help elucidate their function (or dysfunction) in cancer cells and can be used as a mechanistic tool for anticancer agents that target mitochondria.

Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID.

Emerging clinical data from the current COVID-19 pandemic suggests that ~ 40% of COVID-19 patients develop neurological symptoms attributed to viral encephalitis while in COVID long haulers chronic neuro-inflammation and neuronal damage result in a syndrome described as Neuro-COVID. We hypothesize that SAR-COV2 induces mitochondrial dysfunction and activation of the mitochondrial-dependent intrinsic apoptotic pathway, resulting in microglial and neuronal apoptosis. The goal of our study was to determine the effect of SARS-COV2 on mitochondrial biogenesis and to monitor cell apoptosis in human microglia non-invasively in real time using Raman spectroscopy, providing a unique spatio-temporal information on mitochondrial function in live cells.

Targeting the mitochondrial unfolded protein response in cancer: opportunities and challenges.

Increasing evidence indicates that a mitochondria-specific stress response referred to as the 'mitochondrial unfolded protein response' (UPR) is activated to maintain mitochondrial integrity and support tumor growth. In this forum article, we discuss the recent advances and current challenges in therapeutically targeting UPR in cancer.

Prognostic value of labs ordered on patients hospitalized with COVID-19.

: Hospitalists at our institution have taken on most non-intensive care unit (ICU) coronavirus disease 2019 (COVID-19) care. Based on sparse research, our institution developed a protocol for ordering labs for this patient population, including routine admission labs in addition to eight COVID-19-specific daily labs. The study goal is to determine if COVID-19-specific admission labs have any prognostic value beyond that provided by routine admission labs and vitals, and costs of labs with no prognostic value.

Mitochondrial Stress Response and Cancer.

Cancer cells survive and adapt to many types of stress including hypoxia, nutrient deprivation, metabolic, and oxidative stress. These stresses are sensed by diverse cellular signaling processes, leading to either degradation of mitochondria or alleviation of mitochondrial stress. This review discusses signaling during sensing and mitigation of stress involving mitochondrial communication with the endoplasmic reticulum, and how retrograde signaling upregulates the mitochondrial stress response to maintain mitochondrial integrity.

Hsp60 and IL-8 axis promotes apoptosis resistance in cancer.

Background: Interleukin-8 (IL-8) and heat shock protein 60 (Hsp60) play crucial roles in cell survival and maintenance of cellular homoeostasis. However, cross talks between these two proteins are not defined.

Methods: IL-8 expression in tumour tissue sections was analysed by immunohistochemistry.

Nimbolide reduces CD44 positive cell population and induces mitochondrial apoptosis in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive disease and current treatment regimens fail to effectively cure PDAC. Development of resistance to current therapy is one of the key reasons for this outcome. Nimbolide (NL), a triterpenoid obtained from Azadirachta indica, exhibits anticancer properties in various cancer including PDAC cells.

[Relation between preoperative prognostic Onodera's Index and postsurgery complications in the R0 gastric carcinoma resection].

Background: It has been postulated in the Asian literature that a low prognostic nutritional index (OI) could be associated with a higher rate of complications following radical gastric cancer surgery, but there is a lack of data concerning western countries. The aim is to analyze the relationship between a low preoperative OI and the frequency and severity of surgical complications in R0 gastric cancer resection.

Patients And Methods: In the present article, 124 cases of gastric cancer with R0 resection were reviewed.

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer.

Abrogation of endoplasmic reticulum (ER) protein folding triggered by exogenous or endogenous factors, stimulates a cellular stress response, termed ER stress. ER stress re-establishes ER homeostasis through integrated signaling termed the ER-unfolded protein response (UPR). In the presence of severe toxic or prolonged ER stress, the pro-survival function of UPR is transformed into a lethal signal transmitted to and executed through mitochondria.

Mitochondrial dysfunction and prostate cancer racial disparities among American men.

The gap between prostate cancer disparities among American men is narrowing, which is mostly due to increased screening of African American (AA) men. However, the biological reasons for prostate cancer disparities among American men still remain undefined. Mitochondrion, an organelle within cells, regulates both cell survival and cell death mechanisms.

Mechanism of neem limonoids-induced cell death in cancer: Role of oxidative phosphorylation.

We have previously reported that neem limonoids (neem) induce multiple cancer cell death pathways. Here we dissect the underlying mechanisms of neem-induced apoptotic cell death in cancer. We observed that neem-induced caspase activation does not require Bax/Bak channel-mediated mitochondrial outer membrane permeabilization, permeability transition pore, and mitochondrial fragmentation.

Coupling to a glioblastoma-directed antibody potentiates antitumor activity of curcumin.

Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-κB, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death.

[Bibliometric analysis of publications in Gastroenterology and Hepatology in Spain from 2000 to 2009].

Introduction: The aim of this study was to analyze the productivity and visibility of Spanish authors in gastroenterology and hepatology between 2000 and 2009 and to compare the results with those for other countries.

Methods: The Web of Science database was used. The analysis (annual and 5-yearly) was restricted to citable documents.

Differential findings regarding molecular epidemiology of tuberculosis between two consecutive periods in the context of steady increase of immigration.

The demographic characteristics of the population of Madrid, with a steady increase in immigrants, from 4.7% in 1998 to 17.4% in 2007, provide an opportunity to study in depth the transmission of TB.

[Analysis of publications on infectious diseases. A comparative study of ten countries in the period 2000-2009].

Objective: We analyse the productivity and visibility of Spanish publications on the subject category of infectious diseases in the period 2000-2009 and compared with the corresponding nine other countries.

Methods: We used the database Web of Science. Analysis (annual and five-year) was restricted to the citable documents.

[Evolution of the literature on clinical neurology in Spain, France, Italy and Germany over the period 2000-2009].

Aim: This study analyzes the productivity and visibility of Spanish publications in the area of clinical neurology in the period 2000-2009 and compared with those for Italy, France and Germany.

Materials And Methods: We used the database Web of Science. The analysis (annual and in five-year) was restricted to the citable documents (original articles, reviews and proceedings papers).