Medical Specialties Commons^™

Diet And Food Chemicals Increasing The Risk Of Colorectal Cancer – Literature Review, Mihail Silviu Tudosie, Andreea Pauna, Cristian Stefani, Iulia Madalina Staicu

Journal of Mind and Medical Sciences

Colorectal cancer is a common form of cancer nowadays. There are many risk factors in the pathogenesis of colorectal cancer. The malignant proliferation is caused by one or more genetic mutations, which activate oncogenes and deactivate tumor suppressor genes. Some factors cannot be changed, such as a person's age or family history. An essential aspect in the pathogenesis of colorectal cancer is the choice of lifestyles, such as a high-fat diet, smoking, and excess alcohol. Carcinogens can be either natural or chemical. The mechanisms by which carcinogens initiate tumor formation are genetic or non-genotoxic. The most common form of colorectal …

The Benign Mimickers Of Carcinoma On Breast Mri, Irmak Durur-Subasi, Adem Karaman, Elif Demirci, Sare Sipal, Mufide Nuran Akcay

Journal of Mind and Medical Sciences

The similarity between benign and malignant pathologies on magnetic resonance imaging (MRI) and a wide-ranging variability of the lesions from benign proliferative changes to invasive breast carcinoma cause a lower and wide-ranging specificity of breast MRI relative to its surpass sensitivity. A wide range of tissue components such as the skin, the adipose tissue, vascular and neural tissues, connective tissues, glandular tissues, ducts, and muscle tissues are found here all together. This pictorial review was aimed at deliberating benign mimickers of breast carcinoma on MRI and trying to call attention to the overlapping and distinctive features.

Modern Interpretation Of Risk Factors In Breast Cancer Of Women, Oana Denisa Bălălău, Răzvan Valentin Scăunașu, Octavian Gabriel Olaru, Anca Silvia Dumitriu, Stana Paunica, Liliana Florina Andronache, Anca Daniela Stănescu

Journal of Mind and Medical Sciences

Breast cancer is a major public health problem, being the most common cancer diagnosed in women and accounting for more than 1 in 10 new diagnoses of cancer each year. It is the most common neoplasm of women under the age of 40 and the second leading cause of cancer death in this age group, with more frequent detection of pathogenic mutations in breast cancer susceptibility genes. Women with BRCA1 and BRCA2 mutations are about 70% more likely to develop breast cancer. The incidence is rising in most countries and it is expected to have a growing trend in the …

The Involvement Of Oxidative Stress In Non-Hodgkin’S Lymphomas; A Review Of The Literature, Ramona Ingrid Corbeanu, Amelia Maria Găman

Journal of Mind and Medical Sciences

Non-Hodgkin’s malignant lymphomas are a heterogeneous group of hematological malignancies, characterized by a variety of clinical, morphological, histopathological, immuno-histochemical, molecular and evolutionary features. They represent a form of cancer that develops from the lymphatic tissue, as a result of the malignant transformation of B (85%) or T (15%) lymphocytes. Lymphomagenesis is described as a multi-stage process involving the mutation and proliferation of cell clones. Oxidative stress is defined as an imbalance of cellular redox status caused by the production of reactive oxygen species (ROS) and/ or by decreasing antioxidant systems that allows their accumulation in the cell. Small quantities of …

Exploiting 4–1bb Immune Checkpoint To Enhance The Efficacy Of Oncolytic Virotherapy For Diffuse Intrinsic Pontine Gliomas, Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucía Marrodán, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martínez-Vélez, Iker Ausejo-Mauleon, Daniel De La Nava, Guillermo Herrador-Cañete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E De Andrea, María Villalba, Oren Becher, Massimo Squatrito, Verónica Matía, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed …

Lymphocyte Depletion Rate As A Biomarker Of Radiation Dose To Circulating Lymphocytes During Fractionated Partial-Body Radiation Therapy, Susannah G Ellsworth, Anirudh Yalamanchali, Tim Lautenschlaeger, Stuart A Grossman, Clemens Grassberger, Steven H Lin, Radhe Mohan

Faculty, Staff and Student Publications

Purpose: Radiation causes exponential depletion of circulating lymphocyte populations; in turn, radiation-induced lymphopenia is associated with worse survival for many solid tumors, possibly owing to attenuated antitumor immune responses. Identifying reliable and reproducible methods of calculating the radiation dose to circulating immune cells may facilitate development of techniques to reduce the risk and severity of radiation-induced toxic effects to circulating lymphocytes.

Methods and materials: Patient-specific lymphocyte loss rates were derived from a clinical data set including 684 adult patients with solid tumors. Multivariable linear regression was used to model the relationship between the lymphocyte loss rate and physical parameters of …

Hsp90-Cdc37 Functions As A Chaperone For The Oncogenic Fgfr3-Tacc3 Fusion, Tao Li, Farideh Mehraein-Ghomi, M Elizabeth Forbes, Sanjeev V Namjoshi, E Ashley Ballard, Qianqian Song, Ping-Chieh Chou, Xuya Wang, Brittany C Parker Kerrigan, Frederick F Lang, Glenn Lesser, Waldemar Debinski, Xuejun Yang, Wei Zhang

Faculty, Staff and Student Publications

The FGFR3-TACC3 (F3-T3) fusion gene was discovered as an oncogenic molecule in glioblastoma and bladder cancers, and has subsequently been found in many cancer types. Notably, F3-T3 was found to be highly expressed in both untreated and matched recurrence glioblastoma under the concurrent radiotherapy and temozolomide (TMZ) treatment, suggesting that targeting F3-T3 is a valid strategy for treatment. Here, we show that the F3-T3 protein is a client of heat shock protein 90 (HSP90), forming a ternary complex with the cell division cycle 37 (CDC37). Deprivation of HSP90 or CDC37 disrupts the formation of the ternary complex, which destabilizes glycosylated …

Chronic Alcohol Exposure Induces Hepatocyte Damage By Inducing Oxidative Stress, Satb2 And Stem Cell-Like Characteristics, And Activating Lipogenesis, Wei Yu, Yiming Ma, Sushant K. Shrivastava, Rakesh K. Srivastava, Sharmila Shankar

School of Medicine Faculty Publications

Alcohol is a risk factor for hepatocellular carcinoma (HCC). However, the molecular mechanism by which chronic alcohol consumption contributes to HCC is not well understood. The purpose of the study was to demonstrate the effects of chronic ethanol exposure on the damage of human normal hepatocytes. Our data showed that chronic exposure of hepatocytes with ethanol induced changes similar to transformed hepatocytes that is, exhibited colonies and anchorage-independent growth. These damaged hepatocytes contained high levels of reactive oxygen species (ROS) and showed induction of the SATB2 gene. Furthermore, damaged hepatocytes gained the phenotypes of CSCs which expressed stem cell markers …

Genetic Evaluation For Hereditary Cancer Syndromes Among African Americans: A Critical Review, Ambreen Khan, Charles R Rogers, Carson D Kennedy, Ana Maria Lopez, Joanne Jeter

Department of Medical Oncology Faculty Papers

While hereditary cancer syndromes have been described and studied for centuries, the completion of the human genome project fueled accelerated progress in precision medicine due to the introduction of genetic testing in the 1990s, creating avenues for tailored treatments and medical management options. However, genetic testing has not benefited everyone equitably, with nearly all of the published work based on individuals of non-Hispanic White/European ancestry. There remains a gap in knowledge regarding the prevalence, penetrance, and manifestations of common hereditary cancer syndromes in the African-American population due to significant disparities in access and uptake of genetic testing. This review summarizes …

Targeting The Nrf2/Ho-1 Antioxidant Pathway In Flt3-Itd-Positive Aml Enhances Therapy Efficacy, Sankaranarayan Kannan, Mary E Irwin, Shelley M Herbrich, Tiewei Cheng, Lanisha L Patterson, Marisa J L Aitken, Kapil Bhalla, M James You, Marina Konopleva, Patrick A Zweidler-Mckay, Joya Chandra

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a molecularly heterogenous hematological malignancy, with one of the most common mutations being internal tandem duplication (ITD) of the juxtamembrane domain of the fms-like tyrosine kinase receptor-3 (FLT3). Despite the development of FLT3-directed tyrosine kinase inhibitors (TKI), relapse and resistance are problematic, requiring improved strategies. In both patient samples and cell lines, FLT3-ITD raises levels of reactive oxygen species (ROS) and elicits an antioxidant response which is linked to chemoresistance broadly in AML. NF-E2-related factor 2 (NRF2) is a transcription factor regulating the antioxidant response including heme oxygenase -1 (HO-1), a heat shock protein implicated …

Mcph1: A Novel Case Report And A Review Of The Literature, Stefano Giuseppe Caraffi, Marzia Pollazzon, Muhammad Farooq, Ambrin Fatima, Lars Allan Larsen, Roberta Zuntini, Manuela Napoli, Livia Garavelli

Department of Biological & Biomedical Sciences

Microcephaly primary hereditary (MCPH) is a congenital disease characterized by nonsyndromic reduction in brain size due to impaired neurogenesis, often associated with a variable degree of intellectual disability (ID). The genetic etiology of MCPH is heterogeneous and comprises more than 20 loci, nearly all following a recessive inheritance pattern. The first causative gene identified, MCPH1 or Microcephalin, encodes a centrosomal protein that modulates chromosome condensation and cell cycle progression. It is also involved in DNA damage response and telomere maintenance in the nucleus. Despite numerous studies on MCPH1 function, MCPH1-affected individuals are rare and the available clinical reports are …

18 Fdg Pet/Ct Imaging In Carcinoma Cesophagus, Maseeh Uz Zaman, Nosheen Fatima

Department of Radiology

No abstract provided.

Artificial Intelligence And Machine Learning For Early Detection And Diagnosis Of Colorectal Cancer In Sub-Saharan Africa, Akbar K. Waljee, Eileen M. Weinheimer-Haus, Amina Abubakar, Anthony Ngugi, Geoffrey H. Siwo, Gifty Kwakye, Amit G. Singal, Arvind Rao, Christopher Opio, Mansoor Saleh

Institute for Human Development, East Africa

No abstract provided.

An Analysis Of The Psychological And Physical Effects Of A Physical Activity Program During In-Patient Pediatric Cancer Treatment, Zoë Winters

Undergraduate Theses

There is limited published research regarding the use of physical activity in cancer treatment programs, and even fewer in pediatric treatment plans; however, there is a common consensus that following the conclusion of cancer treatment an individual’s physical fitness has been majorly impacted. The inactivity that commonly coexists with cancer treatment often results in extended periods of time in rehabilitation programs and decreased independence. Along with the physical detriments caused by inactivity, increased dependence on others often brings about feelings of helplessness that can further cause emotional detriments. It has however been demonstrated in previous research that adding physical activity …

The Write Stuff - Spring 2022 (Vol. 19, No. 2), Research Medical Library

Write Stuff 2022

• New PRISMA guidelines for systematic reviews
• Top tips for writing article titles
• Key points from NIH seminar: “Including diverse populations in NIH-funded clinical research”
• Unusual terms used in scientific writing and publishing: NISO

Perceptions And Knowledge Towards Covid-19 Vaccine Hesitancy Among A Subpopulation Of Adults In Kenya: An English Survey At Six Healthcare Facilities, Jasmit Shah, Abdulaziz Mansur Abeid, Karishma Sharma, Soraiya Manji, Jamila Nambafu, Robert Korom, Keya Patel, Rajiv Patel, Reena Shah, Sayed Karar

Brain and Mind Institute

Background: Vaccine hesitancy, as defined by the WHO, is the reluctance or refusal to vaccinate despite the availability of vaccines and is one of the ten threats to global health in 2019. Vaccine hesitancy remains a complex matter influenced by multiple factors, especially in sub-Saharan Africa.

Methods: We conducted a cross-sectional study between November 2021 and January 2022 among the general adult public seeking care at six different healthcare facilities in Kenya. The survey, in English, consisted of questions based on demographics, knowledge, and attitudes, including hesitancy towards the COVID-19 vaccine.

Results: Of the 3996 surveys collected, 55.1% were from …

T Cell Therapy: Underlying Mechanisms And Current Advancements, Griffin Mccloy

Senior Honors Theses

As the second leading cause of death in 2016, cancer is one of the most serious diseases facing the world today. T cell therapy is a current area of research attempting to address the disease with two primary division: CAR-T and TCR-T cell therapy. The immune system naturally produces T lymphocytes to aid in the recognition and removal of cells infected with viruses or transformed into cancer. Under normal circumstances, T lymphocytes identify and destroy cancerous cells; however, some cancerous cell types can evade this system. With the use of genetic editing technology, T lymphocytes can gain the ability to …

A Quantitative Dose Pertubation Comparison Study Between Gold And Platinum Visicoil Fiducial Markers In Proton Beam Therapy, Xuanfeng Ding, Gang Liu, Weili Zheng, Jessica Vadas, Xiaoqiang Li, Lewei Zhao, An Qin, Daniel Krauss, Di Yan

Conference Presentation Abstracts

Purpose: To quantitatively investigate the dose perturbations difference between gold and platinum VISICOILTM fiducial markers in proton beam therapy Method: Gold and platinum VISICOILTM fiducial markers with two different dimensions were tested, including 0.35 & 0.5mm in diameter and 5mm in length. Total four kinds of markers. Gafchromic EBT2 was used to measure dose perturbations along the beam path in a ‘‘sandwich’’ setup (Figure 1). Dose perturbation was reported in each depth (0.3mm, 1.65mm, 3.00mm, 5.40mm, 7.80mm, 10.20mm, 12.60mm, 18.15mm). Relative proton stopping power relative to water were calculated through National Institute of Standards and Technology database and SRIM (version …

Assessing The Interplay Effect Based On A Precise Machine-Specific Delivery Sequence And Time For Cyclotron Accelerator Proton Therapy System., Lewei Zhao, Gang Liu, Jiajian Sher, Andrew Lee, Di Yan, Rohan Deraniyagala, Craig Stevens, Xiaoqiang Li, Shikui Tang, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: We proposed an experimental approach to build a precise machine-specific model for standard, volumetric, and layer repainting delivery based on a cyclotron accelerator system. Then, we assessed the interplay effect using a 4D mobile lung target phantom compared to a generic delivery sequence model from West German Proton Therapy Essen (WPE). Methods: The machine delivery log files, from an IBA ProteusPLUSt system, were retrospectively analyzed to quantitatively model energy layer switching time, spot switching time, and spot drill time for standard and volumetric repainting delivery. To quantitatively evaluate the interplay effect, a series of digital thoracic 4DCT image sets …

Contralateral Control Rate With Unilateral Proton Beam Radiotherapy For Oropharyngeal Scc: A Multi-Institutional Prospective Study From The Proton Collaborative Group, Aleksander Vayntraub, Thomas Quinn, John Chang, Noah Kalman, Sanford Katz, James Urbanic, Arpi Thukral, Jason Molitoris, Craig Stevens, Rohan Deraniyagala

Conference Presentation Abstracts

Introduction: Select patients with oropharyngeal SCC are candidates for unilateral radiation therapy. We sought to investigate if ipsilateral targeting leads to increased contralateral recurrences. Methods: We queried the PCG database for patients treated with unilateral proton RT for head and neck SCC from 2015 – 2020 at 12 institutions. DICOMs were evaluated to ensure dose delivered matched a unilateral proton treatment plan. Demographic, clinical and pathological, toxicity and dosimetry information were compiled. Results: We found 43 cases treated with unilateral proton RT. 94% (n¼16) of recurrent cases received prior radiation. Oropharyngeal sites included tonsillar fossa (n¼32), and base of tongue …

The First Modeling Of The Spot-Scanning Proton Arc(Sparc) Delivery Sequence And Investigating Its Efficiency Improvement, Xuanfeng Ding, Gang Liu, Lewei Zhao, Rohan Deraniyagala, Craig Stevens, Di Yan, Xiaoqiang Li

Conference Presentation Abstracts

Purpose: Introduce an experimental approach to model a precise prototype arc system and quantitatively assess its efficiency improvement in the routine proton clinical operation. Methods: The SPArc delivery sequence model(DSMSPArc) includes two kinds of parameters:(1) mechanical parameters. (2) irradiation parameters. Log files and an independent gantry inclinometer were used to derive the irradiation parameters through a series of test plans. The in-house DSMSPArc was established by fitting both mechanical and irradiation parameters. Eight SPArc plans from different disease sites were used to validate the model’s accuracy. To assess the treatment efficiency improvement, the DSMSPArc was used to simulate the SPArc …

A Direct Machine-Specific Parameters Incorporated Spot-Scanning Proton Arc (Sparc) Algorithm, Gang Liu, Lewei Zhao, Di Yan, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To address the challenges of generating a deliverable and efficient spot-scanning proton arc (SPArc) plan for a proton therapy system. We developed a novel SPArc optimization algorithm (SPArcDMSP) by directly incorporating machinespecific parameters such as mechanical constraints and delivery sequence. Method and Material: A SPArc delivery sequence model (DSMarc) was built based on the machine-specific parameters of the prototype arc delivery system IBA ProteusONEt. The SPArcDMSP resamples and adjusts each control point’s delivery speed based on the DSMarc calculation through the iterative approach (Fig1). Users could set the expected delivery time and gantry max acceleration as a mechanical constraint …

Enzymatic Characterization Of Mrna Cap Adenosine-N6 Methyltransferase Pcif1 Activity On Uncapped Rnas, Dan Yu, Nan Dai, Eric J Wolf, Ivan R Corrêa, Jujun Zhou, Tao Wu, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

The phosphorylated RNA polymerase II CTD interacting factor 1 (PCIF1) is a methyltransferase that adds a methyl group to the N6-position of 2′O-methyladenosine (Am), generating N6, 2′O-dimethyladenosine (m6Am) when Am is the cap-proximal nucleotide. In addition, PCIF1 has ancillary methylation activities on internal adenosines (both A and Am), although with much lower catalytic efficiency relative to that of its preferred cap substrate. The PCIF1 preference for 2′O-methylated Am over unmodified A nucleosides is due mainly to increased binding affinity for Am. Importantly, it was recently reported that PCIF1 can methylate viral RNA. Although some viral RNA can be translated in …

Loss Of Rnf43 Accelerates Kras-Mediated Neoplasia And Remodels The Tumor Immune Microenvironment In Pancreatic Adenocarcinoma, Abdel Nasser Hosein, Gita Dangol, Takashi Okumura, Jason Roszik, Kimal Rajapakshe, Megan Siemann, Mohamed Zaid, Bidyut Ghosh, Maria Monberg, Paola A Guerrero, Aatur Singhi, Cara L Haymaker, Hans Clevers, Lotfi Abou-Elkacem, Sonja M Woermann, Anirban Maitra

Faculty, Staff and Student Publications

Background & aims: RNF43 is an E3 ubiquitin ligase that is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC) and precursor cystic neoplasms of the pancreas. The impact of RNF43 mutations on PDAC is poorly understood and autochthonous models have not been characterized sufficiently. In this study, we describe a genetically engineered mouse model (GEMM) of PDAC with conditional expression of oncogenic Kras and deletion of the catalytic domain of Rnf43 in exocrine cells.

Methods: We generated Ptf1a-Cre;LSL-KrasG12D;Rnf43flox/flox (KRC) and Ptf1a-Cre; LSL-KrasG12D (KC) mice and animal survival was assessed. KRC mice were sacrificed at 2 months, 4 months, and at moribund …

An Efficient Magnetic Resonance Image Data Quality Screening Dashboard, Evan D H Gates, Adrian Celaya, Dima Suki, Dawid Schellingerhout, David Fuentes

Faculty, Staff and Student Publications

Purpose: Complex data processing and curation for artificial intelligence applications rely on high-quality data sets for training and analysis. Manually reviewing images and their associated annotations is a very laborious task and existing quality control tools for data review are generally limited to raw images only. The purpose of this work was to develop an imaging informatics dashboard for the easy and fast review of processed magnetic resonance (MR) imaging data sets; we demonstrated its ability in a large-scale data review.

Methods: We developed a custom R Shiny dashboard that displays key static snapshots of each imaging study and its …

Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Akash Mukherjee, Denái R Milton, Elias J Jabbour, Alison M Gulbis, Tapan Kadia, Nitin Jain, Celina Ledesma, Jan Burger, Alessandra Ferrajoli, William Wierda, L Jeffrey Medeiros, Hagop Kantarjian, Richard Champlin, Issa F Khouri

Faculty, Staff and Student Publications

We aimed to study the risks of graft-versus-host disease (GVHD), non-relapse mortality (NRM) and survival outcomes of allogeneic stem cell transplantation (alloSCT) in patients with chronic lymphocytic leukemia (n = 17), Richter's syndrome (n = 14), or lymphoma (n = 18) after small molecule inhibitors (SMIs). Patients had a median of 4 prior therapies, including ibrutinib (n = 46; 94%), venetoclax (n = 19; 39%), and idelalisib (n = 6; 12%). Twenty-one (43%) had >1 SMI. P53 mutation was detected in 58% of patients. The 3-year overall and progression-free survival rates were 68% and …

Standardisation Of Protocols Can Be Crucial In Long Non-Coding Rna Research, Kinga Németh, George A Calin

Faculty, Staff and Student Publications

In this issue, Traversa et al. [1] reviewed our current knowledge about the role of circular and linear forms of PVT1 non-coding RNA in cancer and human diseases. They highlighted the technical challenges of these studies and raised a potential bias in the publications, which require more attention from researchers.

Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable With Isolated Isochromosome 17q Represents A Distinct Clinico-Biologic Subset: A Multi-Institutional Collaborative Study From The Bone Marrow Pathology Group, Rashmi Kanagal-Shamanna, Attilio Orazi, Robert P Hasserjian, Daniel A Arber, Kaaren Reichard, Eric D Hsi, Adam Bagg, Heesun Joyce Rogers, Julia Geyer, Faezeh Darbaniyan, Kim-Anh Do, Kyle M Devins, Olga Pozdnyakova, Tracy I George, Paola Dal Cin, Patricia T Greipp, Mark J Routbort, Keyur Patel, Guillermo Garcia-Manero, Srdan Verstovsek, L Jeffrey Medeiros, Sa A Wang, Carlos Bueso-Ramos

Faculty, Staff and Student Publications

Classification of myeloid neoplasms with isolated isochromosome i(17q) [17p deletion with inherent monoallelic TP53 loss plus 17q duplication] is controversial. Most cases fall within the WHO unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U) category. The uniformly dismal outcomes warrant better understanding of this entity. We undertook a multi-institutional retrospective study of 92 adult MDS/MPN-U cases from eight institutions. Twenty-nine (32%) patients had isolated i(17q) [MDS/MPN-i(17q)]. Compared to MDS/MPN without i(17q), MDS/MPN-i(17q) patients were significantly younger, had lower platelet and absolute neutrophil counts, and higher frequency of splenomegaly and circulating blasts. MDS/MPN-i(17q) cases showed frequent bilobed neutrophils (75% vs. 23%; P = 0.03), hypolobated …

Pgc1Α/Β Expression Predicts Therapeutic Response To Oxidative Phosphorylation Inhibition In Ovarian Cancer, Carmen Ghilardi, Catarina Moreira-Barbosa, Laura Brunelli, Paola Ostano, Nicolò Panini, Monica Lupi, Alessia Anastasia, Fabio Fiordaliso, Monica Salio, Laura Formenti, Massimo Russo, Edoardo Arrigoni, Ferdinando Chiaradonna, Giovanna Chiorino, Giulio Draetta, Joseph R Marszalek, Christopher P Vellano, Roberta Pastorelli, Mariarosa Bani, Alessandra Decio, Raffaella Giavazzi

Faculty, Staff and Student Publications

Ovarian cancer is the deadliest gynecologic cancer, and novel therapeutic options are crucial to improve overall survival. Here we provide evidence that impairment of oxidative phosphorylation (OXPHOS) can help control ovarian cancer progression, and this benefit correlates with expression of the two mitochondrial master regulators PGC1α and PGC1β. In orthotopic patient-derived ovarian cancer xenografts (OC-PDX), concomitant high expression of PGC1α and PGC1β (PGC1α/β) fostered a unique transcriptional signature, leading to increased mitochondrial abundance, enhanced tricarboxylic acid cycling, and elevated cellular respiration that ultimately conferred vulnerability to OXPHOS inhibition. Treatment with the respiratory chain complex I inhibitor IACS-010759 caused mitochondrial swelling …

Camk2/Camkii Activates Mlkl In Short-Term Starvation To Facilitate Autophagic Flux, Qionghui Zhan, Jaepyo Jeon, Ying Li, Yu Huang, Jian Xiong, Qiaochu Wang, Tian-Le Xu, Yong Li, Fu-Hai Ji, Guangwei Du, Michael X Zhu

Faculty, Staff and Student Publications

MLKL (mixed lineage kinase domain like pseudokinase) is a well-known core component of necrosome that executes necroptotic cell death upon phosphorylation by RIPK3 (receptor interacting serine/threonine kinase 3). Recent studies also implicate a role of MLKL in endosomal trafficking, which is not always dependent on RIPK3. Using mouse Neuro-2a and L929 as well as human HEK293 and HT29 cells, we show here that MLKL is phosphorylated in response to serum and amino acid deprivation from the culture medium, in a manner that depends on CAMK2/CaMKII (calcium/calmodulin dependent protein kinase II) but not RIPK3. The starvation-induced increase in MLKL phosphorylation was …