Medical Specialties Commons^™

Pegzilarginase In Combination With Agonist Anti-Ox40 Therapy Enhances T Cell Priming And Effector Function Leading To Improved Tumor Regression And Survival, Melissa Kasiewicz, Annah Rolig, Elizabeth Sturgill, Mark Badeaux, Scott Rowlinson, William L. Redmond

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Tumor cells defective in enzymes required for arginine biosynthesis are dependent upon arginine uptake from the environment. Extracellular depletion of arginine directly affects tumor cells, inducing autophagy and apoptosis. Pegzilarginase (AEB1102) is a bioengineered, pegylated, human arginase 1 (Aeglea Biotherapeutics) currently in phase I clinical trials. This arginine-depleting agent has been shown to both inhibit arginine auxotrophic tumor growth and to enhance the efficacy of PD-L1 blockade in preclinical models. In the current study, we investigated the therapeutic efficacy and mechanism of action of combined pegzilarginase/anti-OX40 (aOX40) immunotherapy. We hypothesized that pegzilarginase/aOX40 treatment would synergize to enhance T cell …

Integrative Spatially-Resolved, High-Plex Digital Profiling Enables Characterization Of Complex Immune Biology In The Tumor Microenvironment Of Mesothelioma, Carmen Ballesteros-Merino, Moritz Widmaier, Sarah Church, Thomas Herz, Alexei Budco, Das Medrikova, Ivan Kanchev, Andrew White, Douglas Hinerfeld, Shawn Jensen, John Handy, Rachel Sanborn, Carlo Bifulco, Sarah Warren, Joseph Beechem, Bernard .. Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Malignant mesothelioma is an aggressive cancer with poor prognosis and few effective therapies. Since mesothelioma is derived from the mesothelium of the lung, we hypothesize that immune cells in the tumor microenvironment (TME) may behave differently than other solid tumors. In our previous studies, utilizing multi-plexed immunofluorescence, we did not find immune phenotypes associated with improved patient survival. Here we describe a novel combination of two technologies to spatially characterize the interface between mesothelioma cells, stroma and immune cells in the TME in a high-plex capacity.

Methods: Ten FFPE mesothelioma tumors were characterized by Definiens’ Immune-Oncology Profiling (IOP) and …

Preliminary Results From A First-In-Human Phase 1 Study Of The Cd40 Agonist Monoclonal Antibody (Mab) Cdx-1140, Rachel Sanborn, Michael S. Gordon, Mark O'Hara, Nina Bhardwaj, Yi He, Tracey Rawls, Tibor Keler, Michael Yellin

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Agonist CD40 mAbs can mediate antitumor immunity through multiple mechanisms, including enhancing tumor antigen presentation, activation of tumoricidal macrophages, and direct growth inhibition/killing of CD40- expressing tumor cells. To fully exploit these mechanisms may require the mAb to be dosed at levels that provide significant tumor and tissue penetration, without dose-limiting-toxicities (DLT) from systemic CD40 activation. Our agonist CD40 mAb, CDX-1140, was selected based on its unique and linear dose-dependent in vitro and in vivo activity and is postulated will achieve maximum agonist activity at dose levels associated with good systemic exposure. CDX-1140 is a fully human IgG2 agonist …

Nktr-214 (Cd122-Biased Agonist) And Nktr-262 (Tlr7/8 Agonist) Combination Treatment Pairs Local Innate Immune Activation With Systemic Cd8+ T Cell Expansion To Enhance Anti-Tumor Immunity, Annah S. Rolig, Daniel Rose, Saul Kivimäe, Deborah Charych, Werner Rubas, Jonathan Zalevsky, William L. Redmond

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Radiation therapy (RT) remains the standard of care for many human cancers. Combining NKTR-214, a CD122-biased cytokine agonist conjugated with releasable polyethylene-glycol (PEG) chains, with local RT significantly enhanced therapeutic efficacy in preclinical models. Mechanistically, NKTR-214 provides sustained signaling through the IL-2 receptor pathway (IL-2Rβγ) to preferentially activate and expand effector CD8+ T and NK cells and RT modulates the tumor microenvironment (TME) to induce antigen-release. Together, NKTR-214/RT treatment resulted in improved therapeutic responses compared to either treatment alone. However, abscopal responses in murine tumors were modest, leading us to explore alternative approaches with the potential to elicit more …

Combined Anti-Pd-1 And Anti-Lag-3 Checkpoint Blockade Enhances Cd8+ Til Effector Function While Reducing Tregs Leading To Reduced Immune Suppression And Improved Overall Survival, Elizabeth Sturgill, Courtney Mick, David Jenkins, Johanna Kaufmann, William L. Redmond

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Checkpoint inhibition is a potent strategy to reinvigorate T cells. However, aCTLA-4 or aPD-1 monotherapy has not been effective for the majority of patients, resulting in the exploration of combinatorial approaches to improve treatment efficacy. One such target is LAG-3, which is upregulated on T cells that have experienced repeated antigen exposure, such as in the tumor microenvironment (TME), and is associated with reduced T cell effector function. In addition, high LAG-3 expression on regulatory T cells (Tregs) has been reported for patients with varying cancer types, providing an additional rationale for targeting LAG-3 with the aim of reducing …

Tumor Infiltrating Lymphocyte Recruitment After Peri-Lymphatic Irx-2 Cytokine Immunotherapy In Resectable Breast Cancer And Head And Neck Carcinoma, Joanna Pucilowska, Venkatesh Rajamanickam, Nikki Moxon, Monil Shah, Maritza Martel, Alison Conlin, James E. Egan, David B. Page

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: The IRX-2 biologic is a subcutaneous injectable immunotherapy composed of IL-2 and other cytokines derived from stimulated lymphocytes. Preclinically, IRX-2 activates T cells, natural killer cells, macrophages, and dendritic cells, and facilitates maturation of antigen-presenting cells.Tumor-infiltrating lymphocytes (TILs) are associated with improved outcomes in many cancers including early stage breast cancer (ESBC) and head and neck squamous cell carcinoma (HNSCC). We report data on TIL recruitment associated with pre-operative IRX-2 in a phase Ib ESBC trial, as well as phase Ib and IIa HNSCC trials.

Methods: The pre-operative IRX-2 regimen was evaluated in both ESBC and HNSCC trials for …

Single Cell Sequencing To Identify Tcrs That Recognize Autologous Tumor Cells After Vaccination With Allogeinic Dribble Vaccine, Hong-Ming Hu, Christopher C. Paustian, Zhifa Wen, Tarsem L. Moudgil, Traci L. Hilton, Sam Bookhardt, Guangjie Yu, Eric Tran, Venkatesh Rajamanickam, Walter Urba, Rachel E. Sanborn, Bernard A. Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Adoptive immunotherapy with tumor-specific TCR gene-modified T cells has the potential to eradicate bulky disease. Traditional methods of TCR identification require lengthy in vitro culture to generate clonal T-cell populations, which adds time and complexity to this promising therapy. Here we described a simplified and reliable method to identify TCRs by single cell TCR sequencing of cells sorted with antibodies against T-cell surface markers that are up-regulated only when they are stimulated with specific tumor cell antigens.

Methods: A tumor-infiltrating lymphocyte (TIL) culture with T cells reactive against autologous tumor was generated from a brain metastasis of a patients …

Delayed Immune-Related Events After Discontinuation Of Immunotherapy – Dire Syndrome?, Marcus Couey, R. Bryan Bell, Ashish Patel, Marka R Crittenden, Brendan Curti, Rom Leidner

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Although the temporality of immune-related adverse events (irAE) is well-recognized during immunotherapy to be highly variable and often delayed,[1] post-immunotherapy irAE are rarely described and potentially under-recognized. In 2013, two cases were reported in abstract form in Deutschen Dermatologischen Gesellschaft.[2] In July 2018 a case of autoimmune hepatitis eight months post-immunotherapy was reported in The Oncologist[3] and a dermatologic series appeared online in JAMA Dermatology.[4] With expanding indications for IO and an increasing number of clinical trials in the curative-neoadjuvant setting, larger numbers of patients are being treated in earlier stages of disease and often for short courses. Given …

Classification Of Intensity-Modulated Proton Therapy Plans, Louise Gabrielle Lima '19, Alice Liu '19

Student Publications & Research

Proton Radiotherapy

Proton radiotherapy is a form of radiation treatment that uses energized protons to break DNA, leading to cell death and killing cancers.

Synthesis And Biological Evaluation Of Phaeosphaeride A Derivatives As Antitumor Agents, Victoria Abzianidze, Petr Beltyukov, Sofya Zakharenkova, Natalia Moiseeva, Jennifer Mejia, Alvin Holder, Yuri Trishin, Alexander Berestetskiy, Victor Kuznetsov

Chemistry & Biochemistry Faculty Publications

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor activity studies were carried out on the HCT-116, PC3, MCF-7, A549, К562, NCI-Н929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All of the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 was potent against six cancer cell lines, HCT-116, PC-3, K562, NCI-H929, Jurkat, and RPMI8226, showing a 47, 13.5, 16, 4, 1.5, and 7-fold increase in anticancer activity comparative to those of etoposide, respectively. Compound 1 possessed selectivity toward the NCI-H929 cell line (IC …

Open-Source Digital Image Analysis Of Whole-Slide Multiplex Immunohistochemistry, Nikhil Lonberg, Carmen Ballesteros-Merino, Shawn Jensen, Bernard A Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Successful digital image analysis (DIA) of cancer tissue is accurate and reproducible. These points of emphasis have brought procedures like the tissue microarray (TMA) and hotspot regions of interest (ROI) under scrutiny. The nature in which a pathologist selects TMAs and ROIs is conducive to bias. Whole Slide Imaging (WSI) offers a solution in its unbiased region selection and consideration of a larger tissue sample. However, options for softwares that can handle such large throughput are scarce. Additionally, while multiplex immunohistochemistry (mIHC) is becoming popular [1], documentation of its digital analysis tools remains minimal [2]. The combination of these …

Inducible T Cell Co-Stimulator (Icos) Is Upregulated On Lymphocytes Following Radiation Of Tumors And Icos Agonism In Combination With Radiation Results In Enhanced Tumor Control, Michael J. Gough, Shelly Bambina, Monica Gostissa, Christopher Harvey, David Friedman, Marka R Crittenden

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Radiation and co-stimulatory ligands or checkpoint inhibitors have demonstrated improved anti-tumor immunity and overall survival in preclinical animal studies. However, the results of human trials suggest we have not yet found the optimal combination. Here we demonstrate upregulation of ICOS expression on T cells following focal tumor radiation and test the hypothesis that ICOS agonism in combination with radiation will enhance the immunologic effect of radiation resulting in increased survival.

Methods: BALB/c mice bearing CT26 tumors or C57BL/6 mice bearing Panc02 tumors were treated at d14 with 20Gy CT guided radiation therapy and anti-ICOS antibody or isotype control antibody …

Intratumoral Delivery Of Mdna55, An Interleukin-4 Receptor Targeted Immunotherapy, By Mri-Guided Convective Delivery For The Treatment Of Recurrent Glioblastoma, Achal Achrol, Manish Aghi, Krystof Bankiewicz, Martin Bexon, Sotirios Bisdas, Steven Brem, Andrew Brenner, Nicholas Butowski, Melissa Coello, Seunggu Jude Han, Santosh Kesari, Fahar Merchant, Dina Randazzo, Diana Roettger, Michael Vogelbaum, Frank Vrionis, Miroslaw Zabek, John Sampson

Books, Presentations, Posters, Etc.

No abstract provided.

Predominance Of Triple Wild-Type And Igf2r Mutations In Mucosal Melanomas., Yuuki Iida, Matthew P Salomon, Keisuke Hata, Kevin Tran, Shuichi Ohe, Chester Griffiths, Sandy C Hsu, Nellie Nelson, Dave S B Hoon

Articles, Abstracts, and Reports

BACKGROUND: Primary mucosal melanoma (MM) is a rare subtype of melanoma that arises from melanocytes in the mucosa. MM has not been well profiled for mutations and its etiology is not well understood, rendering current treatment strategies unsuccessful. Hence, we investigated mutational landscape for MM to understand its etiology and to clarify mutations that are potentially relevant for MM treatment.

METHODS: Forty one MM and 48 cutaneous melanoma (CM) tissues were profiled for mutations using targeted deep next-generation sequencing (NGS) for 89 cancer-related genes. A total of 997 mutations within exons were analyzed for their mutational spectrum and prevalence of …

Conference Proceedings: Aurora Scientific Day 2018

Journal of Patient-Centered Research and Reviews

This journal supplement includes selected abstracts from among the more than 50 presented at the 44th annual Aurora Scientific Day research symposium. Held May 25, 2018, in Milwaukee, Wisconsin, Aurora Scientific Day provides a forum for original research conducted by faculty, fellows, residents, and other allied health professionals affiliated with Aurora Health Care, an integrated health system with hospitals and clinics in Wisconsin and Illinois.

Collagen Prolyl 4-Hydroxylase 1 Is Essential For Hif-1Α Stabilization And Tnbc Chemoresistance, Gaofeng Xiong, Rachel L. Stewart, Jie Chen, Tianyan Gao, Timothy L. Scott, Luis M. Samayoa, Kathleen L. O'Connor, Andrew N. Lane, Ren Xu

Markey Cancer Center Faculty Publications

Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived …

Synthesis And Antiproliferative Activities Of Doxorubicin Thiol Conjugates And Doxorubicin-Ss-Cyclic Peptide, Shaban Darwish, Neda Sadeghiani, Shirley Fong, Saghar Mozaffari, Parinaz Hamidi, Thimanthi Withana, Sun Yang, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Myocardial toxicity and drug resistance caused by drug efflux are major limitations of doxorubicin (Dox)-based chemotherapy. Dox structure modification could be used to develop conjugates with an improved biological profile, such as antiproliferative activity and higher cellular retention. Thus, Dox thiol conjugates, Dox thiol (Dox-SH), thiol-reactive Dox-SS-pyridine (SS = disulfide), and a Dox-SS-cell-penetrating cyclic peptide, Dox-SS-[C(WR)4K], were synthesized. Dox was reacted with Traut's reagent to generate Dox-SH. The thiol group was activated by the reaction with dithiodipyridine to afford the corresponding Dox-SS-Pyridine (Dox-SS-Pyr). A cyclic cell-penetrating peptide containing a cysteine residue [C(WR)4K] was prepared using Fmoc solid-phase strategy. Dox-SS-Py was …

Digital Literacy In An Urban Cancer Population: Who Are We Leaving Out?, A. Petok, Msw, Mph, G. Garber, Msw, L. Waldman, Ba, A. Leader, Phd, A. Dicker, Md, Phd, L. Capparella, Mss

Department of Medical Oncology Posters

Background

• With an increase in and rapid development of health care applications, as well as electronic medical records and patient portals, patients have more access to health information than ever.
• Previous research has found an association between integration of electronic patient reported outcomes (ePROs) with increased survival for patients with metastatic cancer compared to usual care.
• Although greater access to health information as well as personal health records and patient portals can be shown to have positive effects on patient outcomes, the digital divide that is pervasive in the general population extends to oncology as well.
• This project aimed to …

Are We Missing The Elephant In The Room? A Case For Thyroid Cancer Overdiagnosis As The Etiology For Its Increasing Incidence In India, Janeesh Sekkath Veedu, Aju Mathew

Internal Medicine Faculty Publications

No abstract provided.

Modulation Of Hypoxia-Induced Chemoresistance To Polymeric Micellar Cisplatin: The Effect Of Ligand Modification Of Micellar Carrier Versus Inhibition Of The Mediators Of Drug Resistance, Hoda Soleymani Abyaneh, Amir Hassan Soleimani, Mohammad Reza Vakili, Rania Soudy, Kamaljit Kaur, Francesco Cuda, Ali Tavassoli, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(-carboxyl-"-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and …

Dual Inhibition Of Bcl-2/Bcl-Xl And Xpo1 Is Synthetically Lethal In Glioblastoma Model Systems, Enyuan Shang, Yiru Zhang, Chang Shu, Chiaki Tsuge Ishida, Elena Bianchetti, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

XPO1 has recently emerged as a viable treatment target for solid malignancies, including glioblastoma (GBM), the most common primary malignant brain tumor in adults. However, given that tumors become commonly resistant to single treatments, the identification of combination therapies is critical. Therefore, we tested the hypothesis that inhibition of anti-apoptotic Bcl-2 family members and XPO1 are synthetically lethal. To this purpose, two clinically validated drug compounds, the BH3-mimetic, ABT263, and the XPO1 inhibitor, Selinexor, were used in preclinical GBM model systems. Our results show that inhibition of XPO1 reduces cellular viability in glioblastoma cell cultures. Moreover, addition of ABT263 significantly …

Screening Mammography Use In Older Women According To Health Status: A Systematic Review And Meta-Analysis, Joshua Demb, Tomi Akinyemiju, Isabel Allen, Tracy Onega, Robert A. Hiatt, Dejana Braithwaite

Epidemiology and Environmental Health Faculty Publications

Background: The extent to which screening mammography (SM) recommendations in older women incorporate life expectancy factors is not well established.

Objective: The objective of this review was to evaluate evidence on SM utilization in older women by life expectancy factors.

Data sources: We searched Medline, Embase and Web of Science from January 1991 to March 2016.

Study selection: We included studies examining SM utilization in women ages ≥ 65 years that measured life expectancy using comorbidity, functional limitations or health or prognostic status.

Data extraction and synthesis: ORs and 95% CIs were extracted and grouped by life expectancy category. Findings …

Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Metformin, an oral anti-hyperglycemic drug which inhibits mitochondrial complex I and oxidative phosphorylation has been reported to correlate with improved outcomes in head and neck squamous cell carcinoma (HNSCC) and other cancers. This effect is postulated to occur through disruption of tumor-driven metabolic and immune dysregulation in the tumor microenvironment (TME). We report new findings on the impact of metformin on the tumor and immune elements of the TME from a clinical trial of metformin in HNSCC. Methods: Human papilloma virus-(HPV-) tobacco+ mucosal HNSCC samples (n = 12) were compared to HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples (n …

Enhanced Detection Of Neoantigen-Reactive T Cells Targeting Unique And Shared Oncogenes For Personalized Cancer Immunotherapy., Rami Yossef, Eric Tran, Drew C Deniger, Alena Gros, Anna Pasetto, Maria R Parkhurst, Jared J Gartner, Todd D Prickett, Gal Cafri, Paul F Robbins, Steven A Rosenberg

Articles, Abstracts, and Reports

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) targeting neoantigens can mediate tumor regression in selected patients with metastatic epithelial cancer. However, effectively identifying and harnessing neoantigen-reactive T cells for patient treatment remains a challenge and it is unknown whether current methods to detect neoantigen-reactive T cells are missing potentially clinically relevant neoantigen reactivities. We thus investigated whether the detection of neoantigen-reactive TILs could be enhanced by enriching T cells that express PD-1 and/or T cell activation markers followed by microwell culturing to avoid overgrowth of nonreactive T cells. In 6 patients with metastatic epithelial cancer, this method led to …

Tumor Biology And Racial Disparities In Reconstruction After Mastectomy: A Seer Database Analysis, Sarah J. Ullrich, Michael C. Smith, Paul J. Chung, Sara Y. Kim, Gainosuke Sugiyama

Journal of Health Disparities Research and Practice

Introduction:

Significant disparities in immediate breast reconstruction after mastectomy have persisted, and may even be increasing, despite large-scale efforts to minimize them, such as the Women’s Health and Cancer Rights Act of 1998. Immediate breast reconstruction has been shown to lead to higher rates of surgical satisfaction, minimize delay in post-operative cancer treatment, and improve the quality of life and overall well-being of mastectomy patients. However only 25-40% of eligible women in the United States receive reconstruction. The rate of reconstruction is even lower in African American and Hispanic women compared to White women. To better understand this disparity, …

Functional Radical Cervical Dissection For Differentiated Thyroid Cancer: The Experience Of A Single Center, Tulin Adrian, Lucian Alecu, Catalina Poiana, Luminita Tomescu, Iulian Slavu, Raluca Tulin, Silviu Pituru, Cristina Orlov, Radu Jecan, Balalau Cristian, Anca Pantea Stoian, Razvan Hainarosie, Cornelia Nitipir

Journal of Mind and Medical Sciences

There is ongoing debate regarding the role of neck dissection in differentiated thyroid cancer, about its usefulness in elective settings, and the increased costs regarding morbidity and operative time. This retrospective study aimed to determine the rate of metastases in cervical lymph nodes, to examine the morbidity of this surgery, and to assess whether a pattern of distribution of tumor cells concerning neck lymphatic compartments exists. The most frequent type of cancer to metastasize was papillary cancer, the majority of patients were young with a median of 30 years, predominantly females. Differentiated thyroid cancer frequently metastasizes to the central and …

Can Non-Small Cell Lung Cancer Histologic Subtypes Predict Survival? A Single Institution Experience, Cornelia Nitipir, Cristina Orlov, Ana-Maria Popa, Mihaela Olaru, Iulian Slavu, Iaciu Cristian, Razvan Hainarosie, Anca Pantea Stoian, Balalau Cristian

Journal of Mind and Medical Sciences

Introduction. The latest histological classification of lung adenocarcinoma includes lepidic, acinar, papillary, micropapillary, and solid as subtypes. Testing these subtypes for their prognostic and predictive value is an ongoing scientific challenge. The present research article aims to describe the influence this classification has on patient survival.

Materials and Methods. Thirty-three patients were included in the trial. The most important enrollment criterion was the clear specification of the adenocarcinoma subtype in the pathology report. Patients were stratified into three groups which included the adenocarcinoma pathological subtypes as follows: lepidic (LEP), acinar and papillary (ACN/PAP), and micropapillary/solid (MIP/SOL). The primary endpoint was …

Sentinel Lymph Node In Early Stage Ovarian Cancer; A Literature Review, Irina Balescu, Nicolae Bacalbasa, Mihaela Vilcu, Vladislav Brasoveanu, Iulian Brezean

Journal of Mind and Medical Sciences

Although sentinel lymph node mapping has been widely implemented in gynecological malignancies in order to minimize the number of unnecessary lymph node dissections and to diminish postoperative morbidity rate, little is known about ovarian cancer sentinel lymph node mapping. This article presents a literature review regarding the effectiveness, safety and benefits of this method.

Sentinel lymph node detection in early stage ovarian cancer seems to be a safe and effective method, able to minimize the rate of patients submitted to unnecessary lymph node dissection. The second goal of the procedure, to minimize the risk of missing involved lymph nodes, seems …

Biological Therapy In The Treatment Of Melanoma, Simona Roxana Georgescu, Mihaela Roxana Ioghen, Maria Isabela Sarbu, Alexandra-Florentina Ion, Ela Ghita, Cristina-Iulia Mitran, Madalina-Irina Mitran, Vasile Benea, Mircea Tampa

Journal of Mind and Medical Sciences

Melanoma is one of the most aggressive tumors and its incidence is on the rise. The low rates of survival in metastatic melanoma has led to the development of new drugs for this type of patient, such as biological therapy which has shown remarkable results. This therapy is based on stimulation of the immune system to fight tumoral cells through: injection of cytokines with immunomodulatory properties (interleukin-2, alpha-interferon), vaccination with tumor antigens or immune cells that process tumor antigens, adoptive immunotherapy, inhibition of immune checkpoints (PD-1, CTLA-4), inhibition or stimulation of immune modulator molecules (OX-40, LAG-3), inhibition of signaling pathways …

Control Of Ccnd1 Ubiquitylation By The Catalytic Saga Subunit Usp22 Is Essential For Cell Cycle Progression Through G1 In Cancer Cells., Victoria J. Gennaro, Timothy J. Stanek, Amy R. Peck, Yunguang Sun, Feng Wang, Shuo Qie, Karen E. Knudsen, Hallgeir Rui, Tauseef Butt, J. Alan Diehl, Steven B. Mcmahon

Department of Biochemistry and Molecular Biology Faculty Papers

Overexpression of the deubiquitylase ubiquitin-specific peptidase 22 (USP22) is a marker of aggressive cancer phenotypes like metastasis, therapy resistance, and poor survival. Functionally, this overexpression of USP22 actively contributes to tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro, and inhibits tumor progression in animal models of lung, breast, bladder, ovarian, and liver cancer, among others. Current models suggest that USP22 mediates these biological effects via its role in epigenetic regulation as a subunit of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional cofactor complex. Challenging the dogma, we report here a nontranscriptional role for USP22 via a direct effect on the …