Lakmani T. Galaniha and Alissa A. Nolden*

Department of Food Science, University of Massachusetts, Amherst, MA 01003, United States

Taste alterations, a common treatment-related side effect among cancer patients, with up to 93% complaining of taste-related symptoms. Even with its high prevalence, patients report a lack in support from clinicians. Clinicians’ perspective regarding taste alterations among cancer patients is not well understood. Thus, this study examines clinicians’ perspectives regarding taste alterations among cancer patients. In an online survey, sixty-seven clinicians practicing in the United States and working with cancer patients complaining of taste problems answered questions on their experience treating patients' taste alteration symptoms.

Clinicians are most concerned about the impact of taste alterations on nutritional intake, emotional distress, and overall quality of life. 73% reported understanding the patient's taste alterations was important or very important. Yet roughly 75% thought it was challenging to recommend strategies to manage their symptoms, and nearly all reported feeling frustrated when supporting patients’ taste alterations. Regarding management strategies, clinicians mostly suggested dietary counseling, drinking plenty of fluids during meals, and changing the texture of the food, with some success reported for these strategies. This study provides new insight into clinicians’ experiences supporting cancer patients with taste alterations, helping identify knowledge gaps. A lack of evidence-based taste management strategies poses a significant challenge for clinicians in managing patients' taste alterations. These results emphasize the need to develop education and training material and identify effective treatment strategies to assist clinicians in providing better-quality care for patients suffering from taste alterations.

DOI: 10.29245/2578-2967/2024/1.1207 View / Download Pdf

Ana Cvetkovic MD PhD1,3*, Dejan Stojiljkovic MD Phd2,3*, Dijana Mircic MD PhD1*, Nada Santrac MD PhD2,3, Milan Zegarac MD PhD2,3, Andrej Jokic MD1, Lazar Glisic MD PhD4

1Department of Anesthesiology with Reanimatology and Intensive Care Unit, Surgical Oncology Clinic, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia

2Department of Surgery, Surgical Oncology Clinic, institute for Oncology and Radiology of Serbia, Belgrade, Serbia

3Medical School, University of Belgrade, Belgrade, Serbia

4University Hospital for Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany

*All authors contributed equally as first authors

Background: Cytoreductive surgery (CRS) with hyperthermic intrathoracic chemotherapy (HITHOC) is a procedure that includes surgical removal of all visible tumor implants and intrathoracic application of gradually heated cytostatic solution. Numerous changes in hemodynamic, respiratory, core body temperature and metabolic parameters are possible during this complex procedure. The aim of this retrospective study was to analyze pathophysiological changes which occur during CRS + HITHOC procedure, and to suggest efficient strategies for perioperative patient care that might reduce complication rate.

Methods: The study included 7 patients who underwent CRS + HITHOC in our cancer center. Enhanced Recovery After Surgery (ERAS) guideline for Thoracic Surgery was applied to all patients. Data on intraoperative hemodynamics (mean arterial pressure, stroke volume, heart rate, cardiac output) and temperature variations were collected from medical records and analyzed in three timelines: during the CRS phase, at the beginning, and the end of cytostatic perfusion. Occurrence of respiratory, renal, and cardiac complications was monitored.

Results: All patients were respiratory stable during one-lung ventilation, with adequate gas exchange. Hemodynamic stability was compromised at the beginning of cytostatic perfusion, with significant decrease of mean arterial pressure and stroke volume. Two patients required vasopressor support. Average core body temperature was satisfactory in all patients. Coagulation disorders and acute renal failure were not recorded in postoperative period. One patient developed atrial fibrillation which was successfully pharmacologically restored.

Conclusion: Our results indicate that goal directed fluid management following ERAS protocol, with maintaining hemodynamic stability and normothermia, could prevent perioperative complications during HITHOC procedure.

DOI: 10.29245/2578-2967/2024/1.1204 View / Download Pdf

Brittany M Watts*, Monika D Vilardo, Christopher J La Placa, Judith Frederick, Siena Tabuena-Frolli, Malinka J Jansson, Kristopher J Kersch, Karina Kulangara, Kelly Martyniuk, Epiphani C Simmons, Stephanie A Hund

Agilent Technologies, Inc., 6392 Via Real, Carpinteria, California, USA

In the United States, the PD-L1 IHC 22C3 pharmDx indications for use have expanded to include the assay’s use as an aid in identifying triple-negative breast cancer (TNBC) patients for treatment with pembrolizumab (KEYTRUDA®). Analytical validation for TNBC was conducted by Agilent Technologies in support of the device performance and FDA-approval. Analytical validation studies included device precision (inter-instrument, inter-operator, inter-day, inter-lot, and intra-run) and external reproducibility (inter- and intra-site, inter- and intra-observer) using the Combined Positive Score (CPS) ≥ 10 cutoff. All precision and external reproducibility studies achieved confidence interval lower bound values of greater than 85% for positive, negative, and overall percent agreement. These analytical validation studies demonstrate that PD-L1 IHC 22C3 pharmDx is precise and reproducible in evaluating PD-L1 protein expression at a CPS ≥ 10 cutoff when used for testing TNBC tissues.

DOI: 10.29245/2578-2967/2023/1.1202 View / Download Pdf

Jennifer A. Marks, MD1, Zahraa Ghandour, MD2, Victoria Collins, MD2, John Schmieg, MD2, Thomas Atkinson, MD3

1Tulane University School of Medicine, New Orleans, LA

2Department of Pathology, Tulane University School of Medicine, New Orleans, LA

3Department of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA

Extranodal Natural Killer/T-cell lymphoma, Nasal Type is a rare and aggressive Non-Hodgkins Lymphoma associated with the Epstein-Barr Virus and Hemophagocytic Lymphohistiocytosis. We describe three patient presentations at two medical centers in New Orleans, Louisiana, observed within a six-month interval. Although the disease has a lower incidence in the US than in Asia and Latin America, the incidence appears to be on the rise. Due to the spectrum of clinical presentations and low index of suspicion for the disease, presenting signs and symptoms of ENKL may be misattributed to a non-neoplastic condition, resulting in a delay in diagnosis. Increased awareness of the clinical and pathologic spectrum of ENKL, particularly in non-endemic areas, remains an essential means of preventing delay in diagnosis and early initiation of treatment.

DOI: 10.29245/2578-2967/2022/3.1200 View / Download Pdf

Bach Ardalan1*, Jose Azqueta1, Jonathan England1, Danny Sleeman1, Rene Hartmann2

1Sylvester Comprehensive Cancer Center

2Baptist Hospital of Miami

Pancreatic adenocarcinoma has increasingly become one of the leading causes of death in western countries. However, presentation with colonic metastases is far less frequently reported in the literature and may be misdiagnosed as colonic adenocarcinoma. This is a case of a female patient with metastatic pancreatic adenocarcinoma that presented with a sigmoid obstruction.

DOI: 10.29245/2578-2967/2022/2.1199 View / Download Pdf

Beibei Liang1,2, Yangyang Xie1, Lisha Zhang1,3, Jian Zhao1,3*

1Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China

2Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai 201318, China

3Shanghai University of Traditional Medicine, Shanghai 201203, China

DOI: 10.29245/2578-2967/2022/1.1198 View / Download Pdf

Thomas E. Beesley1* and Mark V. Beesley2

1TEB Chiral View LLC, Consulting, Towaco, NJ 07082, USA

2MB Manufacturing, Blairstown, NJ 07825, USA

The tyrosine kinase inhibitor Neratinib has demonstrated its efficacy against HER2+ breast cancer metastases as the maleate salt. It has, however, had only a limited success as the maleate acid salt to cross the blood-brain barrier (BBB) due in part to its low oral absorption rate. At high oral doses severe diarrhea occurs. The potential to treat metastasized HER2+ cancer in the cerebellum and spinal cord that effects 30-50% of patients with this condition with a new crystalline salt and a topical application of a dimethyl sulfoxide (DMSO) solution has been investigated. This work proposes to use different Neratinib salts to improve solubility and BBB transport by a transdermal rather than an oral administration protocol. The preparation of the salts is described, and analytical methods developed for LC and LC/MS. The log P coefficient utilizing octanol/buffered water, shake flask method, will be used as a predictor of potential improvement in BBB transfer due to increased lipophilicity. Solubility data is supplied. An extensive review of DMSO and BBB experiments was undertaken leading to the establishment of rules to make this methodology work. First, a log P in the range of 2-4 is essential. Second, amine functions have to be blocked with suitable salts. If an amine function is present, it will be trapped by the endothelial membrane. DMSO has a well-documented favorable toxicological profile and can be sterilized making it safe for oral and parenteral routes. A transdermal protocol using Neratinib succinate in 20/20/60: H2O/EtOH/DMSO is described with all the safety measures presented.

DOI: 10.29245/2578-2967/2022/1.1197 View / Download Pdf

Justina A Ugwah1,4, Martin O’Sullivan2, Brian O’Donnell3, Eric J. Moore1,4*

1Life Sciences Interface, Tynadall National Institute, University College Cork, Ireland

2Department of Surgery, Cork University Hospital, Cork

3Department of Anaesthesia, Cork University Hospital, Cork

4School of Chemistry, University College Cork

Breast cancer is the second most occurring malignant disease in women. 1 in 9 women will be affected by this disease in their lifetime. The gold standard for breast cancer screening is the mammographic technique, which has its limitations especially for women aged below 40 as a result of breast density. Ongoing research are exploring techniques that can improve detection accuracy as well as reduce time and money spent in advanced stage treatment options. This review paper highlights the different technologies that have been developed for breast cancer diagnoses.

DOI: 10.29245/2578-2967/2021/2.1194 View / Download Pdf

Bogdan Domrachev1, Sitanshu Singh1, Dandan Li2, Udo Rudloff1,2*

1Rare Tumor Initiative, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

2Thoracic & GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

Cancer stem cells (CSCs) are subpopulations of tumor cells that possess abilities for self-renewal, differentiation, and tumor initiation. These rare but therapy-recalcitrant cells are assumed to repopulate tumors following administration of systemic chemotherapy driving therapy failure, tumor recurrence, and disease progression. In early clinical trials, anti-CSC therapies have found limited success to-date possibly due to the inherent heterogeneity and plasticity of CSCs and the incomplete characterization of essential CSC targets. Here, we review the role of 3-phosphoinositide dependent protein kinase-1 (PDPK1) as an emerging CSC target. While most previous studies have relied on CSC models which are based on lineage and tissue-specific marker profiles to define the relationships between putative target and CSC traits, this review discusses PDPK1 and its role in CSC biology with an emphasis on CSC systems which are based on proposed function like label-retaining cancer cells (LRCCs).

DOI: 10.29245/2578-2967/2021/1.1194 View / Download Pdf

Justina Ugwah5, Niall Savage1, Walter Messina1, Yineng Wang5, Edel Whelton5, Ann-Marie O’Donovan3, Martin J.O’Sullivan2, Brian D.O. Donnell2,4, Eric J. Moore1,5*

1Life Sciences Interface, Tynadall National Institute, University College Cork, Ireland

2Department of Surgery, Cork University Hospital, Cork

3Department of Pathology, Cork university Hospital, Cork

4Department of Anaesthesia, Cork University Hospital, Cork

5School of Chemistry, University College Cork

Bioimpedance is the opposition to flow of an applied electrical current through biological tissues1. Our research group designed and fabricated bipolar micro-sensors on the tip of a silicone probe, capable of measuring biological tissue impedance. It is known that the bioimpedance of cultured cancer cells differs substantially from that of healthy cell lines. We hypothesised that the bioimpedance of cancer in surgically excised human tissue would be significantly different to surrounding healthy tissue. To test this hypothesis, we designed a study to evaluate the bioimpedance of healthy and diseased breast tissue in surgically excised breast specimens. This manuscript reports the outcome of this study.

DOI: 10.29245/2578-2967/2021/1.1193 View / Download Pdf

Christopher J. La Placa1*, Monika D. Vilardo1, Brittany M. Watts1, Monika D. Polewski1, Siena Tabuena-Frolli1, Malinka Jansson1, Kenneth Emancipator1, Fan Jin1, Burak Gumuscu1, Joy Y. Ge2, Michael DiMaio1, Karina Kulangara1*

1Agilent Technologies, Inc. 6392 Via Real, Carpinteria, California, United States

2Merck & Co., Inc. 2000 Galloping Hill Road, Kenilworth, New Jersey, United States

Objectives: FDA approval of PD-L1 IHC 22C3 pharmDx for use as an aid in identifying head and neck squamous cell carcinoma (HNSCC) patients for treatment with pembrolizumab was based on the results of rigorous analytical and clinical validation testing.

Methods: For the HNSCC indication, the device was validated at Agilent Technologies on the performance of sensitivity and precision using the Combined Positive Score (CPS) ≥ 1 and CPS ≥ 20 cutoffs; external validation studies were performed at three external laboratories. CPS ≥ 1 and CPS ≥ 20 cutoffs were evaluated in KEYNOTE-048, a phase 3 clinical trial.

Results: Analytical validation studies supporting the companion diagnostic indication (CPS ≥ 1) achieved point estimates of > 85% for negative, positive, and overall percent agreement. Clinical validation studies show that HNSCC patients treated with pembrolizumab as a single agent had an overall survival (OS) of 12.3 months at CPS ≥ 1 (95% CI, 10.8-14.9) compared with patients receiving cetuximab, platinum, and 5-fluorouracil (CPS ≥ 1 OS of 10.3 months (95% CI, 9.0-11.5)).

Conclusion: Analytical and clinical validation studies demonstrate that PD-L1 IHC 22C3 pharmDx is a precise companion diagnostic assay, allowing for selection of eligible HNSCC patients for treatment with pembrolizumab.

DOI: 10.29245/2578-2967/2021/1.1190 View / Download Pdf

Julian N. Kenyon1*

1The Dove Clinic, Twyford, Winchester, Hampshire, SO21 1NT, England

Sono and Photodynamic Therapy (SPDT) is a novel therapeutic modality that utilises a non-toxic photosensitive agent with reported ultrasound-activated properties. SPDT has previously demonstrated significant tumour cell inhibition in animal studies. There has been much research into the efficacy of photodynamic therapy and development in understanding of the underlying mechanism of tumour cytotoxicity. Synergistic ultrasound activation represents a promising development to Photodynamic Therapy, as photo-activation is limited by access and penetrance issues. Ultrasound has been demonstrated to activate a number of sono-sensitive agents allowing the possibility of non-invasive targeted treatment of deeper tumour sites than is currently achievable with photodynamic therapy. This case series of 17 consecutive patients with a variety of cancer diagnoses outlines clinical outcomes over a four-year period of SPDT. The results have been encouraging in that all cases who carried our Circulating Tumour Cell Tests before and after SPDT showed a significant drop in tumour cells post-SPDT. SPDT is worthy of further investigation as an effective and well tolerated treatment for a wide variety of primary and metastatic tumours, including those refractory to Chemotherapy.

DOI: 10.29245/2578-2967/2021/1.1195 View / Download Pdf

Yi-Liu Yang1, Lin-Yong Zhao2*

1West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China

2Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China

The AP-2 family of transcription factors consist of DNA-binding proteins: AP-2α to AP-2ε. Members and homologs of this family are also known in frogs, fish and invertebrates. These proteins have the same central basic region and a helix-span-helix dimerization motif, which is necessary for dimerization and DNA binding. This family have been found to influence facial, limbs and kidney development in embryogenesis while regulating differentiation and apoptosis. These proteins are also involved in regulation of endocrine processes. In addition to their influence on growth and development, this family have also been reported to correlate with tumorigenesis and development of cancer. At present, this family have been related to tumors of ovary, melanoma, lung, nasopharynx, breast, glioma, neuroblastoma, colon, etc. They regulate expression of many cancer-related genes and affect the occurrence, development, invasiveness and therapeutic response of cancers. Different expression levels of AP-2s are also related to different survival rate. These findings may bring new idea to the diagnosis, classification, treatment and prognosis of cancer.

DOI: 10.29245/2578-2967/2021/1.1187 View / Download Pdf

Saranya Navaneetha Krishnan1, Jesusa L. Rosales1, Ki-Young Lee1*

1Department of Cell Biology & Anatomy, Arnie Charbonneau Cancer and Alberta Children’s Hospital Research Institutes, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

DOI: 10.29245/2578-2967/2021/1.1189 View / Download Pdf

Cary A. Presant1*, Shanmuga Subbiah1, Gargi Upadhyaya1, Meizi Zheng1

1City of Hope Medical Center, West Covina, CA, USA

In order to determine the frequency of cannabis product (marijuana, THC or CBD) use and determine the patient reported outcomes to control symptoms, an anonymous survey of cannabis product use was conducted in patients who had cancer, non-malignant hematologic disorders or other diseases. Patients reported the degree of control of symptoms using a Likert scale. The use of cannabis products was 23.3% (36 users in 154 patients). This did not vary by age, gender, or disease. Use was predominately CBD in patients over 65, but was either marijuana, THC or CBD in younger patients. Patients reported some degree of control of at least one symptom in 91.9%, and high degree of control in 51.7% of patients. Most patients relied on recommendations of family or friends to try cannabis, but only 4% relied on clinician advice. 53% of patients said they were willing to consider participating in a prospective clinical trial of cannabis products to control symptoms. We conclude that cannabis product use is frequent in cancer patients. Physicians should obtain a detailed history of cannabis product use in patients, and could consider a therapeutic trial of cannabis products in selected patients with symptoms not controlled by usual treatments. Clinicians may need additional education to provide the highest level of evidence-based support for cannabis product use in patients in need of symptom control.

DOI: 10.29245/2578-2967/2020/4.1188 View / Download Pdf

Gerald Zon*

TriLink BioTechnologies, 10770 Wateridge Circle, Suite 200, San Diego, California, 92121, USA

Aptamers, which are short strands of synthetic DNA or RNA selected for binding to target ligands, have proven useful for cell-specific delivery, detection, or both. This mini-review presents selected examples of these applications for cancer published during 2019 – September 2020.

DOI: 10.29245/2578-2967/2020/3.1186 View / Download Pdf

Qianqian Yu1, Zhihuan Li2, Xiaoqi Nie1, Lu Wang1, Chen Gong1, Bo Liu1, Xin Liao3, Ben Zhao1, Qianxia Li1, Mingsheng Zhang1, Hong Qiu1, Xianglin Yuan1*

1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

2Dongguan Enlife Stem Cell Biotechnology Institute, Dongguan 523000, Guangdong, China

3Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China

Irinotecan-based chemotherapy is a fundamental cytotoxic regimen for advanced colorectal cancer. The disposition of irinotecan is known to vary in a fashion partially depending on genetic variations in the drug metabolic pathways. UDP-glucuronosyltransferase (UGT)1A1 is a predominant enzyme that converts the active metabolite of irinotecan to the inactive form via a glucuronidation process. Several UGT1A1 polymorphisms are linked to SN-38 glucuronidation and irinotecan-related adverse events, while the predictive role of UGT1A1 polymorphisms regarding therapeutic outcome is controversial. In this review, we will evaluate the impact of UGT1A1 genotypes on irinotecan-induced toxicity and therapeutic efficacy in colorectal cancer patients receiving irinotecan-based treatment.

DOI: 10.29245/2578-2967/2020/2.1182 View / Download Pdf

Francesca Dionigi1,2*, Valentina Martinelli3, Eugenia Trotti3, Alberta Ferrari2,5, Carlos Alberto Garcia Etienne2, Angelica Della Valle2, Donatella Grasso6, Elisa Ferraris6, Gianpiero Rizzo6, Angioletta Lasagna6, Vincenza Pratico2, Paolo Pedrazzoli, Pierluigi Politi6, Adele Sgarella2,5

1Dottorato di Ricerca in Medicina Sperimentale, Università degli Studi di Pavia, 27100, Pavia, Italy

2Fondazione IRCCS Policlinico “San Matteo”, Unità Operativa Complessa di Chirurgia Generale III a indirizzo Senologico e dei tessuti molli, viale Golgi 19, 27100, Pavia, Italy

3Dipartimento di Medicina e Sanità Pubblica, Università dell'Insubria, via Ottorino Rossi 9, 21010 Varese, Italy

4Department of Biotechnology and Life Sciences, Università degli Studi dell’Insubria, via Ottorino Rossi 9, 21010, Varese, Italy

5Università degli Studi di Pavia, Pavia, Italy

6Fondazione IRCCS Policlinico “San Matteo”, Unità Operativa Complessa di Oncologia Medica, Pavia, Italy

We present our commentary about the case of a 48-year-old woman diagnosed with early breast cancer, already presented as publication. A candidate for mastectomy, she refused immediate reconstruction. She was referred to a psycho-oncologist for further evaluation and support. Psychological sessions helped reveal a history of intimate partner violence and helped clarify the reason for her refusal to undergo immediate reconstruction and other uncommon behavior about oncological treatment and disease paths. Our experience highlights the importance of a multidisciplinary practice in which collaboration between surgeons, oncologists, and mental health professionals leads to a more in-depth understanding of the apparently paradoxical behaviors of patients, and to better care for their needs.

DOI: 10.29245/2578-2967/2020/2.1181 View / Download Pdf

Juwairiya Arshi1, Feng Yin1*

1Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri, USA

Sarcomatoid transformation in a carcinoma is a rare event but frequently associated with advanced disease stage, aggressive clinical behavior and dismal prognosis. It’s likely a result of stepwise gene mutations in pluripotent stem cell and involves the epithelial to mesenchymal transition (EMT). In this review, we discuss the sarcomatoid transformation in various types of cancers. Sarcomatoid transformation in a carcinoma should always be in the differential when there is a sudden increase in size of the tumor during neoadjuvant therapy. Use of agents that interfere with the tyrosine kinase pathway might be the new potential addition to the chemotherapy regimen in these cases. Precision medicine, a rapidly emerging field, seems to be promising in the management of these cancers.

DOI: 10.29245/2578-2967/2020/2.1178 View / Download Pdf

Saranya NavaneethaKrishnan1, Jesusa L. Rosales1, Ki-Young Lee1*

1Department of Cell Biology & Anatomy, Arnie Charbonneau Cancer and Alberta Children’s Hospital Research Institutes, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

DOI: 10.29245/2578-2967/2020/2.1180 View / Download Pdf

Ryan Nguyen1, Cody J. Peer1, William D. Figg1*

1Clinical Pharmacology Program, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Herein, the strengths and weaknesses of a study previously published in Scientific Reports will be discussed. The major aim of this study was to investigate the spatial uptake of enzalutamide by intact prostate tissue using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and histological staining. Additionally, quantitative analysis of in situ tissue enzalutamide concentration was achieved by conventional liquid chromatography-tandem mass spectrometry (LC-MS/MS). The authors demonstrated that enzalutamide rapidly permeates prostate tissue and accumulates in regions containing high epithelial cell counts. While these findings have potential to inform future pharmacodynamic experimental designs and endpoints, this study is limited in its scope by the current state of MALDI-MSI technology, which is not yet sensitive enough to investigate clinically relevant in situ enzalutamide concentrations.

DOI: 10.29245/2578-2967/2020/2.1183 View / Download Pdf

A. H. M. Zuberi Ashraf1,2, Syeda H. Afroze3, Grace A. Osuji2, Saba Y. Kayani3, Natalie Colon3, Ahmed F. Pantho3, Thomas J. Kuehl3, Kimberly A Pilkinton4, M. Nasir Uddin3,5

1Department of Science & Mathematics, Texas A&M University-Central Texas, Killeen, TX, U.S.A.

2Baylor Scott & White Health, Temple, TX, U.S.A.

3Orion Institute for Translational Medicine, Temple, TX, U.S.A.

4Department of Clinical Sciences, University of Houston College of Medicine, Houston, TX, U.S.A.

5Department of Medical Physiology, Texas A&M University College of Medicine, Temple, TX, U.S.A.

The purpose of this article is to review the role of different epigenetic modifications in ovarian cancer. Epigenetic changes can lead to disease development, malignant transformation, and drug resistance of ovarian cancer. Silencing, methylation, and histone modification of genes contribute to ovarian cancer formation. miRNAs have frequently been found to be dysregulated in ovarian cancer cells. Cancer stem cells possess incredible DNA-repair mechanisms and higher rates of mutation; therefore, making them very invasive and resistant to most chemotherapeutic agents. The pathogenesis of ovarian cancer, types of epigenetic modifications, role of miRNA, and cancer stem cells are discussed, as well as targeting of epigenetic pathways with alternative interventions, and application of combination therapies. Using newly discovered combination therapies, it might be possible to create means to manipulate the detrimental epigenetic pathways which can lead to earlier detection, prevention, and treatment of ovarian cancer.

DOI: 10.29245/2578-2967/2020/2.1179 View / Download Pdf

Xianglong Tan1, Mengyang Li2, Zhiming Zhao1*

1The Second Department of Hepatopancreatobiliary Surgery, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, China

2Department of Hepatopancreatobiliary Surgery, The Fourth Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, China

Liver metastases occur during the progression of various malignancies. Similar to colorectal cancer, liver metastases of neuroendocrine cancer, gastrointestinal stromal tumor, and pancreatic cancer also determine patient prognosis to some extent. With the development of surgical techniques, pharmaceutical research, and perioperative treatment, therapeutic strategies for non-colorectal cancer liver metastases have improved greatly during the last two decades, inevitably leading to some controversies. Here, we have reviewed the current treatment options for non-colorectal cancer with the aim of enhancing our understanding of the latest developments in this field.

DOI: 10.29245/2578-2967/2020/2.1177 View / Download Pdf

Sruti Chandra1, Hoang Michael Nguyen1, Kylar Wiltz1, Nicholas Hall1, Shanzay Chaudhry1, George Olverson1, Tarun Mandal2, Srikanta Dash3, Anup Kundu1*

1Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana

2Center for Nanomedicine and Drug Delivery, Xavier University College of Pharmacy, New Orleans, Louisiana

3Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana

OBJECTIVE: The MDR of metastatic breast cancer cells is accompanied by the overexpression of P-gp transporter. This study has been focused to determine whether silencing the expression of P-gp by aptamer-labeled siRNA nanoparticles could enhance the delivery of doxorubicin into breast cancer cells in culture.

METHODOLOGY: The nanoparticle F-31 was prepared using DOTAP, cholesterol, and PLGA, and then incorporating Mal-PEG to facilitate aptamer-binding. The nanoparticles were surface-functionalized with aptamer A6, which targets Her-2 receptors overexpressed on the surface of breast cancer cells.

RESULTS: This study has shown that the uptake of Dox by Dox-resistant 4T1-R is significantly less than Dox-sensitive 4T1-S which is partly attributed to the higher expression of drug-efflux pump P-gp on the surface of the resistant cells. The targeted knockdown of P-gp has been enhanced when the particles carrying P-gp siRNA was labeled with aptamer. Concurrently, the uptake of Dox into the Dox-resistant 4T1-R breast cancer cells has increased significantly when the P-gp was silenced by P-gp siRNA-encapsulated aptamer-labeled nanoparticles.

CONCLUSIONS: This preliminary study concludes that downregulating P-gp expression by targeted delivery of P-gp siRNA using aptamer-labeled lipid-based hybrid nanoparticles could effectively increase the intracellular trafficking of doxorubicin in Dox-resistant mouse breast cancer cells.

DOI: 10.29245/2578-2967/2020/1.1176 View / Download Pdf

Dexter P. Mendoza1, Subba R. Digumarthy1*

1Department of Radiology, Division of Thoracic Imaging and Intervention, Massachusetts General Hospital, USA

DOI: 10.29245/2578-2967/2019/4.1174 View / Download Pdf