16 results on '"Taja Lozar"'
Search Results
2. Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review
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Taja Lozar, Wei Wang, Niki Gavrielatou, Leslie Christensen, Paul F. Lambert, Paul M. Harari, David L. Rimm, Barbara Burtness, Cvetka Grasic Kuhar, and Evie H. Carchman
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prognostic biomarker ,predictive biomarker ,cytokeratin 17 ,stress keratin 17 ,Microbiology ,QR1-502 - Abstract
A growing body of literature suggests that the expression of cytokeratin 17 (K17) correlates with inferior clinical outcomes across various cancer types. In this scoping review, we aimed to review and map the available clinical evidence of the prognostic and predictive value of K17 in human cancers. PubMed, Web of Science, Embase (via Scopus), Cochrane Central Register of Controlled Trials, and Google Scholar were searched for studies of K17 expression in human cancers. Eligible studies were peer-reviewed, published in English, presented original data, and directly evaluated the association between K17 and clinical outcomes in human cancers. Of the 1705 studies identified in our search, 58 studies met criteria for inclusion. Studies assessed the prognostic significance (n = 54), predictive significance (n = 2), or both the prognostic and predictive significance (n = 2). Altogether, 11 studies (19.0%) investigated the clinical relevance of K17 in cancers with a known etiologic association to HPV; of those, 8 (13.8%) were focused on head and neck squamous cell carcinoma (HNSCC), and 3 (5.1%) were focused on cervical squamous cell carcinoma (SCC). To date, HNSCC, as well as triple-negative breast cancer (TNBC) and pancreatic cancer, were the most frequently studied cancer types. K17 had prognostic significance in 16/17 investigated cancer types and 43/56 studies. Our analysis suggests that K17 is a negative prognostic factor in the majority of studied cancer types, including HPV-associated types such as HNSCC and cervical cancer (13/17), and a positive prognostic factor in 2/17 studied cancer types (urothelial carcinoma of the upper urinary tract and breast cancer). In three out of four predictive studies, K17 was a negative predictive factor for chemotherapy and immune checkpoint blockade therapy response.
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- 2023
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3. Betapapillomaviruses in p16-Negative Vulvar Intraepithelial Lesions Associated with Squamous Cell Carcinoma
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Taja Lozar, Aysenur Keske, Racheal S. Dube Mandishora, Qiqi Yu, Adam Bailey, Jin Xu, Massimo Tommasino, Stephanie M. McGregor, Paul F. Lambert, Tarik Gheit, and Megan B. Fitzpatrick
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beta human papillomavirus ,vulvar cancer ,vulvar precancer ,Microbiology ,QR1-502 - Abstract
Approximately 40% of vulvar squamous cell carcinoma (vSCC) cases are etiologically associated with high-risk human papillomaviruses (HPVs) of the alpha genera (α-HPV) that cause other anogenital cancers; however, the etiology of α-HPV-negative vSCC is poorly understood. HPVs of the beta genera (β-HPV) are risk factors for cutaneous squamous cell carcinoma (cSCC) and may be related to carcinomas originating in other cutaneous sites such as the vulva. In this study, we investigate the presence of β-HPVs, with an emphasis on p16-negative squamous lesions adjacent to vSCC. We subjected 28 vulvar squamous intraepithelial lesions adjacent to vSCC for comprehensive HPV genotyping, p16 and p53 immunohistochemistry, and consensus morphology review. Selected cases were subjected to qPCR and RNA in situ hybridization. Clinical data were obtained from medical records. β-HPV DNA was detected in eight of ten p16-negative lesions and three of fourteen p16-positive high-grade squamous intraepithelial lesions. The HPV DNA loads in vulvar squamous intraepithelial lesions ranged between less than 1 HPV DNA copy per cell to more than 100 HPV DNA copies per cell. This is, to the best of our knowledge, the first report of the association of p16-negative vulvar intraepithelial squamous lesions with detection of β-HPVs. These findings expand possible etiologic mechanisms that may contribute to p16-negative lesions of the vulva.
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- 2023
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4. A case of metastatic renal cell carcinoma with concomitant Castleman's disease treated with immunotherapy
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Taja Lozar, Matthew J. Brunner, Sujal I. Shah, Christos E. Kyriakopoulos, and Hamid Emamekhoo
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Castleman's disease ,RCC ,Immunotherapy ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Brief abstract: Castleman's disease (CD) is an uncommon lymphoproliferative process that can present concurrent to other solid organ malignancy, especially in selected populations. Concomitant CD and renal cell carcinoma (RCC) are challenging in terms of diagnosis and treatment. Assessment of CD involvement is a crucial step in selecting the optimal treatment strategy. Here we report a case of metastatic RCC and concurrent CD treated with surgery and immunotherapy.
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- 2021
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5. Preclinical and Clinical Evaluation of Magnetic-Activated Cell Separation Technology for CTC Isolation in Breast Cancer
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Taja Lozar, Tanja Jesenko, Veronika Kloboves Prevodnik, Maja Cemazar, Violeta Hosta, Anja Jericevic, Natasa Nolde, and Cvetka Grasic Kuhar
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liquid biopsy ,magnetic-activated cell separation ,circulating tumor cells ,morphology ,breast cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Circulating tumor cell (CTC) count is an independent prognostic factor in early breast cancer. CTCs can be found in the blood of 20% of patients prior to neoadjuvant therapy. We aimed to assess the suitability of magnetic-activated cell separation (MACS) technology for isolation and cytological characterization of CTCs. In the preclinical part of the study, cell lines were spiked into buffy coat samples derived from healthy donors, and isolated using MACS. Breast cancer cells with preserved cell morphology were successfully isolated. In the clinical part, blood for CTC isolation was drawn from 44 patients with early and locally advanced breast cancer prior to neoadjuvant chemotherapy. Standard Giemsa, Papanicolaou and pancytokeratin staining was applied. 2.3% of samples contained cells that meet both the morphological and immunocytochemical criteria for CTC. In 32.6% of samples, partially degenerated pancytokeratin negative cells with morphological features of tumor cells were observed. In 65.1% of samples, CTCs were not found. In conclusion, our results demonstrate that morphologically intact tumor cells can be isolated using MACS technology. However, morphologically intact tumor cells were not detected in the clinical part of the study. At present, MACS technology does not appear suitable for use in a clinical cytopathology laboratory.
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- 2020
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6. Data from Stress Keratin 17 Expression in Head and Neck Cancer Contributes to Immune Evasion and Resistance to Immune-Checkpoint Blockade
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Paul F. Lambert, Huy Q. Dinh, Megan B. Fitzpatrick, Paul M. Sondel, Aysenur Keske, Jin Xu, Paul M. Harari, Rong Hu, Randall J. Kimple, Justine Y. Bruce, Mitchell Hayes, Ella Ward-Shaw, Ellery Gronski, Denis Lee, Athena E. Golfinos, Taja Lozar, and Wei Wang
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Purpose:We investigated whether in human head and neck squamous cell carcinoma (HNSCC) high levels of expression of stress keratin 17 (K17) are associated with poor survival and resistance to immunotherapy.Experimental Design:We investigated the role of K17 in regulating both the tumor microenvironment and immune responsiveness of HNSCC using a syngeneic mouse HNSCC model, MOC2. MOC2 gives rise to immunologically cold tumors that are resistant to immune-checkpoint blockade (ICB). We engineered multiple, independent K17 knockout (KO) MOC2 cell lines and monitored their growth and response to ICB. We also measured K17 expression in human HNSCC of patients undergoing ICB.Results:MOC2 tumors were found to express K17 at high levels. When knocked out for K17 (K17KO MOC2), these cells formed tumors that grew slowly or spontaneously regressed and had a high CD8+ T-cell infiltrate in immunocompetent syngeneic C57BL/6 mice compared with parental MOC2 tumors. This phenotype was reversed when we depleted mice for T cells. Whereas parental MOC2 tumors were resistant to ICB treatment, K17KO MOC2 tumors that did not spontaneously regress were eliminated upon ICB treatment. In a cohort of patients with HNSCC receiving pembrolizumab, high K17 expression correlated with poor response. Single-cell RNA-sequencing analysis revealed broad differences in the immune landscape of K17KO MOC2 tumors compared with parental MOC2 tumors, including differences in multiple lymphoid and myeloid cell types.Conclusions:We demonstrate that K17 expression in HNSCC contributes to immune evasion and resistance to ICB treatment by broadly altering immune landscapes of tumors.
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- 2023
7. Supplementary Data from Stress Keratin 17 Expression in Head and Neck Cancer Contributes to Immune Evasion and Resistance to Immune-Checkpoint Blockade
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Paul F. Lambert, Huy Q. Dinh, Megan B. Fitzpatrick, Paul M. Sondel, Aysenur Keske, Jin Xu, Paul M. Harari, Rong Hu, Randall J. Kimple, Justine Y. Bruce, Mitchell Hayes, Ella Ward-Shaw, Ellery Gronski, Denis Lee, Athena E. Golfinos, Taja Lozar, and Wei Wang
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Supplementary Data from Stress Keratin 17 Expression in Head and Neck Cancer Contributes to Immune Evasion and Resistance to Immune-Checkpoint Blockade
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- 2023
8. Supplementary Figure from Stress Keratin 17 Expression in Head and Neck Cancer Contributes to Immune Evasion and Resistance to Immune-Checkpoint Blockade
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Paul F. Lambert, Huy Q. Dinh, Megan B. Fitzpatrick, Paul M. Sondel, Aysenur Keske, Jin Xu, Paul M. Harari, Rong Hu, Randall J. Kimple, Justine Y. Bruce, Mitchell Hayes, Ella Ward-Shaw, Ellery Gronski, Denis Lee, Athena E. Golfinos, Taja Lozar, and Wei Wang
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Supplementary Figure from Stress Keratin 17 Expression in Head and Neck Cancer Contributes to Immune Evasion and Resistance to Immune-Checkpoint Blockade
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- 2023
9. Cervical Cancer Screening Postpandemic: Self-Sampling Opportunities to Accelerate the Elimination of Cervical Cancer
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Racheal S. Dube Mandishora, Urška Ivanuš, Rahul Nagvekar, Charles Rohrer, Taja Lozar, and Megan B. Fitzpatrick
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Cervical cancer ,HPV testing ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Incidence (epidemiology) ,Public health ,cervical cancer screening ,Obstetrics and Gynecology ,self-sampling ,COVID-19 ,Review ,Cervical cancer screening ,medicine.disease ,self-collection ,Underserved Population ,Oncology ,Maternity and Midwifery ,Pandemic ,medicine ,business ,Intensive care medicine ,Self sampling - Abstract
The persisting burden of cervical cancer in underserved populations and low-resource regions worldwide, worsened by the onset of the COVID-19 pandemic, requires proactive strategies and expanded screening options to maintain and improve screening coverage and its effects on incidence and mortality from cervical cancer. Self-sampling as a screening strategy has unique advantages from both a public health and individual patient perspective. Some of the barriers to screening can be mitigated by self-sampling, and resources can be better allocated to patients at the highest risk of developing cervical cancer. This review summarizes the implementation options for self-sampling and associated challenges, evidence in support of self-sampling, the available devices, and opportunities for expansion beyond human papillomavirus testing.
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- 2021
10. Stress Keratin 17 expression in head and neck cancer contributes to immune evasion and resistance to immune checkpoint blockade
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Wei Wang, Taja Lozar, Athena E. Golfinos, Denis Lee, Ellery Gronski, Ella Ward-Shaw, Mitchell Hayes, Justine Y. Bruce, Randall J. Kimple, Rong Hu, Paul M. Harari, Jin Xu, Aysenur Keske, Paul M. Sondel, Megan B. Fitzpatrick, Huy Q. Dinh, and Paul F. Lambert
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Cancer Research ,Keratin-17 ,Squamous Cell Carcinoma of Head and Neck ,Article ,Mice, Inbred C57BL ,Mice ,Oncology ,Head and Neck Neoplasms ,Tumor Microenvironment ,Animals ,Humans ,Keratins ,Immune Checkpoint Inhibitors ,Immune Evasion - Abstract
Purpose: We investigated whether in human head and neck squamous cell carcinoma (HNSCC) high levels of expression of stress keratin 17 (K17) are associated with poor survival and resistance to immunotherapy. Experimental Design: We investigated the role of K17 in regulating both the tumor microenvironment and immune responsiveness of HNSCC using a syngeneic mouse HNSCC model, MOC2. MOC2 gives rise to immunologically cold tumors that are resistant to immune-checkpoint blockade (ICB). We engineered multiple, independent K17 knockout (KO) MOC2 cell lines and monitored their growth and response to ICB. We also measured K17 expression in human HNSCC of patients undergoing ICB. Results: MOC2 tumors were found to express K17 at high levels. When knocked out for K17 (K17KO MOC2), these cells formed tumors that grew slowly or spontaneously regressed and had a high CD8+ T-cell infiltrate in immunocompetent syngeneic C57BL/6 mice compared with parental MOC2 tumors. This phenotype was reversed when we depleted mice for T cells. Whereas parental MOC2 tumors were resistant to ICB treatment, K17KO MOC2 tumors that did not spontaneously regress were eliminated upon ICB treatment. In a cohort of patients with HNSCC receiving pembrolizumab, high K17 expression correlated with poor response. Single-cell RNA-sequencing analysis revealed broad differences in the immune landscape of K17KO MOC2 tumors compared with parental MOC2 tumors, including differences in multiple lymphoid and myeloid cell types. Conclusions: We demonstrate that K17 expression in HNSCC contributes to immune evasion and resistance to ICB treatment by broadly altering immune landscapes of tumors.
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- 2022
11. Ototoxicity of Long-Term α-Difluoromethylornithine for Skin Cancer Prevention
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Cynthia L. Chow, Thomas Havighurst, Taja Lozar, Todd D. Jones, KyungMann Kim, and Howard H. Bailey
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Otorhinolaryngology - Abstract
Evaluate the effects of α-difluoromethylornithine (DFMO) on hearing thresholds as part of a randomized, double-blind, placebo-controlled trial.Subjects were randomized and assigned to the control (placebo) or experimental (DFMO) group. DFMO or placebo were administered orally (500 mg/mSubjects taking DFMO had, on average, increased hearing thresholds from baseline across the frequency range compared to subjects in the control group. Statistical analysis revealed this was significant in the lower frequency range.This randomized controlled trial revealed the presence of increased hearing thresholds associated with long-term DFMO use. As a whole, DFMO may help prevent and treat certain types of cancers; however, it can result in some degree of hearing loss even when administered at low doses. This study further highlights the importance of closely monitoring hearing thresholds in subjects taking DFMO. Laryngoscope, 2022.
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- 2022
12. A randomized, double-blind, dose-ranging, pilot trial of piperine with resveratrol on the effects on serum levels of resveratrol
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Taja Lozar, Barbara W. Wollmer, Cameron O. Scarlett, Thomas Havinghurst, Howard H. Bailey, KyungMann Kim, Nihal Ahmad, and Jeremy J. Johnson
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Cancer Research ,endocrine system diseases ,Polyunsaturated Alkamides ,Epidemiology ,Cmax ,Pilot Projects ,Resveratrol ,Pharmacology ,Article ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Alkaloids ,Glucuronides ,0302 clinical medicine ,Piperidines ,Pharmacokinetics ,Animals ,Humans ,Benzodioxoles ,030212 general & internal medicine ,skin and connective tissue diseases ,Adverse effect ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Chemistry ,organic chemicals ,Phytoalexin ,Public Health, Environmental and Occupational Health ,food and beverages ,Bioavailability ,Oncology ,030220 oncology & carcinogenesis ,Piperine ,Toxicity ,Female ,hormones, hormone substitutes, and hormone antagonists - Abstract
Resveratrol (3,4,5-trihydroxystilbene) is a naturally occurring phytoalexin with purported health-promoting effects, but with limited oral bioavailability. Our prior murine modeling research observed enhanced resveratrol bioavailability with piperine co-administration. In this study, single-dose pharmacokinetics of resveratrol with or without piperine and the associated toxicities were studied on a cohort of healthy volunteers. We performed a double-blind, randomized, three-arm pilot study. Participants were randomized to receive a single dose of resveratrol 2.5 g, with piperine in 0 mg, 5 mg, or 25 mg dose. An improved liquid chromatography/mass spectrometry assay was used to determine serum levels of resveratrol and resveratrol-glucuronide. Baseline through 24 h post-study drug serum analyses were performed and adverse events were followed for 30 days. Twenty-four participants were enroled. No significant relationship between dose and pharmacokinetic values were found. In the sex stratified analysis, Cmax for resveratrol in women showed a trend (P = 0.057) toward an increase with piperine. Pharmacokinetic values for resveratrol were: Cmax - 18.5 ± 16 ng/mL resveratrol alone, 29 ± 29 resveratrol + 5 mg piperine, 16 ± 13 resveratrol + 25 mg piperine; area under the concentration × time curve - 1270 ± 852 ng/h/mL resveratrol alone, 2083 ± 2284 resveratrol + 5 mg piperine, 1132 ± 222 resveratrol + 25 mg piperine. All subjects tolerated their protocol therapy with minimal to no toxicity and no evidence of differences between the three groups. The co-administration of resveratrol with piperine at 5 and 25 mg doses did not sufficiently alter the pharmacokinetics of resveratrol or resveratrol-glucuronide to demonstrate the significant enhancement observed in murine modeling.
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- 2020
13. Outcome of Patients with Locally Advanced Metastatic Medullary Thyroid Cancer and Induction Therapy with Tyrosine Kinase Inhibitors in Slovenia
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Maja Music Marolt, Cvetka Grasic Kuhar, Taja Lozar, and Nikola Besic
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Oncology ,Male ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Slovenia ,Tyrosine-kinase inhibitor ,Metastasis ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Thyroid Neoplasms ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies ,Chemotherapy ,business.industry ,Sunitinib ,Medullary thyroid cancer ,Cancer ,General Medicine ,Induction Chemotherapy ,Middle Aged ,medicine.disease ,Primary tumor ,Carcinoma, Neuroendocrine ,Female ,business ,Progressive disease ,medicine.drug - Abstract
The aim of our retrospective study was to evaluate the outcome of patients with metastatic medullary thyroid cancer (MTC) treated with tyrosine kinase inhibitors (TKIs) and/or chemotherapy with the emphasis on analysis on the cohort treated by induction TKI because of locally advanced metastatic MTC. We analyzed the outcome of 30 patients (21 males, 9 females; median age 63.8 years) with metastatic MTC treated between 2000–2020. Sunitinib was used in 20 patients. Median progression-free survival on TKI and on chemotherapy was 10.6 (95% CI 7.1–14) months and 3.5 (95% CI 1.4–5.5) months, respectively. Median overall survival from diagnosis and from metastasis presentation was 38.2 (95% CI 4.7–71.7) months and 20.9 (95% CI 13.8–27.9) months, respectively. Eight patients (five females, three males; 58–86 years of age, median age 70 years) were treated with induction TKI because of inoperable locally advanced and metastatic MTC. The response rate to induction TKI was 50%; two patients (25%) had stable disease, and two patients (25%) had progressive disease. Our data support a new paradigm that TKIs may be the first treatment option in selected patients with locally advanced metastatic MTC, followed by locoregional treatment with surgery and/or external beam radiotherapy. Further studies are required to consolidate the presented data. A new paradigm of surgery after neoadjuvant/induction tyrosine kinase inhibitors is not accepted as a standard of care in patients with medullary thyroid cancer. The aim of our retrospective study was to evaluate the outcome of all patients with metastatic medullary cancer treated in a 20-year period in Slovenia and, among these, the cohort treated with induction tyrosine kinase inhibitors because of locally advanced metastatic medullary thyroid cancer. Our first hypothesis was that the outcome of metastatic medullary cancer treated with tyrosine kinase inhibitors is better than in those treated with chemotherapy. Our second hypothesis was that induction therapy with tyrosine kinase inhibitors was effective in the treatment of initially inoperable primary tumors. In the treatment of metastatic medullary cancer a systemic therapy was used in 83.4% (25/30) patients. Patients on targeted treatment with tyrosine kinase inhibitors had more often a partial remission than on chemotherapy (65% vs. 17%, respectively). Eight patients were treated with induction tyrosine kinase inhibitors because of locally advanced metastatic disease. The computer tomography evaluation of the primary tumor during tyrosine kinase inhibitor therapy revealed partial response in four cases and stable disease in four cases, but surgery was performed in two cases only. Our data support a new paradigm that tyrosine kinase inhibitors may be the first treatment option in patients with locally advanced metastatic medullary thyroid carcinoma followed by locoregional treatment with surgery and/or external beam radiotherapy. However, further studies are required to consolidate the presented data.
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- 2021
14. A case of metastatic renal cell carcinoma with concomitant Castleman's disease treated with immunotherapy
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Matthew J. Brunner, Taja Lozar, Hamid Emamekhoo, Christos Kyriakopoulos, and Sujal I. Shah
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Oncology ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Disease ,Malignancy ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,Medicine ,business.industry ,Optimal treatment ,Castleman's disease ,Immunotherapy ,medicine.disease ,RCC ,Diseases of the genitourinary system. Urology ,030220 oncology & carcinogenesis ,Concomitant ,Solid organ ,RC870-923 ,business - Abstract
Brief abstract: Castleman's disease (CD) is an uncommon lymphoproliferative process that can present concurrent to other solid organ malignancy, especially in selected populations. Concomitant CD and renal cell carcinoma (RCC) are challenging in terms of diagnosis and treatment. Assessment of CD involvement is a crucial step in selecting the optimal treatment strategy. Here we report a case of metastatic RCC and concurrent CD treated with surgery and immunotherapy.
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- 2021
15. Stress keratin 17 as a novel biomarker of response in immune checkpoint blockade–treated head and neck squamous cell carcinoma
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Taja Lozar, Megan Fitzpatrick, Wei Wang, Howard Harry Bailey, Justine Yang Yang Bruce, Paul M. Harari, and Paul Lambert
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Cancer Research ,Oncology - Abstract
3117 Background: Low response rates in immune checkpoint blockade (ICB) treated head and neck squamous cell carcinoma (HNSCC)drive a critical need for robust clinically validated biomarkers that can predict response to ICB. Stress keratin 17 (K17) is a known prognostic marker in various types of cancer, including HNSCC; however, its predictive value for ICB response has not been investigated. Preclinical studies suggest K17 suppresses macrophage-mediated CXCL9/CXCL10 chemokine signaling involved in attracting activated CD8+ T cells into tumors. Furthermore, knocking out K17 results in restored response to ICB in a HNSCC mouse model. Here, we evaluated if K17 protein expression predicts response to ICB in human HNSCC patients. Methods: We conducted a retrospective analysis of 26 HNSCC patients that received at least one cycle of pembrolizumab at the University of Wisconsin-Madison Carbone Cancer Center. Pretreatment, archival, formalin-fixed, paraffin-embeded samples were stained by immunohistochemistry using a K17 monoclonal antibody. Clinical outcomes were investigator-assessed for all patients with at least one post-treatment scan or evidence of clinical progression after treatment initiation. Based on independent pathology review, cases were categorized into K17 high vs K17 low based on a cut-off of > 5% strong cytoplasmic staining intensity of tumor cells in the invasive carcinoma component. Correlation between K17 expression and clinical outcomes was assesed using Fischer's exact test and log rank test. Results: The 26 patients included in this study were 85% male, median age 60.5 years, 74% ECOG performance status < 2, with 80% having received prior chemotherapy. Primary site included oral cavity (54%), oropharynx (23%), larynx (4%), or other (19%). Seventeen tumors (65%) showed high K17 expression, and 9 tumors (35%) showed low K17 expression. Eleven patients (42%) had programmed death ligand 1 (PD-L1)+ tumors as determined by combined positive score. Six patients (23%, all K17 low) achieved clinical benefit, while 20 patients (77%, 17 K17 high and 2 K17 low) had progressive disease. High K17 expression was associated with lack of clinical benefit (p < 0.001), shorter time to treatment failure (p < 0.001), progression-free (p = 0.004) and overall survival (p = 0.02). PD-L1 expression by immunohistochemistry (clone 22C3) did not correlate with K17 expression or clinical outcome. Conclusions: Our findings suggest that K17 expression may predict clinical benefit from ICB in HNSCC patients, thus supporting further validation studies. [Table: see text]
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- 2022
16. The biology and clinical potential of circulating tumor cells
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Maja Cemazar, Taja Lozar, K. Gersak, Cvetka Grasic Kuhar, and Tanja Jesenko
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0301 basic medicine ,Epithelial-Mesenchymal Transition ,Cell Survival ,disseminated tumor cells ,medicine.medical_treatment ,Population ,R895-920 ,Cell Count ,Cell Communication ,Review ,circulating tumor cells ,Metastasis ,Circulating Tumor DNA ,03 medical and health sciences ,Medical physics. Medical radiology. Nuclear medicine ,0302 clinical medicine ,Circulating tumor cell ,Cell Movement ,Neoplasms ,medicine ,Cell Adhesion ,Humans ,metastasis ,cancer ,Radiology, Nuclear Medicine and imaging ,Circulating MicroRNA ,Liquid biopsy ,Neoplasm Metastasis ,education ,education.field_of_study ,liquid biopsy ,business.industry ,Intravasation ,Cancer ,Immunotherapy ,medicine.disease ,Neoplastic Cells, Circulating ,Prognosis ,CTC ,Microvesicles ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Tumor Escape ,business - Abstract
Background Tumor cells can shed from the tumor, enter the circulation and travel to distant organs, where they can seed metastases. These cells are called circulating tumor cells (CTCs). The ability of CTCs to populate distant tissues and organs has led us to believe they are the primary cause of cancer metastasis. The biological properties and interaction of CTCs with other cell types during intravasation, circulation in the bloodstream, extravasation and colonization are multifaceted and include changes of CTC phenotypes that are regulated by many signaling molecules, including cytokines and chemokines. Considering a sample is readily accessible by a simple blood draw, monitoring CTC levels in the blood has exceptional implications in oncology field. A method called the liquid biopsy allows the extraction of not only CTC, but also CTC products, such as cell free DNA (cfDNA), cell free RNA (cfRNA), microRNA (miRNA) and exosomes. Conclusions The clinical utility of CTCs and their products is increasing with advances in liquid biopsy technology. Clinical applications of liquid biopsy to detect CTCs and their products are numerous and could be used for screening of the presence of the cancer in the general population, as well as for prognostic and predictive biomarkers in cancer patients. With the development of better CTC isolation technologies and clinical testing in large prospective trials, increasing clinical utility of CTCs can be expected. The understanding of their biology and interactions with other cell types, particularly with those of the immune system and the rise of immunotherapy also hold great promise for novel therapeutic possibilities.
- Published
- 2019
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