المؤلفون: Dan Zhao, Haiqing Li, Isa Mambetsariev, Tamara Mirzapoiazova, Chen Chen, Jeremy Fricke, Deric Wheeler, Leonidas Arvanitis, Raju Pillai, Michelle Afkhami, Bihong T. Chen, Martin Sattler, Loretta Erhunmwunsee, Erminia Massarelli, Prakash Kulkarni, Arya Amini, Brian Armstrong, Ravi Salgia

المصدر: npj Precision Oncology, Vol 8, Iss 1, Pp 1-12 (2024)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract We conducted spatial immune tumor microenvironment (iTME) profiling using formalin-fixed paraffin-embedded (FFPE) samples of 25 KRAS-mutated non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), including 12 responders and 13 non-responders. An eleven-marker panel (CD3, CD4, CD8, FOXP3, CD68, arginase-1, CD33, HLA-DR, pan-keratin (PanCK), PD-1, and PD-L1) was used to study the tumor and immune cell compositions. Spatial features at single cell level with cellular neighborhoods and fractal analysis were determined. Spatial features and different subgroups of CD68+ cells and FOXP3+ cells being associated with response or resistance to ICIs were also identified. In particular, CD68+ cells, CD33+ and FOXP3+ cells were found to be associated with resistance. Interestingly, there was also significant association between non-nuclear expression of FOXP3 being resistant to ICIs. We identified CD68dim cells in the lung cancer tissues being associated with improved responses, which should be insightful for future studies of tumor immunity.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2397-768XTest

الوصول الحر: https://doaj.org/article/84e066ed9cad48ee852f6917439d4ae5Test

المؤلفون: Charles D. Warden, Preetam Cholli, Hanjun Qin, Chao Guo, Yafan Wang, Chetan Kancharla, Angelique M. Russell, Sylvana Salvatierra, Lorraine Z. Mutsvunguma, Kerin K. Higa, Xiwei Wu, Sharon Wilczynski, Raju Pillai, Javier Gordon Ogembo

المصدر: Infectious Agents and Cancer, Vol 19, Iss 1, Pp 1-2 (2024)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Infectious and parasitic diseases, RC109-216

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-9378Test

الوصول الحر: https://doaj.org/article/4a7c94f3f3064fca8973e56af21ccde2Test

المؤلفون: Ibrahim Aldoss, Parastou Tizro, Davsheen Bedi, James K. Mangan, Mary C. Clark, David Spencer, Joo Y. Song, Sindhu Cherian, Raju Pillai, Young Kim, Nitin Mahajan, Ketevan Gendzekhadze, Mike James, Kenneth Jacobs, Jan Davidson-Moncada, Stephen J. Forman, Huan-You Wang, Michelle Afkhami

المصدر: Haematologica, Vol 108, Iss 12 (2023)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

وصف الملف: electronic resource

العلاقة: https://haematologica.org/article/view/11180Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test

الوصول الحر: https://doaj.org/article/0947cc1b366b42d5b7abf59f6ae225a9Test

المؤلفون: Charles D. Warden, Preetam Cholli, Hanjun Qin, Chao Guo, Yafan Wang, Chetan Kancharla, Angelique M. Russell, Sylvana Salvatierra, Lorraine Z. Mutsvunguma, Kerin K. Higa, Xiwei Wu, Sharon Wilczynski, Raju Pillai, Javier Gordon Ogembo

المصدر: Infectious Agents and Cancer, Vol 17, Iss 1, Pp 1-16 (2022)

مصطلحات موضوعية: Human papillomavirus, Genotyping, High-throughput sequencing, Invasive cervical cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Infectious and parasitic diseases, RC109-216

الوصف: Abstract Background Human papillomavirus (HPV) is the primary cause of invasive cervical cancer (ICC). The prevalence of various HPV genotypes, ranging from oncogenically low- to high-risk, may be influenced by geographic and demographic factors, which could have critical implications for the screening and prevention of HPV infection and ICC incidence. However, many technical factors may influence the identification of high-risk genotypes associated with ICC in different populations. Methods We used high-throughput sequencing of a single amplicon within the HPV L1 gene to assess the influence of patient age, race/ethnicity, histological subtype, sample type, collection date, experimental factors, and computational parameters on the prevalence of HPV genotypes detected in archived DNA (n = 34), frozen tissue (n = 44), and formalin-fixed paraffin-embedded (FFPE) tissue (n = 57) samples collected in the Los Angeles metropolitan area. Results We found that the percentage of off-target human reads and the concentration of DNA amplified from each sample varied by HPV genotype and by archive type. After accounting for the percentage of human reads and excluding samples with especially low levels of amplified DNA, the HPV prevalence was 95% across all ICC samples: HPV16 was the most common genotype (in 56% of all ICC samples), followed by HPV18 (in 21%). Depending upon the genotyping parameters, the prevalence of HPV58 varied up to twofold in our cohort. In archived DNA and frozen tissue samples, we detected previously established differences in HPV16 and HPV18 frequencies based on histological subtype, but we could not reproduce those findings using our FFPE samples. Conclusions In this pilot study, we demonstrate that sample collection, preparation, and analysis methods can influence the detection of certain HPV genotypes and must be carefully considered when drawing any biological conclusions based on HPV genotyping data from ICC samples.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-9378Test

الوصول الحر: https://doaj.org/article/314f82786a814936a4a959e987f69fd1Test

المؤلفون: Ibrahim Aldoss, Raju Pillai, Dongyun Yang, Lixin Yang, Shukaib Arslan, Sally Mokhtari, Monzr M. Al Malki, Amandeep Salhotra, Shilpa Shahani, Haris Ali, Matthew Mei, Andrew Artz, David Snyder, Michelle Afkhami, Saro Armenian, Anthony Stein, Guido Marcucci, Stephen J. Forman, Ryotaro Nakamura, Vinod Pullarkat

المصدر: Blood Cancer Journal, Vol 11, Iss 7, Pp 1-4 (2021)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2044-5385Test

الوصول الحر: https://doaj.org/article/e4e4b6a679c44c52940d83c8d0470e91Test

المؤلفون: Matthew Mei, Raju Pillai, Soyoung Kim, Noel Estrada-Merly, Michelle Afkhami, Lixin Yang, Zhuo Meng, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Christopher Bredeson, Jean-Yves Cahn, Jan Cerny, Edward Copelan, Corey Cutler, Zachariah DeFilipp, Miguel Angel Diaz Perez, Nosha Farhadfar, César O. Freytes, Shahinaz M. Gadalla, Siddhartha Ganguly, Robert Peter Gale, Usama Gergis, Michael R. Grunwald, Betty K. Hamilton, Shahrukh Hashmi, Gerhard C. Hildebrandt, Hillard M. Lazarus, Mark Litzow, Reinhold Munker, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Sagar S. Patel, David Rizzieri, Sachiko Seo, Mithun Vinod Shah, Melhem Solh, Leo F. Verdonck, Ravi Vij, Ronald M. Sobecks, Betul Oran, Bart L. Scott, Wael Saber, Ryotaro Nakamura

المصدر: Haematologica, Vol 108, Iss 1 (2022)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell’s C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.

وصف الملف: electronic resource

العلاقة: https://haematologica.org/article/view/10604Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test

الوصول الحر: https://doaj.org/article/23076c7290164061a98b071548e28bebTest

المؤلفون: Sue Chang, Evita Sadimin, Keluo Yao, Stanley Hamilton, Patricia Aoun, Raju Pillai, David Muirhead, Daniel Schmolze

المصدر: Journal of Pathology Informatics, Vol 13, Iss , Pp 100106- (2022)

مصطلحات موضوعية: Digital pathology, Frozen sections, Whole slide imaging, Computer applications to medicine. Medical informatics, R858-859.7, Pathology, RB1-214

الوصف: Background: In recent years, there has been a surge of interest in clinical digital pathology (DP). Hardware and software platforms have matured and become more affordable, and advances in artificial intelligence promise to transform the practice of pathology. At our institution, we are launching a stepwise process of DP adoption which will eventually encompass our entire workflow. Out of necessity, we began by establishing a whole slide imaging (WSI)-based frozen section service. Methods: We proceeded in a systematic manner by first assembling a team of key stakeholders. We carefully evaluated the various options for digitizing frozen sections before deciding that a WSI-based solution made the most sense for us. We used a formalized evaluation system to quantify performance metrics that were relevant to us. After deciding on a WSI-based system, we likewise carefully considered the various whole slide scanners and digital slide management systems available before making decisions. Results: During formal evaluation by pathologists, the WSI-based system outperformed competing platforms. Although implementation was relatively complex, we have been happy with the results and have noticed significant improvements in our frozen section turnaround time. Our users have been happy with the slide management system, which we plan on utilizing in future DP efforts. Conclusions: There are various options for digitizing frozen section slides. Although WSI-based systems are more complex and expensive than some alternatives, they perform well and may make sense for institutions with a pre-existing or planned larger DP infrastructure.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2153353922007003Test; https://doaj.org/toc/2153-3539Test

الوصول الحر: https://doaj.org/article/9873f38e3643490697b5807e5595de51Test

المؤلفون: Xu Hannah Zhang, Zhirong Yin, Aimin Zhang, Raju Pillai, Brian Armstrong, Steven T Rosen

المصدر: eJHaem, Vol 1, Iss 1, Pp 300-303 (2020)

مصطلحات موضوعية: DNA‐methyltransferase 1 (DNMT1), p38γ (MAPK12: Mitogen‐activated protein kinase 12), Lymph nodes, germinal centers (GC), mantle zone of the follicle, The dark zone (centroblasts) of GC, Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Abstract Lymph nodes are important front‐line defense immune tissues, which also act against inflammatory diseases and cancer. Lymph nodes undergo extensive upheavals within newly formed germinal centers (GCs) when exposed to antigens, the molecular mechanisms of which remain elusive. Recently, p38γ was identified as an important target for multiple cancers, including cutaneous T‐cell lymphoma (CTCL). We previously observed that p38γ is overexpressed in CTCL versus normal cells, but it is not clear if p38γ is expressed in B or T lymphocytes of GCs of patients in response to a stress such as cancer. Therefore, in this study, we obtained non‐metastatic reactive lymph nodes adjacent to cancer lesions (colorectal adenocarcinoma), then performed multicolor immunohistochemical staining for p38γ and other relevant markers. We observed for the first time that p38γ was expressed in the light zone of activated B cells and T helper cells in GCs, whereas DNA‐methyltransferase 1 (DNMT1), a marker for GC B cells, was highly expressed in centrocytes and in the dark zone of GCs. This inverse relationship suggests a novel function for p38γ in T cells that cross‐talk to B cells in response to stress.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2688-6146Test

الوصول الحر: https://doaj.org/article/c534ea0929494478869d33333636f25cTest

المؤلفون: Jin Sun Lee, Susan E. Yost, Suzette Blanchard, Daniel Schmolze, Hongwei Holly Yin, Raju Pillai, Kim Robinson, Aileen Tang, Norma Martinez, Jana Portnow, Wei Wen, John H. Yim, Heather Ann Brauer, Yuqi Ren, Thehang Luu, Joanne Mortimer, Yuan Yuan

المصدر: Breast Cancer Research, Vol 21, Iss 1, Pp 1-13 (2019)

مصطلحات موضوعية: Phase I trial, Eribulin, Everolimus, Metastatic TNBC, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Alteration of the PI3K/AKT/mTOR pathway is a common genomic abnormality detected in triple-negative breast cancer (TNBC). Everolimus acts synergistically with eribulin in TNBC cell lines and xenograft models. This phase I trial was designed to test the safety and tolerability of combining eribulin and everolimus in patients with metastatic TNBC. Methods The primary objective of this study was to evaluate the safety and toxicities of the combination. Patients with metastatic TNBC who had up to four lines of prior chemotherapies were enrolled. The combination of eribulin and everolimus was tested using three dosing levels: A1 (everolimus 5 mg daily; eribulin 1.4 mg/m2 days 1 and 8 every 3 weeks), A2 (everolimus 7.5 mg daily; eribulin 1.4 mg/m2, days 1 and 8 every 3 weeks), and B1 (everolimus 5 mg daily; eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks). Results Twenty-seven patients with median age 55 years were enrolled. Among 8 evaluable patients who received dose level A1, 4 had dose-limiting toxicities (DLTs). Among 3 evaluable patients treated with dose level A2, 2 had DLTs. Among 12 evaluable patients who received dose level B1, 4 had DLTs. The DLTs were neutropenia, stomatitis, and hyperglycemia. Over the study period, 59% had a ≥ grade 3 toxicity, 44% had ≥ grade 3 hematologic toxicities, and 22% had grade 4 hematologic toxicities. The most common hematological toxicities were neutropenia, leukopenia, and lymphopenia. Thirty-three percent had grade 3 non-hematologic toxicities. The most common non-hematological toxicities were stomatitis, hyperglycemia, and fatigue. The median number of cycles completed was 4 (range 0–8). Among 25 eligible patients, 9 patients (36%) achieved the best response as partial response, 9 (36%) had stable disease, and 7 (28%) had progression. The median time to progression was 2.6 months (95% CI [2.1, 4.0]), and median overall survival (OS) was 8.3 months (95% CI [5.5, undefined]). Conclusion Eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks with everolimus 5 mg daily was defined as the highest dose with acceptable toxicity (RP2D). The combination is safe, and efficacy is modest. A post hoc analysis showed that participants that used dexamethasone mouthwash stayed on treatment for one additional cycle. Trial registration ClinicalTrials.gov, NCT02120469. Registered 18 April 2014

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13058-019-1202-4Test; https://doaj.org/toc/1465-542XTest

الوصول الحر: https://doaj.org/article/7dd4eead50f74df9b8ddd632d9e2509eTest

المؤلفون: Dan Zhao, Haiqing Li, Isa Mambetsariev, Tamara Mirzapoiazova, Chen Chen, Jeremy Fricke, Prakash Kulkarni, Victoria Villaflor, Leonidas Arvanitis, Stanley Hamilton, Michelle Afkhami, Raju Pillai, Brian Armstrong, Loretta Erhunmwunsee, Erminia Massarelli, Martin Sattler, Arya Amini, Ravi Salgia

المصدر: Cancers, Vol 14, Iss 19, p 4933 (2022)

مصطلحات موضوعية: KRAS, immune checkpoint inhibitors, next-generation sequencing, precision medicine, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: The molecular and clinical features of KRAS-mutated lung cancer patients treated with immunotherapy have yet to be characterized, which could guide the development of therapeutics targeting KRAS with potential immuno-oncology treatment combinations. Research Question: Do KRAS-mutated patients with different subtypes and comutations have different clinical responses and overall survival (OS) to checkpoint inhibitors? Study Design and Methods: 87 patients with NSCLC at the City of Hope who received immune checkpoint inhibitors were identified and analyzed retrospectively. Tumor genomic alterations were extracted from the clinical data with next-generation sequencing using various platforms. Demographic, clinical, molecular, and pathological information was collected with the approval of the institutional review board of the City of Hope. OS was calculated if it was available at the study time point, and responses were determined according to the RECIST v1.1. Results: Among 87 patients, 32 had a KRAS G12C mutation (36.8%), 19 had G12V (21.9%), 18 had G12D (20.7%), 6 had G12A (6.9%), 3 had G12R (3.45%), and 10 had amplification (11.49%) and other uncommon mutations. G12D had a statistically significant Odds Ratio (OR) between patients who had responses and progression of the disease (OR (95% CI) = 0.31 (0.09–0.95), p < 0.05), with 5 G12D-mutated patients having responses and 11 G12D-mutated patients having progression of the disease. In the univariate analysis with OS, there was a trend of better OS in the G12D-mutated patients, with no statistically significant difference in terms of OS between the patients who had G12D mutation and the patients who had other KRAS mutations (HR (95% CI) = 0.53 (0.21–1.36), p = 0.185). The median OS was significantly worse with KRAS comutation CDKN2A/B loss (4.2 vs. 16.9 months, HR = 3.07 (1.09–8.69), p < 0.05) and MET (3.4 vs. 17 months, HR = 3.80 (1.44–10.05), p < 0.01), which were included for the multivariate analysis. The OS with other KRAS comutations was not statistically significant, including STK11 and KEAP1. Conclusion: KRAS mutation subtypes such as G12D and comutations such as CDKN2/A and MET may modulate the immunotherapy responses and outcomes in lung cancer.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/14/19/4933Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/26c5987efc044f6aa2c8b29a425fcca7Test