Article
Oncology
Xing Li, Yao Ke, Ariel L. Hernandez, Jingjing Yu, Li Bian, Spencer C. Hall, Kyle Nolan, Jing H. Wang, Christian D. Young, Xiao-Jing Wang
Summary: This study investigates the role of transforming growth factor beta (TGF-β) activity in squamous cell carcinoma (SCC) lung metastasis. The researchers used a SCC mouse model and human SCC specimens to identify metastasis drivers and test therapeutic interventions. They found that a TGF-β receptor inhibitor reduces lung metastasis in mice, correlating with reduced myeloid cells positive for inducible nitric oxide synthase (iNOS). Further experiments showed that depleting myeloid cells or inhibiting iNOS can also reduce SCC lung metastasis.
Article
Medicine, General & Internal
Yue Jiang, Chenxing Wang, Yanling Wang, Wei Zhang, Laikui Liu, Jie Cheng
Summary: This study aimed to investigate the densities and locations of CD11b(+) myeloid-derived suppressor cells (MDSCs) in oral squamous cell carcinoma (OSCC) and determine their prognostic significance. High densities of CD11b(+) MDSCs in the tumor center (CT) and invasive margin (IM) were significantly associated with inferior overall and disease-free survival. CD11b CT and CD11b IM were identified as independent prognostic predictors for patient survival, with higher accuracy and specificity compared to other prognostic parameters.
ARCHIVES OF MEDICAL SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Aya A. Mabrouk, Nesrine S. El-Mezayen, Mina I. Tadros, Omaima N. El-Gazayerly, Wessam M. El-Refaie
Summary: Oral squamous-cell carcinoma (OSCC) is a widespread health problem. Myeloid-derived suppressor cells (MDSCs) play a major role in promoting tumor aggressiveness and treatment resistance. Cyclooxygenase-2 (COX-2) regulates MDSCs activity, and targeted delivery of the COX-2 inhibitor celecoxib (CXB) to MDSCs shows promise for OSCC treatment. In this study, mucoadhesive-cubosomal buccal sponges loaded with CXB were developed and demonstrated potential for targeted MDSCs treatment in OSCC.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Review
Medicine, General & Internal
Ashley Wysong
Summary: Squamous-cell carcinoma is a common type of cancer in humans, with most cases being localized and treatable, but a small percentage of cases that recur or spread can be fatal. Immunocompromised patients are at particularly high risk.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Ru Li, Mousumi Beto Mukherjee, Jun Lin
Summary: In this review, the effects of cytokines and chemokines on myeloid-derived suppressor cells in cancer metastasis are summarized. Cytokines and chemokines in the tumor microenvironment alter the functional properties of MDSCs and are involved in their production, infiltration, and immunosuppressive functions. The manipulation of MDSCs by tumors through cytokine and chemokine signaling is discussed, as well as potential treatment strategies targeting these signaling pathways to combat the immunosuppressive activities of MDSCs and improve disease outcomes.
Article
Oncology
Zhenning Li, Lixia Zhang, Fa-yu Liu, Peng Li, Jing He, Cameron L. Kirkwood, Jiho Sohn, Jon M. Chan, William J. Magner, Keith L. Kirkwood
Summary: The study showed that the expression of MKP-1 in oral squamous cell carcinoma is inversely related to oral cancer burden and nodal involvement, and the role of MKP-1 signaling in tumor associated macrophages (TAMs) was assessed in murine models of OSCC. The results indicated that myeloid-based Dusp1 deficiency increases OSCC burden and metastasis through alteration in TAM recruitment, gene profile, and polarity.
Article
Oncology
Yunzhi Dang, Jiao Yu, Shuhong Zhao, Ximing Cao, Qing Wang
Summary: This study reveals that elevated expression of HOXA7 is associated with metastasis and poor prognosis in KRAS mutant colorectal cancer (CRC) patients. HOXA7 overexpression enhances the metastatic ability of KRAS mutant cells and promotes the infiltration of myeloid-derived suppressor cells (MDSCs). Furthermore, blocking MDSC infiltration can effectively suppress the metastasis of KRAS mutant CRC. Therefore, interrupting the HOXA7-mediated loop may provide a promising strategy for the treatment of this disease.
CANCER CELL INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Heejin Lim, Taewoo Yang, Wongeun Lee, Sung-Gyoo Park
Summary: The study demonstrates that MDSCs are a source of MFGE8, which plays a role in tumor metastasis. TME positively regulates MFGE8 production by MDSCs through TGF-beta, suggesting MFGE8 as an important effector molecule for MDSCs to promote tumor metastasis.
Article
Oncology
Yunzhi Dang, Jiao Yu, Shuhong Zhao, Long Jin, Ximing Cao, Qing Wang
Summary: This study reveals a novel role of GOLM1 in promoting CRC metastasis, with its overexpression promoting immune escape and metastasis by recruiting MDSCs. The specific inhibitor of CCR2, PF-04136309, can effectively suppress GOLM1-mediated CRC metastasis, suggesting GOLM1 as a prognostic biomarker in human CRC.
Article
Oncology
Xiaoting Chen, Lanlan Huang, Tingting Yang, Jiexuan Xu, Chengyong Zhang, Zhendong Deng, Xiaorong Yang, Naihua Liu, Size Chen, Shaoqiang Lin
Summary: Recent studies have identified pleiotropic roles of METTL3 in tumor progression, but its specific role in esophageal squamous cell carcinoma (ESCC) is still unclear. Higher METTL3 expression in ESCC tissues was associated with poor prognosis, and it was shown to promote migration and invasion of ESCC cells by regulating GLS2. These findings suggest METTL3/GLS2 signaling as a potential therapeutic target for anti-metastatic strategies against ESCC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Sergio Ortiz-Espinosa, Xabier Morales, Yaiza Senent, Diego Alignani, Beatriz Tavira, Irati Macaya, Borja Ruiz, Haritz Moreno, Ana Remirez, Cristina Sainz, Alejandro Rodriguez-Pena, Alvaro Oyarbide, Mikel Ariz, Maria P. Andueza, Karmele Valencia, Alvaro Teijeira, Kai Hoehlig, Axel Vater, Barbara Rolfe, Trent M. Woodruff, Jose Maria Lopez-Picazo, Silvestre Vicent, Grazyna Kochan, David Escors, Ignacio Gil-Bazo, Jose Luis Perez-Gracia, Luis M. Montuenga, John D. Lambris, Carlos Ortiz de Solorzano, Fernando Lecanda, Daniel Ajona, Ruben Pio
Summary: This study reveals that C5a can enhance the capacity of PMN-MDSCs to promote tumor growth and metastasis by inducing the formation of NETs. The formation of NETs is dependent on the production of HMGB1 by cancer cells. Inhibiting C5a, C5aR1, or NETosis can reduce the number of circulating tumor cells and the metastatic burden in a mouse lung metastasis model. The translational relevance of these findings is supported by the stimulation of migration and NETosis in PMN-MDSCs obtained from lung cancer patients.
Article
Medical Laboratory Technology
Goncalo Outeiro-pinho, Daniela Barros-silva, Filipa Moreira-silva, Joao Lobo, Isa Carneiro, Antonio Morais, Eduarda p. Martins, Celine s. Goncalves, Bruno m. Costa, Margareta p. Correia, Rui Henrique, Carmen Jeronimo
Summary: MiR-30a/c-5p is downregulated and associated with aggressiveness in ccRCC. Downregulation of miR-30a/c-5p is accompanied by increased promoter methylation, which can be restored by decitabine treatment. MiR-30a/c-5p not only decreases cell aggressiveness, but also upregulates epithelial markers and downregulates EMT-promoting players.
TRANSLATIONAL RESEARCH
(2022)
Article
Oncology
Liqing Qiu, Jing Yue, Lingyu Ding, Zihao Yin, Ke Zhang, Hongfang Zhang
Summary: In this review, the impact of cancer-associated fibroblasts (CAFs) on esophageal squamous cell carcinoma (ESCC) is highlighted, including the induction of chemoresistance, radioresistance, migration, invasion, and immune escape. The origin of CAFs and the influence of ESCC cells on CAF activation are also discussed. Furthermore, the clinical prospects and future trends of CAFs-targeted therapies in ESCC are emphasized. A better understanding of the molecular biology of CAFs may contribute to the development of novel anti-ESCC strategies.
Article
Gastroenterology & Hepatology
Bin Sun, Weidan Ji, Chunying Liu, Xuejing Lin, Lei Chen, Haihua Qian, Changqing Su
Summary: miR-2392 is significantly down-regulated in HCC and functions as a tumor suppressor by targeting JAG2 to inhibit proliferation, clonogenicity, mobility, spheroid formation, and maintenance of CSC-like characteristics in HCC cells. CTCs from HCC patients with lower serum miR-2392 levels exhibit stronger spheroid formation ability, and a negative correlation between miR-2392 levels in serum and the number of CTC spheroids has been observed. JAG2 is highly expressed in HCC and is associated with poor prognosis and patient survival.
LIVER INTERNATIONAL
(2022)
Article
Genetics & Heredity
Bowen Zhang, Sainan Min, Qi Guo, Yan Huang, Yuzhu Guo, Xiaolin Liang, Li-ling Wu, Guang-yan Yu, Xiangting Wang
Summary: Evidence has shown that 7SK is down-regulated in human tongue squamous carcinoma (TSCC) and acts as a TSCC suppressor through multiple cell-based assays including a migration assay and a xenograft mouse model. This study identified 27 7SK-regulated genes involved in tumor regulation, with upstream regulatory regions bound by 7SK, and suggested potential involvement of transcription factors FOXJ3 and THRA in 7SK-mediated TSCC progression. FOXJ3 and THRA were found to dramatically promote migration in SCC15 cells, potentially contributing to TSCC progression.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Thalia Pacheco-Fernandez, Greta Volpedo, Chaitenya Verma, Abhay R. Satoskar
Summary: Leishmaniasis is a neglected tropical disease transmitted by sand flies and manifests clinically in various forms. Host immune responses are critical in fighting against the disease, but Leishmania parasites manipulate these responses for their own survival. Factors like sand fly salivary proteins and microbiota also influence disease susceptibility.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Cell Biology
N. Fatima, N. Sheikh, A. R. Satoskar, T. Akhtar, A. Tayyeb, I Ashfaq, N. Ryan, S. Ambreen, B. K. Jha, S. Oghumu
Summary: The study revealed that even short-term exposure to tacrolimus (TAC) can induce changes in antioxidant status and lipid peroxidation in the liver of rats, leading to significant alterations in liver structure and increased inflammatory response.
MEDIATORS OF INFLAMMATION
(2021)
Article
Oncology
Kelvin Anderson, Nathan Ryan, Anastasia Alkhimovitch, Arham Siddiqui, Steve Oghumu
Summary: Inhibition of PI3K p110 gamma may enhance the anti-tumor immune response against poorly immunogenic HNSCC, particularly when used in combination with selective checkpoint inhibitors.
Review
Immunology
Thalia Pacheco-Fernandez, Greta Volpedo, Sreenivas Gannavaram, Parna Bhattacharya, Ranadhir Dey, Abhay Satoskar, Greg Matlashewski, Hira L. Nakhasi
Summary: Leishmaniasis is a disease caused by parasitic protozoa transmitted by infected sandflies, affecting over 1 billion people worldwide. The successful vaccination procedure known as leishmanization, which has been used in the Middle East for decades, is no longer practiced due to safety and ethical concerns. New genome editing technologies may allow for the development of a second generation leishmanization that could enter human trials.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Parasitology
Nargis Shaheen, Chaitenya Verma, Thalia Pacheco-Fernandez, Greta Volpedo, Aneeqa Hamid, Ismail Zeb, Syed Aizaz Ali Shah, Shah Fahad, Attiya Iqbal, Asma Ashraf, Amjad Khan, Misbah Gul, Muhammad Ilyas Khan, Huma Fatima, Muhammad Afzal, Abhay R. Satoskar, Naveeda Akhter Qureshi
Summary: This study aimed to elucidate the molecular characterization and genetic diversity of Leishmania spp. in North Eastern Pakistan. The findings confirmed the presence of Leishmania tropica, Leishmania major, and Leishmania infantum, with Leishmania tropica showing significantly higher nucleotide variation. Recommendations for more extensive investigations to understand the molecular epidemiology of Leishmania in the region were made.
Review
Immunology
Greta Volpedo, Ryan H. Huston, Erin A. Holcomb, Thalia Pacheco-Fernandez, Sreenivas Gannavaram, Parna Bhattacharya, Hira L. Nakhasi, Abhay R. Satoskar
Summary: Leishmaniasis is a significant public health issue globally, requiring effective vaccines for prevention and control. The disease leads to long-term disabilities, psycho-sociological trauma, poverty, and gender disparity. Challenges in research include manufacturing vaccines, conducting clinical trials, and defining correlates of protection.
EXPERT REVIEW OF VACCINES
(2021)
Review
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Erin A. Holcomb, Natalie Cipriano, Blake Cox, Abhay R. Satoskar
Summary: Leishmaniasis is a neglected tropical disease affecting 12 million people worldwide. Cutaneous leishmaniasis (CL) is the most common form, presenting as ulcerating skin lesions that can self-heal or become chronic. The balance of immune response and inflammatory mediators plays a vital role in the clinical presentation and outcome of the disease.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biology
Subir Karmakar, Nevien Ismail, Fabiano Oliveira, James Oristian, Wen Wei Zhang, Swarnendu Kaviraj, Kamaleshwar P. Singh, Abhishek Mondal, Sushmita Das, Krishna Pandey, Parna Bhattacharya, Greta Volpedo, Sreenivas Gannavaram, Monika Satoskar, Sanika Satoskar, Rajiv M. Sastry, Claudio Meneses, Shinjiro Hamano, Pradeep Das, Greg Matlashewski, Sanjay Singh, Shaden Kamhawi, Ranadhir Dey, Jesus G. Valenzuela, Abhay Satoskar, Hira L. Nakhasi
Summary: Karmakar et al. developed a dermotropic, live attenuated centrin gene-deleted Leishmania major (LmCen(-/-)) vaccine against Visceral Leishmaniasis (VL), demonstrating that a single intradermal injection provides robust and durable protection against lethal VL transmitted through sand fly bites.
COMMUNICATIONS BIOLOGY
(2021)
Review
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Parna Bhattacharya, Timur Oljuskin, Ranadhir Dey, Sreenivas Gannavaram, Abhay R. Satoskar, Hira L. Nakhasi
Summary: Leishmaniasis is a disease endemic in tropical and subtropical regions transmitted by infected sand flies. The interactions between Leishmania, host immune cells, and adaptive immunity play a crucial role in disease severity and development. Besides cytokine signals, metabolic shifts in innate cells also influence immune signaling cascades in Leishmania pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Erin A. Holcomb, Wen-Wei Zhang, Patrick Lypaczewski, Blake Cox, Rebecca Fultz, Chelsea Mishan, Chaitenya Verma, Ryan H. Huston, Abigail R. Wharton, Ranadhir Dey, Subir Karmakar, Steve Oghumu, Shinjiro Hamano, Sreenivas Gannavaram, Hira L. Nakhasi, Greg Matlashewski, Abhay R. Satoskar
Summary: Using the CRISPR/Cas9 technique, researchers have successfully generated live attenuated centrin knockout L. mexicana parasites. These parasites exhibit a growth defect and lower parasitic burdens compared to the wild type, as well as increased production of protective cytokines. In pre-clinical models, immunization with the LmexCen(-/-) parasites is safe and efficacious, leading to protective immunity and reduced parasitic burdens at the infection site and draining lymph nodes.
Review
Microbiology
Greta Volpedo, Parna Bhattacharya, Sreenivas Gannavaram, Thalia Pacheco-Fernandez, Timur Oljuskin, Ranadhir Dey, Abhay R. Satoskar, Hira L. Nakhasi
Summary: Leishmaniasis is a neglected tropical disease that affects millions of people worldwide. Current treatments are not highly effective and have high costs and toxicity. The development of a prophylactic vaccine has become a high priority, but the ability of Leishmania to undermine immune recognition has hindered progress. Live attenuated Leishmania parasites that provide a complete range of antigens could be effective vaccine candidates. This review focuses on the development of live attenuated Leishmania vaccines and discusses the challenges of transitioning from the laboratory to human clinical trials.
Article
Biotechnology & Applied Microbiology
Felipe F. F. Lamenza, Nathan M. M. Ryan, Puja Upadhaya, Arham Siddiqui, Pete P. P. Jordanides, Anna Springer, Peyton Roth, Hasan Pracha, O. Hans Iwenofu, Steve Oghumu
Summary: Head and neck squamous cell carcinoma (HNSCC) is a significant public health problem. We optimized a mouse model of tongue carcinogenesis and found that dietary administration of black raspberries can reduce tumor growth and enhance anti-tumor activity.
CANCER GENE THERAPY
(2023)
Article
Immunology
Nebiye Yentur Doni, Paul J. Bertani, Greta Volpedo, Noushin Saljoughian, Sanjay Varikuti, Greg Matlashewski, Wu Lu, Abhay R. Satoskar
Summary: This article introduces the use of immuno field effect transistors (ImmunoFET) biosensors for monitoring and detecting Leishmania parasites. The current methods of leishmanial diagnosis are time-consuming, costly, and require special equipment and trained personnel. The study demonstrates that ImmunoFET biosensors can successfully detect the presence of Leishmania parasites and have the potential to provide earlier and faster detection of leishmaniasis compared to ELISA.
PARASITE IMMUNOLOGY
(2023)
Article
Oncology
Puja Upadhaya, Nathan Ryan, Peyton Roth, Travis Pero, Felipe Lamenza, Anna Springer, Pete Jordanides, Hasan Pracha, Darrion Mitchell, Steve Oghumu
Summary: This study demonstrates that tumor-targeted radiation therapy can generate tumor antigens that induce strong immune responses. These responses show comparable sensitivity but greater specificity for T cell activation compared to conventional antibodies. This information can be utilized to predict patient responses to radiation and immune therapy.
Meeting Abstract
Public, Environmental & Occupational Health
Subir Karmakar, Nevien Ismail, Wenwei Zhang, Oliveira Fabiano, Greta Volpedo, Shinjiro Hamano, Greg Matlashewski, Shaden Kamhawi, Jesus Valenzuela, Abhay Satoskar, Ranadhir Dey, Hira Nakhasi
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2021)
