Review
Oncology
Amita R. Banga, Peace Odiase, Kartik Rachakonda, Amar P. Garg, Samuel E. Adunyah, Girish Rachakonda
Summary: This article discusses the potential value of the interaction between Clostridium perfringens Enterotoxin (CPE) and Claudin-4 in the treatment of breast cancer metastasis to the brain, and introduces the important role of Claudin-4 in cell trafficking and disease development.
Article
Multidisciplinary Sciences
Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud
Summary: The study reveals the molecular and structural basis of how CpE targets susceptible claudins, as well as differences in the primary CpE receptors in mice and humans due to sequence changes in the target motif.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Margaret C. Neville, Patricia G. Webb, Heidi K. Baumgartner, Benjamin G. Bitler
Summary: In this study, the localization of Claudin-4 protein in ovarian tumor cells was investigated. It was found that Claudin-4 is mainly localized in the perinuclear region, plasma membranes, and cytoplasmic puncta, but does not form tight junctions. Additionally, Claudin-4 is mainly localized to the Golgi compartment and is associated with Golgi markers GM130 and plasma membrane receptor Notch2 in dividing cells.
Article
Chemistry, Multidisciplinary
Man Kyu Shim, Jinhee Na, In Kyung Cho, Eun Hyang Jang, Jooho Park, Sangmin Lee, Jong-Ho Kim
Summary: The study developed a claudin-4-targeting drug carrier that efficiently accumulated in pancreatic cancer tissues, suppressed tumor growth with minimal toxicity to normal tissues. This claudin-4-targeting drug carrier may represent a promising new approach for treating pancreatic cancer.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Medicine, General & Internal
Won Shik Kim, Hayeon Kim, Moon Kyung Joo, Byung Il Choi, Ah Young Yoo, Jong-Jae Park, Beom Jae Lee, Seung Han Kim, Hoon Jai Chun
Summary: This study investigated the differential expression of CLDN-4 in early gastric cancer (EGC) and found a significant association between high CLDN-4 expression and intestinal-type EGC, open-type atrophic change, and the presence of synchronous tumors. These findings suggest that CLDN-4 may serve as an auxiliary tool for screening synchronous tumors in patients with EGC.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Masaya Takehara, Keiko Kobayashi, Masahiro Nagahama
Summary: TLR4 plays a crucial role in eliminating Clostridium perfringens by regulating inflammatory cytokine levels and neutrophil production.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Cell Biology
Chinemerem P. Ogbu, Sourav Roy, Alex J. Vecchio
Summary: Claudins are integral membrane proteins that play a crucial role in cell-cell interactions by forming tight junctions. The bacterium Clostridium perfringens causes gastrointestinal disorders by targeting claudins with its enterotoxin (CpE), disrupting the barrier function of the gut. Understanding the structure and function of Claudin and CpE provides insights into the mechanisms underlying the disruption of tight junctions. This review summarizes the current progress in this field and highlights the importance of structural studies in developing therapeutic strategies.
Review
Biochemistry & Molecular Biology
Rina Fujiwara-Tani, Shiori Mori, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Shingo Kishi, Masuo Kondoh, Hiroki Kuniyasu
Summary: CLDN4 is a crucial component of tight junctions in epithelial cells and is overexpressed in many epithelial malignancies. Changes in CLDN4 expression are associated with epigenetic factors, inflammation, and growth factor signaling. CLDN4 plays a role in maintaining the tumor microenvironment and acts as a barrier to anticancer drug entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jie Li, Xiaoyu Huang, Kaihui Xie, Juanli Zhang, Jiaojiao Yang, Zunqiang Yan, Shuangbao Gun
Summary: S100A9 plays an important role in C. perfringens type C-induced infectious diarrhea. Overexpression of S100A9 exacerbates cell damage and inflammatory response, inhibits cell proliferation, and disrupts cell-cell tight junctions. In contrast, inhibition of S100A9 expression alleviates inflammatory injury caused by infectious diarrhea.
Article
Biochemistry & Molecular Biology
Panpan Lin, Rongbang Tan, Ping Yu, Yanyu Li, Yuqian Mo, Wen Li, Jingjing Zhang
Summary: The blood-brain barrier is essential for protecting the central nervous system, but it also hinders efficient drug delivery. This study demonstrates that a mutated fragment of Clostridium perfringens enterotoxin can regulate the dynamics of the endothelial tight junction protein claudin-5 and influence blood-brain barrier permeability.
Review
Biochemistry & Molecular Biology
Wookyeom Yang, Dasol Kim, Dae Kyoung Kim, Kyung Un Choi, Dong Soo Suh, Jae Ho Kim
Summary: Ovarian cancer is a fatal gynecological malignancy, and its treatment remains a challenge. Cancer stem cells (CSCs) play a key role in cancer relapse and treatment resistance, with their malignancy regulated by cell surface receptors and intracellular factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Jolanta Szade, Michal Kunc, Beata Pieczynska-Uzieblo, Maciej Swierblewski, Wojciech Biernat, Jacek Jassem, Elzbieta Senkus
Summary: The study revealed significantly higher expression of claudin-4 in unilateral breast cancer (UBC) compared to bilateral breast cancer (BBC). High claudin-4 expression in BBC was associated with a more aggressive phenotype in breast cancer. The regulation of claudins may depend on different triggers and lead to varying consequences in UBC and BBC.
Review
Cell & Tissue Engineering
Huiying Ma, Tian Tian, Zhumei Cui
Summary: Ovarian cancer is a highly lethal gynecological malignancy characterized by tumor heterogeneity, limited early diagnosis methods, and high incidence of chemoresistant recurrent disease. Cancer stem cells (CSCs) play a crucial role in tumor growth, metastasis, and resistance to treatment. Understanding the role of CSCs in ovarian cancer can provide insights into the disease's progression and resistance mechanisms, leading to the development of novel therapeutic strategies. This review summarizes the current research on targeting ovarian cancer stem cells, including signaling pathways, markers, and drugs, with the aim of improving the management of ovarian cancer patients using CSC-based therapies.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Oncology
Lucas W. Thornblade, Ernest Han, Yuman Fong
Summary: Patients with colorectal cancer ovarian metastasis have favorable long-term survival. Survival rates are higher if the tumor is isolated to the ovary or if metachronous to the primary cancer.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2021)
Article
Medicine, Research & Experimental
Jin Qian, Bauer L. LeSavage, Kelsea M. Hubka, Chenkai Ma, Suchitra Natarajan, Joshua T. Eggold, Yiren Xiao, Katherine C. Fuh, Venkatesh Krishnan, Annika Enejder, Sarah C. Heilshorn, Oliver Dorigo, Erinn B. Rankin
Summary: Ovarian cancer-associated mesothelial cells play a critical role in promoting chemoresistance and stemness in ovarian cancer. The secreted factor osteopontin drives mesothelial-mediated chemoresistance and stemness, and therapeutic targeting of osteopontin may enhance platinum sensitivity in ovarian cancer.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Obstetrics & Gynecology
Sabine Grill, Juliane Ramser, Heide Hellebrand, Nicole Pfarr, Melanie Boxberg, Christine Brambs, Nina Ditsch, Alfons Meindl, Eva Gross, Thomas Meitinger, Marion Kiechle, Anne S. Quante
Summary: TP53germline mutations are rarely reported in the context of hereditary breast and ovarian cancer (HBOC). Through next-generation sequencing on 1876 breast cancer patients, it was found that (likely) pathogenic variants in the TP53 gene were present in 0.6% of the cohort, with higher occurrence in early-onset breast cancer and bilateral cases. Among the HBOC families, a clinical subgroup distinct from classic LFS families was identified, leading to potential for individualized screening efforts.
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2021)
Article
Orthopedics
Kaleb B. Smithson, Sean G. Parham, Simon C. Mears, Eric R. Siegel, Lee Crawley, Brant C. Sachleben
Summary: Approximately 14.6% of patients transferred to a pediatric Level 1 trauma center for isolated orthopedic injuries underwent no surgery or fracture reductions and were discharged directly home. In particular, isolated tibia fractures were more frequently treated without reduction or surgery. Telemedicine consultation for these specific injury types may limit unnecessary and costly transfers to a Level 1 pediatric trauma hospital in the future.
ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY
(2022)
Article
Oncology
Dana M. Roque, Eric R. Siegel, Natalia Buza, Stefania Bellone, Dan-Arin Silasi, Gloria S. Huang, Vaagn Andikyan, Mitchell Clark, Masoud Azodi, Peter E. Schwartz, Gautam G. Rao, Jocelyn C. Reader, Pei Hui, Joan R. Tymon-Rosario, Justin Harold, Dennis Mauricio, Burak Zeybek, Gulden Menderes, Gary Altwerger, Elena Ratner, Alessandro D. Santin
Summary: This multi-center study evaluated the activity and safety of ixabepilone plus bevacizumab compared to ixabepilone alone in platinum-resistant/refractory ovarian cancer. The results showed that the combination of ixabepilone and bevacizumab had a higher overall response rate and longer progression-free survival, with good tolerability. Prior receipt of bevacizumab should not limit the use of ixabepilone plus bevacizumab in treatment.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Stefania Bellone, Dana M. Roque, Eric R. Siegel, Natalia Buza, Pei Hui, Elena Bonazzoli, Adele Guglielmi, Luca Zammataro, Nupur Nagarkatti, Samir Zaidi, Jungsoo Lee, Dan-Arin Silasi, Gloria S. Huang, Vaagn Andikyan, Shari Damast, Mitchell Clark, Masoud Azodi, Peter E. Schwartz, Joan R. Tymon-Rosario, Justin A. Harold, Dennis Mauricio, Burak Zeybek, Gulden Menderes, Gary Altwerger, Elena Ratner, Ludmil B. Alexandrov, Akiko Iwasaki, Yong Kong, Eric Song, Weilai Dong, Julia A. Elvin, Jungmin Choi, Alessandro D. Santin
Summary: This study highlights the prognostic significance of Lynch-like cancers versus sporadic MSI-H/dMMR ECs for objective response rate, progression-free survival, and overall survival when treated with pembrolizumab. Sporadic MSI-H ECs exhibit mechanisms of resistance such as defective antigen processing/presentation and deranged induction in interferon responses. Oligoprogression in MSI-H/dMMR patients can be salvaged with surgical resection and/or local treatment and continuation of pembrolizumab off study. Further clinical studies are warranted to evaluate different MSI-H/dMMR EC subtypes treated with ICIs.
Article
Oncology
Zivojin Jevtic, Vittoria Matafora, Francesca Casagrande, Fabio Santoro, Saverio Minucci, Massimilliano Garre, Milad Rasouli, Olaf Heidenreich, Giovanna Musco, Juerg Schwaller, Angela Bachi
Summary: The study reveals that the NUP98-NSD1 fusion protein plays a transformative role in hematopoietic cells through its interaction and colocalization with SMARCA5. The formation of NUP98-NSD1 nuclear condensates is not enough to maintain the transformed phenotype, suggesting that selectively targeting condensate constituents could be a new therapeutic strategy for NUP98-NSD1 driven AML.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Engineering, Biomedical
D. Escalona-Vargas, E. R. Siegel, S. Oliphant, H. Eswaran
Summary: This study used a non-invasive and novel magnetomyography (MMG) technique to record and characterize the activity of levator ani muscles (LAM) during pregnancy and postpartum. The results showed changes in amplitude and spectral parameters of LAM activity during postpartum. This study provides a new method for studying the changes in LAM activity during pregnancy and postpartum.
IEEE JOURNAL OF TRANSLATIONAL ENGINEERING IN HEALTH AND MEDICINE
(2022)
Article
Surgery
Yihong Kaufmann, Stephanie D. Byrum, Alison A. Acott, Eric R. Siegel, Charity L. Washam, V. Suzanne Klimberg, Anne T. Mancino
Summary: Protein profiling in tears can distinguish patients with and without colon lesions.
AMERICAN JOURNAL OF SURGERY
(2022)
Article
Oncology
Joan R. Tymon-Rosario, Paola Manara, Diego D. Manavella, Stefania Bellone, Tobias Max Philipp Hartwich, Justin Harold, Yang Yang-Hartwich, Margherita Zipponi, Jungmin Choi, Kyungjo Jeong, Levent Mutlu, Kevin Yang, Gary Altwerger, Gulden Menderes, Elena Ratner, Gloria S. Huang, Mitchell Clark, Vaagn Andikyan, Masoud Azodi, Peter E. Schwartz, Ludmil B. Alexandrov, Alessandro D. Santin
Summary: The study found that ovarian and uterine carcinosarcoma with HRD signature were more sensitive to olaparib. The experiments showed that olaparib inhibited the growth of carcinosarcoma cells by blocking the cell cycle and inducing apoptosis. In the xenograft experiment, olaparib significantly suppressed the growth of HRD carcinosarcoma and improved overall survival.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Oncology
Ghanshyam Yadav, Dana M. Roque, Stefania Bellone, Diego D. Manavella, Tobias M. P. Hartwich, Margherita Zipponi, Justin Harold, Joan Tymon-Rosario, Levent Mutlu, Gary Altwerger, Gulden Menderes, Elena Ratner, Natalia Buza, Pei Hui, Gloria S. Huang, Vaagn Andikyan, Mitchell Clark, Masoud Azodi, Peter E. Schwartz, Ludmil B. Alexandrov, Alessandro D. Santin
Summary: The efficacy of neratinib and olaparib as single agents and in combination for uterine serous carcinoma (USC) was evaluated. Neratinib was more effective than olaparib in suppressing the growth of HER2/neu overexpressing USC cell lines. The combination of olaparib and neratinib showed a stronger inhibition of USC cell lines in vitro and suppressed tumor growth in vivo.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Oncology
Ryan D. Chow, Tai Michaels, Stefania Bellone, Tobias M. P. Hartwich, Elena Bonazzoli, Akiko Iwasaki, Eric Song, Alessandro D. Santin
Summary: This study found that patients with mutational MMRd endometrial cancer had higher response rates and longer survival after treatment with the PD-1 inhibitor pembrolizumab compared to those with epigenetic MMRd. However, mutation burden did not correlate with immune checkpoint blockade response. The study also revealed different modes of antitumor immunity between mutational and epigenetic MMRd cancers.
Article
Biochemistry & Molecular Biology
Bernice Nounamo, Fariba Jousheghany, Eric Robb Siegel, Steven R. R. Post, Thomas Kelly, Soldano Ferrone, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi
Summary: The study demonstrated that anti-CSPG4 monoclonal antibodies exhibit anti-tumor activity and therapeutic potential for breast cancer treatment. The specificity and importance of glycan contribution to the binding of specific anti-CSPG4 antibodies to tumor cells were investigated. The mAb VT68.2 displayed strong binding to a carbohydrate-mimicking peptide (CMP) and showed a higher affinity for certain glycans. Furthermore, VT68.2 inhibited cancer cell migration, suggesting its potential as a less toxic therapeutic approach targeting tumor-specific glyco-peptides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Alan P. Baltz, Eric R. Siegel, Arif H. Kamal, Robert Siegel, Mary May Kozlik, Stephanie T. S. Crist, Issam Makhoul, ASCO Quality Publications Task Force
Summary: The American Society for Clinical Oncology released the Choosing Wisely list in 2012, advising against the use of certain imaging procedures for staging early-stage breast cancer. A study was conducted to assess the impact of these guidelines on inappropriate staging imaging among early-stage breast cancer patients.
JCO ONCOLOGY PRACTICE
(2023)
Article
Physiology
Luis Mercado, Diana Escalona-Vargas, Sarah Blossom, Eric R. Siegel, Julie R. Whittington, Hubert Preissl, Kaitlyn Walden, Hari Eswaran
Summary: The study found that maternal pregestational diabetes has an effect on the fetal autonomic nervous system (ANS), which can be assessed using non-invasive fetal magnetocardiography. There were differences in the frequency domain of fetal heart rate variability (fHRV) and heart rate-movement coupling in fetuses of pregestational diabetic mothers compared to non-diabetics. However, the effect on fHRV related to fetal ANS and sympathovagal balance was not as conclusive as observed in neonates of pregestational diabetic mothers.
PHYSIOLOGICAL REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Stefania Bellone, Blair McNamara, Levent Mutlu, Cem Demirkiran, Tobias Max Philipp Hartwich, Justin Harold, Yang Yang-Hartwich, Eric R. Siegel, Alessandro D. Santin
Summary: The use of personalized circulating tumor DNA markers can potentially detect residual tumors and early recurrences in patients with uterine serous carcinoma and carcinosarcomas, leading to earlier treatment and changing clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Lauren C. Morehead, Sarita Garg, Katherine F. Wallis, Camila C. Simoes, Eric R. Siegel, Alan J. Tackett, Isabelle R. Miousse
Summary: The study found that restricting methionine in the diet increased the expression of MHC-I and PD-L1 in colorectal cancer cells, as well as the expression of STING and interferon. This led to a better response to immune checkpoint inhibitors in a mouse model of colorectal cancer.
