Article
Biochemistry & Molecular Biology
Vlad-Adrian Afrasanie, Mihai-Vasile Marinca, Bogdan Gafton, Teodora Alexa-Stratulat, Alexandra Rusu, Eliza-Maria Froicu, Daniel Sur, Cristian Virgil Lungulescu, Larisa Popovici, Andrei-Vlad Lefter, Irina Afrasanie, Anca-Viorica Ivanov, Lucian Miron, Cristina Rusu
Summary: In this study, the frequency, distribution, coexistence, and clinicopathological and molecular correlations of RAS, BRAF, PIK3CA, and TP53 mutations were investigated in 104 patients with metastatic colorectal cancer from Northeastern Romania. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). The study provides novel insights into genetic variations specific to the population from Northeastern Romania and enables the development of genetic profiles in a developing country with limited access to specialized genetic tests.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
J. Sastre, P. Garcia-Alfonso, J. M. Vieitez, M. T. Cano, F. Rivera, J. J. Reina-Zoilo, A. Salud-Salvia, G. Quintero, L. Robles-Diaz, M. J. Safont, A. La Casta, S. Gil, E. Polo, E. Asensio-Martinez, B. Garcia-Paredes, R. L. Lopez, M. Guillot, M. Valladares-Ayerbes, E. Aranda, E. Diaz-Rubio
Summary: The mutational status of BRAF and PIK3CA influences the outcomes of patients with RAS wild-type metastatic colorectal cancer, but does not appear to be helpful in selecting first-line targeted therapy. The efficacy of bevacizumab or cetuximab plus FOLFIRI was similar in both BRAF/PIK3CA wild-type and mutated tumors. Adverse events were comparable between the two treatment groups.
Article
Oncology
Theodora Pappa, Sara Ahmadi, Ellen Marqusee, Hannah L. Johnson, Matthew A. Nehs, Nancy L. Cho, Justine A. Barletta, Jochen H. Lorch, Gerard M. Doherty, Neal I. Lindeman, Erik K. Alexander, Inigo Landa
Summary: Routine genomic sequencing was used to identify additional oncogenic alterations in BRAF(v600E)-mutant papillary thyroid carcinoma (PTC) patients, which were associated with increased risk of recurrence, larger tumor size, and more advanced stage at presentation. Independent oncogenic mutations in the PI3K/AKT/mTOR pathway were also found to be significantly associated with disease-specific mortality (DSM), highlighting the importance of genomic profiling for prognosis and clinical strategy in PTC.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
P. Garcia-Alfonso, G. Garcia-Gonzalez, I Gallego, M. Peligros, L. Ortega, G. Torres Perez-Solero, C. Sandoval, A. Munoz Martin, M. Blanco Codesido, A. Calvo Ferrandiz, M. Martin
Summary: The retrospective analysis in Spanish mCRC patients showed that triple and quadruple WT status were associated with significantly better overall survival. Patients with left-sided tumors, resected primary tumors, and isolated hepatic or pulmonary metastases also had improved survival outcomes.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dennis M. Timmerman, Thomas F. Eleveld, Ad J. M. Gillis, Carlijn C. Friedrichs, Sanne Hillenius, Tessa L. Remmers, Sruthi Sriram, Leendert H. J. Looijenga
Summary: Germ cell tumors (GCTs) have varying responses to platinum-based chemotherapy depending on their anatomical origin, with mediastinal GCTs showing resistance compared to testicular GCTs. TP53 mutations may play a role in causing cisplatin resistance in mediastinal GCTs, suggesting a potential target for treatment. The study provides insights into the underlying mechanisms of TP53 mutant and mediastinal GCTs for alternative treatment approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Health Care Sciences & Services
Antonio Ieni, Roberto Vita, Cristina Pizzimenti, Salvatore Benvenga, Giovanni Tuccari
Summary: Differentiated thyroid tumors (DTTs) exhibit significant molecular variability that could impact therapeutic management, with intra-tumoral heterogeneity (ITH) playing a crucial role in tumor growth, aggressive behavior, and drug resistance. Molecular testing in DTTs indicates a high risk of cancer recurrence associated with specific gene fusions, while intermediate risk may be related to other genetic factors.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Kenneth A. Kesler, Amanda R. Stram, Lava R. Timsina, Mark W. Turrentine, John W. Brown, Lawrence H. Einhorn
Summary: In the treatment of primary mediastinal nonseminomatous germ cell tumors, avoiding bleomycin-containing chemotherapy is important. Pre-and post chemotherapy pathology and postoperative serum tumor markers are independent predictors of long-term survival.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Biochemistry & Molecular Biology
Andre van Helvoort Lengert, Leticia do Nascimento Braga Pereira, Eduardo Ramos Martins Cabral, Izabela Natalia Faria Gomes, Lais Machado de Jesus, Maria Fernanda Santiago Goncalves, Aline Oliveira da Rocha, Tiago Alexandre Tassinari, Luciane Sussuchi da Silva, Ana Carolina Laus, Daniel Onofre Vidal, Mariana Tomazini Pinto, Rui Manuel Reis, Luiz Fernando Lopes
Summary: This study explored new strategies for treating cisplatin-resistant testicular germ cell tumors (TGCTs). Differential mRNA expression profiles were evaluated in a CDDP-resistant cell line and a parental cell line. The proteasome inhibitor MG-132 demonstrated cytotoxic activity and enhanced the sensitivity of the cell lines to cisplatin, increasing apoptosis.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2022)
Article
Pathology
Jen-Fan Hang, Jui-Yu Chen, Po-Chung Kuo, Hon-Fan Lai, Tsung-Lun Lee, Shyh-Kuan Tai, Chin-Sung Kuo, Harn-Shen Chen, Wan-Shan Li, Chien-Feng Li
Summary: This study investigates the change in the incidence of BRAF V600E mutations in papillary thyroid carcinoma (PTC) following the 2017 World Health Organization (WHO) classification. The study also characterizes the histologic subtypes and molecular drivers in BRAF-negative cases. The results show a significant increase in the incidence of BRAF V600E mutations in the PTC cohort after the 2017 WHO classification. Different molecular drivers, such as RET fusions, NTRK3 fusions, and BRAF fusions, were identified in BRAF-negative PTCs.
Article
Medicine, Research & Experimental
Raie T. Bekele, Amruta S. Samant, Amin H. Nassar, Jonathan So, Elizabeth P. Garcia, Catherine R. Curran, Justin H. Hwang, David L. Mayhew, Anwesha Nag, Aaron R. Thorner, Judit Borcsok, Zsofia Sztupinszki, Chong-Xian Pan, Joaquim Bellmunt, David J. Kwiatkowski, Guru P. Sonpavde, Eliezer M. Van Allen, Kent W. Mouw
Summary: The study identified RAF1 activation as a dependency in a subset comprising nearly 20% of urothelial tumors, suggesting that targeting RAF1-mediated signaling may represent a rational therapeutic strategy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Biochemistry & Molecular Biology
Massimo De Felici, Francesca Gioia Klinger
Summary: Several studies have demonstrated that the PI3K/PTEN/AKT signaling pathways play critical roles in regulating ovarian function, including primordial germ cell development and maintenance of the ovarian primordial follicle reserve. Dysregulation of these pathways may contribute to the development of certain types of germ cell tumors and ovarian dysfunctions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Dentistry, Oral Surgery & Medicine
Isadora Pereira Gomes, Leticia Martins Guimaraes, Thais dos Santos Fontes Pereira, Nubia Pereira Braga, Manoela Domingues Martins, Ricardo Santiago Gomez, Carolina Cavalieri Gomes
Summary: This study aimed to assess the activation of PI3K/AKT and MAPK/ERK signaling pathways in oral lymphatic malformations. The results showed that these pathways play a role in the pathogenesis of oral lymphatic malformations.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
(2022)
Article
Oncology
Samuel A. Funt, Deaglan J. McHugh, Stephanie Tsai, Andrea Knezevic, Devon O'Donnell, Sujata Patil, Deborah Silber, Maria Bromberg, Maryann Carousso, Victor E. Reuter, Brett S. Carver, Joel Sheinfeld, Robert J. Motzer, Dean F. Bajorin, George J. Bosl, Darren R. Feldman
Summary: The study analyzed the outcomes of 944 patients with good-risk germ cell tumors treated with EPx4 between 1982 and 2016. The results showed that EPx4 is highly effective and well tolerated, with a favorable response rate and disease-specific survival of 98%. Full-dose administration of etoposide and cisplatin and complete resection of residual disease lead to optimal outcomes. EPx4 should be recommended for certain patient groups at increased risk for bleomycin pulmonary toxicity and during ongoing transmission of severe acute respiratory syndrome coronavirus 2.
Article
Gastroenterology & Hepatology
Serdar Arici, Jamshid Hamdard, Abdullah Sakin, Selma Sengiz Erhan, Muhammed Mustafa Atci, Ruhper Cekin, Burcu Saka, Emin Kose, Tuba Saydam, Caglayan Geredeli, Sener Cihan, Ahmet Bilici
Summary: This study investigated the RAS discordance between initial and recurrent metastasectomy specimens in mCRC patients treated with chemotherapy plus biological agents. The results suggest that re-biopsy is necessary for optimal second-line treatment decision in mCRC patients, especially in those with wild-type RAS mCRC.
COLORECTAL DISEASE
(2021)
Article
Urology & Nephrology
Takashi Matsumoto, Masaki Shiota, Takeshi Uchiumi, Shohei Ueda, Shigehiro Tsukahara, Takahiro Toshima, Shinya Matsumoto, Nozomi Noda, Masatoshi Eto, Dongchon Kang
Summary: This study investigated somatic mutation profiles of testicular germ cell tumors in Japanese men and identified a low mutation rate, 18 novel mutations, and PDGFRA amplification. Mutations in genes such as KIT, BCR, PIK3CG, PIK3CA, and PDGFRA were found to be involved in aberrant signaling of the KIT-PI3K-AKT pathway.
INTERNATIONAL JOURNAL OF UROLOGY
(2021)
Letter
Oncology
Nima Almassi, Eugene J. Pietzak, Judy Sarungbam, Satish K. Tickoo, Victor E. Reuter, David B. Solit, Hikmat A. Al-Ahmadie
JOURNAL OF PATHOLOGY
(2020)
Article
Pathology
Alexander S. Taylor, Jesse K. McKenney, Adeboye O. Osunkoya, May P. Chan, Hikmat A. Al-Ahmadie, Daniel E. Spratt, Douglas R. Fullen, Arul M. Chinnaiyan, Noah A. Brown, Rohit Mehra
Article
Oncology
Sounak Gupta, Chad Vanderbilt, Wassim Abida, Samson W. Fine, Satish K. Tickoo, Hikmat A. Al-Ahmadie, Ying-Bei Chen, Sahussapont J. Sirintrapun, Kalyani Chadalavada, Gouri J. Nanjangud, Ann Bialik, Michael J. Morris, Howard I. Scher, Marc Ladanyi, Victor E. Reuter, Anuradha Gopalan
PROSTATE CANCER AND PROSTATIC DISEASES
(2020)
Review
Urology & Nephrology
Joshua J. Meeks, Hikmat Al-Ahmadie, Bishoy M. Faltas, John A. Taylor, Thomas W. Flaig, David J. DeGraff, Emil Christensen, Benjamin L. Woolbright, David J. McConkey, Lars Dyrskjot
NATURE REVIEWS UROLOGY
(2020)
Article
Pathology
Chen Yang, Robert S. Cimera, Ruth Aryeequaye, Gowtham Jayakumaran, Judy Sarungbam, Hikmat A. Al-Ahmadie, Anuradha Gopalan, S. Joseph Sirintrapun, Samson W. Fine, Satish K. Tickoo, Jonathan Epstein, Victor E. Reuter, Yanming Zhang, Ying-Bei Chen
Summary: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma, typically with an indolent course but potentially exhibiting aggressive clinical behavior in some cases. Genomic studies have shown that MTSCCs with aggressive clinical behavior may have evolved through clonal evolution, with CDKN2A/B deletion and additional complex genomic abnormalities playing a role in this process. Recognizing the morphologic presentation and adverse histologic features of high-grade MTSCCs can aid in establishing a definitive diagnosis and stratifying patients for treatment and prognostication.
Article
Oncology
Min Yuen Teo, Hikmat Al-Ahmadie, Kenneth Seier, Christopher Tully, Ashley M. Regazzi, Eugene Pietzak, David B. Solit, Satish Tickoo, Victor Reuter, Eugene K. Cha, Harry Herr, Timothy Donahue, Sherri M. Donat, Guido Dalbagni, Bernard H. Bochner, Samuel Funt, Gopakumar Iyer, Dean F. Bajorin, Irina Ostrovnaya, Jonathan E. Rosenberg
Summary: Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial cancer characterized by aggressive behavior and poor chemosensitivity. The efficacy of platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) in PUC patients is limited, with pathologic downstaging not significantly improving clinical outcomes. Increased awareness and recognition of PUC will aid in the development of new treatment strategies for this challenging disease.
BRITISH JOURNAL OF CANCER
(2021)
Article
Medicine, Research & Experimental
Justin Taylor, Mark T. A. Donoghue, Caleb Ho, Kseniya Petrova-Drus, Hikmat A. Al-Ahmadie, Samuel A. Funt, Yanming Zhang, Umut Aypar, Pavitra Rao, Shweta S. Chavan, Michael Haddadin, Roni Tamari, Sergio Giralt, Martin S. Tallman, Raajit K. Rampal, Priscilla Baez, Rajya Kappagantula, Satyajit Kosuri, Ahmet Dogan, Satish K. Tickoo, Victor E. Reuter, George J. Bosl, Christine A. Iacobuzio-Donahue, David B. Solit, Barry S. Taylor, Darren R. Feldman, Omar Abdel-Wahab
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Correction
Oncology
Min Yuen Teo, Hikmat Al-Ahmadie, Kenneth Seier, Christopher Tully, Ashley M. Regazzi, Eugene Pietzak, David B. Solit, Satish Tickoo, Victor Reuter, Eugene K. Cha, Harry Herr, Timothy Donahue, Sherri M. Donat, Guido Dalbagni, Bernard H. Bochner, Samuel Funt, Gopakumar V. Iyer, Dean F. Bajorin, Irina Ostrovnaya, Jonathan E. Rosenberg
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Samuel A. Funt, Michael Lattanzi, Karissa Whiting, Hikmat Al-Ahmadie, Colleen Quinlan, Min Yuen Teo, Chung-Han Lee, David Aggen, Danielle Zimmerman, Deaglan McHugh, Arlyn Apollo, Trey D. Durdin, Hong Truong, Jeffrey Kamradt, Maged Khalil, Bradley Lash, Irina Ostrovnaya, Asia S. McCoy, Grace Hettich, Ashley Regazzi, Marwah Jihad, Neha Ratna, Abigail Boswell, Kaitlyn Francese, Yuanquan Yang, Edmund Folefac, Harry W. Herr, S. Machele Donat, Eugene Pietzak, Eugene K. Cha, Timothy F. Donahue, Alvin C. Goh, William C. Huang, Dean F. Bajorin, Gopa Iyer, Bernard H. Bochner, Arjun V. Balar, Amir Mortazavi, Jonathan E. Rosenberg
Summary: Neoadjuvant gemcitabine and cisplatin (GC) plus atezolizumab (A) showed promising efficacy for patients with muscle-invasive bladder cancer (MIBC). The study suggests that this combination therapy warrants further investigation, despite limitations regarding PD-L1 as a predictive biomarker.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Maria Clara Fernandes, Alexander Shoushtari, Mario M. Jr Jr Leitao, M. Herman Chui, Hikmat Al-Ahmadie, Iva Petkovska
Summary: This case presents a 47-year-old woman with acral lentiginous melanoma metastatic to the lungs, brain, and spleen, who also had lower urinary tract symptoms and dark mass removed from her vaginal canal. MRI showed polypoidal lesions in the urinary bladder and endometrium, consistent with the suspected diagnosis of melanoma metastases. Cystoscopy and biopsy confirmed the presence of bladder and endometrial metastatic lesions, which are rare occurrences.
JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY
(2022)
Article
Pathology
Paari Murugan, Liwei Jia, Renzo G. Dinatale, Melissa Assel, Nicole Benfante, Hikmat A. Al-Ahmadie, Samson W. Fine, Anuradha Gopalan, Judy Sarungbam, S. Joseph Sirintrapun, A. Ari Hakimi, Paul Russo, Ying-Bei Chen, Satish K. Tickoo, Victor E. Reuter
Summary: This study analyzed 199 cases of PRCC with type 1 features and found clinicopathological features associated with outcome, indicating that type 2 features in PRCC with mixed histology represent morphologic variance or clonal evolution.
Article
Multidisciplinary Sciences
Jeppe Sejero Holm, Samuel A. Funt, Annie Borch, Kamilla Kjaergaard Munk, Anne-Mette Bjerregaard, James L. Reading, Colleen Maher, Ashley Regazzi, Phillip Wong, Hikmat Al-Ahmadie, Gopa Iyer, Tripti Tamhane, Amalie Kai Bentzen, Nana Overgaard Herschend, Susan De Wolf, Alexandra Snyder, Taha Merghoub, Jedd D. Wolchok, Morten Nielsen, Jonathan E. Rosenberg, Dean F. Bajorin, Sine Reker Hadrup
Summary: This study demonstrates that the expansion of neoantigen-specific CD8(+) T cells can distinguish between patients with controlled disease and progressive disease in metastatic urothelial carcinoma treated with PD-L1 blockade. Furthermore, the peripheral NARTs derived from patients with disease control exhibit specific cell phenotypes and increased CD39 levels, suggesting their association with treatment response.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
W. Kimryn Rathmell, R. Bryan Rumble, Peter J. Van Veldhuizen, Hikmat Al-Ahmadie, Hamid Emamekhoo, Ralph J. Hauke, Alexander Louie, Matthew Milowsky, Ana M. Molina, Tracy L. Rose, Shankar Siva, Nicholas G. Zaorsky, Tian Zhang, Rubina Qamar, Terry M. Kungel, Bryan Lewis, Eric A. Singer
Summary: The article provides recommendations for the management of patients with metastatic clear cell renal cell carcinoma (ccRCC), including diagnosis, treatment, and participation in clinical trials.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Gil Redelman-Sidi, Anna Binyamin, Anthony C. Antonelli, Will Catalano, James Bean, Hikmat Al-Ahmadie, Achim A. Jungbluth, Michael S. Glickman
Summary: This study reveals that BCG immunotherapy stimulates tumor-specific T-cell immunity and demonstrates that the activation of this immune response requires tumor cell intrinsic expression of CIITA. However, the specific mechanisms of tumor immunity still need to be determined. The findings suggest that different immunotherapy modalities can be employed based on tumor-intrinsic characteristics.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Michal Sarfaty, Mahdi Golkaram, Samuel A. A. Funt, Hikmat Al-Ahmadie, Shannon Kaplan, Fan Song, Ashley Regazzi, Vladimir Makarov, Fengshen Kuo, Irina Ostrovnaya, Venkatraman Seshan, Chen Zhao, Benjamin Greenbaum, Li Liu, Jonathan E. E. Rosenberg, Timothy A. A. Chan
Summary: Whole-exome sequencing of tumor samples from 88 patients with advanced bladder cancer treated with immune checkpoint blockade therapy (ICB) revealed genetic variables associated with treatment benefit. These include ARID1A mutation, tumor mutational burden, intratumoral heterogeneity, immune dN/dS ratio, tumor cell purity, neutrophil-to-lymphocyte ratio, and smoking history. Four molecular subtypes were identified that showed differential sensitivity to ICB. The association of these subtypes with clinical benefit was validated in an independent cohort and their correlation with outcome was shown in patients not receiving ICB treatment.
JOURNAL OF CLINICAL ONCOLOGY
(2023)