Claudio Festuccia

Assunta Leda Biordi

Vincenzo Tombolini

Akira Hara

David Bailey

Targeted Molecular Therapy in Glioblastoma

<i>Background</i>. Primary bone and soft tissue sarcomas are rare tumors requiring wide surgical resection and reconstruction to achieve local control. Postoperative complications can lead to delays in adjuvant therapy, potentially affecting long-term oncologic outcomes. Understanding postoperative complication risks is essential; however, past studies are limited by small sample sizes. <i>Purpose</i>. This study uses a large national registry to characterize the incidence of complications and mortality in the first thirty days following surgical management of primary bone and soft tissue sarcomas of the extremities. <i>Methods</i>. A retrospective review of patients in the National Surgical Quality Improvement Program database was performed. Cases were identified using diagnosis codes for malignant neoplasm of soft tissue or bone and procedure codes for amputation and radical resection. The cohort was subdivided by bone versus soft tissue sarcoma, upper versus lower extremity, and amputation versus limb salvage. <i>Results</i>. One thousand, one hundred eleven patients were identified. The most frequent complications were surgical site infections, sepsis, and venous thromboembolism. The overall incidence of complications was 14.0&#x0025;. Unplanned readmission and reoperation occurred after 7.0&#x0025; and 8.0&#x0025; of cases, respectively. Thirty-day mortality was 0.3&#x0025;, with one intraoperative death. Patient factors and complication rates varied by tumor location and surgical modality. Lower extremity cases were associated with higher rates of wound complications and infectious etiologies such as surgical site infections, urinary tract infections, and systemic sepsis. In contrast, patients undergoing amputation were more likely to experience major medical complications including acute renal failure, cardiac arrest, and myocardial infarction. <i>Conclusion</i>. Approximately 1 in 7 patients will experience a complication in the first thirty days following surgery for primary bone and soft tissue sarcomas of the extremities. The unique risk profiles of lower extremity and amputation cases should be considered during perioperative planning and surveillance.

Kathryn E. Gallaway

Junho Ahn

Alexandra K. Callan

Thirty-Day Outcomes after Surgery for Primary Sarcomas of the Extremities: An Analysis of the NSQIP Database

Panobinostat represents a potent oral nonselective pan-histone deacetylase inhibitor (HDAC) with activity in myeloma patients. It has been approved by the FDA and EMA in combination with bortezomib and dexamethasone for the treatment of multiple myeloma, in patients who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. In order to further explore its clinical potential, it is evaluated in different combinations in relapsed/refractory and newly diagnosed multiple myeloma. This review focuses on available data about panobinostat&#x2019;s pharmacology and its role in clinical practice. This review will reveal panobinostat&#x2019;s efficacy as antimyeloma treatment, describing drug evolution from preclinical experimental administration to administration in phase III trials, which established its role in current clinical practice. Based on the latest data, we will present its mechanism of action, its efficacy, and most important issues regarding its toxicity profile. We will further try to shed light on its role in current and future therapeutic landscape of myeloma patients. Panobinostat retains its role in therapy of multiple myeloma because of its manageable toxicity profile and its efficacy, mainly in heavily pretreated multiple myeloma patients. These characteristics make it valuable also for novel regimens in combination with second-generation proteasome inhibitors, IMiDs, and monoclonal antibodies. Results of ongoing trials are expected to shed light on drug introduction in different therapeutic combinations or even at an earlier level of disease course.

Evangelos Eleutherakis-Papaiakovou

Nikolaos Kanellias

Efstathios Kastritis

Maria Gavriatopoulou

Evangelos Terpos

Meletios Athanasios Dimopoulos

Efficacy of Panobinostat for the Treatment of Multiple Myeloma

Immune checkpoint therapy, such as the reactivation of T-cell activity by targeting programmed cell death 1 (PD-1) and its ligand PD-L1 (also called B7-H1 and CD274) has been found pivotal in changing the historically dim prognoses of malignant tumors by causing durable objective responses. However, the response rate of immune checkpoint therapy required huge improvements. It has been shown that the expression of PD-L1 on cancer cells and immune cell membranes is correlated with a more durable objective response rate to PD-L1 antibodies, which highlights the importance of deeply understanding how this protein is regulated. Posttranslational modifications such as phosphorylation, N-glycosylation, and ubiquitination of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In this review, we summarized the latest findings of PD-L1 protein modification and their clinical applications.

Shu-Man Li

Jie Zhou

Yun Wang

Run-Cong Nie

Jie-Wei Chen

Dan Xie

Recent Findings in the Posttranslational Modifications of PD-L1

Gelsolin (GSN), a cytoskeletal protein, is frequently overexpressed in different cancers and promotes cell motility. The biological function of GSN in hepatocellular carcinoma (HCC) and its mechanism remain unclear. The expression of GSN was assessed in a cohort of 188 HCC patients. The effects of GSN on the migration and invasion of tumour cells were examined. Then, the role of GSN in tumour growth <i>in vivo</i> was determined by using a cancer metastasis assay. The possible mechanism by which GSN promotes HCC progression was explored. As a result, GSN was overexpressed in HCC tissues. High GSN expression was significantly correlated with late Edmondson grade, encapsulation, and multiple tumours. Patients with high GSN expression had worse overall survival (OS) and disease-free survival (DFS) than those with low GSN expression. GSN expression was identified as an independent risk factor in both OS (hazard risk (HR) = 1.620, 95% confidence interval (CI) = 1.105–2.373, <span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6370001pt" id="M1" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 51.1027 9.2729" width="51.1027pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>)</span> and DFS (HR = 1.744, 95% CI = 1.205–2.523, <span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M2" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 51.1027 8.8423" width="51.1027pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g></svg>).</span> Moreover, GSN knockdown significantly inhibited the migration and invasion of HCC tumour cells, while GSN overexpression attenuated these effects by regulating epithelial-mesenchymal transition (EMT) In conclusion, GSN promotes cancer progression and is associated with a poor prognosis in HCC patients. GSN promotes HCC progression by regulating EMT.

Yixi Zhang

Xiaojing Luo

Jianwei Lin

Shunjun Fu

Pei Feng

Hongjun Su

Xiangjun He

Xue Liang

Kunpeng Liu

Wen Deng

Gelsolin Promotes Cancer Progression by Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma and Correlates with a Poor Prognosis

Colorectal cancer (CRC) is the 5<sup>th</sup> leading cancer in China. Alcohol consumption has been reported to be one of the risk factors of CRC. However, it remains unclear whether genetic variants of alcohol metabolic genes are associated with CRC risk. In this study, we tested the coding variants in the alcohol metabolic genes and the risk of CRC, by using 485 cases and 516 controls. A total of 16 germline coding variants in 10 alcohol metabolic genes were genotyped. We identified that rs3741178 in ALDH3B2 was significantly associated with CRC risk with odds ratio being 2.13 (95% CI: 1.24–3.68, <span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M1" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 57.3661 8.8423" width="57.3661pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.013,0,0,-0.013,50.845,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g></svg>).</span> Further functional annotation suggested that this variant may damage the protein function of ALDH3B2. Our results suggested that ALDH3B2 in the alcohol metabolism pathway contributed to the development of CRC, which may contribute to the prevention of this disease in the future.

Zhi-Gang Gao

Yong Yang

Xiao-Feng Han

Yun-Lei Wang

Zhen-Jun Wang

ALDH3B2 Polymorphism Is Associated with Colorectal Cancer Susceptibility

Overactivation of the mitogen-activated protein kinase (MAPK) pathway is an important driver of many human cancers. First line, FDA-approved therapies targeting MAPK signalling, which include BRAF and MEK inhibitors, have variable success across cancers, and a significant number of patients quickly develop resistance. In recent years, a number of preclinical studies have reported alternative methods of overcoming resistance, which include promoting apoptosis, modulating autophagy, and targeting mitochondrial metabolism. This review summarizes mechanisms of resistance to approved MAPK-targeted therapies in BRAF-mutated cancers and discusses novel preclinical approaches to overcoming resistance.

Emily L. Paton

Jacqueline A. Turner

Isabel R. Schlaepfer

Overcoming Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutated Tumours

Philippe-Richard J. Domeyer

Theodoros N. Sergentanis

New Insights into the Screening, Prompt Diagnosis, Management, and Prognosis of Breast Cancer

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<p><em>Journal of Oncology</em> publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.</p>


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<p>Chief Editor, Professor Bruno Vincenzi, is an Associate Professor of Medical Oncology at University Campus Bio-Medico, Italy. His research interests include urogenital neoplasms and the pathophysiology and treatment of bone metastases.</p>


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Journal of Oncology - Table of contents 2020

title

Journal of Oncology publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.

Journal of Oncology