scholarly journals The Molecular Pathogenesis of Osteosarcoma: A Review

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Matthew L. Broadhead ◽  
Jonathan C. M. Clark ◽  
Damian E. Myers ◽  
Crispin R. Dass ◽  
Peter F. M. Choong
Keyword(s):  
Young Adults ◽  
Survival Rate ◽  
Disease Management ◽  
Targeted Therapies ◽  
Molecular Pathogenesis ◽  
Targeted Drugs ◽  
Comprehensive Understanding ◽  
Primary Malignancy ◽  
Translational Studies ◽  
Multiagent Chemotherapy

Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%–70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management.

scholarly journals Targeting the Hippo Pathway for Breast Cancer Therapy

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 422 ◽  
Author(s):  
Liqing Wu ◽  
Xiaolong Yang
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Targeted Therapies ◽  
Hippo Pathway ◽  
Targeted Drugs ◽  
Breast Cancer Therapy ◽  
The World ◽  
Core Components ◽  
Future Direction ◽  
The Hippo Pathway

Breast cancer (BC) is one of the most prominent diseases in the world, and the treatments for BC have many limitations, such as resistance and a lack of reliable biomarkers. Currently the Hippo pathway is emerging as a tumor suppressor pathway with its four core components that regulate downstream transcriptional targets. In this review, we introduce the present targeted therapies of BC, and then discuss the roles of the Hippo pathway in BC. Finally, we summarize the evidence of the small molecule inhibitors that target the Hippo pathway, and then discuss the possibilities and future direction of the Hippo-targeted drugs for BC therapy.

MicroRNA-211-5p promotes apoptosis and inhibits the migration of osteosarcoma cells by targeting proline-rich protein PRR11

2020 ◽  
Vol 98 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Dandan Song ◽  
Kun Yang ◽  
Wei Wang ◽  
Run Tian ◽  
Haoyu Wang ◽  
...  
Keyword(s):  
Young Adults ◽  
Survival Rate ◽  
Personalized Medicine ◽  
Cell Lines ◽  
Clinical Samples ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Expression Levels ◽  
Proline Rich Protein

Osteosarcoma remains fatal in adolescents and young adults, with a 5-year survival rate of less than 20%. However, the details for mechanisms that regulate osteosarcoma metastasis are poorly understood. We analyzed the expression levels of miR-211-5p in clinical samples of osteosarcoma as well as cell lines, and found that the expression of miR-211-5p was reduced in osteosarcoma. Moreover, induction of miR-211-5p in several osteosarcoma cell lines dramatically inhibited their migration and invasiveness. Furthermore, miR-211-5p overexpression led to a significant increase in the apoptosis of osteosarcoma cell. Importantly, our in vivo xenograft experiments showed that miR-211-5p strongly inhibits tumorigenesis. Additionally, functional experiments demonstrated that miR-211-5p suppresses the expression of proline-rich protein 11 (PRR11) by directly binding to the 3′ region of PRR11 mRNA. Moreover, we showed that PRR11 overexpression attenuated the increase of apoptosis and decreased migration and invasiveness when the upstream miR-211-5p was overexpressed. Our data provide new insights into the mechanisms that regulate osteosarcoma metastasis, and novel potential pharmaceutical targets for personalized medicine.

scholarly journals Signalling networks in cholangiocarcinoma: Molecular pathogenesis, targeted therapies and drug resistance

2019 ◽  
Vol 39 (S1) ◽  
pp. 43-62 ◽  
Author(s):  
Laura Fouassier ◽  
Marco Marzioni ◽  
Marta B. Afonso ◽  
Steven Dooley ◽  
Kevin Gaston ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Targeted Therapies ◽  
Molecular Pathogenesis

Neuroendocrine Tumors of the Pancreas: Molecular Pathogenesis and Perspectives on Targeted Therapies

2014 ◽  
Vol 3 (3) ◽  
pp. 141-150
Author(s):  
Dmitry Andreev ◽  
◽  
Igor Maev ◽  
Yuriy Kucheryavyy ◽  
Diana Dicheva
Keyword(s):  
Neuroendocrine Tumors ◽  
Targeted Therapies ◽  
Molecular Pathogenesis

scholarly journals A 26-Year-Old Male with Mesothelioma Due to Asbestos Exposure

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
P. Zarogoulidis ◽  
M. Orfanidis ◽  
T. C. Constadinidis ◽  
E. Eleutheriadou ◽  
T. Kontakiotis ◽  
...  
Keyword(s):  
Young Adults ◽  
Lymph Node ◽  
Survival Rate ◽  
Poor Prognosis ◽  
Asbestos Exposure ◽  
Older Men ◽  
Chemotherapy Treatment ◽  
Supraclavicular Lymph Node ◽  
Occupationally Exposed ◽  
The Right

Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009.

scholarly journals Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shen Zhao ◽  
Zhonghan Zhang ◽  
Jianhua Zhan ◽  
Xin Zhao ◽  
Xinru Chen ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Patient Outcomes ◽  
Targeted Therapies ◽  
Advanced Nsclc ◽  
Clinical Care ◽  
Progression Free Survival ◽  
Targeted Drugs ◽  
Genomic Profiling ◽  
Recent Emergence ◽  
Comprehensive Genomic Profiling

Abstract Background With the identification of new targetable drivers and the recent emergence of novel targeted drugs, using comprehensive genomic profiling in lieu of the routine testing for classic drivers in the clinical care for advanced NSCLC has been increasingly advocated. However, the key assumption justifying this practice, that comprehensive genomic profiling could lead to effective anticancer therapies and improve patient outcomes, remains unproved. Methods Comprehensive genomic profiling was prospectively applied in 1564 advanced NSCLC patients to identify potentially actionable genomic alterations. Patients were assigned to genotype-matched targeted therapies or nonmatched therapies based on the profiling results. Its utility in directing treatments was determined by the proportion of patients receiving genotype-matched targeted therapies and the proportion of patients being enrolled into genotype-matched clinical trials. Its impacts on patient outcomes were assessed by comparing progression-free survival (PFS) and overall survival (OS) between patients who received a genotype-matched and nonmatched therapy. Results From October 2016 to October 2019, tumor genomic profiles were established in 1166 patients, leading to a matched targeted therapy in 37.7% (n = 440) and a genotype-matched trial enrollment in 20.9% of patients (n = 244). Potentially actionable alterations were detected in 781 patients (67.0%). For these patients, a genomic profiling-directed matched therapy significantly improved PFS (9.0 months vs 4.9 months, P < 0.001) and OS (3.9 years vs 2.5 years, P < 0.001) compared with a nonmatched therapy. Excluding patients with standard targeted therapies, genomic profiling led to a matched targeted therapy in 16.7% (n = 24) and a matched trial enrollment in 11.2% (n = 16) of patients. No PFS (4.7 months vs 4.6 months, P = 0.530) or OS (1.9 years vs 2.4 years, P = 0.238) benefit was observed with the use of genotype-matched targeted therapies in this population. Conclusions Comprehensive genomic profiling is of clinical utility in assisting treatment selection, facilitating clinical trial enrollment, and improving patient outcomes in advanced NSCLC. However, for patients carrying alterations without standard-of-care targeted drugs, the interpretation of genomic profiling results should be careful given the low likelihood of benefit from the investigational or off-label use of targeted therapies in this population in the current treatment landscape. Trial registration ChiCTR1900027582 (retrospectively registered on 19 November 2019)

scholarly journals Testicular germ cells tumors in adolescents and young adults: Management and outcomes from a single-center experience

2021 ◽  
Vol 93 (3) ◽  
pp. 301-306
Author(s):  
Claudio Spinelli ◽  
Gianmartin Cito ◽  
Girolamo Morelli ◽  
Marco Ghionzoli ◽  
Alessia Bertocchini ◽  
...  
Keyword(s):  
Young Adults ◽  
Survival Rate ◽  
Active Surveillance ◽  
Germ Cells ◽  
Active Treatment ◽  
Age Groups ◽  
Retroperitoneal Lymphadenectomy ◽  
Group A ◽  
Group B

Objective: To investigate and compare the effectiveness of active surveillance versus post-surgical active treatment, in patients with testicular germ cells tumor (TGCT). Materials and methods: We retrospectively analyzed 52 patients who underwent surgery for TGCT from January 2009 to December 2014. All the patients were divided into two age groups: the Group A included children-adolescents from 18 months to 21 years old, while the Group B comprised young adults from 22 to 39 years old. Clinical, histopathological, therapeutic and follow-up data were collected. Results: Overall, 22 patients (42,3%) were enrolled in the Group A and 30 patients (57.7%) were categorized in the Group B. Inguinal orchiectomy was performed in all patients. Retroperitoneal lymphadenectomy was performed in 4 patients (7.7%). Post-surgical management differed based on clinical stage, resulting in active surveillance or adjuvant therapy. After an average 7 years follow-up period (range: 3.5-9.0 years), the overall survival rate is 100%. The relapse risk is significantly higher for the patients in the Group B, displaying a recurrence free-survival rate of 72% versus 95% (Group A); 11 relapses (21.1%) were recorded 2 years after surgery. Of these, 3 recurrences (12.0%) occurred in patients undergoing an active surveillance approach, while 8 (29.6%) in patients subjected to an active treatment. Conclusions: The excellent prognosis in both age groups confirms the high curability of this neoplasia. The active surveillance could represent an optimal option for low recurrence risk tumors. However, post-surgical treatments should be taken into consideration for TGCT with high risk factors, including tumor size, lymphovascular and rete testis invasion.

scholarly journals Management of Hemato-oncology children during covid-19 crisis

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 369-375
Author(s):  
Ranjit Kumar C S ◽  
Reghu K Sukumaran ◽  
Anil Aribandi ◽  
Ashok kumar K ◽  
Arun Kumar Lingutla ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Young Adults ◽  
Bone Marrow Transplantation ◽  
Mortality Rate ◽  
Disease Management ◽  
Blood Transfusion ◽  
Severe Infection ◽  
Newly Diagnosed ◽  
Immunocompromised Status ◽  
Immunosuppression Therapy

The Coronavirus (COVID-19) caused by severe acute respiratory syndrome, coronavirus 2(SARS-CoV-2). The COVID-19 pandemic has had a catastrophic effect on global health. About 2% of confirmed cases of COVID-19 were among children aged<18yrs old. Children, teens and young adults are at higher risk for severe complication and presentation with multisystem inflammatory disease. Management of children with COVID infection is not yet standardized. However, cancer children are at potential risk due to immunocompromised status and their management is unknown. The immunocompromised children are at risk of severe infection, and they have a high mortality rate. Here in this article, we are describing when to suspect COVID infection, how to manage newly diagnosed cancer children and existing patient including bone marrow transplantation and immunosuppression therapy and also blood transfusion policy during COVID pandemic time.

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