scholarly journals Cabozantinib for HCC Treatment, From Clinical Back to Experimental Models

2021 ◽  
Vol 11 ◽  
Author(s):  
Shanshan Deng ◽  
Antonio Solinas ◽  
Diego F. Calvisi
Keyword(s):  
Early Stage ◽  
Experimental Models ◽  
New Drugs ◽  
Efficacy Evaluation ◽  
Phase 3 ◽  
Multikinase Inhibitor ◽  
Future Directions ◽  
Advanced Hcc ◽  
Related Mortality ◽  
Systemic Therapies

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Patients with early-stage HCC can be treated successfully with surgical resection or liver transplantation. However, the usual late diagnosis of HCC precludes curative treatments, and systemic therapies are the only viable option for inoperable patients. Sorafenib, an orally available multikinase inhibitor, is a systemic therapy approved for treating patients with advanced HCC yet providing limited benefits. Consequently, new drugs have been developed to overcome sorafenib resistance and improve patients’ prognoses. A new promising strategy is using c-MET inhibitors, such as cabozantinib, as activation of c-MET occurs in up to 40% of HCC patients. In particular, cabozantinib, in combination with the checkpoint inhibitor atezolizumab, is currently in phase 3 clinical trial for HCC, and the results are eagerly awaited. Herein, we summarize and review the drugs approved for the treatment of advanced HCC, mainly focusing on the clinical and preclinical efficacy evaluation of cabozantinib. Also, we report the available preclinical data on cabozantinib-based combination therapies for HCC, current obstacles for cabozantinib therapy, and the future directions for cabozantinib-based treatment for HCC.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

Experimental Rodent Models of Vascular Dementia: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Nidhi Tiwari ◽  
Jyoti Upadhyay ◽  
Mohd Nazam Ansari ◽  
Syed Shadab Raza ◽  
Wasim Ahmad ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Small Vessel Disease ◽  
Current Knowledge ◽  
Vascular Cognitive Impairment ◽  
Experimental Models ◽  
New Drugs ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
The Brain ◽  
Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial

2021 ◽  
Vol 22 (2) ◽  
pp. 223-234 ◽  
Author(s):  
Peter Borchmann ◽  
Annette Plütschow ◽  
Carsten Kobe ◽  
Richard Greil ◽  
Julia Meissner ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Open Label ◽  
Phase 3

scholarly journals Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19-Related Mortality during the Early Stage of the Epidemic in the United States

2021 ◽  
Vol 18 (8) ◽  
pp. 4021
Author(s):  
Esteban Correa-Agudelo ◽  
Tesfaye B. Mersha ◽  
Adam J. Branscum ◽  
Neil J. MacKinnon ◽  
Diego F. Cuadros
Keyword(s):  
United States ◽  
Vulnerable Populations ◽  
Mortality Risk ◽  
Early Stage ◽  
The United States ◽  
National Average ◽  
Health Determinants ◽  
White Population ◽  
Latino Population ◽  
Related Mortality

We characterized vulnerable populations located in areas at higher risk of COVID-19-related mortality and low critical healthcare capacity during the early stage of the epidemic in the United States. We analyze data obtained from a Johns Hopkins University COVID-19 database to assess the county-level spatial variation of COVID-19-related mortality risk during the early stage of the epidemic in relation to health determinants and health infrastructure. Overall, we identified highly populated and polluted areas, regional air hub areas, race minorities (non-white population), and Hispanic or Latino population with an increased risk of COVID-19-related death during the first phase of the epidemic. The 10 highest COVID-19 mortality risk areas in highly populated counties had on average a lower proportion of white population (48.0%) and higher proportions of black population (18.7%) and other races (33.3%) compared to the national averages of 83.0%, 9.1%, and 7.9%, respectively. The Hispanic and Latino population proportion was higher in these 10 counties (29.3%, compared to the national average of 9.3%). Counties with major air hubs had a 31% increase in mortality risk compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19-related mortality risk also had lower critical care capacity than the national average. The disparity in health and environmental risk factors might have exacerbated the COVID-19-related mortality risk in vulnerable groups during the early stage of the epidemic.

scholarly journals Evolution of Cancer Vaccines—Challenges, Achievements and Future Directions

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 535
Author(s):  
Ban Qi Tay ◽  
Quentin Wright ◽  
Rahul Ladwa ◽  
Christopher Perry ◽  
Graham Leggatt ◽  
...  
Keyword(s):  
Cancer Vaccines ◽  
New Drugs ◽  
Delivery Methods ◽  
Future Directions ◽  
The Past ◽  
New Directions ◽  
Tumour Antigens ◽  
Target Characteristics ◽  
Toxic Responses ◽  
Shed Light

The development of cancer vaccines has been intensively pursued over the past 50 years with modest success. However, recent advancements in the fields of genetics, molecular biology, biochemistry, and immunology have renewed interest in these immunotherapies and allowed the development of promising cancer vaccine candidates. Numerous clinical trials testing the response evoked by tumour antigens, differing in origin and nature, have shed light on the desirable target characteristics capable of inducing strong tumour-specific non-toxic responses with increased potential to bring clinical benefit to patients. Novel delivery methods, ranging from a patient’s autologous dendritic cells to liposome nanoparticles, have exponentially increased the abundance and exposure of the antigenic payloads. Furthermore, growing knowledge of the mechanisms by which tumours evade the immune response has led to new approaches to reverse these roadblocks and to re-invigorate previously suppressed anti-tumour surveillance. The use of new drugs in combination with antigen-based therapies is highly targeted and may represent the future of cancer vaccines. In this review, we address the main antigens and delivery methods used to develop cancer vaccines, their clinical outcomes, and the new directions that the vaccine immunotherapy field is taking.

Nivolumab/pembrolizumab in Child-Pugh grade B/C patients with advanced HCC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16184-e16184
Author(s):  
Jeffrey Sum Lung Wong ◽  
Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Li ◽  
Roland Ching-Yu Leung ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Refractory Ascites ◽  
Time To Progression ◽  
Advanced Hcc ◽  
Grade 3 ◽  
Experienced Grade ◽  
Systemic Therapies

e16184 Background: Hepatic derangement commonly accompanies advanced HCC (aHCC) and limits the use of systemic therapies. We aimed to evaluate the use of single agent anti-PD-1 nivolumab or pembrolizumab in Child-Pugh (CP) grade B or C patients with aHCC. Methods: Consecutive aHCC patients with CP grade B (CPB) or C (CPC) liver function who received single agent nivolumab or pembrolizumab were analysed. Objective response rate (ORR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Results: Between May 2015 and June 2020, 61 patients were included. The median age was 60 (range 28-82). 81% and 4.8% had hepatitis-B and hepatitis-C related HCCs respectively. 72.1% (n = 44) were of CPB and 27.9% (n = 17) were of CPC. Amongst CPB patients, 19 (31.1% of all patients) had CP score 7 (CP7) and 25 (41.0% of all patients) had CP score 8 or 9. The median follow-up was 2.3 months. The ORR of CPB and CPC patients were 6.8% and 0% respectively (p = 0.553). The TTP of CPB and CPC patients were 2.1 months (95% C.I. 1.4-2.8) and 1.4 months (95% C.I. 0.6-2.1) respectively (p = 0.204). CPB patients had significantly better OS than CPC patients (3.1 months (95% C.I. 1.4-4.7), vs. 1.7 months (95% C.I. 1.0-2.4), p = 0.041). Compared to CP score ≥8 (CP≥8) patients, CP7 patients had significantly better OS (median OS CP7 6.7 months (95% C.I. 4.0-9.3), vs. CP≥8 1.8 months (1.2-2.4), p = 0.002). Patients with diuretic-refractory ascites had significantly worse OS compared to those without (1.7 months (95% C.I. 1.0-2.5) vs. 3.7 months (95% C.I. 0.1-7.3), p = 0.004). Portal vein (PV) thrombosis was also significantly associated with inferior survival, with median OS of patients with any PV thrombosis being 1.8 months (95% C.I. 1.0-2.5), compared to 5.3 months (95% C.I. 2.4-8.1) of those without (p = 0.004). The median number of doses given was 3 (range 1-34). Median treatment duration was 5.0 weeks (range 0-77). Overall, 25.4% of patients experienced TRAEs and 4.8% experienced grade ≥3 TRAEs. The most common TRAEs were skin-related (13.1%) and constitutional symptoms (6.6%). Conclusions: Nivolumab/pembrolizumab had acceptable safety in CPB/C patients with aHCC. CP7, absence of diuretic-refractory ascites and lack of PV thrombosis were associated with better survival.

Placebo Response in Phase 3 Trials of Systemic Therapies for Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Meta-Analysis

Dermatology ◽  
2020 ◽  
pp. 1-8
Author(s):  
Danni Ambikaibalan ◽  
Anna Sophie Quaade ◽  
Anne-Sofie Halling ◽  
Jacob P. Thyssen ◽  
Alexander Egeberg
Keyword(s):  
Systematic Review ◽  
Plaque Psoriasis ◽  
Meta Analysis ◽  
Placebo Response ◽  
Phase 3 ◽  
Severe Plaque Psoriasis ◽  
Systemic Therapies

scholarly journals Assessing the Clinical Benefit of Systemic Adjuvant Therapies for Early Breast Cancer

2017 ◽  
Vol 77 (10) ◽  
pp. 1079-1087 ◽  
Author(s):  
Volker Möbus ◽  
Susanne Hell ◽  
Marcus Schmidt
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Clinical Benefit ◽  
Early Stage ◽  
Survival Rates ◽  
Disease Free Survival ◽  
New Drugs ◽  
Early Stage Breast Cancer ◽  
Risk Of Recurrence ◽  
Adjuvant Therapies

AbstractOncologic therapy is currently undergoing significant changes. A number of innovative targeted medications currently in clinical development have raised high expectations. With that in mind, discussions about terms such as “clinical benefit” and “clinical relevance” are highly topical. This also applies to further developments in the field of adjuvant systemic therapies for early-stage breast cancer. As the treatment aim is curative, assessment of the clinical benefit of adjuvant therapies must be largely based on efficacy outcomes. The focus must be on improving disease-free survival rates and lowering the risk of recurrence. Because of the current low mortality rates, statements about overall survival rates are only possible after very long observation periods. Consequently, new drugs in adjuvant therapies should be considered as offering a clinical benefit, if they reduce the risk of recurrence below current low levels of risk. The evidence for established adjuvant therapy standards in early-stage breast cancer can be used as objective criteria for comparison. This review article considers the requirements for clinical benefit of new adjuvant therapies for early breast cancer, based on examples from adjuvant endocrine therapy, adjuvant polychemotherapy and adjuvant anti-HER2 therapy.

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