scholarly journals Movement Disorders in Oncology: From Clinical Features to Biomarkers

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 26
Author(s):  
Luca Marsili ◽  
Alberto Vogrig ◽  
Carlo Colosimo
Keyword(s):  
Brain Tumors ◽  
Movement Disorders ◽  
Clinical Laboratory ◽  
Checkpoint Inhibitors ◽  
Diagnostic Testing ◽  
Response To Treatment ◽  
Immune Checkpoints ◽  
Laboratory Findings ◽  
Antineuronal Antibodies ◽  
Wide Range

Background: the study of movement disorders associated with oncological diseases and anticancer treatments highlights the wide range of differential diagnoses that need to be considered. In this context, the role of immune-mediated conditions is increasingly recognized and relevant, as they represent treatable disorders. Methods: we reappraise the phenomenology, pathophysiology, diagnostic testing, and treatment of movement disorders observed in the context of brain tumors, paraneoplastic conditions, and cancer immunotherapy, such as immune-checkpoint inhibitors (ICIs). Results: movement disorders secondary to brain tumors are rare and may manifest with both hyper-/hypokinetic conditions. Paraneoplastic movement disorders are caused by antineuronal antibodies targeting intracellular or neuronal surface antigens, with variable prognosis and response to treatment. ICIs promote antitumor response by the inhibition of the immune checkpoints. They are effective treatments for several malignancies, but they may cause movement disorders through an unchecked immune response. Conclusions: movement disorders due to focal neoplastic brain lesions are rare but should not be missed. Paraneoplastic movement disorders are even rarer, and their clinical-laboratory findings require focused expertise. In addition to their desired effects in cancer treatment, ICIs can induce specific neurological adverse events, sometimes manifesting with movement disorders, which often require a case-by-case, multidisciplinary, approach.

scholarly journals Deregulated Expression of Immune Checkpoints on Circulating CD4 T Cells May Complicate Clinical Outcome and Response to Treatment with Checkpoint Inhibitors in Multiple Myeloma Patients

2021 ◽  
Vol 22 (17) ◽  
pp. 9298
Author(s):  
Anna Kulikowska de Nałęcz ◽  
Lidia Ciszak ◽  
Lidia Usnarska-Zubkiewicz ◽  
Irena Frydecka ◽  
Edyta Pawlak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Checkpoint Inhibitors ◽  
Effector Function ◽  
Response To Treatment ◽  
Immune Checkpoints ◽  
Effective Control ◽  
Small Subset

Unlike solid-tumor patients, a disappointingly small subset of multiple myeloma (MM) patients treated with checkpoint inhibitors derive clinical benefits, suggesting differential participation of inhibitory receptors involved in the development of T-cell-mediated immunosuppression. In fact, T cells in MM patients have recently been shown to display features of immunosenescence and exhaustion involved in immune response inhibition. Therefore, we aimed to identify the dominant inhibitory pathway in MM patients to achieve its effective control by therapeutic interventions. By flow cytometry, we examined peripheral blood (PB) CD4 T cell characteristics assigned to senescence or exhaustion, considering PD-1, CTLA-4, and BTLA checkpoint expression, as well as secretory effector function, i.e., capacity for IFN-γ and IL-17 secretion. Analyses were performed in a total of 40 active myeloma patients (newly diagnosed and treated) and 20 healthy controls. At the single-cell level, we found a loss of studied checkpoints’ expression on MM CD4 T cells (both effector (Teff) and regulatory (Treg) cells) primarily at diagnosis; the checkpoint deficit in MM relapse was not significant. Nonetheless, PD-1 was the only checkpoint distributed on an increased proportion of T cells in all MM patients irrespective of disease phase, and its expression on CD4 Teff cells correlated with adverse clinical courses. Among patients, the relative defect in secretory effector function of CD4 T cells was more pronounced at myeloma relapse (as seen in declined Th1/Treg and Th17/Treg cell rates). Although the contribution of PD-1 to MM clinical outcomes is suggestive, our study clearly indicated that the inappropriate expression of immune checkpoints (associated with dysfunctionality of CD4 T cells and disease clinical phase) might be responsible for the sub-optimal clinical response to therapeutic checkpoint inhibitors in MM.

scholarly journals Understanding Inflammasomes and PD-1/PD-L1 Crosstalk to Improve Cancer Treatment Efficiency

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3550
Author(s):  
Anaïs Perrichet ◽  
François Ghiringhelli ◽  
Cédric Rébé
Keyword(s):  
Cancer Treatment ◽  
Checkpoint Inhibitors ◽  
Response To Treatment ◽  
Immune Checkpoints ◽  
Cancer Growth ◽  
Inflammasome Activation ◽  
Treatment Efficiency ◽  
Programmed Death ◽  
Number Of Patients ◽  
Programmed Death 1

Inflammasomes and immune checkpoints have been shown to participate in carcinogenesis, cancer growth and response to treatment. Thus, targeting cytokines resulting from inflammasome activation, such as interleukin (IL)-1β, has emerged as a new tool in the therapeutic arsenal. Moreover, the use of checkpoint inhibitors such as anti-PD-1 or anti-PD-L1 has revolutionized the treatment of some cancer patients. However, inflammasome activation and consecutive cytokine release only occurs in some chemotherapeutic treatments and immune checkpoint inhibitors only work for a restricted number of patients, thus limiting the use of therapies targeting these pathways. Expanding knowledge about the inefficiency of these therapies recently brought forward the hypothesis of targeting both pathways. In this review, we provide an overview of the crosstalk between inflammasomes and programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) that might explain how these two pathways are mutually dependent, and perhaps why targeting only one of them leads to inefficiency of cancer treatment in some patients.

scholarly journals Kinetic Analysis of 2-[11C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Preliminary Patient Results

2002 ◽  
Vol 1 (3) ◽  
pp. 153535002002021
Author(s):  
Joanne M. Wells ◽  
David A. Mankoff ◽  
Janet F. Eary ◽  
Alexander M. Spence ◽  
Mark Muzi ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Kinetic Analysis ◽  
Cellular Proliferation ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Normal Brain ◽  
Arterial Blood ◽  
Pet Tracer ◽  
Wide Range ◽  
Thymidine Transport

2-[11C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. Kinetic analysis of dynamic TdR images was performed to estimate the rate of thymidine transport ( K1t) and thymidine flux ( KTdR) into brain tumors and normal brain. These estimates were compared to MRI and pathologic results. Methods: Twenty patients underwent sequential [11C]CO2 (major TdR metabolite) and TdR PET studies with arterial blood sampling and metabolite analysis. The data were fitted using the five-compartment model described in the companion article. Results: Comparison of model estimates with clinical and pathologic data shows that K1t is higher for MRI contrast enhancing tumors ( p > .001), and KTdR increases with tumor grade ( p > .02). On average, TdR retention was lower after treatment in high-grade tumors. The model was able to distinguish between increased thymidine transport due to blood–brain barrier breakdown and increased tracer retention associated with tumor cell proliferation. Conclusion: Initial analysis of model estimates of thymidine retention and transport show good agreement with the clinical and pathological features of a wide range of brain tumors. Ongoing studies will evaluate its role in measuring response to treatment and predicting outcome.

Non–Small Cell Lung Cancer, PD-L1, and the Pathologist

2016 ◽  
Vol 140 (3) ◽  
pp. 249-254 ◽  
Author(s):  
Keith M. Kerr ◽  
Marianne C. Nicolson
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Immune Checkpoints ◽  
Great Promise ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Wide Range

Context Although most primary cancers of the lung carry a heavy mutational load and will potentially present many “nonself” antigens to the immune system, there are a wide range of possible mechanisms for tumors to avoid so-called immune surveillance. One such mechanism is the adoption of immune checkpoints to inhibit the host immune response. Immune checkpoint inhibitors show great promise in the treatment of advanced non–small cell lung cancer. Objective —To discuss the possibility of biomarker selection of patients for these therapies. This is becoming a much debated issue, and the immunohistochemical detection of Programmed Death Ligand 1 (PD-L1), the ligand for the inhibitory Programmed Death receptor 1 (PD-1) checkpoint, is one possible biomarker. Data so far available show some conflicting results, but PD-L1 immunohistochemistry looks likely to be introduced into clinical use for selecting patients for treatment with anti–PD-1 or anti–PD-L1 therapies. Given that there are 4 such drugs rapidly approaching regulatory approval, each with its own independent PD-L1 immunohistochemistry biomarker test, both oncologists and pathologists face some significant challenges. Data Sources Peer-reviewed literature and meeting proceedings, especially during the last 12 months, were used. Conclusions —The biology of PD-1/PD-L1 is complex, the clinical data for these drugs show considerable variation, the selection performance of the PD-L1 biomarker test is not perfect, and the existence of 4 drug/test combinations adds significantly to the problems faced. This article addresses some of the background to this therapeutic problem and discusses some of the issues ahead.

scholarly journals Immune Checkpoint Inhibitors in Colorectal Cancer: Challenges and Future Prospects

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1075
Author(s):  
Shima Makaremi ◽  
Zahra Asadzadeh ◽  
Nima Hemmat ◽  
Amir Baghbanzadeh ◽  
Alessandro Sgambato ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Poor Response ◽  
New Drugs ◽  
Response To Treatment ◽  
Immune Checkpoints ◽  
Anti Cancer ◽  
Blocking Antibodies

Immunotherapy is a new pillar of cancer therapy that provides novel opportunities to treat solid tumors. In this context, the development of new drugs targeting immune checkpoints is considered a promising approach in colorectal cancer (CRC) treatment because it can be induce specific and durable anti-cancer effects. Despite many advances in the immunotherapy of CRC, there are still limitations and obstacles to successful treatment. The immunosuppressive function of the tumor microenvironment (TME) is one of the causes of poor response to treatment in CRC patients. For this reason, checkpoint-blocking antibodies have shown promising outcomes in CRC patients by blocking inhibitory immune checkpoints and enhancing immune responses against tumors. This review summarizes recent advances in immune checkpoint inhibitors (ICIs), such as CTLA-4, PD-1, PD-L1, LAG-3, and TIM-3 in CRC, and it discusses various therapeutic strategies with ICIs, including the double blockade of ICIs, combination therapy of ICIs with other immunotherapies, and conventional treatments. This review also delineates a new hopeful path in the combination of anti-PD-1/anti-PD-L1 with other ICIs such as anti-CTLA-4, anti-LAG-3, and anti-TIM-3 for CRC treatment.

scholarly journals Clinical and Laboratory Findings among Patients with Toxocaria-sis in Medic Medical Center, Ho Chi Minh City, Vietnam in 2017-2019

2021 ◽  
Author(s):  
Le Dinh Vinh Phuc ◽  
Cao Ba Loi ◽  
Huynh Hong Quang ◽  
Le Duc Vinh ◽  
Cao Truong Sinh ◽  
...  
Keyword(s):  
Significant Relationship ◽  
Eosinophil Count ◽  
Clinical Laboratory ◽  
Clinical Symptoms ◽  
Medical Center ◽  
Elisa Test ◽  
Clinical Findings ◽  
Ho Chi Minh City ◽  
Laboratory Findings ◽  
Wide Range

Background: Human toxocariasis is prevalent in many countries but this disease has been rarely reported from Vietnam. We aimed to investigate the clinical and laboratory findings and assess possible association between these findings in patients with toxocariasis in Vietnam. Methods: A prospectively study, between October 2017 and June 2019 was performed involving 120 toxocariasis patients at Medic Medical Center, Ho Chi Minh City, Vietnam. The diagnosis of toxocariasis was established based on clinical, laboratory (eosinophilia, raised IgE concentration) and serological (positive Toxocara IgG ELISA test) evaluation as well as the exclusion of other helminthic coinfection.   Results: The most frequently reported manifestation was of skin (n = 93, 77.5%), including urticarial (n= 69, 57.5%) followed by neurologic, gastrointestinal and pulmonary signs/symptoms. Hepatic involvement occurred in 8.3% of the patients. No significant relationship between clinical findings and laboratory parameters was found except the higher values of eosinophil count and IgE concentration among patients with liver involvement. There was a significant relationship between eosinophil count and IgE concentration (r=0.389, P<0.001). Serological findings did not show a correlation with clinical and other laboratory findings. Conclusion: Our data revealed a wide range of clinical symptoms/signs and a high incidence of skin manifestations in patients with toxocariasis. Eosinophil count and IgE concentration are valuable markers for the evaluation of the disease.

Immune checkpoint and checkpoint inhibitors in hepatocellular carcinoma

2018 ◽  
Vol 1 (1) ◽  
pp. 28-32
Author(s):  
Piyawat Komolmit
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell Receptor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Receptor ◽  
Immune Checkpoints ◽  
Histocompatibility Complex

การรักษามะเร็งด้วยแนวความคิดของการกระตุ้นให้ภูมิต้านทานของร่างกายไปทำลายเซลล์มะเร็งนั้น ปัจจุบันได้รับการพิสูจน์ชัดว่าวิธีการนี้สามารถหยุดยั้งการแพร่กระจายของเซลล์มะเร็ง โดยไม่ก่อให้เกิดภาวะแทรกซ้อนทางปฏิกิริยาภูมิต้านทานต่ออวัยวะส่วนอื่นที่รุนแรง สามารถนำมาใช้ทางคลินิกได้ ยุคของการรักษามะเร็งกำลังเปลี่ยนจากยุคของยาเคมีบำบัดเข้าสู่การรักษาด้วยภูมิต้านทาน หรือ immunotherapy ยากลุ่ม Immune checkpoint inhibitors โดยเฉพาะ PD-1 กับ CTLA-4 inhibitors จะเข้ามามีบทบาทในการรักษามะเร็งตับในระยะเวลาอันใกล้ จำเป็นแพทย์จะต้องมีความรู้ความเข้าใจในพื้นฐานของ immune checkpoints และยาที่ไปยับยั้งโมเลกุลเหล่านี้ Figure 1 เมื่อ T cells รับรู้แอนทิเจนผ่านทาง TCR/MHC จะมีปฏิกิริยาระหว่าง co-receptors หรือ immune checkpoints กับ ligands บน APCs หรือ เซลล์มะเร็ง ทั้งแบบกระตุ้น (co-stimulation) หรือยับยั้ง (co-inhibition) TCR = T cell receptor, MHC = major histocompatibility complex

Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Elevated Serum ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Prognostic Features ◽  
Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

Immune Checkpoint Inhibitors in Patients with Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Case Report and Literature Review

2020 ◽  
Vol 20 (9) ◽  
pp. 720-727
Author(s):  
Jianguo Qiu ◽  
Wei Tang ◽  
Chengyou Du
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Immune Checkpoint ◽  
Graft Rejection ◽  
Checkpoint Inhibitors ◽  
Liver Graft ◽  
Immune Checkpoints ◽  
Term Survival ◽  
Liver Preservation ◽  
Programmed Death

Background: Immune checkpoint modulators, such as the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor, cytotoxic T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitor have been investigated with encouraging results for hepatocellular carcinoma (HCC). However, the safety of this strategy in patients with previous liver transplantation (LT) is not well studied. Objective: To explore the safety and feasibility of immune checkpoints inhibitors in recurrent and metastatic HCC patients on a background of LT. Methods: A case of recurrent, refractory, metastatic HCC after LT, where PD-1 inhibitor was initiated, was described and related literature was reviewed. Results: There was complete remission in lung metastases and the partial radiological response of metastatic retroperitoneal lymph node to the drug with no liver graft rejection after 13 cycles of PD- 1 inhibitor injection. PD-1inhibitor, at least in this patient, was verified to play an important role in controlling tumor progression and prolonging patient survival. Conclusions: This novel drug might be a useful method to allow doctors to guarantee a better chance for long-term survival in recurrent, metastatic HCC patients with the previous LT. However, it should be used with caution in allograft recipients due to the risk of acute graft rejection, further larger, prospective studies are needed to determine optimal immunomodulatory therapy to achieve optimal anti-tumor efficacy with transplant liver preservation.

New Insight for the Prognosis of CCHF: Clinical, Laboratory and Sonography Findings

2020 ◽  
Vol 16 (9) ◽  
pp. 1125-1130
Author(s):  
Hamid Owaysee Osquee ◽  
Sepehr Taghizadeh ◽  
Mehdi Haghdoost ◽  
Hadi Pourjafar ◽  
Fereshteh Ansari
Keyword(s):  
Odds Ratio ◽  
Clinical Laboratory ◽  
Fatal Outcome ◽  
Hemorrhagic Fever ◽  
Demographic Characteristics ◽  
Pelvic Cavity ◽  
Fatal Disease ◽  
Laboratory Findings ◽  
Report Data ◽  
Sistan And Baluchestan

Introduction: In this article, we report data on confirmed CCHF cases from Iran and describe the association between studying factors and outcomes of the disease. Objective: Crimean Congo Hemorrhagic Fever (CCHF) is an acute and fatal disease with various clinical and paraclinical characteristics. Methods: In the Study design, we evaluated demographic characteristics, clinical, laboratory and sonographic findings of 160 CCHF confirmed cases during 2003 and 2012 in Zabol (A city in Sistan and Baluchestan province of Iran). The association between these factors and the fatal outcome was evaluated by regression analysis. Results: The disease had a fatal outcome in 7 (4.4%) of patients. Females had more severe symptoms and higher odds for death (odds ratio11.57, p=0.005). Leukocytosis (p<0.001), PT (p<0.001) and PTT (p=0.008) elongation, AST (p=0.010) and ALT (p<0.001) elevation were significantly associated with fatal outcome. CNS related symptoms (odds ratio 5.9, p=0.027) in clinical examination and ascites (odds ratio 38.4, p=0.012) and liquid in the pelvic cavity (odds ratio 24.2, p=0.004) were also identified as risk factors of death in this study. Conclusions: Our data suggest that in addition to clinical and laboratory findings practitioners consider sonography for CCHF prognosis.

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