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Anti-programmed cell death protein-1/ligand-1 therapy in different cancers.

Immunologic checkpoint blockade with antibodies against the programmed cell death protein-1 (PD-1) or its ligand (PD-L1) is an effective method for reversing cancer immunosuppression and thereby promoting immune responses against several cancer types. Anti-PD-1 and anti-PD-L1 antibodies have resulted in long-term responses with minimal side effects in significant numbers of patients with melanoma, lung, kidney, bladder and triple-negative breast cancer, as well as in chemotherapy-refractory Hodgkin disease. There is already evidence from at least one randomised trial that anti-PD-1 therapy is

Boosting Immunity against Multiple Myeloma.

Despite the improvement of patient's outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody-drug conjugates or bispecific antibodies broadened the possibility of improving patients' survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residua

Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.

Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, inclu

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… In comparison to epirubicin alone, the Apts-dendrimer-epirubicin combination was less cytotoxic in CHO cells. In MCF-7 cells and C26, the combination was more cytotoxic than epirubicin alone. … Effect of deficiencies in DNA repair on the toxicity of mitomycin C and porfiromycin to CHO cells under aerobic and hypoxic conditions . J. Cancer communications. 1991 , 3 , 29 – 35 . 1899798 Froudarakis M. ; Hatzimichael E. ; Kyriazopoulou L. ; Lagos K. ; Pappas P. ; Tzakos A. …

Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.

Non-small cell lung cancer (NSCLC) is characterized by several molecular alterations that contribute to its development and progression. These alterations include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), and mesenchymal-epithelial transition factor (c-MET). Among these, the hepatocyte growth factor (HGF)/c-MET signaling pathway plays a crucial role in NSCLC. In spite of this, the involvement of the HGF/c-MET signaling axis in remodeling the tumor microenvironment (TME) remains relatively unexplored. This rev

Osteoporosis: the current status of mesenchymal stem cell-based therapy.

Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves

Liquid Biopsy in Cancer: Focus on Lymphoproliferative Disorders.

Within the context of precision medicine, the scientific community is giving particular attention to early diagnosis and intervention, guided by non-invasive methodologies. Liquid biopsy (LBx) is a recent laboratory approach consisting of a non-invasive blood draw, which allows the detection of information about potential prognostic factors, or markers to be used for diagnostic purposes; it might also allow the clinician to establish a treatment regimen and predict a patient's response. Since the discovery of circulating tumor cells (CTCs) in the nineteenth century, the possibility of integrat

Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen

Extensive Intracardiac Cement Embolism in a Patient Undergoing Workup for Bone Marrow Transplant.

Cement emboli are a well-established complication of kyphoplasties and vertebroplasties and can easily be mistaken for wires. While kyphoplasties are commonly performed for vertebral fractures caused by metastases from malignancies such as multiple myeloma, the implication of cement emboli in bone marrow transplant (BMT) patients is not well documented. Our patient presented with an incidental intracardiac cement embolism found while undergoing workup for BMT. He was managed conservatively, but transplant workup was put on hold until the embolism could be removed due to the risks associated wi

Radiotherapy-induced oxidative stress and fibrosis in breast cancer are suppressed by vactosertib, a novel, orally bioavailable TGF-β/ALK5 inhibitor.

Radio-resistance resulting from radiotherapy-induced fibrosis is a major clinical obstacle in breast cancer treatment because it typically leads to cancer recurrence, treatment failure, and patient death. Transforming growth factor-β (TGF-β) is a key signal messenger in fibrosis, which plays an important role in radiation-induced fibrosis and cancer stem cell (CSC) development, may be mediated through the generation of oxidative stress. This study was conducted to confirm the efficacy of vactosertib, a TGF-β/ALK5 inhibitor, as a potent inhibitor in radiation-induced oxidative stress generation

Functional genomics for breast cancer drug target discovery.

Breast cancer is a heterogeneous disease that develops through a multistep process via the accumulation of genetic/epigenetic alterations in various cancer-related genes. Current treatment options for breast cancer patients include surgery, radiotherapy, and chemotherapy including conventional cytotoxic and molecular-targeted anticancer drugs for each intrinsic subtype, such as endocrine therapy and antihuman epidermal growth factor receptor 2 (HER2) therapy. However, these therapies often fail to prevent recurrence and metastasis due to resistance. Overall, understanding the molecular mechani

Clinical Management of Triple-Class Refractory Multiple Myeloma: A Review of Current Strategies and Emerging Therapies.

Major progress has been made in the upfront treatment of multiple myeloma, but the disease ultimately relapses and leads to death in the vast majority of those afflicted. New treatment strategies and modalities are necessary to treat myeloma in relapse, particularly in cases of triple-refractory status defined by disease progression during or shortly after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibody therapy. In this manuscript, we review recent promising developments in the treatment of triple-class refractory myeloma including bispecific an

The Role of Macrophage in the Pathogenesis of Osteoporosis.

Osteoporosis is a systemic disease with progressive bone loss. The bone loss is associated with an imbalance between bone resorption via osteoclasts and bone formation via osteoblasts. Other cells including T cells, B cells, macrophages, and osteocytes are also involved in the pathogenesis of osteoporosis. Different cytokines from activated macrophages can regulate or stimulate the development of osteoclastogenesis-associated bone loss. The fusion of macrophages can form multinucleated osteoclasts and, thus, cause bone resorption via the expression of IL-4 and IL-13. Different cytokines, endoc

Managing Tumor Lysis Syndrome in the Era of Novel Cancer Therapies.

Abstract Tumor lysis syndrome (TLS) is a potentially life-threatening emergency that can develop rapidly after the release of intracellular contents from lysed malignant cells. The advent of novel and targeted therapies that have improved tumor-killing efficacy has the potential to increase the risk of TLS when used as part of front-line therapy. A recent review of TLS risk in patients with hematologic malignancies treated with newer targeted agents highlighted the need to revisit TLS risk stratification and to describe the practical challenges of TLS prevention, treatment, and monitoring. Alt

Current and Emerging Therapeutic Targets for the Treatment of Cholangiocarcinoma: An Updated Review.

Cholangiocarcinoma is a malignancy of the bile ducts that is often associated with late diagnosis, poor overall survival, and limited treatment options. The standard of care therapy for cholangiocarcinoma has been cytotoxic chemotherapy with modest improvements in overall survival with the addition of immune checkpoint inhibitors. The discovery of actionable mutations has led to the advent of targeted therapies against FGFR and IDH-1, which has expanded the treatment landscape for this patient population. Significant efforts have been made in the pre-clinical space to explore novel immunothera

Editorial: Autologous and Allogeneic Stem Cell Transplant in Cancer Therapy.

Over the last 10 to 20 years, there have been significant improvements in the fields of both autologous and allogenic transplantation [...].

Chromatin structure, transcriptional activity and DNA repair efficiency affect the outcome of chemotherapy in multiple myeloma.

BackgroundMelphalan is one of the most active chemotherapeutic agents in the treatment of multiple myeloma (MM). However, the mechanism underlying differential patient responses to melphalan therapy is unknown.MethodsChromatin structure, transcriptional activity and DNA damage response signals were examined following ex vivo treatment with melphalan of both malignant bone marrow plasma cells (BMPCs) and peripheral blood mononuclear cells (PBMCs) of MM patients, responders (n=57) or non-responders (n=28) to melphalan therapy. PBMCs from healthy controls (n=25) were also included in the study.Re

Approaches to the Management of Metastatic Adenoid Cystic Carcinoma.

High rates of recurrence and distant metastasis are a foremost challenge in the management of adenoid cystic carcinoma (ACC), occurring in approximately 40% of all ACC patients. Despite the morbidity and mortality resulting from recurrent/metastatic (R/M) disease, there are no FDA-approved systemic agents for these patients. In this review, we summarize pertinent ACC pathophysiology and its implications for different systemic treatment regimens in R/M ACC. We review the evidence for the most widely used systemic agents - cytotoxic chemotherapy and tyrosine kinase inhibitors (TKIs) targeting VE

Extreme Peripheral Blood Plasmacytosis Mimicking Plasma Cell Leukemia as a Presenting Feature of Angioimmunoblastic T-Cell Lymphoma (AITL).

Angioimmunoblastic T-cell lymphoma (AITL) is one of four major subtypes of nodal peripheral T cell lymphoma, characterized by its cell of origin, the follicular helper T-cell (TFH). Patients typically present with prominent constitutional (B) symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. Here we present a case of a 62-year-old male with progressive cervical adenopathy, fevers and weight loss presenting with extreme polyclonal plasmacytosis and high plasma EBV viral load. While the initial presentation appeared to mimic plasma cell leukemia or severe infection

Какие факторы связаны с неблагоприятным прогнозом у нескольких пациентов с миеломой после операции?

Для изучения прогнозов пациентов с множественной миеломой (ММ) после операции, анализа факторов риска, ведущих к неблагоприятным результатам послеоперационного лечения, и создания номограммы. МЕТОДЫ: Клинические данные 154 пациентов с MM, которые прошли операцию в нашем учреждении между 2007 и 2019 был ретроспективно проанализирован. Оценка и сопоставление уровней боли, качества жизни и функционального состояния пациентов до и после операции (Р) < 0.05) были признаны статистически значимыми. Кривая выживания Каплана-Мейера использовалась для оценки средней продолжительности выживаемости. Отриц

Hemophagocytic Lymphohistiocytosis (HLH) in Patients with Tick-Borne Illness: A Scoping Review of 98 Cases.

Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was r