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The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing.

p53 and p73 are critical tumor suppressors that are often inactivated in human cancers through various mechanisms. Owing to their high structural homology, the proteins have many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the 'guardian of the genome' and together with p73 forms a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni syndrome (LFS), the inherited cance

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… DNA damage and cell cycle arrest induced by protoporphyrin IX in sarcoma 180 cells. Cell Physiol. Biochem. 2013;32:778–788. doi: 10.1159/000354479. 140. Zawacka-Pankau J., Issaeva N., Hossain S., Pramanik A., Selivanova G., Podhajska A.J. …

Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.

In one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not all cancer patients benefit from single or combination therapy with anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number of immune checkpoint proteins (ICPs) have been screened and their effectiveness evaluated in preclinical and clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and T cell immunoreceptor w

Ultra-short stem intercalary prosthetic reconstruction for joint preservation in metaphyseal tumor management: a retrospective review of twenty-five cases.

PURPOSE: This study evaluates the outcomes, survival, and ASL incidence of ultra-short stem intercalary prosthetic reconstruction for tumors involving the metaphysis of bone. METHODS: A retrospective analysis of 25 patients treated at two centers with wide resection for primary or metastatic bone tumors (femur, tibia, humerus) followed by reconstruction using ultra-short stem intercalary prostheses combined extracortical plates. Clinical outcomes were assessed using the Visual Analogue Scale (VAS) and Musculoskeletal Tumor Society (MSTS) score. Survival rates were calculated using the Kaplan-

Current Status of Gene Engineering Cell Therapeutics.

Ex vivo manipulations of autologous patient's cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to in

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study.

IMPORTANCE: The increasing burden due to cancer and other noncommunicable diseases poses a threat to human development, which has resulted in global political commitments reflected in the Sustainable Development Goals as well as the World Health Organization (WHO) Global Action Plan on Non-Communicable Diseases. To determine if these commitments have resulted in improved cancer control, quantitative assessments of the cancer burden are required. OBJECTIVE: To assess the burden for 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus.

Adverse drug reaction profile of microtubule-damaging antineoplastic drugs: A focused pharmacovigilance study in India.

ObjectivesThe aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians.Materials and methodsData on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian

Cytokine-Induced Killer Cells: A Unique Platform for Adoptive Cell Immunotherapy after Allogeneic Hematopoietic Stem Cell Transplantation.

BackgroundImmunotherapies in general, and cellular immunotherapies, in particular are becoming increasingly integrated into current personalized cancer treatment, though still facing some obstacles in the allogeneic hematopoietic stem cell transplantation (HSCT) setting.SummaryThe concept of isolating immune effector cells, expanding their numbers, enhancing their anticancer capabilities by modifying them without increasing their alloreactive potential is the mainstay of adoptive cellular immunotherapy after allogeneic HSCT. In this context, cytokine-induced killer (CIK) cells, a polyfunctiona

Palliative prognostic scores for survival prediction of cancer patients: a systematic review and meta-analysis.

BACKGROUND: The palliative prognostic score is the most widely validated prognostic tool for cancer survival prediction, with modified versions available. A systematic evaluation of palliative prognostic score tools is lacking. This systematic review and meta-analysis aimed to evaluate the performance and prognostic utility of palliative prognostic score, delirium-palliative prognostic score, and palliative prognostic score without clinician prediction in predicting 30-day survival of cancer patients and to compare their performance. METHODS: Six databases were searched for peer-reviewed stud

Emergency department-initiated palliative care for advanced cancer patients: protocol for a pilot randomized controlled trial.

BackgroundFor patients with advanced cancer, visits to the emergency department (ED) are common. Such patients present to the ED with a specific profile of palliative care needs, including burdensome symptoms such as pain, dyspnea, or vomiting that cannot be controlled in other settings and a lack of well-defined goals of care. The goals of this study are: i) to test the feasibility of recruiting, enrolling, and randomizing patients with serious illness in the ED; and ii) to evaluate the impact of ED-initiated palliative care on health care utilization, quality of life, and survival.Methods/de

Opportunistic CT for Prediction of Adverse Postoperative Events in Patients with Spinal Metastases.

The purpose of this study was to assess the value of body composition measures obtained from opportunistic abdominal computed tomography (CT) in order to predict hospital length of stay (LOS), 30-day postoperative complications, and reoperations in patients undergoing surgery for spinal metastases. 196 patients underwent CT of the abdomen within three months of surgery for spinal metastases. Automated body composition segmentation and quantifications of the cross-sectional areas (CSA) of abdominal visceral and subcutaneous adipose tissue and abdominal skeletal muscle was performed. From this,

Clinical and Therapeutic Implications of Epstein-Barr Virus in HIV-Related Lymphomas.

The incidence of lymphomas is increased in people living with HIV (PLWH). Aggressive B-cell non-Hodgkin lymphomas (NHLs) are the most common and are considered an AIDS-defining cancer (ADC). Although Hodgkin lymphoma (HL) is not considered an ADC, its incidence is also increased in PLWH. Among all HIV-related lymphomas (HRL), the prevalence of Epstein-Barr virus (EBV) is high. It has been shown that EBV is involved in different lymphomagenic mechanisms mediated by some of its proteins, contributing to the development of different lymphoma subtypes. Additionally, cooperation between both HIV an

The current socioeconomic and regulatory landscape of immune effector cell therapies.

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T ce

Prospective study evaluating the incidence of bacteraemia and bacteruria in afebrile and febrile neutropaenic dogs undergoing chemotherapy.

The purpose of this prospective study was to determine the incidence and character of bacteraemia and bacteruria in afebrile and febrile neutropaenic dogs undergoing cytotoxic chemotherapy. Fifty-five neutropaenic dogs presenting to the University of Wisconsin Veterinary Medical Teaching Hospital were enrolled for a total of 57 neutropaenic episodes. The overall incidence of bacteraemia was 12.3% (n = 7/57). Three afebrile dogs and four febrile dogs were bacteraemic; this difference was not significant (P = 0.6968). The overall incidence of bacteruria was 7.5% (n = 4/53). Two afebrile dogs and

Viral Vector-Based Melanoma Gene Therapy.

Gene therapy applications of oncolytic viruses represent an attractive alternative for cancer treatment. A broad range of oncolytic viruses, including adenoviruses, adeno-associated viruses, alphaviruses, herpes simplex viruses, retroviruses, lentiviruses, rhabdoviruses, reoviruses, measles virus, Newcastle disease virus, picornaviruses and poxviruses, have been used in diverse preclinical and clinical studies for the treatment of various diseases, including colon, head-and-neck, prostate and breast cancer as well as squamous cell carcinoma and glioma. The majority of studies have focused on i

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

Cancer of Unknown Primary: Challenges and Progress in Clinical Management.

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3-5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based thera

Primary tumours of the calcaneus.

The calcaneus is a rare location for the occurrence and development of primary tumour types. Clinicians are unfamiliar with calcaneal tumour types, which may result in a delay in diagnosis or a missed diagnosis, resulting in unnecessary morbidity and amputation. Heel pain and localized swelling of the ankle are the most common symptoms. X-ray is the first choice for a tentative diagnosis of a calcaneal tumour. The final diagnosis depends on a histological examination. The treatment of calcaneal tumour types varies depending on the Enneking system. The majority of patients with benign tumours h

Nanotechnology-Driven Cancer Therapies for Precision Oncology: Advances and Clinical Outlook.

Cancer continues to pose a global health challenge, with conventional therapies often limited by non-specific toxicity, drug resistance, and an inadequate therapeutic index. Nanotechnology offers transformative opportunities by enabling targeted drug delivery, improved pharmacokinetics, and integrated diagnostic-therapeutic platforms (termed nanotheranostics). This review highlights key nanocarrier systems including liposomes, polymeric nanoparticles, dendrimers, inorganic nanostructures, carbon-based materials, extracellular vesicles, and hybrid platforms with a focus on human studies and cli

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics.

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly a

Rare Diseases of the Orbit.

This article provides an overview of rare orbital diseases. Congenital malformations, inflammatory diseases, benign and malignant neoplasias are described. Although it represents a relatively small area of the body the orbit contains multiple different tissues. Therefore, a great variety of diseases can be found within the orbital space. That is the reason, why both the completeness and the level of detail in the description of particular diseases must be somewhat limited. Nevertheless, clinical manifestations, important aspects of diagnosis, treatment strategies, and, when specific data are a