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Topic Review
Genetic Heterogeneity of Pediatric AML
Despite improvements in therapeutic protocols and in risk stratification, acute myeloid leukemia (AML) remains the leading cause of childhood leukemic mortality. Indeed, the overall survival accounts for ~70% but still ~30% of pediatric patients experience relapse, with poor response to conventional chemotherapy. Thus, there is an urgent need to improve diagnosis and treatment efficacy prediction in the context of this disease. Nowadays, in the era of high throughput techniques, AML has emerged as an extremely heterogeneous disease from a genetic point of view. Different subclones characterized by specific molecular profiles display different degrees of susceptibility to conventional treatments.
  • 588
  • 23 Jun 2021
Topic Review
Hepatocellular Carcinoma, Alpha Fetoprotein, and Liver Transplantation
Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation and has been the treatment of choice due to the oncologic benefit for patients with advanced chronic liver disease (AdvCLD) and small tumors. For HCC patients undergoing liver transplantation, alpha fetoprotein (AFP) has increasingly been applied as an independent predictor for overall survival, disease free recurrence, and waitlist drop out. In addition to static AFP, newer studies evaluating the AFP dynamic response to downstaging therapy show enhanced prognostication compared to static AFP alone.
  • 588
  • 28 Oct 2022
Topic Review
Promotion of Senescent Stroma for Tumor Progression
Cellular senescence is a unique cellular state. Senescent cells enter a non-proliferative phase, and the cell cycle is arrested. However, senescence is essentially an active cellular phenotype, with senescent cells affecting themselves and neighboring cells via autocrine and paracrine patterns. A growing body of research suggests that the dysregulation of senescent stromal cells in the microenvironment is tightly associated with the development of a variety of complex cancers. 
  • 588
  • 17 Apr 2023
Topic Review
Diagnostic Unmet Needs in Gynecological Malignancies
Gynecological malignancies currently affect about 3.5 million women all over the world. Imaging of uterine, cervical, vaginal, ovarian, and vulvar cancer still presents several unmet needs when using conventional modalities such as ultrasound, computed tomography (CT), magnetic resonance, and standard positron emission tomography (PET)/CT.
  • 588
  • 05 May 2023
Topic Review
PD-L1 Immunohistochemical Expression and Cutaneous Melanoma
Cutaneous melanoma (CM) is a highly aggressive type of skin cancer with a high mortality rate.
  • 588
  • 16 Jan 2024
Topic Review
Gender-Related Side Effects Induced by Platinum Compounds
Gender medicine in the field of oncology is an under-researched area, despite the existing evidence towards gender-dependent response to therapy and treatment-induced adverse effects. Oncological treatment aims to fulfil its main goal of achieving high tumour control by also protecting normal tissue from acute or chronic damage. Chemotherapy is an important component of cancer treatment, with a large number of drugs being currently in clinical use. Cisplatin is one of the most commonly employed chemotherapeutic agents, used either as a sole drug or in combination with other agents. Cisplatin-induced toxicities are well documented, and they include nephrotoxicity, neurotoxicity, gastrointestinal toxicity, ototoxicity, just to name the most frequent ones. Some of these toxicities have short-term sequelae, while others are irreversible. Furthermore, research showed that there is a strong gender-dependent aspect of side effects caused by the administration of cisplatin. While evidence towards sex differences in animal models is substantial, clinical studies considering sex/gender as a variable factor are limited. 
  • 587
  • 10 Mar 2022
Topic Review
Neoadjuvant Chemo-Immunotherapy for Locally Advanced Non-Small-Cell Lung Cancer
There is great interest in immunotherapy in non-small cell lung cancer (NSCLC) and its combination with chemotherapy demonstrated to be beneficial. The introduction of such combination in the neoadjuvant treatment could change management strategy and outcomes of resectable NSCLC, especially in the locally advanced stage. In fact, following the results from the CHECKMATE-816 (NCT02998528) trial, the FDA recently approved nivolumab and platinum-based chemotherapy in the neoadjuvant setting for resectable NSCLC.
  • 587
  • 18 Jul 2022
Topic Review
ICIs in Thymic Carcinoma
Thymic carcinoma is a rare neoplasm with a dismal prognosis, and there are no established therapeutic regimens for metastatic or recurrent disease. Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, are widely approved in several human cancers, contributing to prolonging survival in thoracic tumors. Thymic carcinoma exhibits histologic properties of squamous cell carcinoma (SQC), and resembles the SQC of the lung. ICIs are not approved in thymic carcinoma. Thus, several clinical trials have been undertaken to demonstrate if they are therapeutically effective for patients with thymic carcinoma.
  • 586
  • 09 Mar 2021
Topic Review
Type 2 Cystatins in Human Immune and Cancer
Type 2 cystatins are a group of small secreted protease inhibitors that regulate cysteine protease cathepsins and legumain. These enzymes regulate important cellular processes that are linked to the immune response and tumor progression, playing important roles in both autoimmune diseases and various types of cancers. Cysteine cathepsins are associated with the development of autoimmune diseases, tumor progression, and metastasis. Cystatins are categorized into three subfamilies: type 1, type 2, and type 3. The type 2 cystatin subfamily is the largest, containing 10 members, and consists entirely of small secreted proteins. Although type 2 cystatins have many shared biological roles, each member differs in structure, post-translational modifications (e.g., glycosylation), and expression in different cell types. These distinctions allow the type 2 cystatins to have unique biological functions and properties.
  • 586
  • 01 Dec 2023
Topic Review
Mmunotherapy-Based Rational Combinations for RCC
Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. 
  • 585
  • 23 Jun 2021
Topic Review
Prognostic Models for Oral Squamous Cell Carcinoma
An accurate prediction of cancer survival is very important for counseling, treatment planning, follow-up, and postoperative risk assessment in patients with Oral Squamous Cell Carcinoma (OSCC). There has been an increased interest in the development of clinical prognostic models and nomograms which are their graphic representation.
  • 585
  • 22 Nov 2021
Topic Review
Inactivation of the Fragile Histidine Triad Gene
Tumor development follows an evolutionary pattern of "mutation-selection-adaptation", characterized by exogenous oncogenic induction and endogenous replicative stress. The fragile histidine triad (FHIT) is a tumor suppressor. Tumor suppressor genes with regular expression inhibit cell proliferation and tumorigenesis. Decreased FHIT expression leads to the malignant transformation of affected cells and promotes the evolutionary development of cancer. Aberrant transcripts or decreases in the transcription and translation of the FHIT are present in at least 50% of preneoplastic lesions and human cancers, especially in esophageal, lung, liver, stomach, pancreatic, kidney, skin, breast, and cervical cancers. Abnormal expression of the FHIT is also evident in hyperplastic lesions, suggesting that the inactivation of the FHIT plays a vital role in inhibiting the formation of early preneoplastic and premalignant lesions. There are three basic pathways leading to the aberrant expression of the FHIT: replication stress, loss of heterozygous (LOH), and CpG methylation at the promoter region.
  • 585
  • 14 Feb 2023
Topic Review
Cellular Prion Protein in Glioma Tumorigenesis
The carcinogenesis of glial tumors appears complex because of the many genetic and epigenetic phenomena involved. Among these, cellular prion protein (PrPC) is considered a key factor in cell-death resistance and important aspect implicated in tumorigenesis. Autophagy also plays an important role in cell death in various pathological conditions. These two cellular phenomena are related and share the same activation by specific alterations in the cellular microenvironment. Furthermore, there is an interdependence between autophagy and prion activity in glioma tumorigenesis. Glioma is one of the most aggressive known cancers, and the fact that such poorly studied processes as autophagy and PrPC activity are so strongly involved in its carcinogenesis suggests that by better understanding their interaction, more can be understood about its origin and treatment. 
  • 585
  • 27 Mar 2023
Topic Review
Molecularly Targeted HNSCC Therapy
Head and Neck Squamous Cell Carcinoma (HNSCC) is a major threat to public health around the world. Its occurrence is linked to genetic events and environmental factors, including Human Papilloma Virus (HPV) infections. Patients with HPV-positive tumors usually have a better prognosis than those with HPV-negative tumors. According to advances in understanding the molecular basis of HNSCC tumors, targeted therapy is thought to improve treatment outcomes.
  • 585
  • 06 Sep 2023
Topic Review
Epithelial Ovarian Cancer: Providing Evidence of Predisposition Genes
Epithelial ovarian cancer (EOC) is one of the cancers most influenced by hereditary factors. A fourth to a fifth of unselected EOC patients carry pathogenic variants (PVs) in a number of genes, the majority of which encode for proteins involved in DNA mismatch repair (MMR) pathways. PVs in BRCA1 and BRCA2 genes are responsible for a substantial fraction of hereditary EOC. In addition, PV genes involved in the MMR pathway account for 10–15% of hereditary EOC. The identification of women with homologous recombination (HR)-deficient EOCs has significant clinical implications, concerning chemotherapy regimen planning and development as well as the use of targeted therapies such as poly(ADP-ribose) polymerase (PARP) inhibitors. With several genes involved, the complexity of genetic testing increases. In this context, next-generation sequencing (NGS) allows testing for multiple genes simultaneously with a rapid turnaround time.
  • 585
  • 27 Sep 2023
Topic Review
Localized Small Bowel Adenocarcinoma Management
Small bowel adenocarcinoma is a rare but aggressive disease that requires peri-operative treatment. Due to its rarity, there is little data on small bowel adenocarcinoma treatment, and most recommendations come from expert agreements or analogies to the management of colon cancer.
  • 584
  • 21 Jun 2022
Topic Review
Precision Medicine and Melanoma
The treatment and management of patients with metastatic melanoma have evolved considerably in the “era” of personalized medicine. Melanoma was one of the first solid tumors to benefit from immunotherapy; life expectancy for patients in advanced stage of disease has improved. However, many progresses have yet to be made considering the (still) high number of patients who do not respond to therapies or who suffer adverse events. In this scenario, precision medicine appears fundamental to direct the most appropriate treatment to the single patient and to guide towards treatment decisions. The recent multi-omics analyses (genomics, transcriptomics, proteomics, metabolomics, radiomics, etc.) and the technological evolution of data interpretation have allowed to identify and understand several processes underlying the biology of cancer; therefore, improving the tumor clinical management. Specifically, these approaches have identified new pharmacological targets and potential biomarkers used to predict the response or adverse events to treatments.
  • 583
  • 12 Apr 2021
Topic Review
Antibody Secreting Cells in Breast and Ovarian Cancers
Antibody secreting cells (ASCs) constitute a variable fraction of tumor-infiltrating B cells in most solid tumors, and they produce tumor-specific antibodies that can drive distinct immune responses depending on their isotypes and specificities.
  • 583
  • 18 Oct 2022
Topic Review
Different Microenvironments in Neck Squamous Cell Carcinoma
Epidemiological studies have revealed a broad range of risk factors for head and neck squamous cell carcinoma (HNSCC) that can classify these tumors into two main groups: the first group, carcinogen-associated HNSCC, is related to tobacco consumption, alcohol consumption, and exposure to environmental pollutants, and the second group, virus-associated HNSCC, is related to human papillomavirus (HPV) and Epstein–Barr virus (EBV) infections. Interestingly, several risk factors display geographical or cultural and/or habitual prevalence. For instance, in regions such as Southeast Asia and Australia, HNSCC has a high prevalence associated with the consumption of specific carcinogen-containing products, such as betel-nut and tobacco chewing.
  • 583
  • 09 Nov 2022
Topic Review
Immune-Mediated Hepatitis during Immunotherapy in Patients with Cancer
Immune-mediated hepatotoxicity (IMH) is not-so-rare complication during treatment with immune checkpoint inhibitors (ICIs). The majority of cases of IMH are asymptomatic and only a few patients may have clinical conditions. The severity of IMH is usually stratified according to Common Terminology for Clinical Adverse Events (CTCAE) criteria, but these scores may overestimate the clinical severity of IMH compared to the Drug-Induced Liver Injury Network (DILIN) scale. The differential diagnosis of IMH is challenging because the elevated liver enzymes can be due to a number of etiologies such as viral infection, autoimmune and metabolic diseases, liver metastases, biliary diseases, and other drugs. The cornerstones of IMH management are represented by withholding or delaying ICI administration and starting immunosuppressive therapy. 
  • 583
  • 23 Feb 2024
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