A Comprehensive Narrative Review on the History, Current Landscape, and Future Directions of Hepatocellular Carcinoma (HCC) Systemic Therapy.

We provide a comprehensive review of current approved systemic treatment strategies for advanced hepatocellular carcinoma (HCC), starting with the phase III clinical trial of sorafenib which was the first to definitively show a survival benefit. After this trial, there was an initial period of little progress. However, in recent years, an explosion of new agents and combinations of agents has resulted in a markedly improved outlook for patients.

Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome.

Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1.

Viral Evasion of Innate Immune Defense: The Case of Resistance of Pandemic H1N1 Influenza A Virus to Human Mannose-Binding Proteins.

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes.

Health-related quality of life among colorectal cancer survivors of diverse sexual orientations.

Background: The purpose of this study was to examine the health-related quality of life of sexual minority survivors in comparison with heterosexual survivors.

Methods: Four hundred eighty eligible survivors participated in a telephone survey that measured survivors' outcomes, which consisted of physical and mental quality of life and self-rated fair or poor health. These survivors were diagnosed with stage I, II, or III colorectal cancer an average of 3 years before the survey and were recruited from 4 cancer registries.

Follow-up surveillance among colorectal cancer survivors of different sexual orientations.

Purpose: The purpose of this study was to examine receipt of follow-up surveillance among sexual minority and heterosexual survivors and identify survivor-, physician-, and practice-level characteristics associated with follow-up surveillance.

Methods: An average of 3 years after their stage I-III colorectal cancer diagnosis, we recruited survivors from four cancer registries. A questionnaire, which queried about sexual orientation and other eligibility criteria, was mailed to all cancer survivors.

Assessing the relationship between symptoms and health care utilization in colorectal cancer survivors of different sexual orientations.

Objective: The purpose of this study was to determine the association of physical and psychological symptoms with health care utilization in sexual minority and heterosexual colorectal cancer survivors.

Methods: Four hundred eighteen colorectal cancer survivors who were in remission an average of 3 years after their diagnosis were surveyed about their non-emergency health care visits during the preceding 3 months. Survivors reported whether they had experienced any of 21 symptoms common among colorectal cancer survivors in the past week.

Multicohort Retrospective Validation of a Predictive Biomarker for Topoisomerase I Inhibitors.

Purpose: The camptothecin (CPT) analogs topotecan and irinotecan specifically target topoisomerase I (topoI) and are used to treat colorectal, gastric, and pancreatic cancer. Response rate for this class of drug varies from 10% to 30%, and there is no predictive biomarker for patient stratification by response. On the basis of our understanding of CPT drug resistance mechanisms, we developed an immunohistochemistry-based predictive test, P-topoI-Dx, to stratify the patient population into those who did and did not experience a response.

Histone H4 potentiates neutrophil inflammatory responses to influenza A virus: Down-modulation by H4 binding to C-reactive protein and Surfactant protein D.

Neutrophils participate in the early phase of the innate response to uncomplicated influenza A virus (IAV) infection but also are a major component in later stages of severe IAV or COVID 19 infection where neutrophil extracellular traps (NETs) and associated cell free histones are highly pro-inflammatory. It is likely that IAV interacts with histones during infection. We show that histone H4 binds to IAV and aggregates viral particles.

Effects of serum amyloid protein A on influenza A virus replication and viral interactions with neutrophils.

Innate immunity is vital for the early control of influenza A virus (IAV) infection. Serum amyloid A (SAA1) is an acute phase reactant produced in the liver and lung that rises dramatically during IAV infection. The potential role of SAA1 in host defense against IAV is unknown.

Histone H4 directly stimulates neutrophil activation through membrane permeabilization.

Extracellular histones have been implicated as a cause of tissue inflammatory injury in a variety of disorders including sepsis, lung, and liver diseases. However, little is known about their interactions with neutrophils and how this might contribute to injury. Here, it is shown that histone H4 acts as neutrophil activator by inducing hydrogen peroxide production, degranulation, cell adhesion, and IL-8 generation.

Neighborhood Characteristics and Colorectal Cancer Survivors' Quality of Care.

Quality cancer care entails receipt of a Survivorship Care Plan (SCP). The purpose of this study was to determine differences in SCP delivery by patient-level and neighborhood characteristics. We obtained California cancer registry data on individuals who were diagnosed with stage I, II, or III colorectal cancer (CRC) between 2012 and 2015 and resided in predetermined geographic areas.

Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: -Glycan Subtypes in Host-Pathogen Interactions.

Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D). Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes. These can pose a pandemic threat through reassortment and emergence in human populations.

Enhanced Antiviral Activity of Human Surfactant Protein D by Site-Specific Engineering of the Carbohydrate Recognition Domain.

Innate immunity is critical in the early containment of influenza A virus (IAV) infection and surfactant protein D (SP-D) plays a crucial role in innate defense against IAV in the lungs. Multivalent lectin-mediated interactions of SP-D with IAVs result in viral aggregation, reduced epithelial infection, and enhanced IAV clearance by phagocytic cells. Previous studies showed that porcine SP-D (pSP-D) exhibits distinct antiviral activity against IAV as compared to human SP-D (hSP-D), mainly due to key residues in the lectin domain of pSP-D that contribute to its profound neutralizing activity.

Prolonged Treatment Response to Pembrolizumab in a Patient with Pretreated Metastatic Colon Cancer and Lynch Syndrome.

Pembrolizumab and other immunotherapies now play a prominent role in the treatment of metastatic colon cancer. Clinicians have achieved significant response rates even in heavily pretreated patients, particularly those with mismatched repair deficiencies. The endpoint of pembrolizumab treatment for patients who enjoy a strong response remains unclear.

Aging, immune senescence, and immunotherapy: A comprehensive review.

The advent of immune checkpoint inhibitors (ICIs) has changed the landscape of cancer treatment. Older adults represent the majority of cancer patients; however, direct data evaluating ICIs in this patient population is lacking. Aging is associated with changes in the immune system known as "immunosenescence" that could impact the efficacy and safety profile of ICIs.

Treatment of Rectal Cancer in Older Adults.

Purpose Of Review: Rectal cancer is predominantly a disease of older adults but current guidelines do not incorporate the associated specific challenges leading to wide variation in the delivery of cancer care to this subset of population. Here, we will review the current data available regarding the management of rectal cancer in older adults.

Recent Findings: The greatest challenge arises in the management of stage II/III disease as it involves tri-modality treatment that can be harder to tolerate by frail older patients.

Tumor Lysis Syndrome After Bilobectomy for Typical Carcinoid Tumor of the Lung.

Tumor lysis syndrome is a life-threatening complication comprising hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia attributed to release of intracellular contents. Although traditionally associated with leukemia and lymphoma after chemotherapy, it is known to occur in solid malignancies. We herein report a rare case of this syndrome after resection of bulky carcinoid tumor of the lung.

c-Cbl Expression Correlates with Human Colorectal Cancer Survival and Its Wnt/β-Catenin Suppressor Function Is Regulated by Tyr371 Phosphorylation.

The proto-oncogene β-catenin drives colorectal cancer (CRC) tumorigenesis. Casitas B-lineage lymphoma (c-Cbl) inhibits CRC tumor growth through targeting nuclear β-catenin by a poorly understood mechanism. In addition, the role of c-Cbl in human CRC remains largely underexplored.

The Role and Molecular Mechanism of Action of Surfactant Protein D in Innate Host Defense Against Influenza A Virus.

Influenza A viruses (IAVs) continue to pose major risks of morbidity and mortality during yearly epidemics and periodic pandemics. The genomic instability of IAV allows it to evade adaptive immune responses developed during prior infection. Of particular concern are pandemics which result from wholesale incorporation of viral genome sections from animal sources.

Lectin-mediated binding and sialoglycans of porcine surfactant protein D synergistically neutralize influenza A virus.

Innate immunity is critical in the early containment of influenza A virus (IAV) infection, and surfactant protein D (SP-D) plays a crucial role in the pulmonary defense against IAV. In pigs, which are important intermediate hosts during the generation of pandemic IAVs, SP-D uses its unique carbohydrate recognition domain (CRD) to interact with IAV. An -linked CRD glycosylation provides interactions with the sialic acid-binding site of IAV, and a tripeptide loop at the lectin-binding site facilitates enhanced interactions with IAV glycans.

Critical role of C-terminal residues of the Alzheimer's associated β-amyloid protein in mediating antiviral activity and modulating viral and bacterial interactions with neutrophils.

Recent studies have shown that the Alzheimer's associated β-amyloid protein (βA) can inhibit growth of bacteria, fungi and viruses. We reported that the 42 amino acid βA protein inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro and modulates activation of neutrophils and monocytes exposed IAV. We here show that fragments composed of the N and C terminal domain of βA42, including βA22-42 and the 8 amino acid βA35-42, retain viral neutralizing and viral aggregating activity, whereas fragments lacking the C-terminal amino acids 41 and 42 (e.

Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection.

Development of pneumonia is the most lethal consequence of influenza, increasing mortality more than 50-fold compared with uncomplicated infection. The spread of viral infection from conducting airways to the alveolar epithelium is therefore a pivotal event in influenza pathogenesis. We found that mitogenic stimulation with keratinocyte growth factor (KGF) markedly accelerated mortality after infectious challenge with influenza A virus (IAV).

Racial differences in colorectal cancer survival at a safety net hospital.

Background: While racial disparity in colorectal cancer survival have previously been studied, whether this disparity exists in patients with metastatic colorectal cancer receiving care at safety net hospitals (and therefore of similar socioeconomic status) is poorly understood.

Methods: We examined racial differences in survival in a cohort of patients with stage IV colorectal cancer treated at the largest safety net hospital in the New England region, which serves a population with a majority (65%) of non-Caucasian patients. Data was extracted from the hospital's electronic medical record.