Kevan L Hartshorn's research while affiliated with Boston University and other places

Publications (230)

Article
Full-text available
PurposeThe 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 fro...
Article
Full-text available
People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. Since influenza viruses that infect such people do not show consistent genomic variations, it i...
Article
Full-text available
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. In this paper, we evaluated the inhibition of IAV by mannose-binding...
Article
Full-text available
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 the...
Article
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...
Article
Full-text available
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 histon...
Article
Purpose Camptothecin (CPT) analogues topotecan and irinotecan specifically target topoisomerase I (topoI), and are used to treat colorectal, gastric and pancreatic cancer. Patient response rate for this class of drug varies from 10-30% and there is no predictive biomarker for patient stratification by response. Based on our understanding of CPT dru...
Article
Full-text available
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. SAA1 has been reported to directly activate neutrophils and to recruit...
Article
Full-text available
There is abundant evidence that the innate immune response to influenza A virus (IAV) is highly complex and plays a key role in protection against IAV induced infection and illness. Unfortunately it also clear that aspects of innate immunity can lead to severe morbidity or mortality from IAV, including inflammatory lung injury, bacterial superinfec...
Article
Full-text available
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 per...
Article
Purpose: 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. Methods: We obtained California cancer registry data on individuals who were diagnosed with stage I, II, or III colorectal cancer (CRC) between 2012...
Article
Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype. Lung surfactant protein D (SP-D), a key factor in first-line innate im...
Article
Full-text available
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 cell...
Article
Full-text available
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 uncle...
Article
Full-text available
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. Rec...
Article
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 safe...
Article
Full-text available
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. Using a novel quantitative histopathologic technique, we demonstrate...
Article
Full-text available
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 a...
Article
Full-text available
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....
Article
Full-text available
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. W...
Data
LDH assays on MDCK cells treated with βA preparations—LDH assays (n = 4). MDCK cells were treated with the indicated βA preparations at 50 μg/ml for 45 minutes. At 37°C as in the infectious focus assay. LDH was measured by ELISA assay at 18 hrs following the manufacturer’s instruction (Clontech, Mountain View, CA). (PPTX)
Article
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...
Article
Full-text available
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 fact...
Conference Paper
e15090 Background: Aberrant hyperactive Wnt/ß-catenin signaling is critical in colorectal cancer (CRC) tumorigenesis. Casitas B-lineage Lymphoma (c-Cbl) is a negative regulator of Wnt signaling, and functions as a tumor suppressor. The objective of this study was to evaluate c-Cbl expression as a predictive marker of survival in patients with metas...
Article
This commentary highlights the article by Pociask et al that provides new insights into the lingering effects of influenza infection.
Article
Immune checkpoint inhibitors (ICIs) are based on the understanding that there are multilayered checks and balances which can be manipulated to unleash already existing, but paralyzed, immune responses to cancer. These agents are safer and more efficacious than classic cytotoxic drugs making them a very attractive therapeutic option, especially in o...
Article
Full-text available
CK2 genes are overexpressed in many human cancers, and most often overexpression is associated with worse prognosis. Site-specific expression in mice leads to cancer development (e.g., breast, lymphoma) indicating the oncogenic nature of CK2. CK2 is involved in many key aspects of cancer including inhibition of apoptosis, modulation of signaling pa...
Article
Full-text available
Infiltrating activated monocytes are important mediators of damaging inflammation during influenza A virus (IAV) infection. We show that soluble respiratory proteins [collectins, surfactant proteins D (SP-D) and mannose binding lectin (MBL), H-ficolin and LL-37] inhibit replication of seasonal IAV in human monocytes. The collectins and H-ficolin al...
Article
p>There has been significant recent progress in the treatment of advanced colorectal and anal cancers. Improvements in surgical techniques have allowed increasing numbers of patients with oligometastatic colorectal cancer to undergo potentially curative resections. For patients with unresectable metastatic colorectal cancer chemotherapy remains the...
Article
p>Colon and rectal cancers are major health problems worldwide. Anal cancer is less common but still a challenging problem. There has been significant recent advancements in the diagnostic and therapeutic modalities for colorectal and anal cancers. These improvements include the refinement of surgical and radiation techniques, the use of biomarkers...
Article
Full-text available
Despite the loss of Adenomatous Polyposis Coli (APC) in a majority of colorectal cancers (CRC), not all CRCs bear hallmarks of Wnt activation, such as nuclear ?-catenin. This underscores the presence of other Wnt regulators that are important to define, given the pathogenic and prognostic roles of nuclear ?-catenin in human CRC. Herein, we investig...
Article
Full-text available
Influenza A virus (IAV) remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing...
Article
Full-text available
Hepatocellular cancer (HCC) is increasing dramatically in incidence in Europe and the United States due mainly to the hepatitis C epidemic and, to a lesser extent, increased body mass index of the population. In the fairly recent past, HCC was largely considered as untreatable due to detection mainly at late stages and lack of effective drugs for t...
Chapter
There is now abundant evidence that chronic inflammation in the brain is central to the pathogenesis of Alzheimer's disease (AD) and that this is precipitated through accumulation of amyloid beta (Aβ) peptides. In this review, we first outline this evidence and how specific receptors on microglia and monocyte/macrophages determine whether extracell...
Article
Full-text available
Pancreatic cancer is more common in older adults, who are underrepresented in clinical trials and frequently under treated. Chronological age alone should not deter clinicians from offering treatment to geriatric patients, as they are a heterogeneous population. Geriatric assessment, frailty assessment tools, and toxicity risk scores help clinician...
Book
Full-text available
Amyloid protein aggregates are involved in ''protein-misfolding diseases'' of enormous social and economic impact, still with no effective therapies. The most prevalent amyloid pathologies are related to neurodegenerative diseases, but amyloidosis also affects other organs. The majority of the studies includes serious health connotations on amyloid...
Book
Full-text available
Preface Amyloid protein aggregates are involved in a number of “protein-misfolding diseases” of enormous social and economic impact for which there are still no effective therapies or strat‐ egies for their prevention or inhibition available. There is a heterogeneous group of amyloi‐ dogenic proteins associated with amyloid pathologies including am...
Conference Paper
Background: African American (AA) colorectal cancer (CRC) patients experience lower survival compared to Caucasian Americans (CA). Aberrant Wnt/beta catenin (bcat) signaling is the hallmark of CRC pathogenesis, yet its contribution and that of its regulators to racial disparity remains elusive. Recently, Casitas B-lineage Lymphoma (c-Cbl) was ident...
Article
Full-text available
Despite sustained biomedical research effort, influenza A virus remains an imminent threat to the world population and a major healthcare burden. The challenge in developing vaccines against influenza is the ability of the virus to mutate rapidly in response to selective immune pressure. Hemagglutinin is the predominant surface glycoprotein and the...
Article
Histones are known for their ability to bind to and regulate expression of DNA. However, histones are also present in cytoplasm and extracellular fluids where they serve host defense functions and promote inflammatory responses. Histones are a major component of neutrophil extracellular traps that contribute to bacterial killing but also to inflamm...
Article
Full-text available
The human cathelicidin LL-37 has been shown to play a role in host defense against influenza A viruses (IAV) through direct antiviral effects and through modulating inflammatory responses to infection. We recently showed that LL-37 increases neutrophil respiratory burst and neutrophil extracellular trap (NET) responses to IAV through engaging formy...
Article
Full-text available
While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular traps, where they play an important role in NET-mediated antimicrobial killing. Here, we show anti-influenza activit...
Article
Full-text available
Human LL-37, a cationic antimicrobial peptide, was recently shown to have antiviral activity against influenza A virus (IAV) strains in vitro and in vivo. In this study we compared the anti-influenza activity of LL-37 with that of several fragments derived from LL-37. We first tested the peptides against a seasonal H3N2 strain and the mouse adapted...
Article
720 Background: During the last decade, numerous new agents were introduced into the therapy of metastatic colorectal cancer. For those patients who are not curable by resection, life can be extended with chemotherapy. However, it is not possible to predict who can safely take breaks without compromising survival. We sought to evaluate the relation...
Article
Full-text available
Unlabelled: Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogen...
Article
14 Background: Stage IV NSCLC is an incurable illness with significant morbidity. Chemotherapy prolongs average survival from 6 to 10 months and targeted therapies further reduce morbidity and prolong survival. These advances pose financial challenges for safety net hospitals, which may also disproportionately feel the impact of racial disparity. O...
Article
Malignant hypercalcemia occurs in about 20-30% of patients with cancer, both solid tumors and hematologic malignancies. The secretion of parathyroid hormone-related protein (PTH-rP) is the most common cause and has been shown to be the etiology of hypercalcemia associated with neuroendocrine tumors. Here we report the case of a patient with metasta...
Article
Recent studies have shown that the human cathelicidin, LL-37, has antiviral activity against IAV in vitro and in vivo. Neutrophils are important cellular components of the initial innate response to IAV infection. In addition to its direct antimicrobial activities, LL-37 has important immunomodulatory effects. In this study, we explore how LL-37 af...
Article
Full-text available
Accumulation of β-Amyloid (βA) is a key pathogenetic factor in Alzheimer's disease; however, the normal function of βA is unknown. Recent studies have shown that βA can inhibit growth of bacteria and fungi. In this paper we show that βA also inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro. The...
Article
Full-text available
We recently reported that a trimeric neck and carbohydrate recognition domain (NCRD) fragment of human surfactant protein D (SP-D), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (D325A+R343V) exhibits markedly increased antiviral activity for seasonal strains of influenza A virus (IAV). The NCRD binds to glyca...
Article
Full-text available
IAV pneumonia remains a serious global health problem, and preventative and therapeutic strategies remain limited. AM are critical effector cells in the control of influenza, impairing IAV replication, promoting IAV clearance, and promoting efferocytosis and resolution of lung inflammation. MBL, an innate immune pattern recognition molecule, presen...
Article
Surfactant protein D (SP-D), a mammalian C-type lectin, is the primary innate inhibitor of influenza A virus (IAV) in the lung. Interactions of SP-D with highly branched viral N-linked glycans on hemagglutinin (HA), an abundant IAV envelope protein and critical virulence factor, promote viral aggregation and neutralization through as yet unknown mo...
Article
Full-text available
Influenza A viruses (IAVs) remain a major health threat and a prime example of the significance of innate immunity. Our understanding of innate immunity to IAV has grown dramatically, yielding new concepts that change the way we view innate immunity as a whole. Examples include the role of p53, autophagy, microRNA, innate lymphocytes, endothelial c...
Article
The standard treatment strategy for patients with rectal adenocarcinoma having T3 or T4 tumors or positive lymph nodes includes concurrent chemoradiation, surgery and chemotherapy. Population based studies show relatively low rates of usage of standard therapy for rectal cancer in the older adult. Two decades of cases of stage II and stage III rect...
Article
Full-text available
Preoperative chemoradiotherapy (preopCRT) for locally advanced rectal cancer is associated with grade 3 or higher acute gastrointestinal (GI) toxicity. This study was conducted to determine whether intensity-modulated radiation therapy (IMRT) significantly reduces acute GI toxicity, compared to 3-dimensional conformal RT (3D-CRT) in preopCRT for re...
Article
Full-text available
This Commentary highlights the article by Gao et al, which showed protracted viral replication and correlated viral load with illness duration and proinflammatory cytokine levels in lung tissue samples from 2009 H1N1 victims.
Article
Full-text available
The early inflammatory response to influenza A virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which inflammatory cells invade the respiratory tract remain unclear. Uncontrolled inflammation and oxidative stress cause lung damage in response to influenza A infection. We ha...