Anupam Mitra | University of California, Davis (original) (raw)

Papers by Anupam Mitra

Journal of Gastrointestinal Oncology

Background: A growing body of evidence suggests that conventional chemotherapy may not be effecti... more Background: A growing body of evidence suggests that conventional chemotherapy may not be effective in mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC). Alternative strategies, such as immunotherapy, are currently being investigated both in the neoadjuvant and adjuvant setting. Furthermore, immunotherapy is an attractive alternative to the use of combination chemotherapy regimens when treating synchronous primary cancers such as in the setting of inherited cancer syndromes. Case Description: Here we present a case of a middle-aged woman diagnosed with dMMR/MSI-H locally advanced rectal cancer with synchronous upper tract urothelial cancer secondary to Lynch syndrome. The patient was first treated using neoadjuvant chemotherapy followed by chemoradiation, resulting in only a partial pathologic response. Following surgery, the patient was treated with adjuvant combination immunotherapy with nivolumab, a PD-1 inhibitor, and ipilimumab, a CTLA-4 inhibitor, resulting in a durable disease-free interval of nearly 21 months. Conclusions: This case report illustrates the importance of determining dMMR/MSI-H status in LARC and the consideration of immunotherapy (particularly with synchronous primaries as seen in inherited cancer syndromes), reviews the current literature, and calls for further investigation into the use of neoadjuvant and adjuvant immunotherapy in locally advanced rectal cancer along with upper tract urothelial carcinoma (UTUC).

Psoriasis - Types, Causes and Medication, 2013

International Journal of Surgical Pathology

Goblet cell adenocarcinoma and signet-ring cell adenocarcinoma are well-known diagnostic pitfalls... more Goblet cell adenocarcinoma and signet-ring cell adenocarcinoma are well-known diagnostic pitfalls of routine appendectomy specimens. Here we present a case of acute appendicitis with prominent neuronal (ganglion cell) hyperplasia and swelling which histologically mimics goblet cell adenocarcinoma and signet-ring cell adenocarcinoma. Attention to the cytologic features of the lesional cells (absence of atypia, mitotic activity) and their close association with nerves and classic ganglion cells, along with the use of a limited panel of immunostains, ensures proper classification of this rare but striking benign process.

American Journal of Hematology

Journal of Pathology Informatics

Indian Journal of Psychiatry

Clinical reviews in allergy & immunology, Jan 19, 2018

Following publication of this article [1] it came to our attention that we neglected to reference... more Following publication of this article [1] it came to our attention that we neglected to reference an article by Ishwarlal Jialal published in Critical Pathways in Cardiology [2].

Frontiers in immunology, 2017

Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most commo... more Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysisquantitative real-time PCR. All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvol...

Journal of dermatological science, Jan 3, 2017

Molecular & cellular proteomics : MCP, Jan 17, 2016

Although gut host-pathogen interactions are glycan-mediated processes, few details are known abou... more Although gut host-pathogen interactions are glycan-mediated processes, few details are known about the participating structures. Here we employ high-resolution mass spectrometric profiling to comprehensively identify and quantitatively measure the exact modifications of native intestinal epithelial cell surface N-glycans induced by S. Typhimurium infection. Sixty minutes post-infection, select sialylated structures showed decreases in terms of total number and abundances. To assess the effect of cell surface mannosylation, we selectively rerouted glycan expression on the host using the alpha-mannosidase inhibitor, kifunensine, toward overexpression of high mannose. Under these conditions, internalization of S. Typhimurium significantly increased, demonstrating that bacteria show preference for particular structures. Finally, we developed a novel assay to measure membrane glycoprotein turnover rates, which revealed that glycan modifications occur by bacterial enzyme activity rather t...

Veterinary Immunology and Immunopathology, 2016

Metaphyseal osteopathy (MO) (hypertrophic osteodystrophy) is a developmental disorder of unexplai... more Metaphyseal osteopathy (MO) (hypertrophic osteodystrophy) is a developmental disorder of unexplained etiology affecting dogs during rapid growth. Affected dogs experience relapsing episodes of lytic/sclerotic metaphyseal lesions and systemic inflammation. MO is rare in the general dog population; however, some breeds (Weimaraner, Great Dane and Irish Setter) have a much higher incidence, supporting a hereditary etiology. Autoinflammatory childhood disorders of parallel presentation such as chronic recurrent multifocal osteomyelitis (CRMO), and deficiency of interleukin-1 receptor antagonist (DIRA), involve impaired innate immunity pathways and aberrant cytokine production. Given the similarities between these diseases, we hypothesize that MO is an autoinflammatory disease mediated by cytokines involved in innate immunity. To characterize immune dysregulation in MO dogs we measured serum levels of inflammatory markers in 26 MO and 102 control dogs. MO dogs had significantly higher levels (pg/ml) of serum Interleukin-1beta (IL-1β), IL-18, IL-6, Granulocyte-macrophage colony stimulating factor (GM-CSF), C-X-C motif chemokine 10 (CXCL10), tumor necrosis factor (TNF), and IL-10. Notably, recovered MO dogs were not different from dogs during active MO disease, providing a suggestive mechanism for disease predisposition. This is the first documentation of elevated immune markers in MO dogs, uncovering an immune profile similar to comparable autoinflammatory disorders in children.

Drug Design, Development and Therapy, 2015

The treatment of melanoma has improved markedly over the last several years with the advent of mo... more The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy.

Molecular & Cellular Proteomics, 2015

Changes in cell surface glycosylation occur during the development and differentiation of cells a... more Changes in cell surface glycosylation occur during the development and differentiation of cells and have been widely correlated with the progression of several diseases. Because of their structural diversity and sensitivity to intra-and extracellular conditions, glycans are an indispensable tool for analyzing cellular transformations. Glycans present on the surface of intestinal epithelial cells (IEC) mediate interactions with billions of native microorganisms, which continuously populate the mammalian gut. A distinct feature of IECs is that they differentiate as they migrate upwards from the crypt base to the villus tip. In this study, nano-LC/ESI QTOF MS profiling was used to characterize the changes in glycosylation that correspond to Caco-2 cell differentiation. As Caco-2 cells differentiate to form a brush border membrane, a decrease in high mannose type glycans and a concurrent increase in fucosylated and sialylated complex/hybrid type glycans were observed. At day 21, when cells appear to be completely differentiated, remodeling of the cell surface glycome ceases. Differential expression of glycans during IEC maturation appears to play a key functional role in regulating the membrane-associated hydrolases and contributes to the mucosal surface innate defense mechanisms. Developing methodologies to rapidly identify changes in IEC surface glycans may lead to a rapid screening approach for a variety of disease states affecting the GI tract.

The Journal of investigative dermatology, Jan 2, 2015

To analyze usage and availability of sun protection devices, sun protection scores (SPUS and SPAS... more To analyze usage and availability of sun protection devices, sun protection scores (SPUS and SPAS) were created. Points were given for subjects' responses regarding usage of sunscreen, sunglasses, hats/headgear, or shade structures. Sporadic use received 0 points, occasional use received 1 point, and routine use received 2 points. For statistical analysis, independent sample t-tests assuming unequal variance and χ 2 tests were used for group comparisons when appropriate. Pearson's correlation coefficient (r) was used for correlation analyses. A multivariate linear/logistic regression model was designed and performed for sun protection use and for sunburns. Two-tailed P-valueso0.05 were considered to be statistically significant.

Molecular Pathophysiology, Nutritional and Therapeutic Interventions, 2012

PloS one, 2015

Increasing evidence points to a role for the extra-neuronal nerve growth factor (NGF) in acquired... more Increasing evidence points to a role for the extra-neuronal nerve growth factor (NGF) in acquired immune responses. However, very little information is available about its role and underlying mechanism in innate immunity. The role of innate immunity in autoimmune diseases is becoming increasingly important. In this study, we explored the contribution of pleiotropic NGF in the innate immune response along with its underlying molecular mechanism with respect to IL-1β secretion. Human monocytes, null and NLRP3 deficient THP-1 cell lines were used for this purpose. We determined the effect of NGF on secretion of IL-1β at the protein and mRNA levels. To determine the underlying molecular mechanism, the effect of NGF on NLRP1/NLRP3 inflammasomes and its downstream key protein, activated caspase-1, were evaluated by ELISA, immunoflorescence, flow cytometry, and real-time PCR. In human monocytes and null THP-1 cell line, NGF significantly upregulates IL-1β at protein and mRNA levels in a ca...