Adeel Zubair

Role of Nuclear Factor-ĸB in Breast and Colorectal Cancer

The purpose of this review article is to highlight articles and new research regarding the link between NF-ĸB and several cancers. This review presents the most up-to-date NF-ĸB research and how it links this important transcription factor with hematology and oncology. It was written by conducting a thorough search of Pubmed as well as several journals such as Cancer, Nature, Science, Cell and those of one of the authors. The articles relating to the link between NF-ĸB and cancer were used to write this review. The results of this study clarified that there is a critical link between NF-ĸB and cancer. NF-ĸB has often been implicated in a variety of different diseases and it plays a variety of roles in cell survival, differentiation, and proliferation of cells. In cancer, NF-ĸB plays a pivotal role by facilitating oncogenesis as well as metastasis. A thorough understanding of NF-ĸB and its role in cancer can lead to future studies and drug development which could provide a novel option in the treatment of this disease.

Increased incidence and recurrence rates of nonmelanoma skin cancer in patients with non-Hodgkin lymphoma: A Rochester Epidemiology Project population-based study in Minnesota

BACKGROUND Cutaneous malignancy is associated with worse outcomes in patients with chronic lymphocytic leukemia (CLL). OBJECTIVE We sought to identify the incidence and recurrence rate of nonmelanoma skin cancer (NMSC) in patients with non-Hodgkin lymphoma (NHL). METHODS NMSC incidence was calculated and Cox proportional hazards models were used to evaluate associations with risk of recurrence for patients with NHL between 1976 and 2005 who were in the Rochester Epidemiology Project research infrastructure. RESULTS We identified 282 patients with CLL or small lymphocytic lymphoma and 435 with non-CLL NHL. The incidence of basal cell carcinoma and squamous cell carcinoma was 1829.3 (95% confidence interval [CI] 1306.7-2491.1) and 2224.9 (95% CI 1645.9-2941.6), respectively, in patients with CLL. The cumulative recurrence rate at 8 years after treatment with Mohs micrographic surgery was 8.3% (95% CI 0.0%-22.7%) for basal cell carcinoma and 13.4% (95% CI 0.0%-25.5%) for squamous cell carcinoma in patients with CLL. LIMITATIONS This was a retrospective cohort study. CONCLUSIONS After Mohs micrographic surgery and standard excision of NMSC, patients with NHL had a skin cancer recurrence rate that was higher than expected. Careful treatment and monitoring of patients with NHL and NMSC are warranted.

Optimal management of skin cancer in immunosuppressed patients.

Skin cancer is the most common malignancy in humans with basal cell carcinoma representing the majority of cases in the general population. The prevalence of skin cancer is increased amongst immunosuppressed patients such as those with lymphoproliferative disorders including non-Hodgkin lymphoma and chronic lymphocytic leukemia or those with iatrogenic immunosuppression following organ transplantation. In addition, these patients experience greater morbidity and mortality associated with skin cancers. The most common skin cancer in immunosuppressed patients is squamous cell carcinoma, which often presents with more aggressive features and has a greater rate of metastasis. This article reviews the risk factors, etiology, clinical presentation, and prevalence of skin cancer amongst immunosuppressed patients, including organ transplant, lymphoproliferative disorders, autoimmune disorders, and human immunodeficiency virus. We also provide a comprehensive review of treatment guidelines for immunosuppressed patients with cutaneous malignancy. Surgical therapy is the cornerstone of treatment; however, we also discuss pharmacologic treatment options, lifestyle modifications, and revision of immunosuppressive regimens.

Redox signaling is an early event in the pathogenesis of renovascular hypertension

Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.

Lupus Nephritis: Review of the Literature

Physicians in practice should be knowledgeable regarding several aspects of autoimmune disorders, especially systemic lupus erythematosus (SLE) and lupus nephritis. These disorders can present to the clinician’s clinic and private office regardless of their speciality. This review will discuss various aspects of SLE, its mechanisms of disease, role of accelerated atherosclerosis, proinflammatory cytokines, and therapeutic approaches. The role of vascular endothelial growth factor in which and plasma levels have been associated with disease activity, classification of severity, and diagnosis of lupus nephritis is addressed. Current treatment options, prognosis, and future therapeutic approaches and common side effects are also discussed.

Blockade of CCR2 reduces macrophage influx and development of chronic renal damage in murine renovascular hypertension

Renovascular hypertension (RVH) is a common cause of both cardiovascular and renal morbidity and mortality. In renal artery stenosis (RAS), atrophy in the stenotic kidney is associated with an influx of macrophages and other mononuclear cells. We tested the hypothesis that chemokine receptor 2 (CCR2) inhibition would reduce chronic renal injury by reducing macrophage influx in the stenotic kidney of mice with RAS. We employed a well-established murine model of RVH to define the relationship between macrophage infiltration and development of renal atrophy in the stenotic kidney. To determine the role of chemokine ligand 2 (CCL2)/CCR2 signaling in the development of renal atrophy, mice were treated with the CCR2 inhibitor RS-102895 at the time of RAS surgery and followed for 4 wk. Renal tubular epithelial cells expressed CCL2 by 3 days following surgery, a time at which no significant light microscopic alterations, including interstitial inflammation, were identified. Macrophage influx increased with time following surgery. At 4 wk, the development of severe renal atrophy was accompanied by an influx of inducible nitric oxide synthase (iNOS)+ and CD206+ macrophages that coexpressed F4/80, with a modest increase in macrophages coexpressing arginase 1 and F4/80. The CCR2 inhibitor RS-102895 attenuated renal atrophy and significantly reduced the number of dual-stained F4/80+ iNOS+ and F4/80+ CD206+ but not F4/80+ arginase 1+ macrophages. CCR2 inhibition reduces iNOS+ and CD206+ macrophage accumulation that coexpress F4/80 and renal atrophy in experimental renal artery stenosis. CCR2 blockade may provide a novel therapeutic approach to humans with RVH.

NF-κB and systemic lupus erythematosus: examining the link.

Physicians should be knowledgeable regarding several aspects of autoimmune disorders, especially systemic lupus erythematosus (SLE), with which patients can present in their office with urticaria or vasculitis and which may masquerade as another condition. This paper reviews the link between NF-κB and SLE, including B-cell development, signaling and cytokines which play a crucial role in the pathogenesis of SLE and T-cell development, a key player in T-cell activation. The roles of dendritic cells, which can promote tolerance or immunity to antigens, of polymorphisms and of NF-κB, which are linked with SLE, are also discussed. The role of Toll-like receptors which are important in the pathogenesis of SLE and lupus nephritis is also discussed.

Loin pain hematuria syndrome

Loin pain hematuria syndrome (LPHS), first described in 1967, is a rare pain syndrome, which is not well understood. The syndrome is characterized by severe intermittent or persistent flank pain, either unilateral or bilateral, associated with gross or microscopic hematuria. LPHS is a diagnosis of exclusion as there still is not a consensus of validated diagnostic criteria, though several criteria have been proposed. The wide differential diagnosis would suggest a meticulous yet specific diagnostic work-up depending on the individual clinical features and natural history. Several mechanisms regarding the pathophysiology of LPHS have been proposed but without pinpointing the actual causative etiology, the treatment remains symptomatic. Treatment modalities for LPHS are diverse including simple analgesia, opioid analgesic and kidney autotransplantation. This review article summarizes the current understanding regarding the pathophysiology of LPHS along with the steps required for proper diagnosis and a discussion of the different therapeutic approaches for LPHS.

Childhood abuse is associated with worse survival following lung transplantation

Context: Psychosocial factors can impact lung transplant outcomes. However, it is currently unknown whether abuse survivorship influences lung transplant survival. Objective: To characterize the abuse history of adult lung transplant patients and determine whether such history is associated with mortality. Patients and Other Participants: Adult lung transplant recipients evaluated from 2000 to 2004. Main Outcome Measures: The main outcome was post-lung transplantation survival. The secondary outcomes included demographic, transplantation, or psychological assessment differences between those with a history of abuse survivorship and those without. Results: Thirty-three lung transplant recipients (35.5% male, median age: 55 years) were included. A history of abuse survivorship was common (24.2%) and was associated with decreased survival following lung transplantation (P = .003). There was no difference in sex, marital status, or smoking history between abuse survivors and those who denied being the victim of abuse. Abuse survivors had a higher Personality Assessment Screener total score, a measure of maladaptive personality traits (P = .02). Conclusion: Abuse survivorship is common in lung transplant patients and associated with increased posttransplant mortality and increased maladaptive personality traits. This preliminary evidence suggests that lung transplant patients should be screened for abuse history and provided with appropriate treatment of survivorship issues to potentially improve their health outcomes from transplantation.

Surgical Treatment and Outcomes of Patients With Extramammary Paget Disease: A Cohort Study

BACKGROUND Extramammary Paget disease (EMPD) is a rare intraepithelial adenocarcinoma occurring mainly in the anogenital region. Traditional management with wide local excision has shown high recurrence rates, thus Mohs micrographic surgery (MMS) has emerged as a promising treatment option. OBJECTIVE To compare long-term outcomes after treatment with MMS or excision for primary EMPD. METHODS AND MATERIALS Retrospective cohort review was conducted for 207 patients with EMPD treated at Mayo Clinic in Rochester, MN, between 1961 and 2012. RESULTS Of the 25 patients treated with MMS, 19 primary tumors were included for outcome analysis, with an estimated 5-year recurrence-free survival rate of 91% (95% confidence interval [CI], 75–100) using Kaplan–Meier curve analysis. Of 158 patients treated with local excision, 124 were included for the analysis, with an estimated 5-year recurrence-free survival rate of 66% (95% CI, 56–78). The hazard ratio (HR) for association of treatment was 0.4 (95% CI, 0.10–1.65; p = .20). Estimated 5-year overall survival rates were 79% for MMS (95% CI, 61–100) and 68% for excision (95% CI, 59–78) (HR, 1.39 [95% CI, 0.69–2.82]; p = .36). CONCLUSION Although treatment of primary EMPD with MMS versus excision did not show statistical difference, MMS demonstrated favorable long-term outcomes and was associated with a higher recurrence-free survival rate.