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Fulltext Microvessel density and vascular endothelial growth factor receptors in breast carcinoma under the influence of rapamycin and platelet factor 4

Muhammad Sakri MS, Abdul Rahman WFW, Tengku Din TADA, Idris FM, Jaafar H

Indian J Pathol Microbiol, 2020 4 23;63(2):205-209.
PMID: 32317516 DOI: 10.4103/IJPM.IJPM_496_19

Background: Vascular endothelial growth factor receptors (VEGFRs) are major endothelial growth factor receptors that influence the growth of a tumor. Microvessel density.
(: MVD) is the quantification method of various aspects of tumor vasculature that indicates angiogenic activity. This study aims to analyze the correlation between MVD to the expression of VEGFRs on breast cancer tissue.
Materials and Method: A total of 60 N-methyl-N-nitrosourea (MNU)-induced breast carcinomas in rats were suppressed by using antiangiogenic drugs. The rats were then sacrificed, and the tumor was fixed in 10% formalin, paraffin embedded, and immunohistochemistry stained using VEGFRs and CD34.
Result: One-way ANOVA test showed a significant difference in all markers that have been used (P < 0.05) on MNU-breast tumor treated with rapamycin (M= 90.1664, SD= 7.4487), PF4 (M= 93.7946, SD= 7.1303) and rapamycin + PF4 (M= 93.6990, SD= 1.8432). We obtained a significant reduction of MVD count on breast carcinoma for rapamycin group (M= 25.6786, SD= 9.7075) and rapamycin + PF4 group (M= 30.5250, SD= 13.6928) while PF4 group (M=47.7985, SD=4.8892) showed slightly increase compared to control (M= 45.1875, SD= 4.4786). There was a moderately strong, positive correlation between angiogenic markers; Flt-1 (r= 0.544, n=60, P < 0.005) and Flt-4 (r= 0.555, n= 60, P < 0.005) while Flk-1 (r= 0.797, n= 60, P < 0.005) showed a strong, positive correlation with MVD.
Conclusion: MVD was strongly correlated to the VEGFRs expression on breast carcinoma.

Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment

Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.

J Gastroenterol Hepatol, 2018 Jan;33(1):20-29.
PMID: 29023903 DOI: 10.1111/jgh.14019

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Matched MeSH terms: Immunosuppressive Agents/therapeutic use
IgG4-related disease: features and treatment response in a multi-ethnic cohort in Singapore

Fong W, Liew I, Tan D, Lim KH, Low A, Leung YY

Clin Exp Rheumatol, 2018 05 24;36 Suppl 112(3):89-93.
PMID: 29846168

OBJECTIVES: To describe the features and treatment outcomes of IgG4-RD in multi-ethnic patients in Singapore.
METHODS: Retrospective study was performed on IgG4-RD patients identified from patient databases in a tertiary hospital.
RESULTS: Fourty-two patients (76% male) were included; 79% fulfilled the 2011 comprehensive diagnostic criteria for IgG4-RD for definite IgG4-RD. 81% were Chinese and 19% were Malays. Common initial manifestations included jaundice (52%), abdominal pain (36%) and swollen salivary glands (26%). Only 36% had a history of allergy. 83% had ≥ 1 organ involvement. Erythrocyte sedimentation rate, immunoglobulin E, IgG2 and IgG4 levels were elevated in 84%, 100%, 70% and 44% of patients, respectively. The most common histopathological feature was >10 IgG4+ cells per high power field (66%). 94% (34/36) of patients were treated with moderate to high doses of glucocorticoids, including 17 patients with combination immunosuppressants. Of these, all patients responded to therapy by 3 months. With a median (range) follow-up of 4.1 (0.4-13.8) years, 69% (25/36) needed low dose of glucocorticoids to maintain disease remission. Twenty-six per cent had relapse of disease, of which 82% had disease recurrence in the same organs.
CONCLUSIONS: Pancreatitis, lymphoadenopathy and cholangitis were the commonest manifestations in Asians with IgG4-RD. All patients responded to glucocorticoid therapy by 3 months, two-thirds required maintenance therapy with glucocorticoids, and one-quarter developed relapse of disease.

Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
Relapsed Chronic Lymphocytic Leukaemia with Concomitant Extensive Chronic Graft versus Host Disease after Allogeneic Haematopoietic Stem Cell Transplantation Successfully Treated with Oral Venetoclax

Teoh CS, Goh AS

Case Rep Transplant, 2021;2021:8831125.
PMID: 33552611 DOI: 10.1155/2021/8831125

A middle-aged gentleman who was diagnosed with high-risk chronic lymphocytic leukaemia (CLL), Rai stage IV, Binet C with del(17p) and del(13q) underwent allogeneic haematopoeitic stem cell transplantation (allo-HSCT) from a human leukocyte antigen (HLA) identical sister. The patient developed extensive skin, oral, and liver chronic graft versus host disease (GVHD) required tacrolimus, mycophenolate mofetil (MMF), and prednisolone. At seventh month after allo-HSCT, the patient presented with systemic symptoms, right cervical lymphadenopathy, splenomegaly, marked pancytopaenia, and elevated lactate dehydrogenase (LDH). Bone marrow study, immunophenotyping (IP), chromosome analysis, and PET-CT scan confirmed relapsed CLL with no evidence of Richter's transformation or posttransplant lymphoproliferative disease (PTLD). Withdrawal of immunosuppressant (IS) worsened cutaneous and liver GVHD. Chemotherapy was not a suitable treatment option in view of immunodeficiency. The patient underwent extracorporeal photopheresis (ECP) therapy eventually for extensive chronic GVHD, and the IS were gradually tapered to the minimal effective dose. The relapsed CLL was treated successfully with oral venetoclax accessible via a compassionate drug program. This case highlights challenges in managing relapsed CLL and loss of graft-versus-leukaemia (GVL) effect despite extensive chronic GVHD. Venetoclax is an effective and well-tolerated oral novel agent for relapsed CLL after allo-HSCT.

Matched MeSH terms: Immunosuppressive Agents
Fulltext Steroid withdrawal or avoidance in renal transplant recipients

Chang, S.H., Tan, S.Y.

JUMMEC, 2006;9(1):2-6.
MyJurnal

Steroids remain an important component of maintenance immunosuppression after renal transplantation. Their anti-inflammatory action is partly due to the sequestration of CD4+ lymphocytes in the reticuloendothelial system. Steroids bind to intracellular receptors and the resulting steroid-receptor complex alters the transcription of cytokines by binding to glucocorticoid response elements on DNA. Transcription factors whose actions are altered by glucocorticoids include activating protein-1 (AP-1) and nuclear factor-B (NF-B). The main cytokines whose production by antigen-presenting cells is inhibited by steroids are interleukin-1 (IL-1), required for helper T-cell activation, and IL-6, required for B-cell activation. Other pro-inflammatory cytokines such as interferon gamma and tumour necrosis factor are also inhibited. This multiplicity of immunosuppressive actions is not fully replicated by other immunosuppressants. However, there are concerns about the long-term side effects of steroids. This review will examine the attempts at steroid withdrawal or steroid avoidance in renal transplant patients.

Matched MeSH terms: Immunosuppressive Agents
Fulltext Pyoderma gangrenosum and cobalamin deficiency in systemic lupus erythematosus: a rare but non fortuitous association

Teoh SC, Sim CY, Chuah SL, Kok V, Teh CL

BMC Rheumatol, 2021 Mar 03;5(1):7.
PMID: 33653418 DOI: 10.1186/s41927-021-00177-4

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon, idiopathic, ulcerative neutrophilic dermatosis. In many cases, PG is associated with a wide variety of different disorders but SLE in association with PG is relatively uncommon. In this article we present the case of a middle aged patient with PG as the initial clinical presentation of SLE. We also provide a brief review of cobalamin deficiency which occurred in our patient and evidence-based management options.
CASE PRESENTATION: A 35 years old man presented with a 5 month history of debilitating painful lower limb and scrotal ulcers. This was associated with polyarthralgia and morning stiffness involving both hands. He also complained of swallowing difficulties. He had unintentional weight loss of 10 kg and fatigue. Physical examination revealed alopecia, multiple cervical lymphadenopathies, bilateral parotid gland enlargement and atrophic glossitis. There was Raynaud's phenomenon noted over both hands and generalised hyper-pigmented fragile skin. Laboratory results disclosed anaemia, leukopenia, hyponatraemia and hypocortisolism. Detailed anaemic workup revealed low serum ferritin and cobalamin level. The autoimmune screen showed positive ANA, anti SmD1, anti SS-A/Ro 52, anti SSA/Ro 60, anti U1-snRNP with low complement levels. Upper gastrointestinal endoscopy with biopsies confirmed atrophic gastritis and duodenitis. Intrinsic factor antibodies and anti-tissue transglutaminase IgA were all negative. Punch biopsies of the leg ulcer showed neutrophilic dermatosis consistent with pyoderma gangrenosum. Based on the clinical findings and positive immunologic studies, he was diagnosed as systemic lupus erythematosus. His general condition improved substantially with commencement of corticosteroids, immunosuppressants and vitamin supplements.
CONCLUSIONS: We report a case of PG as the first manifestation of SLE which was treated successfully with immunosuppressants and vitamin supplements. Our report highlighted the need to consider connective tissue diseases such as SLE in a patient presenting with PG in order for appropriate treatment to be instituted thereby achieving a good outcome.

Matched MeSH terms: Immunosuppressive Agents
"Fleshy" Skin Cellulitis: A Triggering Factor for ANCA Associated Vasculitis

Yang SC, Mustafar R, Kamaruzaman L, Wei Yen K, Mohd R, Cader R

Acta Med Indones, 2019 Oct;51(4):338-343.
PMID: 32041918

A 59-year-old lady with underlying hypothyroidism presented with acute contact dermatitis progressed to cellulitis with superimposed bacterial infection and acute kidney injury. She responded to initial management with antibiotics, but a week later, she had cutaneous and systemic vasculitis. Her skin biopsy consistent with immune-mediated leuko-cytoclastic vasculitis and her blood test was positive for cytoplasmic-anti-neutrophil cytoplasmic antibody (c-ANCA). A diagnosis of ANCA-associated vasculitis was made and she was treated with immunosuppressant with plasmapheresis and hemodialysis support for her kidney failure. Despite aggressive measures, the patient succumbed to her illness. This case report demonstrates that soft tissue infection could trigger the development of ANCA-associated vasculitis whilst a background of hypothyroidism serves as a predisposing factor as both condition were reported separately in a couple of case studies before.

Matched MeSH terms: Immunosuppressive Agents
Patient with statin-associated immune-mediated necrotizing myopathy presenting with subcutaneous edema, persistent bulbar weakness and absent anti-HMGCR

Ong SG, Ding HJ

Int J Rheum Dis, 2017 Dec;20(12):2175-2178.
PMID: 26692320 DOI: 10.1111/1756-185X.12814
Matched MeSH terms: Immunosuppressive Agents/administration & dosage
Fingolimod affects gene expression profile associated with LPS-induced memory impairment

Omidbakhsh R, Rajabli B, Nasoohi S, Khallaghi B, Mohamed Z, Naidu M, et al.

Exp Brain Res, 2014 Nov;232(11):3687-96.
PMID: 25098558 DOI: 10.1007/s00221-014-4052-4

Lipopolysaccharide is an endotoxin to induce sickness behavior in several animal models to explore the link between immune activation and cognition. Neuroinflammation playing a pivotal role in disease progress is evidently influenced by sphingosine-1-phosphate. As one of the sphingosine analogs in clinical use for multiple sclerosis, fingolimod (FTY720) was shown to substantially affect gene expression profile in the context of AD in our previous experiments. The present study was designed to evaluate the drug efficacy in the context of the mere inflammatory context leading to memory impairment. FTY720 was repeatedly administered for a few days before or after intracerebral lipopolysaccharide (LPS) injection in rats. Animal's brains were then assigned to histological as well as multiplex mRNA assay following memory performance test. Both FTY720 pre-treatment and post-treatment were similarly capable of ameliorating LPS-induced memory impairment as assessed by passive avoidance test. Such amending effects may be partly accountable by the concomitant alterations in transcriptional levels of mitogen-activated protein kinases as well as inflammatory genes determined by QuantiGene Plex analysis. These findings confirming FTY720 application benefits suggest its efficacy may not differ significantly while considered either as a preventive or as a therapeutic approach against neuroinflammation.

Matched MeSH terms: Immunosuppressive Agents/pharmacology
Predictors of thickened carotid intima media thickness among well controlled lupus nephritis patients in a Malaysian tertiary centre

Shaharir SS, Mohamed Said MS, Kong NC

Reumatismo, 2012;64(6):341-9.
PMID: 23285477 DOI: 10.4081/reumatismo.2012.341

OBJECTIVES: To investigate the prevalence of thickened carotid intima media thickness (CIMT) and its associated risk factors in patients with lupus nephritis (LN) who were in remission.
METHODS: This was a cross sectional study in which consecutive LN patients who were in remission and attending our Nephrology/SLE Clinic were included. Their demographic profile, traditional cardiovascular risk factors and treatment medications were evaluated by clinical interview and review of medical records. Carotid intima media thickness (CIMT) was measured using B Mode carotid ultrasonography. CIMT was considered to be abnormally thickened if it exceeded the 75th percentile matched for age-and sex-matched normal controls. The associated factors for thickened CIMT were examined.
RESULTS: A total of 39 patients with a mean remission duration of 29 ± 24.3 months and on a mean prednisolone dose of 9.10 ± 7.83 mg daily completed the study. Six patients (15.4%) had thickened CIMT. On univariate analysis, male gender, patient age, older age at diagnosis, higher serum CRP levels, greater proteinuria and higher mean cumulative azathioprine dose were associated with thickened CIMT (P<0.05). Lower mean cumulative doses of cyclosporine A (CyA) and mycophenolic acid (MPA) (P<0.05) each were associated with thickened CIMT. Using regression analysis, the associated factors of CIMT were older age at diagnosis and proteinuria.
CONCLUSIONS: Lupus factors particularly age at diagnosis and proteinuria were the associated factors of thickened CIMT. Larger prospective trials are indicated to confirm our findings.

Matched MeSH terms: Immunosuppressive Agents