• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6591-6594
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• 2015

Background: Mantle-cell lymphoma (MCL) is a unique entity of peripheral B-cell lymphoma that has a discrete morphologic, immunologic, and genetic phenotype, with more common 'classic' and less frequent 'blastoid' and 'pleomorphic' variants, associated with an aggressive clinical course. The aim of this study was to analyze proliferation (Ki-67) indices of 'classic' (c-MCL) and 'blastoid' (b-MCL) variants of a cohort of MCL and to suggest cut off values for the Ki-67 proliferation index in these two subsets. Materials and Methods: MCL cases diagnosed over $4{\frac{1}{2}}$ years at Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi were retrieved and reviewed. Ki-67 labelling was scored and analysed. Results: A total of 90 of cases of MCL were scrutinized. Mean age ${\pm}SD$ was $60.2{\pm}12.5$ years and the male to female ratio was 4:1, with 67 (75%) cases of c-MCL and 23 (25%) cases of b-MCL. Most samples were lymph node biopsies (n=68), whereas the remainder were from various extranodal sites The mean Ki-67 proliferation index was $29.5%{\pm}14.4%$ in classic variants and $64.4{\pm}15.2%$ for the blastoid variant, the difference being statistically significant (p = 0.029). Conclusions: It was concluded that differential cut-off values of Ki-67 labeling may be used in more objective way to reliably classify MCL into classic or blastoid variants by diagnostic pathologists. We propose a < 40 proliferative index to be suggestive of c-MCL and one of > 50 for the blastoid variant.

• Journal of Microbiology and Biotechnology
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• v.28 no.12
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• pp.2121-2132
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• 2018

Abnormal melanin synthesis results in several hyperpigmentary disorders such as freckles, melanoderma, age spots, and other related conditions. In this study, we investigated the anti-melanogenic effects of an extract from the microalgae Chlamydomonas reinhardtii (CE) and potential mechanisms responsible for its inhibitory effect in B16F10, normal human epidermal melanocyte cells, and human skin-equivalent models. The CE extract showed significant dose-dependent inhibitory effects on ${\alpha}$-melanocyte-stimulating, hormone-induced melanin synthesis in cells. Additionally, the CE extract exhibited suppressive effects on the mRNA and protein expression of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. The CE extract also inhibited the phosphorylation of protein kinase A and extracellular signal-related kinase, which function as upstream regulators of melanogenesis. Using a three-dimensional, reconstructed pigmented epidermis model, the CE-mediated, anti-pigmentation effects were confirmed by Fontana-Masson staining and melanin content assays. Taken together, CE extract can be used as an anti-pigmentation agent.

• Nutrition Research and Practice
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• v.14 no.6
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• pp.593-605
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• 2020

BACKGROUND/OBJECTIVES: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (Aβ) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against Aβ-induced neuroinflammation and the underlying mechanism in C6 glial cells. MATERIALS/METHODS: C6 glial cells were treated with PF and Aβ_25-35, and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and Aβ degradation was determined by Western blot. RESULTS: Aβ_25-35 significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited Aβ_25-35-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-κB) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-κB was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of Aβ degrading enzymes, insulin degrading enzyme and neprilysin. CONCLUSIONS: These findings indicate that PF exerts protective effects against Aβ-mediated neuroinflammation by inhibiting NF-κB signaling, and these effects were associated with the enhanced activity of Aβ degradation enzymes.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4889-4895
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• 2012

Background and Aim: The incidence of extra nodal non Hodgkin lymphoma (ENL) is rising throughout the world. However, data regarding ENL as a group is limited. The aim was to study the epidemiological and histomorphological trends of primary ENL (pENL) in India. Material and Methods: The biopsy materials from sixty eight patients with pENL (45 male, 23 female, M:F= 1.9:1), diagnosed over a five year period (2005-2009), were analysed and pathologically reclassified according to the World Health Organization (WHO) classification, 2008 criteria. Results: Primary extra nodal non Hodgkin lymphomas constituted 22.0% (68/308) of all non Hodgkin lymphomas (NHL). The mean age at presentation for pENL and primary nodal NHL was 43 years and 58 years, respectively with a male predilection (M: F=2:1). Central nervous system (CNS) constituted the most common extranodal site (20/68, 29.5%) followed by gastrointestinal tract (17/68, 25%), and nose/nasopharynx (8/68, 11.8%). Diffuse large B-cell lymphoma (DLBCL, not otherwise specified), extranodal marginal lymphoma of mucosa associated lymphoid tissue (MALT) type, and B cell NHL unclassified (U) were the three most common histological types observed. T-cell phenotype was rarely noted (4%). Follicular lymphomas and anaplastic large cell lymphoma, seen among nodal NHL, were absent at extra nodal sites. Majority (41/68, 60%) of the patients with pENL were immunocompetent and 55% were in stage I-II with favorable prognosis. Conclusion: Central nervous system was the most common site of ENL, followed by gastrointestinal tract. Majority of pENL occurred in immunocompetent hosts with a favorable prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5273-5280
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• 2016

Objective: To evaluate stromal cells of the bone marrow microenvironment (BMM) in bone marrow trephine biopsy (BMTB) specimens, with a focus on fibronectin, tumor necrosis factor- alpha (TNF-${\alpha}$) and L-selectin in Non-Hodgkin's lymphoma (NHL) patients, before and after therapy. Materials and Methods: A total of 80 de novo NHL patients, 64 with B-cell lymphomas 80%, (follicular cell lymphoma (FCL) in 32, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in 12, and diffuse large cell lymphoma in 20) and 16 with T-cell lymphomas (20%) all diagnosed as T-Lymphoblastic lymphomas, were evaluated before and after therapy. For comparison, 25 age and sex matched BM donors, were included as a control group. BMTB material and BM aspirates were taken for morphological assessment of stromal cells, the plasma of these samples being examined for $TNF{\alpha}$ and L-selectin by ELISA, and fibronectin by radial immunodiffusion (RID). Results: BM stromal cells comprising reticular macrophages and fibroblasts were elevated in 53.3% of NHL cases at diagnosis, while BM fibronectin levels were decreased and BM $TNF{\alpha}$ and L-selectin were higher than in controls (p<0.05). In NHL cases, elevated values of BM $TNF{\alpha}$ and BM L-selectin were associated with signs of aggressive disease, including >1 extra nodal sites, detectable B symptoms, high grade, BM and CNS invasion, and a high International prognostic index (IPI) (p<0.05). Conclusion: BMM components, $TNF{\alpha}$, L-selectin and fibronectin, in NHL can be useful in evaluating disease activity, extent and response to treatment and as prognostic markers according to the IPI.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6457-6461
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• 2015

MicroRNAs directly and indirectly influence many biological processes such as apoptosis, cell maintenance, and immune responses, impacting on tumor genesis and metastasis. They modulate gene expression at the posttranscriptional level and are associated with progression of liver disease. Hepatocellular carcinoma (HCC) is a cancer which mostly occurs in males. There are many factors affect HCC development, for example, hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), co-infection, environmental factors including alcohol, aflatoxin consumption and host-related factors such as age, gender immune response, microRNA and single nucleotide polymorphisms (SNPs). Chronic infection with the hepatitis B virus is the major factor leading to HCC progression since it causes the liver injury. At present, there are many reports regarding the association of SNPs on miRNAs and the HCC progression. In this research, we investigated the role of miR-149 (rs2292832) and miR-101-1 (rs7536540) with HCC progression in Thai population. The study included 289 Thai subjects including 104 HCC patients, 90 patients with chronic hepatitis B virus infection (CHB) and 95 healthy control subjects. The allele and genotype of rs2292832 and rs7536540 polymorphisms were determined by TaqMan real-time PCR assay. Our results revealed no significant association between miR-149 (rs2292832) and miR-101-1 (rs7536540) and the risk of HCC in our Thai population. However, this research is the first study of miR-149 (rs2292832) and miR-101-1 (rs7536540) in HCC in Thai populations and the results need to be confirmed with a larger population.

• Korean Journal of Agricultural Science
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• v.46 no.2
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• pp.369-379
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• 2019

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with age, and amyloid beta ($A{\beta}$) is known to cause Alzheimer's disease. In the present study, we investigated the protective effects of Cirsium japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells. The cells treated with $A{\beta}_{25-35}$ showed a decrease in cell viability and an increase in reactive oxygen species (ROS) production compared with the non-treated cells. However, the cells treated with the C. japonicum var. maackii extract and its fractions increased the cell viability and inhibited the $A{\beta}$-induced ROS production. These results demonstrate the neuroprotective effects of C. japonicum var. maackii against $A{\beta}$. To further examine the protective mechanism, we measured inflammation and apoptosis related protein expressions. The cells treated with extract and fractions from C. japonicum var. maackii down-regulated inflammatory related proteins such as cyclooxygenase-2, interleukin $(IL)-1{\beta}$, and IL-6, and attenuated apoptosis related proteins including B-cell lymphoma-2 (Bcl-2) associated X protein/Bcl-2 ratio. In particular, the ethanol and ethylacetate fraction exhibited higher inhibitory effect against ROS production and apoptosis-related protein expressions among the extract and the other fractions. Therefore, this study demonstrated the protective effects of C. japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells through the regulation of oxidative stress, inflammation, and apoptosis, suggesting that it might have potential as a therapeutic for AD.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5945-5950
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• 2015

A 6-year retrospective cohort study was conducted among Thai hematologic malignancy (HM) patients receiving intensive chemotherapy. Of the 145 eligible patients receiving 893 chemotherapy sessions, 46.9% were female, median age was 52 years, and the most common HM diagnosis was diffuse large B-cell lymphoma (46.2%). Febrile neutropenia (FN) occurred in 14.9% of chemotherapy sessions with an incidence of 24.8 per 1,000 chemotherapy cycles per year. Independent factors associated with FN were receiving the first chemotherapy cycle [adjusted hazard ratio (aHR) 4.1], having hemoglobin ${\leq}100g/L$ (aHR 3.7) and platelet ${\leq}140,000/{\mu}L$ (aHR 2.7) on chemotherapy day and receiving acute myeloid leukemia regimens (aHR 20.8). Granulocyte colony stimulating factor was significantly associated with reduced rate of FN when given in those receiving CHOP regimen. With the median follow-up time of 16 months, the overall survival time was significantly longer in patients without FN than those with FN (61.7 vs. 20.8 months; p<0.001).

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.727-731
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• 2013

Background: The aim of this study was to analyze the clinicopathological and immunohistochemical features of primary central nervous system lymphoma (PCNSL) cases occurring in Indian patients and also study the utility of the crush smear preparation in intraoperative diagnosis. Materials and Methods: The immune status, clinical, radiological details, immunohistochemical profile, histopathological findings and cytological features in smear preparation of 32 cases of PCNSL were analyzed. Patients with systemic NHL and skull-base lymphomas were excluded. Results: The mean age of our patients was 52 years with a male: female ratio 1:1. A periventricular location was found in 62.5% of patients. None of our PCNSL cases were associated with AIDS. All cases except one were diffuse large B-cell lymphomas. Intraoperative diagnosis using crush smears allowed correct prediction in 93% of cases. Conclusions: Our study shows that PCNSL is seen predominantly in immunocompetent patients in India. The age of presentation is relatively young as compared to the West. Our study also stresses the utility of crush smear preparation in establishing an intraoperative diagnosis.

• Journal of Ginseng Research
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• v.39 no.2
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• pp.116-124
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• 2015

Background: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. Methods: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-${\kappa}B$). Results: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-${\kappa}B$. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. Conclusion: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-${\kappa}B$ pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.