Pakistan Journal of Biological Sciences

Concordance Between Immunohistochemistry (IHC) and Silver Situ Hybridization (SISH) in Endometrial Carcinoma Diagnosis: Using HER-2/neu

Human epidermal growth factor receptor 2 (Her-2/neu) has been demonstrated as biomarker in Endometrial Carcinoma (EC). This study was conducted to assess the concordance between Sudanese women between immunohistochemistry (IHC) and Silver Situ Hybridization (SISH) for EC diagnosis using HER-2/neu. This was a retrospective cross sectional study performed in the state of Khartoum, Sudan. This research used eighty-eight samples of embedded blocks of formalin fixed paraffin referred to the histopathology lab from 2007-2013. The technique of tissue microarray (TMA) was used in which paraffin blocks were prepared before IHC and SISH were subjected. In this analysis, 88 specimens were previously diagnosed as endometrial adenocarcinoma. The number of Her-2/new oncogene positive cases among Sudanese women by using IHC were (15.9%), however Her-2/neu amplification in EC were 11.5% by using SISH analysis and strong correlation between Her-2/neu IHC and Her-2/neu SISH is existed, since p-value is 0.,000. SISH is a reliable technique that can be used for detecting Her-2/neu oncoprotein and it has many advantages over other methods, also SISH can be used as an alternative to FISH technique.

Effect of Andaliman (Zanthoxylum acanthopodium DC.) Methanol Extract on Rat’s Kidney and Liver Histology Induced by Benzopyrene

The andaliman fruits have anti-inflammatory, antioxidant activity and a strong inhibition in antitumor activity. The purpose of this study was to analyze the effect of extract andaliman on rat's kidney and liver histology induced by benzopyrene. The rats model of cancer-induced benzopyrene. This research consists of 5 groups; K-: Control, K+: Cancer model rats, P1: A dose of 100 mg per b.wt. per day of andaliman, P2: A dose of 200 mg per b.wt. per day and P3: A dose of 400 mg kg-1 b.wt., per day for 30 days. On the 31st day, performed surgically on the subjects. There were significant differences in the value of narrowing of the renal tubules (p<0.001), kidneys cells necrosis (p<0.01), hydrophilic degeneration (p<0.001), parenchymatous degeneration (p<0.01) and necrosis (p<0.001) in the liver after given the extract andaliman. Andaliman methanol extract repairs the damage of the liver and kidney of rats induced by benzopyrene. Andaliman can be recommended as a drug to repair the necrosis in the liver and kidneys caused by cancer.

Suppression of Wnt Expression by Increasing PI3K in Rats Cervical Carcinoma by Andaliman (Zanthoxylum acanthopodium)

&lt;b&gt;Background and Objective:&lt;/b&gt; Cervical cancer is the leading cause of death for women in the world and Indonesia. This disease originates from a malignant tumour of squamous epithelial cells caused by infection with the Human Papilloma Virus (HPV). Antioxidants can reduce oxidative stress in and there are plants from Indonesia that have high antioxidants, namely andaliman (&lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt;). This study aimed to analyze the role of andaliman on PI3K and Wnt signalling in cervical cancer histology. &lt;b&gt;Materials and Methods:&lt;/b&gt; The study includes 5 treatments. The control group (K-), rats cancer model (K+), rats cancer model+the dose is 100 mg/b.wt. of ZAM (P&lt;sub&gt;1&lt;/sub&gt;), rats cancer model+the dose is 200 mg/b.wt. of ZAM (P&lt;sub&gt;2&lt;/sub&gt;) and rats cancer model+the dosage is 400 mg/b.wt. ZAM (P&lt;sub&gt;3&lt;/sub&gt;). On the 30th day after ZAM administration, the rats were dissected for the paraffin block and Wnt and PI3K immunohistochemical staining was prepared. &lt;b&gt;Results:&lt;/b&gt; There was a significant difference between all groups (p<0.001) in Wnt and PI3K expression. The real role of ZAM in cervical cancer tissue was seen at the highest ZAM dose (P&lt;sub&gt;3&lt;/sub&gt;). Irregular mucosal folds and stretched interstitial connective tissue in the K+ group can return to regularity and improve at the P&lt;sub&gt;3&lt;/sub&gt; dose. The administration of ZAM showed a significant difference in cervical tissue after benzopyrene injection. &lt;b&gt;Conclusion:&lt;/b&gt; Andaliman (&lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt;) extract increases PI3K expression through suppression of Wnt expression. It can be developed therapy molecularly to prevent cell growth into cancer.

Cytochrome c Expression by Andaliman (Zanthoxylum acanthopodium) on Cervical Cancer Histology

&lt;b&gt;Background and Objective:&lt;/b&gt; Andaliman is a wild plant in Indonesia and it has been used for centuries as traditional medicine. This study aimed to evaluate the effect of methanol extract of andaliman on apoptosis cancer cells via cytochrome c protein. &lt;b&gt;Materials and Methods:&lt;/b&gt; The rats are divided into 5 groups. K: Control, K&lt;sub&gt;+&lt;/sub&gt;: Cancer model rats, P&lt;sub&gt;1&lt;/sub&gt;: A dose of 100 mg/b.wt./day of andaliman, P&lt;sub&gt;2&lt;/sub&gt;: A dose of 200 mg/b.wt./day and P&lt;sub&gt;3&lt;/sub&gt;: A dose of 400 mg/kg/b.wt./day for 30 days. The rats were dissected, then the cervical tissue was prepared on paraffin blocks, given Immunohistochemistry staining with cytochrome c antibody. &lt;b&gt;Results:&lt;/b&gt; There was a significant difference in body and cervical weight (p<0.01). The histology also showed a significant difference between each treatment (p<0.01) in cytochrome c. The highest cytochrome c expression was at P&lt;sub&gt;2&lt;/sub&gt; and the lowest was at K&lt;sub&gt;-&lt;/sub&gt;. &lt;b&gt;Conclusion:&lt;/b&gt; Andaliman methanol extract can thus be developed into a cervical cancer drug candidate because it can reduce the positive index of cytochrome c in cervical histology.

Histological Alterations of Cervical Cancer Following Zanthoxylum acanthopodium DC Therapy in Relation to E7, pRb, EGFR and p16 Expression

&lt;b&gt;Background and Objective:&lt;/b&gt; Cervical cancer is the second most common cancer in Indonesia, where traditional herbal treatments like &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; (andaliman) are culturally used. Investigating protein biomarkers such as E7, pRb, EGFR and p16 can help assess the efficacy of these treatments. &lt;b&gt;Materials and Methods:&lt;/b&gt; There were 5 groups in this study: 2 control groups (C- and C+) and 3 treatment groups (each receiving one of three doses). Oral administration of andaliman was performed for 30 days in cancer model rats, after which the cervix was dissected, cervical tissue was taken and immunohistochemistry repair was performed. Statistical analysis was performed using the Kruskal-Wallis test with a p<0.05. &lt;b&gt;Results:&lt;/b&gt; As &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; DC dose rose, cervical tissue E7, EGFR and p16 expression decreased. However, greater doses of this plant increased cervical tissue pRb protein. Cervical cancer histology exhibited increased nuclear size, irregular cellular structure, atypical cell shape, higher nuclear-cytoplasmic ratio and various nuclear shape variants. This herb induced tissue to show well-organized non-hyperchromatic cells that resembled normal clusters. &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; DC improved cervical tissue and balanced cervical cancer biomarker proteins such E7, EGFR, pRB and p16.

PDGF-β and IL-18 Expressions on Carcinoma Cervical by Rhodomyrtus tomentosa

&lt;b&gt;Background and Objective:&lt;/b&gt; Cervical cancer, along with lung and breast cancer, is one of Indonesia's most aggressive gynaecological diseases. &lt;i&gt;Rhodomyrtus tomentosa&lt;/i&gt; has antioxidant and antiproliferative properties that could be developed into herbal medicines for molecular therapy. The IL-18 and PDGF-β are tumour-promoting agent proteins that may be therapeutic targets for a variety of cancers that were investigated in this study. &lt;b&gt;Materials and Methods:&lt;/b&gt; Rats were classified into five groups: Group C- is the control group, Group C+ is the cancer model group and Group RHO200 is the &lt;i&gt;Rhodomyrtus tomentosa&lt;/i&gt; 100 mg&lt;sup&gt;1&lt;/sup&gt; b.wt., rat group, Group RHO400 is the &lt;i&gt;Rhodomyrtus tomentosa&lt;/i&gt; 200 mg&lt;sup&gt;1&lt;/sup&gt; b.wt., rat group and Group RHO400 is the &lt;i&gt;Rhodomyrtus tomentosa&lt;/i&gt; 400 mg&lt;sup&gt;1&lt;/sup&gt; b.wt., rat group. The rats were dissected 30 days after receiving &lt;i&gt;Rhodomyrtus tomentosa&lt;/i&gt;. Immunohistochemistry is used to stain cervical tissues. &lt;b&gt;Results:&lt;/b&gt; The expression of IL-18 and PDGF-β was significantly different (p<0.01). The IL-18 and PDGF-β were most abundant at the lowest &lt;i&gt;Rhodomyrtus tomentosa&lt;/i&gt; doses (100-200 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt.), while they were least abundant at the 400 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt., doses. Histological analysis revealed that the highest dose of IL-18 and PDGF-β expression reduced abnormal tissue and the space between tumours, followed by several carcinoma cells that stopped growing. &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;Rhodomyrtus tomentosa&lt;/i&gt; can be used as a herbal therapy to reduce the expression of PDGF-β and IL-18 (two cancer marker agents).

Correlation of Myc Expression with Wee1 Expression by Zanthoxylum acanthopodium in Cervical Carcinoma Histology

&lt;b&gt;Background and Objective:&lt;/b&gt; Natural herbs and molecular therapy can be used to treat cervical cancer. The Myc and Wee1 control tumour cell fate and microenvironmental changes like angiogenesis activation and host immune response suppression. The study aims to know about the correlation of Myc and Wee1 expressions as a molecular therapy given by &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt;. &lt;b&gt;Materials and Methods:&lt;/b&gt; There are five rat groups: Group K&lt;sup&gt;&lt;/sup&gt; is the untreated group, Group K&lt;sup&gt;+&lt;/sup&gt; is the rats injected with benzopyrene, Group P&lt;sub&gt;1&lt;/sub&gt; is the administration of &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; 100 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt., Group P&lt;sub&gt;2&lt;/sub&gt; is the administration of &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; 200 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt. and Group P&lt;sub&gt;3&lt;/sub&gt; is the administration of &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; 400 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt. The rats are dissected 30 days after receiving &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt;. To stain the cervical tissues, immunohistochemistry is performed. &lt;b&gt;Results:&lt;/b&gt; &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; administration caused epithelial thickening and decreased Myc expression in previously uncontrolled carcinomas from untreated malignancies, which now slowed and stopped growing into the normal epithelium. Wee1 expression revealed that this herb could repair tissue by drastically reducing Wee1 expression at a dose of 100-400 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt. Similarly, at the highest dose, cervical carcinoma stops growing and the nucleus begins to form normally (p<0.01). &lt;b&gt;Conclusion:&lt;/b&gt; The higher Myc expression on andaliman administration in cervical carcinoma decreases Wee1 expression in cervical carcinoma so these two proteins have a strong and significant correlation. &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; can be administered at various dosages to lower the number of positive indexes of Myc and Wee1 expression in cervical carcinoma.

Chemical Composition, Antioxidant and Cytotoxic Activities of Hyptis suaveolens (L.) Poit. Essential Oil on Prostate and Cervical Cancers Cells

Hyptis suaveolens is an aromatic plant used in traditional medicine in Burkina Faso for management of various diseases including wounds and inflammatory diseases. Thus, the objective of this work was to characterize the chemical composition, antioxidant and cytotoxic activity of Essential Oil (EO) of H. suaveolens from Burkina Faso on cultured cancer cells. The chemical composition of EO was determined by GC/FID and GC/MS analysis and the antioxidant activity was evaluated through inhibition of DPPH radicals and ABTS +• radical cations. The cytotoxic activity in prostate cancer cells (LNCaP) and cervical cancer cells (HeLa) of EO was evaluated by MTT assay and effect on cells cycle by flow cytometry analysis. A total of 58 compounds were identified in the EO of H. suaveolens of which the major compounds identified are Sabinene 14.03%, β-Pinene 5.92%, Limonene 4.40%, Eucalyptol 12.78%, Trans-Oxide of Linalol 5.43%, β-Caryophyllene 11.27%, Germacrene-D 3.04% and Bicyclogermacrene 8.08%. The EO of H. suaveolens showed antioxidant activity and concentration dependent antiproliferative activities with G0/G1 arrest on LNCaP and HeLa cells. This work help to justify some uses of H. suaveolens in traditional medicine in Burkina Faso and also, presents a promising new application for the essential oil of H. suaveolens in prostate and cervical cancer research.

Human Papillomavirus, MicroRNA and their Role in Cervical Cancer Progression, Diagnosis and Treatment Response: A Comprehensive Review

Human Papillomavirus (HPV) is sexually transmitted and linked with vaginal, vulvar and cervix cancers in females, penile cancer in male, while anal and oropharyngeal cancer in both genders. Cervical cancer is ranked as third most identified cancer among females globally and is the fourth leading reason of cancer related mortality. The main aim of current study is to highlight the key role of miRNA in cervical cancer development, progression and their therapeutic responses. Current study entailed more than 50 PubMed cited articles related to miRNA role in cervical cancer. Studies have elucidated the role of miRNAs regulation in gene expression at post-transcriptional and translational level by targeting significant genes and therefore involved in cervical cancer. miRNAs control several cellular pathways involved in development of pre-malignant to metastatic stage and proliferation to malignancy. Current review elucidated and elaborated the key role of miRNA their application, treatment and therapeutic responses in cervical cancer.

Inhibition of Human Cervical Cancer Hela Cell Line by Meat-Derived Lactic Acid Bacteria of Lactobacillus plantarum IIA-1A5 and Lactobacillus acidophilus IIA-2B4

&lt;b&gt;Background and Objective:&lt;/b&gt; Two Indonesian lactic acid bacteria of&lt;i&gt; L. plantarum &lt;/i&gt;I IA-1A5 and &lt;i&gt;L. acidophilus &lt;/i&gt;IIA-2B4 were previously isolated from beef with some functional probiotic properties. Nevertheless, the possibility of these strains to have anticancer activity remains unknown. Current study aimed to evaluate the inhibitory properties of intra-and extracellular protein extracts of these two strains against cervical cancer HeLa cells. &lt;b&gt;Materials and Methods:&lt;/b&gt; The intracellular and extracellular proteins extract from &lt;i&gt;L. plantarum &lt;/i&gt;IIA-1A5 and &lt;i&gt;L. acidophilus &lt;/i&gt;IIA-2B4 were collected and designated as IP-LP, IP-LA, EP-LP and EP-LA, respectively. The effect of these extracts on the viability and morphology of HeLa cells were observed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and confocal microscopy, respectively. &lt;b&gt;Results:&lt;/b&gt; Both IP-LP and IP-LA inhibited HeLa cells in a concentration-dependent manner, with IC&lt;sub&gt;50&lt;/sub&gt; values of 352.62 and 120.97 μg mL&lt;sup&gt;1&lt;/sup&gt;, respectively. Meanwhile, the inhibition activity was also observed for EP-LP and EP-LA, &lt;i&gt;albeit&lt;/i&gt; very low. The inhibition effect was also confirmed by morphological analysis under confocal electron microscopy which showed the changes in the cell shapes and numbers. &lt;b&gt;Conclusion:&lt;/b&gt; Altogether, for the first time this study proposed that the probiotic isolated from Indonesian beef are promising to inhibit cancer cell lines.