Search results for: oesophageal carcinoma

Authors: Yiding Qu, Svetlana V. Komarova

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Chemokines acting through their cognate chemokine receptors guide the directional migration of the cell along the chemokine gradient. Several chemokine receptors were recently identified as non-signaling (decoy), based on their ability to bind the chemokine but produce no measurable signal in the cell. The function of these decoy receptors is not well understood. We examined the expression of a decoy receptor CCRL1 and a signaling receptor that binds to the same ligands, CCR7, in prostate cancer using publically available microarray data (www.oncomine.org). The expression of both CCRL1 and CCR7 increased in an approximately half of prostate carcinoma samples and the majority of metastatic cancer samples compared to normal prostate. Moreover, the expression of CCRL1 positively correlated with the expression of CCR7. These data suggest that CCR7 and CCRL1 can be used as clinical markers for the early detection of transformation from carcinoma to metastatic cancer. In addition, these data support our hypothesis that the non-signaling chemokine receptors actively stimulate cell migration.

Keywords: bioinformatics, cell migration, decoy receptor, meta-analysis, prostate cancer

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Authors: Ali Kassem, Aly Taha, Abeer Hassan, Kazuhide Higuchi

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Introduction: Trans arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) is usually followed by hepatic dysfunction that limits its efficacy. L-carnitine is recently studied as hepatoprotective agent. Our aim is to evaluate the L-carnitine effects against the deterioration of liver functions after TACE. Method: 53 patients with intermediate stage HCC were assigned into two groups; L-carnitine group (26 patients) who received L-carnitine 300 mg tablet twice daily from 2 weeks before to 12 weeks after TACE and control group (27 patients) without L-carnitine therapy. 28 of studied patients received branched chain amino acids granules. Results: There were significant differences between L-carnitine Vs. control group in mean serum albumin change from baseline to 1 week and 4 weeks after TACE (p < 0.05). L-Carnitine maintained Child-Pugh score at 1 week after TACE and exhibited improvement at 4 weeks after TACE (p < 0.01 Vs 1 week after TACE). Control group has significant Child-Pugh score deterioration from baseline to 1 week after TACE (p < 0.05) and 12 weeks after TACE (p < 0.05). There were significant differences between L-carnitine and control groups in mean Child-Pugh score change from baseline to 4 weeks (p < 0.05) and 12 weeks after TACE (p < 0.05). L-carnitine displayed improvement in (PT) from baseline to 1 week, 4 w (p < 0.05) and 12 weeks after TACE. PT in control group declined less than baseline along all follow up intervals. Total bilirubin in L-carnitine group decreased at 1 week post TACE while in control group, it significantly increased at 1 week (p = 0.01). ALT and C-reactive protein elevation were suppressed at 1 week after TACE in Lcarnitine group. The hepatoprotective effects of L-carnitine were enhanced by concomitant use of branched chain amino acids. Conclusion: L-carnitine and BCAA combination therapy offer a novel supportive strategy after TACE in HCC patients.

Keywords: hepatocellular carcinoma, L-carnitine, liver functions , trans-arterial embolization

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Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

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Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

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Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

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Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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Authors: Carolina L. Cerdeira, Julia V. F. Cortes, Maria E. V. Amarante, Gersika B. Santos

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Skin cancer is the most common cancer in several parts of the world; in a tropical country like Brazil, the situation isn’t different. The Brazilian population is exposed to high levels of solar radiation, increasing the risk of developing cutaneous carcinoma. Aimed at encouraging prevention measures and the early diagnosis of these tumors, a study was carried out that analyzed data on cutaneous melanomas, basal cell, and epidermoid carcinomas, using as primary data source the medical records of 161 patients registered in one pathology service, which performs skin biopsies in a city of Minas Gerais, Brazil. All patients diagnosed with skin cancer at this service from January 2015 to December 2019 were included. The incidence of skin carcinoma cases was correlated with the identification of histological type, sex, age group, and topographic location. Correlation between variables was verified by Fisher's exact test at a nominal significance level of 5%, with statistical analysis performed by R® software. A significant association was observed between age group and type of cancer (p=0.0085); age group and sex (0.0298); and type of cancer and body region affected (p < 0.01). Those 161 cases analyzed comprised 93 basal cell carcinomas, 66 epidermoid carcinomas, and only two cutaneous melanomas. In the group aged 19 to 30 years, the epidermoid form was most prevalent; from 31 to 45 and from 46 to 59 years, the basal cell prevailed; in 60-year-olds or over, both types had higher frequencies. Associating age group and sex, in groups aged 18 to 30 and 46 to 59 years, women were most affected. In the 31-to 45-year-old group, men predominated. There was a gender balance in the age group 60-year-olds or over. As for topography, there was a high prevalence in the head and neck, followed by upper limbs. Relating histological type and topography, there was a prevalence of basal cell and epidermoid carcinomas in the head and neck. In the chest, the basal cell form was most prevalent; in upper limbs, the epidermoid form prevailed. Cutaneous melanoma affected only the chest and upper limbs. About 82% of patients 60-year-olds or over had head and neck cancer; from 46 to 59 and 60-year-olds or over, the head and neck region and upper limbs were predominantly affected; the distribution was balanced in the 31-to 45-year-old group. In conclusion, basal cell carcinoma was predominant, whereas cutaneous melanoma was the rarest among the types analyzed. Patients 60-year-olds or over were most affected, showing gender balance. In young adults, there was a prevalence of the epidermoid form; in middle-aged patients, basal cell carcinoma was predominant; in the elderly, both forms presented with higher frequencies. There was a higher incidence of head and neck cancers, followed by malignancies affecting the upper limbs. The epidermoid type manifested significantly in the upper limbs. Body regions such as the thorax and lower limbs were less affected, which is justified by the lower exposure of these areas to incident solar radiation.

Keywords: basal cell carcinoma, cutaneous melanoma, skin cancer, squamous cell carcinoma, topographic location

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Authors: Susanne Fridsten, Kristina Hellman, Anders Sundin, Lennart Blomqvist

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Background: Patients diagnosed with locally advanced cervical carcinoma are treated with definitive concomitant chemo-radiotherapy. Treatment failure occurs in 30-50% of patients with very poor prognoses. The treatment is standardized with risk for both over-and undertreatment. Consequently, there is a great need for biomarkers able to predict therapy outcomes to allow for individualized treatment. Aim: To explore the role of T2- and diffusion-weighted magnetic resonance imaging (MRI) for early prediction of therapy outcome and the optimal time point for assessment. Methods: A pilot study including 15 patients with cervical carcinoma stage IIB-IIIB (FIGO 2009) undergoing definitive chemoradiotherapy. All patients underwent MRI four times, at baseline, 3 weeks, 5 weeks, and 12 weeks after treatment started. Tumour size, size change (∆size), visibility on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and change of ADC (∆ADC) at the different time points were recorded. Results: 7/15 patients relapsed during the study period, referred to as "poor prognosis", PP, and the remaining eight patients are referred to "good prognosis", GP. The tumor size was larger at all time points for PP than for GP. The ∆size between any of the four-time points was the same for PP and GP patients. The sensitivity and specificity to predict prognostic group depending on a remaining tumor on DWI were highest at 5 weeks and 83% (5/6) and 63% (5/8), respectively. The combination of tumor size at baseline and remaining tumor on DWI at 5 weeks in ROC analysis reached an area under the curve (AUC) of 0.83. After 12 weeks, no remaining tumor was seen on DWI among patients with GP, as opposed to 2/7 PP patients. Adding ADC to the tumor size measurements did not improve the predictive value at any time point. Conclusion: A large tumor at baseline MRI combined with a remaining tumor on DWI at 5 weeks predicted a poor prognosis.

Keywords: chemoradiotherapy, diffusion-weighted imaging, magnetic resonance imaging, uterine cervical carcinoma

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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Authors: Fangtian Fan, Zhaoguo Liu, Yin Lu

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Early recurrence (ER) (< 1 year) after liver resection is one of the most important factors that impacts the prognosis of patients with hepatocellular carcinoma (HCC). However, the molecular mechanisms and predictive indexes of ER after curative resection remain largely unknown. The present study aimed to exploit the role of EGFR signaling in EMT and early recurrence of HCC after curative resection and elucidate the molecular mechanisms. Our results showed that nuclear beta-catenin / PKM2 was a independent predictor of early recurrence after curative resection in EGFR-overexpressed HCC. Mechanistic investigation indicated that nuclear accumulation of beta-catenin and PKM2 induced by EGFR signal promoted HCC cell invasion and proliferation, which were required for early recurrence of HCC. These effects were mediated by PI3K/AKT and ERK pathways rather than the canonical Wnt signaling. In conclusions, EGFR signal induced-nuclear translocation of beta-catenin and PKM2 promotes HCC malignancy and indicates early recurrence after curative resection.

Keywords: beta-catenin, early recurrence, hepatocellular carcinoma, malignancy, PKM2

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Authors: Marin Kanarev, Delyan Stoyanov, Ivanna Popova, Nadezhda Petrova

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Thanks to increased survival rates in patients bearing oncological malignancies due to recent developments in anti-cancer therapies and diagnostic techniques, observation of clinical cases of metachronous cancers is more common and can provide more in-depth knowledge of their development and, as a result, help clinicians apply suitable therapy. This unusual case of three metachronous tumors presented the opportunity to follow their occurrence, progression, and treatment thoroughly. A 77-year-old male presented with carcinoma ventriculi of the pylorus region, which was surgically removed via upper subtotal stomach resection, a lateral antecolical gastro-enteroanastomosis, and a subsequent Braun anastomosis. An EOX chemotherapy regimen followed. A CT scan four months later showed no indication of recurrence or dissemination. The same scan, performed as a part of the follow-up plan two years later, showed an indication of neoplastic growth in the urinary bladder. After the patient had been directed to a urologist, the suspicion was confirmed, and the growth was histologically diagnosed as a carcinoma of the urinary bladder. An immunohistochemistry test showed an expression of PDL1 of less than 5%, which resulted in treatment with GemCis chemotherapy regimen that led to full remission. Two years and seven months after the first surgery, a CT scan showed again that the two carcinomas were gone. However, four months later, elevated tumor markers prompted a PET/CT scan, which showed data indicative of recurring neoplastic growth in the region of the stomach cardia. It was diagnosed as an adenocarcinoma infiltrating the esophagus. Preoperative chemotherapy with the ECF regimen was completed in four courses, and a CT scan showed no progression of the disease. In less than a month after therapy, the patient underwent laparotomy, debridement, gastrectomy, and a subsequent mechanical terminal-lateral esophago-jejunoanasthomosis. It was verified that the tumor originated from metastasis from the carcinoma ventriculi, which was located in the pylorus. In conclusion, this case report highlights the importance of patient follow-up and studying recurring neoplastic growth. Despite the absence of symptoms, clinicians should maintain a high level of suspicion when evaluating the patient data and choosing the most suitable therapy.

Keywords: carcinoma, follow-up, metachronous, neoplastic growth, recurrence

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Authors: Chi-Jung Chung, Chao-Hsiang Chang, Chiu-Shong Liu, Sheng-Wei Li, Mu-Chi Chung, Ting-Jie Wen, Hui-Ling Lee

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Cigarette smoke contains volatile organic compounds (VOCs), such as acrylamide, 1,3-butadiene, and benzene. This study aimed to explore the associations between the urinary levels of cotinine and VOC metabolites and the risk of urothelial carcinoma (UC). A hospital-based case–control study involving two groups matched on the basis of age ( ± 3 years) and gender was designed. UC was clinically diagnosed through urological examinations and pathologically verified. Smoking-related information was collected through questionnaires and face-to-face interviews with all study participants. Urine samples were collected for the analysis of the urinary levels of VOC metabolites, cotinine, and 8-hydroxydeoxygua- nosine (8-OHdG), which was selected as a proxy of oxidative stress. Multiple logistic regressions were applied to estimate the risk of UC. The urinary cotinine and 8-OHdG levels of the UC group were higher than those of the control group. The urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N- acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S- (4- hydroxy-2-buten-1-yl)-Lcysteine-3, trans, trans-muconic acid (t,t- MA), and S-phenylmercapturic acid (SPMA) increased as the urinary levels of cotinine increased. Relevant dose-response relationships between the risk of UC risk and the urinary levels of AAMA , t,t-MA, SPMA, and 8-OHdG were found after adjusting for potential risk factors. The UC risk of participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG were 3.5–6-fold higher than those of other participants. Increased urinary levels of VOC metabolites were associated with smoking-related UC risk. The development of UC should be explored in large-scale in vitro or in vivo studies with the repeated measurement of VOC metabolites.

Keywords: volatile organic compound, urothelial carcinoma, cotinine, 8-hydroxydeoxyguanosine

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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Non-alcoholic steatohepatitis (NASH) is a chronic liver disease, often associated with type II diabetes, which sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). NASH has become an important health problem worldwide, buttherapeutic agents for NASH have not yet been approved, and animal models with high clinical correlation are required. TheSTAM™ mouse shows the same pathological progression as human NASH patients and has been widely used for both drug efficacy and basic research, such as lipid profiling and gut microbiota research. In this study, we analyzed the RNA-seq data of STAM™mice at each pathological stage (steatosis, steatohepatitis, liver fibrosis, and HCC) and examined the clinical correlation at the genetic level. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin solution 2 days after birth and feeding with high fat dietafter 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16, and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80˚C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. The gene expression of the canonical pathways in NASH progression from steatosis to hepatocellular carcinoma were analyzed, such as immune system process, oxidation-reduction process, lipid metabolic process. Moreover, since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM™mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. These results indicated a clinical correlation of gene profiles in the STAM™mouse.

Keywords: steatosis, non-alcoholic steatohepatitis, fibrosis, hepatocellular carcinoma, RNA-seq

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Authors: Lin Feng, Ling-Ling E., Hong-Chen Liu

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The development of chemoresistance in patients represents a major challenge in cancer treatment. Lactate dehydrogenase‑A (LDHA) is one of the principle isoforms of LDH that is expressed in breast tissue, controlling the conversion of pyruvate to lactate and also playing a significant role in the metabolism of glucose. The aim of this study was to identify whether LDHA was involved in oral cancer cell resistance to Taxol and whether the downregulation of LDHA, as a result of cisplatin treatment, may overcome Taxol resistance in human oral squamous cells. The OECM‑1 oral epidermal carcinoma cell line was used, which has been widely used as a model of oral cancer in previous studies. The role of LDHA in Taxol and cisplatin resistance was investigated and the synergistic cytotoxicity of cisplatin and/or Taxol in oral squamous cells was analyzed. Cell viability was analyzed by MTT assay, LDHA expression was analyzed by western blot analysis and siRNA transfection was performed to knock down LDHA expression. The present study results showed that decreased levels of LDHA were responsible for the resistance of oral cancer cells to cisplatin (CDDP). CDDP treatments downregulated LDHA expression and lower levels of LDHA were detected in the CDDP‑resistant oral cancer cells compared with the CDDP‑sensitive cells. By contrast, the Taxol‑resistant cancer cells showed elevated LDHA expression levels. In addition, small interfering RNA‑knockdown of LDHA sensitized the cells to Taxol but desensitized them to CDDP treatment while exogenous expression of LDHA sensitized the cells to CDDP, but desensitized them to Taxol. The present study also revealed the synergistic cytotoxicity of CDDP and Taxol for killing oral cancer cells through the inhibition of LDHA. This study highlights LDHA as a novel therapeutic target for overcoming Taxol resistance in oral cancer patients using the combined treatments of Taxol and CDDP.

Keywords: cisplatin, Taxol, carcinoma, oral squamous cells

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Authors: Rubab Z. Kahlon, Ibtisam Butt, Isma Younis, Aamer G. Mufti

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Worldwide lung cancer 1.61 million cases were seen in both genders. Lung carcinoma is the major cause of both morbidity and mortality in the world. Purpose of the present study was to describe the spatio- temporal trends of lung cancer in both genders. A retrospective study was conducted. Total 1498 patients of lung carcinoma were examined. Only lung cancer patients from all over the Punjab were included in the present study. MS Excel 2010 was used for data tabulation and calculation while the Arc GIS version 9.3 was used for geographical representation of the data. 1498 cases of Lung cancer were found from 2008-2012. The number of male patients was 1236 and female was 262. Majority of the patients were from Lahore districts with 807 patients. Lung cancer was more prevalent in male as compared to female in our region. Increase in the prevalence of lung cancer was prominently seen in the most populated and industrial areas of the Punjab province. Time trend of five years showed fluctuation in the lung cancer incidence during the study period.

Keywords: districts, gender, lung cancer trends, Punjab province of Pakistan

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Authors: N. A. Kazemi Sefat, M. M. Mohammadi, J. Hadjati, S. Talebi, M. Ajami, H. Daneshvar

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Colorectal cancer metastases result in a significant number of cancer related deaths. Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (SB) is a short chain fatty acid, belongs to HDAC inhibitors which is released in the colonic lumen as a consequence of fiber fermentation. In this study, we are about to assess the effect of sodium butyrate on HCT116 human colorectal carcinoma cell line. The viability of cells was measured by microscopic morphologic study and MTT assay. After 48 hours, treatments more than 10 mM lead to cell injury in HCT116 by increasing cell granulation and decreasing cell adhesion (p>0.05). After 72 hours, treatments at 10 mM and more lead to significant cell injury (p<0.05). Our results may suggest that the gene expression which is contributed in cell proliferation and apoptosis has been changed under pressure of HDAC inhibition.

Keywords: colorectal cancer, sodium butyrate, cytotoxicity, MTT

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Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Marcin Kruszewski, Barbara Sochanowicz, Sylwia Męczyńska-Wielgosz, Maria Wojewódzka, Lucyna Kapka-Skrzypczak

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Metallic NPs are widely used in a number of applications in industry, science and medicine. Among metallic NPs foreseen to be widely used in medicine are gold nanoparticles (AuNPs) due to their low toxicity, and silver NPs (AgNPs) due to their strong antimicrobial activity. In this study, we compared an effect of AgNPs and gold NPs (AuNPs) on the formation of DNA damage and global DNA methylation and in A2780 and 4T1 cell lines, widely used models of human ovarian carcinoma and murine mammary carcinoma, respectively. The cells were treated with AgNPs coated with citrate (AgNPs(cit) or PEG (AgNPs(PEG), or AuNPs. A global DNA methylation was investigated with ELISA, whereas the formation of DNA damage was investigated by a comet +/- FPG. AgNPs decreased global DNA methylation and increased the formation of DNA lesions in both cell lines. The effect was dependent on the type of NPs used, it's coating, and cell line used. In conclusion, the epigenetic and genotoxic effects of NPs strongly depends on NP nature and cellular context. Epigenetic changes observed upon the action of AgNPs may play a crucial role in NPs-induced changes in protein expression.

Keywords: DNA damage, gold nanoparticles, methylation, silver nanoparticles

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Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy

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Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.

Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus

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Authors: Ralene Sim, Stefan Mueller, N. Gopalakrishna Iyer, Ngian Chye Tan, Khee Chee Soo, R. Shetty Mahalakshmi, Hiang Khoon Tan

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Background: Regional failure in nasopharyngeal carcinoma (NPC) is managed by salvage treatment in the form of neck dissection. Radical neck dissection (RND) is preferred over modified radical neck dissection (MRND) since it is traditionally believed to offer better long-term disease control. However, with the advent of more advanced imaging modalities like high-resolution Magnetic Resonance Imaging, Computed Tomography, and Positron Emission Tomography-CT scans, earlier detection is achieved. Additionally, concurrent chemotherapy also contributes to reduced tumour burden. Hence, there may be a lesser need for an RND and a greater role for MRND. With this retrospective study, the primary aim is to ascertain whether MRND, as opposed to RND, has similar outcomes and hence, whether there would be more grounds to offer a less aggressive procedure to achieve lower patient morbidity. Methods: This is a retrospective study of 66 NPC patients treated at Singapore General Hospital between 1994 to 2016 for histologically proven regional recurrence, of which 41 patients underwent RND and 25 who underwent MRND, based on surgeon preference. The type of ND performed, primary treatment mode, adjuvant treatment, and pattern of recurrence were reviewed. Overall survival (OS) was calculated using Kaplan-Meier estimate and compared. Results: Overall, the disease parameters such as nodal involvement and extranodal extension were comparable between the two groups. Comparing MRND and RND, the median (IQR) OS is 1.76 (0.58 to 3.49) and 2.41 (0.78 to 4.11) respectively. However, the p-value found is 0.5301 and hence not statistically significant. Conclusion: RND is more aggressive and has been associated with greater morbidity. Hence, with similar outcomes, MRND could be an alternative salvage procedure for regional failure in selected NPC patients, allowing similar salvage rates with lesser mortality and morbidity.

Keywords: nasopharyngeal carcinoma, neck dissection, modified neck dissection, radical neck dissection

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Authors: Baljit Singh Khehra, Amar Partap Singh Pharwaha

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Clusters of Microcalcifications (MCCs) are most frequent symptoms of Ductal Carcinoma in Situ (DCIS) recognized by mammography. Least-Square Support Vector Machine (LS-SVM) is a variant of the standard SVM. In the paper, LS-SVM is proposed as a classifier for classifying MCCs as benign or malignant based on relevant extracted features from enhanced mammogram. To establish the credibility of LS-SVM classifier for classifying MCCs, a comparative evaluation of the relative performance of LS-SVM classifier for different kernel functions is made. For comparative evaluation, confusion matrix and ROC analysis are used. Experiments are performed on data extracted from mammogram images of DDSM database. A total of 380 suspicious areas are collected, which contain 235 malignant and 145 benign samples, from mammogram images of DDSM database. A set of 50 features is calculated for each suspicious area. After this, an optimal subset of 23 most suitable features is selected from 50 features by Particle Swarm Optimization (PSO). The results of proposed study are quite promising.

Keywords: clusters of microcalcifications, ductal carcinoma in situ, least-square support vector machine, particle swarm optimization

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: Onmanee Prajuabjinda, Pakakrong Thondeeying, Jipisute Chunthorng-Orn, Bhanuz Dechayont, Arunporn Itharat

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A Thai medicinal preparation has been used for cancer treatment more than ten years ago in Khampramong Temple. Tectona grandis stem is one ingredient of this Thai medicinal remedy. The ethanolic extract of Tectona grandis stem showed the highest cytotoxic activities against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23) (IC50 = 3.92 and 7.78 µg/ml, respectively). It was isolated by bioassay-guided isolation method. Tectoquinone, a anthraquinone compound was isolated from this plant. This compound showed high specific cytotoxicity against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23)(IC50 =16.15 and 47.56 µg/ml or 72.67 and 214.00 µM, respectively). However, it showed less cytotoxic activity than the crude extract. In conclusion, tectoquinone as a main compound, is not the best cytotoxic compound from Tectona grandis, so there are more active cytotoxic compounds in this extract which should be isolated in the future. Moreover, tectoquinone displayed specific cytotoxicity against only human breast adenocarcinoma (MCF-7) which is a good criterion for cancer treatment.

Keywords: Tectona grandis, SRB assay, cytotoxicity, tectoquinone

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Authors: Vandana Singh, Subash Singh

Abstract:

Introduction: Oral squamous cell carcinoma is the most common malignant tumor of the oral cavity. Normally the death of cell and the growth are active processes and depend not only on external factors but also on the expression of genes like Bcl-2, which activate and inhibit apoptosis. The term Bcl-2 is an acronym for B-cell lymphoma/ leukemia -2 genes. Objectives: An attempt was made to evaluate Bcl-2 oncoprotein expression in patients with oral precancer and cancer and to assess possible correlation between Bcl-2 oncoprotein expression and clinicopathological features of oral precancer and cancer. Material and Methods: This is a selective prospective clinical and immunohistochemical study. Clinicopathological examination is correlated with immunohistochemical findings. The immunolocalization of Bcl-2 protein is performed using the labeled streptavidin biotin (LSAB) method. To visualize the reaction, 3, 3-diaminobenzidine (DAB) is used. Results: Bcl-2 expression was positive in 11 [36.66 %, low Bcl-2 expression 3 (10.00 %), moderate Bcl-2 expression 7 (23.33 %), and high Bcl-2 expression 1 (3.33 %)] oral cancer cases and in 14 [87.50 %, low expression 8 (50 %), moderate expression 6 (37.50 %)] precancer cases. Conclusion: On the basis of the results of our study we conclude that positive Bcl-2 expression may be an indicator of poor prognosis in oral cancer and precancer. Relevance: It has been reported that there is deregulation of Bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. It can be used for revealing progression of epithelial dysplasia to malignancy and as a prognostic marker in oral precancer and cancer.

Keywords: BcL-2, immunohistochemistry, oral cancer, oral precancer

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: Darya O. Prima, Elena V. Vorontsova, Yuri G. Slizhov, Andrey V. Zibarev

Abstract:

A broad family of carbocycle-fluorinated aza-heterocycles including 1,3-benzodiazoles (benzimidazoles), 1,2,3-benzotriazoles, 2,1,3-benzothia/selenadiazoles and 1,4-benzodiazines (quinoxalines) was synthesized in the unified way and assessed for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma, a kind of oral cancer) cells. The diazoles, triazoles and selenadiazoles revealed low medium inhibitory concentrations IC50 = 2.2-26.4 µМ and induced the cells’ apoptosis at low concentrations C = 1-25 µМ. For selenadiazoles, cell death dynamics was observed already in the first hours after the treatment. Replacement of one atom F by group Me2N in some cases enlarged apoptotic activity of the compounds towards the Hep2 cells. In contrast, the archetypal (i.e. non-fluorinated) 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole were low toxic (IC50 > 100 µM) and induced apoptosis only at high concentrations. The chlorinated congeners of the heterocycles under discussion were highly toxic towards the Hep2 cells but revealed insignificant ability to induce their apoptosis. Overall, the findings above suggest that fluorinated 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole derivatives can be considered as potential anticancer drugs. For the laryngeal epidermoid carcinoma (for which, according to available statistics, the five-year survival rate remained ~50% during the past 30 years), it is especially important since surgical treatment is seriously complicated here thus encouraging medicament one.

Keywords: Apoptosis, aza-heterocycles, cytotoxicity, fluorinated, Hep2 cells, synthesis

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Authors: M. Pourshirazi, M. Esmaelifar, A. Aliahmadi, F. Yazdian, A. S. Hatamian Zarami, S. J. Ashrafi

Abstract:

Medicinal fungi are the new potential source of drugs to improve the treatment of diseases with association to oxidative agents such as cancers. Monascus purpureus contains functional components potentially effective in improving human health. In the present work, ethanolic extract of Monascus purpureus (EEM) was evaluated for health improving potential mainly focusing on antioxidant and anticancer activities. Ferric ion reducing power (FRAP), scavenging of DPPH radicals and determining viability of breast carcinoma MCF-7 and cervical carcinoma HeLa cells with MTT assay were evaluated. Our data showed a significant antioxidant activity of EEM with 142.45 µg/ml inhibition concentration of 50% DPPH radicals and 2112.33 µg eq.Fe2+/mg extract of FRAP assay. These results might be caused by antioxidant components such as pigments and phenolic compounds. Further, the results demonstrated that EEM caused significant reduction in the viability of MCF-7 with IC50 of 7 µg/ml but not have good effect against viability of HeLa cells. Accordingly, Monascus purpureus is presented as a strong potential of breast cancer treatment. In further study, the mechanistic studies are needed to determine the mechanisms of anticancer activity of EEM.

Keywords: Monascus purpureus, antioxidant, cancer, ethanolic extract

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Authors: Maha Soltan, Amal Z. Hassan, Howaida I. Abd-Alla, Atef G. Hanna

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Two naturally known cardenolides; acovenoside A and acobioside A were isolated from the Egyptian cultivar; Acokanthera spectabilis leaves. It is an ornamental and poisonous plant that has been traditionally claimed for their medicinal properties against infectious microbes, killing worms and curing some inflammations at little amounts. We examined the growth inhibition effects of both cardenolides against four types of human cancer cell lines using Sulphorhodamine B assay. In addition, the clonogenic assay was also performed for testing the growth inhibiting power of the isolated compounds. An in vitro mechanistic investigation was further accomplished against hepatocellular carcinoma HepG2 cell line. Microscopic examination, colorimetric ELISA and flow cytometry techniques were our tools of proving at least part of the anticancer pathway of the tested compounds. Both compounds were able to inhibit the growth of 4 human cancer cell lines at less than 100 nM. In addition, they were able to activate the executioner Caspase-3 and apoptosis was then induced as a consequence of cell growth arrest at G2/M. An attention must be payed to those bioactive agents particularly when giving their activity against cancer cells at considerable small values while presenting safe therapeutic margins as indicated by literature.

Keywords: anticancer, cardenolides, Caspase-3, apoptosis

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Authors: Laila Seada, Hanan Oreiby, Fawaz Al Rashid, Ashraf Negm

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Background and Objective: In most areas of the world, the incidence of thyroid cancer has been increasing over the last decade, mostly due to a combination of early detection of the neoplasm resulting from sensitive procedures and increased population exposure to radiation and unrecognized carcinogens. Methods: Cases of thyroid cancer have been retrieved from the cancer registry at King Khalid Hospital during the period from August 2012 to April 2016. Age, gender and histopathologic types have been recorded. Results: Thyroid carcinoma ranked as the second most common malignancy in females (25%) after breast cancer (31%). It constituted 20.8% of all newly diagnosed cancer cases. As for males, it ranked the 4^th type of malignancy after gastrointestinal cancer, lymphomas and soft tissue sarcomas. Mean age for females and males was 38.7 +/- 13.2 and 60.25 +/- 11.5 years, respectively, and the difference between the two groups was statistically significant (p value = 0.0001). Fifty-five (82%) were papillary carcinomas including 10 follicular variant of papillary (FVPC), and eight papillary micro carcinomas (PMC) and two tall cell/oncocytic variants. Follicular carcinomas constituted two (3.1%), while two (3.1%) were anaplastic, and two (3.1%) were medullary. Conclusion: Thyroid cancer incidence in Hail is ranking as the 2^nd most common female malignancy similar to other regions in the Kingdom. However, this high incidence contrasts with much lower rates worldwide.

Keywords: thyroid, hail, papillary, microcarcinoma

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Authors: Di Luo, Maria Buchberger, Anja Pickhard

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Objectives: The purpose of this study was to assess and compare the diagnostic accuracy of four common morphological approaches, including sonography, computed tomography (CT), positron emission tomography/computed tomography (PET/CT), and magnetic resonance imaging (MRI) for the evaluation of cervical lymph node metastases in head and neck squamous cell carcinoma (HNSCC) patients. Material and Methods: Included in this retrospective study were 26 patients diagnosed with HNSCC between 2010 and 2011 who all underwent sonography, CT, PET/CT, and MRI imaging before neck dissection. Morphological data were compared to the corresponding histopathological results. Statistical analysis was performed with SPSS statistic software (version 26.0), calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for detection of cervical lymph node metastases. Results: The 5-year survival rate of the patient collective was 55.5%.Risk factors for survival included initial primary tumor stage, initial lymph node stage, initial metastasis status, and therapeutic approaches. Cox regression showed initial metastasis status(HR 8.671, 95%CI 1.316-57.123, p=0.025) and therapeutic approaches(HR 6.699, 95%CI 1.746-25.700, p=0.006)to be independent predictive risk factors for survival. Sensitivity was highest for MRI (96% compared to 85% for sonography and 89% for CT and PET/CT). Specificity was comparable with 95 % for CT and 98 % for sonography and PET/CT, but only 68% for MRI. While the MRI showed the least PPV (34%) compared to all other methods (85% for sonography,75% for CT, and 86% for PET/CT), the NPV was comparable in all methods(98-99%). The overall accuracy of cervical lymph node metastases detection was comparable for sonography, CT, and PET/CT with 96%,97%,94%, respectively, while MRI had only 72% accuracy. Conclusion: Since the initial status of metastasis is an independent predictive risk factor for patients’ survival, efficient detection is crucial to plan adequate therapeutic approaches. Sonography, CT, and PET/CT have better diagnostic accuracy than MRI for the evaluation of cervical lymph node metastases in HNSCC patients.

Keywords: cervical lymph node metastases, diagnostic accuracy, head and neck squamous carcinoma, risk factors, survival

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Authors: Pelin Balcik Ercin

Abstract:

Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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Authors: Soodabeh Shahid Sales, Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Kazem Anvari, Mohammad Sadegh Khorrami, Saeideh Ahmadi Simab, Ali Moradi, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A. Ferns, Amir Avan

Abstract:

Background Esophageal cancer has been reported as the eighth most common cancer universal and the seventh cause of cancer-related death in men .recent studies have revealed that cytochrome P450, family 1, subfamily B, polypeptide 1, which plays a role in metabolizing xenobiotics, is associated with different cancers. Therefore in the present study, we investigated the impact of CYP1B1-rs1056836 on esophagus squamous cell carcinoma (ESCC) patients. Method: 317 subjects, with and without ESCC were recruited. DNA was extracted and genotyped via Real-time PCR-Based Taq Man. Kaplan Meier curves were utilized to assess overall and progression-free survival. To evaluate the relationship between patients clinicopathological data, genotypic frequencies, disease prognosis, and patients survival, Pearson chi-square and t-test were used. Logistic regression was utilized to assess the association between the risk of ESCC and genotypes. Results: the genotypic frequency for GG, GC, and CC are respectively 58.6% , 29.8%, 11.5% in the healthy group and 51.8%, 36.14% and 12% in ESCC group. With respect to the recessive genetic inheritance model, an association between the GG genotype and stage of ESCC were found. Also, statistically significant results were not found for this variation and risk of ESCC. Patients with GG genotype had a decreased risk of nodal metastasis in comparison with patients with CC/CG genotype, although this link was not statistically significant. Conclusion: Our findings illustrated the correlation of CYP1B1-rs1056836 as a potential biomarker for ESCC patients, supporting further studies in larger populations in different ethnic groups. Moreover, further investigations are warranted to evaluate the association of emerging marker with dietary intake and lifestyle.

Keywords: Cytochrome P450, esophagus squamous cell carcinoma, dietary intake, lifestyle

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