Search results for: colorectal carcinoma

Authors: Salma Mirza, Syeda Asma Naqvi, Khalid Mohammed Khan, M. Iqbal Choudhary

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In this study twenty-five (25) newly synthesized compounds substituted aryl thiazoles (SAT) 1-25 were synthesized, and in vitro cytotoxicity of these compounds was evaluated against four cancer cell lines namely, MCF-7 (ER+ve breast), MDA-MB-231 (ER-ve breast), HCT116 (colorectal), and, HeLa (cervical) and compared with the standard anticancer drug doxorubicin with IC50 value of 1.56 ± 0.05 μM. Among them, compounds 1, 4-8 and 19 were found to be active against all four cell lines. Compound 20 was found to be selectively active against MCF7 cells with IC50 value of 40.21 ± 4.15 µM, whereas compound 19 was active against only MCF7 and HeLa cells with IC50 values of 46.72 ± 1.8 and 19.86 ± 0.11 μM, respectively. These results suggest that aryl thiazoles 1 and 4 deserve to be investigated further in vivo as anti-cancer agents.

Keywords: anticancer agents, breast cancer cell lines (MCF7, MDA-MB-231), colorectal cancer cell line (HCT-116), cervical cancer cell line (HeLa), Thiazole derivatives

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Authors: Naya Masood, Russell Hodgson, Mark Tacey

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Purpose: Patients with acute diverticulitis (AD) have an increased risk of underlying colorectal cancer (CRC); however, those with uncomplicated AD may have the same underlying population risk. This study informs on an Australian AD population who were not routinely offered colonoscopic follow-up. Methods: A 2-year (July 2016 – June 2018) retrospective study of patients admitted with CT-confirmed acute diverticulitis was conducted. CT findings were categorised as ‘complicated’ and ‘uncomplicated’ and were correlated with the detection of cancer in subsequent colonoscopy or follow-up. Results: 67.7% (n=292) of 431 patients were seen to have had complicated AD on an abdominopelvic CT scan. Patients were complicated most commonly due to bowel wall thickening reported on CT (90.4%), perforation (20.2%), or an abscess (12%). Follow-up colonoscopic evaluation was conducted in 52.9% (n=228) of total cases of AD, out of which 156 suffered complicated AD and the rest uncomplicated. None of the uncomplicated AD patients in our cohort were found to have CRC. Of those with complicated AD, six were found to have CRC. Conclusion: The only CRC diagnoses were made in patients with complicated AD. Despite available evidence, a significant proportion of uncomplicated AD patients were still undergoing colonoscopy. There is scope to further safely decrease the number of colonoscopies performed in AD patients.

Keywords: acute diverticulitis, colonoscopy, colorectal cancer, advanced adenoma, complicated diverticulitis

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Authors: Hongmeng Su, Luyu Zhao, Yanyan Qian, Hong Fan

Abstract:

Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that endanger human health seriously. RNA methylation, especially N6-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C), a crucial epigenetic transcriptional regulatory mechanism, plays an important role in tumorigenesis, progression and prognosis. This research aims to systematically evaluate the prognostic value of m⁶A and m⁵C modulators in HCC patients. Methods: Twenty-four modulators of m⁶A and m⁵C were candidates to analyze their expression level and their contribution to predict the prognosis of HCC. Consensus clustering analysis was applied to classify HCC patients. Cox and LASSO regression were used to construct the risk model. According to the risk score, HCC patients were divided into high-risk and low/medium-risk groups. The clinical pathology factors of HCC patients were analyzed by univariate and multivariate Cox regression analysis. Results: The HCC patients were classified into 2 clusters with significant differences in overall survival and clinical characteristics. Nine-gene risk model was constructed including METTL3, VIRMA, YTHDF1, YTHDF2, NOP2, NSUN4, NSUN5, DNMT3A and ALYREF. It was indicated that the risk score could serve as an independent prognostic factor for patients with HCC. Conclusion: This study constructed a Nine-gene risk model by modulators of m⁶A and m⁵C and investigated its effect on the clinical prognosis of HCC. This model may provide important consideration for the therapeutic strategy and prognosis evaluation analysis of patients with HCC.

Keywords: hepatocellular carcinoma, m⁶A, m⁵C, prognosis, RNA methylation

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Authors: Sonia A. Stoica, Lexi Frankel, Amalia Ardeljan, Selena Rashid, Ali Yasback, Omar Rashid

Abstract:

Introduction Enterococcus is a vast genus of lactic acid bacteria, gram-positivecocci species. They are common commensal organisms in the intestines of humans: E. faecalis (90–95%) and E. faecium (5–10%). Rare groups of infections can occur with other species, including E. casseliflavus, E. gallinarum, and E. raffinosus. The most common infections caused by Enterococcus include urinary tract infections, biliary tract infections, subacute endocarditis, diverticulitis, meningitis, septicemia, and spontaneous bacterial peritonitis. The treatment for sensitive strains of these bacteria includes ampicillin, penicillin, cephalosporins, or vancomycin, while the treatment for resistant strains includes daptomycin, linezolid, tygecycline, or streptogramine. Enterococcus faecalis CECT7121 is an encouraging nominee for being considered as a probiotic strain. E. faecalis CECT7121 enhances and skews the profile of cytokines to the Th1 phenotype in situations such as vaccination, anti-tumoral immunity, and allergic reactions. It also enhances the secretion of high levels of IL-12, IL-6, TNF alpha, and IL-10. Cytokines have been previously associated with the development of cancer. The intention of this study was to therefore evaluate the correlation between Enterococcus infections and incidence of bone carcinoma. Methods A retrospective cohort study (2010-2019) was conducted through a Health Insurance Portability and Accountability Act (HIPAA) compliant national database and conducted using International Classification of Disease (ICD) 9th and 10th codes for bone carcinoma diagnosis in a previously Enterococcus infected population. Patients were matched for age range and Charlson Comorbidity Index (CCI). Access to the database was granted by Holy Cross Health for academic research. Chi-squared test was used to assess statistical significance. Results A total number of 17,056 patients was obtained in Enterococcus infected group as well as in the control population (matched by Age range and CCI score). Subsequent bone carcinoma development was seen at a rate of 1.07% (184) in the Enterococcal infectious group and 3.42% (584) in the control group, respectively. The difference was statistically significant by p= 2.2x10-¹⁶, Odds Ratio = 0.355 (95% CI 0.311 - 0.404) Treatment for enterococcus infection was analyzed and controlled for in both enterococcus infected and noninfected populations. 78 out of 6,624 (1.17%) patients with a prior enterococcus infection and treated with antibiotics were compared to 202 out of 6,624 (3.04%) patients with no history of enterococcus infection (control) and received antibiotic treatment. Both populations subsequently developed bone carcinoma. Results remained statistically significant (p<2.2x10-), Odds Ratio=0.456 (95% CI 0.396-0.525). Conclusion This study shows a statistically significant correlation between Enterococcus infection and a decreased incidence of bone carcinoma. The immunologic response of the organism to Enterococcus infection may exert a protecting mechanism from developing bone carcinoma. Further exploration is needed to identify the potential mechanism of Enterococcus in reducing bone carcinoma incidence.

Keywords: anti-tumoral immunity, bone carcinoma, enterococcus, immunologic response

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Authors: Vinai K. Singh

Abstract:

In Neural Network-based Learning techniques, there are several models of Convolutional Networks. Whenever the methods are deployed with large datasets, only then can their applicability and appropriateness be determined. Clinical and pathological pictures of lobular carcinoma are thought to exhibit a large number of random formations and textures. Working with such pictures is a difficult problem in machine learning. Focusing on wet laboratories and following the outcomes, numerous studies have been published with fresh commentaries in the investigation. In this research, we provide a framework that can operate effectively on raw photos of various resolutions while easing the issues caused by the existence of patterns and texturing. The suggested approach produces very good findings that may be used to make decisions in the diagnosis of cancer.

Keywords: lobular carcinoma, convolutional neural networks (CNN), deep learning, histopathological imagery scans

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Authors: Dalia M. Abouelfadl, Noha N. Yassen, Marwa E. Shabana

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Background: The evolution of immune therapy motivated many to study the relation between immune response and progression of cancer. Little is known about expression of PD-L1 (a newly evolving immunotherapeutic drug) in papillary thyroid carcinoma (PTC) arising de-novo and PTC arising on top of autoimmune thyroiditis (Hashimoto's (HT) and lymphocytic thyroiditis (LT)). The aim of this work is to study the alteration of expression of PD-L1 in PTCs arising from de-novo or on top of HT OR LT using immunohistochemistry and image analyser system. Method: 100 paraffin blocks for PTC cases were collected retrospectively for staining using PD-L1 rabbit monoclonal antibody (BIOCARE-ACI 3171 A, C). The antibody expression is measured digitally using Image Analyzer Leica Qwin 3000, and the membranous and cytoplasmic expression of PD-L1 in tumor cells was considered positive. The results were correlated with tumor grade, size, and LN status. Results: The study samples consisted of 41 cases of PTC arising De novo, 36 cases on top of HT, and 23 on top of LT. Expression of PD-L1 was highest among the PTC-HL group (25 case-69%) followed by PTC-TL group (14 case-60.8%) then de-novo PTC (19 case-46%) with P Value < 0.05. PD-L1 expression correlated with nodal metastasis and was not relevant to tumor size or grade. Conclusion: The severity of the immune response in tumor microenvironment directly influences PTC prognosis. The anti PD-L1 Ab can be a very successful therapeutic agent for PTC arising on top of HT.

Keywords: carcinoma, Hashimoto's, lymphocytic, papillary, PD-L1, thyroiditis

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Authors: Timmis W., Simms M., Thomas C.

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This case discusses the management of two floors of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk and second primary cancer development.

Keywords: alcohol dependence, biopsy, oral carcinoma, tobacco

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Authors: Yaya Gao, Jifeng Liu, Yafeng Liu

Abstract:

Objectives: This study aimed to improve clinicians' understanding and diagnosis of the Mammary analogue secretory carcinoma of the salivary gland（MASC）. Methods: The clinical features of a MASC patient who was admitted to WestChina Hospital of Sichuan University in July 2020 were reviewed and analyzed. A 49-year-old woman with left upper neck pain for three months was admitted to the hospital. She underwent adenoma resection of the left submandibular gland 14 years ago and mucoepidermoid carcinoma resection surgery five years ago. Three months before admission, the patient developed pain in the left mandibular angle after "fatigue" and gradually developed radiation pain in the left ear, which could be relieved after rest. A mass of 1cm could be touched at the mandibular, with tenderness, poor mobility, and hard texture. No swelling, heat, pain, rupture, or pus was found on the surrounding skin. Color doppler ultrasonography of the salivary gland indicated a weak echo mass of 23*14*17mm in the left parotid gland. Results: Surgical excision was completed. Immunohistochemistry of the tumor samples after operation showed that P63（a few，+）, CK7（+）, S100（+）, DOG1（-）, Ki67（MIB-1）（+，5%），pan-TRK（+）, PAS(+) . ETV-6 gene translocation was detected in FISH in postoperative pathology, which indicated MASC. After this diagnosis, the patient sent the postoperative specimen of the second submandibular tumor to our hospital for consultation. The morphology of the two was similar. FISH detected ETV-6 gene translocation, so the second pathological diagnosis was revised to MASC. Conclusion: MASC of the salivary gland is a rare salivary gland tumor whose diagnosis depends on the result of the ETV6-NTRK3 fusion gene.

Keywords: mammary analogue secretory carcinoma, ETV6-NTRK3, salivary gland, misdiagnosed

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Authors: Imeobong Joseph Inyang, Aniekan-Augusta Okon Eyo, Abel William Essien

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Hepatitis B virus (HBV) is one of the known human carcinogens. The presence of HBsAg in liver tissues indicates active viral replication. More than 85% of Hepatocellular Carcinoma (HCC) cases occur in countries with increased rates of chronic HBV infection. An evaluation study to determine the relationship between positivity for HBsAg and development of HCC and its distribution between age and gender of subjects was done. Shikata Orcein and Haematoxylin and Eosin (H&E) staining techniques were performed on liver sections. A total of 50 liver tissue specimens comprising 38 biopsy and 12 post-mortem specimens were processed. Thirty-five of the 50 specimens were positive for HBsAg with Orcein stain whereas only 16 were positive with H&E stain, and these were also positive with Orcein stain, giving an HBsAg prevalence of 70.0% (35/50). The prevalence of HCC in the study was 56.0% (28/50), of which 21 (75.0%) cases were positive for HBsAg, 18 (64.3%) were males while 10 (35.7%) were females distributed within the age range of 20-70 years. The highest number of HBsAg positive HCC cases, 7/21 (33.3%) occurred in the age group 40-49 years. There was no relationship in the pattern of distribution of HCC between age and gender using the Pearson correlation coefficient (r = 0.0474; P < 0.05). HBV infection predisposed to HCC. Orcein technique was more specific and is therefore recommended for screening of liver tissues where facilities for immunohistochemistry are inaccessible.

Keywords: Hepatitis B. surface antigen, hepatocellular carcinoma, orcein, pathology

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Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

Abstract:

In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul

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Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.

Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase

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Authors: Mohamed Abdel-Hamid, Olfat Gamil Shaker, Doha El-Sayed Ellakwa, Eman Fathy Abdel-Maksoud

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Introduction: Despite advances in the knowledge of the molecular virology of hepatitis C virus (HCV), the mechanisms of hepatocellular injury in HCV infection are not completely understood. Hepatitis C viral infection (HCV) influences the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. Aim of this study: was to examine whether BCL-2 gene polymorphism at codon 43 (+127G/A or Ala43Thr) has an impact on development of hepatocellular carcinoma caused by chronic hepatitis C Egyptian patients. Subjects and Methods: The study included three groups; group 1: composing of 30 patients with hepatocellular carcinoma (HCC), group 2 composing of 30 patients with HCV, group 3 composing of 30 healthy subjects matching the same age and socioeconomic status were taken as a control group. Gene polymorphism of BCL2 (Ala43Thr) were evaluated by PCR-RFLP technique and measured for all patients and controls. Results: The summed 43Thr genotype was more frequent and statistically significant in HCC patients as compared to control group. This genotype of BCL2 gene may inhibit the programmed cell death which leads to disturbance in tissue and cells homeostasis and reduction in immune regulation. This result leads to viral replication and HCV persistence. Moreover, virus produces variety of mechanisms to block genes participated in apoptosis. This mechanism proves that HCV patients who have 43Thr genotype are more susceptible to HCC. Conclusion: The data suggest for the first time that the BCL2 polymorphism is associated with the susceptibility to HCC in Egyptian populations and might be used as molecular markers for evaluating HCC risk. This study clearly demonstrated that Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.

Keywords: BCL2 gene, Hepatitis C Virus, Hepatocellular carcinoma, sensitivity, specificity, apoptosis

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Authors: N. J. Nawarathna, N. R. Kmarasinghe, D. Chandrasekara, B. M. R. S. Balasooriya, R. A. A. Shaminda, R. J. K. Senevirathne

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Introduction: Thyroid malignancy associated with hyperthyroidism is considered rare. Retrospective studies have shown the incidence of thyroid malignancy in hyperthyroid patients to be low (0.7-8.5%). To assess the clinical relevance of this association, thyroid status in a cohort of patients with thyroid malignancy were analyzed. Method: Thyroid malignancies diagnosed histologically in 56 patients, over a 18 month period beginning from April 2013, in a single surgical unit at Teaching Hospital Kandy were included. Preoperative patient details and progression of thyroid status were asessed with Thyroid Stimulating Hormone, free Thyroxin and free Triiodothyronine levels. Results: Amongst 56 patients Papillary carcinoma was diagnosed in 44(78.6%), follicular carcinomas in 7(12.5%) and 5(8.9%) with medullary and anaplastic carcinomas. 12(21.4%) were males and 44(78.6%) were females. 20(35.7%) were less than 40years, 29(51.8%) were between 40 to 59years and 7(12.5%) were above 59years. Cross tabulation of Type of carcinoma with Gender revealed likelihood ratio of 6.908, Significance p = 0.032. Biochemically 12(21.4%) were hyperthyroid. Out of them 5(41.7%) had primary hyperthyroidism and 7(58.3%) had secondary hyperthyroidism. Mean age of euthyroid patients was 43.77years (SD 10.574) and hyperthyroid patients was 53.25years(SD 16.057). Independent Samples Test t is -2.446, two tailed significance p =0.018. When cross tabulate thyroid status with Age group Likelihood Ratio was 9.640, Significance p = 0.008. Conclusion: Papillary carcinoma is seen more among females. Among the patients with thyroid carcinomas, those with biochemically proven hyperthyroidism were more among the older age group than those who were euthyroid. Hence careful evaluation of elderly hyperthyroid patients to select the most suitable therapeutic approach is justified.

Keywords: age, hyperthyroidism, thyroid malignancy, thyroid status

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Authors: Shangqing Song, Bin Xu, Yajun Cheng, Zhong Wang

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miRNAs derived from exosomes exist in a body fluid such as urine were regarded as potential biomarkers for various human cancers diagnosis and prognosis, as mature miRNAs can be steadily preserved by exosomes. However, its potential value in clear cell renal cell carcinoma (ccRCC) diagnosis and prognosis remains unclear. In the present study, differentially expressed miRNAs from urinal exosomes were identified by next-generation sequencing (NGS) technology. The 16 differentially expressed miRNAs were identified between ccRCC patients and healthy donors. To explore the specific diagnosis biomarker of ccRCC, we validated these urinary exosomes from 70 early-stage renal cancer patients, 30 healthy people and other urinary system cancers, including 30 early-stage prostate cancer patients and 30 early-stage bladder cancer patients by qRT-PCR. The results showed that urinary exosome miR-30c-5p could be stably amplified and meanwhile the expression of miR-30c-5p has no significant difference between other urinary system cancers and healthy control, however, expression level of miR-30c-5p in urinary exosomal of ccRCC patients was lower than healthy people and receiver operation characterization (ROC) curve showed that the area under the curve (AUC) values was 0.8192 (95% confidence interval was 0.7388-0.8996, P= 0.0000). In addition, up-regulating miR-30c-5p expression could inhibit renal cell carcinoma cells growth. Lastly, HSP5A was found as a direct target gene of miR-30c-5p. HSP5A depletion reversed the promoting effect of ccRCC growth casued by miR-30c-5p inhibitor, respectively. In conclusion, this study demonstrated that urinary exosomal miR-30c-5p is readily accessible as diagnosis biomarker of early-stage ccRCC, and miR-30c-5p might modulate the expression of HSPA5, which correlated with the progression of ccRCC.

Keywords: clear cell renal cell carcinoma, exosome, HSP5A, miR-30c-5p

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Aliaa M. Issa, Mahmoud N. ElRouby, Sahar A. S. Ahmad, Mahmoud M. El-Merzabani

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Sider honey is a type of honey produced by bees feeding on the nectar of Sider tree, Ziziphus spina-christi (L) Desf . Honey is an effective agent for preventing, inhibiting and treating the growth of human and animal cancer cell lines in vitro and in vivo. The aim of the present study was to evaluate the impact of different dilutions from crude Sider honey and different duration times of exposure on the growth of six tumor cell lines (human cervical cancer cell line, HeLa; human hepatocellular carcinoma cell line, HepG-2; human larynx carcinoma cell line, Hep-2; brain tumor cell line, U251) as well as one animal cancerous cell line (Ehrlich ascites carcinoma cells line, EAC) and one normal cell line, Homo sapiens, human, (WISH) CCL-25. Different concentrations and treatment durations with Sider honey were tested on the growth of several cancer cell lines types. Histopathological changes in the tumor masses, animal survival, apoptosis and necrosis of the used cancer cell lines (using flow cytometry) were evaluated. Sider honey was administers either to the tumor mass itself by intratumoral injection or via drinking water. One-way ANOVA test was used for the analysis of (the means + standard error) of the optical density obtained from the Elisa reader and flow cytometry. The study revealed that different concentrations of Sider honey affected the growth patterns of all the studied cancer cell lines as well as their histopathological changes, and it depended on the cell line nature and the concentration of honey used. It is obvious that the relative animal survival percentage (bearing Ehrlich ascites carcinoma, EAC cells) was proportionally increased with the increase in the used honey concentrations. The study of apoptosis and necrosis using the flow cytometry technique emphasized the viability results. In conclusion, Sider honey was effective as antitumor agent, in the used concentrations.

Keywords: antitumor, honey, sider, tumor cell lines

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Authors: Sagri Sharma

Abstract:

Analysis of diseases integrating multi-factors increases the complexity of the problem and therefore, development of frameworks for the analysis of diseases is an issue that is currently a topic of intense research. Due to the inter-dependence of the various parameters, the use of traditional methodologies has not been very effective. Consequently, newer methodologies are being sought to deal with the problem. Supervised Learning Algorithms are commonly used for performing the prediction on previously unseen data. These algorithms are commonly used for applications in fields ranging from image analysis to protein structure and function prediction and they get trained using a known dataset to come up with a predictor model that generates reasonable predictions for the response to new data. Gene expression profiles generated by DNA analysis experiments can be quite complex since these experiments can involve hypotheses involving entire genomes. The application of well-known machine learning algorithm - Support Vector Machine - to analyze the expression levels of thousands of genes simultaneously in a timely, automated and cost effective way is thus used. The objectives to undertake the presented work are development of a methodology to identify genes relevant to Hepatocellular Carcinoma (HCC) from gene expression dataset utilizing supervised learning algorithms and statistical evaluations along with development of a predictive framework that can perform classification tasks on new, unseen data.

Keywords: artificial intelligence, biomarker, gene expression datasets, hepatocellular carcinoma, machine learning, supervised learning algorithms, support vector machine

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Authors: Peri Harish Kumar, Sai Sharan Dwarka, Tajbinder Singh Bains, Suneet John Joseph, Chaitanya Kiran, Sambhu Dutta, Sarah Makram, Mohamed Sayed Zaazouee, Alaa Ahmed Elshanbary

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Objective: To identify cancer and non-cancer causes of death in hepatocellular carcinoma (HCC) patients over different time periods after diagnosis and to compare the mortality risk of each cause in HCC patients with the general population. Methods: In this retrospective cohort study, data of 67,637 HCC patients from 1975 to 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. We investigated the association between different causes of death and the following variables: age, race, tumor stage at diagnosis, and treatment (surgery, chemotherapy, and radiotherapy); each according to the periods of <1 year, 1-5 years, 5-10 years, and >10 years following the diagnosis. Standardized mortality ratios (SMRs) and their 95% confidence intervals (CIs) were calculated for cancer and non-cancer deaths in each of the mentioned periods following diagnosis. Results: Data of 67,637 patients, of whom 50,571 patients died during the follow-up period, were analyzed. Most deaths were due to HCC itself (35,535, 70.3%), followed by other cancers (3,983, 7.9%). Common causes of non-cancer mortality included infectious and parasitic diseases including HIV (2,823 patients, SMR=105.68, 95% CI: 101.82-109.65), chronic liver disease (2,719 patients, SMR=76.56, 95% CI: 73.71,79.5), and heart diseases (1,265 patients, SMR=2.26, 95% CI: 2.14-2.39), with higher mortality risk in HCC patients than in the general population. Conclusion: Cancers stand for most deaths in patients with HCC. Besides, infectious, and parasitic diseases including HIV represent the commonest non-cancer cause of mortality.

Keywords: hepatocellular carcinoma, seer, causes of death, mortality

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Authors: Ching-Yi Yiu, Hui-Chen Hsu

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Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35％, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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Authors: Felipa De Mello-Sampayo

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Background: The aim of this study is to undertake, from a patient perspective, an economic analysis of presurgical teledermatology, comparing it with a conventional referral system. Store-and-forward teledermatology allows surgical planning, saving both time and number of visits involving travel, thereby reducing patients’ out-of-pocket expenses, i.e., costs that patients incur when traveling to and from health providers for treatment, visits’ fees, and the opportunity cost of time spent in visits. Method: Patients’ out-of-pocket expenses-effectiveness of presurgical teledermatology were analyzed in the setting of a public hospital during two years. The mean delay in surgery was used to measure effectiveness. The teledermatology network covering the area served by the Hospital Garcia da Horta (HGO), Portugal, linked the primary care centers of 24 health districts with the hospital’s dermatology department. The patients’ opportunity cost of visits, travel costs, and visits’ fee of each presurgical modality (teledermatology and conventional referral), the cost ratio between the most and least expensive alternative, and the incremental cost-effectiveness ratio were calculated from initial primary care visit until surgical intervention. Two groups of patients: those with squamous cell carcinoma and those with basal cell carcinoma were distinguished in order to compare the effectiveness according to the dermatoses. Results: From a patient perspective, the conventional system was 2.15 times more expensive than presurgical teledermatology. Teledermatology had an incremental out-of-pocket expenses-effectiveness ratio of €1.22 per patient and per day of delay avoided. This saving was greater in patients with squamous cell carcinoma than in patients with basal cell carcinoma. Conclusion: From a patient economic perspective, teledermatology used for presurgical planning and preparation is the dominant strategy in terms of out-of-pocket expenses-effectiveness than the conventional referral system, especially for patients with severe dermatoses.

Keywords: economic analysis, out-of-pocket expenses, opportunity cost, teledermatology, waiting time

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Authors: Gerard Bray, Arya Bahadori, Sachinka Ranasinghe

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Renal cell carcinoma (RCC) is among the top 10 most common cancers worldwide, where metastatic disease carries a poor prognosis. Herein, we present a 74-year-old male presenting with asymptomatic solitary metachronous metastasis to the gall bladder 4 years following nephrectomy for clear cell RCC. Solitary RCC metastasis to the gall bladder following nephrectomy is rarely reported in the literature and brings with it a clinical conundrum of whether surgical resection or systemic therapy should be utilized. In this case, surgical excision with cholecystectomy was employed without systemic therapy. We, therefore, contribute a rare and interesting case that highlights that metastasectomy of a solitary metastasis can improve survival according to current literature.

Keywords: renal cell carcinoma, gall bladder metastasis, solitary metastasectomy, metachronous

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Authors: Ki-Yeo Kim

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Trends in genetics are transforming in order to identify differential coexpressions of correlated gene expression rather than the significant individual gene. Moreover, it is known that a combined biomarker pattern improves the discrimination of a specific cancer. The identification of the combined biomarker is also necessary for the early detection of invasive oral squamous cell carcinoma (OSCC). To identify the combined biomarker that could improve the discrimination of OSCC, we explored an appropriate number of genes in a combined gene set in order to attain the highest level of accuracy. After detecting a significant gene set, including the pre-defined number of genes, a combined expression was identified using the weights of genes in a gene set. We used the Principal Component Analysis (PCA) for the weight calculation. In this process, we used three public microarray datasets. One dataset was used for identifying the combined biomarker, and the other two datasets were used for validation. The discrimination accuracy was measured by the out-of-bag (OOB) error. There was no relation between the significance and the discrimination accuracy in each individual gene. The identified gene set included both significant and insignificant genes. One of the most significant gene sets in the classification of normal and OSCC included MMP1, SOCS3 and ACOX1. Furthermore, in the case of oral dysplasia and OSCC discrimination, two combined biomarkers were identified. The combined genomic expression achieved better performance in the discrimination of different conditions than in a single significant gene. Therefore, it could be expected that accurate diagnosis for cancer could be possible with a combined biomarker.

Keywords: oral squamous cell carcinoma, combined biomarker, microarray dataset, correlated genes

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

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Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

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Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

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Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

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Authors: Mohamed Shafi Bin Mahboob Ali

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Introduction: Synchronous tumor is defined as the presence of more than one primary malignant lesion in the same patient at the indexed diagnosis. It is a rare occurrence, especially in the spectrum of colorectal cancer, which accounts for less than 4%. The underlying pathology of a synchronous tumor is thought to be due to a genomic factor, which is microsatellite instability (MIS) with the involvement of BRAF, KRAS, and the GSRM1 gene. There are no specific sites of occurrence for the synchronous colorectal tumor, but many studies have shown that a synchronous tumor has about 43% predominance in the ascending colon with rarity in the sigmoid colon. Case Report: We reported a case of a young lady in the middle of her 30's with no family history of colorectal cancer that was diagnosed with a synchronous adenocarcinoma at the descending colon and rectosigmoid region. The lady's presentation was quite perplexing as she presented to the district hospital initially with simple, uncomplicated hemorrhoids and constipation. She was then referred to our center for further management as she developed a 'football' sized right gluteal swelling with a complete intestinal obstruction and bilateral lower-limb paralysis. We performed a CT scan and biopsy of the lesion, which found that the tumor engulfed the sacrococcygeal region with more than one primary lesion in the colon as well as secondaries in the liver. The patient was operated on after a multidisciplinary meeting was held. Pelvic exenteration with tumor debulking and anterior resection were performed. Postoperatively, she was referred to the oncology team for chemotherapy. She had a tremendous recovery in eight months' time with a partial regain of her lower limb power. The patient is still under our follow-up with an improved quality of life post-intervention. Discussion: Synchronous colon cancer is rare, with an incidence of 2.4% to 12.4%. It has male predominance and is pathologically more advanced compared to a single colon lesion. Down staging the disease by means of chemoradiotherapy has shown to be effective in managing this tumor. It is seen commonly on the right colon, but in our case, we found it on the left colon and the rectosigmoid. Conclusion: Managing a synchronous colon tumor could be challenging to surgeons, especially in deciding the extent of resection and postoperative functional outcomes of the bowel; thus, individual treatment strategies are needed to tackle this pathology.

Keywords: synchronous, colon, tumor, adenocarcinoma

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Authors: Abdul Aziz, Muhammad Qamar Masood, Saadia Sattar, Saira Fatima, Najmul Islam

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Introduction: The most common endocrine tumor is thyroid cancer. Follicular Thyroid Carcinoma (FTC) accounts for 5%–10% of all thyroid cancers. Patients with FTC frequently present with more advanced stage diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery, while radioactive iodine therapy is the main adjuvant therapy as per ATA guidelines. In many developing countries, surgical facilities and radioactive iodine are in short supply; therefore, understanding follicular thyroid cancer trends may help developing countries plan and use resources more effectively. Methodology: It was a retrospective observational study of FTC patients of age 18 years and above conducted at Aga Khan University Hospital, Karachi, from 1st January 2010 to 31st December 2019. Results: There were 404 patients with thyroid carcinoma, out of which forty (10.1%) were FTC. 50% of the patients were in the 41-60 years age group, and the female to male ratio was 1.5: 1. Twenty-four patients (60%) presented with complain of neck swelling followed by metastasis (20%) and compressive symptoms (20%). The most common site of metastasis was bone (87.5%), followed by lung (12.5%). The pre-operative thyroglobulin level was done in six out of eight metastatic patients (75%) in which it was elevated. This emphasizes the importance of checking thyroglobulin level in unusual presentation (bone pain, fractures) of a patient having neck swelling also to help in establishing the primary source of tumor. There was no complete documentation of ultrasound features of the thyroid gland in all the patients, which is an important investigation done in the initial evaluation of thyroid nodule. On FNAC, 50% (20 patients) had Bethesda category III-IV nodules, while 10% ( 4 patients ) had Bethesda category II. In sixteen patients, FNAC was not done as they presented with compressive symptoms or metastasis. Fifty percent had a total thyroidectomy and 50% had subtotal followed by completion thyroidectomy, plus ten patients had lymph node dissection, out of which seven had histopathological lymph node involvement. On histopathology, twenty-three patients (57.5%) had minimally invasive, while seventeen (42.5%) had widely invasive follicular thyroid carcinoma. The capsular invasion was present in thirty-three patients (82.5%); one patient had no capsular invasion, but there was a vascular invasion. Six patients' histopathology had no record of capsular invasion. In contrast, the lymphovascular invasion was present in twenty-six patients (65%). In this study, 65 % of the patients had clinical stage 1 disease, while 25% had stage 2 and 10% had clinical stage 4. Seventeen patients (42.5%) had received RAI 30-100 mCi, while ten patients (25%) received more than 100 mCi. Conclusion: FTC demographic and clinicopathological presentation are the same in Pakistan as compared to other countries. Surgery followed by RAI is the mainstay of treatment. Thus understanding the trend of FTC and proper planning and utilization of the resources will help the developing countries in effectively treating the FTC.

Keywords: thyroid carcinoma, follicular thyroid carcinoma, clinicopathological features, developing countries

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Authors: Sung Yong Kim, Byung Joo Song

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Background: Circulating 25-hydroxyvitamin D (25(OH)D) levels has been considered to be inversely related to breast cancer development, recurrence risk, and mortality. Mean vitamin D levels in Korean population is lower than western countries due to higher incidence of lactose intolerance and lower exposure to sunlight. The purpose of this study was to assess incidence of 25(OH)D deficiency at diagnosis and after adjuvant chemotherapy and to investigate the correlation serum 25(OH)D levels with clinicopathologic features. Methods: From December 2011 to October 2012, 280 breast cancer patients seen at a single tertiary cancer center were enrolled. Serum 25(OH)D was measured at the time of surgery and after completion of adjuvant chemotherapy. Statistical analyses used chi-square test, Fisher's exact test, t-test, and ANOVA. Results: Mean serum 25(OH)D was 18.5 ng/ml. The 25(OH)D levels were deficient (<20 ng/ml) in 190 patients (67.9%), insufficient (20-29 ng/ml) in 51 patients(18.2%), and sufficient (30-150 ng/ml) in 39 patients(13.9%). A notable decrease in 25(OH)D concentration was observed(p<0.001) after chemotherapy but was not related to chemotherapy regimens. It was found significant lower 25(OH)D levels at winter season(from October to March, p=0.030). Subjects with invasive carcinoma (IDC or ILC) had significantly lower circulating levels of 25(OH)D than those with ductal carcinoma in situ(DCIS) (p=0.010). Patients with larger tumor size tends to have lower serum 25(OH)D but there were no statistical significance. Conclusions: Most of the breast cancer patients showed deficient or insufficient serum 25(OH)D concentration. Incidence of vitamin D deficiency was higher in invasive carcinoma than DCIS. Serum 25(OH)D levels were decreased after chemotherapy. Consideration should be given to the supplement of vitamin D to those patients.

Keywords: breast neoplasms, vitamin D, Korean population, breast cancer

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Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

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In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

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Authors: Ga-Young Lee, Hyun-Man Kim

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The modulation of the cell-cell junction is critical in epithelial-mesenchymal transition during tumorigenesis. As RhoA activity is known to be up-regulated to dissociate cell-cell junction by contracting acto-myosin complex in various cancer cells, the present study investigated if RhoA activity was also associated with the disruption of the cell-cell junction of oral cancer cells. We studied SCC-25 cells which are established from oral squamous cell carcinoma if their E-cadherin junction (ECJ) was under control of RhoA. Interestingly, development of ECJ of SCC-25 cells depended on the amount of fibronectin (FN) coated on the culture dishes. Seeded cells promptly aggregated to develop ECJ on the substrates coated with a low amount of FN, whereas they were retarded in the development of ECJ on the substrates coated with a high amount of FN. However, it was an unexpected finding that total RhoA activity was lower in the dissociated cells on the substrates of high FN than in the aggregated cells on the substrates of low FN. Treating the dissociated cells on the substrates of high FN with LPA, a RhoA activator, promoted the development to ECJ. In contrast, treating the aggregated cells on the substrates of low FN with Clostridium botulinum C3, a toxin decreasing RhoA activity, dissociated cells concomitant with the disruption of ECJ. Genetical knockdown of RhoA expression by transfecting RhoA siRNA also down-regulated the development of ECJ in SCC-25 cells. Furthermore, PMA, an activator of protein kinase C (PKC), down-regulated the development of ECJ junction of SCC-25 cells on the substrates coated with low FN. In contrast, GO6976, a PKC inhibitor, up-regulated the development of ECJ of SCC-25 cells with the activation of RhoA on the substrates coated with high FN. In conclusion, in the present study, we demonstrated unexpected results that the activation of RhoA promotes the development of ECJ, whereas the inhibition of RhoA retards the development of ECJ in SCC-25 cells.

Keywords: E-cadherin junction, oral squamous cell carcinoma, PKC, RhoA, SCC-25

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