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ORIGINAL ARTICLES
Perceived benefits and barriers toward cervical cancer screening among women ≥15 years in Arsi Zone, Southeastern Ethiopia: Application of the health belief model in a community-based cross-sectional study
Gemechu Chemeda Feyisa, Haftom Temesgen
January-March 2019, 6(1):7-17
DOI:10.4103/JCRP.JCRP_1_18  
Introduction: The rate of cancer mortality is18.4/100,000 in Ethiopia, and cancer of the cervix is the second-most common cancer, with an incidence of 16.4/100,000. Cancer of the cervix is easily prevented through vaccinations against human papilloma virus, regular screening, and treatment. Assessing the perception of women with regard to the benefits and barriers of cervical cancer screening among women is important to decrease the barriers and increase the screening rate for early detection. The aim of this study was to describe women's perceived benefits and barriers to cervical cancer screening and their associated factors in Arsi zone, Southeastern Ethiopia. Materials and Methods: This community-based cross-sectional study design was conducted in Arsi zone, Southeastern Ethiopia among 906 women aged >15 years using a multi-stage sampling technique. After data had been coded and entered into Epi info, it was exported into SPSS for analysis. A binary logistic regression model was used to determine associations between sociodemographic characteristics and reproductive variables on the knowledge of cervical cancer and perception of screening at a value of P < 0.05. Results: Most of the participants had higher perceptions of the benefits and barriers to screening (567 [62.6%] and 487 [53.8%], respectively). The women who would like to undergo cervical cancer screening in the future when the service was available were 2.6 times more likely to believe in the benefits of undergoing screening than those who did not wish to undergo screening (adjusted odds ratio [AOR] = 2.3, 95% confidence interval [CI]: [1.2–4.6]). Women living in rural areas were four times more likely to perceive the benefits of cervical cancer screening than those living in semi-urban areas (AOR = 3.9, 95% CI: [1.9–7.7]). Women who started sexual intercourse at age <16 years were two times more likely to perceive barriers to cervical cancer screening than those who started sexual intercourse at age >16 years (AOR = 2.2, 95% CI: [1.5–3.3]). Moreover, the women who had >3 children were 1.5 times more likely to perceive barriers to cervical cancer screening than those who had <3 children (AOR = 1.5, 95% CI: [1.1–2.0]). Conclusion and Recommendation: There were high perceived benefits and barriers to screening in the community. We recommend decreasing the perceived barriers toward screening through education intervention and expanding screening services, as this can increase the uptake of screening in the community.
  1,149 224 -
REVIEW ARTICLE
A Review on the Recent Advancement in “Tumour Spheroids-on-a-Chip”
M Ibrahim Khot, Mark A Levenstein, Nikil Kapur, David G Jayne
April-June 2019, 6(2):55-63
DOI:10.4103/JCRP.JCRP_23_18  
Introduction: Three-dimensional (3D) cell cultures are identified as more accurate and representative models of human cancers than conventional two-dimensional monolayer cell cultures. However, currently established 3D culturing techniques are technically challenging, time- and resource-consuming, and performed using traditional laboratory tissue culturing equipment. In recent years, microfluidics has been introduced into biomedical research, allowing cells and tissues to be cultured in microfabricated devices. The current challenge is to adapt existing 3D cell culturing techniques to microfluidic devices, allowing for the fabrication of low-cost, rapid evaluation devices to facilitate biomedical research and clinical application. The aim of this review was to evaluate microfluidics and 3D cell culture research with particular relevance to oncological research. Methods: Journal articles were acquired from different scientific databases and were identified using specific keywords. Three-Dimensional Cell Culturing Microfluidic Concepts: Various 3D cell culturing microfluidic devices have been designed, based on existing 3D cell culturing methods. This includes non-cell adherent-based devices, matrix-embedding, hanging drop, and droplet-based culturing methods. These platforms facilitate the culturing, treatment, and analysis of 3D spheroids, while simultaneously scaling down traditional experimental requirements. Limitations and Future Perspectives: Beyond superficial analysis, a major drawback in the current scope of 3D cell culturing microfluidic devices is the inability to extract spheroids for examining histology. Polydimethylsiloxane is the preferred material to fabricate devices but may need revision for commercializing microfluidic platforms in the future. Integrating 3D bioprinting and organoid cultures could potentially improve the quality of 3D models in microfluidic devices. Conclusion: 3D spheroids are an effective representation of in vivo cancers and microfluidics has streamlined the culture, treatment, and analysis of 3D models. Considerable improvements have been made in combining the two entities, but further work is required to manufacture 3D cell culturing microfluidic devices on a commercial scale.
  1,084 243 -
The roles of microRNA-331 Family in Cancers
Stefanie Mei En Shee, Rhun Yian Koh, Kenny Gah Leong Voon, Soi Moi Chye, Iekhsan Othman, Khuen Yen Ng
January-March 2019, 6(1):1-6
DOI:10.4103/JCRP.JCRP_6_18  
MicroRNAs (miRNAs) are single-stranded noncoding RNA strands that are involved in various pathological and physiological processes. Even though they do not code for any gene, they regulate gene expression by posttranscriptional modification through cleavage or translational repression of messenger RNA. Many miRNAs (for example, lethal-7 and miRNA-21) have been found to be involved in the pathogeneses of many diseases including cancers. The miRNA-331 family includes three miRNAs, namely, miRNA-331, miRNA-331-3p, and miRNA-331-5p. Recent studies have revealed that the miRNA-331 family is associated with the pathology of some cancers, including colorectal cancer, leukemia, hepatocellular carcinoma, prostate cancer, pancreatic cancer, breast cancer, melanoma, and lung cancer. Therefore, it is important to have a good understanding about how the miRNA-331 family regulates the pathogeneses of these cancers. In this review, we discuss the pathological and physiological roles of the miRNA-331 family. Understanding how these miRNAs regulate the gene expression levels of their targets and their involvement in cancers may lead to better therapeutic strategies to treat cancers.
  1,021 194 -
ORIGINAL ARTICLES
Perspectives of visual inspection of the cervix with acetic acid as an alternative to Pap smear test as a preventive measure of cervical cancer among female nurses in University College Hospital, Ibadan, Nigeria
Christene E Umukoro, Olufemi Y Makinde
January-March 2019, 6(1):18-25
DOI:10.4103/JCRP.JCRP_10_18  
Background: Visual inspection of the cervix with acetic acid (VIA) has been recommended by the World Health Organization as an alternative to the Pap smear test in preventing cervical cancer in low-resource healthcare settings. However, the level of awareness and uptake is still very low in Nigeria. In this study, the awareness and acceptance of VIA as a preventive measure against cervical cancer among female nurses at the University College Hospital (UCH), Ibadan was assessed. Materials and Methods: A pretested questionnaire on the knowledge of the risk factors of cervical cancer, uptake of the Pap smear test, and awareness and acceptance of VIA was administered to 301 female nurses at UCH, Ibadan. Results: The majority of the respondents (99%) knew about cervical cancer, but only 62.4% of them were aware that human papilloma virus is a causative agent. Early marriage (73.6%), high parity (64.0%), multiple sexual partners (91.1%), smoking (54.8%), and poor socioeconomic status (42.9%) were identified as risk factors for the disease. The proportion of those that had heard of VIA (43.6%) was low when compared with the Pap smear test (99%). However, 72.4% of them thought that female staff at the screening centers should promote VIA. Moreover, 61.5% believed that definitive treatment of cases could commence immediately after a VIA test. The age, duration of service, and educational qualification did not significantly (P > 0.05) influence the respondents' awareness of VIA as a cervical cancer screening technique. Conclusion: Adoption of VIA as part of routine checkups during postnatal visits and its integration into the nation l healthcare policy is recommended.
  867 124 -
REVIEW ARTICLES
Future of 5-fluorouracil in cancer therapeutics, current pharmacokinetics issues and a way forward
Sania Zafar Iqbal, Farhat Jubeen, Farooq Sher
October-December 2019, 6(4):155-161
DOI:10.4103/JCRP.JCRP_10_19  
Background: In addition to exhibiting antitumor potential, antitumor drugs exhibit toxicity due to a poor pharmacokinetic profile. An enormous amount of research has been carried out and is still ongoing to obtain more targeted, potent, and safe drugs to treat cancer, and pharmacokinetic evaluations of anticancer drugs are needed. Objectives: The present review examined different delivery systems and methodologies designed in recent years to investigate the pharmacokinetics of the anticancer drug, 5-fluorouracil (5-FU). These methodologies highlight how the issues of bioavailability, absorption, half-life, targeted neoplastic cell potential, and high therapeutic index of 5-FU are resolved. Results: A number of naturally occurring macromolecules such as modified starch, porphyran, peptides, and folic acids have been found to be successful in vitro to improve the permeability and retention effect of 5-FU against solid tumors. A promising approach for targeted 5-FU delivery to oncoproteins has resulted in a number of potentially sound anticancer nanocomposites. Chitosan nanoparticles loaded with 5-FU have been shown to exhibit cytotoxicity equivalent to 5-FU injections against gastric carcinoma. At the level of inter- and intra-molecular interactions, the co-crystal approach has been found to be successful against colorectal cancer proteins. Because of the 5-FU ligand-like nature and its metal-binding potential, researchers have shifted attention toward the synergistic co-administration of gold complexes with this drug. Conclusions: This study highlighted the techniques used to improve the pharmacokinetics of 5-FU and that "nanocarriers" are a promising approach in this field. The conclusion is supported by solid evidence.
  791 83 -
Thyroid hormone, PD-L1, and cancer
Yi-Ru Chen, Zi-Lin Li, Ya-Jung Shih, Paul J Davis, Jaqueline Whang-Peng, Hung-Yun Lin, Kuan Wang
October-December 2019, 6(4):162-169
DOI:10.4103/JCRP.JCRP_26_19  
Objective: Thyroid hormone plays a vital role in maintaining whole-body physiological activities. However, several different disorders can arise when thyroid hormone is abnormal. Even more, thyroid hormone has been shown to stimulate cancer cell proliferation at physiological concentration. By binding to cell surface integrin αvβ3, thyroid hormone, especially thyroxine activates ERK1/2 activation and sequentially stimulates cell proliferation. Different mechanisms have been demonstrated to be involved in thyroxine-induced cancer proliferation. Checkpoint, PD-1/PD-L1, has shown highly correlated to cancer proliferation and survival. Data Sources: We examined actions of thyroxine and Nano-diamino-tetrac (NDAT; Nanotetrac) on PD-L1 mRNA abundance (qPCR) and PD-L1 protein content in various cancer cells. Methodologies used are qPCR, Western blot analyses, confocal microscopy, and xenograft. Study Selection: We investigate mechanisms involved in thyroid hormone-induced PD-L1 expression and inhibitory effect of NDAT on thyroid hormone-induced PD-L1 expression. Either blocking thyroid hormone-binding on integrin αvβ3 or using NDAT can inhibit PD-L1 expression. Results: Our studies indicate that thyroid hormone induces PD-L1 expression via activating ERK1/2, PI3K, and STAT3 in different types of cancer cells. NDAT inhibits the cancer cell PI3-K and MAPK signal transduction pathways that are critical to PD-L1 gene expression. Other studies on PubMed also indicate thyroxine's actions are via integrin αvβ3. Conclusions: Thyroid hormone-induced PD-L1 expression not only facilitates cancer cell proliferation but also interferes with chemotherapy. In this current review, we will discuss mechanisms involved in thyroid hormone-induced PD-L1 expression. In addition, role of PD-L1 in thyroid hormone-induced cancer growth and metastasis will be addressed.
  773 34 -
REVIEW ARTICLE
Sorafenib resistance and autophagy in hepatocellular carcinoma: A concealed threat
K Ashokachakkaravarthy, Biju Pottakkat
July-September 2019, 6(3):107-116
DOI:10.4103/JCRP.JCRP_6_19  
Objective: To investigate the relationship between sorafenib resistance and autophagy in hepatocellular carcinoma (HCC). Data Sources: Literature from PubMed (ncbi) database relevant to autophagy and sorafenib resistance in HCC. Study Selection: Studies were selected based on their experimental and observational nature with regards to autophagy and sorafenib resistance in HCC. Observational human studies and sorafenib clinical trials were selected to analyze the epidemiology of HCC, pharmacological properties of sorafenib, autophagy in human HCC, sorafenib treatment in humans, and sorafenib resistance in HCC. In-vivo and In-vitro preclinical studies were selected to analyze the effect of sorafenib on autophagy in HCC and the effect of sorafenib-induced autophagy in HCC. Results: Sorafenib blocked the Akt/mTOR and MEK/ERK pathways which are downstream of ras/raf signaling. By blocking these pathways, sorafenib altered autophagic regulatory signaling pathways, thereby initiating autophagy as a collateral effect. In addition, sorafenib paradoxically activated AMPK, thereby initiating autophagy in human HCC cells. Sorafenib also increased autophagy by upregulating pro-autophagic proteins such as beclin-1, Atg5, LC3II and Vps34. Sorafenib resistance developed in HCC as a consequence of autophagy. Conclusion: Autophagy induced by sorafenib could be a mechanism for the development of sorafenib resistance in HCC.
  639 152 -
CASE REPORTS
Hyperprogressive disease after nivolumab in a patient with microsatellite instability-high ampullary cancer
Yi-Hsuan Lai, Shih-Hung Yang
January-March 2019, 6(1):50-54
DOI:10.4103/JCRP.JCRP_9_18  
Ampullary cancer is a rare type of cancer with a limited choice of systemic therapy. Anti-programmed death-1 monoclonal antibodies have shown promising clinical benefits in multiple types of cancer, especially in tumors with microsatellite instability-high (MSI-H)/defective DNA mismatch repair and high tumor mutation burden. We report a case of a 61-year-old woman with MSI-H ampullary cancer who initially had slow progression without chemotherapy after recurrence. She experienced hyperprogressive disease with a dramatic deterioration of liver metastases following a short duration of nivolumab treatment.
  688 60 -
ORIGINAL ARTICLES
Modulation of oxidative stress by doxorubicin loaded chitosan nanoparticles
Ankita Leekha, Vijay Kumar, Imran Moin, Bahadur Singh Gurjar, Anita Kamra Verma
April-June 2019, 6(2):76-84
DOI:10.4103/JCRP.JCRP_18_18  
Purpose of the Research: Chitosan nanoparticles (CHNP) are being used to modulate the generation of reactive oxygen species (ROS), as unwarranted generation of ROS can damage proteins, lipid membranes, and DNA of host cells. CHNP possess exceptional abilities to modulate antioxidants and suppress oxidative stress damage caused by the CHNP themselves in normal cells. Methods and Results: CHNP were prepared by ionic gelation in the size range of ~115 nm, with a polydispersity index of 0.365. Doxorubicin (DOX) was encapsulated in CHNP with entrapment efficiency ~48%. The modulation of free radicals and antioxidative enzymes by DOX-loaded CHNP (DLCHNP) was evaluated. The glutathione s-transferase and glutathione levels induced by DLCHNP were lower in Ehrlich ascites carcinoma cells(EACs) cells (6.60 ± 0.02 nM/min/mg protein and 0.92 ± 0.05 nM/min/mg protein, respectively) compared to void CHNP and DOX per se decreased levels of nitric oxide and superoxide dismutase (0.03 ± 0.001 nMoles and 28.84 ± 0.016 Unit/mg protein), elevated levels of GSSG (11.69 ± 0.004 nM/min/mg protein), marginally reduced levels of GSH reductase (1.87 ± 0.002 Unit/mg protein), reduced levels of GPx (31.35 ± 0.022 Unit/mg protein) and significantly enhanced levels of LPO (1.56 ± 0.01 nMoles/mg protein) indicated cellular damage. As observed in DNA fragmentation assay, void nanoparticles did not show any DNA damage whereas DLCHNP caused significant damage. Enhanced gene expressions of Cyt. C and p21 on EACs cells was observed in DLCHNP-treated cells compared to DOX per se. Conclusion: CHNP were not efficient in generating remarkable oxidative stress, but when coupled with a drug (i.e., DLCHNP) severe damage was caused to the cancer cells compared to the free drug. This indicated the potential of our encapsulated nanoparticles in drug delivery.
  590 96 -
High-intensity focused ultrasound for localized prostate Cancer in Cathay General Hospital
Shu-Wei Tsai, Teh-Sheng Hsieh
April-June 2019, 6(2):64-67
DOI:10.4103/JCRP.JCRP_13_18  
Purpose: The purpose of this study is to report our results regarding the use of transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. Materials and Methods: From January 2012 to January 2017, 57 patients with localized prostate cancer (cT1c-T2cN0M0) were treated with an Ablatherm™ HIFU device. Of these patients, we excluded those with <12 months of follow-up. In total, 33 patients with localized prostate cancer were enrolled in this study. We assessed the efficacy according to posttreatment prostate-specific antigen (PSA) levels and complications. PSA levels were monitored immediately after HIFU therapy as well as every 3 months thereafter. Biochemical failure was defined as an increase in PSA of 2 ng/mL or more above the PSA nadir. Result: The mean age of all patients was 69.12 ± 8.21 (range: 49–80) years,and the average pretreatment PSA level was 15.19 ± 12.89 (range: 4.44–62.91) ng/mL. The Gleason score ranged from 6 (3 + 3) to 9 (4 + 5) and the mean prostate volume was 38.72 ± 17.90 (range: 21–77) mL. The mean follow-up duration was 36.4 ± 10.8 (range: 13–60) months.Ten patients were classified as low risk, 10 patients were classified as intermittent risk, and 13 patients were classified as high risk according to the National Comprehensive Cancer Network guidelines regarding the risk of recurrence. The PSA levels of all patients decreased significantly after HIFU therapy, and an undetectable PSA (0.04 ng/mL) level was observed in four patients (12.12%). The posttreatment mean PSA nadir was 0.609 ± 0.91 (range: 3.21–0.04) ng/mL, and the mean follow-up duration was 3.1 ± 1.9 (range: 1–8) months. The survival rate was 100%. The PSA biochemical failure rate was 27.3% (9/33). Posttreatment complications included urge incontinence (3/33), total urinary incontinence (0/33), bladder neck contracture (5/33), and urethral stricture (1/33). Conclusion: HIFU therapy appeared to be an effective minimally invasive therapy with acceptable complication rate in selected localized prostate cancer patients.
  577 87 -
CASE REPORTS
Primary small-cell carcinoma of the glottic larynx: A case report from Northern Pakistan
Kanwal Awan, Humera Mahmood, Hadia Fatima, Sarosh Arif, Mohammad Faheem
January-March 2019, 6(1):30-32
DOI:10.4103/JCRP.JCRP_2_18  
Extrapulmonary neuroendocrine small-cell carcinoma is a rare tumor accounting for only 2.5%–4% of all small-cell carcinomas, and during the past 30 years, only 160 cases of primary small-cell carcinoma of the larynx have been reported worldwide. Most previously reported cases were metastatic small-cell carcinomas. Herein, we report the case of a 51-year-old male who was treated at the Atomic Energy Cancer Hospital, NORI, Islamabad, Pakistan for small-cell carcinoma of the larynx.
  564 91 -
SHORT COMMUNICATION
Improving colorectal, oral, breast, and cervical cancer screening rates using an inreach approach
Lee-Kiat Ban, Ailun Heather Tseng, Hung-Chun Hsing, Henry Hsin-Chung Lee
January-March 2019, 6(1):26-29
DOI:10.4103/JCRP.JCRP_5_18  
The Taiwanese national cancer screening program was established in 1985 by providing Pap smear tests for women. At the same time, trial-based screening for colorectal, oral, and breast cancer screening was initiated. In 1999, outreach services for cancer screening were started and gradually scaled up to the national level. Our hospital is located in Hsinchu, Taiwan. Like many hospitals in Taiwan, we provide cancer screening services to the community. Our baseline screening rate was 96.6% in 2016. Aiming to increase the overall cancer (including colorectal, oral, breast, and cervical cancer) screening rates, we implemented two strategies. First, we modified the cancer screening workflow so that patients could receive screening counseling before the scheduled appointment. Second, we redesigned the clinic waiting room layout by moving check-in and cancer screening counters next to each other. By the end of 2017, the overall cancer screening rate increased from 96.6% to 105.4%. Our future efforts will be focused on collecting patient feedback, increasing coverage of hard-to-reach populations, and understanding barriers to cancer screening for specific groups of patients.
  539 95 -
ORIGINAL ARTICLES
Neutrophil lymphocyte ratio is an independent prognosticator in patients with locally advanced head and neck squamous cell carcinoma receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil
Hsiang-Lan Lai, Yeh Tang, Chih-Yen Chien, Fu-Min Fang, Tai-Lin Huang, Tai-Jan Chiu, Shau-Hsuan Li
October-December 2019, 6(4):170-178
DOI:10.4103/JCRP.JCRP_12_19  
Background: The aim of the present study was to evaluate the prognostic value of neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF). Materials and Methods: We performed a single-center retrospective analysis of 126 patients with locally advanced HNSCC treated with TPF as induction chemotherapy at Kaohsiung Chang Gung Memorial Hospital. NLR and PLR were calculated from blood tests before induction chemotherapy and correlated with clinical parameters and treatment outcomes. Results: A NLR ≧3 was significantly associated with advanced clinical American Joint Committee on Cancer (AJCC) 7th stage, higher clinical T classification, oral cavity primary tumor site, and alcohol history. A PLR ≧120 was significantly correlated with advanced clinical AJCC 7th stage and oral cavity primary tumor site. The overall response rates of induction chemotherapy were 70% and 50% (P = 0.022) in patients with a NLR <3 and NLR ≧3 and 78% and 52% (P = 0.008) in patients with a PLR <120 and PLR ≧120, respectively. Univariate analysis showed 5-year progression-free survival (PFS) rates of 58% and 32% (P < 0.001) in the patients with a NLR <3 and NLR ≧3 and 59% and 38% (P = 0.022) in those with a PLR <120 and PLR ≧120, respectively. The 5-year overall survival (OS) rates were 51% and 24% (P < 0.001) in the patients with a NLR <3 and NLR ≧3 and 52% and 31% (P = 0.011) in those with a PLR <120 and PLR ≧120, respectively. In multivariate analysis, NLR ≧3 was significantly independently associated with worse PFS (P = 0.018, odds ratio [OR]: 2.11) and OS (P = 0.026, OR: 1.87). Conclusions: Our findings suggested that an elevated NLR was independently associated with the prognosis of patients with locally advanced HNSCC treated with induction chemotherapy with TPF, and that, it may be helpful in clinical practice.
  537 41 -
CASE REPORTS
Brenner tumor of the ovary: Incidental finding with unusual combinations
Hema Udawat, Vandana Nunia, Natasha Agarwal, Arpita Jindal
January-March 2019, 6(1):33-36
DOI:10.4103/JCRP.JCRP_3_18  
The most common ovarian tumors are surface epithelial tumors, comprising 58% of all ovarian tumors. Among them, serous and mucinous cystadenomas are the most common (35%). A Brenner tumor is a rare, mostly benign type of ovarian epithelial neoplasm with an incidence of 1%–2%. Rarely, they occur in other locations, including the testis. The majority of Brenner tumors are benign; however, some can be malignant. These are most frequently found incidentally on pelvic examinations or during laparotomy. In the present case series, we report three cases of Brenner tumors diagnosed incidentally on histopathology. The first case was a rare combination of serous cystadenoma, with a focus showing a Brenner tumor in the wall of serous cystadenoma. The second case was a proliferating Brenner tumor in the wall of mucinous cystadenoma, and the third case had bilateral benign Brenner tumors.
  509 63 -
ORIGINAL ARTICLES
Antiproliferative effect of oxidative stress induced by tellurite in breast carcinoma cells
Ayesha Noreen, Abdul Rehman, Saira Aftab, Abdul Rauf Shakoori
April-June 2019, 6(2):68-75
DOI:10.4103/JCRP.JCRP_5_19  
Background: Recent studies have revealed that tellurium (Te) compounds have pharmacological and/or antioxidant properties against tumors as they have antitumor and chemoprotective properties. The toxic nature of tellurium compounds and their beneficial effects as antitumor agents have led to an increasing number of studies on their toxicological and pharmacological modes of action. Materials and Methods: The breast cancer cell line, MDA-MB-231, was cultured in the absence or presence of tellurite for biochemical and morphological analysis to measure the extent of cell death. The roles of antioxidant compounds 3-methyladenine, N-acetylcysteine, and 1,2-bis (2-aminophenoxy) ethane-N, N, N′, N′-tetra acetic acid (acetoxymethyl ester) in supporting proliferation in the presence of tellurite were investigated. Results: There was significant oxidative stress in the tellurite-exposed cells, which curtailed cell Adenosine triphosphate (ATP) levels. Tellurite-induced cytotoxicity substantially increased lactate dehydrogenase leakage, lipid peroxidation, and DNA damage, as analyzed by micronuclei and comet formation. Conclusions: Tellurite-induced damage led to cell cycle arrest, resulting in cell death by activating apoptotic machinery by increasing p21 gene expression in tellurite-treated cells.
  478 81 -
CASE REPORTS
Postmolar metastatic choriocarcinoma mimicking primary lung cancer
Chih-Chieh Yen, Hung-Wen Tsai, Chia-Jui Yen
January-March 2019, 6(1):41-44
DOI:10.4103/JCRP.JCRP_7_18  
Postmolar choriocarcinoma with delayed recurrence can be aggressive and has only been published in a few reports. We describe a postmenopausal woman with a molar pregnancy 10 years previously who presented with respiratory and neurological symptoms. Metastatic choriocarcinoma of the lungs with extensive metastases to various sites mimicking primary lung cancer was noted. She was successfully treated with systemic chemotherapy and had stable disease status 8 months after the diagnosis. Metastatic choriocarcinoma originating from an antecedent molar pregnancy can be overlooked given a prolonged latency. We review the published literature of postmolar choriocarcinoma and discuss the diagnosis and updates on treatment.
  487 69 -
ORIGINAL ARTICLES
Anticancer effect of Andrographis paniculata by suppression of tumor altered hypoxia signaling cascade in mouse melanoma cells
Tanmoy Paul, Sharmita Basu, Nimai Chandra Saha
July-September 2019, 6(3):117-123
DOI:10.4103/JCRP.JCRP_9_19  
Background: Intratumor hypoxia, the main factor responsible for the angiogenic switch, represents one of the major events leading to tumor progression. Tumor hypoxia leads to the stabilization of hypoxia-inducible factor-1α (HIF-1α) which influences tumor angiogenesis. The new blood vessels formed by the HIF-1α-vascular endothelial growth factor (VEGF) signaling axis create the tumor microenvironment, which inhibits drug delivery to solid tumors. The present study aimed to investigate the effect of Andrographis paniculata leaf extract as a powerful anticancer agent targeting the HIF-1α-VEGF signaling axis in mouse melanoma cell. Materials and Methods: We induced hypoxia-mimicking conditions in mouse B16 melanoma cell with cobalt chloride. Total RNA was isolated followed by reverse transcriptase polymerase chain reaction to study the transcriptional expressions of HIF-1α and VEGF. Further confirmation of the transcriptional profiling was done at the protein level with Western blot analysis. Expression profiling of transcriptional factors involved in the hypoxia signaling cascade was done. An immunofluorescence study was also used to confirm the results obtained from transcriptional and translational analyses. Results: A. paniculata leaf extract significantly downregulated the expressions of HIF-1α and VEGF both at the transcriptional and translational level. Sp1, p300, CBP expressions were also downregulated, whereas the expression of Sp3 was significantly upregulated by A. paniculata leaf extract in B16 melanoma cells. Conclusion: In the present study, A. paniculata-treated cells demonstrated lower expressions of VEGF and HIF-1α both at the transcriptional and translational level. The mechanism of the downregulation of HIF-1α was probably through the altered expressions of transcriptional factors involved in the hypoxia-signaling cascade.
  464 89 -
CASE REPORTS
A Patient with refractory metastatic germ cell tumor successful salvaged after treatment with paclitaxel, ifosfamide, and high-dose 5-Fluorouracil infusional therapy
Keng-Man Chiang, Ann-Lii Cheng
April-June 2019, 6(2):85-88
DOI:10.4103/JCRP.JCRP_17_18  
We report a case of a 24-year-old male with a metastatic extragonadal germ cell tumor (GCT) which was refractory to conventional chemotherapy and progressed after high-dose chemotherapy. The addition of a 24-h infusion of high-dose 5-fluorouracil (5-FU) with leucovorin regimen to a salvage regimen of paclitaxel and ifosfamide provided a durable clinical response. We also discuss the potential of repurposing 5-FU for the treatment of a refractory GCT.
  455 88 -
A huge retroperitoneal cystic lymphangioma mimicking an adnexal cyst
Yan-Fong Lu, Lee-Wen Huang, Yuh-Yu Chou, Tsen-Long Yang
July-September 2019, 6(3):147-150
DOI:10.4103/JCRP.JCRP_7_19  
We present a case of retroperitoneal cystic lymphangioma mimicking an adnexal cyst. The clinical presentation and prognosis of the disease, histological features with unique staining patterns, and differential diagnoses are discussed. A 60-year-old woman presented with acid reflux and a bulging left abdominal mass. Abdominal computed tomography revealed an 18-cm well-defined retroperitoneal tumor occupying the left side of her abdomen with descending colon and aorta displacement. The retroperitoneal tumor was resected; its diameter was approximately 18 cm with up to 2000 mL of the chylous fluid. Histopathological analysis, including immunohistochemical staining, confirmed the definitive diagnosis of retroperitoneal cystic lymphangioma.
  504 37 -
ORIGINAL ARTICLES
Netrin-1 expression in breast cancer
Shyr-Ming Sheen-Chen, Ching-Hua Tsai, Yueh-Wei Liu, Chao-Cheng Huang
July-September 2019, 6(3):124-127
DOI:10.4103/JCRP.JCRP_8_19  
Background: Breast cancer is a collection of molecularly and clinically distinct neoplastic disease. Recent research has shown that the gene expression in breast cancer can be useful when designing an optimal treatment plan and may also provide with prognostic information. The development of tissue microarrays (TMAs) has allowed for rapid immunohistochemical analysis of thousands of tissue samples in parallel with minimal damage to the original blocks. The aim of this study was to use TMAs to analyze the netrin-1 (NTN 1) status in patients with breast cancer with the hope of elucidating the possible relationship between NTN 1 expressions and breast cancer. Materials and Methods: Archival tissue specimens from 106 patients with primary invasive breast cancer were analyzed for NTN 1 expression using immunohistochemical staining with TMAs. Results were compared to clinicopathological data using multivariate analysis. Results: Tumor-node-metastasis stage was significantly related to the overall 5-year survival rate; however, NTN 1 expression was not significantly associated with overall 5-year survival. Conclusion: Immunohistochemical staining with TMAs was convenient and feasible to analyze the expression of NTN 1, in patients with breast cancer. Our preliminary results showed that NTN 1 expression had no significant prognostic value in breast cancer.
  436 88 -
CASE REPORTS
Paraneoplastic Systemic Sclerosis in a Patient with Metastatic Thymic Carcinoma
Hsing-Wu Chen, Ko-Jen Li, Hung-Yang Kuo
January-March 2019, 6(1):45-49
DOI:10.4103/JCRP.JCRP_8_18  
Thymic malignancies cause alterations in the immune system. Thymomas are known to be associated with paraneoplastic syndrome and autoimmunity, including myasthenia gravis, systemic lupus erythematosus, inappropriate antidiuretic hormone secretion, pure red cell aplasia, pernicious anemia, pemphigus, and autoimmune thyroid diseases. However, paraneoplastic syndrome has rarely been observed in patients with thymic carcinoma. The management of patients with paraneoplastic autoimmune disease is difficult, and treatment of the underlying malignancy is important. Herein, we present a case of thymic carcinoma who developed systemic sclerosis 3 years after the initial diagnosis during disease progression.
  458 63 -
Cervical cancer with breast metastasis
Ching-Ting Wei, Cheuk-Kwan Sun, Jen-Wei Tsai, Chi-Feng Fu
April-June 2019, 6(2):100-102
DOI:10.4103/JCRP.JCRP_14_18  
Breast metastasis from extramammary solid malignancies is rare, and cervical cancer is an especially uncommon origin. It is clinically challenging to differentiate a primary breast cancer from a metastatic lesion if the patient presents with inflammatory breast skin, axillary lymphadenopathy, and ipsilateral upper-limb lymphedema. Herein, we described the first case of cervical squamous cell carcinoma with breast metastasis presenting as an inflammatory breast lesion in Taiwan. A 41-year-old woman visited our outpatient clinic with edema of bilateral lower legs as well as a reddish left breast and indurated skin. After systemic workup, she was diagnosed as having cervical cancer with peritoneal carcinomatosis and breast and multiple lymph node metastases for which she received palliative chemotherapy. However, bone metastasis developed, and she died 9 months after the diagnosis. We also reviewed relevant literature on breast metastases from an extramammary origin.
  464 51 -
Complete radiographic response of a rectal gastrointestinal stromal tumor to imatinib mesylate
Hsing-Yu Yang, Ming-Hung Lee
January-March 2019, 6(1):37-40
DOI:10.4103/JCRP.JCRP_4_18  
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. These tumors occur rarely in the rectal region, with an incidence of <3%. In this case report, an 80-year-old man complained of abdominal fullness and difficulty in defecating during a visit to our outpatient department. A radiographic image survey showed an extraluminal lesion over the rectum, and the pathological diagnosis was GIST. Imatinib mesylate, a neoadjuvant agent, was administered. The patient then refused further surgical intervention and continued imatinib mesylate treatment. Subsequent magnetic resonance images revealed no obvious lesion occupying the pelvic cavity. In addition to this case, we also performed a literature review of rectal GIST treatment strategies.
  419 63 -
Pulmonary pleomorphic carcinoma harboring epidermal growth factor receptor mutation: Response to afatinib
Abeer Hussien Anter, Majid Al-Jahel, Rasha Mohamed AbdelLatif, Mohamed Fouad AbdELmohsen, Ahmed Shata
April-June 2019, 6(2):103-106
DOI:10.4103/JCRP.JCRP_16_18  
Pulmonary pleomorphic carcinoma (PPC) of the lung is a rare type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy. We report a case of a 56-year-old female, diagnosed with PPC of the lung at clinical Stage IV in July 2017. She underwent first-line chemotherapy. The disease progressed after 6 cycles of chemotherapy, and we shift to afatinib due to presence of epidermal growth factor receptor (EGFR) mutation in exon 19. We then started second-line treatment in the form of molecular targeted therapy (afatinib), to which she had a partial response. Hence, we recommend the evaluation of driver gene alterations such as EGFR in the treatment of advanced PPC.
  414 46 -
Juxtaglomerular cell tumor with lung metastases in a young male patient
Pei-Wei Huang, Yung-Chang Lin, Kuei-Fang Wu, Ting-Wen Sheng, Po-Jung Su
July-September 2019, 6(3):128-131
DOI:10.4103/JCRP.JCRP_19_18  
Juxtaglomerular cell tumor (JGCT) is a rare pathologically benign renal neoplasm mostly reported as localized disease, which can secrete renin and induce hypertension, hypokalemia, and hyperaldosteronism. In this report, a young male was diagnosed with JGCT with lung metastases. In general, the diagnosis of JGCT is made by a pathological examination, and the standard treatment of localized disease is to resect the tumor completely. However, there is currently no standard treatment for metastatic or unresectable JGCT, and chemotherapy plays a debatable role.
  360 76 -