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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.
  3,005 464 -
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.
  2,474 362 -
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.
  2,461 286 2
REVIEW ARTICLE
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.
  2,170 294 -
REVIEW ARTICLES
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.
  2,084 188 1
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.
  1,902 288 -
Dissecting the functional pleiotropism of lysine demethylase 5B in physiology and pathology
Oluwaseun Adebayo Bamodu, Tsu-Yi Chao
April-June 2020, 7(2):49-59
DOI:10.4103/JCRP.JCRP_5_20  
Background: The last two decades has been characterized by accruing evidence of the translational relevance of chromatin modification in normal genomic function, regulation, and pathology, especially with piqued interest in the intrinsic regulatory dynamism of histone methylation, and the increasing documentation of new members of the histone demethylase family. Recent studies provide functional and mechanistic insight into the peculiar biological role of these histone demethylases and their putative implication in pathological processes. Objective: This review aims to provide a summary of the latest findings related to pleiotropic roles of the Jumonji/AT-rich interactive domain (JARID) domain-containing lysine demethylase 5B (KDM5B, also known as JARID1B or PLU1) in physiology and pathology, with a focus on its therapeutic potentials. Results: KDM5B/JARID1B/PLU1 is restrictively expressed, evolutionarily conserved across mammalian species, and belonging to the α-ketoglutarate-dependent hydroxylase superfamily. KDM5B is actively involved in various physiological processes, including regulation of transcription elongation and alternative splicing in embryonic stem cells, epigenetic modulation of gene expression, neurogenesis, mammary gland development, and osteogenesis. Conversely, KDM5B is one of the earliest identified histone lysine demethylases associated with human disease, with several studies indicating that KDM5B plays a vital role in the initiation and progression of various malignancies, including lung, hypopharynx, brain, and breast cancers. Conclusion: This study provides concise insight into the functional pleiotropism of KDM5B in physiology and pathology, as well as highlights it role as an actionable therapeutic target.
  1,912 164 -
CASE REPORTS
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.
  1,937 125 -
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.
  1,815 226 -
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.
  1,819 183 1
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.
  1,646 217 -
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.
  1,726 125 -
ORIGINAL ARTICLES
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.
  1,630 168 -
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.
  1,563 214 -
Association between serum folate level and invasive cervical cancer at a university teaching hospital in South-West Nigeria
Adebayo I Sekumade, Kehinde S Okunade, Gbenga Olorunfemi, Ebunoluwa O Daramola, Muisi A Adenekan, Adeyemi A Okunowo, Rose I Anorlu
October-December 2019, 6(4):179-183
DOI:10.4103/JCRP.JCRP_24_19  
Background: Cervical cancer is a common cause of cancer-related morbidity and mortality in developing countries. Serum folate may modify cancer risk through its role in DNA synthesis and methylation. Objective: To determine the association between serum folate levels and the occurrence of cervical cancer among women seen at a university teaching hospital in South-West Nigeria. Patients and Methods: This was an analytical cross-sectional study involving two groups of participants including 50 cases with invasive cervical cancer (ICC) and 50 controls with a normal cervix. Data analysis was performed between discrete baseline characteristics of the cases and controls using the Pearson's Chi-square test, whereas the mean serum folate levels of the cases and controls were compared using the independent sample t-test. P<0.05 was considered statistically significant. Results: There was no significant positive association between low serum folate and the occurrence of ICC (adjusted odds ratio: 2.99; P = 0.088). Conclusions: The findings of this study showed that low serum folate was not independently associated with an increased risk of ICC. However, a robust multicenter long-term longitudinal study will provide further evidence on the role of serum folate in the occurrence of ICC.
  1,475 156 -
CASE REPORTS
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.
  1,442 140 -
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.
  1,413 166 -
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.
  1,388 171 -
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.
  1,365 176 -
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.
  1,378 154 -
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.
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CASE REPORTS
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.
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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.
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Identification of docetaxel, cisplatin, and 5-fluorouracil regimen hypersensitivity by In vitro T-cell activation assay
Hang Huong Ling, Chun-Bing Chen, Cheng-Hsu Wang, Yen-Min Huang
October-December 2019, 6(4):184-187
DOI:10.4103/JCRP.JCRP_11_19  
An in vitro T-cell activation assay measuring granulysin and granzyme B has been used to identify the drug hypersensitivity of common causative drugs, but not of chemotherapeutic drugs. Both granulysin and granzyme B are cytotoxic molecules involved in skin eruptions during drug hypersensitivity. Herein, we report the first clinical application of an in vitro T-cell activation assay to identify the causative agent in docetaxel, cisplatin, and 5-fluorouracil (5-FU)-related hypersensitivity in a patient with head-and-neck cancer. A significant increase in granulysin and granzyme B was observed for 5-FU rather than for docetaxel or cisplatin. Despite several limitations, we were still able to pinpoint 5-FU as the culprit drug in a chemotherapy combination without further drug rechallenge in our patient. In conclusion, an in vitro T-cell activation assay measuring granulysin and granzyme B can be a safe and alternative tool to determine the causative agent of hypersensitivity reactions in cancer patients who need combination chemotherapy.
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REVIEW ARTICLE
Clinical application of 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography for cancer cells in lung cancer
Seyyed Hossein Hassanpour, Jafar Nikbakht, Seyyedeh Zeinab Karami
January-March 2020, 7(1):1-10
DOI:10.4103/JCRP.JCRP_16_19  
Purpose: One of the most important tools used in the diagnosis and treatment of lung cancer in patients with or suspected of having lung cancer is positron emission tomography-computed tomography XS(PET-CT). The popularity of this method is rapidly increasing. Material and Review Method: We searched papers on the topic of the recognition of cancer cells in lung cancer using18F-fluoro-2-deoxy-D-glucose (FDG) PET-CT using keywords such as18F-FDG PET-CT and lung cancer, 18F-FDG PET-CT imaging in oncology, cancer and nuclear medicine, diagnosis of lung cancer and imaging, molecular imaging in cancer, false-positive18F-FDG PET-CT scans and oncology, application of18F-FDG PET-CT in staging and metabolic activity assessment of cancer, and PET-CT imaging method. Results: In this review, we found the following results: 1.Due to the high diagnostic sensitivity of PET-CT scans, it is possible to reject malignancy in pulmonary cells using this method 2. PET-CT scans decrease the number of unnecessary procedures. 3. According to the findings of this review study, high sensitivity in PET-CT is the major advantage compared to other methods used to rule out the possibility of malignancy of lung cells; it is necessary but not sufficient. Conclusions: Regarding the imaging of abnormal pulmonary cells using PET-CT, except for a few exceptions, if the result of a PET-CT scan is negative, these abnormalities can confidently be considered to be benign. These exceptions include nonsolid and small (<1 cm) pulmonary nodules. Until all metastases in the pulmonary cells are imaged and detected by PET-CT, no drug regimen should be started. Finally, lymph node tumor metastasis cannot be ruled out solely based on a negative result of PET-CT imaging with these abnormalities, and to confirm it, aggressive staging should be performed in most patients before mediastinal metastasis is confirmed or rejected.
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