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   Table of Contents - Current issue
Coverpage
July-September 2019
Volume 6 | Issue 3
Page Nos. 107-154

Online since Tuesday, August 20, 2019

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REVIEW ARTICLE  

Sorafenib resistance and autophagy in hepatocellular carcinoma: A concealed threat Highly accessed article p. 107
K Ashokachakkaravarthy, Biju Pottakkat
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.
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ORIGINAL ARTICLES Top

Anticancer effect of Andrographis paniculata by suppression of tumor altered hypoxia signaling cascade in mouse melanoma cells p. 117
Tanmoy Paul, Sharmita Basu, Nimai Chandra Saha
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.
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Netrin-1 expression in breast cancer p. 124
Shyr-Ming Sheen-Chen, Ching-Hua Tsai, Yueh-Wei Liu, Chao-Cheng Huang
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.
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CASE REPORTS Top

Juxtaglomerular cell tumor with lung metastases in a young male patient p. 128
Pei-Wei Huang, Yung-Chang Lin, Kuei-Fang Wu, Ting-Wen Sheng, Po-Jung Su
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.
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Recurrent malignant phyllodes tumor of breast with gastric metastasis p. 132
Hsin-Chen Lin, Cheng-Wei Chou
DOI:10.4103/JCRP.JCRP_21_18  
Malignant phyllodes tumor of the breast (MPTB) is a rare breast malignancy. Surgery is the primary treatment for this malignant tumor. Adjuvant radiotherapy should be considered if the surgical margin is positive. The lungs and bone are the most frequent metastatic sites of MPTB; however, gastric involvement is rare. Herein, we report a 64-year-old woman with MPTB. Surgery was the initial treatment; however, lung and gastric metastases were found 5 years later. Palliative chemotherapy with the CyVADIC regimen (cyclophosphamide, vincristine, doxorubicin, and dacarbazine) achieved a partial response. In conclusion, systemic chemotherapy can be one of the treatment options for patients with metastatic MPTB.
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Myoepithelial carcinoma of soft tissue: A report of two cases p. 136
K V.Vinu Balraam, Divya Shelly, Prabha Shankar Mishra, Isha Sharma, KS Sampath, Reena Bharadwaj
DOI:10.4103/JCRP.JCRP_22_18  
Primary myoepithelial neoplasms of soft tissue are rare tumors that have only recently been recognized. Due to the presence of varied architectural and cytological features both within a lesion and between different tumors, immunohistochemistry may be required to diagnose these tumors. Herein, we report two cases of myoepithelial carcinoma of soft tissue, one of whom had an aggressive clinical course.
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Pathologic complete response to bevacizumab-FOLFIRI in metastatic colonic undifferentiated carcinoma with rhabdoid features p. 140
Tien-Chan Hsieh, Hung-Wei Liu, Chao-Wen Hsu
DOI:10.4103/JCRP.JCRP_24_18  
Undifferentiated colorectal carcinoma with rhabdoid features is unusual, aggressive, and resistant to chemotherapy. Compared to rhabdoid phenotype, immunohistochemistry is a more reliable way of detecting undifferentiated colorectal carcinoma with rhabdoid features. An increasing number of studies have reported that defects in core subunits of the switch/sucrose-nonfermenting complex may play an important role in the formation of rhabdoid tumors. Herein, we report the first case, to the best of our knowledge, with a pathologic complete response after neoadjuvant chemotherapy. A 65-year-old Taiwanese female had carcinoma over the ascending colon and multiple metastases to mesenteric lymph nodes and peritoneum. The immunohistochemical findings resembled those of rhabdoid features. She had received neoadjuvant chemotherapy with bevacizumab plus irinotecan with leucovorin and 5-fluorouracil (modified FOLFIRI). Follow-up computed tomography and surgical specimens revealed a favorable outcome. The effectiveness of neoadjuvant multiagent therapy for this rare carcinoma may inspire future research of tumorigenesis and novel treatments.
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A huge retroperitoneal cystic lymphangioma mimicking an adnexal cyst p. 147
Yan-Fong Lu, Lee-Wen Huang, Yuh-Yu Chou, Tsen-Long Yang
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.
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Disseminated and massive tumor burden in a case of primary thymic mucinous adenocarcinoma p. 151
Hui-Wen Liu, Chih-Yi Liu, Yi-Chen Yeh
DOI:10.4103/JCRP.JCRP_13_19  
Primary thymic mucinous adenocarcinoma is an extremely rare type of thymic carcinoma that is resistant to radiation and chemotherapy. We present a case of primary thymic mucinous adenocarcinoma with disseminated metastases and rapid progression, after concurrent chemoradiation and platinum-based doublet chemotherapy. Case and literature review also revealed poor outcomes for primary thymic mucinous adenocarcinoma patients receiving surgery and adjuvant therapy. We concluded the poor response of either resectable or unresectable primary thymic mucinous adenocarcinoma.
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