Cancer Research and Practice

A Review on the Recent Advancement in "Tumour Spheroids-on-a-Chip" M Ibrahim Khot, Mark A Levenstein, Nikil Kapur, David G Jayne Journal of Cancer Research and Practice 2019 6(2):55-63 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.

High-intensity focused ultrasound for localized prostate Cancer in Cathay General Hospital Shu-Wei Tsai, Teh-Sheng Hsieh Journal of Cancer Research and Practice 2019 6(2):64-67 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.

Antiproliferative effect of oxidative stress induced by tellurite in breast carcinoma cells Ayesha Noreen, Abdul Rehman, Saira Aftab, Abdul Rauf Shakoori Journal of Cancer Research and Practice 2019 6(2):68-75 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.

Modulation of oxidative stress by doxorubicin loaded chitosan nanoparticles Ankita Leekha, Vijay Kumar, Imran Moin, Bahadur Singh Gurjar, Anita Kamra Verma Journal of Cancer Research and Practice 2019 6(2):76-84 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.

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 Journal of Cancer Research and Practice 2019 6(2):85-88 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.

Detection of anaplastic lymphoma kinase gene rearrangement in a patient with right colon cancer Chun-Hui Lee, Chung-Ta Lee, Yi-Lin Chen, Bo-Wen Lin, Peng-Chang Lin, Meng-Ru Shen, Yu-Min Yeh Journal of Cancer Research and Practice 2019 6(2):89-91 Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity worldwide. Recent genome-scale molecular analyses have uncovered several potential therapeutic targets for this disease, including BRAF mutation, ERBB2 amplification, and neurotropic tropomyosin receptor kinase fusion gene. Gene rearrangements involving anaplastic lymphoma kinase (ALK) gene have been identified as oncogenic drivers in lung adenocarcinomas, and to be highly sensitive to selective kinase inhibitors. To the best of our knowledge, CRC harboring the ALK fusion gene has rarely been reported. Herein, we report a patient with right colon cancer harboring an ALK gene rearrangement and review the clinicopathologic features as well as potential therapeutic targeting of ALK-rearranged CRC in the literature.

Pembrolizumab-induced uveitis in a patient with metastatic urothelial carcinoma Lo-Ho Chen, Jhe-Cyuan Guo Journal of Cancer Research and Practice 2019 6(2):92-95 Immune checkpoint blockade, especially targeting the programmed cell death protein-1/programmed death-ligand 1 axis, has changed the paradigm of anticancer therapy in several cancer types. For urothelial carcinoma (UC), pembrolizumab is an immune checkpoint inhibitor approved by the US Food and Drug Administration for locally advanced or metastatic disease. The new anticancer modalities are complicated with immune-related adverse events (irAEs) which are significantly different from conventional treatment such as chemotherapy or targeted therapy. Herein, we present an 85-year-old man with metastatic UC who developed a rare kind of irAE, uveitis, under pembrolizumab therapy, who fortunately partially recovered with local and systemic steroids.

Inflammatory Pseudotumor of the Liver Tsen-Long Yang, Hong-Chuen Chang Journal of Cancer Research and Practice 2019 6(2):96-99 Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion, characterized by chronic infiltration of inflammatory cells and areas of necrosis mimicking a malignant tumor. Few cases have been reported, and the precise etiology is still unknown. Patients usually present with abdominal pain, fever, and jaundice. Herein, we report the case of a 78-year-old male with a history of diabetes mellitus who had abdominal fullness and body weight loss for 4 months. A computed tomography scan showed a 15-cm liver tumor in segment 2 and 3 and suspected hepatocellular carcinoma. Left hepatectomy was performed, and the pathology showed IPT. After surgery, the symptom of abdominal fullness subsided.

Cervical cancer with breast metastasis Ching-Ting Wei, Cheuk-Kwan Sun, Jen-Wei Tsai, Chi-Feng Fu Journal of Cancer Research and Practice 2019 6(2):100-102 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.

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 Journal of Cancer Research and Practice 2019 6(2):103-106 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.

Alexandros Sfakianakis
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