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   2022| January-March  | Volume 9 | Issue 1  
    Online since March 7, 2022

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JM-17 Induces G0/G1 Cell cycle arrest in human breast cancer cells through the downregulation of androgen receptors and cyclin-dependent kinase 4 protein expression
Guan-Yi Lai, Hardy Chan, Tzu-Chi Chen, Wen-Jui Lee, Yuan-Soon Ho
January-March 2022, 9(1):1-10
Background: Locally advanced breast cancer (BC) remains a clinical challenge for patients as many will eventually develop distant metastases despite receiving appropriate therapies. Materials and Methods: In this study, we have analyzed the expression of androgen receptors (AR) in a series of BC cell lines and found their expressions rather ubiquitous across many different cell lines. Moreover, we have demonstrated that JM-17 [(1E,4Z,6E)-4-(cyclobutylmethyl)-1,7-bis (3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one], a synthetic curcumin derivative, exhibited suitable antitumor activities on most of the BC cell lines tested. Results: Human MDA-MB-231 cells were treated with JM-17, and the results demonstrated that JM-17-induced cell cycle proliferation arrested at the G0/G1 phase in a dose-dependent manner. Cell cycle-regulated proteins, such as cyclin-dependent kinases 4 (CDK4), were downregulated and p21 was upregulated. We further demonstrated that JM-17 treatment reduced AR expressions in MDA-MB-231 cells. The AR/CDK4 protein complex was demonstrated for the first time using a fluorescence resonance energy transfer (FRET) activity assay and immunohistochemistry (IHC) staining. JM-17 reduced the FRET activity in vitro. An in vivo study further demonstrated that JM-17 (20 mg/kg) decreased considerably MDA-MB-231 xenograft tumor growth. Conclusion: AR-mediated BC formation is a factor that clinicians often neglect. Our study demonstrated that JM-17 could be a promising agent against specific targets in AR-positive BC patients.
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Pembrolizumab as a bridge to autologous stem cell transplantation in refractory gray zone lymphoma
Chun-Kuang Tsai, Po-Shen Ko, San-Chi Chen
January-March 2022, 9(1):26-28
Gray zone lymphoma (GZL), a rare type of B-cell lymphoma (BCL), has features between diffuse large BCL and classical Hodgkin lymphoma (cHL) and an unfavorable outcome. The expression of PD-L1, encoded by chromosome 9p24.1, has been positively correlated with the copy number alteration of 9p24.1, and it has been associated with a high response rate to anti-PD-1 treatment in cHL and primary mediastinal large BCL (PMBCL). GZL shares similar genomic alterations with cHL and PMBCL, and thus, it may also respond well to anti-PD-1 treatment. However, little is known about the efficacy of anti-PD-1 treatment and the predictive role of PD-L1 expression in GZL. Here, we present a case of GZL refractory to first-line chemotherapy. The patient had a high expression of PD-L1 and was successfully treated with pembrolizumab as a salvage treatment, followed by autologous stem cell transplantation (ASCT) in January 2018. The patient still had a complete metabolic response 42 months after ASCT.
  1,855 159 -
Clinical features, prognostic factors, and treatment outcomes in 611 patients with phyllodes tumors of the breast: The experience of a single institution in Taiwan
Chun Hui Lin, Po-Sheng Yang, Yuan-Ching Chang, Wen-Ching Ko, Hung-Bun Lam, Pao-Shu Wu
January-March 2022, 9(1):11-21
Background: Phyllodes tumors are uncommon biphasic breast tumors for which clinical findings remain insufficient to determine the optimal management strategy. The aim of this study was to report our experience of the clinicopathological features, prognostic factors, surgical treatment, and outcomes of patients presenting with phyllodes tumors in two different periods. Materials and Methods: We retrospectively reviewed the clinical and pathological data of 611 patients with histologically proven phyllodes tumors. The patients were separated into two groups: Period A, those who were treated from January 2006 to August 2013, and period B, those who were treated from September 2013 to September 2019. Clinical characteristics, histopathologic parameters, and outcomes were collected from patient records, and parameters were compared between the two periods. Results: The median follow-up was 7 months (range 0.5–84) in treatment period A and 14 months (range 0.5–118) in treatment period B. The median age was 38 years (range 12–75) in treatment period A and 40 years (range 12–79) in treatment period B. Analysis of the two treatment periods revealed an increase in tumor size at the diagnosis from 3.6 cm during period A to 4.5 cm during period B (P = 0.001). Most tumors were found in the upper outer quadrant, with an equal propensity to occur in either breast (34.6% vs. 42.2%). The pathologic diagnoses included 419 benign, 97 borderline, and 40 malignant lesions. Sixty cases (20 in period A and 40 in period B) experienced recurrence after surgery, including 35 benign phyllodes tumors (43% vs. 57%), 16 borderline tumors (38% vs. 63%), and 9 malignant tumors (44% vs. 56%) in either period (P = 0.003). Three cases (0.5%) (1 in period A and 2 in period B) had pulmonary metastases (0.3% vs. 0.7%). Multivariable linear regression analysis revealed that tumor size and a positive or undetermined surgical margin were the independent predictors of recurrence (P = 0.006, 0.020, and 0.004, respectively). Conclusion: Breast-conserving surgery with clear margins is technically feasible and a safe treatment for phyllodes tumors, but this strategy does not effectively further reduce local recurrence. Our findings demonstrated that clinical characteristics, tumor size, surgical margin, and pathologic features are the important predictors for tumor recurrence in patients with phyllodes tumors.
  1,508 174 -
Immune-related neuromuscular junction disorder after immune checkpoint inhibitor treatment
Shang-Hsuan Peng, Yu-Yun Shao
January-March 2022, 9(1):22-25
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and prolonged the survival of patients with various malignancies. Nevertheless, the expanded usage of ICIs is associated with increased reports of immune-related adverse events (irAEs), some of which can impair functional outcomes and worsen the prognosis. We present a fatal case of a patient presenting with progressive generalized weakness diagnosed with immune-related neuromuscular junction (NMJ) disorder after nivolumab treatment. By describing this case, we hope to raise awareness of rare irAEs such as immune-related NMJ disorder because prompt intervention is essential to minimize long-term sequelae and improve outcomes.
  1,373 185 -
Skin metastasis of a p16-positive squamous cell carcinoma mimicking radiation recall dermatitis
Chia-Wei Shen, Jo-Pai Chen, Fu-Jen Hsueh, Henry Wing-Cheung Leung
January-March 2022, 9(1):29-33
Radiation recall dermatitis is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. Herein, we report the case of a 48-year-old man irradiated for bilateral supraclavicular and right axillary lymph nodal metastases from p16-positive esophageal or occult head-and-neck squamous cell carcinoma (SCC). Several months after the completion of radiotherapy, systemic therapy with a combination of methotrexate and pembrolizumab was commenced. The patient developed increased skin pigmentation and inflammation generally consistent with the region that had previously been irradiated. The skin reaction progressed with a protruding mass after prednisolone treatment. A biopsy confirmed p16-positive SCC. Systemic therapy was given, but the patient died 2 months after the confirmation of skin metastasis. We believe that ionizing radiation can modulate the tissue microenvironment of skin and subsequently promote carcinogenesis. It may also alter the tissue response to anticancer therapy, including anti-programmed death-1/PD-ligand 1. Corticosteroids may worsen the skin lesions and conflict with immunotherapy.
  1,160 168 -
Long-term remission by nivolumab monotherapy for sorafenib-refractory hepatocellular carcinoma
Chia-Yu Chen, Li-Yuan Bai
January-March 2022, 9(1):41-44
Hepatocellular carcinoma (HCC) is considered to be a relatively chemotherapy-resistant tumor. There was no standard systemic therapy for patients with metastatic HCC until 2007 when sorafenib was demonstrated to be superior to supportive care. Lenvatinib has also been used as a first-line choice since a randomized phase III noninferiority trial was conducted in 2018. In the second-line setting, regorafenib was the first drug to be approved for sorafenib-refractory advanced HCC. Other drugs such as cabozantinib and ramucirumab have also shown benefits in a second-line setting. Immunotherapy is another novel and well-tolerated treatment option for patients who are refractory to tyrosine kinase inhibitors. Here, we present a patient with HCC which progressed after sorafenib treatment, and who subsequently achieved a nearly complete remission after nivolumab monotherapy. Maintenance therapy with nivolumab every 2–3 months was prescribed to sustain the good response based on a previous study that used rituximab maintenance therapy in a patient with follicular lymphoma.
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Clinical presentation of advanced extragonadal embryonal carcinoma mimicking classical hodgkin lymphoma
Wei-Nung Liu, Tsung-Ying Yu
January-March 2022, 9(1):34-36
A 22-year-old man presented with a 2-week history of abdominal pain, fatigue, fever, and night sweats. Enlarged neck and paraaortic lymph nodes were noted, but no testicular lesions were found using imaging tools. Pathology revealed poorly differentiated embryonal carcinoma (EC) of the metastatic neck lymph node. The patient presented with clinical symptoms similar to Hodgkin lymphoma (HL), but the final diagnosis was advanced-stage extragonadal EC. To our knowledge, this is a rare case report of EC presenting as classic HL.
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Neutropenic necrotizing enterocolitis: A life-threatening complication after aggressive chemotherapy for leukemia
Chih-Ching Chin, Junping Shiau, Chi-Wen Lou, Mei-Ren Pan, Fang-Ming Chen, Ming-Feng Hou
January-March 2022, 9(1):37-40
Neutropenic enterocolitis can occur after aggressive chemotherapy with a wide range of severity from mild to life threatening. Neutropenic necrotizing enterocolitis (NNE) is a catastrophic condition that has rarely been discussed in the literature. Here, we present the case of a 27-year-old previously healthy female who was diagnosed with acute myeloid leukemia and underwent a first course of chemotherapy. Severe neutropenia, high fever, and abdominal pain were noted 5 days later. After medical treatment had failed, emergent laparotomy was performed. Several patches of transmural necrosis were seen at the jejunum, and resection with primary anastomosis was done. However, more newly formed necrotic patches were found over the small bowel during second-look surgery 2 days later. This report emphasizes that NNE is an irreversible ongoing process refractory to medical or surgical treatments, and physicians should be cautious of this syndrome when using aggressive chemotherapy.
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