isolation-expansion-cytotoxic-cytokine-induced-killer-t-cells-for

Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment

Adoptive cellular immunotherapy focuses on restoring cancer recognition via the immune system and improves effective tumor cell killing. Cytokine-induced ...

Wan Fang Hospital

Taipei Medical University

Taipei Medical University Bilingual Education Center

Pseudosarcomatous myofibroblastic proliferation (PMP) of the bladder is a rare, benign, and proliferative lesion of the submucosal stroma. We report a 38-year-old female patient who was initially diagnosed with urothelial carcinoma of the urinary bladder under intravenous pyelography. Bladder tumor was resected by the transurethral method, and pathology disclosed a picture compatible with pseudosarcomatous myofibroblastic proliferation. However, local recurrence was found 2 months later, and tumor resection was performed again. The patient has been followed-up at our outpatient department for a year without any evidence of recurrence.

Pseudosarcomatous myofibroblastic proliferation of the urinary bladder.

Most extraperitoneal bladder ruptures can be treated conservatively with catheter drainage only. However, in patients with concomitant intrabladder blood clot formation and extraperitoneal bladder rupture, surgery for blood clot evacuation and bladder repair are usually needed due to occlusion of the urinary catheter. In our patient, we used a ureteral catheter to bypass the clots in the bladder to provide adequate urinary drainage. This procedure serves as a valuable tool in the conservative treatment of extraperitoneal bladder injury.

Conservative treatment of concomitant extraperitoneal bladder rupture and intrabladder blood clot formation: Case report of application of ureteral catheterization.

Mefloquine (MQ) is currently in clinical use as a prophylactic treatment for malaria. Previous studies have shown that MQ induces oxidative stress . The present study investigated the anticancer effects of MQ treatment in PC3 cells. The cell viability was evaluated using sulphorhodamine-B (SRB) staining, while annexin V and propidium iodide (PI) were used as an assay for cell death. Reactive oxygen species (ROS) formation was detected with 2',7'-dichlorofluorescein-diacetate (DCFH-DA), a sensitive intracellular probe, and the alteration of cellular status was defined by trypan blue staining. The results of the present study indicated that MQ has a high cytotoxicity that causes cell death in PC3 cells. MQ markedly inhibited the PC3 cells through non-apoptotic cell death. MQ also induced significant ROS production. The MQ treatment mediated G1 cell cycle arrest and cyclin D1 accumulation through p21 upregulation in the PC3 cells. Moreover, the use of MQ improved the survival of the treatment group compared with the control group in the experimental mice. The present study indicates that MQ possesses potential therapeutic efficacy for the treatment of prostate cancer (PCa) . These findings provide insights that may aid the further optimization and application of new and existing therapeutic options.

Mefloquine induces cell death in prostate cancer cells and provides a potential novel treatment strategy 

Mefloquine (MQ) is a prophylactic anti-malarial drug. Previous studies have shown that MQ induces oxidative stress . Evidence indicates that reactive oxygen species (ROS) may be used as a therapeutic modality to kill cancer cells. This study investigated whether MQ also inhibits prostate cancer (PCa) cell growth. We used sulforhodamine B (SRB) staining to determine cell viability. MQ has a highly selective cytotoxicity that inhibits PCa cell growth. The antitumor effect was most significant when examined using a colony formation assay. MQ also induces hyperpolarization of the mitochondrial membrane potential (MMP), as well as ROS generation. The blockade of MQ-induced anticancer effects by N-acetyl cysteine (NAC) pre-treatment confirmed the role of ROS. This indicates that the MQ-induced anticancer effects are caused primarily by increased ROS generation. Moreover, we observed that MQ-mediated ROS simultaneously downregulated Akt phosphorylation and activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and adenosine monophosphate-activated protein kinase (AMPK) signaling in PC3 cells. These findings provide insights for further anticancer therapeutic options.

Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling.

Lung fibrosis is a poor prognostic factor for pulmonary adenocarcinoma, and the effect of a rigid microenvironment on cancer behavior is unclear. We cultured A549 cells on matrices of 0.2, 2, and 25 kPa to mimic the rigidities of normal lung parenchyma, progressive fibrotic change, and lung fibrosis, respectively. Lung tissue from patients with pulmonary adenocarcinoma was used to confirm the in vitro findings. Increased matrix rigidity promoted cell proliferation and upregulated the epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-Met), and Snail expression in A549 cells. A549 cells became more resistant to the EGFR inhibitor (Erlotinib) and c-Met inhibitor (PHA-665752) when matrix rigidity increased; however, a high concentration of PHA-665752 reversed the rigidity-induced morphological pleomorphism. In human lung tissue, expression of type I collagen was more consistent with clinical fibrosis than the expression of alpha-smooth muscle antibody was. c-Met- and Snail-expressing tumor cells, rather than EGFR-experssing cells, were localized with lung parenchyma rich in type I collagen. Our findings suggest that c-Met causes the rigidity-induced biophysical reaction in pulmonary adenocarcinoma. Treatment targeting both EGFR and c-Met should be considered for patients with lung fibrosis and who are abundant type I collagen expression in the tumor mass. 

Regulation of metastatic ability and drug resistance in pulmonary adenocarcinoma by matrix rigidity via activating c-Met and EGFR.

Testicular torsion is a urological emergency and infertility is a common complication due to ischemic injury. Surgical reduction and orchiopexy is indicated, but to date there is no effective method for restoration of spermatogenesis. The effects of mesenchymal stem cells (MSCs) on acute tissue injury have been demonstrated, and the abilities of paracrine support, differentiation and immune-modulation may benefit to testicular torsion-induced infertility. We investigate the therapeutic efficacy and the mechanisms of MSCs in testicular torsion-induced germ cell injury when injected locally.

Local injection of mesenchymal stem cells protects testicular torsion-induced germ cell injury.

Immunosuppressive therapies decrease the incidence of acute kidney rejection after kidney transplantation, but also increase the risk of infections and sepsis. This study aimed to identify the risk factors associated with complications and/or graft failure in kidney transplant patients with sepsis. A total of 14,658 kidney transplant patients with sepsis, identified in the National Inpatient Sample (NIS) database (data from 2005-2014), were included in the study and classified into three groups: patients without complications or graft failure/dialysis (Group 1), patients with complications only (Group 2), and patients with complications and graft failure/dialysis (Group 3). Multinomial logistic regression analyses were conducted to evaluate factors associated with kidney transplant recipients. Multivariate analysis showed that, compared to Group 1, patients from Group 2 or Group 3 were more likely to be Black and to have cytomegalovirus infection, coagulopathy, and glomerulonephritis (p ≤ 0.041). Also, Group 2 was more likely to have herpes simplex virus infection, and Group 3 was more likely to have hepatitis C infection and peripheral vascular disorders, compared to Group 1 (p ≤ 0.002). In addition, patients in Group 3 were more likely to be Black and to have hepatitis C infection, peripheral vascular disorders, coagulopathy, and hypertension compared to Group 2 (p ≤ 0.039). Age and female gender were associated with lower odds of complications after kidney transplantation regardless of graft rejection/dialysis (p ≤ 0.049). Hyperlipidemia and diabetes decreased the chance of complications and graft failure/dialysis after kidney transplant (p < 0.001). In conclusion, the study highlights that black race, male gender, and specific comorbidities can increase the risk of complications and graft failure in kidney transplant patients with sepsis.

Risk factors for complications and graft failure in kidney transplant patients with sepsis.

Urinary bladder hemangiomas are rare, especially in children and adolescents. We present a case of a 17-year-old young man with persistent gross hematuria for 1 month. Computed tomography revealed a 3.6 cm mass on the superior anterior wall of the urinary bladder, which was highly suspected as an urachal tumor. We carried out an en bloc resection of the urachus and bladder tumor. The pathologic report indicated a cavernous hemangioma of the urinary bladder. No tumor recurrence or bleeding was found during the 2-year follow-up. Urinary bladder hemangioma is an important differential diagnosis in young patients with hematuria.

A Large Urinary Bladder Hemangioma Mimicking Urachal Cancer: A Case Report and Literature Review.

Bladder cancer is one of the most common types of malignant tumor worldwide. Current treatments, including chemo-/radiotherapy, only have limited efficacy on bladder cancer progression. Honokiol is an active component of  with multiple biological effects that may provide promising health benefits. In the present study, the anti-cancer properties of honokiol against bladder cancer cells were investigated by flow cytometric analysis. The results revealed that honokiol exhibited significant anti-proliferative effects on bladder cancer cell lines, particularly on BFTC-905 human transitional cell carcinoma cells. Furthermore, honokiol at low doses (≤25 µM) induced cell cycle arrest in G/G phase, while it induced significant apoptotic cell death at high doses (≥50 µM; P<0.05). Furthermore, a significant accumulation of reactive oxygen species was identified in honokiol-treated cells. In addition, honokiol induced hyperpolarization of the mitochondrial membrane, which may lead to mitochondrial dysfunction. Finally, caspase-3/7 activation was identified in high-dose honokiol-treated bladder cancer cells. These results suggest that honokiol induces apoptosis via the mitochondrial pathway and honokiol-containing traditional herbal remedies may have a potential clinical application in the treatment of bladder cancer.

Honokiol induces apoptotic cell death by oxidative burst and mitochondrial hyperpolarization of bladder cancer cells.

Testicular torsion is an urological emergency that may lead to infertility due to ischemic injury. Promptly surgical correction by orchiopexy is the only way to avoid infertility and no effective treatment for restoration of spermatogenesis. We previously reported that mesenchymal stem cells (MSCs), through local injection upon testicular torsion-detorsion, restored the spermatogenesis without differentiation into sperm. In this study, molecular mechanisms of MSCs in regulating germ cell activity induced by testicular torsion-detorsion were investigated.

Article	Year
Pseudosarcomatous myofibroblastic proliferation of the urinary bladder. Journal of the Chinese Medical Association : JCMA\| PubMed ID: 18772126	2008
Conservative treatment of concomitant extraperitoneal bladder rupture and intrabladder blood clot formation: Case report of application of ureteral catheterization. Canadian Urological Association journal = Journal de l'Association des urologues du Canada\| PubMed ID: 23283098	2012
Mefloquine induces cell death in prostate cancer cells and provides a potential novel treatment strategy Oncology letters\| PubMed ID: 23759954	2013
Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling. Oncology letters\| PubMed ID: 23760395	2013
Regulation of metastatic ability and drug resistance in pulmonary adenocarcinoma by matrix rigidity via activating c-Met and EGFR. Biomaterials\| PubMed ID: 26000960	2015
Local injection of mesenchymal stem cells protects testicular torsion-induced germ cell injury. Stem cell research & therapy\| PubMed ID: 26025454	2015
Risk factors for complications and graft failure in kidney transplant patients with sepsis. Bosnian journal of basic medical sciences\| PubMed ID: 30242808	2019
A Large Urinary Bladder Hemangioma Mimicking Urachal Cancer: A Case Report and Literature Review. Urology\| PubMed ID: 30308263	2019
Honokiol induces apoptotic cell death by oxidative burst and mitochondrial hyperpolarization of bladder cancer cells. Experimental and therapeutic medicine\| PubMed ID: 30988795	2019
Mesenchymal stem cells restore the sperm motility from testicular torsion-detorsion injury by regulation of glucose metabolism in sperm. Stem cell research & therapy\| PubMed ID: 31445515	2019

Chi-Hao Hsiao

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