• The Korean Journal of Pain
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• v.33 no.4
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• pp.318-325
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• 2020

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. Methods: Sprague-Dawley rats (weight 150-180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. Results: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. Conclusions: NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

• Journal of Digestive Cancer Research
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• v.4 no.1
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• pp.32-35
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• 2016

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterized by profuse jelatinous materials in the abdominal cavity and pelvis with mucinous implants on the peritoneal surface. There are some studies for serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125), to assess the risk of recurrence following cytoreductive surgery and intraperitoneal chemotherapy. However, rare cases were reported about recurrence with increasing serum CEA levels. Herein, we report a case of recurrence of PMP according to serially elevated serum CEA.

• Journal of Gastric Cancer
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• v.18 no.4
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• pp.379-391
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• 2018

Purpose: Gastric cancer (GC) patients with peritoneal metastasis (PM) have poor prognosis. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with systemic chemotherapy is a novel treatment option for patients in stage IV of the disease. Materials and Methods: Between November 2015 and June 2018, prospective data collection was performed in 24 patients with GC and PM (median age, 57; range, 44-75 years). These patients underwent 46 PIPAC procedures with a median number of 2 interventions per patient (range, 1-6). A laparoscopic access was used and a combined therapy of cisplatin and doxorubicin aerosol was administered. Results: The median peritoneal carcinomatosis index before the 1st PIPAC was 14 (range, 2-36), and the median ascites volume in patients before the 1st PIPAC was 100 mL (range, 0-6 mL, 300 mL). Eleven patients, who received 2 or more PIPAC procedures, had decreased and stable volumes of ascites, while only 3 patients displayed increasing volume of ascites. The median overall survival was 121 days (range, 66-625 days) after the 1st PIPAC procedure, while 8 patients who received more than 3 PIPAC procedures had a median survival of 450 days (range, 206-481 days) (P=0.0376). Conclusions: Our data show that PIPAC is safe and well tolerated, and that the production of ascites can be controlled by PIPAC in GC patients. Patients, who received 2 or more PIPAC procedures, reported a stable overall quality of life. Further studies are required to document the significance of PIPAC as a palliative multimodal therapy.

• Journal of Haehwa Medicine
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• v.26 no.1
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• pp.25-32
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• 2017

Objectives : The purpose of this study is to investigate the effects of Hyangsayangwi-tang (Xiangshayangwei-tang) intravenous herbal acupuncture (HYT-IVHA) on emesis and gastric hypomotility induced by chemotherapy in rats. Methods : The experimental animals were randomly allocated into six groups (normal, cisplatin, saline, HYT-1, HYT-2, HYT-3), and each group included five rats. The rats in the normal group did not receive any treatment. Those in the cisplatin group had no additional treatment after intraperitoneal injection of cisplatin (7 mg/kg). Those in the saline group were injected with saline $0.4m{\ell}$ via the tail vein after the injection of cisplatin. Those in the HYT-1 group, HYT-2 group, HYT-3 group were injected with $0.4m{\ell}$ of Hyangsayangwi-tang (Xiangshayangwei-tang) intravenous herbal acupuncture solution (HYT-IVHAS) via tail vein after the injection of cisplatin, and the concentrations were 0.199 g/kg, 0.066 g/kg, 0.022 g/kg respectively. Then we measured body weight, food intake and kaolin consumption before and at 12h, 24h and 36h after the injection of cisplatin. The remaining amount of food within the rat's stomach was also measured at 36h after cisplatin injection. Results : Kaolin consumption was significantly increased in the cisplatin group compared to the normal group, while significantly reduced in HYT-1, HYT-2, HYT-3 groups compared to the cisplatin group. The remaining amount of food in stomach was significantly increased in the cisplatin group and HYT-1 group compared to the normal group, but significantly reduced in the HYT-3 group compared to the cisplatin group. Conclusions : HYT-IVHA has an therapeutic effect on chemotherapy-induced emesis and gastric hypomotility.

• Molecules and Cells
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• v.37 no.12
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• pp.865-872
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• 2014

Premature ovarian failure (POF) is a long-term adverse effect of chemotherapy treatment. However, current available treatment regimens are not optimal. Emerging evidence suggests that bone marrow-derived mesenchymal stem cells (BMSCs) could restore the structure and function of injured tissues, but the homing and restorative effects of BMSCs on chemotherapy injured ovaries are still not clear. In this study, we found that granulosa cell (GC) apoptosis induced by cisplatin was reduced when BMSCs were migrated to granulosa cells (GCs) in vitro. Chemotherapy-induced POF was induced by intraperitoneal injection of cisplatin in rats. BMSCs labeled with enhanced green fluorescent protein (EGFP) were injected into the rats via the tail vein to investigate the homing and distribution of BMSCs in vivo. The number of BMSCs in the ovarian hilum and medulla was greater than in the cortex, but no BMSCs were found in the follicles and corpus lutea. In addition, the BMSCs treatment group's antral follicle count and estradiol levels increased after 30 days, compared with the POF group. Hence, our study demonstrates that intravenously delivered BMSCs can home to the ovaries, and restore its structure and function in POF model rats.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.139-145
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• 2005

Gastric cancer is the most prevalent cancer in Korea and comprises the second cause of cancer death. Surgery only can provide chance of cure, but most locally advanced cancers recur after a curative resection, even though important advances in the surgical and nonsurgical treatments of gastric cancer have taken place. Preoperative chemotherapy theoretically can provide the advantages of reducing the bulk of tumor, which might improve the R0 resection rate, and of treating micrometastases early. Also, preoperative chemotherapy is expected to render unresectable tumors resectable without increasing postoperative morbidity and mortality. There are many new chemo-therapeutic agents available for the treatment of advanced gastric cancer, but still the most effective agent, the optimal time and number of cycle for administration are still not known. The addition of postoperative chemotherapy through an intraperitoneal route and/or radiotherapy might affect the outcome of surgery favorably, but that hasn't been proved yet. A multicenter prospective randomized phase III trial should be peformed to answer for those questions and to improve the curability of gastric cancer treatment.

• Journal of Veterinary Clinics
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• v.25 no.3
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• pp.182-186
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• 2008

An 11-year-old mixed breed male dog was presented with a thoracoabdominal wall mass of 3-year duration. Initial tentative diagnosis of osteosarcoma was made. Despite chemotherapy treatment, 72 days following the date of presentation, the dog was euthanized. Based upon necropsy and histopathologic findings, the tumor was definitely diagnosed as a combined type osteosarcoma of the rib. At necropsy examination, the tumor extended the left kidney and diaphragm, but distant metastasis was not found. The tumor's weight was 2.3kg and that was 38.3% of the dog's weight. This case report describes the clinicopathological, computed tomographic, histopathologic and immunohistochemical findings of extensive rib osteosarcoma in a small breed dog.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.291-299
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• 2020

Background: Ginseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg₁, Re, Rb₁, Rc, Rb₂, Rb₃, Rd, Rk₃, Rh₄, 20 (S)-Rg₃, 20 (R)-Rg₃, Rk₁, Rg₅, salidroside, and so on. Results: G, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-forming unit-granulocyte macrophage, burst-forming unit-erythroid, colony-forming unit-erythroid, and colony-forming unit-megakaryocyte and amount of G₂/M and S phase cells (P < 0.01). They also significantly decreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemical components in G-LLA changed, and the change of rare saponin was the most obvious. Conclusion: These results show that G-LLA herb pair might produce synergistic or complementary compatibility effects on bone marrow suppression after chemotherapy. It suggests that the substance basis of G-LLA for treating bone marrow suppression may be effective chemical components.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3907-3912
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• 2015

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.