• The Korean Journal of Pain
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• 제28권4호
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• pp.236-243
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• 2015

Background: Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. Methods: Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. Results: Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. Conclusions: Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain.

• The Korean Journal of Pain
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• 제33권4호
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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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• 제4권1호
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• pp.32-35
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• 2016

복막 가성점액종은 표준치료인 종양감축수술과 함께 복강 내 고온열 항암요법과의 병합치료로 생존율의 향상을 기대할 수 있다. 재발성 병변에 대해서는 추가적인 종양감축 수술이 권고되고 있지만, 치료시기에 따른 이환율과 사망률의 차이가 있어 조기발견이 중요하다. 수술 전 혈청 종양표지자 검사의 수치 이상 여부에 따른 재발과 생존율의 상관관계를 알아보고자 하는 연구들은 있지만, 추적관찰 중 수치 이상에 따른 재발여부에 관한 연구는 거의 없다. 저자들은 CSR과 HIPEC, 그리고 전신 항암화학요법을 시행받은 환자에서 CEA의 수치 상승이 질병의 재발과 상관관계가 있었음을 경험하였기에 보고하는 바이다.

• Journal of Gastric Cancer
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• 제18권4호
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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.

• 혜화의학회지
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• 제26권1호
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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.

• Journal of Gastric Cancer
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• 제24권3호
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• pp.246-256
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• 2024

Purpose: Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells. Materials and Methods: A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX. Results: Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%. Conclusions: The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system's potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.

• Molecules and Cells
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• 제37권12호
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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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• 제5권3호
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• pp.139-145
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• 2005

위암은 한국에서 가장 발생빈도가 높은 암이며 암 사망원인의 2위를 차지하고 있다. 치료법 중에서 수술이 유일하게 완치의 기회를 제공하나, 진행 암에서는 근치적 절제(R0 resection, R0 절제)수술 후에도 약 50%의 환자에서 재발을 보여, 보다 효과적인 치료법의 개발이 필요하다. 선행화학요법은 병소가 급격하게 성장, 팽창하는 것을 막고 내성을 지닌 세포의 출현을 예방하며 그렇게 함으로써 완치의 기회를 늘리고, 암의 국소 조절을 더 잘 함으로서 수술의 범위를 줄여 수술로 인한 부담을 줄이며, 절제 불가능한 암을 절제 가능한 암으로 만드는 것이 목표이다. 따라서 치유절제가 불가능할 것으로 판단되었던 위암의 병기를 낮추어 R0 절제 후 완치율을 높일 것으로 기대되고 있으며 계속되는 연구에서 수술로 인한 이환율과 사망률을 높이지 않는 것으로 나타나고 있다. 선행 화학요법에 사용할 수 있는 항암제는 여러 가지이나 가장 높은 효과를 보이는 항암제가 결정되지 않았고 또 항암제를 투여하는 시기, 선행 화학요법 후에 재발을 방지하기 위한 항암제의 복강 내 투여나 방사선 치료의 병용 등이 복막 전이와 국소재발을 줄이는 데 도움이 되는지 등이 향후 시행될 연구에서 규명되어야 하겠고, 또 적절한 수술방법에 관하여도 합의가 이루어져야 하겠다. 선행 화학요법과 관련된 여러 가지 의문들을 해결하기 위한 노력은 다기관이 참여하는 전향적 무작위 3상 임상연구를 통하여 이루어져야 할 것으로 생각된다.

• 한국임상수의학회지
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• 제25권3호
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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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• 제15권23호
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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.