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Sample records for intraarterial cisplatin infusion

  1. Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer

    OpenAIRE

    Homma, A; Sakashita, T; Yoshida, D; Onimaru, R; Tsuchiya, K; Suzuki, F; Yasuda, K; Hatakeyama, H; Furusawa, J; Mizumachi, T; Kano, S; Inamura, N; Taki, S; Shirato, H; Fukuda, S

    2013-01-01

    Background: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). Methods: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120mgm(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-...

  2. Intraarterial infusion of cisplatin with and without preoperative concurrent radiation for urinary bladder cancer. A preliminary report

    International Nuclear Information System (INIS)

    Monzen, Yoshio; Mori, Hiromu; Matsumoto, Shunro

    1995-01-01

    We evaluated the clinical efficacy of treating urinary bladder cancer by intraarterial infusion of cisplatin using an implanted reservoir with and without preoperative concurrent radiation. No previous reports have compared the results obtained by these two methods of treatment. Twenty-three patients with bladder cancer were treated by intraarterial infusion of cisplatin using an implanted reservoir with (n=13) and without (n=10) concurrent radiation. The cisplatin plus radiation group received intraarterial cisplatin at a total dose of 200-400 mg and concurrent radiation to a total dose to 30 Gy. The cisplatin group received intraarterial cisplatin at a total dose of 100-600 mg. In the cisplatin plus radiation group, the overall tumor response rate was 92%. Seven of 13 (53%) patients obtained complate response (CR), and the 2-year actuarial survival rate was 92%. Only one of the seven complete responders has had a local recurrence. In the cisplatin group, the overall tumor response rate was 90%. Four of 10 (40%) patients obtained CR, and median survival was 8 months. Three of the four complete responders have had local recurrence. There was no significant difference between these two groups in the frequency of side effects. Concurrent radiation therapy with intraarterial cisplatin resulted in a very low rate of recurrence of bladder cancer compared with intraarterial cisplatin therapy alone. This method was useful for urinary bladder cancer and may become the treatment of choice for this type of cancer. (author)

  3. Combined intraarterial cisplatin infusion and radiation therapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Mizoguchi, Hiroaki; Nomura, Yoshio; Terada, Katsuhiko; Nakagawa, Masayuki; Ogata, Jiro

    1995-01-01

    Twenty-three patients with invasive bladder cancer (T2 in 17, T3 in 6) were treated initially with combined intraarterial cisplatin infusion and radiation therapy. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was given. In 23 patients, 6 received additional cisplatin infusion and the other 17 had transurethral resection of bladder tumor (TURBT). Two of the patients undergoing total cystectomy exhibited a complete response (CR). Thus overall response rate was 87% (CR in 13 and partial response in 7). CR was achieved in 53% for T2 patients and 67% for T3 patients. CR was slightly higher in patients with non-papillary cancer than those with papillary one. Toxic reaction included a decrease in bladder capacity in 2 patients and severe diarrhea due to methicillin-resistant Staphylococcus aureus colitis in one. The other toxicities, including nausea, vomiting, neurotoxicity and myelosuppression, were tolerable. All except for one are alive. Seven patients had a local recurrence of bladder cancer. One patient developed invasive bladder cancer reaching the prostatic urethra. One other patient had recurrence at the same site as the previous tumor. Five others had superficial bladder cancer and were managed by TURBT. Bladder function was preserved in 65% at a mean follow-up of 29 months. In conclusion, the combined intraarterial cisplatin infusion and radiation therapy is useful for the initial treatment of invasive bladder cancer. (N.K.)

  4. Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer.

    Science.gov (United States)

    Homma, A; Sakashita, T; Yoshida, D; Onimaru, R; Tsuchiya, K; Suzuki, F; Yasuda, K; Hatakeyama, H; Furusawa, J; Mizumachi, T; Kano, S; Inamura, N; Taki, S; Shirato, H; Fukuda, S

    2013-12-10

    The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg m(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions. We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

  5. Treatment of advanced and recurrent squamous carcinoma of the uterine cervix with constant intraarterial infusion of cisplatin

    International Nuclear Information System (INIS)

    Rettenmaier, M.A.; Moran, M.F.; Ramsinghani, N.F.; Colman, M.; Syed, N.A.; Puthawala, A.; Jansen, F.W.; DiSaia, P.J.

    1988-01-01

    Twelve patients with primary or locally recurrent squamous carcinoma of the cervix were treated with constant internal iliac artery infusion of cisplatin (CDDP) via a totally implantable chemotherapy pump. Seven previously untreated patients received standard external and interstitial radiotherapy (RT) in conjunction with CDDP infusion. Five patients with isolated pelvic recurrences received CDDP therapy only. The chemotherapy pump was refilled weekly on an outpatient basis. All nine evaluable patients developed unilateral or bilateral lower extremity pain which responded to dosage reduction. No renal or marrow toxicity was seen. Both of the evaluable patients treated for recurrent tumor died 32 and 60 weeks after initiation of treatment. The seven patients treated primarily with RT + CDDP infusion include one who expired with persistent tumor and one with no evidence of disease (NED) after exenteration for a pelvic recurrence at 48 and 85 weeks respectively. The five remaining patients are NED at 12 to 60 weeks. Constant internal iliac artery infusion of CDDP via an implantable chemotherapy pump can be performed with acceptable toxicity. The preliminary results suggest that further study in previously untreated undergoing concurrent radiotherapy is warranted

  6. Selective intraarterial chemoradiation therapy for oropharyngeal carcinoma with high-dose cisplatin

    International Nuclear Information System (INIS)

    Nishio, Ryota; Saito, Kazuhiro; Ito, Hiroyuki

    2011-01-01

    Cisplatin has shown a high tumor response rate among head and neck carcinomas, and the tumor response is related to the cisplatin dosage. The purpose of this study was to evaluate the efficacy and toxicity of selective intraarterial chemoradiation therapy for oropharyngeal carcinomas with high-dose cisplatin. This retrospective study consisted of 21 patients with oropharyngeal carcinoma, stages II-IVB, in whom intraarterial chemoradiation therapy was performed between 2000 and 2008. All patients were given two courses of selective intraarterial infusions of cisplatin (300 mg/m 2 ), systemic chemotherapy with 5-fluorouracil, and simultaneous radiation therapy (58-61 Gy/30 fractions), with a 1-week rest period. The 2-year overall survival rate of the 15 patients who completed the therapeutic regimen was 71.3%. The 2-year locoregional control rate and disease-free survival rate were 95.0% and 67.7%, respectively. Selective intraarterial high-dose cisplatin chemotherapy with concomitant radiation therapy shows results similar to those of original methods in terms of survival and locoregional control with a reduction in the number of procedure times. (author)

  7. Superselective intra-arterial infusion of high-dose cisplatin combined with radiation therapy for head and neck carcinoma. Experience of Yamagata University Hospital

    Energy Technology Data Exchange (ETDEWEB)

    Hamamoto, Yasushi; Niino, Keiji; Ishiyama, Hiromichi; Koike, Shuji; Hosoya, Takaaki; Aoyagi, Masaru [Yamagata Univ. (Japan). School of Medicine

    2003-03-01

    Local effectiveness and complication of superselective intra-arterial infusion of high-dose cisdiamminedichloroplatinum (CDDP) (SIC) combined with radiation therapy (RT) were investigated. Between 1998 and 2000, 18 head and neck carcinomas including 10 maxillary carcinomas (T3; 1, T4; 9), 3 oral cavity carcinomas (T2; 1, T4; 2), and 5 oropharyngeal carcinomas (T2; 2, T4; 3) were treated with SIC and RT with or without surgery. CDDP of 100-150 mg/body was administered weekly in principle for 2-9 weeks (mean: 4.9) with the simultaneous administration of sodium thiosulfate. Radiation doses ranged from 40 Gy to 70 Gy (mean: 56.8 Gy). Complete response was obtained in 7 of 10 maxillary carcinomas, 2 of 3 oral-cavity carcinomas, and 2 of 5 oropharyngeal carcinomas, respectively. When surgical intervention was performed if necessary, 2-year local control rates for maxillary carcinoma, and other carcinoma including oral-cavity carcinoma and oropharyngeal carcinoma were 80% and 63% respectively. Two-year local control rates for T4 maxillary carcinoma, and other T4 carcinoma including oral-cavity carcinoma and oropharyngeal carcinoma were 78% and 40% respectively. Two-year overall survival rates for all cases, maxillary carcinoma, and oral-cavity/oropharyngeal carcinoma were 88%, 90% and 86% respectively. All local recurrences occurred within 6 months from the initiation of treatment. The systemic toxicity of weekly SIC was comparatively mild; however, a total CDDP dose of 1,000 mg or more and/or RT of 70 Gy induced complications of local soft tissue such as mucosal ulcer and fistula. SIC combined with RT is useful to improve the local control/survival rates and to avoid the aggressive surgery for locally advanced head and neck carcinoma. A high total dose of CDDP and/or RT of a comparatively high dose may be risk factors for local soft tissue complications. (author)

  8. Chemoradiotherapy using retrograde superselective intra-arterial infusion for advanced oral cancer

    International Nuclear Information System (INIS)

    Mitsudo, Kenji; Iwai, Toshinori; Mitsunaga, Sachiyo

    2011-01-01

    Concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion demonstrates good local control and overall survival rates due to the advantage of simultaneous infusion of anticancer agent with the synergistic effects of chemotherapy and radiotherapy. This study evaluated the therapeutic results, overall survival and local control rates in patients with advanced oral cancer treated with definitive concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion. A total of 688 patients with carcinoma of the head and neck were referred to our institution between January 2001 and December 2006. Among them, 175 patients with carcinoma of the oral cavity underwent definitive concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion. Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m 2 , cisplatin, total 125-150 mg/m 2 ) and daily concurrent radiotherapy (total 50-60 Gy) for 5-6 weeks. Four weeks after the completion of all treatments, patients underwent biopsy of the primary lesion and radiological examinations. Complete response (CR) of the primary site was achieved in 160 (91.4%) of the 175 patients. Residual disease at the primary site was seen in 15 patients (8.6%), and 14 patients (8.0%) showed local recurrence during follow-up. Five-year survival and local control rates were 71.6% and 82.2%, respectively. (author)

  9. A combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Okuno, Yumiko; Zaitsu, Masayoshi; Mikami, Koji; Takeuchi, Takumi; Matsuda, Izuru; Arahira, Satoko

    2017-01-01

    The gold standard for the treatment of muscle-invasive bladder cancer Without metastasis is radical cystectomy. However, there increase patients very elderly and with serious complications. They are not good candidates for invasive surgical operation. Intraarterial infusion of 70 mg/m 2 of cisplatin and 30 mg/m 2 of pirarubicin into bilateral bladder arteries was conducted for 5 patients diagnosed with muscle invasive bladder cancers without distant metastasis. Right and left distribution of anti-cancer drugs was determined based on the location of bladder tumor(s). External beam radiation therapy was commenced immediately following intraarterial infusion. The patients were followed up with clinical and radiographic investigations and bladderbiopsy was performed as needed. Patients were all males who are smoking or with smoking history ranging from 73 to 85 years of age (median 82). The duration between transurethral resection of bladder tumors (TUR-Bt) and intraarterial infusion of anti-cancer drugs was 47.4 days (range 26-68), the median follow-up period after intraarterial infusion was 21.5 months (range 87-547) without death. Total radiation dose was 59.2 ±3.0 Gy. Complete remission was accomplished in all cases. One patient showed intravesical recurrence of non muscle-invasive tumors 45.8 months following intraarterial infusion and underwent TUR-Bt. Two cases underwent bladder biopsies showing no tumors. All patients but one case with bladder recurrence were free of tumor recurrence with radiographic investigation. For adverse events, acute renal failure was in one case and leukocytopenia was in all 5 cases, Grade 2 for one and Grade 3 for 4 cases. Follow-up periods are not long enough, but early results of a combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer were good. (author)

  10. Intra-Arterial Chemotherapy with Doxorubicin and Cisplatin Is Effective for Advanced Hepatocellular Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ming-Chun Ma

    2014-01-01

    Full Text Available Advanced hepatocellular carcinoma (HCC remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m2 and cisplatin (50 mg/m2 infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I and those who received several cycles (group II. The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (P<0.0001. The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (P<0.0001. The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT.

  11. Intra-arterial cisplatin and concurrent radiation for invasive bladder cancer

    International Nuclear Information System (INIS)

    Miyanaga, Naoto; Ohtani, Mikinobu; Noguchi, Ryosuke

    1991-01-01

    Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6 Gy over 3 weeks) prior to a planned cystectomy. Cisplatin, in total 200 mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef.3 in 1 case, Ef.2 in 6. Ef.1b in 1 and Ef.1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there were no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated. (author)

  12. Intra-arterial cisplatin and concurrent radiation for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Miyanaga, Naoto; Ohtani, Mikinobu; Noguchi, Ryosuke (Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine) (and others)

    1991-10-01

    Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6 Gy over 3 weeks) prior to a planned cystectomy. Cisplatin, in total 200 mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef.3 in 1 case, Ef.2 in 6. Ef.1b in 1 and Ef.1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there were no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated. (author).

  13. Clinical effects and safety of intra-arterial infusion therapy of cisplatin suspension in lipiodol combined with 5-fluorouracil versus sorafenib, for advanced hepatocellular carcinoma with macroscopic vascular invasion without extra-hepatic spread: A prospective cohort study.

    Science.gov (United States)

    Nakano, Masahito; Niizeki, Takashi; Nagamatsu, Hiroaki; Tanaka, Masatoshi; Kuromatsu, Ryoko; Satani, Manabu; Okamura, Shusuke; Iwamoto, Hideki; Shimose, Shigeo; Shirono, Tomotake; Noda, Yu; Koga, Hironori; Torimura, Takuji

    2017-12-01

    Although sorafenib and hepatic arterial infusion chemotherapy (HAIC) have been proven to improve prognosis in hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MVI), the most appropriate approach remains unclear. The present multicenter, non-randomized, prospective cohort study aimed to compare the efficacy and safety of HAIC and sorafenib in patients with advanced HCC and MVI, without extra-hepatic spread (EHS) and Child-Pugh class A disease. The present study was performed between April 2008 and March 2014, and 64 HCC patients with MVI, without EHS and Child-Pugh class A disease were registered. Of these patients, 44 were treated with HAIC and 20 with sorafenib. HAIC involved cisplatin (50 mg fine powder in 5-10 ml lipiodol) and a continuous infusion of 5-fluorouracil (FU) (1,500 mg/5 days), which is referred to as new 5-FU and cisplatin therapy (NFP). The primary outcome was progression-free survival, and the secondary outcome was overall survival (OS). Clinical factors influencing OS and the therapeutic effect were identified using univariate and multivariate analyses. There were no differences in clinical factors between the two groups. The median progression-free survival was 5.1 and 9.5 months in the sorafenib and NFP groups, respectively (P=0.001). The complete response (CR) or partial response (PR) rates were 10 and 71% in the sorafenib and NFP groups, respectively (P<0.001). The median OS in the sorafenib and NFP groups was 13.2 and 30.4 months, respectively (P=0.013). Multivariate analysis revealed that the independent predictors of survival were Child-Pugh score (5, P=0.022, 95% CI, 0.191-0.892), grade of portal vein invasion (brunch, P=0.009, 95% CI, 0.220-0.752), and therapeutic effect (CR or PR, P<0.001, 95% CI, 0.220-0.752), and the independent predictor of therapeutic effect was therapeutic regimen (NFP, P<0.001, 95% CI, 0.006-0.199). NFP should be the first choice for patients with advanced HCC and MVI, without EHS and

  14. Apoptosis and histological response of preoperative intraarterial chemotherapy infusion for colorectal carcinoma

    International Nuclear Information System (INIS)

    Yuan Jianhua; Hu Tingyang; Yu Wenqiang; Chen Fanghong; Luo Zuyan; Mao Yinmin; Zhao Zhongsheng; Ru Guoqing; Deng Gaoli; Dong Quanjin; Tu Shiliang

    2003-01-01

    Objective: To investigate apoptosis and histological response of preoperative intraarterial chemotherapy infusion for colorectal carcinoma. Methods: Fifty patients with colorectal carcinoma were treated by intraarterial infusion of anti-cancer drugs. Surgical resection of the tumor was performed 5-30 days after the intraarterial infusion (mean 12 days). The histological response was evaluated. The density and distribution of the apoptosis cells were observed by DNA nick end labelling technique. 22 biopsy specimens before the intraarterial chemotherapy and 25 normal mucosa (obtained from surgery specimen) were used as controls. Results: The total histological response rate was 100% with grade I in 20 cases, grade II in 21 cases, and grade III in 9 cases. The density of the apoptosis cells was 31.47±5.58 before and 76.69±17.12 after the intraarterial chemotherapy infusion, and 8.01±3.39 in normal mucosa, respectively. The density of the apoptosis cells after the intraarterial chemotherapy was significantly higher than that before the intraarterial chemotherapy (t=13.701, P 2 =4.696, P>0.30). The apoptosis of adenocarcinoma was significantly different with different histological response (F=7.73, P 0.05) and for adenocarcinoma with different pathological stages (F=0.001376, P>0.05). Conclusion: As an effective and safe procedure, preoperative transcatheter intraarterial chemotherapy infusion achieves a significant histological response and apoptosis in colorectal adenocarcinoma

  15. Intra-arterial infusion of prostaglandin EI in Buerger's disease

    International Nuclear Information System (INIS)

    Kim, Yang Min; Park, Jae Hyung; Kim, Sang Joon

    1990-01-01

    In Buerger's disease, arterial occlusion is so peripheral that reopening procedure such as reconstructive vascular surgery, percutaneous transluminal angioplasty and local fibrinolysis are not feasible, and major amputation is the only alternative. Prostaglandin E1, a potent vasodilator and inhibitor of platelet aggregation, has been used to treat the patients with severe arterial occlusive disease. In three cases of Buerger's disease, who are manifested by resting pain, non-healing ischemic ulcer, or impending gangrene and who were not candidates for direct arterial reconstructive procedure, we infused Prostaglandin El intraarterially at a fixed dosage to evaluate its effectiveness. We report our experience with the use of this drug in relieving the ischemic symptoms, healing the intractable ulcer, or avoiding the major amputation

  16. Stages III and IV Squamous Cell Carcinoma of the Mouth: Three-Year Experience with Superselective Intraarterial Chemotherapy Using Cisplatin Prior to Definitive Treatment

    International Nuclear Information System (INIS)

    Hirai, Toshinori; Korogi, Yukunori; Hamatake, Satoshi; Nishimura, Ryuichi; Baba, Yuji; Takahashi, Mutsumasa; Uji, Yasuyoshi; Taen, Akira

    1999-01-01

    Purpose: This study was designed to assess the 3-year experience with superselective intraarterial chemotherapy prior to definitive treatment for stages III and IV squamous cell carcinomas of the mouth. Methods: Twenty-two patients prospectively received superselective intraarterial chemotherapy using relatively low-dose cisplatin via a transfemoral approach. The locations of the tumors were the tongue (n= 12), gingiva (n= 5), buccal mucosa (n= 2), hard palate (n= 1), floor of the mouth (n= 1), and lip (n= 1). After intraarterial chemotherapy, 21 patients underwent surgery (n= 14), radiation therapy (n= 6), or both (n= 1). The survival rate of 25 patients who underwent surgery with/without radiation therapy until 1992 at Kumamoto University Hospital was also evaluated as a historical control. The survival curve was calculated with the Kaplan-Meier method, and the statistical difference between survival curves was determined with the generalized Wilcoxon test. Results: The overall response rate was 95% [complete response (tumor completely resolved), 24%; partial response (tumor reduction ≥50%), 71%]. Fifty-two intraarterial infusions were performed without any catheter-related complications. Mild and transient local toxicity such as edema or mucositis of the infused area was relatively common. One patient died of renal failure from cisplatin. After a median follow-up of 20 months (range 2-41 months), the estimated 3-year survival rate for patients who underwent intraarterial chemotherapy plus surgery was 91%. The survival of the patients who underwent intraarterial chemotherapy plus surgery tended to be longer than that of the historical control. Conclusions: Early tumor reduction without delay of subsequent treatments can be obtained by intraarterial chemotherapy while minimizing complications and possibly improving survival. Further investigations of long-term survival with larger series need to be performed

  17. Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

    International Nuclear Information System (INIS)

    Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

    1996-01-01

    To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

  18. Drug selection principles in intra-arterial infusion chemotherapy

    International Nuclear Information System (INIS)

    Wang Gefang; Cheng Yongde

    2009-01-01

    The intra-arterial infusion chemotherapy is an effective treatment for malignant tumors. The following ten principles should be taken into account when the choice of infusion medication is to be made. (1) The tumor-sensitive drugs should be selected. (2) Pay attention to the compatibility of medicines. (3) Select the type of drug compatibility and drug interactions. (4) Concentration-dependent drugs are the drugs of first choice. (5) Pay attention to side effects when anti-cancer drug compatibility is considered.(6) The perfusion anti-cancer drugs exert their killing effect on the tumor cells in their prototype. (7) Pay attention to the administration order of the drugs and the intervals of treatment. (8) The medication should be individualized as the physical condition and tumor's heterogeneity are different from patient to patient. It is one of the fundamental principles to formulate a specific scheme for every given patient. (9) Make full use of the pharmacokinetics features of the anti-cancer drugs in clinical practice. (10) To be familiar with commonly used drugs and common tumor chemotherapeutic formulae is a matter of cardinal significance. (authors)

  19. Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Homma, Akihiro; Oridate, Nobuhiko; Suzuki, Fumiyuki

    2010-01-01

    The survival and functional outcome for hypopharyngeal cancer (HPC) still remains poor despite aggressive standard treatment involving debilitating surgery and postoperative radiation therapy. We reviewed our experience in the management of advanced HPC using rapid superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT) as organ preservation therapy. Twenty-one previously untreated patients with HPC were given superselective intra-arterial infusions of cisplatin (100-120 mg/m 2 /week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and conventional external beam radiotherapy from 2000 through January, 2009. During the median follow-up period of 43 months, the 5-year overall survival and local control rate were 42.8% and 77.8%, respectively. All patients with N0-1 (n=10) are alive without disease so far. However, the 5-year overall survival of patients with N2b-3 (n=24) were 19%. It is not technically easy and sometimes dangerous to treat patients with HPC by intra-arterial chemotherapy. Recently, we consider that patients with T3-4a and N0-1, and primary tumor limited in one side are good candidate for RADPLAT. (author)

  20. Endovascular Hypothermia in Acute Ischemic Stroke: Pilot Study of Selective Intra-Arterial Cold Saline Infusion

    NARCIS (Netherlands)

    Chen, Jian; Liu, Liqiang; Zhang, Hongqi; Geng, Xiaokun; Jiao, Liqun; Li, Guilin; Coutinho, Jonathan M.; Ding, Yuchuan; Liebeskind, David S.; Ji, Xunming

    2016-01-01

    We conducted a pilot feasibility and safety study of selective brain cooling with intra-arterial infusion of cold saline combined with endovascular reperfusion for acute ischemic stroke. Patients with large-vessel occlusion within 8 hours after symptom onset were enrolled. All patients received

  1. Effects of intra-arterial infusion therapy or systemic chemotherapy with docetaxel for VX2 tumor in rabbit hind limb

    International Nuclear Information System (INIS)

    Qian Yuanxin; Wu Xiaomei; He Miao; Liu Tao; Deng Duo

    2010-01-01

    Objective: To discuss the efficacy and safety of intra-arterial infusion therapy with docetaxel. Methods: Animal model of VX2 tumor in rabbit hind limb was set up. Intra-arterial infusion therapy or systemic chemotherapy with docetaxel was performed. Concentrations of docetaxel in VX2 tumor, wall of stomach, liver, kidney and plasma of rabbits with VX2 tumors in hind limbs were determined. Difference of drug concentrations between intra-arterial infusion therapy and systemic chemotherapy was compared using Student t-test. Results: Concentrations of docetaxel in VX2 tumor and wall of stomach of rabbits with intra-arterial infusion therapy were significantly higher than those with systemic chemotherapy (p<0.05). The drug concentration in VX2 tumor of rabbits with intra-arterial infusion was 14 times higher than that with systemic chemotherapy. Concentration of docetaxel in plasma of rabbits with intra-arterial infusion therapy was not significantly lower than that with systemic chemotherapy (P<0.05). Conclusion: Intra-arterial infusion therapy with docetaxel for tumor is effective. However, there is increased risk of toxicity and the dose should adjusted accordingly. (authors)

  2. Intra-arterial cis-diamminedichloroplatinum infusion treatment for widespread hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Park, Sung Il; Yang, Hee Chul; Lee, Do Yon; Shim, Yong Woon; Kim, Sang Heum; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik

    1997-01-01

    The purpose of this study is to evaluate the therapeutic efficacy of intra-arterial infusion of Cis-diamminedichloroplatinum (C-DDP) for the treatment of hepatocellular carcinomas with widespread involvement. We retrospectively analyzed 22 patients who between July 1994 and June 1996 had undergone intra-arterial c-DDP infusion therapy for the treatment of hepatocellular carcinomas with widespread involvement. The hepatomas involved both lobes in ten, portal venous obstructions in fourteen, arterio-portal shunts in nine, and arterio-venous shunts in two. Proper hepatic artery was selected for infusion of 100 mg/BSA of C-DDP. The same procedure was repeated every 3 to 4 weeks, and the total number of infusions was 65. On the basis of WHO criteria, response was classified as complete remission, partial remission, stable, or progression of the disease. Six-month and one-year survival rates were estimated, and adverse reactions were evaluated. Although the response rate is not high, intra-arterial C-DDP infusion therapy can be used as an alternative treatment for hepatocellular carcinomas with widespread involvement; adverse reactions are tolerable. (author). 16 refs., 3 figs

  3. Radiotherapy with concomitant carboplatin (CBDCA) vs cisplatin (CDDP) and superselective arterial infusion of decadose CDDP

    International Nuclear Information System (INIS)

    Homma, Akihiro; Furuta, Yasushi; Nagahashi, Tatsumi

    2003-01-01

    We compared the effectiveness between carboplatin (CBDCA) and cisplatin (CDDP) as a single-agent chemotherapy and concomitant radiotherapy in operable head and neck cancer by a prospective randomized trial. The CBDCA-treated group (n=60) showed significantly better 5-year local control rate (56.2%) than the CDDP-treated group (n=59, 35.5%, p=0.03). There was no difference in toxicities, which were considered acceptable. We suggest choosing weekly CBDCA rather than daily low-dose CDDP as a chemotherapeutic agent for concomitant chemoradiotherapy in patients with operable cancer, although a dose of CDDP may be too small. Superselective arterial infusion for patients with advanced head and neck cancer has increasingly applied in Japan. We analyzed our experiences and evaluated the efficacy and safety of this treatment. Twenty nine patients received superselective intra-arterial infusion therapy of cisplatin (100-120 mg/m 2 /week) and conventional concomitant extrabeam radiotherapy. Two year overall survival rate was 42.9%. The primary lesions were well controlled in 21 patients (72.4%). High-frequent acute toxic effects were leukopenia and mucositis. Severe toxic events occurred in three cases, namely, methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, sepsis, and tetraplasia. We confirmed the effectiveness and safety of superselective arterial infusion and concomitant radiotherapy. Furthermore, we must establish the optimal procedures and schedule, as well as the indications for this treatment. This treatment protocol expected the cure of patients with unresectable disease and patients rejecting surgical treatment. (author)

  4. Guide to intra-arterial infusion chemotherapy for pancreatic cancers (draft text)

    International Nuclear Information System (INIS)

    2012-01-01

    Pancreatic cancer is one of most malignant solid tumors. Trans-arterial infusion chemotherapy has been used for the inoperable pancreatic cancers. The local drug concentration in intra-arterial infusion chemotherapy is much higher than that in intravenous chemotherapy. Thus, a better therapeutic effect can be surely achieved, the disease-related symptoms can be well improved, the patient's survival time can be markedly prolonged, and the liver metastases can be effectively reduced. This paper aims to suggest a more detailed and standardized therapeutic scheme to perform intra-arterial infusion chemotherapy for inoperable pancreatic cancers, focusing on the relevant concept, contraindications, indications, preoperative preparation, methods of operation, postoperative treatment, the prevention and treatment of complications, etc. The scheme will help domestic interventional physicians to make reasonable decisions in their clinical practice. Of course, the scheme proposed here is not a mandatory standard, and it can not resolve all the problems which might be encountered in employing intra-arterial infusion chemotherapy for patients with inoperable pancreatic cancer. Therefore, the interventional physicians should fully understand the most useful medical evidence of a given patient and sincerely take the patient's own will into consideration before an individualized and reasonable therapeutic plan is able to be worked out. (authors)

  5. Intraarterial infusion chemotherapy for the treatment of metastatic liver cancer

    International Nuclear Information System (INIS)

    Arai, Yasuaki; Kido, Choichiro

    1987-01-01

    Some techniques of the most recent interventional radiology are very useful for the treatment of metastatic liver cancer and changing the style of hepatic infusion chemotherapy. This report shows our latest results and methods of hepatic infusion chemotherapy for metastatic liver cancer. 1. For the catheter placement, a new catheterization route via the left subclavian artery into the hepatic artery was developed and performed in 132 cases. Superselective catheterization succeeded in 123 cases (93.2 %). This procedure is less invasive than laparotomy and less troublesome than other percutaneous routes. 2. For useful infusion system, an implantable injection port ''Reservoir'' was developed and it was used in 87 cases. This method makes arterial infusion chemotherapy easy, and imploves their quality of life. 3. To acquire adequate drug delivery, arterial redistribution by steel coils was done, and 109 arteries in 80 cases were occluded. This method is very useful to make multiple hepatic artery single and it is important to avoid gasroduodenal complications. 4. Now, using these techniques, the phase II study of 5FU, ADM, MMC combined hepatic infusion in patients with non-resectable metastatic liver cancer is done. Up to this time, such a phase study on arterial infusion chemotherapy was difficult because of technical problems, but these new techniques make it possible. In conclusion, these new methods change the style and conception of hepatic infusion, and these make much progress on the treatment of patients with metastatic liver cancer. (author)

  6. [Plasma platinum concentration and anti-tumor effects after intra-arterial infusion of lipiodol-CDDP suspension evaluation with VX 2 rabbit liver cancer model and 7.0 Tesla MRI system].

    Science.gov (United States)

    Sonoda, Akinaga; Nitta, Norihisa; Ohta, Shinichi; Itoh, Ryuta; Takahashi, Masashi; Murata, Kiyoshi; Morikawa, Shigehiro; Inubushi, Toshiro; Miyagawa, Yoshihiro; Takamori, Michie; Oonaka, Yasuo

    2006-07-01

    To evaluate the usefulness of combination chemotherapy with cisplatin powder, which was newly designed for intra-arterial infusion (IA CALL) and lipiodol, for the VX 2 liver cancer model of the rabbit, sequential change of the plasma platinum concentration within the first 24 hours, as well as the tissue platinum concentration at 24 hours was measured after intra-arterial infusion of IA CALL. The infused materials were either IA CALL alone (C) or the combination of lipiodol+IA CALL (CL). In addition,the reduction rate of the VX 2 tumor was calculated among four therapeutic groups (C, CL, lipiodol alone (L), and saline alone (S)) after one week of intra-arterial infusion on the basis of 7.0 Tesla MR images. Total plasma platinum concentrations within the first 24 hours were kept low in group CL. No increase in the tissue platinum concentration in group CL was observed. On the other hand, the tumor reduction rate tended to be higher in group CL (group CL>group L=group C>group S). These results suggested that the intra-arterial infusion of IA CALL with lipiodol is more effective than that of IA CALL alone.

  7. Intraarterial digital subtraction angiography in bronchogenic carcinoma treated with bronchial artery infusion

    International Nuclear Information System (INIS)

    Gao-Jun Teng; Xi-Lei Chai; Guang-Ru Gao; Cheng-Fong Chu; Xian-Guang Zhou; Zhu-Yi Zhang; Ru-Li Xiang

    1991-01-01

    Intra-arterial digital subtraction angiography (IADSA) has been used with advantage for control of the results of bronchial artery infusion of drugs for primarily unresectable bronchogenic carcinoma. The IADSA has been performed as road mapping prior to therapy. Drug treatment has been performed with 4 different regimes, depending on tumour type. Debulking and in some cases complete healing are the results, which are superior to other reported treatments. (author). 7 refs.; 4 figs.; 3 tabs

  8. Intra-Arterial Prostaglandin E1 Infusion in Patients with Rest Pain: Short-Term Results

    Directory of Open Access Journals (Sweden)

    A. Chatziioannou

    2012-01-01

    Full Text Available Purpose. To present our results after short-term (1 month intra-arterial infusion therapy of PGE1-alprostadil via a port system implanted in the ipsilateral external iliac artery (EIA in patients with severe rest pain. Methods. Ten patients with severe rest pain were included. All patients showed extensive peripheral vascular disease below the knee. The tip of the catheter was introduced via a retrograde puncture in the ipsilateral external iliac artery (EIA. The patients received intraarterial infusion of PGE1, 20 mgr alprostadil daily, via the port catheter for 1 month. Results. Clinical success was evaluated according to subjective grading of pain (group A significant decrease, group B moderate decrease and group C no response. A significant decrease of rest pain was observed in 8 (group A, 80% patients, a moderate decrease in 2 (Group B, 20%, whereas no patients demonstrated any significant response. Both patients of group B had Buergers' disease and continue to smoke during therapy. No peripheral thrombosis or clinical deterioration was noticed. Conclusion. Intraarterial infusion of PGE1 alprostadil on a daily basis, using a port catheter into the ipsilateral EIA, in selected patients with severe rest pain, seems to be very effective, without any serious complications.

  9. Intra-arterial cisplatin and concurrent radiation in the treatment of invasive bladder cancer in the elderly: 10 years of experience

    International Nuclear Information System (INIS)

    Eapen, L.; Stewart, D.; Grimard, L.; Crook, J.; Aref, I.; Huan, S.; Futter, N.; Rasuli, P.; Peterson, R.

    1998-01-01

    Analysis of the results obtained in elderly (75 years and older) included a phase II trial combining intra-arterial cisplatin and concurrent radiation into invasive bladder cancer. Thirty-five patients (28 males and 7 females) were accrued from 1985 to 1996. There were 1 Ta, 4 T2, 11 T3A, 12 T3B, 3 T4A, and 4 T4B patients. Nine had unilateral hydronephrosis and two bilateral hydronephrosis. There were 28 trans-urethral resections which were incomplete in 23 patients. Intra-arterial cisplatin was given as 2-4 hours infusion (60-90 mg/m 2 ) split through both internal iliac arteries on day 1, 14, 21, and 42. Irradiation to the pelvis was started on day 14 and consisted of 40 Gy/20 fractions followed by a boost of 20 Gy/10 fractions to the tumor with margins of 2 cm. Thirty (86%) completed fully the protocol. One patient died from sepsis secondary to the treatment. The tumor response was evaluable in 29 patients and complete response was observed for 27> of them. Five of these 27 patients had an isolated bladder relapse which was salvaged by by cystectomy in two patients. There were 11 deaths from bladder cancer (31% of the patients): 9 from deaths metastases, one from local failure, and one from treatment. This combined modality yields excellent results with high complete response rate and good tolerance. This approach may therefore be particularly appropriate for the elderly. (author)

  10. Pilot study of intra-arterial cisplatin and intravenous vinblastine and dacarbazine in patients with melanoma in-transit metastases.

    Science.gov (United States)

    Eton, O; East, M; Legha, S S; Bedikian, A; Buzaid, A C; Papadopoulos, N; Hodges, C; Gianan, M; Carrasco, C H; Benjamin, R S

    1999-10-01

    For melanoma, in-transit metastases (ITMs) are a harbinger of systemic disease in over 70% of patients and thus warrant a systemic approach to management. In this study, previously untreated patients with ITMs (n=15) received a systemic regimen of 'CVD' in 21 day cycles (median, three cycles) as follows: dacarbazine 800 mg/m2 intravenously (i.v.) on day 1, vinblastine 1.6 mg/m2 i.v. on days 1-5, and cisplatin (CDDP) 100 mg/m2 by 24 h intra-arterial (i.a.) infusion in 1l of heparinized saline via the iliac or subclavian artery on day 3. There were three clinical complete responses (CRs) in patients with a modest burden of ITMs (< 3 cm in size) and seven partial responses (PRs), yielding a 67% response rate (95% confidence interval, 38-88%). One of the clinical CRs had microscopic residual disease at surgery (a pathological PR). The times to progression (TTP) for the CRs were 5, 21 and 38+ months; the median TTP for the PRs was 4.5 months (range, 2-10 months). Overall median survival was 31 months. Systemic toxicities were similar to those induced by i.v. CVD. However, patients noted more pronounced paraesthesia in the infused extremity. Also, two patients experienced severe CDDP-induced burns, one patient developed brachial plexopathy, and one patient had a haemorrhage in an occult brain metastasis. The high clinical activity of this regimen will have to be confirmed in more patients before a first-pass i.a. advantage can be claimed. Furthermore, the dose, schedule and technique of i.a. CDDP delivery must be further refined before it can be routinely incorporated in regimens as an alternative to isolated regional hyperthermic perfusion, which is technically more difficult and is not readily available in community-based hospitals.

  11. Hepatic arterial infusion therapy with a fine powder formulation of cisplatin for advanced hepatocellular carcinoma with portal vein tumor thrombosis

    International Nuclear Information System (INIS)

    Kondo, Masaaki; Morimoto, Manabu; Numata, Kazushi; Nozaki, Akito; Tanaka, Katsuaki

    2011-01-01

    We retrospectively evaluated the antitumor effect, survival and toxicities of hepatic arterial infusion therapy using a fine powder formulation of cisplatin (cisplatin powder) in hepatocellular carcinoma patients with portal vein tumor thrombosis. Twenty-four patients classified as Child-Pugh class A or B underwent a single session of hepatic arterial infusion therapy using cisplatin powder. The treatment was repeated every 4-6 weeks in patients with no evidence of tumor progression or unacceptable toxicity. The treatment response was evaluated using contrast-enhanced computed tomography performed 1 month after each treatment. The survival rate was evaluated using the Kaplan-Meier method, and predictors of a better outcome were identified using univariate analysis. The mean follow-up period was 11.2 months (range, 1.3-44.2 months). A total of 57 sessions of intra-arterial infusion (1-6 sessions per patient; mean, 2.4 sessions) with cisplatin powder were performed. A complete response and a partial response were obtained in one and four patients, respectively (objective response rate=20.8%). The median survival time for all the patients was 7.0 months; the median survival times for the 5 responders and 19 non-responders were 37.3 and 5.6 months, respectively. The 1- and 2-year survival rates were 38% and 16%, respectively. Significant prognostic factors related to survival were the therapeutic effect, patient age and serum alanine aminotransferase level. Severe adverse reactions resulting in treatment discontinuation were not observed, and all the toxicities were successfully managed using conservative treatment. Hepatic arterial infusion therapy with a fine powder formulation of cisplatin was safe, well-tolerated and might help to prolong the life span of advanced hepatocellular carcinoma patients with portal vein tumor thrombosis. (author)

  12. Long-term results of the maxillary sinus carcinoma with irradiation and intraarterial infusion of 5-FU

    International Nuclear Information System (INIS)

    Sakaguchi, Masanori; Netsu, Kiminori; Kawarada, Kazuo; Yachiyama, Hitoshi.

    1990-01-01

    Therapeutic results of 33 primary cases of maxillary sinus carcinoma treated with irradiation and intraarterial infusion of 5-FU between 1972 and 1984 were analyzed. The 5-year crude survival rate for the group with stage T2 carcinoma (n=10) was 50.0%, and for those with T3 (n=15) and T4 (n=8) it was 46.7% and 25.0%, respectively. The overall 5-year crude survival rate was 42.4%. Eight patients who did not undergo maxillectomy survived for 5 years after irradiation and intraarterial infusion. Recurrence of the tumor after the irradiation and intraarterial infusion occurred in 63.6%, and was frequently observed at the ethmoidal region and the orbita. In the areas in which the tumor extended to regions such as the ethmoid sinus and orbita, which are nourished by arteries other than the maxillary artery, conventional intraarterial infusion was ineffective for complete tumor eradication. Therefore, in most of the patients with advanced maxillary sinus carcinoma, partial or total maxillectomy following combined therapy of intraarterial infusion and irradiation is necessary to improve a prognosis. (author)

  13. Local Intraarterial Thrombolysis: In Vitro Comparison Between Automatic and Manual Pulse-Spray Infusion

    International Nuclear Information System (INIS)

    Froelich, Jens J.; Freymann, Christina; Hoppe, Martin; Thiel, Thomas; Wagner, H. Joachim; Barth, Klemens H.; Klose, Klaus J.

    1996-01-01

    Purpose: Manual and automatic pulse-spray infusion techniques are compared in vitro to evaluate the efficacy of thrombolysis and the distribution of urokinase and saline solution within thrombus using a pulse-spray catheter. Methods: A pulse-spray catheter was introduced into a human thrombus within a stenotic flow model. Automatic and manual pulsed infusion of urokinase and automatic pulsed infusion of saline solution were compared. To quantify the efficacy of thrombolysis, pressure gradients were recorded proximal and distal to the thrombus and during the course of infusion. Distribution of infused urokinase was assessed radiographically. Results: The fastest and most homogeneous dissolution of the thrombus was achieved with automatic pulsed infusion of urokinase, shown by decreasing transthrombotic pressure gradients (p < 0.001, Wilcoxon, matched pairs). Manual pulsed infusion of urokinase or saline solution resulted in inhomogeneous thrombus dissolution and delayed thrombolysis. Conclusion: Application of automatic pulse-spray injectors seems beneficial for more effective and homogeneous intraarterial pulse-spray thrombolysis when compared with conventional manual pulsed technique

  14. The availability of DSA used continuous intraarterial infusion tubes founded various malignancy

    International Nuclear Information System (INIS)

    Minakuchi, Kazuo; Kobayashi, Nobuyuki; Yamada, Tetsuya

    1987-01-01

    DSA was employed using continuous intraarterial infusion tubes for various malignancies (73 cases) which were examined a total of 135 times. In head and neck malignancy (50 cases), the general position of the infusion tube had been determined beforehand by dye infusion, but DSA from the tube showed that the tubes in 24 cases (48 %) were located in the wrong position, especially in tongue cancer (21 cases) where many tubes were discovered to be in an erroreous position (71 %) such as the common carotid artery. We were unable to determine the effect of chemotherapy and radiation using DSA only. In 9 cases of breast cancer for which fixation of the tube was not attempted under X-ray fluoroscopy, 7 (78 %) showed an unusual tube position such as the intraaortic arch. In 5 cases of abdominal malignancy, only the tube position for sigmoid colon cancer was unusual. We were able to observe the effect of chemotherapy by DSA in 2 cases. For DSA in one out of 3 hepatomas using a Port-A-Cath, we observed that infusion of anticancer drug with degradable starch microspheres caused a reduction in tumor size. However, in the two remaining cases, we were unable to observe any effect of infusion of these drugs by DSA for various mechanical reasons. DSA from an infusion tube revealed not only the location of the tube accurately and promptly, but also the effect of chemotherapy. (author)

  15. Thermochemoradiation Therapy Using Superselective Intra-arterial Infusion via Superficial Temporal and Occipital Arteries for Oral Cancer With N3 Cervical Lymph Node Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Mitsudo, Kenji, E-mail: mitsudo@yokohama-cu.ac.jp [Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Koizumi, Toshiyuki; Iida, Masaki; Iwai, Toshinori; Oguri, Senri [Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Yamamoto, Noriyuki [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya (Japan); Itoh, Yoshiyuki [Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Kioi, Mitomu; Hirota, Makoto; Tohnai, Iwai [Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-08-01

    Purpose: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer. Methods and Materials: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m{sup 2}; CDDP, total 100-150 mg/m{sup 2}) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks. Results: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971;1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively. Conclusions: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3

  16. Changes in MR imaging appearance of breast cancer after intra-arterial infusion chemotherapy

    International Nuclear Information System (INIS)

    Kitamura, Kouji; Yoshioka, Hiroyasu; Tanigawa, Noboru; Makino, Shigeru; Hanai, Jyun; Tatsuta, Masayuki; Yoshimura, Hideaki

    2000-01-01

    The purpose of this study was to evaluate whether the characteristic change in breast cancer related to chemotherapeutic response (CR) and the effect of invasion and toxicity in the skin and pectoralis muscle exist on MR imaging after intra-arterial infusion chemotherapy. A total of 11 patients with histologically proven breast cancer underwent MR study before and after chemotherapy. Changes in images and the dynamic curveafter-chemotherapy were evaluated, including time to maximum signal intensity (SI) and the early phase enhance ratio (EPER) in the tumor. In the tumor, changes in the dynamic curve, time to maximum SI, EPER and necrosis did not correlate with CR, but change in SI on T2-weighted images was suggested to do so. Changes in the dynamic curve and images in the pectoralis muscle and in images on the skin were suggested to correlate with CR. In addition, images changed for the worse in many cases of invasion and toxicity in the pectoralis muscle and in some cases of invasion in the skin. In conclusion, tumors had fewer imaging changes correlating with CR after intra-arterial infusion chemotherapy. Changes for the worse in images of the pectoralis muscle and skin may be useful for the evaluation of invasion. (author)

  17. Combined intra-arterial infusion and systemic chemoradiotherapy for stage IV squamous cell carcinoma of the mandibular gingiva

    International Nuclear Information System (INIS)

    Nakasato, Tatsuhiko; Akahane, Akio; Kikuchi, Koyo; Ehara, Shigeru; Izumisawa, Mitsuru; Shoji, Satoru; Kogi, Shintaro; Mizuki, Harumi; Sugiyama, Yoshiki

    2012-01-01

    The purpose of this study was to show the effectiveness of combining intra-arterial infusion and systemic chemotherapy with concurrent radiotherapy for treatment of stage IV mandibular gingival cancer. A total of 23 patients with mandibular gingival cancer were treated with either docetaxel by intra-arterial infusion followed by systemic chemoradiotherapy with cisplatinum and 5-fluorouracil as a monthly regimen, or with docetaxel and cisplatinum by intra-arterial infusion followed by systemic chemoradiotherapy with 5-fluorouracil as a weekly or biweekly regimen. Tumor responses, locoregional control, overall survival, disease-specific survival, and adverse events were evaluated. Of the 23 patients enrolled in the study, 22 completed the treatment. With regard to clinical stages, 82% were diagnosed as IVA and 18% IVB. Complete and partial response was observed in 82 and 18%, respectively. Five-year overall survival, disease-specific survival, and locoregional control were 51, 70, and 72%, respectively. No statistically significant difference was seen between the monthly regimen and the weekly plus biweekly regimen, although the latter resulted in longer survival and 88% control. Combined intra-arterial infusion and systemic chemoradiotherapy may be an effective treatment for patients with stage IV mandibular gingival cancer. (author)

  18. Changes in distribution of hepatic blood flow induced by intra-arterial infusion of angiotensin II in human hepatic cancer

    International Nuclear Information System (INIS)

    Sasaki, Y.; Imaoka, S.; Hasegawa, Y.

    1985-01-01

    Changes in the distribution of the hepatic blood flow induced by intra-arterial infusion of angiotensin II (AT-II) were studied in human hepatic cancers using extremely short-lived radioisotope (RI) (krypton 81 m [/sup 81m/Kr]; half-life, 13 seconds). After the start of continuous infusion of AT-II, the radioactivity of the tumor showed about a two-fold increase, whereas that of the nontumor region decreased to about one half as much as the level before the infusion. Consequently, the mean ratio of the arterial blood flow in the tumor region to that in the nontumor region (T/N ratio) increased to 3.30 (P less than 0.001). The T/N ratio showed a peak before the peripheral blood pressure reached the maximum, and thereafter tended to decrease. Intra-arterial infusion of AT-II raised the T/N ratio more obviously than did intravenous infusion of the drug, with less rise in the peripheral blood pressure. It is believed that intra-arterial infusion chemotherapy with local use of AT-II enables better accessibility of chemotherapeutic drugs to tumors

  19. Intra-arterial infusion of prostaglandin EI in Buerger's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yang Min; Park, Jae Hyung; Kim, Sang Joon [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    1990-10-15

    In Buerger's disease, arterial occlusion is so peripheral that reopening procedure such as reconstructive vascular surgery, percutaneous transluminal angioplasty and local fibrinolysis are not feasible, and major amputation is the only alternative. Prostaglandin E1, a potent vasodilator and inhibitor of platelet aggregation, has been used to treat the patients with severe arterial occlusive disease. In three cases of Buerger's disease, who are manifested by resting pain, non-healing ischemic ulcer, or impending gangrene and who were not candidates for direct arterial reconstructive procedure, we infused Prostaglandin El intraarterially at a fixed dosage to evaluate its effectiveness. We report our experience with the use of this drug in relieving the ischemic symptoms, healing the intractable ulcer, or avoiding the major amputation.

  20. Outcome evaluation of intra-arterial infusion of urokinase for acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Hai Bin [First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Suh, Dae Chul; Lim, Soo Mee [Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of); And Others

    2000-06-01

    To evaluate the results of intra-arterial urokinase thrombolysis in cases of acute ischemic stroke and to define the factors affecting prognosis. Forty-eight patients with angiographically proven occlusion of the intracranial arteries were treated with local intra-arterial infusion of urokinase within six hours of the onset of symptoms. Neurologic status was evaluated on admission and on discharge using the NIH (National Institute of Health) stroke scale score (SSS). When the SSS decreased by at least four points, this was considered indicative of an improved clinical outcome. Complete recanalization was achieved in 17/48 patients (35%), including 8 of 13 (62%) with occlusion of the vertebrobasilar artery (VBA), 9 of 20 (45%) with occlusion of the middle cerebral artery (MCA), and none of 15 with occlusion of the internal carotid artery (ICA). Neurologic status improved in 12 (60%) of patients with MCA occlusion, in five (38%) of those with VBA occlusion and in three (20%) of those with ICA occlusion (p less than 0.005). Patients in whom occluded MCA was completely recanalized showed greater clinical improvement than those with partial or no recanalization (p less than 0.05). The overall mortality rate was 21%, 43% (9/21) in patients in whom CT revealed signs of early infarct, but only 4% (1/27) in those without this sign (p less than 0.05). The mortality rate of patients with parenchymal hematoma (4/5) was higher than that of those with hemorrhagic infarct (3/9) or without hemorrhage (3/34) (p less than 0.005). In patients in whom occluded MCA was completely recanalized, the clinical outcome was better, while patients with VBA occlusion did not benefit from recanalization. The presence on CT scans of signs of early infarct and of parenchymal hematoma after thrombolysis correlated with a high mortality rate. (author)

  1. Brain SPECT by intraarterial infusion of 99mTc-HMPAO for assessing the cerebral distribution of carotid artery infusions in patient with brain tumor

    International Nuclear Information System (INIS)

    Kosuda, Shigeru; Kusano, Shoichi; Aoki, Shigeki

    1993-01-01

    In order to assess the cerebral distribution of intracarotid chemotherapy, 17 postoperative patients with brain tumor underwent brain SPECT obtrained by intraarterial infusion of 18.5 MBq of 99m Tc-d,l,-hexamethylpropyleneamine oxime ( 99m Tc-HMPAO). Injection methods were continuous (5.0 ml/min) or pulsatile infusion with supra- or infraophthalmic catheterization. The findings obtained by brain SPECT were frequently different from those of angiography and/or DSA. In supraophthalmic catheterization with continuous infusion, only 2 of 10 studies (20%) had homogeneous distribution and 5 of them (50%) had maldistribution of 99m Tc-HMPAO which appears in association with laminar flow effect. The remaining 3 studies showed localized distribution (two: tumor localization, one: healthy brain localization). On the other hand, all of 5 studies with pulsatile infusion had homogeneous distribution of 99m Tc-HMPAO. In infraophthalmic catheterization, all but one of 5 studies had homogeneous distribution with continuous infusion. These results suggest that pulsatile infusion may be effective in eliminating maldistribution of 99m Tc-HMPAO in supraophthalmic catheterization. In conclusion, we are convinced that 99m Tc-HMPAO is a useful intraarterial agent for assessing cerebral distribution of intracarotid chemotherpay. (author)

  2. Efficacy of superselective intra-arterial infusion chemotherapy with concomitant radiotherapy for advanced hypopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Bandoh, Nobuyuki; Takahara, Miki; Moriai, Shigetaka; Katayama, Akihiro; Katada, Akihiro; Hayashi, Tatsuya; Harabuchi, Yasuaki; Nagasawa, Kenichi

    2008-01-01

    Patients with advanced hypopharyngeal carcinoma still have a poor outcome in spite of radical surgery with chemoradiotherapy. We started superselective intra-arterial infusion chemotherapy with concomitant radiotherapy (IA chemoradiation) for advanced hypopharyngeal carcinoma in 2003. The complete response (CR) rate for local and neck lesions was 94.1% and 60%, respectively. After neck dissection the total CR rate was 82.4%. There was no significant difference in survival rates between groups with IA chemoradiation (n=22) and with surgery with preoperative chemoradiotherapy (n=57). However, Kaplan-Meier analysis showed that the cause-specific survival rate in N3 patients and larynx preservation rate was significantly higher in patients treated with IA chemoradiation than in those with surgery with preoperative chemoradiotherapy (p<0.05 and p<0.001). Subjective symptoms are not so severe in patients without the disease after IA chemoradiation. IA chemoradiation is effective for patients with advanced hypopharyngeal carcinoma to maintain quality of life such as voice and swallowing. (author)

  3. Experimental study on intra-arterial infusion of basic fibroblast growth factor in the ischemic limbs of rabbit model

    International Nuclear Information System (INIS)

    Zhang Jing; Yang Wenduo

    2005-01-01

    Objective: To evaluate the effect of intra-arterial infusion of basic fibroblast growth factor (bFGF) on improving neovascularization, vascular perfusion and the function of partially ischemic limbs of rabbits. Methods: Twenty-seven New Zealand male rabbits were selected. Partial ischemia model was induced by surgical ligation of the primary branches of right femoral artery in each animal, and the left hind limb of each animal was served as a nonischemic control. Then, 27 rabbits were randomly assigned to three groups: intra-arterial (IA) infusion of bFGF (n=9), intravenous (IV) infusion of bFGF and IA infusion of saline (n=9). Infusion was separately performed immediately after vascular ligation, 8th and 15th days post-surgery with 10 μg (4 ml) of bFGF per-time (or the same volume of saline). The differences between three groups and between ischemic and nonischemic limbs of the same group were compared and evaluated by the following indexes: (1) vessel section count (VSC), vessel section surface area (VSS) and vessel section perimeter (VSP) in the field of ischemic muscle tissues taken at 22nd day postoperatively; (2) capillary refilling time of ischemic limbs; and (3) functional and trophic changes of ischemic limbs. Statistical differences were evaluated by one-way ANOVA and T test. Results: VSC, VSS and VSP of the IA-bFGF group were significantly increased than those of the IV-bFGF and IA-saline groups (P<0.01). At 22nd day postoperatively, the capillary refilling time, new hair growth, the appearance and function of all ischemic limbs in IA-bFGF group were approximately normal. However, in IA-saline group, the ischemic changes, capillary refilling time and the function of ischemic limbs were not improved significantly. All the indexes of IV-bFGF group showed no difference statistically from those of IA-saline group. Conclusions: This experimental study identifies that intra-arterial infusion of bFGF may significantly promote neovascularization and vascular

  4. Feeding Arteries of Primary Tongue Cancers on Intra-arterial Infusion Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kamitani, Takeshi, E-mail: kamitani@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan); Kawanami, Satoshi, E-mail: kawanami-01@mac.com [Kyushu University, Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences (Japan); Asayama, Yoshiki, E-mail: asayama@radiol.med.kyushu-u.ac.jp; Matsuo, Yoshio, E-mail: yymatsuo@radiol.med.kyushu-u.ac.jp; Yonezawa, Masato, E-mail: ymasato@radiol.med.kyushu-u.ac.jp; Yamasaki, Yuzo, E-mail: yyama@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan); Nagao, Michinobu, E-mail: minagao@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences (Japan); Yamanouchi, Torahiko, E-mail: tora0228@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan); Yabuuchi, Hidetake, E-mail: h-yabu@med.kyushu-u.ac.jp [Kyushu University, Department of Health Sciences, Graduate School of Medical Sciences (Japan); Nakamura, Katsumasa, E-mail: nakam@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan); Nakashima, Torahiko, E-mail: nakatora@qent.med.kyushu-u.ac.jp [Kyushu University, Department of Otorhinolaryngology, Graduate School of Medical Sciences (Japan); Honda, Hiroshi, E-mail: honda@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan)

    2016-02-15

    PurposeTo evaluate the frequency and the predictive factor of each feeding artery on intra-arterial infusion chemotherapy (IAIC) in primary tongue cancer.Materials and MethodsWe retrospectively evaluated 20 patients who received IAIC for primary tongue cancer. The main and accompanying feeding arteries were identified on super-selective angiography of the branches of the external carotid artery. Tumor diameter, and extension to the contralateral side, tongue extrinsic muscles (TEMs), and lateral mesopharyngeal wall were determined based on magnetic resonance imaging or computed tomography findings.ResultsThe main feeding artery was the ipsilateral lingual artery (LA) in 15 of the 20 examined tumors and the contralateral LA in the other 5. Ten cancers had only one feeding artery, and multiple feeding arteries were detected in the remaining 10. Tumors >4 cm (n = 9), those with extension to the contralateral side (n = 13), and those with extension to TEMs (n = 15) were supplied by significantly larger numbers of feeding arteries compared to tumors without these features (P = 0.01, 0.049, and 0.02, respectively). The frequency of feeding from the contralateral LA was 64 % (9/14) and 17 % (1/6) in tumors with and without extension to the contralateral side, respectively. Feeding from a facial artery (FA) was not detected in tumors ≤4 cm, while 5 of the 9 (56 %) tumors >4 cm were supplied by a FA (P = 0.01).ConclusionA careful search for feeding arteries is required, especially in large tumors with extension to the contralateral side or to TEMs.

  5. Influence of the catheter-top-position upon the distribution pattern of continuous intra-arterially infused chemotherapeutic agent

    International Nuclear Information System (INIS)

    Ichinohe, Hyobu

    1980-01-01

    The whole body scanning showed the distribution pattern of infused drug in continuous intra-arterially infused chemotherapy by using a gamma camera and infused RI (sup(99m)Tc-MAA) from catheter. I measured the whole body scanning counts without shield (A) and with lead shield (B) on ROI and natural back ground counts (BG). Then I calculated the distribution ratio on ROI as following. [(A-B)/(A-BG)] x 100(%). It was easy to find a certain relation between the catheter-top-position and the distribution ratio. As a result of investigating data, there were about 4 catheter-top-positions in aorta. Case by case, we putted the catheter-top in better position and prevented technical side effects and measured roughly total dose on ROI. (author)

  6. Intra-arterial infusion of MTX for the treatment of cesarean scar pregnancy: a comparative study between different doses

    International Nuclear Information System (INIS)

    Gu Weijin; Wang Haiyun; Wan Jun; Zhang Lei; Wang Ying; Wang Wei; Ji Fang; Ji Lihua

    2010-01-01

    Objective: To investigate the effective dose of methotrexate (MTX) via intra-arterial infusion for the treatment of cesarean scar pregnancy. Methods: Thirty-six cases of incisional scar pregnancy at the gestational age of 5-9 weeks received bilateral uterine arterial infusion of MTX. According to the dose of MTX used, the patients were randomly and equally divided into four groups with MTX dose of 60, 100, 150 and 200 mg respectively. After the perfusion was completed the embolization of both uterine arteries with Gelfoam was carried out until the uterine arteries were no longer visualized on DSA. Uterine curettage was conducted within 1-7 days after the treatment. Results: In one week after the procedure, the difference in the decreasing rate of serum β-HCG and progesterone between group 60 mg and group 200 mg was of statistical significance (P 0.05). The hospitalization days of group 60 mg was the longest, while that of group 200 mg was the shortest. Conclusion: The recommended dose of MTX used via intra-arterial infusion in treating cesarean scar pregnancy is 200 mg. The interventional procedure can kill the embryo tissue and quickly lower the serum β-HCG and progesterone levels,it can also shorten the patient's hospitalization time. (authors)

  7. Quality assessment of clinical research on liver cancer treated by intra-arterial infusion of Chinese medicine.

    Science.gov (United States)

    Zhai, Xiao-Feng; Qiao, Cui-Xia; Liu, Qun; Chen, Zhe; Ling, Chang-Quan

    2014-11-01

    To assess the methodological quality of clinical research on Chinese medicine (CM) applied by intra-arterial infusion in treating primary liver cancer (PLC). Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and three Chinese databases, including Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI) and China Academic Journal (VIP) were searched. Chinese articles were also searched manually in 16 journals. Two reviewers independently selected studies, the quality of literatures were assessed according to the Cochrane Collaboration method of quality assessment. A total of 14 articles met the inclusion criteria for this review. Only three of these articles described the randomization method used. None of the studies was blinded. All of the articles didn't report the calculation of the sample size. Only six studies mentioned adverse reactions. All of the studies were of grade C according to the Cochrane Collaboration method. Six studies reported results of survival, and only two of these reported better efficacy in the treatment groups. The quality of studies concerned intra-arterial infusion of CM in treating with PLC was poor and the exact effect of these medicines still need evaluation. Well designed RCTs with large sample sizes, adequate follow-up data and reliable methods of assessment are needed to better appraise the real effect of CMs in the treatment of PLC patients.

  8. Intra-arterial infusion of Solcoseryl: a clinical trial of a method of treatment for pre-gangrene of the lower limb.

    Science.gov (United States)

    Charlesworth, D; Harris, P L; Palmer, M K

    1975-05-01

    A randomized double blind trial of the drug Solcoseryl given by intra-arterial infusion was carried out on 57 patients with pre-gangrene of the lower limb. A sequential analysis was carried out and the trial stopped when the results showed a statistically significant result in favour of the active drug.

  9. Percutaneous implantation of intra-arterial port system for regional drug infusion: results and complications in 110 cases

    International Nuclear Information System (INIS)

    Won, Je Hwan; Lee, Jong Hyuk; Ko, Kyung Hee; Won, Jong Yoon; Park, Sung Il; Lee, Do Yun; Kang, Byung Chul

    2000-01-01

    To investigate the feasibility and complications of a percutaneously implantable port system for regional drug infusion. For intra-arterial drug infusion, a 5.8 or 5-F pediatric venous port system was implanted in 110 patients with hepatocellular carcinoma (n=79), liver metastasis (n=16), gallbladder cancer (n=4), stomach cancer (n=3), pancreatic cancer (n=3), Burger's diseases mellitus (n=2), or lymphoma (n=1). All intra-arterial port implantations were performed percutaneously in an angiographic ward through the common femoral artery (n=98), left subclavian artery (n=10), or left superficial femoral artery (n=2). Complications were evaluated during the follow-up period, which ranged from 21 to 530 (mean, 163) days. The technical success rate for percutaneous implantation of the system was 97.3% (107 of 110 patients). The tips of the port catheter were located in the common hepatic artery (n=34), proper hepatic artery (n=49), right hepatic artery quick resulthepatic artery (n=1), descending aorta at T9 level (n=10), left popliteal artery (n=2), right external iliac artery (n=1), left external iliac artery (n=1), or left deep femoral artery (n=1). Complications were encountered in 24 patients (22.4%), namely chamber site infection (n=7), catheter dislodgement (n=7), catheter occlusion (n=3), migration of coil (n=2), disconnection between chamber and catheter (n=1), kinking of catheter (n=1), arterial occlusion (n=1), necrosis of overlying skin (n=1), and leakage around port chamber (n=1). Outcomes of complications included removal of port systems or cessation of therapy in 12 cases (11.2%), correction of catheter location using a guide wire in five (4.7%), thrombolysis with urokinase in three (2.8%), and straightening using a snare in one (0.9%). In three patients, the port system was used without reintervention. Percutaneous implantation of an intra-arterial port system showed a high technical success rate and a low rate of serious complications. The method may be

  10. Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma.

    Science.gov (United States)

    Sakuma, Kaname; Tamura, Ryuki; Hanyu, Shintaro; Takahashi, Haruka; Sato, Hideaki; Oneyama, Takahiro; Yamaguchi, Akira; Tanaka, Akira

    2017-12-01

    Using trace three-dimensional culture, the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) can be tested even in cases with a small number of cells, including oral squamous cell carcinoma (OSCC), and evaluation of the antitumor effect with a drug concentration close to the in vivo level is possible. The present report aimed to evaluate the utility of the CD-DST in the assessment of the in vitro efficacy of single-agent and multidrug combination chemotherapy for OSCC in comparison with the clinical response rates and to examine the possible clinical application of CD-DST for such cases. A total of 33 OSCC patients from whom 33 samples were obtained from January 2010 to September 2015 were included. CD-DST was performed, individually and in combination, on the three drugs [i.e., cisplatin (CDDP), 5-fluorouracil (5-FU), and docetaxel (DOC)] and on super selective intra-arterial infusion chemoradiotherapy (IACRT). The overall evaluable rate of the CD-DST in OSCC was 81.8% (27 of 33 cases) and the sensitivity to each anticancer drug was evaluated. The in vitro efficacy rates of IACRT, cisplatin + 5-fluorouracil, and docetaxel + cisplatin + 5-fluorouracil (TPF) confirmed the estimated clinical response rates. In 14 of 33 patients, the results of CD-DST were compared with clinical efficacy, which was judged based on measurable lesions on imaging. For TPF therapy, the sensitivity test of the IACRT had a positive predictive value of 90.9% (10 of 11 cases) and a negative predictive value of 100% (3 of 3 cases); the accuracy of the susceptibility test for the anticancer agents was 92.8% (13 of 14 cases). The CD-DST may be useful in selecting multidrug combination chemotherapy and IACRT for OSCC, however, accumulation of further clinical data is required in the future.

  11. Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Kawaoka, Tomokazu; Aikata, Hiroshi; Takaki, Shintaro; Katamura, Yoshio; Hiramatsu, Akira; Waki, Koji; Takahashi, Shoichi; Hieda, Masashi; Toyota, Naoyuki; Ito, Katsuhide; Chayama, Kazuaki

    2009-01-01

    We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0-67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10-390 mg). Survival rates were 86% at 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.

  12. Better Clinical Efficiency of TILs for Malignant Pleural Effusion and Ascites than Cisplatin Through Intrapleural and Intraperitoneal Infusion.

    Science.gov (United States)

    Chu, Hongjin; Du, Fengcai; Gong, Zhaohua; Lian, Peiwen; Wang, Zhixin; Li, Peng; Hu, Baohong; Chi, Cheng; Chen, Jian

    2017-08-01

    To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis. The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group. The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs

    Directory of Open Access Journals (Sweden)

    Hongting Jin

    2016-01-01

    Full Text Available This study aimed to investigate if autologous bone marrow mesenchymal stem cells (MSCs could treat osteonecrosis of the femoral head (ONFH and what the fate and distribution of the cells are in dogs. Twelve Beagle dogs were randomly divided into two groups: MSCs group and SHAM operated group. After three weeks, dogs in MSCs group and SHAM operated group were intra-arterially injected with autologous MSCs and 0.9% normal saline, respectively. Eight weeks after treatment, the necrotic volume of the femoral heads was significantly reduced in MSCs group. Moreover, the trabecular bone volume was increased and the empty lacunae rate was decreased in MSCs group. In addition, the BrdU-positive MSCs were unevenly distributed in femoral heads and various vital organs. But no obvious abnormalities were observed. Furthermore, most of BrdU-positive MSCs in necrotic region expressed osteocalcin in MSCs group and a few expressed peroxisome proliferator-activated receptor-γ (PPAR-γ. Taken together, these data indicated that intra-arterially infused MSCs could migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. It suggests that intra-arterial infusion of autologous MSCs might be a feasible and relatively safe method for the treatment of femoral head necrosis.

  14. Quality of life in patients diagnosed with primary hepatocellular carcinoma: hepatic arterial infusion of Cisplatin versus 90-Yttrium microspheres (Therasphere).

    Science.gov (United States)

    Steel, Jennifer; Baum, Andrew; Carr, Brian

    2004-02-01

    The aims of the study were to test the difference in health-related quality (HRQL) of life and survival in patients diagnosed with primary hepatocellular carcionma (HCC) and treated with either hepatic arterial infusion (HAI) of Cisplatin or 90-Yttrium microspheres (Therasphere). The design of the study was a non-randomized parallel cohort study. Twenty-eight patients participated in the present study. HRQL was assessed by administration of the Functional Assessment of Cancer Therapy-Hepatobiliary. Survival was measured using Kaplan Meier methods. The results of present study suggest treatment with Therasphere) had an advantage in regard to HRQL and survival when compared to Cisplatin. At 3-month follow-up, patients who were treated with Therasphere had a higher level of functional well-being as well as overall quality of life when compared to patients treated with Cisplatin. At 6-month follow-up patients (treated with Therasphere) continued to have better functional well-being when compared to patients being treated with HAI of Cisplatin. At 6-month follow-up, survival was found to be similar for patients treated with Therasphere when compared to patients being treated with Cisplatin. Preliminary data suggest that treatment with Therasphere has a modest advantage in regard to HRQL when compared patients treated with HAI of Cisplatin. Future research with Therasphere, that includes a larger sample size and longer follow-up, is necessary to make definitive conclusions regarding the efficacy and effect on HRQL. Copyright 2003 John Wiley & Sons, Ltd.

  15. Superselective intra-arterial infusion via the superficial temporal artery and occipital artery for gingival carcinoma of the mandible. Simultaneous catheter placement to the maxillary artery and facial artery

    International Nuclear Information System (INIS)

    Iwai, Toshinori; Mitsudo, Kenji; Fukui, Takafumi

    2009-01-01

    Superselective intra-arterial infusion via the superficial temporal artery (STA) has become useful for oral cancer. Approaching via the occipital artery (OA) enables superselective intra-arterial infusion when catheter placement via the STA is impossible. Therefore, simultaneous catheter placement via the STA and OA is possible. We report a surgical method of simultaneous catheter placement via the STA and OA to achieve retrograde superselective intra-arterial infusion for gingival carcinoma of the mandible. Preoperatively, three-dimensional computed tomography angiography was performed to identify the route of the external carotid artery and branches such as the STA, OA, maxillary artery, and facial artery (FA). Thirteen patients with mandibular gingival cancer underwent catheter placement via the STA and OA under local anesthesia. Catheter placement via the STA and OA was superselectively successful in all the patients. The mean operating time was 150.8 min. Catheter placed to the FA via the OA was dislocated during the treatment in one patient, and so the catheter was replaced. This method is useful to enable superselective intra-arterial chemotherapy to the whole gingival carcinoma of the mandible from the start of treatment compared with approaching via the STA. (author)

  16. Concomitant infusion cisplatin and hyperfractionated radiotherapy for locally advanced nasopharyngeal and paranasal sinus tumors

    International Nuclear Information System (INIS)

    Choi, Kwang N.; Rotman, Marvin; Aziz, Hassan; Sohn, Chul K.; Schulsinger, Alan; Torres, Camilo; Har-El, Gady; Chandra, Pradeep; Bradley, Thomas; Rosenthal, C. Julian

    1997-01-01

    Purpose: This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisplatin chemotherapy and hyperfractionated radiotherapy. Methods and Materials: From 1983 to 1993, 21 patients with locally advanced nasopharyngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors involving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fraction/bid) and concomitant infusion cisplatin (5-10 mg/m 2 /24 h). The therapy was given in three separate 2-week sessions with 1 to 2 week breaks between sessions. Seventeen of 21 patients were treated with curative intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy. Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation. Results: Sixteen of 17 patients (94%) treated curatively achieved a complete response. Of the 16 patients who achieved complete response, 7 patients (50%) were alive at the time of analysis (36 to 126 months). One patient was alive at 4 years with no evidence of disease, and died in 10 years at the age of 80 of unknown cause. Two patients died of local recurrence at 21 and 45 months and one patient died of a cerebrovascular accident at 12 months with disease status unknown. Five patients died of distant metastases. The one patient who had a partial response died in 25 months with local disease and metastases to the bone and lung. Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field. All had near complete responses, but died within a year of treatment, with the exception of one patient who died at 23 months. Acute reactions included erythema of the mucosa in all patients. Five of 21 (23%) developed punctate mucositis and 3 of 21 (14

  17. Superselective intra-arterial chemoradiotherapy for laryngeal cancer. Is it reasonable to treat glottic cancer in a similar way to supraglottic cancer?

    International Nuclear Information System (INIS)

    Yoshizaki, Tomokazu; Murono, Shigeyuki; Wakisaka, Naohiro; Kondo, Satoru; Furukawa, Mitsuru

    2006-01-01

    The standard treatment for advanced laryngeal cancer has been shifting from total laryngectomy to various organ preservation therapies such as subtotal laryngectomy and chemoradiotherapy. Robbins showed remarkable results with RADPLAT, the superselective intra-arterial infusion of supradose cisplatin (150 mg/m 2 ), against advanced head and neck cancer. However, the volume of laryngeal cancer is smaller than those of the other sites of head and neck cancers, and so a swaller less dose of cisplatin could save advanced laryngeal cancer patients. It may be reasonable to treat these subtypes of laryngeal cancer with a different modality. Thirty-five patients with laryngeal cancer were treated with tri-weekly intra-arterial infusion of cisplatin (100 mg/body). A 200 times molar excessive amount of sodium thiosulfate was intravenously infused to reduce the toxicity of cisplatin. Ten of 16 patients with glottic cancer and 10 of 19 patients with supraglottic cancer were followed for more than 2 years. Larynx preservation rate of glottic and supraglottic cancer was 80% and 70%, and progression-free survival rate was 80% and 50%, respectively. Grade III and IV toxic events were less frequent than with RADPLAT or systemic administration of a similar dose of cisplatin. Glottic and supraglottic cancers show different clinical behaviors. Our protocol with less cisplatin than RADPLAT is especially effective for glottic cancer. (author)

  18. Intra-arterial infusion of prostaglandin E1 in normal subjects and patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Nielsen, P E; Nielsen, S L; Holstein, P

    1976-01-01

    Acute vasodilatation was produced by infusion of prostaglandin E1 (PGE1) in the femoral artery in 6 patients with occlusive arterial disease of the legs and in 3 normal subjects. The effect on blood flow and on blood pressure was measured at different segments of the leg with the strain gauge...

  19. Intra-arterial infusion of prostaglandin E1 in normal subjects and patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Nielsen, P E; Nielsen, S L; Holstein, P

    1976-01-01

    Acute vasodilatation was produced by infusion of prostaglandin E1 (PGE1) in the femoral artery in 6 patients with occlusive arterial disease of the legs and in 3 normal subjects. The effect on blood flow and on blood pressure was measured at different segments of the leg with the strain gauge...... technique, isotope clearance technique, and photoelectric technique. Skin temperature was measured at different levels by using thermocouples. The blood pressure on the legs decreased at all segments during vasodilatation as well in patients as in controls. The blood flow increased in all segments in normal...... controls. In patients the blood flow increased proximally in the legs. Distally, however, no increase could be demonstrated. As a good effect of PGE1, on ischaemic rest pains has been reported, mechanisms other than vasodilatation should probably be considered....

  20. The effect of selective intraarterial infusion of the anticancer agents on cerebral hemodynamics: Concerned with the change of CBF in the non-tumoral tissue. Quantitative evaluation using 123-IMP-SPECT

    International Nuclear Information System (INIS)

    Hirano, Hiroko; Tomura, Noriaki; Kobayashi, Mitsuru; Ohyama, Yoichi; Watarai, Jiro

    1996-01-01

    The effect of intraarterial chemotherapy on cerebral blood flow (CBF) of patients with brain tumor was quantitatively studied by means of single photon emission computed tomography (SPECT). The subjects consisted of twenty patients with brain tumor (2 fibrillary astrocytoma grade II, 9 malignant astrocytoma grade III, 7 glioblastoma grade IV, 1 pineoblastoma grade IV and 1 malignant glioma). In twenty patients, twenty-four intraarterial infusions (IAs) were performed. IA chemotherapy was selectively performed through the Tracker-18 catheter, using nimustine (ACNU) in 22 infusions and tumor necrotizing factor-α (TNF) in 2 infusions. CBF was quantitatively measured by Kuhl's method, using N-isopropyl-p= 123 I=-iodoamphetamine (IMP). All patients underwent a baseline SPECT scan 1-10 days prior to IA chemotherapy, and a scan 1-22 days after IA. The change of CBF before and after IA, particularly in the non-tumoral tissue, was highlighted. CBF in the infused region as well as in the non-infused region variously changed after IA. The mean CBF of the whole brain before IA was 47.8±11.9 (mean±SD, n=24) ml/100 ml/min and than after IA was 49.3±12.4. CBF in the infused region changed (-17-+52%) after IA chemotherapy. In 12 patients whose CBF measurement was performed within 5 days after IA, CBF increased in 6 patients compared with that measured before IA. In 3 patients whose CBF measurement was performed more than 10 days after IA, CBF decreased in all of patients. This result suggested that the increase of CBF may possibly be an early change after IA chemotherapy, and that an augmented cellular metabolism and/or acute inflammatory reaction may explain this early change after IA chemotherapy. (author)

  1. Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy for gingival carcinoma

    International Nuclear Information System (INIS)

    Mukai, Y.; Hata, M.; Koike, I.; Inoue, T.; Mitsudo, K.; Koizumi, T.; Oguri, S.; Kioi, M.; Tohnai, I.; Omura, M.

    2014-01-01

    The aim of this study was to review the efficacy and toxicity of radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy in the treatment of gingival carcinoma. In all, 34 patients (21 men and 13 women) with squamous cell carcinoma of the gingiva underwent radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy. Treatment consisted of daily external irradiation and concurrent retrograde superselective intra-arterial infusion with cisplatin and docetaxel. A median total dose of 60 Gy in 30 fractions was delivered to tumors. Of the 34 patients, 29 (85 %) achieved a complete response (CR) and 5 had residual tumors. Of the 29 patients with a CR, 2 had local recurrences and 1 had distant metastasis 1-15 months after treatment. Twenty-six of the 36 patients had survived at a median follow-up time of 36 months (range 12-79 months); 4 died of cancer and 4 died of non-cancer-related causes. At both 3 and 5 years after treatment, the overall survival rates were 79 % and the cause-specific survival rates were 85 %. Osteoradionecrosis of the mandibular bone only developed in 1 patient after treatment. Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy was effective and safe in the treatment of gingival carcinoma. This treatment may be a promising curative and organ-preserving treatment option for gingival carcinoma. (orig.) [de

  2. Hepatic Arterial Infusion Therapy with Cisplatin using Protein Binding Inhibition : Pharmacokinetics and Antineoplastic Effects of Cisplatin Combined with L-Cysteine in Rats

    OpenAIRE

    徳永, 仁; 松尾, 徳子; 高村, 徳人; 杉本, 龍星; 岡崎, 愛; 永井, 和正; 青木, 傳; 緒方, 賢次; 瀬戸口, 奈央; 吉田, 裕樹; 永田, 将司; 岸本, 修一; 福島, 昭二; 池田, 理; 西尾, 豊隆

    2014-01-01

    Cisplatin の蛋白結合には共有結合が関与しており、L-cysteine はcisplatin の共有結合を低下させる。そこで、この蛋白結合阻害を利用してcisplatin の肝動注療法の応用性について検討を行った。実験では、Donryu系雄性ラットにおけるL-cysteine 併用時におけるcisplatin の体内動態と抗腫瘍効果の影響について検討した。その結果、L-cysteine 併用においてcisplatin のtotal とfree 濃度に有意な差はみられなかった。また肝癌ラットを使用したin vivo 実験系において、L-cysteine を併用したcisplatin の肝動注はcisplatin のみの投与に比べ、腫瘍増殖率が抑えられる傾向であることを示した。さらに肝組織中における腫瘍部と非腫瘍部におけるcisplatin 濃度において、L-cysteine 併用により腫瘍部と非腫瘍部に有意な差を認めることができた (p...

  3. Simultaneous intra-arterial chemotherapy and radiotherapy for carcinoma of oropharynx without neck metastasis

    International Nuclear Information System (INIS)

    Tomita, Kichinobu; Higaki, Yuichiro

    2000-01-01

    We evaluated the usefulness of simultaneous intra-arterial chemotherapy and radiotherapy for oropharyngeal cancer without neck metastasis. Fifty eight cases without neck metastasis out of previously untreated 117 patients with oropharyngeal cancer treated at National Kyushu Cancer Center from 1972 to 1995 were examined. Seventeen patients were in T1, 27 in T2, 10 in T3, 4 in T4. Fourteen patients of 58 patients were treated by simultaneous intra-arterial chemotherapy and radiation therapy. The 5-year survival rate by Kaplan-Meier method for intra-arterial infusion group and non intra-arterial infusion group were 86% and 71%, respectively. Thirty one patients were treated with irradiation without surgery. In 31 cases without surgery, the 5-year survival rate for intra-arterial infusion group (13 cases) was 85%, while that for non intra-arterial infusion group (18 cases) was 60%, and the local control rate for intra-arterial infusion group is 92%, while that for non intra-arterial infusion group was 56%. Simultaneous intra-arterial chemotherapy and radiotherapy for oropharyngeal cancer without neck metastasis is useful to improve the prognosis with preserving the function. (author)

  4. Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits.

    Science.gov (United States)

    Ohta, Shinichi; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi; Takemura, Shizuki; Tabata, Yasuhiko; Murata, Kiyoshi

    2009-12-01

    To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. The renal parenchymal platinum concentrations (microg/ml) with 4.51+/-2.25 (day 0), 1.59+/-0.70 (day 1), 0.72+/-0.10 (day 3) and 0.20+/-0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99+/-0.55, 0.08+/-0.03, 0.18+/-0.01 and 0.10+/-0.07, respectively. Relative tumor growth rates resulted in 84.5%+/-26.4 (group I); 241.4%+/-145.1 (II); 331.9%+/-72.2 (III), and 413.6%+/-103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an increased and prolonged anti-cancer effect compared to cisplatin alone

  5. Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Shinichi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan)], E-mail: junryuhei@yahoo.co.jp; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan); Takemura, Shizuki [Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga (Japan); Tabata, Yasuhiko [Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto (Japan); Murata, Kiyoshi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan)

    2009-12-15

    Purpose: To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. Materials and methods: Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. Results: The renal parenchymal platinum concentrations ({mu}g/ml) with 4.51 {+-} 2.25 (day 0), 1.59 {+-} 0.70 (day 1), 0.72 {+-} 0.10 (day 3) and 0.20 {+-} 0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99 {+-} 0.55, 0.08 {+-} 0.03, 0.18 {+-} 0.01 and 0.10 {+-} 0.07, respectively. Relative tumor growth rates resulted in 84.5% {+-} 26.4 (group I); 241.4% {+-} 145.1 (II); 331.9% {+-} 72.2 (III), and 413.6% {+-} 103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. Conclusions: With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering

  6. Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits

    International Nuclear Information System (INIS)

    Ohta, Shinichi; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi; Takemura, Shizuki; Tabata, Yasuhiko; Murata, Kiyoshi

    2009-01-01

    Purpose: To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. Materials and methods: Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. Results: The renal parenchymal platinum concentrations (μg/ml) with 4.51 ± 2.25 (day 0), 1.59 ± 0.70 (day 1), 0.72 ± 0.10 (day 3) and 0.20 ± 0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99 ± 0.55, 0.08 ± 0.03, 0.18 ± 0.01 and 0.10 ± 0.07, respectively. Relative tumor growth rates resulted in 84.5% ± 26.4 (group I); 241.4% ± 145.1 (II); 331.9% ± 72.2 (III), and 413.6% ± 103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. Conclusions: With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an

  7. Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy for gingival carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Mukai, Y.; Hata, M.; Koike, I.; Inoue, T. [Yokohama City University Graduate School of Medicine, Department of Radiology, Kanazawa-ku, Yokohama, Kanagawa (Japan); Mitsudo, K.; Koizumi, T.; Oguri, S.; Kioi, M.; Tohnai, I. [Yokohama City University Graduate School of Medicine, Department of Oral and Maxillofacial Surgery, Yokohama, Kanagawa (Japan); Omura, M. [Shonankamakura General Hospital, Department of Radiation Oncology, Kamakura, Kanagawa (Japan)

    2014-02-15

    The aim of this study was to review the efficacy and toxicity of radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy in the treatment of gingival carcinoma. In all, 34 patients (21 men and 13 women) with squamous cell carcinoma of the gingiva underwent radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy. Treatment consisted of daily external irradiation and concurrent retrograde superselective intra-arterial infusion with cisplatin and docetaxel. A median total dose of 60 Gy in 30 fractions was delivered to tumors. Of the 34 patients, 29 (85 %) achieved a complete response (CR) and 5 had residual tumors. Of the 29 patients with a CR, 2 had local recurrences and 1 had distant metastasis 1-15 months after treatment. Twenty-six of the 36 patients had survived at a median follow-up time of 36 months (range 12-79 months); 4 died of cancer and 4 died of non-cancer-related causes. At both 3 and 5 years after treatment, the overall survival rates were 79 % and the cause-specific survival rates were 85 %. Osteoradionecrosis of the mandibular bone only developed in 1 patient after treatment. Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy was effective and safe in the treatment of gingival carcinoma. This treatment may be a promising curative and organ-preserving treatment option for gingival carcinoma. (orig.) [German] Das Ziel dieser Studie war die Ueberpruefung der Effizienz und Toxizitaet einer Strahlenbehandlung des Gingivakarzinoms mit gleichzeitiger retrograder, superselektiver intraarterieller Chemotherapie. Insgesamt 34 Patienten (21 Maenner und 13 Frauen) mit Zahnfleischplattenzellkarzinom erhielten eine Strahlenbehandlung mit gleichzeitiger retrograder, superselektiver intraarterieller Chemotherapie. Die Behandlung umfasste eine taegliche externe Bestrahlung mit gleichzeitiger retrograder, superselektiver intraarterieller Infusion von Cisplatin und

  8. Treatment results of selective intra-arterial chemoradiotherapy for oropharyngeal carcinoma

    International Nuclear Information System (INIS)

    Fukahori, Mioko; Chitose, Shun-ichi; Maeda, Akiteru; Umeno, Hirohito; Nakashima, Tadashi

    2010-01-01

    Fourteen patients who had oropharyngeal carcinoma were treated with intra-arterial chemoradiotherapy between December 2002 and December 2008. The patients were classified as 3 stage II, 3 stage III and 8 stage IV cases. According to the subsite of the oropharynx, the patients were classified as 6 lateral wall (LW), 5 anterior wall (AW) and 3 superior wall (SW) cases. Intra-arterial infusion chemotherapy by cisplatin was given weekly with concurrent radiotherapy for approximately four weeks, and the total number of infusions was decided according to intermediate judgments of effectiveness. The total dose of radiation was 60-81.4 Gy (average 65.3 Gy). As a result of this treatment, there were 12 complete response (CR) (85.7%) and 2 partial response (PR) (14.3%) for primary tumor and 4 CR (57.1%), 2 PR (28.6%), and 1 no change (NC) (14.3%) for lymph node. Regarding survival, 7 were alive and cancer-free (50%), 2 were alive with cervical lymph node metastasis (14.3%), 4 died of the primary tumor (28.6%) and 1 died of other disease (7.1%). The local control rates by subsite were 75% in LW, 66.7% in AW and 33.3% in SW. These results indicate in terms of both local control rate and functional preservation, that advanced AW cancer seems to be a good indication for intra-arterial chemoradiotherapy, but the therapy should be determined cautiously with respect to indications for LW and SW oropharyngeal carcinoma. (author)

  9. Successful treatment of nonocclusive mesenteric ischemia after aortic valve replacement with continuous arterial alprostadil infusion: A case report

    Directory of Open Access Journals (Sweden)

    Kunio Ogi

    2017-01-01

    Conclusions: In a patient with recurrent NOMI despite appropriate treatment including intra-arterial infusion of papaverine, continuous intra-arterial infusion of PGE1 may limit the extent of intestinal resection needed. Continuous intra-arterial infusion of PGE1 may be a useful treatment for patients with refractory NOMI.

  10. Superselective arterial infusion and concomitant radiotherapy for advanced head and neck cancer

    International Nuclear Information System (INIS)

    Homma, Akihiro; Furuta, Yasushi; Ushikoshi, Satoshi

    2003-01-01

    Superselective arterial infusion for patients with advanced head and neck cancer has increasingly been applied in Japan. We analyzed our experiences and evaluated the efficacy and safety of this treatment. Forty-four patients, who were considered contraindicated for surgery or rejected radical surgery, received superselective intra-arterial infusion therapy of cisplatin (100-120 mg/m 2 /week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity, and conventional concomitant extrabeam radiotherapy (65 Gy/26 f/6.5 weeks). During the median follow-up period of 17 months, 2-year progression-free survival rate of primary lesion was 66.9%, and that of patients with T4b diseases 57%. The 2-year overall survival rate was 52.4%. Although acute toxic effects were considered acceptable, severe toxic events occurred in some cases, namely, cranial nerve palsy, Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, sepsis, and osteoradionecrosis. We confirmed the high effectiveness of superselective arterial infusion and concomitant radiotherapy, which can concentrate the attack of decadose cisplatin on locoregional disease. Moreover, even patients with unresectable disease can be cured. We must clarify the treatment results and late side effects, and establish the indications for this treatment. (author)

  11. Superselective arterial infusion and concomitant radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Homma, Akihiro; Suzuki, Fumiyuki; Inuyama, Yukio; Fukuda, Satoshi [Hokkaido Univ., Sapporo (Japan). School of Medicine

    2003-05-01

    Superselective arterial infusion for patients with advanced head and neck cancer has been increasingly applied in Japan. We analyzed our experiences and evaluated the efficacy and safety of this treatment. Through October 1999 to March 2002, 29 patients, ranging in age between 33 and 71 years (median 52 years), received superselective intra-arterial infusion therapy of cisplatin (100-120 mg/m{sup 2}/week) with simultaneous intravenous infusion of thiosulfate for neutralizing cisplatin toxicity, and conventional concomitant extrabeam radiotherapy (65 Gy/26 f/6.5 weeks). Four patients were diagnosed with stage III and 25 with stage IV. Thirteen patients were considered contraindicated for surgery, and the other 16 patients rejected radical surgery. Primary tumor sites included paranasal sinus (11 patients), hypopharynx (7), oropharynx (6), oral cavity (4), and parotid gland (1). During the median follow-up period of 20 months, there was no apparent recurrence in 14 (48.3%) of 29 patients. Eleven (37.9%) patients died of disease, and three (10.3%) were alive with disease. In twenty-one patients (72.4%) the primary lesions were well-controlled. Acute toxic effects were moderate, and severe toxic events occurred in four cases, namely, methicillin-resistant staphylococcus aureus (MRSA) pneumonia, sepsis, tetraplasia, and osteoradionecrosis. We confirmed the effectiveness and safety of superselective arterial infusion and concomitant radiotherapy. Furthermore, we must establish the optimal procedures and schedule, as well as the indications for this treatment. This treatment protocol may improve the prognosis of patients with unresectable disease and patients rejecting surgical treatment. Further study in this particular area is needed. (author)

  12. Superselective arterial infusion and concomitant radiotherapy

    International Nuclear Information System (INIS)

    Homma, Akihiro; Suzuki, Fumiyuki; Inuyama, Yukio; Fukuda, Satoshi

    2003-01-01

    Superselective arterial infusion for patients with advanced head and neck cancer has been increasingly applied in Japan. We analyzed our experiences and evaluated the efficacy and safety of this treatment. Through October 1999 to March 2002, 29 patients, ranging in age between 33 and 71 years (median 52 years), received superselective intra-arterial infusion therapy of cisplatin (100-120 mg/m 2 /week) with simultaneous intravenous infusion of thiosulfate for neutralizing cisplatin toxicity, and conventional concomitant extrabeam radiotherapy (65 Gy/26 f/6.5 weeks). Four patients were diagnosed with stage III and 25 with stage IV. Thirteen patients were considered contraindicated for surgery, and the other 16 patients rejected radical surgery. Primary tumor sites included paranasal sinus (11 patients), hypopharynx (7), oropharynx (6), oral cavity (4), and parotid gland (1). During the median follow-up period of 20 months, there was no apparent recurrence in 14 (48.3%) of 29 patients. Eleven (37.9%) patients died of disease, and three (10.3%) were alive with disease. In twenty-one patients (72.4%) the primary lesions were well-controlled. Acute toxic effects were moderate, and severe toxic events occurred in four cases, namely, methicillin-resistant staphylococcus aureus (MRSA) pneumonia, sepsis, tetraplasia, and osteoradionecrosis. We confirmed the effectiveness and safety of superselective arterial infusion and concomitant radiotherapy. Furthermore, we must establish the optimal procedures and schedule, as well as the indications for this treatment. This treatment protocol may improve the prognosis of patients with unresectable disease and patients rejecting surgical treatment. Further study in this particular area is needed. (author)

  13. Clinical and histopathological results after local chemoembolization of oral and oropharyngeal carcinoma - comparison with intraarterial chemoperfusion

    International Nuclear Information System (INIS)

    Rohde, S.; Turowski, B.; Berkefeld, J.; Kovacs, A.

    2006-01-01

    Purpose: retrospective analysis of clinical and histopathological results after neoadjuvant intraarterial chemoembolization (iaCE) as compared to intraarterial chemoperfusion (iaCP) in patients with oral and oropharyngeal squamous cell cancer (SCC), Materials and methods: 289 patients (mean age 60 years, 68% male) with SCC of the oral cavity or the oropharynx (WHO stage I-IV) received (1) neoadjuvant iaCE (n = 103) with a crystalline suspension of cisplatin (150 mg/m 2 , solution ratio 5 mg cisplatin ad 1 ml NaCl 0.9%, total volume 40-60 ml) or (2) iaCP (n = 186) using high-dose cisplatin infusions (150 mg/m 2 1 mg cisplatin ad 1 ml NaCl 0.9%, 400-500 ml). The decision for iaCE or iaCP was made individually for each patient based on tumor localization and expected vascular supply. Four weeks after local chemotherapy, the treatment response was evaluated according (1) to WHO criteria and (2) to histopathological TNM-grading after tumor resection. Results: the overall treatment response was 72.5% after iaCE and 47% after iaCP (p < 0.001). A stable disease was found in 24% and 48%, respectively, and tumor progression was found in 3% for both modalities. Histopathological examination of resected tumors revealed complete remission in 20% after iaCE and 13% after iaCP. The percentage of complete remissions was highest in local T1 and T2 tumors after iaCE (42.9 versus 22.4% after iaCP, p = 0.031). Local side effects were significantly more frequent after iaCE than after iaCP (p < 0.001), especially in obese patients with extended carcinoma of the oral floor or the tongue base. Conclusion: Compared to iaCP, clinical and histopathological remission rates are significantly higher after iaCe, especially in early stages of local tumor growth. However, in view of the higher risk of regional complications, indication for iaCE should be considered cautiously and its application should be limited to small tumors of the oral floor and the oral tongue. (orig.)

  14. Synthesis of [13N]cisplatin

    International Nuclear Information System (INIS)

    Haber, M.T.; Risenspire, K.C.

    1985-01-01

    A method for the ''carrier-added'' synthesis of [ 13 N]cisplatin is described. Yields were approx.1-4 mCi from 20-40 mCi of [ 13 N]ammonia with a total synthesis time of 19-28 minutes. The product was approx.96% radiochemically pure as judged by HPLC analysis and had a specific activity of approx.100 mCi/mmole in 1.0 ml of saline. [ 13 N)Cisplatin was administered intraperitoneally to mice. Of the tissues investigated, concentration of label was highest in kidneys. At 10 min, considerable label in the blood, liver, and kidney was in a form other than cisplatin. However, no evidence was obtained that [ 13 N]ammonia was released from [ 13 N]cisplatin in vivo. [ 13 N]Cisplatin may be used to assess drug delivery to primary and metastatic brain tumors in patients receiving intravenous or intraarterial cisplatin chemotherapy. (author)

  15. Metronidazole distribution following intraarterial administration

    International Nuclear Information System (INIS)

    Konoplyannikov, A.G.; Grigor'ev, A.N.; Zubov, O.G.

    1984-01-01

    An attempt to achieve a high local concentration of metronidazole in tissues at intraarterial administration in experiments with dogs is made. Intraarterial administration makes it possible to ''saturate'' with a radiosensitizer first of all tissues fed by an artery in question. Administration of the drug to a vessel feeding the tumor would, probably, result in a sharp increase in its concentration in the malignant neoplasm as compared with the rest organs and tissues, which should amplify the radiosensitizing effect

  16. Cisplatin Injection

    Science.gov (United States)

    Cisplatin is used combination with other medications to treat cancer of the testicles that has not improved ... after treatment with other medications or radiation therapy. Cisplatin is used alone or in combination with other ...

  17. Influence of amifostine on the pharmacokinetics of cisplatin in cancer patients

    NARCIS (Netherlands)

    Korst, A.E.C.; Sterre, M.L.T. van der; Gall, H.E.; Fichtinger-Schepman, A.M.J.; Vermorken, J.B.; Vijgh, W.J.F. van der

    1998-01-01

    The pharmacokinetics of cisplatin was investigated in 13 patients receiving 18 courses of cisplatin alone or in combination with amifostine to investigate the influence of amifostine (WR 2721; Ethyol) on the pharmacokinetics of cisplatin. Cisplatin was administered as a 1-h i.v. infusion, whereas

  18. Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer

    International Nuclear Information System (INIS)

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi

    2002-01-01

    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m 2 /day) was continuously infused over 24 hours, and CDDP (3-7 mg/m 2 /day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer. (author)

  19. Transarterial Chemoembolization Using Cisplatin Powder in a Rabbit Model of Liver Cancer

    International Nuclear Information System (INIS)

    Morimoto, Kengo; Sakaguchi, Hiroshi; Tanaka, Toshihiro; Yamamoto, Kiyosei; Anai, Hiroshi; Hayashi, Takayuki; Satake, Mitsuo; Kichikawa, Kimihiko

    2008-01-01

    The purpose of this study was to investigate the pharmacological advantages of transarterial chemoembolization (TACE) with cisplatin powder for hypervascular hepatic tumors in animal experiments. VX2 tumors were transplanted to the livers of nine rabbits. Cisplatin (1 mg/kg) was infused into the proper hepatic artery. In the cisplatin-HAI group, cisplatin solution was infused. In the cisplatin-GS-TACE group, after infusion of cisplatin solution, gelatin sponge particles were used for embolization. In the cisplatin-Lp-TACE group, after infusion of a cisplatin powder and lipiodol (10 mg/ml) suspension, gelatin sponge particles were used for embolization. Before and after administration, platinum concentrations in plasma were measured. Using liver specimens that were excised 60 min after infusion, platinum concentrations in tumorous and nontumorous liver tissues were measured. The mean platinum concentration in tumorous tissue was 0.88 μg/ml for the cisplatin-HAI group, 1.23 μg/ml for the cisplatin-GS-TACE group, and 12.65 μg/ml for the cisplatin-Lp-TACE group. The platinum concentration for the cisplatin-Lp-TACE group was significantly higher than that for the cisplatin-HAI group (p = 0.004) and the cisplatin-GS-TAE group (p = 0.004). The mean platinum concentration in nontumorous liver tissue was 0.98 μg/ml for the cisplatin-HAI group, 1.13 μg/ml for the cisplatin-GS-TACE group, and 1.09 μg/ml for the cisplatin-Lp-TACE group; no significant differences were seen. At both 5 and 10 min after infusion, the platinum concentrations for the cisplatin-Lp-TACE group were lower than those for the other two groups. The present results suggest that TACE using cisplatin powder/lipiodol suspension and gelatin sponge for hypervascular hepatic tumors has a number of pharmacological advantages.

  20. Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue.

    Science.gov (United States)

    Salman, Rida; Sebaaly, Mikhael G; Wehbe, Mohammad Rachad; Sfeir, Pierre; Khalife, Mohamad; Al-Kutoubi, Aghiad

    2017-06-01

    Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

  1. Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue

    Energy Technology Data Exchange (ETDEWEB)

    Salman, Rida; Sebaaly, Mikhael G. [American University of Beirut Medical Center, Department of Diagnostic Radiology (Lebanon); Wehbe, Mohammad Rachad; Sfeir, Pierre; Khalife, Mohamad [American University of Beirut Medical Center, Department of General Surgery (Lebanon); Al-Kutoubi, Aghiad, E-mail: mk00@aub.edu.lb [American University of Beirut Medical Center, Department of Diagnostic Radiology (Lebanon)

    2017-06-15

    Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

  2. Intra-arterial chemotherapy as a treatment for intraocular retinoblastoma: alternatives to direct ophthalmic artery catheterization.

    Science.gov (United States)

    Klufas, M A; Gobin, Y P; Marr, B; Brodie, S E; Dunkel, I J; Abramson, D H

    2012-09-01

    Intra-arterial chemotherapy is a very effective treatment option for intraocular retinoblastoma. However, direct catheterization of the OA is not always possible. The purpose of this work was to report our initial results with intra-arterial chemotherapy for intraocular retinoblastoma when delivery of the drug was not via direct catheterization of the OA. Retrospective review of 110 eyes (89 patients) undergoing a total of 351 intra-arterial treatments at our institution between 2006 and 2010 identified 18 eyes (14 patients) that received at least 1 infusion via a vascular route other than direct OA catheterization. Alternatives included catheterization of the orbital branch of the MMA and temporary balloon occlusion of the ICA. Tumor control was observed in 17 of 18 eyes at a mean follow-up of 18.9 months (median, 17.5 months; range, 8-36 months). The mean number of intra-arterial infusions was 3.7 per eye (median, 3; range, 2-9). Treatment routes included the following: MMA only, 3 eyes; MMA + OA, 4 eyes; MMA + balloon, 2 eyes; balloon only, 1 eye; balloon + OA, 7 eyes; balloon + OA + MMA, 1 eye. Intra-arterial chemotherapies included melphalan, topotecan, and carboplatin. Complications were all transient. ERG readings were the following: stable, 10 eyes; improved, 3 eyes; reduced, 5 eyes. One patient died from a second malignancy (pinealoblastoma). This initial experience shows that when direct OA catheterization is not possible, using alternative routes of intra-arterial chemotherapy saves eyes and preserves vision with acceptable side effects.

  3. Evaluation of hematologic toxicity of concurrent chemoradiotherapy using protracted infusion of low-dose cisplatin and 5-FU and radiotherapy for malignant tumors in elderly patients

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Yoshiyuki; Fuwa, Nobukazu; Matsumoto, Akira; Asano, Akiko; Sasaoka, Masahiro; Ii, Noriko; Kimura, Yasuo [Aichi Cancer Center, Nagoya (Japan). Hospital

    1999-06-01

    We evaluated the relationship between hematologic toxicity and the daily dose of CDDP or the field size of radiation in 26 patients with malignant tumors aged>70 years who underwent concurrent chemoradiotherapy consisting of infusion of low-dose CDDP and 5-FU and radiotherapy. None of the 26 patients developed Gr4 toxicity. The incidence of Gr3 toxicity was 23.1% (6/26) for leukocytes, 7.7% (2/26) for platelets, and 3.8% (1/26) for hemoglobin, being high for leukocytes. When the patients were classified into those aged 70-74 years (younger group) and those aged>75 years (older group), the incidence of Gr3 leukocyte and platelet toxicity was low in the former but high in the latter. Concerning the relationship between hematologic toxicity and the field size of radiation, the incidence of Gr3 hemoglobin, leukocyte, and platelet toxicity with a radiation field size<100 cm{sup 2} was 44% (4/9) in the older group but 0% in the younger group. In the older group, the daily CDDP dose tended to be low, and the field size of radiation tended to be small, but the incidence of hematological toxicity was high. In the younger group, the incidence of Gr2 or Gr3 toxicity increased with the daily dose of CDDP and the field size of radiation. (author)

  4. Acute effect of cisplatin on renal hemodynamics and tubular function in dog kidneys

    DEFF Research Database (Denmark)

    Daugaard, G; Abildgaard, U; Holstein-Rathlou, N H

    1986-01-01

    The present study was designed to investigate the early hemodynamic and tubular effects of cisplatin administration on dogs. To localize the nephrotoxic actions of cisplatin, we have taken advantage of the lithium clearance method. After infusion of 5 mg of cisplatin per kg, an immediate and sign......The present study was designed to investigate the early hemodynamic and tubular effects of cisplatin administration on dogs. To localize the nephrotoxic actions of cisplatin, we have taken advantage of the lithium clearance method. After infusion of 5 mg of cisplatin per kg, an immediate.......56 +/- 0.04 and from 4.76 +/- 0.32 mmol/min to 3.92 +/- 0.23 mmol/min, respectively. The results show that administration of cisplatin causes an acute, mainly proximal tubular impairment in dogs without alterations in renal hemodynamics....

  5. Intraarterial Scintigraphy in recurrent Cervix Cancer - The Evaluation of Radionuclide therapeutic Trials -

    International Nuclear Information System (INIS)

    Kim, Eun Young; Suh, Jin Suck; Park, Chang Yun; Lee, Jong Tae; Yoo, Hyung Sik

    1990-01-01

    We performed 17 intraarterial scintigraphies in six patients with recurrent cervix cancer. With Seldinger method, the agent (four different radiopharmaceuticals) was perfused at the same speed of infusion of anticancer drugs (25 cc/hour) through internal iliac artery. There were four different radiopharmaceuticals; 131 I-Lipiodol, 99m Tc(Technetium)-HSA (Human Serum Albumin), 99m Tc-Sucralfate and 99m Tc-MAA (Macroaggregated Albumin). We evaluate the distribution pattern of radioactivity by the use of ratio of Tumor/Extratumor uptake (T/ET ratio). Our results reveals that 99m Tc-MAA scan showed the highest T/ET ratio and the other were not ideal agents for intraarterial therapy of recurrent cervix cancer. In conclusion, an ideal radioisotope and tracer which can block capillary, for example MAA, should be re-evaluated or produced in order to treat the patient with recurrent cervix cancer.

  6. Intra-arterial intervention chemotherapy for sarcoma and cancerous ulcer via an implanted pump.

    Science.gov (United States)

    Liu, Cheng; Cui, Qiu; Guo, Jun; Li, Dingfeng; Zeng, Yanjun

    2014-04-01

    To observe the efficacy of intra-arterial chemotherapy with subcutaneously implanted pump for soft tissue sarcoma in extremities and cancerous ulcer. 31 patients with ulcerative skin squamous cell carcinoma or sarcoma in extremities who received treatment during the period from July 2003 to November 2011 at our hospital were recruited, including 15 male and 16 female patients, aging between 14 and 83 with average age of 49 years old. 10 patients had tumor in upper extremities and 21 patients in lower extremities. The pathological types of studied cases include 9 cases with skin squamous cell carcinoma, 6 cases with synovial sarcoma, 5 cases with malignant fibrous histiocytoma, 3 cases with liposarcoma, 3 cases with osteosarcoma, 2 cases with malignant melanoma, 2 cases with epidermoid sarcoma, and 1 case with protuberans. The main symptoms of cancerous ulcer were pain, infection and hemorrhage; All the studied patients were administrated with cisplatin and doxorubicin by intra-arterial chemotherapy pump, and the patients with squamous cell carcinoma were additionally applied with bleomycin and patients with malignant melanoma were additionally applied with dacarbazine. The chemotherapy efficiency was observed after at 3 cycles of intra-arterial chemotherapy. The total remission rate of pain (RR) was 87 %, and total remission rate of ulcer cicatrization (RR) was 71 %, with ulcer cicatrizing spontaneously in 9 cases and obvious homeostasis in 5 cases with bleeding ulcers. 19 patients underwent surgery after chemotherapy, in which 16 cases had limb-salvage surgery and 3 cases underwent lower leg amputation after chemotherapy, and 3 patients out of 16 cases had local recurrence (19 %). The subcutaneous intra-arterial targeting chemotherapy could be applied to treat refractory sarcoma and cancerous ulcer in extremities to significantly increase the chemotherapeutic concentration at tumor area so as to effectively constrain the tumor rupture induced main symptoms

  7. A low-dose regimen of cisplatin before high-dose cisplatin potentiates ototoxicity.

    Science.gov (United States)

    Harrison, Ryan T; DeBacker, J Riley; Bielefeld, Eric C

    2015-02-01

    Cochlear preconditioning with low doses of kanamycin or noise can reduce susceptibility to noise- and ototoxic drug-induced hearing loss. The current study was undertaken to investigate whether a preconditioning regimen of low-dose cisplatin would alter susceptibility to ototoxicity induced by a single large dose of cisplatin. In vivo study using an animal model. Twenty-six Fischer 344/NHsd rats were used in the study. The low-dose regimen consisted of cisplatin (2 or 3 mg/kg) given every 2 weeks by intraperitoneal injection. Control animals received injections of saline on the same schedule as the cisplatin injections. Four injections were done in total. Following the preconditioning interval, seven of the animals were sacrificed for hair cell analyses. The remaining 19 animals were exposed to 12 mg/kg cisplatin by intraperitoneal infusion to induce cochlear injury. Auditory brainstem response (ABR) thresholds were measured 3 days after cisplatin, and the cochleae from the 19 animals were harvested and analyzed. Statistical analyses revealed no threshold shifts, but mild outer hair cell losses, after the low-dose regimen. ABR threshold shifts in the rats exposed to the 12 mg/kg cisplatin dose were significantly higher at day 3 in the animals that underwent preconditioning with low-dose cisplatin. Outer hair cell losses were also greater in the preconditioned animals. Preconditioning with low-dose cisplatin, using the protocol applied in the current experiment, created potentiation of cisplatin ototoxicity, rather than protection from it. There are numerous possible explanations for this effect that should be considered. NA. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  8. Digital subtraction angiography of inferior gluteal artery through the infusion catheter of chemotherapy for bladder cancer

    International Nuclear Information System (INIS)

    Ishikawa, Satoru; Noguchi, Ryosuke; Kanoh, Shori; Shimazui, Toru; Uchida, Katsunori; Nemoto, Ryosuke; Koiso, Kenkichi

    1987-01-01

    More than fifty patients of invasive bladder cancer had been treated by selective intra-arterial chemotherapy through the inferior or superior gluteal arteries. The distribution of infused drugs had been evaluated by RI-angiography through a thin arterial infusion catheter. This time we performed digital subtraction angiography (DSA) through an infusion catheter in order to know the precise distribution of infused materials in seven patients with locally advanced bladder cancer. Pharmaco-DSA with norepinephrine was also done in four patients. Satisfactory spatial and contrast resolution were gained in four patients and pharmaco-DSA showed better quality. In our experience DSA through intra-arterial infusion catheter was a useful procedure in the evaluation of distribution of infused drugs. (author)

  9. Eating and swallowing ability after treatment for head and neck cancers with superselective intra-arterial chemoradiotherapy

    International Nuclear Information System (INIS)

    Akisada, Takeshi; Harada, Tamotsu; Aihara, Teruhito; Uno, Masako; Imai, Shigeki; Hiratsuka, Junichi; Hiraoka, Takashi; Kumakura, Isami

    2008-01-01

    The objective of this study was to evaluate the preservation of eating and swallowing function following the use of superselective intra-arterial chemoradiotherapy for advanced head and neck cancers. Among the 96 Patients receiving concomitant radiation and intra-arterial docetaxel, systemic cisplatin and 5-fluorouracil (FU) chemotherapy, the videofluoroscopic and videoendoscopy findings and results of a questionnaire were evaluated. A Videofluoroscopic examination revealed an improved swallow function in 2 of 13, no change in 4, slightly worse in 5 and worse in 2 patients. Following treatment, the incidence of aspiration increased in four patients. Videoendoscopy revealed a residual of vallecula in few cases. Most of the patients were able to swallow after chemoradiation. The questionnaire results showed that the eating and swallowing functions were well preserved in almost 80% of the patients. The new chemoradiation protocol is thus considered to be equivalent to the other treatment modalities for maintaining the functions of eating and swallowing. (author)

  10. Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: Analysis of therapeutic results in 112 cases

    International Nuclear Information System (INIS)

    Mitsudo, Kenji; Koizumi, Toshiyuki; Iida, Masaki; Iwai, Toshinori; Nakashima, Hideyuki; Oguri, Senri; Kioi, Mitomu; Hirota, Makoto; Koike, Izumi; Hata, Masaharu; Tohnai, Iwai

    2014-01-01

    Purpose: To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. Materials and methods: One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60 mg/m 2 , cisplatin, total 150 mg/m 2 ) and daily concurrent radiotherapy (total of 60 Gy) for 6 weeks. Results: The median follow-up for all patients was 46.2 months (range, 10–76 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients. Conclusion: Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control

  11. Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer: the memphis experience

    International Nuclear Information System (INIS)

    Robbins, K. Thomas; Kumar, Parvesh; Regine, William F.; Wong, Frank S. H.; Weir, Alva B.; Flick, Pamela; Kun, Larry E.; Palmer, Robert; Murry, Thomas; Fontanesi, James; Ferguson, Robert; Thomas, Randall; Hartsell, William; Paig, Camilo U.; Salazar, George; Norfleet, Linda; Hanchett, Catherine B.; Harrington, Vanessa; Niell, H. Barry

    1997-01-01

    Purpose/Objective: To evaluate the feasibility, response rates, and toxicity of a Phase II study using targeted supradose cisplatin and concurrent radiation therapy in unresectable Stage III-IV head and neck squamous cell carcinoma. Methods and Materials: Sixty patients presenting between (6(93))-(9(94)) were enrolled, 44 (73%) of whom had T4 and/or N2-N3 nodal disease. All patients were treated with rapid targeted superselective intraarterial infusions of cisplatin (150 mg/m 2 weekly x 4) and simultaneous sodium thiosulfate intravenously (9 g/m 2 ) for systemic neutralization of cisplatin. Concurrent (day 1) daily radiation therapy was delivered to the primary tumor and overt nodal disease to 66-74 Gy while the uninvolved lower neck received 50 Gy, at 2.0 Gy/fraction. Results: Fifty-one (85%) patients completed the full RADPLAT protocol as planned. Fifty-seven of 60 patients were evaluable for response. Histological (n = 50) or clinical (n = 7) assessment of primary site revealed a complete response (CR) in 52 patients, partial response (PR) in 4, and stable disease (SD) in 1. Of the 40 patients presenting with nodal metastases, pathological (n = 31) or clinical (n = 6) assessment revealed a CR in 25, PR in 11, and SD in 1, while 3 were unevaluable. Overall, for both primary site and nodal disease, CR was attained in 44 (75%), PR in 12 (23%), and SD in 1 (2%) of the 57 evaluable patients. Only 2 (4%) of 57 evaluable patients have recurred above the clavicle, 1 in the primary site and 1 in the regional lymph nodes. Twelve patients (23%) have failed in distant sites. Grade III/VI toxicity has included gastrointestinal in 6, hematologic in 6, mucosal in 12, vascular in 4, and neurological in 4 patients. Conclusion: Concurrent radiation therapy and targeted supradose cisplatin (i.e., RADPLAT) can be safely delivered with high response rates and excellent loco-regional control in advanced Stage III/IV head and neck squamous cell carcinoma

  12. Infusion cisternography

    International Nuclear Information System (INIS)

    Magnaes, B.; Rootwelt, K.; Sjaastad, O.

    1976-01-01

    A source of error in cerebrospinal fluid (CSF) infusion tests is leakage at the dural puncture site. The addition of a bolus of radionuclide to the infusion fluid was helpful in detecting the existence of leakage as shown by increased infusion pressure in six of eight patients studied with and without scintigraphic evidence of leakage. Comparison of CSF dynamics in 26 patients studied by infusion cisternography and conventional cisternography showed similar patterns, suggesting no alteration of CSF dynamics by the artificial CSF infusion. Combining the two tests, therefore, resulted in simple identification of the leakage and saved the patient time and discomfort

  13. Evaluation for intravenous, arterial and local infusion of a hypoxic cell radiosensitizer RK28 on rabbit VX2 tumor system

    International Nuclear Information System (INIS)

    Kuramitsu, Tatsuya

    1993-01-01

    We evaluated the radiosensitizing effect of intraarterial, intravenous and local infusion of a hypoxic cell radiosensitizer RK28 on rabbit VX2 tumor system. Six rabbits were treated in each infusion group. VX2 tumor was implanted in the left hind leg. Tumor grown up to 3 cm in diameter was treated with 15 Gy of X-ray irradiation just after infusion of radiosensitizer RK28 (80 mg/kg.b.w.). Intratumoral and serum mean concentration of RK28 and its metabolites were measured. Tumor regression curve and survival time were analyzed. The following results were obtained. Mean concentration of RK28 was about 2.5 times greater in local infusion and 1.5 times in intraarterial infusion than in intravenous infusion. Significant regression of tumor was obtained in intraarterial infusion (p<0.01). There was no significant difference in survival time. These data suggest that the usefulness of intraarterial infusion of RK28 for local control using intraoperative radiation therapy and brachytherapy. (author)

  14. Computed tomography after the intra-arterial and intravenous administration of contrast media

    International Nuclear Information System (INIS)

    Young, S.W.

    1981-01-01

    In computed tomography (CT) body scanning, the amount of contrast medium which has accumulated in a tissue is related to the delivery of the contrast agent to the tissue and the contrast medium extraction ratio of the tissue. The two main tissue characteristics responsible for differential contrast medium accumulation are capillary leak and differences in the size of the interstitial space. Given two tissues which leak contrast medium the best CT scanning methodology consists of delivering a rapid bolus of as high a concentration of contrast medium as can be biologically safely delivered. In order to assess the rapid pharmacokinetics, dynamic CT scanning throughout the passage of the bolus is the best technique to employ. Given two tissues, one of which leaks contrast medium and one which does not, optimal technique would utilize a sustained drip infusion, subsequently stopping the infusion, and after the blood pool has declined, obtaining CT scans through the area of interest. The accumulated tissue levels are directly related to the administered concentration, and on this basis, intra-arterial administration is superior to intravenous administration in producing contrast enhancement. The routine intra-arterial administration of contrast medium, although superior, has little practical application in the clinical setting. The contrast enhancement of blood vessels, however, is probably best produced by a sustained bolus infusion, preferably delivered into the vascular structure to be evaluated (i.e., the left foot if the left external iliac vein is to be evaluated). (Auth.)

  15. Preoperative balloon occluded arterial infusion chemotherapy for locally invasive bladder cancer. Accurate staging for bladder preservation

    International Nuclear Information System (INIS)

    Hayashi, Norio; Arima, Kiminobu; Kawamura, Juichi; Tochigi, Hiromi

    1999-01-01

    The possibility of bladder preservation by preoperative balloon occluded arterial infusion (BOAI) chemotherapy was studied in 111 patients with locally invasive bladder cancer. BOAI was performed by blocking the blood flow of the internal iliac artery and by performing intra-arterial infusion of adriamycin (50 mg/body) and cisplatin (100 mg/body). Before BOAI the clinical diagnosis was T2 in 36, T3a in 29, T3b in 27, T4 in 11 and after BOAI it was T0 in 1, T1 in 27, T2 in 25, T3a in 20, T3b in 20, and T4 in 10. Down staging was observed on diagnostic images in 46.6%. Thirty patients (27.0%) received transurethral resection of bladder tumor (TUR-Bt) and their bladder could be preserved. The 5-year cancer-specific survival rate was 100% in pT0 (n=9), 97.5% in pT1 (n=47), 79.9% in pT2 (n=21), 80.0% in pT3a (n=6), 39.9% in pT3b (n=18) and 51.9% in pT4 cases (n=9). For the bladder preservation, accurate staging diagnosis is required. Since 1992, endorectal magnetic resonance imaging (MRI) has been used in addition to imaging diagnosis for improving the accuracy of staging diagnosis. The accuracies of staging diagnosis with and without endorectal MRI were 62.5% and 44.0%, respectively. BOAI as a neoadjuvant chemotherapy has the possibility of bladder-preserving therapy in locally invasive bladder cancer. Also, the endorectal MRI can improve the accuracy of staging diagnosis, which is important for the bladder preservation. (author)

  16. Analysis of cervical cancer cells treated with radiotherapy or arterial infusion chemotherapy

    International Nuclear Information System (INIS)

    Izutu, Toshihiko; Nishiya, Iwao

    1995-01-01

    The present study was designed to analyze cervical cancer cells treated with radiotherapy or intraarterial infusion of CDDP using image analysis. Total nuclear extinction (TE), 5 N-exceeding rate (5 NER) and nuclear area (NA) gradually increased following irradiation, in cervical cancer cases. TE and 5 NER increased markedly following radiotherapy in good response cases. TE, 5 NER and NA were not-changed following irradiation in poor response cases. 5 NER, in good prognostic cases was higher than in poor prognostic cases, significantly among cervical cancer cases treated with radiotherapy. 5 NER and NA increased dramatically in good response cases treated with intraarterial infusion of CDDP. (author)

  17. Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a (10)BSH-containing WOW emulsion.

    Science.gov (United States)

    Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun; Ono, Minoru; Takahashi, Hiroyuki; Eriguchi, Masazumi

    2014-06-01

    A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in-water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that (10)BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Prevention of cisplatin nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Hayati Fatemeh

    2016-01-01

    Full Text Available Cisplatin has a well-established role in the treatment of broad spectrum of malignancies; however its use is limited because of cisplatin-induced nephrotoxicity (CIN which can be progressive in more than 50% of cases. The most important risk factors for CIN include higher doses of cisplatin, previous cisplatin chemotherapy, underlying kidney damage and concurrent treatment with other potential nephrotoxin agents, such as aminoglycosides, nonsteroidal anti-inflammatory agents, or iodinated contrast media. Different strategies have been offered to diminish or prevent nephrotoxicity of cisplatin. The standard approach for prevention of CIN is the administration of lower doses of cisplatin in combination with full intravenous hydration prior and after cisplatin administration. Cisplatin-induced oxidative stress in the kidney may be prevented by natural antioxidant compounds. The results of this review show that many strategies for prevention of CIN exist, however, attention to the administration of these agent for CIN is necessary.

  19. [Intra-arterial thrombolytic therapy of lower limb ischemia].

    Science.gov (United States)

    Juhan, C; Haupert, S; Miltgen, G; Dulac, P; Girard, N; Barthélémy, P; Raybaud, C

    1990-02-01

    Between 1984 and 1989, 35 patients with recent arterial or graft occlusions have been treated with intra-arterial infusion using sequential association of Urokinase (U.K.) and Lys-Plasminogen. Occlusion was thrombotic in 68.5% of the cases ans embolic in 31.5%, involving 28 native arteries and 7 bypass grafts. The mean duration was 16 days (2 to 90). Continuous infusion of U.K.: 84,000 U.I./H and bolus of Lys-Plasminogen 15 microKatals every 30 minutes were delivered through a catheter embedded into the clot. Intra-venous heparin was always associated. The mean duration of lytic drug infusion was 8 H. Complementary arterial reconstruction by vascular surgery of percutaneous transluminal angioplasty was performed in 23% of the patients. Patients with recent alimentary tract bleeding, hemorragic stroke in the last six months or severe high blood pressures were contra-indicated. Complete lysis was obtained in 23 cases (66%), partial lysis in 7 (20%) and no lysis in 5 (14%). The clinical result was excellent in 24 cases (68.5%), good in 3 (8.5%) and bad in 8 (23%) in which amputation was always necessary. 5 local hematoma (14%) treated by surgery or transfusion and one death (3%) due to neurological complication occurring 24 hours after the end of the procedure were observed. The literature survey has shown that the results of low doses of Streptokinase (S.K.) local infusions were not better, and that higher doses of S.K. or U.K. delivered during a shorter infusion time increased the efficacy of lysis and decreased the rate of hemorragic complications. We have proposed the local thrombolytic treatment to the limb threatening ischemic cases when the traditional medical or surgical techniques where thought to be associated to a high risk of failure or complication. The specific indications are the acute or sub-acute ischemic situation due to atheromatous artery thrombosis, distal or old embolism where the Fogarty catheter is inefficient, and graft thrombosis. Severe

  20. Analysis of multi-factors affecting symptomatic intracranial hemorrhage in intraarterial thrombolysis with urokinase for acute ischemic stroke

    International Nuclear Information System (INIS)

    Qiao Qianlin; Zhou Shi; Wang Xuejian; Wu Qinghua; Song Jie

    2005-01-01

    Objective: To explore the causes and preventive measures of symptomatic intracranial hemorrhage in 217 patients with acute cerebral ischemic stroke treated with local intra-arterial urokinase. Methods: From February 1999 to June 2004, 217 patients were treated for acute ischemic stroke with local intra-arterial urokinase in our hospital. Factors associated with symptomatic intracranial hemorrhage of intra-arterial thrombolysis were analyzed by Stepwise logistic regression to identify some factors relating the prediction symptomatic intracranial hemorrhage. Results: Symptomatic intracranial hemorrhage occurred in 8 cases (3.7%). Predictors of the symptomatic intracranial hemorrhage were the elevated systolic blood pressure before therapy (odds ratio, 1.096; 95% CI, 1.006 to 1.194) and urokinase (UK) treatment (odds ratio, 1.068 ; 95% CL, 1.053 to 1.247). Risk of secondary symptomatic intracranial hemorrhage was increased with elevated systolic blood pressure. Other factors like age, initial treating time, NIHSS, diabetes and collateral circulation did not predict the symptomatic intracranial hemorrhage respectively. Conclusions: Predictors of symptomatic intracranial hemorrhage after local intra-arterial infusion of urokinase for acute ischemic stroke were the elevated systolic blood pressure before therapy and urokinase (UK) treatment. (authors)

  1. FDG uptake after intraarterial chemotherapy in head and neck cancer

    International Nuclear Information System (INIS)

    Doebert, N.; Kovacs, A.F.

    2006-01-01

    Aim: the intraarterial chemotherapy (i.a.CHT) using high dose cisplatin combined with systemic neutralization in patients with head and neck cancer (HNSCC) is used to reduce the tumor volume preoperatively. Aim of the study is the evaluation of the influence of i.a.CHT on the metabolism of fluor-18-deoxyglucose (FDG) in the primary and lymph nodes (LN). The value of FDG positron emission tomography (PET) preoperative and as follow-up method otter i.a.CHT is examined. Patients, methods: altogether 16 patients with HNSCC underwent two preoperative FDG PET examinations: the baseline examination one week before and the follow-up three weeks after i.a.CHT. The SUVmax values of the primary and the IN and LN metastases were evaluated and compared with each other and the histopathology. Results: the SUVmax value of the primary decreased after i.a.CHT significantly from a median (25 th percentile/ 75 th percentile) of 6.4 (4.1/ 7.8) to 3.6 (2.4/ 6.7) (p = 0.01). In 11 out of 16 patients cervical LN metastases were detected. The cervical LN metastases showed a decrease of the SUVmax value from 3.6 (2.3/ 4.8) in the pretreatment examination to 2.3 (1.7/ 3.6) after i.a.CHT (p = 0,008). Only in one patient with LN metastases the SUVmax of the nodes increased. The histopathologically measured size of the LN metastases ranged from 2 to 30 mm. Non malignant LN did not reveal a significant SUVmax decrease after i.a.CHT (p = 0.13). Conclusions: as expected, primaries of HNSCC showed a significant reduction of SUV after i.a.CHT. Compared to the primary the SUVmax decrease in LN metastases was less, but also significant. Since cytotoxic levels of cisplatin do not occur systemic, postinflammatory reactions of the LN or a lymphatic drainage of the chemotherapeutic drug into the LN could be an explanation. PET for staging of HNSCC must thus be performed prior to i.a.CHT. (orig.)

  2. Intra-arterial chemotherapy for locally advanced bladder cancer

    International Nuclear Information System (INIS)

    Aota, Yasuhiro; Yoshida, Kazuhiko

    1999-01-01

    A total of 83 patients with locally advanced bladder cancer (T1, n=5; T2, n=28; T3a, n=21; T3b, n=21; T4, n=8) were treated with intra-arterial (i.a.) cisplatin and adriamycin (or epirubicin) chemotherapy. In 51 of the 83 cases, we combined this treatment with radiotherapy. The pathological complete response (CR) rate was 68% for all patients, 84% for i.a. chemotherapy combined with radiotherapy and only 41% for i.a. chemotherapy. The 5-year survival rate was 57% for all patients, 71% for i.a. chemotherapy combined with radiotherapy and only 44% for i.a. chemotherapy. The 5-year survival as a function of the clinical stage was 82% for T1+T2, 66% for T3a, 28% for T3b, 25% for T4 (T1+T2 vs. T3b: p<0.001, T1+T2 vs. T4: p<0.0001, T3a vs. T3b: p<0.0263, T3a vs. T4: p<0.0214, T3b vs. T4: p<0.029). In 46% of all patients, we succeeded in preserving the bladder; especially noteworthy, is that in 65% of the patients undergoing i.a. chemotherapy combined with radiotherapy, we succeeded in preserving the bladder. These results demonstrate that i.a. chemotherapy combined with radiotherapy is a useful method for locally advanced bladder cancer which may make preservation of the bladder function feasible. (author)

  3. Acute effect of cisplatin on renal hemodynamics and tubular function in dog kidneys

    DEFF Research Database (Denmark)

    Daugaard, G; Abildgaard, U; Holstein-Rathlou, N H

    1986-01-01

    The present study was designed to investigate the early hemodynamic and tubular effects of cisplatin administration on dogs. To localize the nephrotoxic actions of cisplatin, we have taken advantage of the lithium clearance method. After infusion of 5 mg of cisplatin per kg, an immediate.......56 +/- 0.04 and from 4.76 +/- 0.32 mmol/min to 3.92 +/- 0.23 mmol/min, respectively. The results show that administration of cisplatin causes an acute, mainly proximal tubular impairment in dogs without alterations in renal hemodynamics....

  4. Treatment of heavy epistaxis by intraarterial embolisation

    Energy Technology Data Exchange (ETDEWEB)

    Bohutova, J.; Kolar, J.; Olejnicek, A.

    1981-02-01

    Therapeutic intraarterial embolisation is a modern and effective approach in the therapy of otherwise untreatable heavy epistaxis. The most important indications for it were in the clinical survey reported here, bleedings after trauma and in arterial hypertension and/or generalised atherosclerosis. Several examples are documented. Therapeutic embolisation in this area necessitates a precise technique because in even small faults serious, mainly neurological complications may arise. For these reasons, this intervention is suitable for specialised laboratories only.

  5. Treatment of heavy epistaxis by intraarterial embolisation

    International Nuclear Information System (INIS)

    Bohutova, J.; Kolar, J.; Olejnicek, A.

    1981-01-01

    Therapeutic intraarterial embolisation is a modern and effective approach in the therapy of otherwise untreatable heavy epistaxis. The most important indications for it were in the clinical survey reported here, bleedings after trauma and in arterial hypertension and/or generalised atherosclerosis. Several examples are documented. Therapeutic embolisation in this area necessitates a precise technique because in even small faults serious, mainly neurological complications may arise. For these reasons, this intervention is suitable for specialised laboratories only. (orig.) [de

  6. MRI evaluation of frequent complications after intra-arterial transplantation of mesenchymal stem cells in rats

    Science.gov (United States)

    Namestnikova, D.; Gubskiy, I.; Gabashvili, A.; Sukhinich, K.; Melnikov, P.; Vishnevskiy, D.; Soloveva, A.; Vitushev, E.; Chekhonin, V.; Gubsky, L.; Yarygin, K.

    2017-08-01

    Intra-arterial transplantation of mesenchymal stem cells (MSCs) is an effective delivery route for treatment of ischemic brain injury. Despite significant therapeutic effects and targeted cells delivery to the brain infraction, serious adverse events such as cerebral embolism have been reported and may restrict potential clinical applications of this method. In current study, we evaluate potential complications of intra-arterial MSCs administration and determine the optimum parameters for cell transplantation. We injected SPIO-labeled human MSCs via internal carotid artery with different infusion parameters and cell dose in intact rats and in rats with the middle cerebral occlusion stroke model. Cerebrovascular complications and labeled cells were visualized in vivo using MRI. We have shown that the incidence of cerebral embolic events depends on such parameters as cell dose, infusion rate and maintenance of blood flow in the internal carotid artery (ICA). Optimal parameters were considered to be 5×105 hMSC in 1 ml of PBS by syringe pump with velocity 100 μ/min and maintenance of blood flow in the ICA. Obtained data should be considered before planning experiments in rats and, potentially, can help in planning clinical trials in stroke patients.

  7. Successful use of continuous vasodilator infusion to treat critical vasospasm threatening a distal bypass

    OpenAIRE

    Gregory A. Magee, MD, MSc; Anastasia Plotkin, MD; Jeniann A. Yi, MD, MS; Kathryn E. Bowser, MD; David P. Kuwayama, MD, MPA

    2018-01-01

    Vasospasm immediately after lower extremity arterial bypass may represent an uncommon cause of early graft failure. We report a successful case of catheter-directed, intra-arterial continuous vasodilator infusion to salvage a bypass graft threatened by severe, refractory vasospasm after incomplete response to nicardipine, verapamil, and nitroglycerin boluses. A continuous nitroglycerin infusion was administered for 24 hours, by which time the vasospasm resolved. At 12 months postoperatively, ...

  8. Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

    Science.gov (United States)

    Kirikoshi, Hiroyuki; Yoneda, Masato; Mawatari, Hironori; Fujita, Koji; Imajo, Kento; Kato, Shingo; Suzuki, Kaori; Kobayashi, Noritoshi; Kubota, Kensuke; Maeda, Shin; Nakajima, Atsushi; Saito, Satoru

    2012-01-01

    AIM: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) resistant to transarterial chemoembolization (TACE). METHODS: This study was conducted on 42 patients who received HAIC for advanced HCC between 2001 and 2010 at our hospital. 5-fluorouracil (5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir. Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU. The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010 (written in Japanese); one group of patients who did not fulfill the criteria for TACE resistance (group A, n = 23), and another group who fulfilled the criteria for TACE resistance (group B, n = 19). We compared the outcomes in terms of the response and survival rates between the two groups. RESULTS: Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B (response rate: 48% vs 16%, P = 0.028, tumor suppression rate: 87% vs 53%, P = 0.014). Furthermore, both the progression-free survival rate and survival time were significantly superior in group A than in group B (3-, 6-, 12-, and 24-mo = 83%, 70%, 29% and 20% vs 63%, 42%, 16% and 0%, respectively, P = 0.040, and 9.8 mo vs 6.2 mo, P = 0.040). A multivariate analysis (Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival (P = 0.007). CONCLUSION: HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE. Other tools for treatment, i.e., molecular-targeting agents may be considered for these cases. PMID:22563174

  9. Uptake and retention of 191Pt in patients undergoing therapy with cisplatin

    International Nuclear Information System (INIS)

    Areberg, J.; Norrgren, K.; Bjoerkman, S.; Einarsson, L.; Mattsson, S.; Nordberg, B.; Scheike, O.; Wallin, R.

    1997-01-01

    191 Pt was produced by firing protons, 70-75 MeV, on stable isotopes. The activity was separated from the target and in the final solution containing 1-2 GBq in the form of 191 PtCl 4 . Synthesis of 191 Pt-cisplatin was performed under sterile conditions. The radionuclide purity, chemical purity, identity of the synthesised cisplatin as well as sterility and absence of endotoxins were checked. About 10% of the amount of cisplatin for a planned chemotherapy administration was replaced by our in-house synthesised cisplatin. This fraction corresponded to 3-10 mg cisplatin and an activity of 25-50 MBq. The drug was administered by a 2 hour infusion to patients undergoing treatment for different types of tumours. The activity distribution was measured with a gamma camera directly after the infusion and at 24 hours and up to 10 days after infusion. The activity yield of the synthesis was 10-36%. The radionuclide purity for the synthesised 191 Pt cisplatin was 99%. About 1% of the total activity was in the form of 1 8 8P t at the time of infusion

  10. Evaluation of clinical efficacy of intraarterial thrombolysis for acute cerebral ischemic stroke

    International Nuclear Information System (INIS)

    Wu Qinghua; Zhou Shi; Song Jie; Wang Xuejian; He Yujie

    2005-01-01

    Objective: To evaluate the clinical efficacy of local intra-arterial thrombolysis (LIT) with urokinase in patients with acute ischemic stroke. Methods: One hundred and sixty two patients with acute ischemic stroke were treated with LIT by using urokinase and relationship of recanalization for different occluded arteries with the Glasgow outcome scale (GOS) scores three months later was analyzed. Results: Angiography showed occlusion of the cerebral artery in 162 patients, among which 119(73.5%) patients showed the sites in the internal carotid artery system, with 27 occlusions in the internal carotid artery (ICA) trunk, 63 (38.89%) in the middle cerebral artery (MCA) and 29 (17.9%) in the anterior cerebral artery (ACA) , and the remaining 43 (26.5%) patients of vertebrobasilar artery (VBA); successful recanalization was achieved in 103 (63.58%) patients, including 11 (40.7%), 49 (77.8%), 20 (69.0%) and 23 (53.3%), respectively, after intraarterial infusion of urokinase. Unsuccessful recanalization occurred in 59 patients (36.42%). Followed up for 90 days, 90 (55.6%) patients obtained a good outcome; 72(44.44%) had poor prognosis including 20(12.35%) deaths. 8 patients associated with hemorrhage (4.9%) 73 with reperfusion injury (45.1%) and 5 arterial re-occlusion (3.1%). Based on statistic analysis, ICA trunk and VBA had low ratio of successful recanalization with poor clinic prognosis MCA and ACA possessed high ratio of successful recanalization and good clinic outcomes. There was a significant relationship between arterial recanalization rate and clinic prognosis (r=0.86). Conclusions: Successful recanalization of cerebral occlusive artery by using intra-arterial thrombolysis could improve clinic prognosis in patients with acute ischemic stroke. Clinical prognosis has a significant relationship with both initial treatment time and arterial recanalization rate. (authors)

  11. Access to the ophthalmic artery by retrograde approach through the posterior communicating artery for intra-arterial chemotherapy of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Chi-Tuan; Blanc, Raphael; Pistocchi, Silvia; Bartolini, Bruno; Piotin, Michel [Fondation Rothschild Hospital, Department of Interventional Neuroradiology, Paris (France); Lumbroso-Le Rouic, Livia [Institut Curie, Department of Ocular Oncology, Paris (France)

    2012-08-15

    Intra-arterial infusion of chemotherapy into the ophthalmic artery for treatment of retinoblastoma has been realized after catheterization of the internal carotid and temporary balloon occlusion beyond the orifice of the ophthalmic artery, or more recently after superselective canulation of the ophthalmic artery by a microcatheter. The superselective catheterization of the ophthalmic artery could be cumbersome because of the implantation of the ostium on the carotid siphon or because of the tortuosity of the carotid siphon. We report our experience of using a retrograde approach through the posterior communicating artery that allows a more direct angle of access to the origin of the ophthalmic artery. (orig.)

  12. Treatment of hydrofluoric acid burn to the face by carotid artery infusion of calcium gluconate.

    Science.gov (United States)

    Nguyen, Lan T; Mohr, William J; Ahrenholz, David H; Solem, Lynn D

    2004-01-01

    Hydrofluoric acid (HF) is highly corrosive substance often used in industrial processes. HF burns to the skin cause local tissue injury. Systemic hypocalcemia may ensue, with the potential to produce life-threatening arrhythmias. Medical treatment consists of local application of topical calcium gels, subcutaneous injection of calcium gluconate, and intravenous or intra-arterial infusion of calcium gluconate. Calcium gluconate infusions have been used for HF burns on distal extremities and digits. We report a case of HF burn to the face that was treated by the use of calcium gluconate infusion via the external carotid artery.

  13. Intra-arterial thrombolysis for acute ischemic stroke

    International Nuclear Information System (INIS)

    Burnette, W.C.; Nesbit, G.M.

    2001-01-01

    Intra-arterial thrombolysis is a maturing treatment for acute thromboembolic stroke that shows promise in restoring cerebral blood supply. Reviewed evidence suggests that intra-arterial treatment has a longer window for treatment than intravenous t-PA and does improve outcome. A favorable outcome is dependent on careful patient selection aimed at avoiding intracranial hemorrhage. This article describes features to evaluate for patient selection and highlights factors along the treatment algorithm to maximize success. (orig.)

  14. Distribution of radiolabeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride in rat brain tumor: intraarterial versus intravenous administration

    International Nuclear Information System (INIS)

    Yamada, K.; Ushio, Y.; Hayakawa, T.; Arita, N.; Huang, T.Y.; Nagatani, M.; Yamada, N.; Mogami, H.

    1987-01-01

    To assess the rationale of intraarterial (i.a.) 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy, distribution of 14 C-labeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea in rat glioma was studied after i.a. or i.v. infusion. Immediately after infusion, the tumor located in the hemisphere of intracarotid infusion received 4.6-fold higher radioactivity than the tumor located contralaterally to intracarotid infusion and 2.8-fold higher radioactivity than i.v. infusion. The difference was kept up to 30 min after i.a. infusion. Autoradiographic observation indicated rather uniform distribution of the tracer in the central portion of i.a. infusion. However, in the periphery of i.a. infusion, distribution of the tracer was nonhomogenous. The results indicate that i.a. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy is useful when the tumor has high blood flow and is located in the center of an infused area

  15. Intraarterial 9-beta-methyl carbacyclin improves canine polytetrafluoroethylene graft patency

    International Nuclear Information System (INIS)

    Dacey, L.J.; Hees, P.S.; Cronenwett, J.L.

    1988-01-01

    This study examined the effect of 9-beta-methyl carbacyclin, a synthetic, stable prostacyclin analog, on canine polytetrafluoroethylene (PTFE) graft patency. Twenty-five dogs had 4 mm x 7 cm PTFE grafts implanted bilaterally into the femoral arteries. A subcutaneous infusion pump was used to deliver either saline solution (control) or 9-beta-methyl carbacyclin (Ciprostine) at 100 (CARB-100) or 200 ng/kg/min (CARB-200) through a femoral artery branch just proximal to one of the femoral grafts, with the contralateral graft serving as a noninfused control. Graft-platelet deposition (with 111 In-labeled platelets) was measured between the fifth and seventh days, with patency determined on the seventh day. Dogs were classified as aggregators (AGG [+]) if the preoperative epinephrine-enhanced sodium arachidonate platelet aggregation was greater than 20%. CARB-200 infusion significantly improved ipsilateral graft patency (80%) compared with noninfused grafts (50%, p less than 0.05), or grafts in control and CARB-100 dogs (43%, p less than 0.05). Anastomotic platelet deposition was decreased bilaterally in CARB-200 dogs by 45% to 59% compared with CARB-100 and control dogs (p less than 0.05). With the exception of grafts infused with CARB-200, AGG (+) dogs had significantly lower graft patency (26%) than nonaggregator AGG (-) dogs (71%, p less than 0.01). CARB-200 infusion significantly improved graft patency in AGG (+) dogs (71%), compared with control and CARB-100-infused grafts (19%, p less than 0.025). Intra-arterial 9-beta-methyl carbacyclin improved early PTFE graft patency and inhibited platelet deposition in a severe canine model, independent of baseline platelet aggregation status, which also had an important effect on graft patency

  16. Superselective intra-arterial chemoradiotherapy for advanced head and neck cancers. Evaluation of preservation of organ function

    International Nuclear Information System (INIS)

    Akisada, Takeshi; Harada, Tamotsu; Imai, Shigeki; Gyoten, Masayuki; Hiraoka, Takashi

    2008-01-01

    The objective of this study was to evaluate preservation of organ function in the treatment of superselective intra-arterial chemoradiotherapy for advanced head and neck cancers. Among 96 patients receiving concomitant radiation and intra-arterial docetaxel, systemic cisplatin and 5-fluorouracil (FU) chemotherapy, we identified laryngeal preservation rate, studied tracheostomy cases and gastrostomy cases, and evaluated videofluoroscopic examination and videoendoscopy. Laryngeal preservation rate of hypopharyngeal cancer is very high at 96.2%, and that of laryngeal cancer is high at 71.4%. Videofluoroscopic examination revealed improved swallowing function in 2 of 12, no change in 3, slightly worse in 5, and worse in 2 patients. Following treatment, the incidence of aspiration increased to 4 patients. Videoendoscopy revealed residual vallecula in a few cases. Only 7 patients (7.3%) required a tracheostomy and 4 patients (4.2%) required a gastrostomy. Most of the patients are able to swallow after chemoradiation. Our new chemoradiation protocol is as good as other treatment modalities for maintaining organ preservation and function. (author)

  17. An experimental study on the influence of infusion speed on the early mechanism of embolic effect of arterially infused absolute Ethanol in the rat

    International Nuclear Information System (INIS)

    Han, Joon Koo; Kim, Woo Ho; Lee, Byung Hee; Park, Kil Sun; Park, Jae Hyung; Kim, Chu Wan; Han, Man Chung

    1990-01-01

    In order to clarify the early mechanism of action of the tissue necrosis induced by intraarterially infused absolute ethanol, abdominal aortography and histopathologic examination after absolute ethanol infusion into aorta at fast (0.4ml/sec) and slow speed (0.04ml/sec) were performed on 22 rats (2 controls, 7 in fast infusion group, 7 in slow infusion group, 3 in fast and 3 in slow infusion groups during aorta compression, respectively). Histopathologic features under the light and scanning electron microscope were correlated with the angiographic findings within 30 minutes after ethanol infusion. The results are as follows : 1. In fast infusion group, histopathologic examination of the kidney showed severe glomerular and tubular damage. Extensive damage on endothelial and medial layer was noted in arteries, and fresh thrombi originated from the damaged arterial wall were seen. 2. Angiographic findings in the fast infusion group were luminal irregularity and early obstruction of large arteries. And circulation time was prolonged. 3. In slow infusion group, histopathologic examination of the kidney showed focal area of severe glomerular and tubular damage on relatively normal background. Endothelial and muscular damage was noted in arteries, but the degree of the damage was less severe than that of the fast infusion group. 4. Angiographic findings in the slow infusion group were focal perfusion defect of the kidney, delayed circulation time, and mild luminal irregularity, but obstruction of the major arteries was not seen

  18. The clinical effect of combination therapy for oral cancer with S-1, superselective intra-arterial chemotherapy, and radiation therapy

    International Nuclear Information System (INIS)

    Yamamoto, Chika; Yoshikawa, Hiromasa; Fukumoto, Shunsuke; Higuchi, Takashi; Yoshida, Masanori; Yasumori, Koutarou; Horinouchi, Yasufumi; Uehara, Satoru

    2011-01-01

    Combination therapy with S-1, superselective intra-arterial infusion of carboplatin (CBDCA) and radiation therapy has been used to treat patients with oral cancer since 2005. In this study, the histopathological effects and toxicities following concurrent chemoradiotherapy were examined. The subjects consisted of 15 patients (10 men and 5 women) who were treated with S-1 (60-80 mg/day, 4 weeks), superselective intra-arterial infusion of CBDCA (300 mg/body) and radiation therapy (total dose 30-36 Gy) in our department from 2005 to 2009. Nine patients, showed T2 disease, 3 showed T3 disease, and another 3 showed T4 diseases. The primary cancer sites were the tongue (6 cases), buccal mucosa (4 cases), mandible gingival (3 cases), maxillary gingival (1 case), and the floor of the mouth (1 case). The histopathological effects were evaluated according to Oboshi-Shimosato classification. Grade IV was shown in 10 cases (66.7%), grade III in 1 case (6.7%), II bin 3 cases (20.0%), and II a in 1 case (6.7%). All patients completed the treatment. The pathological response of the resected tumor was grade IIb or higher in 14 cases (93.3%). While good histological effects were noted, there was one patient for whom viable tumor cells remained in the central part of the tumor. The present study indicates that further investigation is needed to determine the best dosing and dosing schedule. (author)

  19. Facial nerve paralysis after super-selective intra-arterial chemotherapy for oral cancer.

    Science.gov (United States)

    Sugiyama, S; Iwai, T; Oguri, S; Koizumi, T; Mitsudo, K; Tohnai, I

    2017-06-01

    Facial nerve paralysis (FNP) after super-selective intra-arterial chemotherapy (SSIAC) is a relatively rare local side effect of SSIAC to the maxillary artery (MA) or the middle meningeal artery (MMA). The incidence and prognosis of FNP after SSIAC in 381 patients with oral cancer (133 with catheterization of the MA, 248 without) was investigated retrospectively. Only three patients (two male and one female) had FNP, for an incidence of 0.8%. All patients with FNP had undergone catheterization of the MA, and the incidence of FNP in this group was 2.3% (3/133). One of the three patients with FNP had paralysis of the third branch of the trigeminal nerve. FNP occurred a mean of 8.7 days (range 5-11 days) after initial SSIAC, and the mean total dose of cisplatin was 55.8mg (range 42.5-67.2mg) and of docetaxel was 25.4mg (range 17.0-33.6mg). FNP resolved completely a mean of 12.7 months (range 6-19 months) after onset. Because the administration of anticancer agents via the MA or MMA carries a risk of FNP, this information will be useful when obtaining informed consent from patients before treatment. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  20. Intraarterial chemotherapy combined with radiation therapy for advanced cancer of uterine cervix

    International Nuclear Information System (INIS)

    Noguchi, Masato; Murata, Rumi; Sagoh, Tadashi

    1998-01-01

    The results of intraarterial chemotherapy (IA-CT) combined with definitive radiation therapy for 23 advanced and bulky carcinomas of uterine cervix are reported. IA-CT with cisplatin 50 mg and doxorubicin 30 mg was administered by one shot method in bilateral internal iliac arteries. The protocol consisted of one to three treatment sessions every 3 weeks. Nine of eleven patients with clinical stage III achieved a complete local response (82%), and the 3- and 5-year survival in these cases were 72% and 72%, respectively. These results were superior to the response (58%), 3- and 5-year survivals (68%, 58%) obtained in 19 patients treated mainly with radiation therapy alone. The side effect of grade 2 and 3 for the intestine, such as ileus and hemorrhagic colitis, was noted in 3 patients (15%). In addition, 3 of 8 patients with radical surgery and postoperative radiation therapy after IA-CT developed insufficient fracture of pelvic bone. These complications accompanied by IA-CT combined with radiation therapy and/or surgery increased slightly, compared with that by the previous therapy without IA-CT, but were not critical. The results suggest that IA-CT following radiation therapy is effective to improve the prognosis of patients with stage III cervical cancer. (author)

  1. Intra-arterial injection of Tc-99m MDP

    Directory of Open Access Journals (Sweden)

    Ebru Salmanoglu

    2016-03-01

    Full Text Available Bone scintigraphy is applied to evaluate abnormalities of axial skeleton and appendicular skeleton including osteomyelitis, prosthesis infection, prosthesis loosening, avascular necrosis, stress fracture, bone metastasis. Technetium-99m methylene diphosphonate (Tc-99m MDP is most common used radiopharmaceutical. Injection of Tc-99m MDP should be done intravenous but it can be done intra-arterial, accidentally. After intra-arterial injection of Tc-99m MDP, it cause prominent soft tissue uptake distal to the injection site. This situation can create confusion in the scintigraphic images. Usually, it imitate reflex sympathetic dystrophy, so differential diagnosis is important. The aim of this report is to present the appearance of inadvertent intra-arterial injection of Tc-99m MDP. [Cukurova Med J 2016; 41(0.100: 79-82

  2. Intra-arterial digital angiography of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Dalla Palma, L.; Stacul, F.; Maffessanti, M.; Pozzi-Mucelli, R.

    1983-08-01

    The authors report the preliminary results of the intraarterial digital angiography of the liver. A series of 30 patients were examined comparing conventional and digital technique following the injection of the coeliac, splenic, hepatic and mesenteric arteries. The results obtained with the digital technique have been of good quality and sometimes even better in spite of significant dilution of the contrast medium. It is concluded that intraarterial digital angiography of the liver gives some advantages compared with the conventional technique, that is the use of a much lower concentrated contrast medium, the better visualization of the portal branches and its collaterals and the very low cost of the film material.

  3. Phase I study of the cisplatin analogue 1,1-diamminomethylcyclohexane sulfatoplatinum (TNO-6) (NSC 311056)

    DEFF Research Database (Denmark)

    Sørensen, J B; Groth, S; Hansen, S W

    1985-01-01

    The cisplatin derivative TNO-6 was evaluated for clinical toxicity in a phase I trial. TNO-6 was given daily for 5 days every 3 weeks as a 30-min IV infusion without hydration. In all, 39 patients with advanced cancer were treated at doses of 2.5-9.0 mg/m2. No dose-limiting nephrotoxicity occurred...

  4. Studies of radioactive cisplatin ({sup 191}Pt) for tumour imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Areberg, J

    2000-01-01

    A radioactive variant of the cytostatic agent cis-dichlorodiammineplatinum(II), cisplatin, was synthesised from {sup 191}PtCl{sub 4}. The {sup 191}Pt-cisplatin was found to be a sterile product of high radionuclide, radiochemical and chemical purity. The pharmacokinetics of platinum in tumour tissue and organs at risk of fourteen patients undergoing treatment with cisplatin were studied by exchanging a small fraction of the prescribed amount of cisplatin with {sup 191}Pt-cisplatin. The uptake and retention of platinum were investigated by gamma camera measurements up to ten days after infusion of {sup 191}Pt-cisplatin. Highest concentration of platinum was found in the liver, on average 5.7 {+-} 0.5 {mu}g/g normalised to a given amount of 180 mg cisplatin. Corresponding value for the kidneys was 1.9 {+-} 0.3 {mu}g/g. Uptake of platinum in tumours was visualised in five patients with an average maximum concentration of 4.9 {+-} 1.0 {mu}g/g normalised to a given amount of 180 mg cisplatin. The data from the pharmacokinetic study was used together with data from the literature to estimate the absorbed dose and effective dose to patients receiving radioactive cisplatin. The effective doses were calculated to be 0.10 {+-} 0.02 mSv/MBq, 0.17 {+-} 0.04 mSv/MBq and 0.23 {+-} 0.05 mSv/MBq for {sup 191}Pt-, {sup 193m}Pt-, and {sup 195m}Pt-cisplatin respectively. The combined effect of the radio- and chemotoxicity from {sup 191}Pt-cisplatin was investigated both in vitro and in vivo. A cervical cancer cell line was incubated with cisplatin or {sup 191}Pt-cisplatin with various concentrations and specific activities. It was shown that the surviving fraction was smaller for cells treated with {sup 191}Pt-cisplatin than for cells treated with the same concentration of non-radioactive cisplatin. The surviving fraction decreased with increasing specific activity. Isobologram technique showed that the radio- and chemotoxicity interacted in a supra-additive (synergistic) manner. In

  5. Studies of radioactive cisplatin (191Pt) for tumour imaging and therapy

    International Nuclear Information System (INIS)

    Areberg, J.

    2000-01-01

    A radioactive variant of the cytostatic agent cis-dichlorodiammineplatinum(II), cisplatin, was synthesised from 191 PtCl 4 . The 191 Pt-cisplatin was found to be a sterile product of high radionuclide, radiochemical and chemical purity. The pharmacokinetics of platinum in tumour tissue and organs at risk of fourteen patients undergoing treatment with cisplatin were studied by exchanging a small fraction of the prescribed amount of cisplatin with 191 Pt-cisplatin. The uptake and retention of platinum were investigated by gamma camera measurements up to ten days after infusion of 191 Pt-cisplatin. Highest concentration of platinum was found in the liver, on average 5.7 ± 0.5 μg/g normalised to a given amount of 180 mg cisplatin. Corresponding value for the kidneys was 1.9 ± 0.3 μg/g. Uptake of platinum in tumours was visualised in five patients with an average maximum concentration of 4.9 ± 1.0 μg/g normalised to a given amount of 180 mg cisplatin. The data from the pharmacokinetic study was used together with data from the literature to estimate the absorbed dose and effective dose to patients receiving radioactive cisplatin. The effective doses were calculated to be 0.10 ± 0.02 mSv/MBq, 0.17 ± 0.04 mSv/MBq and 0.23 ± 0.05 mSv/MBq for 191 Pt-, 193m Pt-, and 195m Pt-cisplatin respectively. The combined effect of the radio- and chemotoxicity from 191 Pt-cisplatin was investigated both in vitro and in vivo. A cervical cancer cell line was incubated with cisplatin or 191 Pt-cisplatin with various concentrations and specific activities. It was shown that the surviving fraction was smaller for cells treated with 191 Pt-cisplatin than for cells treated with the same concentration of non-radioactive cisplatin. The surviving fraction decreased with increasing specific activity. Isobologram technique showed that the radio- and chemotoxicity interacted in a supra-additive (synergistic) manner. In an in vivo model, nude mice with xenografted tumours were given

  6. Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Takeshi; Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp; Nishiofuku, Hideyuki; Fukuoka, Yasushi [IVR CenterNara Medical University, Department of Radiology (Japan); Sakaguchi, Hiroshi [South Nara General Medical Center, Department of Radiology (Japan); Masada, Tetsuya; Tatsumoto, Shota [IVR CenterNara Medical University, Department of Radiology (Japan); Marugami, Nagaaki [Diagnostic Imaging Center, Department of Radiology (Japan); Takano, Masato [Nara Medical University, Department of Diagnostic Pathology (Japan); Yamato, Ichiro; Sho, Masayuki [Nara Medical University, Department of Surgery (Japan); Ohbayashi, Chiho [Nara Medical University, Department of Diagnostic Pathology (Japan); Hirai, Toshiko [Diagnostic Imaging Center, Department of Radiology (Japan); Kichikawa, Kimihiko [IVR CenterNara Medical University, Department of Radiology (Japan)

    2017-03-15

    PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.

  7. Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model

    International Nuclear Information System (INIS)

    Sato, Takeshi; Tanaka, Toshihiro; Nishiofuku, Hideyuki; Fukuoka, Yasushi; Sakaguchi, Hiroshi; Masada, Tetsuya; Tatsumoto, Shota; Marugami, Nagaaki; Takano, Masato; Yamato, Ichiro; Sho, Masayuki; Ohbayashi, Chiho; Hirai, Toshiko; Kichikawa, Kimihiko

    2017-01-01

    PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.

  8. Intra-arterial nimodipine for cerebral vasospasm after subarachnoid haemorrhage

    DEFF Research Database (Denmark)

    Bashir, Asma; Andresen, Morten; Bartek, Jiri

    2016-01-01

    Intra-arterial nimodipine (IAN) has shown a promising effect on cerebral vasospasm (CV) after aneurysmal subarachnoid haemorrhage. At our institution, Rigshospitalet, IAN treatment has been used since 2009, but the short- and long-term clinical efficacy of IAN has not yet been assessed. The purpo...

  9. Does cisplatin chemotherapy decrease the MDP uptake of normal bone? An experimental study

    International Nuclear Information System (INIS)

    Ozdogan, Ozhan; Ertay, Turkan; Arslan, Gulhan; Sisman, Ali R.; Capa Kaya, Gamze; Yilmaz, Osman; Coker, Canan; Gure, Ataman; Durak, Hatice

    2008-01-01

    Bone scan is the accepted initial imaging modality for skeletal metastases. Cisplatin is a cell-cycle nonspecific antineoplastic agent used in some chemotherapy regimens. Knowing that platinum reacts with phosphate compounds such as methylenediphosphonic acid (MDP), decreases bone resorption and new bone formation, it can be proposed that cisplatin chemotherapy may decrease Tc-99m MDP bone uptake. We aimed to demonstrate, if present, the decrease in bone uptake and to determine the duration of this effect. Thirty male Wistar rats were randomized into five groups, namely, placebo group (G1) and cisplatin groups (G2, G3, G4, G5). Pre-therapy bone scintigraphies were obtained in all the groups. Cisplatin chemotherapy was given as infusion. Post-therapy bone scintigraphies were obtained 10 min, 1 h, 24 h, and 72 h after chemotherapy in groups G2-G5, respectively. A placebo bone scintigraphy was obtained 10 min after infusion of serum physiologic in G1. Plasma samples for cisplatin plasma values were obtained. The graphite furnace atomic absorption spectrophotometry technique was used for cisplatin analysis. Quantitative analysis (bone uptake ratios) was performed by drawing regions of interest on the right femur, vertebral column, and adjacent soft tissues. The injection/examination time delay and the net injected MDP doses were also noted. There was no statistically significant difference in bone uptake values, injected MDP doses or injection/examination time delay in any group. Cisplatin plasma values were significantly different in G2, G3, G4, and G5 (P<0.05) but not in G1. Cisplatin chemotherapy seems to have no effect on the Tc-99m MDP uptake of normal bone. (author)

  10. A retrospective evaluation of furosemide and mannitol for prevention of cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Mach, C M; Kha, C; Nguyen, D; Shumway, J; Meaders, K M; Ludwig, M; Williams-Brown, M Y; Anderson, M L

    2017-06-01

    Nephrotoxicity is a recognized side effect of cisplatin chemotherapy. However, the optimal strategy for preventing cisplatin-induced nephrotoxicity, if any, remains unclear. The primary objective for this study was to determine whether mannitol or furosemide provides better nephroprotection when administered with hydration prior to weekly, low-dose cisplatin concurrently with whole pelvic radiotherapy. Clinical data were abstracted from all women who underwent chemoradiation for FIGO IB2-IVA cervical cancer at a regional safety net health system between January 2009 and December 2014. Creatinine clearance was estimated using the IDMS-traceable MDRD Study Equation. Descriptive statistics were used to summarize patient demographics. Cox proportional hazard models were used to identify factors associated with hypomagnesemia and survival. A total of 133 women received 656 weekly doses of single-agent cisplatin (40 mg/m 2 ) concomitant with whole pelvic radiation. Furosemide (20 mg) was administered intravenously prior to 341 cisplatin doses, whereas mannitol (24 g) was administered prior to 315 doses. Significant magnesium wasting was observed after the second weekly cisplatin infusion regardless of whether furosemide or mannitol was utilized. Repetitive low-dose cisplatin infusion had no impact on measured levels of serum creatinine or estimated glomerular filtration rate. Prior history of hypertension, diabetes mellitus, hepatitis C infection and acute gastrointestinal toxicity were each associated with early onset of hypomagnesemia. Repetitive administration of low-dose cisplatin concurrent with whole pelvic radiation is associated with magnesium wasting. However, choice of diuretic with pretreatment hydration had no significant impact on the severity of this adverse effect. © 2017 John Wiley & Sons Ltd.

  11. Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a 10BSH-containing WOW emulsion

    International Nuclear Information System (INIS)

    Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun

    2014-01-01

    A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a 10 BSH-containing water-in-oil-in-water emulsion ( 10 BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that 10 BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC. - Highlights: • We started the pilot clinical study of BNCT to recurrence hepatic cancer. • The tumor size was remained stable during 3 months after BNCT(SD). • No adverse effect as a result of BNCT was observed during follow-up period. • 10 B-containing WOW emulsion can be applied as a novel intra-arterial boron carrier for BNCT for HCC

  12. Beneficial effects of intra-arterial and intravenous prostaglandin E1 in intestinal ischaemia-reperfusion injury.

    Science.gov (United States)

    San Norberto García, Enrique María; Taylor, James Henry; Cenizo, Noelia; Vaquero, Carlos

    2014-04-01

    Ischaemia-reperfusion (I/R) injury is encountered in conditions that diminish intestinal blood flow. There is no clinically feasible technique available for mucosal preservation. One hundred Wistar rats were subjected to intestinal ischaemia for 15 and 60 min (I15', I60'), followed by 1 and 7 days of reperfusion (R1d, R7d). Rats were subjected to ischaemia by clamping the superior mesenteric artery. Prostaglandin E1 (PGE1) (2.500 ng/kg intra-arterial bolus or 20 ng/kg intravenous infusion) was administered immediately prior to the commencement of the experimental period. Animals were divided into 20 groups: sham (laparotomy alone), sacrificed at 1 or 7 days; saline administration, 15 or 60 min of ischaemia, 1 or 7 days of reperfusion; prostaglandin E1 administration, 15 or 60 min of ischaemia, 1 or 7 days of reperfusion, each one for intra-arterial or intravenous administration. Ileal segments were excised and assessed for histopathological score, polymorphonuclear (PMN) leucocytes encountered and myeloperoxidase (MPO) activity measurement. I/R caused deterioration of histological characteristics. Prophylactic administration of PGE1 resulted in a significant decrease in the histological score compared with the respective saline group (analysis of variance, P prostaglandin E1 prevents I/R injury by diminishing histological damage parameters, inhibiting PMN leucocyte infiltration and attenuating MPO activity.

  13. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma.

    NARCIS (Netherlands)

    Perilongo, G.; Maibach, R.; Shafford, E.; Brugieres, L.; Brock, P.; Morland, B.; Camargo, B. de; Zsiros, J.; Roebuck, D.; Zimmermann, A.; Aronson, D.C.; Childs, M.; Widing, E.; Laithier, V.; Plaschkes, J.; Pritchard, J.; Scopinaro, M.; MacKinlay, G.; Czauderna, P.

    2009-01-01

    BACKGROUND: Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). METHODS: Children with standard-risk

  14. Cisplatin versus Cisplatin plus Doxorubicin for Standard-Risk Hepatoblastoma

    NARCIS (Netherlands)

    Perilongo, Giorgio; Maibach, Rudolf; Shafford, Elisabeth; Brugieres, Laurence; Brock, Penelope; Morland, Bruce; de Camargo, Beatriz; Zsiros, Jozsef; Roebuck, Derek; Zimmermann, Arthur; Aronson, Daniel; Childs, Margaret; Widing, Eva; Laithier, Veronique; Plaschkes, Jack; Pritchard, Jon; Scopinaro, Marcello; MacKinlay, Gordon; Czauderna, Piotr

    2009-01-01

    Background Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). Methods Children with standard-risk

  15. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma

    NARCIS (Netherlands)

    Perilongo, G.; Maibach, R.; Shafford, E.; Brugieres, L.; Brock, P.; Morland, B.; de Camargo, B.; Zsiros, J.; Roebuck, D.; Zimmermann, A.; Aronson, D.; Childs, M.; Widing, E.; Laithier, V.; Plaschkes, J.; Pritchard, J.; Scopinaro, M.; Czauderna, P.

    2009-01-01

    Background: Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). Methods: Children with standard-risk

  16. The suppression effect of the intrahepatic recurrence of transcatheter arterial chemoembolization with cisplatin in the hepatocellular carcinoma patients

    International Nuclear Information System (INIS)

    Moon, Tae Yong; Lee, Suck Hong; Kim, Byung Soo; Kim, Yong Woo

    1997-01-01

    To compare the suppressive effects in hepatocellular carcinoma patients of transhepatic arterial chemoembolization by the infusion of adriamycin-lipiodol emulsion and of this plus 10ml of cisplatin solution. In a total of 151 cases, the frequency of intrahepatic recurrence was compared with follow-up angiographic findings after the first and second transhepatic arterial chemoembolization with adriamycin-lipiodol emulsion and adriamycin-lipiodol emulsion plus 10ml of cisplatin solution, respectively. Among 46 patients whose first single infusion was after mean 119 days, the recurrence rate was 22% ; for 42 who were given their first multiple infusion after mean 76 days this rate was 5% ; for 35 whose second single infusion was administered after mean 147 days, the rate was 34%, and among 28 whose second multiple infusion was after mean 110 days, the rate was 43%. During the first trial of transcatheter arterial chemoembolization with adriamycinlipiodol plus cisplatin solution, hepatocellular carcinoma recurred much less frequently, but during the second trial with cisplatin, recurrence was not suppresed

  17. Renal function of cancer patients "fit" for Cisplatin chemotherapy: physician perspective.

    Science.gov (United States)

    Montoya, J; Luna, H G; Amparo, J R; Casasola, C; Cristal-Luna, G

    2014-07-01

    Renal insufficiency is prevalent among cancer patients and it poses a hindrance in using cisplatin. We sought to describe the baseline renal function of our patients who were considered "fit" for cisplatin, along with saline hydration and mannitol diuresis, and determine occurrence of nephrotoxicity during chemotherapy. A retrospective study from 2008 to 2012 of 100 patients who were given cisplatin was done. Demographic and clinical variables were recorded. Creatinine Clearance was calculated using Cockcroft-Gault formula. Nephrotoxicity was defined as an increase of 0.5mg/dL or more after cisplatin infusion. Descriptive statistics, ANOVA, logistic regression analysis were done. A total of 100 patients were "fit" for cisplatin, with a mean age of 52 years, mean creatinine of 0.83mg/dL, CrCl of 94.14ml/ min, and ECOG performance status of 0-2. 12 patients have Chronic Kidney Disease (CKD) stage of 3, 42 patients with stage 2, 46 patients with stage 1. After cisplatin treatment, mean creatinine increased to 0.95mg/dL, and mean CrCl decreased to 83.7ml/min. Nine patients developed nephrotoxicity; all resolved with hydration. Patients with nephrotoxicity were significantly different from those without, in terms of weight p 0.012. None of the variables were predictors of nephrotoxicity. With hydration and mannitol diuresis, patients with ECOG 2, normal creatinine, CKD stage 3 or better, CrCl of 50ml/min and above are "fit" for cisplatin. During the study period, 9% of the patients "fit" for cisplatin developed nephrotoxicity, all resolved with conservative management. There was an increase in mean creatinine and a decrease in the mean CrCl after cisplatin.

  18. Intra-arterial AICA-riboside administration induces NO-dependent vasodilation in vivo in human skeletal muscle.

    Science.gov (United States)

    Bosselaar, Marlies; Boon, Hanneke; van Loon, Luc J C; van den Broek, Petra H H; Smits, Paul; Tack, Cees J

    2009-09-01

    In animal models, administration of the adenosine analog AICA-riboside has shown beneficial effects on ischemia-reperfusion injury and glucose homeostasis. The vascular and/or metabolic effects of AICA-riboside administration in humans remain to be established. AICA-riboside was infused intra-arterially in four different dosages up to 8 mg x min(-1) x dl(-1) in 24 healthy subjects. Forearm blood flow (FBF) and glucose uptake and plasma glucose, free fatty acid, and AICA-riboside concentrations were assessed. We also combined AICA-riboside infusion (2 mg x min(-1) x dl(-1)) with the intra-arterial administration of the adenosine receptor antagonist caffeine (90 microg x min(-1) x dl(-1); n = 6) and with the endothelial NO synthase inhibitor l-NMMA (0.4 mg x min(-1) x dl(-1); n = 6). Additional in vitro experiments were performed to explain our in vivo effects of AICA-riboside in humans. AICA-riboside increased FBF dose dependently from 2.0 +/- 0.2 to 13.2 +/- 1.9 ml x min(-1) x dl(-1) maximally (P AICA-riboside concentrations, forearm glucose uptake did not change. In vitro experiments showed rapid uptake of AICA-riboside by the equilibrative nucleoside transporter in erythrocytes and subsequent phosphorylation to AICA-ribotide. We conclude that AICA-riboside induces a potent vasodilator response in humans that is mediated by NO. Despite high local plasma concentrations, AICA-riboside does not increase skeletal muscle glucose uptake.

  19. Urinary neutrophil gelatinase-associated lipocalin levels predict cisplatin-induced acute kidney injury better than albuminuria or urinary cystatin C levels

    Directory of Open Access Journals (Sweden)

    Hugo You-Hsien Lin

    2013-06-01

    Full Text Available Cisplatin-induced acute kidney injury (AKI is a major concern among clinicians in prescribing cisplatin-based chemotherapy. This study evaluated and compared the ability of urinary biomarkers, including urinary neutrophil gelatinase-associated lipocalin (NGAL, cystatin C, and the urinary albumin to creatinine ratio (ACR to predict cisplatin-induced AKI. Thirty-three cancer patients receiving cisplatin-based chemotherapy were prospectively studied, including 10 (30% who developed AKI (the study group. Changes of urinary biomarkers were compared at 4 hours, 8 hours, and 12 hours, and 1 day, 2 days, 3 days, and 4 days after cisplatin intravenous infusions (75 mg/m2 versus the baseline. There was a significant increase in urinary NGAL levels from 12 hours to 4 days (p<0.05 compared to baseline after cisplatin infusion in the AKI group. The magnitude of these changes over time differed significantly by group (p<0.001. The area under the receiver operating curve describing the relationship between urinary NGAL levels and AKI within 12 hours was 0.865 (95% confidence interval=0.691–1.000. Urinary NGAL levels independently predicted AKI 12 hours after cisplatin (p=0.045 after adjustments for age, gender, body mass index, baseline serum creatinine, and urinary total protein. Urinary NGAL levels may be an early biomarker of AKI in patients receiving cisplatin-based treatment.

  20. Use of Intra-arterial Thrombolytic Therapy for Acute Treatment of Frostbite in 62 Patients with Review of Thrombolytic Therapy in Frostbite.

    Science.gov (United States)

    Gonzaga, Teresa; Jenabzadeh, Kamrun; Anderson, Christopher P; Mohr, William J; Endorf, Frederick W; Ahrenholz, David H

    2016-01-01

    Amputations are common after severe frostbite injuries, often mediated by postinjury arterial thrombosis. Since 1994, the authors have performed angiography to identify perfusion deficits in severely frostbitten digits and treated these lesions with intraarterial infusion of thrombolytic agents, usually combined with papaverine to reduce vasospasm. A retrospective review was performed of patients admitted to the regional burn center with frostbite injury from 1994 to 2007. Patients with severe frostbite, without contraindications to thrombolytic therapy, underwent diagnostic angiography of the affected extremities. Limbs with perfusion defects received intraarterial thrombolytic therapy according to protocol and the response was documented. Delayed amputation was performed for mummified digits. Angiogram results and amputation rates were tabulated. In this 14-year review, 114 patients were admitted for frostbite injuries. There was a male predominance (84%) and the mean age was 40.4 years. Of this group, 69 patients with severe frostbite underwent angiography; 66 were treated with intraarterial thrombolytic therapy. Four treated were excluded due to incomplete data. In the remaining 62 patients, angiography identified 472 digits with frostbite injury and impaired arterial perfusion. At the termination of thrombolytic infusion, a completion angiogram was performed. Partial or complete amputations were performed on only four of 198 digits (2.0%) with distal vascular blush, and in 71 of 75 digits (94.7%) with no improvement. Amputations occurred in 73 of 199 digits (36.7%) with partially restored flow. Overall complete digit salvage rate was 68.6%. Angiography after severe frostbite is a sensitive method to detect impaired arterial blood flow and permits catheter-directed treatment with thrombolytic agents. Improved perfusion after such treatment decreases late amputations following frostbite injury.

  1. Combination hyperthermia and intraarterial 5-FU for metastatic colon carcinoma to liver

    International Nuclear Information System (INIS)

    Moseley, H.S.; Palmquist, M.

    1984-01-01

    Metastatic colorectal carcinoma to the liver remains a formidable challenge. Responses to chemotherapy are brief and the number of effective drugs is very limited. A phase II trial of hepatic hyperthermia and intraarterial chemotherapy was undertaken to attempt to improve response rates and duration. Patients were given a 10 day course of IA 5-FU at 15 mg/kg. During the infusion hyperthermia was given five times using the BSD Annular Phased Array (APA). Thermistors were placed percutaneously into normal liver and tumor using ultrasound or CT scan guidance. Six patients have been treated. Significant problems in positioning ill patients in the APA were encountered, and there was difficulty also in preventing heating throughout the abdominal cavity. Four patients, all with poor performance status, failed to benefit. One patient had improvement in liver function studies for two months and failed to respond on a repeat course. One patient had a complete response which is continuing over 18 months with a liver scan reverting to normal and CEA returning to normal. These preliminary results are promising and warrant further trials

  2. Effectiveness of intra-arterial anesthesia for uterine fibroid embolization using dilute lidocaine

    Energy Technology Data Exchange (ETDEWEB)

    Zhan, Songhua; Li, Yi; Wang, Guoliang; Han, Hongjie; Yang, Zhenyan [Tongji Hospital of Tongji University, Department of Radiology, Shanghai (China)

    2005-08-01

    A modified protocol of uterine fibroid embolization (UFE) is proposed for alleviating the postinterventional pain. This randomized and double-blinded clinical trial is to evaluate the effectiveness of intra-arterial infusion of dilute lidocaine for postinterventional pain relief in UFE. Forty-six patients who underwent UFE were randomly grouped equally. In the test group, after the poly(vinyl alcohol) embolization was complete, a dilute lidocaine solution with 40 mg in 6.0 ml, 3.0 ml for each side or 4.0 and 2.0 ml for two sides, was given through the catheter. In the control group, the patients received 6.0 ml of saline solution as a placebo. A simple pain degree classification method for patient self-evaluation was developed. A questionnaire was completed by each patient to record the degree of pain during five periods; these were during the procedure, the first 12 h, the second 12 h, between 24 and 48 h, and between 48 and 72 h. The numbers of patients with the same degree of pain in the five time segments from the two groups were statistically compared. Compared with the control group, the patients in the test group experienced less pain within 48 h after the procedure (p<0.01). The results suggest that this improved UFE protocol is a simple approach to prevent the acute postinterventional pain of UFE. (orig.)

  3. Intra-artery thrombolytic therapy for acute ischemic cerebral infarction

    International Nuclear Information System (INIS)

    Du Wei; Shao Chengmin; Wang Jianlin; Lei Jin; Jia Fan; Cao Lanfang; Chai Ruchang; Su Wei; Gu Jinchuan

    2004-01-01

    Objective: To evaluate the clinical effects of intra-arterial thrombolytic therapy for acute ischemic cerebral infarction and analyze the factors influencing the clinical prognosis. Methods: 32 patients were treated with intra-arterial thrombolysis using urokinase (median dose, 65 x 10 4 U) within 2-20 hours, after the onset. The patient's condition was assessed by neurologists using National Institutes of Health Stroke Scale (NIHSS) score right at the admission. Clinical outcome was assessed after 3 months and graded as good for Modified Rankin Scale (MRS) scores of 0 to 3 and poor for MRS scores of 4 or 5 and death. Results: Follow up cerebral angiography of 14 cases treated within 6 hours after onset showed complete/partial recanalization in 13 cases. Other 18 patients whose treatment started beyond 6 hours after onset out-came with complete/partial in 7. 20 (62.5%) of the 32 patients had good out-come, 12(37.5%) had poor outcome and two patients(9.4%) died. Cerebral hemorrhage occurred in 2 of the 32 patients. Good outcome was associated with an initial NIHSS score of <20 (P<0.01) and vascular recanalization (P<0.025). Recanalization was more likely to be obtained if thrombolysis began within 6 hours (P<0.05). Conclusion: Intra-arterial thrombolysis is a safe and effective therapy for acute ischemic cerebral infarction. (authors)

  4. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors.

    Science.gov (United States)

    von Pawel, J; von Roemeling, R; Gatzemeier, U; Boyer, M; Elisson, L O; Clark, P; Talbot, D; Rey, A; Butler, T W; Hirsh, V; Olver, I; Bergman, B; Ayoub, J; Richardson, G; Dunlop, D; Arcenas, A; Vescio, R; Viallet, J; Treat, J

    2000-03-01

    A phase III trial, Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors (CATAPULT I), was designed to determine the efficacy and safety of tirapazamine plus cisplatin for the treatment of non-small-cell lung cancer (NSCLC). Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m(2) infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m(2) over 1 hour) or 75 mg/m(2) of cisplatin alone, every 3 weeks for a maximum of eight cycles. A total of 446 patients with NSCLC (17% with stage IIIB disease and pleural effusions; 83% with stage IV disease) were entered onto the study. Karnofsky performance status (KPS) was >/= 60 for all patients (for 10%, KPS = 60; for 90%, KPS = 70 to 100). Sixty patients (14%) had clinically stable brain metastases. The median survival was significantly longer (34.6 v 27. 7 weeks; P =.0078) and the response rate was significantly greater (27.5% v 13.7%; P CATAPULT I study shows that tirapazamine enhances the activity of cisplatin in patients with advanced NSCLC and confirms that hypoxia is an exploitable therapeutic target in human malignancies.

  5. Evaluation of the Role of Cisplatin-conjugated-soluble Gelatin Sponge: Feasibility Study in a Swine Model

    International Nuclear Information System (INIS)

    Ikoma, Akira; Kawai, Nobuyuki; Sato, Morio; Minamiguchi, Hiroyuki; Nakata, Kouhei; Nakai, Motoki; Sanda, Hiroki; Sonomura, Tetsuo; Kanayama, Yoshitaka; Sakai, Yasuo

    2013-01-01

    PurposeTo evaluate the safety and the delivery function of cisplatin-conjugated-soluble gelatin sponge in a swine model.MethodsFifteen healthy young swine were assigned into three groups: transarterial cisplatin infusion group, transarterial chemoembolization (TACE) with cisplatin-conjugated 120-min soluble gelatin sponge (TACE-120) group, and TACE with cisplatin-conjugated 360-min soluble gelatin sponge (TACE-360) group. A total volume of 0.8 mL/kg cisplatin in each group and 8 mg/kg soluble gelatin sponge in TACE-120 and TACE-360 groups were injected from the left hepatic artery in small increments for 10 min. Common hepatic angiography and whole-blood sampling via the left hepatic vein were conducted to explore recanalization immediately after the procedure and again at 10, 30, 60, 90, 120, 180, 240, 300, 360, and 420 min later. The area under the plasma concentration curve (AUC) of non-protein-bound platinum was compared among the three groups. Each liver was removed and cut into 10-cm-thick sections for calculating liver-damaged volume ratio.ResultsSequential angiography depicted gradual recanalization of the occluded hepatic artery and total recanalization at 120 and 360 min after embolization in the TACE-120 and TACE-360 groups, respectively. Of the three groups, AUC 0–30 , AUC 30–120 , and AUC 120–420 were significantly highest in the transarterial cisplatin infusion group (p < 0.001), the TACE-120 group (p < 0.001), and the TACE-360 group (p < 0.001), respectively. The liver-damaged volume ratio in the TACE-360 group was small (8.20 %) but significantly higher than that in the TACE-120 group (2.67 %, p = 0.014).ConclusionCisplatin-conjugated soluble gelatin sponge functions as a cisplatin carrier and is associated with tolerable liver damage

  6. Local intracranial intraarterial thrombolytic therapy in acute cerebral infarction

    International Nuclear Information System (INIS)

    Kim, Sun Yong; Suh, Jung Ho

    1996-01-01

    To evaluate the efficacy of direct intracranial intraarterial thrombolytic therapy in patients with acute atherothrombotic and embolic stroke. Forth-one patients with cerebral thromboembolic disease, all in the area of the middle cerebral artery and including two cases of internal carotid artry occlusion, were treated with microcatheter-directed local intraarterial thrombolysis, using 180,000 to 1,000,000 unit urokinase and 15 to 50 mg of tissue plasminogen activator (tPA). The time elapsed before treatment ranged from 260 to 470 minute (mean : 380 minutes). The effect of treatment was assessed by cerebral angiography, by the clinical outcome. For 25 patients (61%), complete vessel recanalization was successful. In eight and three cases, respectively, the result was partial recanalization and residual stenosis. In 21 patients (51%), both acute neurologic and functional outcomes improved significantly within 24 hours and in 92% of patients, within one month. Hemorrhagic transformations occurred in five patients (12.2%), and in five others there were high density lesions around the basal ganglia and temporal lobe, which was cleared on CT within 24 hours. This suggested transient extrapolation of the contrast media rather than true hemorrhage. tPA showed better results than urokinase in terms of the rate of recanalization (68.7% vs 56.7%) and the occurrence of hemorrhagic infarction(6.3% vs 16.0%). Local intraarterial cerebral thrombolysis is thought be an effective method in the treatment of acute brain infarction, but in some patients may cause intracerebral hemorrhage in some patients

  7. Local intracranial intraarterial thrombolytic therapy in acute cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Yong; Suh, Jung Ho [Ajou Univ. College of Medicine, Suwon (Korea, Republic of)

    1996-06-01

    To evaluate the efficacy of direct intracranial intraarterial thrombolytic therapy in patients with acute atherothrombotic and embolic stroke. Forth-one patients with cerebral thromboembolic disease, all in the area of the middle cerebral artery and including two cases of internal carotid artry occlusion, were treated with microcatheter-directed local intraarterial thrombolysis, using 180,000 to 1,000,000 unit urokinase and 15 to 50 mg of tissue plasminogen activator (tPA). The time elapsed before treatment ranged from 260 to 470 minute (mean : 380 minutes). The effect of treatment was assessed by cerebral angiography, by the clinical outcome. For 25 patients (61%), complete vessel recanalization was successful. In eight and three cases, respectively, the result was partial recanalization and residual stenosis. In 21 patients (51%), both acute neurologic and functional outcomes improved significantly within 24 hours and in 92% of patients, within one month. Hemorrhagic transformations occurred in five patients (12.2%), and in five others there were high density lesions around the basal ganglia and temporal lobe, which was cleared on CT within 24 hours. This suggested transient extrapolation of the contrast media rather than true hemorrhage. tPA showed better results than urokinase in terms of the rate of recanalization (68.7% vs 56.7%) and the occurrence of hemorrhagic infarction(6.3% vs 16.0%). Local intraarterial cerebral thrombolysis is thought be an effective method in the treatment of acute brain infarction, but in some patients may cause intracerebral hemorrhage in some patients.

  8. Intra-arterial DSA in hypervascular bone neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Arlart, I.P.; Merk, J.; Baehren, W.

    1984-11-01

    In order to evaluate intra-arterial DSA in malignant bone tumors (osteosarcoma n=2, aggressive osteoblastoma n=1) three patients were examined angiographically including conventional arteriography and DSA. Compared with conventional angiograms DSA imaging demonstrated a reduced peripheral vascular information due to reduced spatial resolution. Advantages of DSA were an improved visualization of tumor blush and atypical venous return and in addition a reduction of volume rsp. concentration of the contrast material using a iodine concentration of 200 mg/ml for preoperative vascular mapping and of 300 mg/ml for diagnostic tumor imaging.

  9. Intra-arterial DSA in hypervascular bone neoplasms

    International Nuclear Information System (INIS)

    Arlart, I.P.; Merk, J.; Baehren, W.

    1984-01-01

    In order to evaluate intra-arterial DSA in malignant bone tumors (osteosarcoma n=2, aggressive osteoblastoma n=1) three patients were examined angiographically including conventional arteriography and DSA. Compared with conventional angiograms DSA imaging demonstrated a reduced peripheral vascular information due to reduced spatial resolution. Advantages of DSA were an improved visualization of tumor blush and atypical venous return and in addition a reduction of volume rsp. concentration of the contrast material using a iodine concentration of 200 mg/ml for preoperative vascular mapping and of 300 mg/ml for diagnostic tumor imaging. (orig.) [de

  10. Update on Intra-Arterial Chemotherapy for Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Mario Zanaty

    2014-01-01

    Full Text Available The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

  11. Experience of combined cisplatin and radiation therapy for advanced urinary tract transitional cell carcinoma

    International Nuclear Information System (INIS)

    Yoshioka, Toshiaki; Utsunomiya, Masato; Itoh, Hiroshi; Itatani, Hiroaki; Namiki, Mikio.

    1987-01-01

    Since March, 1981, 13 patients with locally advanced transitional cell carcinoma were treated by combined cisdiamminedichloroplatinum (cisplatin) and full dose radiotherapy. They were 10 men and 3 women. The patient ages ranged from 42 to 79 years, with a median of 59.5 years. The primary sites of transitional cell carcinoma were bladder in 5, ureter in 6, renal pelvis in 1 and prostate in 1. Radiotherapy consisted of a mean tumor dose of 48.7 gray, with a range of 40 to 66.4 gray, was administered with cobalt 60. Cisplatin was infused 5 days a week with a daily dose of 20 to 30 mg. 4 patients recieved 2 courses of cisplatin infusion and others 1 or less. Of the 4 evaluable patients 3 (75 %) achieved a complete response. Toxicity was evaluated for the 13 patients. Mainly gastrointestinal toxicity was noted: appetite loss in 9 (69.2 %), nausea and/or vomiting in 5 (38.5 %) and diarrhea in 5 (38.5 %). Leukocytopenia was noted in 7 patients (53.9 %), but in no one leukocyte count was less than 2000/mm 3 . Mild thrombocytopenia was noted only in 3 patients (23.1 %). All of these toxicities were mild, and the patients recovered soon after the therapy. Herein it is discussed about future problems such as solution of interaction mechanism, detection of practical dose and administering method of cisplatin and radiation. (author)

  12. Selective intra-arterial administration of 18F-FDG to the rat brain - effects on hemispheric uptake

    International Nuclear Information System (INIS)

    Arnberg, Fabian; Samen, Erik; Lundberg, Johan; Grafstroem, Jonas; Soederman, Michael; Stone-Elander, Sharon; Holmin, Staffan; Lu, Li

    2014-01-01

    The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery. All animal experiments were carried out in accordance with Karolinska Institutet's guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague-Dawley rats. Here, injection dynamics of iodine contrast was assessed using digital subtraction angiography. Maintaining the catheter position, the animals were placed in a micro PET and small-animal positron emission tomography (PET) was used to analyze injections [2- 18 F]-2-fluoro-2-deoxy-d-glucose ( 18 F-FDG). Microcatheters had to be placed in the intracranial carotid artery (iICA) for the infusate to distribute to the brain. Selective injection via the iICA resulted in a 9-fold higher uptake of 18 F-FDG in the injected hemisphere (p < 0.005) compared to both intravenous and more proximal carotid artery injections. Furthermore, selective injection gave a dramatically improved contrast between the brain and extracranial tissue. Intra-arterial injection increases the cerebral uptake of a radiotracer dramatically compared to systemic injection. This technique has potential applications for endovascular treatment of malignancies allowing intra-interventional modifications of injection strategy, based on information on tumor perfusion and risk to surrounding normal parenchyma. Furthermore the technique may increase diagnostic sensitivity and avoid problems due to peripheral pharmacological barriers and first passage metabolism of labile tracers. (orig.)

  13. Selective intra-arterial administration of {sup 18}F-FDG to the rat brain - effects on hemispheric uptake

    Energy Technology Data Exchange (ETDEWEB)

    Arnberg, Fabian; Samen, Erik; Lundberg, Johan; Grafstroem, Jonas; Soederman, Michael; Stone-Elander, Sharon; Holmin, Staffan [Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska University Hospital-Solna, Department of Neuroradiology, Stockholm (Sweden); Lu, Li [Karolinska University Hospital-Solna, KERIC, Stockholm (Sweden)

    2014-05-15

    The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery. All animal experiments were carried out in accordance with Karolinska Institutet's guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague-Dawley rats. Here, injection dynamics of iodine contrast was assessed using digital subtraction angiography. Maintaining the catheter position, the animals were placed in a micro PET and small-animal positron emission tomography (PET) was used to analyze injections [2-{sup 18}F]-2-fluoro-2-deoxy-d-glucose ({sup 18}F-FDG). Microcatheters had to be placed in the intracranial carotid artery (iICA) for the infusate to distribute to the brain. Selective injection via the iICA resulted in a 9-fold higher uptake of {sup 18}F-FDG in the injected hemisphere (p < 0.005) compared to both intravenous and more proximal carotid artery injections. Furthermore, selective injection gave a dramatically improved contrast between the brain and extracranial tissue. Intra-arterial injection increases the cerebral uptake of a radiotracer dramatically compared to systemic injection. This technique has potential applications for endovascular treatment of malignancies allowing intra-interventional modifications of injection strategy, based on information on tumor perfusion and risk to surrounding normal parenchyma. Furthermore the technique may increase diagnostic sensitivity and avoid problems due to peripheral pharmacological barriers and first passage metabolism of labile tracers. (orig.)

  14. Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won Tae; Kim, Yong Kan; Lee, Ju Hye; Kim, Dong Hyun; Park, Dahl; Cho, Kyu Sup; Kim, Dong Won [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Nam, Ji Ho; Roh, Hwan Jung [Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2013-09-15

    The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery. Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m2) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT. At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence. Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens.

  15. Future opportunities in preventing cisplatin induced ototoxicity

    NARCIS (Netherlands)

    van den Berg, J. H.; Beijnen, J. H.; Balm, A. J. M.; Schellens, J. H. M.

    2006-01-01

    Cisplatin is one of the most commonly used cytotoxic agents. Ototoxicity is an important and dose-limiting side-effect of cisplatin therapy. It is believed that cisplatin suppresses the formation of endogenous anti-oxidants that normally prevent the inner ear against reactive oxygen species (ROS).

  16. Matricaria chamomilla attenuates cisplatin nephrotoxicity.

    Science.gov (United States)

    Salama, Ragaa H M

    2012-07-01

    Matricaria chamomilla is extensively consumed as a tea or tonic. Despite its widespread use as a home remedy, relatively few trials evaluated its benefits in nephro protection. Hence, this study evaluates the protective role of M. chamomilla in cisplatin nephrotoxicity rat model. The study was conducted on 32 rats divided into four groups. The first group (G1) was injected with saline intra-peritoneally (IP); G2 was injected with 5 mg/kg cisplatin on day 0 of the experiment and repeated four times, with five days free interval. G3 and G4 were injected daily with M. chamomilla (50 mg/kg) IP, starting five days before the experiment (-5 day); in addition, G4 was injected with cisplatin. On day 16, animals were scarified and serum and/or kidney tissue was used to determine: (a) kidney function tests (serum urea, creatinine, gamma glutamyl transferase (GGT), NAG, β-gal), (b) oxidative stress indices (NO, LPO), (c) antioxidant activities (SOD, GSH, total thiols), (d) apoptotic indices (Cathepsin D, DNA fragmentation) and (e) mineral (calcium). M. chamomilla significantly increased the body weight, normalized the kidney functions, improved the apoptotic markers, reduced the oxidative stress markers and corrected the hypo-calcemia that resulted from cisplatin nephrotoxicity. M. chamomilla is a promising nephro-protective compound reducing cisplatin nephrotoxicity most probably by its antioxidant activities and inhibition of gamma glutamyl transferase activity.

  17. Matricaria chamomilla attenuates cisplatin nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Ragaa H.M. Salama

    2012-01-01

    Full Text Available Matricaria chamomilla is extensively consumed as a tea or tonic. Despite its widespread use as a home remedy, relatively few trials evaluated its benefits in nephro protection. Hence, this study evaluates the protective role of M. chamomilla in cisplatin nephrotoxicity rat model. The study was conducted on 32 rats divided into four groups. The first group (G1 was injected with saline intra-peritoneally (IP; G2 was injected with 5 mg/kg cisplatin on day 0 of the experiment and repeated four times, with five days free interval. G3 and G4 were injected daily with M. chamomilla (50 mg/kg IP, starting five days before the experiment (-5 day; in addition, G4 was injected with cisplatin. On day 16, animals were scarified and serum and/or kidney tissue was used to determine: (a kidney function tests (serum urea, creatinine, gamma glutamyl transferase (GGT, NAG, β-gal, (b oxidative stress indices (NO, LPO, (c antioxidant activities (SOD, GSH, total thiols, (d apoptotic indices (Cathepsin D, DNA fragmentation and (e mineral (calcium. M. chamomilla significantly increased the body weight, normalized the kidney functions, improved the apoptotic markers, reduced the oxidative stress markers and corrected the hypo-calcemia that resulted from cisplatin nephrotoxicity. M. chamomilla is a promising nephro-protective compound reducing cisplatin nephrotoxicity most probably by its antioxidant activities and inhibition of gamma glutamyl transferase activity.

  18. Intraarterial therapy for acute ischemic stroke. Investigation of prognostic factors

    International Nuclear Information System (INIS)

    Noguchi, Tomoyuki; Yoshiura, Takashi; Oguri, Shuichi

    2007-01-01

    Intraarterial therapy (IAT) for acute cerebral infarction has been proven to be profitable. However, the criteria for the indications, the choice of the thrombolytic agents, and the use of adjunctive agents are controversial. We retrospectively analyzed the prognostic factors of IAT. From 1994 to 2003, 28 patients underwent IAT due to middle cerebral artery occlusion (17 women and 11 men; median age, 69 years old). We evaluated the following prognostic parameters: institution of treatment, degree of paralysis at visit, size of high-intensity area on diffusion-weighted images, dose of intraarterial urokinase administration, elapsed time from symptom onset to completion of IAT, presence of penetration of embolus by microcatheter and microguidewire, recanalization after IAT, intracranial hemorrhage (ICH) within 24 hours after IAT, and intravenous heparin administration after IAT. The outcome was evaluated at discharge and was classified into the following categories according to the modified Rankin Scale: independence (0 to 2), dependence (3 to 5), and death (6). Seven patients were judged to be independent, 16 patients were judged to be dependent, and five patients died. Patients with recanalization after IAT had a better outcome than those without (p<0.05); patients with intracranial hemorrhage had a worse outcome than those without (p<0.05); and patients with intravenous heparin administration after IAT had a better outcome in activities of daily living than those without (p<0.05). In addition to ICH and recanalization, our results suggested that intravenous heparin administration after IAT had a favorable effect on patient outcome. (author)

  19. Continuous-infusion adriamycin

    International Nuclear Information System (INIS)

    Benjamin, R.S.; Chawla, S.P.; Ewer, M.S.; Hortobagyi, G.N.

    1986-01-01

    This chapter discusses the diminished cardiotoxicity as well as diminished nausea and vomiting with continuous infusions of adriamycin to patients undergoing radiation therapy, particularly with infusions of 48 hours or longer, and best with 96-hour infusions, the longest duration that has been studied systematically. In breast cancer, data show that more adriamycin is better, but only for a selected subgroup of patients: those with complete remission. The diminished cardiotoxicity makes the use of adriamycin more attractive in the adjuvant situation, where increased safety will decrease the chances of long-term complications and make retreatment easy for cured patients who develop second malignancies

  20. Curative and organ-preserving treatment with intra-arterial carboplatin induction followed by surgery and/or radiotherapy for advanced head and neck cancer: single-center five-year results

    Directory of Open Access Journals (Sweden)

    Tinelli Carmine

    2007-04-01

    Full Text Available Abstract Background This study evaluated the feasibility, toxicity, response rate and survival of neoadjuvant superselective intra-arterial infusion of high dose carboplatin in advanced head and neck cancer. Methods Forty-six patients with primary head and neck squamous cell carcinoma received 3 cycles of intra-arterial carboplatin (300 to 350 mg/m2 per cycle every 2 weeks, followed by radiotherapy or surgery plus radiotherapy. Results No complications or severe toxicity occurred. Sixteen patients (35% were complete responders, 20 (43% partial responders while 10 (22% did not respond to treatment. After completion of the multimodality treatment, 38/46 patients (83% were complete responders. After a 5-year follow-up period, 18/46 patients (39% are alive and disease-free, 3 (6,5% have died of a second primary tumor and 25 (54,5% have died of the disease. Conclusion Intra-arterial carboplatin induction chemotherapy is a safe, well-tolerated technique that discriminates between responders and non-responders and so may have prognostic significance in planning further integrated treatments aimed to organ preservation for advanced head and neck carcinomas.

  1. Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat

    International Nuclear Information System (INIS)

    Saris, S.C.; Wright, D.C.; Oldfield, E.H.; Blasberg, R.G.

    1988-01-01

    Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer-- 14 C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions

  2. Intra-Arterial Treatment in Patients with Acute Massive Gastrointestinal Bleeding after Endoscopic Failure: Comparisons between Positive versus Negative Contrast Extravasation Groups

    International Nuclear Information System (INIS)

    Chang, Wei Chou; Liu, Chang Hsien; Hsu, Hsian He; Huang, Guo Shu; Hsieh, Tasi Yuan; Tsai, Shin Hung; Hsieh, Chung Bao; Yu, Chin Yung; Tung, Ho Jui

    2011-01-01

    To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemo stasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage.

  3. Temporal evolution of vasospasm and clinical outcome after intra-arterial vasodilator therapy in patients with aneurysmal subarachnoid hemorrhage.

    Directory of Open Access Journals (Sweden)

    Laleh Daftari Besheli

    Full Text Available Intra-arterial (IA vasodilator therapy is one of the recommended treatments to minimize the impact of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm refractory to standard management. However, its usefulness and efficacy is not well established. We evaluated the effect IA vasodilator therapy on middle cerebral artery blood flow and on discharge outcome. We reviewed records for 115 adults admitted to Neurointensive Care Unit to test whether there was a difference in clinical outcome (discharge mRS in those who received IA infusions. In a subset of 19 patients (33 vessels treated using IA therapy, we tested whether therapy was effective in reversing the trends in blood flow. All measures of MCA blood flow increased from day -2 to -1 before infusion (maximum Peak Systolic Velocity (PSV 232.2±9.4 to 262.4±12.5 cm/s [p = 0.02]; average PSV 202.1±8.5 to 229.9±10.9 [p = 0.02]; highest Mean Flow Velocity (MFV 154.3±8.3 to 172.9±10.5 [p = 0.10]; average MFV 125.5±6.3 to 147.8±9.5 cm/s, [p = 0.02] but not post-infusion (maximum PSV 261.2±14.6 cm/s [p = .89]; average PSV 223.4±11.4 [p = 0.56]; highest MFV 182.9±12.4 cm/s [p = 0.38]; average MFV 153.0±10.2 cm/s [p = 0.54]. After IA therapy, flow velocities were consistently reduced (day X infusion interaction p<0.01 for all measures. However, discharge mRS was higher in IA infusion group, even after adjusting for sex, age, and admission grades. Thus, while IA vasodilator therapy was effective in reversing the vasospasm-mediated deterioration in blood flow, clinical outcomes in the treated group were worse than the untreated group. There is need for a prospective randomized controlled trial to avoid potential confounding effect of selection bias.

  4. Minimizing Systemic Leakage of Cisplatin during Percutaneous Isolated Pancreas Perfusion Chemotherapy: A Pilot Study.

    Science.gov (United States)

    Murata, Satoru; Onozawa, Shiro; Mine, Takahiko; Ueda, Tatsuo; Sugihara, Fumie; Yasui, Daisuke; Kumita, Shin-ichiro; Shimizu, Akira; Satake, Mitsuo

    2015-07-01

    To evaluate the feasibility of percutaneous isolated pancreas perfusion (PIPP) by using a pig model. All experiments were approved by the institutional Animal Experiment Ethics Committee. Fifteen pigs were assigned to five groups, and PIPP was performed. Angiographic and dye injection studies were performed to confirm the patency of the PIPP system (group 1). Blood that contained cisplatin (1.5 mg per kilogram of body weight) in an extracorporeal circuit was circulated through the pancreas at three infusion rates (40, 60, and 80 mL/min) to determine the optimal infusion rate in terms of safety and pharmacologic effectiveness (groups 2, 3, and 4, respectively). Chronological laboratory data and histologic findings were assessed in group 5, which received the optimal infusion rate. Maximum platinum concentration (Cmax) and area under the platinum concentration-time curve were compared by using the Kruskal-Wallis and Mann-Whitney U tests. Angiography and dye injection confirmed the patency of the PIPP system. Histopathologic examinations showed no abnormalities in the pancreas or other organs at a 40 mL/min infusion rate of cisplatin. However, edematous changes in the pancreas were observed at higher infusion rates. The pharmacologic effectiveness did not differ significantly among groups; therefore, the optimal infusion rate of 40 mL/min was selected. The median pancreatic-to-systemic exposure ratios were 71.8 for Cmax and 54.8 for the area under the curve. All laboratory data remained normal or returned to pretreatment levels within 1 week. PIPP at a 40 mL/min infusion rate appears to be safe and feasible for perfusion of the pancreas.

  5. Intra-arterial thrombolysis of digital artery occlusions in a patient with polycythemia vera.

    Science.gov (United States)

    Jud, Philipp; Hafner, Franz; Gary, Thomas; Ghanim, Leyla; Lipp, Rainer; Brodmann, Marianne

    2017-01-01

    There are limited therapeutic options for the resolution of digital artery occlusions. Intra-arterial thrombolysis with anticoagulative and thrombolytic drugs successfully restored the blood flow in the affected digital arteries.

  6. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal...

  7. Intra-arterial thrombolysis in acute embolic stroke

    International Nuclear Information System (INIS)

    Shi Mingchao; Fang Shaokuan; Li Dong; Zhu Hui; Pang Meng; Wu Jiang; Wang Shouchun

    2008-01-01

    Objective: To evaluate the efficacy and safety of intra-arterial thrombolysis in acute embolic stroke (AES). Methods: 21 patients with AES were undertaken urokinase or recombinated tissue plasminogen activator through percutaneous femoral intraarterial thrombolysis (IAT) as the treated group, and another 42 patients without thrombolytic treatment were assigned as the control group, which were matched to the baseline National Institutes of Health Stroke Scale (NIHSS) scores with selected gender and age. 24 h NIHSS scores, 90 d modified Rankin Scale (mRS) scores, incidences of hemorrhagic transformation (HT) and mortalities of the two groups were compared after the treatment. Results: (1) The results of cerebral angiography showed that the total re-perfusion rate was 61.90%. The middle cerebral artery (MCA), the internal carotid artery (ICA) and the basilar artery (BA) re-perfusion rates were 83.33%, 28.57% and 50.00%, respectively. (2) The NIHSS scores after 24 h were lower in the treated (IAT) group than those in the control group (12.05±5.61 vs, 14.83±4.05, P<0.05). A favorable outcome (mRS of 0-2) was more frequently observed in the 1AT group (66.67%) than that in the control group (35.71%, P<0.05). (3) There was no significant difference between the rates of HT (28.57% vs. 16.77%) and also the similar mortality rates (19.05% vs. 16.67%) not significant between the two groups. No patient died of HT in both two groups. Conclusion: IAT may be an effective treatment for AES with comparative safety. (authors)

  8. Intra-Arterial Thrombolysis for Deep Vein Thrombosis of the Lower Extremity: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moo Sang; Roh, Byung Suk [Dept. of Radiology, Wonkwang University School of Medicine, Iksan (Korea, Republic of)

    2011-09-15

    If the appropriate catheterization of the affected vein was not possible because of a narrowed or thrombus-filled venous lumen, successful treatment gets into trouble during catheter directed regional thrombolysis for treatment of deep vein thrombosis. In this situation, intra-arterial thrombolysis can be considered as an alternative treatment, but to the best of our knowledge, only two reports have been described. We present here cases of successful intra-arterial thrombolysis in patients with deep vein thrombosis.

  9. Spontaneously resolving periocular erythema and ciliary madarosis following intra-arterial chemotherapy for retinoblastoma

    OpenAIRE

    Marr Brian; Gobin Pierre; Dunkel Ira; Brodie Scott; Abramson David

    2010-01-01

    Purpose and Design: To describe an unusual clinical finding seen in children undergoing intra-arterial chemotherapy for retinoblastoma. Materials and Methods: A retrospective review of 69 eyes of 63 patients receiving intra-arterial chemotherapy over a 3-year period. Charts and photographs of 69 consecutive cases were reviewed, and data were collected on patients with clinical evidence of a hyperemic cutaneous periocular abnormality following the procedure. Results: A blanching erythemat...

  10. Successful Intra-Arterial Thrombolysis for Acute Ischemic Stroke in the Immediate Postpartum Period: Case Report

    International Nuclear Information System (INIS)

    Mendez, Jose C.; Masjuan, J.; Garcia, N.; Lecinana, M. de

    2008-01-01

    Stroke in pregnancy and the puerperium is a rare but potentially devastating event. We present the case of a previously healthy woman who underwent a cesarean delivery and experienced a middle cerebral artery thrombosis in the immediate postpartum period that was subsequently lysed with intra-arterial urokinase. The patient made a complete neurologic recovery. To the best of our knowledge, this is the first reported case of successful intra-arterial thrombolysis for ischemic stroke in the postpartum period

  11. Membrane Transition Temperature Determines Cisplatin Response

    Science.gov (United States)

    Raghunathan, Krishnan; Ahsan, Aarif; Ray, Dipankar; Nyati, Mukesh K.; Veatch, Sarah L.

    2015-01-01

    Cisplatin is a classical chemotherapeutic agent used in treating several forms of cancer including head and neck. However, cells develop resistance to the drug in some patients through a range of mechanisms, some of which are poorly understood. Using isolated plasma membrane vesicles as a model system, we present evidence suggesting that cisplatin induced resistance may be due to certain changes in the bio-physical properties of plasma membranes. Giant plasma membrane vesicles (GPMVs) isolated from cortical cytoskeleton exhibit a miscibility transition between a single liquid phase at high temperature and two distinct coexisting liquid phases at low temperature. The temperature at which this transition occurs is hypothesized to reflect the magnitude of membrane heterogeneity at physiological temperature. We find that addition of cisplatin to vesicles isolated from cisplatin-sensitive cells result in a lowering of this miscibility transition temperature, whereas in cisplatin-resistant cells such treatment does not affect the transition temperature. To explore if this is a cause or consequence of cisplatin resistance, we tested if addition of cisplatin in combination with agents that modulate GPMV transition temperatures can affect cisplatin sensitivity. We found that cells become more sensitive to cisplatin when isopropanol, an agent that lowers GPMV transition temperature, was combined with cisplatin. Conversely, cells became resistant to cisplatin when added in combination with menthol that raises GPMV transition temperatures. These data suggest that changes in plasma membrane heterogeneity augments or suppresses signaling events initiated in the plasma membranes that can determine response to cisplatin. We postulate that desired perturbations of membrane heterogeneity could provide an effective therapeutic strategy to overcome cisplatin resistance for certain patients. PMID:26484687

  12. Phase II study of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Specht, L; Larsen, S K; Hansen, H S

    2000-01-01

    BACKGROUND: Results with docetaxel as single drug in squamous-cell head and neck cancer have been encouraging. The purpose of the present phase II study is to evaluate the antitumour efficacy and toxicity of the combination of docetaxel and cisplatin in patients with recurrent or disseminated......; no previous systemic chemotherapy (prior radiotherapy and/or surgery were allowed), no other previous or concurrent malignancy; no peripheral neuropathy. Treatment consisted of docetaxel 75 mg/m2 in a one-hour infusion after pre-treatment with prednisolone, followed by cisplatin 75 mg/m2 in a half...... but one patient. Grade 3 neuropathy occurred in one patient, none had grade 4. Grade 3 oral mucositis occurred in three patients, none had grade 4. Grade 2-3 hypomagnesaemia occurred in 10 patients requiring magnesium infusion. CONCLUSIONS: Docetaxel and cisplatin is an active combination in patients...

  13. Intra-arterial injection, a rare but serious complication of sclerotherapy.

    Science.gov (United States)

    Hafner, F; Froehlich, H; Gary, T; Brodmann, M

    2013-03-01

    Intra-arterial injections represent the most feared complication of sclerotherapy for varicose veins. We present a case of an inadvertent intra-arterial injection of polidocanol at the left medial calf in a 59-year-old woman with subsequent arterial occlusions of the posterior tibial artery and foot arteries. Despite several therapeutic interventions, lower-limb amputation could not be prevented. We conducted a PubMed search for articles reporting arterial complications related to sclerotherapy, in order to evaluate aetiology, clinical presentation, therapeutic management and outcome of sclerotherapy-associated intra-arterial injections during the past 50 years. Intra-arterial injection of a sclerosing solution was reported in 63 cases, mostly after injection near the ankle region or the distal medial calf. Clinical presentation was frequently characterized by immediate pain during injection and distal ischaemia with subsequent tissue loss. Despite several treatment approaches, amputation could not be prevented in 31 cases (52.5%). The pathophysiology of arterial complications related to intra-arterial injection and advisable therapeutic interventions are discussed. Inadvertent intra-arterial injection represents a limb-threatening complication of sclerotherapy. Target-oriented and prompt therapy seems inevitable in order to reduce the risk of permanent tissue loss and amputation.

  14. Intra-arterial port implantation for intra-arterial chemotherapy : comparison between PIPS(Percutaneously Implantable Port System) and port system

    International Nuclear Information System (INIS)

    Yoon, Sang Jin; Shim, Hyung Jin; Jung, Hun Young; Choi, Yong Ho; Kim, Yang Soo; Song, In Sup; Kwak, Byung Kook

    1999-01-01

    To compare the techniques and complications of intra-arterial port implantation for intra-arterial chemotherapy between PIPS and the port system. For intra-arterial port implantation, 27 cases in 27 patients were retrospectively evaluated using PIPS(PIPS-200, William Cook Europe, Denmark) while for 21 cases in 19 patients a pediatric venous port system(Port-A-Cath, 5.8F, SIMS Deltec, U. S. A.) was used. All intra-arterial port implantation was performed percuteneously in an angiographic ward. Hepatocellular carcinoma was diagnosed in 18 patients and hepatic metastasis in 16. Peripheral cholangiocarcinoma, and pancreatic gastric, ovarian, renal cell and colon carcinoma were included. We compared the techniques and complications between PIPS and the port system. The follow up period ranged from 23 to 494(mean, 163) days in PIPS and from 12 to 431(mean, 150) days in the port system. In all cases, intra-arterial port implantations were technically successful. Port catheter tips were located in the common hepatic artery(n=8), proper hepatic artery(n=7), right hepatic artery(n=5), gastroduodenal artery(n=2), left hepatic artery(n=1), pancreaticoduodenal artery(n=1), inferior mesenteric artery(n=1), lumbar artery(n=1), and renal artery(n=1) in PIPS, and in the proper hepatic artery(n=6), gastroduodenal artery(n=6), common hepatic artery(n=3), right hepatic artery(n=4), inferior mesenteric artery(n=1), and internal iliac artery(n=1) in the port system. Port chambers were buried in infrainguinal subcutaneous tissue. Using PIPS, complications developed in seven cases(25.9%) and of these, four (57.1%) were catheter or chamber related. In the port system, catheter or chamber related complications developed in four cases(19.0%). Because PIPS and the port system have relative merits and demetrits, successful intra-arterial port implantation is possible if equipment is properly selected

  15. Continuous radioisotope infusion

    International Nuclear Information System (INIS)

    Soederborg, B.; Asaba, H.; Gunnarsson, B.; Jekell, K.; Kiibus, A.; Sandqvist, S.

    1978-01-01

    Continuous infusion of a radioactive marker was used instead of a conventional bolus injection to improve haemodynamic studies. Tc-99m was infused into the blood circulation at a constant rate for 100-300 seconds and the activity in the target structure was measured by a gamma camera with a computer system or by a single detector. The concentration of the marker increased linearly at the same rate throughout the circulating system. Due to variations in transport time from infusion site to different parts of the system the rise of activity occurred at different times. A theory for the calculations was presented and consequently confirmed in a model study. Blood flow patterns in artificial kidneys and alterations in renal blood flow induced by angiotensin were studied. The results are presented as time-function curves or as computer images. This technique can be used to evaluate distributions and alterations of flow in separate parts of a complex circulating system. (author)

  16. Transcatheter Arterial Infusion of Autologous CD133+ Cells for Diabetic Peripheral Artery Disease

    Directory of Open Access Journals (Sweden)

    Xiaoping Zhang

    2016-01-01

    Full Text Available Microvascular lesion in diabetic peripheral arterial disease (PAD still cannot be resolved by current surgical and interventional technique. Endothelial cells have the therapeutic potential to cure microvascular lesion. To evaluate the efficacy and immune-regulatory impact of intra-arterial infusion of autologous CD133+ cells, we recruited 53 patients with diabetic PAD (27 of CD133+ group and 26 of control group. CD133+ cells enriched from patients’ PB-MNCs were reinfused intra-arterially. The ulcer healing followed up till 18 months was 100% (3/3 in CD133+ group and 60% (3/5 in control group. The amputation rate was 0 (0/27 in CD133+ group and 11.54% (3/26 in control group. Compared with the control group, TcPO2 and ABI showed obvious improvement at 18 months and significant increasing VEGF and decreasing IL-6 level in the CD133+ group within 4 weeks. A reducing trend of proangiogenesis and anti-inflammatory regulation function at 4 weeks after the cells infusion was also found. These results indicated that autologous CD133+ cell treatment can effectively improve the perfusion of morbid limb and exert proangiogenesis and anti-inflammatory immune-regulatory impacts by paracrine on tissue microenvironment. The CD133+ progenitor cell therapy may be repeated at a fixed interval according to cell life span and immune-regulatory function.

  17. A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer. A prospective study

    International Nuclear Information System (INIS)

    Miyanaga, Naoto; Akaza, Hideyuki; Okumura, Toshiyuki

    2000-01-01

    A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. lntra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function. (author)

  18. Parthenolide reduces cisplatin-induced renal damage

    International Nuclear Information System (INIS)

    Francescato, Heloisa D.C.; Costa, Roberto S.; Scavone, Cristoforo; Coimbra, Terezila M.

    2007-01-01

    Inflammatory events contribute to cisplatin-induced renal damage. Cisplatin promotes increased production of reactive oxygen species, which can activate nuclear factor-κB (NF-κB) that lead to increased expression of proinflammatory mediators which could intensify the cytotoxic effects of cisplatin. In this study, we evaluated the effect of parthenolide, a selective inhibitor of NF-κB, on renal damage caused by cisplatin use. A total of 94 male Wistar rats were divided into six groups: Group A (18 rats) were treated with saline; Group B (12 rats) received dimethylsulfoxide plus saline (the solvent for parthenolide); Group C (12 rats) received parthenolide (3 mg/kg) plus saline; Group D (20 rats) received cisplatin (5 mg/kg, i.p.); Group E (12 rats) received dimethylsulfoxide plus cisplatin (5 mg/kg, i.p.); and Group F (21 rats) received parthenolide (3 mg/kg) plus cisplatin (5 mg/kg, i.p.). Dimethylsulfoxide or parthenolide were administered at 24 h and 1 h prior to cisplatin injection, and again at 24 h and 48 h after. At 2, 3 and 5 days after saline or cisplatin injection, blood and urine samples were collected for measurement of creatinine, sodium and potassium and the kidneys removed for histological, morphometric, electrophoretic mobility shift assay (EMSA), apoptosis and immunohistochemical studies. Cisplatin-treated rats presented higher plasma creatinine, as well as greater immunostaining for ED1 (macrophages/monocytes) and NF-κB in the renal cortices and outer medullae. The increase of NF-κB activation was confirmed by EMSA. Cisplatin-injected rats also presented higher urinary levels of lipid peroxidation and acute tubular necrosis. All of these alterations were reduced by treatment with parthenolide. This effect seems to be related, at least in part, to the restriction of renal inflammatory process observed in parthenolide + cisplatin treated rats

  19. Antineoplastic therapy by radioactive cisplatin in experiment

    International Nuclear Information System (INIS)

    Dikiy, N.P.; Dovbnya, A.N.; Lyashko, Yu.V.; Medvedeva, E.P.; Medvedev, D.V.; Uvarov, V.L.

    2007-01-01

    The method of 195m Pt production on linear electron accelerators and cyclotron of NSC KIPT are described. The method of 195m Pt separation from the irradiated samples are developed. The methods of cisplatin synthesis with use of a radioactive isotope of 195m Pt are realized. Results of biological tests of radioactive cisplatin on animals are described. Our preliminary results demonstrate the feasibility of radioactive cisplatin for treatment of cancer diseases

  20. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... nerve were 50-60% reduced, whereas no definite changes occurred at lower doses. The SNAP conduction velocities were reduced by 10-15% at cumulative doses of 400-700 mg/m2 consistent with loss of large myelinated fibres. SNAPs from primarily Pacinian corpuscles in digit 3 and the dorsolateral side...... of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal...

  1. Concurrent chemoradiation with daily low dose cisplatin for advanced stage head and neck carcinoma

    International Nuclear Information System (INIS)

    Hoebers, Frank J.P.; Heemsbergen, Wilma; Balm, Alfons J.M.; Zanten, Mathilde van; Schornagel, Jan H.; Rasch, Coen R.N.

    2007-01-01

    Background and purpose: To evaluate treatment results of concurrent chemoradiation with daily low dose cisplatin. Materials and methods: 121 patients with advanced stage HNSCC were treated with RT (35 x 2 Gy) and cisplatin (6 mg/m 2 i.v. x20, daily before RT). After 47 patients, the treatment protocol (Standard Group) was changed: Daily i.v. prehydration and accelerated RT were given to the subsequent 74 patients (Hydr-Ac-RT Group). Results: Mean follow-up was 29 months (range 7-62). More chemotherapy could be administered in the Hydr-Ac-RT Group (maximum no. of 20 cisplatin-infusions increased from 59% to 91% of patients, p = 0.008), with less renal toxicity (p < 0.001) and less hospital admissions (p < 0.02). However, mucositis was more pronounced and tubefeeding more frequent in the Hydr-Ac-RT Group. The CR rate of the primary tumor increased from 74% (Standard Group) to 90% (Hydr-Ac-RT Group) (p = 0.06), although this did not lead to an improvement in loco-regional control. Conclusions: Concurrent chemoradiation with daily low dose cisplatin is feasible and effective for selected patients with advanced HNSCC. Although the addition of accelerated RT resulted in more mucositis and tubefeeding, the introduction of prehydration led to better compliance to therapy with more chemotherapy administered and less hospital admissions

  2. Intra-arterial chemotherapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ozono, Seiichiro; Kim, Sung-Chul; Takashima, Kenji [Nara Medical Univ., Kashihara (Japan)] [and others

    1999-02-01

    The present investigation was conducted to examine the effects of intra-arterial chemotherapy (IAC) for patients with invasive bladder cancer. A total of 37 patients were treated with IAC at Nara Medical University and its affiliated hospitals between January, 1993 and August, 1997. There were 27 patients in the poor risk group. The remaining 10 patients underwent anti-tumor IAC. Thirty of the 37 patients received chemotherapeutic agents via a reservoir, and the remaining 7 patients received a one-shot injection of agents followed by transcatheter arterial embolization (TAE). In the reservoir group, there were 18 patients who received IAC in combination with radiation therapy. As a result, reduction of tumor size was noted in 53%, and the 3-year cause-specific survival rate was 54% in all cases. There was a significant difference in the 3-year survival rate between the radiation-treated group and the group without radiation. The adverse events included anemia, leukopenia, thrombocytopenia and gastrointestinal symptoms, but none of them were severe. The results of the present study indicate that IAC is useful in the treatment of invasive bladder cancer for poor risk patients. (author)

  3. Intra-arterial mitomycin C treatment of unresectable liver tumours

    International Nuclear Information System (INIS)

    Starkhammar, H.; Haakansson, L.; Morales, O.; Svedberg, J.; Linkoeping Univ.; Linkoeping Univ.

    1987-01-01

    Regional chemotherapy might be more efficient if the cytostatic drug is injected together with degradable starch microspheres (DSM), which induce temporary blockage of arterioles and trap the co-injected drug in tumour. Eighteen patients with non-resectable liver cancer were included. Mitomycin C (15 mg/m 2 ) was injected intra-arterially mixed with 900 mg of DSM every six weeks. For estimation of the effect of DSM in the liver a radiolabelled tracer was injected via the same route. Its passage through the liver to the systemic circulation was continuously measured by a detector situated over peripheral blood vessels. The effect of DSM on the tracer passage varied considerably between different patients. The study also indicated opening of new vascular pathways some minutes after the initial injection. The dose of DSM for total blockage of the arterial blood flow, indicated by angiography, also varied. In some patients 540 mg induced total occlusion. In others neither angiographic nor tracer passage were affected by the microspheres although 900 mg (or even more) were injected. Factors such as size of the vascular bed, portal and arterial blood flow and arterio-venous shunting seemed to be of great importance and should be controlled in order to optimize the use of DSM in conjunction with chemotherapy of liver tumours. (orig.)

  4. Intra-arterial delivery of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Mitsuyoshi Watanabe

    2016-01-01

    Full Text Available While treatments have been developed to combat stroke, such as intravenous recombinant tissue plasminogen activator and endovascular recanalization therapies, their ability to decrease the long-term disability that accompanies stroke is limited. Currently, stem cell research focused on mesenchymal stem cells (MSCs. MSCs are multipotent, nonhematopoietic stem cells found in the stromal fraction of the bone marrow, along with the connective tissue of most organs. MSCs are an increasingly appealing cell source due to the relative ease in which they can be retrieved, developed, and handled in vitro. Despite the fact that numerous paths of stem cell transport to the brain in acute ischemic stroke (AIS exist, the intra-arterial (IA route of stem cell transport is most attractive. This is due to its great potential for clinical translation, especially considering the growing clinical application of endovascular treatment for AIS. Here, we evaluate research examining IA delivery of MSCs to the stroke region. The results of the study revealed the maximum tolerated dose and that the optimal time for administration was 24 h, following cerebral ischemia. It is important that future translational studies are performed to establish IA administration of MSCs as a widely used treatment for AIS.

  5. Unrecognized hand ischemia after intraarterial drug injection: successful management of a "near miss" event

    Directory of Open Access Journals (Sweden)

    Vogt Peter M

    2008-12-01

    Full Text Available Abstract Background Complications arising from accidental intraarterial drug injections have been described in the past. However, given the multitude of injected substances and complex pathophysiology, guidelines regarding diagnosis and management of patients with intraarterial injections remain vague. As such it remains unclear, when to expect limb ischemia and whether and for how long to monitor patients after intraarterial injections. Case report We present the case of a "near miss event" in an i.v. drug abuser presenting to the emergency department 3 hours after injection of water dissolved zolpidem (Ambien™ tablets into the right ulnar artery. Chief complaint was forearm pain. Clinical examination at the time revealed no concern for limb ischemia and patient was discharged. The patient returned unplanned 18 hours after injection with an ischemic right hand. Angiography revealed no flow in the distal ulnar artery and minimal flow in the palmar arch. Emergent intraarterial thrombolysis with Urokinase was performed and restored hand perfusion. Clinical follow-up 3 months after injury showed full recovery with regular recapillarisation and normal Allen test. Conclusion This case report highlights the need to rigorously monitor patients with suspected intraarterial injections for potential delayed onset of limb ischemia. This is to our knowledge the first described case report of a successful revascularization after prolonged ischemia with delayed onset after zolpidem injection. We recommend close monitoring of these patients for at least 24 hours in addition to starting prophylactic anticoagulation.

  6. Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

    Directory of Open Access Journals (Sweden)

    Iftekhar Hassan

    Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

  7. Hearing loss due to concurrent daily low-dose cisplatin chemoradiation for locally advanced head and neck cancer

    International Nuclear Information System (INIS)

    Zuur, Charlotte L.; Simis, Yvonne J.W.; Verkaik, Roxanna S.; Schornagel, Jan H.; Balm, Alfons J.M.; Dreschler, Wouter A.; Rasch, Coen R.N.

    2008-01-01

    Background and purpose: Cisplatin-based chemo-irradiation (CRT) is increasingly used for head and neck squamous cell carcinoma (HNSCC). We aimed to assess hearing deterioration due to low-dose cisplatin chemoradiation and to compare the observed hearing loss with hearing loss in our previously described high-dose cisplatin CRT cohort. Materials and methods: A prospective analysis of hearing thresholds at low and (ultra)-high frequencies obtained before and after treatment in 60 patients. Patients received low-dose cisplatin (6 mg/m 2 , daily infusions, 20-25 days) with concomitant accelerated radiotherapy (70 Gy). Results: Audiometry up to 16 kHz was performed before therapy and 31 days (median) post-treatment. The total incidence of ototoxicity in CTCAEv3.0 was 31% in audiograms up to 8 kHz, and 5% of ears tested qualified for HAs due to treatment. The mean hearing loss at speech frequencies was 2.6 dB (SD 5.7) and 2.3 dB (SD 9.2) at PTA 1-2-4 kHz air-conduction and bone-conduction, respectively. The mean hearing loss at ultra-high frequencies (PTA AC 8-10-12.5 kHz) was 9.0 dB (SD 8.1). Low-dose cisplatin CRT caused less acute hearing loss (CTCAE 31%), compared to high-dose cisplatin CRT (CTCAE 78%). Conclusions: Low-dose cisplatin chemo-irradiation for HNSCC is a relatively safe treatment protocol with respect to ototoxicity

  8. Carotid artery mixing with diastole-phased pulsed drug infusion

    International Nuclear Information System (INIS)

    Saris, S.C.; Shook, D.R.; Blasberg, R.G.; Dedrick, R.L.; Doppman, J.L.; Bankiewicz, K.S.; Blacklock, J.B.; Oldfield, E.H.

    1987-01-01

    Focal injury to the brain or retina is a frequent complication of drug delivery to the internal carotid artery (ICA) and may be due to poor mixing of the drug with blood at the infusion site. Rhesus monkeys were studied to determine whether phased drug delivery during diastole from a modified pulsatile angiographic injector would improve drug mixing in vivo. A radiolabeled flow tracer, carbon-14-iodoantipyrine ( 14 C-IAP), was injected into the ICA of three monkeys in 80-msec pulses, each ending at least 50 msec before the end of local diastole. Local isotope concentration in the brain was determined by quantitative autoradiography. The ratio of highest to lowest concentration was 1.86 +/- 0.26 (mean +/- standard deviation) in the frontoparietal cortex, 1.65 +/- 0.42 in the frontoparietal white matter, 1.89 +/- 0.28 in the temporal cortex, and 1.39 +/- 0.17 in the basal ganglia. These results were similar to recordings in three control animals that received intravenous 14 C-IAP to demonstrate complete drug mixing (1.37 +/- 0.12, 1.41 +/- 0.11, 1.70 +/- 0.08, 1.22 +/- 0.24, respectively), and contrasted to findings in five animals which received continuous intracarotid infusions to demonstrate standard ICA drug delivery (4.54 +/- 2.07, 2.94 +/- 1.45, 5.43 +/- 3.57, 3.60 +/- 2.90, respectively). Pulsed intra-arterial infusion during diastole provides a technically simple method for improving intravascular drug mixing, and results in drug delivery to tissue capillaries that is proportional to blood flow

  9. Intravenous lidocaine infusion.

    Science.gov (United States)

    Soto, G; Naranjo González, M; Calero, F

    2018-02-26

    Systemic lidocaine used in continuous infusion during the peri-operative period has analgesic, anti-hyperalgesic, as well as anti-inflammatory properties. This makes it capable of reducing the use of opioids and inhalational anaesthetics, and the early return of bowel function, and patient hospital stay. The aim of this narrative review was to highlight the pharmacology and indications for clinical application, along with new and interesting research areas. The clinical applications of peri-operative lidocaine infusion have been reviewed in several recent systematic reviews and meta-analyses in patients undergoing open and laparoscopic abdominal procedures, ambulatory procedures, and other types of surgery. Peri-operative lidocaine infusion may be a useful analgesic adjunct in enhanced recovery protocols. Potential benefits of intravenous lidocaine in chronic post-surgical pain, post-operative cognitive dysfunction, and cancer recurrence are under investigation. Due to its immunomodulation properties over surgical stress, current evidence suggests that intravenous lidocaine could be used in the context of multimodal analgesia. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Nanoparticle formulations of cisplatin for cancer therapy

    Science.gov (United States)

    Duan, Xiaopin; He, Chunbai; Kron, Stephen J.; Lin, Wenbin

    2016-01-01

    The genotoxic agent cisplatin, used alone or in combination with radiation and/or other chemotherapeutic agents, is an important first-line chemotherapy for a broad range of cancers. The clinical utility of cisplatin is limited both by intrinsic and acquired resistance and dose-limiting normal tissue toxicity. That cisplatin shows little selectivity for tumor versus normal tissue may be a critical factor limiting its value. To overcome the low therapeutic ratio of the free drug, macromolecular, liposomal and nanoparticle drug delivery systems have been explored toward leveraging the enhanced permeability and retention (EPR) effect and promoting delivery of cisplatin to tumors. Here, we survey recent advances in nanoparticle formulations of cisplatin, focusing on agents that show promise in preclinical or clinical settings. PMID:26848041

  11. Clinical nursing of pelvic neoplasm treated with infusion chemotherapy by using an anti-reflux arterial port-catheter system

    International Nuclear Information System (INIS)

    Xing Li; Yuan Chanjuan

    2011-01-01

    Objective: To discuss the clinical nursing care for patients with pelvic neoplasm who were treated with infusion chemotherapy by using an anti-reflux arterial port-catheter system. Methods: After the implantation of an anti-reflux arterial port-catheter system was successfully completed, intra-arterial infusion chemotherapy was carried out in 17 patients with pelvic neoplasm and the infusion chemotherapy was repeated for several times. The pre-procedural clinical nursing care was well done and the technique of proper placement was well grasped. The side effects of chemotherapy drugs and complications were dealt with in time. Medical orientation at discharge time included the protection methods for port-catheter system. Results: Seventeen patients received infusion chemotherapy successfully several times (ranged from 3 to 8 times) with a scheduled regular interval time. No severe complications occurred. No catheter leakage nor obvious irritation and compression symptoms of local skin developed during infusion period. Of the 17 patients, 6 had a complete response, 9 achieved a partial response, while the remaining 2 failed to respond. Conclusion: In accordance with characteristics of infusion chemotherapy by using an anti-reflux arterial port-catheter system, the reasonable and effective nursing care is important to guarantee the achievement of a successful performance and a satisfactory therapeutic result. (authors)

  12. Effect of intra arterial nimodipine infusion for the treatment of symptomatic cerebral vasospasm following an aneurysmal subarachnoid hemorrhage

    International Nuclear Information System (INIS)

    Lee, Jin Young; Shin, Hwa Seon; Choi, Hye Young; Chung, Sung Hoon; You, Jin Jong; Choi, Dae Seob; Son, Seung Nam; Ryu, Jae Wook

    2012-01-01

    Symptomatic cerebral vasospasm following an aneurysmal subarachnoid hemorrhage (SAH) is one of the major factors which cause morbidity and mortality of patients. The purpose of this study was to evaluate the effectiveness of intra-arterial nimodipine (IAN) infusion therapy in patients with symptomatic cerebral vasospasm. Between February 2005 and April 2011, fifty patients with symptomatic cerebral vasospasm following an aneurysmal SAH were treated with IAN infusion. After selective arterial catheterization, nimodipine was infused at a rate of 0.1 mg/min and a total of 2-3 mg per vessel was infused. We retrospectively reviewed the immediate angiographic results and clinical outcome at discharge. A grade of 5 and 4 in the Glasgow Outcome Scale (GOS) were considered favorable outcomes. In 50 patients, 117 procedures of IAN infusion (1-7; mean, 2.3)were done. After the treatment, immediate angiographic improvement was achieved in 113 (96.6%) of 117 procedures. No major complications occurred. At discharge, 38 (76%) patients showed a favorable clinical outcome in the GOS. IAN infusion therapy is safe and effective for the treatment of cerebral vasospasm following an aneurysmal SAH. However, the limitation is that repeated treatment is needed

  13. Human adipose-derived mesenchymal stem cells repair cisplatin-induced acute kidney injury through antiapoptotic pathways.

    Science.gov (United States)

    Yao, Weiqi; Hu, Qinyong; Ma, Yuhong; Xiong, Wenping; Wu, Tingting; Cao, Jun; Wu, Dongcheng

    2015-08-01

    Cisplatin has been hypothesized to induce nephrotoxicity through triggering the apoptosis of tubular cells; however, the drug remains widely administered for the treatment of tumors. Recently, mesenchymal stem cells (MSCs) have been demonstrated to protect the kidney from the adverse effects induced by cisplatin. The aim of the present study was to investigate the mechanisms underlying the protective effects of human adipose-derived MSCs (AD-MSCs) on kidney function and tubular cells. Sprague-Dawley rats were divided into three groups, which included the healthy controls, those subjected to cisplatin-induced acute kidney injury (AKI) for 24 h without subsequent treatment and those subjected to cisplatin-induced AKI for 24 h, followed by AD-MSC engraftment. The rats were sacrificed at day 5 and the effects were analyzed using various methods, including biochemical analysis, structural examination and cell tracking experiments. In addition, an in vitro experiment with NRK-52E cells was performed. The cells were divided into three groups, including the healthy control, cisplatin induction and cisplatin induction with co-culture of AD-MSCs, and were subsequently assessed with a Transwell assay. After culture for four days, the cells were lysed and the total protein extract was subjected to western blot analysis. Cisplatin-induced renal dysfunction and tissue damage was shown to recover following AD-MSC infusion, although there were few AD-MSCs observed around the injured kidney tubules in the kidney. When the cisplatin-treated NRK-52E cells were co-cultured with AD-MSCs, the activation of p38 and BAX were inhibited, while the expression of Bcl-2 was upregulated, as compared with the cisplatin-treated NRK-52E cells that were not co-cultured. Therefore, AD-MSCs were shown to markedly improve cisplatin-induced renal failure and tubular cells necrosis through the secretion of certain factors, which subsequently inhibited the apoptosis pathway in vitro . It was hypothesized

  14. Repeated Intra-Arterial Thrombectomy within 72 Hours in a Patient with a Clear Contraindication for Intravenous Thrombolysis

    Directory of Open Access Journals (Sweden)

    Mona Laible

    2015-01-01

    Full Text Available Introduction. Treating patients with acute ischemic stroke, proximal arterial vessel occlusion, and absolute contraindication for administering intravenous recombinant tissue plasminogen activator (rtPA poses a therapeutic challenge. Intra-arterial thrombectomy constitutes an alternative treatment option. Materials and Methods. We report a case of a 57-year-old patient with concomitant gastric adenocarcinoma, who received three intra-arterial thrombectomies in 72 hours due to repeated occlusion of the left medial cerebral artery (MCA. Findings. Intra-arterial recanalization of the left medial cerebral artery was performed three times with initially good success. However, two days later, the right medial cerebral artery became occluded. Owing to the overall poor prognosis at that time and knowing the wishes of the patient, we decided not to perform another intra-arterial recanalization procedure. Conclusion. To our knowledge, this is the first case illustrating the use of repeated intra-arterial recanalization in early reocclusion of intracranial vessels.

  15. Cisplatin and low dose rate irradiation in cisplatin resistant and sensitive human glioma cells

    International Nuclear Information System (INIS)

    Wilkins, David E.; Cheng, E. Ng; Raaphorst, G. Peter

    1996-01-01

    Purpose: Human glioma cell lines resistant (U373MG CP ) and sensitive (U373MG) to cisplatin were used to evaluate the effect of cisplatin as a sensitizer to low dose rate irradiation (LDRI). Methods and Materials: A cisplatin resistant glioma cell line U373MG CP was developed by chronic exposure of parental U373MG cells to cisplatin. Plateau phase cells were treated with cisplatin, high dose rate (HDR) irradiation (1.12 Gy/min), LDRI (0.0088 Gy/min), or cisplatin concurrent with LDRI. Cell survival was determined by the colony forming assay. Results: Both cell lines showed increased resistance to radiation at LDR compared with HDR, with Dose Modifying Factors (DMF at 10% survival level) of 1.7 for U373MG and 2.5 for U373MG CP . The increased LDR sparing effect in the cisplatin resistant U373MG CP cells indicates increased repair proficiency. The resistant cell line showed a fourfold increase in resistance to cisplatin cytotoxicity at the 10% survival level compared with the parental U373MG cells. Cisplatin enhanced the response of both cell lines to LDRI. The DMFs were 1.2, 1.2, and 1.7, respectively, for the sensitive U373MG cell line given 1 μg/ml, and the resistant cell line given 3 or 6 μg/ml cisplatin treatments concurrent with LDRI. Conclusions: These data show that cisplatin can be an effective sensitizer to LDRI in both cisplatin resistant and sensitive glioma cell lines. However, in the resistant cell line, higher concentrations of cisplatin were necessary to achieve the same level of sensitization as in the sensitive cell line

  16. Insights into RNA binding by the anticancer drug cisplatin from the crystal structure of cisplatin-modified ribosome

    Science.gov (United States)

    Melnikov, Sergey V.; Söll, Dieter; Steitz, Thomas A.

    2016-01-01

    Abstract Cisplatin is a widely prescribed anticancer drug, which triggers cell death by covalent binding to a broad range of biological molecules. Among cisplatin targets, cellular RNAs remain the most poorly characterized molecules. Although cisplatin was shown to inactivate essential RNAs, including ribosomal, spliceosomal and telomeric RNAs, cisplatin binding sites in most RNA molecules are unknown, and therefore it remains challenging to study how modifications of RNA by cisplatin contributes to its toxicity. Here we report a 2.6Å-resolution X-ray structure of cisplatin-modified 70S ribosome, which describes cisplatin binding to the ribosome and provides the first nearly atomic model of cisplatin–RNA complex. We observe nine cisplatin molecules bound to the ribosome and reveal consensus structural features of the cisplatin-binding sites. Two of the cisplatin molecules modify conserved functional centers of the ribosome—the mRNA-channel and the GTPase center. In the mRNA-channel, cisplatin intercalates between the ribosome and the messenger RNA, suggesting that the observed inhibition of protein synthesis by cisplatin is caused by impaired mRNA-translocation. Our structure provides an insight into RNA targeting and inhibition by cisplatin, which can help predict cisplatin-binding sites in other cellular RNAs and design studies to elucidate a link between RNA modifications by cisplatin and cisplatin toxicity. PMID:27079977

  17. Mechanisms of cisplatin-induced muscle atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Hiroyasu, E-mail: sakai@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sato, Ken [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Chiba, Yoshihiko [Department of Biology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Yamazaki, Mitsuaki [Department of Anesthesiology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 9300194 (Japan); Matoba, Motohiro [Department of Palliative Medicine and Psychooncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045 (Japan); Narita, Minoru, E-mail: narita@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan)

    2014-07-15

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.

  18. Mechanisms of cisplatin-induced muscle atrophy

    International Nuclear Information System (INIS)

    Sakai, Hiroyasu; Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara; Sato, Ken; Chiba, Yoshihiko; Yamazaki, Mitsuaki; Matoba, Motohiro; Narita, Minoru

    2014-01-01

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin

  19. Intra-arterial chemotherapy for retinoblastoma: First Indian report

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2015-01-01

    Full Text Available Aim: To describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC for retinoblastoma (RB in Indian eyes. Materials and Methods: Single center, retrospective interventional case series of 6 eyes with RB who underwent IAC using Melphalan (3 mg/5 mg/7.5 mg and topetecan (1 mg (n = 4 or melphalan (3 mg/5 mg/7.5 mg alone (n = 2 between December 2013 and June 2014. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seeds control and globe salvage rates. Results: IAC was employed as primary (n = 1 or secondary (n = 5 modality of treatment. Each eye received mean 3 IAC sessions (median: 3; range: 1-4 sessions. Eyes were classified according to international classification of RB as Group B (n = 1, C (n = 1, D (n = 2 and E (n = 2. Following IAC, complete regression of the main tumor was seen in 3 cases (50%, partial regression in 2 (33%, while 1 case (15% showed no response. Of 4 eyes with subretinal seeds, 1 (25% eye had complete regression while 3 (75% eyes had partial regression. Of 5 eyes with vitreous seeds, 2 (40% eyes had complete regression while 3 (60% eyes had a partial response. Globe salvage was achieved in 5 of 6 eyes (83%. Diffuse choroidal atrophy and vitreous hemorrhage were observed in 1 (17% eye, each. No hematologic toxicity or cerebro-vascular events were observed. Mean follow-up period was 5.5 months (median: 6 months, range: 1-6 months. Conclusion: IAC is an effective therapy for globe preservation in eyes with RB. Larger studies with longer follow-up are required to validate these results.

  20. Retinoblastoma Control With Primary Intra-arterial Chemotherapy: Outcomes Before and During the Intravitreal Chemotherapy Era.

    Science.gov (United States)

    Shields, Carol L; Alset, Adel E; Say, Emil Anthony T; Caywood, Emi; Jabbour, Pascal; Shields, Jerry A

    2016-09-01

    To compare outcomes of intra-arterial chemotherapy for retinoblastoma as primary therapy before (Era I) and during (Era II) the intravitreal chemotherapy era. In this retrospective interventional case series at a tertiary referral center, 66 eyes of 66 patients with untreated unilateral retinoblastoma were used. intraarterial chemotherapy into the ophthalmic artery under fluoroscopic guidance was performed using melphalan in every case, with additional topotecan as necessary. Intravitreal chemotherapy using melphalan and/or topotecan was employed as needed for active vitreous seeding. Globe salvage was measured based on the International Classification of Retinoblastoma (ICRB) during two eras. The two eras encompassed 2008 to 2012 (intraarterial chemotherapy alone, Era I) and 2012 to 2015 (intraarterial chemotherapy plus intravitreal chemotherapy, Era II). Over this period, there were 66 patients with unilateral untreated retinoblastoma treated with primary intra-arterial chemotherapy. A comparison of features (Era I vs Era II) revealed no significant difference in mean patient age (24 vs 24 months), ICRB groups, mean largest tumor diameter (19 vs 17 mm), mean largest tumor thickness (10 vs 10 mm), vitreous seed presence (56% vs 59%), subretinal seed presence (67% vs 62%), retinal detachment (70% vs 66%), or vitreous hemorrhage (0% vs 5%). There was no significant difference in mean number of intra-arterial chemotherapy cycles (3 vs 3.1) or intraarterial chemotherapy dosages. Following therapy, there was a significant difference (Era I vs Era II) in the need for enucleation overall (44% vs 15%, P = .012), especially for group E eyes (75% vs 27%, P = .039). Four of the eyes that initiated therapy in Era I later required intravitreal chemotherapy during Era II. The enucleation rate was 0% for groups B and C in both eras and non-significant for group D (23% vs 13%). There were no patients with stroke, seizure, limb ischemia, extraocular tumor extension, secondary

  1. Clinical study on external carotid artery infusion (trans-femoral) treatment of recurrent nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zhou Zejian; Li Chong; Luo Pengfei; Shao Peijian; Zhang Liangming; Li Weike; Li Yong; Xu Rongde; Zhuang Wenxing; Zhang Hua

    2002-01-01

    Objective: To evaluate the effect and safety of external carotid artery infusion treatment of recurrent nasopharyngeal carcinoma (NPC). Methods: 20 cases of recurrent NPC (13 male and 7 female, age 36-65 years, mean 50 years) diagnosed by clinical examination (including nasopharyngoscope), serology (VCA-IgA) and imaging (CT, MR) and treated by external carotid artery infusion (trans-femoral) with adriamycin (or epi-adriamycin), cisplatin (or carboplatin), Pingyangmycin and 5-Fluorouracil. Results: Of all the patients, 8 cases (40%) had a complete response (CR), 7 cases (35%) had a partial response (PR). The overall response rate (CR + PR) was 75%. Cumulative survival rates at 1, 3 years were 90% (18/20), 50%(10/20) respectively. No severe side-effects and complications found. Conclusion: External carotid artery infusion (trans-femoral) should be effective and safe in the treatment of recurrent NPC

  2. ASNA-1 activity modulates sensitivity to cisplatin.

    Science.gov (United States)

    Hemmingsson, Oskar; Kao, Gautam; Still, Maria; Naredi, Peter

    2010-12-15

    Cancer can be cured by platinum-based chemotherapy, but resistance is a major cause of treatment failure. Here we present the nematode Caenorhabditis elegans as a model to study interactions between the platinum drug cisplatin and signaling pathways in vivo. Null mutation in a single gene, asna-1, makes worms hypersensitive to cisplatin. The metalloregulated ATPase ASNA-1 promotes insulin secretion and membrane insertion of tail-anchored proteins. Using structural data from ASNA-1 homologues, we identify specific ASNA-1 mutants that are sensitive to cisplatin while still able to promote insulin signaling. Mutational analysis reveals that hypersensitivity of ASNA-1 mutants to cisplatin remains in absence of CEP-1/p53 or apoptosis. Human ASNA1 can substitute for the worm gene, indicating a conserved function. Cisplatin sensitivity is not affected by decreased insulin signaling in wild-type nematodes or restored insulin signaling in asna-1 mutants. These findings provide a functional insight into ASNA-1, demonstrate that C. elegans can be used to characterize cisplatin resistance mechanisms, and suggest that rationally designed drugs against ASNA-1 can sensitize cancer cells to cisplatin. ©2010 AACR.

  3. Rescue localized intra-arterial thrombolysis for hyperacute MCA ischemic stroke patients after early non-responsive intravenous tissue plasminogen activator therapy

    International Nuclear Information System (INIS)

    Kim, Dong Joon; Kim, Dong Ik; Kim, Seo Hyun; Lee, Kyung Yeol; Heo, Ji Hoe; Han, Sang Won

    2005-01-01

    The outcome of patients who show no early response to intravenous (i.v.) tissue plasminogen activator (tPA) therapy is poor. The objective of this study was to evaluate the feasibility of rescue localized intra-arterial thrombolysis (LIT) therapy for acute ischemic stroke patients after an early non-responsive i.v. tPA therapy. Patients with proximal MCA occlusions who were treated by LIT (n=10) after failure of early response [no improvement or improvement of National Institute of Health Stroke Scale (NIHSS) scores of ≤3] to i.v. tPA therapy (0.9 mg/kg - 10% bolus and 90% i.v. infusion over 60 min) were selected. The recanalization rates, incidence of post-thrombolysis hemorrhage and clinical outcomes [baseline and discharge NIHSS scores, mortality, 3 months Barthel index (BI) and modified Rankin score (mRS)] were evaluated. Rescue LIT therapy was performed on ten MCA occlusion patients (male:female=3:7, mean age 71 years). The mean time between the initiation of i.v. tPA therapy and the initiation of intra-arterial urokinase (i.a. UK) was 117±25.0 min [time to i.v. tPA 137±32 min; time to digital subtraction angiography (DSA) 221±42 min; time to i.a. UK 260±46 min]. The baseline NIHSS scores showed significant improvement at discharge (median from 18 to 6). Symptomatic hemorrhage and, consequent, mortality were noted in 2/10 (20%) patients. Three months good outcome was noted in 4/10 (40%, mRS 0-2) and 3/10 (30%, BI ≥95). In conclusion, rescue LIT therapy can be considered as a treatment option for patients not showing early response to full dose i.v. tPA therapy. Larger scale studies for further validation of this protocol may be necessary. (orig.)

  4. Glutamine protects against cisplatin-induced nephrotoxicity by decreasing cisplatin accumulation

    OpenAIRE

    Kim, Hyun-Jung; Park, Dong Jun; Kim, Jin Hyun; Jeong, Eun Young; Jung, Myeong Hee; Kim, Tae-Ho; Yang, Jung Ill; Lee, Gyeong-Won; Chung, Hye Jin; Chang, Se-Ho

    2015-01-01

    Cisplatin is a chemotherapeutic drug but induces acute kidney injury (AKI). Cisplatin-induced AKI depends on several signaling pathways leading to apoptosis in tubular epithelial cells. Glutamine is a substrate for the synthesis of glutathione, the most abundant intracellular thiol and antioxidant, and plays an important role in protecting cells from apoptosis induced by different stimuli. In the present study, we investigated the protective effect of glutamine on cisplatin-induced AKI. Rats ...

  5. Na(+)/K(+)-ATPase inhibition by cisplatin and consequences for cisplatin nephrotoxicity.

    Science.gov (United States)

    Kubala, Martin; Geleticova, Jaroslava; Huliciak, Miroslav; Zatloukalova, Martina; Vacek, Jan; Sebela, Marek

    2014-06-01

    Cisplatin is a widely used chemotherapeutic. However, it is associated with numerous adverse effects. The aim of our study was examination of cisplatin interaction with Na(+)/K(+)-ATPase (NKA, the sodium pump). This enzyme is of crucial importance for all animal cells and particularly for the kidney, which is frequently damaged during chemotherapy. The entire NKA was isolated from porcine kidney. Its large cytoplasmic segment connecting transmembrane helices 4 and 5 (C45), was heterologously expressed in E.coli (wild-type or C367S mutant). The ATPase activity was evaluated according to the inorganic phosphate production and the interaction of isolated C45 with cisplatin was studied using chronopotentiometry and mass spectrometry. Our experiments revealed that cisplatin can inhibit NKA. The finding that other platinum-based drugs with a low nephrotoxicity, carboplatin and oxaliplatin, did not inhibit NKA, suggested that NKA/cisplatin interaction is an important factor in cisplatin adverse effects. The inhibitory effect of cisplatin could be prevented by preincubation of the enzyme with reduced glutathione or DTT. Using chronopotentiometry and mass spectrometry, we found that cisplatin is bound to C45. However, our mutagenesis experiment did not confirm that the suggested Cys367 could be the binding site for cisplatin. Unintended interactions of drugs present serious limitations to treatment success. Although a large number of membrane pumps have been identified as potential targets of cisplatin, vis-a-vis nephrotoxicity, NKA inhibition seems to be of crucial importance. Experiments with isolated large cytoplasmic segment C45 revealed that it is the main target of cisplatin on NKA and that the reaction with cysteine residues plays an important role in cisplatin/NKA interactions. However, further experiments must be performed to identify the interacting amino acid residues more precisely.

  6. Duration of cisplatin excretion in breast milk.

    Science.gov (United States)

    Hays, Karen E; Ryu, Rachel J; Swisher, Elizabeth M; Reed, Eddie; McManus, Terry; Rybeck, Blanche; Petros, William P; Hebert, Mary F

    2013-11-01

    Cisplatin, a platinum-based chemotherapy agent, is commonly used in treating cancers that may affect women of childbearing age, including cervical cancer, triple-negative breast cancer, and pediatric tumors in adolescents. The authors found that platinum was undetectable in breast milk at 66 hours and beyond following a 70-mg dose of intravenous cisplatin. Relative infant dose of platinum was calculated to be between 0.29% and 0.40% of the maternal dose corrected for body weight. This case demonstrates minimal exposure to platinum via breast milk, following a single 70-mg intravenous dose of cisplatin.

  7. Combining iodine-131 Lipiodol therapy with low-dose cisplatin as a radiosensitiser: preliminary results in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Brans, B.; Van Laere, K.; Gemmel, F.; Dierckx, R.A.; Defreyne, L.; Vanlangenhove, P.; Troisi, R.; Hemptinne, B. de; Van Vlierberghe, H.; Colle, I.

    2002-01-01

    A prospective pilot trial was performed in 20 patients randomised to receive either 131 I-Lipiodol therapy alone (n=10) or 131 I-Lipiodol combined with a short low-dose cisplatin infusion (n=10), the aim being to evaluate the possible positive influence of a radiosensitiser on toxicity and tumour response. An activity of 1,354-2,128 MBq (mean 1,824 MBq) [36.6-57.5 mCi (mean 49.3 mCi)] 131 I-labelled Lipiodol was administered by selective instillation in the hepatic artery. Cisplatin was given in a dose of 30 mg/m 2 at day -1 and day +6 (day 0: 131 I-Lipiodol). The primary endpoint of this trial was toxicity of therapy; points of secondary interest were tumour response and survival at 6 months. With the use of cisplatin we found a higher percentage of stable or diminished tumour size (90%, vs 40% without). A benefit in group survival at 6 months was not evident. Low-grade stomatitis in one patient and minor changes in peripheral blood count were probably directly related to cisplatin, but its administration is unlikely to be associated with an excess of serious side-effects. The use of low-dose cisplatin infusion as a radiosensitising agent in 131 I-Lipiodol therapy for hepatocellular carcinoma seems safe and may be beneficial for tumour control. Larger patient groups are necessary for confirmation and to establish the future role of 131 I-Lipiodol in hepatocellular carcinoma. (orig.)

  8. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  9. Suramin protects from cisplatin-induced acute kidney injury

    Science.gov (United States)

    Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

    2015-01-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

  10. Digital subtraction angiography and intraarterial contrast medium injection for coronary examinations

    Energy Technology Data Exchange (ETDEWEB)

    Tobio, R.; Kallmeyer, C.; Castello, J.

    1985-01-01

    Digital subtraction angiography (DSA) is an established method of vasography, most extensively used as i.v. DSA. Intraarterial injection, however, applying selective or non-selective contrast medium injection, seems to be at least as important a technique although it has not yet met with corresponding interest. The article explains advantages of the technique for angiographic examinations, in particular of coronary angiography.

  11. Hepatic Chemoembolization: Effect of Intraarterial Lidocaine on Pain and Postprocedure Recovery

    International Nuclear Information System (INIS)

    Hartnell, George G.; Gates, Julia; Stuart, Keith; Underhill, Jonathan; Brophy, David P.

    1999-01-01

    Purpose: To determine if intraarterial lidocaine reduces pain during and after chemoembolization, and whether it influences postprocedure recovery. Methods: Two patient cohorts undergoing selective hepatic chemoembolization were compared. Chemoembolization was performed without lidocaine (control group) in 27 patients and intraarterial lidocaine was used (lidocaine group) in 29 similar patients. Objective changes in patient management were assessed. Pain reduction in 31 more procedures with lidocaine (total 60) was assessed and related to tumor type. Results: During chemoembolization, intraarterial lidocaine reduced the need for additional intravenous analgesics from 69% to 19%. After chemoembolization the mean Dilaudid dose in the first 24 hr was reduced from 9.5 mg to 4.15 mg; accordingly, the mean length of hospital stay was reduced from 67.5 to 53.5 hr. During the day of chemoembolization, the mean oral fluid intake increased from 420 ml (control group) to 487 ml (lidocaine group); the percentage of patients taking solid food on the day of chemoembolization increased from 3% to 43%. Conclusion: Intraarterial lidocaine during chemoembolization reduces the severity and duration of pain after chemoembolization resulting in faster recovery thus reducing the length of hospitalization

  12. Local intra-arterial thrombolysis in a 4-year-old male with vertebrobasilar artery thrombosis

    NARCIS (Netherlands)

    Janmaat, Mirjam; Gravendeel, Joost P; Uyttenboogaart, Maarten; Vroomen, Patrick C; Brouwer, Oebele F; Luijckx, Gert-Jan

    We report the case of a 4-year-old male with vertebrobasilar artery thrombosis for which he was treated with local intra-arterial urokinase 60 hours after onset of symptoms. Initially the patient had dysarthria and dysphagia. Brain magnetic resonance imaging (MRI) in a community hospital showed

  13. Combined chemotherapy and intra-arterial chemotherapy of retinoblastoma

    Directory of Open Access Journals (Sweden)

    Saerom Choi

    2013-06-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Retinoblastoma (RB is the most common primary malignant intraocular tumor in children. Although systemic chemotherapy has been the primary treatment, intra-arterial chemotherapy (IAC represents a new treatment option. Here, we performed alternate systemic chemotherapy and IAC and retrospectively reviewed the efficacy and safety of this approach. &lt;b&gt;Methods:&lt;/b&gt; Patients diagnosed with intraocular RB between January 2000 and December 2011 at Severance Children’s Hospital, Yonsei University, were reviewed. Before February 2010, the primary treatment for RB was chemotherapy (non-IAC/CTX. Since February 2010, the primary treatment for RB has been IAC (IAC/CTX. External beam radiotherapy or high-dose chemotherapy (HDCTX were used as “last resort” treatments just prior to enucleation at the time of progression or recurrence during primary treatment. Enucleation-free survival (EFS and progression-free survival were assessed. &lt;b&gt; Results:&lt;/b&gt; We examined 19 patients (median age, 11.9 months; range, 1.4 to 75.6 months with a sum of 25 eyes, of which, 60.0% were at advanced Reese Ellsworth (RE stages. The enucleation rate was 33.3% at early RE stages and 81.8% at advanced RE stages (P =0.028. At 36 months, EFS was significantly higher in the IAC/CTX group than in the non-IAC/CTX group (100.0% vs. 40.0%, P=0.016. All 5 patients treated with IAC achieved eye preservation, although most patients were at advanced RE stages (IV-V. &lt;b&gt;Conclusion:&lt;/b&gt; Despite the limitation of a small sample size, our work shows that an alternative combined approach using IAC and CTX may be safe and effective for eye preservation in advanced RB.

  14. Magnesium improves cisplatin-mediated tumor killing while protecting against cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Kumar, Gopal; Solanki, Malvika H; Xue, Xiangying; Mintz, Rachel; Madankumar, Swati; Chatterjee, Prodyot K; Metz, Christine N

    2017-08-01

    Approximately 30% of all cancer patients treated with cisplatin, a widely used broad-spectrum chemotherapeutic agent, experience acute kidney injury (AKI). Almost all patients receiving cisplatin have magnesium (Mg) losses, which are proposed to aggravate AKI. Currently, there are no methods to successfully treat or prevent cisplatin-AKI. Whereas Mg supplementation has been shown to reduce AKI in experimental models and several small clinical trials, the effects of Mg status on tumor outcomes in immunocompetent tumor-bearing mice and humans have not been investigated. The purpose of this study was to further examine the effects of Mg deficiency (±Mg supplementation) on cisplatin-mediated AKI and tumor killing in immunocompetent mice bearing CT26 colon tumors. Using a model where cisplatin alone (20 mg/kg cumulative dose) produced minimal kidney injury, Mg deficiency significantly worsened cisplatin-mediated AKI, as determined by biochemical markers (blood urea nitrogen and plasma creatinine) and histological renal changes, as well as markers of renal oxidative stress, inflammation, and apoptosis. By contrast, Mg supplementation blocked cisplatin-induced kidney injury. Using LLC-PK 1 renal epithelial cells, we observed that Mg deficiency or inhibition of Mg uptake significantly enhanced cisplatin-induced cytotoxicity, whereas Mg supplementation protected against cytotoxicity. However, neither Mg deficiency nor inhibition of Mg uptake impaired cisplatin-mediated killing of CT26 tumor cells in vitro. Mg deficiency was associated with significantly larger CT26 tumors in BALB/c mice when compared with normal-fed control mice, and Mg deficiency significantly reduced cisplatin-mediated tumor killing in vivo. Finally, Mg supplementation did not compromise cisplatin's anti-tumor efficacy in vivo. Copyright © 2017 the American Physiological Society.

  15. Cisplatin induces stemness in ovarian cancer.

    Science.gov (United States)

    Wiechert, Andrew; Saygin, Caner; Thiagarajan, Praveena S; Rao, Vinay S; Hale, James S; Gupta, Nikhil; Hitomi, Masahiro; Nagaraj, Anil Belur; DiFeo, Analisa; Lathia, Justin D; Reizes, Ofer

    2016-05-24

    The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility.

  16. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... higher than 300 mg/m2 the patients lost distal tendon and H-reflexes and displayed reduced vibration sense in the feet and the fingers. The amplitudes of sensory nerve action potentials (SNAP) from the fingers innervated by the median nerve and the dorsolateral side of the foot innervated by the sural...... of the foot evoked by a tactile probe showed similar changes to those observed in SNAPs evoked by electrical stimulation. At these doses, somatosensory evoked potentials (SEPs) from the tibial nerve had increased latencies of peripheral, spinal and central responses suggesting loss of central processes...

  17. Infusion's greenfield subsidiary in Poland

    NARCIS (Netherlands)

    Williams, C.; van Eerde, W.; The, D.

    2012-01-01

    The president of Infusion Development Corporation was reviewing the progress of the new subsidiary the company had set up 15 months earlier in Krakow, Poland. The purpose of the subsidiary was to work with other Infusion offices around the world to provide innovative software development services to

  18. Efficacy and Toxicity of Pemetrexed or Gemcitabine Combined with Cisplatin in the Treatment of Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xingsheng HU

    2012-10-01

    Full Text Available Background and objective Due to the various inter-individual differences in the biological characteristics of tumor cells, as well as issues on the efficacy, adverse reactions, and defects of existing drugs, we compared the clinical efficacy and toxicity of pemetrexed and gemcitabine combined with cisplatin for the treatment of previously untreated advanced non-small cell lung cancer (NSCLC. Methods 251 patients were randomly divided into pemetrexed combined with cisplatin group (PP group with 127 cases and gemcitabine combined with cisplatin group (GP group with 124 cases. PP group received pemetrexed 500 mg/m2 iv infusion d1 and cisplatin 75 mg/m2 iv infusion d1, whereas GP group received gemcitabine 1,000 mg/m2 iv infusion d1,8 and cisplatin 75 mg/m2 iv infusion d1. The treatment cycle was once every three weeks. In addition, folic acid, vitamin B12, and dexamethasone were administered in both groups. Results The total clinical effective rates in PP group and GP group were 25.20% and 17.74%, respectively. The total efficiencies of non-squamous cell carcinoma were 27.62% and 16.00%. The tumor progression duration in these two groups was 6.5 and 5.6 months, respectively. The median survival time in the two groups was 16.9 and 17.0 months, respectively, with 59.62% and 65.87% survival rates of 1 year and 27.28% and 27.93% survival rates of 2 years, respectively. The total efficacy of non-squamous cell carcinoma in the PP group was significantly higher than that in GP group. The results were statistically significant. However, there were no significant differences in total response rates, tumor progression duration, and median survival rates of 1 and 2 years. The rate of adverse reactions, including white blood cell reduction, lower platelet count, lower hemoglobin, and hair loss in the PP group was significantly lower than that in the GP group. The results were statistically significant. Conclusion The clinical efficacy of pemetrexed and

  19. Dietary inclusion of sorghum (Sorghum bicolour) straw dye protects against cisplatin-induced nephrotoxicity and oxidative stress in rats.

    Science.gov (United States)

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Agbebi, Oluwaseun J; Oyeleye, Sunday I

    2014-07-01

    Sorghum straw (dried leaves and stem fiber) extracts and infusion are employed in the management of several ailments in folklore, and it is also a natural dye source used in food preparation. This study sought to investigate the modulatory effect of dietary inclusion of Sorghum straw dye on cisplatin-induced nephrotoxicity and antioxidant status in rats. Adult male rats were randomly divided into four groups of six animals each. Groups I (normal rats) and II (control rats) were fed with basal diet while Groups III and IV were fed with diets containing 0.5% and 1% sorghum straw dye, respectively. Nephrotoxicity was induced in Groups I-IV on the 20th day by the administration of a single dose of cisplatin solution (7 mg/kg body weight, i.p.) and the experiment was terminated 3 d after. Thereafter, the kidney and plasma of the rats were analyzed for kidney function (creatinine, urea, uric acid, and blood urea nitrogen) and antioxidant indices [superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), malondialdehyde (MDA), vitamin C, and reduced glutathione (GSH)]. The average feed intake of the rats in all the groups ranged from 9.0 to 9.5 (g/rat/day). Furthermore, the result indicated that administration of cisplatin caused significant (p cisplatin-induced nephrotoxicity.

  20. Transient elevation of serum cystatin C concentrations during perioperative cisplatin-based chemotherapy in esophageal cancer patients.

    Science.gov (United States)

    Kume, Manabu; Yasui, Hiroyuki; Yoshikawa, Yutaka; Horinouchi, Masanori; Higashiguchi, Kanae; Kobayashi, Yoko; Kuroda, Daisuke; Hirano, Takeshi; Hirai, Midori; Nakamura, Tsutomu

    2012-06-01

    In the present study, the time-concentration profile of platinum (Pt) in plasma was compared to that of serum cystatin C (Cys C) in Japanese esophageal cancer patients receiving perioperative cisplatin-based chemotherapy. Five male and one female patients receiving 2 successive cycles of cisplatin-based chemotherapy combined with 5-fluorouracil, the treatment for esophageal squamous cell carcinoma, participated in this study. The pharmacokinetic parameters in each patient were calculated from the individual plasma Pt concentration-time curve after intravenous infusion of cisplatin using the one-compartment model. Within a week of starting the first cycle of chemotherapy, serum Cys C concentrations increased in all patients from 122.6 to 143.0%, subsequently returning to baseline levels in approximately 10 days. A similar increase in serum Cys C levels also occurred during the second treatment cycle. However, no increase in serum creatinine levels was observed during either treatment cycle. In addition, the concentration of plasma Pt 2 days after treatment in the first and second cycles did not correlate with those of either serum Cys C or creatinine. Finally, the half-life of Pt in plasma during the first treatment cycle was not significantly different from that in the second cycle. These findings suggest that concentration fluctuations in serum Cys C are unlikely to correlate with Pt elimination from the plasma and that renal function estimates based on serum Cys C concentration might be underestimated during perioperative cisplatin-based chemotherapy for esophageal cancer.

  1. Modulatory effect of Althaea officinalis L root extract on cisplatin ...

    African Journals Online (AJOL)

    AORE) on cisplatininduced cytotoxicity and cell proliferation in a lung cancer cell line. Methods: Aqueous AORE was obtained from peeled and powdered roots. The effect of cisplatin on cytotoxicity and cell proliferation was studied. The cisplatin ...

  2. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion.

    Science.gov (United States)

    Yanagie, Hironobu; Kumada, Hiroaki; Nakamura, Takemi; Higashi, Syushi; Ikushima, Ichiro; Morishita, Yasuyuki; Shinohara, Atsuko; Fijihara, Mitsuteru; Suzuki, Minoru; Sakurai, Yoshinori; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Nishimura, Ryohei; Ono, Koji; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Takahashi, Hiroyuki

    2011-12-01

    Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of (10)B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared (10)BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), (10)BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. The (10)B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that (10)B entrapped WOW emulsion could be applied to novel intra-arterial boron delivery carrier

  3. Tumour resistance to cisplatin: a modelling approach

    International Nuclear Information System (INIS)

    Marcu, L; Bezak, E; Olver, I; Doorn, T van

    2005-01-01

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

  4. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Madaric, Juraj, E-mail: jurmad@hotmail.com [National Institute of Cardiovascular Diseases (NUSCH) and Slovak Medical University, Department of Cardiology and Angiology (Slovakia); Klepanec, Andrej [National Institute of Cardiovascular Diseases, Department of Diagnostic and Interventional Radiology (Slovakia); Mistrik, Martin [Clinic of Hematology and Transfusiology, Faculty Hospital (Slovakia); Altaner, Cestmir [Slovak Academy of Science, Institute of Experimental Oncology (Slovakia); Vulev, Ivan [National Institute of Cardiovascular Diseases, Department of Diagnostic and Interventional Radiology (Slovakia)

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  5. Effects of cisplatin on potassium currents in CT26 cells

    OpenAIRE

    Naveen Sharma; Janardhan Prasad Bhattarai; Sun Young Kim; Pyoung Han Hwang; Min Sun Kim; Seong Kyu Han

    2016-01-01

    Aims: Cisplatin, a platinum-based drug, is an important weapon against many types of cancer. It is well-known that cisplatin induces apoptosis. Potassium channel plays very important role in several signaling pathways. To investigate the possibility that potassium channels also have a role in the cellular response to cisplatin, we examined the effect of cisplatin on the activity of potassium channels on CT26 cell, the colon carcinoma cell line. Materials and Methods: The cells were culture...

  6. Radio-chemo-therapy with 5FU and cisplatin for bladder cancer after TUR-bladder

    International Nuclear Information System (INIS)

    Schuchardt, U.; Birkenhake, S.; Leykam, S.; Martus, P.; Sauer, R.

    1996-01-01

    Purpose/Objective: To determine toxicity and efficacy of radio-chemo-therapy (RCT) with 5FU and cisplatin in patients with bladder cancer. Endpoints are initial response, cystectomy-rates and overall-survival. Materials and Methods: From 11/93 to 1/95 13 patients suffering from bladder cancer were first treated with TUR-bladder (TURB). Patient characteristics were as follows: Within 6 weeks after operation the pelvis was irradiated with 54.0 Gy (median) in conventional fractionation (10 MV photons 4-field-box). The bladder was boosted up to 59.4 Gy (median) in isocentric rotation technique. 7 patients were treated with 45 Gy paraaortal. During the first and 5th treatment week chemotherapy (CT) was simultaneously given: 800 mg/m 2* d CISPLATIN as bolus-infusion 30 min prior to RT. 2 months later a further TURB was performed for restaging. Cystectomy was recommended, if invasive cancer was found at this time. Acute hematological and gastrointestinal toxicity was recorded according to the WHO-criteria. Results: At least 81% (e.g. 75% of 2nd course) of CT was applied in 10/13 patients. Median doses were 3500 mg/m 2 5FU and 200 mg/m 2 CISPLATIN. Acute toxicity to bladder and bowel reached grade 2 WHO only. Hematotoxicity (median values) and results ar shown in the following table. Conclusion: Concomitant RCT with 5FU and CISPLATIN seems to be a promising modality for organ-preserving therapy of bladder cancer. Preliminary results show sufficient effect and acceptable toxicity. Since patient number is still low, further investigation is recommended

  7. Low-dose LBH589 increases the sensitivity of cisplatin to cisplatin-resistant ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Yen-Ying Ma

    2011-06-01

    Conclusion: We hypothesized that combination of cisplatin and LBH589 can override cisplatin-associated resistance in ovarian cancer cells. These results provide initial evidence for testing this combination in clinical use.

  8. Concomitant low dose-rate irradiation and cisplatin treatment in ovarian carcinoma cell lines sensitive and resistant to cisplatin treatment

    International Nuclear Information System (INIS)

    Raaphorst, G.P.; Wang, G.; Stewart, D.; Ng, C.E.

    1996-01-01

    Human ovarian carcinoma parental and cisplatin-resistant cells were evaluated for their radiation sensitivity to high and low dose-rate irradiation and for the effectiveness of cisplatin in radiosensitization. The cisplatin resistant variant A2780 cp showed increased radiation resistance for both low dose-rate (LDRI) and high dose-rate irradiation. For cisplatin treatment for 1 h before and after HDRI there was radiosensitization in only the cisplatin-resistant variant. Concomitant cisplatin treatment during LDRI resulted in radiosensitization in both cell lines with dose-modifying factors ranging from 1.6 to 5.8. In this case greater radiosensitization was achieved in the parental cell line. In both cell lines the dose-modifying factors were larger when the cisplatin was refreshed every 6 h instead of 12 h during LDRI. These data show that cisplatin may be a very effective radiosensitizer when given during LDRI which is used in brachytherapy. (author)

  9. The mechanism of interaction between cisplatin and selenite

    NARCIS (Netherlands)

    Baldew, G S; Mol, J G; de Kanter, F J; van Baar, B; De Goeij, J J; Vermeulen, N P

    1991-01-01

    Cisplatin is a widely used antitumor drug, highly effective in the treatment of several tumors. Cisplatin exerts its antitumor activity through an interaction with DNA, which results in the formation of bidentate adducts. An important side-effects of cisplatin is nephrotoxicity. Selenite can reduce

  10. Role of Autophagy in Cisplatin Resistance in Ovarian Cancer Cells*

    Science.gov (United States)

    Wang, Juan; Wu, Gen Sheng

    2014-01-01

    Cisplatin-based treatment is the first line chemotherapy for several cancers including ovarian cancer. The development of cisplatin resistance results in treatment failure, but the underlying mechanisms are not fully understood. Here we show that the induction of autophagy plays an important role in cisplatin resistance in ovarian cancer cells. Specifically, we show that cisplatin resistance is correlated with autophagy induction in a panel of ovarian cancer cells but not in immortalized human ovarian surface epithelial cells. Mechanistically, cisplatin treatment activates ERK and subsequently promotes autophagy. The inhibition of ERK activation with MEK inhibitors or knockdown of ERK expression with siRNA decreases cisplatin-induced autophagy and subsequently sensitizes ovarian cancer cells to cisplatin-induced apoptosis. In ovarian cancer cells that have developed acquired cisplatin resistance, both ERK activation and autophagy induction are increased. Importantly, knockdown of ERK or inhibition of autophagy promotes cisplatin-induced apoptosis in acquired cisplatin-resistant cells. Collectively, our data indicate that ERK-mediated autophagy can lead to cisplatin resistance and suggest that cisplatin resistance can be overcome by inhibition of autophagy in ovarian cancer cells. PMID:24794870

  11. Attenuation of cisplatin-induced nephrotoxicity in rats using ...

    African Journals Online (AJOL)

    The rats received a single dose injection of 10 mg/kg cisplatin. Other groups of rats received zerumbone (100 and 200 mg/kg), corn oil or the vehicle, dimethyl sulfoxide (DMSO) intraperitoneally for 4 days prior to cisplatin-injections. All animals were decapitated 16 h after cisplatin injection. Trunk blood was collected and ...

  12. Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins

    Directory of Open Access Journals (Sweden)

    Gayani N. P. Dedduwa-Mudalige

    2015-09-01

    Full Text Available Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA including siRNA, spliceosomal RNAs, tRNA, and rRNA. All of these RNAs play vital roles in the cell, such as catalysis of protein synthesis by rRNA, and therefore serve as potential drug targets. This work focused on platination of two highly conserved RNA hairpins from E. coli ribosomes, namely pseudouridine-modified helix 69 from 23S rRNA and the 790 loop of helix 24 from 16S rRNA. RNase T1 probing, MALDI mass spectrometry, and dimethyl sulfate mapping revealed platination at GpG sites. Chemical probing results also showed platination-induced RNA structural changes. These findings reveal solvent and structural accessibility of sites within bacterial RNA secondary structures that are functionally significant and therefore viable targets for cisplatin as well as other classes of small molecules. Identifying target preferences at the nucleotide level, as well as determining cisplatin-induced RNA conformational changes, is important for the design of more potent drug molecules. Furthermore, the knowledge gained through studies of RNA-targeting by cisplatin is applicable to a broad range of organisms from bacteria to human.

  13. UFT plus cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer. Its application to outpatient practice

    International Nuclear Information System (INIS)

    Yano, Tokujiro; Koga, Tadashi; Nomiyama, Hiroyuki; Hidaka, Hiromu

    2003-01-01

    Combination chemotherapy with tegafur-uracil (UFT) and cisplatin is active and less toxic for advanced non-small cell lung cancer. This treatment is likely to be applied to concurrent chemoradiotherapy for locally advanced non-small cell lung cancer, especially in the outpatient setting. Ten patients with unresectable stage III non-small cell lung cancer received the UFT plus cisplatin treatment combined with concurrent radiotherapy. The chemotherapeutic regimen consisted of oral administration of UFT 400 mg/m 2 daily and venous infusion of cisplatin 20-25 mg/m 2 on days 8-10. The administration of cisplatin was repeated every 3-4 weeks. Thoracic radiation started on day 8, and was completed to a total dose of 60-70 Gy. Adverse events (grade 3 or 4) occurred in 2 patients (esophagitis 2, leukopenia/neutropenia 1) with no treatment-related death. There were 7 partial responses (response rate 70.0%; 95% confidence interval (C.I.), 41.6-98.4%). The median survival time was 18.7 months with a 1-year survival rate of 77.8%. Two patients uneventfully received the treatment in an outpatient setting. With regard to the quality of life of patients, UFT plus cisplatin with concurrent radiotherapy might be the treatment of choice for unresectable stage III non-small cell lung cancer. (author)

  14. Hypoglycaemia secondary to labetalol infusion.

    Science.gov (United States)

    Immanni, Sudhir; Khan, Ehtesham Izhar; Staunton, Michael

    2011-05-01

    A 42-year-old multigravida with severe pre-eclampsia had an emergency caesarean section under spinal anaesthesia. Peri-operatively, her arterial pressure was controlled with oral methyldopa and an intravenous infusion of labetalol. Postoperatively, in the Intensive Care Unit, she had recurrent episodes of hypoglycaemia which required treatment with intravenous glucose. These episodes resolved when the labetalol infusion was stopped. Clinicians should be aware of the potential of labetalol to cause hypoglycaemia.

  15. Intra-arterial colforsin daropate for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage

    International Nuclear Information System (INIS)

    Suzuki, Satoshi; Ito, Osamu; Sayama, Tetsuro; Goto, Katsuya

    2010-01-01

    Cerebral vasospasm (CV) remains a major cause of mortality and morbidity in patients with subarachnoid hemorrhage (SAH). Here, we examined the effectiveness and safety of intra-arterial injection of colforsin daropate hydrochloride (CDH). A consecutive series of 29 patients with angiographically confirmed CV received intra-arterial CDH (IAC) therapy. Angiographic changes in spastic vessels and the cerebral circulation time (CCT) were assessed before and after IAC treatment, together with the change in clinical status. IAC treatment was performed in 53 procedures in 29 patients. Angiographic improvement was observed following all procedures (100%), and clinical improvement was observed following 36 of 42 procedures (86%) in symptomatic cases. CCT improved significantly. At the 3-month follow-up, 19 patients (66%) showed good recovery or moderate disability on the Glasgow Outcome Scale. Major adverse effects were headache and increased heart rate. IAC treatment was effective and safe for the treatment of CV after SAH. (orig.)

  16. A review of the literature for intra-arterial chemotherapy used to treat retinoblastoma.

    Science.gov (United States)

    Wyse, Emily; Handa, James T; Friedman, Alan D; Pearl, Monica S

    2016-08-01

    Retinoblastoma is a malignancy of the retina that usually presents before the age of 5 years. Sporadic retinoblastoma is most often unilateral and with no hereditary influence, whereas familial retinoblastoma presents unilaterally or bilaterally in conjunction with genetic inheritance. Several treatments have been attempted with the goals of saving the child's life, salvaging the eye, and preserving vision. Alternative methods including external beam radiation, systemic chemotherapy and focal therapies have been shown to be effective but carry a risk of enucleation and other complications proportional to the severity of the tumor. Selective intra-arterial chemotherapy for retinoblastoma began in 1988 in Japan and has emerged in the last 7 years in the United States as a feasible, effective and minimally invasive treatment option. We review the retinoblastoma treatment literature focusing on intra-arterial chemotherapy.

  17. Combined use of intraarterial digital subtraction angiography with conventional retrograde brachial vertebral angiography

    International Nuclear Information System (INIS)

    Yamaguchi, Tatsuo; Ogawa, Toshihide; Inugami, Atsushi; Kawata, Yasushi; Shishido, Fumio; Uemura, Kazuo

    1985-01-01

    For 102 patients who had the examination of conventional bilaterally retrograde brachial vertebral angiography (retrograde VAG), intraarterial digital subtraction angiography (DSA) was successively performed to investigate steno-occlusive lesions of proximal vertebral and subclavian arteries. All the patients had no complication due to the DSA procedure. In 50% of 72 ischemic stroke cases, positive findings were found either in the origin of the vertebral artery or in the subclavian artery. Stenosis of more than 50% of the lumen of the vertebral artery were found in 14% of the cases at the origin of the right one and also in 14% in the left one. Occlusion of the vertebral artery was found in 4% in the left side only. In 30 cases with non-ischemic brain diseases, positive findings were noted in 10%. Intraarterial DSA combined with retrograde VAG was thought to be useful, especially in the examination for ischemic stroke. (author)

  18. Technological development of injectable cisplatin solution

    International Nuclear Information System (INIS)

    Gato del Monte, Armando; Padron Yaquis, Alejandro Saul

    2012-01-01

    To develop a cisplatin formulation at 1mg/mL concentration by setting the solution preparation procedure for parenteral administration, with good physical, chemical, biological and microbiological stability. two formulation variants of cisplatin: one solution with and the other without acetate buffer. Both were followed in terms of physical and chemical stability for 3 months. The formulations used raw material from IMPEX SA company, which has 99.74 % power as certified by the manufacturer analysis. Three batches of 10mg cistoplatin at pilot scale in amber 10 R vials, 3 batches of 50 mg cisplatin in amber 50 H vials and the dose was 1mg/ml. Excipients were used to give isotony and stability to the formulation with 0.1 N chlorhydric acid and injection water for vehicle. The high performance liquid chromatography allowed evaluating the stability to determine the expiry date of the drug. The biological and microbiological methods determined lack of pyrogens and sterility respectively

  19. Persistent renal enhancement after intra-arterial versus intravenous iodixanol administration

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Shinn-Huey; Wang, Zhen J.; Kuo, Jonathan; Cabarrus, Miguel; Fu Yanjun; Aslam, Rizwan; Yee, Judy; Zimmet, Jeffrey M.; Shunk, Kendrick; Elicker, Brett [Department of Radiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0628 (United States); Yeh, Benjamin M., E-mail: Benjamin.Yeh@ucsf.edu [Department of Radiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0628 (United States)

    2011-11-15

    Purpose: To examine the clinical significance of persistent renal enhancement after iodixanol administration. Methods: We retrospectively studied 166 consecutive patients who underwent non-enhanced abdominopelvic CT within 7 days after receiving intra-arterial (n = 99) or intravenous (n = 67) iodixanol. Renal attenuation was measured for each non-enhanced CT scan. Persistent renal enhancement was defined as CT attenuation >55 Hounsfield units (HU). Contrast-induced nephropathy (CIN) was defined as a rise in serum creatinine >0.5 mg/dL within 5 days after contrast administration. Results: While the intensity and frequency of persistent renal enhancement was higher after intra-arterial (mean CT attenuation of 73.7 HU, seen in 54 of 99 patients, or 55%) than intravenous contrast material administration (51.8 HU, seen in 21 of 67, or 31%, p < 0.005), a multivariate regression model showed that the independent predictors of persistent renal enhancement were a shorter time interval until the subsequent non-enhanced CT (p < 0.001); higher contrast dose (p < 0.001); higher baseline serum creatinine (p < 0.01); and older age (p < 0.05). The route of contrast administration was not a predictor of persistent renal enhancement in this model. Contrast-induced nephropathy was noted in 9 patients who received intra-arterial (9%) versus 3 who received intravenous iodixanol (4%), and was more common in patients with persistent renal enhancement (p < 0.01). Conclusion: Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients.

  20. Persistent renal enhancement after intra-arterial versus intravenous iodixanol administration

    International Nuclear Information System (INIS)

    Chou, Shinn-Huey; Wang, Zhen J.; Kuo, Jonathan; Cabarrus, Miguel; Fu Yanjun; Aslam, Rizwan; Yee, Judy; Zimmet, Jeffrey M.; Shunk, Kendrick; Elicker, Brett; Yeh, Benjamin M.

    2011-01-01

    Purpose: To examine the clinical significance of persistent renal enhancement after iodixanol administration. Methods: We retrospectively studied 166 consecutive patients who underwent non-enhanced abdominopelvic CT within 7 days after receiving intra-arterial (n = 99) or intravenous (n = 67) iodixanol. Renal attenuation was measured for each non-enhanced CT scan. Persistent renal enhancement was defined as CT attenuation >55 Hounsfield units (HU). Contrast-induced nephropathy (CIN) was defined as a rise in serum creatinine >0.5 mg/dL within 5 days after contrast administration. Results: While the intensity and frequency of persistent renal enhancement was higher after intra-arterial (mean CT attenuation of 73.7 HU, seen in 54 of 99 patients, or 55%) than intravenous contrast material administration (51.8 HU, seen in 21 of 67, or 31%, p < 0.005), a multivariate regression model showed that the independent predictors of persistent renal enhancement were a shorter time interval until the subsequent non-enhanced CT (p < 0.001); higher contrast dose (p < 0.001); higher baseline serum creatinine (p < 0.01); and older age (p < 0.05). The route of contrast administration was not a predictor of persistent renal enhancement in this model. Contrast-induced nephropathy was noted in 9 patients who received intra-arterial (9%) versus 3 who received intravenous iodixanol (4%), and was more common in patients with persistent renal enhancement (p < 0.01). Conclusion: Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients.

  1. Decreased cisplatin uptake by resistant L1210 leukemia cells

    International Nuclear Information System (INIS)

    Hromas, R.A.; North, J.A.; Burns, C.P.

    1987-01-01

    Cisplatin resistance remains poorly understood compared to other forms of anti-neoplastic drug resistance. In this report radiolabelled cisplatin and rapid separation techniques were used to compare drug uptake by L1210 leukemia cells that are sensitive (K25) or resistant (SCR9) to cisplatin. Uptake of cisplatin by both cell lines was linear without saturation kinetics up to 100 μM. The resistant ZCR9 cells had 36-60% reduced drug uptake as compared to its sensitive parent line, K25. In contrast, there was no difference in the rate of efflux. We conclude that a decreased rate of uptake is one possible mechanism of cellular cisplatin resistance. (Author)

  2. Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study

    Directory of Open Access Journals (Sweden)

    Volkan Hancı

    Full Text Available Abstract Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Methods: Rabbits were randomly divided into 4 groups. Group Control (n = 7; no intervention performed. Group Catheter (n = 7; a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n = 7; rabbits were given 4 mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n = 7; rabbits were given 1 µg/kg dexmedetomidine into the central artery of the ear. After 72 h, the ears were amputated and histologically investigated. Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p < 0.05. There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

  3. Risk factors for severe neutropenia following intra-arterial chemotherapy for intra-ocular retinoblastoma.

    Directory of Open Access Journals (Sweden)

    Ira J Dunkel

    Full Text Available PURPOSE: Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (≥ grade 3 neutropenia. METHODS: Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1 blood count results were available in the 7 to 14 days post-treatment interval and (2 concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: 54 cycles (29% were associated with grade 3 (n = 43 or grade 4 (n = 11 neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33-12.73, p = 0.01, but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis. CONCLUSIONS: Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted.

  4. Superselective intra-arterial fibrinolysis for acute cerebral ischemic infarct : usefulness of diffusion weighted MR imaging

    International Nuclear Information System (INIS)

    Byun, Woo Mok; Lee, Se Jin; Kim, Yong Sun; Han, Gun Soo; Bae, Won Kyong

    1999-01-01

    To evaluate the efficacy of superselective intra-arterial fibrinolysis for acute cerebral stroke and the usefulness of pre-and postfibrinolysis diffusion-weighted MRI (DWI). In 41 patients with acute ischemic stroke whose treatment involved intra-arterial fibrinolysis, the occlusion site, degree of recanalization, and clinical results were compared. In 12 patients, diffusion weighted MRI was performed before fibrinolysis, and eight of these also underwent diffusion-weighted MRI after fibrinolysis. Using diffusion-weighted MRI, neurological outcomes were compared with signal intensity ratio (SIR, or the average signal intensity within the region of interest divided by that in the contralateral, nonischemic, homologous region). Twenty patients showed complete recanalization, nine partial recanalization, and in twelve there was no recanalization. Fourteen patients (34%) improved neurologically. No relationship existed between occlusion sites, degree of recanalization, and clinical outcome. Among 12 patients who underwent DWI before fibrinolysis, complete recanalization was noted in eight. Neurological improvement was seen in four patients with low SIR( 1.7), neurological outcome was poor despite complete recanalization. Although superselective intra-arterial fibrinolysis for acute cerebral stroke is a good therapeutic method for recanalization, the clinical outcome can be disappointing. We therefore suggest that in cases of acute cerebral ischemic infaret, SIR-as seen on DWI-might be useful for predicting the benefits of recanalization. In such cases, further investigation of the use of DWI prior to fibrinolysis is therefore needed

  5. Knockdown of OCT4 may sensitize NSCLC cells to cisplatin.

    Science.gov (United States)

    Liu, X; Ma, M; Duan, X; Zhang, H; Yang, M

    2017-05-01

    Cisplatin is commonly used in non-small-cell lung cancer (NSCLC) chemotherapy; however, chemoresistance to cisplatin remains a great clinical challenge. Octamer-binding protein 4 (OCT4) has been reported to be overexpressed in NSCLC. In this study, we aimed to investigate the potential role of OCT4 in NSCLC with chemoresistance to cisplatin. Expressions of OCT4 was detected in NSCLC tissues and cell lines. We utilized siRNA to knock down OCT4 expression in human NSCLC cells and analyzed their phenotypic changes. We found that the difference of OCT4 expression between NSCLC and the adjacent non-tumourous tissues was statistically significant. Knockdown of OCT4 in NSCLC cells could decrease cell proliferation, and potentiate apoptosis induced by cisplatin, suggesting OCT4 may contribute to cisplatin resistance in NSCLC. Our findings indicate that targeting OCT4 could improve cisplatin effect in NSCLC, confirming their role in modulating cisplatin sensitivity.

  6. Mechanisms of Cisplatin-Induced Apoptosis and of Cisplatin Sensitivity: Potential of BIN1 to Act as a Potent Predictor of Cisplatin Sensitivity in Gastric Cancer Treatment

    OpenAIRE

    Tanida, Satoshi; Mizoshita, Tsutomu; Ozeki, Keiji; Tsukamoto, Hironobu; Kamiya, Takeshi; Kataoka, Hiromi; Sakamuro, Daitoku; Joh, Takashi

    2012-01-01

    Cisplatin is the most important and efficacious chemotherapeutic agent for the treatment of advanced gastric cancer. Cisplatin forms inter- and intrastrand crosslinked DNA adducts and its cytotoxicity is mediated by propagation of DNA damage recognition signals to downstream pathways involving ATR, p53, p73, and mitogen-activated protein kinases, ultimately resulting in apoptosis. Cisplatin resistance arises through a multifactorial mechanism involving reduced drug uptake, increased drug inac...

  7. Intraarterial CT Angiography Using Ultra Low Volume of Iodine Contrast – Own Experiences

    International Nuclear Information System (INIS)

    Garcarek, Jerzy; Kurcz, Jacek; Guziński, Maciej; Banasik, Mirosław; Miś, Marcin; Gołębiowski, Tomasz

    2015-01-01

    High volume of intravenous contrast in CT-angiography may result in contrast-induced nephropathy. Intraarterial ultra-low volume of contrast medium results in its satisfactory blood concentration with potentially good image quality. The first main purpose was to assess the influence of the method on function of transplanted kidney in patients with impaired graft function. The second main purpose of the study was to evaluate the usefulness of this method for detection of gastrointestinal and head-and-neck haemorrhages. Between 2010 and 2013 intraarterial CT-angiography was performed in 56 patients, including 28 with chronic kidney disease (CKD). There were three main subgroups: 18 patients after kidney transplantation, 10 patients with gastrointestinal hemorrhage, 8 patients with head-and-neck hemorrhage. Contralateral or ipsilateral inguinal arterial approach was performed. The 4-French vascular sheaths and 4F-catheters were introduced under fluoroscopy. Intraarterial CT was performed using 64-slice scanner. The scanning protocol was as follows: slice thickness 0.625 mm, pitch 1.3, gantry rotation 0.6 sec., scanning delay 1–2 sec. The extent of the study was established on the basis of scout image. In patients with CKD 6–8 mL of Iodixanol (320 mg/mL) diluted with saline to 18–24 mL was administered at a speed of 4–5 mL/s. Vasculature was properly visualized in all patients. In patients with impaired renal function creatinine/eGFR levels remained stable in all but one case. Traditional arteriography failed and CT-angiography demonstrated the site of bleeding in 3 of 10 patients with symptoms of gastrointestinal bleeding (30%). In 8 patients with head-and-neck bleeding CT-angiography did not prove beneficial when compared to traditional arteriography. 1. Ultra-low contrast intraarterial CT-angiography does not deteriorate the function of transplanted kidneys in patients with impaired graft function. 2. 3D reconstructions allow for excellent visualization of

  8. Brown algae phlorotannins enhance the tumoricidal effect of cisplatin and ameliorate cisplatin nephrotoxicity.

    Science.gov (United States)

    Yang, Yeong-In; Ahn, Ji-Hye; Choi, Youn Seok; Choi, Jung-Hye

    2015-02-01

    The clinical application of cisplatin is limited due to its drug resistance and side effects. We investigated the effect of a phlorotannin-rich extract from the edible brown alga Ecklonia cava (PREC) and its major phlorotannin (dieckol) on cisplatin responsiveness and side effects. The A2780 and SKOV3 ovarian cancer cell lines and the SKOV3-bearing mouse model were used. The MTT assay was applied to assess cell viability, and the annexin V assay was employed for apoptosis analysis. Reactive oxygen species (ROS) production and protein expression were assessed by H2DCFDA staining and Western blotting, respectively. We found that PREC enhanced the tumor growth-inhibitory effect of cisplatin and diminished cisplatin-induced nephrotoxicity and weight loss in SKOV3-bearing mice. PREC augmented cisplatin-induced apoptosis by activating caspases in SKOV3 and A2780 ovarian cancer cells. In addition, a combination of PREC and cisplatin-induced ovarian cancer cell apoptosis by downregulating the Akt and NFκB pathways. We further demonstrated that PREC increased intracellular ROS and that antioxidants significantly attenuated Akt-NFκB activation and apoptosis in ovarian cancer cells. In contrast, PREC inhibited cisplatin-induced ROS production and cell death in normal HEK293 kidney cells. Dieckol, a major compound in PREC, significantly enhanced the inhibition of tumor growth by cisplatin with less weight loss and kidney damage in a mouse model. These data suggest that brown algae phlorotannins may improve the efficacy of platinum drugs for ovarian cancer by enhancing cancer cell apoptosis via the ROS/Akt/NFκB pathway and reduce nephrotoxicity by protecting against normal kidney cell damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Tomato pomace powder ameliorated cisplatin-induced ...

    African Journals Online (AJOL)

    Tomato (Lycopersicon esculentum) pomace powder (TPP) may be a preventive agent by virtue of its known antioxidant property. The possible protective role of TPP against cisplatin-induced alteration of the microanatomy of rat brain was investigated. Thirty rats were divided equally into five groups: control, propylene glycol ...

  10. Cytotoxicity of Nanoliposomal Cisplatin Coated with Synthesized ...

    African Journals Online (AJOL)

    Purpose: To evaluate the cytotoxicity of pegylated nanoliposomal cisplatin on human ovarian cancer cell line A2780CP. Methods: Synthesized methoxypolyethylene glycol (mPEG) propionaldehyde was characterized by 1Hnuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectroscopy (FTIR) and used ...

  11. Accuracy of a new wrist cuff oscillometric blood pressure device: comparisons with intraarterial and mercury manometer measurements.

    Science.gov (United States)

    Watson, S; Wenzel, R R; di Matteo, C; Meier, B; Lüscher, T F

    1998-12-01

    Accurate measurement of arterial blood pressure is of great importance for the diagnosis and treatment of hypertension. Because of the chronic nature of antihypertensive drug therapy, the involvement of the patient in blood pressure control is desirable. Such an involvement, however, is only feasible if simple, user-friendly, and precise blood pressure measurement devices are available. In this study we tested a new wrist cuff oscillometric blood pressure measurement device in 100 consecutive patients undergoing cardiac catheterization. Blood pressures were simultaneously taken intraarterially (axillary artery) and with a mercury manometer and stethoscope or noninvasive measurement device (OMRON R3). Intraarterial measurements were directly compared with two measurements taken in random order with either an arm cuff mercury manometer or the wrist cuff device. Systolic and diastolic blood pressure as assessed with the mercury manometer was higher, especially when compared with the intraarterial and the wrist cuff values, which were comparable. Correlations of blood pressure values with intraarterial measurement were 0.86 systolic and 0.75 diastolic (P manometer measurements. Reproducibility of both measurements was good for the wrist cuff device ([systolic/diastolic]: r = 0.94/0.92; P manometer (r = 0.97/0.88; P manometer were higher than intraarterial values and those of the wrist cuff. Both noninvasive devices overestimated high diastolic values.

  12. Molecular approaches to potentiate cisplatin responsiveness in carcinoma therapeutics.

    Science.gov (United States)

    Jain, Aayushi; Jahagirdar, Devashree; Nilendu, Pritish; Sharma, Nilesh Kumar

    2017-09-01

    Cisplatin has been considered as the crucial regimen of widely prescribed chemotherapy treatment for cancer. The advancing treatment of cancers has reached the border line, where tumors show resistance to cisplatin and may thwart its use. Other than issues of drug resistance, cisplatin has been reported to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there is a compelling need to untangle the problems associated with cisplatin treatment in carcinoma. Areas covered: In this review, we summarize the current status of combinatorial options to bring about better pre-clinical and clinical cisplatin drug responses in carcinoma. We begin with problems associated with cisplatin drugs and current avenues such as depicting molecular modulation of enhanced influx and reduced efflux. We also discuss the scope of the DNA damage response landscape and contribution of regulatory small RNAs towards potentiation of cisplatin responses. Expert commentary: The extensive use of cisplatin and incessant high drug dose have prompted the scientific community to limit the burden of cisplatin without compromising therapeutic success. Currently, there are reports on the potential use of other non-toxic small molecule inhibitors, interference RNAs and peptide mimetics to get rid of cellular adversities responsible for cisplatin resistance and high dose effects.

  13. LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells.

    Science.gov (United States)

    Gao, Yuxiu; Shan, Ning; Zhao, Cheng; Wang, Yunhai; Xu, Fuliang; Li, Jiacun; Yu, Xiaoqian; Gao, Lifeng; Yi, Zhengjun

    2015-01-01

    Ovarian cancer is among the most lethal of all malignancies in women. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. Because transforming growth factor-beta (TGF-β) could increase survival of ovarian cancer cells in the presence of cisplatin, we conducted a preclinical study of the antitumor effects of the TGF-β type I (TβRI) and type II (TβRII) kinase inhibitor LY2109761 in combination with cisplatin. SKOV3, OV-90 and SKOV3(DDP) cells were treated with LY2109761, and/or cisplatin, and cell viability, apoptosis mRNA and protein expression levels were then evaluated. Furthermore, the efficacy of LY2109761 combined with cisplatin was further examined in established xenograft models. LY2109761 was sufficient to induce spontaneous apoptosis of ovarian cancer cells. Combination with LY2109761 significantly augmented the cytotoxicity of cisplatin in both parental and cisplatin resistant ovarian cancer cells. LY2109761 significantly increased apoptotic cell death in cisplatin-resistant cells. Combination treatment of LY2109761 and cisplatin showed antiproliferative effects and induced a greater rate of apoptosis than the sum of the single-treatment rates and promoted tumor regression in established parental and cisplatin resistant ovarian cancer xenograft models. Chemotherapeutic approaches using LY2109761 might enhance the treatment benefit of the cisplatin in the treatment of ovarian cancer patients.

  14. Protective Effect of Tempol against Cisplatin-Induced Ototoxicity.

    Science.gov (United States)

    Youn, Cha Kyung; Kim, Jun; Jo, Eu-Ri; Oh, Jeonghyun; Do, Nam Yong; Cho, Sung Il

    2016-11-18

    One of the major adverse effects of cisplatin chemotherapy is hearing loss. Cisplatin-induced ototoxicity hampers treatment because it often necessitates dose reduction, which decreases cisplatin efficacy. This study was performed to investigate the effect of Tempol on cisplatin-induced ototoxicity in an auditory cell line, House Ear Institute-Organ of Corti 1 (HEI-OC1). Cultured HEI-OC1 cells were exposed to 30 μM cisplatin for 24 h with or without a 2 h pre-treatment with Tempol. Cell viability was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and apoptotic cells were identified using terminal deoxynucleotidyl transferase dUTP nick end labeling of nuclei (TUNEL) assay and flow cytometry. The effects of Tempol on cisplatin-induced cleaved poly(ADP-ribose) polymerase, cleaved caspase, and mitochondrial inducible nitric oxide synthase expression were evaluated using western blot analysis. Levels of intracellular reactive oxygen species (ROS) were measured to assess the effects of Tempol on cisplatin-induced ROS accumulation. Mitochondria were evaluated by confocal microscopy, and the mitochondrial membrane potential was measured to investigate whether Tempol protected against cisplatin-induced mitochondrial dysfunction. Cisplatin treatment decreased cell viability, and increased apoptotic features and markers, ROS accumulation, and mitochondrial dysfunction. Tempol pre-treatment before cisplatin exposure significantly inhibited all these cisplatin-induced effects. These results demonstrate that Tempol inhibits cisplatin-induced cytotoxicity in HEI-OC1, and could play a preventive role against cisplatin-induced ototoxicity.

  15. Protective Effect of Tempol against Cisplatin-Induced Ototoxicity

    Directory of Open Access Journals (Sweden)

    Cha Kyung Youn

    2016-11-01

    Full Text Available One of the major adverse effects of cisplatin chemotherapy is hearing loss. Cisplatin-induced ototoxicity hampers treatment because it often necessitates dose reduction, which decreases cisplatin efficacy. This study was performed to investigate the effect of Tempol on cisplatin-induced ototoxicity in an auditory cell line, House Ear Institute-Organ of Corti 1 (HEI-OC1. Cultured HEI-OC1 cells were exposed to 30 μM cisplatin for 24 h with or without a 2 h pre-treatment with Tempol. Cell viability was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay and apoptotic cells were identified using terminal deoxynucleotidyl transferase dUTP nick end labeling of nuclei (TUNEL assay and flow cytometry. The effects of Tempol on cisplatin-induced cleaved poly(ADP-ribose polymerase, cleaved caspase, and mitochondrial inducible nitric oxide synthase expression were evaluated using western blot analysis. Levels of intracellular reactive oxygen species (ROS were measured to assess the effects of Tempol on cisplatin-induced ROS accumulation. Mitochondria were evaluated by confocal microscopy, and the mitochondrial membrane potential was measured to investigate whether Tempol protected against cisplatin-induced mitochondrial dysfunction. Cisplatin treatment decreased cell viability, and increased apoptotic features and markers, ROS accumulation, and mitochondrial dysfunction. Tempol pre-treatment before cisplatin exposure significantly inhibited all these cisplatin-induced effects. These results demonstrate that Tempol inhibits cisplatin-induced cytotoxicity in HEI-OC1, and could play a preventive role against cisplatin-induced ototoxicity.

  16. Effects of systemic and local phenylephrine and arginine vasopressin infusions in conscious postnatal sheep.

    Science.gov (United States)

    Velaphi, Sithembiso C; Roy, Timothy; Despain, Kevin; Rosenfeld, Charles R

    2005-07-01

    Mean arterial pressure (MAP) increases after birth, however, the mechanisms remain unclear. Systemic angiotensin II (ANG II) infusions increase MAP in newborn sheep, but the direct effects of ANG II on peripheral vascular resistance (PVR) are minimal. Thus, its systemic pressor effects may reflect release of other pressor agents, e.g. alpha-agonists and/or AVP, suggesting they contribute to postnatal regulation of MAP and PVR. To address this, we performed studies in conscious sheep at 7-14, 15-21, and 22-35 d postnatal, infusing phenylephrine (PE) or AVP systemically or intra-arterially into the hindlimb while measuring MAP, heart rate (HR), and femoral blood flow (FmBF). Basal MAP and FmBF rose, whereas HR and femoral vascular resistance (FmVR) fell (p sheep. Moreover, FmVR increases more than MAP at all doses, suggesting these agonists may contribute to postnatal MAP regulation and could mediate the effects of systemic ANG II on postnatal MAP.

  17. Determination of free cisplatin in medium by differential pulse polarography after ultrasound and cisplatin treatment of a cancer cell culture

    International Nuclear Information System (INIS)

    Bernard, Vladan; Skorpikova, Jirina; Mornstein, Vojtech; Fojt, Lukas

    2011-01-01

    The in vitro study was carried out for detection of the cisplatin in free form and in culture medium, depending on various conditions of sonodynamic human ovarian cancer cells A2780 treatment by differential pulse polarography (DPP). For sonodynamic treatment, we used cisplatin alone and combined cisplatin/ultrasound treatments. The ultrasound exposure intensity of 1.0 and 2.0 Wcm 2 in far field for incubation periods 1, 24 and 48 h was used. The parameters of DPP measurements were - 1 s drop time, 5 mV.s -1 voltage scan rate, 50 mV modulation amplitude and negative scanning direction; platinum wire served as counter electrode and Ag|AgCl|3 M KCI as reference electrode. The results showed the dependence of free platinum quantities in culture medium on incubation time and treatment protocol. We found difference in concentration of free cisplatin between conventional application of cisplatin and sonodynamic treatment. The sonodynamic combined treatment of cisplatin and ultrasound field showed a higher cisplatin content in the culture medium than cisplatin treatment alone; a difference of 20% was observed for incubation time 48 h. The results also showed the influence of a time sequence of ultrasound and cytostatics in the sonodynamic treatment. The highest amount of free cisplatin in the solution was found for primary application of cisplatin and the subsequent ultrasound exposure. The quantity of free cisplatin increased with time, namely for time intervals 1-24 h. There was no difference between the DPP signal of cisplatin in reaction mixture containing cells in small quantities and micro-filtered mixture without cells. Thus, the DPP method is suitable for the detection and quantification of free cisplatin in the culture medium of cell suspension. Ultrasound field can be important factor during cytostatic therapy. (author)

  18. Infusion of radionuclides throughout pregnancy

    International Nuclear Information System (INIS)

    Mountford-Lister, P.G.; Lambert, B.E.; Milner, A.C.; Kang, X.Z.

    1992-01-01

    This work is part of a long-term study to examine the cancer incidence in the offspring of mice exposed to 239 Pu or 147 Pm throughout pregnancy. The need to model the human intake scenario and the possibility of a critical period during uterine development necessitates constant availability of radionuclides throughout pregnancy. Various methods (multiple daily injections, infusion by external cannula and infusion by indwelling osmotic pump) have been examined and osmotic infusion pumps chosen. These pumps result in a near-constant blood concentration for up to 21 days. Part of the study is the estimation of dose to the critical haemopoietic tissues of the pup from a knowledge of the radionuclide distribution and kinetics. At present the distribution has been followed from birth to 180 days. Activity in the suckling pups at 7 days old is around 1 percent of the infused activity, though most of this is accounted for by the contents of the stomach and gastrointestinal tract. The liver and femur account for around 0.025 percent and 0.012 percent respectively per pup. Activity increases in both liver and femur during lactation after which both concentration and activity fall with time. Long-term studies with the pups of dams exposed to a range of 239 Pu concentrations between 0-70 kBq/kg are underway. Correlation of average organ dose with tumour incidence will be determined at completion of the life-span study. (Author) 39 refs., 5 tabs., 6 figs

  19. Combined intravenous and intra-arterial thrombolytic therapy for acute ischemic stroke: a comparative study with simple intra-arterial thrombolytic therapy

    International Nuclear Information System (INIS)

    Xu Haowen; Li Minghua; Guan Sheng; Song Bo; Wang Jianbo; Gu Binxian

    2011-01-01

    Objective: to evaluate the feasibility, efficacy, safety and risk of combined intravenous and local intra-arterial thrombolytic therapy (IV + IA) for ischemic stroke and to compare the results with those obtained by simple intra-arterial thrombolytic therapy (IA). Methods: A total of 46 consecutive patients with ischemic strokes, who were suitable candidates for thrombolytic therapy, were randomly divided into (IV + IA) group (n=24) and IA group (n=22). After the treatment, the arterial recanalization rates, the early clinical improvement, the occurrence of symptomatic intracerebral hemorrhage, the favourable outcome rate and the mortality were evaluated, and the results were compared between the two groups. Results: The average interval between the onset of symptoms and the start of thrombolytic therapy in (IV + IA) group was 255 minutes, which was remarkably lower than that in IA group (310 minutes) with P=0.012. After the thrombolytic therapy, the arterial recanalization rate for (IV + IA) group and IA group was 54.1% and 40.9% respectively (P=0.226). The occurrence of symptomatic intracerebral hemorrhage for (IV + IA) group and IA group was 16.7% and 22.7% respectively (P=0.361). There months after the treatment the favourable outcome rate (modified Rankin Scale, 0 to 2) of (IV + IA) group was 54.2%, which was higher than that of IA group (36.4%), and the mortality in (IV + IA) group and IA group was 8.3% and 9.1% (P=0.927) respectively. No statistically significant difference in recanalization rate and mortality existed between the two groups. Conclusion: This pilot indicates that both (IV + IA) thrombolytic therapy and simple IA thrombolytic therapy are clinically feasible and safe in treating acute ischemic stroke. Compared to simple IA thrombolytic therapy, (IV + IA) thrombolytic therapy is more effective with rather minimal risks. The conclusion of this study needs to be further proved by double-blind and controlled studies with large sample. (authors)

  20. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion

    International Nuclear Information System (INIS)

    Yanagie, Hironobu; Kumada, Hiroaki; Nakamura, Takemi; Higashi, Syushi; Ikushima, Ichiro; Morishita, Yasuyuki; Shinohara, Atsuko; Fijihara, Mitsuteru; Suzuki, Minoru; Sakurai, Yoshinori; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Nishimura, Ryohei; Ono, Koji; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Takahashi, Hiroyuki

    2011-01-01

    Introduction: Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10 B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of 10 B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared 10 BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), 10 BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. Materials and methods: WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. Results and discussions: The 10 B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that 10 B entrapped WOW emulsion could be

  1. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Yanagie, Hironobu, E-mail: yanagie@n.t.u-tokyo.ac.jp [Dept of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)] [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kumada, Hiroaki [Proton Medical Research Center, University of Tsukuba, Ibaraki (Japan); Nakamura, Takemi [Japan Atomic Energy Research Institute, Ibaraki (Japan); Higashi, Syushi [Dept of Surgery, Ebihara Memorial Hospital, Miyazaki (Japan)] [Kyushu Industrial Sources Foundation, Miyazaki (Japan); Ikushima, Ichiro [Dept of Radiology, Miyakonojyo Metropolitan Hospital, Miyazaki (Japan); Morishita, Yasuyuki [Dept of Human and Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo (Japan); Shinohara, Atsuko [Dept of Humanities, Graduate School of Seisen University, Tokyo (Japan); Fijihara, Mitsuteru [SPG Techno Ltd. Co., Miyazaki (Japan); Suzuki, Minoru; Sakurai, Yoshinori [Research Reactor Institute, Kyoto University, Osaka (Japan); Sugiyama, Hirotaka [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kajiyama, Tetsuya [Kyushu Industrial Sources Foundation, Miyazaki (Japan); Nishimura, Ryohei [Dept of Veternary Surgery, University of Tokyo Veternary Hospital, Tokyo (Japan); Ono, Koji [Research Reactor Institute, Kyoto University, Osaka (Japan); Nakajima, Jun; Ono, Minoru [Dept of Cardiothracic Surgery, University of Tokyo Hospital, Tokyo (Japan); Eriguchi, Masazumi [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)] [Department of Surgery, Shin-Yamanote Hospital, Saitama (Japan); Takahashi, Hiroyuki [Dept of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)] [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)

    2011-12-15

    Introduction: Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between {sup 10}B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of {sup 10}B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared {sup 10}BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), {sup 10}BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. Materials and methods: WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. Results and discussions: The {sup 10}B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that {sup 10}B

  2. Treatment of recurrent glioblastoma with intra-arterial BCNU [1, 3-bis (2-chloroethyl-1-nitrosourea] Tratamento do glioblastoma recorrente com BCNU [1, 3-bis (2-chloroethyl-1-nitrosourea] intra arterial

    Directory of Open Access Journals (Sweden)

    Eberval Gadelha Figueiredo

    2010-10-01

    Full Text Available Contemporary therapies for patients with glioblastomas remain marginally efficient, and recurrence following surgery, radiation therapy and adjuvant chemotherapy is practically universal. The major obstacles to the successful use of chemotherapy for CNS tumors are the drug delivery to the tumor site and the infusion of chemotherapeutic agents directly into the arterial supply of a tumor. The latter could provide a pharmacokinetic advantage by enhancing drug delivery to the tumor. Sixteen patients with recurrent unilateral glioblastomas treated with intra-arterial BCNU were evaluated retrospectively. During the infusion, eleven patients referred pain in the ipsilateral eye, five patients were nauseated, three reported headache, one patient presented mental confusion, while two presented focal signs. There were two deaths during the course of therapy. Four patients achieved temporary clinical improvement, seven showed disease stability, and three presented clinical deterioration. The median total survival time was 87.9 weeks. Unilateral vision loss and focal signs were observed as delayed complications of this treatment. This study has confirmed previous reports indicating that arterial chemotherapy is clearly not curative, and presents serious toxicity. Only through a randomized prospective study performed in a large series of patients can the questions concerning survival period increment be answered properlyOs tratamentos atuais para pacientes com glioblastoma permanecem pouco eficientes e a recorrência, acompanhando cirurgia, radioterapia e quimioterapia, é a regra geral. O maior obstáculo para o sucesso da quimioterapia para os tumores do SNC é a disponibilização da droga no sitio do tumor sendo que a infusão do agente quimioterápico diretamente na trama arterial da lesão pode proporcionar vantagens por maior liberação da substância diretamente no tumor. Estudamos retrospectivamente dezesseis pacientes com glioblastomas

  3. Intraarterial contrast-enhanced MR aortography with and without parallel acquisition technique in patients with peripheral arterial occlusive disease.

    Science.gov (United States)

    Potthast, Silke; Bongartz, Georg M; Huegli, Rolf; Schulte, Anja-Carina; Schwarz, Jochen G; Aschwanden, Markus; Bilecen, Deniz

    2007-03-01

    Repeated intraarterial gadolinium injections are necessary in endovascular MRI-guided interventions; therefore a low-dose protocol with a short acquisition time is preferable. The purpose of this study was to conduct a quantitative comparison of intraarterial MR aortograms obtained with and without high-speed parallel acquisition technique. Intraarterial MR aortography was performed at 1.5 T on nine patients with peripheral arterial occlusive disease and in an aortic phantom with pulsatile flow. A 3D fast low-angle shot MRI sequence was used for standard technique (acquisition time, 20 seconds) and for parallel acquisition technique (acquisition time, 14 seconds). In all patients, a pigtail catheter was left in the suprarenal position after digital subtraction angiography. Contrast-enhanced intraarterial MR aortography was performed after automated injection of 50 mmol/L gadoterate dimeglumine at an injection rate of 4 mL/s. Contrast-to-noise ratio (CNR) and image quality were evaluated in both imaging series at different locations. In an aortic phantom with pulsatile flow, CNR was determined 1, 30, and 60 cm distal to the catheter tip with standard and parallel acquisition techniques. In all patients, intraarterial MR aortography was feasible with both acquisition techniques. No significant difference in CNR or image quality was observed in the patient study. Similar results were calculated for the pulsatile aortic flow phantom at all locations. Intraarterial MR aortography is feasible with parallel acquisition technique without a significant loss of CNR. This technique reduces contrast agent consumption approximately 30% owing to an approximately 30% reduction in acquisition time.

  4. Human bone marrow mesenchymal stem/stromal cells produce efficient localization in the brain and enhanced angiogenesis after intra-arterial delivery in rats with cerebral ischemia, but this is not translated to behavioral recovery.

    Science.gov (United States)

    Mitkari, Bhimashankar; Nitzsche, Franziska; Kerkelä, Erja; Kuptsova, Kristina; Huttunen, Joanna; Nystedt, Johanna; Korhonen, Matti; Jolkkonen, Jukka

    2014-02-01

    Intravascular cell therapy is a promising approach for the treatment of stroke. However, high accumulation of cells to lungs and other filtering organs is a major concern after intravenous (i.v.) cell transplantation. This can be circumvented by intra-arterial (i.a.) cell infusion, which improves homing of cells to the injured brain. We studied the effect of i.a. delivery of human bone marrow-derived mesenchymal cells (BMMSCs) on behavioral and histological outcome in rats after middle cerebral artery occlusion (MCAO). Sixty male Wistar rats were subjected to transient MCAO (60 min) or sham-operation. BMMSCs (1×10(6)) were infused into the external carotid artery on postoperative day 2 or 7. Histology performed after a 42-day follow-up did not detect any human cells (MAB1281) in the ischemic brain. Endothelial cell staining with RECA-1 revealed a significant increase in the number of blood vessels in the perilesional cortex in MCAO rats treated with cells on postoperative day 7. Behavioral recovery as assessed in three tests, sticky label, cylinder and Montoya's staircase, was not improved by human BMMSCs during the follow-up. In conclusion, human BMMSCs did not improve functional recovery in MCAO rats despite effective initial homing to the ischemic hemisphere and enhanced angiogenesis, when strict behavioral tests not affected by repeated testing and compensation were utilized. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Intraarterial Microdosing, a Novel Drug Development Approach, Proof-of-Concept PET Study in Rats

    Science.gov (United States)

    Burt, Tal; Rouse, Douglas C.; Lee, Kihak; Wu, Huali; Layton, Anita T.; Hawk, Thomas C.; Weitzel, Douglas H.; Chin, Bennett B.; Cohen-Wolkowiez, Michael; Chow, Shein-Chung; Noveck, Robert J.

    2016-01-01

    Intraarterial microdosing (IAM) is a novel drug development approach combining intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM leads to target exposure similar to that of systemic full-dose administration but with minimal systemic exposure. IAM could enable the safe, inexpensive, and early study of novel drugs at the first-in-human stage and the study of established drugs in vulnerable populations. Methods Insulin was administered intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats just before blood sampling or 60-min 18F-FDG uptake PET imaging of ipsilateral and contralateral leg muscles (lateral gastrocnemius) and systemic muscles (spinotrapezius). The 18F-FDG uptake slope analysis was used to compare the interventions. Plasma levels of insulin and glucose were compared using area under the curve calculated by the linear trapezoidal method. A physiologically based computational pharmacokinetics/pharmacodynamics model was constructed to simulate the relationship between the administered dose and response over time. Results 18F-FDG slope analysis found no difference between IAM and systemic full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], −0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly greater than systemic microdose (0.0018; 95% CI, −0.045 to −0.007; P = 0.0147) and sham intervention (−0.0015; 95% CI, 0.023–0.058; P = 0.0052). The pharmacokinetics/pharmacodynamics data were used to identify model parameters that describe membrane insulin binding and glucose–insulin dynamics. Conclusion Target exposure after IAM was similar to systemic full dose administration but with minimal systemic effects. The computational pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body response. Findings should be validated in larger, controlled studies in animals and humans using a range of targets and classes of drugs. PMID

  6. Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity

    OpenAIRE

    Xu Cao; Xiaowei Nie; Siping Xiong; Lei Cao; Zhiyuan Wu; Philip K. Moore; Jin-Song Bian

    2018-01-01

    Cisplatin is a major chemotherapeutic drug for solid tumors whereas it may lead to severe nephrotoxicity. Despite decades of efforts, effective therapies remain largely lacking for this disease. In the current research, we investigated the therapeutic effect of hydrogen polysulfide, a novel hydrogen sulfide (H2S) derived signaling molecule, in cisplatin nephrotoxicity and the mechanisms involved. Our results showed that polysulfide donor Na2S4 ameliorated cisplatin-caused renal toxicity in vi...

  7. Effects of cisplatin on potassium currents in CT26 cells.

    Science.gov (United States)

    Sharma, Naveen; Bhattarai, Janardhan Prasad; Kim, Sun Young; Hwang, Pyoung Han; Kim, Min Sun; Han, Seong Kyu

    2016-01-01

    Cisplatin, a platinum-based drug, is an important weapon against many types of cancer. It is well-known that cisplatin induces apoptosis. Potassium channel plays very important role in several signaling pathways. To investigate the possibility that potassium channels also have a role in the cellular response to cisplatin, we examined the effect of cisplatin on the activity of potassium channels on CT26 cell, the colon carcinoma cell line. The cells were cultured in DMEM, supplemented with 10experiment with more than two groups. Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA) chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192cisplatin (0.5 mM). Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells. Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA) chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192cisplatin (0.5 mM). Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells.

  8. CT findings in ischaemic hepatic failure due to intra-arterial embolisation: A case report

    International Nuclear Information System (INIS)

    Catalano, O.

    1997-01-01

    Liver infarction is relatively uncommon. It may be secondary to several conditions such as sepsis, shock, sickle-cell anaemia, eclampsia, vasculitis, metastatic disease, bacterial endocarditis, rheumatic heart disease, trauma, portal venous occlusion or compression, oral contraception, anaesthesia, hepatic artery thrombosis, therapeutical or inadvertent hepatic artery ligation, intra-arterial chemotherapy or embolisation. A case of hepatic infraction, unusual for iatrogenic pathogenesis, submassive extension with acute hepatic failure, and CT findings of an internally branching pattern due to intravascular gas was observed. (orig./AJ)

  9. Reperfusion demonstrated by apparent diffusion coefficient mapping after local intra-arterial thrombolysis for ischaemic stroke

    International Nuclear Information System (INIS)

    Taleb, M.; Loevblad, K.O.; El-Koussy, M.; Guzman, R.; Oswald, H.; Remonda, L.; Schroth, G.; Bassetti, C.; Arnold, M.

    2001-01-01

    Diffusion-weighted MRI (DWI) is becoming important for diagnosis and investigation of acute cerebral ischaemia. It has been reported that apparent diffusion coefficient (ADC) maps could be an indicator of reperfusion. Our aim was to use echo-planar technology to investigate this phenomenon. We report 19 patients treated by local intra-arterial thrombolysis for middle cerebral artery stroke within 6 h of the onset of symptoms, in whom we performed follow-up DWI. ADC were found to be higher in the patients with angiographically proven reperfusion. (orig.)

  10. Advantages and limitation of intra-arterial digital subtraction angiography (i.a. DSA)

    International Nuclear Information System (INIS)

    Beduhn, D.

    1986-01-01

    Among 3000 digital subtraction angiographies which have been performed in our institute, 850 patients have been examined intraarterially. The advantage of i.a. DSA is due to the excellent demonstration of vessels in survey angiograms by small amounts of contrast medium (10-20 ml in the aorta), without risk of selective catheterisation into the neck vessels, the saving of expensive film series, the short duration of vessel examinations and the small complication rate. i.a. DSA can be carried out on outpatients also, using the 4/5 F-catheter, which saves hospital charges. Impressive examples show the advantages of i.a. DSA. (orig.) [de

  11. Cisplatin cytotoxicity is dependent on mitochondrial respiration in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Santhipriya Inapurapu

    2017-01-01

    Full Text Available Objective(s: To understand the role of mitochondrial respiration in cisplatin sensitivity, we have employed wild-type and mitochondrial DNA depleted Rho0 yeast cells. Materials and Methods: Wild type and Rho0 yeast cultured in fermentable and non-fermentable sugar containing media, were studied for their sensitivity against cisplatin by monitoring growth curves, oxygen consumption, pH changes in cytosol/mitochondrial compartments, reactive oxygen species production and respiratory control ratio. Results: Wild-type yeast grown on glycerol exhibited heightened sensitivity to cisplatin than yeast grown on glucose. Cisplatin (100 μM, although significantly reduced the growth of wild- type cells, only slightly altered the growth rate of Rho0 cells. Cisplatin treatment decreased both pHcyt and pHmit to a similar extent without affecting the pH difference. Cisplatin dose-dependently increased the oxidative stress in wild-type, but not in respiration-deficient Rho0 strain. Cisplatin decreased the respiratory control ratio. Conclusion: These results suggest that cisplatin toxicity is influenced by the respiratory capacity of the cells and the intracellular oxidative burden. Although cisplatin per se slightly decreased the respiration of yeast cells grown in glucose, it did not disturb the mitochondrial chemiosmotic gradient.

  12. RRx-001 protects against cisplatin-induced toxicities.

    Science.gov (United States)

    Oronsky, Bryan; Reid, Tony R; Larson, Christopher; Carter, Corey A; Brzezniak, Christina E; Oronsky, Arnold; Cabrales, Pedro

    2017-09-01

    RRx-001, a minimally toxic tumor-associated macrophage and neutrophil-repolarizing agent, is under investigation in Phase II clinical trials as a sensitizer/resensitizer to cisplatin and carboplatin. On the basis of anecdotal clinical observations of improved platinum tolerability following a priming period with RRx-001 as well as preclinical studies that have previously demonstrated radioprotection of intestinal stem cells and cardioprotection from doxorubicin, the in vivo cytoprotective potential of RRx-001 pretreatment against cisplatin-induced bone marrow suppression and renal toxicity was investigated. BALB/c mice were divided into three groups: (1) no treatment, (2) vehicle and cisplatin only, and (3) RRx-001 and cisplatin. RRx-001 treatment (5 mg/kg every other day for 3 days) was initiated 3 days prior to cisplatin administration. Blood was collected from the femoral vein at different intervals to measure total hemoglobin and leukocyte counts as well as renal functional markers (serum urea, creatinine and creatinine clearance). Metaphase spreads were prepared from whole bone marrow cells as markers of clastogenicity. RRx-001 pretreatment significantly decreased (P cisplatin group compared to the cisplatin-only group was observed. This study is the first to demonstrate that RRx-001 has nephro-, geno- and myeloprotective effects in vivo. Importantly, RRx-001 did not protect sarcoma-180 solid tumor xenografts against cisplatin-induced cytotoxicity. These results potentially support the use of RRx-001 as a chemoprotector against cisplatin-induced toxicities.

  13. Is Glutathione the Major Cellular Target of Cisplatin?

    DEFF Research Database (Denmark)

    Kasherman, Yonit; Stürup, Stefan; gibson, dan

    2009-01-01

    Cisplatin is an anticancer drug whose efficacy is limited because tumors develop resistance to the drug. Resistant cells often have elevated levels of cellular glutathione (GSH), believed to be the major cellular target of cisplatin that inactivates the drug by binding to it irreversibly, forming...... [Pt(SG)2] adducts. We show by [1H,15N] HSQC that the half-life of 15N labeled cisplatin in whole cell extracts is 75 min, but no Pt-GSH adducts were observed. When the low molecular mass fraction (cisplatin, binding to GSH was observed probably due to removal...

  14. An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

    Science.gov (United States)

    Karasawa, Takatoshi; Steyger, Peter S.

    2015-01-01

    Cisplatin is one of the most widely-used drugs to treat cancers. However, its nephrotoxic and ototoxic side-effects remain major clinical limitations. Recent studies have improved our understanding of the molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. While cisplatin binding to DNA is the major cytotoxic mechanism in proliferating (cancer) cells, nephrotoxicity and ototoxicity appear to result from toxic levels of reactive oxygen species and protein dysregulation within various cellular compartments. In this review, we discuss molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. We also discuss potential clinical strategies to prevent nephrotoxicity and ototoxicity and their current limitations. PMID:26101797

  15. A Role for Tubular Necroptosis in Cisplatin-Induced AKI

    Science.gov (United States)

    Xu, Yanfang; Ma, Huabin; Shao, Jing; Wu, Jianfeng; Zhou, Linying; Zhang, Zhirong; Wang, Yuze; Huang, Zhe; Ren, Junming; Liu, Suhuan; Chen, Xiangmei

    2015-01-01

    Cell death and inflammation in the proximal tubules are the hallmarks of cisplatin-induced AKI, but the mechanisms underlying these effects have not been fully elucidated. Here, we investigated whether necroptosis, a type of programmed necrosis, has a role in cisplatin-induced AKI. We found that inhibition of any of the core components of the necroptotic pathway—receptor-interacting protein 1 (RIP1), RIP3, or mixed lineage kinase domain-like protein (MLKL)—by gene knockout or a chemical inhibitor diminished cisplatin-induced proximal tubule damage in mice. Similar results were obtained in cultured proximal tubular cells. Furthermore, necroptosis of cultured cells could be induced by cisplatin or by a combination of cytokines (TNF-α, TNF-related weak inducer of apoptosis, and IFN-γ) that were upregulated in proximal tubules of cisplatin-treated mice. However, cisplatin induced an increase in RIP1 and RIP3 expression in cultured tubular cells in the absence of cytokine release. Correspondingly, overexpression of RIP1 or RIP3 enhanced cisplatin-induced necroptosis in vitro. Notably, inflammatory cytokine upregulation in cisplatin-treated mice was partially diminished in RIP3- or MLKL-deficient mice, suggesting a positive feedback loop involving these genes and inflammatory cytokines that promotes necroptosis progression. Thus, our data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI. PMID:25788533

  16. Oxytocin as a protective agent in cisplatin-induced ototoxicity.

    Science.gov (United States)

    Bekmez Bilmez, Zekiye Eda; Aydin, Sedat; Şanli, Arif; Altintoprak, Niyazi; Demir, Mehmet Gökhan; Atalay Erdoğan, Banu; Kösemihal, Ebru

    2016-04-01

    Cisplatin is a potent chemotherapeutic drug with serious side effects such as ototoxicity which is characterized by irreversible, bilateral, progressive sensorineural hearing loss. Oxytocin, which is a well-known hormone secreting during pregnancy, has antioxidant and antiinflammatory effect. Our study aims to test and compare the effect of intratympanic (IT) and intraperitoneal (IP) oxytocin on cisplatin ototoxicity with DPOAE. A total of 24 Wistar albino rats were randomly divided into four groups: Group 1 received 0.1-0.3 ml IT saline + IP saline solutions for 4 days (n = 6), Group 2 received cumulative dose of 20 mg/kg IP cisplatin divided into two equal doses in first and second days of experiment + 0.1-0.3 ml IT saline for 4 days, Group 3 received same dose of cisplatin as Group 2 + 0.1-0.3 ml IT oxytocin for 4 days, and Group 4 received same dose of cisplatin as Groups 2 and 3 + IP oxytocin with dose of 1 mg/kg. DPOAE was performed prior to procedure and at the end of the experiment on day 5. Group 2 showed severe ototoxic effect of cisplatin according to DPOAE result (p cisplatin ototoxicity. We suggest oxytocin in cisplatin ototoxicity, especially via IT route even with high-dose cisplatin.

  17. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells

    Science.gov (United States)

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-01

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal–regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors. PMID:28085111

  18. Molecular mechanisms of cisplatin resistance in cervical cancer

    Science.gov (United States)

    Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

    2016-01-01

    Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. PMID:27354763

  19. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells.

    Science.gov (United States)

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-12

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na⁺/H⁺ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal-regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors.

  20. Combination of radiotherapy with cisplatin for esophageal cancer

    International Nuclear Information System (INIS)

    Tohnosu, Noriyuki; Onoda, Shoichi; Okuyama, Kazuaki; Yamamoto, Yoshikazu; Kimura, Masayuki; Awano, Tomotaka; Tsukamoto, Soichiro; Isono, Kaichi; Ishikawa, Tatsuo.

    1986-01-01

    Combination of radiotherapy with Cisplatin was performed in order to improve the results obtained with radiotherapy alone in the treatment of esophageal cancer. The therapeutic effect of this regimen and administration of Cisplatin were analyzed in 7 primary and 8 recurrent esophageal cancer patients from April 1983 to February 1985 in N.I.R.S. Cisplatin 10 mg/m 2 , without hydration and diuresis, was given daily followed by radiotherapy of 2 Gy daily for five consecutive days. The course was performed for two consecutive weeks and repeated after a one-week withdrawal of Cisplatin alone. Total doses of Cisplatin were 200 mg and the total dosage of radiotherapy including fast neutrons was TDF 110 to 120. Cisplatin 30 to 50 mg/m 2 was continued monthly for maintenance every four weeks after the second course. Response rates in primary and recurrent cases were 71.4 % and 62.5 % respectively. Administration of Cisplatin 10 mg/m 2 daily was useful since nausea and vomiting rarely appeared and bone marrow toxicity and renal dysfunction as side effects were mild and reversible. In the combination of radiotherapy with Cisplatin, it seemed most effective to perform radiotherapy immediately after Cisplatin administration, considering the change in serum concentration. (author)

  1. Effects of cisplatin on potassium currents in CT26 cells

    Directory of Open Access Journals (Sweden)

    Naveen Sharma

    2016-01-01

    Conclusion: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM. Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells.

  2. Functional and histopathological changes in dog kidneys after administration of cisplatin

    DEFF Research Database (Denmark)

    Daugaard, G; Abildgaard, U; Larsen, S

    1987-01-01

    The nephrotoxic effect of cisplatin (5 mg/kg i.v.) was evaluated in 8 dogs 48-72 h after administration. The lithium clearance method was used for assessing the absolute and fractional reabsorption rates of sodium and water in proximal as well as in more distal segments of the total nephron...... population, before and during saline loading (infusion of 5 ml/kg of isotonic saline i.v.). Histological examinations of the kidney biopsies were used to evaluate the degree of renal tissue injury. During 48-72 h after administration of cisplatin blood urea nitrogen and plasma creatinine increased....../min, respectively) were significantly lower than in 6 control animals (212 +/- 8 ml/min, 49.0 +/- 2.0 ml/min, 0.36 +/- 0.001 and 10.1 +/- 1.3 ml/min, respectively). In contrast, urinary excretion rates of sodium, potassium and water were significantly higher, while fractional as well as absolute proximal and distal...

  3. 21 CFR 880.5725 - Infusion pump.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or a...

  4. Radiosensitizers in cervical cancer. Cisplatin and beyond

    Directory of Open Access Journals (Sweden)

    Cetina Lucely

    2006-05-01

    Full Text Available Abstract Cervical cancer continues to be a significant health burden worldwide. Globally, the majority of cancers are locally advanced at diagnosis; hence, radiation remains the most frequently used therapeutical modality. Currently, the value of adding cisplatin or cisplatin-based chemotherapy to radiation for treatment of locally advanced cervical cancer is strongly supported by randomized studies and meta-analyses. Nevertheless, despite these significant achievements, therapeutic results are far from optimal; thus, novel therapies need to be assayed. A strategy currently being investigated is the use of newer radiosensitizers alone or in combination with platinum compounds. In the present work, we present preclinical information on known and newer cytotoxic agents as radiosensitizers on cervical cancer models, as well as the clinical information emanating from early phase trials that incorporate them to the cervical cancer management. In addition, we present the perspectives on the combined approach of radiation therapy and molecular target-based drugs with proven radiosensitizing capacity.

  5. A comparison inhibitory effects of cisplatin and MNPs-PEG-cisplatin on the adhesion capacity of bone metastatic breast cancer.

    Science.gov (United States)

    Mokhtari, Mohammad Javad; Koohpeima, Fatemeh; Mohammadi, Hadi

    2017-10-01

    To date, high mortality in women due to malignancy breast cancer related to the metastasis to the bone is a significant challenge. As, magnetic nanoparticles (MNPs) conjugated with the biocompatible polymers was employed for the delivery of some hydrophobic anticancer agents, the main aim of the current research was to assess whether cisplatin-loaded MNPs enhanced the anticancer effect of free cisplatin in breast cancer cells. MNPs decorated with PEG were synthesized by an improved coprecipitation technique, and then cisplatin was loaded onto the MNPs via a simple mixing method. Afterward, its morphology, size, chemical structure, magnetic property, hydrodynamic diameter, zeta potential, and crystal structure were characterized by scanning and transmittance electron microscopy, Fourier transforms infrared spectroscopy, vibrating sample magnetometer, dynamic light scattering, and X-ray powder diffraction and flame atomic absorption spectroscopy respectively. Additionally, the effects of cisplatin and MNPs-PEG-cisplatin on viability, migration and adhesion capacity of T47D cells were investigated by evaluating α2-integrin and β1-integrin; mRNAs were assessed by real-time RT-PCR. Consequently, the in vitro assay results showed a considerable dose-dependent inhibitory effect of cisplatin and MNPs-PEG-cisplatin on proliferation, migration, and adhesion of T47D cells. Finally, current research was shown that MNPs-PEG-cisplatin strongly increased anticancer effects compared with free cisplatin in the T47D cell line. © 2017 John Wiley & Sons A/S.

  6. Comparison cisplatin with cisplatin plus 5FU in head and neck cancer patients received postoperative chemoradiotherapy.

    Science.gov (United States)

    Chen, Chien-Chih; Lin, Jin-Ching; Chen, Kuan-Wen

    2017-06-01

    To compare the treatment outcomes and toxicity of both cisplatin and cisplatin plus 5FU chemotherapy in head and neck cancer patients who have received surgery, in addition to postoperative chemoradiotherapy. From May 1991 to December 2012, a total of 113 head and neck cancer patients who received surgery, along with postoperative chemoradiotherapy were analyzed. The primary sites were oral cavity (86), oropharynx (17), hypopharynx (4), and larynx (6). Thirty-nine patients received cisplatin (P), while 74 patients received cisplatin plus 5FU (PF). The endpoints were overall survival (OS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS). The median follow up time was 43months, with a range of 4-222months. The 3-year rates of OS, LFFS, and DMFS were 62.1%, 71.3%, and 82.4%, respectively. The 3-year OS for P and PF were 71.3% and 57.5% (p=0.27). A multivariate analysis revealed that various chemotherapy regimens displayed no statistical difference for OS (Hazard Ratio [HR]=1.81; 95% Confidence Interval [CI]=0.963-3.408; p=0.065), LFFS (HR=0.98; 95% CI=0.458-2.127; p=0.973), and DMFS (HR=1.25; 95% CI=0.463-3.398; p=0.656). Grade 3 and 4 mucositis for P and PF group were 61.5% and 64.9%. A greater than grade 3 dermatitis for P and PF group were 7.7% and 14.9%. Postoperative chemoradiotherapy with cisplatin alone appeared to have higher 3-year OS and lower severe mucositis and dermatitis than cisplatin plus 5FU. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment

    Science.gov (United States)

    Simard, J. Marc; Aldrich, E. Francois; Schreibman, David; James, Robert F.; Polifka, Adam; Beaty, Narlin

    2015-01-01

    Object Aneurysmal subarachnoid hemorrhage (aSAH) predisposes to delayed neurological deficits, including stroke and cognitive and neuropsychological abnormalities. Heparin is a pleiotropic drug that antagonizes many of the pathophysiological mechanisms implicated in secondary brain injury after aSAH. Methods The authors performed a retrospective analysis in 86 consecutive patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who presented within 36 hours and were treated by surgical clipping within 48 hours of their ictus. Forty-three patients were managed postoperatively with a low-dose intravenous heparin infusion (Maryland low-dose intravenous heparin infusion protocol: 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr) beginning 12 hours after surgery and continuing until Day 14 after the ictus. Forty-three control patients received conventional subcutaneous heparin twice daily as deep vein thrombosis prophylaxis. Results Patients in the 2 groups were balanced in terms of baseline characteristics. In the heparin group, activated partial thromboplastin times were normal to mildly elevated; no clinically significant hemorrhages or instances of heparin-induced thrombocytopenia or deep vein thrombosis were encountered. In the control group, the incidence of clinical vasospasm requiring rescue therapy (induced hypertension, selective intraarterial verapamil, and angioplasty) was 20 (47%) of 43 patients, and 9 (21%) of 43 patients experienced a delayed infarct on CT scanning. In the heparin group, the incidence of clinical vasospasm requiring rescue therapy was 9% (4 of 43, p = 0.0002), and no patient suffered a delayed infarct (p = 0.003). Conclusions In patients with Fisher Grade 3 aSAH whose aneurysm is secured, postprocedure use of a low-dose intravenous heparin infusion may be safe and beneficial. PMID:24032706

  8. Cisplatin-induced renal inflammation is ameliorated by cilastatin nephroprotection.

    Science.gov (United States)

    Humanes, Blanca; Camaño, Sonia; Lara, Jose Manuel; Sabbisetti, Venkatta; González-Nicolás, María Ángeles; Bonventre, Joseph V; Tejedor, Alberto; Lázaro, Alberto

    2017-10-01

    Cisplatin is a potent chemotherapeutic drug whose nephrotoxic effect is a major complication and a dose-limiting factor for antitumoral therapy. There is much evidence that inflammation contributes to the pathogenesis of cisplatin-induced nephrotoxicity. We found that cilastatin, a renal dehydropeptidase-I inhibitor, has protective effects in vitro and in vivo against cisplatin-induced renal damage by inhibiting apoptosis and oxidation. Here, we investigated the potential use of cilastatin to protect against cisplatin-induced kidney injury and inflammation in rats. Male Wistar rats were divided into four groups: control, cilastatin-control, cisplatin and cilastatin-cisplatin. Nephrotoxicity was assessed 5 days after administration of cisplatin based on blood urea nitrogen, creatinine, glomerular filtration rate (GFR), kidney injury molecule (KIM)-1 and renal morphology. Inflammation was measured using the electrophoretic mobility shift assay, immunohistochemical studies and evaluation of inflammatory mediators. Compared with the control rats, cisplatin-administered rats were affected by significant proximal tubule damage, decreased GFR, increased production of inflammatory mediators and elevations in urea, creatinine and tissue KIM-1 levels. Cilastatin prevented these changes in renal function and ameliorated histological damage in cisplatin-administered animals. Cilastatin also reduced pro-inflammatory cytokine levels, activation of nuclear factor-κB and CD68-positive cell concentrations. Cilastatin reduces cisplatin-induced nephrotoxicity, which is associated with decreased inflammation in vivo. Although the exact role of decreased inflammation in nephroprotection has not been fully elucidated, treatment with cilastatin could be a novel strategy for the prevention of cisplatin-induced acute kidney injury. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  9. Intra-arterial Ultra-low-Dose CT Angiography of Lower Extremity in Diabetic Patients

    Energy Technology Data Exchange (ETDEWEB)

    Özgen, Ali, E-mail: draliozgen@hotmail.com [Yeditepe University Hospital, Department of Radiology (Turkey); Sanioğlu, Soner [Yeditepe University Hospital, Department of Cardiovascular Surgery (Turkey); Bingöl, Uğur Anıl [Yeditepe University Hospital, Department of Plastic Surgery (Turkey)

    2016-08-15

    PurposeTo image lower extremity arteries by CT angiography using a very low-dose intra-arterial contrast medium in patients with high risk of developing contrast-induced nephropathy (CIN).Materials and MethodsThree cases with long-standing diabetes mellitus and signs of lower extremity atherosclerotic disease were evaluated by CT angiography using 0.1 ml/kg of the body weight of contrast medium given via 10-cm-long 4F introducer by puncturing the CFA. Images were evaluated by an interventional radiologist and a cardiovascular surgeon. Density values of the lower extremity arteries were also calculated. Findings in two cases were compared with digital subtraction angiography images performed for percutaneous revascularization. Blood creatinine levels were followed for possible CIN.ResultsIntra-arterial CT angiography images were considered diagnostic in all patients and optimal in one patient. No patient developed CIN after intra-arterial CT angiography, while one patient developed CIN after percutaneous intervention.ConclusionIntra-arterial CT angiography of lower extremity might be performed in selected patients with high risk of developing CIN. Our limited experience suggests that as low as of 0.1 ml/kg of the body weight of contrast medium may result in adequate diagnostic imaging.

  10. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy

    Science.gov (United States)

    Shields, C L; Fulco, E M; Arias, J D; Alarcon, C; Pellegrini, M; Rishi, P; Kaliki, S; Bianciotto, C G; Shields, J A

    2013-01-01

    In this report, we explore retinoblastoma diagnostic accuracy and review chemotherapy alternatives for retinoblastoma using intravenous, intra-arterial, periocular, and intravitreal routes. A review of 2775 patients referred for management of retinoblastoma, disclosed 78% with confirmed retinoblastoma and 22% with simulating lesions, termed pseudoretinoblastomas. Children ≤2 years old showed leading pseudoretinoblastomas of persistent fetal vasculature, Coats disease, and vitreous haemorrhage, whereas those >5 years showed simulators of Coats, toxocariasis, and familial exudative vitreoretinopathy. The diagnosis of retinoblastoma should be established before planning therapeutic strategy. Chemotherapy strategy depends on tumour laterality and stage of disease. If bilateral retinoblastoma, intravenous chemotherapy (IVC) is important as first-line therapy for control of intraocular disease, prevention of metastasis, and reduction in prevalence of pinealoblastoma and long-term second malignant neoplasms. Bilateral groups D and E retinoblastoma receive additional subtenon's carboplatin boost for improved local control. If unilateral disease is present, then intra-arterial chemotherapy (IAC) is often considered. IAC can be salvage therapy following chemoreduction failure. Unilateral retinoblastoma of groups D and E are managed with enucleation or globe-conserving IVC and/or IAC. Intravitreal chemotherapy is cautiously reserved for recurrent vitreous seeds following other therapies. In conclusion, the strategy for retinoblastoma management with chemotherapy depends on tumour laterality and stage of disease. Bilateral retinoblastoma is most often managed with IVC and unilateral retinoblastoma with IAC, but if advanced stage, combination IVC plus IAC or enucleation. PMID:22995941

  11. The role of thromboxane in experimental inadvertent intra-arterial drug injections.

    Science.gov (United States)

    Zachary, L S; Smith, D J; Heggers, J P; Robson, M C; Boertman, J A; Niu, X T; Schileru, R E; Sacks, R J

    1987-03-01

    Inadvertent intra-arterial injection of drugs produces a well-defined clinical syndrome whose pathophysiology remains unclear. This study was designed to determine the role of the inflammatory mediator, thromboxane, in intra-arterial drug injections. The rabbit ear model, as described by Kinmonth and Sheppard, was used. Five of the experimental groups were treated with specific or nonspecific thromboxane blocking agents and two groups served as controls. Immunohistochemical staining of the control ears showed elevated levels of thromboxane within the first 6 hours postinjury. The specific thromboxane blocking agents, methimazole and Aloe vera, showed almost complete blockade of thromboxane production. The percentage of ear survival was significantly greater in the group treated with topical Aloe vera (p less than 0.05) and even greater survival was achieved in the combined Aloe vera/methimazole group (p less than 0.01). On the basis of these results, we have begun treatment of such injuries with specific and nonspecific thromboxane blocking agents.

  12. Impact of Pretreatment Noncontrast CT Alberta Stroke Program Early CT Score on Clinical Outcome After Intra-Arterial Stroke Therapy

    NARCIS (Netherlands)

    Yoo, Albert J.; Zaidat, Osama O.; Chaudhry, Zeshan A.; Berkhemer, Olvert A.; González, R. Gilberto; Goyal, Mayank; Demchuk, Andrew M.; Menon, Bijoy K.; Mualem, Elan; Ueda, Dawn; Buell, Hope; Sit, Siu Po; Bose, Arani

    2014-01-01

    The efficacy of intra-arterial treatment remains uncertain. Because most centers performing IAT use noncontrast CT (NCCT) imaging, it is critical to understand the impact of NCCT findings on treatment outcomes. This study aimed to compare functional independence and safety among patients undergoing

  13. Value of Computed Tomographic Perfusion-Based Patient Selection for Intra-Arterial Acute Ischemic Stroke Treatment

    NARCIS (Netherlands)

    Borst, Jordi; Berkhemer, Olvert A.; Roos, Yvo B. W. E. M.; van Bavel, Ed; van Zwam, Wim H.; van Oostenbrugge, Robert J.; van Walderveen, Marianne A. A.; Lingsma, Hester F.; van der Lugt, Aad; Dippel, Diederik W. J.; Yoo, Albert J.; Marquering, Henk A.; Majoie, Charles B. L. M.; Fransen, Puck S. S.; Beumer, Debbie; van den Berg, Lucie A.; Schonewille, Wouter J.; Vos, Jan Albert; Nederkoorn, Paul J.; Wermer, Marieke J. H.; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A.; Lycklama à Nijeholt, Geert J.; Boiten, Jelis; Brouwer, Patrick A.; Emmer, Bart J.; de Bruijn, Sebastiaan F.; van Dijk, Lukas C.; Kappelle, L. Jaap; Lo, Rob H.; van Dijk, Ewoud J.; de Vries, Joost; de Kort, Paul L. M.; van den Berg, Jan S. P.; van Hasselt, Boudewijn A. A. M.; Aerden, Leo A. M.; Dallinga, René J.; Visser, Marieke C.; Bot, Joseph C. J.; Vroomen, Patrick C.; Eshghi, Omid; Schreuder, Tobien H. C. M. L.; Heijboer, Roel J. J.; Keizer, Koos; Tielbeek, Alexander V.; den Hertog, Heleen M.; Gerrits, Dick G.; van den Berg-Vos, Renske M.; Karas, Giorgos B.; Steyerberg, Ewout W.; Flach, H. Zwenneke; Sprengers, Marieke E. S.; Jenniskens, Sjoerd F. M.; Beenen, Ludo F. M.; van den Berg, René; Koudstaal, Peter J.; Brown, Martin M.; Liebig, Thomas; Stijnen, Theo; Andersson, Tommy; Mattle, Heinrich; Wahlgren, Nils; van der Heijden, Esther; Ghannouti, Naziha; Fleitour, Nadine; Hooijenga, Imke; Puppels, Corina; Pellikaan, Wilma; Geerling, Annet; Lindl-Velema, Annemieke; van Vemde, Gina; de Ridder, Ans; Greebe, Paut; de Bont-Stikkelbroeck, José; de Meris, Joke; Janssen, Kirsten; Struijk, Willy; Simons, Tiny; Messchendorp, Gert; van der Minne, Friedus; Bongenaar, Hester; Licher, Silvan; Boodt, Nikki; Ros, Adriaan; Venema, Esmee; Slokkers, Ilse; Ganpat, Raymie-Jayce; Mulder, Maxim; Saiedie, Nawid; Heshmatollah, Alis; Schipperen, Stefanie; Vinken, Stefan; van Boxtel, Tiemen; Koets, Jeroen; Boers, Merel; Santos, Emilie; Jansen, Ivo; Kappelhof, Manon; Lucas, Marit; Geuskens, Ralph; Barros, Renan Sales; Dobbe, Roeland; Csizmadia, Marloes

    2015-01-01

    The utility of computed tomographic perfusion (CTP)-based patient selection for intra-arterial treatment of acute ischemic stroke has not been proven in randomized trials and requires further study in a cohort that was not selected based on CTP. Our objective was to study the relationship between

  14. Relationship between cisplatin administration and the development of ototoxicity

    NARCIS (Netherlands)

    Rademaker-Lakhai, Jeany M.; Crul, Mirjam; Zuur, Lot; Baas, Paul; Beijnen, Jos H.; Simis, Yvonne J. W.; van Zandwijk, Nico; Schellens, Jan H. M.

    2006-01-01

    PURPOSE: To determine the auditory toxicity associated with dose- and schedule- intensive cisplatin/gemcitabine chemotherapy in non-small-cell lung carcinoma patients. PATIENTS AND METHODS: Patients were treated with gemcitabine followed by cisplatin according to an interpatient dose-escalation

  15. Therapeutic effects of cisplatin on rat experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Li, Xiao-Bo; Schluesener, Hermann J

    2006-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a prototypic Th1-mediated autoimmune inflammatory disease of the central nervous system (CNS), and serves as a model for the human demyelinating disease, multiple sclerosis. Cisplatin is a drug widely used in the treatment of a variety of human neoplasias, such as advanced bladder carcinoma, adrenal cortex carcinoma, breast cancer, head and neck or lung carcinoma. Cisplatin binds to DNA and interferes with cellular repair and other mechanism, which eventually result into cell death. It is known that cisplatin can induce immunosuppressive effects through inhibition of T cell activity. Therefore we analyzed the anti-inflammatory effects of cisplatin in a rat EAE model. EAE was induced in male LEW rats by immunizing with a synthetic peptide of guinea pig myelin basic protein. The development of EAE and neurological signs were evaluated by a standard protocol. Immunohistochemistry was applied to show immune cell infiltration into the CNS. Early treatment of EAE rats with cisplatin effectively ameliorated the development of disease and provided a significant protective effect compared to control rats. Further, histological analysis demonstrated that the formation of the typical perivascular cuffs and brain infiltration of monocytes and lymphocytes were complete absent in cisplatin treated rats, while abundant T cell infiltration was seen in the CNS of EAE rats. Our data show that cisplatin has protective effects in EAE, indicating that cisplatin could be a candidate in the treatment of human CNS autoimmunity.

  16. Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles

    Science.gov (United States)

    Saha, Sounik; Robertson, David J.; McMeekin, Scott; Bhattacharya, Resham; Mukherjee, Priyabrata

    2014-01-01

    Recently we reported that gold nanoparticles (AuNPs) inhibit ovarian tumor growth and metastasis in mice by reversing epithelial-mesenchymal transition (EMT). Since EMT is known to confer drug resistance to cancer cells, we wanted to investigate whether anti-EMT property of AuNP could be utilized to sensitize ovarian cancer cells to cisplatin. Herein, we report that AuNPs prevent cisplatin-induced acquired chemoresistance and stemness in ovarian cancer cells and sensitize them to cisplatin. AuNPs inhibit cisplatin induced EMT, decrease the side population cells and key stem cell markers such as ALDH1, CD44, CD133, Sox2, MDR1 and ABCG2 in ovarian cancer cells. Mechanistically, AuNPs prevent cisplatin-induced activation of Akt and NF-κB signaling axis in ovarian cancer cells that are critical for EMT, stem cell maintenance and drug resistance. In vivo, AuNPs sensitize orthotopically implanted ovarian tumor to a low dose of cisplatin and significantly inhibit tumor growth via facilitated delivery of both AuNP and cisplatin. These findings suggest that by depleting stem cell pools and inhibiting key molecular pathways gold nanoparticles sensitize ovarian cancer cells to cisplatin and may be used in combination to inhibit tumor growth and metastasis in ovarian cancer. PMID:25071019

  17. Chemopreventive effect of tadalafil in cisplatin-induced ...

    African Journals Online (AJOL)

    Summary: Nephrotoxicity remains a common untoward effect of cisplatin therapy with limited effective chemopreventive options available till date. This study aims to evaluate the possible chemopreventive effect and mechanism(s) of action of 2 mgkg-1 and 5 mgkg-1 of Tadalafil in cisplatin-induced nephrotoxic rats. In this ...

  18. Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy

    International Nuclear Information System (INIS)

    Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya; Amarasiriwardena, Chitra J; Lupoli, Nicola

    2011-01-01

    The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) copolymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibits an IC 50 = 0.77 ± 0.11 μM comparable to that of free cisplatin (IC 50 = 0.44 ± 0.09 μM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and release cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibit significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo, with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.

  19. X-ray angiography perfusion imaging with an intra-arterial injection: comparative study with 15O-gas/water positron emission tomography.

    Science.gov (United States)

    Asai, Katsunori; Nakamura, Hajime; Watabe, Tadashi; Nishida, Takeo; Sakaguchi, Manabu; Hatazawa, Jun; Yoshimine, Toshiki; Kishima, Haruhiko

    2017-12-04

    X-ray angiography perfusion (XAP) is a perfusion imaging technique based on conventional DSA. In this study, we aimed to validate parameters derived from XAP by comparing them with 15 O-gas/water positron emission tomography (PET), using data from patients with chronic ischemic cerebrovascular disease. 18 consecutive patients were included. XAP was performed with intra-arterial infusion of contrast media, and a time-density curve was constructed for each cerebral hemisphere. From the curves, the relative values of mean transit time (rMTT) and wash-in rate (rWiR) were obtained by dividing the values of the right hemisphere by those of the left hemisphere. These were then compared with the relative values of cerebral blood flow (rCBF) and rMTT calculated from the PET data. XAP rWiR correlated strongly with PET rCBF (r=0.86, P<0.0001). rMTT measurements from the two modalities were also strongly correlated (r=0.85, P<0.0001). Bland-Altman analysis revealed a bias of 0.14±0.18 (95% limits of agreement -0.22 to 0.51) for PET rCBF versus XAP rWiR, and 0.016±0.093 (95% limits of agreement -0.17 to 0.20) for rMTT between the two modalities. The relative values obtained from XAP were validated across a population of patients with chronic ischemic cerebrovascular disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Intra-Arterial Chemotherapy as Primary Therapy for Retinoblastoma in Infants Less than 3 Months of Age: A Series of 10 Case-Studies.

    Directory of Open Access Journals (Sweden)

    Miaojuan Chen

    Full Text Available Retinoblastoma is the most common primary malignant intra-ocular tumor in children. Although intra-arterial chemotherapy (IAC by selectively infusing chemotherapy through the ophthalmic artery has become an essential technique in the treatment of advanced intra-ocular retinoblastoma in children, the outcome of IAC as primary therapy for infants less than 3 months of age remains unknown. In this retrospective study, we reviewed the outcome of IAC as primary therapy for retinoblastoma in infants less than 3 months of age.We retrospectively reviewed ten retinoblastoma patients attending our center from January 2009 to September 2015 and beginning primary IAC before the age of 3 months. The patient characteristics, overall outcomes and therapy-related complications were assessed.The mean patient age at the first IAC treatment was 10.4 weeks (range 4.9-12.9 weeks. These eyes were classified according to the International Classification of Retinoblastoma (ICRB as group A (n = 0, B (n = 2, C (n = 0, D (n = 9, or E (n = 2. A total of 28 catheterizations were performed, and the procedure was stopped in one patient because of internal carotid artery spasm. Each eye received a mean of 2.6 cycles of IAC (range 2-4 cycles. After IAC with a mean follow-up of 28.3 months (range 9-65 months, tumor regression was observed in 12 of 13 eyes. One eye was enucleated due to tumor progression. All patients are alive and no patient has developed metastatic disease or other malignancies.Our experience suggests IAC as primary therapy is a feasible and promising treatment for retinoblastoma in infants less than 3 months of age.

  1. A study of the diagnosis and treatment of nonocclusive mesenteric ischemia (NOMI) with special reference to the effectiveness of arterial infusion therapy

    International Nuclear Information System (INIS)

    Kataoka, Yuichi; Shimada, Ken; Kashimi, Fumie; Kanoh, Tomomichi; Hanajima, Tasuku; Woodhams, Reiko; Soma, Kazui

    2011-01-01

    At our hospital, 17 patients with NOMI have been treated in the past 6 years of these, 5 (29%) died in hospital. Angiography was proactively performed when NOMI was suspected on the basis of clinical findings and CT. Arterial infusion therapy was performed in 13 patients: 2 patients improved without surgery; 3 patients underwent laparotomy but intestinal resection was avoided; and for 1 patient the extent of resection was reduced during second-look surgery. Arterial infusion therapy comprised continuous intra-arterial administration of papaverine following bolus administration of prostaglandin E1 via a catheter placed in the superior mesenteric artery. If persistent peritoneal signs were evident, surgery was performed. Surgery was carried out in 12 patients. Mortality among the 8 patients who underwent both arterial infusion therapy and laparotomy was 25%. Patients who died had already developed multiple organ failure when treatment was started, as it had taken time for the diagnosis to be made. Early diagnosis and arterial infusion therapy on the assumption of surgery should contribute to improving therapeutic outcomes. (author)

  2. Crystals of Na(+)/K(+)-ATPase with bound cisplatin.

    Science.gov (United States)

    Huliciak, Miroslav; Reinhard, Linda; Laursen, Mette; Fedosova, Natalya; Nissen, Poul; Kubala, Martin

    2014-12-01

    Cisplatin is the most widely used chemotherapeutics for cancer treatment, however, its administration is connected to inevitable adverse effects. Previous studies suggested that cisplatin is able to inhibit Na(+)/K(+)-ATPase (NKA), the enzyme responsible for maintaining electrochemical potential and sodium gradient across the plasma membrane. Here we report a crystallographic analysis of cisplatin bound to NKA in the ouabain bound E2P form. Despite a moderate resolution (7.4 Å and 7.9 Å), the anomalous scattering from platinum and a model representation from a recently published structure enabled localization of seven cisplatin binding sites by anomalous difference Fourier maps. Comparison with NKA structures in the E1P conformation suggested two possible inhibitory mechanisms for cisplatin. Binding to Met151 can block the N-terminal pathway for transported cations, while binding to Met171 can hinder the interaction of cytoplasmic domains during the catalytic cycle. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Knockdown of MACC1 expression increases cisplatin sensitivity in cisplatin-resistant epithelial ovarian cancer cells.

    Science.gov (United States)

    Zhang, Ruitao; Shi, Huirong; Ren, Fang; Li, Xia; Zhang, Minghui; Feng, Wei; Jia, Yanyan

    2016-04-01

    Abnormal expression of metastasis-associated in colon cancer 1 (MACC1) was found to be closely associated with several types of malignant tumors. The present study aimed to verify the relationship between MACC1 and cisplatin resistance in ovarian cancer cells and the possible mechanisms, which was implemented by inhibition of the expression of MACC1 in cisplatin-resistant human ovarian cancer cell lines A2780/DDP and COC1/DDP. MACC1 shRNA eukaryotic plasmids and negative control plasmids were transfected into A2780/DDP and COC1/DDP cells, respectively, while A2780/DDP and COC1/DDP cells were used as blank controls. Western blotting and sqRT-PCR were used to detect the expression of MACC1 in the different cell groups. Different concentrations of cispaltin (0, 10, 20, 30, 40, 50 and 60 µmol/l) were used to treat the cell groups, respectively, and then the chemosensitivity of cisplatin and cell apoptosis were examined by MTT and flow cytometry, respectively. The activity of caspase-3 was determined by spectrophotometry. Expression levels of p-ERK1/2, permeability glycoprotein (P-gp), B-cell lymphoma 2 (Bcl-2), Bcl-XL, Bax and Bad protein were detected in the different ovarian cancer cells by western blotting. After MACC1 knockdown, the chemosensitivity of cisplatin in the ovarian cancer cells was enhanced, and the cell growth inhibition and apoptosis rates were increased. The expression levels of Bax and Bad were upregulated, the activity of caspase-3 was increased, while the expression levels of p-ERK1/2, P-gp, Bcl-2 and Bcl-XL were downregulated as a result of MACC1 inhibition. These results indicate that inhibition of MACC1 improves the chemosensitivity of cisplatin in epithelial ovarian cancer cells, through the regulation of the ERK1/2 signaling pathway on P-gp and its downstream apoptosis proteins.

  4. Effects of Arsenic Trioxide on Radiofrequency Ablation of VX2 Liver Tumor: Intraarterial versus Intravenous Administration

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Nak Jong; Yoon, Chang Jin; Kang, Sung Gwon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Chung, Jin Wook; Kim, Hyo Cheol; Park, Jae Hyung [Seoul National University Hospital, Seoul (Korea, Republic of)

    2012-03-15

    Arsenic trioxide (As{sub 2}O{sub 3}) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As{sub 2}O{sub 3} on RF-induced ablation in an experimentally induced liver tumor. VX2 carcinoma was grown in the livers of 30 rabbits. As{sub 2}O{sub 3} (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA {+-} 35; 90 {+-} 5 degrees Celsius). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. The overall ablation areas were 156 {+-} 28.9 mm{sup 2} (group A), 119 {+-} 31.7 (group B), and 92 {+-} 17.4 (group C, p < 0.04). The ablation area of the tumor was significantly larger in group A (73 {+-} 19.7 mm{sup 2}) than both group B (50 {+-} 19.4, p = 0.02) and group C (28 {+-} 2.2, p < 0.01). The ratios of the tumoral ablation area to the overall ablation area were larger in group A (47 {+-} 10.5%) than that of the other groups (42 {+-} 7.3% in group B and 32 {+-} 5.6% in group C) (p < 0.03). Radiofrequency-induced ablation area can be increased with intraarterial or intravenous administration of As{sub 2}O{sub 3}. The intraarterial administration of As{sub 2}O{sub 3} seems to be helpful for the selective ablation of the tumor.

  5. Correlation of Noninvasive Blood Pressure and Invasive Intra-arterial Blood Pressure in Patients Treated with Vasoactive Medications in a Neurocritical Care Unit.

    Science.gov (United States)

    Saherwala, Ali A; Stutzman, Sonja E; Osman, Mohamed; Kalia, Junaid; Figueroa, Stephen A; Olson, DaiWai M; Aiyagari, Venkatesh

    2018-03-22

    The correlation between noninvasive (oscillometric) blood pressure (NBP) and intra-arterial blood pressure (IAP) in critically ill patients receiving vasoactive medications in a Neurocritical Care Unit has not been systematically studied. The purpose of this study is to examine the relationship between simultaneously measured NBP and IAP recordings in these patients. Prospective observational study of patients (N = 70) admitted to a neurocritical care unit receiving continuous vasopressor or antihypertensive infusions. Paired NBP/IAP observations along with covariate and demographic data were abstracted via chart audit. Analysis was performed using SAS v9.4. A total of 2177 paired NBP/IAP observations from 70 subjects (49% male, 63% white, mean age 59 years) receiving vasopressors (n = 21) or antihypertensive agents (n = 49) were collected. Paired t test analysis showed significant differences between NBP versus IAP readings: ([systolic blood pressure (SBP): mean = 136 vs. 140 mmHg; p blood pressure (DBP): mean = 70 vs. 68 mmHg, p blood pressure (MAP): mean = 86 vs. 90 mmHg, p blood pressures. Pearson correlation coefficients show strong positive correlations for paired MAP (r = 0.82), SBP (r = 0.84), and DBP (r = 0.73) recordings. An absolute NBP-IAP SBP difference of > 20 mmHg was seen in ~ 20% of observations of nicardipine, ~ 25% of observations of norepinephrine, and ~ 35% of observations of phenylephrine. For MAP, the corresponding numbers were ~ 10, 15, and 25% for nicardipine, norepinephrine, and phenylephrine, respectively. Despite overall strong positive correlations between paired NBP and IAP readings of MAP and SBP, clinically relevant differences in blood pressure are frequent. When treating with vasoactive infusions targeted to a specific BP goal, it is important to keep in mind that NBP and IAP values are not interchangeable.

  6. Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer cells

    OpenAIRE

    Wang, Juan; Zhou, Jun-Ying; Zhang, Lianfeng; Wu, Gen Sheng

    2009-01-01

    Although cisplatin is a very effective anticancer agent against several types of cancer including ovarian cancer, the mechanisms of acquired resistance are not fully understood. By chronically exposing cisplatin to ovarian cancer cell lines, we established two cisplatin-resistant cell lines OV433 and tOV112D. Our results indicate that the mechanisms underlying their cisplatin resistance are distinct. In OV433 cells, cisplatin resistance is associated with increased expression of mitogen-activ...

  7. Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1-regulated cancer metabolism

    OpenAIRE

    Ai, Zhihong; Lu, Yang; Qiu, Songbo; Fan, Zhen

    2016-01-01

    Cisplatin is currently one of the most effective chemotherapeutic drugs used for treating ovarian cancer; however, resistance to cisplatin is common. In this study, we explored an experimental strategy for overcoming cisplatin resistance of human ovarian cancer from the new perspective of cancer cell metabolism. By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-...

  8. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    OpenAIRE

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho; Yee, Sung-Tae

    2009-01-01

    Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of ...

  9. EPS8 inhibition increases cisplatin sensitivity in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Lidija K Gorsic

    Full Text Available Cisplatin, a commonly used chemotherapeutic, is associated with ototoxicity, renal toxicity and neurotoxicity, thus identifying means to increase the therapeutic index of cisplatin may allow for improved outcomes. A SNP (rs4343077 within EPS8, discovered through a genome wide association study of cisplatin-induced cytotoxicity and apoptosis in lymphoblastoid cell lines (LCLs, provided impetus to further study this gene. The purpose of this work was to evaluate the role of EPS8 in cellular susceptibility to cisplatin in cancerous and non-cancerous cells. We used EPS8 RNA interference to determine the effect of decreased EPS8 expression on LCL and A549 lung cancer cell sensitivity to cisplatin. EPS8 knockdown in LCLs resulted in a 7.9% increase in cisplatin-induced survival (P = 1.98 × 10(-7 and an 8.7% decrease in apoptosis (P = 0.004 compared to control. In contrast, reduced EPS8 expression in lung cancer cells resulted in a 20.6% decrease in cisplatin-induced survival (P = 5.08 × 10(-5. We then investigated an EPS8 inhibitor, mithramycin A, as a potential agent to increase the therapeutic index of cisplatin. Mithramycin A decreased EPS8 expression in LCLs resulting in decreased cellular sensitivity to cisplatin as evidenced by lower caspase 3/7 activation following cisplatin treatment (42.7% ± 6.8% relative to control P = 0.0002. In 5 non-small-cell lung carcinoma (NSCLC cell lines, mithramycin A also resulted in decreased EPS8 expression. Adding mithramycin to 4 NSCLC cell lines and a bladder cancer cell line, resulted in increased sensitivity to cisplatin that was significantly more pronounced in tumor cell lines than in LCL lines (p<0.0001. An EGFR mutant NSCLC cell line (H1975 showed no significant change in sensitivity to cisplatin with the addition of mithramycin treatment. Therefore, an inhibitor of EPS8, such as mithramycin A, could improve cisplatin treatment by increasing sensitivity of tumor relative to normal cells.

  10. Efeitos cardiovasculares e renais da injeção intra-arterial de contraste radiológico iônico em cães com restrição hídrica Efectos cardiovasculares y renales de la inyección intra-arterial de contraste radiológico iónico en perros con restricción hídrica Cardiovascular and renal effects of intra-arterial injection of ionic radiological contrast in dogs under fluid restriction

    Directory of Open Access Journals (Sweden)

    Marisa Aparecida Lima Verderese

    2005-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O objetivo desta pesquisa foi estudar os efeitos agudos do contraste radiológico em situações de restrição de volume, avaliando-se os efeitos renais e cardiovasculares após a injeção intra-arterial de contraste radiológico de alta osmolaridade. MÉTODO: Participaram do estudo 16 cães anestesiados com tiopental sódico (15 mg.kg-1 e fentanil (15 µg.kg-1 em bolus, seguido de infusão contínua nas doses de 40 µg.kg-1.min-1 (tiopental sódico e 0,1 µg.kg-1.min-1 (fentanil. Foi feita hidratação com solução de glicose a 5% (0,03 mL.kg-1.min-1 e a ventilação pulmonar foi controlada mecanicamente com ar comprimido. Foram verificados os seguintes atributos: freqüência cardíaca (FC; pressão arterial média (PAM; pressão da veia cava inferior (PVI; débito cardíaco (DC; hematócrito (Ht; fluxo plasmático efetivo renal (FPER; fluxo sangüíneo renal (FSR; ritmo de filtração glomerular (RFG; fração de filtração; resistência vascular renal (RVR; volume urinário (VU; osmolaridade plasmática e urinária; depuração osmolar, depuração de água livre e depuração de sódio e de potássio; sódio e potássio plasmáticos; excreção urinária e fracionária de sódio e potássio e temperatura retal. Estes atributos foram avaliados em quatro momentos: 30 (M1, 60 (M2, 90 (M3 e 120 (M4 minutos após o início da infusão de para-aminohipurato de sódio e creatinina (início da experiência. No momento 2, no grupo G1 foi feita injeção intra-arterial de solução fisiológica a 0,9% (1,24 mL.kg-1, e no grupo G2 foi injetado contraste radiológico (1,24 mL.kg-1 pela mesma via. RESULTADOS: O grupo G1 apresentou aumento da FC, do FPER, do FSR, da osmolaridade plasmática, da depuração de sódio e da excreção urinária de sódio; apresentou ainda diminuição da osmolaridade urinária, do potássio plasmático, da depuração de potássio e da temperatura retal. No grupo G2 ocorreu aumento da FC, da

  11. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

    DEFF Research Database (Denmark)

    Daugaard, G; Skoneczna, I; Aass, N

    2011-01-01

    To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor......-prognosis germ-cell cancer (GCC). Patient and methods: Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual....

  12. [Intra-arterial regional chemotherapy and intensive loco-regional radiotherapy in the treatment of locally advanced cancer of the breast].

    Science.gov (United States)

    Nicolato, A

    1990-09-01

    A multimodal treatment combining intra-arterial chemotherapy and intensive loco-regional radiotherapy was administered to 55 patients with locally advanced breast cancer. Adjuvant polychemotherapy followed, and eventually endocrino-therapy. Combined intra-arterial chemotherapy and intensive radiotherapy gave excellent results in both primary and lymph node lesions, with 90.9% and 92.2% complete/partial response rates. Three-year and 5-year actuarial survival rates were 69% and 59%, respectively. Patients showing better local responses to combined intra-arterial chemotherapy and intensive radiotherapy had longer survival and less frequent local recurrences. Combined intra-arterial chemotherapy and intensive loco-regional radiotherapy seems to be an effective modality for the treatment of locally advanced breast cancer.

  13. Intraarterial digital subtraction angiography after plastic surgery by thin-needle puncture

    Energy Technology Data Exchange (ETDEWEB)

    Langer, M.; Fiegler, W.; Claussen, C.; Koehler, D.; Felix, R.; Hepp, W.

    1984-06-01

    Over the period of a year (1983), 44 intraarterial digital subtraction angiographies (DSA) via direct thin-needle puncture of a vascular bypass or following vascular graft were carried the rough. The only complication that occurred: paravasal injection, was clinically insignificant and could be avoided by a change in the puncture-technique. It was possible to carry through the investigation in out-patients. In all cases, diagnostically useful picture material for a possible surgical intervention was obtained. The pictures always were high-grade, independently of the patient's circulation time. Because this is a simple investigation and because of the small risk of complications, it has come to be regularly carried through as a routine in the authors' clinic. According to investigations carried through on the collective of patients of a vascular surgery department, occlusions or anastomotic aneurismus account for most of the angiological disorders.

  14. Local intra-arterial thrombolysis in acute ischemic stroke of the anterior circulation

    International Nuclear Information System (INIS)

    Zhang Yongwei; Liu Jianmin; Hong Bo; Deng Benqiang; Xu Yi; Ding Suju

    2003-01-01

    Objective: To evaluate the safety and efficacy of local intra-arterial thrombolysis (LIT) using urokinase in patients with acute ischemic stroke of the anterior circulation. Methods: Fifty-four patients were treated with LIT using urokinase. The locations of occlusion included 3 of internal carotid artery (ICA), 46 of middle cerebral artery (MCA) and 5 of anterior cerebral artery. Results: Outcome was good in 41 patients (75.9%). Recanalization >50% was obtained in 72.2% of patients and <50% recanalization in 27.8% of patients. Cerebral hemorrhage occurred in 11 patients (20.4%). Four patients died (7.4%). Conclusion: LIT using urokinase can improve the recanalization rate and achieve better functional recovery in patients of acute ischemic stroke

  15. Intraarterial digital subtraction angiography after plastic surgery by thin-needle puncture

    International Nuclear Information System (INIS)

    Langer, M.; Fiegler, W.; Claussen, C.; Koehler, D.; Felix, R.; Hepp, W.

    1984-01-01

    Over the period of a year (1983), 44 intraarterial digital subtraction angiographies (DSA) via direct thin-needle puncture of a vascular bypass or following vascular graft were carried the rough. The only complication that occured: paravasal injection, was clinically insignificant and could be avoided by a change in the puncture-technique. It was possible to carry through the investigation in out-patients. In all cases, diagnostically useful picture material for a possible surgical intervention was obtained. The pictures always were high-grade, independently of the patient's circulation time. Because this is a simple investigation and because of the small risk of complications, it has come to be regularly carried through as a routine in the authors' clinic. According to investigations carried through on the collective of patients of a vascular surgery department, occlusions or anastomotic aneurismus account for most of the angiological disorders. (orig.) [de

  16. Preoperative localization of endocrine pancreatic tumours by intra-arterial dynamic computed tomography

    International Nuclear Information System (INIS)

    Ahlstroem, H.; Magnusson, A.; Grama, D.; Eriksson, B.; Oeberg, K.; Loerelius, L.E.; Akademiska Sjukhuset, Uppsala; Akademiska Sjukhuset, Uppsala

    1990-01-01

    Eleven patients with biochemically confirmed endocrine pancreatic tumours were examined with intra-arterial (i.a.) dynamic computed tomography (CT) and angiography preoperatively. Seven of the patients suffered from the multiple endocrine neoplasia type 1 (MEN-1) syndrome. All patients were operated upon and surgical palpation and ultrasound were the peroperative localization methods. Of the 33 tumours which were found at histopathologic analysis of the resected specimens in the 11 patients, 7 tumours in 7 patients were correctly localized by both i.a. dynamic CT and angiography. Six patients with MEN-1 syndrome had multiple tumours and this group of patients together had 28 tumours, of which 5 (18%) were localized preoperatively by both CT and angiography. I.a. dynamic CT, with the technique used by us, does not seem to improve the localization of endocrine pancreatic tumours, especially in the rare group of MEN-1 patients, as compared with angiography. (orig.)

  17. Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach

    Directory of Open Access Journals (Sweden)

    Navin Sarin

    2018-03-01

    Full Text Available The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding for a systems pharmacology approach to understand a whole cell’s reaction to the drug. In this study, the cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer cells and their cisplatin-resistant sub-line A549rCDDP2000 was screened with a whole genome array for relevant gene candidates. By combining statistical methods with available gene annotations and without a previously defined hypothesis HRas, MAPK14 (p38, CCL2, DOK1 and PTK2B were identified as genes possibly relevant for cisplatin resistance. These and related genes were further validated on transcriptome (qRT-PCR and proteome (Western blot level to select candidates contributing to resistance. HRas, p38, CCL2, DOK1, PTK2B and JNK3 were integrated into a model of resistance-associated signalling alterations describing differential gene and protein expression between cisplatin-sensitive and -resistant cells in reaction to cisplatin exposure.

  18. Combination effect of cisplatin and radiation in murine solid tumors

    International Nuclear Information System (INIS)

    Egawa, Shin; Lee, Kan-ei; Ishibashi, Akira; Komiyama, Hiroki; Umezawa, Iwao.

    1986-01-01

    The combination effect of cisplatin and radiation was studied using the two different murine systems of sarcoma 180 and Ehrlich solid tumors. In sarcoma 180 solid tumor the minimal effective doses (MED) of cisplatin and radiation were 19.5 mg/kg and 10375 rad respectively whereas these doses did not show any effective antitumor activity practically. Administration of cisplatin with a doses of 9 mg/kg given 24 hours before radiation (1000 rad), however, showed synergistic antitumor activity. In Ehrlich solid tumor the MED of cisplatin and radiation were 13.8 mg/kg and 2892 rad respectively. Treatment with cisplatin, 3, 6 or 9 mg/kg, given 24 hours before radiation (1000 rad) showed also synergistic antitumor activity also. Sodium thiosulfate (STS) rescue was effective in reducing toxicity of cisplatin on combined use of the drug with radiation. Cell kinetics of sarcoma 180 solid tumor in vivo after the combined treatment was analyzed by computer aided flowcytometry. Accumulation of cells in the radiosensitive G 2 + M phase was observed 18 to 42 hours after a single intraperitoneal administration of 9 mg/kg of cisplatin. It is strongly suggested that this synchronization is one of the mechanisms of the synergism in the combination therapy. (author)

  19. Pathophysiology of Cisplatin-Induced Acute Kidney Injury

    Science.gov (United States)

    Ozkok, Abdullah; Edelstein, Charles L.

    2014-01-01

    Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality. PMID:25165721

  20. Acute application of cisplatin affects methylation status in neuroblastoma cells.

    Science.gov (United States)

    Tabata, Keiichi; Sakai, Hayato; Nakajima, Ryosuke; Saya-Nishimura, Reiko; Motani, Kou; Okano, Soichiro; Shibata, Yasuko; Abiko, Yoshimitsu; Suzuki, Takashi

    2011-06-01

    The pharmacological mechanism of the anti-cancer effect of cisplatin is well known to be DNA intercalation, but the direct or indirect effects of cisplatin on protein expression in cancer cells remain to be explained. In this study, we used a proteomic approach to clarify the early impact of cisplatin on protein expression. In a 2-dimensional gel electrophoresis proteomic experiment, the application of cisplatin for 24 h increased the expression of four proteins and decreased the levels of one protein in neuroblastoma IMR-32 cells. Levels of S-adenosyl-L-homocysteine hydrolase, a key enzyme in methylation metabolism, were increased the most. Therefore, we examined the methylation status of histone proteins. Histone H3K9 methylation was reduced by the application of cisplatin for 24 h. These results suggest that acute cisplatin treatment alters methylation status. Thus, these data can help clarify the unknown pharmacological mechanisms of cisplatin, including the anticancer effect, adverse effects and/or the mechanism of drug resistance.

  1. Recurrent cisplatin hypersensitivity reaction after first exposure: A case report.

    Science.gov (United States)

    Solomon, Benjamin; Colonna, Sarah

    2017-01-01

    Purpose Hypersensitivity reactions to platinum-based chemotherapies are well documented and are often a limiting factor in treating a variety of cancers. Allergy skin testing has been used to determine if repeat exposure is safe. We report a case of a false negative skin allergy test in an atypical presentation of cisplatin hypersensitivity reaction. Case report A 64-year-old male diagnosed with stage IVa squamous cell carcinoma of the hypopharynx who developed a delayed reaction of face swelling and dysphagia following exposure to a single dose of cisplatin. Skin allergy testing performed and was negative. On second dosing of cisplatin, the patient developed an immediate hypersensitivity reaction. Cisplatin was discontinued, and the patient was transitioned to cetuximab. The rest of chemoradiation therapy was completed without further incident. Discussion This case demonstrates the limited efficacy of skin allergy testing for cisplatin. Furthermore, it is an atypical presentation of cisplatin-related hypersensitivity as it occurred following the patient's first dose despite no prior exposure to platinum-based chemotherapy. Conclusion Skin allergy testing has limited sensitivity for platinum-based chemotherapy and caution should be exercised in weighing risk and benefits of re-exposure. Although rare, cisplatin hypersensitivity can present after first exposure.

  2. Evaluation of nanoparticle delivered cisplatin in beagles

    Science.gov (United States)

    Feldhaeusser, Brittany; Platt, Simon R.; Marrache, Sean; Kolishetti, Nagesh; Pathak, Rakesh K.; Montgomery, David J.; Reno, Lisa R.; Howerth, Elizabeth; Dhar, Shanta

    2015-08-01

    Intracranial neoplasia is a significant cause of morbidity and mortality in both human and veterinary patients, and is difficult to treat with traditional therapeutic methods. Cisplatin is a platinum (Pt)-containing chemotherapeutic agent approved by the Food and Drug Administration; however, substantial limitations exist for its application in canine brain tumor treatment due to the difficulty in crossing the blood-brain barrier (BBB), development of resistance, and toxicity. A modified Pt(iv)-prodrug of cisplatin, Platin-M, was recently shown to be deliverable to the brain via a biocompatible mitochondria-targeted lipophilic polymeric nanoparticle (NP) that carries the drug across the BBB and to the mitochondria. NP mediated controlled release of Platin-M and subsequent reduction of this prodrug to cisplatin allowed cross-links to be formed with the mitochondrial DNA, which have no nucleotide excision repair system, forcing the overactive cancer cells to undergo apoptosis. Here, we report in vitro effects of targeted Platin-M NPs (T-Platin-M-NPs) in canine glioma and glioblastoma cell lines with results indicating that this targeted NP formulation is more effective than cisplatin. In both the cell lines, T-Platin-M-NP was significantly more efficacious compared to carboplatin, another Pt-based chemotherapy, which is used in the settings of recurrent high-grade glioblastoma. Mitochondrial stress analysis indicated that T-Platin-M-NP is more effective in disrupting the mitochondrial bioenergetics in both the cell types. A 14-day distribution study in healthy adult beagles using a single intravenous injection at 0.5 mg kg-1 (with respect to Platin-M) of T-Platin-M-NPs showed high levels of Pt accumulation in the brain, with negligible amounts in the other analyzed organs. Safety studies in the beagles monitoring physical, hematological, and serum chemistry evaluations were within the normal limits on days 1, 7, and 14 after injection of either 0.5 mg kg-1 or 2 mg kg

  3. Cisplatin Analogs Confer Protection against Cyanide Poisoning.

    Science.gov (United States)

    Nath, Anjali K; Shi, Xu; Harrison, Devin L; Morningstar, Jordan E; Mahon, Sari; Chan, Adriano; Sips, Patrick; Lee, Jangwoen; MacRae, Calum A; Boss, Gerry R; Brenner, Matthew; Gerszten, Robert E; Peterson, Randall T

    2017-05-18

    Cisplatin holds an illustrious position in the history of chemistry most notably for its role in the virtual cure of testicular cancer. Here we describe a role for this small molecule in cyanide detoxification in vivo. Cyanide kills organisms as diverse as insects, fish, and humans within seconds to hours. Current antidotes exhibit limited efficacy and are not amenable to mass distribution requiring the development of new classes of antidotes. The binding affinity of the cyanide anion for the positively charged metal platinum is known to create an extremely stable complex in vitro. We therefore screened a panel of diverse cisplatin analogs and identified compounds that conferred protection from cyanide poisoning in zebrafish, mice, and rabbits. Cumulatively, this discovery pipeline begins to establish the characteristics of platinum ligands that influence their solubility, toxicity, and efficacy, and provides proof of concept that platinum-based complexes are effective antidotes for cyanide poisoning. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Weekly nanoparticle albumin bound-paclitaxel in combination with cisplatin versus weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese patients with advanced esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang HY

    2016-09-01

    Full Text Available Hai-ying Wang, Zhi-hua Yao, Hong Tang, Yan Zhao, Xiao-san Zhang, Shu-na Yao, Shu-jun Yang, Yan-yan Liu Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China Objective: More effective regimens for advanced esophageal squamous cell carcinoma (ESCC are urgently needed. Therefore, a retrospective study concerning the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin (nab-TP versus solvent-based paclitaxel plus cisplatin (sb-TP as a first-line therapy was conducted in Chinese patients with advanced ESCC.Methods: From June 2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2 on the first and eighth days (30 minutes infusion and cisplatin (75 mg/m2 on the second day every 21 days (nab-TP arm. Also, 43 patients were treated with solvent-based paclitaxel (80 mg/m2 intravenously on the first and eighth days and the same dose of cisplatin (sb-TP arm. The two groups were compared in terms of objective response rate (ORR, disease control rate, progression-free survival (PFS, overall survival (OS, and safety profile. OS and PFS were estimated using Kaplan–Meier methods to determine associations between chemotherapy regimens and survival outcomes.Results: Nab-TP demonstrated a higher ORR (50% vs 30%; P=0.082 and disease control rate (81% vs 65%; P=0.124 than sb-TP. Median OS was similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269. However, nab-TP resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3–6.9] than sb-TP (5.0 months [95% confidence interval: 4.4–5.6] (P=0.029. The most common adverse events included anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia in both the groups and no statistically significant differences were observed between the groups. With statistically significant differences, significantly less grade ≥3 peripheral neuropathy

  5. Probenecid Sensitizes Neuroblastoma Cancer Stem Cells to Cisplatin.

    Science.gov (United States)

    Campos-Arroyo, Denise; Maldonado, Vilma; Bahena, Ivan; Quintanar, Valeria; Patiño, Nelly; Carlos Martinez-Lazcano, Juan; Melendez-Zajgla, Jorge

    2016-01-01

    We used both in vitro cultures of neuroblastoma cell lines and nude-mice xenotransplants to explore the effects of co-administration of cisplatin and probenecid. Probenecid sensitized neuroblastoma cells, including tumor cells with stem features, to the effects of cisplatin, both in vitro and in vivo. This effect was mediated by an increase in the apoptotic cell death and a concomitant decrease in cell proliferation. This effect is accompanied by modulation of the mRNA and protein of the drug efflux transporters MDR1, MRP2, and BCRP. The co-administration of probenecid with cisplatin should be explored as a possible therapeutic strategy.

  6. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

    DEFF Research Database (Denmark)

    Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

    2010-01-01

    PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...... share features suggesting common pathogenesis, we conducted a neoadjuvant trial of cisplatin in TNBC and explored specific biomarkers to identify predictors of response. PATIENTS AND METHODS Twenty-eight women with stage II or III breast cancers lacking estrogen and progesterone receptors and HER2/Neu...

  7. Temozolomide and cisplatin in relapsed/refractory acute leukemia

    Directory of Open Access Journals (Sweden)

    Rasul Muhammad

    2009-05-01

    Full Text Available Abstract Cisplatin depletes MGMT and increases the sensitivity of leukemia cells to temozolomide. We performed a phase I study of cisplatin and temozolomide in patients with relapsed and refractory acute leukemia. Fifteen patients had AML, 3 had ALL, and 2 had biphenotypic leukemia. The median number of prior chemotherapy regimens was 3 (1–5. Treatment was well tolerated up to the maximal doses of temozolomide 200 mg/m2/d times 7 days and cisplatin 100 mg/m2 on day 1. There was one complete remission in this heavily pretreated patient population. Five of 20 (25% patients demonstrated a significant reduction in bone marrow blasts.

  8. Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath, E-mail: palakurthi@tamhsc.edu [Texas A and M Health Science Center, Irma Lerma Rangel College of Pharmacy (United States)

    2013-09-15

    Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH{sub 2} and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was {approx}11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC{sub 50} values in ovarian cancer cells when compared with carboxylate surface dendrimers (p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase (p < 0.05) in expression of apoptotic genes (Bcl2, Bax, p53) and 13.2- to 27.1-fold increase (p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

  9. Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

    Science.gov (United States)

    Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

    2013-09-01

    Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase ( p < 0.05) in expression of apoptotic genes ( Bcl2, Bax, p53) and 13.2- to 27.1-fold increase ( p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

  10. Changes arterial flow patterns in each posture during intrahepatic arterial continuous infusion using {sup 81m}Kr perfusion scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kameyama, Masao; Nakamori, Shouji; Imaoka, Shingi; Furukawa, Hiroshi; Hasegawa, Yoshihisa [Osaka Prefectural Center for Adult Diseases (Japan); Iwanaga, Tsuyoshi

    1997-06-01

    The purpose of this study was to investigate whether or not arterial flow patterns would differ depending on the patients posture during hepatic arterial infusion chemotherapy. Four colorectal cancer patients underwent hepatic resection for liver metastases and intrahepatic catheter placement in order to prevent recurrence in the liver remnant. Before starting chemotherapy, {sup 81m}Kr was continuously infused at a rate or 8 ml/min in four postures (supine (S), right side down (R), left side down (L), and upright (U)). The same area of region of interest (ROI) was set in 3 regions (right lower, right upper, and left), and the radioactivity was calculated for each ROI. Postures obtaining the largest number of RI counts in the left region were (R) in 3 patients and (L) in 1 patients. In the right upper region, they were (L) in 2 patients and (U) in 2 patients. In the right lower region, they were (R) in 2 patients and (L) in 2 patients. Consequently, optimal postures derived from RI counts radio among 3 regions were (R) in 2 patients, (L) in 1 patient, and (U) in 1 patient. Preliminary data may indicate that different perfusion patterns exist in each patient. It may be assumed that an optimal posture applied for each patient improves the response to intraarterial chemotherapy. (author)

  11. General-purpose infusion pumps.

    Science.gov (United States)

    1998-01-01

    General-purpose infusion pumps deliver liquid medications to patients through intravenous or epidural routes at specified flows. They are most often used in hospitals and alternative care settings (e.g., physician' offices, patients' homes) when liquid medications need to be administered with greater accuracy or at higher flows than can be provided through a manually adjusted gravity administration set. In this Update of our February 1997 Evaluation of infusion pumps (Health Devices 26[2]), we tested 3 additional pumps from 3 suppliers. We also rated and ranked them in comparison with the 16 units from the February 1997 study that are still being produced. With a few exceptions, we tested the new pumps against the same criteria and using the same test methods as those in the previous Evaluation. However, for this Update, the focus of our findings has broadened: although we continue to place strong emphasis on the pumps' protection against gravity free-flow, we also give significant weight to their overall safety, performance, and human factors design. As a result, our ratings and rankings scheme has changed, affecting the rankings of some of the previously evaluated units. Of the 19 currently available units that have been evaluated to date, we rated 13 units Acceptable, with 5 of those units ranked above the other 8. A further 5 units were rated Conditionally Acceptable; we consider them Acceptable if they are used with the available free-flow protection. And 1 unit had performance problems that caused us to rate it Unacceptable (this unit has been recalled by its supplier; see the inset on page 162). As always, we caution readers not to base selection and purchasing decisions on our conclusions alone, but on a thorough understanding of the issues behind those conclusions, which can be gained by reading this Evaluation in its entirety and carefully reviewing the February 1997 issue.

  12. Sensitivity of Vi phages to γ- radiation in the presence of cisplatin

    International Nuclear Information System (INIS)

    Dabrowski, T.; Kwiatkowski, B.

    2005-01-01

    In this study we determined Vi bacteriophage III sensitivity to native cisplatin, γradiation ( 60 Co) or to irradiated cisplatin, and checked the possibility of enhanced Vi bacteriophage III inactivation under combined exposure to cisplatin and γ radiation. We used highly purified phage suspensions in 0.9% NaCl solution or phosphate-buffered saline. Phage suspensions were titrated using a double agar layer method. Our study implies that survival of Vi bacteriophage III shows an exponential inverse correlation with cisplatin concentration in incubation medium and the time of phage incubation in the presence of cisplatin. The use of irradiated cisplatin reduces phage survival in comparison with suspensions containing non-irradiated cisplatin. Irradiation of phage suspension with cisplatin causes a significant increase of phage inactivation in comparison with either treatment alone. Our results suggest that presence of cisplatin in irradiated medium enhances the radiobiological effect on Vi bacteriophages III. (author)

  13. The History of Target-Controlled Infusion

    NARCIS (Netherlands)

    Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

  14. The Infusion Approach to Teacher Development.

    Science.gov (United States)

    Kowalski, Ellen M.

    1995-01-01

    The underlying premise of infusion is that information about individuals with disabilities must be more systematically integrated throughout an entire curriculum. This article describes the infusion approach to teacher development, explaining three central premises, providing sample program applications for each premise, and discussing brain…

  15. Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity

    Science.gov (United States)

    Kothandapani, Anbarasi; Sawant, Akshada; Dangeti, Venkata Srinivas Mohan Nimai; Sobol, Robert W.; Patrick, Steve M.

    2013-01-01

    Base excision repair (BER) and mismatch repair (MMR) pathways play an important role in modulating cis-Diamminedichloroplatinum (II) (cisplatin) cytotoxicity. In this article, we identified a novel mechanistic role of both BER and MMR pathways in mediating cellular responses to cisplatin treatment. Cells defective in BER or MMR display a cisplatin-resistant phenotype. Targeting both BER and MMR pathways resulted in no additional resistance to cisplatin, suggesting that BER and MMR play epistatic roles in mediating cisplatin cytotoxicity. Using a DNA Polymerase β (Polβ) variant deficient in polymerase activity (D256A), we demonstrate that MMR acts downstream of BER and is dependent on the polymerase activity of Polβ in mediating cisplatin cytotoxicity. MSH2 preferentially binds a cisplatin interstrand cross-link (ICL) DNA substrate containing a mismatch compared with a cisplatin ICL substrate without a mismatch, suggesting a novel mutagenic role of Polβ in activating MMR in response to cisplatin. Collectively, these results provide the first mechanistic model for BER and MMR functioning within the same pathway to mediate cisplatin sensitivity via non-productive ICL processing. In this model, MMR participation in non-productive cisplatin ICL processing is downstream of BER processing and dependent on Polβ misincorporation at cisplatin ICL sites, which results in persistent cisplatin ICLs and sensitivity to cisplatin. PMID:23761438

  16. Successful Thrombolysis and Spasmolysis of Acute Leg Ischemia after Accidental Intra-arterial Injection of Dissolved Flunitrazepam Tablets

    International Nuclear Information System (INIS)

    Radeleff, B.; Stampfl, U.; Sommer, C.-M.; Bellemann, N.; Hyhlik-Duerr, A.; Weber, M.-A.; Boeckler, D.; Kauczor, H.-U.

    2011-01-01

    A 37-year-old man with known intravenous drug abuse presented in the surgical ambulatory care unit with acute leg ischemia after accidental intra-arterial injection of dissolved flunitrazepam tablets into the right femoral artery. A combination of anticoagulation, vasodilatation, and local selective and superselective thrombolysis with urokinase was performed to salvage the leg. As a result of the severe ischemia-induced pain, the patient had to be monitored over the complete therapy period on the intensive care unit with permanent administration of intravenous fluid and analgetics. We describe the presenting symptoms and the interventional technique, and we discuss the recent literature regarding the management of accidental intra-arterial injection of dissolved flunitrazepam tablets.

  17. Regional cerebral blod flow studied by xenon-133. Intra-arterial injection studies and inhalation studies using emission tomography

    DEFF Research Database (Denmark)

    Lassen, N A

    1980-01-01

    .) technique is insensitive both to hyperemia and ischemia yielding essentially only a mean flow value. A new rapidly moving single photon tomograph following D. Kuhl's principle is presented applicable to Xe-133. Preliminary clinical data show that this technique is able to detect ischemic areas both with Xe......A survey of the Xenon-133 techniques for measurement of regional cerebral blood flow, rCBF, in man is presented. The intra-arterial Xe-133 injection method is very sensitive for detecting even small hyperemic areas, but cannot "see" smaller ischemic areas. The Xe-133 inhalation (or i.v. inj......-133 intra-arterial injection and with Xe-133 inhalation. The practical and economic advantages of Xe-133 or Xe-127 tomography over positron tomography for rCBF are discussed....

  18. Intravenous drugs infusion safety through smart pumps

    Directory of Open Access Journals (Sweden)

    C. Gómez-Baraza

    2014-07-01

    Full Text Available Objective: To analyze the role of smart infusion pumps in reducing errors related with the administration of intravenous medications. Method: Retrospective, observational study analyzing the implementation of a system with smart intravenous infusion pumps (Hospira MedNetTM and the role of the safety system for the detection of errors during the administration of drugs, sera, and blood. We included infusions administered at the day-care hospitals of hematology, oncology, rheumatology, and oncopediatrics. We analyzed adherence to the safety system, the number of programming errors detected, the commonly implicated drugs in these errors, and improvement actions. Results: During the study period, 120 smart pumps were implemented and data on 70,028 infusions were gathered. The rate of adherence to the safety program was 62.30% in hematology (6,887 infusions, 60,30% in oncology (28,127 infusions, 46,50% in rheumatology (1,950 infusions and 1.8% in oncopediatrics (139 infusions. 3,481 out of the established limits programming alerts were generated by the pumps: 2,716 of relative limit and 765 of absolute limit. En 807 infusions (2.17%, errors that could have had consequences for the patients could be prevented. These findings allowed implementing a series of strategies aimed at minimizing these errors in the future. Conclusions: The Hospira MedNetTM system detects deviations from the established protocols of intravenous infusion, preventing in this way potential adverse events for the patients. It also allows establishing correction measures and implementing the improvement strategies.

  19. Thymoquinone enhances cisplatin-induced neprotoxicity in high dose

    Directory of Open Access Journals (Sweden)

    Ahmet Dirican

    2016-01-01

    Conclusions: This study showed that the administration of cisplatin and high dose of TQ act synergistically to produce nephrotoxicity and the involvement of apoptotic pathway and proximal tubule damage might be the leading cause of on this effect.

  20. Ginger Essential Oil Ameliorates Cisplatin-Induced Nephrotoxicity in ...

    African Journals Online (AJOL)

    HP

    30114867; Fax: 55-44-30114999. Received: 25 June 2013. Revised accepted: 16 October 2013. Abstract. Purpose: To investigate the effect of ginger essential oil (GEO) in an experimental model of cisplatin- induced nephrotoxicity. Methods: Male ...

  1. Femoral infarction following intraarterial chemotherapy for osteosarcoma of the leg: A possible pitfall in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Ollivier, L.; Leclerc, J.; Pouillart, P.; Vanel, D.; Forest, M.; Tomeno, B.; Riche, M.C.

    1991-01-01

    Bone infarction of the distal femur is reported in two patients with osteosarcoma of the leg (1 tibia, 1 fibula) treated by preoperative chemotherapy including intraarterial chemotherapy (IAC) by Cis-platinum. Both patients were examined by magnetic resonance imaging before chemotherapy and again prior to limb salvage surgery. The location of these lesions in the distal femur must suggest bone infarction especially if the tumor has decreased in size under treatment. (orig.)

  2. Comparison of classification methods for voxel-based prediction of acute ischemic stroke outcome following intra-arterial intervention

    Science.gov (United States)

    Winder, Anthony J.; Siemonsen, Susanne; Flottmann, Fabian; Fiehler, Jens; Forkert, Nils D.

    2017-03-01

    Voxel-based tissue outcome prediction in acute ischemic stroke patients is highly relevant for both clinical routine and research. Previous research has shown that features extracted from baseline multi-parametric MRI datasets have a high predictive value and can be used for the training of classifiers, which can generate tissue outcome predictions for both intravenous and conservative treatments. However, with the recent advent and popularization of intra-arterial thrombectomy treatment, novel research specifically addressing the utility of predictive classi- fiers for thrombectomy intervention is necessary for a holistic understanding of current stroke treatment options. The aim of this work was to develop three clinically viable tissue outcome prediction models using approximate nearest-neighbor, generalized linear model, and random decision forest approaches and to evaluate the accuracy of predicting tissue outcome after intra-arterial treatment. Therefore, the three machine learning models were trained, evaluated, and compared using datasets of 42 acute ischemic stroke patients treated with intra-arterial thrombectomy. Classifier training utilized eight voxel-based features extracted from baseline MRI datasets and five global features. Evaluation of classifier-based predictions was performed via comparison to the known tissue outcome, which was determined in follow-up imaging, using the Dice coefficient and leave-on-patient-out cross validation. The random decision forest prediction model led to the best tissue outcome predictions with a mean Dice coefficient of 0.37. The approximate nearest-neighbor and generalized linear model performed equally suboptimally with average Dice coefficients of 0.28 and 0.27 respectively, suggesting that both non-linearity and machine learning are desirable properties of a classifier well-suited to the intra-arterial tissue outcome prediction problem.

  3. Intra-arterial thrombolysis vs. standard treatment or intravenous thrombolysis in adults with acute ischemic stroke: a systematic review and meta-analysis.

    Science.gov (United States)

    Nam, Julian; Jing, He; O'Reilly, Daria

    2015-01-01

    Recent evidence has suggested that intra-arterial thrombolysis may provide benefit beyond intravenous thrombolysis in ischemic stroke patients. Previous meta-analyses have only compared intra-arterial thrombolysis with standard treatment without thrombolysis. The objective was to review the benefits and harms of intra-arterial thrombolysis in ischemic stroke patients. We undertook a meta-analysis of randomized controlled trials comparing the efficacy and safety of intra-arterial thrombolysis with either standard treatment or intravenous thrombolysis following acute ischemic stroke. Primary outcomes included poor functional outcomes (modified Rankin Scale 3-6), mortality, and symptomatic intracranial hemorrhage. Study quality was assessed, and outcomes were stratified by comparison treatment received. Four trials (n = 351) comparing intra-arterial thrombolysis with standard treatment were identified. Intra-arterial thrombolysis reduced the risk of poor functional outcomes (modified Rankin Scale 3-6) [relative risk (RR) = 0·80; 95% confidence interval = 0·67-0·95; P = 0·01]. Mortality was not increased (RR = 0·82; 95% confidence interval = 0·56-1·21; P = 0·32); however, risk of symptomatic intracranial hemorrhage was nearly four times more likely (RR = 3·90; 95% confidence interval = 1·41-10·76; P = 0·006). Two trials (n = 81) comparing intra-arterial thrombolysis with intravenous thrombolysis were identified. Intra-arterial thrombolysis was not found to reduce poor functional outcomes (modified Rankin Scale 3-6) (RR = 0·68; 95% confidence interval = 0·46-1·00; P = 0·05). Mortality was not increased (RR = 1·12; 95% confidence interval = 0·47-2·68; P = 0·79); neither was symptomatic intracranial hemorrhage (RR = 1·13; 95% confidence interval = 0·32-3·99; P = 0·85). Differences in time from symptom onset-to-treatment and type of thrombolytic administered were found

  4. Royal Jelly Modulates Hepatotoxic Effect of Rats Treated with Cisplatin

    International Nuclear Information System (INIS)

    Ashry, K.; Elkady, A.A.

    2014-01-01

    isplatin (CP) is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as hepatotoxicity and nephrotoxicity. The aim of this study was focused on investigating the possible protective effect of royal jelly (RJ) against oxidative stress caused by CP injury of the liver and inflammatory changes in male albino rats. Twenty four albino rats were divided into four equal groups as follows: control group, cisplatin group : (rats injected i.p. with single dose from cisplatin (CP, 7 mg / kg body weight,), royal jelly RJ group : rats treated for 15 consecutive days by gavage with RJ (300 mg/kg/day/orally), royal jelly-cisplatin group, rats treated with royal jelly orally for 15 consecutive days by gavage (300 mg/kg/day) followed by a single injection i.p. from CP (7 mg / kg body weight). The obtained results revealed that the administration of royal jelly with cisplatin in rats significantly ameliorated the changes occurred in the biochemical parameters (GSH, GPx and CAT were significantly decreased in liver of cisplatin-treated rats and increasing ALT and AST). The histopathological results showed distinctive pattern of hepatotoxic changes in cisplatin group, while in the royal jelly-cisplatin group the liver tissues showed reductions lesions. In conclusion, royal jelly acts in the liver as a potent scavenger of free radicals to prevent or ameliorates the toxic effects of CP as shown by biochemical and histopathological investigations and might provide substantial protection against cisplatin-induced hepatotoxicity and inflammatory

  5. The chemoimmunotherapy based on dendritic cells and cisplatin in experiment

    OpenAIRE

    Gorbach, O.; Khranovska, N.; Skachkova, O.; Sydor, R.; Pozur, V.

    2014-01-01

    The aim of the study was to develop a scheme of combined chemoimmunotherapy and to investigate antitumor and immunomodulatory activity of chemoimmunotherapy regimen using the vaccine based on dendritic cells and low-doses of cisplatin in CBA mice with sarcoma-37. Maximal antitumor and immunomodulatory effects were observed after application of the vaccine based on dendritic cells in combination with doses of cisplatin concentration of 2 mg/kg. Among significant immunomodulatory effects of com...

  6. Intra-arterial and intra-venous chemotherapy combined with radiation in the treatment of brain tumours

    International Nuclear Information System (INIS)

    Watne, K.

    1992-01-01

    The present investigations were undertaken to study the effect of combining different modalities of chemotherapy with radiation in post-operative treatment of brain tumours. The conclusions and clinical implication of the investigations are as follows: The combination of combined intra-arterial chemotherapy followed by radiation leads to an increased median survival with more long term survivors in patients with anaplastic astrocytomas and in patients older than 40 years with astrocytomas. In patients with glioblastoma multiforme, this modality of treatment do not improve median survival, but an increased number of long-term survivors may be seen. Patients younger than 40 years with astrocytomas do not benefit from this modality of treatment. A parallelism exists between sensitivity to chemotherapy and response to radiotherapy. Patients who will benefit from the treatment may be selected early, normally two months after treatment start. Combining intra-arterial chemotherapy and radiation does not lead to an increased incidence of adverse CNS reactions. Specific transient abnormalities in the brain may occur during the first year after treatment and may be misinterpreted as tumour recurrence. EEG may be valuable in predicting adverse CNS reactions following treatment. Nuclear brain scan may be of valuable in selecting the patients who are in danger of developing adverse CNS reactions. Intra-arterial chemotherapy does have an effect in patients with brain tumours who have recurrent tumour after radiation. The most important prognostic factors are age, corticosteroid dependency at treatment start, performance status, histology and frontal lobe location. 103 refs., 2 tabs

  7. Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral Effects.

    Science.gov (United States)

    Cerri, Silvia; Greco, Rosaria; Levandis, Giovanna; Ghezzi, Cristina; Mangione, Antonina Stefania; Fuzzati-Armentero, Marie-Therese; Bonizzi, Arianna; Avanzini, Maria Antonietta; Maccario, Rita; Blandini, Fabio

    2015-09-01

    Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for Parkinson's disease (PD) and systemic administration of these cells has been tested in preclinical and clinical studies. However, no information on survival and actual capacity of MSCs to reach the brain has been provided. In this study, we evaluated homing of intraarterially infused rat MSCs (rMSCs) in the brain of rats bearing a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract, to establish whether the toxin-induced damage is sufficient to grant MSC passage across the blood-brain barrier (BBB) or if a transient BBB disruption is necessary. The rMSC distribution in peripheral organs and the effects of cell infusion on neurodegenerative process and motor deficits were also investigated. rMSCs were infused 14 days after 6-OHDA injection. A hyperosmolar solution of mannitol was used to transiently permeabilize the BBB. Behavioral impairment was assessed by adjusting step test and response to apomorphine. Animals were sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable delivery of rMSCs to the brain of 6-OHDA-lesioned animals can be obtained only after mannitol pretreatment. A notable percentage of infused cells accumulated in peripheral organs. Infusion of rMSCs did not modify the progression of 6-OHDA-induced damage or the motor impairment at the stepping test, but induced progressive normalization of the pathological response (contralateral turning) to apomorphine administration. These findings suggest that many aspects should be further investigated before considering any translation of MSC systemic administration into the clinical setting for PD treatment. This study demonstrates that mesenchymal stem cells infused through the carotid artery do not efficiently cross the blood-brain barrier in rats with a Parkinson's disease-like degeneration of nigrostriatal neurons, unless a permeabilizing agent (e.g., mannitol) is used. The infusion

  8. The role of low dose cisplatin plus 5-fluorouracil for treatment of recurrent and/or advanced squamous cell carcinoma of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Kohno, Naoyuki; Kitahara, Satoshi; Tamura, Etsuyo; Tanabe, Tetuya; Nakanoboh, Manabu [National Defence Medical Coll., Tokorosawa, Saitama (Japan); Kawada, Masahiro; Shirasaka, Tetsuhiko

    2000-05-01

    To improve survival rate in advanced head and neck cancer, we scheduled 90 patients to receive low dose cisplatin plus 5-fluorouracil regimen as neoadjuvant (NAC), concurrent (CC), adjuvant (AC), and second line chemotherapy (SC) setting. Our regimen consisted of cisplatin (CDDP 5 mg/m{sup 2}/1 hr infusion on days 1-5, 8-12, 15-19, 22-26) and 5-fluorouracil (5-FU 200 mg/m{sup 2}/24 hr infusion or oral administration of tegaful-uracil (UFT-E) 400 mg/body on days 1-28). The concurrent chemoradiotherapy consisted of conventional irradiation with 1.6-2.0 Gy/day on five days per week up to a total dose around 60 Gy, and CDDP 3 mg/m{sup 2} by intravenous infusion over 1 hour plus 5-FU 150 mg/m{sup 2} by intravenous infusion over 24 hours per day on five days per week. For SC, 24 patients evaluable for response, 4 CR and 6 PR with RR of 42% were achieved. For NAC, 14 patients were evaluated for response, 2 CR and 7 PR were achieved. CC was indicated for locally unresectable cases. Of the 33 patients evaluable for response were 17 CR and 9 PR with RR of 79%. Dose limiting toxicities for chemotherapy were anemia and leukopenia and chemoradiotherapy was mucositis. Our treatment modality showed marginal toxicity and good response. Moreover, our regimen could be given in an outpatient setting safely so quality of life for patients was identical. We concluded that for advanced head and neck cancer, these treatment options were effective for second line and adjuvant setting. Chemoradiotherapy with this regimen also gave a impact for improving local control and survival period for locally unresectable cases. (author)

  9. Possible therapeutic use of radiolabeled cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Alexandre S.; Bernardes, Felipe D.; Gonçalves, Natalia A.Z., E-mail: asleal@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    The cisplatin, cis-diamminedichloroplatinum (II), (NH{sub 3}){sub 2}PtCl{sub 2} or (CDDP) is a very common chemotherapeutical agent used in the treatment of ovary, lungs, testicle, head and neck carcinoma. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. However, because of the drug resistance and numerous undesirable side effects, a lot of work involving new formulations or administration of the CDDP has been done. In this work, we present a preliminary discussion about the possibilities of using the radiolabeled CDDP or CDDP⁎, as new alternative therapy. The works based on previous very positive in-vitro results of using the CDDP⁎ compared to CDDP in the cytotoxic effect of some kind of tumor cells. The preparation and characterization of the CDDP⁎ as well as the dose of CDDP⁎ required are presented and discussed. (author)

  10. Raman scattering of Cisplatin near silver nanoparticles

    Science.gov (United States)

    Mirsaleh-Kohan, Nasrin; Duplanty, Michael; Torres, Marjorie; Moazzezi, Mojtaba; Rostovtsev, Yuri V.

    2018-03-01

    The Raman scattering of Cisplatin (the first generation of anticancer drugs) has been studied. In the presence of silver nanoparticles, strong modifications of Raman spectra have been observed. The Raman frequencies have been shifted and the line profiles are broadened. We develop a theoretical model to explain the observed features of the Raman scattering. The model takes into account self-consistently the interaction of molecules with surface plasmonic waves excited in the silver nanoparticles, and it provides a qualitative agreement with the observed Raman spectra. We have demonstrated that the using silver nanoparticles can increase sensitivity of the technique, and potentially it has a broader range of applications to both spectroscopy and microscopy.

  11. Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yu-Chi Su

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients.

  12. Cisplatin-Rich Polyoxazoline-Poly(aspartic acid) Supramolecular Nanoparticles.

    Science.gov (United States)

    Zhang, Peng; Yuan, Kangjun; Li, Cheng; Zhang, Xiaoke; Wu, Wei; Jiang, Xiqun

    2017-12-01

    Cisplatin-rich supramolecular nanoparticles are constructed through the supramolecular inclusion interaction between the admantyl (Ad)-terminated poly(aspartic acid) (Ad-P(Asp)) and the β-cyclodextrin (β-CD)-terminated poly(2-methyl-2-oxazoline). In the formation of the nanoparticles, the β-CD/admantane inclusion complex integrates poly(2-methyl-2-oxazoline) and poly(aspartic acid) chains to form pseudoblock copolymers, followed by the coordination between carboxyl groups in P(Asp) block and cisplatin. This coordination interaction drives the formation of nanoparticle and enables cisplatin incorporated into the nanoparticles. The spherical cisplatin-rich supramolecular nanoparticles have 53% cisplatin-loading content, good stability, and effective inhibition of the cell proliferation when it is tested in H22 cancer cells. Near-infrared fluorescence imaging of tumor bearing mice reveals that the cisplatin-rich nanoparticles can target the tumor in vivo effectively. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. YAP promotes tumorigenesis and cisplatin resistance in neuroblastoma.

    Science.gov (United States)

    Yang, Chao; Tan, Juan; Zhu, Jun; Wang, Shan; Wei, Guanghui

    2017-06-06

    The transcriptional co-activator Yes-associated protein (YAP) is essential for Hippo pathway-driven tumorigenesis in various cancers. However, the expression and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was highly expressed in Neuroblastoma (NB) and expression levels correlated with advanced tumor staging. Knockdown of YAP significantly impaired neuroblastoma proliferation, tumorigenesis, and invasion in vitro. Injection of the YAP inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor growth by efficiently downregulating YAP expression in tumors. Additionally, less proliferative and more apoptotic cells were found in the Peptide 17 treatment group. Furthermore, YAP inhibition significantly inhibited cisplatin-resistant neuroblastoma proliferation, tumorigenesis, and invasion in vitro. The combination of Peptide 17 with low-dose cisplatin efficiently impaired cisplatin-resistant NB subcutaneous tumor growth, being as effective as high-dose cisplatin. Notably, the combination therapy caused lesser liver toxicity in mice compared to the high-dose cisplatin treatment group. Collectively, this work identifies YAP as a novel regulator of neuroblastoma proliferation, tumorigenesis, and invasion and indicates that YAP is a potential therapeutic target for cisplatin-resistant neuroblastoma.

  14. The synthesis, structure-toxicity relationship of cisplatin derivatives for the mechanism research of cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Hu, Jing; Wu, Tian-Ming; Li, Hong-Ze; Zuo, Ze-Ping; Zhao, Ying-Lan; Yang, Li

    2017-08-01

    Cisplatin is a widely used antineoplastic drug, while its nephrotoxicity limits the clinical application. Although several mechanisms contributing to nephrotoxicity have been reported, the direct protein targets are unclear. Herein we reported the synthesis of 29 cisplatin derivatives and the structure-toxicity relationship (STR) of these compounds with MTT assay in human renal proximal tubule cells (HK-2) and pig kidney epithelial cells (LLC-PK1). To the best of our knowledge, this study represented the first report regarding the structure-toxicity relationship (STR) of cisplatin derivatives. The potency of biotin-pyridine conjugated derivative 3 met the requirement for target identification, and the preliminary chemical proteomics results suggested that it is a promising tool for further target identification of cisplatin-induced nephrotoxicity. Copyright © 2017. Published by Elsevier Ltd.

  15. Strontium-rubidium infusion pump with in-line dosimetry

    International Nuclear Information System (INIS)

    Barker, S.L.; Loberg, M.D.

    1986-01-01

    A strontium-rubidium infusion system is described which consists of: (a) means for generating rubidium 82 in a solution which can be infused into a patient; (b) means for infusing the solution into a patient; (c) means for measuring the radioactivity present in the solution as it is infused into the patient; and (d) means for controlling the means for infusing in response to the amount of radioactivity which has been infused into the patient

  16. The effect of glucagon on infusion cholangiography

    International Nuclear Information System (INIS)

    Evans, A.F.; Whitehouse, G.H.

    1979-01-01

    An assessment has been made of the effects of glucagon on biliary tract opacification during intravenous cholangiography. Two series of infusion cholangiograms were obtained at two investigating centres designated A and B. In series A, 41 patients had ioglycamide infusions at a rate of 0.2833 g min -1 over 1 h. In series B, 31 patients had ioglycamide infusions at a rate of 0.3886 g min -1 over 30 min. Radiographs were taken in both series immediately at the end of the infusion, 10 min later and 30 min after the infusion. Two mg of intravenous glucagon was injected into alternate cases in both series A and B immediately after the first radiograph was taken at the completion of the ioglycamide infusion. Two observers in each series then assessed the radiographic opacification of the biliary system without prior knowledge of which patients had received the glucagon. Delineation of the biliary system was considered better in both series in those patients who received glucagon when compared with the controls. Gallbladder opacification was definitely increased in series A in those receiving glucagon, and a similar tendency was shown in series B. The amount of contrast in the upper intestine was increased in series A in the glucagon group, but not in series B. It is concluded that glucagon improves visualisation of the biliary tract, especially the gallbladder at infusion cholangiography. (author)

  17. Pharmacokinetics and toxicology of continuously infused nitroimidazoles

    International Nuclear Information System (INIS)

    Eifel, P.J.; Brown, J.M.

    1984-01-01

    The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C 3 H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures

  18. Infliximab-Related Infusion Reactions: Systematic Review

    Science.gov (United States)

    Ron, Yulia; Kivity, Shmuel; Ben-Horin, Shomron; Israeli, Eran; Fraser, Gerald M.; Dotan, Iris; Chowers, Yehuda; Confino-Cohen, Ronit; Weiss, Batia

    2015-01-01

    Objective: Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. Methods: We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. Results: We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. Conclusions: There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms. PMID:26092578

  19. Biodegradable polymeric system for cisplatin delivery: Development, in vitro characterization and investigation of toxicity profile

    International Nuclear Information System (INIS)

    Alam, Noor; Khare, Vaibhav; Dubey, Ravindra; Saneja, Ankit; Kushwaha, Manoj; Singh, Gurdarshan; Sharma, Neelam; Chandan, Balkrishan; Gupta, Prem N.

    2014-01-01

    Cisplatin is one of the most potent anticancer agent used in the treatment of various solid tumors, however, its clinical use is limited due to severe adverse effects including nephrotoxicity. In this investigation cisplatin loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles were developed and characterized for various in vitro characteristics including size distribution, zeta potential, drug loading and release profile. PLGA nanoparticles were successfully developed as investigated using scanning electron microscopy and exhibited average particles size and zeta potential as 284.8 nm and − 15.8 mV, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated an absence of any polymer–drug interactions. Cisplatin nanoparticles exhibited in vitro anticancer activity against A549 cells comparable to that of cisplatin solution. The biodistribution study in mice indicated that the kidney cisplatin level was significantly (p < 0.01) lower with cisplatin nanoparticles than cisplatin solution. Following two cycles of cisplatin treatment, a week apart, blood urea nitrogen level was found to be higher in case of cisplatin solution as compared to cisplatin nanoparticles. Further, there was a significant (p < 0.01) increase in plasma creatinine level in case of cisplatin solution as compared to cisplatin nanoparticles. Histopathological examination of kidney from cisplatin nanoparticles treated group revealed no kidney damage, however, a sign of nephrotoxicity was observed in the case of cisplatin solution. The results suggest that PLGA nanoparticle based formulation could be a potential option for cisplatin delivery. - Highlights: • Cisplatin is detected by LCMS following complexation with DDTC. • Nanoparticles showed lower cisplatin accumulation in the kidney. • Nephrotoxicity was evaluated by BUN and creatinine level and by histopathology. • Nanoparticles exhibited lower nephrotoxicity

  20. Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1-regulated cancer metabolism.

    Science.gov (United States)

    Ai, Zhihong; Lu, Yang; Qiu, Songbo; Fan, Zhen

    2016-04-01

    Cisplatin is currently one of the most effective chemotherapeutic drugs used for treating ovarian cancer; however, resistance to cisplatin is common. In this study, we explored an experimental strategy for overcoming cisplatin resistance of human ovarian cancer from the new perspective of cancer cell metabolism. By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. We found that cisplatin downregulated the level of the regulatable α subunit of HIF-1, HIF-1α, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1α degradation but did not downregulate HIF-1α in their cisplatin-resistant counterparts. Overexpression of a degradation-resistant HIF-1α (HIF-1α ΔODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1α or pharmacological promotion of HIF-1α degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. We further demonstrated that knockdown of HIF-1α improved the response of cisplatin-resistant ovarian cancer cells to cisplatin by redirecting the aerobic glycolysis in the resistant cancer cells toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of reactive oxygen species. Our findings suggest that the HIF-1α-regulated cancer metabolism pathway could be a novel target for overcoming cisplatin resistance in ovarian cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Bradykinin receptor blockade restores the baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal failure rats.

    Science.gov (United States)

    Abdulla, M H; Duff, M; Swanton, H; Johns, E J

    2016-11-01

    This study investigated the effect of renal bradykinin B1 and B2 receptor blockade on the high- and low-pressure baroreceptor reflex regulation of renal sympathetic nerve activity (RSNA) in rats with cisplatin-induced renal failure. Cisplatin (5 mg/kg) or saline was given intraperitoneally 4 days prior to study. Following chloralose/urethane anaesthesia, rats were prepared for measurement of mean arterial pressure (MAP), heart rate and RSNA and received intrarenal infusions of either Lys-[des-Arg 9 , Leu 8 ]-bradykinin (LBK), a bradykinin B1 receptor blocker, or bradyzide (BZ), a bradykinin B2 receptor blocker. RSNA baroreflex gain curves and renal sympatho-inhibitory responses to volume expansion (VE) were obtained. In the control and renal failure groups, basal MAP (89 ± 3 vs. 80 ± 8 mmHg) and RSNA (2.0 ± 0.3 vs. 1.7 ± 0.6 μV.s) were similar but HR was lower in the latter group (331 ± 8 vs. 396 ± 9 beats/min). The baroreflex gain for RSNA in the renal failure rats was 39% (P renal failure rats. Intrarenal LBK infusion in the renal failure rats normalized the VE induced renal sympatho-inhibition whereas BZ only partially restored the response. These findings suggest that pro-inflammatory bradykinin acting at different receptors within the kidney generates afferent neural signals which impact differentially within the central nervous system on high- and low-pressure regulation of RSNA. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  2. Concurrent hyperfractionated accelerated radiotherapy with 5-FU and once weekly cisplatin in locally advanced head and neck cancer. The 10-year results of a prospective phase II trial

    Energy Technology Data Exchange (ETDEWEB)

    Budach, V.; Boehmer, D.; Badakhshi, H.; Jahn, U.; Stromberger, C. [Campus Virchow Klinikum, Charite Universitaetsmedizin Berlin, Department for Radiooncology, Clinic for Radiooncology, Berlin (Germany); Becker, E.T. [Charite Universitaetsmedizin, Department of Otorhinolaryngology, Berlin (Germany); Wernecke, K.D. [Sostana Statistics GmbH, Charite Universitaetsmedizin Berlin, Berlin (Germany)

    2014-03-15

    In this study, the acute toxicity and long-term outcome of a hyperfractionated accelerated chemoradiation regimen with cisplatin/5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinomas of head and neck were evaluated. From 2000-2002, 38 patients with stage III (5.3 %) and stage IV (94.7 %) head and neck cancer were enrolled in a phase II study. Patients received hyperfractionated-accelerated radiotherapy with 72 Gy in 15 fractions of 2 Gy followed by 1.4 Gy twice daily with concurrent, continuous infusion 5-FU of 600 mg/m{sup 2} on days 1-5 and 6 cycles of weekly cisplatin (30 mg/m{sup 2}). Acute toxicities (CTCAEv2.0), locoregional control (LRC), metastases-free (MFS), and overall survival (OS) were analyzed and exploratively compared with the ARO 95-06 trial. Median follow-up was 11.4 years (95 % CI 8.6-14.2) and mean dose 71.6 Gy. Of the patients, 82 % had 6 (n = 15) or 5 (n = 16) cycles of cisplatin, 5 and 2 patients received 4 and 3 cycles, respectively. Grade 3 anemia, leukopenia, and thrombocytopenia were observed in 15.8, 15.8, and 2.6 %, respectively. Grade 3 mucositis in 50 %, grade 3 and 4 dysphagia in 55 and 13 %. The 2-, 5-, and 10-year LRC was 65, 53.6, and 48.2 %, the MFS was 77.5, 66.7, and 57.2 % and the OS 59.6, 29.2, and 15 %, respectively. Chemoradiation with 5-FU and cisplatin seems feasible and superior in terms of LRC and OS to the ARO 95-06C-HART arm at 2 years. However, this did not persist at the 5- and 10-year follow-ups. (orig.) [German] Untersuchung der Akuttoxizitaet und des Langzeitueberlebens einer hyperfraktioniert-akzelerierten simultanen Radiochemotherapie mit Cisplatin/5-Fluorouracil (5-FU) bei Patienten mit lokal fortgeschrittenen Kopf-Hals-Tumoren. Von 2000 bis 2002 wurden 38 Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region im Stadium III (5,3 %) und IV (94,7 %) eingeschlossen. Es erfolgte eine simultane hyperfraktionierte akzelerierte Radiochemotherapie mit 72 Gy in 15 Fraktionen a 2 Gy

  3. Photonuclear production and antitumor effect of radioactive cisplatin (195mPt)

    International Nuclear Information System (INIS)

    Elena Nicole Bodnar; Mikola Petrovich Dikiy; Elena Pavlivna Medvedeva

    2015-01-01

    Incorporation of a radioisotope of platinum prepared with sufficiently high specific activity into the cisplatin molecule may significantly enhance the antitumor effect and decrease the therapeutically effective dosage of cisplatin chemotherapy. The objectives of our research were to develop a method of preparation of 195m Pt with high specific activity and then implement the synthesis of 195m Pt-cisplatin for in vitro and animal studies of its antitumor effect in comparison with non-radioactive cisplatin. Investigation of cisplatin and 195m Pt-cisplatin on Ehrlich solid carcinoma demonstrated tumor growth inhibition of 35 and 65 %, respectively, indicating 195m Pt-cisplatin is more effective than non-radioactive cisplatin in antitumor activity. (author)

  4. Discovery – Cisplatin and The Treatment of Testicular and Other Cancers

    Science.gov (United States)

    Prior to the discovery of cisplatin in 1965, men with testicular cancer had few medical options. Now, thanks to NCI research, cisplatin and similar chemotherapy drugs are known for curing testicular and other forms of cancer.

  5. Antitumorigenic Evaluation of Thalidomide Alone and in Combination with Cisplatin in DBA2/J Mice

    Directory of Open Access Journals (Sweden)

    Jean Marie B. Ruddy

    2002-01-01

    thalidomide failed to inhibit cell proliferation. However, cisplatin treatment with or without thalidomide, significantly inhibited the multiplication of both cell lines in a dose dependent manner. Thalidomide does not appear to be a beneficial adjuvant to cisplatin treatment.

  6. Local intra-arterial thrombolysis in the carotid territory: does recanalization depend on the thromboembolus type?

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H.; Wilhelm, K.; Flacke, S.; Schild, H.H. [Department of Radiology/Neuroradiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany); Hartmann, A.; Pohl, C.; Klockgether, T. [Department of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany); Omran, H. [Department of Cardiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany)

    2002-08-01

    Little is known about whether recanalization of carotid territory occlusions by local intra-arterial thrombolysis (LIT) depends on the type of the occluding thromboembolus. We retrospectively analysed the records of 62 patients with thromboembolic occlusions of the intracranial internal carotid artery (ICA) bifurcation or the middle cerebral artery who were undergoing LIT with urokinase within 6 h of symptom onset. We determined the influence of thromboembolus type (according to the TOAST criteria), thromboembolus location, leptomeningeal collaterals, time interval from onset of symptoms to onset of thrombolysis, and patient's age on recanalization. The thromboembolus type was atherosclerotic in six patients, cardioembolic in 29, of other determined etiology in four, and of undetermined etiology in 23 patients. Thirty-three (53%) thromboembolic occlusions were recanalized. The thromboembolus location but not the TOAST stroke type nor other parameters affected recanalization. In the TOAST group of patients with cardioembolic occlusions recanalization occurred significantly less frequently when transoesophageal echocardiography showed cardiac thrombus. The present study underlines the thromboembolus location as being the most important parameter affecting recanalization. The fact that thromboembolic occlusions originating from cardiac thrombi had a lower likelihood of being resolved by thrombolysis indicates the thromboembolus type as another parameter affecting recanalization. (orig.)

  7. Local intra-arterial thrombolysis in the carotid territory: does recanalization depend on the thromboembolus type?

    International Nuclear Information System (INIS)

    Urbach, H.; Wilhelm, K.; Flacke, S.; Schild, H.H.; Hartmann, A.; Pohl, C.; Klockgether, T.; Omran, H.

    2002-01-01

    Little is known about whether recanalization of carotid territory occlusions by local intra-arterial thrombolysis (LIT) depends on the type of the occluding thromboembolus. We retrospectively analysed the records of 62 patients with thromboembolic occlusions of the intracranial internal carotid artery (ICA) bifurcation or the middle cerebral artery who were undergoing LIT with urokinase within 6 h of symptom onset. We determined the influence of thromboembolus type (according to the TOAST criteria), thromboembolus location, leptomeningeal collaterals, time interval from onset of symptoms to onset of thrombolysis, and patient's age on recanalization. The thromboembolus type was atherosclerotic in six patients, cardioembolic in 29, of other determined etiology in four, and of undetermined etiology in 23 patients. Thirty-three (53%) thromboembolic occlusions were recanalized. The thromboembolus location but not the TOAST stroke type nor other parameters affected recanalization. In the TOAST group of patients with cardioembolic occlusions recanalization occurred significantly less frequently when transoesophageal echocardiography showed cardiac thrombus. The present study underlines the thromboembolus location as being the most important parameter affecting recanalization. The fact that thromboembolic occlusions originating from cardiac thrombi had a lower likelihood of being resolved by thrombolysis indicates the thromboembolus type as another parameter affecting recanalization. (orig.)

  8. Intra-arterial blood pressure monitoring in the evaluation of the hypertensive athlete.

    Science.gov (United States)

    Palatini, P; Mos, L; Mormino, P; Munari, L; Del Torre, M; Valle, F; Scaldalai, E; Pessina, A C

    1990-04-01

    To compare the blood pressure (BP) changes during a long-distance run with those during bicycle ergometry, nine normotensive and 18 hypertensive joggers were studied by means of ambulatory intra-arterial monitoring. In all subjects the ergometric test caused a progressive increase in systolic and little change in diastolic BP. Exertional BP levels were closely related to pre-exercise baseline values (P less than 0.001). A different BP pattern was observed during track running, as a sharp rise in systolic BP reaching maximum values 2-4 min after the start was recorded. Subsequently, systolic BP progressively declined throughout the run, only to increase again during the final sprint. Diastolic BP fell markedly at the onset of the run and then remained substantially stable throughout. A poor relationship was observed between the BP values at peak exercise and baseline levels (P less than 0.05) as the normotensives showed a significantly higher BP response than the hypertensives. On the contrary, during the ergometric test a parallel increase in BP was recorded in the normotensive and the hypertensive joggers. No correlation was found between the BP response to track running and to bicycle ergometry. These results indicate that the BP response to a standard stress test is not predictive of the BP changes determined by a long-distance run. The BP increase with strenuous effort seems to be reduced in hypertensive individuals, probably because of latent impairment of cardiac performance.

  9. TiO2microspheres containing magnetic nanoparticles for intra-arterial hyperthermia.

    Science.gov (United States)

    Kanetaka, Hiroyasu; Liu, Gengci; Li, Zhixia; Miyazaki, Toshiki; Furuya, Maiko; Kudo, Tada-Aki; Kawashita, Masakazu

    2017-11-01

    Magnetic microspheres measuring 15-35 µm in diameter are believed to be useful for intra-arterial hyperthermia. In this study, we attempted to prepare titanium dioxide (TiO 2 ) microspheres containing magnetic nanoparticles (MNPs). MNP-containing TiO 2 microspheres with diameters of approximately 30 µm were successfully obtained by sol-gel reaction of titanium tetraisopropoxide in a water-in-oil emulsion with added cosurfactant of 1-butanol and subsequent heat treatment at 200°C. The microspheres showed ferrimagnetism owing to high content of MNPs in approximately 60 wt % and had a low-crystalline TiO 2 matrix. Furthermore, the agar phantom was heated to above 43°C after approximately 1 min under an alternating magnetic field of 100 kHz and 300 Oe and showed in vitro biocompatibility similar to that of MNP-free TiO 2 microspheres. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2308-2314, 2017. © 2016 Wiley Periodicals, Inc.

  10. Outcome of intra-arterial chemotherapy for retinoblastoma and its influencing factors: a retrospective study.

    Science.gov (United States)

    Chen, Miaojuan; Jiang, Hua; Zhang, Jing; Shen, Gang; Jiang, Yizhou; Li, Haibo; Liu, Zhenyin

    2017-09-01

    Intra-arterial chemotherapy (IAC) has become an essential technique for the treatment of advanced and relapsed intra-ocular retinoblastoma. The outcome of IAC for retinoblastoma is influenced by a variety of medical and non-medical factors. In this study, we aimed to examine the outcome of IAC and determine the factors influencing clinical outcome. A total of 107 eyes of 73 patients with retinoblastoma undergoing IAC between January 2011 and April 2013 were retrospectively reviewed for clinical outcomes. The factors influencing clinical outcomes were determined using univariate and multivariate analyses. After IAC, an overall globe salvage rate of 78.5% was observed during follow-up periods. Specifically, globe salvage was achieved in Group B (100%), Group C (100%), Group D (78.6%), and Group E (62%). Short-term ocular adverse events included eyelid oedema (14%), bulbar conjunctiva congestion (29.9%) and excessive tearing (9.3%). Long-term complications included vitreous haemorrhage (8.4%), subretinal haemorrhage (9.3%), retinal vasculopathy (7.5%) and ophthalmic artery spasm with reperfusion (4.7%). Univariate and multivariate analyses showed that the globe salvage of IAC was significantly associated with tumour staging and previous treatment (p retinoblastoma. Patients with advanced retinoblastoma and previous failed treatment may have a poor outcome after IAC. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Favorable outcome of alternate systemic and intra-arterial chemotherapy for retinoblastoma.

    Science.gov (United States)

    Hahn, Seung Min; Kim, Hyo Sun; Kim, Dong Joon; Lee, Sung Chul; Lyu, Chuhl Joo; Han, Jung Woo

    2016-02-01

    The recent trend of treatment for retinoblastoma is to salvage the eye globes as well as achieving patients' survival. Intra-arterial chemotherapy (IAC) is one of the current standard treatment; however, it cannot exclude the risk of occult micrometastases in the central nervous system in advanced-stage retinoblastoma. Alternate fashion of intravenous chemotherapy (IVC) and IAC strategy was developed to increase the eye salvage rate and to reduce the metastatic risk. Between January 2012 and December 2014, 13 eyes of 12 patients with newly diagnosed retinoblastoma received alternate chemotherapy using IVC and IAC in Yonsei Cancer Center. Eye salvage rate was assessed by the eye preservation time, which was defined as the duration from the diagnosis to the time of enucleation. Total 13 eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group B (n = 1, 7.7%), group C (n = 2, 15.4%), group D (n = 5, 38.5%), or group E (n = 5, 38.5%). IAC was performed, 3 to 5 times (median: 4 times) for each eye, total 54 times. Five to 15 courses (median: 8 courses) of systemic chemotherapy were performed in the patients. During the median follow-up period of 30.4 months, overall eye salvage rate was 63.9 ± 14.7%. All patients survived. The treatment was tolerable without significant complications. These results showed that primary alternate IVC-IAC was tolerable and effective for retinoblastoma.

  12. Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment

    Directory of Open Access Journals (Sweden)

    Jason A. Ellis

    2015-01-01

    Full Text Available Effective treatment for glioblastoma (GBM will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed.

  13. Clinical application of cerebral circulation time measured by intra-arterial digital subtraction angiography

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Yoshikazu; Shima, Takeshi; Nishida, Masahiro; Yamane, Kanji; Okita, Shinji; Yoshida, Akira; Naoe, Yasutaka; Shiga, Naoko (Chugoku Rosai Hospital, Hiroshima (Japan))

    1994-08-01

    Digital subtraction angiography (DSA) made it possible not only to visualize the intracranial fine vasculature but also measure the density of contrast medium at the arbitrary region of interest (ROI). In this study we applied this intra-arterial DSA (IA-DSA) to measure cerebral circulation time by obtaining time-density curve at the two ROI's at the C3-C4 portion and the Rolandic vein. Circulation time was defined by the time difference between the peak optical density time at the two sites. The control value of circulation time was 3.4 sec on the average, which correlated with the age of cases. In patients with occlusive cerebrovascular diseases such as carotid arterial occlusion or with mass lesions such as hematoma and brain tumor, circulation time was significantly delayed. On the contrary, circulation time in arteriovenous malformation was demonstrated to be very short. Additionally circulation time was investigated in subarachnoid hemorrhage due to ruptured aneurysm. Circulation time in patients with none, slight to moderate and severe vasospasm following subarachnoid hemorrhage were 3.6, 4.3 and 6.8 sec on the average, respectively. And ten patients presenting with low densitity area on CT scans showed significantly long circulation time, 7.0 sec on the average. From these studies cerebral circulation time by IA-DSA would be one of the useful methods to clarify cerebral hemodynamics. (author).

  14. Carbon Nanotube Infused Launch Vehicle Structures

    Data.gov (United States)

    National Aeronautics and Space Administration — For the past 5 years Orbital ATK has been investing in, prototyping, and testing carbon nanotube infused composite structures to evaluate their impact on launch...

  15. Concomitant weekly cisplatin and radiotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Homma, Akihiro; Inamura, Naoya; Oridate, Nobuhiko

    2011-01-01

    The most common chemoradiotherapy regimen is high-dose (100 mg/m 2 ) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer. Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m 2 ) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m 2 cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%). Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy. (author)

  16. Phosphodiester-mediated reaction of cisplatin with guanine in oligodeoxyribonucleotides.

    Science.gov (United States)

    Campbell, Meghan A; Miller, Paul S

    2008-12-02

    The cancer chemotherapeutic agent cis-diamminedichloroplatinum(II) or cisplatin reacts primarily with guanines in DNA to form 1,2-Pt-GG and 1,3-Pt-GNG intrastrand cross-links and, to a lesser extent, G-G interstrand cross-links. Recent NMR evidence has suggested that cisplatin can also form a coordination complex with the phosphodiester internucleotide linkage of DNA. We have examined the effects of the phosphodiester backbone on the reactions of cisplatin with oligodeoxyribonucleotides that lack or contain a GTG sequence. Cisplatin forms a stable adduct with TpT that can be isolated by reversed phase HPLC. The cis-Pt-TpT adduct contains a single Pt, as determined by atomic absorption spectroscopy (AAS) and by electrospray ionization mass spectrometry (ESI-MS), and is resistant to digestion by snake venom phosphodiesterase. Treatment of the adduct with sodium cyanide regenerates TpT. Similar adduct formation was observed when T(pT)(8) was treated with cisplatin, but not when the phosphodiester linkages of T(pT)(8) were replaced with methylphosphonate groups. These results suggest that the platinum may be coordinated with the oxygens of the thymine and possibly with those of the phosphodiester group. As expected, reaction of a 9-mer containing a GTG sequence with cisplatin yielded an adduct that contained a 1,3-Pt-GTG intrastrand cross-link. However, we found that the number and placement of phosphodiesters surrounding a GTG sequence significantly affected intrastrand cross-link formation. Increasing the number of negatively charged phosphodiesters in the oligonucleotide increased the amount of GTG platination. Surrounding the GTG sequence with nonionic methylphosphonate linkages inhibited or eliminated cross-link formation. These observations suggest that interactions between cisplatin and the negatively charged phosphodiester backbone may play an important role in facilitating platination of guanine nucleotides in DNA.

  17. MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines

    Directory of Open Access Journals (Sweden)

    Kumar Smriti

    2011-09-01

    Full Text Available Abstract Background Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Methods The present study is focused on identifying the differential expression of regulatory microRNAs (miRNAs between cis-platin sensitive (A2780, and cis-platin resistant (A2780/CP70 cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin. Differential expression patterns of miRNA between cis-platin sensitive and cis-platin resistant cell lines were analyzed using novel LNA technology. Results Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and 6 were down regulated as compared to cis-platin sensitive A2780 cells. Our microRNA data was further validated by quantitative real-time PCR for these selected miRNAs. Ingenuity Pathway Analysis (IPA and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis was performed for the selected miRNAs and their putative targets to identify the potential pathways and networks involved in cis-platin resistance. Conclusions Our data clearly showed the differential expression of 11 miRNAs in cis-platin resistant cells, which could potentially target many important pathways including MAPK, TGF-β signaling, actin cytoskeleton, ubiquitin mediated

  18. Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in Carbohydrate Residues

    OpenAIRE

    Dilek Akşit; Alper Yazıcı; Hasan Akşit; Esin S. Sarı; Arzu Yay; Onur Yıldız; Adil Kılıç; Sıtkı S. Ermiş; Kamil Seyrek

    2016-01-01

    Background: Investigate alterations in the expression and localization of carbohydrate units in rat retinal cells exposed to cisplatin toxicity. Aims: The aim of the study was to evaluate putative protective effects of selenium on retinal cells subjected to cisplatin. Study Design: Animal experiment. Methods: Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2. Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of each rat was ...

  19. Cisplatin- vs. oxaliplatin-based radiosensitizing chemotherapy for squamous cell carcinoma of the esophagus. A comparison of two preoperative radiochemotherapy regimens

    International Nuclear Information System (INIS)

    Fakhrian, K.; Ordu, A.D.; Molls, M.; Haller, B.; Theisen, J.; Lordick, F.; Bisof, V.; Geinitz, H.

    2014-01-01

    To compare the outcomes of two neoadjuvant radiochemotherapy (N-RCT) regimens for squamous cell carcinoma of the esophagus (ESCC). The standard N-RCT regimen for ESCC at our institution between 2002 and 2011 was a total dose of 45 Gy (1.8-Gy fractions) with concomitant cisplatin (20 mg/m 2 , days 1-5 and 29-33) and 5-fluorouracil (5-FU; 225 mg/m 2 , 24 h continuous infusion on days 1-33). During the same period, a phase I/II study comparing the standard ESCC N-RCT protocol with a regimen identical except for the replacement of cisplatin with weekly oxaliplatin (40-50 mg/m 2 ) was performed at our center. The standard regimen was used to treat 40 patients; 37 received the oxaliplatin regimen. All patients subsequently underwent radical resection with reconstruction according to tumor location and two-field lymph node dissection. Median follow-up time from the start of N-RCT was 74 months (range 3-116 months). The two patient groups were comparable in terms of demographic and baseline tumor characteristics. R0 resection was achieved in 37/39 patients (95 %) in the cisplatin-based N-RCT group, compared to 24/37 (65 %) in the oxaliplatin-based group (p = 0.002). A pathological complete response (pCR) was seen in the resection specimens from 18/39 patients (46 %) in the cisplatin-based N-RCT group and in 8/37 (22 %) oxaliplatin-group patients. In the cisplatin group, 2- and 5-year overall survival (OS) rates were 67 ± 8 % and 60 ± 8 %, respectively (median OS 103 months), compared to 38 ± 8 % and 32 ± 8 %, respectively, for the oxaliplatin group (median OS 17 months; hazard ratio, HR 0.452; 95 % confidence interval, CI 0.244-0.839; p = 0.012). Oxaliplatin-based N-RCT resulted in poorer outcomes in ESCC patients and should not routinely replace cisplatin-based N-RCT. (orig.) [de

  20. Concurrent hyperfractionated accelerated radiotherapy with 5-FU and once weekly cisplatin in locally advanced head and neck cancer. The 10-year results of a prospective phase II trial

    International Nuclear Information System (INIS)

    Budach, V.; Boehmer, D.; Badakhshi, H.; Jahn, U.; Stromberger, C.; Becker, E.T.; Wernecke, K.D.

    2014-01-01

    In this study, the acute toxicity and long-term outcome of a hyperfractionated accelerated chemoradiation regimen with cisplatin/5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinomas of head and neck were evaluated. From 2000-2002, 38 patients with stage III (5.3 %) and stage IV (94.7 %) head and neck cancer were enrolled in a phase II study. Patients received hyperfractionated-accelerated radiotherapy with 72 Gy in 15 fractions of 2 Gy followed by 1.4 Gy twice daily with concurrent, continuous infusion 5-FU of 600 mg/m 2 on days 1-5 and 6 cycles of weekly cisplatin (30 mg/m 2 ). Acute toxicities (CTCAEv2.0), locoregional control (LRC), metastases-free (MFS), and overall survival (OS) were analyzed and exploratively compared with the ARO 95-06 trial. Median follow-up was 11.4 years (95 % CI 8.6-14.2) and mean dose 71.6 Gy. Of the patients, 82 % had 6 (n = 15) or 5 (n = 16) cycles of cisplatin, 5 and 2 patients received 4 and 3 cycles, respectively. Grade 3 anemia, leukopenia, and thrombocytopenia were observed in 15.8, 15.8, and 2.6 %, respectively. Grade 3 mucositis in 50 %, grade 3 and 4 dysphagia in 55 and 13 %. The 2-, 5-, and 10-year LRC was 65, 53.6, and 48.2 %, the MFS was 77.5, 66.7, and 57.2 % and the OS 59.6, 29.2, and 15 %, respectively. Chemoradiation with 5-FU and cisplatin seems feasible and superior in terms of LRC and OS to the ARO 95-06C-HART arm at 2 years. However, this did not persist at the 5- and 10-year follow-ups. (orig.) [de

  1. Infusion Antihypoxants in Children with Critical Conditions

    Directory of Open Access Journals (Sweden)

    Yu. S. Aleksandrovich

    2014-01-01

    Full Text Available Hypoxia and mitochondrial damage are a key component of the pathogenesis and tanatogenesis of a critical condition, suggesting the need for its prevention and maximally rapid elimination. Objective: to analyze the efficacy and safety of infusion antihypoxants used in critically ill children from the results of researches. Materials and methods. Available investigations dealing with infusion therapy in children and papers on the use of infusion antihypoxants in adults in 2005 to 2013 were sought in the medical databases PubMed and Cochrane Library with their free availability and analyzed. Results. The analysis included 70 trials. The pathophysiology and pathobiochemistry of hypoxia in critically ill children are given; the current principles of its correction by infusion therapy are considered in detail. Particular emphasis is placed on trials evaluating the efficacy and safety of succinic acid solutions in children. Main indications for and contraindications to their use are demonstrated. Conclusion. The use of Krebs cycle substrate-based infusion antihypoxants (malate, succinate is an effective and promising procedure for the intensive therapy and correction of hypoxia in both adults and children with critical conditions. Considering the fact that papers on the use of infusion antihypoxants in children are scanty, there is a need for further investigations. 

  2. Effect of baseline Alberta Stroke Program Early CT Score on safety and efficacy of intra-arterial treatment: a subgroup analysis of a randomised phase 3 trial (MR CLEAN)

    NARCIS (Netherlands)

    Yoo, Albert J.; Berkhemer, Olvert A.; Fransen, Puck S. S.; van den Berg, Lucie A.; Beumer, Debbie; Lingsma, Hester F.; Schonewille, Wouter J.; Sprengers, Marieke E. S.; van den Berg, René; van Walderveen, Marianne A. A.; Beenen, Ludo F. M.; Wermer, Marieke J. H.; Nijeholt, Geert J. Lycklama À; Boiten, Jelis; Jenniskens, Sjoerd F. M.; Bot, Joseph C. J.; Boers, Anna M. M.; Marquering, Henk A.; Roos, Yvo B. W. E. M.; van Oostenbrugge, Robert J.; Dippel, Diederik W. J.; van der Lugt, Aad; van Zwam, Wim H.; Majoie, Charles B. L. M.

    2016-01-01

    Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis of the

  3. Effect of baseline Alberta Stroke Program Early CT Score on safety and efficacy of intra-arterial treatment: a subgroup analysis of a randomised phase 3 trial (MR CLEAN)

    NARCIS (Netherlands)

    Yoo, A.J.; Berkhemer, O.A.; Fransen, P.S.; Berg, L.A. van den; Beumer, D.; Lingsma, H.F.; Schonewille, W.J.; Sprengers, M.E.; Berg, R. van den; Walderveen, M.A. van; Beenen, L.F.; Wermer, M.J.; Nijeholt, G.J.; Boiten, J.; Jenniskens, S.F.M.; Bot, J.C.; Boers, A.M.; Marquering, H.A.; Roos, Y.B.; Oostenbrugge, R.J. van; Dippel, D.W.; Lugt, A. van der; Zwam, W.H. van; Majoie, C.B.; et al.,

    2016-01-01

    BACKGROUND: Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis

  4. Influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia

    NARCIS (Netherlands)

    Hoogeveen, J. F.; van der Kracht, A. H.; Wondergem, J.; Gonzalez Gonzalez, D.; Haveman, J.

    1993-01-01

    The influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia was investigated. Rats received 1.7 mg/kg cisplatin i.p., twice a week for 6 weeks, up to a cumulative dose of 20.4 mg/kg. After termination of cisplatin treatment, a 5 mm segment of the nerve was locally

  5. Antitumor activity and biodistribution of cisplatin nanocapsules in nude mice bearing human ovarian carcinoma xenografts

    NARCIS (Netherlands)

    Staffhorst, R.W.H.M.; van der Born, K.; Erkelens, C.A.M.; Hamelers, I.H.L.; Peters, G.J.; Boven, E.; de Kroon, A.I.P.M.

    2008-01-01

    Cisplatin nanocapsules represent a novel lipid formulation of the anticancer drug cis-diamminedichloridoplatinum(II) (cisplatin), characterized by an unprecedented cisplatin-tolipid molar ratio, and exhibiting strongly increased in-vitro cytotoxicity compared with the free drug. In this study,

  6. Preparation and stability of lipid-coated nanocapsules of cisplatin: anionic phospholipid specificity

    NARCIS (Netherlands)

    Velinova, M. J.; Staffhorst, R. W. H. M.; Mulder, W. J. M.; Dries, A. S.; Jansen, B. A. J.; de Kruijff, B.; de Kroon, A. I. P. M.

    2004-01-01

    Cisplatin nanocapsules represent a novel lipid formulation of the anti-cancer drug cis-diamminedichloroplatinum(II) (cisplatin), in which nanoprecipitates of cisplatin are coated by a phospholipid bilayer consisting of a 1:1 mixture of zwitterionic phosphatidylcholine (PC) and negatively charged

  7. Structural changes of linear DNA molecules induced by cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhiguo, E-mail: cn.zguoliu@yahoo.com [State Engineering Laboratory of Bio-Resource Eco-Utilization, Harbin 150040 (China); Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040 (China); Key Laboratory of Forest Plant Ecology of Ministry of Education, Northeast Forestry University, Harbin 150040 (China); Liu, Ruisi; Zhou, Zhen; Zu, Yuangang; Xu, Fengjie [State Engineering Laboratory of Bio-Resource Eco-Utilization, Harbin 150040 (China); Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040 (China); Key Laboratory of Forest Plant Ecology of Ministry of Education, Northeast Forestry University, Harbin 150040 (China)

    2015-02-20

    Interaction between long DNA molecules and activated cisplatin is believed to be crucial to anticancer activity. However, the exact structural changes of long DNA molecules induced by cisplatin are still not very clear. In this study, structural changes of long linear double-stranded DNA (dsDNA) and short single-stranded DNA (ssDNA) induced by activated cisplatin have been investigated by atomic force microscopy (AFM). The results indicated that long DNA molecules gradually formed network structures, beads-on-string structures and their large aggregates. Electrostatic and coordination interactions were considered as the main driving forces producing these novel structures. An interesting finding in this study is the beads-on-string structures. Moreover, it is worth noting that the beads-on-string structures were linked into the networks, which can be ascribed to the strong DNA–DNA interactions. This study expands our knowledge of the interactions between DNA molecules and cisplatin. - Highlights: • We investigate structural changes of dsDNA and ssDNA induced by cisplatin. • AFM results indicated long dsDNA formed network, beads-on-string and aggregates. • ssDNA can form very similar structures as those of long linear dsDNA. • A possible formation process of theses novel structure is proposed.

  8. Mechanisms of Cisplatin-Induced Ototoxicity and Otoprotection

    Directory of Open Access Journals (Sweden)

    Sandeep Sheth

    2017-10-01

    Full Text Available Evidence of significant hearing loss during the early days of use of cisplatin as a chemotherapeutic agent in cancer patients has stimulated research into the causes and treatment of this side effect. It has generally been accepted that hearing loss is produced by excessive generation of reactive oxygen species (ROS in cell of the cochlea, which led to the development of various antioxidants as otoprotective agents. Later studies show that ROS could stimulate cochlear inflammation, suggesting the use of anti-inflammatory agents for treatment of hearing loss. In this respect, G-protein coupled receptors, such as adenosine A1 receptor and cannabinoid 2 receptors, have shown efficacy in the treatment of hearing loss in experimental animals by increasing ROS scavenging, suppressing ROS generation, or by decreasing inflammation. Inflammation could be triggered by activation of transient receptor potential vanilloid 1 (TRPV1 channels in the cochlea and possibly other TRP channels. Targeting TRPV1 for knockdown has also been shown to be a useful strategy for ensuring otoprotection. Cisplatin entry into cochlear hair cells is mediated by various transporters, inhibitors of which have been shown to be effective for treating hearing loss. Finally, cisplatin-induced DNA damage and activation of the apoptotic process could be targeted for cisplatin-induced hearing loss. This review focuses on recent development in our understanding of the mechanisms underlying cisplatin-induced hearing loss and provides examples of how drug therapies have been formulated based on these mechanisms.

  9. Magnetic nanoparticle hyperthermia enhancement of cisplatin chemotherapy cancer treatment.

    Science.gov (United States)

    Petryk, Alicia A; Giustini, Andrew J; Gottesman, Rachel E; Kaufman, Peter A; Hoopes, P Jack

    2013-12-01

    The purpose of this study was to examine the therapeutic effect of magnetic nanoparticle hyperthermia (mNPH) combined with systemic cisplatin chemotherapy in a murine mammary adenocarcinoma model (MTGB). An alternating magnetic field (35.8 kA/m at 165 kHz) was used to activate 110 nm hydroxyethyl starch-coated magnetic nanoparticles (mNP) to a thermal dose of 60 min at 43 °C. Intratumoral mNP were delivered at 7.5 mg of Fe/cm(3) of tumour (four equal tumour quadrants). Intraperitoneal cisplatin at 5 mg/kg body weight was administered 1 h prior to mNPH. Tumour regrowth delay time was used to assess the treatment efficacy. mNP hyperthermia, combined with cisplatin, was 1.7 times more effective than mNP hyperthermia alone and 1.4 times more effective than cisplatin alone (p hyperthermia can result in a safe and significant therapeutic enhancement for cisplatin cancer therapy.

  10. Optimizing Liposomal Cisplatin Efficacy through Membrane Composition Manipulations

    Science.gov (United States)

    Zisman, Natalia; Dos Santos, Nancy; Johnstone, Sharon; Tsang, Alan; Bermudes, David; Mayer, Lawrence; Tardi, Paul

    2011-01-01

    The first liposomal formulation of cisplatin to be evaluated clinically was SPI-077. Although the formulation demonstrated enhanced cisplatin tumor accumulation in preclinical models it did not enhance clinical efficacy, possibly due to limited cisplatin release from the formulation localized within the tumor. We have examined a series of liposomal formulations to address the in vivo relationship between cisplatin release rate and formulation efficacy in the P388 murine leukemia model. The base formulation of phosphatidylcholine: phosphatidylglycerol: cholesterol was altered in the C18 and C16 phospholipid content to influence membrane fluidity and thereby impacting drug circulation lifetime and drug retention. Phase transition temperatures (Tm) ranged from 42–55°C. The high Tm formulations demonstrated enhanced drug retention properties accompanied by low antitumor activity while the lowest Tm formulations released the drug too rapidly in the plasma, limiting drug delivery to the tumor which also resulted in low antitumor activity. A formulation composed of DSPC : DPPC : DSPG : Chol; (35 : 35 : 20 : 10) with an intermediate drug release rate and a cisplatin plasma half-life of 8.3 hours showed the greatest antitumor activity. This manuscript highlights the critical role that drug release rates play in the design of an optimized drug delivery vehicle. PMID:22312548

  11. Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Xu Cao

    2018-05-01

    Full Text Available Cisplatin is a major chemotherapeutic drug for solid tumors whereas it may lead to severe nephrotoxicity. Despite decades of efforts, effective therapies remain largely lacking for this disease. In the current research, we investigated the therapeutic effect of hydrogen polysulfide, a novel hydrogen sulfide (H2S derived signaling molecule, in cisplatin nephrotoxicity and the mechanisms involved. Our results showed that polysulfide donor Na2S4 ameliorated cisplatin-caused renal toxicity in vitro and in vivo through suppressing intracellular reactive oxygen species (ROS generation and downstream mitogen-activated protein kinases (MAPKs activation. Additionally, polysulfide may inhibit ROS production by simultaneously lessening the activation of NADPH oxidase and inducing nucleus translocation of nuclear factor erythroid 2-related factor 2 (Nrf2 in RPT cells. Interestingly, polysulfide possesses anti-cancer activity and is able to add on more anti-cancer effect to cisplatin in non-small cell lung cancer (NSCLC cell lines. Moreover, we observed that the number of sulfur atoms in polysulfide well reflected the efficacy of these molecules not only in cell protection but also cancer inhibition which may serve as a guide for further development of polysulfide donors for pharmaceutical usage. Taken together, our study suggests that polysulfide may be a novel and promising therapeutic agent to prevent cisplatin-induced nephrotoxicity.

  12. Cisplatin and radiation: Interaction probabilities and therapeutic possibilities

    International Nuclear Information System (INIS)

    Begg, A.C.

    1990-01-01

    This paper examines the probability of interactions occurring between drug lesions and radiation lesions in DNA for the cytotoxic and radiosensitizing agent cisplatin. The number of cisplatin-induced DNA adducts and radiation-induced strand breaks after a given dose of each agent are known for given cell systems, from which the probability that these lesions will interact can be estimated. Results of these calculations indicate that the probability of interaction could be high, depending on the distance over which two lesions can interact and the probability of repair of the interaction lesion. Calculated lesion numbers have been compared with known data on radiation modification, including illustrations of inconsistencies. In the second part of the paper, ways in which combined therapy with cisplatin and radiation can be improved are described. Development of methods to predict which types of tumor and which individual tumors within a given type are sensitive to the cytotoxic and radiosensitizing effects of the drug would aid rational selection of patients for combination treatments. Immunocytochemical methods sensitive enough to monitor cisplatin-DNA interactions in patients are available and may be useful in this context. The delivery and maintenance of higher tumor concentrations of radiosensitizer offers a further possibility for improvement. Studies of intratumoral injection of cisplatin have shown promise for achieving this goal while limiting normal tissue toxicity.46 references

  13. Impact of Methadone on Cisplatin Treatment of Bladder Cancer Cells.

    Science.gov (United States)

    Michalska, Marta; Schultze-Seemann, Susanne; Kuckuck, Irina; Katzenwadel, Arndt; Wolf, Philipp

    2018-03-01

    Cisplatin-based chemotherapy is the treatment of choice for advanced bladder cancer. Since many tumor cells show inherent or acquired cisplatin resistance, research is needed to improve the therapeutic efficacy. Since the analgesic methadone is discussed as being a sensitizer for chemotherapy, we tested its effects on the cisplatin treatment of bladder cancer cells. T24 and HT-1376 bladder cancer cells were incubated with cisplatin in combination with methadone. Cytotoxicity was examined using the WST-1 viability assay and induction of apoptosis was analyzed via phase-contrast microscopy, flow cytometry, and western blot analysis. Methadone was shown to enhance the cytotoxic effects of cisplatin on T24 cells based on the induction of apoptosis. In contrast, HT-1376 cells were identified as non-responders to methadone. Methadone could act as a chemosensitizer in the future treatment of advanced bladder cancer. Further research is needed to identify the underlying molecular mechanisms. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Light microscopy study of cisplatin-induced ototoxicity in rats.

    Science.gov (United States)

    de Freitas, M R; de Castro Brito, G A; de Carvalho, J V; Gomes, R M; Barreto Martins, M J; de Albuquerque Ribeiro, R

    2009-06-01

    Although most studies on animal ototoxicity employ scanning electron microscopy, all cochlear structures may be identified with light microscopy. This paper describes a simple method of histological assessment of cisplatin-induced ototoxicity in rats, and relates morphological changes to functional changes in hearing detected by distortion product evoked otoacoustic emissions. Male Wistar rats were injected with 8 mg/kg/day cisplatin, or with an equivalent volume of saline solution, for three consecutive days. They underwent distortion product evoked otoacoustic emission testing at baseline and at 24 or 48 hours after the last administration. At the end of the experiment, the animals were sacrificed and their cochleae were retrieved and prepared for haematoxylin and eosin staining. A four-point scoring system was used to grade injury to the external ciliated cells, as indicated by the number of cells absent from the basal turn of the cochlear duct. A four-point scoring system was also used to grade stria vascularis injury, as indicated by the degree of shrinkage of the intermediate cells. Scores were significantly higher in groups treated with cisplatin compared with controls. Morphological changes were confirmed by decreased distortion product evoked otoacoustic emission amplitudes in animals treated with cisplatin. This method is simple to perform with routine histology equipment and is appropriate for the study of acute, cisplatin-induced ototoxicity in rats.

  15. Tetraarsenic oxide and cisplatin induce apoptotic synergism in cervical cancer.

    Science.gov (United States)

    Byun, Jung Mi; Jeong, Dae Hoon; Lee, Dae Sim; Kim, Joo Ran; Park, Sae Gwang; Kang, Mi Seon; Kim, Young Nam; Lee, Kyung Bok; Sung, Moon Su; Kim, Ki Tae

    2013-04-01

    Tetraarsenic oxide (As4O6, TAO) is a new arsenic compound that inhibits cell growth and induces apoptosis in human cervical cancer cell lines. In the present study, we report that the growth of tumor cells (CaSki) was inhibited by treatment with TAO alone or in combination with cisplatin or paclitaxel in vitro and in vivo. Proliferation was assessed by WST-1 assay, and apoptosis was assessed by Annexin-V/PI FACS analysis in the CaSki cell line treated with a single agent or with the combinations of two agents. Expression of apoptosis-related proteins was analyzed by western blot analysis. A mouse xenograft model using CaSki cells was used to determine the in vivo activity of tetraarsenic oxide alone and in combination with cisplatin or paclitaxel by estimation of tumor size. At the end of the experiment, tumor tissue from each mouse was removed and processed for TUNEL analysis for confirmation of apoptotic cells. TAO was able to inhibit cell proliferation in a time- and dose-dependent manner. A combination of TAO and cisplatin effectively induced apoptosis by activating caspase-3. Using a mouse xenograft model, the sizes of tumors which were treated with a single agent and with a combination of agents decreased in a time-dependent manner. A combination of TAO and cisplatin resulted in a significantly reduced tumor size (Pcisplatin. Thus, TAO is a good candidate for use in a combined regimen with cisplatin for patients with cervical cancer.

  16. Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct.

    Science.gov (United States)

    Møller, Charlotte; Tastesen, Hanne Sørup; Gammelgaard, Bente; Lambert, Ian Henry; Stürup, Stefan

    2010-12-01

    The accumulation and cytotoxicity of a 10 μmol L⁻¹ equimolar human serum albumin-cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor Cells (EATC) and adherent Ehrlich Lettré Ascites Cells (Lettré). HSA-Pt did not induce apoptosis nor was it taken up by the cells to any significant amount within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared to 10 μmol L⁻¹ cisplatin for which a larger accumulation and cytotoxicity were observed in EATC compared to Lettré. The experiment was performed with cell medium exchange every fourth hour as HSA-Pt and cisplatin were not stable in RPMI-1640 with 10% serum. The stability was determined using size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and after 4 h new platinum peaks were observed. These findings indicate that before conducting cell experiments, the stability of the compound in the cell medium should be investigated especially when long exposure times are applied. Furthermore, HSA-Pt was found to be stable in Hanks Balanced Saline Solution (HBSS) and in Phosphate Buffered Saline (PBS) at pH 5.3, 6.1 and 7.4. Thus, the shift in pH when HSA-cisplatin passes from blood (pH 7.4) to tumor tissue (pH 5-6) is not capable of releasing cisplatin from HSA.

  17. [Experimental study of protective effect of solcoseryl on cisplatin nephrotoxicity].

    Science.gov (United States)

    Satoh, H; Mori, Y

    1992-01-01

    Cis-diamminedichloroplatinum (II) (cisplatin) is known to possess nephrotoxicity. Recently, it is said that the nephrotoxicity closely correlated with active oxygen. In the present study, an attempt was made to examine, whether or not solcoseryl, antioxidant like scavenger, decreases the nephrotoxicity. Three groups of Sprague-dawley rats were injected cisplatin (3mg/kg) only (C group), cisplatin and 2 times solcoseryl (8mg/kg), (CS2 group), and cisplatin and 5 times solcoseryl (CS5 group). BUN levels in C and CS2 groups were elevated compared to CS5 group. In the light microscopy, 62.5% to 100% in C and CS2 groups revealed massive necrosis in straight part of the proximal tubules, while the damage in CS5 group was only 25%. In the electron microscopy, these findings were similar to the light microscopic observations. Solcoseryl is known to have several antioxidative effects such as inhibition of superoxide producing and hyperperoxidation. It is suggested that these effects of solcoseryl might decrease the nephrotoxicity. Solcoseryl seems to be a useful drug for reducing nephrotoxicity and also it is a safe drug. Therefore, solcoseryl can be used for the prevention of cisplatin nephrotoxicity.

  18. Post-treatment Effects of Erythropoietin and Nordihydroguaiaretic Acid on Recovery from Cisplatin-induced Acute Renal Failure in the Rat

    OpenAIRE

    Lee, Dong Won; Kwak, Ihm Soo; Lee, Soo Bong; Song, Sang Heon; Seong, Eun Young; Yang, Byeong Yun; Lee, Min Young; Sol, Mee Young

    2009-01-01

    5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythrop...

  19. A remote drip infusion monitoring system employing Bluetooth.

    Science.gov (United States)

    Amano, Hikaru; Ogawa, Hidekuni; Maki, Hiromichi; Tsukamoto, Sosuke; Yonezawa, Yoshiharu; Caldwell, W Morton

    2012-01-01

    We have developed a remote drip infusion monitoring system for use in hospitals. The system consists of several infusion monitoring devices and a central monitor. The infusion monitoring device employing a Bluetooth module can detect the drip infusion rate and an empty infusion solution bag, and then these data are sent to the central monitor placed at the nurses' station via the Bluetooth. The central monitor receives the data from several infusion monitoring devices and then displays graphically them. Therefore, the developed system can monitor intensively the drip infusion situation of the several patients at the nurses' station.

  20. Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

    International Nuclear Information System (INIS)

    Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

    1986-01-01

    Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125 I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting

  1. The role of apoptosis in cisplatin-induced ototoxicity in rats Papel da apoptose na ototoxicidade por cisplatina em ratos

    Directory of Open Access Journals (Sweden)

    Marcos Rabelo De Freitas

    2009-10-01

    Full Text Available Cisplatin is a chemotherapy agent frequently used to treat different types of neoplasia. Ototoxicity is one of the side-effects which cause significant morbidity and limits its use. This study aimed at assessing the role of apoptosis in cisplatin-induced ototoxicity. DESIGN: experimental study. MATERIALS AND METHODS: male Wistar rats were treated with intraperitoneal cisplatin, in the doses of 24 and 16 mg/kg. The animals were assessed by means of distortion product evoked otoacoustic emissions (DPEOAE or brainstem evoked auditory potentials (BEAP in the third (D3 and fourth (D4 days after drug infusion onset. Following that, their cochleas were removed for immunohistochemical studies of apoptosis - TUNEL method. RESULTS: the group treated with 24 mg/kg showed a significant reduction in DPEOAE amplitude, and such fact was not seen with the 16 mg/kg. Both doses caused an increase in BEAP electrophysiological threshold in D3 and D4. Apoptosis was the injury mechanism responsible for the cisplatin-induced ototoxicity - 16 mg/kg dose, when the animals were assessed on D3. CONCLUSION: apoptosis may be involved in the cisplatin-induced ototoxicity, depending on the dose and time of injury assessment.Cisplatina é um agente quimioterápico frequentemente usado para o tratamento de várias linhagens de neoplasias. A ototoxicidade é um dos efeitos colaterais causadores de significativa morbidade e que limita sua utilização. Este estudo teve por objetivo avaliar o papel da apoptose na ototoxicidade por cisplatina. DESENHO DO ESTUDO: Estudo experimental. MATERIAL E MÉTODO: Ratos Wistar machos foram tratados com cisplatina, via intraperitoneal, nas doses de 24 e 16 mg/kg. Os animais foram avaliados através de emissões otoacústicas evocadas produtos de distorção (EOAPD ou potenciais auditivos evocados de tronco encefálico (PAETE no terceiro (D3 e quarto (D4 dias após o início da infusão das drogas. Em seguida suas cócleas foram removidas para

  2. [Application study on regional infusion chemotherapy by celiac trunk during operation in advanced gastric cancer patients].

    Science.gov (United States)

    You, Xiaolan; Qian, Haixin; Qin, Lei; Wang, Yuanjie; Li, Wenqi; Lian, Yanjun; Zhao, Xiaojun; Xu, Ning; Huang, Chuanjiang; Chen, Zhiyi; Liu, Guiyuan

    2016-09-25

    To explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients. One hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups. The baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9±14.8) hours vs. (68.9±15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1±17.1) ml vs.(61.9±18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), χ 2 =0.256, P=0.613], and the long-term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), χ 2 =0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, χ 2 =5.382, P=0.020; 58.4% vs. 34.4%, χ 2 =6.636, P=0.010). Regional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate.

  3. Impact of pretreatment noncontrast CT Alberta Stroke Program Early CT Score on clinical outcome after intra-arterial stroke therapy.

    Science.gov (United States)

    Yoo, Albert J; Zaidat, Osama O; Chaudhry, Zeshan A; Berkhemer, Olvert A; González, R Gilberto; Goyal, Mayank; Demchuk, Andrew M; Menon, Bijoy K; Mualem, Elan; Ueda, Dawn; Buell, Hope; Sit, Siu Po; Bose, Arani

    2014-03-01

    The efficacy of intra-arterial treatment remains uncertain. Because most centers performing IAT use noncontrast CT (NCCT) imaging, it is critical to understand the impact of NCCT findings on treatment outcomes. This study aimed to compare functional independence and safety among patients undergoing intra-arterial treatment stratified by the extent of ischemic change on pretreatment NCCT. The study cohort was derived from multicenter trials of the Penumbra System. Inclusion criteria were anterior circulation proximal occlusion, evaluable pretreatment NCCT, and known time to reperfusion. Ischemic change was quantified using the Alberta Stroke Program Early CT Score (ASPECTS) and stratified into 3 prespecified groups for comparison: 0 to 4 (most ischemic change) versus 5 to 7 versus 8 to 10 (least ischemic change). A total of 249 patients were analyzed: 40 with ASPECTS 0 to 4, 83 with ASPECTS 5 to 7, and 126 with ASPECTS 8 to 10. For ASPECTS 0 to 4, 5 to 7, and 8 to 10, respectively, good outcome (modified Rankin Scale score, 0-2) rates were 5%, 38.6%, and 46% (P<0.0001), and mortality rates were 55%, 28.9%, and 19% (P=0.0001). The only significant pairwise differences were between ASPECTS 0 to 4 and other groups. Symptomatic hemorrhage was more common with lower ASPECTS (P=0.02). Shorter time to reperfusion was significantly associated with better outcomes among patients with ASPECTS 8 to 10 (P=0.01). A similar relationship was seen for ASPECTS 5 to 7 but was not statistically significant. No such relationship was seen for ASPECTS 0 to 4. NCCT seems useful for excluding patients with the greatest burden of ischemic damage from futile intra-arterial treatment, which is unlikely to result in patient functional independence and increases the risk of hemorrhage.

  4. Histopathological studies of radiation-combined intra-arterial chemotherapy on squamous cell carcinoma of the mandible

    International Nuclear Information System (INIS)

    Yonemochi, Takemi

    1996-01-01

    The 2nd Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Hospital, Iwate Medical University has performed radiation-combined intra-arterial chemotherapy as a preoperative treatment and subsequent mandibulectomy. During a 20 year-period from 1975 to 1994, clinical and histopathological examination of the above therapy was made for its effect and usefulness by using 15 primary cases of mandibular gingival squamous cell carcinoma, which were all identifiable. Roentgenological examination by bone resorptive pattern (invasive type, erosive type) and by bone resorptive depth (degree 0-III) revealed that early infiltration case and advanced case were predominant in the erosive type and the invasive type respectively. Histopathologically, the therapeutical effect of the radiation-combined intra-arterial chemotherapy on the tumor cells was examined using osteoclast, fibrous connective tissue, osteoblast, new bone, site of neoosteogenesis, and post-treatment site of residual tumor ceils as findings in the healing process. The histological therapeutic effect was good on well-differentiated type cases, and the histological effect on osteo-infiltrated region was as good as, or better than on soft tissue region. The cases with good histological therapeutic effect scarcely showed osteoclast, but showed remarkable hyperplasia of fibrous connective tissue, appearance of osteoblast and repair mechanism via neoosteogenesis. Invasive type tumor was persistent in the depth of the mandible, while erosive type tumor showed a tendency to be persistent in superficial layer. The results suggested that the application of the present radiation-combined intra-arterial chemotherapy to mandibular gingival squamous cell carcinoma is very useful leading to the improvement in radical curability of the tumor in its primary focus and the preservation of mandibular continuity in surgery. (author)

  5. Epoetin alfa ja namaluva nefrotoksicnosta inducirana so cisplatin kaj staorci

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    Dimce Zafirov

    2006-06-01

    Full Text Available Klinickata efikasnost na cisplatin kako antitumorski lek e nesomnena, no dozno-limitiracki faktor za negova upotreba pretstavuva izrazitata nefrotoksicnost. Najnovite istrazuvawa pokazuvaat deka epoetin alfa moze da ima znacajna uloga ne samo vo terapiski celi za korekcija na razni vidovi na anemii, tuku istiot moze da bide efikasen i kako nevroprotektiv, hepatoprotektiv, kardioprotektiv i osobeno znacajno kako nefroprotektiv kaj nefrotoksicnost inducirana od preparati na baza na platina. Glavna cel na ovaa studija bese da se utvrdi efektot na epoetin alfa vo prevencijata na nefrotoksicnost eksperimentalno inducirana so dolgotrajna administracija na cisplatin vo doza od 2 mg/kg/t.t./nedela vo tek na 8 nedeli, kaj Wistar staorci. Dobienite rezultati od ovaa studija pokazuvaat deka epoetin alfa signifikantno gi ublazuva funkcionalnite bubrezni poremetuvawa inducirani so dolgotrajna administracija na cisplatin, ja podobruva opstata sostojba i go namaluva mortalitetot kaj ispituvanite zivotni.

  6. Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct

    DEFF Research Database (Denmark)

    Møller, Charlotte; Tastesen, Hanne Sørup; Gammelgaard, Bente

    2010-01-01

    significant amount within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared to 10 µmol L¿¹ cisplatin for which a larger accumulation and cytotoxicity were observed in EATC compared to Lettré. The experiment was performed with cell medium exchange every fourth hour as HSA......-Pt and cisplatin were not stable in RPMI-1640 with 10% serum. The stability was determined using size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and after 4 h new platinum peaks were observed. These findings indicate that before conducting cell experiments, the stability......The accumulation and cytotoxicity of a 10 µmol L¿¹ equimolar human serum albumin-cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor Cells (EATC) and adherent Ehrlich Lettré Ascites Cells (Lettré). HSA-Pt did not induce apoptosis nor was it taken up by the cells to any...

  7. RHEGMATOGENOUS RETINAL DETACHMENT AFTER INTRAARTERIAL CHEMOTHERAPY FOR RETINOBLASTOMA: The 2016 Founders Award Lecture.

    Science.gov (United States)

    Shields, Carol L; Say, Emil A T; Pefkianaki, Maria; Regillo, Carl D; Caywood, Emi H; Jabbour, Pascal M; Shields, Jerry A

    2017-08-01

    To evaluate rhegmatogenous retinal detachment (RRD) in eyes with retinoblastoma after intraarterial chemotherapy (IAC). Retrospective case series. Chart review. Development of RRD in the IAC era. Of 167 eyes in 157 consecutive patients, mean patient age at diagnosis of retinoblastoma was 19 months. Intraarterial chemotherapy was primary (75/167, 45%) or secondary (92/167, 55%). There were 10 eyes (10/167, 6%) that developed RRD after IAC. The RRD was mostly related to rapid tumor regression with atrophic retinal hole, occurring within one month (n = 8) or 12 months (n = 2) of IAC. Rhegmatogenous retinal detachment was found after primary (6/75, 8%) or secondary (4/92, 4%) IAC. Of primary cases, RRD was found in Group D (1/38 [3%], P = 0.1075) or Group E (5/30 [17%], P = 0.0348). For primary IAC (n = 75 eyes), RRD was found in endophytic (5/22 [23%], P = 0.0073), exophytic (0/29 [0%], P = 0.0760), or combined endophytic/exophytic pattern (1/24 [4%], P = 0.6575). A comparison of eyes with RRD (n = 10) versus without RRD (n = 157) found significant differences including greater mean age at presentation (38 vs. 18 months, P = 0.0522), greater 4-quadrant vitreous seeding (5/10, 50% vs. 27/157, 17%, P = 0.0236), and absence of subretinal fluid (3/10, 30% vs. 102/157, 65%, P = 0.0236). The cause of RRD was tumor regression-related atrophic retinal hole(s) in 7 (7/10, 70%) (unifocal [1/10, 10%] or multifocal [6/10, 60%] holes), cryotherapy-induced single atrophic hole in 2 (2/10, 20%), and single flap-tear from posterior vitreous detachment in one (1/10, 10%). In 4 (4/10, 40%) eyes with RRD, proliferative vitreoretinopathy was noted. The RRD was not related to intravitreal injection in any case, as in primary IAC no case had previous injection and in secondary IAC the injections were performed many months previously. Primary RRD repair involved pars plana vitrectomy in three, scleral buckle without drainage in one, laser barricade in one, and observation in five eyes

  8. Development of intraarterial contrast-enhanced 2D MRDSA with a 0.3 tesla open MRI system

    International Nuclear Information System (INIS)

    Masumoto, Tomohiko; Hayashi, Naoto; Mori, Harushi; Aoki, Shigeki; Abe, Osamu; Ohtomo, Kuni

    2003-01-01

    The purpose of this study was to develop a new technique for a high temporal resolution two-dimensional MR digital subtraction angiography (2D MRDSA) sequence under intraarterial injection of contrast material to permit the visualization of vascular anatomy and hemodynamics. 2D MRDSA was imaged on a 0.3T open MR scanner with a T 1 -weighted fast gradient echo sequence. The phantom study examined vials containing gadolinium (Gd) solutions ranging in concentration from 0.5 mmol/L to 100 mmol/L. Repetition time and echo time were fixed at minimal values in order to achieve high temporal resolution, and only the flip angle was changed in 10-degree increments between 10 and 90 degrees. The in vivo study examined a brachial artery of a human volunteer. MRDSA images were acquired continuously during intraarterial injections of Gd solutions ranging in concentration from 0.5 mmol/L to 100 mmol/L. The subtracted images were displayed on the monitor in real time at a frame rate of one frame per second and evaluated to determine the optimal concentration of contrast material. In the phantom study, a 10-mmol/L Gd concentration with a flip angle of 50 deg-90 deg and a 25-mmol/L Gd concentration with a flip angle of 60 deg-90 deg showed high signal-to-noise ratios. In the human brachial artery experiment, the forearm arteries were well visualized when solutions of 5-50 mmol/L Gd concentration were used. The 10- and 25-mmol/L Gd concentrations were considered optimal. The palmar digital arteries were also visualized. Higher Gd concentrations showed a paradoxical signal increase when diluted by blood. We successfully developed an intraarterial contrast-enhanced 2D MRDSA sequence. With appropriate settings of imaging parameters and Gd concentrations, we obtained acceptable vessel visualization in the human study. The low Gd concentration for optimal visualization permits repeated intraarterial injections. This technique can be a useful tool for investigating the vascular anatomy and

  9. Experimental and clinical studies on the intraarterial injection of holmium-166 chitosan complex in the treatment of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Lee, Jong Tae; Kim, Eun Kyung; Won, Jong Yoon; Lee, Do Yun; Lee, Jong Doo; Yoo, Hyung Sik; Yoo, Nae Choon; Park, Kyung Bae

    2001-01-01

    The purposes of this study were to evaluate the biodistribution and effect of Ho-166 radionuclide by intra-arterial injection of the Ho-166 chitosan complex in dogs and to assess the clinical efficacy and side effects of this complex in the treatment of hepatocellular carcinoma (HCC). In an experimental study, 20 mCi of Ho-166 chitosan complex was injected into the left hepatic artery of six adult dogs. The distribution of radioactivity in each organ was calculated using a gamma camera scan at regular intervals. A beta ray radioactivity count (cpm) of blood and urine was performed periodically, and hematologic and hepatic function were regularly assessed. At 4, 8 and 12 weeks after intra-arterial injection, bone marrow and liver were pathologically evaluated. Twenty-five patients with a single, nodular HCC mass 3-9 cm in diameter were treated by intra-arterial injection of Ho-166 chitosan complex, and immediately after the procedure a gamma camera scan was obtained. A beta ray radioactivity count(CPM) of blood was performed periodically, hematologic and hepatic function were regularly evaluated, and CT scans and angiograms were obtained 3 months after the procedure. On the basis of the CT and angiographic findings, the treatment effects were classified as complete (CR), partial (PR) or non-response(NR). In the animal study, blood radioactivity peaked immediately in each organ per whole body was 25% in the left lobe of the liver, 7% in the right lobe, 3% in the lung, 1.4-3% in the bladder, and 2% in bone. WBC and platelet counts declined maximally at 3-4 weeks and recovered at 12 weeks the cellularity of bone marrow was 25% at 4 weeks and 55% at 12 weeks, findings which correlated well with the observed hematologic changes. In the clinical study of 25 HCC patients, CR was achieved in 17 (68%) cases, PR in 5 (20%) and NR in 3 (12%). At gamma camera imaging immediately after treatment, tumor radioactivity was localized in 76% of cases. In six cases (24%) WBC and

  10. Hydraulic and hemodynamic performance of a minimally invasive intra-arterial right ventricular assist device.

    Science.gov (United States)

    Hsu, Po-Lin; Graefe, Roland; Boehning, Fiete; Wu, Chen; Parker, Jack; Autschbach, Rüdiger; Schmitz-Rode, Thomas; Steinseifer, Ulrich

    2014-09-01

    Right ventricular assistance is still in the early phase of development compared to left ventricular assist device (LVAD) technology. In order to provide flexible pulmonary support and potentially reduce the known complications, we propose a minimally invasive right ventricular assist device (MIRVAD), located in the pulmonary artery (PA) and operating in series with the right ventricle (RV). The MIRVAD is an intra-arterial rotary blood pump containing a single axial impeller, which is not enclosed by a rigid housing but stent-fixed within the vessel. The impeller geometry has been designed with the assistance of analytical methods and computational fluid dynamics (CFD). The hydraulic performance of the impeller was evaluated experimentally with a customized test setup using blood synthetic medium (HES). The blade-tip clearance (BTC) was varied between 0.25-4.25 mm to evaluate the effect of different PA sizes on impeller performance. Furthermore, the Langrangian particle-tracking method was used to estimate the level of hemolysis and generate numerical blood damage indexes.The impeller design generated 25.6 mmHg for flow rates of 5 lpm at a speed of 6,000 rpm at the baseline condition, capable of providing sufficient support for the RV. The BTC presented a significant effect on the static pressure generation and the efficiency, but the operational range is suitable for most vessel sizes. The numerical results demonstrated a low risk of blood damage at the design point (mean Lagrangian damage index 2.6*10(-7)). The preliminary results have encouraged further impeller optimization and development of the MIRVAD.

  11. A case of pulmonary edema developed after intraarterial injection of iodinated contrast medium

    International Nuclear Information System (INIS)

    Min, Byoung Chol; Chun, Kang Woo; Koh, Jae Hyu; Yoon, Jong Sup

    1982-01-01

    Pulmonary edema is a rare adverse reaction to the iodinated contrast medium. Complaining of huge abdominal mass, a 52 years old female was admitted to the Hangang Sungsim Hospital. On physical examination, the patient appeared to be healthy. She had stable vital signs, i.e. BP: 120/80 mmHg, pulse rate: 80/min.etc. An adult head sized mass was palpated in the left mid and lower abdomen. Otherwise nonspecific. On laboratory studies the positive findings were 8-10 WBC/HPF in urine, 25.6 mg/dl for BUN and PVC in EKG. It was negative for urine protein, serum creatinline and liver function test. We injected 100 ml and 30 ml of Urografin 60 through the abdominal aorta dividing 3 times and major branches of the abdominal aorta, respectively. Immediately after complicating angiography, interstitial pulmonary edema was found, showing blurring of the vascular margins, perivascular haziness and thickening of the interlobular septal lines in the both lower lung fields. The blood pressure was dropped to 80/60 mmHg, but pulse rate was normal. She did not complain of dyspnea, and cyanosis was not developed. The urine volume was normally maintained. She was treated for pulmonary edema, which was completely absorbed after 20 hours. And the blood pressure was also normalized. We have experienced a case of pulmonary edema developed after intraarterial injection of the iodinated contrast medium without underlying cardiac, renal and hepatic problems, and reviewed the literatures on mechanisms of pulmonary edema caused by intravascular injection of the iodinated contrast materials

  12. Collateral status and tissue outcome after intra-arterial therapy for patients with acute ischemic stroke.

    Science.gov (United States)

    Boers, Anna Mm; Jansen, Ivo Gh; Berkhemer, Olvert A; Yoo, Albert J; Lingsma, Hester F; Slump, Cornelis H; Roos, Yvo Bwem; van Oostenbrugge, Robert J; Dippel, Diederik Wj; van der Lugt, Aad; van Zwam, Wim H; Marquering, Henk A; Majoie, Charles Blm

    2017-11-01

    Intra-arterial therapy (IAT) for ischemic stroke aims to save brain tissue. Collaterals are thought to contribute to prolonged penumbra sustenance. In this study, we investigate the effect of collateral status on brain tissue salvage with IAT. In 500 patients randomized between IAT and standard care, collateral status was graded from 0 (absent) to 3 (good). Final infarct volumes (FIV) were calculated on post-treatment CT. FIVs were compared between treatment groups per collateral grade. Multivariable linear regression with interaction terms was performed to study whether collaterals modified IAT effect on FIV. Four-hundred-forty-nine patients were included in the analysis. Median FIV for the IAT group was significantly lower with 54.5 mL (95% IQR: 21.8-145.0) than for the controls with 81.8 mL (95% IQR: 40.0-154.0) ( p = 0.020). Treatment effect differed across collateral grades, although there was no significant interaction (unadjusted p = 0.054; adjusted p = 0.105). For grade 3, IAT resulted in a FIV reduction of 30.1 mL ( p = 0.024). For grade 2 and 1, this difference was, respectively, 28.4 mL ( p = 0.028) and 28.4 mL ( p = 0.29). For grade 0, this was 88.6 mL ( p = 0.28) in favour of controls. IAT saves substantially more brain tissue as compared to standard care. We observed a trend of increasing effect of IAT with higher collateral grades.

  13. Prevalence and rupture rate of cerebral aneurysms discovered during intra-arterial chemotherapy of brain tumors.

    Science.gov (United States)

    Bourekas, E C; Newton, H B; Figg, G M; Slone, H W

    2006-02-01

    During the administration of intra-arterial (IA) chemotherapy for the treatment of brain tumors (BTs), angiography may demonstrate asymptomatic, incidental cerebral aneurysms. The prevalence and complication rate of incidental aneurysms in patients undergoing IA chemotherapy remains unknown. It remains unclear whether the presence of an aneurysm represents an increased risk or a contraindication to this form of treatment. We performed a chart and angiography review of BT patients receiving IA chemotherapy over the previous 16 months. Seventy-eight patients were identified with primary (39) and metastatic (39) BTs. The cohort consisted of 40 men and 38 women, with a mean age of 47.8 years (range, 22-80 years). During initial angiography, 8 patients (10.3%) were identified with incidental cerebral aneurysms. The aneurysms were saccular and varied in size from 2-4 mm (mean, 3 mm). Seven of the 8 patients continued IA chemotherapy after detection of the aneurysm, for a total of 35 IA procedures. Of these 7 patients, 5 expired from nonaneurysmal complications (mean survival, 5.4 months; range, 2-10 months); 4 from the primary tumor, and one from an infected craniotomy site. Two patients continue to survive; one remains in treatment, and the other has completed 12 months of IA therapy. There were no aneurysmal complications during or after IA treatment in any of the BT patients. Incidental aneurysms may be more common in patients with BTs than the general population. In our patient population, there was no indication that an incidental aneurysm was reason to preclude or delay the use of IA chemotherapy.

  14. Combined, sequential intravenous and intra-arterial chemotherapy (bridge chemotherapy for young infants with retinoblastoma.

    Directory of Open Access Journals (Sweden)

    Y Pierre Gobin

    Full Text Available BACKGROUND: Intra-arterial (i.a. chemotherapy has more risks of procedural complications in neonates and young infants. For these reasons, we have developed a strategy of bridge intravenous single agent chemotherapy to postpone i.a. chemotherapy in these children PROCEDURE: Neonates and young infants with retinoblastoma who required chemotherapy were treated with systemic carboplatin chemotherapy (18.7 mg/kg i.v. every 3-4 weeks until they reached the age of 3 months and a weight of 6 Kg. If necessary, i.a. chemotherapy was subsequently performed at 4 weeks intervals. Efficacy was judged by tumor regression on ophthalmological examination. Retinal toxicity was judged by electroretinography. RESULTS: Eleven children (19 eyes were treated. All patients are alive and no patient has developed metastatic disease or second malignancies (mean follow-up 27 months, range 9-46 months. Intravenous carboplatin (median 2 cycles, range 1-5 combined with cryotherapy and laser was given to all children. This was effective for five eyes, which did not require i.a. chemotherapy. I.a. chemotherapy was administered to 14 eyes (median 3.5 cycles per eye, range 1 to 6. No radiation therapy was required. The Kaplan Meier estimate of ocular radiation-free survival was 94.7% at one year (95% confidence interval 68.1-99.2%. One eye was enucleated due to tumor progression. ERG showed no deterioration of retinal function. CONCLUSION: Bridge i.v.-i.a. chemotherapy was feasible and safe, and is a promising strategy to treat retinoblastoma in neonates and young infants.

  15. Successful Treatment of Two Cases of Squamous Cell Carcinoma on the Ear with Intra-Arterial Administration of Peplomycin through a Superficial Temporal Artery

    Directory of Open Access Journals (Sweden)

    Takahiro Haga

    2014-09-01

    Full Text Available Cutaneous squamous cell carcinoma (SCC is the second most common non-melanoma skin cancer and tends to develop in sun-exposed cosmetic areas, including the ear. In this report, we describe two cases of SCC on the ear successfully treated with intra-arterial administration of peplomycin through a superficial temporal artery. In addition to this selective chemotherapy, we administered oral tegafur, which achieved complete remission of the tumor. These findings suggest that intra-arterial administration of peplomycin with tegafur is one of the optimal therapies for the treatment of SCC developing on the ear.

  16. Selection of agents for prevention of cisplatin-induced hepatotoxicity.

    Science.gov (United States)

    Liao, Yingjun; Lu, Xiuqiang; Lu, Chunwei; Li, Gexin; Jin, Yaping; Tang, Hao

    2008-02-01

    The objective of this study was to explore the optimal combination of agents used along with cisplatin for protection of hepatotoxicity. Animal experiment was carried out based on the orthogonal design L(8) (2(7)) setting seven factors with two different levels of each, and eight groups of mice were needed. The agents tested in this study were zinc, selenium, fosfomycin, sodium thiosulfate (STS), N-acetyl-cysteine (NAC), methionine and taurine. Mice were supplemented by gavage with various combinations of agents as designed in the orthogonal table once a day for nine days beginning two days before cisplatin administration. 3.5mg/kg body weight of cisplatin was given intraperitoneally once a day for five days simultaneously. After cessation of cisplatin administration, the agents were supplemented continuously for two days. Activities of alanine aminotransferase (ALT) in serum, levels of glutathione (GSH) and malondialdehyde (MDA) in liver were analyzed after cessation of supplementation. Results showed zinc, fosfomycin and methionine were the effective factors for protection of weight loss; fosfomycin and methionine were the effective factors for prevention of decreased liver ratio; selenium, fosfomycin and STS were the effective factors for prevention of increased ALT activities in serum. On the other hand, methionine was the only effective factor for prevention of decreased GSH levels in liver; zinc, selenium and fosfomycin were the effective factors for prevention of increased MDA levels in liver. Based on the data observed in this study, the optimum combinations of agents were selenium, fosfomycin, methionine and taurine, and zinc, selenium, STS and methionine. In conclusion, each agent used in this study could play a beneficial role for prevention of cisplatin hepatotoxicity, however, none could play the crucial role. The potentiated actions for prevention of cisplatin hepatotoxicity could be achieved via combined use of these agents.

  17. Induction chemotherapy with docetaxel, cisplatin and S-1 followed by proton beam therapy concurrent with cisplatin in patients with T4b nasal and sinonasal malignancies

    International Nuclear Information System (INIS)

    Okano, Susumu; Tahara, Makoto; Zenda, Sadamoto

    2012-01-01

    For the treatment of patients with T4b nasal and sinonasal malignancies, definitive chemoradiotherapy was contraindicated due to the risk of brain damage and blindness. However, combination chemotherapy with docetaxel, cisplatin and S-1 is well tolerated and effective. We conducted a retrospective analysis to evaluate the efficacy and feasibility of induction chemotherapy using docetaxel, cisplatin and S-1 followed by proton beam therapy concurrent with cisplatin. Thirteen patients treated with docetaxel, cisplatin and S-1 were analyzed. Docetaxel, cisplatin and S-1 consisted of 60-70 mg/m 2 /day docetaxel on day 1, 70 mg/m 2 /day cisplatin on day 1 and 60-80 mg/m 2 /day S-1 on days 1-14. Treatment was repeated every 3-4 weeks with a maximum number of three treatment cycles. According to the response to docetaxel, cisplatin and S-1, patients received either proton beam therapy concurrent with 20 mg/m 2 /day cisplatin on days 1-4 every 3 weeks or proton beam therapy alone. Neutropenia represented the most common Grade 3/4 hematological toxicity (76.9%), while the most frequently observed non-hematological toxicity was nausea (23.0%). After the completion of docetaxel, cisplatin and S-1, the overall response rate was 38.4% (5 of 13), with 1 patient achieving complete response and 4 patients achieving partial response. Subsequently, 10 patients received proton beam therapy concurrent with cisplatin, 2 received proton beam therapy alone and 1 received palliative radiation. No severe toxicity was observed during proton beam therapy. After the completion of proton beam therapy, 11 patients (84.6%) achieved complete response and no brain damage or blindness occurred. Induction chemotherapy with docetaxel, cisplatin and S-1 followed by proton beam therapy concurrent with cisplatin is well tolerated and displays promising antitumor activity that warrants further investigation. (author)

  18. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Scagliotti, G.V.; Parikh, P.; Pawel, J. von

    2008-01-01

    , in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/ gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P .../gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type Udgivelsesdato: 2008/7/20...

  19. Inhibition of the CSF-1 receptor sensitizes ovarian cancer cells to cisplatin.

    Science.gov (United States)

    Yu, Rong; Jin, Hao; Jin, Congcong; Huang, Xuefeng; Lin, Jinju; Teng, Yili

    2018-03-01

    Ovarian cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely used in locally advanced ovarian cancer patients. Acquired or de novo cisplatin resistance remains the barrier to patient survival, and the mechanisms of cisplatin resistance are still not well understood. In the current study, we found that colony-stimulating-factor-1 receptor (CSF-1R) was upregulated in cisplatin-resistant SK-OV-3 and CaoV-3 cells. Colony-stimulating-factor-1 receptor knockdown suppressed proliferation and enhanced apoptosis in cisplatin-resistant SK-OV-3 and CaoV-3 cells. However, CSF-1R overexpression had inverse effects. While parental SK-OV-3 and CaoV-3 cells were more resistant to cisplatin after CSF-1R overexpression, CSF-1R knockdown in SK-OV-3 and CaoV-3 cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that CSF-1R significantly promoted active AKT and ERK1/2 signalling pathways in cisplatin-resistant cells. Furthermore, a combination of cisplatin and CSF-1R inhibitor effectively inhibited tumour growth in xenografts. Taken together, our results provide the first evidence that CSF-1R inhibition can sensitize cisplatin-refractory ovarian cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumours. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

    Science.gov (United States)

    Yakabi, Koji; Sadakane, Chiharu; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Chinen, Katsuya; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hideaki; Hattori, Tomohisa

    2010-08-01

    Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

  1. Imperatorin acts as a cisplatin sensitizer via downregulating Mcl-1 expression in HCC chemotherapy.

    Science.gov (United States)

    Hu, Jianjian; Xu, Changlong; Cheng, Bihuan; Jin, Lingxiang; Li, Jie; Gong, Yuqiang; Lin, Wei; Pan, Zhenzhen; Pan, Chenwei

    2016-01-01

    Acquisition of cisplatin resistance is the common and critical limitation for hepatocellular carcinoma (HCC) therapy. Our study was aimed to determine whether there were conditions under which the addition of imperatorin would reverse the resistance of HCC cells to cisplatin-based therapy. In this study, we found that addition of imperatorin significantly enhanced the cytotoxicity of cisplatin to HCC cells. Since the Mcl-1 was overexpressed in HCC cell lines (HepG2, HepG3B, PLC, Huh7) compared with normal liver cell line (L-O2), we found that the Mcl-1 expression was downregulated by imperatorin but not influenced by cisplatin in HCC cells. In addition, our results showed the combination of imperatorin and cisplatin induced apoptosis and ∆Ψm collapse more significantly compared with treatment of imperatorin or cisplatin alone. Furthermore, the imperatorin-induced sensitization for cisplatin-cytotoxicity to HCC cells was abolished by the transfection of Mcl-1 expression plasmid. Finally, we found that the addition of imperatorin significantly reversed the resistance to cisplatin in cisplatin-resistant HCC cells, which was Mcl-1 dependent. In summary, our study revealed that combination with imperatorin could enhance the antitumor activity of cisplatin via targeting Mcl-1 and reverse the resistance to cisplatin in HCC.

  2. Encapsulation of cisplatin in a pegylated calcium phosphate nanoparticle (CPNP) for enhanced cytotoxicity to cancerous cells.

    Science.gov (United States)

    Ding, Yang; Zhai, Kang; Pei, Pei; Lin, Yue; Ma, Yinchu; Zhu, Huixia; Shao, Mingfeng; Yang, Xianzhu; Tao, Wei

    2017-05-01

    Exchange of the chloride ion (Cl - ) ligands of cisplatin with carboxylates is widely used in fabricating cisplatin loaded nanoparticles for improved cancer therapy. However, the dynamic exchange may cause premature cisplatin release and even disintegration of the nanoparticles in Cl - -containing medium such as in plasma. Molecules bearing carboxylates are capable of mediating the mineralization process of calcium phosphate; therefore, it is possible to overcome the disadvantage by sequestering cisplatin in a calcium phosphate nanoparticle (CPNP). With the hypothesis, precipitation reaction of calcium nitrate and disodium hydrogen phosphate was performed in a solution of poly(ethylene glycol)-poly(acrylic acid) block copolymers with their carboxylates partly conjugated with cisplatin. Then, structure, physicochemical properties, and bioactivity of the product were carefully investigated with multiple characterization methods. It was revealed a pegylated, cisplatin encapsulated CPNP was prepared; and with appropriate mole ratio of cisplatin to carboxylates, the nanoparticle encapsulated cisplatin efficiently (>90%), was stable and almost entirely prevented the cisplatin release in Cl - -containing medium at pH 7.4 but released them in an acidic condition, and showed moderately and greatly enhanced cytotoxicities to the lung cancer cell line A549 and its cisplatin resistance form A549R respectively in comparison with the free cisplatin. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Structural damage of chicken red blood cells exposed to platinum nanoparticles and cisplatin

    DEFF Research Database (Denmark)

    Kutwin, Marta; Sawosz, Ewa; Jaworski, Sławomir

    2014-01-01

    Side effects and resistance of cancer cells to cisplatin are major drawbacks to its application, and recently, the possibility of replacing cisplatin with nanocompounds has been considered. Most chemotherapeutic agents are administered intravenously, and comparisons between the interactions...... of platinum nanoparticles (NP-Pt) and cisplatin with blood compartments are important for future applications. This study investigated structural damage, cell membrane deformation and haemolysis of chicken embryo red blood cells (RBC) after treatment with cisplatin and NP-Pt. Cisplatin (4 μg/ml) and NP-Pt (2......,6 μg/ml), when incubated with chicken embryo RBC, were detrimental to cell structure and induced haemolysis. The level of haemolytic injury was increased after cisplatin and NP-Pt treatments compared to the control group. Treatment with cisplatin caused structural damage to cell membranes...

  4. Home infusion: overcoming the barriers to entry.

    Science.gov (United States)

    Franklin, David M

    2010-01-01

    The field of pharmacy service is evolving rapidly, as is the delivery of healthcare in general. From patients with infectious diseases dying because there was nothing available to fight the infections, to the involvement of an episodic-based model of care with patients traversing inpatient- and outpatient-based delivery systems, to the new frontier of chronic care and with supports such as the one by the Centers for Disease Control that hospital-acquired infections are killing about 100,000 Americans every year, the home infusion business has become a major alternative to in-hospital treatment. This article discusses the barriers to entry into the home infusion business and assists in the evaluation of a home infusion reimbursement organization.

  5. Design of Infusion Schemes for Neuroreceptor Imaging

    DEFF Research Database (Denmark)

    Feng, Ling; Svarer, Claus; Madsen, Karine

    2016-01-01

    for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [(11)C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [(11)C...... state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [(11)C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous...

  6. Forearm metabolism during infusion of adrenaline

    DEFF Research Database (Denmark)

    Simonsen, L; Stefl, B; Bülow, J

    2000-01-01

    Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were...... catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured...... by the local 133Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a-v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0.3 nmol kg-1 min-1. No difference in the metabolic information obtained in the fasting...

  7. shRNA-mediated AMBRA1 knockdown reduces the cisplatin-induced autophagy and sensitizes ovarian cancer cells to cisplatin.

    Science.gov (United States)

    Li, Xiaoyan; Zhang, Lijuan; Yu, Lili; Wei, Wei; Lin, Xueyan; Hou, Xiaoman; Tian, Yongjie

    2016-02-01

    Recent research has revealed a role for Ambra1, an autophagy-related gene-related (ATG) protein, in the autophagic pro-survival response, and Ambra1 has been shown to regulate Beclin1 and Beclin1-dependent autophagy in embryonic stem cells and cancer cells. However, whether Ambra1 plays an important role in the autophagy pathway in ovarian cancer cells is unknown. In this study, we hypothesized that Ambra1 is an important regulator of autophagy and apoptosis in ovarian cancer cells. We firstly confirmed autophagic activity in ovarian cancer OVCAR-3 cells which were treated with cisplatin by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3) localization and the presence of autophagosomes and LC3 protein levels in OVCAR-3 cells. Cell apoptosis and viability were measured by annexin-V and PI staining and MTT assays. We then knocked down Ambra1 expression with transfection with the plasmid expressing the small hairpin RNA (shRNA) targeting AMBRA1, then re-evaluated autophagy in the OVCAR-3 cells subject to cisplatin treatment, and re-determined the sensitivity of OVCAR-3 cells to cisplatin. Results demonstrated that cisplatin treatment induced autophagy in OVCAR-3 cells in association with Ambra1 upregulation in the ovarian cancer cells. When Ambra1 expression was reduced by shRNA, the ovarian cancer cells were more sensitive to cisplatin. In conclusion, Ambra1 is a crucial regulator of autophagy and apoptosis in ovarian cancer cells subject to cisplatin to maintain the balance between autophagy and apoptosis. And the Ambra1-targeting inhibition might be an effective method to sensitize ovarian cancer cells to chemotherapy.

  8. Role of Insulin-Like Growth Factor-1 Signaling Pathway in Cisplatin-Resistant Lung Cancer Cells

    International Nuclear Information System (INIS)

    Sun Yunguang; Zheng Siyuan; Torossian, Artour; Speirs, Christina K.; Schleicher, Stephen; Giacalone, Nicholas J.; Carbone, David P.; Zhao Zhongming; Lu Bo

    2012-01-01

    Purpose: The development of drug-resistant phenotypes has been a major obstacle to cisplatin use in non–small-cell lung cancer. We aimed to identify some of the molecular mechanisms that underlie cisplatin resistance using microarray expression analysis. Methods and Materials: H460 cells were treated with cisplatin. The differences between cisplatin-resistant lung cancer cells and parental H460 cells were studied using Western blot, MTS, and clonogenic assays, in vivo tumor implantation, and microarray analysis. The cisplatin-R cells were treated with human recombinant insulin-like growth factor (IGF) binding protein-3 and siRNA targeting IGF-1 receptor. Results: Cisplatin-R cells illustrated greater expression of the markers CD133 and aldehyde dehydrogenase, more rapid in vivo tumor growth, more resistance to cisplatin- and etoposide-induced apoptosis, and greater survival after treatment with cisplatin or radiation than the parental H460 cells. Also, cisplatin-R demonstrated decreased expression of insulin-like growth factor binding protein-3 and increased activation of IGF-1 receptor signaling compared with parental H460 cells in the presence of IGF-1. Human recombinant IGF binding protein-3 reversed cisplatin resistance in cisplatin-R cells and targeting of IGF-1 receptor using siRNA resulted in sensitization of cisplatin-R-cells to cisplatin and radiation. Conclusions: The IGF-1 signaling pathway contributes to cisplatin-R to cisplatin and radiation. Thus, this pathway represents a potential target for improved lung cancer response to treatment.

  9. Role of Insulin-Like Growth Factor-1 Signaling Pathway in Cisplatin-Resistant Lung Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun Yunguang [Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN (United States); Zheng Siyuan [Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN (United States); Torossian, Artour; Speirs, Christina K.; Schleicher, Stephen; Giacalone, Nicholas J. [Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN (United States); Carbone, David P. [Department of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN (United States); Zhao Zhongming, E-mail: zhongming.zhao@vanderbilt.edu [Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN (United States); Lu Bo, E-mail: bo.lu@vanderbilt.edu [Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN (United States)

    2012-03-01

    Purpose: The development of drug-resistant phenotypes has been a major obstacle to cisplatin use in non-small-cell lung cancer. We aimed to identify some of the molecular mechanisms that underlie cisplatin resistance using microarray expression analysis. Methods and Materials: H460 cells were treated with cisplatin. The differences between cisplatin-resistant lung cancer cells and parental H460 cells were studied using Western blot, MTS, and clonogenic assays, in vivo tumor implantation, and microarray analysis. The cisplatin-R cells were treated with human recombinant insulin-like growth factor (IGF) binding protein-3 and siRNA targeting IGF-1 receptor. Results: Cisplatin-R cells illustrated greater expression of the markers CD133 and aldehyde dehydrogenase, more rapid in vivo tumor growth, more resistance to cisplatin- and etoposide-induced apoptosis, and greater survival after treatment with cisplatin or radiation than the parental H460 cells. Also, cisplatin-R demonstrated decreased expression of insulin-like growth factor binding protein-3 and increased activation of IGF-1 receptor signaling compared with parental H460 cells in the presence of IGF-1. Human recombinant IGF binding protein-3 reversed cisplatin resistance in cisplatin-R cells and targeting of IGF-1 receptor using siRNA resulted in sensitization of cisplatin-R-cells to cisplatin and radiation. Conclusions: The IGF-1 signaling pathway contributes to cisplatin-R to cisplatin and radiation. Thus, this pathway represents a potential target for improved lung cancer response to treatment.

  10. Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Zhang Ping

    2006-09-01

    Full Text Available Abstract Background Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. Methods A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. Results Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 μM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. Conclusion The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis

  11. Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

    International Nuclear Information System (INIS)

    Zhang, Ping; Zhang, Zhiyuan; Zhou, Xiaojian; Qiu, Weiliu; Chen, Fangan; Chen, Wantao

    2006-01-01

    Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 μM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis and further intervention in cisplatin resistance

  12. Sex-based differences in the effect of intra-arterial treatment of stroke: analysis of the PROACT-2 study.

    Science.gov (United States)

    Hill, Michael D; Kent, David M; Hinchey, Judith; Rowley, Howard; Buchan, Alastair M; Wechsler, Lawrence R; Higashida, Randall T; Fischbein, Nancy J; Dillon, William P; Gent, Michael; Firszt, Carolyn M; Schulz, Gregory A; Furlan, Anthony J

    2006-09-01

    Sex influences outcome after intravenous thrombolysis. In a combined analysis of the tissue plasminogen activator clinical trials, a sex-by-treatment interaction was observed. We sought to confirm that observation in an independent data set. Data were from the Pro-Urokinase for Acute Cerebral Thromboembolism-2 (PROACT-2) trial. Baseline factors were compared by sex. The primary outcome was an assessment of a sex-by-treatment interaction term within a logistic regression model, using a modified Rankin Scale score intra-arterial stroke thrombolysis, in both women and men, prourokinase resulted in better outcomes than control. A sex by prourokinase treatment interaction was observed, with women showing a larger treatment effect (20% absolute benefit) compared with men (10% absolute benefit). The reason for this interaction is that thrombolytic treatment nullifies the worse outcome for untreated women compared with men. The reasons for effect modification do not include improved recanalization at 2 hours among women. Women with middle cerebral artery ischemic stroke benefit more from intra-arterial therapy. Further study of how sex affects stroke outcome is needed.

  13. Contrast-enhanced ultrasonography with intraarterial administration of SonoVue for guidance of transarterial chemoembolization: an initial experience.

    Science.gov (United States)

    Moschouris, Hippocrates; Malagari, Katerina; Kalokairinou, Marianna; Stamatiou, Konstantinos; Marinis, Athanasios; Papadaki, Marina Georgiou

    2011-12-01

    To describe the technique and to evaluate the feasibility of contrast-enhanced ultrasound with intraarterial administration of echo-enhancer (i.a CEUS) as a method for guidance of transarterial chemoembolization (TACE). Twelve patients with 17 target liver tumors underwent superselective TACE, guided with i.a CEUS. After microcatheter placement in a (sub)segmental artery suspected as a tumor feeder, a diluted suspension of SonoVue was injected through the microcatheter, and imaging of the target tumor was performed with a low mechanical index technique and with contrast-specific software. If intraarterial injection of SonoVue was associated with immediate, strong tumoral enhancement, the injected artery was considered as tumor-feeding and TACE was performed, otherwise another artery was evaluated. From 25 segmental or subsegmental arteries evaluated i.a CEUS confirmed that 16 arteries were actually tumor feeders and unequivocal excluding 4 arteries as a tumor arterial supply. The remainder 5 arterial branches could not be safely characterized due to artifacts or technical limitations. In 8 patients in which tumoral vascular supply could not be elucidated by angiography alone, i.a CEUS increased the accuracy of supereselective embolization, and provided other clinically relevant information in 2 of these patients. No adverse effects were observed. For guidance of superselective TACE i.a CEUS is a safe and feasible method..

  14. Clinical experience of intra-arterial therapy in patients with acute ischemic stroke from a single institute

    International Nuclear Information System (INIS)

    Park, So Young; Lee, Han Bin; Kim, Jong Guk; Oh, Seung Hun; Kim, Jin Kwon; Kim, Sang Heum; Kim, Ok Joon; Kim, Nam Keun

    2016-01-01

    To compare the efficacy and safety between intra-arterial therapy (IAT) and intra-venous and intra-arterial combined therapy (IVIACT) in patients with acute ischemic stroke in the anterior circulation territory. Forty-one patients treated with IAT using Solitaire were retrospectively reviewed. Nineteen patients were treated with IAT, twenty-two patients were treated with IVIACT, and ten patients of the forty-one patients were managed with multimodal treatment like stent, balloon angioplasty etc. We investigated the rate of recanalization and hemorrhage, NIH stroke scale and 3-month modified Rankin Scale. The overall recanalization rate was 93% and symptomatic ICH occurred in 10% of the patients. There was no difference in hemorrhage, recanalization rate, and early improvement between IAT and IVIACT. Good outcome was more frequently observed in 59% of the patients with IVIACT than 36% of the patients treated with IAT without any significant difference. The patients managed with multimodal treatment did not show any significant hemorrhage outcome. IAT using Solitaire is a useful treatment method without high risk in patients with acute ischemic stroke in the anterior circulation territory. Also, IVIACT and multimodal treatment might be considered as reasonable therapeutic options in these patients

  15. Comparison of Intra-arterial and Subcutaneous Testicular Hyaluronidase Injection Treatments and the Vascular Complications of Hyaluronic Acid Filler.

    Science.gov (United States)

    Wang, Muyao; Li, Wei; Zhang, Yan; Tian, Weidong; Wang, Hang

    2017-02-01

    Hyaluronidase is a key preventative treatment against vascular complications of hyaluronic acid (HA) filler injection, but the degradation profile of HA to hyaluronidase is limited, and the comparison between intra-arterial and subcutaneous injections of hyaluronidase has not been studied. To evaluate HA degradation to hyaluronidase and compare different treatments between intra-arterial and subcutaneous testicular hyaluronidase injections. The authors observed HA degradation to hyaluronidase in vitro via microscopic examination and particle analysis. Rabbit ears were used for the in vivo study. There were 2 control groups receiving ligation or HA-induced embolism in the arteries, respectively, and 2 intervention groups receiving hyaluronidase treatments in different regions. The laser Doppler blood perfusion monitoring measurements were made at defined time points, and biopsies were taken on Day 2. Nearly, all of the HAs degraded in vitro at the 1-hour time point. Subcutaneous hyaluronidase treatment showed better recovery of blood perfusion. Histology showed severe inflammation in the embolism group and mild inflammation in the intervention groups. A complete enzymatic degradation of HA filler to hyaluronidase needs a certain time, and subcutaneous hyaluronidase treatment may be the better option.

  16. Clinical experience of intra-arterial therapy in patients with acute ischemic stroke from a single institute

    Energy Technology Data Exchange (ETDEWEB)

    Park, So Young [Dept. Neurology, Seoul National University-Seoul Metropolitan Government Boramae Medical Center, Seoul (Korea, Republic of); Lee, Han Bin; Kim, Jong Guk; Oh, Seung Hun; Kim, Jin Kwon; Kim, Sang Heum; Kim, Ok Joon [CHA Bundang Medical Center, CHA University, Seongnam (Korea, Republic of); Kim, Nam Keun [Institute for Clinical Research, School of Medicine, CHA University, Seongnam (Korea, Republic of)

    2016-11-15

    To compare the efficacy and safety between intra-arterial therapy (IAT) and intra-venous and intra-arterial combined therapy (IVIACT) in patients with acute ischemic stroke in the anterior circulation territory. Forty-one patients treated with IAT using Solitaire were retrospectively reviewed. Nineteen patients were treated with IAT, twenty-two patients were treated with IVIACT, and ten patients of the forty-one patients were managed with multimodal treatment like stent, balloon angioplasty etc. We investigated the rate of recanalization and hemorrhage, NIH stroke scale and 3-month modified Rankin Scale. The overall recanalization rate was 93% and symptomatic ICH occurred in 10% of the patients. There was no difference in hemorrhage, recanalization rate, and early improvement between IAT and IVIACT. Good outcome was more frequently observed in 59% of the patients with IVIACT than 36% of the patients treated with IAT without any significant difference. The patients managed with multimodal treatment did not show any significant hemorrhage outcome. IAT using Solitaire is a useful treatment method without high risk in patients with acute ischemic stroke in the anterior circulation territory. Also, IVIACT and multimodal treatment might be considered as reasonable therapeutic options in these patients.

  17. Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion Center Setting.

    Science.gov (United States)

    Schmier, Jordana; Ogden, Kristine; Nickman, Nancy; Halpern, Michael T; Cifaldi, Mary; Ganguli, Arijit; Bao, Yanjun; Garg, Vishvas

    2017-08-01

    Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Cisplatin- vs. oxaliplatin-based radiosensitizing chemotherapy for squamous cell carcinoma of the esophagus. A comparison of two preoperative radiochemotherapy regimens

    Energy Technology Data Exchange (ETDEWEB)

    Fakhrian, K. [University Clinic of the Ruhr University Bochum, Department of Radiation Oncology, Marien Hospital Herne, Herne (Germany); University of Bochum, Department of Radiation Oncology, Bochum (Germany); Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Ordu, A.D.; Molls, M. [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Haller, B. [Technische Universitaet Muenchen, Department of Epidemiology and Medical Statistics, Klinikum rechts der Isar, Munich (Germany); Theisen, J. [Technische Universitaet Muenchen, Department of Surgery, Klinikum rechts der Isar, Munich (Germany); Lordick, F. [University Clinic Leipzig, University Cancer Center Leipzig (UCCL), Leipzig (Germany); Technische Universitaet Muenchen, Department of Internal Medicine III (Hematology/Oncology), Klinikum rechts der Isar, Munich (Germany); Bisof, V. [Clinical Hospital Centre Zagreb, Department of Oncology, Zagreb (Croatia); Geinitz, H. [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Krankenhaus der Barmherzigen Schwestern Linz, Department of Radiation Oncology, Linz (Austria)

    2014-11-15

    To compare the outcomes of two neoadjuvant radiochemotherapy (N-RCT) regimens for squamous cell carcinoma of the esophagus (ESCC). The standard N-RCT regimen for ESCC at our institution between 2002 and 2011 was a total dose of 45 Gy (1.8-Gy fractions) with concomitant cisplatin (20 mg/m{sup 2}, days 1-5 and 29-33) and 5-fluorouracil (5-FU; 225 mg/m{sup 2}, 24 h continuous infusion on days 1-33). During the same period, a phase I/II study comparing the standard ESCC N-RCT protocol with a regimen identical except for the replacement of cisplatin with weekly oxaliplatin (40-50 mg/m{sup 2}) was performed at our center. The standard regimen was used to treat 40 patients; 37 received the oxaliplatin regimen. All patients subsequently underwent radical resection with reconstruction according to tumor location and two-field lymph node dissection. Median follow-up time from the start of N-RCT was 74 months (range 3-116 months). The two patient groups were comparable in terms of demographic and baseline tumor characteristics. R0 resection was achieved in 37/39 patients (95 %) in the cisplatin-based N-RCT group, compared to 24/37 (65 %) in the oxaliplatin-based group (p = 0.002). A pathological complete response (pCR) was seen in the resection specimens from 18/39 patients (46 %) in the cisplatin-based N-RCT group and in 8/37 (22 %) oxaliplatin-group patients. In the cisplatin group, 2- and 5-year overall survival (OS) rates were 67 ± 8 % and 60 ± 8 %, respectively (median OS 103 months), compared to 38 ± 8 % and 32 ± 8 %, respectively, for the oxaliplatin group (median OS 17 months; hazard ratio, HR 0.452; 95 % confidence interval, CI 0.244-0.839; p = 0.012). Oxaliplatin-based N-RCT resulted in poorer outcomes in ESCC patients and should not routinely replace cisplatin-based N-RCT. (orig.) [German] Unser Ziel war es, die Ergebnisse zweier neoadjuvanter Radiochemotherapie- (N-RCT-) Konzepte mit nachfolgender Resektion beim fortgeschrittenen Plattenepithelzellkarzinom des

  19. Effect of steel and teflon infusion catheters on subcutaneous adipose tissue blood flow and infusion counter pressure in humans

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Skov-Jensen, Camilla; Kaastrup, Peter

    2009-01-01

    BACKGROUND: Subcutaneous tissue is an important target for drug deposition or infusion. A local trauma may induce alterations in local microcirculation and diffusion barriers with consequences for drug bioavailability. We examined the influence of infusion catheters' wear time on local...... microcirculation and infusion counter pressure. METHODS: One steel catheter and one Teflon (Dupont, Wilmington, DE) catheter were inserted in subcutaneous, abdominal adipose tissue (SCAAT) in 10 healthy, lean men. The catheters were infused with isotonic saline at a rate of 10 microL/h for 48 h. Another steel...... catheter and a Teflon catheter were inserted contralateral to the previous catheters after 48 h. The infusion counter pressure was measured during a basal infusion rate followed by a bolus infusion. The measurements during a basal rate infusion were repeated after the bolus infusion. Adipose tissue blood...

  20. Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment

    Directory of Open Access Journals (Sweden)

    Manish Jain

    2016-09-01

    Full Text Available Photodynamic therapy (PDT, which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus this intra-arterial PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®, efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Methods and Results: Visudyne® (100, 200 and 500 ng/ml was perfused for 5-30 minutes in atherosclerotic aorta isolated from ApoE-/- mice. The fluorescence Intensity (FI after 15 minutes of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8, 200 (FI-31.9 ± 1.9 or 500 ng/ml (FI-42.9 ± 1.2. Visudyne® (500 ng/ml uptake also increased with the administration time from 5 minutes (FI-9.8 ± 2.5 to 10 minutes (FI-23.3 ± 3.0 and 15 minutes (FI-42.9 ± 3.4 before reaching saturation at 30 minutes (FI-39.3 ± 2.4 contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm2, irradiance-334 mW/cm2 applied immediately after Visudyne® perfusion (500 ng/ml for 15 minutes using a cylindrical light diffuser coupled to a diode laser (690 nm, led to an increase of ROS (Dihydroethidium (FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9 and apoptotic cells (TUNEL (2.5 ± 1.6 %, 41.3 ± 15.3 %, 58.9 ± 6 %, mainly plaque macrophages (immunostaining (0.3 ± 0.2 %, 37.6 ± 6.4 %, 45.3 ± 5.4 % at light doses of 0, 100 or 200 J/cm2 respectively. Limited apoptosis was observed in the medial wall (0.5 ± 0.2 %, 8.5 ± 4.7 %, 15.3 ± 12.7 %. Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram. Conclusion: We demonstrated that sufficient accumulation of

  1. Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne®: Implication for Atherosclerotic Plaque Treatment.

    Science.gov (United States)

    Jain, Manish; Zellweger, Matthieu; Frobert, Aurélien; Valentin, Jérémy; van den Bergh, Hubert; Wagnières, Georges; Cook, Stéphane; Giraud, Marie-Noelle

    2016-01-01

    Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this "intra-arterial" PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®), efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Visudyne® (100, 200, and 500 ng/ml) was perfused for 5-30 min in atherosclerotic aorta isolated from ApoE(-/-) mice. The fluorescence Intensity (FI) after 15 min of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8), 200 (FI-31.9 ± 1.9) or 500 ng/ml (FI-42.9 ± 1.2). Visudyne® (500 ng/ml) uptake also increased with the administration time from 5 min (FI-9.8 ± 2.5) to 10 min (FI-23.3 ± 3.0) and 15 min (FI-42.9 ± 3.4) before reaching saturation at 30 min (FI-39.3 ± 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm(2), irradiance-334 mW/cm(2)) was applied immediately after Visudyne® perfusion (500 ng/ml for 15 min) using a cylindrical light diffuser coupled to a diode laser (690 nm). PDT led to an increase of ROS (Dihydroethidium; FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9) and apoptotic cells (TUNEL; 2.5 ± 1.6, 41.3 ± 15.3, 58.9 ± 6%), mainly plaque macrophages (immunostaining; 0.3 ± 0.2, 37.6 ± 6.4, 45.3 ± 5.4%) respectively without laser irradiation, or at 100 and 200 J/cm(2). Limited apoptosis was observed in the medial wall (0.5 ± 0.2, 8.5 ± 4.7, 15.3 ± 12.7%). Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram). We demonstrated that sufficient accumulation of Visudyne® within plaque could be achieved in short

  2. Reduction of cellular cisplatin resistance by hyperthermia - a review

    NARCIS (Netherlands)

    Hettinga, JVE; Konings, AWT; Kampinga, HH

    1997-01-01

    Resistance to cisplatin (cDDP) is a major limitation to its clinical effectiveness. Review of literature data indicates that cDDP resistance is a multifactorial phenomenon. This provides an explanation why attempts to reverse or circumvent resistance using cDDP-analogues or combination therapy with

  3. Comparative Efficacy of Cisplatin vs. Gemcitabine as Concurrent ...

    African Journals Online (AJOL)

    no previous treatment. Patients were randomized to receive either weekly Cisplatin 40mg/m2 intravenously or Gemcitabine 100mg/m2 intravenously for 5 cycles concurrent with external beam radiation therapy 50Gy/25# as 5# / weeks, followed by single application of medium does rate intracavitory brachytherapy to deliver ...

  4. Interaction of cisplatin with a CCHC zinc finger motif.

    Science.gov (United States)

    Castiglione Morelli, Maria Antonietta; Ostuni, Angela; Cristinziano, Pier Luigi; Tesauro, Diego; Bavoso, Alfonso

    2013-04-01

    The interaction between cisplatin and an 18-residue CCHC zinc finger motif derived from a retroviral nucleocapsid protein (PyrZf18) has been studied using UV-visible, CD and (1)H NMR spectroscopies and ESI-MS spectrometry. Cisplatin irreversibly blocks the cysteine zinc binding groups in the free peptide and is able to slowly eject zinc from the zinc-peptide complex. The observed end product of the reaction with cisplatin is a complex in which only one ammonia molecule is coordinated to platinum. After an initial binding with two cysteine residues and the formation of the (PyrZf18)-platinum-(NH3)2 complex, a release of one ammonia molecule occurs because of trans-labilization, and the third cysteine is coordinated, leading to a mixture of isomers and/or conformers of the (PyrZf18)-platinum-NH3 complex. The results are discussed with respect to the potential antiretroviral activity of platinum(II) compounds and to the possible interaction of cisplatin with the cellular nucleic acid binding proteins. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

  5. Membrane Transporters as Mediators of Cisplatin Effects and Side Effects

    Directory of Open Access Journals (Sweden)

    Giuliano Ciarimboli

    2012-01-01

    Full Text Available Transporters are important mediators of specific cellular uptake and thus, not only for effects, but also for side effects, metabolism, and excretion of many drugs such as cisplatin. Cisplatin is a potent cytostatic drug, whose use is limited by its severe acute and chronic nephro-, oto-, and peripheral neurotoxicity. For this reason, other platinum derivatives, such as carboplatin and oxaliplatin, with less toxicity but still with antitumoral action have been developed. Several transporters, which are expressed on the cell membranes, have been associated with cisplatin transport across the plasma membrane and across the cell: the copper transporter 1 (Ctr1, the copper transporter 2 (Ctr2, the P-type copper-transporting ATPases ATP7A and ATP7B, the organic cation transporter 2 (OCT2, and the multidrug extrusion transporter 1 (MATE1. Some of these transporters are also able to accept other platinum derivatives as substrate. Since membrane transporters display a specific tissue distribution, they can be important molecules that mediate the entry of platinum derivatives in target and also nontarget cells possibly mediating specific effects and side effects of the chemotherapeutic drug. This paper summarizes the literature on toxicities of cisplatin compared to that of carboplatin and oxaliplatin and the interaction of these platinum derivatives with membrane transporters.

  6. Mechanisms and circumvention of cellular resistance to cisplatin.

    NARCIS (Netherlands)

    Hospers, Geesiena Alberdina Petronella

    1989-01-01

    Cisplatin (CDDP) is an active cytostatic agent. A limitation to its effectiveness initially or appearing during cystatic treatment is the occurrence of resistance. This thesis describes mechanisms wich are responsible for acquired cellular CDDP resistance. To investigate cellular CDDP resistance, a

  7. Competitive reactions among glutathione, cisplatin and copper-phenanthroline complexes.

    Science.gov (United States)

    Cadoni, Enzo; Valletta, Elisa; Caddeo, Graziano; Isaia, Francesco; Cabiddu, Maria Grazia; Vascellari, Sarah; Pivetta, Tiziana

    2017-08-01

    A large number of cancers are treated with cisplatin (CDDP). However, its use is limited by drug resistance, which is often related to intracellular levels of thiol-containing molecules such as glutathione (GSH). The role of GSH in cisplatin-resistant cancer cells is still unclear. GSH may form adducts with CDDP which results in the deactivation of the drug, and, actually, a high intracellular level of GSH was observed in some cisplatin-resistant cancers. To overcome drug resistance, CDDP is often administered in combination with one or more drugs to exploit a possible synergistic effect. In previous studies, we observed that the sensitivity to CDDP of leukemic and ovarian cisplatin-resistant cancer cells was restored in the presence of [Cu(phen) 2 (H 2 O)](ClO 4 ) 2 (C0) (phen is 1,10-phenathroline). In order to clarify the possible interactions between GSH and CDDP, the reactivity and competitive reactions among CDDP, C0 and GSH in binary and ternary mixtures were studied. The investigation was extended also to [Cu(phen)(H 2 O) 2 (ClO 4 ) 2 ] (C10) and GSSG, the oxidized form of GSH. It was observed that CDDP was able to react with the studied copper complexes and with GSH or GSSG. However, in mixtures containing CDDP, GSH or GSSG and C0 or C10, only copper-glutathione complexes were detected, while no platinum-glutathione adducts were found. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Nutritional shortage augments cisplatin-effects on murine melanoma cells.

    Science.gov (United States)

    Antunes, F; Pereira, G J; Jasiulionis, M G; Bincoletto, C; Smaili, S S

    2018-02-01

    Melanoma incidence increases every year worldwide and is responsible for 80% of skin cancer deaths. Due to its metastatic potential and resistance to almost any treatments such as chemo, radio, immune and targeted-therapy, the patients still have a poor prognosis, especially at metastatic stage. Considering that, it is crucial to find new therapeutic approaches to overcome melanoma resistance. Here we investigated the effect of cisplatin (CDDP), one of the chemotherapeutic agents used for melanoma treatment, in association with nutritional deprivation in murine melanoma cell lines. Cell death and autophagy were evaluated after the treatment with cisplatin, nutritional deprivation and its association using an in vitro model of murine melanocytes malignant transformation to metastatic melanoma. Our results showed that nutritional deprivation augmented cell death induced by cisplatin in melanoma cells, especially at the metastatic subtype, with slight effects on melanocytes. Mechanistic studies revealed that although autophagy was present at high levels in basal conditions in melanoma cells, was not essential for cell death process that involved mitochondrial damage, reactive oxygen species production and possible glycolysis inhibition. In conclusion, nutritional shortage in combination with chemotherapeutic drugs as cisplatin can be a valuable new therapeutic strategy to overcome melanoma resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Amelioration of Cisplatin-Induced Nephrotoxicity in Rats by ...

    African Journals Online (AJOL)

    Purpose: To investigate the possible protective role of curcumin and α-tocopherol against cisplatininduced nephrotoxicity in rat. Methods: Male Wistar rats were divided into five groups. Groups 1 and 2 were intraperitoneally (i.p.) injected with normal saline and cisplatin (20 mg/kg), respectively. Groups 3, 4 and 5 were ...

  10. Modulatory effect of Althaea officinalis L root extract on cisplatin ...

    African Journals Online (AJOL)

    Herbarium, Chinese Academy of Sciences. (IBSC) with tTaxon Id # 20001368. Experimental design and cell cultures. The entire study was performed in three steps, as follows: (1) ascertain the 50 % inhibitory concentration (IC50) value of cisplatin in A549 cells, (2) ascertain the effect of direct exposure to an AOR extract on ...

  11. Protective effects of cistanches herba aqueous extract on cisplatin ...

    African Journals Online (AJOL)

    Materials and Methods: We administered low- and high-concentration CH to cisplatin-induced POF mice for 2 weeks and determined body and ovarian weights, as well as serum follicle-stimulating hormone (FSH) and estradiol concentrations, to evaluate ovarian function. In addition, we evaluated the protective mechanisms ...

  12. High prevalence of cisplatin-induced ototoxicity in Cape Town ...

    African Journals Online (AJOL)

    Background. Cisplatin is administered as the first-line treatment of soft-tissue cancers. It has a reported cure rate of up to 85%, but is associated with a high incidence of ototoxicity, characterised by irreversible bilateral hearing loss and affecting 23 - 50% of adults who receive the drug. Objectives. To determine the incidence ...

  13. (Turcz) Schisandraceae seed extracts and cisplatin on cytotoxicity ...

    African Journals Online (AJOL)

    Purpose: Schisandra chinensis is a plant used in traditional Chinese and Russian medicine. An S. chinensis seed extract was tested for its ability to potentiate the effects of the anticancer agent cisplatin in MCF-7 breast cancer cells. Methods: S. chinensis seeds were extracted with ethanol and the ethanol was evaporated ...

  14. Effects of cisplatin chemotherapy on the osseointegration of titanium implants.

    Science.gov (United States)

    Al-Mahalawy, Haytham; Marei, Hesham F; Abuohashish, Hatem; Alhawaj, Hussain; Alrefaee, Munir; Al-Jandan, Badr

    2016-04-01

    The effect of chemotherapy on the osseointegration of dental implants has received less interest compared with radiotherapy. Thus, the aim of the current study was to investigate the effect of cisplatin chemotherapy on the osseointegration of dental implants in a rabbit model. Sixteen New Zealand White rabbits were randomly assigned to two groups of treatment of either cisplatin at 2.5 mg/kg/week for 4 weeks (n = 8) or placebo (n = 8), in which the first dose was administered 2 days prior to the surgical procedure. Each rabbit received one titanium dental implant inserted in the right distal femoral condyle. Four rabbits from each group were sacrificed 4 and 8 weeks after implant insertion. Osseointegration of the dental implants was analysed using micro-computed tomography and histomorphometric evaluation. Analysis of micro-computed tomography data and histomorphometric data showed that the osseointegration parameters, including the ratio of bone volume to total volume (BV/TV) and bone-implant contact (BIC%) for the cisplatin group, were significantly lower compared to the control group at 4 and 8 weeks. (P ≤ 0.05). Cisplatin chemotherapy had a negative effect on the osseointegration of dental implants when inserted throughout the chemotherapeutic regimens in a rabbit model. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  15. COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

    Science.gov (United States)

    Crabb, Simon J; Martin, Karen; Abab, Julia; Ratcliffe, Ian; Thornton, Roger; Lineton, Ben; Ellis, Mary; Moody, Ronald; Stanton, Louise; Galanopoulou, Angeliki; Maishman, Tom; Geldart, Thomas; Bayne, Mike; Davies, Joe; Lamb, Carolynn; Popat, Sanjay; Joffe, Johnathan K; Nutting, Chris; Chester, John; Hartley, Andrew; Thomas, Gareth; Ottensmeier, Christian; Huddart, Robert; King, Emma

    2017-12-01

    Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Routine saline infusion sonohysterography prior to assisted ...

    African Journals Online (AJOL)

    53.85%), 8 (30.77%) and 4 (15.38%) respectively. The average duration of the procedure was 6 minutes with a range of 4-9 minutes. Saline infusion sonohysterography is a reliable, cost effective and safe diagnostic tool in the evaluation of the ...

  17. Forearm metabolism during infusion of adrenaline

    DEFF Research Database (Denmark)

    Simonsen, L; Stefl, B; Bülow, J

    2000-01-01

    Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were cathete...

  18. Comparison of infusion pumps calibration methods

    Science.gov (United States)

    Batista, Elsa; Godinho, Isabel; do Céu Ferreira, Maria; Furtado, Andreia; Lucas, Peter; Silva, Claudia

    2017-12-01

    Nowadays, several types of infusion pump are commonly used for drug delivery, such as syringe pumps and peristaltic pumps. These instruments present different measuring features and capacities according to their use and therapeutic application. In order to ensure the metrological traceability of these flow and volume measuring equipment, it is necessary to use suitable calibration methods and standards. Two different calibration methods can be used to determine the flow error of infusion pumps. One is the gravimetric method, considered as a primary method, commonly used by National Metrology Institutes. The other calibration method, a secondary method, relies on an infusion device analyser (IDA) and is typically used by hospital maintenance offices. The suitability of the IDA calibration method was assessed by testing several infusion instruments at different flow rates using the gravimetric method. In addition, a measurement comparison between Portuguese Accredited Laboratories and hospital maintenance offices was performed under the coordination of the Portuguese Institute for Quality, the National Metrology Institute. The obtained results were directly related to the used calibration method and are presented in this paper. This work has been developed in the framework of the EURAMET projects EMRP MeDD and EMPIR 15SIP03.

  19. Effect of intravenous dexmedetomidine infusion on some ...

    African Journals Online (AJOL)

    Background: This study was designed to evaluate the effect of intravenous dexmedetomidine infusion in patients undergoing major abdominal surgery on stress response markers as plasma interleukin-6, cortisol and blood glucose level. It also assessed its effect on recovery profile and postoperative pain. Methods: Thirty ...

  20. Targeted Intra-arterial Transplantation of Stem Cells to the Injured CNS is More Effective than Intravenous Administration - Engraftment is Dependent on Cell Type and Adhesion Molecule Expression

    DEFF Research Database (Denmark)

    Lundberg, Johan; Södersten, Erik; Sundström, Erik

    2011-01-01

    with inflammation, such as traumatic brain injury, there is a transient up-regulation of ICAM-1 and VCAM-1 which might provide enviromental cues for migration of stem cells from blood to parenchyma. The aim of this study was to i) analyze the effect of intra-arterial administration on cellular engraftment, ii...

  1. Cost-Effectiveness of Magnetic Resonance Angiography Versus Intra-arterial Digital Subtraction Angiography to Follow-Up Patients With Coiled Intracranial Aneurysms

    NARCIS (Netherlands)

    Schaafsma, Joanna D.; Koffijberg, Hendrik; Buskens, Erik; Velthuis, Birgitta K.; van der Graaf, Yolanda; Rinkel, Gabriel J. E.

    Background and Purpose-To follow up patients with coiled intracranial aneurysms, magnetic resonance angiography (MRA) is a promising noninvasive alternative to current standard intra-arterial digital subtraction angiography (IA-DSA). MRA test results do not always concord with those of IA-DSA, and

  2. Cost-effectiveness of magnetic resonance angiography versus intra-arterial digital subtraction angiography to follow-up patients with coiled intracranial aneurysms

    NARCIS (Netherlands)

    Schaafsma, Joanna D.; Koffijberg, Hendrik; Buskens, Erik; Velthuis, Birgitta K.; van der Graaf, Yolanda; Rinkel, Gabriël J.E.

    Background and Purpose-: To follow up patients with coiled intracranial aneurysms, magnetic resonance angiography (MRA) is a promising noninvasive alternative to current standard intra-arterial digital subtraction angiography (IA-DSA). MRA test results do not always concord with those of IA-DSA, and

  3. Computational fluid dynamics study of intra-arterial chemotherapy for oral cancer.

    Science.gov (United States)

    Kitajima, Hiroaki; Oshima, Marie; Iwai, Toshinori; Ohhara, Yoshihito; Yajima, Yasuharu; Mitsudo, Kenji; Tohnai, Iwai

    2017-05-15

    Intra-arterial chemotherapy (IAC) for oral cancer can deliver a higher concentration of anticancer agent into a tumor-feeding artery than intravenous systemic chemotherapy. However, distribution of anticancer agent into several branches of the external carotid artery (ECA) in IAC has not demonstrated sufficient treatment efficacy. To improve the effectiveness of IAC, the flow distribution of anticancer agent into the branches of the ECA in several IAC methods was investigated using computational fluid dynamics (CFD). Patient-specific three-dimensional vessel models were created from CT images of 2 patients with tongue cancer. Catheter models were combined with the vessel models. Thirty-two models were generated with varying vertical and horizontal positions of the catheter tip. With the use of a zero-dimensional resistance model of the peripheral vessel network, conventional IAC and superselective IAC were simulated in 30 and 2 models, respectively. The flow distribution of anticancer agent into the branches of the ECA was investigated in 32 models. Additionally, the blood streamline was traced from the inlet of the common carotid artery toward each outlet to examine the flow of anticancer agent in all models, and the wall shear stress of the vessel was calculated for some models. The CFD simulations could be conducted within a reasonable computational time. In several models, the anticancer agent flowed into the target artery only when the catheter tip was located below the bifurcation of the ECA and each target artery. Furthermore, the anticancer agent tended to flow into the target artery when the catheter tip was shifted toward the target artery. In all ECA branches that had flow of anticancer agent, the blood streamlines to the target arteries contacted the catheter tip. Anticancer agent flowed into only the target artery in patients' models for superselective IAC. However, high wall shear stress was observed at the target artery in one patient's model. This

  4. Intra-Arterial Chemotherapy (Ophthalmic Artery Chemosurgery for Group D Retinoblastoma.

    Directory of Open Access Journals (Sweden)

    David H Abramson

    Full Text Available To report globe salvage rates, patient survival and adverse events of ophthalmic artery chemosurgery (OAC for International Classification of Retinoblastoma (ICRB group D retinoblastoma (naive and after prior failures.Single institution retrospective review of all Group D eyes treated with OAC from 5/2006-12/2012. Patients were treated according to our previously-published techniques. Primary outcome was globe retention without need for external beam radiotherapy (EBRT. Demographics, prior treatments, OAC agents used, and adverse events were also recorded.112 group D eyes (103 patients that underwent OAC were included (average follow-up was 34 months, range: 2-110 months. 47 eyes were treatment-naïve, 58 eyes received prior treatments elsewhere, and 7 young infants (7 eyes underwent our published "bridge therapy" (single agent intravenous carboplatin until old enough to undergo OAC. Median number of OAC sessions/eye was 3 (range 1-9. 110/112 eyes received intra-arterial melphalan, but only 31 eyes received melphalan alone. 43 eyes received carboplatin, and 78 eyes received topotecan (never as a single agent. 80/112 eyes received >1 drug over their treatment course, and 39 eyes received all three agents. 24 eyes (16 pretreated, 7 treatment-naïve, 1 bridge failed treatment and required enucleation during the study period. Enucleation and EBRT were avoided in 88/112 eyes (78.6%; including 40/47 [85.1%] treatment-naïve eyes, 42/58 [72.4%] previously-treated eyes, and 6/7 eyes [85.7%] among bridge patients. By Kaplan-Meier survival analysis, globe salvage rate was 74% at 110 months among all patients, and 85% at 110 months in the treatment-naïve subgroup. Transient grade 3/4 neutropenia was more common in patients receiving OAC bilaterally. No child died of metastatic disease.OAC is effective for curing group D retinoblastoma, achieving rates of globe salvage many times higher than systemic chemotherapy (10-47%, even in eyes that previously

  5. Renoprotective Effect of Plantago Major Against Nephrotoxicity and Oxidative Stress Induced by Cisplatin.

    Science.gov (United States)

    Parhizgar, Soghra; Hosseinian, Sara; Hadjzadeh, Mousa-Al-Reza; Soukhtanloo, Mohammad; Ebrahimzadeh, Alireza; Mohebbati, Reza; Naji Ebrahimi Yazd, Zohreh; Khajavi Rad, Abolfazl

    2016-07-01

    The aim of this study was to investigate the possible renoprotective effect of Plantago major extract against cisplatin-induced nephrotoxicity in rats. Rats were divided into 6 groups. The first group was the control, group 2 was treated with cisplatin (7 mg/kg, single dose), and groups 3 to 6 received cisplatin with vitamin E (100 mg/kg) and Plantago major  extract at doses of 300 mg/kg, 600 mg/kg, and 1200 mg/kg, for 20 days. On day12, serum concentration of urea, creatinine, and potassium significantly increased and sodium concentration significantly decreased in the cisplatin group compared with the control rats. However, serum creatinine, urea, and potassium concentrations were significantly lower in all of the Plantago major groups compared to the cisplatin group. Also, there was a significant elevation in serum sodium concentration in the Plantago major 600 mg/kg group compared to the cisplatin group on day12. Injection of cisplatin caused a significant elevation in malondialdehyde concentration but a significant decrease in catalase activity and total thiol content compared to the control group. Plantago major extract at 1200 mg/kg significantly improved malondialdehyde concentration and total thiol content compared to the cisplatin group. Catalase activity with Plantago major significantly increased at all doses compared to the cisplatin group. The current study suggests that Plantago major extract and vitamin E are able to improve kidney function as well as oxidative stress in cisplatin-induced renal toxicity in the rat.

  6. Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS

    Science.gov (United States)

    Crone, Barbara; Aschner, Michael; Schwerdtle, Tanja; Karst, Uwe; Bornhorst, Julia

    2015-01-01

    Cis-diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 µm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable. PMID:25996669

  7. Inhibition of PTEN activity aggravates cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Zhou, Jun; Fan, Youling; Tang, Simin; Wu, Huiping; Zhong, Jiying; Huang, Zhengxing; Yang, Chengxiang; Chen, Hongtao

    2017-11-28

    Cisplatin (cis-Diamminedichloroplatinum II) has been widely and effectively used in chemotherapy against tumors. Nephrotoxicity due