生物活性

• 描述The important features of cancer cells include uncontrolled cell proliferation, genome instability and mutations, which allow DNA damaging agents to be applied to cancer cells. Cisplatin is such an inorganic platinum complex which can inhibit DNA synthesis by conforming DNA adducts in tumor cells. Cisplatin induces formation of DNA adducts which activate several signal transduction pathways, including Erk, p53, p73, and MAPK, which culminates in the activation of apoptosis. The IC50 value of Cisplatin is about 20 μM but vary in different kind of cell types. In HeLa cells, Cisplatin (30 μM) treated for 6 h induces an apparent activation of Erk. Cisplatin also shows an effective antineoplastic activity by inducing tumor cells death. Cisplatin displays ability to cause renal proximal tubular cell (RPTC) apoptosis, causing cell shrinkage, a 50-fold increase in caspase 3 activity, a 4-fold increase in phosphatidylserine externalization, and 5- and 15-fold increases in chromatin condensation and DNA hypoploidy, respectively. In many animal tumors models, like head and neck cancer xenografts, cervical squamous carcinoma xenografts, Cisplatin can also be efficient in regression tumor growth. Cisplatin (5 mg/kg) given weekly i.v. at the day 1 and 7 induces a tumor growth inhibition (GI) of 77.5% and 85.1% of the serous xenografts Ov.Ri(C) and OVCAR-3, respectively. In a neuropathic pain rat model, treated with cisplatin at 2 mg/kg/day produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. In a phase 1 clinical trial, cisplatin was used in treating patients with Non-Small-Cell lung tumors. No dose-limiting toxicities occurred during the first 6 weeks of treatment, Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47% and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression.
• 作用机制Reaction with DNA by culminating in either repair of the DNA damage and cell survival or activation of the irreversible apoptotic program^[1].

• 动物研究
  剂量	Rat: 6 mg/kg[3] (i.v.); 7.5 mg/kg[4] (i.p.) Mice: 5.5 mg/kg[5] (i.p.), 10 mg/kg - 26 mg/kg[6] (i.p.)
  给药途径	i.v., i.p.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02128282	Cholangiocarcinoma	Phase 1 Phase 2	Recruiting	November 2021	United States, Arizona ... more >> Mayo Clinic Recruiting Scottsdale, Arizona, United States, 85259-5499 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Mitesh Borad, M.D.          United States, Colorado University of Colorado- Denver Recruiting Aurora, Colorado, United States, 80045 Contact: Amy Szilard    720-848-0702    Amy.Szilard@ucdenver.edu    Principal Investigator: Sarah (Lindsey) Davis, MD          United States, Florida Mayo Clinic Recruiting Jacksonville, Florida, United States, 32224 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Kabir Mody, MD          United States, Minnesota Mayo Clinic Recruiting Rochester, Minnesota, United States, 55905 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Joleen Hubbard, MD          United States, Texas Texas Oncology - Baylor Charles A. Sammons Cancer Center Recruiting Dallas, Texas, United States, 75246 Contact: Tammy Carmical, RN    214-370-1937    tammy.carmical@usoncology.com    Principal Investigator: Carlos Becerra, M.D.          Texas Oncology-Tyler Recruiting Tyler, Texas, United States, 75702 Contact: Karen Poe, RN    903-579-9869    karen.poe@usoncology.com    Principal Investigator: Donald A Richards, M.D.          Korea, Republic of Asan Medical Center Recruiting Seoul, Songpa-gu, Korea, Republic of, 138-736 Contact: Heung-Moon Chang, MD    82-3010-3219 ext 3210    changhm@amc.seoul.kr    Contact: Seok kyung Jeong    82-2-3010-5634    jsk0213@amc.seoul.kr    Samsung Medical Center Recruiting Seoul, Korea, Republic of Contact: Eunyou Lee    82-2-3410-0955    ley0709@samsung.com    Principal Investigator: Joon Oh Park, MD          Seoul National University Hospital Recruiting Seoul, Korea, Republic of Contact: Myoungsun Choi    82-2-2072-7612    iamyou3@hanmail.net    Principal Investigator: Do-Youn Oh, MD          Severance Hospital, Yonsei University Health System Recruiting Seoul, Korea, Republic of Contact: So Young Hwang    82-2-2228-8180    syhwang@yuhs.ac    Principal Investigator: Sun Young Rha, MD          Taiwan China Medical University Hospital Recruiting Taichung City, Taiwan Contact: Pei-Chen Hsu    +886-4-2205-2121    peggyshiu0807@gmail.com    Principal Investigator: Li-Yuan Bai, M.D. Collapse <<
  NCT00915382	Advanced Gastric Cancer	Phase 3	Completed	-	Korea, Republic of ... more >> Department of Oncology, Asan Medical Center Seoul, Korea, Republic of, 138-736 Collapse <<
  NCT03427359	Nasopharyngeal Carcinoma	Phase 2	Completed	-	-

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