Antitumour property and toxicity of Barringtonia racemosa Roxb seed extract in mice

Ethnomedical survey has shown that the seeds of Barringtonia racemosa Roxb are traditionally used in certain remote villages of Kerala (India) to treat cancer like diseases. So the seed extracts were tested for their antitumour activity and toxicity. Intraperitoneal (i.p.) daily administration of 50% methanol extract of this seed to mice challenged with 1 million Dalton's Lymphoma Ascitic (DLA) cells resulted in remarkable dose dependent anti-DLA activity in mice. The optimum dose was found to be 6 mg/kg. This dose protected all the animals challenged with the tumour cells. The efficacy of the drug was found to be better than that of a standard drug, vincristine in this tumour model. However, the oral administration showed only marginal activity compared to i.p. administration. The extract was found to be devoid of conspicuous acute and short-term toxicity to mice, when administered daily, (i.p.) for 14 days up to a dose of 12 mg/kg (which was double the concentration of optimum therapeutic dose). The treated mice showed conspicuous toxic symptoms only at 24 mg/kg. The LD(50) to male mice for a single i.p. dose was found to be 36 mg/kg. The seed extract is an attractive material for further studies leading to drug development.     

Inhibitory effects of Ixora javanica extract on skin chemical carcinogenesis in mice and its antitumour activity.

Topical application of 100 mg/kg body weight of Ixora javanica flower extract inhibited the growth and delayed the onset of papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil. The extract at the same dose, when administered orally inhibited the growth of subcutaneously injected 20-methylcholanthrene (MCA)-induced soft tissue fibrosarcomas significantly. Oral administration of 200 mg/kg of the extract inhibited the growth of intraperitoneally transplanted sarcoma-180 and Ehrlich ascites carcinoma tumours besides showing an increase in the life span of the treated mice. Toxicity studies showed that the blood urea nitrogen levels were elevated post treatment. The active compounds responsible for the above inhibitory effects on tumour growth were identified as ferulic acid (4-hydroxy-3-methoxy cinnamic acid) and its regionmer 3-hydroxy-4-methoxy cinnamic acid.     

Antitumour principles from Ixora javanica

The antitumour agent from Ixora javanica flowers shows broad activity against transplantable solid tumours (DLA) in mice by inhibiting the growth of tumour and arresting the growth of already formed tumours; with lesser activity against Ascites tumours. In vitro cytotoxic studies showed 50% cytotoxicity to Dalton's lymphoma (DLA) and Ehrlich Ascites tumour cells at a concentration of 12 micrograms and 65 micrograms, respectively, with no activity against normal lymphocytes but preferential activity for lymphocytes derived from leukemia patients (ALL) (CML), and K 562 suspension cell culture. Tritiated thymidine incorporation studies indicated the mechanism of action of the agent at the site of DNA synthesis. The purified fractions contained Ferulic acid, Pyrocatacheuic acid and caffeic acid.     

Checkpoint Inhibitors,Palliative Care,or Hospice

Purpose

Checkpoint (CTLA-4, PD-1, and PD-L1) inhibitors have changed the face of oncology. A subset of patients enjoys long, gratifying treatment responses. Unfortunately, most patients do not respond even when expressing favorably markers such as PD-L1. Checkpoint inhibitors are largely palliative (though a subset have long-term cancer responses) and as such patient-related outcome measures should be included when evaluating benefits. The purpose of this review is to place checkpoint inhibitor trials within a palliation context. Included is a discussion on potential adverse effects on end-of-life care.

Recent Findings

Pivotal studies have presented efficacy and safety data but we have little published data on quality of life or symptom responses. Extension of life is approximately 2–3 months with some long-term responses in a minority of patients. The cost of checkpoint inhibitors is high for utility (as measured by quality-adjusted life-year saved) and ranges from 81,000 to over 200,000 USD for quality-adjusted life-year saved. Adverse effects were suboptimally reported in multiple studies. Meaningful responses in many trials as defined by the European Society of Medical Oncology are modest.

Summary

Because at least for now, checkpoint inhibitors are used in advanced cancer and largely palliative patients should be seen by palliative specialists, symptoms related to cancer assessed, and advanced directives addressed. Treatment-related autoimmune diseases represent toxicities which oncologists and palliative specialists must understand. This means that palliative care specialists should know about the benefits and adverse effects of these agents. Whether checkpoint inhibitors increase or decrease aggressive care, hospice referrals, and costs at the end of life is yet to be determined.

     

Chemoprotective effect of Ixora coccinea L. flowers on cisplatin induced toxicity in mice.

The active fraction from Ixora coccinea flowers prevented a decrease in body weight, haemoglobin levels and leucocyte counts of mice treated with cisplatin. It also significantly prolonged the life span of cisplatin treated mice and maintained their blood urea nitrogen levels in the near normal range, indicating its chemoprotective effects.     

Phase I/II randomized trial of intrahepatic arterial infusion chemotherapy with cisplatin and chemoembolization with cisplatin and polyvinyl sponge in patients with ocular melanoma metastatic to the liver

Ocular melanoma has a unique metastatic predilection for the liver and is refractory to most forms of therapy. The dual blood supply of the liver with differential perfusion of metastatic lesions and normal hepatocytes by the hepatic artery and portal vein, respectively, has led to the evaluation of intrahepatic chemotherapy and chemoembolization in this disease. Despite suggestion of efficacy in phase II trials, this therapy has not been systematically evaluated. We conducted a randomized phase I/II trial evaluating escalating doses of intrahepatic chemotherapy with cisplatin with or without polyvinyl sponge (PVS) in 19 patients with ocular melanoma and liver metastases. The cisplatin dose was initiated at 100 mg/m and was increased in 25% increments. Patients were randomized to receive cisplatin alone or cisplatin plus PVS. Seven patients were treated with intrahepatic cisplatin at 100 mg/m: four with PVS, and three without. The dose was escalated to 125 mg/m with or without PVS in the remaining 12 patients. The maximum tolerated dose for intra-hepatic cisplatin was determined to be 125 mg/m with or without PVS. The overall response rate was 16%. Dose-limiting toxicities included renal, hepatic and haematological effects. This therapy produces a modest response rate in patients with ocular melanoma and liver metastases.     

Cytotoxic and antitumour principles from Ixora coccinea flowers

The antitumour activity of Ixora coccinea L. (Rubiaceae) flowers was studied in comparison to intraperitoneally transplanted Dalton's lymphoma (ascitic and solid tumours) and Ehrlich ascites carcinoma (EAC) tumours in mice. Intraperitoneal administration of 200 mg/kg of the active fraction (AF) of the I. coccinea flower increased the life-span of DLA and EAC ascitic tumour-bearing mice by 113 and 68%, respectively. The AF showed less activity against solid tumours (DLA) as compared to ascitic tumours. The same active fraction showed 50% cytotoxicity to DLA, EAC and Sarcoma-180 (S-180) cells in vitro at concentrations of 18, 60 and 25 μg/ml, respectively. It was not toxic to normal lymphocytes, whereas it was toxic to transformed lymphocytes from leukaemic patients, acute lymphoblastic leukaemia (ALL) and chronic myelogenous leukaemia (CML) and K-562 suspension cell cultures. The AF inhibited tritiated thymidine incorporation in cellular DNA.