Cancer Drugs - Side Effects
Therapeutic Potential of Cannabinoids in Counteracting Chemotherapy-induced Adverse Effects: An Exploratory Review
- Sattar Ostadhadi1,
- Mahdieh Rahmatollahi1,
- Ahmad-Reza Dehpour1,2 and
- Reza Rahimian1,*
Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed.
Source : Phytotherapy Research
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Radioprotective Potential of Nigella Sativa Extract in Swiss Albino Mice Exposed to Whole Body
Ganesh Chandra Jagetia and Ravikiran PB
The radioprotective activity of Nigella sativa extract (NSE) was ascertained by administering mice orally with 25, 50, 100, 150, 200, 400 or 500 mg/kg b. wt. of NSE, once daily for five consecutive days prior to 10 Gy γ-irradiation. One hour after the last administration of NSE on fifth day, the animals were whole body exposed to 10 Gy radiation. The exposure of animals to 10 Gy irradiation resulted in the death of all irradiated animals within 16 days post-irradiation, whereas administration of mice with different doses of NSE reduced the radiation-induced mortality and increased the animal survival significantly (p<0.05). The maximum number of survivors (60%) was observed in the group of animals treated with 150 mg/kg NSE. A further increase in the NSE dose up to 500 mg/kg did not significantly elevate the animal survival when compared to 150 mg/kg. Since maximum number of survivors was observed with 150 mg/kg of NSE, it was considered as an optimum dose for radioprotection and further experiments were performed using this dose. In another set of experiments the animals were administered with 150 mg/kg b. wt. of NSE orally once daily for five consecutive days before exposure to 7, 8, 9, 10 or 11 Gy γ-radiation, where the animals were monitored daily up to thirty days post-irradiation for the development of symptoms of radiation sickness and mortality. Treatment of mice with NSE before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the double distilled water (DDW) treated irradiated controls. The LD50/30 was found to be 8 Gy for DDW + irradiation group, whereas the NSE treatment increased LD50/30 up to 9.6 Gy with a dose reduction factor (DRF) of 1.2. The in vitro studies in cell free system revealed that NSE inhibited the generation of various free radicals including 2,2-diphenyl-2-picryl hydrazyl (DPPH), 3-ethyl benzothiazoline-6-sulphonic acid (ABTS•+), hydroxyl (OH•) and superoxide (O2•-) in a concentration dependent manner. The radioprotective effect of NSE may be due to free radical scavenging and increased antioxidant status
Source : Journal Alternative and Integrative Medicine
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The Herbal Preparation SAMITAL® Shows Promise for Pediatric Patients with Chemotherapy-induced Mucositis
Bertoglio JC, Folatre I, Bombardelli E, et al. Management of gastrointestinal mucositis due to cancer therapies in pediatric patients: results of a case series with SAMITAL®. Future Oncol. November 2012;8(11):1481-1486.
Mucositis is characterized by inflammatory lesions of the mucosal lining, and often occurs in the oral and/or gastrointestinal tract of patients with cancer after they receive chemotherapy and/or radiotherapy. This condition causes pain, dysphagia, nutritional problems, susceptibility to infections, and decreases the desire to eat or drink, especially in children. Due to the lack of effective therapies available for this condition, novel treatments are being investigated. Several herbal extracts or extract combinations have shown some promise in adults, including SAMITAL® (Indena S.p.A.; Milan, Italy), an herbal formula consisting of extracts of bilberry (Vaccinium myrtillus), plume poppy (Macleaya cordata) fruits, and echinacea (Echinacea angustifolia) roots.1 There is no further information about the product in the article or on Indena's website. The objective of this case-series study was to assess the use of SAMITAL for the prevention and treatment of chemotherapy-induced gastrointestinal mucositis in pediatric patients.
Pediatric patients included in this study (aged 4 months to 17 years) were from the Hospital Clinico Regional de Valdivia in Valdivia, Chile (n=20) and were either undergoing treatment for leukemia (n=15) or solid tumors (n=5). Both male (n=11) and female patients (n=9) had difficulty eating or drinking and did not respond well to conventional therapy for treatment of painful oral or gastrointestinal mucositis. From June 2009 to September 2010, patients were instructed to mix 1 sachet of SAMITAL with 20 ml of water and then divide the mixture into 3 to 4 teaspoonful aliquots; 3 to 4 sachets were used each day. [Note: The instructions given in the article on p. 1482 seem to suggest 1 sachet per day, though it is not entirely clear; however, on p. 1484, the minimum number of treatment days (4) and the minimum total SAMITAL dose (15 sachets) indicate that 3-4 sachets were used daily, likewise with the maximum days (21) and total dose (68 sachets).] Each patient was told to swish a teaspoonful around the mouth for 1 minute and either spit out or swallow the mixture. Patients were also instructed not to consume anything or rinse their mouths for at least 10 minutes after the treatments. Infants or very young children had the herbal preparation administered in a similar manner by a nurse.
The primary efficacy variable of SAMITAL was based on the evaluation of oral mucositis severity (World Health Organization [WHO] Mucositis Grading Scale), which ranged from grade I (mild: oral soreness, erythema) to grade IV (life-threatening severe: oral alimentation impossible). The secondary efficacy variable was based on a quality-of-life assessment of the variables of irritation, pain, and inflammation (assessed by the Chemotoxic Digestive Tract Mucositis Reference Chart). These assessments were made at baseline and at the end of the treatment period (4-21 days with a dose of 15-68 sachets of SAMITAL for a total of 34 chemotherapy cycles). The initial use of the herbal preparation was for the treatment of mucositis, but it was also used prophylactically in subsequent treatments. Analgesics, anti-inflammatory, and antibacterial medications were also concomitantly administered as needed throughout the study.
For 20 patients, there were a total of 35 episodes of mucositis. The most severe symptom for patients was pain, and all but 2 patients had upper gastrointestinal mucositis. The mean mucositis scores were significantly reduced (P<0.001) from baseline (3.2 ± 0.7) to the end of the treatment period with SAMITAL (0.4 ± 0.6). Moreover, pain, stomatitis, gastritis, diarrhea, dysphagia, and feeding impairment also improved significantly from baseline to the end of treatment (P<0.001). Most of these improvements were observed after the first administration. When given prophylactically, the mucositis severity grade remained below 3. Due to these improvements, all patients were able to continue/complete chemotherapy during the study. Moreover, no adverse events or antagonistic interactions were observed throughout the study.
The authors conclude that SAMITAL is effective, well tolerated, and functions as a prophylactic for chemotherapy-induced oral mucositis in pediatrics. Moreover, the authors also noted that this treatment reduced the need for parenteral nutrition. Although this was not a controlled study, patients that were otherwise untreatable with conventional medicine markedly improved with this herbal preparation. Furthermore, the efficacy of this herbal treatment is consistent with a phase II, randomized, and placebo-controlled clinical study in adults.1 The authors suggest that the anti-inflammatory, antimicrobial, and analgesic effects of this herbal extract mixture were able to treat all 5 stages of mucositis. However, it is unfortunate that they did not specifically report distinctions as to whether or not the extracts were swallowed or the frequency of concurrent use of systemic analgesic, anti-inflammatory, and antibiotic drugs. Assessments were based only on symptoms and oral visual inspection. Further studies are needed to confirm these specific benefits, and endoscopic evaluations should also be performed in all patients. Moreover, phase II, controlled, clinical trials are warranted to verify the efficacy of this herbal preparation in pediatrics.
--Laura M. Bystrom, PhD
Source : American Botanical Council
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Qigong Improves Quality of Life for Breast Cancer Patients Undergoing Radiation Therapy
Researchers from The University of Texas MD Anderson Cancer Center have found qigong, an ancient mind-body practice, reduces depressive symptoms and improves quality of life in women undergoing radiotherapy for breast cancer.The study, published in the journal Cancer, is the first to examine qigong in patients actively receiving radiation therapy and include a follow-up period to assess benefits over time. Even though individual mind-body practices such as meditation and guided imagery appear to reduce aspects of distress and improve quality of life, questions remain about their effectiveness when conducted in conjunction with radiation therapy.
"We were also particularly interested to see if qigong would benefit patients experiencing depressive symptoms at the start of treatment," said Lorenzo Cohen, Ph.D., professor in MD Anderson's Departments of General Oncology and Behavioral Science and director of the Integrative Medicine Program. "It is important for cancer patients to manage stress because it can have a profoundly negative effect on biological systems and inflammatory profiles."
For the trial, Cohen, the corresponding author, and his colleagues enrolled 96 women with stage 1-3 breast cancer from Fudan University Shanghai Cancer Center in Shanghai, China. Forty-nine patients were randomized to a qigong group consisting of five 40-minute classes each week during their five-to-six week course of radiation therapy, while 47 women comprised a waitlist control group receiving the standard of care.
The program incorporated a modified version of Chinese medical qigong consisting of synchronizing one's breath with various exercises. As a practice, qigong dates back more than 4,000 years when it was used across Asia to support spiritual health and prevent disease.
Participants in both groups completed assessments at the beginning, middle and end of radiation therapy and then one and three months later. Different aspects of quality of life were measured including depressive symptoms, fatigue, sleep disturbances and overall quality of life.
Results show benefits emerged over time
Patients in the qigong group reported a steady decline in depressive symptom scores beginning at the end of radiation therapy with a mean score of 12.3, through the three month post-radiation follow-up with a score of 9.5. No changes were noted in the control group over time.
The study also found qigong was especially helpful for women reporting high baseline depressive symptoms, Cohen said.
"We examined women's depressive symptoms at the start of the study to see if women with higher levels would benefit more," Cohen said. "In fact, women with low levels of depressive symptoms at the start of radiotherapy had good quality of life throughout treatment and three months later regardless of whether they were in the qigong or control group. However, women with high depressive symptoms in the control group reported the worst levels of depressive symptoms, fatigue, and overall quality of life that were significantly improved for the women in the qigong group."
As the benefits of qigong were largely observed after treatment concluded, researchers suggest qigong may prevent a delayed symptom burden, or expedite the recovery process especially for women with elevated depressive symptoms at the start of radiotherapy.
Cohen notes the delayed effect could be explained by the cumulative nature of these modalities, as the benefits often take time to be realized.
Future research needed
The authors note several limitations to the study, including the absence of an active control group making it difficult to rule out whether or not the effects of qigong were influenced by a patient's expectations or simply being a light exercise. Additionally, the homogeneity of the group, Chinese women at a single site, limits the ability of applying the results to other populations.
According to the authors, the findings support other previously reported trials examining qigong benefits, but are too preliminary to offer clinical recommendations. Additional work is needed to understand the possible biological mechanisms involved and further explore the use of qigong in ethnically diverse populations with different forms of disease.
Source : Newswise
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Chemotherapy Tweaks DNA of Mouse Offspring Too
A new paper in PNAS reports that three common chemotherapy drugs destabilize DNA in mice enough to trigger new mutations long after exposure to the drugs has ceased—mutations which are then passed down to their untreated offspring.
A similar phenomenon has been observed in mice exposed to radiation.
Nature News reports on the original radiation findings:
[Co-author and geneticist Yuri] Dubrova and his colleagues were studying the effects of radiation when, purely by chance, they decided to look at mutation rates in the offspring of exposed mice. 'What we found was the biggest surprise of my life,' he says. The children had several times more mutations in their eggs and sperm than their radiation-treated parents. 'The genomes were unstable, and we still don't know why.'
The researchers surmised that chemotherapy drugs might trigger even stronger genetic effects, since chemotherapy is given systemically and radiation therapy isn't. So they investigated three common drugs—cyclophosphamide, mitomycin C and procarbazine—at mouse doses comparable to people doses, in the offspring of treated male mice. From the PNAS paper:
After paternal exposure to any one of these three drugs, expanded simple tandem repeat mutation frequencies were significantly elevated in the germ line (sperm) and bone marrow of their offspring. This... was attributed to elevated mutation rates at the alleles derived from both the exposed fathers and from the nonexposed mothers, thus implying a genome-wide destabilization.
.The researchers caution:
Our data also raise important issues concerning delayed transgenerational effects in the children of survivors of anticancer therapy.
Although Nature News points out that mice only live two years and so pass on their damaged DNA before there's much time for internal repair, whereas most humans treated for cancer are post-reproductive adults or adults made sterile by treatment:
'So we're talking about one group only: childhood cancer survivors,' says Dubrova. One recent study found no significant impact of radiation or chemotherapy on the rate of birth defects in 4,699 children of childhood cancer survivors.
Source : Mother Jones
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