As usual we turn more and more to the plant world for all sorts of treatments, a new study suggests that a plant used for centuries in Indian Ayurvedic medicine may be a powerful weapon in the fight against deadlymalignant mesothelioma.
The bioactive compound Withaferin A (WA) is isolated from the root of Withania somnifera, a plant in the nightshade family also known as Indian ginseng. A number of previous scientific studies have found evidence to suggest that WA has anti-inflammatory, immuno-modulatory, anti-angiogenic, and anti-cancer properties.
In the latest study, published online in the open-access peer-reviewed journal PLos One, researchers at the Karmanos Cancer Institute in Detroit tested the compound in live mice (in vivo) as well as in mesothelioma cells taken from human patients (in vitro). Their objective was to determine whether WA would have an effect on mesothelioma cell growth and, if so, the molecular mechanism behind that effect.
The study found that WA inhibited the growth of the murine (mouse) mesothelioma cells as well as the growth of those derived from human patients. The WA seemed to work, in part, by modulating the levels of certain regulatory proteins involved the cell life cycle. WA also suppressed mesothelioma growth by increasing the rate of apoptosis (cell death). Finally, gene-array based analyses found that WA suppressed a number of genes that promote cell growth and metastasis.
In a summary of their findings for PLoS One, the research team concludes “Together, our in vitro and in vivo studies suggest that WA suppresses malignant pleural mesothelioma growth by targeting multiple pathways that include blockage of proteasome activity and stimulation of apoptosis, and thus holds promise as an anti-MPM agent.”
Double-blind, placebo-controlled human trials would have to take place before any WA-based mesothelioma treatment could be sanctioned by the FDA and used to treat patients. As always, patients should consult their healthcare professional before using any type of supplement.
We braved the weather and headed out on Saturday to our local theatre followed by a great meal out at a nearby restaurant. Had a great meal, one of the best we have had out for some time. In fact since the last time we went to that restaurant. We are definitely spoilt where we live for good places to eat and because there is so much competition they tend to be rally good value as well.
After our activities on Saturday we felt we could stay in and watch the tennis during the day, although we did head out for a very short walk in the evening, just missing the rain.
Ray has had a few days of feeling very sore, so has been on a higher dose of the painkillers. Today seems a little better, today he describes more as though he has an itchy lung ( hope this isn’t a sinister development)
This week is going to see the Ducatti rebuild well underway ( I already know far more than I wanted about cam belts). Next weekend is a big weekend for his parents, as their local church is having an event for everyone in the diocese whose 50th wedding anniversary is due this year. We will be going along for the occasion as they are allowed two guests . It will mean a huge amount to his mum to have this time with him.
An oral leukemia medicine doctor’s had hoped might help certain mesothelioma patients won’t be moving on to the next level of clinical trials.
Phase II drug trials use human subject to determine a drug’s safe dose and measure its effectiveness. In Phase II trials of dasatinib, a drug currently used for leukemia patients that have failed other treatments, mesothelioma researchers found the medicine had “no activity” and was too toxic to justify its use. Because of dasatinib’s success as a second-line treatment for chronic myeloid leukemia, doctors reasoned that it might help patients with inoperable mesothelioma.
In the study to test this hypothesis, 46 mesothelioma patients were given 70 mg of dasatinib twice daily as part of a 28-day cycle. To track the drug’s effectiveness, researchers measured blood levels of several cancer growth indicators, including vascular endothelial growth factor, colony stimulating factor 1 (CSF-1) and mesothelin at the start of treatment and during therapy.
Half of the first study participants had side effects so severe that their dose had to be dropped to 50 mg. As the study progressed, eleven percent of mesothelioma patients experienced severe fatigue and 9% developed pleural effusion (lung fluid buildup). But the worst news of all was that progression-free survival at 24 weeks was just 23%.
In the end, researchers concluded that dasatinib was not worth moving on to Phase III trials and should be dropped in favor of testing other drugs against mesothelioma. Currently, several classes of drugs are being explored for mesothelioma, including those that alter the DNA of cancer cells (CBP501), those that interfere with cancer cell blood supply or replication (cediranib, bevacizumab, NGR-hTNF, vorinostat), and those that attempt to use the immune system to fight cancer (MORAb-009, WT1, thalidomide).
Results of the dasatinib trial for mesothelioma were published in the Journal of Thoracic Oncology.
Interesting report from Italy, it mentions the use of EPP, which is now considered less attractive as an option in the the UK, due to the high degree of complications. However the Italian study is still interesting for its combination with radiotherapy – of course if you can undergo EPP, you’ve got to be pretty strong to start with, so not sure if these patients wouldn’t have survival in the upper range anyway.
A team of Italian researchers recently analyzed the records of 56 mesothelioma patients who had been treated with adjuvant radiotherapy after extrapleural pneumonectomy surgery (EPP) between 2005 and 2010. Extrapleural pneumonectomy is a radical surgical procedure that involves removing not only the mesothelioma tumors, but also the lung closest to the tumor and a portion of the diaphragm.
Although EPP is controversial due to its high rate of complications, a number of studies have shown it to increase survival, especially in carefully-chosen, otherwise healthy patients with the epithelioid type of mesothelioma.
Four of the EPP-treated mesothelioma patients in the retrospective Italian study were treated with Intensity Modulated Radiotherapy (IMRT,) and two with helical tomotherapy. The patients were all treated with 45 to 50Gy to the affected areas inside the chest. Twenty of the patients also got a simultaneous “boost” of 60Gy to the margins around the tumor in an effort to destroy any remaining mesothelioma cells.
For 90 percent of patients, the mesothelioma was kept under control in the region of the surgery for three years. Sixty-six percent of patients did not experience spread (metastasis) of their mesothelioma during that time. Fifty seven percent of patients were considered disease-free for at least three years.
Sad news this week at the death of an Australian meso warrier, Anita was diagnosed around 2007 in her forties, not only did she survive the initial diagnosis , she also had the miracle of a baby girl, despite chemo. Her memory now lives on in that baby girl.
It has been a difficult few months, having to say goodbye too so many warriers, Ray’s scan is due in two weeks and it is difficult to stay positive and keep some hope for the future. Research is ongoing but it seems so slow.
This week although the pain has been under control, seems to have been the week of nose bleeds. This happened during the second phase of chemotherapy but nothing since. This week , seems to be every day , over dinner , at breakfast or walking down the road, usually at a time of maximum hassle. No idea what has brought this on, possibly the ibrufen has built up , but other than that no idea.
Although this may sound minor it is really depressing, it is yet another reminder that you aren’t normal, yet another reminder of being ill. So emotionally I know that it brings him really down.
Any ideas gratefully received as to how to stop them occurring!
Further evidence of the global nature of this cancer this week, firstly , new research under way in Korea suggest they are going to see an increasing number of cases over the next 30 years. The a neew study from one of the country’s leading cancer centers suggests that the nuclei of mesothelioma cells may hold vital clues for predicting patient survival.
Though as an individual not sure you would want to know, but anything that suggest they are learning more about Mr Nasty has to be good.Epithelioid mesothelioma is the most common subtype. Doctors often use the cancer’s stage – a measure of cancer extent and severity – to predict how well patients will respond to treatment. But now a group of scientific researchers from Memorial Sloan-Kettering Cancer Center in the U.S. and Kagawa University in Japan believe they have found an even more effective prognostic indicator – inside the nucleus of mesothelioma cells.
To conduct their experiment, the researchers examined the slides of 232 patients who had been diagnosed with the epithelioid type of malignant pleural mesothelioma. They then examined the nuclei of the cell samples to evaluate them on seven different features.
Thorough analysis of each mesothelioma cell sample revealed that two of the features, nuclear atypia and mitotic count, were directly related to patient prognosis.
“Not only was nuclear grade an independent predictor of overall survival, but it was also a stronger discriminator of survival than all currently available factors,”
Good to see that the research into this is going on all over the world
Illinois-based Pinnacle Biologics have announced they are applying for orphan drug status for their product Photofrin® (porfimer sodium), which they believe will prove to be a successful adjuvant to surgery for individuals suffering from malignant pleural mesothelioma.
According to the company, the drug is used in photodynamic therapy (PDT), a treatment procedure that has shown some success in treating mesothelioma patients. A two-stage process, PDT is accomplished by first injecting the Photofrin intravenously into the patient. About 40-50 hours later, patients are exposed to a non-burning laser light in the area of the tumor. The Photofrin is attracted to cancer cells and lingers in them. The light causes a biochemical reaction to occur in the cancer cells where the Photofrin remains, thus killing the cells.
Dr. Joseph S. Friedberg of the Department of Thoracic Surgery at Penn Presbyterian Medical Center in Philadelphia, has been experimenting with photodynamic therapy.
Friedberg said: “In studies completed at Penn, photodynamic therapy (PDT), in conjunction with surgery, has shown some very promising results for the treatment of mesothelioma. By utilizing PDT as an intraoperative treatment, we have been able to develop a technique where we can reliably preserve the patient’s lung. When compared to other treatments, this combination of lung-sparing surgery, PDT and standard chemotherapy appears to have a positive impact on both survival and quality of life. Based upon our clinical observations, characterizing the PDT effect and working on techniques to magnify it has become a major focus of our research.”
Heard today the sad news about Ronny, had so hoped for some good news after her last update. Thoughts must be with her family at this time. When I first heard the name mesothelioma, Ronny’s blog was one of the first I found and it helped us both at a terrible time.
It seems so shocking how quickly this has all happened, a sharp reminder of how precious this time is together.
Well the new scan is booked for tomorrow , so another fun packed three hour hospital visit . The PET scan takes a lot longer than the CT, as once they have injected the radioactive glucose, which takes around 30 mins, you then have to rest for around 90 mins for it to be taken up around the body , then have the scan itself.
We have a follow up appointment booked with the surgeon to discuss the results the following Wednesday and the oncologist on Friday 14th, so by the end of next week we will know the extent of the bad news.
We know the little darling is back, now we need to know just how quickly it is growing . The last scan was done on the 27th July and showed no conclusive evidence of any meso, so this one will show us the spikes in glucose uptake where it has developed.
From the areas of pain,it appears most likely to be in the chest wall and diaphragm. Today as well as pain in his back, his chest wall was also tight on the right hand side. At the moment neurofen in the morning and evening is just about controlling it , we have also been prescribed some much harder hitting painkillers.( dihydrocodeine)
What’s really scary is four weeks ago, we were having a great weekend in Goodwood, no pain at all. Then an ache around 2 weeks ago, now we are talking about serious painkillers just to get through the day. I really don’t want to think about just how quickly this is growing or how to deal with the pain.
As so few of his family know about the situation, it is coming very close to having to sit down and tell everyone , including his teenage son, just what is going on and how much time is possibly left.
Slight set back today, having read about the mesothelioma patients day on October 1st, found out the mesothelioma scientific day for the medical profession is also at St Pancras, the day before on the 30th, with Dr Steele in attendance , so no way we’ll be seeing him on the Friday at our appointment.
Checked with the oncology nurse who agreed we would be seeing one of the other doctors, who would assess the morning scan. Our experience of other doctors has been a bit variable. One we didn’t get on with at all well, another tends to list out every possible option or opinion, which leaves us confused and/or depressed.
Decided we would be better off delaying everything a week, then realised we had already booked a weekend away for the first week in October, which we were really keen not to cancel as been looking forward to for ages. After much thought have put back scan and appointment by two weeks to mid October.
He is working on theory that if all the pain is being caused by the tumour regrowing , then we might as well enjoy the weekend , whist we still have uncertainty , and therefore hope. He is now taking paracetemol regularly , the pain seems to be in his back around the area of the right kidney at the base of the right lung.
Pyschologically , trying to get our heads round not knowing for another month, at times I struggle to stay positive and keep myself together, so no idea how he is managing.