Hej igen tor,
To whom it may concern
Colostrum affords mucosal protection in oncology -
We have studied the gastrointestinal side effects during cytotoxic therapy and radiotherapy (1-7), caused by an injury to the rapidly proliferating intestinal cells. The patients experience distressful symptoms such as abdominal pain, nausea/vomiting/diarrhoea and anorexia. These symptoms will increase resource utilization such as hospital care, i.v. nutrition, analgesics and antibiotics.
Further, the epithelial injury impairs the normal intestinal barrier function and bacteria and fungi may permeate the intestinal wall. After chemotherapy, a coexistent depressed immune system may lead to serious or even life-threatening systemic infections. After radiation therapy to the pelvis (indicated in uterine, rectal and anal cancer) there are no concomitant effects to the immune system and thus, the risk of systemic infections is not increased. However, the same injury will develop in the epithelium and cause acute (diarrhoea, painful and frequent defecation) as well as long term side effects (such as fibrosis of the anal channel leading to faecal incontinency).
Taken together, these side effects decrease quality of life, increase resource utilization, may
be potentially life threatening and, if the cancer therapy has to be withheld, may endanger the
therapeutic result. Today, there is no effective prophylaxis against these side effects. One
drug (palifermin) has been approved for the prophylaxis against painful ulcerations in the oral
cavity after bone marrow transplantation. We have recently found that palifermin exert some
protective effects upon the intestinal tract (8). However, bone marrow transplantation is only
indicated in haematology (leukaemia and aggressive lymphoma). In addition, palifermin
stimulates the regeneration of mucosal cells and there are concerns that the malignant
counterpart, constituting the large group of gastrointestinal tumours, would be stimulated by
palifermin too. Therefore, palifermin will only be used during the treatment of haematological
cancers (5 % of all malignancies). The other approved drug – amifostin – is a scavenger
which detoxifies free radicals generated by radiation therapy. It has its one and only
indication in radiation therapy for head/neck cancer, is expensive and has significant side
effects. Therefore, it has not been introduced into clinical practice in Sweden. To summarize
– there is a great need in cancer therapy for effective prophylaxis against the
Colostrum is vital for the newborn ruminant. It contains antibodies and other mucosal
protectants (e.g. transforming growth factor B - TGF B and lactoferrin) and protects the new
born against intestinally derived infections.
Our hypothesis is that the same protection could be beneficial in the context of cancer
therapy. We have the organization and the protocols ready to study this hypothesis in clinical
As partners to ColoPlus AB, MALMO, Sweden, we are now conducting two phase II studies
(one in abdominal radiation therapy and one in chemotherapy) on their patented
colostrumbased therapeutic food product named ColoPlus ONCARE
Scientific background for the choice of colostrum
We were able to show that immunoglobulin A, an important component of colostrum,
protected the intestinal mucosa during intensive chemotherapy (9). Other investigators have
demonstrated a protection by colostrum after intake of anti-inflammatory drugs and during
HIV associated diarrhoea (10-11). In laboratory studies bacterial translocation was reduced
after the intake of colostrum (12). Thus, these observations provide a basis for clinical studies
with colostrum. Our research plan is, in the first part of the developmental program, to study
the efficacy, safety and feasibility in two clinical situations:
1. Treatment of colorectal cancer – causing extensive symptoms from the gastrointestinal
2. Radiation therapy to the abdomen (after surgery for cancer of the body of uterus,
before surgery for rectal cancer and finally, as a curative treatment for anal cancer)
ColoPlus is today available as a therapeutic food product, IMCARE
and could without side effects be recommended to the patients.
was specifically designed for this collaboration and based on its concept
of effective exposure to and regulated transport of bioactivs in the intestine area. If the clinical
studies demonstrate clinical benefit this would translate into important symptom reduction for
the patients and an increase in quality of life during and after cancer treatment. Finally, it
could be speculated that these beneficial effects may, by maintaining the therapeutic schedule,
translate into improvements in the results of the therapy. Commercial potential
Will depend upon the demonstration of clinical efficacy:If important end points, such as the
need for hospitalization and/or artificial nutrition or the numbers of serious infections are
significantly reduced, ColoPlus ONCARE
will quickly be recommended in cancer centres (the
problem is well recognized among clinicians). Only in the western region of Sweden
(population 1.6 million inhabitants) 20000 cytotoxic treatments are given annually. An
estimate is that ¼ of these are associated with side effects to a degree that it could be expected
that the patients would experience a benefit from prophylaxis with ColoPlus ONCARE.
Our aim is to prove a beneficial effect by ColoPlus ONCARE
upon the gastrointestinal side
effects during cancer therapy (chemotherapy and abdominal irradiation). If our aim could be
reached, the commercial potential would be of a substantial magnitude.
Tor Ekman, Consultant, Ass Prof. Member of the Board of the Swedish Cancer foundation Dept of oncology, Sahlgrenska University Hospital S 413 45 Gothenburg, Sweden
1 Gastro-intestinal toxicity related to bone marrow transplantation: disruption of
the intestinal barrier precedes clinical findings. Bone Marrow Transplant 1997; 19(9): 921-5 Johansson JE, Ekman T.
2 The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell
transplantation with reduced intensity conditioning. Bone Marrow Transplant. 2001 Oct;28(8):737-42. Johansson JE, Brune M, Ekman T.
3 Gut mucosa barrier preservation during haemopoietic stem cell transplantation
predicts acute graft-versus-host disease severity - A comparison between myeloablative and reduced intensity conditioning (RIC) Jan-Erik Johansson and Tor Ekman. Dig Dis Sci 2007 Published on line 20070406
4 Disturbance of purine nucleotide metabolism; A possible early key-event in the
development of intestinal damage induced by chemotherapy. Johansson J-E, Bagge U., Soussi B. and Ekman T. Dig Dis Sci 2001; 46(2):257-261
5 Early disturbance of microvascular function precedes chemotherapy-induced
intestinal injury Abel E, Ekman T, Warnhammar E, Hultborn R, Jennische E and Lange S. Dig Dis Sci. 2005 Sep;50(9):1729-33.
6 Assessment and management of cancer-related fatigue in adults Ahlberg, K.,
Ekman, T., Gaston-Johansson, F., Mock, V. (2003). Lancet, 23;362(9384), 640-650.
7 Fatigue, psychological distress, coping resources and functional status during
radiotherapy for uterine cancer. Ahlberg K, Ekman T, Gaston-Johansson F. Oncology Nursing Forum 2005; 32 (3), 633-640
8 Johansson JE et al. Gut protection by palifermin during autologous
haematopoietic stem cell transplantation. Bone Marrow Transplant 2008 Dec 1. [Epub ahead of print]
9 Gut mucosa barrier preservation by orally administered IgA-IgG to patients
undergoing bone marrow transplantation: a randomised pilot study. Johansson JE and Ekman T. Bone Marrow Transplant 1999;24:35-39
10 Florén CH, Chinenye S, Elfstrand L, Hagman C, Ihse I. ColoPlus, a new
product based on bovine colostrum, alleviates HIV-associated diarrhoea. Scand J Gastroenterol. 2006 Jun;41(6):682-6.
11 Playford RJ, MacDonald CE, Calnan DP, Floyd DN, Podas T, Johnson W,
Wicks AC, Bashir O, Marchbank T. Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability. Clin Sci (Lond). 2001 Jun;100(6):627-33.
12 Kim JW, Jeon WK, Kim EJ. Combined effects of bovine colostrum and
glutamine in diclofenac-induced bacterial translocation in rat. Clin Nutr. 2005 Oct;24(5):785-93.
13 Immunoglobulins and TGF B2 in bovine colostrum and derived products.
Thesis 2000 Lidia Elfstrand Lunds universitet.
Estrogen, Progesterone And Breast Cancer :: Health-Science.Com :: Estrogen, Progesterone And Breast Cancer What Effect do Hormones Have? Molecular biologist, Dr. Ben Formby of Copenhagen, Denmark and Dr. T.S. Wiley at the University of California in Santa Barbara have researched two genes, BCL2 and P53, and their effect on female-specific cancers and Cells
Deeper Web Paper - 2012 Part II :- Subject : Biology Day and Date : Duration : 12.00 pm to 1.30 pm Tuesday, 08 May 2012 Total Marks : 100 This is to certify that, the entries of MHT-CET-12 No. and Answer Sheet No. have been correctly written and Verified Invigilator's / Parents Signature Instructions to Candidates This question booklet contains 100 Objective Type Questio