PSK en PSP, (zie ook pagina andere alternatieven-PSK voor info over PSK en PSP) zijn twee afgeleide middelen van paddestoelen die een goed effect hebben bij maagkanker. Hier een klein onderdeel in het Engels over het effect van PSK bij maagkanker zoals aangetoond in een aantal wetenschappelijke studies. Zie ook literatuurlijst van E. Valstar voor studies over PSK.

PSK and Stomach Cancer

Stomach cancer continues to inflict major mortality in Japan and has been the object of more clinical trials with PSK than any other cancer. Beginning in 1970, Kaibara and his colleagues at Kyushu University in Fukuoka, Japan, began adding PSK immunotherapy to their existing chemotherapy protocols.24 Hoping to achieve a clearcut result after two years, they chose to study patients with advanced (Stage IV) cases with invasion and metastasis, since few such patients survive an additional two years. They first performed conventional surgical resection, administering Mitomycin-C (MMC) beginning on the day of surgery. The patients were then put on a long-term chemotherapy regimen of Futraful, a 5-fluorouracil (5-FU) derivative, with periodic MMC treatments. PSK was added at 3 grams per day orally. The overall combination regimen was named "chemoimmunotherapy." This group was retrospectively compared against a patient group treated in earlier years with surgery and MMC, but not with the chemoimmunotherapy regimen.

Kaibara's group found survival was better in the chemoimmuno- group by more than double (34% vs 11%, p<0.05) after two years.24 This finding was later supported by a similar trial conducted by Fujimoto and associates at Chiba University.25 In addition, Hattori's group at Hiroshima University did a trial in which they also monitored immune competence using skin DTH (delayed-type-hypersensitivity) reactions and lymphocyte blastogenesis following induction by mitogens.26 Treatment after surgery with the combination of PSK as immunotherapeutic (6 grams/day) and 5-FU as chemotherapeutic was again found more effective for long-term survival of stomach cancer patients compared to treatment with MMC only after surgery. In this trial, the combination of PSK with 5-FU very likely increased three-year survival. Although the statistical analysis was flawed, survival data clearly indicated benefit after the first year, and among Stage III patients taking the combination all survived greater than two years. PSK showed a tendency toward protecting against the immunosuppression that typically accompanies surgery and long-term chemotherapy. By the early 1980s, once more reinforced by the results of Kodama et al,27 the use of PSK as the immuno-component of chemoimmunotherapy consistently doubled the two-year survival rate for stomach cancer in Japan.

In a 1985 double-blind trial with PSK in stomach cancer, patients with Stage III stomach cancer were treated with PSK or a placebo post-surgery, without the use of chemotherapy.28 PSK significantly extended the disease-free period over 80 months, although survival rate was not significantly extended. The investigators criticized their decision to administer PSK so tentatively: 3 grams/day for the first two months, 2 grams/day for up to 14 months, then 1 gram/day thereafter for the remainder of the trial. They speculated their results would have been better had PSK been given at 3 grams/day for the duration of the trial. The only statistically significant adverse effect from PSK was darkened pigmentation of the fingernails, occurring in four of 77 patients. After two months on PSK in this trial, patient immunocompetence was significantly improved, as judged by increased DTH (delayed-type hypersensitivity) on skin tests and enhanced chemotactic migration of neutrophils. Interestingly, this group also found PSK would improve DTH in aged men who had lowered immunity, but did not have cancer. As the trials progressed it became evident that individuals with very low immunity were less likely to benefit from PSK therapy than were individuals with some degree of remaining immunity.

During the 1980s and 90s, four trials established that PSK improved survival in stomach cancer patients up to five years, including some patients with advanced Stage III and IV cases with metastasis.29-32 Another trial conducted during this period, which enrolled more than 5,400 participants, had design flaws that make it useless to interpret.33

A 1986 trial by Mitomi and Ogoshi was the first attempt to separate the PSK-induced increase in stomach cancer survival from the effects of long-term chemotherapy. Significantly better five-year survival was reported with PSK. Two years later, in the Niimoto prospective randomized trial on 579 patients,30 another direct comparison of long-term chemotherapy versus long-term chemotherapy with PSK also concluded that PSK contributed significantly to five-year survival (p<0.01). Furthermore, patients found to benefit most from PSK were those with invasion and/or metastasis and those with better immune competence prior to surgery, as measured by skin DTH tests.

After Maehara's group showed PSK combined with chemotherapy can improve survival as far as 15 years ,31 their group investigated possible connections of PSK-responsiveness with known immunity mechanisms.34 Tsujitani et al at Kyushu University observed earlier that dendritic cells could infiltrate cancerous stomach lesions in their patients.34 Further examination of biopsy material revealed that patients who achieved extended survival were those who exhibited the most marked dendritic cell infiltration of their tumors prior to surgery.

Certain immune cells which resemble macrophages are located in the skin and virtually all other tissues, and very likely act as an early warning system for the body's immune defenses. Having dendritic or finger-like projections, they are called dendritic cells, unless they are present in the skin, where they are termed Langerhans cells. These immune cells often are the first to detect the presence of foreign antigens and initiate an appropriate response against them. These cells first ingest the foreign material, then break it down to smaller pieces. Subsequently they can "present" the antigens to T-cells, with which they habitually interact at close range to cooperatively mount immune responses, including cytotoxic activity against cancerous tissue. Dendritic-killer cell coordinated responses are the prototypical mechanism for tumor cell killing.

Further retrospective examination of tissue samples from 53 patients with Stage III stomach cancer, of whom 20 had received PSK as immunotherapy, demonstrated that among patients manifesting marked tumor infiltration by dendritic cells at the time of surgery, five-year survival was greater than 90 percent; yet PSK did not significantly enhance survival. Among patients with low dendritic cell infiltration, five-year survival was a mere 10 percent. Thus, of nine such patients subjected to conventional chemotherapy without PSK, none survived beyond three years. Of 20 who received the same chemotherapy regimen with PSK, nine (45 percent) were still alive at three years. The investigators concluded for stomach cancer patients who show limited dendritic cell infiltration prior to surgery, PSK immunotherapy is likely to significantly increase their chance for long-term survival.

In 1994, The Lancet published the findings from a well-designed trial on PSK therapy in the treatment of stomach cancer conducted by the Study Group of Immunochemotherapy with PSK for Gastric Cancer of Japan.32 Chemotherapy with PSK was compared against chemotherapy without PSK, and PSK was again found to significantly improve both five-year survival and disease-free survival. No toxic effects could be observed for PSK, "even after meticulous review of all the patient records.É" Although the exact degree of benefit from PSK was subsequently challenged,35 this trial has great clinical significance.


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