Ovarian

Comparing thousands of cases across Scandinavia has shown lower progression risk in users of antihistamines especially loratadine. Similarly,  patient studies for vitamin D3 levels and outcomes confirm the advantages in having relatively high levels. Vitamin D3 deficiency is common in many cancers including ovarian, and is reported to be a marker for worsened prognosis. Also from case data, use of low dose aspirin has its highest impact in post-diagnosis users, increasing progression free time and, importantly, reducing all cause risk even in advanced stages. The researchers make the comparision with result of adding an immunotherapy drug to the chemotherapy treatment. Its apparent that during stages I to III, low dose aspirin has by far the larger impact in slowing down progression.

Aspirin can also amplify the actions of statins, and the latter are also shown from patient data to measurably improve the prognosis with post-diagnostic use. Increased cholesterol activity is one common finding in how many cancers can grow and progress. Comparing users to non users in studies has shown lowered risks for progression in ovarian cancer management. Where a prescription for something like atorvastatin is not available, the well proven supplement red yeast rice is the natural source of lovastatin. There are several oncology drug classes often increasing lipid levels, so sustained use is beneficial. Effects are often reported as highest in those who respond with lower LDL levels.

New research in Sweden shows strongly elevated levels of so called gal-3 inflammatory proteins at both local and metastatic sites. The study shows how natural immune response is turned off in a third of patients. This recent finding links with evidence that responders to citrus pectin therapy, about a quarter to half of patients respond positively. Importantly, citrus pectin especially combined with marine alginates has been reported to remove heavy metals. Studies implicate high serum copper as a factor in progression rate. During a recurrence phase, researchers have also reported a large drop in zinc levels. The mechanisms behind this include cancer switching immune system activity to allow its growth. So far there are no trials to show effects of supplementation. Healthy pre-diagnostic zinc-selenium levels are strongly linked with better outcomes in several cancers, and now high dose selenium within oncology has shown some striking results. These include a pilot trial in advanced ovarian cancers where up to a quarter of patients showed sustained progression free responses with chemotherapy.

A crucial hormone for whole body health, melatonin is frequently very depressed in a variety of cancer patients at diagnosis not least ovarian. Even at very late stages, some patients across multiple disease types respond to moderate to high dose melatonin with boh stable disease and improved quality of life.

Having a diverse healthy gut microbiota is a driver of lower risk and better treatment results. Studies find the bacteria strain called akkermansia is deficient in ovarian cancer limiting immune response to cancer. Akkermansia with lactate (e.g probiotic yoghurt) can also help regulate metabolism of tryptophan, and amino acid linked to high progression risk when dysregulated by ovarian cancer to fuel growth. Functional foods such as nut consumption increase levels of akkermansia and and many other beneficial bacteria strains. In dietary interventions there are current ongoing trials with crushed flaxseed also, which can act help balance hormone levels and improve microbiome at the same time.

Systemic inflammation is linked with increased risks for progression, especially in later stages. Both acute type inflammatory responses (measured by c-reactive protein or CRP), and immune system related inflammation (NLR or neutrophil-to-lymphocyte ratios). Maintaining relatively lower levels of both make a substantial difference. Commonly used Astragalus root has evidence of improving immune system balance and NLR while curcumin and other other functional foods including garlic can help bring down systemic inflammation (and so lower CRP).

The so called Th1/Th2 immune system balance is strongly linked to the progression and to treatment resistance. Molecular iodine solutions are emerging in this area in breast cancer management and seen boosting Th1 anti tumor activity and helping suppress over active Th2 used in resistance. The has improved results in surgery plus chemotherapy and may support increased response immunotherapy (see Supplement Library). For immunotherapy the presence of high sodium levels is now identfied as a key marker for success in other cancers. Also in other cancers, AM treatment programs are substantially more effective that PM/evening sessions

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Antihistamines have large scale analysis supporting their use in most cancers

  • Up to 35% relative reduced risks for progression with loratadine
  • Tendencies to increased effects over longer time periods also reported
  • Specific to the H1 class and loratadine in two large studies, not H2 class

In conclusion, in a nationwide cohort study, we provide epidemiologic evidence suggesting that antihistamines with CAD characteristics at current doses may provide a prognostic benefit in ovarian cancer patients. The plausibility of this finding was confirmed in vitro in ovarian cancer cell lines. Further efforts are required to confirm our results in other study populations, and to elucidate the precise biological mechanism. Given that current antihistamines are well-tolerated, inexpensive, and already commonly used in cancer patients, CAD antihistamines may become promising candidates as ...

Vitamin D3 and its immune system health actions are key, higher doses being trialed in oncology

  • Research reports vitamin D3 levels at diagnosis strongly influence outcomes
  • Over 50% risk reductions when comparing higher to lower levels in data
  • Somewhat higher association is shown here for early stage patients

Our data suggest that circulating 25(OH)D at diagnosis is a predictor of survival among women with ovarian cancer, independent of known prognostic factors, including age, stage of disease, and residual disease after surgery. This association was somewhat stronger for women with earlier stage disease and thus an inherently better outcome than for those with more advanced disease…. our data show that serum 25(OH)D concentrations at diagnosis were independently associated with survival after a diagnosis of ovarian cancer, suggesting that measurement of serum 25(OH)D at diagnosis may prov...

Aspirin has a majority of analysis in its favor including all-cause mortality

  • 25% increased progression free and 35% overall risk reductions shown
  • Somewhat higher aspirin benefits seen for post-diagnosis users vs others
  • Notably, care is taken to include over the counter use, not only prescriptions

Our data suggest improved survival associated with both prediagnosis and postdiagnosis use of NSAIDs, with little difference between new and continuous users (vs never users). The association was driven by frequent use (which was primarily daily lowdose aspirin) and would translate to a 2.5-month difference in mean survival at 5 years. Although the survival increase is small, other treatments used for OC [ovarian cancer] may not confer a much greater benefit….Our findings confirm a previous study suggesting NSAID use might improve OC survival.

Red Yeast Rice or where possible a prescription statin impacts include lower all cause risk

  • Post-diagnostic statin use is reported with 32% increased relative survival
  • Effects are larger for early stage, and here all patients used statins for elevated cholesterol
  • Other studies report high responders are those who see cholesterol decreases with use

 

Our results confirm previous observations that women with ovarian cancer who take statins after their diagnosis may have better survival than women who do not use statins. However, it is impossible to rule out all potential sources of bias in observational studies. Particularly important in a population like this, where a high proportion of women are likely to be experiencing side-effects of both treatment and the disease, is the possibility of reverse causation. There are also no data about the potential effects of statins among women who do not have high cholesterol levels

Citrus Pectin removes heavy metals such as copper and has its own anti-cancer mechanisms

  • Palliative stage patients including some uterine cancers, a third saw over 4 months stable disease
  • 20% of this subgroup were shown as stable for more than 6 months despite advanced stage
  • Lower gal-3 is linked in other studies with a 50% or more reduction in relative risk

In this context, it is remarkable, that in our study the treatment with MCP over a period of 8 weeks was associated with an overall clinical benefit response of 20,7% (6 patients out of 29) as well as an improvement of quality of life. However, the high drop out rate of 20 patients already 8 weeks after the start of treatment has to be considered, reflecting the poor clinical condition of most patients entering our trial and compliance issues in advanced disease…Nevertheless, this is the first Good Clinical Practice (GCP) conformant study showing relevant measurable clinical effects o...

Zinc levels need maintaining at healthy levels according to patient data in many cancers

  • Disease recurrence reported nearly 5X more likely with insufficient zinc
  • 83% of patients with disease recurrence showed zinc deficiency
  • Deficiency is reported as independent of diet, treatment or other factors

 

However, patients with gynecologic cancer exhibited significantly lower serum zinc concentrations following treatment, and patients with recurrent cancer were 4.8 times more likely to develop zinc deficiency than those with nonrecurrent cancer. A serum zinc concentration of <61 μg/dL was an independent predictor of recurrence. Once zinc deficiency occurred, the recurrence rate of zinc deficiency reached as high as 69%. Overall, our study indicates that zinc deficiency is associated with recurrence in gynecological cancers and physicians should monitor zinc levels during disease manageme...

Selenium is developing in kidney and ovarian cancer, high doses pulsed with oncology drugs

  • Progression Free Survival increased equally to adding an immunotherapy drug, about 50%
  • Around 20% of patients are reported with substantially lower risk levels following supplementation
  • Notably its also 20% of the patient group actually recieved the dose level targeted for phase II

 

 

Of the 3 patients found to have a deleterious mutation in either BRCA1 or BRCA2, one patient experienced a PR with an overall survival (OS) of 79 months, while two patients receiving adjuvant therapy are alive with disease at 81 and 105 months. Interestingly, seven of the nine patients in this tested group without a deleterious germline BRCA1/2 mutation experienced prolonged OS ranging from 60–120 months. Of those seven patients, three patients remain with no evidence of disease at 62, 69, and 114 months, while one patient is alive with disease at 120 months….Overall, the addition o...

Lactoferrin increases iron balance and reduces anemia rates, countering cancers use of iron

  • Cancers can progress by upregulating circulating iron stored as ferritin
  • This report shows large benefit to having normal hemoglobin and relatively low ferritin
  • It also show large risk reductions for lowering inflammation (CRP biomarker)

The Kaplan-Meier survival analyses of serum ferritin expression revealed that the high ferritin level group had significantly less survival time than normal and low ferritin level groups. It indicates that serum ferritin could predict a poor prognosis for patients with gynecological malignant tumors. The univariable Cox regression analysis identified patients with a high level of ferritin (150
g/L) had a significant correlation with the risk of death compared to the patients with low and normal ferritin levels. Studies have also shown iron elevation in cancer is significant.

Akkermansia supplements can be useful but a functional food diet is attractive for microbiome

  • Ovarian cancer patients levels of akkermansia reduced by 75%
  • Mouse model of tumor samples shows clear link to immune response
  • Akkermansia is a driver of response in immunotherapy with colorectal cancer

Overall, patients with OC [ovarian cancer] have a different gut microbiota signature [akkermansia was severely reduced]… Our findings provide a perspective for connecting the immune microenvironment of OC with the gut microbiota and may lead to the corresponding treatment strategies regarding gut homeostasis. Considering gut bacteria administration is convenient to access, biologically safe, and possesses the ability to facilitate immune surveillance of OC, the Akkermansia or its analogs might warrant being validated in clinical trials for late-stage OC in the near future.

Melatonin trials have shown longer survival rates, even in late stages, and improved side effects

  • Similar benefits in a wide variety of patients at least some Ovarian cancers in the data
  • Specific studies referenced include fascinating late stage trials with high doses
  • Very detailed pre-clinical studies map the ovarian cancer specific effects

This meta-analysis shows a significant positive effect for cancer patients with the use of oral MLT [melatonin], alone and in combination with chemotherapy. Benefits were seen on survival rates, treatment response rates, and disease progression and on the toxicity profile of a number of chemotherapy agents. It is important to note that these benefits were observed despite the fact that the analysis combined a wide variety of biologically and clinically distinct cancer types, across which MLT nonetheless demonstrated similar results. The large effect sizes and good safety profile of this int...

Flax has evidence of activity and other hormonal cancers, an active functional food

  • Decent evidence in breast cancer, pending research results in ovarian cancer
  • Promising lab studies have led to a pilot 2 year study in advanced stage disease recurrence
  • Stronger evidence in breast cancer is reported for post-menopausal women

For stages III and IV, the risk of recurrence is very high, with 5-year survival rates ranging from just 13% to 44%. Furthermore, OC represents a high potential for metastases even in the setting of complete response to initial therapy. Efforts to devise new treatment strategies are therefore essential in order to improve survival. In this grant application, the investigators postulate that utilizing dietary supplementation of flaxseed for maintenance therapy in patients with OC in clinical remission following treatment with platinum-based regimens will be tolerable and prolong their progre...

Curcumin has evidence for reducing levels of systemic inflammation used by cancers

  • Lower levels of inflammation in patient data are linked to better outcome
  • Around a fifth lower risk overall and a third lowered progression risk
  • Inflammation tends to increase with advanced stages and ascites (fluid build up)

Our results indicated that elevated CRP [c-reactive protein, the measure for classic inflammation] levels were markedly associated with shortened OS and inferior PFS [progression free survival] in patients with OC. Furthermore, higher CRP levels exhibited a significant relationship with advanced FIGO stage, larger residual tumor size, higher histological grade, and ascites volume ≥ 500 mL. Collectively, these data suggest that elevated CRP level is a prognostic marker for poor short- and long-term survival in patients with OC. Increased CRP levels are also predictive of clinicopatholo...

Astragalus actions include restoring balanced immune responses often with clear effects reported

  • Low Neutrophil-to-Lymphocyte ratio, NLR, strongly reduces risks
  • A 90% reduced progression free survival risk with low NLR
  • Large scale meta-analysis reports overall risk reductions of a third

We found that the NLR value at baseline was not associated with response to NACT [chemo], while a decrease in NLR after three cycles was correlated with a better response to NACT. Also, values of CRP, IL-6, ferritin, and mGPS after three cycles of NACT (but not at baseline) were significantly associated with clinical response…patients with a low NLR value after 3 cycles of NACT, but not at baseline, had a significantly higher PFS than patients with high NLR after 3 cycles of NACT. In conclusion, NLR change during treatment could serve as a predictive marker of response to NACT in pati...

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