Patent Application
20240358769
The field of the invention is cancer chemotherapy, in particular cancer chemotherapy in combination with a nutritional supplement.
The background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Chemotherapy protocols utilized in the treatment of cancer can clearly benefit patients, but can be ineffective or less effective with some cancers, particularly recurring or resistant tumors. In addition chemotherapy is associated with significant side effects, including nausea, weight loss, hair loss, immunosuppression, and skin irritation.
Attempts have also been made to enhance the effects of chemotherapy. Some studies have suggested that consumption of fish oil can improve results from chemotherapy, however other research has suggested that fish oil can interfere (Daenen et al, JAMA Oncol (2015) 1(3):350-358). Formulation of chemotherapeutic agents as nanoparticles has also been attempted (Xu et al, Coll. Surf. B: Biointerfaces (2006) 48(1):50-57). It is unclear, however, if all chemotherapeutic drugs are suitable for such reformulation. Codelivery of chemotherapeutic drugs with siRNA designed to interfere with multi-drug resistance has also been explored. Such siRNAs, however, are sequence specific and may not be suitable for some tumors.
Mitigation of the side effects of chemotherapy is generally directed at providing symptomatic relief. For example, antiemetics can be used to reduce nausea, along with diet modification and eating small, frequent meals that avoid certain foods. Unfortunately such approaches are not always effective. In some instances chemotherapeutic agents are selected to have reduced toxicity in order to reduce side effects, however such agents may also have reduced effectiveness against tumor cells.
Attempts have also been made to improve the sensitivity of cancer cells that are resistant to chemotherapeutic agents. For example, U.S. Pat. No. 7,906,554, to Kelley, describes the use of isoflavones in improving the effectiveness of chemotherapeutic agents. Since the only data provided is directed to a compound that is known to have significant anti-cancer activity (dehydroequol) on its own, however, the effect does not appear to be clearly demonstrated. U.S. Pat. No. 83,463,943, to Kim and Kim, describe the use of glucosamine in sensitizing cancer cells to chemotherapeutic agents. It is not clear, however, if the concentration of glucosamine that was found to be effective (1 mM or higher) can be achieved in vivo. U.S. Pat. No. 9,095,602, to Gleave et al, describes the use of anti-sense DNA to suppress TRPM-2 gene activity in order to enhance chemosensitivity in resistant cancers. Such an approach, however, requires a means of safely and selectively providing the anti-sense DNA to a tumor. In addition, it is not clear that such specific gene suppression will be effective across different cancer cell types and chemotherapeutic mechanisms.
Thus, there is still a need for safe and effective compositions and methods to enhance the effectiveness and/or reduce the side effects of cancer chemotherapy and increase the sensitivity of chemotherapy resistant cancer cells.
The inventive subject matter provides compositions and methods in which a supplement that includes fish oil and selenium can be used either alone or in combination with chemotherapeutic agents to reduce inflammation, for example inflammation associated with cancer and/or treatment of cancer with a chemotherapeutic agent. A specific formulation for a preferred dietary supplement that includes fish oil and selenium, which has proven to be both effective and palatable, is provided.
Embodiments include a nutritional supplement containing fish oil and selenium in amounts that are effective to reduce inflammation in an individual in need of treatment for inflammation, for example inflammation due to or characterized by increased expression of IL-6. Such an individual can be suffering from cancer, and can be undergoing chemotherapy for cancer. Such a supplement can be formulated to include the ingredients list in Table 1.
Embodiments include methods of treating inflammation by administration of a nutritional supplement as described above to an individual in need of treatment for inflammation. Such inflammation can include elevated expression of IL-6. Such an individual in need of treatment can be suffering from cancer, and can be undergoing chemotherapy for cancer. Such a supplement can be formulated to include the ingredients list in Table 1.
Embodiments include methods of reducing IL-6 expression in an individual in need of treatment by administration of a nutritional supplement as described above to the individual in need of treatment. Such elevated IL-6 expression can be associated with inflammation, such as inflammation associated with cancer. Such an individual in need of treatment can be suffering from cancer, and can be undergoing chemotherapy for cancer. Such a supplement can be formulated to include the ingredients list in Table 1.
Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.
The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
The inventive subject matter provides compositions and methods in which a nutritional supplement (such as a supplement that includes fish oil, selenium in the form of selenium yeast, chromium, and certain plant-derived materials (Nutra Well) and/or a supplement that includes a selenium and fish oil) is used in combination with chemotherapy. Combination therapy with chemotherapeutic agents and the supplement surprisingly provides a significant synergistic effect in reduction of tumor size and/or reducing cell proliferation. In addition, side effects of radiotherapy are mitigated and expression of genes related to apoptosis is modulated in tumor cells. Surprisingly, supplements of the inventive concept were also found to increase the sensitivity of resistant cancer cells to chemotherapeutic agents.
One should appreciate that the disclosed techniques provide many advantageous technical effects including enhancing the effectiveness of current chemotherapy protocols used in the treatment of cancer while reducing the side effects associated with these approaches, and in the treatment of cancer that are resistant to chemotherapy.
The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
While the some findings described below are directed to the use of fish oil and a selenium source, the Applicant notes that the nutritional supplement formulation provided in Table 1 (i.e. NutraWell) incorporates fish oil and selenium. The selenium is preferably provided as selenium yeast or components thereof (such as peptides and/or amino acids prepared from selenium yeast). As such effects found in fish oil and selenium yeast studies can be extended to the use of this nutritional supplement. NutraWell has been found to have a high level of acceptance and to have unanticipated beneficial anti-tumor activity in combination with conventional therapies. As shown below, such a nutritional supplement also shows striking beneficial effects when used in combination with one or more chemotherapeutic agents.
Lact.
Acidophilus (app. 10 billion total)
Bifido
Bifidium (app. 10 billion total)
Lac.
Bulgaricus (app. 10 billion total)
Bifido
Longum (app. 10 billion total)
Strep.
Thermophilus (app. 10 billion total)
The composition shown in Table 1 includes components in addition to selenium and fish oil that have various physiological and biochemical effects, including anti-inflammatory activity. lowering of blood glucose levels, lowering of cholesterol, and anti-tumor activity. In preferred embodiments the nutritional supplement includes at least three components as represented in Table 1. Such additional components provide supplementation of necessary vitamins, minerals, and amino acids at elevated levels. Other components (e.g. enzymes, lecithin) serve to aid in digestion and absorption of components of the composition when consumed. The combination of these complementary activities provides a synergistic effect that exceeds the simple additive effect of individual components. It should be appreciated that the composition shown in Table 1 also includes certain flavorants (e.g. brown sugar, honey, vanilla flavor and masking agent) that serve to improve palatability and acceptance. Certain components (e.g. honey, brown sugar, milk, rice protein, casein) can provide both flavor and caloric energy. The Inventor has found that the combination of flavorants described above is effective in providing compliance with consumption of the nutritional supplement in effective amounts. In some embodiments, such flavorants can be excluded without negatively impacting the effectiveness of the nutritional supplement.
Components shown in Table 1 can be provided as a single formulation (for example, as a pill, tablet, capsule, powder, liquid, suspension, etc.) or can be segregated into different formulations (for example, as pills, tablets, capsules, powders, liquids, suspensions, or combinations thereof). The amounts shown in Table 1 are exemplary, and represent typical daily dosages provided to an adult of normal stature and otherwise normal health. These amounts can be adjusted to account for differences in body mass, gender, medical condition, etc. For example, a relatively small patient weighing 40 kilos or less may receive benefit from dosages provided at or below the low end of the ranges provided, whereas a relatively large patient weighing 100 kilograms or more may require dosages provided at the high end of the ranges noted (or more). In some embodiments such a daily dose can be distributed as multiple doses throughout the day. In some of such embodiments the composition of each of such distributed doses can be identical. In other embodiments the composition of such distributed doses can be different, provided the summation of such doses provides the required supplementation.
Surprisingly, the Inventor has found that treatment of various cancer cells with a combination of fish oil and selenium yeast has a direct impact on cell proliferation, particularly when used in combination with cancer chemotherapeutic agents. Examples of the effects of co-treatment of tumor cells with chemotherapeutic agents and with a nutritional supplement that includes fish oil and a selenium peptide can be seen in
Inventors have surprisingly found that co-treatment with chemotherapeutic agents and a fish oil/selenium peptide supplement also provides similar effects in an unrelated triple-negative breast cancer cell line (MDA-MB-231). Typical results of co-treatment of these cells with Docetaxel and fish oil/selenium supplement for 72 hours on cell proliferation are shown in
The effects of a nutritional supplement that includes fish oil and selenium in combination with chemotherapeutic drugs were also identified in in vivo studies, where the Ki-61 proliferative index marker was identified in mammary gland tumors of murine models by immunocytochemistry. Typical results of such studies are shown in
Overall, the Inventor has found that a nutritional supplement that includes fish oil and selenium (for example, in the form of selenium yeast or yeast products) can reduce proliferation in a variety of tumor cell types, and can provide a synergistic effect when used in combination with a variety of different chemotherapeutic agents. The effect is seen both in cell culture and in in vivo animal models of human disease.
The Inventor has also found that a nutritional supplement that includes fish oil and selenium reduces tumor size in in vivo animal models of human disease, and surprisingly can do so in a synergistic manner when used in combination with chemotherapeutic drugs. 8FIG8A provides an example of a typical testing protocol for such a nutritional supplement (“Nutrawell”) and the chemotherapeutic drug Tarceva. Initial body weights of mice used in such studies, which can be used to calculate tumor weight, are shown in
Similar results were found in mice implanted with cells derived from a human breast cancer and treated with a fish oil/selenium nutritional supplement in combination with chemotherapeutic drugs commonly used to treat breast cancer (e.g. Taxol, Adriamycin, Avastin, etc.).
Surprisingly, cotherapy with a fish oil/selenium nutritional supplement was found to potentiate the effects of chemotherapeutic reagents in a synergistic manner. As shown in
The effects of cotreatment with a nutritional supplement containing fish oil and selenium and the chemotherapeutic drug Iressa on tumor weight in mice implanted with lung cancer cells can be seen in
Further in vivo studies were performed using the protocol shown in Table 2.
To determine if the results of in vivo studies were influenced by general nutritional status of animal subjects receiving nutritional supplementation Inventors compared the results of cotreatment with a nutritional supplement containing fish oil and selenium (“TNuF”) and equivalent caloric supplementation with a commercial nutritional supplement (Prosure™, “P”). As shown in
In many instances growth of solid tumors is promoted by angiogenesis and/or neovascularization, leading to the development of blood vessels within the tumor mass. Inventors have also found that a nutritional supplement containing fish oil and selenium can reduce angiogenesis/neovascularization in tumors, both alone and when used in combination with chemotherapeutic agents. Surprisingly, the Inventor also noted reduced angiogenesis/neovascularization effects for some chemotherapeutic agents alone. The Inventor believes that such a reduction in neovacularization induces oxidative stress in tumors and/or renders tumors so treated more susceptible to oxidative stress.
Inventors have found that the use of a nutritional supplement containing fish oil and selenium in combination with chemotherapeutic agents (e.g. taxol, adriamycin, avastin) has a direct and observable effect on vascularization of tumors in in vivo murine models of breast cancer. In an exemplary study mice were treated as shown in the scheme depicted in
The effects on angiogenesis/neovascularization of treatment with a supplement containing fish oil and selenium and chemotherapeutic agents can also be observed on a molecular level. VEGF and CD31 are markers related to tumor angiogenesis, via the HIF-α pathway.
The Inventor has found that cotherapy with a nutritional supplement containing fish oil and selenium and chemotherapy drugs also has a profound effect on the cell cycle phase distribution of cancer cells, both in vivo and in vitro. As shown in
It is apparent that treatment with a supplement containing fish oil and selenium in combination with various chemotherapeutic drugs can shift the cell cycle distribution of cancer cells towards sub-G1 phase. It should be appreciated that sub-G1 phase is associated with apoptosis; as such combined therapy with a chemotherapeutic drug and a supplement containing fish oil and selenium can be useful in inducing apoptosis and/or apoptic events in cancer cells.
Apoptosis/Autophagy
As noted above, studies of cell cycle phase distribution suggest that cotherapy with a supplement containing fish oil and selenium in combination with a chemotherapy drug can induce apoptosis and/or apoptic events in cancer cells. Inventors have found that nutritional supplements containing fish oil and selenium are effective in enhancing apoptosis in tumors in in vivo models for breast cancer. For example,
Results of similar studies directed to Bcl-2, p-Bcl-2, and Caspase 3 are shown in
In addition to biochemical markers of apoptosis, apoptic effects can be observed directly. For example, as shown in
The Inventor have found that nutritional supplements of the inventive concept are effective in enhancing oxidative stress of tumors in in vivo models for breast cancer (e.g. inhibiting the ability of a tumor to respond to oxidative stress). For example,
The Inventor has also found that a nutritional supplement containing fish oil and selenium in combination with chemotherapeutic drugs can be effective in reducing stem cell characteristics of cancer cells. Development of cancer cells showing such characteristics is thought to be involved in both metastasis and in the development of resistance to chemotherapeutic drugs. It should be appreciated that sphere cells that form in cell culture are thought to replicate, at least in part, the development of cancer stem cells in vivo.
As shown in
A similar effect is observed in MDA-MB-231 breast cancer sphere cells. As shown in
The effects of Cisplatin, selenium, fish oil, selenium and fish oil in combination, and Cisplatin with the combined supplement on cell cycle phase distribution are shown in 8FIG3C. As shown selenium and fish oil alone provide a very modest shift towards sub-G1, whereas selenium and fish oil in combination provide a relatively large shift. Cisplatin alone provides a modest shift toward sub-G1, which is enhanced when used in combination with a supplement containing fish oil and selenium. Results are tabulated in Table 4.
Similar results are found for A549 lung cancer sphere cells treated with Alimta, Tarceva, and these chemotherapeutic agents in combination with a supplement containing fish oil and selenium, as shown in
It should be appreciated that sub-G1 is associated with apoptosis. As such, the Inventor believes that use of a combination of a supplement containing fish oil and selenium in combination with a chemotherapeutic agent can be effective in inducing apoptosis in cancer sphere or stem cells, even when such cells are resistant to the chemotherapeutic agent.
The Inventor has also found that the use of a supplement containing fish oil and selenium in combination with a chemotherapeutic agent can modify expression of biochemical markers associate with cancer sphere or stem cells, bringing them into accordance with levels associated with non-stem cancer cells. As shown in
As shown in
While the above studies focused on A549 sphere cells, similar results were obtained from in vivo studies of animal models of human breast cancer.
Overall, the Inventor has found that use of a nutritional supplement that includes fish oil and selenium can reduce stem cell characteristics and/or “stemness” in cancer cells, and can do so in a synergistic manner when used in combination with chemotherapeutic drugs.
As noted above, development of stem cell characteristics (e.g. “stemness”) in cancer cells has been associated with the development of drug resistance. Surprisingly, the Inventor has found that a nutritional supplement that includes fish oil and selenium is effective in sensitizing drug-resistant cancer cells to chemotherapeutic drugs to which they have demonstrated resistance. For example, HCC827Gr cells are human lung cancer-derived cells that have developed resistance to chemotherapeutic agents, such as Iressa. The result of exposure of such cells in culture to Iressa in the presence and absence of a selenium+fish oil supplement are shown in
This sensitization effect is also found when cell proliferation is characterized. As shown in
As shown in
The Inventor has also found that treatment of such resistant cancer cells with fish oil and selenium yeast modifies the cell cycle phase distribution of these cells, as shown in
Inventors have found, surprisingly, that pre-treatment of chemotherapy resistant cells (such as HCC827GR) with a nutritional supplement containing fish oil and selenium yeast can have the effect of sensitizing these resistant cells to subsequent exposure to a chemotherapeutic agent to which they have demonstrated resistance. XFIG4 shows the results of pre-treatment of Iressa-resistant HCC827GR cells with a nutritional supplement containing fish oil and selenium for 72 hours prior to exposure of the cells to Iressa. As shown, such pre-treated cells show a significant decrease in cell proliferation relative to cells pre-treated with PBS.
As shown in FIG. 62, such pre-treatment with a nutritional supplement containing fish oil and selenium yeast also impacts cell cycle phase distribution relative to untreated cells. Numerical results of such a study are summarized in Table 7.
As shown, pre-treatment with a nutritional supplement containing fish oil and selenium yeast alters the cell cycle phase distribution of these Iressa-resistant cells towards a significantly higher proportion of SubG1 and S phase cells. Application of Iressa to such pre-treated cells provides a still higher percentage of cells in Sub-G1 phase. It should be appreciated that the sub-G1 phase is associated with apoptosis.
The Inventor has found that a supplement containing fish oil and selenium can effectively reduce tumor metastasis and/or progression, particularly when used in combination with a chemotherapeutic agent. For example, Inventors have found that use of a nutritional supplement containing fish oil and selenium in combination with a chemotherapeutic agent can reduce metastasis from a primary tumor site. As shown in
A reduction in metastasis when a nutritional supplement containing fish oil and selenium was used in combination with multiple chemotherapeutic drug therapies was also found. Cotherapy with a nutritional supplement containing fish oil and selenium and chemotherapeutic drugs can also reduce the incidence of metastasis relative to the use of chemotherapeutic drugs alone. As shown in
In addition to observation of a reduction in metastatic tumors and tumor cells, a reduction in biochemical markers associated with tumor metastasis and progression was also found on treatment with a nutritional supplement containing fish oil and selenium, which was potentiated by cotherapy with chemotherapeutic agents. As shown in
Surprisingly, the Inventor has also found that use of a nutritional supplement containing fish oil and selenium can reduce the number of circulating cancer cells in human patients. Data from a patient treated for 16 weeks with a nutritional supplement containing fish oil and selenium is shown in
While chemotherapeutic agents have long been used in treating cancer, more recently immunological approaches have been explored. Often such approaches are directed to the modulation of immune checkpoint molecules, providing activation of components of the immune system and/or inhibition of components that reduce immune response to tumor cells.
Surprisingly, the Inventor has found that a nutritional supplement containing fish oil and selenium can modify the expression of such immune checkpoint molecules. For example, the Inventor has found that nutritional supplements containing fish oil and selenium are effective in reducing immune checkpoint proteins (e.g. CD279, CD274), and are also capable of doing so when used in combination with conventional chemotherapy drugs (e.g. Taxol (“tax”), Adriamycin (“adyri”), Avastin), as shown in
Modulation of PD-L1 in tumor cells and PD-1 in T cells in animal models treated with a nutritional supplement containing fish oil and selenium, either alone or in combination with various chemotherapeutic agents (Taxol, Adriamycin, Avastin) is shown for lung cancer cells in
Clinical data also demonstrate improved immune function in cancer patients receiving a nutritional supplement containing fish oil and selenium. For example, as shown in
Overall, the Inventor believes that this indicates that nutritional supplements containing fish oil and selenium can enhance, in a complementary, additive, or synergistic manner, immunotherapeutic approaches to cancer treatment. The Inventor believes that this indicates that nutritional supplements containing fish oil and selenium can enhance, in a complementary, additive, or synergistic manner, immunotherapeutic approaches to cancer treatment.
Individuals with cancer frequently present with weight loss, due to loss of fatty tissue and muscle wasting (cachexis). This weight loss can result in serious health issues in addition to those resulting directly from tumor growth and progression. The Inventor has found that a nutritional supplement that includes fish oil and selenium can reduce cachectic symptoms, particularly when used in combination with one or more chemotherapeutic agents. Mice having tumors, with or without treatment with chemotherapeutic agents also experience cachexis. Using such an animal model the Inventor has found, surprisingly, that treatment with a nutritional supplement that includes fish oil and selenium can reduce these effects. As shown in
As shown in
In addition to the burden provided by a tumor, chemotherapy itself is associated with a variety of unpleasant and potentially dangerous cachectic effects. Surprisingly, the Inventor has found that these cachectic effects can be reduced or eliminated by providing a nutritional supplement that includes fish oil and selenium as cotherapy with chemotherapeutic drugs. An example of a typical study utilizing human tumor cells implanted in mice is shown in
As shown in
Reduction in cachectic symptoms on treatment with a nutritional supplement that includes fish oil and selenium in combination with a chemotherapeutic agent is also evident on a molecular level. The Inventor has observed that use of such a nutritional supplement is effective in preventing or reversing changes in the expression of specific biochemical markers associated with muscle wasting and inflammation, whether used in isolation or in combination with chemotherapeutic agents (e.g. Taxol, Adriamycin, Avastin). This is also apparent at the molecular level, as shown in
Treatment with a nutritional supplement containing fish oil and selenium, with or without cotherapy using chemotherapeutic agents, was also found to modulate expression of biochemical markers associated with fat tissue and metabolism. As shown in
Surprisingly, treatment with a nutritional supplement that includes fish oil and selenium was also found to reduce expression of PTHrP in tumor bearing animals (TN, see top left panel of
Improvement in cachexia in patients with head and neck cancer on use of a nutritional supplement that includes fish oil and selenium was also observed in clinical studies. As shown in
Presence of a tumor and use of chemotherapy is frequently associated with nausea and loss of appetite, which can contribute to cachexia. Surprisingly, the Inventor has found that use of a nutritional supplement that includes fish oil and selenium can increase feed intake in animal models, despite the additional calories provided by the supplement itself (see
The presence of tumors is frequently associated with inflammation, a process that is at least in part mediated by cytokines. Cytokines can also be involved in other tumor-related processes, such as angiogenesis. Surprisingly, the Inventor has found that a nutritional supplement that includes fish oil and selenium can modulate levels of various cytokines, particularly when used in combination with chemotherapeutic drugs. As shown in
As shown in
Conversely, the Inventor has found that the use a nutritional supplement containing fish oil and selenium can increase plasma concentrations of some cytokines, both in isolation and in combination with chemotherapeutic drugs. For example, as shown in
Overall, the Inventor believes that a nutritional supplement that includes fish oil and selenium can be useful to reduce plasma concentrations of cytokines associated with inflammation and tumor growth/progression, both as a monotherapy and in combination with one or more chemotherapeutic drugs. It should be appreciated that such a reduction can be provided even when such chemotherapeutic drugs result in an increase in the plasma concentration of such cytokines when used in the absence of such a supplement, and that the reduction is potentiated by cotherapy (indicating a synergistic effect). Similarly, use of such a supplement can result in increased plasma concentrations of immune-activating cytokines, both when used as a monotherapy and when used in combination with one or more chemotherapeutic drugs.
As shown in
In some embodiments of the inventive concept, Inventors have found that a nutritional supplement that includes fish oil and selenium is particularly effective in modifying AXL signaling in cells, particularly drug resistant tumor cells. As shown in
The Inventor has further investigated mechanisms by which the described nutritional supplement can be modulating AXL protein concentrations in the cell.
Surprisingly, the Inventor has found that a supplement containing a combination of selenium yeast (Nutrient A) and fish oil (Nutrient B) reduces both AXL and HSP90 in drug (Iressa)-resistant HCC827GR cells (see
The mTOR pathway has also been implicated in drug resistance in tumor cells. As shown in
Studies of the effect of a nutritional supplement containing fish oil and selenium, both alone and in combination with chemotherapeutic agents, were also studied using in vivo animal models of triple negative human breast cancer. Results are shown in
As noted above, use of a nutritional supplement containing fish oil and selenium has numerous beneficial effects in regards to treatment of cancer, including reduction in tumor cell proliferation, tumor size and vascularization, resistance to chemotherapy, and metastasis. These effects are potentiated in a synergistic fashion by cotherapy with one or more chemotherapeutic agents. In addition, such supplements are able to reduce or reverse symptoms of cachexia associated with cancer, as well as modify plasma cytokine concentrations. Such benefits directly address many quality of life issues for persons living with cancer. In addition, the Inventor has found that use of a nutritional supplement containing fish oil and selenium also provide a direct benefit in regards to survival rate. As shown in
It should be apparent to those skilled in the art that many more modifications besides those already described are possible without departing from the inventive concepts herein. The inventive subject matter, therefore, is not to be restricted except in the spirit of the appended claims. Moreover, in interpreting both the specification and the claims, all terms should be interpreted in the broadest possible manner consistent with the context. In particular, the terms “comprises” and “comprising” should be interpreted as referring to elements, components, or steps in a non-exclusive manner, indicating that the referenced elements, components, or steps may be present, or utilized, or combined with other elements, components, or steps that are not expressly referenced. Where the specification claims refers to at least one of something selected from the group consisting of A, B, C . . . and N, the text should be interpreted as requiring only one element from the group, not A plus N, or B plus N, etc.
This application is a continuation of U.S. patent application Ser. No. 17/163,793, filed Feb. 1, 2021, which is a divisional application of U.S. Pat. No. 10,905,725, filed Jun. 13, 2018, which claims the benefit of U.S. Provisional Application No. 62/519,093, filed on Jun. 13, 2017, U.S. Provisional Application No. 62/519,096, filed on Jun. 13, 2017, U.S. Provisional Application No. 62/595,002 filed on Dec. 5, 2017, and U.S. Provisional Application No. 62/670,275 filed on May 11, 2018. These and all other referenced extrinsic materials are incorporated herein by reference in their entirety. Where a definition or use of a term in a reference that is incorporated by reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein is deemed to be controlling.
| Number | Date | Country | |
|---|---|---|---|
| 62595002 | Dec 2017 | US | |
| 62519096 | Jun 2017 | US | |
| 62670275 | May 2018 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16007539 | Jun 2018 | US |
| Child | 17163793 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 17163793 | Feb 2021 | US |
| Child | 18768946 | US |
