Success That Lasts

Pursuing success can feel like shooting in a landscape of moving targets: Every time you hit one, five more pop up from another direction. We are under constant pressure to do more, get more, be more. But is that really what success is all…more

A 55-year-old, highly successful venture capitalistis thinking about his next investment. He’s not certain he has the energy to start another seven-year round of intense financing and consulting activity. “I just can’t imagine enjoying that pace again, and frankly, it’s time I paid attention to my family. But I’d really feel a loser if I didn’t play the game as hard as everyone else. I guess I should retire.”

The president of a $1 billion divisionof a consumer products company discovers that manufacturing and distribution bugs will delay the scheduled rollout of a new product line. Retailers are eager for the product, pressures on share price are intense, and the president’s bonus is tied to the rollout’s success. If he goes ahead, the product is sure to be on top – but only temporarily. The costs down the road from disappointed consumers and time invested in having to fix mistakes will clearly hurt the bottom line. What is success under these circumstances?

A fast-track 32-year-old software engineerwith a second degree in sacred music feels that something is missing in her career strategy. She wants the lifestyle of a well-paid manager, but software doesn’t feel as socially significant as playing the organ for a congregation. And she someday wants a house and a family. “Why can’t I find the career path that will get me all of these things?” she wonders. “Are they really so unreasonable?”

Different as these examples may be, these individuals have a similar problem: They all need a comprehensive framework for thinking about success. And they’re far from alone.

Survey after survey shows a high degree of job dissatisfaction and burnout among the general working population, even among those with plenty of options. In the collective soul-searching prompted by September 11, 2001, many high achievers revisited their notion of success. The wave of corporate scandals that followed soon after only made the questions more acute. Even the most dedicated employees wondered aloud whether they would ever recommend their own careers and companies to their children.

Pursuing success is like shooting at a series of moving targets. Every time you hit one, five more pop up from another direction. Just when we’ve achieved one goal, we feel pressure to work harder to earn more money, exert more effort, possess more toys. Standards and examples of “making it” constantly shift, while a fast-paced world of technological and social change constantly poses new obstacles to overcome.

During the past decade, traditional career paths suddenly became pointless. Professionals found themselves overworked and undersatisfied in the boom, then overworked and competitively vulnerable in the bust. And far too many businesses discovered they were using the wrong measures to gauge success, winning big in the 1990s only to lose big for their shareholders and employees at the turn of the millennium. The climb to success can feel like an Escher drawing of a staircase that goes nowhere.

In the face of such instability, many people assume success requires a winner-takes-all approach. They believe that success depends on putting all your energy into achieving one goal, be it a single-minded focus on your job or a commitment to being the best soccer mom in your community. But no matter how noble, one goal can’t satisfy all of a person’s complex needs and desires, as the examples at the beginning of the article demonstrate. The same holds true for the goals of a business.

Fortunately, success doesn’t have to be seen as a one-dimensional tug-of-war between achievement and happiness. If developed in the right way, your ideals of the good life for yourself and society can become powerful—and manageable—factors of success. We studied hundreds of high achievers who realize lasting success, make a positive difference, and enjoy the process. And we learned that some of the most successful people have gotten where they are precisely because they have a greater understanding of what success is really about and the versatility to make good on their ideals. In this article, we’ll introduce a practical framework that will help you see success in these same terms. But first, a closer examination of how we arrived at this model.

What Is Enduring Success?

Our research took a fresh look at the assumptions behind success. We were interested in real, enduring success—where getting what you want has rewards that are sustainable for you and those you care about. This type of attainment delivers a sense of legitimacy and importance; its satisfactions endure far beyond the momentary rewards of a bonus or a new position. Lasting success is emotionally renewing, not anxiety provoking.

Unlike an equation for a successful market strategy, no one person or company can fully embody lasting success for others. Everyone (and every business) has a unique vision of real success, and that notion changes over time. A family-oriented person would hardly call the absentee life of a top executive a success but might find travel and adventure just the ticket after the kids grow up. A born investment banker would hardly regard mixing cement as a successful career, whereas a construction worker who just completed an extraordinary bridge might point to the structure with pride for the rest of his or her life. No one, however, has unreserved success, not even the most obvious winner. Recognizing how important it is for each person to understand and develop his or her unique definition of success over time, we chose not to report on one or two well-known examples of success as the perfect model to follow.

Nonetheless, for the purposes of research, we posited five common characteristics of individuals who by most standards had achieved enduring success: high achievement, multiple goals, the ability to experience pleasure, the ability to create positive relationships, and a value on accomplishments that endure.

We held more than 60 interviews with successful professionals, surveyed 90 top executives attending Harvard Business School management programs, and informally observed high achievers with whom we live and work. We conducted more than a dozen model-testing sessions with between 50 and 110 executives in each. Most of these groups were drawn from HBS graduates or current members of the Young Presidents’ Organization. We also reviewed the problems that the general population has reported about success, using sources that ranged from media reports to conversations with friends, students, and colleagues. We talked to people from all different walks of life, at every level of the economy, both in and out of business careers. Some of them were stay-at-home parents who had once worked full time; others were at the pinnacle of their careers.

The Complexity of Success

Success involves more than a heart-pounding race to the finish line. Our research uncovered four irreducible components of enduring success: happiness (feelings of pleasure or contentment about your life); achievement (accomplishments that compare favorably against similar goals others have strived for); significance (the sense that you’ve made a positive impact on people you care about); and legacy (a way to establish your values or accomplishments so as to help others find future success).

These four categories form the basic structure of what people try to gain through the pursuit and enjoyment of success. Take away any one component, and it no longer feels like “real” success. If you were wildly wealthy because you had mastered a certain business problem but couldn’t experience pleasure, for instance, would you consider yourself successful? If building your power base kept you from being there for others, would your success feel morally right? If you left your career to be a full-time parent, would you have enough of an outlet for your talents? Just as a steady diet of the same four foods would hardly be satisfying over the long term, the four components of success cannot be satisfied by the presence of a single flavor in each category. That is why you cannot neatly categorize the realms of your life, assigning happiness to self, achievement to work, significance to family, legacy to community.

Unless you hit on all four categories with regularity, any one win will fail to satisfy. You’ll experience what we call the “wince factor”: You know you’re doing what is right, but it still feels like a loss. You’re preoccupied with thoughts of the other things you could be doing or getting. Your achievements and pleasures fade almost as soon as they occur. By contrast, success that encompasses all four kinds of accomplishment is enriching; it endures. You can create this synergy within a single event, but you can also create it through a juxtaposition of activities. Taking time out in the middle of a high-stress period or stopping to give back to the community while in the midst of pursuing your most self-advancing goals are good examples of this.

If you think about what constitutes a moment of lasting satisfaction in your own life—maybe it’s your daily practice of a musical instrument—it may be surprisingly trivial in comparison with your major commitments at work or at home. The activity draws force from accomplishing something distinctive in each of the four categories over time. The musical instrument provides release and pleasure (happiness), it is a challenge to master and build on (achievement), and it becomes even more fulfilling when you join a band that competes with other bands or play concerts at hospitals (significance). Those who also turn these “lesser” vocations into legacies that build the same opportunity for the next generation—say, through getting involved in recruiting and training younger musicians—will find an even deeper sense of success from so-called hobbies.

Anyone who takes the four elements of success seriously soon realizes how complicated it can be to touch on all four with regularity. As you scale up your goals, the four-part mix becomes more difficult to achieve. Each factor has a different set of characteristics. Satisfying different needs, they draw on distinctive emotional drives and prioritize self and others in different ways. That’s why people who tell you that happiness, achievement, and significance will come automatically if you simply do the work you love are misguided. Regardless of how much you care about your job, you will still feel conflicting desires—between work and home, between working forever on a problem and taking a break from it, between going for more market share today and investing in the company’s needs for tomorrow. The skills you use to compete are totally different from those you employ in moments of enjoyment. You can be there for a friend, and you can care about a customer, but these acts (in the significance category) can’t be substituted for the kind of thinking and prioritization that is necessary to structure favorable financial terms for your own firm (in the achievement category).

People who tell you that happiness, achievement, and significance will come automatically if you simply do the work you love are misguided.

Understanding the distinctive features of the four areas of success can help you articulate what you are seeking in a certain activity. You can then create a diagnostic for determining how to achieve the most appropriate goal. You may be expecting too many categories to be fulfilled without incorporating the right resources and perspectives, or you may be falling prey to a mismatch.

Matching your expectations to the right category is a critical skill for achieving sustainable success. If you expect happiness to come primarily from competition (an achievement skill), you’ll probably turn into someone neither you nor those around you can tolerate—and wonder why success has made you so lonely. People who report having trouble defining the right goals for themselves or for their companies are often caught in such mismatches. For instance, a self-described family-friendly company might hold critical staff meetings over late dinners or during extended weekend retreats.

The act of categorizing in and of itself can help you take more decisive action and channel the right emotions and perspectives to the task at hand. You can stop measuring a job only by how happy it makes you or calculating a business success only in terms of your ability to achieve mastery over something. Instead, you’ll see how one task fits into a larger context. By the same token, you’ll be able to anticipate what kind of emotional capital you’ll need to bring to a task. If you try to bring feelings of happiness or contentment to your achievement goals, you’ll stunt your performance from the start. If you don’t put achievement in its place, however, you’ll trap yourself in a workaholic restlessness.

Those in our research who achieved satisfying, enduring, multidimensional success consciously went after victories in all four categories without losing touch with their values and special talents. They seemed to understand intuitively the paradox we uncovered at the heart of enduring success: To get to more wins on the various important measures that make up your notion of the good life, success has to rest on a paradigm of limitation in any one activity for the sake of the whole. Or, as we call it, “on the reasoned pursuit of just enough.”

This principle flies in the face of the popular opinion that success is all about breaking through limitations, that it’s about having more, being more, doing more. Our research shows that the high-powered people who experienced real satisfaction achieved it through the deliberate imposition of limits. They all shared a versatile talent that we call “switching and linking”: They were able to focus intensely on one task until it gave them a particular sense of satisfaction, then put it down and jump to the next category with a feeling of accomplishment and renewed energy. This versatile refocusing could occur within the same activity (say, when you base your product strategy on accomplishing your profit goal and on caring for the customer), or it can involve switching attention between two realms (taking a break from work to joke with a friend).

The people in our research who were particularly skilled at sifting through the moving targets and going after only those that would produce lasting rewards shared two characteristics. First, they viewed success as a broad and dynamic experience of accomplishment, one that factored in all four categories. They didn’t attribute their success to one single event or even one single realm of life. Second, their concrete examples of what counted as “real” success included accomplishments of wildly varying magnitude. They weren’t setting maximum goals for themselves in each category; rather, they set some at a small scale and some at a scale that demanded sustained effort. The baseline for these individuals wasn’t the amount of activity or number of rewards in any one category, but the securing of a proportionate mix of all four. Anyone can learn to do this; you just need to have a larger framework in which to understand the dynamics of the four categories.

The Kaleidoscope Strategy

We compare an effective success strategy to a kaleidoscope—that simple mechanical device with a lens, mirror, and a long tube housing separate chambers. Each chamber holds pieces of glass that constantly shift as the tube is moved. Although the chambers are separate, the eye sees one unique picture made up of the various chambers. Mirrors reflect the entire set of glass chips and enhance the complexity of the pattern. The beauty of that pattern comes from the variety and symmetry of the design. Although the patterns in a kaleidoscope are inherently unstable, changed by your own movements or by outside forces, the pieces provide ongoing satisfaction as they take their places within new patterns.

Now imagine a slightly different kind of kaleidoscope, one that is your own vision of a successful life. This kaleidoscope also has four chambers—happiness, achievement, significance, and legacy—and you can add brilliant glass pieces (goals sought and fulfilled) over a lifetime, making your unique pattern richer and richer. In this metaphor, success is about choice, movement, pattern, and a structure that holds all the separate activities together. And, just like a kaleidoscope, you have to hold this pattern up to the light. By regularly assessing the picture you are creating in all four chambers, you can quickly spot “holes”—places you feel require more attention—in your activities and be assured that you are justified in interrupting other work to attend to them. The rest of the chips will be enough for the moment, but not enough for the rest of your life.

Success is about choice, movement, pattern, and a structure that holds all the separate activities together.

Through our research, we discovered that the people who achieve enduring success rely on a kaleidoscope strategy to structure their aspirations. Not only do they continually create new chips in each of the four categories, but they also choose their actions so that the whole picture will display a pleasing proportionality. Feeling deep satisfaction in each category strengthens these achievers’ ability to turn away from one category when another needs attention. It allows them to say, “I don’t need to work away at this particular thing until I’m satiated and hate the very sight of it. This is just enough.” They recognize the importance of setting their own standards for “enough” and not falling prey to the lure of the infinite “more.”

This is exactly the kind of thinking you see in good leaders: They anticipate what will be needed in all four dimensions of success despite pressures to deliver to the maximum in one. This is what the subjects in the three examples at the beginning of this article were lacking. They had no framework in which to identify and sort multiple desires so that they could go after their conflicting goals sequentially in a proportionate mix.

The burned-out venture capitalist needs to understand that scaling back his achievement goals is part of a larger picture of expansion in the other categories, rather than a paralyzing prospect of loss and “doing nothing.” This kaleidoscope view will allow him space to cultivate the emotional relationships he craves with his family. That doesn’t mean he should give up all forms of achievement; he simply needs to readjust the level of energy he puts into that category. Doing so will require more creative thought and versatility than he’s exhibiting now.

The executive overseeing the problematic product rollout was framing his dilemma in terms of short-term versus long-term achievement. He would do better to reframe his challenge in terms of legacy: What kind of platform would he be creating for the success of this product and that of future managers in the company if he decided to release incomplete products? Thinking about the problem from this perspective helped him clarify his priorities. Instead of feeling that he had to make a trade-off in a negative sense, he could take a positive view of what needed the most attention and what was worth sacrificing for. In the end, he delayed rolling out the new product line—and not only were the retailers delighted with the final results, but the product division, in crafting the solution, discovered a new way to coordinate and leverage its technological capabilities across three countries.

The software engineer torn between computers and church music needed to shrink or redirect her goals in some activities and develop them in others. When she tried the kaleidoscope strategy, she quickly saw that church music registered high in her significance category but would always be a limited outlet for achievement. She had neither the skill nor the opportunity to become a star musician. Software had more potential for significance than she had previously thought. She needed to learn how to change her job in ways that emphasized the social value she was creating in the products she worked on and the help she provided to others. She began to see benefits in framing church music primarily as an exercise in significance rather than in achievement, with all its competitive and financial associations. But to fill both chambers, she’d need to restructure her job commitments in order to minimize travel and commit to choir practice. When she looked at the whole picture of goals she could satisfy through the sum of these activities, scaling back suddenly seemed more positive. The pieces were enough. And, she recognized, taking this path would require continued growth on her part—something she had forgotten she valued and which she now had the confidence to pursue strategically. Enduring success required enduring commitment.

Building Your Own Kaleidoscope

To create your own kaleidoscope, start by sketching out your framework. Take a piece of paper and draw four intersecting circles. Label them happiness, achievement, significance, and legacy. In each circle, list self, family, work, and community. This will enable you to do a full inventory of the mix and determine how each piece falls in the context of each major domain of your life. (See the exhibit “My Personal Kaleidoscope.”)

My Personal Kaleidoscope

Next, quickly jot down examples of your successes or great satisfactions. You don’t have to come up with one for every item in every circle—this is just a quick sketch of your beliefs about yourself, not the full picture. Don’t spend time worrying about whether you should put a particular target next to a particular item. Just work with your first impulses.

Take your college degree as an example. You may feel that graduating from college was a major achievement, a benchmark in your overall career plans and something you will value for your whole life. Your degree represents a mastery of skills. You had to compete successfully to get there and get the grades. You felt satisfaction when you were successful. So you would write “college” in your achievement chamber, next to the word “work.”

But what if college represented other things for you? Significance in your family life, for example, because your parents or spouse really valued what you were doing? In that case, you might also put college in your significance chamber, next to “family.”

The point is not to compulsively divide your life into little circles and lists. Rather, it is to help you assess the various types of satisfactions you have already experienced and see what they add up to. The answer is often more surprising or richer than you may have suspected.

Depending on your age, you might even want to fill out framework profiles for several periods in your life. Did you want the same things at 40 as you did at 20? Will you want the same things at 60? At 85? Could you ever fully abandon one of the categories and still feel that you were a success? (This is the trap that many retirees and those who downscale their careers to become full-time parents fall into.)

Now, metaphorically speaking, you can hold your kaleidoscope up to the light. Look at it objectively, and ask yourself:

1. How integrated is your profile? Are some of the domains empty? Are others too full? Is each realm of your identity—self, family, work, community—a depository of only one satisfaction, or is there a broader basis for success in each of these areas?

2. How varied is your profile? Where are most of your greatest successes and satisfactions so far? Where are the holes? The obsessions? Are the chambers and realms evolving or repeating the same things over and over?

3. What have you learned about what you actually do? Where is your time going? How does it speak to what you really want from success? Research into success has shown that one of the biggest causes of failure is an overreliance on one’s greatest strengths. Are you favoring what you do best and neglecting your need for fulfillment in all four categories?

Here’s how the kaleidoscope strategy helped John, the owner of a large real estate company, find enduring success. John was having trouble deciding what to do with his business. After a blowout with his teenage child and a series of relentless, debilitating headaches, he decided he had to cut back on his work. He had already bought a plane—against his family’s wishes—and he had increased his time for himself, but he was still suffering. “I know I should sell part of this business for the sake of my happiness,” he said, “but I just can’t do it.”

We suggested he try putting this sale in another category, one that seemed rather empty. Why not think about the sale as an active engagement in legacy rather than as a platform for happiness? The pieces fit. Legacy is about building on your achievements and values to help others succeed after you’re gone. John remembered a young manager who had left the firm, someone who knew John’s values and was quite accomplished in his own right. This person would probably welcome the chance to head the new spin-off, and he’d be likely to extend the kind of business John had spent his life building. The buyers would need such a person, and John would be comfortable doing business with them.

After seeing the situation from a different perspective, John was more decisive about the sale and had a richer platform of concrete goals around which to structure the transaction: the terms in which legacy would be fulfilled, the new time frame for his own enjoyment of life, a revitalizing and more realistic set of achievement goals, and a sense of providing the space to be there for his daughter and wife without giving up all the challenges of the real estate business.

Identifying where his activities were located in the kaleidoscope gave John immediate insight into what he was seeking and getting from his efforts—as well as what was lacking. In channeling your efforts effectively toward what you really seek from success, it’s critical to test your profile against your idealized view of yourself. What do you want your profile of accomplishments in each of the four categories to look like tomorrow? Next month? Over your lifetime?

The Kaleidoscope Strategy for Businesses

What makes for the enduring success of a company? In our view, businesses prosper when they enable individuals and …

Getting to “Just Enough”

If you pay attention to the four categories and their relation to one another, you can enrich the potential for any activity to satisfy you on numerous dimensions, whether at work, in your leisure time, or in some other aspect of your life. The high achievers in our study were able to accomplish great things for themselves and others by recognizing they had multiple goals that were critical to their idea of real success and by being fully committed to whatever activity they were engaged in. By switching and linking, they limited their attention to one task, and when other needs pressed, they were able to make lightning fast changes of focus and emotional energy. Instead of feeling cheated because they couldn’t get it all, they were renewed by following the cycle of attention to each category.

How do you know when it’s time to stop your work in one category and switch your attention to another? That’s where the concept of “just enough” becomes critical. Conventional interpretations of “enough” don’t capture its full potential. People tend to use the term to express dissatisfaction, as in, “That’s it! I’ve had enough!” or as a code for mediocrity or passivity, as in, “If I’m just happy every day, that’s enough.” We mean something else by enough, closer to its root definition: occurring in sufficient quantity or quality to satisfy demands or needs. If you have a firm idea of the big picture in your kaleidoscope of success, it becomes easier to determine and appreciate “enough” in any one activity. Without losing your energy for high aspirations, you set reachable goals. “Just enough” is the antidote to society’s addiction to the infinite “more.” Seen in that light, it becomes a vehicle for actively making choices that allow you to do and get more, not less, through achieving satisfaction in more areas of your life.

“Just enough” is the antidote to society’s addiction to the infinite “more.”

Ganoderma: A Cancer Immunotherapy Review

Yu Cao1,2Xiaowei Xu3Shujing Liu3Linfang Huang1* and Jian Gu2*

  • 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
  • 2Department of Pharmacy, Southwest University for Nationalities, Chengdu, China
  • 3Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

Ganoderma is a significant source of natural fungal medicines and has been used for the treatment of various diseases for many years. However, the use of Ganoderma in cancer immunotherapy is poorly elucidated. In this study, we have analyzed 2,398 English-language papers and 6,968 Chinese-language papers published between 1987 and 2017 by using bibliometrics. A steady growth in the number of publications was observed before 2004, followed by an exponential increase between 2004 and 2017. The most common category for publications about Ganoderma was “Pharmacology & Pharmacy,” in which immunomodulation (25.60%) and cancer treatment (21.40%) were the most popular subcategories. Moreover, we have provided an overview of the bioactive components and combinatorial immunomodulatory effects for the use of Ganoderma in the treatment of cancer, including the major pathways of immune cells. Immunomodulatory protein and polysaccharides are the key bioactive factors responsible for cancer immunotherapy, and the NF-κB and MAPK pathways are the most comprehensively investigated major pathways. Our results indicate that Ganoderma has a broad-spectrum application for the treatment of cancer through the regulation of the immune system. This review provides guidance for future research into the role of Ganoderma in cancer immunotherapy.

Introduction

Ganoderma, also called Lingzhi, is one of the most well-known medicinal species. Regarded as the “marvelous herb,” it is used widely in China, America, Japan, Korea, and other countries (Meng et al., 2011). According to traditional Chinese medicine (TCM) theory, Ganoderma has the ability to enhance body resistance, i.e., “Fuzheng Guben” (Yue et al., 2006). “Channel tropism” (Gui-Jing) links the functions of herbal drugs to their corresponding internal organs, channels, and various body parts to allow the interpretation of their functional mechanisms. The channel tropism of Ganoderma is the heart, lung, and liver, according to Gui-Jing theory. The main Ganoderma species are G. lucidum, G. sinensis, G. applanatum, G. tsugae, G. atrum, and G. formosanumG. lucidum and G. sinensis are recorded in ChP2015 (Pharmacopeia of the People’s Republic of China), and G. lucidum is recorded in USP40-NF35 (U.S. Pharmacopeia/National Formulary; Gao et al., 2004). The production of Ganoderma occurs mainly through artificial cultivation, which has provided an abundance of materials for the market; the yield has already surpassed that of wild Ganoderma (Chen et al., 2017). Methods used for Ganoderma identification include microscopy, TLC, spectroscopy, chromatography, chemical fingerprinting, and DNA sequencing. DNA sequencing has recently been used for classification of different Ganoderma species, with HPLC, UPLC, LC-Q-TOF-MS, HPTLC, and GC-MS have been commonly applied for quality evaluation (Toh Choon et al., 2012Hennicke et al., 2016). Ganoderma has been used for the clinical treatment of chronic bronchitis, bronchial asthma, leukopenia, coronary heart disease, arrhythmia, and acute infectious hepatitis. However, at present, it does not have the potential to be used as first-line therapy, but only as an addition to conventional therapy in a clinical setting (Gao and Zhou, 2003Unlu et al., 2016).

Chemical drugs for cancer treatment, such as cisplatin and cyclophosphamide, can cause side effects, such as nephrotoxicity, which are detrimental to the quality of life of patients (Aguirre-Moreno et al., 2013). In addition to this toxicity, the resistance of some cancer cells to treatment has led to the need for the evaluation of alternative approaches. Hence, chemotherapy does not completely meet the treatment need and immunotherapy is a promising alternative method as it results in fewer side effects. The use of cancer immunotherapy has gained acceptance because immune cells play notable roles in the control of cancer (Blattman and Greenberg, 2004). Immune cells can identify cancer cells as dangerous and consequently attack them; thus, the use of cancer vaccines to treat growing tumors is considered an excellent therapeutic strategy (Rosenberg et al., 2004). Herbal medicines have also been examined in clinical trials for cancer immunotherapy. Shing et al. found that a 6 months treatment using G. lucidum increased the mitogen-induced lympho-proliferative responses in immunocompromised children with tumors (Shing et al., 2008).

Bibliometrics is a method of document analysis that can count and analyze a large number of articles and monitor the trends in research (Kim and Park, 2011). Previous studies have reviewed the anticancer and/or immunomodulatory effects of G. lucidum and their potential immunological mechanisms (Lin and Zhang, 2004Xu et al., 2011). However, the bioactive substances and corresponding immunoregulatory effects of Ganoderma in the treatment of cancer have not yet been investigated. Therefore, we have provided an overview of the research trend on Ganoderma determined from bibliometrics and reviewed its bioactive components and combinatorial immunomodulatory effects for use as a cancer treatment. We have also summarized the major diseases and pathways involved, clinical studies, and preliminary assessments of toxicity.

Literature Analysis

Bibliometrics is defined as the application of statistics and mathematics to analyze bibliographical metadata linked to scholarly publications. Bibliometrics uses a literature system and literature metrology characteristics as research objects to quantitatively and qualitatively analyze the studies. Bibliometrics can be used to monitor the trends in the scientific development of a research domain; it can be used to analyze the trends and provide a comprehensive perspective on a topic. Therefore, we analyzed a specific question from the review of published literature by using current software programs (Aggarwal et al., 2016). Using professional bibliometrics software, such as CiteSpaceV (Chen et al., 2014) and RAWGraphs, we performed a bibliometric analysis of the publications on Ganoderma between 1987 and 2017 from the Web of Science (WoS), PubMed, and CNKI databases, which were the most suitable databases for this type of evaluation. We found 2,205 articles in WoS and 1,368 articles in PubMed with “Ganoderma,” “Lingzhi,” or “Reishi” as the key words. After removal of the duplicates, a total of 2,398 English-language articles (included in the Science Citation Index) were retrieved. We also found 6,968 Chinese-language articles on CNKI with the Chinese word for “Lingzhi” as the key word. We analyzed publication counts, cooperation between countries, and research categories. We found that immunomodulation and antitumor research were the most popular research subcategories; subsequently, from examination of the relevant literature, the topic of this review was determined to be cancer immunotherapy.

Publication Counts

The publication counts for each year from 1987 to 2017 are shown in Figure 1. From on the number of publications, This 30 years period was preliminarily divided into three stages: Stage 1, from 1987 to 1993, was considered as the budding period, when <100 papers were published annually; Stage 2, from 1994 to 2003, was known as the development period, when the number of annual publications increased linearly from 100 to 300; Stage 3, from 2004 to 2017, was the “boom period,” when the annual number of papers increased rapidly; in particular, the number of English-language papers doubled annual. Research interest into Ganoderma widened over the years examined; moreover, the number of English-language studies has recently increased rapidly, revealing the potential research value of Ganoderma.FIGURE 1

Figure 1. Statistical analysis for published articles of genus Ganoderma.

Cooperation Between Countries

The relationships between many countries with active Ganoderma researchers, based on their publications included in the Science Citation Index, are illustrated in Figure 2. In total, 84 countries were involved in the study of Ganoderma. China, the United States, Malaysia, Japan, and South Korea have the highest output and the most extensive cooperation was found among these countries.FIGURE 2

Figure 2. Statistical analysis for relationship among countries for Ganoderma research. Different countries are represented by different colors, and the size represents the number of publications.

Subject Categories and Major Historical Developments

The categories of articles about Ganoderma that were included in the Science Citation Index are shown in Figure 3A. After the software analysis, we have displayed only subjects with a frequency of 50 or more. The most abundant category, “Pharmacology & Pharmacy,” had a frequency of 519, followed by the categories of “Chemistry” (422) and “Biochemistry & Molecular Biology” (400). From further reading, we found 1,512 Chinese-language articles and 880 English-language articles included in the Science Citation Index that described the pharmacological effects of Ganoderma. These pharmacological effects were subdivided into several specific effects (Figures 3B,C), such as immunomodulation, cancer treatment, antioxidation, cardiovascular treatment, diabetic treatment, liver protection, and neuropharmacology. The immunomodulation effect-related studies occupied the largest proportion of the eight areas of pharmacology, followed by cancer treatment, both in Chinese-language articles (24.73 and 24.47%, respectively) and in English-language articles (24.72 and 22.57%, respectively). Furthermore, in English-language articles, the number of citations was 17,692 and the average citation per item, which is the average number of articles cited for all items in the results set, was 20.43.FIGURE 3

Figure 3. Analysis for subject categories of Ganoderma(A) Subjects of 50 frequencies or more (included in Science Citation Index). Nodes represent objects analyzed. And the larger nodes, the more frequently they occur. The connections among nodes represent the cooperative relationships. The thicker the connections, the closer they consociate. (B) Classification of pharmacological effects in Chinese articles (C) Classification of pharmacological effects in English articles.

Further analysis of the English-language articles led to the identification of a total of 196 articles related to cancer immunotherapy. The timeline of major historical developments that are related to Ganoderma in cancer immunotherapy is shown in Figure 4. We found three types of fungal immunomodulatory proteins (Fips) that played important roles; Lz-8 was the first of these discovered. Moreover, the first study of the effect of Ganoderma on the inhibition of tumor growth occurred as early as 1991. In 2003, Ganopoly appeared as a new drug, and has since been used widely in clinical practice. Furthermore, the toxicology and immunology of Ganoderma were partly addressed in 2011 and its chemoprotective effects against cyclophosphamide-induced immunosuppression were studied in 2015. In addition, prebiotics were investigated as a novel approach for the treatment of carcinoma in 2017. Cancer immunotherapy has emerged one of the most popular fields of Ganoderma research. Hence, we have focused on the immunomodulatory effects of this genus and its constituent active components for use in cancer treatment.FIGURE 4

Figure 4. Timeline of major historical developments of Ganoderma on cancer treatment.

Immunomodulatory Effects of Ganoderma and Its Active Components on Cancer Treatment

Many pharmacological and clinical studies have shown that Ganoderma can play an antitumor role through the regulation of the immune system (Boh et al., 2007). The therapeutic effects of Ganoderma are attributed to fungal immunomodulation proteins (FIPs), polysaccharides, and triterpenoids. Furthermore, we have specifically summarized active components of Ganoderma and their corresponding pharmacological effects.

Fungal Immunomodulation Proteins

FIPs are small molecular proteins purified from various fungi, such as Ganoderma. These proteins are functional families of Ganoderma components with anticancer effects (Table 1). Four types of immunoregulatory proteins, Lingzhi-8 (Lz-8), Fip-gts, GMI, and Fip-gat, have been isolated and purified from Ganoderma.TABLE 1

Table 1. Pharmacological effects of immunomodulatory proteins of Ganoderma.

Lz-8, an immunomodulatory protein from G. lucidum, was first isolated and cloned in 1989. Primarily composed of 110 amino acids, Lz-8 has an immunoglobulin-like structure that forms non-covalently linked homodimers with biological activity (Kino et al., 1989). Lz-8 exerted significant therapeutic effects on gastric cancer and specific lung cancers. Liang et al. found that recombinant Lz-8 (rLz-8) induced autophagic cell death through aggregation in the endoplasmic reticulum (ER), which triggered ER stress and the ATF4-CHOP pathway in SGC-7901 human gastric cancer cells (Liang et al., 2012). Moreover, rLz-8 might be a useful chemotherapeutic agent for the treatment of lung cancer because owing the key role of FAK targets in metastasis (Lin and Hsu, 2016). In addition, Lin et al. reported a novel anticancer effect of rLz-8 through targeting EGFR mutation or overexpression and EGFR-dependent processes in lung cancer cells (Lin et al., 2017).

Fip-gts is an immunomodulatory protein purified from G. tsugae. The DNA encoding this protein was isolated from a cDNA library by using a reverse transcriptase-polymerase chain reaction (Lin et al., 1997). The recombinant FIP-gts (rFip-gts) suppressed telomerase activity in a dose-dependent manner through the downregulation of the telomerase catalytic subunit (Liao et al., 2006). RFip-gts inhibited telomerase activity in lung cancer cells in vitro through effects on nuclear export mechanisms, which may have been mediated by the ER stress-induced intracellular calcium level (Liao et al., 2007). In vivo studies showed that the growth of A549 cells in nude mice treated with rFIP-gts was significantly slower than those treated with PBS, which confirmed that lung tumor growth could be inhibited by rFIP-gts (Liao et al., 2008). Moreover, this protein was also shown to affect cervical cancer cells.

GMI is an immunomodulatory protein cloned from G. microsporum. The amino acid sequence of this protein shared 83% homology with that of FIP-gts (Chiu et al., 2015). In vitro studies found that GMI inhibited the EGF-induced phosphorylation and activation of EGFR and AKT pathway kinases in a dose-dependent manner (Lin et al., 2010). Hsin et al. found that autophagosomal accumulation induced autophagic cell death in a model of GMI treatment, and ATP6V0A1, a subunit of vesicular H+-ATPases, regulated autophagosome lysosome fusion. Hsin et al. also revealed that GMI and cisplatin induced apoptosis via autophagy/caspase-7-dependent and survivin- and ERCC1-independent pathways (Hsin et al., 2012). In vivo studies suggested that the oral administration of GMI inhibited tumor growth and induced autophagy in nude mice that were administered a subcutaneous injection of A549 cells (Hsin et al., 2011).

Fip-gat is an immunomodulatory protein from G. atrum containing 111 amino acids. Xu et al. treated MDA-MB-231 cells with different concentrations of recombinant Fip-gat in vitro and found that this protein reduced cell viability in a dose-dependent manner (Xu et al., 2016). Treatment with FIP-gat triggered a significant degree of cell cycle arrest in the G1/S transition and a pronounced increase in the apoptotic cell population.

Polysaccharides and Other Active Components

Polysaccharides (Meng et al., 2014) and other active components of Ganoderma also play key roles in its use for cancer treatment owing to their immunomodulatory effects (Table 2). Their effects are described below relative to different diseases.TABLE 2

Table 2. Pharmacological effects of other bioactive components than proteins of Ganoderma.

Lung Cancer

Feng et al. evaluated the inhibitory effect of triterpenes of G. lucidum on cell proliferation and tumor growth. The IC50 of triterpenes on A549 cells was 24.63 μg/mL (Feng et al., 2013). Triterpenes could significantly inhibit tumor growth in Lewis tumor-bearing mice (30, 60, and 120 mg/kg), and the indices of immune organs, including the spleen and thymus, were increased remarkably by the treatment with triterpenes. Moreover, an in vitro study by Liao et al. found that the L-fucose (Fuc)-enriched Reishi polysaccharide fraction (FMS) could inhibit the growth of cancer cells through an increase in the antibody-mediated cytotoxicity and the reduction of the production of tumor-associated inflammatory mediators, particularly monocyte chemoattractant protein-1 (MCP-1). In vivo studies showed a significant increase in the peritoneal B1 B-cell population, suggesting the FMS-mediated anti-glycan IgM production (Liao et al., 2013). Sun et al. recently showed that the plasma of patients with lung cancer suppressed the proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA (Sun et al., 2014). These effects were partially or fully reversed by G. lucidum polysaccharides (GLPS). Furthermore, Que et al. suggested that Ganoderic acid Me, a pure lanostane triterpene of G. lucidum contributing to the indoleamine 2,3-dioxygenase, helped create a tolerogenic milieu in lung tumors by directly inducing T cell apoptosis, inhibiting CD8+T cell activation, and enhancing Treg-mediated immunosuppression (Que et al., 2014).

Liver Cancer

Zhang et al. indicated that, in addition to its direct tumoricidal activity, the lipid extract from G. sinensis spores could exert an anticancer effect through the stimulation of the activation of human macrophages/monocytes (Zhang et al., 2009). Furthermore, Shen et al. found that the anticancer mycelia of GLPS could be used to disclose the differential expression of miRNA in human hepatocarcinoma cells through the comprehensive investigation of miRNA expression in polysaccharide-treated cancer cells (Shen et al., 2014). Li et al. elaborated that GLPS significantly suppressed the tumor growth in hepatoma-bearing mice. This effect was associated with an increase in the ratio of the effector T cells (Teffs) to regulatory T cells (Tregs) (Li A. M. et al., 2015). Moreover, GLPS eliminated the Treg-induced suppression Teff proliferation through increased IL-2 secretion.

Melanoma

Sun et al. found that GLPS promoted B16F10 melanoma cells to induce lymphocyte proliferation, CD69 and FasL expression, and IFN-γ production. The authors also indicated that GLPS improved the ability of B16F10 cells to activate lymphocytes (Sun et al., 2011b). In addition, the culture supernatant of B16F10 melanoma cells (B16F10-CS) inhibited lymphocyte proliferation and the production of perforin and granzyme B in lymphocytes after induction with phytohemagglutinin and lymphocyte proliferation in the mixed lymphocyte reaction (Sun et al., 2011a). They also found that GLPS could enhance the activity of major histocompatibility complex (MHC) class I molecules and costimulatory molecules, and improve the efficiency of immune cell-mediated cytotoxicity against B16F10 cells (Sun et al., 2012). Barbieri et al. demonstrated that the ethanolic extracts of G. lucidum significantly inhibited the release of IL-8, IL-6, MMP-2, and MMP-9 in cancer cells under pro-inflammatory conditions (Barbieri et al., 2017). Wang et al. revealed that the continuous administration of the G. formosanum polysaccharide PS-F2 activated the host immune responses against ongoing tumor growth (Wang et al., 20112014).

Leukemia

Wang et al. revealed that GLPS might play an indirect role in potentiating antitumor immunity in vivo through an increase in the levels of IL-1 and IL-6 (Wang et al., 1997). Lin et al. showed that GLPS promoted the cytotoxicity of specific cytotoxic T-lymphocytes (CTL) induced by dendritic cells (DCs) (Cao and Lin, 2003). These lymphocytes were pulsed with P815 tumor antigens during the stage of antigen presentation and the reported mechanisms of cytotoxicity involved the IFNγ and granzyme B pathways. In addition, the found that GLPS (400 or 100 mg/mL), which promoted CIK cell proliferation and cytotoxicity, enhanced IL-2 and TNF production, and the protein and mRNA expression of granzyme B and perforin in CIK cells through a synergistic interaction with cytokines, decreasing doses of IL-2 and anti-CD3 by 75 and 50%, respectively, which might be irrelevant to nitric oxide (NO) (Zhu and Lin, 2006). Moreover, Chan et al. suggested that GLPS could induce selected monocytic leukemic cell differentiation into DCs with immunostimulatory function (Chan et al., 2007). Chang et al. prepared a water extract of G. lucidum and examined its effect on natural killer (NK) cells; they observed that the treatment increased cytotoxicity in NK cells through the stimulation of perforin and granulysin secretion (Chang et al., 2014).

Colon Cancer

Zhang et al. found that G. atrum polysaccharides could activate macrophages via TLR4-dependent signaling pathways, improve immunity, and inhibit tumor growth (Zhang et al., 2013). Wang et al. revealed that the continuous administration of G. formosanum polysaccharide PS-F2 activated the host immune responses against ongoing tumor growth (Wang et al., 2014). In addition, Yu et al. indicated that the chemoprotective effects of G. atrum polysaccharide might be attributable to its ability to activate peritoneal macrophages and spleen lymphocytes in cyclophosphamide-treated mice (Yu et al., 2015a).

Major Pathways of Cancer Immunotherapy of Ganoderma in Immune Cells

Dendritic Cells and T-Lymphocytes

Toll-like receptor (TLR)-4 inhibited the GLPS-induced production of IL-12 and IL-10, which suggested a vital role in DC signaling after incubation with GLPS. Further studies showed that GLPS could augment the activity of κB (IκB) kinase and nuclear factor (NF)-κB inhibitors, as well as the phosphorylation of IκBα and p38 mitogen-activated protein kinase (MAPK) (Lin et al., 2005; Figure 5A).FIGURE 5

Figure 5. Major pathways of cancer immunotherapy of Ganoderma in immune cells. (A) GLPS induces NF-κB activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation in DC. GLPS might activate T cells via inositol triphosphate/Ca2+ (IP3/Ca2+) and protein kinase C (PKC) pathways. (B) F3 induces the expression of Blimp-1mRNA through p38 MAPK pathway and mediates intracellular signal through NF-κB pathway in B cell. The water extract of G. lucidum activates NK cells by the mechanism of activating NKG2D/NCR receptors and MAPK signaling pathway. (C) The polysaccharide of G. atrum induced macrophage activation through MAPK (JNK, ERK1/2) and NF-κB signaling pathways.

Sun et al. revealed that GLPS enhanced the effect of H-2Kb and H-2Db, and B7-1 and B7-2 (two prominent MHC class I molecules in C57BL mice) on B16F10 cells and that the mRNAs of these molecules improved the efficiency of the antitumor cytotoxicity in GLPS-treated cells (Sun et al., 2012). Li et al. inferred that GLPS might activate T cells via the inositol triphosphate/Ca2+ (IP3/Ca2+) and protein kinase C (PKC) pathways, because the extracellular receptor was bound by GLPS (Li et al., 2013Li X. L. et al., 2015; Figure 5A).

B Lymphocytes and Natural Killer Cells

Lin et al. showed that the interaction of F3 (the main polysaccharide fraction of G. lucidum) with TLR4/TLR2, followed by signaling through p38 MAPK, was involved in the induction of Blimp-1 mRNA (Figure 5B) and that the intracellular signal was mediated by the NF-κB pathway (Lin et al., 2006).

Chang et al. indicated that G. lucidum induced cytotoxicity in various cancer cell lines through the activation of the NKG2D/NCR receptors and MAPK signaling pathways, which ultimately culminated in the exocytosis of perforin and granulysin (Chang et al., 2014; Figure 5B).

Macrophage

Kuo et al. revealed that the dried mycelia of G. lucidum also induced NF-κB activation in murine RAW264.7 macrophages, which indicated that NF-κB activation was one of the most important signaling pathways (Kuo et al., 2006). Pro-inflammatory cytokines (TNF-α, IL-1β, or IFN-γ) were able to bind to their respective receptors and induce iNOS expression via the activation of NF-κB. Yu et al. indicated that the signaling mechanism might be that of G. atrum polysaccharide-induced macrophage activation through TLR4-mediated NF-κB and MAPK (p38, ERK1/2, and JNK) signaling pathways, thereby initiating the release of cytokines, such as TNF-α and IL-1β, and effector molecules, such as NO, in macrophages (Yu et al., 2015b). The results suggested that the polysaccharide of G. atrum exerted its antitumor activity through the improvement of immune system functions and acted as an antitumor agent with immunomodulatory activity (Figure 5C). Yu et al. concluded that the polysaccharide of G. atrum induced TNF-α secretion through the TLR4/ROS/PI3K/Akt/MAPKs/NF-κB pathways during macrophage activation (Yu et al., 2014). To investigate the possible signaling pathways involved in the activation of macrophages of S180 tumor-bearing mice by the polysaccharide of G. atrum, Huang et al. simulated macrophages and observed an increase in the phosphorylation of NF-κB, Akt, and MAPK family proteins, which was indicative of the activation of the NF-κB pathway (Huang et al., 2016). These findings further indicated the possible involvement of the NF-κB signaling pathway in TNF-α secretion and mRNA expression (Figure 5C).

Clinical Studies

Selections of clinical studies are presented. In 2003, Gao et al. investigated the effects of Ganopoly on the immune function of 34 patients with advanced-stage cancer. They found that it enhanced the immune responses in patients with advanced-stage cancer through an increase in the number of CD3+ (and similar) cells (Gao et al., 2003). In 2008, Shing et al. found that a 6 months treatment G. lucidum increased the mitogen-induced lympho-proliferative responses in immune-compromised children with tumors (Shing et al., 2008). In 2012, a pilot study suggested that the spore powder of G. lucidum had beneficial effects on cancer-related fatigue and quality of life in 48 patients with breast cancer undergoing endocrine therapy, without any significant adverse effects. The experimental group made statistically significant improvements in the domains of physical well-being and the fatigue subscale after intervention (Zhao et al., 2012). In addition, a study of five patients with gynecological cancer showed that they achieved stability in the disease after the ingestion of Lingzhi in the form of fruit body water extract and spores (Suprasert et al., 2014). Some modest benefit was also found when the mushroom was administered with standard chemotherapy (Chen and Alpert, 2016).

Toxicology

The toxicology and immunology of Ganoderma have been partly investigated in current studies. Wanmuang et al. presented a case in which fatal fulminant hepatitis occurred after taking Lingzhi powder for 1–2 months (Wanmuang et al., 2007). In addition, a patient was diagnosed with non-Hodgkins lymphoma and presented with chronic watery diarrhea whilst taking Lingzhi (Suprasert et al., 2014). However, no abnormal clinical-symptoms or deaths and no significant difference in body weight and food intake rate was found in Wistar rats during the 30 days administration period (Cheng et al., 2008). No mutagenicity was observed, as indicated by negative results from the Ames test, micronucleus test of polychromatic erythrocyte, sperm abnormality test, and chromosome aberration test in Kunming mice (Zhang et al., 2016).

Disscusion

The present review provides the most up-to-date analysis of Ganoderma research over a 30-years period by using CiteSpaceV and RAW Graphs. We found that the number of studies have increased significantly over time, especially during Stage 3 (Figure 1). We inferred that chemical drugs may exhibit certain side effects. Hence, the medicinal capabilities of the Ganoderma fungi have been gradually elucidated. In addition, China, the United States, Malaysia, Japan, and South Korea are the world leaders in Ganoderma research, based on outputs and close cooperation among the 84 countries active in the research area (Figure 2). Remarkably, the output of China is ~20% of the total output, which gives it the highest output of these countries. Based on a large amount of data, we summarized the subject categories of the research and found that “Pharmacology & Pharmacy” is the leading category. In the subcategories within pharmacology, immunomodulatory effects and cancer treatment occupy the largest proportion of the eight areas of pharmacology in Chinese-language and English-language articles. These finding revealed a new trend, which was the use of Ganoderma in cancer immunotherapy research.

Cancer is a disease with a high death rate. Chemotherapy does not completely meet the needs for cancer treatment and immunotherapy is a promising alternative method owing to the fewer side effects observed. Ganoderma, a medicinal mushroom, could be administered as an adjunct to conventional treatment to enhance the tumor response and stimulate host immunity. At the species level, studies on G. lucidum predominate; other species are less well-studied. With regard to the effective components, FIPs and polysaccharides are dominant; of which Lz-8 and polysaccharides from G. lucidum are the most researched. Ganoderma also plays important roles in many aspects of immune regulation for cancer treatment, not only the activation of T or B lymphocytes, macrophages, NK cells, and other immune cells, but in the promotion of the in vitro proliferation of undifferentiated spleen cells, and the production of cytokines and antibodies. NF-κB and MAPK, the most comprehensively investigated major pathways, are shown to be activated and release cytokines that subsequently inhibit the growth of tumor cells. TLR-4 is an effective receptor involved in the host defense mechanism of the immune response to polysaccharides. In addition, some researchers have used Ganoderma in combination with drug treatments for cancer, such as the combination of GMI and cisplatin and the combination of G. atrum polysaccharides with cyclophosphamide to reduce the side effects of the drug. We found that the immunotherapy of lung cancer, liver cancer, melanoma, leukemia, and colon cancer were thoroughly studied in vivo and vitro, particularly lung and liver cancers. This observation was basically consistent with the channel tropism of Ganoderma in TCM theory. Moreover, this review has made a preliminary analysis of the safety of Ganoderma through the exploration of the reported toxicology. With regard to adverse effects, there were generally no serious side effects from the use of Lingzhi, but patients should be monitored while receiving Lingzhi, as liver toxicity and chronic watery diarrhea are reported side effects.

Ganoderma is one of the most widely used herbal fungi and is a promising anticancer immunotherapy agent owing to its low toxicology and efficacy as a combination therapy. However, the mechanistic pathways lack specificity and do not accurately select specific targets; in addition, most results are derived from in vitro studies. Future studies should focus on the combination therapies of Ganoderma and clinical chemotherapy drugs to alleviate the side effects of these drugs. Furthermore, the safety and toxicity should be thoroughly explored. The major bioactive components should to be investigated and corresponding in vivo pharmacokinetic studies should be performed. The mechanisms underlying immune modulation and interactions should be determined.

Author Contributions

YC conducted and designed the review and wrote the MS. XX and SL contributed to the language editing. LH and JG conducted the designed the review.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

Funding from the National Natural Science Foundation of China (No. 81473315) and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2016-12M-3-015) are gratefully acknowledged.

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Keywords: Ganoderma, lingzhi, bibliometrics, cancer immunotherapy, mechanism

Citation: Cao Y, Xu X, Liu S, Huang L and Gu J (2018) Ganoderma: A Cancer Immunotherapy Review. Front. Pharmacol. 9:1217. doi: 10.3389/fphar.2018.01217

Received: 23 May 2018; Accepted: 05 October 2018;
Published: 25 October 2018.

Edited by:Ruiwen Zhang, University of Houston, United States

Reviewed by:Ulrike Lindequist, University of Greifswald, Germany
Dejan S. Stojkovic, University of Belgrade, Serbia

Copyright © 2018 Cao, Xu, Liu, Huang and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Linfang Huang, lfhuang@implad.ac.cn
Jian Gu, gujiancd@163.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

2 Comments – Emmanuella Daniel and Mohammad Imano.

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  • 8:50 AM, 06 November 2020

Mohammad Imano You wrote very well. thank you. Ganoderma is known in the world as King of herbs. Of the thirty-six known species of Ganoderma, Ganoderma lucidum is the most medicinal. Studies on this miraculous herb show that it can support the immune system and slow down the growth of tumors in the body. It can prevent cancer cells from multiplying and migrating. In fact, research has shown that when people with tumors consume these fungi for 30 days, the immune system is greatly improved. Research has even found that these same people experience less radiation chemotherapy and side effects and have a greater rate of recovery after surgery. It has also been shown to help prevent and slow the spread of cancer cells, lower high blood pressure and even increase the risk of herpes sores and herpes. It also makes the body resistant to stroke and heart disease and eliminates fatigue.We study Ganoderma in the Middle East: our website : https://ganoderm.ir

  • 3:35 AM, 09 July 2021