The seed and the soil

seedlings

One of the things that researchers are studying like crazy is the process by which cancer takes root and grows in the body. Our diet plays a huge role in this process (witness the much lower incidence of cancers in India, for example, despite the much higher incidence of carcinogens!).  For your own health, and for the health of your future patients, I highly recommend David Servan-Schreiber’s book, Anticancer: A New Way of Life, which came out last year. David is an MD who developed brain cancer and went through successful medical treatment. However, his tumor recurred, and at that point he decided he needed to change his way of life. This book describes the effects diet and stress have on the growth of cancer – and before you blow that off as being too foofy or alternative, you should know that he backs up every point he makes with tons of research from accomplished scientists at respected places like Harvard and M.D. Anderson. Much of this post is from information described in David’s book.

The process of tumor growth is much like the growth of weeds. Tumors grow in three phases: 1) initiation, 2) promotion, and 3) progression. Initiation is the phase when a seed settles in the soil, promotion is the phase when the seed becomes a plant, and progression is the phase when the plant becomes a weed (developing beyond control, invading flower beds and growing right up to the sidewalk).

Initiation (the planting of the seed) depends largely on our genes and on toxins (radiation, carcinogens, etc.). But promotion (the growth of the seed) depends on having the right survival conditions: favorable soil, water, and sun. The cool thing is that promotion is reversible! If you can change the tumor’s environment, you can prevent it from spreading. Diet plays a role – probably a big role – in the creation of a favorable vs. unfavorable tumor environment.

Cancer “fertilizers”

Here are some dietary substances that create a fertile soil for cancers:

Refined sugars (drive up proinflammatory insulin and insulin-like growth factor, or IGF)
Insufficient omega-3s/excess omega-6s (favor inflammation)
Growth hormones in meat and non-organic dairy products (stimulate IGF)

Okay, what diet does this sound like? Lots of sugar, bad fats, and meat – the typical Western diet.

Cancer inhibitors

So, what should we eat? In addition to avoiding saturated fat, sugar, meat and non-organic stuff, a good cancer-fighting diet would include some/all of the following:

Catechins (in green tea) – inhibit angiogenesis

Phytoestrogens (in soy products) – block overstimulation of tumors by estrogen; prevent angiogenesis

Curcumin (in turmeric) – inhibits inflammation, inhibits angiogenesis, promotes apoptosis in tumor cells

Ellagic acid (in berries) – inhibits angiogenesis, blocks transformation of environmental carcinogens into toxic substances

Anthocyanidins (in blueberries, cranberries, cinnamon, dark chocolate) – promote apoptosis in tumor cells

Terpenes (in mint, thyme, marjoram, oregano, basil, rosemary) – inhibit tumor cell invasion, promote apoptosis in tumor cells, inhibit angiogenesis

Gingerol (in ginger) – inhibits inflammation and angiogenesis

Sulforaphane, indole-3-carbinol (in cruciform veggies) – prevent precancerous cells from becoming malignant; promote apoptosis of tumor cells, inhibit angiogenesis

Sulfur compounds (in garlic and onions) – reduce carcinogenic effects of nitrosamines (created in overgrilled meat and present in tobacco); promote apoptosis in tumor cells; help regulate blood sugar levels.

Lycopene (in carrots, yams, other bright colored veggies and fruits) – stimulates NK cells to become more aggressive; inhibits tumor cell growth

Long-chain omega-3 fatty acids (in fatty fish) – reduce cancer cell growth, prevent metastasis

Vitamin D (sun, cod liver oil, milk (tiny amount), vitamins) – dramatically reduces risk of several cancers

Polyphenols (red wine, chocolate) – block NF-kappa B (important in all three stages of cancer development: initiation, promotion, progression), limit angiogenesis

Photo credit: L’eau Bleue (http://www.flickr.com/photos/8175535@N05/3536354514/), under cc license.

Tumor differentiation

Squamous cell carcinoma, well-differentiated

Well-differentiated squamous cell carcinoma

Squamous cell carcinoma, moderately-differentiated

Moderately-differentiated squamous cell carcinoma

Squamous cell carcinoma, poorly-differentiated

Poorly-differentiated squamous cell carcinoma

“Differentiation” is a term used to describe the microscopic appearance of tumors. (more…)

What’s the connection between dysplasia and neoplasia?

dysplastic vs. normal epithelium

Q. What is the connection between dysplasia and neoplasia? I understand that dysplasia is a precancerous condition. Grades I and II are not neoplastic. But grade III dysplasia, also called carcinoma in situ, is neoplastic, right? But is it a true carcinoma, or is it not at that point malignant?

A. Dysplasia is not a neoplastic process. While it is often a precursor to neoplasia, not all cases will evolve into malignancy (e.g., mild cervical dysplasia usually does not progress to carcinoma. We watch patients who have it carefully, though, to catch those patients that do go down that path.).

Carcinoma in situ is neoplastic. The cells in carcinoma in situ have the potential to invade (and definitely will, if left alone and untreated). They have acquired enough genetic mutations to have the characteristics of malignant cells (they are able to invade, able to grow on their own without growth signals, insensitive to growth-inhibiting signals, able to metastasize, etc).

Some classification schemes equate grade III dysplasia with carcinoma in situ, while others leave carcinoma in situ in its own category at the far end of the nastiness spectrum. Personally, I prefer the latter way of looking at things, because keeps the separation between dysplasia and neoplasia intact.

The important thing to remember, no matter what semantics you choose, is that the chances of evolution into overt carcinoma rise with the degree of dysplasia. Mild dysplasia usually does not evolve into carcinoma, whereas severe dysplasia usually does.

The image above shows a portion of cervical epithelium that has undergone dysplastic change. The right hand side of the image shows normal squamous epithelium, and the left hand side of the image shows moderately dysplastic epithelium. The dysplastic epithelial cells are pleomorphic (varying in size and shape) and hyperchromatic (darkly-staining) nuclei. Their architecture is also disrupted. Instead of the nice basal layer and orderly maturation and flattening-out of cells that you see in normal epithelium, much of the epithelial thickness resembles the basal layer.

Cytogenetics quiz

chromosomes

Many hematopoietic malignancies have characteristic cytogenetic changes, such as translocations or inversions. It’s important to know about these because they can be used for diagnosis in tough cases, and they often carry a prognostic significance. (more…)

Metaplasia vs. neoplasia

adenocarcinoma
 
 
Q. My professor asked this on an exam: What’s the difference in molecular mechanism between metaplasia and neoplasia?

 

A. Metaplasia is the changing of one cell type to another. The term is used most often in reference to epithelial cells, for example, when the normal glandular epithelium of the cervix is replaced with squamous epithelium, it is called “squamous metaplasia”. It simply means that the basal cells (the stem cells of the epithelial layer) switch from making one type of epithelial cell to another.

 

Though it is not malignant or even premalignant, in and of itself, metaplasia sometimes indicates that there has been damage to the area, and if the insult continues, dysplasia or even frank malignancy can occur. This is fairly common in the lung: metaplasia of the bronchial epithelium is followed by dysplasia, which is followed by carcinoma. The molecular mechanisms of this whole process of metaplasia are not well understood.

 

“Neoplasia” literally means “new growth.” Neoplastic cells have several characteristics that make them nasty: they grow autonomously without any need for growth signals, they are insensitive to normal growth-inhibitory signals, they don’t die off like they should, they are capable of limitless replication, and – if they are malignant neoplastic cells – they invade vessels and travel to different parts of the body and set up shop.

 

There are lots of molecular mechanisms (and corresponding genetic mutations) that underlie these neoplastic qualities; most neoplasms have several such mutations. A cancer cell can have mutations in many different genes – for example, the genes encoding growth factor receptors, signal-transducing proteins, nuclear transcription factors, or cyclins.

 

Sometimes these mutations turn on a gene that promotes growth. The normal variants of these growth-promoting genes are called “proto-oncogenes” and the mutated variants are called “oncogenes.” An example of just such a gene is the RAS proto-oncogene, which makes a signal transduction protein involved in cell growth. Many neoplasms have a mutated RAS gene (called the RAS oncogene) that has been altered in such a way that it is always turned on. Which means that the cells containing the mutation are always transducing growth signals, and always growing and dividing.

 

Another type of mutation can occur in genes (called “tumor suppressor genes”) that normally put brakes on cell growth. An example of this type of gene is the retinoblastoma tumor-suppressor gene, which normally stops cells at the G1 checkpoint in the cell cycle. In certain tumors, the retinoblastoma gene is mutated in such a way that it doesn’t work. Cells that have this mutated gene proceed without pause through the G1 checkpoint, heading full-tilt on to mitosis.

 

So, to summarize: the molecular mechanisms of metaplasia are not well understood. The molecular mechanisms underlying neoplasia are numerous and complex.