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About Cancer
Tumor Biology

Tumors result from carcinogenesis and loss of control of normal cells. The major biological characteristics of cancer cells include abnormal appearance, functions, metabolism and uncontrollable proliferation. Uncontrollable growth is the major reason responsible for so many tumor-specific manifestations on morphology and pathology. A series of clinical symptoms, such as pain, loss of weight and even death occur due to a large amount of cells pile up and result in mass rapidly, as well as the fast-growing tumor cells transferring to other regions of human bodies.

1. Mechanism of carcinogenesis
There are many reasons that can result in tumor cells, which include a variety of carcinogenic factors, such as chemicals, radiation, viruses and etc. It is also related to the abnormality of DNA, inheritance as well as the immune and endocrine systems. Although almost everybody might have contacted carcinogenic factors, not everyone can develop cancers. The susceptibility is largely related to individual inherited condition. The abnormal growth and differentiation of malignant cells is because they have escaped from the normal cell controlling mechanism. And the uncontrollable growth is due to the defect of the genes controlling cell division, for example, the abnormality of genes in leukocytes can result in leukemia. Therefore, tumors can be called as a kind of genetic deficiency. Changes in genetic material can easily occur at active cell proliferation stages, such as pregnancy, infancy and early childhood. At these stages, many organs and systems can grow and differentiate rapidly and numerous cell divisions occur. Therefore the possibility of normal cells transforming into malignant cells resulted from one or more genes mutations are correspondingly increased.

A tumor is a kind of disease caused by many reasons, via multiple stages and multiple mutations. Almost all of tumors are originated from a single mutated cell. Before they show clinical manifestations, these cells usually have existed for more than ten years. During this period, carcinogenic cells usually experienced four times but less than ten times of mutations (Figure 1). The first mutation makes the mutated cell easier to divide than normal cells. This mutated cell and its offspring become very active, which is called hyperplasia. At a certain point of this stage, one of these cells undergoes mutation again, which makes the division of its offspring uncontrollable and show an abnormal appearance, which is usually called abnormal growth. Following that, a cell undergoes another mutagenesis. The growth and appearance of this cell and its offspring show to be abnormal. If the mutated cells still stay at the original location, it is called original cancer. However, if some of the cells undergo another mutation, which makes it possess the ability to invade other organs, the tumor has been changed into malignancy. Therefore, cancergenisis is the result of accumulation of mutations. These mutations enable malignant cells to grow rapidly and/or to block apoptosis, or to possess both features. At present, the study of molecular biology show that the abnormality of two groups of genes (oncogenes, tumor-suppressor genes) play significant roles in the occurrence of tumors. When oncogenes are activated and/or tumor-suppressor genes are lost, cancers may occur. Under normal conditions, cancer genes play regulatory effects on the growth, differentiation and development of cells. However, during the processes of chromosome translocation, point mutations and gene duplications, cancer gene could be activated abnormally, which results in abnormal cell growth. But the loss of tumor-suppressor genes is achieved by a way that many mutations appear in cells, loss, rearrangements and point mutations. All these changes can result in loss of cell growth inhibition, which can further cause cancers.

2. Characteristics of tumor growth
The characteristics of tumor growth include growth speed and growth pattern. In comparison to normal cells, the growth of tumor cells is much faster. Generally speaking, well-differentiated benign tumors grow relatively slow but low-differentiated malignant cells grow faster. Clinically, the double time of tumor is about 20-120 days. However, if a tumor is originated from a cell, it will take about 30 duplication times until a 1 cm tumor mass containing 1 billion cells is formed. In terms of growth pattern, tumor growth includes expansive, infiltrative and exogenous growth. Expansive growth is the major growth pattern of most malignant tumors. As tumor size increase, it can expand and compress the surrounding tissues but do not invade tissues nearby. The major clinical manifestations of this type of tumors include pressing and blocking symptoms. Infiltrative growth is the major growth pattern of malignant tumors (Figure 2A). Due to loss of contact inhibition, malignant cells will have the ability of invasion and metastasis. Tumors extend to the adjacent tissues in a way similar to roots infiltrating into the adjacent tissue space, blood vessels, lymphatic ducts and etc, which makes them difficult to be separated from the adjacent tissues. Therefore, they are not easy to be removed by operation and may be easier to relapse after operation.

3. Tumor morphology and structural characteristics of the tissue
The number of tumors could be a single mass, but could be also appear in diverse tissue types as multiple tumors. From the appearance, the tumors present with a variety of forms, including nodular, lobular, cauliflower-like, papillary, cystic and ulcerative shapes (Figure 2B). Tumors growing on skin and mucosa usually are shown to be nodular, lobular and cauliflower-like. In addition, the size of tumors is not consistent, from invisible by eye to as large as forty kilograms, such as ovarian cystadenoma. Based on appearance, tumor exhibits offwhite color, but the color is also different based on the amount of blood in the tumors. The hardness of tumors is determinated by the nature of in the parenchyma and the amount of the fiber in stroma, for example, fatty tumors is the softest one but osteoma is very hard.

Tissue composition of tumors is very diverse. But these tissues can basically divided into parenchyma and stroma. Parenchyma refers to cancer cells, which determines the characteristic of tumors. Stroma is mainly composed of blood vessels and fiber tissues, which is mainly for providing parenchyma with nutrition and support. Generally, benign tumor are very similar to their originated tissues, therefore their origin can be identified by the tumor structures. For example, fibroma is very similar to normal fiber tissue with only difference on pattern of arrangement from normal tissues, exhibiting network pattern. Malignant tumors are however quite different from their originated tissues. Their cells distribute chaotically and loss of normal pattern and organization. For example, fibrosarcoma have more tumor cells, less fibers, disordered arrangement, which is quite different from normal fibrous tissues.

4. Morphological characteristics of tumor cells
The difference between tumor cells and normal cells is that the differentiation of the former is relatively lower, which can't reach to normal maturation. Benign tumors cells have relatively high differentiation, which is similar to their originated tissues; but malignant tumor cells have low level of differentiation. They are quite different from normal cells on morphology, functions and metabolism and exhibit irregular size and shape. Another prominent changes include changes of cell nucleus and skeleton. They are important in the determination of the clinical characteristics of tumors.

Nucleus: The shape and structure of cell nucleus are quite different from those of normal originated tissues. The nucleuses enlarge and the shape becomes irregular. Due to the increase of DNA, the number of chromosomes also increases correspondingly. Therefore, they appear to be crassitude, dark staining and irregularly distributed. Meanwhile, due to the increased demand of protein synthesis, the amount of rRNA in nucleolus also increases, nucleolus also enlarges and the numbers also increase. In addition, it usually exhibits pathological caryokinesis, such as asymmetry and multipolarity etc (Figure 3). All these changes become important indicator of tumor diagnosis, grading and staging.

Cell skeleton: Under electron microscope, it was found that the distribution and activity of cellular microtubules and microfilaments have undergone great changes. These changes in turn result in changes of cellular morphology, the relationship between the adjacent cells as well as the adherence and mobility. Due to the decrease of the adherence between tumor cells and cell-cell matrix, the decrease of adherence makes cells capable of moving, migration and spreading. This is one of the reasons of tumor shedding, infiltration and metastasis.

Other changes: Other cellular organelles such as mitochondria, endoplasmic reticulum and Golgi apparatus etc are usually not rich, irregular, strange-shaped and irregularly distributed. In addition, tumors can also generate some enzymes, which can digest the adjacent barrier nearby and therefore make them capable to invade tissues nearby.

5. Metabolic characteristics of tumor cells: Because tumor cells grow very rapid, their metabolism is also very active too. Although tumor cells are similar to normal cells in nature, there is prominent difference in terms of quantity. For example, tumor cells mainly use glycolysis to obtain energy, which is mainly caused by functional deficiency in mitochondria. In addition, as described before, the synthesis of DNA and RNA also increase in tumor cells. The increase of these inherited materials is related to the division of tumor cells and proliferation. The changes of the enzymes in tumor cells are also very complicated. Some of them are increases and some of them decreased. For example, oxidases (cytochrome oxidase and succinic dehydrogenase) decrease, but the acid phosphatase increase dramatically in prostate cancer. In addition, protein metabolism is also increased in order to meet the need of cell growth.

6. Tumor markers: Tumor markers are the synthesized products of tumor cells or generated by human body in responsive to tumors. Some of these proteins are tumor-type specific and some are also expressed in other tumors. Some of the tumor-type specific markers include tumor specific antigens, tumor specific enzymes and tumor specific hormones. These markers are very important in making early diagnosis, appraisal of clinical efficacy and prognosis. The markers used for screening could be highly specific for tumor patients who are at early stages, asymptomatic and curable. For example, PSA can be used in screening prostate cancers. CEA can be used in prognosis and examination of residual tumors to test the degree of malignancy. The increase of CEA level suggests that tumor relapse and prognosis are bad. At present, only a limited number of markers have been clarified. Researches on these markers are significant to tumor diagnosis and prevention.

7. Other tumor characteristics: Except for the characteristics mentioned above, other fields that are being studied extensively include tumor related genes (oncogenes, tumor-suppressor genes and susceptibility genes); apoptosis and cell differentiation; cell cycle and signal transudation; gene engineering and gene engineered antibody; cytokines; tumor drug resistance and reversion; tumor metastasis and reversion, tumor immunology, etc. Elucidation of these mechanisms will generate deeper influence to prevention and treatment of tumors.

         
         
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