Cell culture is practiced extensively throughout the world today. The techniques
required to allow cells to grow and be maintained outside the body have been developed
throughout the 20th century. In the 50 years since the publication of the first
human cancer cell line, HeLa (1), thousands of cell lines representing most of the
spectrum of human cancer have been derived. These have provided tools to study in
depth the biochemistry and molecular biology associated with individual cancer types
and have helped enormously in our understanding of normal as well as cancer cell
Mechanisms of Oncogene Activation Mechanisms that upregulate (or activate) cellular oncogenes fall into three broad categories: point mutation, DNA amplification, and chromosomal rearrangement.
Point mutation is a common mechanism of oncogene activation. For example, mutations in one of the RAS genes (HRAS, KRAS, or NRAS) are present in up to 85% of pancreatic cancers and 50% of colon cancers but are relatively uncommon in other cancer types. Remarkably—and in contrast to the diversity of mutations found in tumor-suppressor genes (Fig.
Chromosomal Instability in Solid Tumors Solid tumors are generally highly aneuploid, containing an abnormal number of chromosomes; these chromosomes also exhibit structural alterations such as translocations, deletions, and amplifications. Again, colon cancer has proven to be a particularly useful model for the study of chromosomal instability (CIN). As described above, some familial cases are characterized by the presence of MIN.
Prostate cancer is one of the most common types of cancer in men and its treatment was constricted to surgery for confined state and androgen ablation for advanced disease until new options have become available. The present book covers a broad range of novel aspects of prostate cancer diagnosis, treatment and patient care, as well as new research on relevant cell biology.
Lung cancer is the most frequent cause of cancer deaths in both men and
women in the U.S. (1). Although tobacco smoking is accepted as the number
one cause of this devastating disease, our understanding of the acquired genetic
changes leading to lung cancer is still rudimentary. Lung cancer is classifi ed
into two major clinic-pathological groups, small cell lung carcinoma (SCLC)
and non-small cell lung carcinoma (NSCLC) (2). Squamous cell carcinoma,
adenocarcinoma, and large cell carcinoma are the major histologic types of
Tumor angiogenesis is a complex process involving many different cell types that must proliferate, migrate, invade, and differentiate in response to signals from the tumor microenvironment. Endothelial cells (ECs) sprout from host vessels in response to VEGF, bFGF, Ang2, and other proangiogenic stimuli. Sprouting is stimulated by VEGF/VEGFR2, Ang2/Tie-2, and integrin/extracellular matrix (ECM) interactions.
Other Nonmelanoma Cutaneous Malignancies
Neoplasms of cutaneous adnexa and sarcomas of fibrous, mesenchymal, fatty, and vascular tissues make up 1–2% of NMSC (Table 83-6). Some can portend a poor prognosis such as Merkel cell carcinoma, which is a neural crestderived, highly aggressive malignancy that exhibits a metastatic rate of 75% and a 5-year survival rate of 30–40%. Others, such as the human herpes virus 8-induced, HIV-related Kaposi's sarcoma, exhibit a more indolent course.
In developed countries, cancer is the second leading cause
of death exceeded only by cardiovascular diseases. There are
more than 100 types of cancers that can inflict any part of the
body. In 2005, 7.6 million people died of cancer, which constitutes
13% of the 58 million deaths worldwide. Approximately,
1.3 million people are diagnosed each year with cancer in the
United States, and ~ 1500 of them die every day.
In spite of the massive efforts being made worldwide to
understand molecular genetics and epigenetic factors
responsible for the initiation and progression of cancer,
the statistics on this malignancy have remained enormously
negative; the following data testify to this unfortunate
human condition. There are more than 100 types of
cancers that can inflict any part of the body. In 2005, 7.6
million people died of cancer, which makes up 13% of
the 58 million deaths worldwide. Approximately 1.
There are four types of cutaneous melanoma (Table 83-2). In three of these—superficial spreading melanoma, lentigo maligna melanoma, and acral lentiginous melanoma—the lesion has a period of superficial (so-called radial) growth during which it increases in size but does not penetrate deeply. It is during this period that the melanoma is most capable of being cured by surgical excision. The fourth type—nodular melanoma—does not have a recognizable radial growth phase and usually presents as a deeply invasive lesion, capable of early metastasis.
While most autosomal dominant inherited cancer syndromes are due to mutations in tumor-suppressor genes (Table 79-1), there are a few interesting exceptions. Multiple endocrine neoplasia type II, a dominant disorder characterized by pituitary adenomas, medullary carcinoma of the thyroid, and (in some pedigrees) pheochromocytoma, is due to gain-of-function mutations in the protooncogene RET on chromosome 10. Similarly, gain-of-function mutations in the tyrosine kinase domain of the MET oncogene lead to hereditary papillary renal carcinoma.
The level of suspicion of infections with certain organisms should depend on the type of cancer diagnosed (Table 82-3). Diagnosis of multiple myeloma or CLL should alert the clinician to the possibility of hypogammaglobulinemia. While immunoglobulin replacement therapy can be effective, in most cases prophylactic antibiotics are a cheaper, more convenient method of eliminating bacterial infections in CLL patients with hypogammaglobulinemia.
Typhlitis Typhlitis (also referred to as necrotizing colitis, neutropenic colitis, necrotizing enteropathy, ileocecal syndrome, and cecitis) is a clinical syndrome of fever and right-lower-quadrant tenderness in an immunosuppressed host. This syndrome is classically seen in neutropenic patients after chemotherapy with cytotoxic drugs.
Table 87-5 Hereditable (Autosomal Dominant) Gastrointestinal Polyposis Syndromes
tion of Polyps gic Type
Familial adenomatous polyposis
Large intestine a
fibromas, lipomas, epidermoid cysts, ampullary cancers, congenital hypertrophy retinal of
Large intestine a
Endometri and ovarian
posis syndrome int...
Harrison's Internal Medicine Chapter 89. Pancreatic Cancer
Pancreatic Cancer: Introduction
Over 90% of pancreatic cancers are ductal adenocarcinomas of the exocrine pancreas. These tumors occur twice as frequently in the pancreatic head compared to the rest of the organ, and tend to be aggressive, often presenting when locally inoperable or after distal metastases have occurred. Patients with pancreatic cancer have a poor prognosis, with a 5-year survival of only 5%. The discussion of pancreatic cancer here will be limited to ductal adenocarcinomas.
It has been said that the control of disease has three goals, which, in
increasing order of attraction are palliation, cure, and prevention. For most types
of disseminated cancer, medical science has achieved only the first of these
objectives, while for some malignancies the side effects of the therapeutic agents
employed rival the disease itself in precluding a desirable quality of life.
No matter where a cancer may spread, it is always named for the place where it started. For
example, breast cancer that has spread to the liver is still called breast cancer, not liver
cancer. Likewise, prostate cancer that has spread to the bone is metastatic prostate cancer, not
Different types of cancer can behave very differently. For example, lung cancer and breast
cancer are very different diseases. They grow at different rates and respond to different
treatments. That is why people with cancer need treatment that is aimed at their particular
kind of cancer.
Several general principles have arisen from these studies. Bevacizumab appears to potentiate the effects of many different types of active chemotherapeutic regimens used to treat a variety of different tumor types. No phase III trials have demonstrated single-agent activity for bevacizumab; colon and lung cancer trials have demonstrated a lack of activity when used alone. An exception may be renal cell cancer (RCC), a tumor that is specifically dependent upon VEGF as the result of deletion of the VHL tumor suppressor and activation of the HIF-1α transcription factor (see above).
The average annual incidence rates of certain cancers, including cervical, esophageal, liver, oral
cavity and pharynx, and stomach cancer were significantly higher in the poorest areas in New
Jersey as compared to the wealthiest areas. Among men, lung cancer incidence rates were
significantly higher in the poorest areas, while lung cancer rates for women did not differ
substantially among the three poverty area groups (areas with high poverty, medium poverty, and
Talk with your doctor or nurse if you are not sure what to eat during cancer
treatment. Ask him or her to refer you to a dietitian. A dietitian is the best person
to talk with about your diet. He or she can help choose foods and drinks that are
best for you during treatment and after. ...