Lung Cancer and Lymphoma - DNA Analysis and Molecular Genetics

DNA analysis (i.e., molecular genetics) can be used in evaluating lung cancer, and can reliably separate lung tumors into their morphologic categories of squamous, large cell, small cell, and adenocarcinoma. Gene expression profiling (GEP) may have even more utility in the assessment of patients with non-small cell lung cancers (NSCLCs) and similar histology.

Several investigators have attempted to subclassify these tumors by correlating GEP patterns with clinicopathologic variables.
A series that included 41 lung adenocarcinomas identified three prognostically separate subgroups. The genes involved in this classification included thyroid transcription factor, hepsin, cathepsin L, vascular endothelial growth factor C (VEGF-C), and the intercellular adhesion molecule-1 (ICAM-1).
In another report of 139 lung adenocarcinomas defined four distinct subclasses. Tumors expressing neuroendocrine-type genes had a significantly less favorable survival than those lacking such characteristics. The genes that defined the neuroendocrine cluster adenocarcinomas included dopa decarboxylase, achaete-scute homolog 1, and the serine protease kallikrein 11.
Others used GEP to predict outcome from surgery in 67 patients with resected stage I adenocarcinoma. A specific group of genes distinguished high-risk from lower risk groups, with significantly different survival. Among the 50 genes comprising the risk index were erbB2, VEGF, S100P, cytokeratin 7 and 18, and fas-associated death domain protein.
In another series of 125 patients from Taiwan with surgically resected NSCLC, 16 genes were identified that correlated with increased or decreased survival. Further RT-PCR validation assay confirmed the microarray findings and showed that survival was significantly associated with five of the 16 genes (DUSP6, MMD, STAT1, ERBB3, and LCK). The five-gene signature was further validated in microarray data from patients of Western population and was an independent predictor of recurrence and overall survival for patients with surgical resection of NSCLC without any adjuvant therapy. This GEP profile is being used to select high risk patients for adjuvant chemotherapy in prospective clinical trials.
Lymphoma - Gene expression profiling (GEP) by means of DNA microarrays is an evolving approach to classification, diagnosis, and prognostication of Non-Hodgkin's Lymphoma (NHL).
As an example, diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous disease in which approximately 40 percent of patients with advanced stage disease respond well to combination chemotherapy and are long-term survivors. Using GEP, DLBCL has been subclassified into three distinct molecular subgroups, germinal center B-cell-like (GCB), activated B-cell-like (ABC), and other (type 3), that appear to be derived from different stages of B-cell differentiation, utilize different oncogenic mechanisms, and differ clinically in their ability to be cured by multiagent chemotherapy.
Patients whose tumors express genes characteristic of germinal center B cells (GCB) have a significantly better outcome from chemotherapy than those whose gene expression is more typical of activated B cells (ABC). In one series for example, a clustering algorithm applied to 58 patients with DLBCL receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy separated patients into two groups with very different five-year overall survival rates (70 versus 12 percent).
Although most of the early studies used fresh frozen tissue sections, similar results have been reported with GEP performed on formalin-fixed, paraffin-embedded material. No formal head-to-head comparisons of GEP from fresh versus archived materials have yet been performed.
GEP has also been used to develop a more precise molecular diagnosis of primary mediastinal B-cell lymphoma, a clinically unfavorable entity that cannot be reliably distinguished from other types of diffuse large B-cell lymphoma. These tumors do poorly with CHOP chemotherapy alone and may need more aggressive therapy than used for standard DLBCL.

Finally, GEP has the potential to reveal new therapeutic molecular targets. As an example, the ABC subtype of DLBCL is characterized by constitutive activation of the nuclear factor kappaB (NF-kappaB) signaling pathway; interference with this pathway selectively kills these lymphoma cells. The ubiquitin-proteasomal pathway and the NF-kappaB axis are intimately involved in the control of apoptosis. Inhibitors of this pathway (eg, proteasome inhibitors) can induce apoptosis in human leukemia cells that ectopically express the antiapoptotic protein Bcl-2. One such agent, the synthetic dipeptide boronic acid bortezomib, is a potent promoter of apoptosis in several human tumor cell types.
Summary - The rapidly evolving field of DNA microarray analysis and gene expression profiling has wide-ranging implications for the molecular classification of tumors, refinement of prognostic estimates, and prediction of response to therapy. Despite its exciting potential and significant recent advances, this field remains relatively new, and it is premature to conclude that microarray data can be used as a sole means of classifying cancers or predicting outcomes of treatment.
Among the specific challenges that must be met are the need for larger studies with appropriate validation, standardization of methods and establishment of guidelines for the conduct and reporting of studies, and the formation of repositories and registries where research institutions may deposit data for comparison with independent works involving the same malignant disorder. Finally, DNA microarray-based tests must demonstrate utility in prospectively designed clinical trials before this technology is considered a routine part of clinical evaluation. These studies may eventually establish a new treatment paradigm in personalized cancer therapy in the future.

Dr. Richard Graydon, http://www.medauthor.com, trained as an Oncologist, holding both M.D. and PhD degrees, andspecializes in molecular genetics and cancer research. His education and experience have provided him analytical and clinical skills for keen insight into diagnosis, treatment, and care of cancer patients. See http://www.medauthor.com for further information

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Smoking, Cancer, and Chemotherapy

Adverse Effects Tobacco Has ON The Brain:
Like cocaine, heroin, and marijuana, nicotine increases levels of the neurotransmitter dopamine, which affects the brain pathways that control reward and pleasure. For many tobacco users, long-term brain changes induced by continued nicotine exposure results in addiction, a condition of compulsive drug seeking and use, even in the face of negative consequences. Studies suggest that additional compounds in tobacco, such as acetaldehyde, may enhance nicotine's effects on the brain. Studies indicate the adolescents are especially vulnerable to these effects and may be more likely than adults to develop an addiction to tobacco.
Cancer:
When people think of cancers caused by smoking, the first one that comes to mind is lung cancer. Close to 90% of lung cancer deaths are in men, with about 80% in women caused by cigarette smoking. There are several other forms of cancer.
· They include the oral cavity
· Pharynx
· Larynx
· Esophagus
· Bladder
· Stomach
· Cervix
· Kidney
· Pancreas
· And acute myeloid leukemia
· Head and neck
· Tongue
· Lip
· Mouth
Lung Cancer-The Big One:
The association between tobacco use and lung cancer stands as a classic in public health. On average, smokers increase risk of lung cancer between 5 and 10-fold and in developed countries, smoking is responsible for upwards of 80% of all lung cancers. Using American data 24% of men who smoke can expect to develop lung cancer during their expected lifetime.
Lung cancer remains a disease with a dismal prognosis. Although one-year all-stage survival is reported to have increased from 32% in 1973 to 41% in 1994, five year survival has remained unchanged at 14%.
Chemotherapy- One Form of Treatment for Cancer:
Chemotherapy is in general a way of treating cancer. People diagnosed with cancer undergo this therapy for their treatment. It is the most popular way of treating cancer worldwide. Chemotherapy is applied to treat leukemia and lymphoma.
Under chemotherapy, use of chemotherapy drugs or medicines is made to kill the cancer-causing cell or reduce their growth. Chemotherapy drugs are known as cytotoxic drugs.
Whenever a person is diagnosed as suffering from cancer, the possibility of he or she undergo some form of chemotherapy treatment is seemingly inevitable. The only question is how the cancer will be administered.
Chemotherapy treatment takes place in cycles. These cycles normally run between three to four weeks consecutively. Between the cycles, there are intervals of around the same time. The thinking behind this in conventional medicine is to allow the healthy cells to recover and reproduce, and the cancerous cells to die. The chemotherapy course of treatment is completed when the doctors are sufficiently sure that all the cancerous cells have been removed from the patient's body.
The dosage of chemotherapy administered is calculated by measuring the height and weight of the patient. Using this method, the doctors and tailor a program "tailor made" for each patient. However, the dose levels can be reduced or increased based on reactions experienced by the patient and routine tests carried out.

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Smoking Soon After Waking Raises Risk of Lung and Head and Neck Cancers

Two new studies have found that smokers who tend to take their first cigarette soon after they wake up in the morning may have a higher risk of developing lung and head and neck cancers than smokers who refrain from lighting up right away. The findings by researchers at Columbia University's Mailman School of Public Health and Penn State College of Medicine may help identify smokers who have an especially high risk of developing cancer and would benefit from targeted smoking interventions to reduce their risk.

The research was published early online in Cancer, journal of the American Cancer Society.

Cigarette smoking increases one's likelihood of developing various types of cancers. But why do only some smokers get cancer? The researchers investigated whether nicotine dependence as characterized by the time to first cigarette after waking affects smokers' risk of lung and head and neck cancers independent of cigarette smoking frequency and duration.

The lung cancer analysis included 4,775 lung cancer cases and 2,835 controls, all of whom were regular cigarette smokers. Compared with individuals who smoked more than 60 minutes after waking, individuals who smoked 31 to 60 minutes after waking were 1.31 times as likely to develop lung cancer, and those who smoked within 30 minutes were 1.79 times as likely to develop lung cancer. Read Journal article on Lung Cancer Risk.

The head and neck cancer analysis included 1,055 head and neck cancer cases and 795 controls, all with a history of cigarette smoking. Compared with individuals who smoked more than 60 minutes after waking, individuals who smoked 31 to 60 minutes after waking were 1.42 times as likely to develop head and neck cancer, and those who smoked within 30 minutes were 1.59 times as likely to develop head and neck cancer.

These findings indicate that the need to smoke right after waking in the morning may increase smokers' likelihood of getting cancer. "These smokers have higher levels of nicotine and possibly other tobacco toxins in their body, and they may be more addicted than smokers who refrain from smoking for a half hour or more," said Joshua Muscat, PhD, of the Penn State College of Medicine in Hershey and first author. "It may be a combination of genetic and personal factors that cause a higher dependence to nicotine."

Dr. Steven D. Stellman, professor of clinical epidemiology at the Mailman School of Public Health and director of the overall research program under which the data were gathered, stated, "Our finding that time to first cigarette raises the risk of cancer is the latest in a long series of studies that grew directly out of Dr. Ernst Wynder's work, published in JAMA in 1950, which first described the link between cigarette smoking and lung cancer. Research has steadily expanded our knowledge of the hazards of tobacco use."

According to the authors, because smokers who light up first thing in the morning are a group that is at even higher risk of developing cancer than other smokers, they would benefit from targeted smoking cessation programs. Such interventions could help reduce tobacco's negative health effects as well as the costs associated with its use.

The research was supported by a grant from the National Cancer Institute.

Soure

http://www.sciencedaily.com

The Stigma of Lung Cancer Why Are Lung Cancer Patients Treated Differently Than Other Cancer Patients?

Being diagnosed with lung cancer carries a certain stigma.

”How long did you smoke?” “I didn’t know you were a closet smoker.” “Too bad he didn’t quit smoking sooner.” Unlike the unconditional support given to those with other forms of cancer, people with lung cancer often feel singled out, like somehow they “deserve” to have cancer. Where does this stigma come from?

Public Perception of a Diagnosis of Lung Cancer

There is a feeling among the general public, that lung cancer is a self-inflicted disease. Smoking is responsible for 80 to 90% of lung cancers, but let’s put this in perspective: Twice as many women die from lung cancer in the United States each year as die from breast cancer, and 20% of these women have never touched a cigarette. Even for those who smoke and develop lung cancer, why do we attach such a stigma to them? Many cancers, and other chronic diseases, are related to lifestyle choices. We don’t seem to judge as harshly those who overeat, are sedentary or sunbathe extensively.

Physicians’ Attitude Regarding Lung Cancer

Physicians are people too, and the bias we see among the public is present in the doctor's office as well. Joan Schiller, MD, the President and Founder of National Lung Cancer Partnership, and a physician who has done a lot of research on the stigma of lung cancer, surveyed primary care physicians in Wisconsin with some saddening results. Though the physicians stated that the type of cancer was not a factor in their referral decisions, results showed that:

• When hypothetical patients were presented as having advanced cancer, physicians were less likely to refer lung cancer patients to an oncologist than they were to refer breast cancer patients.
• More physicians were aware that chemotherapy improves survival in advanced breast cancer than with advanced lung cancer.
• Breast cancer patients were more likely to be referred for further therapy, whereas lung cancer patients were often referred only for symptom control.

Lung Cancer Patient’s Perceived Stigma

Those who are diagnosed with lung cancer experience more embarrassment than those with prostate or breast cancer, and individuals tend to feel stigmatized whether they smoked or not. Some people have even concealed their diagnosis leading to negative financial consequences and lack of social support.

Funding for Lung Cancer Research vs Other Cancers

Sadly, even though lung cancer kills more people than breast cancer, prostate cancer and colon cancer combined, federal funding lags behind. Funding from the private sector also pales in comparison to fund-raising efforts for some other cancers.

Clearly, lung cancer carries a stigma that extends from the government down to the individual. That said, we won’t move forward by pointing the finger and blaming ourselves, physicians, the public and the government. Each of us can make a difference by supporting those with lung cancer as we would support someone with any other form of cancer. Whether you are a lung cancer survivor, the loved one of someone living with lung cancer or a professional working with those with lung cancer, we need to raise awareness. Those living with lung cancer need and deserve our care and support, not an evaluation of the possible causes.

_Sources:

_{Chapple A, Zieband S, McPherson A. Stigma, shame, and blame experienced by patients with lung cancer: qualitative study. British Medical Journal. 2004. 328(7454).}

_{LeConte NK, Else-Quest NM, Eickhoff J, Hyde J, Shiller JH. Assessment of guilt and shame in patients with non-small-cell lung cancer compared with patients with breast and prostate cancer. Clinical Lung Cancer. 2008. 9(3):171-8.}

_{Wassenarr TR, Eickhoff JC, Jarzemsky DR, Smith SS, Larson ML, Shiller JH. Differences in primary care clinicians’ approach to non-small cell lung cancer patients compared with breast cancer. Journal of Thoracic Oncology. 2007. 2(8):722-8.}