Cancer Gift

[ChenPengFi]

Thought this might be appropriate here:

Jack Andraka, the Teen Prodigy of Pancreatic Cancer
A high school sophomore won the youth achievement Smithsonian American Ingenuity Award for inventing a new method to detect a lethal cancer

http://www.smithsonianmag.com/scienc...179996151.html

Video here:
http://www.smithsonianmag.com/multim...JATqCyyjiopO42

[jspeedy]

As a radiation therapist, what do you feel are the major challenges of your profession in the next 10 years? How are the current best practices changing with the times and how are they improving the treatment of patients?

Challenges for the next 10 years? I'm sure as newer treatments develop radiation therapy (xrt)will have to find more reasons/ways to stay competitive.

For now xrt improvements are being made in dose conformity and treatment localization via imaging (ultrasound, xray,pet/ct). For example, in the 90s a prostate was treated with 4 radiation fields AP/PA and 2 laterals (for laymen one from the front,one from the back and two from the sides. Now there are up to 18 imrt fields (intensity modulated radiation therapy) moving leaves in the path of the beam turn a straight open beam into beamlets to deliver precise dose to a specific area. Because the radiation dose if more confined more radiation can be given and there a fewer side effects. Image guidance is also used daily to ensure the treatment volume is perfectly alligned.

Cyber knife/gamma knife offers non invasive options for tumors where surgery isn't an option.

Proton therapy although very expensive to provide uses proton particles rather than x-rays. The bragg peak of the protons eliminates exit dose, this makes it possible to treat tumors near vital organs with reduced side effects.

I doubt xrt will be obsolete within my life time. It seems many cancer treatments involve a three pronged approach of surgery, chemo, and xrt used in combination. Certain cancers are less sensitive to radiation than others, I believe it's the same with chemo. Radiation therapy is a localized treatment option rather than a systemic one like chemo. I can get into more specifics if necessary but I don't want to bore everyone. I'd be interested to learn if there are any cancers that were previously treated with xrt that now don't. The only one I'm aware of off the top of my head is leukemia, TBI (total body irradiation) used be an option followed by bone marrow transplant. I believe chemo is now the mainstay for leukemia.

[jubei33]

As a radiation therapist, what do you feel are the major challenges of your profession in the next 10 years? How are the current best practices changing with the times and how are they improving the treatment of patients?

[jubei33]

Yes, I feel they will ultimately be replaced with more effective and target specific chemo therapies designed from knowledge gleaned from molecular biology. Perhaps in the future these will then be replaced with RNA-DNA based therapies that target the broken genes in question and then, rather than remission, we could be looking at a specific cure as its thought of in the common parlance. On that note, we should be on the lookout for micro RNA based diagnostics and, if we're so lucky, therapies very soon.

[jspeedy]

I've avoided joining this thread because I feel it is way over my head, but as a Radiation Therapist I feel have more of a grasp on the subject than most people. This thread has mainly focused on chemo treatments but what does the OP think about radiation treatments for caner and other therapies? Often times chemo is used with radiation and surgery to treat cancer but I don't recall seeing it mentioned much here.

In addition diseases such as leukemia were once frequently treated with radiation but are now less commonly treated. Does the OP think other forms of radiation therapy will ultimately be replaced by chemo?

[jubei33]

What exactly is a tyrosine kinases and what does it do?

Read more here....

[jubei33]

Here's a pic of the two compounds in question. Notice the key differences in red and their very close similarity. It was developed in the 40s for cancer treatment and is used even today. This drug was first developed by a little known Indian scientist named Yellapragada Subbarao, who did a lot of very important work in early biochemistry, but sadly went mostly unnoticed.

Rectify this injustice mofos! Tell others of this sorrowful tale.

[jubei33]

Different kinds of cancers develop resistances to the drugs used to treat them. Its interesting that in many cases these are very similar to bacterial resistances against antibiotics. Take for example, the classic cancer drug methotrexate. Methotrexate is the first of a class of drugs called anti-folates that are used to starve dividing cells of the purine and pyramidine nitrogenous bases needed DNA replication. It blocks the enzyme dihydrofolate reductase that eventually produces the folate necessary for this. Without the ability to produce more, dividing cells are limited in their ability to replicate DNA, a step necessary in cell division. Since cancer cells are promiscuous towards cell division, it affects them more than the normal cells of a given tissue.

However, cancer cells can resist this kind of treatment. In response to methotrexate exposure some cancer cells can amplify the DHFR gene, producing more of the enzyme. This requires more of the drug to overcome the resistant strain, but this may not practical in terms of toxicity for the patient.

Other resistance methods change the ability of the cell to acquire or retain the drug. Drugs like methotrexate (and others) utilize a drug transport receptor called the Reduced Folate carrier (RFC) for transport into the cell. Mutations have been recognized in this carrier in resistant cells, such that there is less methotrexate accumulation into the cell. Furthermore, some cancers have been noted to produce less of this receptor all together. The opposite strategy, in this case, is also true of cancer cells: they increase their ability to remove toxic drugs as well. Cancer cells are know to express drug transporters known as the ABC transporters. Perhaps these are best known for providing the safety net for the brain (and gonads): the' blood brain barrier'. These export chemicals from a cell, yielding resistance to a wide selection of drugs. In the case of cancer, proteins identified of note are the breast cancer resistance protein (BCRP) and the multi-drug resistance protein (MDR), both often found in cancer cell phenotypes that were less responsive to chemotherapies.

[jubei33]

Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg).
Nimptsch K, Rohrmann S, Linseisen J.
Source

Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
Abstract
BACKGROUND:

Anticarcinogenic activities of vitamin K have been observed in various cancer cell lines, including prostate cancer cells. Epidemiologic studies linking dietary intake of vitamin K with the development of prostate cancer have not yet been conducted.
OBJECTIVE:

We evaluated the association between dietary intake of phylloquinone (vitamin K1) and menaquinones (vitamin K2) and total and advanced prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition.
DESIGN:

At baseline, habitual dietary intake was assessed by means of a food-frequency questionnaire. Dietary intake of phylloquinone and menaquinones (MK-4-14) was estimated by using previously published HPLC-based food-content data. Multivariate-adjusted relative risks of total and advanced prostate cancer in relation to intakes of phylloquinone and menaquinones were calculated in 11 319 men by means of Cox proportional hazards regression.
RESULTS:

During a mean follow-up time of 8.6 y, 268 incident cases of prostate cancer, including 113 advanced cases, were identified. We observed a nonsignificant inverse association between total prostate cancer and total menaquinone intake [multivariate relative risk (highest compared with lowest quartile): 0.65; 95% CI: 0.39, 1.06]. The association was stronger for advanced prostate cancer (0.37; 0.16, 0.88; P for trend = 0.03). Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat. Phylloquinone intake was unrelated to prostate cancer incidence (1.02; 0.70, 1.48).
CONCLUSIONS:

Our results suggest an inverse association between the intake of menaquinones, but not that of phylloquinone, and prostate cancer. Further studies of dietary vitamin K and prostate cancer are warranted.

Pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of aerobic glycolysis in cancer cells and plays important roles in cancer metabolism and growth. Here we show that vitamin K3 and K5 (VK3 and VK5) are relatively specific PKM2 inhibitors. VK3 and VK5 showed a significantly stronger potency to inhibit PKM2 than to inhibit PKM1 and PKL, 2 other isoforms of PK dominantly expressed in most adult tissues and liver. This study combined with previous reports supports that VK3 and VK5 have potential as adjuvant for cancer chemotherapy.

and it can save your ass if you get poisoned by warfarin. (Keep in mind these are a bit early.)

[jubei33]

Ok, this is the paper in question. It was research done by Evangelos D. Michelakis at the University of Alberta in Canada and its quite interesting. The problem is mostly the hysteria and conspiracy attached to it. These kind of things, (meaning: early successful experiments) often dredge up the nutcases enmasse.

The tests were conducted in rats and in vitro tests, which aren't the same as or equivalent to tests in humans. Though animals are a judicious choice for early testing, they cannot adequately substitute for the human factor.

Many of our current cancer drugs have had similarly successful in vitro tests. There's kind of a long history of cancer cure false positives in this theme, where early results are touted as fantastic and the end of cancer!!, but these haven't run the distance to date. Often the results they get when tested in humans are less dramatic, though still quite useful. I'm thinking of Imatinib, I think, which is a tyrosine kinase inhibitor and is first line for chronic myelogenic leukemia. (it might have been an earlier monoclonal antibody that received all the hype, though..but oh well.)

12/9 edit: I started this yesterday with the mindset of "Oh, this again", but now that I re-read it. It sounds quite negative. I don't want to give the impression that his work is at fault. That's not it at all, its a very good start. All the spin, you can blame that on half of the nutcases out there with their conspiracy mindset. In this way, this work is more of a sideshow to all these grandstanding bozos, they take away the depth and importance of this guy's efforts.

[jubei33]

I vote no, too. At least until human trials and clear evidence of positive results.

Dichloroacetate was discussed earlier on page 3 or 4. I can't remember which one, but we were talking about the Warburg hypothesis, which is an interesting discussion by itself.

Cancer is just a complicated beast, one that affects us at the core (our genes).

edit: I'll give you a better, more in depth answer when I'm not at work.

[PizDoff]

I'm going to ask in this thread, as some people here seem to demonstrate a tad more understanding of cancer than I.

Is cancer cured?
Snopes says no. Also it links to this which I scanned then somehow got an immediate headache.
http://scienceblogs.com/insolence/20..._deja_vu_a.php

[jubei33]

piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells.

Cheng J, Deng H, Xiao B, Zhou H, Zhou F, Shen Z, Guo J.
Source

Ningbo University School of Medicine, Ningbo 315211, China.
Abstract

Piwi-interacting RNAs (piRNAs), new non-coding small RNAs, are association with chromatin organization, messenger RNA stability and genome structure. However, the roles of piRNA in carcinogenesis are not clearly defined. By using real-time reverse transcription-polymerase chain reaction technology, we found that the expression level of piR-823 in gastric cancer tissues was significant lower than that in non-cancerous tissues. After increase the level of piR-823 in gastric cancer cells, cell growth was inhibited. The results of xenograft nude mice model confirmed its tumor suppressive properties. All of the evidences indicated that piR-823 play a crucial role in the occult of gastric cancer.

[jubei33]

and while we're on the subject:

Epidermal growth factor receptor in relation to tumor development: EGFR-targeted anticancer therapy

Keywords:

epidermal growth factor receptor (EGFR) mutation;
KRAS mutation;
monoclonal antibodies;
tyrosine kinase inhibitor

The discovery that signaling by the epidermal growth factor receptor (EGFR) plays a key role in tumorigenesis prompted efforts to target this receptor in anticancer therapy. Two different types of EGFR-targeted therapeutic agents were subsequently developed: mAbs, such as cetuximab and panitumumab, which target the extracellular domain of the receptor, thereby inhibiting ligand-dependent EGFR signal transduction; and small-molecule tyrosine kinase inhibitors, such as gefitinib and erlotinib, which target the intracellular tyrosine kinase domain of the EGFR. Furthermore, recent clinical and laboratory studies have identified molecular markers that have the potential to improve the clinical effectiveness of EGFR-targeted therapies. This minireview summarizes the emerging role of molecular profiling in guiding the clinical use of anti-EGFR therapeutic agents.

[jubei33]

Uh oh--NOW YOU IN FORIT ! I got into the liquor cabinet again:

Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non–Small Cell Lung Cancer: A Randomized Trial

Abstract

Context: More persons in the United States die from non–small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib.

Objective To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib.

Design, Setting, and Patients Double-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens.

Intervention Daily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo).

Main Outcome Measures Improvement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies).

Results Of 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P = .26), radiographic tumor regression (P = .51), and projected 1-year survival (P = .54). The 500-mg dose was associated more frequently with transient acne-like rash (P = .04) and diarrhea (P = .006).

Conclusions Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.

Gefitnib is of a new class of tyrosine kinase inhibitors, which were developed out of a clearer understanding of molecular biology.