Re: [MOL] Some important info. for our mol friends! [02748] Medicine On Line


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Re: [MOL] Some important info. for our mol friends!



Dear Lil,
Thank you for posting this, it was very informative. The article regarding
infection by helicobactor pylori was especially so to me, as many people I
work with have this bug. One point to note is that H. Pylori often does not
have any symptoms. If you don't have an ulcer, or other gastric problems,
you wouldn't know you had it. It is detected by breath, sputum or blood
samples. The treatment is pretty heavy, three different antibiotics taken
together (in various combinations) over about three weeks. So some suffer
the side effects of high dose antibiotics, such as diarrhoea, etc. However,
there is increasing evidence here too, that a very high percentage of
ulcers are caused by H. pylori bacteria. Since the presence of ulcers is a
factor in many forms of primary gastric cancer, then it makes sense to look
at H. pylori, if not as the cause, at least as a contributing factor.
Love Mam 

----------
> From: Lillian Jennings <Firefly@islc.net>
> To: mol cancer <mol-cancer@lists.meds.com>
> Subject: [MOL] Some important info. for our mol friends!
> Date: Sunday, 1 November 1998 6:29
> 
> Vitamins: Tretinoin for Promyelocytic Leukemia
> 
> The natural and synthetic derivatives of vitamin A -- the retinoids --
are
> involved in a number of vital physiologic processes, including vision,
cell
> differentiation and proliferation, and embryonic development. Each cell
> type appears to manufacture its own pool of retinoids, and these interact
> with retinoic acid receptors in the cell nucleus to modulate gene
> transcription. Two large families of nuclear retinoic acid receptors have
> been described and are part of the steroid- thyroid-retinoid receptor
> super-family. Because they can stimulate cell differentiation, retinoids
> have been clinically investigated in a number of premalignant and
malignant
> conditions and have proved active in cutaneous T- cell lymphomas,
> leukoplakia, and some skin cancers. 
> 
> All-trans-retinoic acid is a natural vitamin A metabolite formed by
> enterocytes from beta-carotene and from tissue metabolism of retinol and
> retinaldehyde. Topical all-trans-retinoic acid (tretinoin, Retin-A/Ortho
> Pharmaceuticals) has attracted attention because it improves the
appearance
> of photoaged skin. All- trans-retinoic acid has also attracted attention
> because it induces remission in patients with acute promyelocytic
leukemia
> (APL). About 10% of the acute myeloblastic leukemias in adults are
> promyelocytic. Patients often present with a bleeding diathesis that is
> exacerbated by cytotoxic chemotherapy. Early mortality rates are high (8%
> to 47%) and are related to the extent of leukocytosis, thrombocytopenia,
> and hypofibrinogenemia. Conventional chemotherapy involves the use of an
> anthracycline combined with cytarabine. Complete remission occurs in 60%
to
> 80% of patients; five-year survival ranges from 35% to 45%. 
> 
> In the mid-1970s, researchers found that patients with APL show a
> consistent chromosomal abnormality, an exchange of information between
> chromosomes 15 and 17. It wasn't until the late 1980s that the transposed
> material on chromosome 17 was found to contain the gene for the retinoic
> acid receptor. For this reason, researchers began the clinical
> investigation of all-trans-retinoic acid for the treatment of APL. They
> found that all-trans-retinoic acid in a dose of 45 mg/m2 per day (given
> once daily or in two equally divided doses) appears to induce
promyelocytes
> to differentiate into mature granulocytes. By 1993, 1500 or so patients
> with a clinical diagnosis of APL had been treated worldwide with all-
> trans-retinoic acid. The initial rate of response was 95% in patients
shown
> by cytogenetic or molecular analysis to have the 15:17 translocation, and
> clinical effectiveness correlated with in vitro response. Median time to
> achieve remission was 38 to 44 days. 
> 
> All-trans-retinoic acid is highly effective for inducing remission, but
it
> does not seem to maintain remission. Still, follow-up with standard
> chemotherapy results in remission at least as long as and probably longer
> than with conventional chemotherapy alone. All-trans-retinoic acid
therapy
> is considerably safer than most other regimens. Side effects include
> headaches, dermatol-ogic problems, xerostomia, and cheilitis. According
to
> Memorial Sloan-Kettering oncologist RP Warrell, "Perhaps the most
important
> advance in this field is not the specific actions of all-trans-retinoic
> acid in acute promyelocytic leukemia, but rather the conclusive
> documentation of differentiation as a practical and consistently
effective
> method of treating human cancer... Just as the practical usefulness of
> all-trans-retinoic acid in combination with conventional treatments
> continues to evolve, the use of differentiation agents in combination
> represents a novel and promising approach for oncologic therapy in the
next
> decade." (Warrell RP et al. N Engl J Med. 1993; 329: 177-189. Kurzrock R
et
> al. J Clin Oncol. 1993; 11: 1489- 1495.) 
> 
> Antibiotics: Amoxicillin/Metronidazole for Gastric Cancer
> 
> It is widely documented that the bacterium Helicobacter pylori causes
both
> gastric and duodenal ulcers and is a contributing factor in gastric
> carcinoma. Nevertheless, ulcers are still treated with antacids and
> antisecretory agents rather than antibiotics, and many patients still
> believe their ulcers are caused by stress and anchovy pizza. According to
> Lancet editorialist CS Goodwin, "Many doctors continue to claim that
these
> bacteria are irrelevant, even in duodenal and gastric ulcer, blithely
> ignoring the hundreds of papers (980 during 1992 alone) indicating its
> importance, particularly in peptic ulcer." What about its importance in
> gastric cancer? "H. pylori does not shout at us," said Goodwin, who asks,
> "Do we hear a whisper that some gastric cancer can be prevented by
> antibiotic treatment?" Can some gastric cancer can actually be reversed
> with antibiotics? 
> 
> Peptic ulceration occurs when acid/peptic attack overcomes a gastric
mucosa
> weakened by chronic gastritis associated with long-standing H. pylori
> infection. Chronic infection causes inflammation and increased acid
> secretion, and eventually atrophic gastritis, gastric metaplasia, and
> achlorhydria. Achlorhydria and low luminal concentrations of ascorbic
acid
> promote gastric colonization by other pathogenic bacteria. Duodenal
> ulceration is similar to peptic ulceration in that ulcers occur where the
> mucosa has been damaged by chronic infection and inflammation. H. pylori
> does not colonize the normal duodenal epithe-lium but resides in areas of
> gastric metaplasia within the duodenum. Chronic inflammation of these
areas
> compromises the duodenal mucosa, and excess acid reaching the duodenum
> causes further damage. (Dixon M. Lancet. 1993; 342: 384- 385.) 
> 
> Not all patients infected with H. pylori have duodenal ulcers, but those
> who do show increased gastrin release and an exaggerated acid secretion
in
> response to gastrin stimulation. In one study, H. pylori-positive
duodenal
> ulcer patients showed a 6-fold increase in gastrin-stimulated acid
> secretion compared with H. pylori-negative subjects, and eradication of
the
> organism resulted in a 66% reduction in gastrin-mediated acid secretion 1
> month after treatment. (El-Omar E et al. Gut. 1993; 34: 1060-1065.) Moss
> and Calam also showed that eradication of H. pylori significantly
decreases
> basal acid secretion in duodenal ulcer patients, thus healing the ulcers.
> (Moss SF, Calam J. Gut. 1993; 34: 888-892.) 
> 
> What about gastric cancer? In their evaluation of data from 13 countries,
> the Eurogast Study Group found a close association between high gastric
> cancer rates and H. pylori infection. This was expected since gastric
> carcinoma is commonly preceded by atrophic gastritis and intestinal
> metaplasia, which are caused by H. pylori. On the cellular level,
> persistent H. pylori infection and inflammation induce cell proliferation
> (possibly by increased production of epidermal growth factor) and damage
> DNA, which can lead to activation of oncogenes or inactivation of tumor
> suppressor genes. Low intakes of fruits and vege-tables and a high-salt
> diet are proposed co-factors for gastric carcinoma, although study
results
> are inconsistent. Overcrowding living conditions are highly associated
with
> H. pylori infection, and inadequate housing is associated with gastric
> cancer. 
> 
> Since survival rates are lower after diagnosis of gastric cancer than for
> other common cancers, methods of detection and treatment are needed.
> Detection is a problem, since gastric cancer is often silent. Studies
have
> shown that up to 70% of patients do not have dyspepsia until late in the
> course of the disease. Treatment is also a problem, since antibiotic
> therapy induces antibiotic resistance. Even so, attempts to eradicate H.
> pylori may still be the best protective measure against gastric
carcinoma.
> Studies have shown that H. pylori infection can be cleared with a 2-week
> course of tetracycline plus metronidazole and bismuth, or alternately
with
> amoxicillin plus omeprazole or amoxicillin plus ranitidine plus
> metronidazole. 
> 
> Clearance of H. pylori infection may be useful not only for preventing
> cancer, but also for treating certain malignancies. Several investigators
> have reported that clearance of H. pylori is accompanied by tumor
> regression in a specific type of gastric B-cell lymphoma, referred to as
> gastric MALT lymphoma. The acquisition of lymphoid tissue resembling
> intestinal tissue (mucosa-associated lymphoid tissue or MALT) precedes
the
> onset of B-cell lymphomas of the MALT type. The normal stomach contains
no
> MALT; acquisition of this tissue is a result of chronic infection of the
> mucosa with H. pylori, indeed, this organism is present in more than 90%
of
> gastric MALT lymphomas. Apparently the organism stimulates the production
> of oncogenic products by T-cells. Co-culture of H. pylori and cells from
> MALT lymphomas resulted in the proliferation of neoplastic B-cells and
> non-neoplastic T-cells, with different strains of H. pylori capable of
> different stimulatory effects. Removal of the T-cells reduced this
> proliferation. (Hussell T et al. Lancet. 1993; 342: 571-574.) 
> 
> To investigate whether eradication of H. pylori could influence tumor
> growth, Wotherspoon et al treated six patients with primary gastric
B-cell
> MALT lymphoma with antibiotics (ampicillin with metronidazole and a
bismuth
> compound, or ampicillin with omeprazole). Clearing the infection caused
> tumor regression in five of the six patients. Follow-up biopsies showed
> eradication of H. pylori in all six, with no morphological or molecular
> evidence of lymphoma in five of the patients and only a residual
infiltrate
> in the sixth. Stolte and Eidt also administered antibiotics to patients
> with suspected low-grade MALT lymphomas. After 10 to 14 days of
amoxicillin
> plus omeprazole, lymphatic aggregates regressed in 19 of 32 patients. In
12
> patients with confirmed low- grade MALT lymphomas, tumors regressed when
H.
> pylori was eradicated. "Compared with surgery or chemotherapy, antibiotic
> treatment of H. pylori is harmless and inexpensive," said Wotherspoon et
> al. "There is no urgency for radical treatment, and anti-H. pylori
> treatment should, therefore, be the first line of treatment."
(Wotherspoon
> AC et al. Lancet. 1993; 324: 575-577. Stolte M, Eidt S. Lancet. 1993;
342:
> 568.) 
> 
> 
> 
> Dietary Modification: The Role of Red Meat in Prostate Cancer
> 
> In the United States, prostate cancer is the second leading cause of
cancer
> mortality, after lung cancer. Approximately 122,000 American men had new
> diagnoses of prostate cancer in 1991, and 32,000 died of the disease.
> Worldwide, prostate cancer is a common occurrence, with 15% to 30% of men
> over the age of 50 showing histologic evidence of this malignancy.
> Cross-cultural and migrant studies have shown differences in dietary fat
> intake between high- and low-risk areas, which may explain why latent
> cancers found at autopsy show a similar frequency worldwide, while the
> incidence of clinically evident cancers is higher in western Europe,
> Canada, and the United States, where dietary fat intake is higher.
Because
> American men obtain approximately 36% of daily calories from dietary fat,
> Giovannucci et al. decided to study the effects of dietary fat intake on
> the risk of prostate cancer. They used data from the on-going Health
> Professionals Follow-Up Study, which had 51,529 participants aged 40 to
75
> when the study began in 1986. Questionnaires were evaluable from 47,855
of
> these participants; 300 had been diagnosed with prostate cancer during
the
> study period (1988-1990), and 126 had advanced cases. 
> 
> The investigators found the higher the intake of dietary fat, especially
> fat from red meat, the greater the risk of advanced pros-tate cancer.
This
> association was not valid for early prostate cancer. Men with the highest
> fat intake had a 79% higher risk of advanced prostate cancer than men
with
> the lowest intake, and red meat (beef, pork, and lamb) was associated
with
> a 164% increased risk in the high-intake group compared with the
> lowest-intake group. Fats from fish and dairy products (except butter)
and
> from vegetables were not related to the risk of advanced prostate cancer.
> Ingestion of chicken with skin was assoc-iated with an elevated risk, but
> ingestion of chicken without skin was inversely associated with risk.
> Advanced prostate can-cer was associated with various fatty acids --
> saturated and monounsaturated fatty acids and alpha-linolenic acid (but
not
> linoleic acid) -- but when these fatty acids were controlled for each
> other, only the association with alpha-linolenic acid persisted. 
> 
> The association between the risk of advanced prostate cancer and
> consumption of red meat and alpha-linolenic acid persisted after
> adjustments for age, energy intake, body mass index, physical activity,
> geographic residence, ancestry, marital status, vasectomy status, and
> dietary intake of other nutrients (long-chain omega-3 fatty acids,
> trans-fatty acids, cholesterol, retinol, carotene, and other
antioxidants,
> protein, carbohydrates, fiber, vitamins, and alcohol). The effects of fat
> on prostate cancer progression are unknown. Animal fats (or carcinogens
in
> cooked fats) may alter sex hormone levels, immune responses, cell
membrane
> function, cell proliferation, tissue invasiveness, and metastasis. The
> investigators concluded that their findings support recommendations to
> lower the intake of red meat to reduce the risk of prostate cancer. "The
> potential roles of carcino- gens formed in cooking animal fat and of
> alpha-linolenic acid in the progression of prostate cancer need to be
> explored." (Gio-vannucci E et al. J Natl Cancer Inst. 1993; 85:
1571-1579.
> Pienta KJ, Esper PS. J Natl Cancer Inst. 1993; 85: 1538-1540.) 
> 
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