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Occupation and cancer in London: an investigation into nasal and bladder cancer using the Cancer Atlas.

The Atlas of Cancer Mortality for England and Wales showed pronounced excesses of male mortality from nasal and bladder cancer in certain London boroughs. These excesses were investigated by case-referent studies using death certificate data for male deaths, 1968-78. Nasal cancer was found to be significantly associated with occupations involving heavy exposure to wood dust. Bladder cancer was significantly associated with occupations in road transport driving and in the handling of leather, whereas consistently raised relative risk ratios were also found for wood-workers, engineering fitters, printers, machinists, plumbers, and motor mechanics. These findings highlight the potential role of occupational factors in cancer causation in London.

Humans↗

Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype.

PURPOSE: The presence of disseminated tumor cells (DTC) in the bone marrow of breast cancer patients is an acknowledged independent prognostic factor. The biological metastatic potential of these cells has not yet been shown. The presence of putative breast cancer stem cells is shown both in primary tumors and distant metastases. These cells with a CD44(+)CD24(-/low) phenotype represent a minor population in primary breast cancer and are associated with self-renewal and tumorigenic potential. Recognizing the potential effect of prevalence of putative stem cells among DTC, we evaluated the bone marrow DTC. EXPERIMENTAL DESIGN: We employed the double/triple-staining immunohistochemistry protocol and modified the established bone marrow cytokeratin (CK) staining protocol by adding steps for additional antigens, CD44 and/or CD24. We evaluated 50 bone marrow specimens, previously categorized as CK(+) from early breast cancer patients. CK(+) cells were examined for CD44 and CD24 expression by light microscopy, fluorescence microscopy, and spectral imaging. RESULTS: We detected the putative stem cell-like phenotype in all CK(+) specimens. The mean prevalence of putative stem/progenitor cells was 72% and median prevalence was 65% (range, 33-100%) among the overall DTC per patient, compared with primary tumors where this phenotype is reported in <10% of cells. CONCLUSIONS: This is the first evidence of the existence of the putative stem-like phenotype within the DTC in bone marrow in early breast cancer patients. All patients had a putative stem cell phenotype among the DTC and most individual DTC showed such phenotype. Future molecular characterization of these cells is warranted.

Bone Marrow↗

Breast cancer, colorectal cancer, and esophageal cancer.

This is the second of a six-part series on metastatic spread and natural history of 18 common tumors. Part one summarized symptom/problem anticipation, cancer metastasis, and the 18 tumors that each cause more than 6,000 deaths per year in the United States. Bladder and brain cancer were discussed, with information given on tumor types, metastatic spread and invasion, and common symptoms. Part two charts the natural histories of breast, colorectal, and esophageal cancers. Each of these cancers is presented separately, with information given on mortality rates, the most common tumor types, sites of metastases, common problems, and common oncologic emergencies. Sites of spread, resulting problems (including site-specific symptoms), and assessment parameters are presented as tables. Material is presented so that clinicians will be able to anticipate the spread of these cancers and thus identify problems early in their development so that the problems are more easily managed.

Breast Neoplasms↗

Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors.

BACKGROUND: Typical high throughput microarrays experiments compare gene expression across two specimen classes - an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies. METHODS: To examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors. RESULTS: Statistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues. CONCLUSIONS: The up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue can undergo genetic changes in response to or in expectation of morphologic cancer. A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.

Adult↗

Ten-year results of a randomized trial evaluating prolonged low-dose adjuvant chemotherapy in node-positive breast cancer: a joint European Organization for Research and Treatment of Cancer-Dutch Breast Cancer Working Party Study. Cooperating Investigators.

PURPOSE: To investigate whether treatment with prolonged low-dose adjuvant chemotherapy could improve survival of patients with axillary node-positive breast cancer. PATIENTS AND METHODS: Four hundred fifty-two patients with axillary node-positive breast cancer who received postoperative irradiation were prospectively randomized in a trial (European Organization for Research and Treatment of Cancer [EORTC] 09771) that compared surgery followed by prolonged low-dose chemotherapy versus surgery alone. Chemotherapy was given for a period of 2 years and consisted of monthly courses of cyclophosphamide 50 mg/m2 orally on days 1 to 14, methotrexate 15 mg/m2 intravenously on days 1 and 8, and fluorouracil 350 mg/m2 intravenously on days 1 and 8 (CMF). RESULTS: At a median follow-up time of 10 years, the overall survival duration was significantly prolonged in the chemotherapy arm (hazards ratio, 0.75; 95% confidence interval, 0.56 to 0.99; P = .04). Ten-year overall survival rates (+/- SE) were 59% (+/- 3.6%) for the chemotherapy arm and 50% (+/- 3.7%) for the control arm. Time to local relapse was significantly prolonged in the chemotherapy arm (hazards ratio, 0.63; 95% confidence interval, 0.42 to 0.94; P = .02). Patients with one to three positive axillary nodes and patients with estrogen receptor-negative tumors especially benefited from chemotherapy. Toxicity was observed in 93% of patients. CONCLUSION: We conclude that prolonged low-dose adjuvant CMF can significantly prolong overall survival in patients with node-positive breast cancer. However, considering the fact that toxicity was still considerable despite reducing the dose of chemotherapy by 50%, we believe that conventionally dosed short-term regimens are preferable in the treatment of node-positive breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

High local recurrence risk after breast-conserving therapy in node-negative premenopausal breast cancer patients is greatly reduced by one course of perioperative chemotherapy: A European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study.

PURPOSE: Patients with invasive breast cancer may develop a local recurrence (LR) after breast-conserving therapy (BCT). Younger age has been found to be an independent risk factor for LR. Within a group of premenopausal node-negative breast cancer patients, we studied risk factors for LR and the effect of perioperative chemotherapy (PeCT) on LR. PATIENTS AND METHODS: The European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial (EORTC 10854) to compare surgery followed by one course of PeCT (fluorouracil, doxorubicin, and cyclophosphamide) with surgery alone. From patients treated on this trial, we selected premenopausal patients with node-negative breast cancer who were treated with BCT to examine whether histologic characteristics and the expression of various proteins (estrogen receptor, progesterone receptor, p53, Ki-67, bcl-2, CD31, c-erbB-2/neu) are risk factors for subsequent LR. Also, the effect of one course of PeCT on the LR risk (LRR) was studied. RESULTS: Using multivariate analysis, age younger than 43 years (relative risk [RR], 2.75; 95% confidence interval [CI], 1.46 to 5.18; P =.002), multifocal growth (RR, 3.34; 95% CI, 1.27 to 8.77; P =.014), and elevated levels of p53 (RR, 2. 14; 95% CI, 1.13 to 4.05; P =.02) were associated with higher LRR. Also, PeCT was found to reduce LRR by more than 50% (RR, 0.47; 95% CI, 0.25 to 0.86; P =.02). Patients younger than 43 years who received PeCT achieved similar LR rates as those of patients younger than 43 years who were treated with BCT alone. CONCLUSION: In premenopausal node-negative patients, age younger than 43 years is the most important risk factor for LR after BCT; this risk is greatly reduced by one course of PeCT. The main reason for administering systemic adjuvant treatment is to improve overall survival. The important reduction of LR after BCT is an additional reason for considering systemic treatment in young node-negative patients with breast cancer.

Adult↗

High relative risk of a second pulmonary cancer in patients affected by laryngeal cancer: differences by specific site of occurrence and lung cancer histotype.

The frequency of a second primary lung tumor in patients affected by laryngeal cancer has been evaluated on the basis of 128,532 biopsies and 27,753 autopsies carried out from January 1, 1979 through December 31, 1988. Among these cases, 432 laryngeal cancers and 44 synchronous or metachronous pulmonary cancers have been detected (7 during life, 37 at autopsy). The highest risk of developing a lung tumor has been evidenced in patients affected by supraglottic cancer during the first 2 years of follow-up (relative risk [RR]: 32.56 for supraglottic patients versus 5.55 for glottic patients). This is particularly true of patients affected by multicentric supraglottic tumors (RR: 62.5). A significant hyperfrequency of undifferentiated lung cancers also has been noted in supraglottic patients (RR: 45.45 for supraglottic versus 14.28 for glottic patients). The information provided by autopsy allows for a more realistic and detailed outlining of the issue of tumor multiplicity, stressing the importance of strict preventive and follow-up protocols.

Actuarial Analysis↗

Beneficial effects and side effects of DHEA: true anti-aging and age-promoting effects, as well as anti-cancer and cancer-promoting effects of DHEA evaluated from the effects on the normal and cancer cell telomeres and other parameters.

The author evaluated the effects of DHEA (Dehydroepiandrosterone) on the amount of telomeres of normal cells and cancer cells and found the following: Contrary to the literature, which often recommended 25-50 mg of DHEA daily for the average adult human being, the author found that, depending on the individual, the maximum increase of normal cell telomere was obtained by a single optimal dose of 1.25-12.5 mg. This was examined in 50 people, both males and females, between the ages of 20-80 years old. When one optimal dose was given to each individual, the average telomere amount in normal tissues, measured in Bi-Digital O-Ring Test units, often increased from anywhere between 25-300 ng to between 500-530 ng. Cancer cell telomere reduced from higher than 1100 ng to less than 1 yg (=10(-24) g) with equally significant normalization of abnormal cancer parameters (such as Integrin alpha5beta1, Oncogen C-fosAb2, Acetylcholine, etc.). Circulatory improvement and an increase in grasping force of up to 25% were also detected, along with the changing of a few white hairs to black hairs. The beneficial effects of one optimal dose of DHEA generally lasted between 1 to 4 months, though in some individuals it lasted for a much shorter period of time due to a number of negative factors such as excessive stress/work, excessive exposure to low temperatures and toxic substances, or use of common pain medicines. On the other hand, if a patient took an excessive dose of DHEA, the amount of normal cell telomere decreased, while there was an increase in cancer cell telomere. It was found that those who took an overdose of 25-50 mg daily for more than 3 months had a high incidence of cancer of the prostate gland, breast, colon, lung, and stomach. Also, when the average normal cell telomere levels were less than 110 ng, compared with a normal value of 120-130 ng, and when DHEA in different parts of the body was also extremely low (less than 1-2 ng), one could suspect the possible presence of a malignant tumor somewhere in the body. When normal cell telomere was less than 110 ng, most individuals felt very weary with marked tiredness in the eyes, and grasping force was often reduced.

Adjuvants, Immunologic↗

[Comparison of the histopathological findings among the biopsies of non-cancerous gastric mucosa of patients with gastric cancer and the biopsies of gastric mucosa of dyspeptic patients without gastric cancer].

Gastric biopsies of the non neoplastic area of 46 patients with gastric cancer and 59 gastric biopsies of dyspeptic patients without gastric cancer were reviewed by one pathologist, without knowing from which group they were coming, to determine the histopathologic findings. The results of both groups were compared. Intestinal metaplasia was found to be significantly higher in gastric cancer patients than in patients without neoplasia (54,3 and 25,4% respectively) (p=0,001). Also in patients with cancer and intestinal metaplasia, this was of the complete type in about 80% of the cases. A number of items were assessed using logistic regression, we found that the presence of complete metaplasia, gastric atrophy and hypertrophy of the mucinogenous vacuole correlates with the presence of gastric cancer (p=0,0159 0,0080 y 0,0280 respectively). H.pylori presence was similar in both groups. The study was done between November 1997 and November 1998 at the Cayetano Heredia National Hospital and the National Institute of Neoplastic Diseases.

Aged↗

The effect of adjuvant tamoxifen: the latest results from the Cancer Research Campaign Adjuvant Breast Trial. Cancer Research Campaign Breast Cancer Trials Group.

The CRC Adjuvant Breast Trial, launched in 1980 to repeat both the Nolvadex Adjuvant Trial Organisation tamoxifen trial and the Scandinavian trial of perioperative cyclophosphamide trial, randomised 2230 stage I or II early breast cancer patients in a 2 x 2 factorial design to investigate the benefits of a short course of perioperative cyclophosphamide or tamoxifen daily for 2 years. At a median follow-up of 7.8 years, no significant benefit is noted for perioperative cyclophosphamide, however the main effect analysis for adjuvant tamoxifen demonstrates a significant improvement in disease-free survival which increases with time over the follow-up period. These results are in keeping with the World Overview of Trials of Adjuvant Tamoxifen. However, this study is unique, having a large number of node negative patients and over 500 premenopausal women in a comparison of tamoxifen and control. The relative risk reductions for the node negative patients for disease-free survival are greater than for node positive patients. This might suggest that the absolute benefit for adjuvant tamoxifen is similar in both groups of patients, bearing in mind the increase risk of relapse with node positive patients. No trend for interaction emerges according to age or menopausal status suggesting an identical benefit for pre and postmenopausal women. Similar relative risk reductions are seen when the data are stratified according to tumour size, suggesting a similar positive benefit may be seen for all patients irrespective of tumour size. Of particular interest is the incidence of contralateral breast cancer, the initial overall effect which emerged at the third year of follow-up ceases to be apparent. However subgroup analysis according to menopausal status suggests a trend for interaction with a reduction in the risk of contralateral breast cancer in the postmenopausal women and a marginal increase in the risk of contralateral breast cancer in premenopausal women. Plausible mechanisms exist to explain this difference in outcome and these data need to be confirmed or refuted by other large trials of adjuvant tamoxifen especially at this time when the chemoprophylaxis of breast cancer in high risk premenopausal women by tamoxifen is being considered.

Antineoplastic Combined Chemotherapy Protocols↗

[A comparative study of pepsinogen (PG) and lactic acid dehydrogenase (LDH) activities and isoenzyme patterns in tissues from human primary gastric cancer, gastric cancer xenografts in nude mice and gastric cancer cell lines].

Tissue and cell homogenates were prepared for PG and LDH study from 20 samples of histologically proven gastric cancer (GC), 6 samples of gastric cancer xenografts (THPGC-1) of different passages (GCXG) and cultured cells of 3 different gastric cancer cell lines (GCCL). Normal gastric mucosa (NGM) was also obtained from the resected stomach far distant from the primary tumor and histologically tumor free. The results indicated that the expression of PG isoenzymes was low or absent and the PG activities were significantly decreased in GC, GCXG and GCCL as compared to NGM. The activity of LDH was also significantly increased in GC, GCXG and GCCL. In addition, there was a change in isoenzyme pattern in GC and GCXG in which isoenzyme type M was observed whereas isoenzyme type H was preponderent in NGM. The results show that the human gastric cancer xenograft, THPGC-1, has biological properties very similar to those of the primary tumor suggesting that THPGC-1 is a reliable model for the study of the molecular biology of human gastric cancer.

Adenocarcinoma↗

Cancer screening behaviors among U.S. women: breast cancer, 1987-1989, and cervical cancer, 1988-1989.

Data from the Behavioral Risk Factor Surveillance System (BRFSS) were used to examine trends in breast and cervical cancer screening behaviors among U.S. women in selected states. Data reported are from the 1987, 1988, and 1989 BRFSS for breast cancer screening (mammography) and from the 1988 and 1989 BRFSS for cervical cancer screening (Papanicolaou [Pap] smear). Results are presented as either state-specific or state-aggregate data for the years noted above. State-specific analyses indicated that self-reported mammography utilization increased between 1987 and 1989. Although whites and blacks reported similar mammography utilization rates both for screening and for a current or previous breast problem, disparities were evident among women of different ages and incomes. The proportion of women who reported ever having had a Pap smear and having heard of a Pap smear were extremely high and remained fairly consistent across the 2 survey years. State-aggregate analyses, however, showed that the percentage of women who had had a Pap smear within the previous year was negatively associated with age and positively associated with income. A higher proportion of blacks than whites obtained Pap smears. These results indicate that certain segments of the population are not taking full advantage of available breast and cervical cancer screening technologies. Public health strategies, such as those outlined in the Breast and Cervical Cancer Mortality Prevention Act of 1990 (Public Law 101-354), should enhance screening opportunities for these women.

Adult↗

[An autopsy case of triple primary cancers consisting of glioblastoma multiforme of the pons, colon cancer and rectal carcinoid--a statistical analysis of cases of brain tumor combined with other primary cancers in Japan autopsy annuals].

An autopsy case of glioblastoma multiforms of the pons with a colon cancer, a rectal carcinoid, a renal adenoma and three gastric leiomyomas in a 81-year-old-woman is reported with a statistical analysis on multiple primary cancers associated with primary brain tumors as reported in the Japan autopsy annuals. Out of 329, 705 autopsy cases from 1975 to 1984 in the Japan autopsy registry, double cancers and triple cancers that included a primary brain tumor amounted to 123 cases (0.037%) and 12 cases (0.0036%), respectively. Other sites for primary cancers were the thyroid (23%), the stomach (15%), the lungs (12%), and the colon (10%) in that order of frequency.

Adenoma↗

Update in cancer chemotherapy: genitourinary tract cancer, Part 2: Wilms' tumor and bladder cancer.

An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series. Included in the review are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 2 focuses on Wilms' tumor and bladder cancer.Major advances have been made in the control of Wilms' tumor in children. The combination of surgery, chemotherapy, and radiotherapy have significantly improved survival rates. Likewise, the early diagnosis and control of bladder cancer has also improved survival. Surgery predominates among the treatment modalities for carcinoma of the bladder. Important progress is being made in the control of these conditions, as well as with other tumors of the genitourinary tract, with the use of cancer chemotherapy.

Antineoplastic Agents↗

[An in vitro sensitivity assay for anti-cancer agents by measuring the inhibition rate of DNA synthesis (3H-thymidine uptake of cancer cells). II. Clinical study of 110 cases of breast cancer].

The sensitivity of cancer cells to anti-cancer agents (ACA) was assessed in 110 cases of breast cancer (87 primary cases and 23 recurrent cases). The cancer cells were cultured with ACAs: Mitomycin C (MMC), Adriamycin (ADR), 5-Fluorouracil (5-FU), Cytosine Arabinoside (Ara-C), Carboquone (CQ), Nimustine Hydrochloride (ACNU), Cis-platinum Diammine Dichloride (CPDD) or Vincristine (VCR) for 3 days and their sensitivity was estimated by the inhibition rate (I.R.) of DNA synthesis (3H-thymidine uptake) of cancer cells. The DNA synthesis was higher in recurrent cases than in primary cases. The primary cases showed high sensitivity to ADR or CQ, and the recurrent cases showed high sensitivity to ADR. Histologically, papillotubular or medullary tubular carcinoma showed high sensitivity to CQ, and scirrhous carcinoma showed high sensitivity to ADR, CQ or 5-FU. The sensitivities of medullary tubular or scirrhous carcinoma to ADR, 5-FU and CQ in patients with stage III and IV were lower than those in patients with stages I and II. No difference of ACA sensitivity was observed between estrogen receptor (+) and (-) cases. All recurrent cases were treated with 5-FU or its derivatives. The 50% survival period in the 5-FU high sensitivity (I.R. greater than 80%) group was 7.0 months and that of the low sensitivity (I.R. less than 80%) group 3.0 months, respectively.

Adenocarcinoma↗

Update in cancer chemotherapy: genitourinary tract cancer, Part 3: Cancer of the prostate.

An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series: included are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 3 is a review of treatments for cancer of the prostate.The role of cancer chemotherapeutics as adjuvant therapy and in combination modalities in the treatment of prostatic carcinoma has yet to be determined. No single agent or combination can be considered standard therapy. The role of chemotherapy in prostatic carcinoma needs further definition. Only through randomized trials will better guides to better treatment be established.

Adenocarcinoma↗

[Neoadjuvant chemotherapy with tegafur suppository for rectal cancer--effects of tegafur on nuclear DNA content of cancer cells--Tochigi Colorectal Cancer Study Group].

To assess the significance of neoadjuvant chemotherapy for large bowel cancer, we investigated an effect of tegafur on cancer cell kinetics by DNA content flow cytometric analysis. The pathologic specimens analyzed in this study were obtained from 28 patients with rectal cancer who had received tegafur suppositories prior to surgery. Mean cumulative doses administered were 13.4 g, and mean duration was 12.7 days. In 24 of the 28 specimens, the DNA ploidy and DNA index of the cancer cells were essentially unchanged after the chemotherapy, and DNA aneuploidy was present in 67%. The proportion of cells in S-phase in DNA aneuploid tumors was significantly higher than in DNA diploid tumors. The proportion of cells in G0G1-phase was inversely correlated to that in S-phase. After the chemotherapy, the proportions of cells in S-phase increased both in DNA diploid and aneuploid tumors, although a significantly higher mean value was found only for the latter (p < 0.05). In the DNA aneuploid tumors, there was a higher frequency of responders confirmed by histological evaluation (44%) as compared to the DNA diploid tumors (25%), and a tendency for increases in S-phase fraction of the responders to be greater than in non-responders. These results suggest that DNA flow cytometry-derived parameters may conceivably be useful in predicting the antitumor effect of 5-FU and its derivatives against large bowel cancer.

Aged↗