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PubMed1986

Systemic infusional chemotherapy for liver metastasis: an improved schedule for 5-fluorouracil.

The clinical studies of infusion schedules for cancer chemotherapy have established that this schedule substantially alters the pattern of drug toxicity without necessarily compromising therapeutic effectiveness. Although increased tumor cell killing has not been definitively established, in at least two prospective comparative trials of 5-FU the infusion schedule was superior to bolus delivery in terms of response rate. It is possible that the infusion schedule may be the primary determinant of the effectiveness of hepatic arterial chemotherapy, and preliminary reports of prospective trials comparing systemic infusion with hepatic infusion do suggest that response rates for both routes are similar. An important consideration with regard to infusion schedules is establishing whether or not tumor cell resistance is augmented by the continuous exposure. Almost all chronic disease therapy necessitates maintaining adequate drug levels to ensure disease control including infections, seizure disorders, arthritis, and cardiovascular diseases. For cancer, the intermittent schedule of drug delivery has been dictated by the concept of the primacy of dose and the substantial toxicity associated with these agents. With the technological capability of providing an ambulatory setting for infusion chemotherapy and the substantial modification of toxicity, therapeutic regimens may be more cost effective with the constant infusion schedule.

Clinical Trials as Topic↗
PubMed1993

Occupational physical activity, socioeconomic status, and risks of 15 cancer sites in Turkey.

A multiple-site case-control study of 15 cancers (stomach; colon; rectum; larynx; lung; melanoma; skin; female breast; male breast; cervix; ovary; uterus; prostate; testis; and bladder) was conducted to evaluate their association with occupational physical activity and socioeconomic status (SES). A hospital-based study population (3,486 male cases and 379 female cases, and 2,127 male and 244 female controls) was established in an oncological treatment center in Istanbul, Turkey, from 1979-84. Assessment of physical activity and SES was based on job titles held by the study subjects. Two measures of physical activity were developed based on energy expenditure and 'sitting time' during working hours. Observed risks were adjusted for age, smoking, and SES. Elevated risks were observed among workers who held sedentary jobs for cancers of the colon (odds ratio [OR] = 1.6), rectum (OR = 1.3), melanoma (OR = 1.9), male breast (OR = 1.4), prostate (OR = 5.0), and ovary (OR = 2.0). Cancers of the cervix and uterus showed significantly decreasing risks with decreased activity. Risks of cancers of the colon, rectum, larynx, ovary, and melanoma were enhanced after risks for physical activity indices were adjusted for SES, while the associations between physical activity and cancers of the prostate, cervix, and uterus were weakened after SES adjustment. Risks of melanoma rose significantly with both activity indices after SES adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1996

Smoking habits and risk of cancers other than lung cancer: 28 years' follow-up of 26,000 Norwegian men and women.

The impact of tobacco smoking on lung cancer risk has been investigated thoroughly since the 1950s, but other types of cancer also have been associated with smoking. In the present study, the aim was to explore the variation in risk connected with cigarette, cigar, and pipe smoking of suspected smoking-associated cancers other than lung cancer. Data were obtained from a survey of a random sample of the Norwegian population. A self-administered mailed questionnaire, which included questions about smoking habits, was completed by 26,000 men and women in 1965 (response rate: 76 percent). The cohort was followed from 1966 through 1993, including registration of all incident cancer cases. A dose-response relationship of cigarette smoking to the risk of urinary bladder cancer and cancers of the upper digestive and respiratory tract was observed. For the latter forms of cancer, a dose-response relationship of pipe smoking also was observed. In cancer of the pancreas, a stronger association between cigarette smoking and cancer risk was observed when the analysis was confined to histologically confirmed cases only. Current cigarette smokers at baseline had a significantly higher risk of cervical cancer than those who never smoked cigarettes. In cancers of the stomach, colon, rectum, breast, corpus uteri, ovary, and prostate, and in leukemia, no association between smoking and cancer risk was observed.

Adult↗
PubMed1990

Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption.

International variations and national time trends in disease rates suggest major associations between dietary fat and several important cancers. In contrast, case-control and cohort studies of dietary fat in relation to the same cancers generally report weak associations, or have failed to detect any association with fat intake. This study was undertaken in an attempt to understand the apparent discrepancy between these observations. The results provide an insight into the magnitude of cancer risk reduction that may follow from a practical reduction in dietary fat. Regression analyses of international variations in cancer incidence rates were used to estimate relative risks (RR) as a function of fat intakes for both males and females. These analyses focused on cancers of the breast, colon, rectum, ovary, and endometrium in females, and colon, rectum, and prostate cancers in males. Ages 55-69 and 30-44 were considered in order to compare RR estimates between an older and younger age group, and between post- and pre-menopausal women. Corresponding RR estimates were also calculated, based on the regression of changes in disease rates from the mid-1960s to 1980 on changes in dietary fat, using data from several countries. A strong degree of consistency with the RR estimates from international comparisons was observed. The international regression analyses were also used to project changes in cancer rates among Japanese migrants to the United States. A high level of consistency with the observed disease-rate changes was noted. Similarly, the international data analyses were used to project RRs for the fat intake categories used in specific case-control and cohort studies, while acknowledging measurement error in individual dietary assessment. Although certain exceptions are noted, considerable consistency was found between the aggregate and analytic data results, leaving open the strong possibility that a practical reduction in dietary fat could result in a major reduction in the incidence of several prominent cancers in the United States and in other nations having high fat consumption.

Adult↗
PubMed1995

Cancer in Mediterranean migrants--based on studies in France and Australia.

Whether non-European Mediterranean populations also benefit from the protective effect on health of the so-called Mediterranean diet is not know yet, as national mortality statistics are available in neither North Africa nor the Near East. This article investigates the cancer profile of Maghrebian and Near Eastern migrants, by gathering and discussing data from recent studies on cancer mortality in Mediterranean migrants of various origins in France and Australia. In France, the migrants originating from Morocco, and in Australia, the migrants originating from the Near East, have a lower mortality from all cancers than their host countries and than Italian migrants. Concerning specific sites, Moroccan and Near Eastern migrants have a cancer profile which is quite similar to that of the Italian migrants, with relatively low risks compared with the local-born for certain cancers typical of affluent societies (colon and rectum, breast, ovary, and prostate). In addition, the non-European Mediterranean migrants are protected even more than the Italians in the same host country from esophagus cancer, and Moroccans in France have a much lower risk than the local-born for lung cancer. Lastly, they tend to have a relatively high risk for some cancers which are likely to have a viral etiology: e.g., nasopharynx (Italians and Near Easterners), liver (Near Eastern males), and possibly cervix (Moroccans).

Africa, Northern↗
PubMedDate not supplied

Distribution of metastases at necropsy in colorectal cancer.

A series of 372 necropsies on patients with colorectal cancer (CRC) was examined retrospectively. Patients were excluded if the primary tumour was not removed, if the operation was palliative or if death occurred within three months of operation. Only 43 cases remained after these exclusions and of these six died of intercurrent disease. The 37 remaining patients were all thought to have undergone a curative resection, following which they died with recurrent tumour. They represent the group of patients who might have benefited from adjuvant chemotherapy. The pattern of metastases and the cause of death was examined in these 37 patients. Local recurrence was found more commonly (25 cases, 68 per cent) than hepatic metastases (21 cases, 57 per cent) or metastases at other sites. This finding indicates that excision of the primary tumour must be as complete as possible and that adjuvant therapies must be directed both locally as well as systemically.

Adult↗
PubMed1989

Phase I clinical and pharmacokinetic study of LY 195448.

LY 195448 is a phenethanolamine that has shown anti-tumour activity in a range of murine tumour models, although its mechanism of action is unknown. Pre-clinical studies have indicated the absence of "standard" side effects such as myelosuppression and gastrointestinal toxicity. The present phase I trial was carried out in nine patients at doses ranging up to 133 mg/m2. The major toxicities up to that dose were mild, reversible hypotension, tachycardia and tremor. No haematological or biochemical toxicity was observed. Murine pharmacokinetics were assessed at a dose level that was effective in experimental tumours and compared with human pharmacokinetic parameters derived from this study. The results indicated the clinical possibility of reaching peak drug levels associated with experimental activity. However, no responses were seen at the doses used. This study was terminated prior to its completion due to an unexplained loss of activity against murine tumours since September 1987. No significant loss of the in vitro anti-mitotic activity originally reported by Boder et al. [3] was observed. Possible reasons for the apparent loss of in vivo activity have been intensively investigated, but no cause has been determined. Therefore, clinical trials with LY 195448 have been discontinued.

Adult↗
PubMed1985

In vitro evaluation of anticancer drugs in relation to development of drug resistance in the human tumor clonogenic assay.

The efficacy of anticancer drugs against ovarian cancer, breast cancer, and colorectal cancer has been evaluated in vitro by the human tumor clonogenic assay developed by Hamburger and Salmon. The in vitro colony assay method used in this study is a minor modification of their method and was used in 83 patients with ovarian cancer, 47 patients with breast cancer, and 13 patients with colorectal cancer. The total numbers of assays performed in vitro were 258 for ovarian cancer, 87 for breast cancer, and 38 for colorectal cancer. The average chemosensitivity rates to single agents tested were 35% and 32% in the untreated patients with ovarian and breast cancer, respectively. In contrast to this result, the chemosensitivity rate of the untreated patients with colorectal cancer was only 16%. Consisting the clinical efficacy of anticancer drugs against these tumors, these results suggest that there is a correlation between chemosensitivity in the human tumor clonogenic assay and clinical responsiveness. In this assay the chemosensitivity in specimens from ovarian cancer patients who had had prior chemotherapy was significantly lower than in those from nonpretreated patients (P less than 0.05). This seems to indicate the development of drug resistance after treatment with anticancer drugs. These results suggest that the human tumor clonogenic assay is a useful tool for the evaluation of antitumor effects of drugs in vitro.

Antineoplastic Agents↗
PubMed1975

[The evaluation of the cyclophosphamide sensitivity of human tumours by determining the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumor cells in vitro in presence of 4-hydroxycyclophosphamide (author's transl)].

A new in vitro assay for screening the sensitivity of human tumour cells against Cyclophosphamide has been developed. While biologically activated Cyclophosphamide was unsuitable because of unpurities in the material, synthetic 4-Hydroxycyclophosphamide was shown to inhibit the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumour cells in vitro. 29 tumours including 14 mammarial carcinomas, 8 ovarial carcinomas and 7 other malignant tumours were tested. While 12 tumours showed a significant and 5 only a slight inhibition of the 3H-uridine incorporation in vitro. 12 tumours showed no effect. Histologically none-differentiated tumours were more sensitive against 4-Hydroxycyclophosphamide as compared with the more differentiated ones. First observations point to 4-Hydroperoxycyclophosphamide instead of 4-Hydroxycyclophosphamide as a more suitable form of activated Cyclophosphamid for the in vitro assay of Cyclophosphamide sensitiveness because of the higher stability and better availability of this compound.

Antineoplastic Agents↗
PubMed1993

Distribution of type-VII collagen in xenografted human carcinomas.

The distribution of type-VII collagen, the main molecular component of the anchoring fibrils (AF) attaching the basal lamina (BL, lamina densa of the basement membrane) to the surrounding connective tissue, was investigated in four xenografted human carcinomas of the hypopharynx (H-Stg 1), the lung (L 261), the sigmoid colon (CA 1), and the rectum (R 85). The studies were performed with a recently prepared, affinity-purified and highly specific antibody to type-VII collagen by using the indirect immunofluorescence and the APAAP (alkaline phosphatase anti-alkaline phosphatase) techniques. For comparison, the localization of the intrinsic BL components laminin and type-IV collagen were additionally analyzed in all four carcinomas. It was shown that type-VII collagen usually colocalized to laminin and type-IV collagen and was deposited at the borderline between carcinoma cell clusters and the surrounding strands of connective tissue in a similar, but more diffuse and less continuous distribution than both intrinsic BL components. In the squamous cell carcinoma H-Stg 1 and the adenocarcinoma L261, type-VII collagen was additionally accumulated in enlarged extracellular spaces between carcinoma cells, away from the contact zone to the connective tissue and again colocalized to laminin and type-IV collagen. Numerous carcinoma cells of both xenografts showed remarkable intracytoplasmic immunoreactivity for the antibody to type-VII collagen. Even in the case of the gastrointestinal carcinomas CA 1 and R 85, faint immunoreactivity for type-VII collagen was found at the contact zone between the mucosal epithelium and the surrounding connective tissue. These results confirm that epithelial carcinoma cells are obviously involved with the synthesis of the main molecular component of AF usually attaching the BL to the adjacent connective tissue and hint at a possible correlation between the localization of type-VII collagen and the observed pattern of the BL. However, it cannot be decided whether there is a direct causal relation between both phenomena or whether they are both the consequence of an independent but common cause, such as abnormal cellular differentiation of carcinoma cells. In no case, can the discontinuities in the distribution of type-VII collagen be explained by active tumor cell invasion since xenografted human carcinomas neither invade nor metastasize.

Adenocarcinoma↗
PubMed1991

Organoid reorganization of human tumors under in vitro conditions.

In the present study we describe a new method to cultivate human tumors, which allows organoid differentiation under in vitro conditions. Diverse tumors of different origin and various histopathology which had been heterotransplanted to athymic mice were dissociated into single cells and seeded at high cell density onto a membrane filter consisting of cellulose nitrate at the gas-medium interface. Within a few days, the tumor cells reorganized and differentiated into organoid structures which exhibited the typical histological characteristics of the original tissues. Due to the formation of organoid aggregates, which was also previously seen with normal fetal cells, this type of culture has been described as 'organoid culture'. In the case of adenocarcinomas of the lung and the colon including the rectum, glandular structures with central lumina, adjacent microvilli, and junctional complexes were formed. Numerous specific intercellular contacts such as desmosomes and tight junctions occurred as well as interdigitations of adjacent cell membranes. In a tumor of the rectum, a typical brush border differentiated at the surface of the reorganized tumor-tissue aggregate. Epidermoid carcinomas of the head and neck developed structures resembling the spinous layer of the epidermis, exhibiting numerous desmosomes and intracytoplasmic bundles of tonofilaments radiating into the desmosomes. Most tumors produced a fragmentary monolayered or multilayered basal lamina of similar morphological appearance as under in vivo conditions. These results illustrate the organoid reorganization and differentiation of human tumor cells under the experimentally rather simple conditions of the organoid culture systems and clearly demonstrate that this in vitro system comes close to the in vivo situation as far as certain differentiation phenomena are concerned.

Adenocarcinoma↗
PubMed1984

A case of bilateral Wilms' tumour of the kidneys and the retrourethral region.

Bilateral Wilms' tumour of the kidneys and the retrouretheral region in a 52-day-old boy is reported. These tumours are of the same histological appearance, similar to that of a malignant rhabdoid tumour of the kidney. We suggest that these tumours have arisen from the mesonephric duct or the mesonephros and Wilms' tumour may have originated from mesonephros or an even earlier developmental stage.

Autopsy↗