Biomedical subjects
Publications and source records attributed to S Chaitchik.
Three cases of renal cell carcinoma in a congenital solitary kidney are presented. Treatment with recombinant interferon alpha-C was administered in two cases. A subjective response occurred in one case. The literature is reviewed with respect to treatment options and prognostic factors.
Five out of 38 patients (13%) with metastatic renal cell carcinoma had mental deterioration 3 weeks to 13 months after the start of treatment with recombinant interferon alpha-C. Metastatic spread to the brain, paraneoplastic effect of the tumor on the central nervous system and other causes of dementia were excluded. Computed tomography of the brain in these patients was normal and the width of the cerebral sulci and ventricles did not correlate with the severity of dementia. Specific patterns of atrophy were not seen. General deterioration, assessed by the change in Karnofsky performance status, was associated with dementia. The dementia may have been caused by a neurotoxic effect of interferon.
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Though the benefits of early detection of breast cancer are generally known, only few women attend breast-screening examinations. The study was designed to gain insight into the problem by exploring the psychological profile of clinic attenders. In order to find out whether there is such a profile, 210 self-referred women were compared with 210 nonattending women, from the same working and social environments, matched in age, education and occupational level. All subjects were administered 10 tests in 7 domains. The tests were administered as part of a health survey. The results showed that clinic attenders scored higher on negative emotions and total emotions and lower on positive emotions; higher on repression; lower on daydreams; lower on range of self-concept, references to others and negative self-references but higher on positive self-references; scored higher on self-references describing oneself in a functional and in a passive way and scored lower on those describing oneself in terms of one's attitudes, body and appearance; scored lower on neuroticism; scored lower on different somatic complaints and health orientation but higher in alexithymia. No differences were found in authoritarianism, locus of control and self-complexity. Conclusions are that there is a psychological profile of clinic attenders, that it is focused on dysphoric emotions, psychological disease promotion and defensiveness and that it includes characteristics of the construct that is sometimes called the cancer-prone personality.
Recombinant interferon alpha-C is a new strain of the alpha interferon family. It was given to 33 patients with measurable metastatic renal cell carcinoma of whom 31 were evaluable. Protocol consisted of 3 million U/d for 2 weeks, then 3 million U/m2 every other day until progression. No complete response was observed. Three patients (9.7%) had partial response for a mean duration of 5.6 months and eight patients (25.8%) were stabilized for a mean of 4.3 months. Responsive sites were mainly lung, bone, and kidney, while side effects were generally mild. better results were observed in previously nephrectomized patients who had not received chemotherapy or hormonotherapy for recurrent or metastatic disease (p less than 0.05), and also in patients with a brief disease-free interval and short delay from presenting symptoms of the primary tumor until interferon treatment (p less than 0.05). Median survival was significantly longer in responders than in progressors (p less than 0.05). We suggest that the efficacy of recombinant interferon alpha-C in a low-dose regime versus other types of interferon as first-line therapy for inoperable, metastatic, or locally recurrent renal cell carcinoma should be investigated in a prospective, controlled, randomized study.
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alpha-Interferon, 3 x 10(6) U/m2 every other day, and dacarbazine, up to 800 mg/m2 every 3 weeks, were given to nine patients with metastatic malignant melanoma who had progressed on a combination of interleukin-2 and dacarbazine. Partial response was documented in two patients for 9 and 4 months. Responsive sites were the lungs, lymph nodes, liver, and skin. Failure to respond to one biologic response modifier does not predict the response to another modifier.
Time-dependent toxicity of 3 anti-cancer drugs was demonstrated in BALB/c mice. Cisplatinum, adriamycin and cyclophosphamide were injected at 4 different circadian stages, either together (combined injection) or separately, to different groups of mice. Toxicity was evaluated by body-weight changes, mortality and white blood cell counts. Maximal body-weight loss was caused by the administration of either Cisplatinum or the combination of all 3 drugs at 15.00 hr and 21.00 hr, i.e., 9 and 15 hr after light on (HALO). Only moderate body weight loss was induced when adriamycin was injected at 09.00 hr or at 21.00 hr (3 and 15 HALO). In contrast to Cisplatinum and adriamycin, cyclophosphamide induced no significant change in body weight when injected at either time. The highest level of mortality was caused by the injection of all 3 drugs together at 21.00 hr (15 HALO). No death occurred when drugs were administered separately. The rate of recovery (as assessed by weight regain) also exhibited dependence upon the time of drug administration and was the slowest after injections at 21.00 hr (15 HALO). It appears, therefore, that the time-dependence modes of toxicity and recovery (as assessed by body-weight change) are different. The decrease in white blood cell count also exhibited a time-dependence pattern which differed from that of weight loss and death.
We have generated a mouse monoclonal antibody (H23) against the retrovirus-like particles (human mammary tumor virus) released in vitro by the human breast adenocarcinoma cell line T47D. This antibody reacts specifically with a glycoprotein with an apparent molecular mass of 68 kDa (gp68) that is detected in the growth medium of T47D cells as well as in pleural effusion fluids from breast adenocarcinoma patients. No detectable levels of this antigen could be observed in pleural effusions of patients with cancers other than of breast origin. The H23-related antigen was localized in the cytoplasm of breast tumor cells as well as on the cell surface of both T47D cells and metastatic cells from breast cancer patients. A survey of tissue from 812 patients was performed by using H23 in an indirect immunoperoxidase assay. The results showed that the antigen was detectable in 91% of all breast tumors tested. No cytoplasmic staining was observed in either normal tissues or nonbreast carcinomas. Only one of the benign breast tissues tested (out of a total of 56 samples of tissue) was positive for this antigen. Given the ability of this antibody to specifically detect breast tumor cells, H23 may be of importance in diagnosis and in clinical follow-up of patients for the detection of metastatic lesions by imaging and for therapy.
Renal Cell Carcinoma (RCC) in a single kidney is a rare occurrence, more so when it concerns agenesis of the kidney. Chemotherapy of metastatic renal cell carcinoma has a poor effect. We report a case of a man, 49 years of age, with agenesis of one kidney, admitted with a metastatic RCC of his only kidney. Survival of 15 months duration was achieved by therapy combining Provera, Vinblastine and Alpha-C-Recombinant Interferon.
A significant accumulation of copper, zinc, iron, rubidium and bromine, in addition to platinum, was observed in kidneys and liver of mice treated with cis-DDP. This observation suggests that the toxicity of cis-DDP is due to the overall accumulation of trace elements and not only to the expected high platinum levels. Sodium selenite administration prior to cis-DDP results in fast clearance of all these trace elements from kidneys and liver; control levels are reached within 6 days. This may explain the important reduction in cis-DDP toxicity following selenite administration. An X-ray fluorescence (XRF) facility was used for the evaluation of the trace elements.
The SCM test (structuredness of the cytoplasmic matrix) consists of measuring the fluorescence polarization of fluorescein which is introduced into a particular sub-group of peripheral lymphocytes. The test has a non-specific part for the general detection of cancer and a specificity procedure which is based on the use of specific cancer extracts. In this article we deal only with the latter in relation to breast cancer. Blood samples from 94 patients have been tested; six of these had mastectomy performed previously; 83 underwent consecutively a surgical procedure and histology was obtained; five were only clinically examined. In 45/49 (92%) patients, correlation between a positive specificity test and tissue malignancy was found. Out of 35 patients with non-malignant proliferative lesions (as found by histology), 25 reacted positively in the test. Two out of five patients with non-malignant, non-proliferative lesions reacted positively in the test. Five patients who were defined as normals by clinical examination reacted negatively in the test. These results indicate the potential of the SCM test for detecting breast malignancy. The clinical implications of the test for cancer diagnosis are discussed.
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The gastrointestinal (GI) tract is a common site for malignant melanoma. Diagnosis of lesions in the GI tract is usually delayed until complications occur, such as obstruction, bleeding, or perforation of the GI tract. Of 348 patients with malignant melanoma treated during a 10-year period, 11 had GI involvement either in a metastatic form or as a primary melanoma. Three of these patients were treated surgically for metastatic lesions in the small bowel causing intussusception, two for peritonitis secondary to perforation of the small bowel, and one for massive bleeding from metastatic melanoma in the stomach. Another patient had a primary melanoma in the esophagus and underwent esophagectomy. Three patients had primary melanomas of the anal canal and one of the rectum. Three of them underwent abdominoperineal resections, and two had bilateral groin dissection in addition. Six of the patients are alive 6 months to 4 years following diagnosis. The remaining five died of metastatic melanoma from 6 months to 4 years post-surgery.
Clinical and experimental data suggest a synergistic antitumoral effect with the combined treatment of radiotherapy and 5-fluorouracil (5-FU) serving as a radiosensitizer. This combined modality was studied in 30 malignant melanoma patients with advanced locoregional or isolated, bulky, soft-tissue or visceral metastases. All patients were symptomatic, pain being the chief complaint, followed by symptoms related to large tumors. Treatment was given on an ambulatory basis, twice weekly, and consisted of 5-FU, 500 mg/m2 administered in 8-h i.v. drip infusion, followed by radiotherapy 8 h after completion of the 5-FU administration. 60Co teleunit, delivering 400 rad per dose per fraction, was given over 6 1/2 weeks to a total of 5,200 rad. The overall response rate was 70% (21 of 30 patients). Three patients (10%) achieved a complete response lasting from 3 to 11 months, and 18 (60%) achieved a partial response lasting from 3 to 13 months. The response rate was 82% for skin, 75% for lymph node, and 43% for visceral metastases. Symptomatic relief was obtained in 83% (25 of 30) of the patients. This palliative therapy was well-tolerated, and patients were able to maintain their routine lifestyles throughout. Only in one patient was 5-FU abandoned after 3 weeks, due to cardiac ischemia. Similar response rates have only been achieved with radiotherapy alone employing individual fractions of 600 rad or higher. Since the 5-FU we added is known to have a very limited effect on malignant melanoma, this study suggests its potential as a radiosensitizer in malignant melanoma.
In order to analyze which features determine a poorer prognosis we undertook a study of 91 consecutive patients with pathological Stage I breast cancer operated on at Beth Israel Medical Center (1968-71). Tumor tissue slides were reviewed and features such as: tumor size, histologic type, nuclear grade, lymphocytic and perivenular lymphocytic infiltration, as well as sinus histiocytosis in the lymph nodes removed. Records were reviewed and classified according to age and ethnic background. Survival and recurrence data were recorded up to 14 years post-mastectomy. Also determined was the presence of an antigen, previously detected in certain human breast cancer tumor tissues, which has been found to cross-react immunologically with the 52,000 dalton major envelope protein of the mouse mammary tumor virus (MMTV--gp52). Ten-year cumulative disease-free survival was 0.65. Univariate analysis of survival within various factors revealed that the only statistically significant influencing factor was the presence or absence of the antigen. Factors such as perivenous lymphocytic infiltration, diffuse lymphoid infiltration and sinus histiocytosis in regional lymph nodes also showed trends in favor of improved survival but the sample may be too small for statistical significance. The presence or absence of the antigen was independent of the host immunological reaction. There was no relationship between localization of tumor, whether medial or lateral and survival, nor with presence or absence of antigen.
Biopsies from 61 women with breast cancer were assessed for various histological features. These results were statistically analyzed for associations of gross tumor size, patient age, stage of disease, tumor hormone receptor status, with accepted systems of nuclear and histological grading for differentiation. Tumors with highly differentiated grading had smaller cell nuclei, stromal elastasis, intraduct carcinoma and tubular formations. Poorly differentiated tumors had large vesicular cell nuclei and increased mitotic indices. Gross tumor size was also linked with stromal elastosis, intraduct carcinoma, a specific pattern of stromal infiltration, and mitotic index. No relationship could be found between any of the above features and the patients clinical statuses or their tumors' hormone receptivities. The existence of two distinct histological patterns of breast carcinoma is proposed; the patterns may either represent stages in the development of the tumor or different biological types.