The effect of recombinant human tumor necrosis factor (TNF) on the capillary growth was evaluated using an in vitro angiogenesis model recently developed. Sprague-Dawley rat microvessel fragments, from epididymal fat pads, seeded onto the confluent culture of myofibroblastic cells from the same tissue origin, gave rise to microvascular networks on and in the multilayered myofibroblastic cells. In contrast, the capillary growth from the vessel fragments was markedly inhibited in the presence of 10-1,000 U TNF/ml. Monoclonal antibody against TNF completely neutralized the capillary growth inhibitory activity of TNF. The mode of angiogenesis inhibitory action of TNF was also examined by use of bovine capillary endothelial (BCE) cells and rat myofibroblastic cells. TNF exerted growth inhibitory and cytotoxic actions against BCE cells cultivated on the various basement membrane components, such as extracellular matrix secreted by BCE cells, fibronectin, laminin, and type IV collagen. An irreversible damage to most of the BCE cells was observed ultrastructurally after 60 hours' exposure to TNF. TNF, however, did not injure the myofibroblastic cells but rather stimulated their growth. These findings indicate that TNF inhibits in vitro capillary growth by its direct cytostatic and cytotoxic actions to microvascular endothelial cells.—JNCI 1987; 79:1383-1391.
利用新近建立的体外血管生成模型评价重组人肿瘤坏死因子（TNF）对毛细血管生长的影响。将Sprague-Dawley大鼠附睾脂肪垫的微血管片段植入到来自同一组织来源的肌成纤维细胞的融合培养中，在多层肌成纤维细胞上和细胞内产生微血管网络。相比之下，在10-1,000 U TNF/ml的存在下，血管碎片的毛细血管生长明显受到抑制。抗TNF单克隆抗体完全中和TNF的毛细生长抑制活性。利用牛毛细血管内皮细胞（BCE）和大鼠肌成纤维细胞，研究了TNF抑制血管生成的作用模式。TNF对培养在各种基底膜成分上的BCE细胞有生长抑制和细胞毒性作用，如BCE细胞分泌的细胞外基质、纤维连接蛋白、层粘连蛋白和IV型胶原。暴露于TNF 60小时后，在超微结构上观察到大多数BCE细胞的不可逆损伤。然而，TNF不会损伤肌成纤维细胞，反而会刺激它们的生长。这些发现表明，TNF通过其对微血管内皮细胞的直接细胞抑制和细胞毒性作用抑制体外毛细血管生长。-JNCI 1987;79:1383 - 1391。
{"title":"Tumor Necrosis Factor Inhibiting Angiogenesis In Vitro","authors":"Noboru Sato, Koichi Fukuda, Hideo Nariuchi, Nakami Sagara","doi":"10.1093/jnci/79.6.1383","DOIUrl":"https://doi.org/10.1093/jnci/79.6.1383","url":null,"abstract":"The effect of recombinant human tumor necrosis factor (TNF) on the capillary growth was evaluated using an in vitro angiogenesis model recently developed. Sprague-Dawley rat microvessel fragments, from epididymal fat pads, seeded onto the confluent culture of myofibroblastic cells from the same tissue origin, gave rise to microvascular networks on and in the multilayered myofibroblastic cells. In contrast, the capillary growth from the vessel fragments was markedly inhibited in the presence of 10-1,000 U TNF/ml. Monoclonal antibody against TNF completely neutralized the capillary growth inhibitory activity of TNF. The mode of angiogenesis inhibitory action of TNF was also examined by use of bovine capillary endothelial (BCE) cells and rat myofibroblastic cells. TNF exerted growth inhibitory and cytotoxic actions against BCE cells cultivated on the various basement membrane components, such as extracellular matrix secreted by BCE cells, fibronectin, laminin, and type IV collagen. An irreversible damage to most of the BCE cells was observed ultrastructurally after 60 hours' exposure to TNF. TNF, however, did not injure the myofibroblastic cells but rather stimulated their growth. These findings indicate that TNF inhibits in vitro capillary growth by its direct cytostatic and cytotoxic actions to microvascular endothelial cells.—JNCI 1987; 79:1383-1391.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert Kiss, Yvan de Launoit, Mireille L'Hermite-Balériaux, Marc L'Hermite, Robert J Paridaens, Andre J Danguy, Jean-Lambert Pasteels
With the use of an in vivo tritiated thymidine ([3H]dThd) nuclear labeling followed by autoradiography, the effects at different times before sacrifice of prolactin (PRL) and/or 17β-estradiol (E2) were studied in C57BL × DBA/2f)F1 mice given transplants of the MXT hormone-sensitive mammary tumor whose growth was previously shown to be influenced by E2 and/or progesterone. Uteri were chosen as controls for the methodology. Experiments were conducted on ovariectomized mice submitted to endocrine manipulation to achieve plasma PRL modifications. In addition to E2, the proliferation of cancer cells, assessed by the measurement of thymidine labeling indices (TLIs), was demonstrated to be enhanced by ovine prolactin (oPRL) and Sulpiride and strongly slowed down by castration and 2-bromo-α-ergokryptin treatment, thus emphasizing the great importance of PRL in mammary cancer development. Moreover, a pulse of 1 mg oPRL/animal produced a marked TLI rise in tumors, lasting from the 6th to the 48th hour after its injection and reaching a maximum at 24 hours. PRL had no proliferative effect on the uterine luminal epithelium. When PRL and E2 were injected concomitantly, the profile of stimulation was quite similar to that obtained with E2 alone; i.e., a maximum stimulation was observed at the 24th and 36th hours after hormonal pulse. From these data it is concluded that, in spayed mice, not only E2 but also PRL is of major importance leading to enhanced proliferation of MXT mammary neoplastic cells. Further investigations are needed to throw light on the cellular events presiding over the action of PRL and E2 at the cancer cell level.—JNCI 1987; 78:993-998.
{"title":"Effect of Prolactin and Estradiol on Cell Proliferation in the Uterus and the MXT Mouse Mammary Neoplasm","authors":"Robert Kiss, Yvan de Launoit, Mireille L'Hermite-Balériaux, Marc L'Hermite, Robert J Paridaens, Andre J Danguy, Jean-Lambert Pasteels","doi":"10.1093/jnci/78.5.993","DOIUrl":"https://doi.org/10.1093/jnci/78.5.993","url":null,"abstract":"With the use of an in vivo tritiated thymidine ([3H]dThd) nuclear labeling followed by autoradiography, the effects at different times before sacrifice of prolactin (PRL) and/or 17β-estradiol (E2) were studied in C57BL × DBA/2f)F1 mice given transplants of the MXT hormone-sensitive mammary tumor whose growth was previously shown to be influenced by E2 and/or progesterone. Uteri were chosen as controls for the methodology. Experiments were conducted on ovariectomized mice submitted to endocrine manipulation to achieve plasma PRL modifications. In addition to E2, the proliferation of cancer cells, assessed by the measurement of thymidine labeling indices (TLIs), was demonstrated to be enhanced by ovine prolactin (oPRL) and Sulpiride and strongly slowed down by castration and 2-bromo-α-ergokryptin treatment, thus emphasizing the great importance of PRL in mammary cancer development. Moreover, a pulse of 1 mg oPRL/animal produced a marked TLI rise in tumors, lasting from the 6th to the 48th hour after its injection and reaching a maximum at 24 hours. PRL had no proliferative effect on the uterine luminal epithelium. When PRL and E2 were injected concomitantly, the profile of stimulation was quite similar to that obtained with E2 alone; i.e., a maximum stimulation was observed at the 24th and 36th hours after hormonal pulse. From these data it is concluded that, in spayed mice, not only E2 but also PRL is of major importance leading to enhanced proliferation of MXT mammary neoplastic cells. Further investigations are needed to throw light on the cellular events presiding over the action of PRL and E2 at the cancer cell level.—JNCI 1987; 78:993-998.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gerald Shklar, Joel Schwartz, Diane P Trickler, Khadjik Niukian
Vitamin E was shown to regress established epidermoid carcinomas of Syrian hamster buccal pouch in 20 experimental animals following tumor induction by applications three times a week of 0.5% 7,12-dimethylbenz[a]anthracene (CAS: 57-97-6) in mineral oil for 13 weeks. The vitamin E was injected into the tumor-bearing buccal pouch twice weekly for 4 weeks in a dose of 250 μg in minimum essential medium. Twenty animals were maintained as untreated controls, and another 20 animals were sham-inoculated vehicle controls. Microscopic examination of buccal pouches with regressed tumor showed small epidermoid carcinomas with degeneration of tumor cells and a dense infiltrate of leukocytes, lymphocytes, and histiocytes. Buccal pouches of control animals showed large well-differentiated or moderately differentiated epidermoid carcinomas. The hamster buccal pouch cancer model presents many similarities to human oral cancer, including expression of the same oncogene, and these results offer hope for the chemotherapy of human oral cancer with the use of a relatively nontoxic agent injected locally.—JNCI 1987; 78:987-992.
{"title":"Regression by Vitamin E of Experimental Oral Cancer","authors":"Gerald Shklar, Joel Schwartz, Diane P Trickler, Khadjik Niukian","doi":"10.1093/jnci/78.5.987","DOIUrl":"https://doi.org/10.1093/jnci/78.5.987","url":null,"abstract":"Vitamin E was shown to regress established epidermoid carcinomas of Syrian hamster buccal pouch in 20 experimental animals following tumor induction by applications three times a week of 0.5% 7,12-dimethylbenz[a]anthracene (CAS: 57-97-6) in mineral oil for 13 weeks. The vitamin E was injected into the tumor-bearing buccal pouch twice weekly for 4 weeks in a dose of 250 μg in minimum essential medium. Twenty animals were maintained as untreated controls, and another 20 animals were sham-inoculated vehicle controls. Microscopic examination of buccal pouches with regressed tumor showed small epidermoid carcinomas with degeneration of tumor cells and a dense infiltrate of leukocytes, lymphocytes, and histiocytes. Buccal pouches of control animals showed large well-differentiated or moderately differentiated epidermoid carcinomas. The hamster buccal pouch cancer model presents many similarities to human oral cancer, including expression of the same oncogene, and these results offer hope for the chemotherapy of human oral cancer with the use of a relatively nontoxic agent injected locally.—JNCI 1987; 78:987-992.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The effects of glycosaminoglycans and several enzymes on the integrity of the human placental amnion and the consequent effects on the permeability of this structure to virally transformed cells and their parent line were examined. Treatment of the amnion with hyaluronate, heparin, and chondroitin ABC lyase affected the structure of both the epithelium and the extracellular matrix and resulted in a significant increase in tumor cell invasion, but it had no significant effect on the invasion of the parent cell line. These polymers promoted the disorganization of the epithelial cell layer, and their presence resulted both in the matting of collagen fibrils in the stroma and in the loosening of the basement membrane. Pronase treatment removed epithelial cells and stripped collagen fibrils of granules, but it did not promote tumor or parent cell invasion, perhaps as a result of loss of attachment factors. Chondroitin sulfate did not affect the epithelial structure or the rate of tumor invasion and had only slight effects on the structure of the basement membrane and the stroma. These results are consistent with the thesis that the continuity of epithelium is critical to resisting tumor cell invasion and suggest that glycosaminoglycans, in addition to certain enzymes, can alter this integrity.—JNCI 1987; 78:787-795.
{"title":"Effect of Glycosaminoglycans and Enzymes on the Integrity of Human Placental Amnion as a Barrier to Cell Invasion","authors":"E Turley, M Tretiak, K Tanguay","doi":"10.1093/jnci/78.5.787","DOIUrl":"https://doi.org/10.1093/jnci/78.5.787","url":null,"abstract":"The effects of glycosaminoglycans and several enzymes on the integrity of the human placental amnion and the consequent effects on the permeability of this structure to virally transformed cells and their parent line were examined. Treatment of the amnion with hyaluronate, heparin, and chondroitin ABC lyase affected the structure of both the epithelium and the extracellular matrix and resulted in a significant increase in tumor cell invasion, but it had no significant effect on the invasion of the parent cell line. These polymers promoted the disorganization of the epithelial cell layer, and their presence resulted both in the matting of collagen fibrils in the stroma and in the loosening of the basement membrane. Pronase treatment removed epithelial cells and stripped collagen fibrils of granules, but it did not promote tumor or parent cell invasion, perhaps as a result of loss of attachment factors. Chondroitin sulfate did not affect the epithelial structure or the rate of tumor invasion and had only slight effects on the structure of the basement membrane and the stroma. These results are consistent with the thesis that the continuity of epithelium is critical to resisting tumor cell invasion and suggest that glycosaminoglycans, in addition to certain enzymes, can alter this integrity.—JNCI 1987; 78:787-795.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gernot Grimmer, Horst Brune, Reintraud Deutsch-Wenzel, Gerhard Dettbarn, Jürgen Misfeld
For identification of the substances chiefly responsible for the carcinogenic action of the emission condensate from coal-fired residential furnaces, the implantation method was used as a carcinogen-specific bioassay for comparison of the carcinogenic effect of various fractions with that of a total sample of flue gas condensate tested in 2 or 3 different doses. After implantation into the lungs of Osborne-Mendel rats. the condensate from coal-fired residential furnaces, a fraction containing polycyclic aromatic hydrocarbons (PAHs) and thiaarenes [sulfur-containing polycyclic aromatic compounds (S-PACs)] with 4-7 rings, as well as fraction containing more polar polycyclic aromatic compounds (PACs) and PAHs with higher molecular weight, induced lung carcinomas and sarcomas. According to probit analysis, the fraction containing PAHs plus S-PACs with 4-7 rings accounted for about 68.2% of the total carcinogenicity of flue gas condensate, whereas the fraction containing more polar PACs and higher PAHs accounted for about 54.6%. All other fractions, such as nonaromatic compounds and PACs with 2 and 3 rings, constituting about 70% of the weight of the total condensate, seemed not to be carcinogenic. Only 1.4% of the total carcinogenicity of the flue gas condensate was found to be attributable to the amount of benzo[a]pyrene (CAS: 50-32-8) present in the condensate (1.14 mg/g condensate). The contribution of more than 100% of both active fractions to the total carcinogenicity (68.2 and 54.6%) may suggest an interrelation of the fractions.—JNCI 1987; 78:935-942.
{"title":"Contribution of Polycyclic Aromatic Hydrocarbons and Polar Polycyclic Aromatic Compounds to the Carcinogenic Impact of Flue Gas Condensate From Coal-Fired Residential Furnaces Evaluated by Implantation Into the Rat Lung","authors":"Gernot Grimmer, Horst Brune, Reintraud Deutsch-Wenzel, Gerhard Dettbarn, Jürgen Misfeld","doi":"10.1093/jnci/78.5.935","DOIUrl":"https://doi.org/10.1093/jnci/78.5.935","url":null,"abstract":"For identification of the substances chiefly responsible for the carcinogenic action of the emission condensate from coal-fired residential furnaces, the implantation method was used as a carcinogen-specific bioassay for comparison of the carcinogenic effect of various fractions with that of a total sample of flue gas condensate tested in 2 or 3 different doses. After implantation into the lungs of Osborne-Mendel rats. the condensate from coal-fired residential furnaces, a fraction containing polycyclic aromatic hydrocarbons (PAHs) and thiaarenes [sulfur-containing polycyclic aromatic compounds (S-PACs)] with 4-7 rings, as well as fraction containing more polar polycyclic aromatic compounds (PACs) and PAHs with higher molecular weight, induced lung carcinomas and sarcomas. According to probit analysis, the fraction containing PAHs plus S-PACs with 4-7 rings accounted for about 68.2% of the total carcinogenicity of flue gas condensate, whereas the fraction containing more polar PACs and higher PAHs accounted for about 54.6%. All other fractions, such as nonaromatic compounds and PACs with 2 and 3 rings, constituting about 70% of the weight of the total condensate, seemed not to be carcinogenic. Only 1.4% of the total carcinogenicity of the flue gas condensate was found to be attributable to the amount of benzo[a]pyrene (CAS: 50-32-8) present in the condensate (1.14 mg/g condensate). The contribution of more than 100% of both active fractions to the total carcinogenicity (68.2 and 54.6%) may suggest an interrelation of the fractions.—JNCI 1987; 78:935-942.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
All Alaskan Native patients diagnosed with leukemia, lymphoma, multiple myeloma, and related cancers during the time period 1969-83 were identified. Of 72 biopsy-confirmed cases, lymphoma was diagnosed in 37 (including mycosis fungoides in 5), leukemia in 22, multiple myeloma in 11, and other lymphoreticular cancers in 2. Compared to the rates for U.S. whites, incidence rates were low for leukemia and lymphoma (especially Hodgkin's disease), but not for multiple myeloma in males. There was an apparent increase over time in lymphomas in males, while no increase occurred in females, nor for leukemia or multiple myeloma in either sex.—JNCI 1987; 78:831-837.
{"title":"Leukemia, Lymphoma, and Multiple Myeloma in Alaskan Natives","authors":"Steven R Albertsa, Anne P Lanier","doi":"10.1093/jnci/78.5.831","DOIUrl":"https://doi.org/10.1093/jnci/78.5.831","url":null,"abstract":"All Alaskan Native patients diagnosed with leukemia, lymphoma, multiple myeloma, and related cancers during the time period 1969-83 were identified. Of 72 biopsy-confirmed cases, lymphoma was diagnosed in 37 (including mycosis fungoides in 5), leukemia in 22, multiple myeloma in 11, and other lymphoreticular cancers in 2. Compared to the rates for U.S. whites, incidence rates were low for leukemia and lymphoma (especially Hodgkin's disease), but not for multiple myeloma in males. There was an apparent increase over time in lymphomas in males, while no increase occurred in females, nor for leukemia or multiple myeloma in either sex.—JNCI 1987; 78:831-837.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alfredo A Molinolo, Claudia Lanari, Eduardo H Charreau, Norberto Sanjuan, Christiane Dosne Pasqualini
Mammary adenocarcinomas induced by medroxy-progesterone acetate (MPA) in female BALB/c mice were investigated as to their morphology and immunohistochemistry and their content of steroid, prolactin (PHL), and epidermal growth factor (EGF) receptors. Histologically, these tumors were mainly of ductal origin, since hyperplastic alveolar nodules were observed only in 3 cases. No viral particles were encountered in electron microscopic studies. Estrogen and/or progesterone, PRL, and EGF receptors were detected in MPA-induced tumors, as well as in the occasional spontaneous mammary tumors of multiparous females. EGF was detected, by a radioimmunoassay, in the cystic fluid of 12 mammary adenocarcinomas. MPA treatment was found to induce uterine secretory changes, glandular cystic hyperplasia, and eventually deciduomas that stained strongly for desmin and to a lesser degree for vimentin, suggesting a muscular differentiation. Consequently, MPA-induced adenocarcinomas can be considered as ductal tumors that possess estrogen and/or progesterone, PRL, and EGF receptors. Whether MPA induces tumor growth directly via progesterone receptors remains to be investigated.—JNCI 1987; 79:1341-1350.
{"title":"Mouse Mammary Tumors Induced by Medroxyprogesterone Acetate: Immunohistochemistry and Hormonal Receptors","authors":"Alfredo A Molinolo, Claudia Lanari, Eduardo H Charreau, Norberto Sanjuan, Christiane Dosne Pasqualini","doi":"10.1093/jnci/79.6.1341","DOIUrl":"https://doi.org/10.1093/jnci/79.6.1341","url":null,"abstract":"Mammary adenocarcinomas induced by medroxy-progesterone acetate (MPA) in female BALB/c mice were investigated as to their morphology and immunohistochemistry and their content of steroid, prolactin (PHL), and epidermal growth factor (EGF) receptors. Histologically, these tumors were mainly of ductal origin, since hyperplastic alveolar nodules were observed only in 3 cases. No viral particles were encountered in electron microscopic studies. Estrogen and/or progesterone, PRL, and EGF receptors were detected in MPA-induced tumors, as well as in the occasional spontaneous mammary tumors of multiparous females. EGF was detected, by a radioimmunoassay, in the cystic fluid of 12 mammary adenocarcinomas. MPA treatment was found to induce uterine secretory changes, glandular cystic hyperplasia, and eventually deciduomas that stained strongly for desmin and to a lesser degree for vimentin, suggesting a muscular differentiation. Consequently, MPA-induced adenocarcinomas can be considered as ductal tumors that possess estrogen and/or progesterone, PRL, and EGF receptors. Whether MPA induces tumor growth directly via progesterone receptors remains to be investigated.—JNCI 1987; 79:1341-1350.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
One hundred fifty-nine 3-year survivors of childhood soft tissue sarcoma and their relatives were surveyed to determine the frequency of second malignant neoplasms (SMNs) in patients and cancer in their relatives. The cancer experience of the patients, their offspring, siblings, parents, parental siblings, and grandparents was compared to that expected of the general population based on age-, sex- and calendar year-specific rates from the Connecticut Tumor Registry. A significant excess of SMNs was observed in the patients (observed:expected = 8:0.38). Among 758 first-degree relatives, a significant cancer excess was observed (34:20.68), attributable largely to cancer of soft tissue and bone (6:0.44) and breast (9:3.39) and to cancers occurring before age 35 years (12:4.14). Overall, a significantly lower than expected cancer incidence was confirmed in the 1,693 second-degree relatives (142:178). To identify patient characteristics associated with higher than expected familial cancer risk, kindreds were partitioned by patient age at diagnosis, tumor type, tumor site, SMN, and other factors. A highly significant cancer excess was observed in the relatives of SMN patients (26:12.78). The tumor types occurring in excess in close relatives were also observed as SMNs in the patients. The findings confirm an association among childhood soft tissue sarcoma and cancers of the breast, bone, joint, or soft tissue as SMN in patients and in close relatives and suggest that the risk of a second tumor is associated with a familial predisposition to cancer.—JNCI 1987; 79:1213-1220.
{"title":"Cancer in Survivors of Childhood Soft Tissue Sarcoma and Their Relatives","authors":"Louise C Strong, Mark Stine, Tierney L Norsted","doi":"10.1093/jnci/79.6.1213","DOIUrl":"https://doi.org/10.1093/jnci/79.6.1213","url":null,"abstract":"One hundred fifty-nine 3-year survivors of childhood soft tissue sarcoma and their relatives were surveyed to determine the frequency of second malignant neoplasms (SMNs) in patients and cancer in their relatives. The cancer experience of the patients, their offspring, siblings, parents, parental siblings, and grandparents was compared to that expected of the general population based on age-, sex- and calendar year-specific rates from the Connecticut Tumor Registry. A significant excess of SMNs was observed in the patients (observed:expected = 8:0.38). Among 758 first-degree relatives, a significant cancer excess was observed (34:20.68), attributable largely to cancer of soft tissue and bone (6:0.44) and breast (9:3.39) and to cancers occurring before age 35 years (12:4.14). Overall, a significantly lower than expected cancer incidence was confirmed in the 1,693 second-degree relatives (142:178). To identify patient characteristics associated with higher than expected familial cancer risk, kindreds were partitioned by patient age at diagnosis, tumor type, tumor site, SMN, and other factors. A highly significant cancer excess was observed in the relatives of SMN patients (26:12.78). The tumor types occurring in excess in close relatives were also observed as SMNs in the patients. The findings confirm an association among childhood soft tissue sarcoma and cancers of the breast, bone, joint, or soft tissue as SMN in patients and in close relatives and suggest that the risk of a second tumor is associated with a familial predisposition to cancer.—JNCI 1987; 79:1213-1220.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Lehnert, Eleanor E Deschner, Rashida A Karmali, Jerome J DeCosse
The effect of exogenous synthetic prostaglandins and the inhibition of endogenous prostaglandin synthesis on gastrointestinal tumorigenesis induced by N-methyl-N’-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7] was studied in female Wistar rats (100 g). Animals were divided into 6 groups: Group I was treated with MNNG alone (No.=43); group II was treated with MNNG after application of the cyclo-oxygenase inhibitor flurbiprofen (No.=44); group III was treated with MNNG after oral administration of 16,16-dimethyl-prostaglandin E2(16.16-dm-PGE2; No.=43); group IV received flurbiprofen alone (No.=15); group V was treated with 16,16-dm-PGE2 alone (No.=11). Animals in group VI served as controls (No.=15). All drugs were administered orally. Hyperkeratosis and hyperplasia of the forestomach developed by 10 days after the first treatment with the carcinogen. Later, benign papillomas and dysplastic lesions were noted. Progressive ingrowth of squamous epithelium from the forestomach ridge into the glandular stomach started as early as day 13 and was more frequent in animals treated with a combination of MNNG plus flurbiprofen (P < .001). The first squamous cell carcinomas of the forestomach were detected on day 51. Their incidence was 38, 60, and 42% in groups I, II, and III, respectively. This difference was not statistically significant. The incidence of mesenchymal tumors (leiomyosarcoma) in the stomach and duodenum was higher following treatment with MNNG plus flurbiprofen as compared to the incidence following treatment with MNNG alone or in combination with 16,16-dm-PGE2 (P < .005). No malignant tumors developed in the gastrointestinal tracts of animals treated with flurbiprofen or 16,16-dm-PGE2 alone or in controls. The higher incidence of gastric and duodenal leiomyosarcomas after treatment with flurbiprofen suggests that reduction of prostaglandin synthesis favored the development of MNNG-induced cancer in mesenchymal tissues of the upper gastrointestinal tract.—JNCI 1987; 78:923-929.
{"title":"Effect of Flurbiprofen and 16,16-Dimethyl-prostaglandin E2 on Gastrointestinal Tumorigenesis Induced by N -Methyl- N’ -nitro- N -nitrosoguanidine in Rats. I. Squamous Epithelium and Mesenchymal Tissue","authors":"Thomas Lehnert, Eleanor E Deschner, Rashida A Karmali, Jerome J DeCosse","doi":"10.1093/jnci/78.5.923","DOIUrl":"https://doi.org/10.1093/jnci/78.5.923","url":null,"abstract":"The effect of exogenous synthetic prostaglandins and the inhibition of endogenous prostaglandin synthesis on gastrointestinal tumorigenesis induced by N-methyl-N’-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7] was studied in female Wistar rats (100 g). Animals were divided into 6 groups: Group I was treated with MNNG alone (No.=43); group II was treated with MNNG after application of the cyclo-oxygenase inhibitor flurbiprofen (No.=44); group III was treated with MNNG after oral administration of 16,16-dimethyl-prostaglandin E2(16.16-dm-PGE2; No.=43); group IV received flurbiprofen alone (No.=15); group V was treated with 16,16-dm-PGE2 alone (No.=11). Animals in group VI served as controls (No.=15). All drugs were administered orally. Hyperkeratosis and hyperplasia of the forestomach developed by 10 days after the first treatment with the carcinogen. Later, benign papillomas and dysplastic lesions were noted. Progressive ingrowth of squamous epithelium from the forestomach ridge into the glandular stomach started as early as day 13 and was more frequent in animals treated with a combination of MNNG plus flurbiprofen (P &lt; .001). The first squamous cell carcinomas of the forestomach were detected on day 51. Their incidence was 38, 60, and 42% in groups I, II, and III, respectively. This difference was not statistically significant. The incidence of mesenchymal tumors (leiomyosarcoma) in the stomach and duodenum was higher following treatment with MNNG plus flurbiprofen as compared to the incidence following treatment with MNNG alone or in combination with 16,16-dm-PGE2 (P &lt; .005). No malignant tumors developed in the gastrointestinal tracts of animals treated with flurbiprofen or 16,16-dm-PGE2 alone or in controls. The higher incidence of gastric and duodenal leiomyosarcomas after treatment with flurbiprofen suggests that reduction of prostaglandin synthesis favored the development of MNNG-induced cancer in mesenchymal tissues of the upper gastrointestinal tract.—JNCI 1987; 78:923-929.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Plasma levels of growth hormone (GH) and the effect of GH treatment have been evaluated in adult nongrowing sarcoma-bearing mice (C57BL/6.1). Prepubertal tumor-bearing mice, tumor-bearing hypophysectomized Sprague-Dawley rats, and malnourished non-tumor-bearing animals served as additional groups of study and control animals. Adult sarcoma-bearing mice showed an increase in plasma levels of GH early following tumor implantation, GH levels increased further with tumor progression. The anorexia and the state of malnutrition in sarcoma-bearing mice were the major factors behind increased GH levels. Muscle wasting and body composition in the tumor-bearing host were not improved by GH treatment at doses that increased growth rate in normal growing mice with intact pituitaries or partially normalized growth rate in hypophysectomized rats. Exogenous GH supported tumor growth and host body growth to the same extent in hypophysectomized rats. Exogenous GH in excess of endogenous GH did not stimulate tumor growth further. It is suggested that increased GH production in a tumor-bearing host acts in concert with other hormones to stimulate endogenous substrate mobilization and in tumor-bearing animals to prevent substrate deficiency and hypoglycemia. On the basis of this conclusion, it is unlikely that GH supplementation to a freely eating tumor-bearing host will support replenishment of host tissues—JNCI 1987; 79:1359-1365.
{"title":"Growth Hormone and Experimental Cancer Cachexia","authors":"Gösta Svaninger, Olle Isaksson, Kent Lundholm","doi":"10.1093/jnci/79.6.1359","DOIUrl":"https://doi.org/10.1093/jnci/79.6.1359","url":null,"abstract":"Plasma levels of growth hormone (GH) and the effect of GH treatment have been evaluated in adult nongrowing sarcoma-bearing mice (C57BL/6.1). Prepubertal tumor-bearing mice, tumor-bearing hypophysectomized Sprague-Dawley rats, and malnourished non-tumor-bearing animals served as additional groups of study and control animals. Adult sarcoma-bearing mice showed an increase in plasma levels of GH early following tumor implantation, GH levels increased further with tumor progression. The anorexia and the state of malnutrition in sarcoma-bearing mice were the major factors behind increased GH levels. Muscle wasting and body composition in the tumor-bearing host were not improved by GH treatment at doses that increased growth rate in normal growing mice with intact pituitaries or partially normalized growth rate in hypophysectomized rats. Exogenous GH supported tumor growth and host body growth to the same extent in hypophysectomized rats. Exogenous GH in excess of endogenous GH did not stimulate tumor growth further. It is suggested that increased GH production in a tumor-bearing host acts in concert with other hormones to stimulate endogenous substrate mobilization and in tumor-bearing animals to prevent substrate deficiency and hypoglycemia. On the basis of this conclusion, it is unlikely that GH supplementation to a freely eating tumor-bearing host will support replenishment of host tissues—JNCI 1987; 79:1359-1365.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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