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[Energy metabolism in spontaneous regression of transplantable tumors].

In spontaneous regression of rat sarcoma 45, Walker carcinosarcoma in rats and Brown-Pearce carcinoma in rabbits there was found biochemically and histochemically the enhancement of oxidation processes in the organism of animals, which was associated with the reduction of the ATP content, the increased rate of the coupling of oxidation to phosphorylation. Not only the normalization of all steps of the energetic provision chain in observed but also the exceeding of separate parameters of the energy homeostasis with relation to normal values.

Animals↗

Modulation of the toxicity and antitumour activity of alkylating drugs by steroids.

The steroids prednisolone and progesterone significantly altered the therapeutic indices of the alkylating agents, nitrogen mustard, melphalan, cyclophosphamide, phenyl acetic mustard and chlorambucil. For nitrogen mustard, chlorambucil and phenyl acetic mustard, prednisolone reduced host toxicity in the rat and enhanced the antitumour effectiveness against alkylating-agent-resistant strains of the Yoshida sarcoma and Walker carcinosarcoma. Progesterone also increased the therapeutic index of chlorambucil in the rat by decreasing its systemic toxicity. Two other alkylating agents, melphalan and cyclophosphamide, exhibited lower therapeutic indices in combination with prednisolone against alkylating-agent-sensitive tumours. This was due to the greater host toxicity of the combination than of the alkylating agent alone. In alkylating-agent-resistant tumours, however, a significant increase in growth delay was achieved if prednisolone was combined with the alkylating agent.

Alkylating Agents↗

[The monoaminergic receptors of the internal organs in rats with a tumor and after partial hepatectomy].

Sensitivity to phenylephrine, isoproterenol, serotonin, oxytocin, acetylcholine and barium chloride of vas deferens uterus und fundus strip was studied comparatively in hepatectomized and sarcoma-45, sarcoma-M1, Walker carcinosarcoma and Zajdela ascites hepatoma bearing rats. The contractile response to monoamines and oxytocin was considerably lower or absent at certain periods after hepatectomy or tumour grafting. Effects of biogenic amine antagonists were also substantially altered. The response to isoproterenol, acetylcholine and barium chloride remained unchanged. Apparently a selective alteration of a response of visceral smooth muscles mediated through alpha-adrenergic and D-serotonin receptors occurred not only during the tumour growth but also in the case of active (extensive) proliferation of the normal tissue.

Animals↗

Uterine sarcomas in South African black women: a clinicopathologic study with ethnic considerations.

BACKGROUND: There is considerable evidence for a higher incidence of uterine sarcomas in blacks when compared to whites. However, whether this higher incidence is related to differences in clinicopathologic presentation is not known. PATIENTS AND METHODS: We reviewed slides and clinical charts of 81 patients with a primary diagnosis of uterine sarcoma referred between 1991 and 1999 to Kalafong Academic and Pretoria Academic Hospital. After review, 49 cases remained for study. RESULTS: Uterine sarcomas were distributed between leiomyosarcoma (LMS) (39%), carcinosarcoma (CS) (49%) and endometrial stromal sarcoma (ESS) (12%). LMS and ESS tend to present at an earlier age when compared to CS (respectively p < 0.008 and 0.02). Of women with LMS more women are premenopausal when compared to CS (p < 0.009). Lower abdominal pain is more common in LMS (p < 0.009), whereas bleeding is more common in women suffering from CS (p < 0.01). Lymphovascular space involvement and cervical involvement are more common in CS when compared to LMS. In CS, the carcinoma component has most of the metastatic potential. CONCLUSION: Among black South African women different clinicopathologic features for uterine LMS, CS and ESS are observed. We also present genetic and/or hormonal factors possibly contributing to the pathophysiology of uterine sarcomas in blacks.

Age Factors↗

A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study.

OBJECTIVE: The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population. METHODS: Patients were randomized to receive ifosfamide (1.5 g/m(2)/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m(2)/day) times 5 days. No patient had received previous chemotherapy. RESULTS: Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for "other" metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test). CONCLUSION: The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination.

Adult↗

Carcinosarcoma of the uterine cervix composed of an adenoid cystic carcinoma and an homologous stromal sarcoma. A case report.

A case of primary cervical carcinosarcoma is presented. The tumor occurred in a 76-year-old multiparous woman and it replaced the uterine cervix, extending to the vaginal wall and to the uterine corpus. Histologically, the carcinomatous component was exclusively an adenoid-cystic carcinoma and the sarcomatous component was an homologous stromal sarcoma. Immunohistochemically, both the carcinomatous and the sarcomatous elements were stained with smooth muscle actin. Only two other similar cases have been reported.

Aged↗

Effective gene transfer to solid tumors using different nonviral gene delivery techniques: electroporation, liposomes, and integrin-targeted vector.

In this study, we measured transfection efficiency in vitro and in vivo using the following nonviral approaches of gene delivery: injection of plasmid DNA, electroporation-assisted, liposome-enhanced, and integrin-targeted gene delivery, as well as the combination of these methods. Four histologically different tumor models were transfected with a plasmid encoding the green fluorescent protein (GFP) (B16 mouse melanoma, P22 rat carcinosarcoma, SaF mouse sarcoma, and T24 human bladder carcinoma) using adherent cells, dense cell suspensions, and solid tumors. Emphasis was placed on different electroporation conditions to optimise the duration and amplitude of the electric pulses, as well as on different DNA concentrations for effective gene delivery. In addition, transfection efficiency was correlated with cell density of the tumors. The major in vivo findings were: (a) electroporation-assisted gene delivery with plasmid DNA, employing long electric pulses with low amplitude, yielded significantly better GFP expression than short electric pulses with high amplitude; (b) electroporation combined with liposome-DNA complexes yielded the highest percentage of transfected tumor area in B16F1 tumor (6%); (c) transfection efficiency of electroporation-assisted plasmid DNA delivery was dependent on tumor type; (d) integrin-targeted vector, alone or combined with electroporation, was largely ineffective. In conclusion, our results demonstrate that some nonviral methods of gene delivery are feasible and efficient in transfecting solid tumors. Therefore, this makes nonviral methods attractive for further development.

Animals↗

Preferential mammary carcinogenic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in human c-Ha-ras proto-oncogene transgenic rats.

In order to clarify the susceptibility of the Hras128 rat harboring copies of the human c-Ha-ras proto-oncogene to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), Hras128 rats were intragastically treated with 100 mg/kg PhIP 8 times (females) or 80 mg/kg PhIP 10 times (males) over a 9-week period, then sacrificed at weeks 12 and 30. Multiple mammary tumors of adenocarcinoma type were induced in all females, while 83% of treated males developed adenocarcinomas, sarcomas and transitional carcinosarcomas, as evidenced by casein and vimentin immunoreactivity. All tumors examined had mutations in the c-Ha-ras transgene, while the endogenous rat c-Ha-ras gene was intact. Our results indicate that 1) Hras128 rats of both sexes are preferentially susceptible to mammary carcinogenesis with PhIP; 2) activation of the transgene, but not the endogenous c-Ha-ras gene, may be important in this regard; 3) the variety of tumor types evident in male rats indicates that immature mammary gland cells of the terminal end buds may be a target of PhIP; 4) although the transgene is expressed in all organs, susceptibility to PhIP is limited to mammary glands.

Animals↗

Gallium-67 localization in rat and mouse tumors.

Various nonosseous tumors in mice and rats concentrate gallium-67-ESR-586 preputial gland carcinoma, P-1798 lymphosarcoma, C3H/ HeJ mammary tumor, AKR/J thymic lymphoma, R-3259 giant cell sarcoma, Walker-256 carcinosarcoma, and a new transplantable neoplasm of rats. This last tumor showed the greatest affinity for galliun. Viable tumor cells are mainly responsible for uptake of gallium-67; autoradiographic studies indicate it is chiefly located in tumor cytoplasm.

Animals↗

[Uterine sarcomas. Cytological diagnosis and differential diagnosis].

Cytomorphological findings in 8 cases of uterine sarcomas are being presented (2 endometrial stromal sarcomas, 2 so-called pleomorphic sarcomas, 3 leiomyosarcomas, 1 carcinosarcoma). The differential cytologic criteria are being discussed and demonstrated by microphotograms. By means of these cytologic findings in our opinion prospective cytologic diagnosis is possible also in these kinds of tumors. Final statistical conclusions in respect to cytologic criteria may only be drawn by greater numbers of cases, which can be reached only by cooperative studies on these relatively rare tumors.

Biopsy↗

[Respiratory phosphorylation in the liver mitochondria of rats with transplantable sarcomas].

The method of polarography was used to study respiration and phosphorylation capacity of the hepatic mitochondria in rats with transplantable sarcoma 45 and Walker carcinosarcoma in different terms after transplantation, and in spontaneous regression of the tumors involved, as well. In the hepatic mitochondria of tumor-bearing animals a marked dissociation of respiration and phosphorylation is observed, being mostly manifested in oxidation of glutamate and endogenic NAD-dependent substrates. Non-phosphorylating oxidation suffers to a less extent. Experiments with the use of rhothenon indicated that an impaired rate of the coupling of oxidation and phosphorylation was also related with a destroyed succinate site in the respiratory chain. In the presence of serum albumin an up to normal values restoration of the rate of respiration and phosphorylation coupling is observed in the hepatic mitochondria of tumor-bearing animals. The degree of interference in the respiratory phosphorylation process is mostly significant at late stages of tumors development and sharply declines in their spontaneous regression.

Animals↗

A gastric carcinosarcoma with neuroendocrine cell differentiation and undifferentiated spindle-shaped sarcoma component possibly progressing from the conventional tubular adenocarcinoma; an immunohistochemical and ultrastructural study.

A 56-year-old Japanese man underwent total gastrectomy with lymph-node dissection for a gastric tumor. In the oral rim of the excised large ulcerated tumor, a small nodular mass demonstrated a unique histology of a carcinosarcoma composed of more than three distinctive components. A major part of the large ulcerated tumor tissue consisted of conventional tubular adenocarcinoma, with the coincidental focal distribution of solid cell nests of poorly differentiated or neuroendocrine cell (small cell) carcinoma. Sarcoma cells were another of the constituents of the small nodular tumor with atypical spindle-shaped cells. All the excised lymph-node metastasis demonstrated the histology of tubular adenocarcinoma. In the sarcoma cells, many of the lineage-specific immunohistochemical markers were negative. Only vimentin was positive. Electron microscopy revealed that the neuroendocrine cell carcinoma contained cells with abundant small aggregations of neurosecretory-type granules in their cellular cytoplasm. Primitive cellular junctions and incomplete basal lamina were seen in the sarcoma cells. No transitional or hybrid-type cells were seen between carcinoma and sarcoma cells. The interfaces between the cancer cell nests and the proliferation of sarcoma cells are clearly discerned. It was speculated that the unique histology of carcinosarcoma might have progressed from the conventional type of pre-existing advanced tubular adenocarcinoma.

Adenocarcinoma↗

Esophageal sarcomas.

The clinical and pathologic characteristics of five patients with esophageal sarcomas are presented, including the only recorded esophageal Triton tumor (malignant schwannoma), the third recorded synovial sarcoma, two patients with carcinosarcoma, and one with leiomyosarcoma. All five patients were males who presented with dysphagia. Three tumors were in the cervical esophagus, and the remaining two were in the distal esophagus. On endoscopic examination, three of the tumors were noted to be polypoid, while the other two were sessile. Two patients presented with disseminated disease, and a third was locally unresectable. These three patients were treated with palliative intent. The remaining two patients underwent surgical excision and postoperative radiation therapy, and are alive and well 6 and 7 years following treatment. This experience suggests that combined modality therapy employing postoperative radiation may be effective in managing these rare lesions.

Adolescent↗

Esophageal sarcomas: report of three cases.

BACKGROUND/AIMS: Sarcomas of the esophagus, including carcinosarcoma, are rare neoplasms. METHODS: The clinical and pathologic characteristics of 3 patients with esophageal sarcomas are presented, including the only recorded esophageal carcinosarcoma and 2 patients with leiomyosarcoma. RESULTS: All 3 patients were males who presented with dysphagia or an abnormal shadow of the mediastinum on a plain chest X-ray. Two tumors were in the middle esophagus, and the remaining one was in the distal esophagus. On endoscopic examination, all three tumors were noted to be polypoid. These patients underwent surgical excision. One patient died 7 days following the operation, and the remaining 2 patients died of liver metastasis 10 and 22 months following the treatment. CONCLUSION: Esophagectomy or esophagogastrectomy is a surgical choice. Even if metastases are present, a palliative resection can still be performed.

Aged↗

Cervical sarcomas: an analysis of incidence and outcome.

OBJECTIVE: Cervical sarcomas are exceedingly rare neoplasms associated with a poor prognosis. The objective of this study was to examine the treatment and outcome of women with cervical sarcomas. METHODS: A hospital-based tumor registry was searched to identify all patients with cervical sarcomas treated between 1986 and 2003. The medical records of all patients were reviewed. All pathologic specimens were reviewed by a single pathologist. RESULTS: Among 1583 with cervical malignancies, 8 cervical sarcomas were identified. All patients presented with vaginal bleeding. The lesions were clinically staged as IB1 (2), IB2 (4), IIIA (1), and IIIB (1). Five of the tumors were carcinosarcomas. Other histologies included sarcoma NOS (12.5%), leiomyosarcoma (12.5%), and endometrial stromal sarcoma (12.5%). Initial treatment included surgery in 5 patients, radiation in 2, and chemoradiation in 1. Six patients were treated with curative intent, 5 received adjuvant therapy. While both patients treated palliatively died from progressive disease, the other 6 patients remain alive after a mean follow-up of 2.5 years. Two patients have recurred. One patient underwent a thoracotomy for an isolated pulmonary metastasis and is alive with no evidence of disease. The second patient developed pulmonary metastases and is alive 8 months after recurrence. CONCLUSIONS: Cervical sarcomas are rare neoplasms. Most patients present with vaginal bleeding and a palpable cervical mass. While the optimal management of these tumors is uncertain, aggressive primary therapy can result in prolonged survival and cure.

Adult↗

Cisplatin-based chemotherapy regimen (DECAV) for uterine sarcomas.

Uterine sarcomas are an extremely rare event. There is no standard therapy for cases of relapse, although chemotherapy is commonly used. We studied the use of a cisplatin-based chemotherapy regimen for uterine sarcomas with an unusually long follow-up. Thirty-nine women with a median age of 50 years (32-71) entered the study. Histologically, leiomyosarcomas (26), carcinosarcomas (8), and stromal sarcomas (5) were represented. Group 1 consisted of patients undergoing adjuvant therapy (for initial disease, eight patients; for pelvic recurrence, two patients); Group 2 consisted of patients with advanced disease (locoregional after initial local therapy, five patients; local recurrence, six patients) or metastatic disease (stage IV, four patients; recurrence, 14 patients). DECAV therapy consisted of doxorubicin 50 mg/m2 d1, dacarbazine (DTIC) 200 mg/m2/d d1-3, vindesine 2 mg/day d1-2, cisplatin 100 mg/m2 d3, and either cyclophosphamide (CPM) 200 mg/m2/d d1-3 (n = 21), or ifosfamide (IFM) 2 g/m2/d d1-3 with mesna every 4 weeks Toxicity included 18 hospital stays for cytopenia (nine patients), including 13 cases of febrile neutropenia. Twenty blood transfusions in 10 patients and 12 platelet transfusions in seven patients were required. One toxicity-related death (hemorrhage) occurred. The overall response rate was 54% (3 complete response, 11 partial response) with a median duration of 13 months (4-36). Median overall survival was 14 month overall, 45 months for Group 1 and 13 months for Group 2. We conclude that the DECAV regimen is clearly active in uterine sarcomas but is too toxic to be recommended routinely.

Adult↗