BIOMAGNETISM OF DRUG-SENSITIVE AND DRUG-RESISTANT MALIGNANT TUMORS AFTER INJECTION OF FERROMAGNETIC NANOCOMPOSITE.

Magnetic signals emitted by living organisms, regardless of a biological species, are important biophysical indicators. The study of these indicators is very relevant and promising for the visualization of the tumor process and the development of technologies using artificial intelligence when it comes to malignant neoplasms, particularly resistant to chemotherapy. AIM: To measure magnetic signals from transplantable rat tumors and their counterparts resistant to cytostatics for evaluating the features of the accumulation of iron-containing nanocomposite Ferroplat. MATERIALS AND METHODS: Doxorubicin (Dox)-sensitive and Dox-resistant Walker-256 carcinosarcoma and cisplatin-sensitive and cisplatin-resistant Guerin's carcinoma transplanted in female Wistar rats were studied. The magnetism of tumors, liver and heart was determined using Superconductive Quantum Interference Device (SQUID) - magnetometry in a non-contact (13 mm over the tumor) way using specially designed computer programs. In a group of the experimental animals, a ferromagnetic nanocomposite (Ferroplat) was administered as a single intravenous injection and biomagnetism was assessed in 1 h. RESULTS: The magnetic signals coming from Dox-resistant Walker-256 carcinosarcoma in the exponential growth phase were significantly higher in comparison with sensitive tumor. Intravenous administration of Ferroplat increased biomagnetism by at least an order of magnitude, especially in resistant tumors. At the same time, the magnetic signals of the liver and heart were within the magnetic noise. CONCLUSION: The use of SQUID-magnetometry with ferromagnetic nanoparticles as a contrast agent is a promising approach for visualization of malignant neoplasms with varying sensitivity to chemotherapy.

Curcumin augments the cytostatic and anti-invasive effects of mitoxantrone on carcinosarcoma cells in vitro.

Numerous adverse effects limit the applicability of mitoxantrone for the treatment of drug-resistant tumors, including carcinosarcoma. Here, we estimated the additive effects of mitoxantrone and curcumin, a plant-derived biomolecule isolated from Curcuma longa, on the neoplastic and invasive potential of carcinosarcoma cells in vitro. Curcumin augmented the cytostatic, cytotoxic and anti-invasive effects of mitoxantrone on the Walker-256 cells. It also strengthened the inhibitory effects of mitoxantrone on the motility of drug-resistant Walker-256 cells that had retained viability after a long-term mitoxantrone/curcumin treatment. Thus, curcumin reduces the effective doses of mitoxantrone and augments its interference with the invasive potential of drug-resistant carcinosarcoma cells.

Carcinosarcoma of the fallopian tube with disappearance of carcinoma cells by neoadjuvant chemotherapy: case study.

The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

Humoral hypercalcemia caused by uterine corpus carcinosarcoma consisting of squamous cell carcinoma in its epithelial component.

Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome primarily caused by a tumor-producing parathyroid hormone-related protein (PTH-rP). We describe the first reported case of a uterine carcinosarcoma causing HHM. A 70-year-old patient was transferred to our hospital for a uterine tumor accompanied by impaired consciousness. The laboratory tests indicated anemia, malnutrition, elevated serum calcium and elevated PTH-rP. Emergency surgery, including abdominal hysterectomy and bilateral salpingo-oophorectomy, was performed due to uncontrollable uterine bleeding. The pathological diagnosis was carcinosarcoma consisting of pure squamous cell carcinoma in its epithelial component. Postoperatively, chemotherapy with paclitaxel and carboplatin was performed. The patient had recurrent tumors at the para-aortic lymph nodes 11 months after the initial surgery and underwent a pelvic and para-aortic lymphadenectomy, which removed all of the recurrent tumors.

Metronomic doxifluridine chemotherapy combined with the anti-angiogenic agent TNP-470 inhibits the growth of human uterine carcinosarcoma xenografts.

Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Metronomic chemotherapy is accepted as a new approach for cancer treatment, and its underlying mechanism seems to involve the suppression of angiogenesis. However, the efficacy of metronomic and anti-angiogenic therapies against uterine carcinosarcoma is unknown. The anti-angiogenic effect of doxifluridine was assessed in vitro using human umbilical vein endothelial cells (HUVEC) co-cultured with FU-MMT-1 human uterine carcinosarcoma cells. The antitumor and anti-angiogenic effects of metronomic doxifluridine (delivered via oral gavage) in combination with TNP-470 were evaluated in vivo. Tumor vascularity was assessed by contrast-enhanced color Doppler ultrasound, laser Doppler and microvessel density staining. Doxifluridine suppressed tube formation of HUVEC and vascular endothelial growth factor production by FU-MMT-1 cells. Metronomic doxifluridine alone significantly suppressed tumor growth compared with the untreated (control) group, while metronomic doxifluridine in combination with TNP-470 significantly inhibited tumor growth compared with each treatment alone. A significant reduction of intratumoral vascularity was observed in FU-MMT-1 xenografts following treatment with metronomic doxifluridine in combination with TNP-470, as compared with each treatment alone. Intestinal bleeding was only observed when the maximum tolerated dose of doxifluridine was administered in combination with TNP-470. Metronomic doxifluridine chemotherapy in combination with TNP-470 might be effective for uterine carcinosarcoma without marked toxicity, possibly acting via its potent anti-angiogenic effects. Clinical studies are needed to evaluate the safety and efficacy of this treatment in humans.

Prostate sarcomatoid carcinoma as accidental finding in transurethral resection of prostate specimen. A case report and systematic review of current literature.

BACKGROUND: Sarcomatoid carcinoma of the prostate is an extremely rare and highly aggressive neoplasm that accounts for less than 0.1% of primary prostate malignancies. Long-term survival rates for adult patients with prostate sarcomatoid carcinoma are poor. Surgical treatment seems to be the most effective therapeutic approach. In contrast radiation therapy alone has shown limited efficacy. AIM: The purpose of the study is to present a case of sarcomatoid carcinoma of the prostate treated with a combination of radiotherapy and TURP. CASE REPORT: A 76-year-old man treated with TURP due to acute urinary retention was finally diagnosed with sarcomatoid carcinoma upon pathology examination of the surgical specimen. Patient was initially treated with external beam radiotherapy. Six months later, he presented with urinary retention suggesting extension of the tumor into the bladder neck. Pathology report diagnosed prostate sarcomatoid carcinoma containing also large areas of necrosis. Patient underwent an extensive TURP and he received a second round radiotherapy. One year after the initial diagnosis of sarcomatoid carcinoma, patient is free of symptoms and follow up investigation shows no evidence of metastatic disease. CONCLUSIONS: Radiation therapy in combination with extensive TURP may delay disease progression.

A phase II study of sorafenib in advanced uterine carcinoma/carcinosarcoma: a trial of the Chicago, PMH, and California Phase II Consortia.

OBJECTIVES: To determine the efficacy and safety of single agent sorafenib, an oral multi-targeted tyrosine kinase inhibitor, in patients with advanced uterine carcinoma and carcinosarcoma. METHODS: This multi-institutional non-randomized phase II trial enrolled two cohorts: patients with uterine carcinoma (cohort A) and uterine carcinosarcoma (cohort B). Eligibility criteria included measurable disease, 0-1 prior chemotherapy regimens, and ECOG performance status

Variantes histológicas del carcinoma urotelial con implicaciones diagnósticas, pronósticas y terapéuticas / Histological variants of urothelial carcinoma with diagnostic, prognostic and therapeutical implications

La mayoría de los carcinomas uroteliales (CU) tienen un patrón de crecimiento histológico de tipo papilar o de tipo sólido; sin embargo, en algunos casos existen variedades histológicas que difieren significativamente de estos patrones habituales En este artículo se han seleccionado aquellas variantes de CU que por su dificultad diagnóstica e implicaciones pronósticas o terapéuticas tienen que ser perfectamente identificadas y conocidas por los patólogos y los urólogos. Las variantes que hemos considerado de mayor interés tanto clínico como patológico han sido: CU variedad en nidos y/o tubular, CU variedad microquística, CU variedad micropapilar, CU con intenso estroma linfoide, tipo linfoepitelioma, CU variedad plasmocitoide y CU sarcomatoide. De cada uno de estos patrones se ha realizado una revisión de la literatura valorando los criterios diagnósticos, el comportamiento clínico y las posibilidades terapéuticas actuales. Además, sugerimos que estas variedades de CU deben ser reflejadas explícitamente en el informe del diagnóstico anatomopatológico, debido a sus implicaciones clínicas

Most of urothelial carcinomas (UC) have a pattern of histological growth of papillary or solid type; nevertheless, in some cases there are histological types that significantly differ from these habitual patterns In this paper we have selected those UC variants that by its diagnosis difficulty and therapeutical or prognosis implications have to be perfectly identified and known by pathologists and urologist. The variants that we have considered of greater clinical and pathological interest have been: tubular and/or nested UC, microcystic UC, micropapillary UC, lymphoepithelioma like UC, plasmacytoid UC and sarcomatoid UC. A revision of the literature has been made of each one of these patterns evaluating the criteria diagnoses, clinical behavior and the present therapeutic options. In addition, we suggest that these UC variants must be explicitly reflected in the pathology report, due to its clinical implications

Adjuvant post-operative chemotherapy in bitches with mammary cancer.

The survival time in a group of eight bitches with malignant mammary tumours given adjuvant post-operative chemotherapy was compared with survival in another group of eight bitches with mammary cancer which were treated by surgical excision alone. The same surgical procedure was used in both groups. All bitches had stage III disease according to the World Health Organization clinical staging system. Histologically, 10 of the bitches had complex carcinomas (carcinomatous mixed tumours), the remaining six bitches had carcinosarcomas. The chemotherapeutic protocol used was a combination of 5-fluorouracil (150 mg/m2 of body surface area) and cyclophosphamide (100 mg/m2) given on the same day, intravenously, every week for four consecutive weeks. Chemotherapy was started one week post-surgery. Selected haematological parameters (packed cell volume, white blood cell count, platelet count and differential white blood cell count) and serum biochemical parameters (alanine aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine) were measured before and during chemotherapy. Survival analysis indicated that the chemotherapeutic regimen had a positive influence on the disease-free interval and the survival time of the eight bitches (P < 0.05). Although leucocyte numbers were significantly decreased (P < 0.001) during chemotherapy, the mean leucocyte counts remained within normal limits. Temporary leukopenia was noted only in one bitch. Packed cell volume and alkaline phosphatase increased significantly (P < 0.05) but within normal limits. Creatinine was also increased significantly (P < 0.01) but the mean creatinine concentrations were within normal limits, although in half of the bitches the concentrations occasionally rose above normal.

[Chemotherapy in the treatment of ovarian carcinosarcoma]. / La chemioterapia nel trattamento del carcinosarcoma dell'ovaio.

Carcinosarcoma of the ovary is a rare neoplasm representing 1% of this organ malignancies. The disease appears almost exclusively in advanced stage having an unfavourable prognosis. Three patients affected by carcinosarcoma (MMMT) of the ovary admitted to our Operative Unit have been treated. All patients underwent surgery and subsequently chemotherapy. Two patients were affected by heterologous MMMT and were stage IV and IIIc respectively, the other one, affected by homologous MMMT, was stage IIIc. Stage IV patient was submitted to 6 cycles of CARBO + IFX + CDDP, second look and further 6 cycles of TAX. After 23 months she was submitted to colostomy for intestine occlusion. At the 35 months she died for cachexia and intestine occlusion. Stage IIIc heterologous patient was submitted to 6 cycles of CDDP + EPI + IFX + MESNA for 3 days; at 6 months from diagnosis she did not present any sign of disease. Stage IIIc homologous patient, affected by chronic renal insufficiency and submitted to dialysis, underwent 5 cycles of TAX and at 11 months from diagnosis presented partial response. Carcinosarcoma of the ovary, because of its rarity, and of the poor record of cases in the literature, is a much debated topic in particularitis complementary therapy. Opinions of the several authors are in contrast regarding the use of CHT + RT at the same time. Only RT after surgery does not seem to improve the survival of these patients. Personal experience, with the reported outlines, compared with survival, seems to confirm the use of CDDP and of IFX and to give new horizons to TAX, waiting for further findings.

[Changes in clonogenic properties of bone marrow and transplantable mice tumor cells during combined use of cyclophosphane and biological response modifiers of adaptogenic origin]. / Izmenenie klonogennykh svoistv kletok kostnogo mozga i perevivaemykh opukholei myshei pri kombinirovannom primenenii tsiklofosfana i modifikatorov biologicheskogo deistviia adaptogennoi prirody.

The clonogenic activity of tumors and blood marrow cells has been studied in experiments on CBA, BALB/C and C57B1/6 mice with the Ehrlich adenocarcinoma and Lewis lung carcinosarcoma treated with adaptogenic drugs of Rhodiola Rosea extract, a synthetic analog of Rhodiola phenol derivative, methyluracil and their combinations with cyclophosphamide. The extract and derivative are shown to protect the myelopoietic tissue from the toxic action of cyclophosphamide, retaining or increasing the suppressive effect of the latter towards clonogenic tumors cells. These data can be the reason for using the extract and derivative during the antitumor chemotherapy as biological response modifiers.

Indicine-N-oxide: the antitumor principle of Heliotropium indicum.

Extracts of Heliotropium indicum Linn. (Boraginaceae) showed significant activity in several experimental tumor systems. The active principle is isolated and shown to be the N-oxide of the alkaloid, indicine, previously isolated from this plant. Supporting structural data and anti-tumor data are provided.

[Demonstration of tumor inhibiting properties of a strongly immunostimulating low-molecular weight substance. Comparative studies with ifosfamide on the immuno-labile DS carcinosarcoma. Stimulation of the autoimmune activity for approx. 20 days by BA 1, a N-(2-cyanoethylene)-urea. Novel prophylactic possibilities]. / Nachweis krebshemmender Eigenschaften einer stark immunstimulierenden Verbindung kleiner Molekülmasse. Versuche am immunlabilen DS-Karzinosarkom im Vergleich mit Ifosfamid. Stimulierung der körpereigenen Abwehr über etwa 20 Tage durch BA 1, einen N-(2-Cyanthylen)-harnstoff. Neue prophylaktische Möglichkeiten

A report is given on the recent discovery of outstanding immunological properties in BA 1 [N-(2-cyanoethylene)-urea] having a (low) molecular mass M = 111.104. Experiments in 214 DS carcinosarcoma bearing Wistar rats have shown that BA 1, at a dosage of only about 12 percent LD50 (150 mg kg) and negligible lethality (1.7 percent), results in a recovery rate of 40 percent without hyperglycemia and, in one test, of 80 percent with hyperglycemia. Under otherwise unchanged conditions the reference substance ifosfamide (IF) -- a further development of cyclophosphamide -- applied without hyperglycemia in its most efficient dosage of 47 percent LD50 (150 mg kg) brought about a recovery rate of 25 percent at a lethality of 18 percent. (Contrary to BA 1, 250-min hyperglycemia caused no further improvement of the recovery rate.) However this comparison is characterized by the fact that both substances exhibit two quite different (complementary) mechanisms of action. Leucocyte counts made after application of the said cancerostatics and dosages have shown a pronounced stimulation with BA 1 and with ifosfamide, the known suppression in the post-therapeutic interval usually found with standard cancerostatics. In combination with the cited plaque test for BA 1, blood pictures then allow conclusions on the immunity status. Since IF can be taken as one of the most efficient cancerostatics--there is no other chemotherapeutic known up to now that has a more significant effect on the DS carcinosarcoma in rats -- these findings are of special importance. Finally, the total amount of leucocytes and lymphocytes as well as their time behaviour was determined from the blood picture of tumour-free rats after i.v. application of BA 1. The thus obtained numerical values clearly show that further research work on the prophylactic use of this substance seems to be necessary and very promising.