pyrophosphate and Ovarian-Neoplasms

Vγ9Vδ2 cells are cytotoxic T cells that are able to recognize epithelial ovarian carcinoma (EOC) cells. Therefore, Vγ9Vδ2 cell-based adoptive transfer is an attractive therapy for EOC. However, the inefficient ex vivo expansion after specific stimulation of Vγ9Vδ2 cells from some patients and the relationships between Vγ9Vδ2 cells and clinical course of EOC are issues that remain to be clarified. Herein, peripheral blood mononuclear cells (PBMCs) from 60 EOC patients were stimulated with bromohydrin pyrophosphate (BrHPP) or zoledronate, which are specific agonists of Vγ9Vδ2 cells. The compounds differed in their efficacies to induce ex vivo Vγ9Vδ2 PBMC expansion, but 16/60 samples remained inefficiently expanded with both stimuli. Interestingly, the Vγ9Vδ2 cells in these low-responding PBMCs displayed before expansion (ex vivo PBMCs) an altered production of the pro-inflammatory cytokines IFN-γ and TNF-α, a decreased naive fraction and a reduced frequency. No evidence of an involvement of CD4(+)CD25(+)Foxp3(+) regulatory cells was observed. Importantly, our data also demonstrate that a Vγ9Vδ2 cell frequency of 0.35% or less in EOC PBMCs could be used to predict low responses to both BrHPP and zoledronate. Moreover, our data highlight that such a deficiency is not correlated with advanced EOC stages but is associated with more refractory states to platinum-based chemotherapy and is an independent predictor of shorter disease-free survival after treatment. These results are the first to suggest a potential contribution of Vγ9Vδ2 cells to the anti-tumor effects of chemotherapeutic agents and they strengthen interest in strategies that might increase Vγ9Vδ2 cells in cancer patients.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Ovarian Epithelial; CD3 Complex; Cell Proliferation; Cells, Cultured; Combined Modality Therapy; Diphosphates; Diphosphonates; Disease-Free Survival; Drug Resistance, Neoplasm; Humans; Imidazoles; Interferon-gamma; Middle Aged; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prognosis; Survival Analysis; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory; Treatment Outcome; Tumor Necrosis Factor-alpha; Zoledronic Acid

Combined examination of 96 patients with different gynecological diseases included methods of ultrasound tomography, scintigraphy of the small pelvis with 99mTc-pyrophosphate, immunoscintigraphy and radioimmunoassay for determination of the blood level of CA 125. New diagnostic methods for ovarian cancer using 131I labeled monoclonal antibodies and an algorithm for data processing were developed. Of 96 patients 39 had ovarian cancer, 6 patients--uterine tumors, and 51 patients (controls) with nontumorous and benign lesions of the ovaries and uterus. The diagnostic effectiveness of these methods was determined by the indices of sensitivity, specificity and accuracy. The radioimmunoassay for determination of CA 125 possessed the highest sensitivity, ultrasound tomography showed the highest specificity and accuracy. Immunoscintigraphy with Imacis-2 was shown to possess the highest diagnostic effectiveness and unique informative value. An optimum algorithm for the use of the above methods in patients with suspected ovarian cancer was proposed on the basis of these investigations.

Topics: Algorithms; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Diphosphates; Female; Humans; Immunoglobulin Fab Fragments; Iodine Radioisotopes; Ovarian Neoplasms; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate; Ultrasonography

The authors present a method with the use of 99mTc-pyrophosphate for differential diagnosis of malignant and benign ovarian tumors. A total of 46 patients were examined. Of these, the sample hyperfixation in the zone of malignant ovarian tumors with the rate of differential accumulation of 200-260% was observed in 7. In benign tumors and inflammatory ovarian changes, radiopharmaceutical hyperfixation was either not observed or it did not exceed 130%. Diagnosis in all the patients was verified at operation with subsequent histological examination.

Topics: Diphosphates; Female; Humans; Middle Aged; Ovarian Neoplasms; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Calcinosis; Cystadenoma; Diphosphates; Female; Humans; Middle Aged; Ovarian Neoplasms; Radionuclide Imaging; Technetium

Three patients with foregut (bronchial), hindgut (rectal) or (ovarian) carcinoid tumors had symptomatic bone metastasis with abnormal 99m Tc pyrophosphate bone scans and bone roentgenograms. Six patients with midgut (small intestine or caecal) carcinoid) carcinoid tumors who had no symptoms of bone metastasis had no evidence of bone metastasis on bone scan or bone roentgenographic examination. This study supports the clinical impression that patients with midget carcinoid tumors have a low incidence of bone metastasis.

Topics: Bone Neoplasms; Carcinoid Tumor; Diphosphates; Female; Femoral Neoplasms; Frontal Bone; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Ovarian Neoplasms; Radionuclide Imaging; Rectal Neoplasms; Ribs; Spinal Neoplasms; Technetium

An ovarian carcinoma which avidly accumulated 99mTc-pyrophosphate was imaged during a bone scan. The primary tumor and its implants over the liver surface were both visualized. Although imaging of such an ovarian malignancy has not been previously reported, it offers a potential method for assessing neoplastic size and spread.

Topics: Adult; Bone Diseases; Cystadenoma; Diphosphates; Female; Humans; Ovarian Neoplasms; Radionuclide Imaging; Technetium