[show abstract][hide abstract] ABSTRACT: In ovarian cancer patients, chemotherapy resistance is the principal factor restricting long-term treatment. Paclitaxel (Pac) has been previously reported to be a ligand to Toll-like receptor 4 (TLR4). It was determined that TLR4 signaling is divided into the following two pathways: Myeloid differentiation factor 88 (MyD88)-dependent and MyD88-independent. The present study investigated the effect of TLR4 ligation by Pac in MyD88-positive (MyD88(+)) and MyD88-negative (MyD88(-)) human ovarian cancer cell lines. An RNA interference expression vector was specifically constructed to target TLR4 mRNA, which was stably transfected into the human ovarian cancer cell lines (SKOV3, OVCAR3, A2780 and 3AO). Cytokines, including interleukin (IL)-6 and IL-8, were detected. Cell proliferation and apoptosis were assessed in the cells transfected with scramble control and TLR4 shRNA to explore the possible functions of TLR4 in ovarian cancer cell growth. It was found that lipopolysaccharide and Pac significantly increase the secretion of IL-6 and IL-8 in the SKOV3 cell line. Similarly, Pac resulted in a significant upregulation of IL-6 and IL-8 in OVCAR3 cells, but not in A2780 and 3AO cells. These results suggested that in MyD88(+) ovarian cancer cell lines, TLR4 depletion shows increased sensitivity to Pac treatment in inhibiting cell proliferation compared with in cells without TLR4 knockdown. On the contrary, such changes were not found in MyD88(-) cells (A2780 and 3AO). TLR4 negatively regulates Pac chemotherapy, particularly in terms of cell proliferation, and TLR4 may be a novel treatment target in Pac-resistant ovarian cancer.
[show abstract][hide abstract] ABSTRACT: To evaluate the clinical value of sentinel lymph nodes (SLN) in predicting pelvic lymph node status for early cervical squamous cell carcinoma, and approach the clinical significance of SLN detection for guiding radical abdominal trachelectomy (RAT).Outcomes of follow up and fertility were also observed.
A total of 31 patients with stageIa2-Ib1 squamous cell carcinoma planned to be given RAT and pelvic lymphadenectomy were enrolled. (99m)Tc-?????labeled phytate was injected before surgery.Intraoperatively, SLN were identified, excised, and submitted to fast frozen section.Systematic bilateral pelvic lymphadenectomy was performed, and then RAT was performed in patients with negative SLN. All nodes were sent for routine pathological examination and immunostained with anti-cytokeratin antibody to detect micrometastases.
SLN were detected in all patients (100%,31/31). A total of 109 SLN were identified with a mean number of 3.5 per patient.Of these, SLN of 2 patients were positive on frozen sections and proved to be metastasis by final pathologic examination and quitted the RAT. No missed micrometastasis was found using immunohistochemical staining in SLN and other lymph nodes using histologically node-negative cases. No false negative cases was found and the negative value was 100% (31/31). The sensitivity, accuracy, and false negative rates were 100%, 100%, and 0, respectively. Perioperative complications occured in 5 patients including 2 cases of bladder injury and 3 cases of uterine artery injury.No relapses occurred during follow-up.Five of 19 patients with procreative desire conceived pregnancies (4 spontaneous abortion and 1 premature birth) after surgery.
The identification of SLN using (99m)Tc-labeled phytate could predict the pelvic lymph node status in early stage cervical cancer. Under the guidance of SLN detection, RAT is a feasible operative modality with well prognosis and low complications for young patients who desire to preserve reproductive function.
[show abstract][hide abstract] ABSTRACT: To evaluate the efficacy and toxicities of gemcitabine combined with ifosfamide and anthracycline chemotherapy for recurrent platinum resistant ovarian epithelial cancer.
Gemcitabine 800 mg/m(2) (day 1, 8), ifosfamide 1.5 g/m(2) (day 1 - 3), adriamycin 40 mg/m(2) or epirubicin 60 mg/m(2) (day 1) or mitoxantrone 10 mg/m(2) (day 1, 8) were used in recurrent platinum resistant/refractory ovarian cancer patients, the cycle was repeated at interval of 21 to 28 days.
A total of 60 patients received 172 cycles combined chemotherapy. There were no one cases complete response, while partial response 22 (37%, 22/60), stable 23 (38%, 23/60) and progression 15 (25%, 15/60) were observed, with clinical benefit rate 75% (45/60). The median time of progression-free survival was 7 months, and the median overall survival time was 20 months. The main side effect was hematologic toxicity with leukopenia rate of 82% (49/60), among which III-IV accounted for 31% (15/49). Digestive reaction was all in I-II, accounted for 42% (25/60).
The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.
Zhonghua fu chan ke za zhi 11/2010; 45(11):808-12.
[show abstract][hide abstract] ABSTRACT: To explore the clinicopathological characteristics of hereditary ovarian cancer syndrome (HOCS).
From Jan. 2000 to Jan. 2007, among 580 cases of primary ovarian cancer, 42 cases (hereditary group), who had a positive family history of ovarian cancer and met the diagnostic criteria of HOCS, were analyzed retrospectively. One hundred cases without a family history of ovarian cancer were enrolled randomizely as control group (sporadic group).
The incidence of HOCS was 7.2% (42/580). Forty-two cases associated tumors affected at least 2 successive generations in 31 families and affected 1 generation in 8 families. Eighty-seven percent (27/31) was from maternal lineage, while 13% (4/31) from paternal lineage. Earlier age of onset was significantly difference between two groups [(49 +/- 10) years vs. (55 +/- 10) years, P < 0.05]. There were 90% belong to serous adenocarcinoma in the hereditary group, while 84% in the sporadic group. There was statistical difference in the proportion of mucinous adenocarcinoma (0 vs. 11%, P < 0.05). The most common clinical manifestations were abdominal distention and anorexia (64% vs. 70%, P > 0.05), International Federational of Gynecology Obstetrics (FIGO) stage III (62% vs. 63%, P > 0.05) between two groups. Fourteen cases (33%,14/42) were previously untreated in the hereditary group, while 40 cases (40%, 40/100) in the sporadic group. There were 15 cases (36%, 15/42) underwent secondary surgery and 15 cases (36%, 15/42) underwent third surgery or more in hereditary group, while 50 cases (50%,50/100) and 27 cases (27%, 27/100) in the sporadic group. The mean number of chemotherapy cycles received in two groups was 13.3 and 11.8 (P > 0.05). The 3-year and 5-year survival rate in hereditary group were 73.6% and 54.9% respectively, compared with 47.4% and 21.2% (P < 0.05) in sporadic group.
Hereditary ovarian cancer mostly from maternal lineage are featuring in early age of onset, serous adenocarcinoma, advanced stage (stage III), and better prognosis after the comprehensive treated by cytoreductive surgery plus with chemotherapy.
[show abstract][hide abstract] ABSTRACT: To investigate the distribution of metastatic pelvic lymph nodes in the women with early stage cervical carcinoma, and the feasibility of dividing these nodes into three stations in those patients.
(99m)Tc-DX of 2 ml was injected into the cervix to a depth of 5 to 10 mm at 3, 6, 9, 12 o'clock positions preoperatively in 196 patients with early stage cervical cancer. Pelvic lymphadenectomy and radical hysterectomy were performed in all patients. Pelvic lymph nodes were detected by gamma-probe. The sentinel lymph nodes (SLN) were determined if the radioactivity reached 5 times higher than that in the ipsilateral nodes. All resected pelvic lymph nodes were examined by histopathology with HE stained serial sections.
Of the 196 patients, 41 were found to have metastasis in 83 lymph nodes. The metastatic rate was 78.3% (65/83) in the parametrial and obturator lymph nodes, 20.5% (17/83)in the internal and external iliac lymph nodes, 1.2% (1/83) in the commmon iliac lymph nodes. Of the 22 patients with metastatic parametrial lymph nodes, metastatic external iliac lymph nodes were detected in 5 patients, and metastatic internal iliac lymph nodes in 3 patients. Among the 19 patients with metastatic obturator lymph nodes, metastatic external iliac lymph nodes were found in 4 patients, and metastatic internal iliac lymph nodes in 3 cases. It was shown by Chi-sqare test that the metastases in parametrial and/or obturator lymph nodes were positively correlated with lymph node metastases in other pelvic sites. Eighty-one SLN were found to have metastasis. The metastatic rate of parametrial and obturator SLN was 79.0% (64/81) versus 21.0% (17/81) of internal and external iliac SLN. No statistically significant difference in 1- and 3-yr survival was observed between the groups with and without metastasis in parametrial and obturator lymph nodes, while the 5-yr survival rate in the patients without metastatic lymph node was 93.2%, significantly higher than that of patients with lymphatic metastasis (65.1%).
It is feasible for cervical cancer to divide the pelvic lymph nodes into three levels. The level I lymph nodes consist of parametrial and obturator lymph nodes. Internal and external iliac lymph nodes can be considered as level II lymph nodes, and the common iliac and inguinal lymph nodes as level III nodes. A rational treatment plan can be made according to the distribution of metastatic pelvic lymph nodes.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 07/2008; 30(6):452-5.
[show abstract][hide abstract] ABSTRACT: To investigate the value of intensity modulated radiation therapy (IMRT) for patient with gynecological malignancies after treatment of hysterectomy and chemotherapy/radiotherapy.
All 32 patients with cervical or endometrial cancer after hysterectomy received full course IMRT after 1 to 3 cycles of chemotherapy (Karnofsky performance status(KPS) > or =70). Seventeen of these patients underwent postoperative preventive irradiation and the other 15 patients were pelvic wall recurrence and/or retroperitoneal lymph node metastasis, though postoperative radiotherapy and/or chemotherapy had been given after operation.
The median dose delivered to the PTV was 56.8 Gy for preventive irradiation, and 60.6 Gy for pelvic wall recurrence or retroperioneal lymph node metastasis irradiation. It was required that 90% of iso-dose curve could covere more than 99% of GTV. However, The mean dose irradiated to small intestine, bladder, rectum, kidney and spinal cord was 21.3 Gy, 37.8 Gy, 35.3 Gy, 8.5 Gy, 22.1 Gy, respectively. Fourteen patients presented grade I (11 patients) or II (3 patients) digestive tract side-effects, Five patients developed grade I or II bone marrow depression. Twelve patients had grade I skin reaction. The overall 1-year survival rate was 100%. The 2- and 3- year survival rate for preventive irradiation were both 100%, but which was 5/7 and 3/6 for the patients with pelvic wall recurrence or retroperioneal lymph node metastasis.
Intensity modulated radiation therapy can provide a better dose distribution than traditional radiotherapy for both prevention and pelvic wall recurrence or retroperioneal lymph node metastasis. The toxicity is tolerable. The adjacent organs at risk can well be protected.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 05/2007; 29(4):305-8.
[show abstract][hide abstract] ABSTRACT: To study the value of sentinel lymph nodes (SLN) in prediction of the pelvic lymph nodes status and to determine the significance of SLN detection in pelvic lymph nodes dissection in patients with early stage cervical carcinoma.
From November 2002 to August 2003, 23 patients with early stage cervical carcinoma planned to undergo radical hysterectomy and extensive pelvic lymph nodes dissection received an intracervical injection of technetium-labeled sulfur colloid as well as blue dye to identify and perform resection of SLNs. The SLNs were pathologically compared with non-SLNs with frozen section, paraffin section, and anti-cytokeratin immunohistochemical staining.
Out of 23 patients, SLNs were detected in 19 patients. A total of 59 SLNs were identified and the mean was 3 per patient. The detection rate of SLN was 83%. Sensitivity, specificity and accuracy of the SLN biopsy were 83%, 100% and 95%, respectively.
SLNs detection can predict the pelvic lymph nodes status in early stage cervical carcinoma, but the feasibility and safety of this technique to substitute conventional surgical modality should be evaluated by large series of prospective studies.