CXCL13 inhibition induce the apoptosis of MDA-MB-231 breast cancer cells through blocking CXCR5/ERK signaling pathway.

OBJECTIVE: Treatment of the high-risk triple negative breast cancer (TNBC) is a critical clinical challenge. Here we aimed to explore a novel strategy for TNBC treatment by blocking the tumor-associated chemokine CXCL13 in the MDA-MB-231 TNBC cells. MATERIALS AND METHODS: MDA-MB-231 cells were treated with anti-CXCL13 antibodies (inhibition group), or phosphate-buffered saline (PBS) (control group), followed by determining the levels of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α) and transforming growth factor beta-1 (TGF-ß1) with enzyme-linked immunosorbent assay (ELISA). The effects of CXCL13 inhibition on cell proliferation and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Quantitative Real Time-PCR (qRT-PCR) and Western blot were used to compare the levels of CXCL13, CXCR5, extracellular signal-regulated kinase (ERK). The levels of cyclin D1 and cleaved caspase-9 were detected by Western blot. RESULTS: The levels of IL-1, TNF-α and TGF-ß1 in MDA-MB-231 cells treated with anti-CXCL13 antibodies were significantly downregulated (p<0.05). Meanwhile, CXCL13 blockade decreased the cell proliferation and increased the apoptosis rate of MDA-MB-231 cells. The inhibition of CXCL13 led to marked reduction in CXCL13 and CXCR5 mRNA and an increase in ERK mRNA. The inhibition of CXCL13 resulted in the downregulation of CXCL13, CXCR5, p-ERK/ERK, cyclin D1 and upregulation of cleaved caspase-9 proteins. CONCLUSIONS: CXCL13 blockade effectively suppressed the proliferation of MDA-MB-231 cells by promoting cell apoptosis. This effect is presumably associated with the downregulation of CXCL13 and suppression of the CXCR5/ERK signaling pathway.

Combined intracavitary and external beam irradiation for superficial transitional cell carcinoma of the bladder: an alternative to cystectomy for patients with recurrence after intravesical chemotherapy.

A total of 17 patients with superficial transitional cell carcinoma of the bladder underwent treatment with pelvic external beam irradiation followed by an intracavitary 137cesium implant via a triple lumen Foley catheter. Of these patients 11 had recurrent and multifocal superficial cancer, with 8 having relapse after prior intravesical chemotherapy. External beam doses of 3,600 to 5,066 cGy. were followed by implant doses delivering 2,000 to 3,200 cGy. to the bladder mucosa, with the sum of external and intracavitary doses totaling 6,500 to 7,500 cGy. Of 15 patients evaluable with a median followup of 48 months, and including 13 followed for more than 2 years, 11 (73 per cent) remain free of disease, 3 (20 per cent) have recurrence in the bladder but have retained the bladder and only 1 has required cystectomy. All 4 failures occurred in the subgroup of 8 patients who had received prior intravesical chemotherapy. This bladder-sparing approach is well tolerated, is an alternative to cystectomy in patients with recurrent superficial transitional cell carcinoma of the bladder and in our series has salvaged 50 per cent (4 of 8) of the patients even after failure of intravesical chemotherapy.

Adenocarcinoma of the colon: an autopsy study with implications for new therapeutic strategies.

Clinical, pathologic, and autopsy records of 53 patients who had localized adenocarcinoma of the proximal colon and had undergone potentially curative surgery were analyzed to define ultimate patterns of recurrence and final patterns of dissemination. Ten patients (19%) died with locoregional recurrence alone (operative bed and retroperitoneal nodes). Liver metastases were present in 31 patients, accompanied by other sites of infradiaphragmatic failure in 29 patients (94%). Twenty-three patients (43%) died with cancer confined to the abdomen, retroperitoneum, and liver. The distribution of involved sites points to potential refinements in the surgical staging of this cancer and suggests a rational strategy for planning adjuvant therapy designed to address all the principal early mechanisms of disease dissemination.

Adjuvant postoperative pelvic radiation for carcinoma of the uterine cervix: pattern of cancer recurrence in patients undergoing elective radiation following radical hysterectomy and pelvic lymphadenectomy.

Thirty-seven patients with invasive cervical cancer have been referred to the Department of Radiation Oncology at the University of Washington following radical hysterectomy and pelvic lymphadenectomy. Patients at high-risk for tumor recurrence were selected for adjuvant pelvic irradiation because of adverse risk factors identified on pathological study of the hysterectomy specimen. All patients were treated because of possible residual, microscopic carcinoma. Fourteen patients (38%) developed recurrent cancer, of whom 10 (27%) manifested initial failure within the irradiated volume. Possible explanations for this observation are discussed.

Intracavitary irradiation for carcinoma of the urinary bladder: rationale, technique, and preliminary results.

Twelve patients with transitional cell carcinoma of the bladder have been treated employing a combination of external beam radiation (4000 to 5040 cGy/4 to 5.5 weeks) supplemented by intracavitary irradiation (1500 to 3000 cGy mucosal dose) using a triple lumen balloon catheter containing a central 137Cs source. The rationale, patient selection, and preliminary results are reported, and the technique of the intracavitary brachytherapy is described.

Electron beam therapy of mycosis fungoides.

Sixteen patients with mycosis fungoides were treated with a 3.3 MeV skin electron beam to a dose of 30 Gy over 40 days. Nine patients achieved a complete remission which was generally short. Only two patients remained free of disease one year following treatment. All patients received palliative benefit from treatment, but no significant increase in survival can be anticipated.