Laparoscopic Single-Incision Triangulated Umbilical Surgery Adrenalectomy for Large (>5 cm) Tumors of the Adrenal Gland: Initial Experience with 16 Cases.

Background and ObjectivesLaparoscopic single-incision triangulated umbilical surgery (SITUS), which enables the extraction of intraabdominal specimens through a single umbilical incision, has yet to be used to perform adrenalectomy. We have modified SITUS to enable extraction of large (>5 cm) adrenal masses with optimal cosmetic outcomes and investigated efficacy and safety. Methods. In this retrospective study, we analyzed data of 16 patients with adrenal tumors >5 cm who had undergone adrenalectomy by SITUS between October 2015 and April 2018. Two C-shaped incisions were made around the umbilicus and sutured centripetally. After extracting the specimen, we evaluated these patients' operative/postoperative data. Results. SITUS was performed in all 16 patients without conversion to laparoscopic or open surgery. The mean operation time was 75.31 ± 21.54 min (intraperitoneal time 41.94 ± 17.57 min; incision suturing time 33.38 ± 6.34 min). The estimated median blood loss was 57.5 mL (range 30-610 mL). Drainage time and duration of hospital stay were 55.69 ± 12.92 h and 3.94 ± 0.90 d, respectively. After surgery, all incisions were hidden under the umbilicus. Three patients developed keloid diathesis, resulting in enlargement of their scars. Conclusions. SITUS is a safe and feasible procedure for removing large adrenal tumors. In addition to its cosmetic advantages, SITUS facilitates functional recovery, particularly in patients with large adrenal tumors.

Inhibition of both EGFR and IGF1R sensitized prostate cancer cells to radiation by synergistic suppression of DNA homologous recombination repair.

Reduced sensitivity of prostate cancer (PC) cells to radiation therapy poses a significant challenge in the clinic. Activation of epidermal growth factor receptor (EGFR), type 1 insulin-like growth factor receptor (IGF1R), and crosstalk between these two signaling pathways have been implicated in the development of radiation resistance in PC. This study assessed the effects of targeting both receptors on the regulation of radio-sensitivity in PC cells. Specific inhibitors of EGFR and IGF1R, Erlotinib and AG1024, as well as siRNA targeting EGFR and IGF1R, were used to radio-sensitize PC cells. Our results showed that co-inhibiting both receptors significantly dampened cellular growth and DNA damage repair, and increased radio-sensitivity in PC cells. These effects were carried out through synergistic inhibition of homologous recombination-directed DNA repair (HRR), but not via inhibition of non-homologous end joining (NHEJ). Furthermore, the compromised HRR capacity was caused by reduced phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent interaction with Rad51. The synergistic effect of the EGFR and IGF1R inhibitors was also confirmed in nude mouse xenograft assay. This is the first study testing co-inhibiting EGFR and IGF1R signaling in the context of radio-sensitivity in PC and it may provide a promising adjuvant therapeutic approach to improve the outcome of PC patients to radiation treatment.

[Expression of Smad4 in prostate cancer LNCaP and ARCaP cell lines with different metastatic potentials and its significance].

OBJECTIVE: To observe the expression of Smad4, the core of TGF-beta/Smads signal transduction pathway in different prostate cancer cell lines, and explore their molecular mechanism of bone metastatic potential. METHODS: The Millicell polycarbonate filter coated with matrigel was used to confirm the invasive potency of LNCaP and ARCaP cell lines (IF11 and IA8). The expressions of the Smad4 protein and mRNA in these prostate cancer cells with different metastatic potentials were detected by Western blotting and RT-PCR, respectively. RESULTS: ARCaP cell lines (IF11 and IA8) exhibited a stronger potency of invasion than LNCaP (P < 0.01). The Smad4 protein and mRNA highly expressed in the LNCaP cell line that was well-known with a low metastatic potential, but not in the ARCaP (IF11 or IA8) cells with high metastatic potentials (P < 0.01). CONCLUSION: Smad4 expresses differently in LNCaP and ARCaP cell lines with different metastatic potentials and, as a tumor suppressive gene, its deficient expression may play an important role in the invasion and metastasis of advanced prostate cancer.

[Identification of TGF-beta/Smads pathway in human prostate cancer cell lines and its significance].

OBJECTIVE: To determine the TGF-beta/Smads signal pathway in different human prostate cancer cell lines, and to explore the role of the TGF-beta/Smads pathway in the progression and metastasis of prostate cancer and its possible mechanisms. METHODS: We detected the expressions of the key proteins involved in the TGF-beta/Smads pathway, TbetaR II, Smad2/3, p-Smad2 and Smad4, in prostate cancer cell lines LNCaP, PC-3, DU145, IF11 and IA8 with different metastatic potentials by Western blotting. RESULTS: TbetaR II was expressed highly in PC-3, DU145, IF11 and IA8, but extremely lowly in LNCaP. Smad2/3 was highly expressed in all the cell lines with different intensity, while p-Smad2 only in PC-3 and DU145. The expression of Smad4 was detected in LNCaP, PC-3 and DU145, but not in IF11 and IA8. CONCLUSION: The status of the TGF-beta/Smads pathway differs in the cell lines with different metastatic potentials, only active in PC-3 and DU145. The TGF-beta/Smads pathway may be involved in the invasion and metastasis of prostate cancer through altering the expressions of the key proteins in it.

[Over-expression of hypoxia-inducible factor 1 alpha increases angiogenesis of LNCaP cells in vivo].

OBJECTIVE: To observe the influence of hypoxia-inducible factor 1 alpha (HIF-1alpha) on angiogenesis in prostate carcinoma in vivo and to investigate its molecular mechanism. METHODS: LNCaP/HIF-1alpha and LNCaP cells were cultured, the level of PSA in the supernatant of the culture medium detected by ELISA assay before and after the transfection, and the cellular cycle measured by flow cytometry. Nude mouse models of subcutaneous tumor were established with LNCaP/HIF-1alpha and LNCaP cells, the tumor growth observed, and tumor specimens collected for immunohistochemical staining. RESULTS: Compared with the LNCaP cells, LNCaP/HIF-1alpha cells showed an obviously decreased PSA level (t = 8.243, P < 0.05) and enhanced proliferous activity. The tumorigenesis rate increased and the tumorigenesis time advanced in the LNCaP/HIF-1alpha group of the nude mice. Immunohistochemistry displayed higher expressions of VEGF, iNOS and Ang-2 in the LNCaP/HIF-1alpha than in the LNCaP group. CONCLUSION: The over-expression of HIF-1alpha can up-regulate VEGF and iNOS involved in angiogenesis in vivo and contribute to the invasive potency of LNCaP cells. HIF-1alpha may have no influence on Ang-2 either in vitro or in vivo, while the expression of Ang-2 is regulated by other factors in vivo.

[Transforming growth factor beta upregulates the expression of invasion and metastasis associated proteins in prostate cancer LNCaP cell lines in vitro].

OBJECTIVE: To determine the effect of the transforming growth factor beta (TGF-beta) on the expression of invasion and metastasis associated proteins in the prostate cancer LNCaP cell line in vitro. METHODS: The prostate cancer cell line LNCaP was treated with TGF-beta in vitro. Western blotting was used to detect the expression of the "invasion and metastasis" associated proteins E-Cadherin, N-Cadherin and Vimentin. RESULTS: The expression of N-Cadherin and Vimentin of the LNCaP cells treated with TGF-beta for 12 hours was significantly upregulated, but not that of E-Cadherin. CONCLUSION: TGF-beta may induce epithelial-mesenchymal transition (EMT) of LNCaP cells which might be of importance in promoting prostate cancer cells invading to ambient tissues and metastasizing to distant organs.

[Over-expression of hypoxia-inducible factor-1 alpha increases angiogenesis of LNCaP cells].

OBJECTIVE: To evaluate the effect of hypoxia-inducible factor-1 alpha (HIF-la) on angiogenesis in human prostate cancer cells. METHODS: Human prostate cancer cells of the line LNCaP were cultured and transfected by the recombinant plasmid pcDNA3. 1(-)/HIF-1alpha containing the gene HIF-1alpha with the Lipofectamine 2000 system. The positive clone cells were selected by G418 and confirmed by Western blotting and immunofluorescence (LNCaP/HIF-1alpha cells). The expressions of VEGF, iNOS and Ang-2 were detected by Western blotting. RESULTS: The expression of HIF-1alpha in the LNCaP/HIF-1alpha cells was distinctly higher than that in the LN-CaP cells. Compared with the LNCaP cells, the expressions of VEGF and iNOS were up-regulated, whereas Ang-2 remained unchanged in the LNCaP/HIF-1alpha cells. CONCLUSION: The over-expression of HIF-1alpha can induce an increase in angiogenesis proteins and improve the angiogenesis potency of prostate cancer.