Efficacy and Safety of Disitamab Vedotin Combined with Programmed Death-1 Inhibitor for Advanced Urothelial Cancer: A Case-Series Study.

INTRODUCTION: Antibody-drug conjugate (ADC) and programmed death-1 (PD-1) inhibitors play crucial roles in the treatment of advanced urothelial cancer (aUC). Increasingly, combination treatment modalities are used in patients with aUC intolerant to platinum-based chemotherapy (PBC). However, clinical evidence on the efficacy and safety of disitamab vedotin plus PD-1 inhibitors for aUC is limited. This case series aims to address this knowledge gap. METHODS: Patients with aUC who were refractory or intolerant to PBC were included. All patients received combined treatment with disitamab vedotin (one of the ADC drugs) and PD-1 inhibitors for at least three cycles. The clinical characteristics of examination, histopathology, outcomes, and adverse events (AEs) were retrospectively collected. RESULTS: Among this case series, eight patients received disitamab vedotin plus PD-1 inhibitors, of which three achieved a complete response (CR) and two had a partial response (PR). The most common AE was peripheral neuropathy (4/8); the remaining AEs were mostly of mild to moderate severity or unknown and were manageable by supportive care. CONCLUSIONS: Disitamab vedotin combined with PD-1 inhibitors exhibits a favorable efficacy and safety profile, but subsequent larger cohort clinical studies are required to provide evidence-based medicine for the universal application of this regimen.

MLF1 interacting protein: a potential gene therapy target for human prostate cancer?

Here, we investigated the role of one gene that has been previously associated with human prostate carcinoma cells-myelodysplasia/myeloid leukemia factor 1 interacting protein (MLF1IP)-in order to better ascertain its role in human prostate carcinogenesis. The prostate cancer cell line PC-3 was lentivirally transfected to silence endogenous MLF1IP gene expression, which was confirmed by real-time quantitative PCR (RT-qPCR). Cellomics ArrayScan VTI imaging and MTT assays were conducted to assess cell proliferation. Cell cycle phase arrest and apoptosis were assayed by flow cytometry. Colony formation was assessed by fluorescence microscopy. MLF1IP gene expression was also analyzed by RT-qPCR in sixteen prostate cancer tissue samples and six healthy control prostate tissue samples from human patients. Cell proliferation was significantly inhibited in MLF1IP-silenced cells relative to control cells. G1 phase, S and G2/M phase cell counts were not significantly changed in MLF1IP-silenced cells relative to control cells. Apoptosis was significantly increased in MLF1IP-silenced cells, while MLF1IP-silenced cells displayed a significantly reduced number of cell colonies, compared to control cells. The 16 human prostate cancer tissue samples revealed no clear upregulation or downregulation in MLF1IP gene expression. MLF1IP significantly promotes prostate cancer cell proliferation and colony formation and significantly inhibits apoptosis without affecting cell cycle phase arrest. Further study is required to conclusively determine whether MLF1IP is upregulated in human prostate cancer tumors and to determine the precise cellular mechanism(s) for MLF1IP in prostate carcinogenesis.

[Expression of COX10 in human non-obstructive azoospermia testes].

OBJECTIVE: To evaluate the expression of COX10 mRNA in the testes of non-obstructive azoospermia patients and normal men. METHODS: A cDNA microarray containing COX10 and some other genes as RBM and EIF1AY was used to identify the differential gene expression profiles in the normal and azoospermic testes. The cDNA probes were prepared by labeling mRNA from azoospermic and normal testis tissues with Cy5-dUTP and Cy3-dUTP respectively through reverse transcription. The mixed cDNA probes were then hybridized with cDNA microarray. Later the fluorescent signals were scanned and the values of Cy5-dUTP and Cy3-dUTP on each spot were calculated and analyzed. After that an ISH was employed to detect the expression of COX10 mRNA in 10 fertile and 39 non-obstructive azoospermic testes, and the expression levels were compared to evaluate the significance. RESULTS: We obtained 128 differentially expressed genes that might be related with azoospermia, among which 56 were up-regulated and 72 down-regulated, with the expression of COX10 significantly decreased. In situ hybridization confirmed that the mRNA expression of COX10 was stronger in the spermatogenic cells of the normal fertile than the azoospermic testes. CONCLUSION: COX10 may play a certain role in the development and progression of azoospermia. The technique of cDNA microarray can be applied to further studies of screening non-obstructive azoospermia associated genes.

In vitro and in vivo inhibitory effect evaluation of cyclooxygenase-2 inhibitors, antisense cyclooxygenase-2 cDNA, and their combination on the growth of human bladder cancer cells.

Overexpression of cyclooxygenase (COX)-2 is associated with the progression of various malignancies, but the contribution of COX-2 expression, bioactivity or their cooperation to bladder cancer growth calls for further clarification. In this study, we investigated the inhibitory effect of COX-2 inhibitors, antisense COX-2 nucleotide, and their combination on the growth of bladder cancer cells (5637, 5637-P and 5637-AS). Suppression of either COX-2 expression or activity caused reduced cell proliferation, enhanced cell numbers in G(1) phase, and increased apoptosis; the joint suppression of COX-2 expression and bioactivity enhanced the degree of cell growth inhibition. COX-2 antisense-expressing 5637-AS tumors showed a 41.42+/-3.08% growth inhibition as compared with 5637 controls. Oral administration of indomethacin (3mg/kg) or celecoxib (15 mg/kg) caused tumor growth inhibition by 31.5+/-14.87% or 83.17+/-1.17%, respectively. When COX-2 antisense cDNA and COX-2 inhibitor celecoxib were combined, the tumor growth inhibition rate was further increased up to 88.78+/-3.10%. These results provide evidence that celecoxib has potential therapeutic effect on bladder cancer, and the joint use of COX-2 antisense cDNA with celecoxib may improve their individual therapeutic effect, especially significantly increase the growth inhibitory effect of COX-2 antisense cDNA.

[Clinical investigation of renal angiomyolipoma].

OBJECTIVE: To study the diagnosis and management of renal angiomyolipoma (RAML), and to identify risk factors affecting spontaneous angiomyolipoma rupture. METHODS: The data of 68 patients with RAML from 1989 to 2002 were retrospectively reviewed. These patients were divided in two groups on the basis of tumor size, 35 patients in group A ( 4 cm). RESULTS: Seven patients were identified by image-guided percutaneous biopsy, and no major complications was noted. Sixteen patients with RAML were examined with angiography and 9 of 16 patients had got spontaneous rupture. 41.2% of patients were symptomatic, 4 cases (11.4%) in group A and 24 (72.7%) cases in group B (P < 0.01). There were significant differences in mean tumor size (11.6 cm +/- 5.1 cm vs 5.3 cm +/- 2.9 cm, P < 0.01) and mean aneurysm size (13.6 mm +/- 5.8 mm vs 2.6 mm +/- 3.0 mm, P < 0.01) between 9 cases of the ruptured tumor and 59 cases of unruptured tumor, 9 cases of the ruptured and 7 cases of unruptured tumor with angiography, respectively. Treatment consisted of conservative observation in 10 patients (no radiographic changes during the follow-up of 2 - 7 years); partial nephrectomy in 14 patients, tumor enucleation in 30 patients, total nephrectomy in 14 and posterior laparoscopic nephrectomy in 3 (no recurrence and complication correlation to operation during the follow-up of 2 - 144 months). CONCLUSIONS: It is an important role that percutaneous biopsy guided by ultrasonography or computerized tomography performs in managing suspicious and/or indeterminate RAML. A higher probability of rupture is related to tumor and/or aneurysms size. Nephron-sparing surgery is the first choice for surgical treatment of RAML.

Expression and significance of Rap1A in testes of azoospermic subjects.

AIM: To evaluate the Rap1A mRNA expression and its significance in the testes of normal and azoospermic subjects. METHODS: A cDNA microarray that contained Rap1A and some other genes such as RBM, EIF1AY was used to identify the differential gene expression profiles between the normal and azoospermic testes. cDNA probes were prepared by labeling mRNA from azoospermic and normal testicular tissues through reverse transcription with Cy5-dUTP and Cy3-dUTP, respectively. The mixed cDNA probes were then hybridized with cDNA microarray (each containing 4096 unique human cDNA sequences). The fluorescent signals were scanned and the values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated. In situ hybridization was employed to detect the expression of Rap1A in the testes of 10 fertile and 39 azoospermic subjects. RESULTS: One hundred and twenty-eight differentially expressed genes were found to be possibly related to azoospermia, of which 56 were up-regulated and 72, down-regulated genes. The mRNA expression of Rap1A in the spermatogenic cells of azoospermic was stronger than that in those of the fertile testes. CONCLUSION: Rap1A may play certain roles in the development of azoospermia.

[Diagnosis and treatment of seminal vesicle cyst].

OBJECTIVES: To deepen the understanding of patients with seminal vesicle cyst for correct diagnosis and treatment. METHODS: Sixteen patients with seminal vesicle cysts were treated in the period of January 1980-May 2002. Their symptoms, diagnostic results, treatment and outcomes were analyzed retrospectively. The mean age of these patients at diagnosis was 31 years (range 19 - 43). Two patients were associated with ipsilateral renal agenesis. Symptoms included hematospermia in 12 (75%) patients, urinary frequency in 8 (50%), hematuria after ejaculation in 6 (27.5%), perineal malaise in 6 (27.5%), infertility in 3 (13.7%), pain after ejaculation in 3 (13.7%), scrotal pain in 2 (12.5%) and dysuria in 1 (6.3%). Cyst was palpable in 81.3% patients on digital rectal examination. All patients underwent intravenous urography and cystoscopy. Others received ultrasonography, CT scanning, MRI, and vasovesiculography. The size of masses ranged from 3.8 cm x 3.0 cm x 2.6 cm to 9.6 cm x 5.2 cm x 5.0 cm. Final open surgery consisted of vesiculectomy (4 patients) and partial vesiculectomy (12). RESULTS: Postoperative course was uneventful except in 1 patient with epididymitis. All patients were free of symptoms after open surgery. CONCLUSIONS: Seminal vesicle cysts are rare but should be considered in men with hematospermia and otherwise inexplicable bladder irritation symptoms, perineal discomfort or other genitourinary complaints of unknown etiology. Diagnosis consists of digital rectal examination, transrectal and abdominal ultrasonography, CT scan or MRI. Vesiculectomy and partial vesiculectomy give excellent results.

[The biological characteristics of beta glucuronidase cDNA transfected renal cancer cell line GRC 1/betaG].

AIM: To establish a renal carcinoma cell line which can highly express beta-glucuronidase(betaG), and to observe the biological characteristics of the transfected cells. METHODS: Recombinant eukaryotic expression vector pcDNA3.1-betaG was constructed. It was transfected into renal cancer cells GRC-1 via liposome. The transcription and expression of betaG gene were detected by dot blot and Western blot. The biological characteristics of the betaG gene transfected cells was observed under light microscope, transmission electron microscope and flow cytometry. RESULTS: Dot blot and Western blot detection confirmed that the betaG gene had been stably integrated into the genomic DNA of the GRC-1 cells and was highly expressed. Transmission electron microscope observation showed that the lysosomes and endoplasmic reticulum were abundant, the number of microvili and process was significantly increased in the transfected cells, but growth condition and cell cycle of GRC-1 cells had no notable difference before and after transfection. CONCLUSION: A renal carcinoma cell line that can highly express betaG gene was established, which lays the foundation for further study on gene therapy.

[The relationships of PSA, FPSAR, clinical and pathological stage in patients with prostate cancer].

OBJECTIVES: To investigate the relationship between clinical and pathological stage, serum prostate specific antigen (PSA) concentration and free-to-total PSA ratio (FPSAR) in patients with prostate cancer. METHODS: Clinical and pathological stage were determined on the basis of pathological examination and clinic material in 42 prostate cancer patients treated by prostatectomy. PSA and FPSAR were measured before the operation. Spearman rank correlation was applied to evaluate the relationship between clinical and pathological stage, serum PSA concentration and FPSAR. RESULTS: Serum PSA concentration was significantly positively correlated with pathological stage(P < 0.05) but not correlated with clinical stage (P > 0.05) in prostate cancer patients. FPSAR was significantly correlated with pathological stage and negatively correlated with clinical stage in prostate cancer patients (P < 0.05). CONCLUSIONS: FPSAR is a more powerful predictor of clinical stage, pathological stage and prognosis than PSA.

Diagnosis and treatment of renal trauma in 298 patients.

OBJECTIVE: To investigate the diagnosis and treatment of renal trauma. METHODS: Retrospective analysis of 298 patients with renal trauma was carried out. Among them, 272 (91.3%) had blunt renal injuries and 26 (8.7%) had penetrating injuries; 123 (41.3%) had multiple complicated intraabdominal injuries and 56 (18.8%) had concomitant shock. Normal-dose-IVU examination was used in 39 patients and double-dose-IVU in 44 patients, ultrasonography in 109 patients, and CT in 45 patients. Conservative and supportive therapy was done in 193 patients (64.8%) and operation in 105 patients (35.2%). RESULTS: The positive rate was 48.7% by the normal-dose-I VU examination and 90.9% by double-dose-IVU, 78.8% by ultrasonography, and 95.6% by CT. One hundred and eighty-three patients were cured by conservative therapy and 101 by operation. Fourteen patients died. CONCLUSIONS: B-ultrasound can be conveniently used for primary assessment of renal injuries, while CT shows rapid, accurate and proper condition of a renal trauma patient. The treatment depends on the severity of the injury. The conservative therapy is employed in most cases which present slight or moderate injury and no evident massive bleeding. Severe injury requires surgical exploration. The operative approach is by using a transabdominal incision, which makes it relatively easy to explore intraabdominal organs and control the injured kidney. It is also very important to control shock and prevent other severe complications in the early stage of the treatment.