Background and aim A new marker, CD208, was recently explored as a mature interdigitating dendritic cell (DC), and the correlation between the infiltration of CD208-positive cells and clinical ...factors has been reported in various types of cancers. In this study, we tried to clarify the clinical implication of CD208-positive cell infiltration in gastric cancer immunohistochemically. Patients and methods A total of 128 gastric cancer patients who underwent a curative operation were enrolled. DCs in tumor nests were identified with two DC markers, CD208 and S-100 protein (S100), by immunohistochemistry. The correlation between clinicopathological features and the CD208- or S100-positive cell infiltration degree was analyzed. Results Infiltration of S100-positive cells did not correlate with the degree of CD208-positive cell infiltration. Patients with high CD208-positive cell infiltration in the peritumor had a poorer surgical outcome than those with low CD208 infiltration (p < 0.05). Multivariate analysis revealed that CD208-positive cell infiltration was not an independent prognostic factor. Conclusion We showed that intratumoral CD208-positive cells, as mature DCs, had an inverse correlation to patients' postoperative outcome in gastric cancer, unlike a conventional DC marker. Evaluation of CD208-positive cell infiltration with S100-positive cell infiltration in gastric cancer is useful to predict antitumor immunological conditions in gastric cancer.
Although robotic surgery is becoming more widespread worldwide, it is still in its infancy. This study aimed to confirm the safety and feasibility of the induction of robotic-assisted gastric surgery ...at a local hospital.
For five years, between 2016 and 2020, 42 laparoscopic and 71 robotic distal gastrectomies were performed at the same institution. Patients diagnosed with gastric cancer were retrieved from the database. Propensity score matching was performed based on covariates such as Age, Sex, BMI, the American Society of Anesthesiologists Physical Status, Tumor Location, pT, and pN. Clinicopathological characteristics, surgical performance, postoperative outcomes, and pathological data were retrospectively collected and compared by the Chi-square test, the Fisher's exact test, the Student's t-test, and the Mann–Whitney U test.
Billroth II reconstruction was often selected for the robotic group more than the laparoscopic group (59.4% and 15.6%, respectively). In addition, the number of lymph nodes harvested after D2 dissection tended to be more significant in the robotic group than in the laparoscopic group (52.1 ± 7.6 and 29.1 ± 3.7, respectively; p = 0.00934). The mean operative time was 271.4 ± 10.5 min for the robotic group and 220.8 ± 12.3 min for the laparoscopic group (p = 0.00005). There were no differences in short-term clinical outcomes between the two groups.
Although a single-center, small comparative study, the results showed that the robotic surgery group was not inferior to the laparoscopic group in feasibility and safety. Moreover, robotic surgery enables harvesting a higher number of lymph nodes, which may be more advantageous than laparoscopic surgery. This study also showed that as the surgeon gains experience with robotic surgery, its operative time becomes significantly shorter.
Efficient adenovirus infection requires coxsackie-adenovirus receptor (CAR) and alpha(v) integrin. Whereas many malignant cells express these proteins poorly, normal tissues, especially liver, ...express high levels and are susceptible to adenovirus infection. Our previous studies showed that treatment of cancer cell lines with low concentrations of the histone deacetylase inhibitor FK228 (FR901228, depsipeptide), a drug in Phase II clinical trials, before infection was associated with an increase in adenovirus transgene expression. The purpose of these studies was to analyze the effects of FK228 on cultured normal human cells before initiating animal studies.
Cancer and normal cells from the corresponding tissue were treated with FK228 and analyzed for the proteins needed for infection and the infection efficiency.
Treatment of cancer cell lines with 1 ng/ml FK228 increased CAR RNA, alpha(v) integrin RNA, and histone H3 acetylation levels, and was associated with a 4-10-fold increase in the number of infected cells expressing the transgene. Similar treatment of normal human mammary epithelial cells, renal proximal tubule epithelial cells, and hepatocytes had little effect. The insensitivity of cultured normal cells may be explained, in part, by expression of the drug efflux pump P-glycoprotein, because addition of the P-glycoprotein inhibitor XR9576 (tariquidar) with FK228 resulted in increased histone acetylation and CAR expression.
These studies suggest that low concentrations of FK228 preferentially increase the efficiency of adenoviral transgene expression in cancer cells compared with cultured normal cells from the corresponding tissue and may increase the efficiency of adenovirus therapies in vivo.
The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is expressed at higher levels in a wide variety of solid tumors compared to adjacent normal ...tissues. Patients with PD-ECGF/TP-positive colon and esophageal tumors have a poorer prognosis than those with negative tumors. The expression of PD-ECGF/TP is a prognostic factor independent of microvessel density suggesting that TP has effects on tumor progression independent of its angiogenic activity. Evidence that hypoxia and apoptosis affect tumor growth prompted us to determine whether increased expression of PD-ECGF/TP prevents apoptosis induced by hypoxia. KB/TP cells transfected with a PD-ECGF/TP cDNA were resistant to hypoxia-induced apoptosis. Among the degradation products of thymidine produced by PD-ECGF/TP, 2-deoxy-D-ribose and thymine partially prevented hypoxia-induced apoptosis. The ability of 1 μM 2-deoxy-D-ribose in combination with the same concentration of thymine to prevent hypoxia-induced apoptosis was similar to that of the overexpressed TP in KB cells. A concentration of 1 μM 2-deoxy-L-ribose abrogated the effects of these degradation products of thymidine. These findings suggested that TP can confer resistance to apoptosis induced by hypoxia and the degradation products of thymidine are involved in this resistance. Expression of PD-ECGF/TP may play an important role in the progression of solid tumors, and inhibitors of TP and analogs of the degradation products of thymidine may suppress the growth of tumors by promoting apoptosis.
An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced ...by hypoxia. 2-Deoxy-
d-ribose, a degradation product of thymidine generated by TP enzymatic activity partially prevented hypoxia-induced apoptosis. 2-Deoxy-
d-ribose inhibits a number of components of the caspase-mediated hypoxia-induced apoptotic pathway. It inhibits hypoxia-induced caspase 3 activation, mitochondrial cytochrome
c release, downregulation of Bcl-2 and Bcl-x
L, upregulation of hypoxia-inducible factor (HIF)-1α, and loss of mitochondrial transmembrane potential in human leukemia HL-60 cell line. These findings suggest a molecular mechanism by which 2-deoxy-
d-ribose confers the resistance to apoptosis. Thus 2-deoxy-
d-ribose-modulated suppression of HIF-1α expression could prevent the hypoxia-induced decrease of the anti-apoptotic Bcl-2 and Bcl-x
L on the mitochondria. 2-Deoxy-
l-ribose and its analogs may enhance apoptosis and suppress the growth of tumors by competitively inhibiting the activities of 2-deoxy-
d-ribose and thus these analogs show promise for anti-tumor therapy.
Purpose
This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil (FOLFOX4) as a second-line therapy for ...Japanese patients with unresectable advanced or metastatic colorectal cancer.
Methods
A total of 53 patients with progressive disease after first-line chemotherapy were enrolled in the study. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or the patient chose to discontinue the treatment.
Results
Four patients were ineligible and one did not receive the protocol therapy. Therefore, the response rate, overall survival (OS), and progression-free survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52 patients, excluding the patient who had not received the protocol therapy. A partial response was observed in 10 patients. The overall response rate was 20.8% (95% confidence interval CI, 10.5%–35.0%). The median PFS was 5.6 months (95% CI, 4.1–7.0 months) and the median OS was 19.6 months (95% CI, 11.4–24.3 months). The most frequently encountered grade 3/4 hematological symptom was neutropenia (43.1%). The toxicity profile was generally predictable and manageable.
Conclusion
The results showed good tolerability and efficacy for second-line FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise of this regimen as an effective second-line therapy for advanced colorectal cancer in the Japanese population.
A Case of Hernia of Morgagni Treated by Laparoscopic Surgery Ohyama, Tomohiro; Kitazono, Masaki; Ikeda, Naotaka ...
Nihon Fukubu Kyukyu Igakkai Zasshi (Journal of Abdominal Emergency Medicine),
2022/09/30, Volume:
42, Issue:
6
Journal Article
Open access
A 72-year-old woman presented to us with the chief complaints of sudden right hypochondrial pain and breathlessness. Abdominal computed tomography revealed herniation of the transverse colon, small ...intestine and greater omentum into the right thoracic cavity, and we diagnosed the patient as having hernia of Morgagni based on the position of the hernial orifice. We elected to perform laparoscopic surgical repair, and during the laparoscopic surgery, the hernial orifice was found on the right side and behind the sternum, confirming our preoperative finding. Even though all of the transverse colon, small intestine and greater omentum had invaginated into the hernial orifice, which was 7×5 cm in diameter, we were able to easily reduce them into the abdominal cavity. We sutured the hernial orifice and covered it with SymbotexTM Composite Mesh. The patient was discharged seven days after the surgery, and has had no relapse until now, 2 years since the operation. Hernia of Morgagni is relatively rare, and no standard surgical treatment method has been established. Laparoscopic surgical repair using a mesh may be an easy and minimally invasive treatment method for hernia of Morgagni.
Abstract Background : Several tumor-suppressor genes, such as 53-kDa protein (p53), are inactivated in some pancreatic cancers. The lack of a functional p53 has been proposed to be a component of ...resistance to chemotherapy, resulting in the inhibition of apoptosis. Therefore, reintroduction of wild-type p53 is a commonly used gene therapy strategy for the treatment of various types of cancer, including pancreatic cancer. Objective : The aim of this study was to examine the ability of the histone deacetylase inhibitor, sodium butyrate (NaB), to modulate the expression of p53. Methods : Five human pancreatic carcinoma cell lines (SW-1990, BxPC-3, PANC-1, MIA PaCa-2, JHP-1) were utilized. Two of the cell lines (SW-1990 and JHP-1) lacked p53 expression, as determined by Western blot analysis, and were investigated further. Expression of p53 was determined by densitometry of all bands present in the Western blot. Drug sensitivity was measured with a tetrazolium-based assay by exposing the cells to graded concentrations of NaB and/or anticancer drugs (cisplatin, fluorouracil, SN-38, and paclitaxel). Apoptosis was observed using gel electrophoresis. Results : In the SW-1990 and JHP-1 cell lines, use of 1 mM NaB was found to induce histone acetylation and p53 expression compared with those not treated with NaB ( P = 0.01 and P = 0.018, respectively). Sensitivity to cisplatin ( P = 0.021), fluorouracil ( P = 0.046), and SN-38 ( P = 0.039) was significantly enhanced by NaB treatment compared with nontreatment. However, sensitivity to paclitaxel was not significantly different between untreated and NaB-treated cells. A higher frequency of apoptosis was observed in NaB-treated cells compared with that of control cells. Conclusion : This in vitro study found that NaB induced p53 expression in 2 pancreatic cancer cell lines (SW-1990 and JHP-1). Moreover, NaB acted on a biochemical modulator for antieuplastic therapy. Future research is necessary to assess the value of these findings.
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