Fuzheng Huayu recipe inhibits bleomycin-induced pulmonary fibrosis in rats by inhibiting M2 polarization of macrophages via the oxidative phosphorylation pathway.

Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.

Oleanolic acid regulates the proliferation and extracellular matrix of keloid fibroblasts by mediating the TGF-ß1/SMAD signaling pathway.

BACKGROUND: Keloid (KD) is a unique pathological fibroproliferative disease that seriously affects the appearance of patients. This study investigated the effect of oleanolic acid (OA) on the proliferation of keloid fibroblasts (KFs) and the expression of extracellular matrix (ECM)-related proteins. METHODS: The proliferation of KFs was evaluated using an MTT assay. The effects of OA on intra- and extracellular levels of fibronectin (FN), procollagen I, matrix metalloproteinase-1 (MMP-1), and α-smooth muscle actin (α-SMA) were evaluated using Western blotting. To simulate the KD microenvironment, TGF-ß1 was added to the serum-free culture medium, and KFs were incubated with TGF-ß1 and OA for 24 h. The intra- and extracellular levels of the ECM-related proteins and the effect of OA on TGF-ß1-induced phosphorylation of the SMAD2 and SMAD3 proteins were evaluated using Western blotting. RESULTS: OA inhibited the proliferation of KFs in a concentration- and time-dependent manner. Furthermore, OA treatment of KFs reduced the intra- and extracellular levels of FN, procollagen I, and α-SMA and increased those of MMP-1. OA also reduced TGF-ß1-induced increases in the intra- and extracellular levels of FN, procollagen I, and α-SMA and increased the levels of the MMP-1 protein. Additionally, OA significantly reduced TGF-ß1-induced phosphorylation of SMAD2 and SMAD3 in KFs. CONCLUSIONS: OA inhibited KF proliferation and reduced ECM deposition through the TGF-ß1/SMAD pathway, which suggests that OA may be an effective drug for the prevention and treatment of KD.

Structurally diverse diterpenoids with eight carbon skeletons from Rhododendron micranthum and their antinociceptive effects.

Seventeen diterpenoids (1-17), classified into eight diverse carbon skeleton types, grayanane (1, 2, and 12), micranthane (3, 4, and 13), mollane (5-7 and 14), 1,5-seco-grayanane (8), kalmane (9-11), 1,5-seco-kalmane (15), A-homo-B-nor-ent-kaurane (16), and leucothane (17), respectively, were isolated from the leaves extract of Rhododendron micranthum. Among them, diterpenoids 1-9 are new compounds and their structures were elucidated via extensive spectroscopic methods, quantum chemical calculations including the 13C NMR-DP4+ analysis and electronic circular dichroism (ECD) calculations, and the single-crystal X-ray diffraction analysis. Micranthanol A (1) represents the first example of a 5αH,9αH-grayanane diterpenoid and a 6-hydroxy-6,10-epoxygrayanane diterpenoid, and micranthanone B (3) is the first 6,10-epoxymicranthane and the 5α-hydroxy-micranthane diterpenoids. 14-epi-Mollanol A (5) and mollanol B (6) represent the first examples of 14ß-hydroxymollane diterpenoids. It is the first time to report mollane, 1,5-seco-kalmane, and A-homo-B-nor-ent-kaurane type diterpenoids from Rhododendron micranthum. All the seventeen diterpenoids showed significant antinociceptive activities at a dose of 5.0 mg/kg, and it is the first time to evaluate the antinociceptive activity of 1,5-seco-kalmane diterpenoid. Among them, compounds 3, 11, 14, and 15 exhibited significant antinociceptive activities even at a lower dose of 1.0 mg/kg. A preliminary structure-activity relationship for the antinociceptive effects of diterpenoids 1-17 is discussed, which provided a new basis to develop novel potent analgesics.

Gelstriamine A, a Triamino Monoterpene Indole Alkaloid with a Caged 6/5/7/6/6/5 Scaffold and Analgesic Alkaloids from Gelsemium elegans Stems.

A novel triamino monoterpene indole alkaloid with an unprecedented skeleton, gelstriamine A (1), four new monoterpene indole alkaloids (2-5), and 12 known analogues (6-17) were isolated from Gelsemium elegans. The structures of 1-5 were established using extensive spectroscopic techniques, NMR calculations with iJ/dJ-DP4 and 2D C-H COSY ANNs analysis, ECD calculations, chemical methods, and single crystal X-ray diffraction analysis. Gelstriamine A (1) possesses an unprecedented 6/5/7/6/6/5 heterohexacyclic scaffold bearing a unique hexahydrooxazolo[4,5-b]pyridin-2(3H)-one motif, and a plausible biosynthetic pathway was proposed. All the isolated alkaloids 1-17 showed discernible analgesic activities in an acetic acid-induced writhing test in mice, and N-desmethoxyhumantenine N4-oxide (3) exhibited more potent analgesic activities than those of morphine at doses of 0.04 and 0.2 mg/kg.

Melochia corchorifolia extract inhibits melanogenesis in B16F10 mouse melanoma cells via activation of the ERK signaling.

BACKGROUND: Numerous researches have focused on discovering available inhibitors of melanogenesis from natural medicinal plants with stable efficacy and safety to resolve cutaneous hyperpigmentary problems. Melochia corchorifolia Linn. (MC) has been used as folk medicine to treat various diseases. However, the effect of MC on melanogenesis remains unknown. AIM: In this study, we investigated the effect of MC extract on melanogenesis and its underlying mechanisms in B16F10 mouse melanoma cells. METHODS: B16F10 cells were treated with MC extract, and then, cell viability, melanin content, and tyrosinase activity were analyzed. The mRNA and protein expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Phosphorylated or total protein levels in MC extract-induced signaling pathways were analyzed by Western blotting. RESULTS: Treatment of B16F10 cells with MC extract inhibited melanin synthesis and intracellular tyrosinase activity in a dose-dependent manner with no cytotoxicity. Protein and mRNA expressions of tyrosinase and MITF were also significantly decreased by MC extract treatment. In addition, phosphorylated level of extracellular signal-regulated kinase (ERK) was obviously increased by MC extract, but AKT pathway was not activated. Inhibited ERK phosphorylation by pretreatment with a selective ERK inhibitor PD98059 significantly reversed the decreased melanin content induced by treatment with MC extract in B16F10 cells. CONCLUSION: MC extract inhibits melanogenesis in B16F10 mouse melanoma cells through suppression of MITF-tyrosinase signaling pathway by ERK activation.

Clinicopathological Characteristics and Prognosis of Proximal and Distal Gastric Cancer during 1997-2017 in China National Cancer Center.

BACKGROUND: The prognostic relevance of gastric tumor location has been reported and debated. Our study was conducted to examine the differences in clinicopathological features, prognostic factors, and overall survival (OS) between patients with proximal gastric cancer (PGC) and distal gastric cancer (DGC). PATIENTS AND METHODS: Patients with PGC or DGC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1997-2017. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: We reviewed 16,119 cases of gastric cancer patients, including 6,479 of PGC and 9,640 of DGC. PGC patients presented as older patients (61.5 versus 56.4 years, P<0.001) and more males (82.9% versus 68.2%, P<0.001). Compared with DGC, PGC was more likely to be in later pT stage (pT3 and pT4, 65.0% versus 52.8%, P<0.001) and lymph node metastasis (54.8% versus 50.9%, P<0.001). In univariate analysis, PGC patients had a worse survival outcome in stage I (Hazard ratio [HR] = 2.04, 95% CI: 1.42-2.94) but a better prognosis in stage IV (HR = 0.85, 95% CI: 0.73-0.98) when compared to DGC patients. However, multivariate analysis demonstrated that PGC was not an independent predictor for poor survival (HR = 1.07, 95% CI: 1.00-1.14). Results from multivariate analysis also revealed that pT4, lymph node metastasis, distant metastasis, no gastrectomy, and Borrmann IV were independent predictors associated with poor survival for both PGC and DGC patients. Additional prognostic factors for PGC patients included underweight (BMI < 18.5) (HR = 1.29, 95% CI: 1.06-1.58), linitis plastica (HR = 2.13, 95% CI: 1.25-3.65), and overweight (23 ≤ BMI <27.5) (HR = 0.80, 95% CI: 0.71-0.90). During the 20-year study period, the 5-year OS increased significantly for both PGC and DGC, with the increase rate of 91.7% and 67.7%, respectively. CONCLUSION: In China, PGC significantly differed from DGC in clinicopathological characteristics and prognostic factors. However, there was no significant relationship between survival outcome and gastric tumor location.

The UbL-UBA Ubiquilin4 protein functions as a tumor suppressor in gastric cancer by p53-dependent and p53-independent regulation of p21.

Ubiquilin4 (Ubqln4), a member of the UbL-UBA protein family, serves as an adaptor in the degradation of specific substrates via the proteasomal pathway. However, the biological function of Ubqln4 remains largely unknown, especially in cancer. Here, we reported that Ubqln4 was downregulated in gastric cancer tissues and functioned as a tumor suppressor by inhibiting gastric cancer cell proliferation in vivo and in vitro. Overexpression of Ubqln4-induced cellular senescence and G1-S cell cycle arrest in gastric cancer cells and activated the p53/p21 axis. Moreover, Ubqln4 regulated p21 through both p53-dependent and p53-independent manners. Ubqln4 interacted with RNF114, an E3 ubiquitin ligase of p21, and negatively regulated its expression level, which in turn stabilized p21 by attenuating proteasomal degradation of p21. These effects of Ubqln4 were partly abrogated in gastric cancer cells upon silencing of p21. Our findings not only establish the anti-tumor potential of Ubqln4 in gastric cancer but also reveal a role for Ubqln4 in regulation of the cell cycle and cellular senescence via stabilizing p21.

A nation-wide retrospective epidemiological study of gastroenteropancreatic neuroendocrine neoplasms in china.

BACKGROUND: Representative data on the gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) in Asian patients is rare, especially in China. This study aims to create a GEP-NENs profile of Chinese patients. METHODS: This was a hospital-based, nation-wide, and multi-center 10-year (2001-2010) retrospective study which collected GEP-NEN patients' information in tertiary referral hospitals. All 2010 inpatient GEP-NEN cases with confirmed pathology in the selected hospitals were included. The primary GEP-NEN sites were measured and the epidemiological and clinical information of each tumor site were compared. RESULTS: The most common primary sites for GEP-NEN were the pancreas (31.5%) and rectum (29.6%), followed by the cardia (11.6%) and body (15.4%) of stomach. Small intestinal and colonic NENs took up a relatively small proportion of all patients. Pancreatic and rectal NENs, rather than cardiac and gastric body NENs, tended to be found in younger (P<0.001), female (P<0.001), urban (P<0.001) residents with a higher education level (P=0.032) and were also diagnosed at earlier stage (P<0.001) and lower grade (P<0.001). Surgery remained the primary treatment method in all groups. CONCLUSIONS: More studies on the commonality and heterogeneity of GEP-NENs are warranted to improve diagnosis efficiencies and treatment outcomes.

CYP2A6 Polymorphisms Associate with Outcomes of S-1 Plus Oxaliplatin Chemotherapy in Chinese Gastric Cancer Patients.

Gastric carcinoma is a heterogeneous malignant disease involving genetic factors. To identify predictive markers for gastric cancer treatment in Chinese patients, we evaluated the association between polymorphisms of the gene encoding cytochrome P450 2A6 (CYP2A6) and outcomes of S-1 plus oxaliplatin (SOX) chemotherapy treatment. Clinical data on 60 consecutive gastric cancer patients receiving SOX regimen were collected prospectively. We sequenced all exons of CYP2A6 and a total of 22 different polymorphisms were detected in the present study. Comprehensive analyses of these genetic polymorphisms were performed to determine their association with both safety and efficacy of SOX regimen. Our results showed that polymorphisms of CYP2A6 were associated with the safety and efficacy of SOX treatment. Among them, missense mutations CYP2A6 rs60823196 and rs138978736 could be possible risk factors (P<0.05) for severe diarrhea induced by SOX, whereas CYP2A6 rs138978736 could be a conceivable predictor for overall survival of patients treated with SOX adjuvant chemotherapy. Further large-scale randomized prospective studies are warranted to confirm these findings.

Vasoactive intestinal peptide stimulates melanogenesis in B16F10 mouse melanoma cells via CREB/MITF/tyrosinase signaling.

Vasoactive intestinal peptide (VIP), one of the major skin neuropeptides, has been suggested to have active roles in the pathogenesis of inflammatory skin disorders such as atopic dermatitis and psoriasis, which can commonly cause post-inflammatory hyperpigmentation. However, the effect of VIP on melanogenesis remains unknown. In this study, we showed that the melanin contents, tyrosinase activity, and gene expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were significantly increased by treatment with VIP in B16F10 mouse melanoma cells and the stimulatory melanogenic effect was further examined in human epidermal melanocytes (HEMns). In addition, phosphorylated levels of CRE-binding protein (CREB) and protein kinase A (PKA) were markedly increased after VIP treatment, but not p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), or Akt, indicating the possible PKA-CREB signaling pathway involved in VIP-induced melanogenesis. This result was further verified by the fact that VIP induced increased melanin synthesis, and protein levels of phosphorylated CREB, MITF, tyrosinase were significantly attenuated by H89 (a specific PKA inhibitor). These data suggest that VIP-induced upregulation of tyrosinase through the CREB-MITF signaling pathway plays an important role in finding new treatment strategy for skin inflammatory diseases related pigmentation disorders.

The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways.

Ubiquitin C-terminal hydrolase-L1 (UCHL1) is a de-ubiquitinating enzyme, which enzymatic activity relies on the C90 site. The function of UCHL1 is controversial in different types of cancer, and its role in gastric cancer progression remains unclear. In this study, immunohistochemistry staining was applied to detect the expression of UCHL1 in primary gastric cancer and liver metastases from gastric cancer. MKN45 and BGC823 cell lines with stable expression of de-ubiquitinase active UCHL1 or inactive UCHL1-variant C90S were established by lentiviral infection. The effect of UCHL1 on cell proliferation was evaluated by MTT and colony formation assays. The abilities of cell migration and invasion were determined by transwell assay. Protein expression levels were determined by Western blot. The results indicated that UCHL1 had a significantly higher positive expression rate in liver metastases from gastric cancer compared with primary gastric cancer. Overexpression of UCHL1 in MKN45 and BGC823 cells promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity. UCHL1 activated Akt and Erk1/2, which process also required enzymatic activity and was necessary for mediating cell migration and invasion. These findings demonstrated that UCHL1 promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity by activating Akt and Erk1/2, which may account for its higher positive expression rate in liver metastases from gastric cancer. UCHL1 could be a candidate biomarker and a therapeutic target for gastric cancer metastasis.

Evaluation of the optimal dosage of S-1 in adjuvant SOX chemotherapy for gastric cancer.

Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. The usual treatment of GC consists of surgery with additional adjuvant chemotherapy. In the present study, the feasibility and safety of adjuvant S-1 plus oxaliplatin (SOX) chemotherapy for patients with GC and the optimal dosage of S-1 were determined. Eligible patients were randomly assigned to either arm A (30 cases) receiving 70 mg/m2 S-1 (in two seperate half doses) daily or arm B (30 cases) receiving 80 mg/m2 S-1 (in two seperate half doses) daily. The S-1 was administered twice daily for 14 days followed by a 7-day rest period for the third week. A total of 130 mg/m2 oxaliplatin was administered on day 1 every 3 weeks for each arm. The cumulative rates of the relative total administration dose of S-1 at 100% in the 6th treatment course was 71.4% [95% confidence interval (CI), 56.5-90.3%] in arm A, which was significantly higher than 21.4% (95% CI, 10.5-43.6%) in arm B (P=0.001). The most common grade 3/4 toxicities were neutropenia (19.6%), thrombocytopenia (19.6%) and vomiting (16.1%). Grade 3/4 thrombocytopenia was observed in 7.1% of patients in arm A and in 32.1% of patients in arm B (P=0.019). With regard to the adverse events induced by S-1 administration, the incidence of diarrhea (3.6 vs. 42.9%; P<0.001) was significantly higher in arm B than in arm A, as anticipated. Collectively, adjuvant SOX therapy for GC is feasible and safe, and when combined with 130 mg/m2 oxaliplatin, 70 mg/m2/day S-1 appears to the optimal dose.

NAIF1 inhibits gastric cancer cells migration and invasion via the MAPK pathways.

PURPOSE: Nuclear apoptosis-inducing factor 1 (NAIF1) could induce apoptosis in gastric cancer cells. Previously, we have reported that the expression of NAIF1 protein is down-regulated in gastric cancer tissues compared with the adjacent normal tissues. However, the role of NAIF1 in gastric cancer cells is not fully understood. METHODS: The effects of NAIF1 on cell viability were evaluated by MTT and colony formation assays. The ability of cellular migration and invasion were analyzed by transwell assays. The expression levels of targeted proteins were determined by western blot. The relative RNA expression levels were analyzed using quantitative polymerase chain reaction assays. Xenograft experiment was employed to determine the anti-tumor ability of NAIF1 in vivo. RESULTS: The study demonstrates that transient transfection of NAIF1 in gastric cancer cells BGC823 and MKN45 could inhibit the cell proliferation, migration, and invasion of the two gastric cancer cell lines. The tumor size is smaller in NAIF1-overexpressed MKN45 cell xenograft mice than in unexpressed group. Further in-depth analysis reveals that NAIF1 reduces the expression of MMP2 as well as MMP9, and inhibits the activation of FAK, all of which are key molecules involved in regulating cell migration and invasion. In addition, NAIF1 inhibits the expression of c-Jun N-terminal kinase (JNK) by accelerating its degradation through ubiquitin-proteasome pathway. Meanwhile, NAIF1 reduces the mRNA and protein expression of ERK1/2. CONCLUSIONS: Our study revealed that NAIF1 plays a role in regulating cellular migration and invasion through the MAPK pathways. It could be a therapeutic target for gastric cancer.

Overexpression of nuclear apoptosis-inducing factor 1 altered the proteomic profile of human gastric cancer cell MKN45 and induced cell cycle arrest at G1/S phase.

Nuclear apoptosis-inducing factor 1 (NAIF1) was previously reported to induce apoptosis. Moreover, the expression of NAIF1 was significantly down-regulated in human gastric cancer tissues compared to adjacent normal tissues. However, the mechanism by which the NAIF1 gene induces apoptosis is not fully understood. Our results show that NAIF1 was minimally expressed in all the tested gastric cancer cell lines. Our data also demonstrates that NAIF1 is localized in the nuclei of cells as detected by monitoring the green fluorescence of NAIF1-GFP fusion protein using fluorescent confocal microscopy. Next, a comparative proteomic approach was used to identify the differential expression of proteins between gastric cancer cell lines MKN45/NAIF1 (-) and MKN45/NAIF1 (+). We found five proteins (proteasome 26S subunit 2, proteasome 26S subunit 13, NADH dehydrogenase Fe-S protein 1, chaperonin containing TCP1 subunit 3 and thioredoxin reductase 1) that were up-regulated and three proteins (ribonuclease inhibitor 1, 14-3-3 protein epsilon isoform and apolipoprotein A-I binding protein) that were down-regulated in the MKN45 cells overexpressing NAIF1. We also discovered that NAIF1 could induce cell cycle arrest at G1/S phase by altering the expression of cell cycle proteins cyclinD1, cdc2 and p21. The differentially expressed proteins identified here are related to various cellular programs involving cell cycle, apoptosis, and signal transduction regulation and suggest that NAIF1 may be a tumor suppressor in gastric cancer. Our research provides evidence that elucidates the role of how NAIF1 functions in gastric cancer.

Dose-finding study on adjuvant chemotherapy with S-1 plus oxaliplatin for gastric cancer.

Gastric cancer (GC) is the fourth most common type of cancer, accounting for an estimated one million new cases annually worldwide. Locally advanced GC often recurs, even following curative surgical resection. Therefore, there is a need for an effective adjuvant chemotherapy regimen. The aim of this trial was to investigate the maximum tolerated dose (MTD) of S-1 when administered in combination with oxaliplatin in postoperative GC patients. Oxaliplatin was administered at a fixed dose of 130 mg/m2 on day 1. S-1 was administered from day 1 to 14 of a 3-week cycle and escalated by 10 mg/m2/day from 60 to 80 mg/m2/day. A total of 15 patients were enrolled in this study. No dose-limiting toxicities (DLTs) occurred at level 1 (S-1, 60 mg/m2; n=3). One case of DLT (grade 3 vomiting) occurred at level 2 (S-1, 70 mg/m2; n= 6), whereas 2 cases of grade 3 vomiting were observed at level 3 (S-1, 80 mg/m2; n=6). Based on these results, the MTD of S-1 was initially determined to be 70 mg/m2. Furthermore, we observed that cytochrome P450 2A6 (CYP2A6) 41349640C>G was associated with severe neutropenia (C/C vs. C/G vs. G/G = 0 vs. 33.33 vs. 100%; P=0.03297, Fisher's exact test) during the entire course of the treatment.

Comparison study of fractional carbon dioxide laser resurfacing using different fluences and densities for acne scars in Asians: a randomized split-face trial.

BACKGROUND: Ablative 10,600-nm carbon dioxide (CO2 ) fractional laser treatments have shown favorable outcomes for atrophic acne scars. OBJECTIVE: To compare the efficacy and complications of fractional CO2 laser treatments with different fluences and densities for acne scars. METHODS: Twenty patients were treated using a single session of fractional CO2 laser in Deep FX mode. In Group A (n = 10), half of the face was treated with 20 mJ, density 10% and the other half with 20 mJ, density 20%. In Group B (n = 10), half of the face was treated with 10 mJ, density 10% and the other half with 20 mJ, density 10%. Patients were evaluated at baseline and 3 days, 1 week, 1 month, and 3 months after the procedure. RESULTS: There was no significant difference in efficacy between different laser settings within the groups, although adverse effects were more evident in patients treated with higher densities or fluences. CONCLUSION: Factional CO2 laser treatment using the Deep FX mode may provide a significant efficacy with lower fluence and density with fewer complications than with higher energies for acne scars.

[Clinical analysis of 17 cases of gastric small cell carcinoma].

OBJECTIVE: To analyze the clinical data and prognosis of gastric small cell carcinoma (GSCC), summarize recent progress in diagnosis and therapy of this disease reported in the literature, and to provide the theoretical basis for its appropriate treatment. METHODS: Clinicopathological data of 17 patients with pathologically confirmed GSCC, treated in our hospital between 1999 to 2012, were retrospectively reviewed. RESULTS: There were 16 males and 1 female, ranged from 46 to 75 years (mean 64.6 years). The tumor was located in the gastric cardia in 13 cases, three in the gastric fundus, and one in the gastric body. All the 17 patients received surgery and 10 of them received postoperative adjuvant chemotherapy, one received preoperative adjuvant chemotherapy. Thirteen patients were followed up. Among them, two 1ived for 40 months all along, the other 3 cases died of recurrence and extensive metastasis in 6 month after operation. The median survival was 13.0 months. The median survival of the patients with and without lymph node metastasis were 42 months and 13 months, respectively. The median survival time of stage II and III patients were 24 months and 14 months, respectively. CONCLUSIONS: It is difficult to make a definite diagnosis before or during the operation for GSCC. Radical operation could be done according to other gastric cancers and lymph node dissection could be simplified. Postoperative chemotherapy with the same scheme as lung small cell carcinoma may help to improve the outcome and prolong the survival of the patients.

[Diagnosis and treatment of primary colorectal non-Hodgkin's lymphoma: analysis of 52 cases].

OBJECTIVE: To summarize and analyze the diagnosis, clinical features and therapy of primary colorectal non-Hodgkin's lymphoma (NHL). METHODS: The clinicopathological data of 52 patients with primary colorectal NHL diagnosed and treated in our department from January 2000 to January 2010 were reviewed and analyzed retrospectively in this study. RESULTS: This group of patients was composed of 45 cases of B cell and 7 T cell lymphomas, including 33 males and 19 females, with a male to female ratio of 1.7:1, and the age at diagnosis was 16 - 74 years old, with a median age of 50 years. The ileocecal region was most frequently involved site, acounted for 48.1%. The common symptoms encountered were abdominal pain (66.7%), diarrhea (15.6%), blood stool (24.4%), and body weight loss (8.9%). All patients were eventually diagnosed by histopathology, and the DLBCL subtype took up 64.4%. Among the 45 cases of B cell subtype, 33 cases (73.3%) were of early stage (IE and IIE confirmed), and the 5-year survival rate was 78.1%, while those of stage IIIE and IVE comprised 26.7%, with a 5-year survival rate of 45.5% (P < 0.05). The 5-year survival rate of all patients was 71.1%. Surgery was employed in 36 cases, and 9 patients received chemotherapy alone. Radical surgery could significantly increase the patients' overall survival rate, as compared with the chemotherapy alone group and palliative surgery group (P < 0.05). CONCLUSIONS: Colorectal non-Hodgkin's lymphoma is a rare malignancy of the gastrointestinal tract. B cell type, male predominance and DLBCL subtype are most encountered manifestations in clinics. Multi-modality management with radical surgical resection of the primary lesion followed by standard chemotherapy, affords better local disease control, and a better survival outcome. Early detection and tailored immunotherapy can obviously prolong the long-term survival time.

[The diagnosis, treatment and prognosis evaluation of gastric small cell carcinoma: analysis of 41 cases].

OBJECTIVE: To summarize and analyze the clinical feature, therapeutic methods and prognosis of gastric small cell carcinoma (SCC). METHODS: The clinical and pathological data of 41 patients diagnosed of gastric SCC were analyzed in this research. Also, the factors which may potentially affect the patients' survival outcome were evaluated. There were 35 male and 6 female patients. The age at diagnosis was 39-84 years, median age was 62 years. The 31 cases (75.6%) of gastric SCC patients were involved in the upper third of the stomach, 3 cases (7.3%) in the middle, 7 cases (17.1%) in the lower third. RESULTS: The time from the event of symptoms to final confirmation was 1 to 13 months, the median time was 3 months. The longest diameter of tumors was from 2.5 to 15.0 cm, the average was 6.5 cm. The 38 cases (92.7%) chosed surgery as the first treatment, among which 25 cases (61.0%) were performed radical tumor resection, 13 cases (31.7%) went through palliative resection, and 3 cases (7.3%) just employed chemotherapy. The initial II, III, IV stage were 2, 31 and 8 cases, respectively. The overall median survival time was 19 months, median disease free survival time was 11 months, 1-, 2-, 5-years survival rates were 70.7%, 46.3% and 36.6%, respectively. In univariate survival analysis, the tumor size (χ² = 5.565), change of the body weight (χ² = 3.688), type of operation (χ² = 11.747) and relapse or not (χ² = 17.966) were obviously correlaed with the prognosis (P < 0.05). CONCLUSIONS: Gastric SCC is a rare disease of the gastrointestinal tract, the misdiagnosis rate is high, and the prognosis is dismal. Muti-modality management, with radical surgical resection of the primary lesion followed by standard adjuvant-chemotherapy, affords better local disease control and a better survival outcome.

Clinicopathologic characteristics and prognostic factors of 63 gastric cancer patients with metachronous ovarian metastasis.

OBJECTIVE: This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis. METHODS: Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis. RESULTS: The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre-menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane (87.3%). The metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%), and peritoneal membrane (73%). Total resection of metastatic sites was performed (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis (P<0.01). CONCLUSION: Effective control of peritoneal seeding-induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis.