Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM) used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy

Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells.

IntroductionAlthough breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors.MethodsParaffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation.ResultsImmunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes.ConclusionsOur findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations

Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells.

FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts. Silencing of FUT2, but not FUT1, significantly changed the cuboidal morphology to dense clusters of small and round cells with reduced adhesion to polystyrene and extracellular matrix, including laminin, fibronectin and collagen. Silencing of FUT1 or FUT2 suppressed cell migration in wound healing assay, whereas FUT1 and FUT2 overexpression increased cell migration and invasion in vitro and metastasis of breast cancer in vivo. A decrease in mesenchymal like markers such as fibronectin, vimentin, and twist, along with increased epithelial like marker, E-cadherin, was observed upon FUT1/2 knockdown, while the opposite was noted by overexpression of FUT1 or FUT2. As expected, FUT1 or FUT2 knockdown reduced Globo H, whereas FUT1 or FUT2 overexpression showed contrary effects. Exogenous addition of Globo H-ceramide reversed the suppression of cell migration by FUT1 knockdown but not the inhibition of cell adhesion by FUT2 silencing, suggesting that at least part of the effects of FUT1/2 knockdown were mediated by Globo H. Our results imply that FUT1 and FUT2 play important roles in regulating growth, adhesion, migration and CSC properties of breast cancer, and may serve as therapeutic targets for breast cancer

Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression.

ST3Gal1 is a key sialyltransferase which adds α2,3-linked sialic acid to substrates and generates core 1 O-glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1-silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF-β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC-MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O-glycans are sialyl-3T and disialyl-T. ST3GAL1-silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF-β1 by 2- to 3-fold and thereby dampening TGF-β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse-free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence (p = 0.025, HR = 2.967, 95% CI = 1.14-7.67). Since TGF-β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF-β1 upregulates ST3Gal1 to circumvent the negative impact of VASN

Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells

INTRODUCTION: Although breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors. METHODS: Paraffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation. RESULTS: Immunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH(+) cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH(-) cells. GD2(+) cells showed a 3.9-fold greater capacity than GD2(-) cells. ALDH(+)/GD2(+)cells displayed 12.8-fold greater mammosphere forming ability than ALDH(-)/GD2(-) cells. In vivo, the tumor-initiating frequency of ALDH(+)/GD2(+) cells were up to 33-fold higher than that of ALDH(+) cells, with as few as 50 ALDH(+)/GD2(+) cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH(+)/GD2(+) cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH(+) or ALDH(+)/GD2(+) cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes. CONCLUSIONS: Our findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH(+) and ALDH(+)/GD2(+) subpopulations

Wikstroemia fragrans (Thymelaeaceae, Daphneae), a new species from Mount Danxia, China based on morphological and molecular evidence

A new species, Wikstroemia fragrans (Thymelaeaceae, Daphneae), from Danxiashan National Park, Shaoguan, Guangdong of China is described and illustrated. It is similar to the sympatric W. trichotoma, but can be differentiated easily from the latter by its shorter racemose inflorescences, yellowish green calyx tube, and smaller leaves. It also resembles the allopatric W. fargesii, but differs from it by its strigose-pubescent ovary and disk scale that is 2- or 3-dentate apically. Phylogenetic analysis using the nuclear DNA internal transcribed spacer (ITS) region revealed that W. fragrans falls within the Wikstroemia clade; based on current sampling, W. fragrans is closely-related to W. capitata. It is also the first species of Wikstroemia known to be endemic to the Danxia landform and is classified provisionally as Critically Endangered according to the IUCN Red List Categories and Criteria

A comparison of absorbable polymetric clips and metallic clips in laparoscopic appendectomy

Background: Laparoscopic appendectomy is the most common emergent surgery, and various techniques were used for the closure of appendicular stump and appendiceal artery. Aim: This study aimed to compare the clinical impacts of absorbable polymeric clips and traditional metallic clips. Methods: We reviewed the laparoscopic appendectomies performed from June 2020 to May 2021 in a medical center. We analyzed the characteristics and intraoperative and postoperative data of patients receiving absorbable or metallic clips during laparoscopic appendectomy. Results: A total of 120 patients were enrolled in this study. Fifty-nine patients received lapro-clips for the ligation of appendicular stump and artery (Group A), whereas 61 patients received titanium clips (Group B). The operative time for both groups was 63.6 ± 18.9 min and 65.5 ± 19.2 min, respectively (P 610.586). There was no significant difference in postoperative complications (P = 0.958). The length of hospital stay for each group was 3.07 ± 1.14 days and 2.90 ± 1.18 days, respectively (P = 0.435). Conclusion: The application of absorbable polymetric clips is feasible and safe with the additional benefit of leaving no foreign body for the closure of appendicular stump and ligation of appendiceal artery for laparoscopic appendectomy

Ovarian metastases from gallbladder mimics primary ovarian neoplasm in young patient: a case report

Abstract Background Gallbladder cancer is unusually seen but can result in highly mortality rate. It makes challenge to diagnose for clinicians due to present asymptomatic or non-specific clinical presentation including abdominal pain, anorexia. It usually also accompanies with cholelithiasis (incidence is 1–2%) and incidentally detected by radiologic examination such as ultrasound, computed tomography or intra-operative intervention accidentally. Gallbladder cancer results in highly fatal malignancy because it is difficult to early detect. The ovarian metastases from gallbladder mimics primary neoplasm isn’t seen before and mentioned in English literatures before. Case presentation A 28-year-old woman suffered from intermittently lower abdominal tenderness and nausea after meals for 3 years. The abdominal ultrasound revealed a right ovarian mass with fluid accumulation and the contrast CT of abdomen revealed a gallbladder fundus mass and liver tumor lesion located at segment 4. We arranged surgical intervention with radical cholecystectomy and debulking operation with salpingo-oophorectomy. The pathologic report revealed adenocarcinoma of gallbladder with liver, peritoneum, and right ovarian invasion. After surgical intervention, she also received adjuvant chemotherapy with Gemcitabine, Cetuximab, Cisplatin and Cyberknife. Conclusion The non-specific symptoms make the challenge to difference the primary malignant neoplasm. The rarely diagnosis must take in consider if the gastrointestinal tract tumours coexist with ovarian tumours