Primary liver cancer is the fifth most frequently diagnosed cancer globally and the second leading cause of cancer death. Liver cancers are malignant tumors that grow on the surface or inside the liver. They are formed from either the liver itself or from structures within the liver, including blood vessels or the bile duct. Liver tumors are discovered on medical imaging equipment (often by accident) or present themselves symptomatically as an abdominal mass, abdominal pain, jaundice, nausea or liver dysfunction. The leading cause of liver cancer is viral infection with hepatitis B virus or hepatitis C virus. The cancer usually forms secondary to cirrhosis caused by these viruses. For this reason, the highest rates of liver cancer occur where these viruses are endemic, including East Asia and sub-Saharan Africa. Liver cancers should not be confused with liver metastases, also known as secondary liver cancer, which are cancers that originate from organs elsewhere in the body and migrate to the liver.

The most frequent liver cancer, accounting for approximately 75% of all primary liver cancers, is hepatocellular carcinoma (HCC). HCC is a cancer formed by liver cells, known as hepatocytes, that become malignant. Liver cancer can also form from other structures within the liver such as the bile duct, blood vessels and immune cells. Cancer of the bile duct (cholangiocarcinoma and cholangiocellular cystadenocarcinoma) account for approximately 6% of primary liver cancers. There is also

a variant type of HCC that consists of both HCC and cholangiocarcinoma.

A liver metastasis is a malignant tumor in the liver that has spread from another organ affected by cancer. Because of its rich, dual blood supply (the liver receives blood via the hepatic artery and portal vein), the liver is a common site for metastatic disease, which is 20 times more common than primary ones.

In 50% of all cases of liver cancer the primary tumor is gastrointestinal tract; other common sites include the breast, ovaries, bronchus and kidney.

In some tumors, notably arising from the colon and rectum, apparently solitary metastases to one or other lobes may be resected. Careful search for other metastases is required, including local recurrence of original primary tumor (e.g. colonoscopy) and dissemination elsewhere (e.g. CT of thorax); 5-year survival rates of 30-40% have been reported following resection.

Sources

Jemal A, Bray F, Center MM, et al. (2011) Global cancer statistics. CA: a cancer journal for clinicians 61 (2): 69–90.

Ahmed I & Lobo DN. (2009) Malignant tumors of the liver. Surgery (Oxford) 27 (1): 30–37. January 2009.doi:10.1016/j.mpsur.2008.12.005 http://www.surgeryjournal.co.uk/article/S0263-9319%2808%2900285-8/abstract

Merck Manual. Metastatic Liver Cancer. (2013) http://www.merckmanuals.com/home/liver_and_gallbladder_disorders/tumors_of_the_liver/metastatic_liver_cancer.html

 

Liver Cancer
Cell Type	Herb Source(s)	Isolate	Refs
BEL-7402	Gentian waltonii	Waltonitone	Zhang et al., 2009 b
H22	Aconitum coreanum	ACP-a1	Li et al., 2013
H22	aconitum	Monkshood polysaccharide	Dong et al., 2006; Zhang, Liu, Song, Hou, & Lu, 2006
H22	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Wang et al., 2011
HA22T	Solanum incanum	Solanum indicum saponins	Gao et al., 2011
Hep G2,Hep 3B	Alkanna cappadocica	5-O-methyl-11-O-acetylalkannin	Sevimli-Gur et al., 2010
Hep G2,Hep 3B and SK-Hep1	Scutellaria rivularis Scutellaria baicalensis	Wogonin	Chang, 2002
Hep G2,Hep 3B and SK-Hep1	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalein	Chang, 2002
Hep G2,Hep 3B and SK-Hep1	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalin	Chang, 2002
Hep3B	Alismatis Rhizoma	Alisol B acetate	Chou, Pan, Teng, & Guh, 2003
Hep3B	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalein	Chou, Pan, Teng, & Guh, 2003
Hep3B	Phyllanthus niruri, Punica granatum, Caesalpinia coriaria, Alchornea glandulosa	Corilagin	Hau et al., 2010
Hep3B	Gardenia fructus	Geniposide	Chou, Pan, Teng, & Guh, 2003
Hep3B	Gentiana root	Gentiopicroside	Chou, Pan, Teng, & Guh, 2003
Hep3B	Phellinus igniarius	Hispolon	Huang et al., 2011
Hep3B	Nelumbo nucifera	Neferine	Yoon et al., 2013
Hep3B	Bupleurum radix	Saikosaponin-D	Chou, Pan, Teng, & Guh, 2003
Hep3B and Huh7	various Garcinia species	Gambogic acid	Lee et al., 2013
HepG2	Antrodia Camphorata	Antcin B	Hsieh et al., 2011
HepG2	Rheum palmatum., Senna obtusifolia, Fallopia japonica, Kalimeris indica, Ventilago madraspatana, Rumex nepalensis, Fallopia multiflora, Cassia occidentalis, Senna siamea, Acalypha australis	Emodin	Narender et al., 2013
HepG2		Galangin	Wen et al., 2012
HepG2	soy, fava, and kudzu	Genistein	Pugeat et al., 2009
HepG2	Antrodia Camphorata	Methylantcinate B	Hsieh et al., 2011
HepG2	Citrus aurantium	Naringin	Arul et al., 2013
HepG2	fruits, vegetables, leaves, grains, red wine	Quercetin	Kioka et al., 1992
HepG2	Bupleurum radix	Saikosaponin-A	Wen-Sheng, 2003
HepG2	Solanum nigrum	Solanine	Ji et al., 2008
HepG2	Solanum nigrum	Solanine	Gao et al., 2006
HepG2	Nigella sativa	Thymoquinone	Attoub et al., 2012
HepG2	tomato	Tomatine/Tomatidine	Friedman et al., 2009
HepG2	Torilis japonica	Torilin	Kim et al., 2000
HepG2	soy, fava, and kudzu	Genistein	Mousavi et al., 1993q
HepG2, SMMC-7721	Paeonia suffruticosa	Paeoniflorin	Hu et al., 2013
HepG2, SMMC-7721	Salvia miltiorrhiza	Tanshinone II A	Yuxian et al., 2009
HepG2-DR	Alismatis Rhizoma	Alisol B acetate	Wang et al., 2004
Huh7, HepG2, Hep3B	Antrodia Camphorata	Antcin A	Hsieh et al., 2010
Huh7, HepG2, Hep3B	Antrodia Camphorata	Antcin C	Hsieh et al., 2010
K-HEP-1	various plants	Kaempferol	Huang et al., 2013
Mahlavu, PLC/PRF/5 and HepG2	Rheum palmatum., Senna obtusifolia, Fallopia japonica, Kalimeris indica, Ventilago madraspatana, Rumex nepalensis, Fallopia multiflora, Cassia occidentalis, Senna siamea, Acalypha australis	Emodin	Jing et al., 2002
Metastasis	Salvia miltiorrhiza	Tanshinone II A	Xu et al., 2009
R-HepG2	Scutellaria barbata	Pheoborbide	Tang et al., 2007
SMMC-7721	brown seaweed	Fucoidan	Yang et al., 2013
SMMC-7721	Cortex periplocae	Periplocin	Zhao et al., 2009
SMMC-7721	Bupleurum radix	Saikosaponin-D	Wang et al., 2013
Non specific	various fruits, vegetables, and herbs	Apigenin	Baliga, 2013
Non specific	cotton plant	Apogossypolone	Zubair et al., 2012
Non specific	Berberis amurensis Berberis vulgaris	Berbamine	Meng et al., 2013
Non specific	Berberis amurensis Berberis vulgaris	Berbamine	Wang et al. 2007
Non specific	Berberis amurensis	Berberine	Lin et al., 2004
Non specific		Carnosic acid	Ngo et al., 2011
Non specific	Rosmarinus officinalis Salvia pachyphylla	Carnosol	Ngo et al., 2011
Non specific	various Garcinia species	Gambogic acid	Qi et al., 2008
Non specific	Gardenia fructus	Genipin	Cao et al., 2010
Non specific	Rosa woodsii, Prosopis glandulosa, Phoradendron juniperinum, Syzygium claviflorum, Hyptis capitata Ternstromia gymnanthera	Oleanolic acid	Wang et al., 2013
Non specific	Rabdosia rubescens	Oridonin	Tang & Eisenbrand, 1992
Non specific		Rosmarinic acid	Ngo et al., 2011
Non specific	Bupleurum radix	Saikosaponin-D	Jia et al., 2012
Non specific	Stephania tetrandra	Tetrandrine	Lai et al., 1998 Ng et al., 2006 Wu et al., 2010 He et al., 2011
Non specific	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Ngo et al., 2011
Non specific	Gentian waltonii	Waltonitone	Zhang et al., 2009a

Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader group of diseases affecting the blood, bone marrow, and lymphoid system, which are all known as hematological neoplasms. Most treatments involve chemotherapy, medical radiation therapy, hormone treatments, or bone marrow transplant. The rate of cure depends on the type of leukemia as well as the age of the patient.

Acute leukemia is characterized by a rapid increase in the number of immature blood cells. Immediate treatment is required in acute leukemia due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children.

Chronic leukemia is characterized by the excessive build up of relatively mature, but still abnormal., white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal., resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group.

The diseases are subdivided according to which kind of blood cell is affected. This split divides leukemias into lymphoblastic or lymphocytic leukemias and myeloid or myelogenous leukemias:

• In lymphoblastic or lymphocytic leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form lymphocytes, which are infection-fighting immune system cells. Most lymphocytic leukemias involve a specific subtype of lymphocyte, the B cell.

• In myeloid or myelogenous leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form red blood cells, some other types of white cells, and platelets.

Combining these two classifications provides a total of four main categories. Within each of these four main

categories, there are typically several subcategories.

• Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older. The survival rates vary by age: 85% in children and 50% in adults. Subtypes include precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt’s leukemia, and acute biphenotypic leukemia.

• Chronic lymphocytic leukemia (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children. Two-thirds of affected people are men. The 5-year survival rate is 75%. It is incurable, but there are many effective treatments.

• Acute myelogenous leukemia (AML) occurs more commonly in adults than in children, and more commonly in men than women. AML is treated with chemotherapy. The 5-year survival rate is 40%, except for APL, which is over 90%.

• Chronic myelogenous leukemia (CML) occurs mainly in adults; a very small number of children also develop this disease. Treatment is with imatinib (Gleevec in United States, Glivec in Europe) or other drugs. The 5-year survival rate is 90%. One subtype is chronic monocytic leukemia.

•
Hairy cell leukemia (HCL) is sometimes considered a subset of chronic lymphocytic leukemia, but does not fit neatly into this pattern. About 80% of affected people are adult men. Survival is 96% to 100% at ten years.

• Large granular lymphocytic leukemia may involve either T-cells or NK cells; like hairy cell leukemia, which involves solely B cells, it is a rare and indolent (not aggressive) leukemia.

• Adult T-cell leukemia is caused by human T-lymphotropic virus (HTLV), a virus similar to HIV.

Source

SEER Stat Fact Sheets: Leukemia. National Cancer Institute. 2011.

Finding Cancer Statistics È Cancer Stat Fact Sheets http://seer.cancer.gov/statfacts/html/leuks.html

American Cancer Society (22 March 2012). Typical treatment of acute myeloid leukemia (except promyelocytic M3). Detailed Guide: Leukemia – Acute Myeloid (AML). American Cancer Society. Retrieved 31 Oct 2013.

Wikipedia. http://en.wikipedia.org/wiki/Leukemia

 

Leukemia
Cell Type	Herb Source(s)	Isolate	Refs
B-CLL	Magnolia genus	Honokiol	Battle et al., 2005
HL-60	Aconitum taipeicum	3-isopropyl-tetrahydropyrrolo [1,2-a] pyrimidine-2,4(1H,3H)-dione and 1-acetyl-2,3,6-triisopropyl-tetrahydropyrimidin-4(1H)-one	Xu, Guo, & Wu, 2010
HL-60	Artemisia annua	Artemisinin	Kim, 2003
HL-60	Berberis amurensis	Berberine	Hsing et al., 1999
HL-60	Rheum palmatum., Senna obtusifolia, Fallopia japonica, Kalimeris indica, Ventilago madraspatana, Rumex nepalensis, Fallopia multiflora, Cassia occidentalis, Senna siamea, Acalypha australis	Emodin	Huang et al., 2005
HL-60	Magnolia genus	Honokiol	Hirano et al., 1994; Wang et al., 2004; Hibasami et al., 1998; Konoshima et al., 1991; Yang et al., 2002; Kong et al., 2005
HL-60	Hippophae rhamnoides	Isorhamnetin	Zhu et al. 2005
HL-60	Juglans mandshurica Maxim	Juglone	Xu et al., 2010
HL-60	Trigonella foenumgraecum	Protodioscin	Hibasami et al., 2003
HL-60	Silybum marianum	Silibinin	Kang et al., 2001
HL-60	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Qian et al., 2011
HL-60	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Zhang et al., 2006
HL-60 and K562	Berberis amurensis Berberis vulgaris	Berbamine	Dong et al., 1997; Sun et al., 2006; Xu et al., 2006
HL60 and U937	Commiphora wightii	Guggulsterones	Samudio et al., 2005
HL-60/ADR	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalin	Zheng et al., 2009
HL-60/ADR	Rheum palmatum., Senna obtusifolia, Fallopia japonica, Kalimeris indica, Ventilago madraspatana, Rumex nepalensis, Fallopia multiflora, Cassia occidentalis, Senna siamea, Acalypha australis	Emodin	Chen et al., 2007
Jurkat	various Garcinia species	Gambogic acid	Wang et al., 2008
K562	Trigonella foenum-graecum	Diosgenin	Liu et al., 2005
K562	Panax genus	Ginsenosides	Cai et al., 2012
K562	Panax genus	Ginsenosides	Cai et al., 2012
K562	Hippophae rhamnoides	Isorhamnetin	Zhu et al., 2005
K562	Hippophae rhamnoides	Isorhamnetin	Boubaker et al., 2012
K562	Cortex periplocae	Periplocin	Zhao et al., 2009
K562	Salvia miltiorrhiza	Tanshinone A	Zhen et al., 2011
K562	Salvia miltiorrhiza	Tanshinone II A	Zhen et al., 2011
K562	Stephania tetrandra	Tetrandrine	Xu et al., 2012
K562	Trichosanthes kirilowii	Trichosanthin	Kang et al., 1998
K562	Lagerstroemia speciosa, Crataegus pinnatifida	Corosolic acid	Ahn et al., 1998
K562, K562/Adr	Lithospermum erythrorhizon	Shikonin	Wu et al., 2013
K562/A02		Garlicin	Yu M, et al., 2008
K562-DR	Alismatis Rhizoma	Alisol B acetate	Wang et al., 2004
KBM-5	Salvia miltiorrhiza	Tanshinone II A	Yun et al.,2013
L1210	derived from the greater celandine	Chelidonine	Kaminsky, Lin, Filyak, & Stoika, 2008
L1210	Sanguinaria canadensis	Sanguinarine	Kaminsky, Lin, Filyak, & Stoika, 2008
MDR K562/A02	Solanum incanum	Solamargine alkaloid	Li et al., 2011
MT-4	derived from the greater celandine	Chelidonine	Philchenkov et al., 2008
MT-4	Sanguinaria canadensis	Sanguinarine	Philchenkov et al., 2008
NB4	Berberis amurensis Berberis vulgaris	Berbamine	Zhao et al., 2007
NB4	Rabdosia rubescens	Oridonin	Ikezoe et al., 2003
Non specific	Berberis amurensis Berberis vulgaris	Berbamine	Kapoor, 2012
Non specific	Berberis amurensis Berberis vulgaris	Berbamine	Xie, 2009
Non specific	Berberis amurensis Berberis vulgaris	Berbamine	Zhao et al., 2011
Non specific	Betula platyphylla, Betula X caerulea, Betula cordifolia, Betula papyrifera, Betula populifolia, Dillenia indica	Betulin	Rzeski, 2009
Non specific		Carnosic acid	Ngo et al., 2011
Non specific	Rosmarinus officinalis Salvia pachyphylla	Carnosol	Johnson, 2011
Non specific	Rosmarinus officinalis Salvia pachyphylla	Carnosol	Ngo et al., 2011
Non specific	derived from the greater celandine	Chelerythrine	Funakoshi et al., 2011
Non specific	Scutellaria baicalensis, Passiflora caerulea, Passiflora incarnate, honey, and propolis	Chrysin	Khoo et al., 2010
Non specific	Saussurea lappa	Costunolide	Choi et al., 2009
Non specific	Curcuma longa	Curcumin	Anand et al., 2008
Non specific	Syzygium aromaticum	Eugenol	Jaganathan et al., 2012
Non specific	soy, fava, and kudzu	Genistein	Sarkar & Li, 2003; Magee & Rowland, 2004
Non specific	Panax genus	Ginsenosides	Chen et al., 2013
Non specific	Panax genus	Ginsenosides	Chung et al., 2012
Non specific	Gynostemma pentaphyllum	Gypenosides	Hsu et al., 2011
Non specific	Cephalotaxus harringtonia	Homoharringtonine/Omacetaxine	Kantarjian, O’Brien, & Cortes, 2013
Non specific	Cephalotaxus harringtonia	Homoharringtonine/Omacetaxine	Xie et al., 2006
Non specific	Cephalotaxus harringtonia	Homoharringtonine/Omacetaxine	Luo et al., 2004
Non specific	Magnolia genus	Honokiol	Munroe et al., 2007; Chen et al., 2009; Fried, & Arbiser, 2009
Non specific	Magnolia genus	Honokiol	Wang et al., 2010
Non specific	several species of the genus Epimedium	Icaritin	Zhu et al., 2011
Non specific	Isatis (L.) genus	Indirubin	Eisenbrand et al., 2004
Non specific	Isatis (L.) genus	Indirubin	Nam et al., 2012
Non specific	Didemnum psammatodes	Methyl Myristate	Takeara et al., 2008
Non specific	Didemnum psammatodes	Methyl Palmitate	Takeara et al., 2008
Non specific	Didemnum psammatodes	Methyl Stearate	Takeara et al., 2008
Non specific	Tanacetum parthenium	Parthenolide	Guzman et al., 2005
Non specific	Platycodon grandiflorum	Platycodin D	Kim et al., 2008
Non specific	Pueraria lobata	Puerarin	Shao et al., 2010
Non specific	fruits, vegetables, leaves, grains, red wine	Quercetin	Cheng et al., 2010
Non specific		Rosmarinic acid	Ngo et al., 2011
Non specific	Sanguinaria canadensis	Sanguinarine	Funakoshi et al., 2011
Non specific	Sanguinaria canadensis	Sanguinarine	Kaminskyy, Kulachkovskyy, & Stoika, 2008
Non specific	Lithospermum erythrorhizon	Shikonin	Wiench et al., 2012
Non specific	Salvia miltiorrhiza	Tanshinone I	Liu et al., 2010
Non specific	Salvia miltiorrhiza	Tanshinone II A	Liu et al., 2009
Non specific	Stephania tetrandra	Tetrandrine	Lai et al., 1998; Ng et al., 2006; Wu et al., 2010; He et al., 2011
Non specific	Stephania tetrandra	Tetrandrine	Xu et al., 2006
Non specific	Trichosanthes kirilowii	Trichosanthin	Sha et al., 2013
Non specific	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Ngo et al., 2011
P388	Rabdosia rubescens	Oridonin	Zhou et al., 2007
RS4;11 and MV4;1	Isatis (L.) genus	Indirubin	Choi et al., 2010
t(8;21)	Rabdosia rubescens	Oridonin	Zhou et al., 2007
U937		Rosmarinic acid	Moon, Kim, Lee, Choi, & Kim, 2010
U937, HL60 and K562	Betula pubescens, Ziziphus mauritiana, Prunella vulgaris, Triphyophyllum peltatum and Ancistrocladus heyneanus, etc.	Betulinic acid	Kumar, 2009
U937	Cortex periplocae	Periplocin	Bloise et al., 2009

Laryngeal cancer may also be called cancer of the larynx or laryngeal carcinoma. Most laryngeal cancers are squamous cell carcinomas, reflecting their origin from the squamous cells which form the majority of the laryngeal epithelium. Cancer can develop in any part of the larynx, but the cure rate is affected by the location of the tumor. For the purposes of tumor staging, the larynx is divided into three anatomical regions: the glottis (true vocal cords, anterior and posterior commissures); the supraglottis (epiglottis, arytenoids and aryepiglottic folds, and false cords); and the subglottis.

Epithelial tumors are classified according to the guidelines set by the International Union Against Cancer (UICC).

The T classification represents the extent of the primary tumor.

Supraglottis

• T1 – Tumor is limited to one side of the supraglottis with normal mobility of the vocal cord(s).

• T2 – Tumor invades the vocal cord without fixation of the larynx.

• T3 – Tumor is limited to the larynx with fixation of the vocal cord and/or infiltration of the postcricoid area, pre-epiglottic tissues or, most likely, erosion of thyroid cartilage.

• T4a – Tumor invades through thyroid cartilage or down into the trachea and soft tissue contents of the neck.

• T4b – Tumor invades prevertebral space, mediastinal structures or encases carotid artery.

Glottis

• T1 – Tumor limited to vocal cord(s) with normal mobility. a – Tumor limited to one vocal cord. b ¬ – Tumor involves both vocal cords.

• T2 – Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility.

• T3 – Tumor limited to larynx with vocal cord fixation and/or invades paraglottic space or with probable thyroid cartilage erosion.

• T4a – Tumor invades through thyroid cartilage, the trachea, soft tissues of the neck/tongue. T4b – Tumor invades prevertebral space, mediastinal structures, or carotid artery.

Subglottis is very rare.

N classification

The N classification represents spreading to regional lymph nodes on the neck. The widest diameter is measured.

• N0 – no regional lymph node metastases

• N1 – single ipsilateral lymph node metastasis ≤ 3 cm N2 a – single ipsilateral lymph node metastasis > 3 cm ≤ 6 cm b – multiple ipsilateral lymph node metastases ≤ 6 cm c – bilateral or contralateral lymph node metastases ≤ 6 cm

• N3 – lymph node metastases > 6 cm M classification

The M classification represents distant metastases.

• M0 – no distance metastases

• M1 – distant metastases

Sources

Mount Sanai Hospital. (2013) http://www.mountsinai.org/patient-care/health-library/diseases-and-conditions/laryngeal-cancer

ACS. http://www.cancer.org/cancer/laryngealandhypopharyngealcancer/

Mirisola, V., Mora, R., Esposito, A.I., et al. (2011). A prognostic multigene classifier for squamous cell carcinomas of the larynx. Cancer Letters 307 (1): 37–46. doi:10.1016/j.canlet.2011.03.013.

 

Laryngeal Cancer
Cell Type	Herb Source(s)	Isolate	Refs
Hep2	Trigonella foenum-graecum	Diosgenin	Das et al., 2012
Hep2	Nigella sativa	Thymoquinone	Das et al., 2012
Hep2	Solanum incanum	Solanum indicum saponins	Gao et al., 2011

The two most common types of kidney cancer are renal cell carcinoma (RCC) and urothelial cell carcinoma (UCC) of the renal pelvis. The different types, such as RCC and UCC, have different etiologies, with different prognosis. RCC is responsible for approximately 80% of primary renal cancers, and UCC accounts for the majority of the remainder.

Treatment for kidney cancer depends on the type and stage of the disease. Usually treatment does not involve chemotherapy and radiotherapy, as kidney cancers often do not respond to these treatments. If the cancer has not spread, it will usually treated by nephrectomy. Where the tumor is confined to the renal parenchyma,

the 5-year survival rate is 60-70%, but this is lowered considerably where there are metastases.

Stage I: Tumor of a diameter of 7 cm (approx. 2^3Ú4 inches) or smaller, and limited to the kidney. No lymph node involvement or metastases to distant organs.

Stage II: Tumor larger than 7.0 cm but still limited to the kidney. No lymph node involvement or metastases to distant organs.

Stage III any of the following:

• Tumor of any size with involvement of a nearby lymph node but no metastases to distant organs. Tumor of this stage may be with or without spread to fatty tissue around the kidney, with or without spread into the large veins leading from the kidney to the heart.

• Tumor with spread to fatty tissue around the kidney and/or spread into the large veins leading from the kidney to the heart, but without spread to any lymph nodes or other organs.

Stage IV any of the following:

• Tumor that has spread directly through the fatty tissue and the fascia ligament-like tissue that surrounds the kidney.

• Involvement of more than one lymph node near the kidney

• Involvement of any lymph node not near the kidney

• Distant metastases, such as in the lungs, bone, or brain.

Sources

Mulders, P.F., Brouwers, A.H., Hulsbergen-van der Kaa C,A., et al. (2008) Guideline ‘Renal cell carcinoma. Ned Tijdschr Geneeskd (in Dutch; Flemish) 152 (7): 376–80.

Ramana, J. (2012) ‘CDB: Renal Cancer Gene Database. BMC Research Notes 5 (1): 246. doi:10.1186/1756-0500-5-246

Cohen, H.T., McGovern, F.J. (2005) Renal-Cell Carcinoma. New England Journal of Medicine 353 (23): 2477–2490. doi:10.1056/NEJMra043172

Kidney Cancer / General Information at Weill Cornell Medical College, James Buchanan Brady Foundation, Department of Urology. https://www.cornellurology.com/clinical-conditions/kidney-cancer/renal-cell-carcinoma/

Head and neck cancer refers to a group of biologically similar cancers that start in the lip, oral cavity, nasal cavity, paranasal sinuses, pharynx, and larynx. Ninety percent of head and neck cancers are squamous cell carcinomas (SCCHN), originating from the mucosal lining (epithelium) of these regions. Head and neck cancers often spread to the lymph nodes of the neck, and this is often the first (and sometimes only) sign of the disease at the time of diagnosis. Head and neck cancer is strongly associated with certain environmental and lifestyle risk factors, including tobacco smoking, alcohol consumption, UV light, particular chemicals used in certain workplaces, and certain strains of viruses, such as human papilloma virus.

These cancers are frequently aggressive in their biologic behavior; patients with these types of cancer are at a higher risk of developing another cancer in the head and neck area. Head and neck cancer is highly curable

if detected early, usually with some form of surgery, but radiation therapy may also play an important role, while chemotherapy is often ineffective.

Although early-stage head and neck cancers (especially laryngeal and oral cavity) have high cure rates, up to 50% of head and neck cancer patients present with advanced disease. Cure rates decrease in locally advanced cases, whose probability of cure is inversely related to tumor size and even more so to the extent of regional node involvement.

Sources

Ridge, J.A., Glisson, B.S., Lango, M.N., et al. (2008) Head and Neck Tumors in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.

NCI. Head and Neck Cancer http://www.cancer.gov/cancertopics/types/head-and-neck

Gourin, C., Podolsky, R. (2006) Racial disparities in patients with head and neck squamous cell carcinoma. Laryngoscope 116 (7): 1093–106. doi:10.1097/01.mlg.0000224939.61503.83.

 

Head and Neck Cancer
Cell Type	Herb Source(s)	Isolate	Refs
CAL-27, FaDu	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalin	Franek, 2005
squamous	soy, fava, and kudzu	Genistein	Sarkar & Li, 2003; Magee & Rowland, 2004
Non specific	Curcuma longa	Curcumin	Anand et al., 2008
Non specific	fruits and vegetables, particularly green tea Camellia sinensis	Green Tea 95% Polyphenols	Zhang et al., 2008
Non specific	Isatis (L.) genus	Indirubin	Kim et al., 2011

Glioblastoma multiforme (GBM), WHO classification name ‘glioblastoma’, is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. GBM is rare, with incidence of 2–3 cases per 100,000. It presents two variants: giant cell glioblastoma and gliosarcoma. Median survival with standard-of-care radiation and chemotherapy with temozolomide is 15 months.  Median survival without treatment is 4½

months. Surgery is controversial because no randomized controlled trials have ever been done.

Sources

Johnson, D.R., & O’Neill, B.P. (2011) Glioblastoma survival in the United States before and during the temozolomide era. Journal of Neuro-Oncology 107 (2): 359–64. doi:10.1007/s11060-011-0749-4.

Van Meir, E.G., Hadjipanayis, C.G., Norden, A.D., et al. (2010) Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma. CA: A Cancer Journal for Clinicians 60 (3): 166–93. doi:10.3322/caac.20069.

 

Glioblastoma
Cell Type	Herb Source(s)	Isolate	Refs
C6	Gardenia fructus	Penta-acetyl geniposide [(Ac)(5)GP]	Huang et al., 2009
GBM8401/TSGH	Solanum incanum	Solanum indicum saponins	Gao et al., 2011
LN-229	derivative of artemisinin	Artesunate	Berdelle, 2011
T98G	Berberis amurensis	Berberine	Eom et al., 2010
U118, U138	Rabdosia rubescens	Oridonin	Ikezoe et al., 2003
U251	Vitex rotundifolia	Casticin	Liu et al., 2013
U251	Nerium oleander	Oleandrin	Lin, Ho, & Newman, 2010
U373	Anemarrhena asphodeloides	Mangiferin	Chen et al., 2009
U87	Aloe vera	Aloe-emodin	Ismail, et al., 2013
U87MG, Hs683, and M059K	Lithospermum erythrorhizon	Shikonin	Chen et al., 2012
Non specific	Betula platyphylla, Betula X caerulea, Betula cordifolia, Betula papyrifera, Betula populifolia, Dillenia indica	Betulin	Rzeski, 2009
Non specific	Betula pubescens, Ziziphus mauritiana, Prunella vulgaris, Triphyophyllum peltatum and Ancistrocladus heyneanus, etc.	Betulinic acid	Wolfgang, 1999
Non specific	Lagerstroemia speciosa, Crataegus pinnatifida	Corosolic acid	Fujiwara et al., 2010
Non specific	various Garcinia species	Gambogic acid	Qi et al., 2008
Non specific	Panax genus	Ginsenosides	Choi et al., 2013
Non specific	Panax ginseng	RG3	Choi et al., 2013
Non specific	Anemarrhena asphodeloides	Mangiferin	Jung et al., 2012

Genitourinary cancers include those of the prostate, kidney, bladder and testis, as well as less common cancers such as those of the penis, ureters and other urinary organs. In 2013, more than 388,000 people in the United States are expected to be diagnosed with genitourinary cancers, with an estimated more than 60,000 deaths. The most common genitourinary cancer is prostate cancer, which, according to estimates, will be diagnosed in more than 238,000 men in the United States in 2013, and claim more than 29,000 lives.

Sources

http://www.clinical-genitourinary-cancer.com/

Research from the 2013 Genitourinary Cancers Symposium highlights new insights on high-risk prostate cancer prevalence and treatment, compares benefit of surveillance and surgery for management of small kidney tumors. http://www.eurekalert.org/pub_releases/2013-02/asoc-sbf021213.php

Held-Warmkessel, J. (2009) Site-Specific Cancer Series: Genitourinary Cancer. Oncology Nursing Society; 1 edition (September 30, 2009) ISBN-10: 1890504858 http://www.ons.org/Publications/Books/Excerpts/INPU0587ch1

 

Genitourinary Cancer
Cell Type	Herb Source(s)	Isolate	Refs
Non specific	Curcuma longa	Curcumin	Anand et al., 2008

Gallbladder cancer is a relatively uncommon cancer. It has peculiar geographical distribution, being common in Central and South America, central and eastern Europe, Japan, and northern India; it is also common in certain ethnic groups, e.g. Native American Indians and Hispanics. The outlook is poor for recovery if the cancer is found after symptoms have started to occur, with a 5-year survival rate close to 3%.

Risk Factors: Gender: Approx. twice more common in women than men, usually in seventh and eighth decades.

Obesity increases the risk for gallbladder cancer. Primary carcinoma is linked to chronic cholecystitis and cholelithiasis.

Sources

NCI http://www.cancer.gov/cancertopics/types/gallbladder

Kapoor, V.K. (2001) Incidental gallbladder cancer. Am. J. Gastroenterol. 96 (3): 627–9. doi:10.1111/j.1572-0241.2001.03597.x.

 

Bladder Cancer
Cell Type	Herb Source(s)	Isolate	Refs
BIU-87 and T24	Berberis amurensis	Berberine	Yan et al., 2011
EJ		Dauricine	Wang et al., 2012
EJ, T24, 5637	Sanguinaria canadensis	Sanguinarine	Han et al., 2013
T24	Saussurea lappa	Costunolide	Rasul et al., 2013
T24	Cortex periplocae	Periplocin	Zhao et al., 2009
T24	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Zheng et al., 2012
TSGH8301	berries, walnuts, pecans, pomegranate, cranberries, and longan	Ellagic acid	Ho et al., 2013
Non specific	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalein	Chao et al., 2007
Non specific	berries, walnuts, pecans, pomegranate, cranberries, and longan	Ellagic acid	Ho et al., 2013
Non specific	Phellinus igniarius	Hispolon	Lu et al., 2009
Non specific	Magnolia officinalis	Magnolol	Chen et al., 2013
Non specific	Silybum marianum	Silibinin	Wu et al., 2013
Non specific	Stephania tetrandra	Tetrandrine	Lai et al., 1998 Ng et al., 2006 Wu et al., 2010 He et al., 2011

 

Gallbladder Cancer
Cell Type	Herb Source(s)	Isolate	Refs
GBC-SD	Scutellaria rivularis Scutellaria baicalensis	Wogonin	Dong et al., 2011
non specific	Herba epimedii	Icariin	Zhang et al., 2013

Fibrosarcoma (fibroblastic sarcoma) is a malignant mesenchymal tumor derived from fibrous connective tissue and characterized by the presence of immature proliferating fibroblasts or undifferentiated anaplastic spindle cells in a storiform pattern.  It originates in fibrous tissues of the bone and invades long or flat bones such as femur, tibia, and mandible. It also involves periosteum and overlying muscle.

The tumor may present different degrees of differentiation: low grade (differentiated), intermediate malignancy

and high malignancy (anaplastic).

Survival:

• 5 year – 41%, 10 year –29%

• Better if tumor is superficial and better differentiated, low mitotic rate, no necrosis

Source

http://sarcomahelp.org/fibrosarcoma.html

Pathology Outlines (2012) http://www.pathologyoutlines.com/topic/softtissuefibrosarcoma.html

 

Fibrosarcoma
Cell Type	Herb Source(s)	Isolate	Refs
HT1080	Alismatis Rhizoma	Alisol B acetate	Lee et al., 2001
HT1080	Angelica gigas (Nakai)	Decursin	Lu et al., 2007
HT1080	Panax genus	Ginsenosides	Park et al., 1999
KBV20C	Curcuma longa	Curcumin	Um et al., 2008

 

Sarcoma
Cell Type	Herb Source(s)	Isolate	Refs
180	Angelica gigas (Nakai)	Decursin	Lee et al., 2004
180	Angelica gigas	Decursinol angelate	Lee et al., 2004
180	Lithospermum erythrorhizon	Shikonin	Sankawa et al., 1977
Non specific	Lagerstroemia speciosa, Crataegus pinnatifida	Corosolic acid	Horlad et al., 2013
Non specific	Curcuma longa	Curcumin	Anand et al., 2008

There are various subtypes of esophageal cancer, primarily squamous cell cancer and adenocarcinoma. Most esophageal cancers fall into one of two classes: squamous cell carcinomas, which are similar to head and neck cancer in their appearance and association with tobacco and alcohol consumption, and adenocarcinomas, which are often associated with a history of gastroesophageal reflux disease and Barrett’s esophagus. A general rule of thumb is that a cancer in the upper two-thirds is a squamous cell carcinoma and one in the lower one-third is an adenocarcinoma.

In general., the prognosis of esophageal cancer is quite poor, because most patients present with advanced disease. By the time the first symptoms such as dysphagia start manifesting themselves, the cancer has already well progressed. The overall 5-year survival rate (5YSR) is approximately 15%, with most patients dying within the first year of diagnosis.

The following stages are used for squamous cell carcinoma of the esophagus:

Stage 0 (High-grade Dysplasia)

In stage 0, abnormal cells are found in the inner (mucosal) layer of the esophageal wall. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called high-grade dysplasia.

Stage I is divided into Stage IA and Stage IB, depending on where the cancer is found.

• Stage IA: Cancer has formed in the inner (mucosal) layer of the esophageal wall. The tumor cells look a lot like normal cells under a microscope.

• Stage IB: Cancer has formed: in the inner (mucosal) layer of the esophageal wall. The tumor cells do not look at all like normal cells under a microscope; or in the inner (mucosal) layer and spread into the middle (muscle) layer or the outer (connective tissue) layer of the esophageal wall. The tumor cells look a lot like normal cells under a microscope.

Stage II is divided into Stage IIA and Stage IIB, depending on where the cancer has spread.

• Stage IIA: Cancer has spread: into the middle (muscle) layer or the outer (connective tissue) layer of the esophageal wall. The tumor cells look a lot like normal cells under a microscope. The tumor is in either the upper or middle esophagus; or into the middle (muscle) layer or the outer (connective tissue) layer of the esophageal wall.

• Stage IIB: Cancer: has spread into the middle (muscle) layer or the outer (connective tissue) layer of the esophageal wall. The tumor is in either the upper or middle esophagus; or is in the inner (mucosal) layer and may have spread into the middle (muscle) layer of the esophageal wall. Cancer is found in 1 or 2 lymph nodes near the tumor.

Stage III is divided into Stage IIIA, Stage IIIB, and Stage IIIC, depending on where the cancer has spread.

• Stage IIIA: Cancer: is in the inner (mucosal) layer and may have spread into the middle (muscle) layer of the esophageal wall. Cancer is found in 3 to 6 lymph nodes near the tumor; or has spread into the outer (connective tissue) layer of the esophageal wall. Cancer is found in 1 or 2 lymph nodes near the tumor; or has spread into the diaphragm, sac around the heart, or tissue that covers the lungs and lines the inner wall of the chest cavity. The cancer can be removed by surgery.

• Stage IIIB: Cancer has spread into the outer (connective tissue) layer of the esophageal wall. Cancer is found in 3 to 6 lymph nodes near the tumor.

• Stage IIIC: Cancer has spread: into the diaphragm, sac around the heart, or tissue that covers the lungs and lines the inner wall of the chest cavity; the cancer can be removed by surgery. Cancer is found in 1 to 6 lymph nodes near the tumor; or has spread into other nearby organs such as the aorta, trachea, or spine, and the cancer cannot be removed by surgery; or to 7 or more lymph nodes near the tumor.

In Stage IV, cancer has spread to other parts of the body.

Sources

Enzinger, P.C., Mayer, R.J. (2003) Esophageal cancer. N. Engl. J. Med. 349 (23): 2241–52. doi:10.1056/NEJMra035010.

NCI. (2013) Stages of Esophageal Cancer. http://www.cancer.gov/cancertopics/pdq/treatment/esophageal/Patient/page2

 

esophageal Cancer
Cell Type	Herb Source(s)	Isolate	Refs
Eca-109	Hippophae rhamnoides	Isorhamnetin	Shi et al., 2012
EC109	Betula pubescens, Ziziphus mauritiana, Prunella vulgaris, Triphyophyllum peltatum and Ancistrocladus heyneanus, etc.	Betulinic acid	Cai, 2006
TE-13, Eca-109	Cortex periplocae	Periplocin	Zhao et al., 2009
YES-2	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Yamai et al., 2009
Non specific	Derivative of artemisinin	Artesunate	Zhou et al., 2013
Non specific	Magnolia genus	Honokiol	Munroe et al., 2007; Chen et al., 2009; Fried & Arbiser, 2009
Non specific	Rabdosia rubescens	Oridonin	Tang & Eisenbrand, 1992

Surface epithelial-stromal tumors are a class of ovarian neoplasms that may be benign or malignant. Neoplasms in this group are thought to be derived from the ovarian surface epithelium (modified peritoneum) or from ectopic endometrial or Fallopian tube (tubal) tissue. Tumors of this type are also called ovarian adenocarcinoma. This group of tumors accounts for 90% to 95% of all cases of ovarian cancer. Serum CA-125 is often elevated but is only 50% accurate so it is not a useful tumor marker to assess the progress of treatment.

The 5-year survival rates of borderline and malignant tumors confined to the ovaries are 100% and 70%

respectively. If the peritoneum is involved, these rates become 90% and 25%. While the 5-year survival rates of borderline tumors are excellent, this should not be seen as evidence of cure, as recurrences can occur many years later.

Sources

Kosary, C.L. (2007) Chapter 16: Cancers of the Ovary. In Baguio, RNL; Young, JL; Keel, GE; Eisner, MP; Lin, YD; Horner, M-J. SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, 1988-2001, Patient and Tumor Characteristics. SEER Program. NIH Pub. No. 07-6215. Bethesda, MD: National Cancer Institute. pp. 133–144.

Bradshaw, K.D., Schorge, J.O., Schaffer, J., et al. (2008) Williams’ Gynecology. McGraw-Hill Professional. ISBN 0-07-147257-6.

A cancer that begins in squamous cells. Squamous cells are thin, flat cells that look like fish scales, and are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the lining of the respiratory and digestive tracts. Most cancers of the anus, cervix, head and neck, and vagina are epidermoid carcinomas. Also called squamous cell

carcinoma. It can be located in the lung, anus, head and neck, skin, as well as elsewhere.

Source

NCI. Dictionary of Cancer Terms. http://www.cancer.gov/dictionary?cdrid=46419

http://medical-dictionary.thefreedictionary.com/epidermoid+carcinoma

 

Epidermoid Cancer
Cell Type	Herb Source(s)	Isolate	Refs
KB-C2	Commiphora wightii	Guggulsterones	Nabekura, et al., 2008
A431	Berberis amurensis	Berberine	Mantena et al., 2006

Endometrial cancer is any of several types of malignancies that arise from the endometrium of the uterus. The incidence is on a slow rise, secondary to an increasing population age and an increasing body mass index, with 39% of cases attributed to obesity. The most common subtype, endometrioid adenocarcinoma, typically occurs within a few decades of menopause, and is associated with obesity, excessive estrogen exposure.

Type I endometrial cancers occur most commonly in pre-and peri-menopausal women, and are more common in European women, often with a history of endometrial hyperplasia. Type I endometrial cancers are often low-grade, minimally invasive into the underlying uterine wall (myometrium), and are of the endometrioid type, and carry a good prognosis.

Type II endometrial cancers usually occur in older, post-menopausal women, are more common in African women, and are not associated with increased exposure to estrogen. Type II endometrial cancers are often high-grade, with deep invasion into the underlying uterine wall (myometrium), and are of the serous or clear cell type, and carry a poorer prognosis.

Sources

Felix, A.S. (2010) Factors associated with Type I and Type II endometrial cancer. Cancer Causes Control. 2010 November; 21(11): 1851–1856. doi: 10.1007/s10552-010-9612-8 www.ncbi.nlm.nih.gov/pmc/articles/PMC2962676/

Hoffman, B.L. (2012). Williams Gynecology: Chapter 33, Endometrial Cancer (2nd ed.). New York: McGraw-Hill Medical. ISBN 978-0071716727.

Oldenburg, C.S., et al. (2013) The relationship of body mass index with quality of life among endometrial cancer survivors: a study from the population-based PROFILES registry. Gynecologic Oncology, 129 (1), April 2013, page 216–21

Cholangiocarcinoma is a form of cancer that is composed of mutated epithelial cells (or cells showing characteristics of epithelial differentiation) that originate in the bile duct. It is a relatively rare neoplasm that is classified as an adenocarcinoma; a cancer that forms glands or secretes significant amounts of mucins. Cholangiocarcinoma is considered to be an incurable and rapidly lethal malignancy unless both the primary tumor and any metastases can be fully resected.

Sources

Zervos, E., Osborne, D., Goldin, S., et al. (2005) Stage does not predict survival after resection of hilar cholangiocarcinomas promoting an aggressive operative approach. Am J Surg 190 (5): 810–5. doi:10.1016/j.amjsurg.2005.07.025.

Feldman, M., Friedman, L.S., Lawrence J. Brandt, L.J., Eds. (2006) Sleisenger and Fordtran’s Gastrointestinal and Liver Disease (8th ed.). Saunders. pp. 1493–6. ISBN 978-1-4160-0245-1.

 

Cholangiocarcinoma
Cell Type	Herb Source(s)	Isolate	Refs
KKU-100 and KKU-M156 CCA	Garcinia hanburyi	Isomorellin	Hahnvajanawong C et al., 2012

Cervical cancer is a malignant neoplasm arising from cells originating in the cervix uteri. One of the most common symptoms of cervical cancer is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer has progressed to an advanced stage. Cancer screening using the Pap smear can identify precancerous and potentially precancerous changes in cervical cells and tissue. Most cervical cancers are squamous cell carcinomas. Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (http://www.figo.org/) staging system, which is based on clinical examination, rather than surgical findings. It allows only the following diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervical conization (cone biopsy).

The following stages are used for cervical cancer:

In carcinoma in situ (stage 0), abnormal cells are found in the innermost lining of the cervix. These abnormal cells may become cancer and spread into nearby normal tissue.

• In stage I, cancer is found in the cervix only. Stage I is divided into stages IA and IB, based on the amount of cancer that is found.

• In stage IA1, the cancer is not more than 3 millimeters deep and not more than 7 millimeters wide.

• In stage IA2, the cancer is more than 3 but not more than 5 millimeters deep, and not more than 7 millimeters wide.

• In stage IB1: the cancer can only be seen with a microscope and is more than 5 millimeters deep and more than 7 millimeters wide; or the cancer can be seen without a microscope and is 4 centimeters or smaller.

• In stage IB2, the cancer can be seen without a microscope and is larger than 4 centimeters.

In stage II, cancer has spread beyond the cervix but not to the pelvic wall or to the lower third of the vagina. Stage II is divided into stages IIA and IIB, based on how far the cancer has spread.

• Stage IIA: Cancer has spread beyond the cervix to the upper two thirds of the vagina but not to tissues around the uterus. Stage IIA is divided into stages IIA1 and IIA2, based on the size of the tumor.

• In stage IIA1, the tumor can be seen without a microscope and is 4 centimeters or smaller.

• In stage IIA2, the tumor can be seen without a microscope and is larger than 4 centimeters.

• Stage IIB: Cancer has spread beyond the cervix to the tissues around the uterus.

In stage III, cancer has spread to the lower third of the vagina, and/or to the pelvic wall, and/or has caused kidney problems. Stage III is divided into stages IIIA and IIIB, based on how far the cancer has spread.

In stage IV, cancer has spread to the bladder, rectum, or other parts of the body. Stage IV is divided into stages IVA and IVB, based on where the cancer is found.

• Stage IVA: Cancer has spread to nearby organs, such as the bladder or rectum.

• Stage IVB: Cancer has spread to other parts of the body, such as the liver, lungs, bones, or distant lymph nodes.

Sources

Kumar, V., Abbas, A.K., Fausto, N., Mitchell, R.N. (2007) Robbins Basic Pathology ((8th ed.) ed.). Saunders Elsevier. pp. 718–721. ISBN 978-1-4160-2973-1.

American Family Physician. (2000) http://www.aafp.org/afp/2000/0301/p1369.html

NCI. (2013) Stages of Cervical Cancer. http://www.cancer.gov/cancertopics/pdq/treatment/cervical/Patient/page2

 

Cervical Cancer
Cell Type	Herb Source(s)	Isolate	Refs
Ca Ski	Curcuma zedoaria	Alismol	Syed Abdul Rahman, Abdul Wahab, & Abd Malek, 2013
Ca Ski	Curcuma zedoaria	Curzerenone	Syed Abdul Rahman, Abdul Wahab, & Abd Malek, 2013
HeLa	Alkanna cappadocica	5-O-methyl-11-O-acetylalkannin	Sevimli-Gur et al., 2010
HeLa	Lagerstroemia speciosa, Crataegus pinnatifida	Corosolic acid	Xu et al., 2009
Hela	Panax genus	Ginsenosides	Ji et al., 2012
HeLa	Juglans mandshurica Maxim	Juglone	Zhang et al., 2012
Hela	Cortex periplocae	Periplocin	Zhao et al., 2009
HeLa	Solanum incanum	Solanum indicum saponins	Gao et al., 2011
HeLa	Scutellaria rivularis Scutellaria baicalensis	Wogonin	He et al., 2012
HeLa and Siha	Bupleurum radix	Saikosaponin-A	Wang et al., 2010
HeLa, CaSki	Trichosanthes kirilowii	Trichosanthin	Huang et al., 2012
HeLaLiver cancerHepG2	Bupleurum radix	Saikosaponin-D	Wong et al., 2013
HPV-associated		Retinoids	Sah et al., 2002
KB-C2	Callyspongia siphonella	Sipholenol A	Abraham et al., 2010
KB-C2 and KB-V1	Callyspongia siphonella	Sipholenol A	Shi et al., 2007
SiHa and CaSki	Berberis amurensis	Berberine	Komal., Singh, & Deshwal., 2013
U14	Betula pubescens, Ziziphus mauritiana, Prunella vulgaris,Triphyophyllum peltatum and Ancistrocladus heyneanus, etc.	Betulinic acid	Wang, 2012
Non specific	honeybee hives	Caffeic acid phenethyl ester (CAPE)	Hsu et al., 2013
Non specific	Astragalus membranaceus	Formononetin	Lo et al., 2013
Non specific	Citrus aurantium	Naringin	Ramesh & Alshatwi, 2013
Non specific	Salvia miltiorrhiza	Tanshinone II A	Pan et al., 2010
Non specific	Trichosanthes kirilowii	Trichosanthin	Sha et al., 2013

Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite. It is a positive risk factor for death, meaning if the patient has cachexia, the chance of death from the underlying condition is increased dramatically and response to standard treatment is usually poor. Cachexia

includes sarcopenia (the degenerative loss of skeletal muscle mass) as a part of its pathology.

Source

Bossola, M., et al. Novel treatments for cancer cachexia. August 2007, Vol. 16, No. 8 , Pages 1241-1253 doi:10.1517/13543784.16.8.1241

 

Cachexia-Inducing
Cell Type	Herb Source(s)	Isolate	Refs
MKN45cl85 and 85As2mLuc		Isoflavones	Yanagihara et al., 2013

Breast cancer is a type of cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas, while those originating from lobules are known as lobular carcinomas. The benefit vs. harm of breast cancer screening is controversial. The characteristics of the cancer determine the treatment, which may include surgery, medications (hormonal therapy and chemotherapy), radiation and/or immunotherapy. Surgery provides the single largest benefit, and to increase the likelihood of cure, several chemotherapy regimens are commonly given in addition. Radiation is used after breast-conserving surgery and substantially improves local relapse rates and in many circumstances also overall survival.

Breast cancer staging using the TNM system is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.

Some genetic susceptibility may play a minor role in most cases. Overall, however, genetics is believed to be the primary cause of 5–10% of all cases. In those with zero, one or two affected relatives, the risk of breast cancer before the age of 80 is 7.8%, 13.3%, and 21.1% with a subsequent mortality from the disease of 2.3%, 4.2%, and 7.6% respectively.  In those with a first degree relative with the disease the risk of breast cancer between the age of 40 and 50 is double that of the general population.

Grading compares the appearance of the breast cancer cells to the appearance of normal breast tissue. Normal cells in an organ like the breast become differentiated, meaning that they take on specific shapes and forms that reflect their function as part of that organ. Cancerous cells lose that differentiation. In cancer, the cells that would normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade), as the cells progressively lose the features seen in normal breast cells. Poorly differentiated cancers (the ones whose tissue is least like normal breast tissue) have a worse prognosis.

The main stages are:

• Stage 0 is a pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).

• Stages 1–3 are within the breast or regional lymph nodes.

• Stage 4 is ‘metastatic’ cancer that has a less favorable prognosis.

ER+ cancer cells (that is, cancer cells that have estrogen receptors) depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. tamoxifen), and generally have a better prognosis. Untreated, HER2+ breast cancers are generally more aggressive than HER2- breast cancers, but HER2+ cancer cells respond to drugs such as the monoclonal antibody trastuzumab (in combination with conventional chemotherapy), and this has improved the prognosis significantly. Cells that do not have any of these three receptor types (estrogen receptors, progesterone receptors, or HER2) are called triple-negative.

Resistance to Systemic Therapy in Patients with Breast Cancer

Breast cancer is the most common cancer and the second leading cause of cancer death in American women. It was the second most common cancer in the world in 2002, with more than 1 million new cases. Despite advances in early detection and the understanding of the molecular bases of breast cancer biology, about 30% of patients with early-stage breast cancer have recurrent disease. To offer more effective and less toxic treatment, selecting therapies requires considering the patient and the clinical and molecular characteristics of the tumor. Systemic treatment of breast cancer includes cytotoxic, hormonal, and immunotherapeutic agents. These medications are used in the adjuvant, neoadjuvant, and metastatic settings. In general, systemic agents are active at the beginning of therapy in 90% of primary breast cancers and 50% of metastases. However, after a variable period of time, progression occurs. At that point, resistance to therapy is not only common but expected.

Gonzalez-Angulo et al., (2007) reviewed the general mechanisms of drug resistance, including multidrug resistance by P-glycoprotein and the multidrug resistance protein family in association with specific agents and their metabolism, emergence of refractory tumors associated with multiple resistance mechanisms, and resistance factors unique to host-tumor-drug interactions. Important anticancer agents specific to breast cancer are described.

Breast cancer is the most common type of cancer and the second leading cause of cancer death in American women. In 2002, 209,995 new cases of breast cancer were registered, and 42,913 patients died of it. In 5 years, the annual prevalence of breast cancer will reach 968,731 cases in the United States. World wide, the problem is just as significant, as breast cancer is the most frequent cancer after nonmelanoma skin cancer, with more than 1 million new cases in 2002 and an expected annual prevalence of more than 4.4 million in 5 years. Breast cancer treatment currently requires the joint efforts of a multidisciplinary team. The alternatives for treatment are constantly expanding. With the use of new effective chemotherapy, hormone therapy, and biological agents and with information regarding more effective ways to integrate systemic therapy, surgery, and radiation therapy, elaborating an appropriate treatment plan is becoming more complex. Developing such a plan should be based on knowledge of the benefits and potential acute and late toxic effects of each of the therapy regimens.

Despite advances in early detection and understanding of the molecular bases of breast cancer biology, approximately 30% of all patients with early-stage breast cancer have recurrent disease, which is metastatic in most cases. The rates of local and systemic recurrence vary within different series, but in general, distant recurrences are dominant, strengthening the hypothesis that breast cancer is a systemic disease from presentation. On the other hand, local recurrence may signal a posterior systemic relapse in a considerable number of patients within 2 to 5 years after completion of treatment. To offer better treatment with increased efficacy and low toxicity, selecting therapies based on the patient and the clinical and molecular characteristics of the tumor is necessary.

Consideration of these factors should be incorporated in clinical practice after appropriate validation studies are performed to avoid confounding results, making them true prognostic and predictive factors. A prognostic factor is a measurable clinical or biological characteristic associated with a disease-free or overall survival period in the absence of adjuvant therapy, whereas a predictive factor is any measurable characteristic associated with a response or lack of a response to a specific treatment. The main prognostic factors associated with breast cancer are the number of lymph nodes involved, tumor size, histological grade, and hormone receptor status, the first two of which are the basis for the AJCC staging system. The sixth edition of the American Joint Committee on Cancer staging system allows better prediction of prognosis by stage. However, after determining the stage, histological grade, and hormone receptor status, the tumor can behave in an unexpected manner, and the prognosis can vary. Other prognostic and predictive factors have been studied in an effort to explain this phenomenon, some of which are more relevant than others: HER-2/neu gene amplification and protein expression, expression of other members of the epithelial growth factor receptor family, S phase fraction, DNA ploidy, p53 gene mutations, cyclin E, p27 dysregulation, the presence of tumor cells in the circulation or bone marrow, and perineural and lymphovascular space invasion. Systemic treatment of breast cancer includes the use of cytotoxic, hormonal, and immunotherapeutic agents.

All of these agents are used in the adjuvant, neoadjuvant, and metastatic setting. Adjuvant systemic therapy is used in patients after they undergo primary surgical resection of their breast tumor and axillary nodes and who have a significant risk of systemic recurrence. Multiple studies have demonstrated that adjuvant therapy for early-stage breast cancer produces a 23% or greater improvement in disease-free survival and a 15% or greater increase in overall survival rates. Recommendations for the use of adjuvant therapy are based on the individual patient’s risk and the balance between absolute benefit and toxicity. Anthracycline-based regimens are preferred, and the addition of taxanes increases the survival rate in patients with lymph node-positive disease. Adjuvant hormone therapy accounts for almost two thirds of the benefit of adjuvant therapy overall in patients with hormone-receptor-positive breast cancer. Tamoxifen is considered the standard of care in premenopausal patients. In comparison, the aromatase inhibitor anastrozole has been proven to be superior to tamoxifen in postmenopausal patients with early-stage breast cancer. The adjuvant use of monoclonal antibodies and targeted therapies other than hormone therapy is being studied. Interestingly, some patients have an early recurrence even though they have a tumor with good prognostic features and at a favorable stage. These recurrences have been explained by the existence of certain cellular characteristics at the molecular level that make the tumor cells resistant to therapy. Selection of resistant cell clones of micrometastatic disease has also been proposed as an explanation for these events.

Neoadjuvant systemic therapy, which is the standard of care for patients with locally advanced and inflammatory breast cancer, is becoming more popular. It reduces the tumor volume, thus increasing the possibility of breast conservation, and at the same time allows identification of in vivo tumor sensitivity to different agents. The pathological response to neoadj uvant systemic therapy in the breast and lymph nodes correlates with patient survival. Use of this treatment modality produces survival rates identical to those obtained with the standard adjuvant approach. The rates of pathological complete response (pCR) to neoadjuvant systemic therapy vary according to the regimen used, ranging from 6% to 15% with anthracycline-based regimens to almost 30% with the addition of a noncross-resistant agent such as a taxane. In one study, the addition of neoadjuvant trastuzumab in patients with HER-2-positive breast tumors increased the pCR rate to 65%. Primary hormone therapy has also been used in the neoadjuvant systemic setting. Although the pCR rates with this therapy are low, it significantly increases breast conservation. Currently, neoadjuvant systemic therapy is an important tool in not only assessing tumor response to an agent but also studying the mechanisms of action of the agent and its effects at the cellular level. However, no tumor response is observed in some cases despite the use of appropriate therapy. The tumor continues growing during treatment in such cases, a phenomenon called primary resistance to therapy. The use of palliative systemic therapy for metastatic breast cancer is challenging.

Five percent of newly diagnosed cases of breast cancer are metastatic, and 30% of treated patients have a systemic recurrence. Once metastatic disease develops, the possibility of a cure is very limited or practically nonexistent. In this heterogeneous group of patients, the 5-year survival rate is 20%, and the median survival duration varies from 12 to 24 months. In this setting, breast cancer has multiple clinical presentations, and the therapy for it should be chosen according to the patient’s tumor characteristics, previous treatment, and performance status with the goal of improving survival without compromising quality of life. Treatment resistance is most commonly seen in such patients. They initially may have a response to different agents, but the responses are not sustained, and, in general, the rates of response to subsequent agents are lower.

Isoflavone intake inhibits the development of mammary tumors in normal and ovariectomized rats

A time to another look at the use of phytoestrogens in breast cancer
Considerable epidemiological studies have shown a negative association between soy intake and breast cancer risk (Peeters et al., 2003). Recently, a meta-analysis of prospective studies found that soy isoflavone consumption was not only inversely associated with risk of breast cancer incidence, but also was inversely associated with risk of breast cancer recurrence (Dong et al., 2011). Animal studies have generated conflicting data regarding the ability of isoflavone to reduce mammary tumorigenesis (Gallo et al., 2001; Ueda et al., 2003). In general, most previous studies reported that dietary isoflavone exposure may increase tumor latency (Allred et al., 2004; Peng et al., 2010).

This research paper by Ma et al., (2014) proved that isoflavone intake cannot only increase the mean latent period, but also decrease the tumor incidence. The same results were reported in other animal studies. Hewitt et al., (2003) reported that female Balb/c mice injected with F3II cells and fed diets supplemented with 0.6% soy extract exhibited a significant 90% reduction in mammary tumor weight compared to controls. Moreover, Kang et al., (2009) found that soy phytochemical extraction exerts significant antitumor and anti-angiogenic activity in a postmenopausal animal model with breast cancer.

The mechanisms which isoflavone could alter mammary tumorigenesis are not completely understood. The rat, mouse and human ER exist as two subtypes, ERα and ERβ. The difference in function between the two ER remains to be established, but it is generally assumed that ERα mediates the proliferative actions of estrogens and ERβ may inhibit cellular proliferation by antagonizing the actions of ERα (Lazennec et al., 2001). It is to be noted that ERβ is expressed at a significantly higher level than ERα during early development and in normal adult breast, while in the breast tumor ERα expression is higher than ERβ expression. In addition, isoflavones bind more strongly to ERβ than to ERα (Speirs et al., 2007).

Some studies reported that genistein can exhibit potential anticarcinogenesis activities by the induction of mammary epithelial cell differentiation and activation of ERβ (Kuiper et al., 1998). Recently, Lattrich et al., (2012) tested the effect of ERβ agonists on the growth and gene expression of different ERβ-positive human breast cancer cell lines and found that the ERβ agonists only inhibited the growth of the ERα, ERβ-positive breast cancer cell lines, which suggested that the anti-proliferative effects of the ERβ agonists might be dependent on the presence of both ERs. In the present research, we found that soy isoflavone significantly changed the estrogen receptor expression profiles including the increasing of ERβ expression and ERα expression, which suggested that both ERα and ERβ may be responsible for the inhibition of mammary tumors.

Oxidative stress and increased production of reactive oxygen species (ROS) are involved in various processes of carcinogenesis (Swiatkowska et al., 2002). High level of ROS has been reported to damage many biomolecules and exert diverse cellular changes in gene expression that leads to initiation and promotion of carcinogenesis. Similar, with the results in the present research, Deepalakshmi et al., (2013) have reported that the plasma level of the thiobarbituric acid reactive substances including MDA and 8-OHdG was significantly increased in 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer rats through the overproduction and diffusion of free radicals from the damaged tumor tissues when compared with DMBA-rats. The antioxidant activity of all the soy isoflavones have been proved by ferricreducing ability of plasma assay and Trolox equivalent antioxidant capacity assay in a study (Mitchell et al., 1998).

Since lipid peroxidation is one of the most important expressions of oxidative stress induced by ROS, its end products MDA and 8-OHdG were determined as the oxidative stress indicator in our study. In this present study, the results showed that isoflavone treatment significantly decreased the 8-OHdG content in normal rats and MDA concentrations in ovariectomized rats compared with CG, implicating that this protective effect is probably based on the antioxidant activity of the soy isoflavones which reduces the oxidative damage by blocking the production of free radicals and inhibits lipid peroxidation. Studies have reported that SOD family played a crucial role in ROS scavenging (Kim et al., 2010). Ma et al., (2014) found that isoflavone intake significantly increased SOD content in normal rats but not in ovariectomized rats.

In conclusion, results suggested that isoflavone intake can significantly inhibit the development of mammary tumors in normal rats or in ovariectomized rats through changing the estrogen receptor expression profiles. In addition, antioxidant activity of isoflavone may be also responsible for the carcinogenesis suppression.

Source

World Cancer Report. International Agency for Research on Cancer. 2008. Retrieved 2013-10-26.

Florescu A, Amir E, Bouganim N, Clemons M (2011). Immune therapy for breast cancer in 2010—hype or hope?. Current Oncology 18 (1): e9–e18.

American Cancer Society (2007). Cancer Facts & Figures 2007. Archived from the original on 10 April 2007. Retrieved 2013-10-26.

Watson M (2008). Assessment of suspected cancer. InnoAiT 1 (2): 94–107. doi:10.1093/innovait/inn001.

Breast Cancer. Wikipedia http://en.wikipedia.org/wiki/Breast_cancer

Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. 2007 Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1-22.

Ma Df, et al. (2014) Isoflavone intake inhibits the development of 7,12-dimethylbenz(a)anthracene(DMBA)-induced mammary tumors in normal and ovariectomized rats. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882481/

Allred CD, Allred KF, Ju YH, et al. Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats. Carcinogenesis. 2004;25:211–218.

Deepalakshmi K, Mirunalini S. Modulatory effect of Ganoderma lucidum on expression of xenobiotic enzymes, oxidant-antioxidant and hormonal status in 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats. Pharmacogn Mag. 2013;9:167–175.

Dong JY, Qin LQ. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2011;125:315–323.

Gallo D, Giacomelli S, Cantelmo F, et al. Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy. Breast Cancer Res Treat. 2001;69:153–164.

Hewitt AL, Singletary KW. Soy extract inhibits mammary adenocarcinoma growth in a syngeneic mouse model. Cancer Lett. 2003;192:133–143.

Kang X, Jin S, Zhang Q. Antitumor and antiangiogenic activity of soy phytoestrogen on 7,12-dimethylbenz[α]anthracene-induced mammary tumors following ovariectomy in Sprague–Dawley rats. J Food Sci. 2009;74:H237–H242.

Kim SC, Magesh V, Jeong SJ, et al. Ethanol extract of Ocimum sanctum exerts anti-metastatic activity through inactivation of matrix metalloproteinase-9 and enhancement of anti-oxidant enzymes. Food Chem Toxicol. 2010;48:1478–1482.

Kuiper GG, Lemmen JG, Carlsson B, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998;139:4252–4263.

Lattrich C, Stegerer A, Häring J, Schüler S, Ortmann O, Treeck O. Estrogen receptor β agonists affect growth and gene expression of human breast cancer cell lines. Steroids. 2012;78:195–202.

Lazennec G, Bresson D, Lucas A, Chauveau C, Vignon F. ER beta inhibits proliferation and invasion of breast cancer cells. Endocrinology. 2001;142:4120–4130.

Mitchell JH, Gardner PT, McPhail DB, Morrice PC, Collins AR, Duthie GG. Antioxidant efficacy of phytoestrogens in chemical and biological model systems. Arch Biochem Biophys. 1998;360:142–148.

Peeters PH, Keinan-Boker L, van der Schouw YT, Grobbee DE. Phytoestrogens and breast cancer risk. Review of the epidemiological evidence. Breast Cancer Res Treat. 2003;77:171–183.

Peng JH, Zhu JD, Mi MT, et al. Prepubertal genistein exposure affects erbB2/Akt signal and reduces rat mammary tumorigenesis. Eur J Cancer Prev. 2010;19:110–119.

Speirs V, Walker RA. New perspectives into the biological and clinical relevance of oestrogen receptors in the human breast. J Pathol. 2007;211:499–506.

Swiatkowska M, Szemraj J, Al-Nedawi KN, Pawłowska Z. Reactive oxygen species upregulate expression of PAI-1 in endothelial cells. Cell Mol Biol Lett. 2002;7:1065–1071.

Ueda M, Niho N, Imai T, et al. Lack of significant effects of genistein on the progression of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats. Nutr Cancer. 2003;47:141–147.

 

Breast Cancer cell lines
Cell line	Primary tumor	Origin of cells	Estrogen receptors	Progesterone receptors	ERBB2 amplification
600MPE	Invasive ductal carcinoma		+	–
AU565	Adenocarcinoma		–	–	+
BT-20	Invasive ductal carcinoma	Primary	No	No	No
BT-474	Invasive ductal carcinoma	Primary	Yes	Yes	Yes
BT-483	Invasive ductal carcinoma		+	+
BT-549	Invasive ductal carcinoma		–	–
Evsa-T	Invasive ductal carcinoma, mucin-producing, signet-ring type	Metastasis (ascites)	No	Yes	?
Hs578T	Carcinosarcoma	Primary	No	No	No
MCF-7	Invasive ductal carcinoma	Metastasis (pleural effusion)	Yes	Yes	No
MDA-MB-231	Invasive ductal carcinoma	Metastasis (pleural effusion)	No	No	No
SkBr3	Invasive ductal carcinoma	Metastasis (pleural effusion)	No	No	Yes
T-47D	Invasive ductal carcinoma	Metastasis (pleural effusion)	Yes	Yes	No
4T1		metastatic cancer
BCRP/ABCG2		malignant stem cells
CSC		cancer stem cell
Hs578T			–	–	–
MCF-7	Invasive ductal carcinoma		+
MDA-MB-231		metastatic breast cancer
MB231		metastatic cancer malignant pleural effusion
SK-BR-3			ERalpha and ERbeta-negative		over-expresses the HER2
T47D			+
T47D-V22			+

 

Breast Cancer
Cell Type	Herb Source(s)	Isolate	Refs
4T1	Curcuma zedoaria	Campesterol	Kazlowska, Lin, Chang, & Tsai, 2013
4T1		Cholesterol	Kazlowska et al., 2013
4T1		Schisandrin B	Zhang, Liu, & Hu, 2013
4T1		Schisandrin B	Xu et al., 2011
4T1	P. dentata	sterol	Kazlowska et al., 2013
4T1	Stephania tetrandra	Tetrandrine	Gao et al., 2013
BCRP/ABCG2	Berberis amurensis	Berberine	Tan et al., 2012
Bone metastasis		Plumbagin	Li et al., 2012
chemoprevention	soy, fava, and kudzu	Genistein	Marik et al., 2011
CSC	Salvia miltiorrhiza	Tanshinone II A	Lin et al., 2013
ER+	soy, fava, and kudzu	Genistein	Fox et al., 2013
Hs578T	Camellia sinensis	EGCG	Chen et al., 1998
HS578T	Scutellaria barbata	Pheoborbide	Lai, Mas, Nair, Mansor, & Navaratnam, 2010
HS578T, MDA-MB-231, MCF-7	Pueraria lobata	Puerarin	Lin et al., 2009
lung and bone metastasis of 4T1		Schisandrin B	Liu  et al., 2012
MCF-7	soy, fava, and kudzu	Genistein	Read et al., 1989
MCF-7	soy, fava, and kudzu	Genistein	Wang et al., 1996
MCF-7		Celandine Alkaloids	Kulp & Bragina, 2013
MCF-7	Curcuma zedoaria	Alismol	Syed Abdul Rahman, Abdul Wahab, & Abd Malek, 2013
MCF-7	cotton plant	Apogossypolone	Niu et al., 2012
MCF-7	Berberis amurensis	Berberine	Patil et al., 2010
MCF-7	Terminalia arjuna L.	Casuarinin	Kuo et al., 2005a
MCF-7	Saussurea lappa	Costunolide	Peng et al., 2013
MCF-7	Curcuma zedoaria	Curzerenone	Syed Abdul Rahman, Abdul Wahab, & Abd Malek, 2013
MCF-7		Dauricine	Ye et al., 2001
MCF-7		Deacetyl nomilinic acid glucoside (DNAG)	Lin et al., 2013
MCF-7	Saussurea lappa	Dehydrocostus lactone	Peng, Wang, Gu, Wen, & Yan, 2013
MCF-7	Trigonella foenum-graecum	Diosgenin	Li et al., 2005
MCF-7	Astragalus membranaceus	Formononetin	Chen et al., 2011
MCF-7	soy, fava, and kudzu	Genistein	Xu & Loo, 2001
MCF-7	soy, fava, and kudzu	Genistein	Anastasius et al., 2009
MCF-7	Panax genus	Ginsenosides	King et al., 2006
MCF-7	Herba epimedii	Icariin	Ye et al., 2005
MCF-7	several species of the genus Epimedium	Icaritin	Ye et al., 2005
MCF-7	Isatis (L.) genus	Indirubin	Spink et al., 2003
MCF-7		Isolimonexic acid (ILNA)	Lin et al., 2013
MCF-7		Limonexic acid	Lin et al., 2013
MCF-7		Limonin	Lin et al., 2013
MCF-7	Nelumbo nucifera	Neferine	Ye et al., 2001
MCF-7	citrus fruits (Citrus grandis, Citrus unshiu and Citrus reticulata)	Nomilin	Lin et al., 2013
MCF-7		Nomilinic acid glucoside	Lin et al., 2013
MCF-7	species of blister beetles, \including Mylabris phalerata and Lytta vesicatoria	Norcantharidin	Lin et al., 2013
MCF-7	species of blister beetles, \including Mylabris phalerata and Lytta vesicatoria	Norcantharidin	Shou et al., 2013
MCF-7		Obacunone	Lin et al., 2013
MCF-7	Rosa woodsii, Prosopis glandulosa, Phoradendron juniperinum, Syzygium claviflorum, Hyptis capitata Ternstromia gymnanthera	Oleanolic acid	Hao et al., 2013
MCF-7	Rabdosia rubescens	Oridonin	Chen et al., 2005
MCF-7	Cnidium monnieri	Osthole	Hung et al., 2011
MCF-7	Cortex periplocae	Periplocin	Zhao et al., 2009
MCF-7	Platycodon grandiflorum	Platycodin D	Yu et al., 2010
MCF-7	Lithospermum erythrorhizon	Shikonin	Wu et al., 2013
MCF-7	Lithospermum erythrorhizon	Shikonin	Han et al., 2007
MCF-7	Stephania tetrandra	Tetrandrine	Ye et al., 2001
MCF-7	tomato	Tomatine/Tomatidine	Friedman et al., 2009
MCF-7	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Es-Saady et al., 1996
MCF-7	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Kassi et al., 2009
MCF-7	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Qian et al., 2011
MCF-7	Scutellaria rivularis Scutellaria baicalensis	Wogonin	Ma et al., 2012
MCF-7	Humulus lupulus	Xanthohumol	Viola et al., 2013
MCF-7	Humulus lupulus	Xanthohumol	Del Mar Blanquer-Rosselló et al., 2013
MCF-7 and MDA-231	Trigonella foenum-graecum	Diosgenin	Srinivasan et al., 2009
MCF-7 and MDA-MB-231	Evodia rutaecarpa	Evodiamine	Wang et al., 2013
MCF-7 and T47D	Astragalus membranaceus	Formononetin	Chen & Sun, 2012
MCF-7	blister beetles, including Mylabris phalerata (Pall.) and Lytta vesicatoria (Linnaeus)	Cantharidin	Shou et al., 2013
MCF-7, MCF-7/Adr, MCF-7/Bcl-2, MCF-7/Bcl-x(L)	Lithospermum erythrorhizon	Shikonin	Chen et al., 2011
MCF-7, MDA-231, MDA-435	soy, fava, and kudzu	Genistein	Tanos et al., 2002
MCF-7, MDA-MB231	Rabdosia rubescens	Oridonin	Ikezoe et al., 2003
MCF-7, MDA-MB-231	Berberis amurensis	Berberine	Kim et al., 2009
MCF-7, MDA-MB-231	Saussurea lappa	Costunolide	Choi et al., 2005
MCF-7, MDA-MB-231	Rhizoma curcuma longa	Germacrone	Zhong et al., 2011
MCF-7, MDA-MB-231	Commiphora wightii	Guggulsterones	Jiang et al., 2013
MCF-7, MDA-MB-231	Citrus aurantium	Naringin	Karimi et al., 2012
MCF-7, MDA-MB-231	Bupleurum radix	Saikosaponin-A	Chen, Chang, Chung, & Chen, 2003
MCF-7, MDA-MB-231	Trichosanthes kirilowii	Trichosanthin	Fang et al., 2012
MCF7, MDA-MB-453	several species of the genus Epimedium	Icaritin	Guo et al., 2011
MCF-7, MDA-MB-468	Camptotheca acuminate	10-hydroxycamptothecin (HCPT)	Liu & Zhang, 1998
MCF-7, MDA-MB-468		Camptothecin	Liu & Zhang, 1998
MCF 7, SK BR 3 and ZR 75 1	soy, fava, and kudzu	Genistein	Choi et al., 2013
MCF-7, T-47D	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalin	Franek, 2005
MCF-7, T47D and 549	soy, fava, and kudzu	Genistein	Shao et al., 2000
MCF-7/ADR	Magnolia genus	Honokiol	Xu et al., 2006
MCF-7/adr	Pueraria lobata	Puerarin	Hien et al., 2010
MCF-7/Adr, MCF-7/wt	honeybee hives	Caffeic acid phenethyl ester (CAPE)	Berdowska et al., 2013
MCF-7/TAM	Stephania tetrandra	Tetrandrine	Chen & Chen, 2013
MDA-468, MCF-7 and MCF-7-D-40	soy, fava, and kudzu	Genistein	Peterson et al., 1991
MDA-MB-23	soy, barley, wheat, and rye, including Glycine max, Hordeum vulgare, Triticum (L.) genus and Secale cereale L	Lunasin	Hsieh et al., 2010
MDA-MB-231	various fruits, vegetables, and herbs	Apigenin	Mak, 2009
MDA-MB-231	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalein	Wang et al., 2010
MDA-MB-231	Scutellaria radix, Scutellaria rivularis, Scutellaria baicalensis, Scutellaria lateriflora	Baicalin	Zhu et al., 2008
MDA-MB-231	Saussurea lappa	Costunolide	Choi et al., 2013
MDA-MB-231	Saussurea lappa	Costunolide	Choi et al., 2012
MDA-MB-231	Trichosanthes kirilowii	Cucurbitacin D	Kim et al., 2013
MDA-MB-231	Camellia sinensis	EGCG	Bigelow et al., 2006
MDA-MB-231	Rheum palmatum., Senna obtusifolia, Fallopia japonica, Kalimeris indica, Ventilago madraspatana, Rumex nepalensis, Fallopia multiflora, Cassia occidentalis, Senna siamea, Acalypha australis	Emodin	Narender et al., 2013
MDA-MB-231	various Garcinia species	Gambogic acid	Li et al., 2012
MDA-MB-231	soy, fava, and kudzu	Genistein	Mak, 2009
MDA-MB-231	Glycyrrhiza glabra	Glabridin	Hsu et al., 2011
MDA-MB-231	Dendrobrium loddigesii	Moscatilin	Pai et al., 2013
MDA-MB-231	Rabdosia rubescens	Oridonin	Wang et al., 2013
MDA-MB-231	Cnidium monnieri	Osthole	Guo et al., 2011
MDA-MB-231	Platycodon grandiflorum	Platycodin D	Chun et al., 2013
MDA-MB-231	Sanguinaria canadensis	Sanguinarine	Choi, Kim, Lee, & Choi, 2008
MDA-MB-231	Callyspongia siphonella	Sipholenol A	Foudah et al., 2013
MDA-MB-231	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Yeh et al., 2010
MDA-MB-231 and 4T1	Cnidium monnieri	Osthole	Ye et al., 2013
MDA-MB-231 and MCF-7	Nigella sativa	Thymoquinone	Attoub et al., 2012
MDA-MB-231, Hs578T		Chalcone	Kim et al., 2013
MDA-MB-231, MCF7, AU565, SK-BR-3	Alkanna cappadocica	5-O-methyl-11-O-acetylalkannin	Sevimli-Gur et al., 2010
MDA-MB-453	various fruits, vegetables, and herbs	Apigenin	Choi, 2009
MDA-MB-468	soy, fava, and kudzu	Genistein	Balabhadrapathruni et al., 2000
MDA-MB-468	fruits, vegetables, leaves, grains, red wine	Quercetin	Balabhadrapathruni et al., 2000
SK-BR-3	Rubia cordifolia	Mollugin	Do et al., 2013
T47D	Schisandra chinensis	Schizandrin	Kim et al., 2010
T47D, MDA-MB-231	Salvia miltiorrhiza	Tanshinone II A	Zhao et al., 2010
T47D, MDA-MB-231	Scutellaria rivularis Scutellaria baicalensis	Wogonin	Chung et al., 2008
T-47D, MDA-MB-231	Psoraleae Semen	Bakuchiol	Chen et al., 2010
TICs	Stephania tetrandra	Tetrandrine	Xu et al., 2011
TNBC	Citrus aurantium	Naringin	Camargo et al., 2012
TNBC	Citrus aurantium	Naringin	Li et al., 2013
U937, MDA-MB-231	Salvia miltiorrhiza	Tanshinone I	Nizamutdinova et al., 2008
ZR75.1, MDAMB-231 and BT20	soy, fava, and kudzu	Genistein	Cappelletti et al., 2000
Non specific	Aloe vera	Aloe-emodin	Huang et al., 2013
Non specific	Artemisia annua	Artemisinin	Lai, 2006
Non specific	Berberis amurensis Berberis vulgaris	Berbamine	Wang, 2009
Non specific	Betula platyphylla, Betula X caerulea, Betula cordifolia, Betula papyrifera, Betula populifolia, Dillenia indica	Betulin	Rzeski, 2009
Non specific	Scutellaria barbata	Bezielles	Klawitter et al., 2011
Non specific		Carnosic acid	Ngo et al., 2011
Non specific	Rosmarinus officinalis Salvia pachyphylla	Carnosol	Johnson, 2011
Non specific	Rosmarinus officinalis Salvia pachyphylla	Carnosol	Singletary et al., 1996
Non specific	Rosmarinus officinalis Salvia pachyphylla	Carnosol	Ngo et al., 2011
Non specific	Curcuma longa	Curcumin	Anand et al., 2008
Non specific	Saussurea lappa	Dehydrocostus lactone	Kuo et al., 2009
Non specific	Saussurea lappa	Dehydrocostus lactone	Kuo et al., 2009
Non specific	Trigonella foenum-graecum	Diosgenin	Chiang et al., 2007
Non specific	Trigonella foenum-graecum	Diosgenin	Jagadeesan et al., 2012
Non specific	Camellia sinensis	EGCG	Kavanagh et al., 2001
Non specific	berries, walnuts, pecans, pomegranate, cranberries, and longan	Ellagic acid	Losso et al., 2004; Larrosa et al., 2006; Malik et al., 2011
Non specific	berries, walnuts, pecans, pomegranate, cranberries, and longan	Ellagic acid	Munagala et al., 2013
Non specific	Rheum palmatum., Senna obtusifolia, Fallopia japonica, Kalimeris indica, Ventilago madraspatana, Rumex nepalensis, Fallopia multiflora, Cassia occidentalis, Senna siamea, Acalypha australis	Emodin	Huang et al., 2013
Non specific	Rheum palmatum., Senna obtusifolia, Fallopia japonica, Kalimeris indica, Ventilago madraspatana, Rumex nepalensis, Fallopia multiflora, Cassia occidentalis, Senna siamea, Acalypha australis	Emodin	Kurebayashi, 2001
Non specific	various Garcinia species	Gambogic acid	Qi et al., 2008
Non specific	soy, fava, and kudzu	Genistein	van Duursen et al., 2011
Non specific	soy, fava, and kudzu	Genistein	Kim et al., 1998
Non specific	soy, fava, and kudzu	Genistein	Zava et al., 1997
Non specific	Glycyrrhiza glabra	Glabridin	Tamir et al., 2000
Non specific	Glycine max	Glyceolins	Salvo et al., 2006
Non specific	Commiphora wightii	Guggulsterones	Andujar et al., 2013
Non specific	Phellinus igniarius	Hispolon	Lu et al., 2009
Non specific	Magnolia genus	Honokiol	Munroe et al., 2007; Chen et al., 2009; Fried, & Arbiser, 2009
Non specific		Isoflavones	Wu et al., 2013
Non specific		LCS101	Samuels et al., 2013
Non specific	many plants and foods, including Terminalia chebula, Prunella vulgaris and Perilla frutescens	Luteolin	Tu et al., 2013
Non specific	Anemarrhena asphodeloides	Mangiferin	Li et al., 2013
Non specific	Cnidium monnieri	Osthole	Yang et al., 2010
Non specific	Tanacetum parthenium	Parthenolide	Whipple et al., 2013
Non specific	vegetables and fruits	Phytosterols	Choudhary & Tran, 2011
Non specific	vegetables and fruits	Phytosterols	Woyengo et al., 2009
Non specific		Piperine	Kakarala et al., 2010
Non specific	berries and grapes, plants (including Fallopia japonica, Gnetum cleistostachyum, Vaccinium arboretum, Vaccinium angustifolium, Vaccinium corymbosum	Resveratrol	Lu et al., 1999
Non specific		Rosmarinic acid	Ngo et al., 2011
Non specific	Silybum marianum	Silibinin	Oh et al., 2013
Non specific	Nigella sativa	Thymoquinone	Motaghed et al., 2013
Non specific	Nigella sativa	Thymoquinone	Rajput et al., 2013
Non specific	Rosmarinus officinalis, Salvia officinalis, Prunella vulgaris, Psychotria serpens Hyptis capitata	Ursolic acid	Ngo et al., 2011
risk	soy, fava, and kudzu	Genistein	Rahal et al., 2011